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1.
BMC Genomics ; 24(1): 81, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810020

RESUMO

Trichosanthes kirilowii Maxim. (TK) is a dioecious plant in the Cucurbitaceae family of which different sexes have separate medicinal uses. We used Illumina high-throughput sequencing technology to sequence miRNAs from male and female flower buds of TK. We performed bioinformatics analysis, miRNA identification, and target gene prediction on the data obtained from sequencing, and association analysis was performed in combination with the results of a previous transcriptome sequencing study. As a result, there were 80 differentially expressed miRNAs (DESs) between the female and male plants (48 upregulated and 32 downregulated in female plants). Moreover, 27 novel miRNAs in DESs were predicted to have 282 target genes, and 51 known miRNAs were predicted to have 3418 target genes. By establishing a regulatory network between miRNAs and target genes, 12 core genes were screened, including 7 miRNAs and 5 target genes. Among them, tkmiR157a-5p, tkmiR156c, tkmiR156_2, and tkmiR156k_2 jointly target the regulation of tkSPL18 and tkSPL13B. These two target genes are specifically expressed in male and female plants, respectively, and are involved in the biosynthesis process of BR, which is closely related to the sex differentiation process of TK. The identification of these miRNAs will provide a reference for the analysis of the sex differentiation mechanism of TK.


Assuntos
Cucurbitaceae , MicroRNAs , Trichosanthes , Trichosanthes/genética , MicroRNAs/genética , Regulação da Expressão Gênica de Plantas , Cucurbitaceae/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos
2.
Purinergic Signal ; 19(1): 283-295, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35939197

RESUMO

Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the nervous system and immune system by activating P2 purinergic receptors. Recent increasingly studies showed that extracellular ATP exhibits circadian oscillation with an approximately 24-h periodicity, which participates in regulatory pathways of central oscillator suprachiasmatic nucleus and peripheral oscillator bladder, respectively. Oscillators modulate the protein expression of ATP release channels and ectonucleotidase activity through clock genes; indeed, real-time alterations of ATP release and degradation determine outcomes of temporal character on extracellular ATP rhythm. The regulatory pathways on extracellular ATP rhythm are different in central and peripheral systems. In this review, we summarize the circadian rhythm of extracellular ATP and discuss several circadian regulatory pathways in different organs via ATP release and degradation, to provide a new understanding for purinergic signaling in the regulatory mechanism of circadian rhythm and a potential target to research the circadian regulation of extracellular ATP in other circadian oscillators.


Assuntos
Ritmo Circadiano , Núcleo Supraquiasmático , Ritmo Circadiano/genética , Núcleo Supraquiasmático/metabolismo , Trifosfato de Adenosina/metabolismo
3.
Purinergic Signal ; 19(1): 155-162, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35175489

RESUMO

The basic research indicated that microglial P2Y12 receptors (P2Y12Rs) are involved in the pathophysiology of epilepsy through regulated microglial-neuronal interactions, aberrant neurogenesis, or immature neuronal projections. However, whether the clinic case of epilepsy would be associated with P2Y12 receptor gene polymorphisms is presented with few data. In our study, a total of 176 patients with epilepsy and 50 healthy controls were enrolled. Two single-nucleotide polymorphisms, namely rs1491974 and rs6798347, were selected for analysis. The results revealed that carriers of the G allele of rs1491974 G>A or rs6798347 G>A may be associated with an increased risk of epilepsy (OR = 0.576, 95% CI = 0.368-0.901, p = 0.015; OR = 0.603, 95% CI = 0.367-0.988, p = 0.043). Interestingly, we found that the rs1491974 G>A genotype and allele frequencies have only a significant difference in female instead of male case (p = 0.004 for genotype; p = 0.001 for allele). The subgroup analysis demonstrated that individuals with the rs1491974 G>A genotype might have more frequent seizure (OR = 0.476, 95% CI = 0.255-0.890; p = 0.019). These data implied that both rs1491974 and rs6798347 polymorphisms of P2Y12R would be able to play import roles in epilepsy susceptibility, whereas the rs1491974 polymorphism may be specifically related to seizure frequency.


Assuntos
Epilepsia , Antagonistas do Receptor Purinérgico P2Y , Humanos , Masculino , Feminino , Genótipo , Polimorfismo de Nucleotídeo Único , Frequência do Gene , Convulsões/complicações , Receptores Purinérgicos P2Y12
4.
Inorg Chem ; 62(38): 15711-15718, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37695723

RESUMO

Exploring highly efficient blue-emissive lead-free halide materials is a significant and challenging objective in the study of luminescent materials. This study reports the synthesis of a new zero-dimensional (0D) hybrid zinc halide of [CYP]ZnBr4 (CYP = 1-cyclohexylpiperazine) containing an isolated [ZnBr4]2- tetrahedron. [CYP]ZnBr4 exhibits strong blue light emission with a high photoluminescence quantum yield (PLQY) of 79.22%, surpassing all previously reported 0D zinc halide counterparts. According to the theoretical and experimental studies, the blue light emission is attributed to intrinsic self-trapped excitons resulting from strong electron-phonon coupling and structural deformation. Importantly, [CYP]ZnBr4 demonstrates excellent structural and luminescence stability toward high temperatures (180 °C) over at least half a month. High luminescence efficiency and stability enable [CYP]ZnBr4 to be an efficient blue phosphor to fabricate white light-emitting diodes (LEDs), which produces high-quality white light with a color rendering index (CRI) of 93.1 and a correlated color temperature (CCT) of 5304 K, closely resembling natural sunlight. This white LED also exhibits consistent performance and stability across different drive currents, suggesting the potential for high-power optoelectronic applications. Overall, this study paves the way for the utilization of 0D hybrid halides in advanced solid-state lighting applications.

5.
Skin Res Technol ; 29(12): e13415, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38062667

RESUMO

INTRODUCTION: Chronic wounds are wounds that are not healed or have no healing tendency for more than 1 month due to various factors. In clinical nursing, chronic wounds are often not properly treated, and the treatment efficiency is low. Therefore, it is very important to explore effective methods to deal with chronic wounds. OBJECTIVE: To explore the effect of a self-made negative pressure suction device (NPSD) in the nursing of chronic wounds in the elderly. METHODS: A total of 50 elderly patients with chronic wounds who were hospitalised in our hospital from January 2020 to December 2022 were selected as participants by convenient sampling. According to the random number table method, they were divided into a control group and an observation group, with 25 people in each group. The control group was treated with chloroplast foam dressing, debridement gel and alginate dressing. The observation group was treated with a self-made NPSD on the basis of the control group. The wound healing of the two groups was observed. RESULTS: After the intervention of the self-made NPSD, the granulation tissue coverage rate and wound volume reduction rate of the observation group were significantly increased (p < 0.05), and the positive rate of bacterial infection was significantly decreased (p < 0.05). After 3 months of intervention, the total effective rate of the observation group was significantly higher than that of the control group (χ2  = 3.869, p = 0.0492). CONCLUSION: The self-made NPSD can effectively promote the healing of a chronic wound.


Assuntos
Transplante de Pele , Cicatrização , Humanos , Idoso , Sucção , Resultado do Tratamento , Desbridamento , Transplante de Pele/métodos
6.
Int J Mol Sci ; 24(6)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36982618

RESUMO

Ecto-5'-nucleotidase (CD73) plays a strategic role in calibrating the magnitude and chemical nature of purinergic signals that are delivered to immune cells. Its primary function is to convert extracellular ATP to adenosine in concert with ectonucleoside triphosphate diphosphohydrolase-1 (CD39) in normal tissues to limit an excessive immune response in many pathophysiological events, such as lung injury induced by a variety of contributing factors. Multiple lines of evidence suggest that the location of CD73, in proximity to adenosine receptor subtypes, indirectly determines its positive or negative effect in a variety of organs and tissues and that its action is affected by the transfer of nucleoside to subtype-specific adenosine receptors. Nonetheless, the bidirectional nature of CD73 as an emerging immune checkpoint in the pathogenesis of lung injury is still unknown. In this review, we explore the relationship between CD73 and the onset and progression of lung injury, highlighting the potential value of this molecule as a drug target for the treatment of pulmonary disease.


Assuntos
Pneumopatias , Lesão Pulmonar , Humanos , 5'-Nucleotidase , Adenosina , Trifosfato de Adenosina
7.
Zhongguo Zhong Yao Za Zhi ; 48(3): 681-688, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872231

RESUMO

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.


Assuntos
Bupleurum , Fígado , Animais , Camundongos , Aspartato Aminotransferases
8.
Arch Microbiol ; 204(10): 633, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123413

RESUMO

A urea-utilizing bacterium, designated Q2-2 T, was isolated from landfill. Cells of strain Q2-2 T were Gram stain-negative, aerobic, short-rod bacteria. Strain Q2-2 T was observed to grow at a temperature range of 15-37℃ (optimum 30 â„ƒ), a pH range of 5.5-9.5 (optimum pH 8.0) and 0-4% (w/v) NaCl (optimum 1%). The major respiratory quinone was Q-8, and the major polar lipids were diphosphatidyl glycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, and phosphatidyl glycerol. Based on the 16S rRNA gene sequence, strain Q2-2 T had the highest similarity with Paracandidimonas caeni 24 T (98.0%), followed by Pusillimonas soli MJ07T (97.5%), Parapusillimonas granuli Ch07T (97.2%), Pusillimonas ginsengisoli DCY25T (97.1%) and Paracandidimonas soli IMT-305 T (96.4%). The ANI values between strain Q2-2 T and the above related type strains were 71.02%, 73.52%, 74.32%, 74.59% and 72.29%, respectively. The DNA G + C content of strain Q2-2 T was 61.1%. Therefore, strain Q2-2 T represents a novel species of the genus Paracandidimonas, for which the name Paracandidimonas lactea sp. nov. (type strain Q2-2 T = CGMCC 1.19179 T = JCM 34906 T) is proposed.


Assuntos
Fosfatidiletanolaminas , Ureia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Glicerol , Fosfatidilgliceróis , Filogenia , Quinonas , RNA Ribossômico 16S/genética , Cloreto de Sódio , Instalações de Eliminação de Resíduos
9.
Eur Radiol ; 32(6): 3778-3789, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35020012

RESUMO

OBJECTIVES: To examine the diagnostic accuracy of machine learning-based coronary CT angiography-derived fractional flow reserve (FFRCT) in diabetes mellitus (DM) patients. METHODS: In total, 484 patients with suspected or known coronary artery disease from 11 Chinese medical centers were retrospectively analyzed. All patients underwent CCTA, FFRCT, and invasive FFR. The patients were further grouped into mild (25~49 %), moderate (50~69 %), and severe (≥ 70 %) according to CCTA stenosis degree and Agatston score < 400 and Agatston score ≥ 400 groups according to coronary artery calcium severity. Propensity score matching (PSM) was used to match DM (n  = 112) and non-DM (n  = 214) groups. Sensitivity, specificity, accuracy, and area under the curve (AUC) with 95 % confidence interval (CI) were calculated and compared. RESULTS: Sensitivity, specificity, accuracy, and AUC of FFRCT were 0.79, 0.96, 0.87, and 0.91 in DM patients and 0.82, 0.93, 0.89, and 0.89 in non-DM patients without significant difference (all p > 0.05) on a per-patient level. The accuracies of FFRCT had no significant difference among different coronary stenosis subgroups and between two coronary calcium subgroups (all p > 0.05) in the DM and non-DM groups. After PSM grouping, the accuracies of FFRCT were 0.88 in the DM group and 0.87 in the non-DM group without a statistical difference (p > 0.05). CONCLUSIONS: DM has no negative impact on the diagnostic accuracy of machine learning-based FFRCT. KEY POINTS: • ML-based FFRCT has a high discriminative accuracy of hemodynamic ischemia, which is not affected by DM. • FFRCT was superior to the CCTA alone for the detection of ischemia relevance of coronary artery stenosis in both DM and non-DM patients. • Coronary calcification had no significant effect on the diagnostic accuracy of FFRCT to detect ischemia in DM patients.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Diabetes Mellitus , Reserva Fracionada de Fluxo Miocárdico , Cálcio , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Valor Preditivo dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
Eur Radiol ; 32(8): 5210-5221, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35258672

RESUMO

OBJECTIVES: To propose a novel functional Coronary Artery Disease-Reporting and Data System (CAD-RADS) category system integrated with coronary CT angiography (CCTA)-derived fractional flow reserve (FFRCT) and to validate its effect on therapeutic decision and prognosis in patients with coronary artery disease (CAD). METHODS: Firstly, we proposed a novel functional CAD-RADS and evaluated the performance of functional CAD-RADS for guiding treatment strategies with actual clinical treatment as a reference standard in a retrospective multicenter cohort with CCTA and invasive FFR performed in all patients (n = 466). Net reclassification improvement (NRI) of functional CAD-RADS over anatomical CAD-RADS was calculated. Secondly, the prognostic value of functional CAD-RADS in a prospective two-arm cohort (566 [FFRCT arm] vs. 567 [CCTA arm]) was calculated, after a 1-year follow-up, functional CAD-RADS in FFRCT arm (n = 513) and anatomical CAD-RADS in CCTA arm (n = 511) to determine patients at risk of adverse outcomes were compared with a Cox hazard proportional model. RESULTS: Functional CAD-RADS demonstrated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) and comparable performance to FFR (AUC: 0.828 vs. 0.848, p = 0.253) in guiding therapeutic decisions. Functional CAD-RADS resulted in the revision of management plan as determined by anatomical CAD-RADS in 30.0% of patients (n = 140) (NRI = 0.369, p < 0.001). Functional CAD-RADS was an independent predictor for 1-year outcomes with indexes of concordance of 0.795 and the corresponding value was 0.751 in anatomical CAD-RADS. CONCLUSION: The novel functional CAD-RADS gained incremental value in guiding therapeutic decision-making compared with anatomical CAD-RADS and comparable power in 1-year prognosis with anatomical CAD-RADS in a real-world scenario. KEY POINTS: • The novel functional CAD-RADS category system with FFRCT integrated into the anatomical CAD-RADS categories was originally proposed. • The novel functional CAD-RADS category system was validated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) in guiding therapeutic decisions and revised management plan in 30.0% of patients as determined by anatomical CAD-RADS (net reclassification improvement index = 0.369, p < 0.001). • Functional CAD-RADS was an independent predictor with an index of concordance of 0.795 and 0.751 in anatomical CAD-RADS for 1-year prognosis of adverse outcomes.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Humanos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Tomografia Computadorizada por Raios X
11.
J Org Chem ; 87(2): 1493-1501, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-35014249

RESUMO

Herein, we report an efficient photoinduced radical tandem trifluoromethylation/cyclization reaction of N-cyanamide alkenes for the synthesis of functionalized quinazolinones. Importantly, the reaction is carried out under mild conditions without any additional photosensitizer, metal, or extra additives. A series of trifluoromethyl quinazolinones were prepared efficiently with good yields and excellent functional group tolerance. Preliminary mechanistic experiments were conducted to indicate that the transformation proceeds via a possible mechanism involving photoexcited EDA complex and chain propagation.


Assuntos
Fármacos Fotossensibilizantes , Quinazolinonas , Catálise , Ciclização , Luz
12.
Health Expect ; 25(1): 203-213, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34585465

RESUMO

BACKGROUND: Patients with multimorbidity often experience treatment burden as a result of fragmented, specialist-driven healthcare. The 'family doctor team' is an emerging service model in China to address the increasing need for high-quality routine primary care. OBJECTIVE: This study aimed to explore the extent to which treatment burden was associated with healthcare needs and patients' experiences. METHODS: Multisite surveys were conducted in primary care facilities in Guangdong province, southern China. Interviewer-administered questionnaires were used to collect data from patients (N = 2160) who had ≥2 clinically diagnosed long-term conditions (multimorbidity) and had ≥1 clinical encounter in the past 12 months since enrolment registration with the family doctor team. Patients' experiences and treatment burden were measured using a previously validated Chinese version of the Primary Care Assessment Tool (PCAT) and the Treatment Burden Questionnaire, respectively. RESULTS: The mean age of the patients was 61.4 years, and slightly over half were females. Patients who had a family doctor team as the primary source of care reported significantly higher PCAT scores (mean difference 7.2 points, p < .001) and lower treatment burden scores (mean difference -6.4 points, p < .001) when compared to those who often bypassed primary care. Greater healthcare needs were significantly correlated with increased treatment burden (ß-coefficient 1.965, p < .001), whilst better patients' experiences were associated with lower treatment burden (ß-coefficient -0.252, p < .001) after adjusting for confounders. CONCLUSION: The inverse association between patients' experiences and treatment burden supports the importance of primary care in managing patients with multimorbidity. PATIENT CONTRIBUTION: Primary care service users were involved in the instrument development and data collection.


Assuntos
Multimorbidade , Atenção Primária à Saúde , Estudos Transversais , Atenção à Saúde , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
13.
Chemistry ; 27(2): 609-613, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33044771

RESUMO

The first organocatalytic asymmetric synthesis of an advanced intermediate of (+)-sarain A was achieved. This approach featured the employment of an organocatalytic asymmetric Michael addition reaction and a nitrogen-to-carbon chirality transfer to forge three chiral centers, as well as a catalytic hydrosilylation for the chemoselective reduction of a key lactam intermediate. The tricyclic intermediate contained all the required functionalities for elaborating into (+)-sarain A.

14.
Arch Microbiol ; 203(5): 2425-2430, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33674952

RESUMO

A polyphosphate-producing bacterium, YG09T, was isolated from the rhizosphere of Salvia miltiorrhiza. Its colonies were 2.0-3.0 mm in diameter, smooth, circular, convex and yellow after growth on R2A at 28 °C for 72 h, with aerobic, Gram-stain-negative, non-motile and rod-shaped bacteria. The strain was found to grow at 10-40 °C (optimum 37 °C), pH 5.5-8.0 (optimum 6.0), with 0-0.6% (w/v) NaCl (optimum 0). Chemotaxonomic analysis showed menaquinone-7 as the only quinone present; C15: 1 iso G, C15: 1 iso, C16: 0, C16: 0 3OH, C17: 0 iso 3OH, summed feature 3 (C16:1 ω7c and/or C16:1 ω6c) as the major fatty acids (> 5%), and phosphatidylethanolamine, three unidentified phospholipids, four unidentified polar lipids, three unidentified aminolipids, and one unidentified amino phospholipid as the polar lipids. The DNA G + C content was 44.6 mol%. The 16S rRNA gene sequences of the isolate showed highest similarities to Panacibacter ginsenosidivorans Gsoil 1550T (93.6%), Filimonas endophytica SR2-06T (93.4%), Parasegetibacter terrae SGM2-10T (92.8%), and Arvibacter flaviflagrans C-1-16T (92.7%), within the family Chitinophagaceae of the phylum Bacteroidetes. The ANI values between strain YG09T and Panacibacter ginsenosidivoran Gsoil 1550T, Filimonas endophytica SR2-06T and Filimonas lacunae YT21T were 69.4, 68.3 and 68.7%, respectively. Based on phenotypic, genotypic and phylogenetic analyses, strain YG09T represents a novel genus in the family Chitinophagaceae, for which the name Foetidibacter luteolus gen. sp. nov. is proposed. The type strain is Foetidibacter luteolus YG09T (= MCCC 1K04042T = KCTC 72595T).


Assuntos
Bacteroidetes/classificação , Filogenia , Rizosfera , Salvia miltiorrhiza/microbiologia , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , DNA Bacteriano/genética , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
15.
Eur Radiol ; 31(3): 1482-1493, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32929641

RESUMO

OBJECTIVE: To investigate the effect of coronary calcification morphology and severity on the diagnostic performance of machine learning (ML)-based coronary CT angiography (CCTA)-derived fractional flow reserve (CT-FFR) with FFR as a reference standard. METHODS: A total of 442 patients (61.2 ± 9.1 years, 70% men) with 544 vessels who underwent CCTA, ML-based CT-FFR, and invasive FFR from China multicenter CT-FFR study were enrolled. The effect of calcification arc, calcification remodeling index (CRI), and Agatston score (AS) on the diagnostic performance of CT-FFR was investigated. CT-FFR ≤ 0.80 and lumen reduction ≥ 50% determined by CCTA were identified as vessel-specific ischemia with invasive FFR as a reference standard. RESULTS: Compared with invasive FFR, ML-based CT-FFR yielded an overall sensitivity of 0.84, specificity of 0.94, and accuracy of 0.90 in a total of 344 calcification lesions. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of CT-FFR across different calcification arc, CRI, or AS levels. CT-FFR exhibited improved discrimination of ischemia compared with CCTA alone in lesions with mild-to-moderate calcification (AUC, 0.89 vs. 0.69, p < 0.001) and lesions with CRI ≥ 1 (AUC, 0.89 vs. 0.71, p < 0.001). The diagnostic accuracy and specificity of CT-FFR were higher than CCTA alone in patients and vessels with mid (100 to 299) or high (≥ 300) AS. CONCLUSION: Coronary calcification morphology and severity did not influence diagnostic performance of CT-FFR in ischemia detection, and CT-FFR showed marked improved discrimination of ischemia compared with CCTA alone in the setting of calcification. KEY POINTS: • CT-FFR provides superior diagnostic performance than CCTA alone regardless of coronary calcification. • No significant differences in the diagnostic performance of CT-FFR were observed in coronary arteries with different coronary calcification arcs and calcified remodeling indexes. • No significant differences in the diagnostic accuracy of CT-FFR were observed in coronary arteries with different coronary calcification score levels.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , China , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Aprendizado de Máquina , Masculino , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
16.
J Org Chem ; 86(23): 17156-17163, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34794309

RESUMO

A visible-light-driven multistep tandem reaction between vinyl azides and alkyl bromides has been developed leading to the formation of tetralone skeletons under mild conditions, which can be easily scaled up to the gram scale. Various 1-tetralone derivatives are synthesized and transformed into desired products in good to high yields.

17.
Bioorg Med Chem ; 38: 116130, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33848699

RESUMO

Protein-protein interactions (PPIs) are essentially fundamental to all cellular processes, so that developing small molecule inhibitors of PPIs have great significance despite representing a huge challenge. Studying PPIs with the help of peptide motifs could obtain the structural information and reference significance to reduce the difficulty in the development of small molecules. Computational methods are powerful tools to characterize peptide-protein interactions, especially molecular dynamics simulation and binding free energy calculation. Here, we established an affinity prediction model suitable for Casitas B lymphoma-b (Cbl-b) and phosphorylated motif system. According to the affinity data set of multiple truncated peptides, the force field, solvent model, and internal dielectric constant of molecular mechanics/generalized Born surface area (MM/GBSA) method were optimized. Further, we predicted the affinity of the rationally designed new sequences through this model and obtained a new 6-mer motif with a 7-fold increase in affinity and the comprehensive structure-activity relationship. Moreover, we proposed an insight of unexpected activity of the truncated 5-mer peptide and revealed the possible binding mode of the new highly active 6-mer motif by extended simulation. Our results showed that the activity enhancement of the truncated peptide was caused by the acetyl-mediated conformation change. The side chain of Arg and pTyr in the 6-mer motif co-occupied the site p1 to form numerous hydrogen bond interactions and increased hydrophobic interaction formed with Tyr266, leading to the higher affinity. The present work provided a reference to investigate the PPI of Cbl-b and phosphorylated substrates and guided the development of Cbl-b inhibitors.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-cbl/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Relação Dose-Resposta a Droga , Ligantes , Camundongos , Simulação de Dinâmica Molecular , Estrutura Molecular , Peptídeos/química , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-cbl/química , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Relação Estrutura-Atividade , Especificidade por Substrato
18.
BMC Fam Pract ; 22(1): 224, 2021 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-34774003

RESUMO

BACKGROUND: Follow-up care is crucial but challenging for disease management particularly in rural areas with limited healthcare resources and clinical capacity, yet few studies have been conducted from the perspective of rural primary care physicians (PCPs). We assessed the frequency of follow-up care delivered by rural PCPs for hypertension and type 2 diabetes - the two most common long-term conditions. METHODS: We conducted a multi-centre, self-administered survey study built upon existing general practice course programmes for rural PCPs in four provinces. Information on follow-up care delivery were collected from rural PCPs attending centralised in-class teaching sessions using a set of close-ended, multiple choice questions. Binary logistic regression analysis was performed to examine physician-level factors associated with non-attainment of the target frequency of follow-up care for hypertension and type 2 diabetes, respectively. The final sample consisted of rural PCPs from 52 township-level regions. The Complex Samples module was used in the statistical analysis to account for the multistage sample design. RESULTS: The overall response rate was 91.4%. Around one fifth of PCPs in rural practices did not achieve the target frequency of follow-up care delivery (18.7% for hypertension; 21.6% for type 2 diabetes). Higher education level of physicians, increased volume of daily patients seen, and no provision of home visits were risk factors for non-attainment of the target frequency of follow-up care for both conditions. Moreover, village physicians with less working experiences tended to have less frequent follow-up care delivery in type 2 diabetes management. CONCLUSIONS: Efforts that are solely devoted to enhancing rural physicians' education may not directly translate into strong motivation and active commitment to service provision given the possible existence of clinical inertia and workload-related factors. Risk factors identified for target non-attainment in the follow-up care delivery may provide areas for capacity building programmes in rural primary care practice.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Médicos de Atenção Primária , Assistência ao Convalescente , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Humanos , Hipertensão/epidemiologia , Hipertensão/terapia
19.
Pak J Pharm Sci ; 34(5): 1743-1748, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34803011

RESUMO

The effects of crude extract from the flowers of Trollius chinensis on expressions of mRNA and proteins related to vital genes (TLR 3, TBK 1, IRF 3 and IFN ß) in TLR 3 signaling pathway were investigated in the presence/absence of Polyinosinic acid-polycytidylic acid (PolyI: C) to ascertain the antiviral mechanism of these flowers. Real-time PCR and western blot were applied to determine the expressions of mRNA and proteins, respectively, and immunofluorescence assay was employed to study the effect on IRF 3 distribution between nuclei and cytoplasma. In the absence of PolyI:C, the crude extract reduced the mRNA expression of TLR 3, IRF 3 and IFN ß and the protein expression of TLR 3, and increased the protein expression of IRF 3 and the distribution of IRF 3 in nuclei. In the presence of PolyI:C, the extract reduced the mRNA and protein expressions of TLR 3 and the mRNA expression of IFN ß, meanwhile inhibited the translocation of IRF 3 into nuclei. The antiviral mechanism of the crude extract from the flowers of T. chinensis is to protect the host from inflammatory damage through intervening the TLR 3 signaling pathway and reducing the secretion of inflammatory factors.


Assuntos
Antivirais/farmacologia , Flores/química , Extratos Vegetais/farmacologia , Ranunculaceae/química , Transdução de Sinais/efeitos dos fármacos , Receptor 3 Toll-Like/metabolismo , Animais , Antivirais/química , Sobrevivência Celular , Cães , Regulação da Expressão Gênica/efeitos dos fármacos , Células Madin Darby de Rim Canino , Extratos Vegetais/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor 3 Toll-Like/genética
20.
Chemistry ; 26(43): 9518-9526, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32379364

RESUMO

As redox-active based supercapacitors are known as highly desirable next-generation supercapacitor electrodes, the targeted design of two ferrocene-functionalized (Fc(COOH)2 ) clusters based on coinage metals, [(PPh3 )2 AgO2 CFcCO2 Ag(PPh3 )2 ]2 ⋅7 CH3 OH (SC1 : super capacitor) and [(PPh3 )3 CuO2 CFcCO2 Cu(PPh3 )3 ]⋅3 CH3 OH (SC2 ), is reported. Both structures are fully characterized by various techniques. The structures are utilized as energy storage electrode materials, giving 130 F g-1 and 210 F g-1 specific capacitance at 1.5 A g-1 in Na2 SO4 electrolyte, respectively. The obtained results show that the presence of CuI instead of AgI improves the supercapacitive performance of the cluster. Further, to improve the conductivity, the PSC2 ([(PPh3 )2 CuO2 CFcCO2 ]∞ ), a polymeric structure of SC2 , was synthesized and used as an energy storage electrode. PSC2 displays high conductivity and gives 455 F g-1 capacitance at 3 A g-1 . The PSC2 as a supercapacitor electrode presents a high power density (2416 W kg-1 ), high energy density (161 Wh kg-1 ), and long cycle life over 4000 cycles (93 %). These results could lead to the amplification of high-performance supercapacitors in new areas to develop real applications and stimulate the use of the targeted design of coordination polymers without hybridization or compositions with additive materials.

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