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1.
Cancer Manag Res ; 16: 395-402, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707744

RESUMO

Background: Lymphoepithelioma-like carcinoma of the liver is a rare primary malignancy of the liver. The identification of lymphoepithelioma-like cholangiocarcinoma is very limited as there are currently very few reports of such cases. Although previous studies have reported the lymphoepithelioma-like cholangiocarcinoma pathologic features, few studies have revealed the clinic features, imaging characteristics, and clinical course and outcomes. This study was analyzed from multiple aspects such as contrast-enhanced ultrasound, magnetic resonance imaging, and pathological characteristics, aiming to improve the comprehensive understanding of this rare subtype of disease. Case Presentation: A 43-year-old female with a history of hepatitis B for over 20 years presented with a lesion found in the right lobe of her liver. After discussion by a multidisciplinary team (MDT), malignant tumors cannot be excluded based on contrast-enhanced ultrasound and MRI. Thus, we decided to perform surgery for the patient. Postoperative pathology confirmed lymphoepithelioma-like intrahepatic cholangiocarcinoma. After 3 months of follow-up, the patient was still alive and no recurrence was observed. Conclusion: The purpose of this article is to describe a rare case of lymphoepithelioma-like intrahepatic cholangiocarcinoma and analyze its contrast-enhanced ultrasound and contrast-enhanced MRI features, which will be helpful for physicians in diagnosing this disease. From the perspective of CEUS, the wedge-shaped highly enhanced area around the lesion in the arterial phase appears to be inflammatory but looks malignant based on the extremely fast washout. The lesion showed a low signal on T1WI, a high signal on T2WI and DWI, and an abnormal perfusion shadow can be seen behind the lesion. In particular, this subtype of cholangiocarcinoma has a good prognosis, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.

2.
Sci Rep ; 14(1): 11611, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773355

RESUMO

The educational burden from extracurricular tutoring class has become a pressing social issue in China. This study used data from the China family panel studies (CFPS) in 2014, 2016, and 2018 to empirically analyze the impact of Internet usage on children's participation in extracurricular tutoring class. There are many factors that influence parents' decisions to enroll their children in extracurricular tutoring class. These factors include family income status, the level of importance parents place on their children's education, the marginal returns on educational investment, academic pressure, etc. However, in today's digitalized society, the widespread use of the internet will also become an important influencing factor in parents' decisions regarding educational investment. The study finds that, parents by using the Internet significantly increase the probability of enrolling their children in extracurricular tutoring class. Through mechanism regression analysis, it is concluded that internet usage has a positive influence on parents enrolling their children in extracurricular tutoring class by increasing the frequency of social interaction and raising parents' educational expectations for their children. Based on the empirical results, the following policy suggestions were proposed: 1. Schools should establish a more comprehensive after-school education service system to improve the engagement of students in compulsory education; 2. The government can enhance the accessibility and optimization of educational resources by increasing investment in education, improving the quality of in-school education, and optimizing the management and supervision of extracurricular tutoring class. This ensures that students can access high-quality educational services.


Assuntos
Uso da Internet , Pais , Estudantes , Humanos , Criança , China , Masculino , Feminino , Uso da Internet/estatística & dados numéricos , Instituições Acadêmicas , Adulto , Adolescente , Internet/estatística & dados numéricos
3.
Head Face Med ; 20(1): 31, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745246

RESUMO

BACKGROUND: In this study, we sought to quantify the influence of vertical control assisted by a temporary anchorage device (TAD) on orthodontic treatment efficacy for skeletal class II patients with a hyperdivergent facial type and probe into the critical factors of profile improvement. METHODS: A total of 36 adult patients with skeletal class II and a hyperdivergent facial type were included in this retrospective case-control study. To exclude the effect of sagittal anchorage reinforcement, the patients were divided into two groups: a maxillary maximum anchorage (MMA) group (N = 17), in which TADs were only used to help with anterior tooth retraction, and the MMA with vertical control (MMA + VC) group (N = 19), for which TADs were also used to intrude the maxillary molars and incisors. The treatment outcome was evaluated using dental, skeletal, and soft-tissue-related parameters via a cephalometric analysis and cast superimposition. RESULTS: A significant decrease in ANB (P < 0.05 for both groups), the retraction and uprighting of the maxillary and mandibular incisors, and the retraction of protruded upper and lower lips were observed in both groups. Moreover, a significant intrusion of the maxillary molars was observed via the cephalometric analysis (- 1.56 ± 1.52 mm, P < 0.05) and cast superimposition (- 2.25 ± 1.03 mm, P < 0.05) of the MMA + VC group but not the MMA group, which resulted in a remarkable decrease in the mandibular plane angle (- 1.82 ± 1.38°, P < 0.05). The Z angle (15.25 ± 5.30°, P < 0.05) and Chin thickness (- 0.97 ± 0.45°, P < 0.05) also improved dramatically in the MMA + VC group, indicating a better profile and a relaxed mentalis. Multivariate regression showed that the improvement in the soft tissue was closely related to the counterclockwise rotation of the mandible plane (P < 0.05). CONCLUSIONS: TAD-assisted vertical control can achieve intrusion of approximately 2 mm for the upper first molars and induce mandibular counterclockwise rotation of approximately 1.8°. Moreover, it is especially important for patients without sufficient retraction of the upper incisors or a satisfactory chin shape.


Assuntos
Cefalometria , Má Oclusão Classe II de Angle , Humanos , Má Oclusão Classe II de Angle/terapia , Má Oclusão Classe II de Angle/diagnóstico por imagem , Feminino , Masculino , Estudos Retrospectivos , Adulto , Estudos de Casos e Controles , Adulto Jovem , Resultado do Tratamento , Procedimentos de Ancoragem Ortodôntica/métodos , Procedimentos de Ancoragem Ortodôntica/instrumentação , Ortodontia Corretiva/métodos , Técnicas de Movimentação Dentária/métodos , Dimensão Vertical , Adolescente
4.
Front Pharmacol ; 15: 1361953, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698824

RESUMO

Background: For cesarean delivery (CD), the 90% effective dosage (ED90) of oxytocin for a first bolus has been established. It is not yet known how much oxytocin to inject into obese women undergoing elective discectomy to keep their uterine tone (UT) appropriate. We hypothesized that patients who are overweight need a greater dose of oxytocin infusion; thus, we aimed to determine how the dose-response curve for oxytocin infusion changes following an initial 1 international unit (IU) bolus in obese women undergoing elective CD. Methods: One hundred parturients with a body mass index (BMI) greater than 30 kg/m2 were randomly assigned to receive an infusion rate of 14, 18, 22, or 26 IU/h of oxytocin. When the uterine palpation is as hard as touching the forehead or tip of the nose, it is considered sufficient UT according to the criteria used by obstetricians. The median effective dose (ED50) and ED90 values were determined using probit analysis. Results: We found the ED50 and ED90 values for the infusion dose of oxytocin were around 11.0 IU/h and 19.1 IU/h, respectively. Each group had a different number of parturients who needed rescued oxytocin: 14 IU/h for six, 18 IU/h for three, one for 22 IU/h, and none for 26 IU/h. The correlation between the frequency of rescued oxytocin administration and the amount of oxytocin infusion needed to avoid uterine atony was statistically significant (p = 0.02). Conclusion: The present research showed that the most effective dosage of oxytocin infusion for obese parturients undergoing elective CD is 19.1 IU/h, following an initial loading dose of 1 IU. Patients with obesity should receive a greater dosage of prophylactic oxytocin, and further studies comparing patients with and without obesity (with higher BMI) are required. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=159951, identifier ChiCTR2200059582.

5.
Int Urol Nephrol ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761331

RESUMO

BACKGROUND: Varicocelectomy was considered to be beneficial to patients with varicocele-related infertility. However, there are only a few researchers who have explored the relationship between better timing and postoperative semen improvement in patients. METHODS: We conducted this meta-analysis by enrolling published prospective studies to find out the best waiting time after varicocelectomy to wait for better improvement of semen quality. An extensive search was conducted in PubMed, Web of Science, and Cochrane Library to identify eligible studies. The included studies were then analyzed comprehensively using STATA software and standardized mean differences (SMDs) and their corresponding 95% confidence intervals were calculated. RESULTS: Our comprehensive analysis showed that after varicocelectomy, follow-up results within 3 months or longer showed a significant improvement in semen parameters compared to the preoperative period. Notably, no further improvement in semen parameters was observed when the follow-up period reached six months or longer (semen volume: WMD: - 0.07 (- 0.29, 0.16); sperm concentration: WMD: - 1.33 (- 2.33, - 4.99); sperm motility: WMD: 2.31 (- 0.55, 5.18); sperm morphology: WMD: 1.29 (- 0.66, 3.24); sperm total motile count: WMD: 3.95 (- 6.28, 14.19)). CONCLUSIONS: Three months after varicocelectomy may be the optimal time for semen parameters compared to six months or even longer, which means it is also the preferable time for conception. However, more well-designed prospective studies are needed in the future to validate our conclusion.

6.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1091-1101, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621916

RESUMO

This study aimed to systematically evaluate the effectiveness and safety of Tanreqing Injection in the treatment of severe pneumonia in the elderly. Eighteen randomized controlled trials(RCTs) involving 1 457 elderly patients with severe pneumonia were included in the study after conducting searches in both Chinese and English databases as well as clinical trial registration platforms. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis were conducted using RevMan 5.4 and Stata 17 software, and trial sequential analysis(TSA) was performed using TSA 0.9.5.10 beta software. Meta-analysis results showed that compared with conventional western medicine treatment, Tanreqing Injection + conventional western medical significantly improved the clinical effectiveness in elderly patients with severe pneumonia(RR=1.26, 95%CI[1.20, 1.32], P<0.000 01), arterial oxygen partial pressure(SMD=6.23, 95%CI[3.29, 9.18], P<0.000 1), oxygenation index(SMD=11.72, 95%CI[4.41, 19.04], P=0.002), reduce procalcitonin(SMD=-6.16, 95%CI[-8.10,-4.21], P<0.000 01), C-reactive protein(SMD=-8.50, 95%CI[-11.05,-5.96], P<0.000 01), white blood cell count(SMD=-4.56, 95%CI[-5.73,-3.39], P<0.000 01), and shortened the duration of fever(SMD=-3.12, 95%CI[-4.61,-1.63], P<0.000 1), cough(SMD=-4.84, 95%CI[-6.90,-2.79], P<0.000 01), lung rales(SMD=-0.99, 95%CI[-1.54,-0.44], P=0.000 4), and mechanical ventilation time(SMD=-3.26, 95%CI[-5.03,-1.50], P=0.000 3), increase CD4~+ T-cell levels(SMD=6.73, 95%CI[5.23, 8.23], P<0.000 01) and CD8~+ T-cell levels(SMD=7.47, 95% CI[5.32, 9.61], P<0.000 01) with no significant adverse reactions. TSA confirmed the stability and reliability of the results related to clinical effectiveness. This study suggests that Tanreqing Injection, as a Chinese medicinal preparation, has a significant therapeutic effect and good safety profile in the treatment of severe pneumonia in elderly patients. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.


Assuntos
Medicamentos de Ervas Chinesas , Pneumonia , Idoso , Humanos , Tosse/induzido quimicamente , Medicamentos de Ervas Chinesas/efeitos adversos , Pneumonia/tratamento farmacológico , Reprodutibilidade dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
J Am Chem Soc ; 146(17): 11845-11854, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648548

RESUMO

Organic molecules have been regarded as ideal candidates for near-infrared (NIR) optoelectronic active materials due to their customizability and ease of large-scale production. However, constrained by the intricate molecular design and severe energy gap law, the realization of optoelectronic devices in the second near-infrared (NIR (II)) region with required narrow band gaps presents more challenges. Herein, we have originally proposed a cocrystal strategy that utilizes intermolecular charge-transfer interaction to drive the redshift of absorption and emission spectra of a series BFXTQ (X = 0, 1, 2, 4) cocrystals, resulting in the spectra located at NIR (II) window and reducing the optical bandgap to ∼0.98 eV. Significantly, these BFXTQ-based optoelectronic devices can exhibit dual-mode optoelectronic characteristics. An investigation of a series of BFXTQ-based photodetectors exhibits detectivity (D*) surpassing 1013 Jones at 375 to 1064 nm with a maximum of 1.76 × 1014 Jones at 1064 nm. Moreover, the radiative transition of CT excitons within the cocrystals triggers NIR emission over 1000 nm with a photoluminescence quantum yield (PLQY) of ∼4.6% as well as optical waveguide behavior with a low optical-loss coefficient of 0.0097 dB/µm at 950 nm. These results promote the advancement of an emerging cocrystal approach in micro/nanoscale NIR multifunctional optoelectronics.

8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 301-306, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38686730

RESUMO

Malignant adenomyoepithelioma(MAME)of the breast is a rare tumor with an incidence less than 1% of primary breast cancer.The low incidence and diverse histomorphology pose challenges to the accurate diagnosis and clinical management of MAME.This paper reports a case of MAME of the breast with an intraductal papillary growth pattern and summarizes the clinical features,pathological features,diagnosis,treatment,and prognosis of MAME of the breast in the last 5 years.


Assuntos
Adenomioepitelioma , Neoplasias da Mama , Humanos , Adenomioepitelioma/patologia , Feminino , Neoplasias da Mama/patologia , Pessoa de Meia-Idade
9.
Ecol Evol ; 14(4): e11271, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38617102

RESUMO

The hydrological regime is considered to be the major factor that affects the distribution of arbuscular mycorrhiza (AM) fungi in wetlands. We aimed to investigate the responses of AM fungal community to different hydrological gradients. Illumina Miseq sequencing technology was used to study the AM fungal community structure in roots and rhizosphere soils of Phragmites australis in different moisture areas (dry area, alternating wet and dry area, and flooded area) in Mengjin Yellow River wetland. The rhizosphere soils and roots hosted different AM fungal communities. In roots, the AM fungal colonization and Chao1 richness in dry area were significantly higher than that in alternating wet and dry area and flooded area, but the community composition did not vary clearly under different water conditions. In rhizosphere soils, the Chao1 richness of AM fungi in flooded area was significantly higher than that in alternating wet and dry area and dry area, and the AM fungal community structure obviously differed across different areas. The redundancy analyses indicated that changes in the AM fungal community in soils were associated with altered soil properties, and the abundance of the dominant genus Glomus was mostly positively correlated with alkali-hydrolyzable nitrogen in soils. This study helps us to understand the responses of AM fungal community to hydrological gradients in wetlands.

10.
Sci Data ; 11(1): 359, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594303

RESUMO

The genome of faba bean was first published in 2023. To promote future molecular breeding studies, we improved the quality of the faba genome based on high-density genetic maps and the Illumina and Pacbio RNA-seq datasets. Two high-density genetic maps were used to conduct the scaffold ordering and orientation of faba bean, culminating in an increased length (i.e., 14.28 Mbp) of chromosomes and a decrease in the number of scaffolds by 45. In gene model mining and optimisation, the PacBio and Illumina RNA-seq datasets from 37 samples allowed for the identification and correction 121,606 transcripts, and the data facilitated a prediction of 15,640 alternative splicing events, 2,148 lncRNAs, and 1,752 fusion transcripts, thus allowing for a clearer understanding of the gene structures underlying the faba genome. Moreover, a total of 38,850 new genes including 56,188 transcripts were identified compared with the reference genome. Finally, the genetic data of the reference genome was integrated and a comprehensive and complete faba bean transcriptome sequence of 103,267 transcripts derived from 54,753 uni-genes was formed.


Assuntos
Transcriptoma , Vicia faba , Processamento Alternativo , RNA-Seq , Vicia faba/genética , Melhoramento Vegetal , Mapeamento Cromossômico , Genoma de Planta
11.
Bioorg Med Chem Lett ; 104: 129708, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38521176

RESUMO

Guaianolide dimers represent a unique class of natural products with anticancer activities, but their low content in plants has limited in-depth pharmacological studies. Lavandiolide I is a guaianolide dimer isolated from Artemisia species, and had been synthesized on a ten-gram scale in four steps with 60 % overall yield, which showed potent antihepatoma activity on the HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values of 12.1, 18.4, and 17.6 µM, respectively. To explore more active dimers, 33 lavandiolide I derivatives were designed, synthesized, and evaluated for their inhibitory activity on human hepatoma cell lines. Among them, 10 derivatives were more active than lavandiolide I and sorafenib on the three cell lines. The primary structure-activity relationship concluded that the introduction of aldehyde, ester, azide, amide, carbamate and urea functional groups at C-14' of the guaianolide dimer significantly enhanced the antihepatoma activity. Among these compounds, derivatives 25, 27, and 33 enhanced antihepatoma activity more than 1.2-5.8 folds than that of lavandiolide I, and demonstrated low toxicity to the human liver cell lines (THLE-2) and good safety profiles with selective index ranging from 1.3 to 3.4, while lavandiolide I was more toxic to THLE-2 cells. This work provides new insights into enhancing the antihepatoma efficacy and reducing the toxicity of sesquiterpenoid dimers.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Sesquiterpenos de Guaiano , Humanos , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células , Neoplasias Hepáticas/tratamento farmacológico , Estrutura Molecular , Relação Estrutura-Atividade , Linhagem Celular Tumoral , Sesquiterpenos de Guaiano/síntese química , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/farmacologia
13.
Small ; : e2400313, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552249

RESUMO

Multicolor luminescence of organic fluorescent materials is an essential part of lighting and optical communication. However, the conventional construction of a multicolor luminescence system based on integrating multiple organic fluorescent materials of a single emission band remains complicated and to be improved. Herein, organic alloys (OAs) capable of full-color emission are synthesized based on charge transfer (CT) cocrystals. By adjusting the molar ratio of electron donors, the emission color of the OAs can be conveniently and continuously regulated in a wide visible range from blue (CIE: 0.187, 0.277), to green (CIE: 0.301, 0.550), and to red (CIE: 0.561, 0.435). The OAs show analogous 1D morphology with smooth surface, allowing for full-color waveguides with low optical-loss coefficient. Impressively, full-color optical displays are easily achieved through the OAs system with continuous emission, which shows promising applications in the field of optical display and promotes the development of organic photonics.

14.
Clin. transl. oncol. (Print) ; 26(3): 630-643, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230793

RESUMO

Purpose Metabolic reprogramming is a novel hallmark and therapeutic target of cancer. Our study aimed to establish fatty acid metabolism-associated scores based on gene signature and investigated its effects on immunotherapy in colon cancer. Methods Gene expression and clinical information were collected from Gene Expression Omnibus (GEO) database to identify a gene signature by non-negative matrix factorization (NMF) clustering and Cox regression analysis. Subsequently, we constructed the fatty acid metabolism score (FA-score) model by principal component analysis (PCA) and explored its relativity of prognosis and the response to immunotherapy in colon cancer. Finally, the Cancer Genome Atlas (TCGA) database was introduced and in vitro study was performed for verification. Results The FA-score-high group had a higher level of fatty acid metabolism and was associated with worse patient overall survival. Significantly, FA-score correlated closely with the biomarkers of immunotherapy, and the FA-score-high group had a poorer therapeutic efficacy of immune checkpoint blockade. In vitro experiments demonstrated that ACSL5 may be a critical metabolic regulatory target. Conclusions Our study provided a comprehensive analysis of the heterogeneity of fatty acid metabolism in colon cancer. We highlighted the potential clinical utility of fatty acid metabolism-related genes to be biomarkers of colon cancer prognosis and targets to improve the effect of immunotherapy (AU)


Assuntos
Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Imunoterapia/métodos , Biomarcadores/sangue , Ácidos Graxos , Prognóstico
15.
Clin Interv Aging ; 19: 491-502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525317

RESUMO

Purpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions. Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥1 point between the preoperative and postoperative scale was defined as POCD. Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028-5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057-0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively. Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.


Assuntos
Anestésicos , Disfunção Cognitiva , Delírio , Procedimentos Ortopédicos , Complicações Cognitivas Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , China/epidemiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Sufentanil , Ensaios Clínicos como Assunto
16.
Chem Commun (Camb) ; 60(32): 4338-4341, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38545855

RESUMO

Ru-catalyzed asymmetric hydrogenation of α-substituted α,ß-unsaturated ketones has been developed for the enantioselective synthesis of chiral α-substituted secondary alcohols with high diastereo- and enantioselectivities (up to >99 : 1 dr, 98% ee). Mechanistic experiments suggest that the reaction proceeds via a Ru-catalyzed asymmetric hydrogenation of the CO bond in concert with a base-promoted allylic alcohol isomerization, and the final stereoselectivities were controlled by a DKR process during the asymmetric hydrogenation of the ketone intermediate.

17.
ERJ Open Res ; 10(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38410702

RESUMO

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

18.
Molecules ; 29(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38398602

RESUMO

The use of gaseous CO in Pd-catalyzed carbonylative quinolone synthesis presents challenges related to safety and precise pressure control. In response, a streamlined non-gaseous synthesis of 4-quinolone compounds has been developed. This study introduces a tunable CO-releasing system utilizing Fe(CO)5 activated by a dual-base system of piperazine and triethylamine. This alternative liquid CO resource facilitates the palladium-catalyzed carbonylative C-C coupling and subsequent intramolecular cyclization. By tuning the tandem kinetics of carbonylation and cyclization, this non-gaseous method achieves the successful synthesis of 22 distinct 4-quinolones with excellent yields. This is achieved through the three-component condensation of sub-stoichiometric amounts of Fe(CO)5 with 2-iodoaniline and terminal alkynes. Operando mechanistic studies have revealed a novel CO transfer mechanism that facilitates homogeneous carbonylative cyclization, distinguishing this method from traditional techniques. In addition to addressing safety concerns, this approach also provides precise control over selectivity, with significant implications for pharmaceutical research and the efficient synthesis of pharmaceutical and bioactive compounds.

19.
Heliyon ; 10(2): e24573, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38312597

RESUMO

Ischemia-reperfusion injury (IRI) is a significant contributor to acute kidney injury (AKI) and is associated with substantial morbidity and mortality rates. In this study, we aimed to investigate the role of NAT10 and its ac4C RNA modification in IRI-induced renal injury. Our findings revealed that both the expression level of NAT10 and the RNA ac4C level in the kidneys were elevated in the IRI group compared to the sham group. Functionally, we observed that inhibition of NAT10 activity with Remodelin or the specific knockout of NAT10 in the kidney led to a significant attenuation of IRI-induced renal injury. Furthermore, in vitro experiments demonstrated that NAT10 inhibition and specific knockout of NAT10 in the kidney markedly suppressed global ac4C RNA modification, providing protection against hypoxia/reoxygenation-induced tubular epithelial cell injury and ferroptosis. Mechanistically, our study uncovered that NAT10 promoted ac4C RNA modification of NCOA4 mRNA, thereby enhancing its stability and contributing to IRI-induced ferroptosis in tubular epithelial cells (TECs). These findings underscore the potential of NAT10 and ac4C RNA modification as promising therapeutic targets for the treatment of AKI. Overall, our study sheds light on the critical involvement of NAT10 and ac4C RNA modification in the pathogenesis of IRI-induced renal injury, offering valuable insights for the development of novel AKI treatment strategies.

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