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1.
Onco Targets Ther ; 17: 557-565, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006884

RESUMO

Background/Aims: There are currently few reports describing the liquid-based cytological characteristics of small cell neuroendocrine carcinoma of the cervix. This study aimed to retrospectively analyze these features to reduce missed or misdiagnosis. Methods: A total of 11 patients with histologically diagnosed small cell carcinoma of the cervix from three hospitals between 2017 and 2023 were included in this study. The cytological morphology of small cell carcinoma of the cervix and causes of missed or misdiagnosis were analyzed and summarized through a review of clinical data, liquid-based cytology, histology, immunohistochemistry, and human papillomaviruses (HPV) test results. Results: In this study, the positivity rate of preliminary cytological screening was 63.6% (7/11); however, no cases were accurately diagnosed as small cell carcinoma of the cervix. A total of 36.4% (4/11) of small cell carcinoma of the cervix cases were cytologically negative; retrospective cytology found that two of these were false negatives. The main cytological features of small cell carcinoma of the cervix were summarized. Most of the liquid-based cytology smear cells were dense, and almost all cases showed clustered and scattered cytoplasm-scanty tumor cells. The tumor cells were all deeply stained and relatively consistent small cells. Most cases showed typical nuclear molding, chromatin stippling, and no obvious nucleoli. Mild nuclear smears, nuclear fragments, and mitotic figures were seen in most cases. Conclusion: Liquid-based cytology has a high rate of missed diagnosis and misdiagnosis in small cell carcinoma of the cervix. This study confirms that reviewing cytology results can effectively reduce this proportion and that increasing understanding of small cell carcinoma of the cervix morphology is conducive to improving the cytology-based diagnosis rate.

2.
Curr Med Sci ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39039375

RESUMO

OBJECTIVE: The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population. METHODS: Clinical data of 30 693 inpatients who were diagnosed with type 2 diabetes mellitus (T2DM) and admitted between 2013 and 2018 were retrospectively analyzed. The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data, and risk factors were analyzed by multiple imputation and regression. RESULTS: The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4% and 21.5%, respectively, and 85.2% of the stroke patients had ischemic stroke. Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors. Compared with no-risk-factor clustering, the risk of stroke significantly increased 3-4 times in the presence of more than 4 risk-factor clusters (P<0.001). Hypertension was the most common major risk factor for ischemic stroke [odds ratio (OR), 2.34; 95% confidence interval (CI), 2.18-2.50] and hemorrhagic stroke (OR, 3.68; 95% CI 2.95-4.59; P<0.001). Moreover, a 1-standard-deviation increase in fasting blood glucose (FBG) was significantly negatively correlated with ischemic stroke risk, and the same change in FBG was significantly associated with an 8% increased risk of hemorrhagic stroke. CONCLUSION: The prevalence of stroke in patients with T2DM is rather high, and the clustering of risk factors is associated with the development of stroke in T2DM patients. Risk factors differ in different stroke subtypes. Identifying risk factors for a specific high-risk group is necessary.

3.
Angew Chem Int Ed Engl ; : e202406711, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923764

RESUMO

Spin state is often regarded as the crucial valve to release the reactivity of energy-related catalysts, yet it is also challenging to precisely manipulate, especially for the active center ions occupied at the specific geometric sites. Herein, a π-π type orbital coupling of 3d (Co)-2p (O)-4f (Ce) was employed to regulate the spin state of octahedral cobalt sites (CoOh) in the composite of Co3O4/CeO2. More specifically, the equivalent high-spin ratio of CoOh can reach to 54.7% via tuning the CeO2 content, thereby triggering the average eg filling (1.094) close to the theoretical optimum value. The corresponding catalyst exhibits a superior water oxidation performance with an overpotential of 251 mV at 10 mA cm-2, rivaling most cobalt-based oxides state-of-the-art. The π-π type coupling corroborated by the matched energy levels between Ce t1u/t2u-O and CoOh t2g-O π type bond in the calculated crystal orbital Hamilton population and partial density of states profiles, stimulates a π-donation between O 2p and π-symmetric Ce 4fyz2 orbital, consequently facilitating the electrons hopping from t2g to eg orbital of CoOh. This work offers an in-depth insight into understanding the 4f and 3d orbital coupling for spin state optimization in composite oxides.

4.
Eur J Med Chem ; 275: 116595, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38875808

RESUMO

In the quest for potent α-glucosidase inhibitors to combat diabetes, a series of novel thiosemicarbazide-based ß-carboline derivatives (CTL1∼36) were synthesized and evaluated. CTL1∼36 exhibited remarkable inhibitory effects against α-glucosidase, with IC50 values ranging from 2.81 to 12.40 µM, significantly surpassing the positive control acarbose (IC50 = 564.28 µM). Notably, CTL26 demonstrated the most potent inhibition (IC50 = 2.81 µM) and was characterized as a non-competitive inhibitor. Through a combination assay with fluorescence quenching, 3D fluorescence spectra, CD spectra, and molecular docking, we elucidated that CTL26 formed a complex with α-glucosidase via hydrogen bondings and hydrophobic interactions, leading to α-glucosidase conformation changes that impaired enzymatic activity. In vivo studies revealed that oral administration of CTL26 (25 and 50 mg/kg/d) reduced fasting blood glucose levels, enhanced glucose tolerance, and ameliorated lipid abnormalities in diabetic mice. These findings positioned CTL26 as a promising candidate for the development of α-glucosidase inhibitors with anti-diabetic potential.


Assuntos
Carbolinas , Diabetes Mellitus Experimental , Inibidores de Glicosídeo Hidrolases , Semicarbazidas , alfa-Glucosidases , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Animais , alfa-Glucosidases/metabolismo , Carbolinas/farmacologia , Carbolinas/química , Carbolinas/síntese química , Semicarbazidas/farmacologia , Semicarbazidas/química , Semicarbazidas/síntese química , Camundongos , Relação Estrutura-Atividade , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Estrutura Molecular , Simulação de Acoplamento Molecular , Relação Dose-Resposta a Droga , Masculino , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Glicemia/análise , Humanos
5.
Microbiol Spectr ; 12(6): e0400523, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38709045

RESUMO

Clostridioides difficile infection (CDI) with high morbidity and high mortality is an urgent threat to public health, and C. difficile pathogenesis studies are eagerly required for CDI therapy. The major surface layer protein, SlpA, was supposed to play a key role in C. difficile pathogenesis; however, a lack of isogenic slpA mutants has greatly hampered analysis of SlpA functions. In this study, the whole slpA gene was successfully deleted for the first time via CRISPR-Cas9 system. Deletion of slpA in C. difficile resulted in smaller, smother-edged colonies, shorter bacterial cell size, and aggregation in suspension. For life cycle, the mutant demonstrated lower growth (changes of optical density at 600 nm, OD600) but higher cell density (colony-forming unit, CFU), decreased toxins production, and inhibited sporulation. Moreover, the mutant was more impaired in motility, more sensitive to vancomycin and Triton X-100-induced autolysis, releasing more lactate dehydrogenase. In addition, SlpA deficiency led to robust biofilm formation but weak adhesion to human host cells.IMPORTANCEClostridioides difficile infection (CDI) has been the most common hospital-acquired infection, with a high rate of antibiotic resistance and recurrence incidences, become a debilitating public health threat. It is urgently needed to study C. difficile pathogenesis for developing efficient strategies as CDI therapy. SlpA was indicated to play a key role in C. difficile pathogenesis. However, analysis of SlpA functions was hampered due to lack of isogenic slpA mutants. Surprisingly, the first slpA deletion C. difficile strain was generated in this study via CRISPR-Cas9, further negating the previous thought about slpA being essential. Results in this study will provide direct proof for roles of SlpA in C. difficile pathogenesis, which will facilitate future investigations for new targets as vaccines, new therapeutic agents, and intervention strategies in combating CDI.


Assuntos
Proteínas de Bactérias , Biofilmes , Clostridioides difficile , Infecções por Clostridium , Deleção de Genes , Clostridioides difficile/genética , Clostridioides difficile/patogenicidade , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Humanos , Infecções por Clostridium/microbiologia , Biofilmes/crescimento & desenvolvimento , Antibacterianos/farmacologia , Virulência/genética , Sistemas CRISPR-Cas , Aderência Bacteriana/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo
6.
Res Sq ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38798359

RESUMO

Parkinson's disease (PD) is marked by degeneration in the nigrostriatal dopaminergic pathway, affecting motor control via complex changes in the cortico-basal ganglia-thalamic motor network, including the primary motor cortex (M1). The modulation of M1 neuronal activity by dopaminergic inputs, particularly from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), plays a crucial role in PD pathophysiology. This study investigates how nigrostriatal dopaminergic degeneration influences M1 neuronal activity in rats using in vivo calcium imaging. Histological analysis confirmed dopaminergic lesion severity, with high lesion level rats showing significant motor deficits. Levodopa treatment improved fine motor abilities, particularly in high lesion level rats. Analysis of M1 calcium signals based on dopaminergic lesion severity revealed distinct M1 activity patterns. Animals with low dopaminergic lesion showed increased calcium events, while high lesion level rats exhibited decreased activity, partially restored by levodopa. These findings suggest that M1 activity is more sensitive to transient fluctuations in dopaminergic transmission, rather than to chronic high or low dopaminergic signaling. This study underscores the complex interplay between dopaminergic signaling and M1 neuronal activity in PD symptoms development. Further research integrating behavioral and calcium imaging data can elucidate mechanisms underlying motor deficits and therapeutic responses in PD.

7.
Eur Arch Otorhinolaryngol ; 281(8): 4351-4361, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38724856

RESUMO

BACKGROUND: While treatment advancements have prolonged the lives of patients with head and neck cancer, the subgroups of these patients at higher risk for cardiovascular disease (CVD) mortality remain unclear. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with head and neck cancer from 2000 to 2019. We compared their CVD mortality against the general US population using standardized mortality ratios (SMRs). RESULTS: Our analysis included 474,366 patients, identifying that 14% of deaths were due to CVD, with an SMR of 1.19. Notably, patients under the age of 39 had a CVD SMR increase of over 100-fold. Those with distant tumor stages showed the highest CVD SMR of 1.52 (95% CI 1.50-1.54). An upward trend in SMR to 2.53 (95% CI 2.51-2.56) was observed from 2011 to 2019. Within the initial 5-year post-diagnosis, the SMR for CVD was 3.17 (95% CI 3.14-3.20), which exceeded the general population's rates but declined in the 5-20-year range after diagnosis. Patients who did not any therapy had the greatest CVD SMR of 2.26 (95% CI 2.24-2.28). Hypopharyngeal cancer patients exhibited the highest CVD SMR of 1.54 (95% CI 1.52-1.56). CONCLUSIONS: The study highlights that head and neck cancer patients, especially younger individuals and those with advanced disease stages, face substantial CVD mortality risks. The CVD SMR peaks within 5 years following diagnosis. Patients abstaining from treatment bear the highest risk of CVD mortality. Cardioprotective measures should be considered critical for this patient population.


Assuntos
Doenças Cardiovasculares , Neoplasias de Cabeça e Pescoço , Programa de SEER , Humanos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/epidemiologia , Masculino , Feminino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Pessoa de Meia-Idade , Incidência , Idoso , Adulto , Estados Unidos/epidemiologia , Idoso de 80 Anos ou mais , Fatores de Risco
8.
J Med Chem ; 67(10): 8406-8419, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38723203

RESUMO

Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4-dione derivatives (MY1-41) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds (MY1-41) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC50) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 µM, compared with that of the positive control lithocholic acid (IC50 = 9.62 ± 0.14 µM). The most potent compound, MY17 (IC50 = 0.41 ± 0.05 µM), was a reversible, noncompetitive inhibitor of PTP1B. Circular dichroism spectroscopy and molecular docking were employed to analyze the binding interaction between MY17 and PTP1B. In HepG2 cells, MY17 treatment could alleviate palmitic acid (PA)-induced insulin resistance by upregulating the expression of phosphorylated insulin receptor substrate and protein kinase B. In vivo, oral administration of MY17 could reduce the fasting blood glucose level and improve glucose tolerance and dyslipidemia in mice suffering from DM.


Assuntos
Diabetes Mellitus Experimental , Hipoglicemiantes , Simulação de Acoplamento Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Tiazolidinedionas , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Animais , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , Hipoglicemiantes/uso terapêutico , Células Hep G2 , Camundongos , Tiazolidinedionas/farmacologia , Tiazolidinedionas/química , Tiazolidinedionas/síntese química , Diabetes Mellitus Experimental/tratamento farmacológico , Relação Estrutura-Atividade , Masculino , Tiadiazóis/farmacologia , Tiadiazóis/química , Tiadiazóis/síntese química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Resistência à Insulina , Glicemia/efeitos dos fármacos , Glicemia/análise , Glicemia/metabolismo
9.
BMC Musculoskelet Disord ; 25(1): 377, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741113

RESUMO

BACKGROUND: Periprosthetic joint infection (PJI) is a severe complication that can occur after total joint arthroplasty (TJA). The timely and accurate diagnosis of PJI is the key to treatment. This study investigated the diagnostic value of platelet to lymphocyte ratio (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) in PJI after total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: We performed a retrospective analysis of the patients who underwent revision hip or knee arthroplasty at our Institute between June 2015 and June 2020. Of the 187 patients reviewed, 168 were included in the study. According to the diagnostic criteria of the Musculoskeletal Infection Society (MSIS), 58 patients were in the PJI group, and 110 patients were in the aseptic loosening (AL) group. We recorded and compared the preoperative peripheral blood white blood cell (WBC) count, platelet count (PLT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), PLR, PVR, NLR, and MLR in both groups. The diagnostic performance of the WBC, PLT, PLR, PVR, NLR, and MLR individually and in combination with the ESR and CRP for PJI diagnosis was evaluated by receiver operating characteristic (ROC) curves, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Compared to those in the AL group, the mean WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR in the peripheral blood of the PJI group were significantly greater (P < 0.05). The analysis of the ROC curve revealed that the ESR, CRP, PLR, PVR, NLR, and MLR in peripheral blood had moderate effectiveness in diagnosing PJI, with area under the curve (AUC) values of 0.760 (95% CI: 0.688-0.823), 0.758 (95% CI: 0.687-0.821), 0.714 (95% CI: 0.639-0.781), 0.709 (95% CI: 0.634-0.777), 0.723 (95% CI: 0.649-0.789), and 0.728 (95% CI: 0.654-0.793), respectively. Conversely, the WBC and PLT counts demonstrated poor diagnostic value for PJI, with AUC values of 0.578 (95% CI: 0.499-0.653) and 0.694 (95% CI: 0.619-0.763), respectively. The results of the prediction model calculations revealed that the combined AUC of the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR was the highest at 0.853 (95% CI, 0.790-0.909), indicating good value in the diagnosis of PJI, with a sensitivity of 82.8% and a specificity of 72.7%. Moreover, the novel composite of parameters improved the accuracy and reliability in diagnosing PJI compared to the traditional biomarkers ESR and CRP (P = 0.015). CONCLUSION: Our study suggested that the diagnostic value of the peripheral blood biomarkers PLR, PVR, NLR, and MLR for diagnosing PJI is limited and not superior to that of the ESR or CRP. However, when the WBC, PLT, ESR, CRP, PLR, PVR, NLR, and MLR are combined, the diagnostic performance of PJI in TJA patients can be improved.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Biomarcadores , Infecções Relacionadas à Prótese , Humanos , Estudos Retrospectivos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/sangue , Infecções Relacionadas à Prótese/etiologia , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Biomarcadores/sangue , Contagem de Plaquetas , Proteína C-Reativa/análise , Contagem de Leucócitos , Sedimentação Sanguínea , Neutrófilos , Contagem de Linfócitos , Volume Plaquetário Médio , Idoso de 80 Anos ou mais , Valor Preditivo dos Testes , Curva ROC
10.
iScience ; 27(5): 109803, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38746667

RESUMO

The Covering Location Problem (CLP) is widely used for the efficient facility distribution. However, existing algorithms for this problem suffer from long computation times or suboptimal solutions. To address this, we propose two methods based on graph convolutional networks (GCN) to solve two types of covering location problems: the location set covering problem and the maximum covering location problem. The first method, GCN-Greedy, is a supervised algorithm that synergized with the Greedy algorithm as decoder. It designs a specialized loss function to train the model, tailored to the characteristics of the two covering location problems. The second method, reinforcement learning based on GCN with auto-regressive decoder (GCN-AR-RL), represents a reinforcement learning framework that integrates a GCN encoder with an auto-regressive decoder. The experimental results of these models demonstrate the remarkable accuracy and performance advantages. Additionally, we apply these two models to the realistic dataset and achieve good performance.

11.
Brain Behav Immun ; 119: 154-170, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38570101

RESUMO

Hyperglycemia-induced pathological microglial responses and subsequent neuronal damage are notable characteristics of diabetes-associated cognitive impairment (DACI). Cholesterol accumulation in the brain is a prevalent consequence of diabetes mellitus (DM), exacerbating pathological microglial responses. Regarding disordered glucose and lipid metabolism, the Sterol Regulatory Element-Binding Protein (SREBP) cleavage-activating protein (SCAP), a cholesterol sensor, exhibits increased expression and abnormal translocation from the endoplasmic reticulum to the Golgi, amplifying the inflammatory response. Therefore, we hypothesized that overexpression of microglia-SCAP and cholesterol accumulation in DM mice could induce pathological microglial responses associated with DACI. Our type 2 DM mice model presented an abnormal increase in microglial SCAP expression. The functional loss of microglia-specific SCAP in DM mice improved cognitive impairment, neuronal synaptic plasticity deficits, and abnormal microglial responses. Mechanistically, the accumulated SCAP directly bound to and enhanced the activation of the microglial-specific inflammatory amplifier, NLRP3 inflammasome, in Golgi, thereby increasing pathological microglial responses and promoting neuronal damage. These findings indicate an important regulatory axis of microglial responses from SCAP to the NLRP3 inflammasome pathway in microglia. These underscore the crosstalk between cholesterol disorders and pathological microglial responses, offering a promising avenue for pharmaceutical interventions in DACI.


Assuntos
Disfunção Cognitiva , Inflamassomos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Microglia/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Camundongos , Inflamassomos/metabolismo , Doenças Neuroinflamatórias/metabolismo , Proteínas de Membrana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Colesterol/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Plasticidade Neuronal , Neurônios/metabolismo , Encéfalo/metabolismo
12.
Medicine (Baltimore) ; 103(15): e37675, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608078

RESUMO

This study aimed to scrutinize the relationship between physical exercise and hypertension, taking into account multiple variables such as age, body mass index (BMI), family history, smoking, and alcohol consumption in the Southern Sichuan population, China, using a retrospective approach based on hospital record data. This retrospective study analyzed data from 946 participants obtained from a hospital electronic medical record system. The data included information regarding participants' lifestyle factors, family history, and a clinical diagnosis of hypertension. Univariate and multivariate logistic regression models were employed to identify the association between lifestyle factors and hypertension. The study found a hypertension prevalence of 38.5% in the analyzed population. Multivariate analyses identified significant factors associated with hypertension as age (odds ratio [OR]: 1.045, 95% confidence interval [CI]: 1.036-1.054), BMI (OR: 1.107, 95% CI: 1.084-1.132), smoking (OR: 2.299, 95% CI: 1.674-3.157), alcohol consumption (OR: 0.644, 95% CI: 0.478-0.867), and physical exercise (OR: 0.682, 95% CI: 0.506-0.920). Findings from this hospital record-based retrospective study reinforce the multifactorial nature of hypertension. They highlight the significance of physical exercise, along with maintaining optimal BMI and encouraging healthy habits like nonsmoking and moderate alcohol consumption in hypertension prevention. Our findings also underscore the need for future prospective studies to establish causality and explore the generalizability of these results beyond the Southern Sichuan population.


Assuntos
Exercício Físico , Hipertensão , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Comportamentos Relacionados com a Saúde , Hipertensão/epidemiologia
14.
Org Lett ; 26(15): 3086-3090, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38591933

RESUMO

An organocatalytic enantioselective alkylation of α,α-disubstituted aldehydes with 3-bromooxindoles is reported. Enantioenriched oxindoles with vicinal quaternary stereocenters are accessed by an asymmetric conjugate addition process of branched aldehydes with o-azaxylylene intermediates (indol-2-ones). Key to the success of highly diastereo- and enantioselective transformations is the combined use of a triphenylsilyl-protected ß-amino alcohol catalyst derived from the spiropyrrolidine scaffold and 3,5-dinitrobenzoic acid. This study also presents a rare example of aldehyde alkylation with the formation of consecutive quaternary stereocenters.

15.
PLoS One ; 19(4): e0299261, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635506

RESUMO

'Allen Eureka' is a bud variety of Eureka lemon with excellent fruiting traits, but severe winter defoliation affects the following year's yield, and the response mechanism of lemon defoliation is currently unknown. Two lemon cultivars ('Allen Eureka' and 'Yunning No. 1') with different defoliation traits were used as materials to investigate the molecular regulatory mechanisms of different leaf abscission periods in lemons. The petiole abscission zone was collected at three different defoliation stages, namely, the predefoliation stage (k15), the middefoliation stage (k30), and the postdefoliation stage (k45). Transcriptome sequencing was performed to analyze the gene expression differences between these two cultivars. A total of 1141, 2695, and 1433 differentially expressed genes (DEGs) were obtained in k15, k30, and k45, respectively, and the number of DEGs in k30 was the largest. GO analysis revealed that the DEGs between the two cultivars were mainly enriched in processes related to hydrolase activity, chitinase activity, oxidoreductase activity, and transcription regulator activity in the defoliation stages. KEGG analysis showed that the DEGs were concentrated in k30, which involved plant hormone signal transduction, phenylpropanoid biosynthesis, and biosynthesis of amino acids. The expression trends of some DEGs suggested their roles in regulating defoliation in Lemon. Seven genes were obtained by WGCNA, including sorbitol dehydrogenase (CL9G068822012_alt, CL9G068820012_alt, CL9G068818012_alt), abscisic acid 8'-hydroxylase (CL8G064053012_alt, CL8G064054012_alt), and asparagine synthetase (CL8G065162012_alt, CL8G065151012_alt), suggesting that these genes may be involved in the regulation of lemon leaf abscission.


Assuntos
Secas , Transcriptoma , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica , Reguladores de Crescimento de Plantas/metabolismo
16.
PeerJ ; 12: e17218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38685937

RESUMO

'Allen Eureka' is a bud variety of Eureka lemon with excellent fruiting traits. However, it suffers from severe winter defoliation that leads to a large loss of organic nutrients and seriously affects the tree's growth and development as well as the yield of the following year, and the mechanism of its response to defoliation is still unclear. In order to investigate the molecular regulatory mechanisms of different leaf abscission periods in lemon, two lemon cultivars ('Allen Eureka' and 'Yunning No. 1') with different defoliation traits were used as materials. The petiole abscission zone (AZ) was collected at three different defoliation stages, namely, the pre-defoliation stage (CQ), the mid-defoliation stage (CZ), and the post-defoliation stage (CH). Transcriptome sequencing was performed to analyze the gene expression differences between these two cultivars. A total of 898, 4,856, and 3,126 differentially expressed genes (DEGs) were obtained in CQ, CZ, and CH, respectively, and the number of DEGs in CZ was the largest. GO analysis revealed that the DEGs between the two cultivars were mainly enriched in processes related to oxidoreductase, hydrolase, DNA binding transcription factor, and transcription regulator activity in the defoliation stages. KEGG analysis showed that the DEGs were concentrated in CZ and involved plant hormone signal transduction, phenylpropanoid biosynthesis, glutathione metabolism, and alpha-linolenic acid metabolism. The expression trends of some DEGs suggested their roles in regulating defoliation in lemon. Eight gene families were obtained by combining DEG clustering analysis and weighted gene co-expression network analysis (WGCNA), including ß-glucosidase, AUX/IAA, SAUR, GH3, POD, and WRKY, suggesting that these genes may be involved in the regulation of lemon leaf abscission. The above conclusions enrich the research related to lemon leaf abscission and provide reliable data for the screening of lemon defoliation candidate genes and analysis of defoliation pathways.


Assuntos
Citrus , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Folhas de Planta , Transcriptoma , Citrus/genética , Citrus/metabolismo , Citrus/crescimento & desenvolvimento , Folhas de Planta/genética , Folhas de Planta/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Innovations (Phila) ; 19(2): 125-135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465600

RESUMO

OBJECTIVE: The surgical treatment of aortic stenosis continues to evolve, and sutureless aortic valve replacement (SUAVR) is an emerging technology. With the Perceval S (Corcym, London, UK) as the only true sutureless valve on the market, the objective of this review is to analyze the current literature on Perceval S. Focusing on valve design and deployment as well as applications of the technology for challenging pathology, clinical outcomes are assessed, including a comparison with transcatheter AVR (TAVR). METHODS: PubMed and MEDLINE were searched by 3 authors for studies analyzing SUAVR from inception to May 19, 2023. RESULTS: SUAVR facilitates minimally invasive surgery and offers an alternative strategy for patients with small aortic annuli. It also has a time-saving advantage for patients who require complex operations. SUAVR results in excellent long-term morbidity, mortality, durability, and hemodynamic function. In comparison with conventional surgical AVR (SAVR), SUAVR does have a greater risk of postoperative pacemaker implantation; however, increasing user experience and refinements in implantation technique have contributed to reductions in this outcome. SUAVR results in morbidity and mortality that is similar to rapid-deployment AVR. Midterm outcomes are superior to TAVR; however, further robust investigation into all of these comparisons is ultimately necessary. CONCLUSIONS: SUAVR bridges the gap in technology between SAVR and TAVR. The application of this exciting technology will undoubtedly grow in the coming years, during which additional investigation is paramount to optimize preoperative planning, valve deployment, and reintervention strategies.


Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Procedimentos Cirúrgicos sem Sutura , Substituição da Valva Aórtica Transcateter , Humanos , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Procedimentos Cirúrgicos sem Sutura/métodos , Substituição da Valva Aórtica Transcateter/métodos , Implante de Prótese de Valva Cardíaca/métodos , Implante de Prótese de Valva Cardíaca/instrumentação , Desenho de Prótese , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento
18.
J Exp Bot ; 75(13): 3891-3902, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38486360

RESUMO

Self-incompatibility (SI) is a crucial mechanism that prevents self-fertilization and inbreeding in flowering plants. Citrus exhibits SI regulated by a polymorphic S-locus containing an S-RNase gene and multiple S-locus F-box (SLF) genes. It has been documented that S-RNase functions as the pistil S determinant, but there is no direct evidence that the SLF genes closely linked with S-RNase function as pollen S determinants in Citrus. This study assembled the genomes of two pummelo (Citrus grandis) plants, obtained three novel complete and well-annotated S-haplotypes, and isolated 36 SLF or SLF-like alleles on the S-loci. Phylogenetic analysis of 138 SLFs revealed that the SLF genes were classified into 12 types, including six types with divergent or missing alleles. Furthermore, transformation experiments verified that the conserved S6-SLF7a protein can lead to the transition of SI to self-compatibility by recognizing non-self S8-RNase in 'Mini-Citrus' plants (S7S8 and S8S29, Fortunella hindsii), a model plant for citrus gene function studies. In vitro assays demonstrated interactions between SLFs of different S haplotypes and the Skp1-Cullin1-F-box subunit CgSSK1 protein. This study provides direct evidence that SLF controls the pollen function in Citrus, demonstrating its role in the 'non-self recognition' SI system.


Assuntos
Citrus , Proteínas F-Box , Filogenia , Proteínas de Plantas , Pólen , Ribonucleases , Autoincompatibilidade em Angiospermas , Citrus/genética , Citrus/fisiologia , Citrus/metabolismo , Autoincompatibilidade em Angiospermas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pólen/genética , Pólen/fisiologia , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Ribonucleases/metabolismo , Ribonucleases/genética , Sequência de Aminoácidos
19.
Clin Res Hepatol Gastroenterol ; 48(4): 102315, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38467278

RESUMO

OBJECTIVE: This study aims to perform a meta-analysis to evaluate the safety and efficacy of dexmedetomidine versus midazolam for complex digestive endoscopy procedures, with the goal of offering comprehensive clinical evidence. METHODS: Following predefined inclusion criteria, five databases were systematically searched, with a focus on identifying randomized controlled trials (RCTs) that compared the administration of dexmedetomidine and midazolam during complex digestive endoscopy procedures. The statistical software Stata 15.1 was employed for meticulous data analysis. RESULTS: Sixteen RCTs were encompassed, involving a total of 1218 patients. In comparison to the midazolam group, dexmedetomidine administration was associated with a reduced risk of respiratory depression (RR=0.25, 95 %CI: 0.11-0.56) and hypoxemia (RR=0.22, 95 %CI: 0.12-0.39). Additionally, the dexmedetomidine group exhibited lower incidence rates of choking (RR=0.27, 95 %CI: 0.16-0.47), physical movement (RR=0.16, 95 %CI: 0.09-0.27), and postoperative nausea and vomiting (RR=0.56,95 %CI: 0.34-0.92). Patients and endoscopists in the dexmedetomidine group reported higher levels of satisfaction (patient satisfaction: SMD=0.73, 95 %CI: 0.26-1.21; endoscopist satisfaction: SMD=0.84, 95 %CI: 0.24-1.44). The incidence of hypotension and anesthesia recovery time did not significantly differ between the two groups (hypotension: RR=1.73,95 %CI:0.94-3.20; anesthesia recovery time: SMD=0.02, 95 %Cl: 0.44-0.49). It is noteworthy that the administration of dexmedetomidine was associated with a significant increase in the incidence of bradycardia in patients. CONCLUSION: Compared to midazolam, dexmedetomidine exhibits a favorable safety profile for use in complex gastrointestinal endoscopy by significantly reducing the risk of respiratory depression and hypoxemia. Despite this, dexmedetomidine is associated with a higher incidence of bradycardia. These findings underscore the need for further research through larger, multi-center studies to thoroughly investigate dexmedetomidine's safety and efficacy.

20.
J Med Biochem ; 43(1): 106-115, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38496016

RESUMO

Background: This study aims to uncover the potential correlation between LTC4S -444 A>C polymorphism and susceptibility to asthma. Methods: Literatures reporting the correlation between LTC4S -444 A>C polymorphism and susceptibility to asthma published before 1st June, 2019 were searched in PubMed, Embase, Cochrane, Wanfang and CNKI. Eligible literatures were enrolled and their data were extracted. OR and its 95% CI were calculated for assessing the correlation between LTC4S -444 A>C polymorphism and susceptibility to asthma. The included data were weighted by an inverse variance and then analyzed by a fixed or random effects model. Heterogeneity test and sensitivity analysis were performed on the enrolled reports. STATA12.1 and TSA (trial sequential analysis) were utilized for analyses.

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