Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
1.
Front Endocrinol (Lausanne) ; 15: 1405665, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948524

RESUMO

Background: Increased levels of serum Klotho have been associated with a reduced risk of several cardiovascular diseases (CVD). However, limited studies exist on the association between serum Klotho and mortality in patients with CVD. Methods: We collected data from CVD patients in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2016. We linked NHANES data with the National Death Index to determine the survival status of participants. Univariate and multivariable Cox regression models were used to investigate the relationship between serum Klotho levels and mortality in CVD patients. The relationship between serum Klotho quartiles and mortality in CVD patients was visualized using Kaplan-Meier (KM) curves and restricted cubic spine. Finally, subgroup analyses were used to examine the association between serum Klotho and all-cause mortality in different populations. Results: 1905 patients with CVD were finally enrolled in our study with a mean follow-up of 7.1 years. The average age of the participants was 63.4 years, with 58.40% being male. KM showed that lower Klotho levels were associated with lower survival rates. After adjusting for potential confounders, patients with higher serum Klotho levels had lower all-cause mortality (Q1: 1.00, Q2: 0.58 (0.42-0.80), Q3: 0.69 (0.47-1.01), and Q4:0.64 (0.45-0.92). However, the relationship between serum Klotho levels and cardiovascular mortality was not statistically significant. Dose-response analysis shows a U-shaped relationship between serum Klotho levels and all-cause mortality in patients with CVD (P nonlinear=0.002). Subgroup analysis indicated that participants with a history of hypertension had a higher risk of all-cause mortality in serum Klotho Q4 compared to Q1 (P trend <0.05). Conclusion: The relationship between serum Klotho levels and all-cause mortality in CVD patients exhibits a U-shaped association. The underlying mechanisms of this association need further investigation.


Assuntos
Doenças Cardiovasculares , Proteínas Klotho , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Estados Unidos/epidemiologia , Glucuronidase/sangue , Biomarcadores/sangue , Causas de Morte , Seguimentos , Taxa de Sobrevida
3.
Hepatol Int ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898191

RESUMO

BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is a prevalent adverse reaction in clinical settings. However, there is limited research on age-related differences in DILI. We performed a large-scale retrospective study to delineate the characteristics of DILI across different age groups. METHODS: We collected data on a total of 17,946 patients with confirmed DILI hospitalized at the Fifth Medical Center of the People's Liberation Army (PLA) General Hospital in Beijing, China, from January 1, 2002, to December 31, 2022. The patients were stratified based on age into the following groups: children (< 18 years), young adults (18-44 years), middle-aged individuals (45-64 years), and elderly individuals (≥ 65 years). We gathered demographic information, medical histories, laboratory results, disease severity assessments, and mortality statistics for all patients. RESULTS: Overall, the distribution of DILI cases across different age groups was as follows: 6.57% were children, 24.82% were young adults, 49.06% were middle-aged individuals, and 19.54% were elderly individuals. The percentage of females increased with age, rising from 36.47% in the pediatric group to 60.51% in the elderly group. Notably, central nervous system agents (15.44%) and anti-infectious agents (21.80%) were more commonly associated with DILI in children, while cardiovascular agents (10.58%) and herbal dietary supplements or traditional medicines (H/TMs) (26.29%) were more prevalent among elderly people with DILI. Among all age groups, hepatocellular-type DILI was more common in the pediatric group (p < 0.001), whereas cholestatic-type DILI and chronic DILI were more prevalent in the elderly group (p < 0.001). Acute liver failure (ALF) and fatal outcomes were more prevalent in the pediatric and elderly groups, particularly in the pediatric group (2.04%, p = 0.041; 0.85%, p = 0.007, respectively). CONCLUSIONS: Children and elderly individuals face a higher risk of adverse outcomes following DILI.

4.
Nat Commun ; 15(1): 4431, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789458

RESUMO

Topological lasers (TLs) have attracted widespread attention due to their mode robustness against perturbations or defects. Among them, electrically pumped TLs have gained extensive research interest due to their advantages of compact size and easy integration. Nevertheless, limited studies on electrically pumped TLs have been reported in the terahertz (THz) and telecom wavelength ranges with relatively low output powers, causing a wide gap between practical applications. Here, we introduce a surface metallic Dirac-vortex cavity (SMDC) design to solve the difficulty of increasing power for electrically pumped TLs in the THz spectral range. Due to the strong coupling between the SMDC and the active region, robust 2D topological defect lasing modes are obtained. More importantly, enough gain and large radiative efficiency provided by the SMDC bring in the increase of the output power to a maximum peak power of 150 mW which demonstrates the practical application potential of electrically pumped TLs.

5.
J Med Chem ; 67(6): 4603-4623, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38500250

RESUMO

Osteoarthritis is the most common joint disorder. However, there are no disease-modifying drugs approved for OA treatment. CDC2-like kinase 2 (CLK2) could modulate Wnt signaling via alternative splicing of Wnt target genes and further affect bone differentiation, chondrocyte function, and inflammation, making CLK2 an attractive target for OA therapy. In this study, we designed and synthesized a series of highly potent CLK2 inhibitors based on Indazole 1. Among them, compound LQ23 showed more elevated inhibitory activity against CLK2 than the lead compound (IC50, 1.4 nM) with high CLK2/CLK3 selectivity (>70-fold). Furthermore, LQ23 showed outstanding antiosteoarthritis effects in vitro and in vivo, with the roles specific in decreased inflammatory cytokines, downregulated cartilage degradative enzymes, and increased joint cartilage via suppressing CLK2/Wnt signaling pathway. Overall, these data support LQ23 as a potential candidate for intra-articular knee OA therapy, leveraging its unique mechanism of action for targeted treatment.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/metabolismo , Inflamação/metabolismo , Condrócitos/metabolismo , Via de Sinalização Wnt
6.
J Hazard Mater ; 465: 133192, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38070265

RESUMO

Pollution caused by Copper and hydrogen sulfide pollution has severe adverse effects on the environment and organisms. Real-time, fast and accurate monitoring of Cu2+ and S2- faces serious challenges. In this study, we designed a novel biosensor and synthesized it by mimicking the structure of the main Cu(II)-binding site on bovine serum albumin. As a peptide-based sensor, FGGH (FITC-Gly-Gly-His-NH2) can perform the sequential detection of Cu2+ and S2- by fluorescence and colorimetry. The high water solubility and selectivity make it suitable for monitoring Cu2+ and S2- in environmental water samples with high sensitivity; its limit of detection (LOD) is as low as 1.42 nM for Cu2+ and 22.2 nM for S2-. The paper-based sensing platform of this probe was found to be a promising tool for the on-site visualization of real-time quantitative analysis of Cu2+ and S2- due to its rapid response and recyclable detection characteristics. Additionally, FGGH was successfully used to image Cu2+ and S2- in living cells and zebrafish models with adequate fluorescence stability and low cytotoxicity, providing the first visual evidence of the effect of the interactions between Cu2+ and S2- on the redox homeostasis of organisms.


Assuntos
Colorimetria , Cobre , Animais , Cobre/química , Colorimetria/métodos , Corantes Fluorescentes/química , Peixe-Zebra , Peptídeos/química , Água/química , Espectrometria de Fluorescência/métodos
7.
J Hazard Mater ; 465: 133331, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38142657

RESUMO

Mercury is a harmful heavy metal that seriously threatens the environment and organisms. In this study, we combined the aggregation-induced emission mechanism and the advantages of peptides to design a novel tetraphenylene (TPE)-based peptide fluorescent probe, TPE-Cys-Pro-Gly-His (TPE-CPGH), in which the sulfhydryl group of Cys in the peptide chain and the imidazolium nitrogen provided by His were used to mimic the Hg2+ binding site of metalloproteins. The ß-fold formed by Pro-Gly was used to promote the spatial coordination of the probe with Hg2+ and the formation of the coordination complex aggregates, these changes led to the "turn on" response to Hg2+. The detection of Hg2+ by TPE-CPGH not only showed high specificity and sensitivity (LOD=46.2 nM), but also had the advantages of fast response and applicability for detection over a wide pH range. Additionally, TPE-CPGH effectively detected Hg2+ in environmental samples, living cells and organisms due to its low cytotoxicity, high water solubility and cell membrane permeability. More interestingly, TPE-CPGH was also mitigated Hg2+ exposure-induced oxidative stress toxicity in vitro and in vivo.


Assuntos
Mercúrio , Metais Pesados , Corantes Fluorescentes/química , Limite de Detecção , Peptídeos/química , Espectrometria de Fluorescência
8.
J Org Chem ; 88(24): 17489-17493, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37992127

RESUMO

A method for the syntheses of substituted α,ß-unsaturated δ-lactams (2) from the commercially available compound N-Boc-2,4-dioxopiperidine (1) has been developed. The α-substituents were introduced by a reductive Knoevenagel condensation reaction, and the ß-substituents were installed by palladium-catalyzed cross coupling reactions. More than 20 diverse examples were prepared in 2-3 steps. The synthesis was operationally simple, user-friendly, and easy to scale up.

9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 37(11): 1326-1334, 2023 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-37987040

RESUMO

Objective: To investigate the accuracy, safety, and short-term effectiveness of a domestic robot-assisted system in total knee arthroplasty (TKA) by a multicenter randomized controlled trial. Methods: Between December 2021 and February 2023, 138 patients with knee osteoarthritis who received TKA in 5 clinical centers were prospectively collected, and 134 patients met the inclusion criteria were randomly assigned to either a trial group ( n=68) or a control group ( n=66). Seven patients had lost follow-up and missing data, so they were excluded and the remaining 127 patients were included for analysis, including 66 patients in the trial group and 61 patients in the control group. There was no significant difference ( P>0.05) in gender, age, body mass index, side, duration of osteoarthritis, Kellgren-Lawrence grading, preoperative Knee Society Score (KSS) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score between the two groups. The trial group completed the TKA by domestic robot-assisted osteotomy according to the preoperative CT-based surgical planning. The control group was performed by traditional osteotomy plate combined with soft tissue release. Total operation time, osteotomy time of femoral/tibial side, intraoperative blood loss, and postoperative complications were recorded and compared between the two groups. The radiographs were taken at 5 and 90 days after operation, and hip-knee-ankle angle (HKA), lateral distal angle of femur (LDFA), and posterior tibial slope (PTS) were measured. The difference between the measured values of the above indexes at two time points after operation and the preoperative planning target values was calculated, and the absolute value (absolute error) was taken for comparison between the two groups. The postoperative recovery of lower limb alignment was judged and the accuracy was calculated. KSS score and WOMAC score were used to evaluate the knee joint function of patients before operation and at 90 days after operation. The improvement rates of KSS score and WOMAC score were calculated. The function, stability, and convenience of the robot-assisted system were evaluated by the surgeons. Results: The total operation time and femoral osteotomy time of the trial group were significantly longer than those of the control group ( P<0.05). There was no significant difference in the tibial osteotomy time and the amount of intraoperative blood loss between the two groups ( P>0.05). The incisions of both groups healed by first intention after operation, and there was no infection around the prosthesis. Nine patients in the trial group and 8 in the control group developed lower extremity vascular thrombosis, all of which were calf intermuscular venous thrombosis, and there was no significant difference in the incidence of complications ( P>0.05). All patients were followed up 90 days. There was no significant difference in KSS score and WOMAC score between the two groups at 90 days after operation ( P>0.05). There was significant difference in the improvement rate of KSS score between the two groups ( P<0.05), while there was no significant difference in the improvement rate of WOMAC score between the two groups ( P>0.05). Radiological results showed that the absolute errors of HKA and LDFA in the trial group were significantly smaller than those in the control group at 5 and 90 days after operation ( P<0.05), and the recovery accuracy of lower limb alignment was significantly higher than that in control group ( P<0.05). The absolute error of PTS in the trial group was significantly smaller than that in the control group at 5 days after operation ( P<0.05), but there was no significant difference at 90 days between the two groups ( P>0.05). The functional satisfaction rate of the robot-assisted system was 98.5% (65/66), and the satisfaction rates of stability and convenience were 100% (66/66). Conclusion: Domestic robot-assisted TKA is a safe and effective surgical treatment for knee osteoarthritis, which can achieve favorable lower limb alignment reconstruction, precise implant of prosthesis, and satisfactory functional recovery.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Robótica , Humanos , Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Perda Sanguínea Cirúrgica , Articulação do Joelho/cirurgia , Estudos Retrospectivos
10.
Front Plant Sci ; 14: 1267107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37799546

RESUMO

The basic helix-loop-helix (bHLH) family is one of the most well-known transcription factor families in plants, and it regulates growth, development, and abiotic stress responses. However, systematic analyses of the bHLH gene family in Prunus sibirica have not been reported to date. In this study, 104 PsbHLHs were identified and classified into 23 subfamilies that were unevenly distributed on eight chromosomes. Nineteen pairs of segmental replication genes and ten pairs of tandem replication genes were identified, and all duplicated gene pairs were under purifying selection. PsbHLHs of the same subfamily usually share similar motif compositions and exon-intron structures. PsbHLHs contain multiple stress-responsive elements. PsbHLHs exhibit functional diversity by interacting and coordinating with other members. Twenty PsbHLHs showed varying degrees of expression. Eleven genes up-regulated and nine genes down-regulated in -4°C. The majority of PsbHLHs were highly expressed in the roots and pistils. Transient transfection experiments demonstrated that transgenic plants with overexpressed PsbHLH42 have better cold tolerance. In conclusion, the results of this study have significant implications for future research on the involvement of bHLH genes in the development and stress responses of Prunus sibirica.

11.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 37(10): 819-824;828, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-37828887

RESUMO

Objective:To analyze the clinical diagnosis, treatment ,and surgical timing of otogenic intracranial complications. Methods:The clinical data of 11 patients with intracranial complications with ear symptoms as the first manifestation in Department of Otorhinolaryngology Head and Neck Surgery, Qilu Hospital of Shandong University(Qingdao) from December 2014 to June 2022 were collected, including 8 males and 3 females, aged from 4 to 69 years. All patients had complete otoendoscopy, audiology, imaging and etiology examination, and the diagnosis and treatment plan was jointly developed through multidisciplinary consultation according to the critical degree of clinical symptoms and imaging changes. Among the 11 patients, 5 cases were treated with intracranial lesions first in neurosurgery department and middle ear lesions later in otolaryngology, 3 cases of meningitis, were treated with middle ear surgery after intracranial infection control, 1 case was treated with middle ear lesions and intracranial infection simultaneously, and 2 cases were treated with sigmoid sinus and transverse sinus thrombosis conservatively. They were followed up for 1-6 years. Descriptive statistical methods were used for analysis. Results:All the 11 patients had ear varying symptoms, including ear pain, pus discharge and hearing loss, etc, and then fever appeared, headache, disturbance of consciousness, facial paralysis and other intracranial complication. Otoendoscopy showed perforation of the relaxation of the tympanic membrane in 5 cases, major perforation of the tension in 3 cases, neoplasia in the ear canal in 1 case, bulging of the tympanic membrane in 1 case, and turbidity of the tympanic membrane in 1 case. There were 4 cases of conductive hearing loss, 4 cases of mixed hearing loss and 3 cases of total deafness. Imaging examination showed cholesteatoma of the middle ear complicated with temporal lobe brain abscess in 4 cases, cerebellar abscess in 2 cases, cholesteatoma of the middle ear complicated with intracranial infection in 3 cases, and sigmoid sinus thrombophlebitis in 2 cases. In the etiological examination, 2 cases of Streptococcus pneumoniae were cultured in the pus of brain abscess and cerebrospinal fluid, and 1 case was cultured in streptococcus vestibularis, Bacteroides uniformis and Proteus mirabilis respectively. During the follow-up, 1 patient died of cardiovascular disease 3 years after discharge, and the remaining 10 patients survived. There was no recurrence of intracranial and middle ear lesions. Sigmoid sinus and transverse sinus thrombosis were significantly improved. Conclusion:Brain abscess, intracranial infection and thrombophlebitis are the most common otogenic intracranial complications, and cholesteatoma of middle ear is the most common primary disease. Timely diagnosis, multidisciplinary collaboration, accurate grasp of the timing in the treatment of primary focal and complications have improved the cure rate of the disease.


Assuntos
Abscesso Encefálico , Infecções do Sistema Nervoso Central , Otopatias , Trombose dos Seios Intracranianos , Tromboflebite , Feminino , Humanos , Masculino , Abscesso Encefálico/etiologia , Abscesso Encefálico/terapia , Colesteatoma , Surdez/etiologia , Perda Auditiva/etiologia , Trombose do Seio Lateral/etiologia , Trombose do Seio Lateral/terapia , Estudos Retrospectivos , Tromboflebite/etiologia , Tromboflebite/terapia , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Colesteatoma da Orelha Média/complicações , Colesteatoma da Orelha Média/terapia , Infecções do Sistema Nervoso Central/etiologia , Infecções do Sistema Nervoso Central/terapia , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/terapia , Otopatias/complicações , Otopatias/terapia
12.
Front Public Health ; 11: 1188259, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693723

RESUMO

Using data from the 2018 Chinese General Social Survey (CGSS), this study investigates the impact of internet use on residents' happiness. Empirical results show that internet use significantly enhances residents' happiness. Considering the possible endogeneity problem, a two-stage tool variable estimation is carried out with ownership of a mobile phone as the tool variable. After overcoming the endogenous problem and conducting a series of robustness tests, the conclusion is still valid. The action mechanism finds that social interaction frequency and socioeconomic status (SES) play significant mediating effects in the process of internet use affecting happiness. Specifically, internet use significantly increases the social interaction frequency of residents and enhances their SES. The improvement of social interaction frequency and SES will significantly increase residents' happiness. Therefore, this paper gives policy recommendations from the perspectives of regulating and deepening internet use, increasing the frequency of communication among residents, and improving their SES to better enhance their happiness.


Assuntos
Felicidade , Uso da Internet , Internet , China , Comunicação
13.
Sci Rep ; 13(1): 11245, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37433853

RESUMO

Siberian apricot (Prunus sibirica L.) is a woody tree species of ecological, economic, and social importance. To evaluate the genetic diversity, differentiation, and structure of P. sibirica, we analyzed 176 individuals from 10 natural populations using 14 microsatellite markers. These markers generated 194 alleles in total. The mean number of alleles (13.8571) was higher than the mean number of effective alleles (6.4822). The average expected heterozygosity (0.8292) was higher than the average observed heterozygosity (0.3178). Shannon information index and polymorphism information content were separately 2.0610 and 0.8093, demonstrating the rich genetic diversity of P. sibirica. Analysis of molecular variance revealed that 85% of the genetic variation occurred within populations, with only 15% among them. The genetic differentiation coefficient and gene flow were separately 0.151 and 1.401, indicating a high degree of genetic differentiation. Clustering results showed that a genetic distance coefficient of 0.6 divided the 10 natural populations into two subgroups (subgroups A and B). STRUCTURE and principal coordinate analysis divided the 176 individuals into two subgroups (clusters 1 and 2). Mantel tests revealed that genetic distance was correlated with geographical distance and elevation differences. These findings can contribute to the effective conservation and management of P. sibirica resources.


Assuntos
Prunus armeniaca , Prunus , Humanos , Prunus/genética , Prunus armeniaca/genética , Alelos , Repetições de Microssatélites/genética , Polimorfismo Genético
14.
Int Orthop ; 47(10): 2585-2589, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37421425

RESUMO

PURPOSE: To discuss a static and permanent spacer in the treatment of chronic periprosthetic knee infection. Methods In this study, patients who were diagonised with chronic periprosthetic knee infection and not appropriate to undergo revision operations were included and were treated with static and permanent spacers. Infection recurrence rate was recorded, Visual Analogue Scale (VAS) score and Knee Society Score (KSS) were used to record patients' pain and knee function before the operation and at the final follow-up (minimum 24 months). RESULTS: Fifteen patients were identified for this study. Pain and function were significantly improved at the latest follow-up evaluation. One patient had a recurrent infection and underwent amputation. No patients had signs of residual instability at the final follow-up evaluation, and no breakage or subsidence of the antibiotic spacer were identified at the final radiographic follow-up evaluation. CONCLUSION: Our study provided evidence that the static and permanent spacer was a reliable salvage procedure to treat periprosthetic knee infection in compromised patients.

15.
BMC Genomics ; 24(1): 358, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370033

RESUMO

BACKGROUND: WRKY transcription factors are a prominent gene family in plants, playing a crucial role in various biological processes including development, metabolism, defense, differentiation, and stress response. Although the WRKY gene family has been extensively studied and analysed in numerous plant species, research on Prunus sibirica's WRKY genes (PsWRKY) remains lacking. RESULTS: This study analysed the basic physicochemical properties, phylogeny, gene structure, cis-acting elements, and Gene ontology (GO) annotation of PsWRKY gene family members using bioinformatics methods based on the whole-genome data of P. sibirica. In total, 55 WRKYs were identified in P. sibirica and were heterogeneously distributed on eight chromosomes. Based on the phylogenetic analysis, these WRKYs were classified into three major groups: Group I, Group II (II-a, II-b, II-c, II-d, II-e), and Group III. Members of different subfamilies have different cis-acting elements, conserved motifs, and intron-exon structures, indicating functional heterogeneity of the WRKY family. Prediction of subcellular localisation indicated that PsWRKYs were mainly located in the nucleus. Twenty pairs of duplicated genes were identified, and segmental duplication events may play an important role in PsWRKY gene family expansion. Analysis of the Ka/Ks ratio showed that the PsWRKY family's homologous genes were primarily purified by selection. Additionally, GO annotation analysis showed that the WRKY gene family was mainly involved in responses to stimuli, immune system processes, and reproductive processes. Furthermore, quantitative real-time PCR (qRT-PCR) analysis showed that 23 PsWRKYs were highly expressed in one or more tissues (pistils and roots) and PsWRKYs showed specific expression patterns under different low-temperature stress conditions. CONCLUSIONS: Our results provide a scientific basis for the further exploration and functional validation of WRKYs in P. sibirica.


Assuntos
Prunus , Prunus/genética , Filogenia , Temperatura , Proteínas de Plantas/metabolismo , Genoma de Planta , Plantas/genética , Família Multigênica , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética
16.
Chem Commun (Camb) ; 59(35): 5225-5228, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37039521

RESUMO

A copper-catalyzed [3+2] annulation of O-acyl ketoximes with 2-aryl malonates for the concise synthesis of 3-aryl-4-pyrrolin-2-ones has been developed. The advantage of this method lies in the use of O-acyl oximes as an internal oxidant to generate the nucleophilic enamines and electrophilic p-quinone methides concurrently. The subsequent nucleophilic addition undergoes selectively on the α-C of malonates.

17.
Org Lett ; 25(5): 838-842, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36705486

RESUMO

A copper-catalyzed annulation of O-acyl oximes with cyclic 1,3-diones has been developed for the concise synthesis of 7,8-dihydroindolizin-5(6H)-ones and cyclohexanone-fused furans through the substituent-controlled selective radical coupling process. 2-Alkyl cyclic 1,3-diones undergo C-C radical coupling, while 2-unsubstituted cyclic 1,3-diones undergo C-O radical coupling.

18.
Shock ; 59(3): 368-374, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36562264

RESUMO

ABSTRACT: Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. Patients: We included adult patients (age ≥18 years) who developed SALD within the first 48 hours of intensive care unit (ICU) admission. We excluded patients who died or were discharged from the ICU within the first 48 hours of admission. Patients with abnormal liver function before ICU admission were also excluded. Measurements and Main Results: Patients in the MIMIC-IV 1.0 database served as a derivation cohort. Patients in the eICU database were used as validation cohort. We identified four subphenotypes of SALD (subphenotype α, ß, γ, δ) using K-means cluster analysis in 5234 patients in derivation cohort. The baseline characteristics and clinical outcomes were compared between the phenotypes using one-way analysis of variance/Kruskal-Wallis test and the χ 2 test. Moreover, we used line charts to illustrate the trend of liver function parameters over 14 days after ICU admission. Subphenotype α (n = 1,055) was the most severe cluster, characterized by shock with multiple organ dysfunction (MODS) group. Subphenotype ß (n = 1,179) had the highest median bilirubin level and the highest proportion of patients with underlying liver disease and coexisting coagulopathy (increased bilirubin group). Subphenotype γ (n = 1,661) was the cluster with the highest mean age and had the highest proportion of patients with chronic kidney disease (aged group). Subphenotype δ (n = 1,683) had the lowest 28-day and in-hospital mortality (mild group). The characteristics of clusters in the validation cohort were similar to those in the derivation cohort. In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.


Assuntos
Hepatopatias , Sepse , Humanos , Estudos Retrospectivos , Fenótipo , Análise por Conglomerados , Unidades de Terapia Intensiva
19.
J Gastrointest Oncol ; 13(5): 2234-2248, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388685

RESUMO

Background: N6-methyladenosine (m6A) is the most abundant form of methylation modification in eukaryotic cell messenger RNA (mRNA). However, the role of m6A in gastric cancer (GC), which is one of the most common gastrointestinal malignancies, is unclear. In this study, m6A-relevant mRNA signatures and risk scores were determined to predict the prognosis of GC. Methods: The expression profiles and clinical information of 367 patients were downloaded from The Cancer Genome Atlas (TCGA). Cluster analysis and univariate Cox analysis were performed to identify the regulatory factors of RNA methylation associated with GC prognosis. A co-expression network was constructed using the WGCNA package in R. The correlations between module eigengenes and clinical traits were then calculated to identify the relevant modules. We used univariate Cox analysis to screen for genes that are significantly associated with prognosis in the module. We identified hub genes by least absolute shrinkage and selection operator (LASSO) and multivariate analysis and developed a Cox prognostic model. Finally, the hub gene expression values weighted by the coefficients from the LASSO regression were applied to generate a risk score for each patient, and receiver operating characteristic (ROC) and Kaplan-Meier curves were used to assess the prognostic capacity of the risk scores. The asporin (ASPN) gene in GC cell lines was verified via quantitative polymerase chain reaction (qPCR) and Western blot. Moreover, 5-ethynyl-2'-deoxyuridine (EdU) and transwell assays were applied to evaluate the effects of the proliferation, migration, and invasion abilities in GC cells after ASPN knockdown. Western blot verified the effects of ASPN on the phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (AKT)/mechanistic target of rapamycin kinase (mTOR) pathway and epithelial-mesenchymal transition (EMT) pathway-related gene expression. Results: Our results indicated that AARD, ASPN, SLAMF9, MIR3117 and DUSP1 were hub genes affecting the prognosis of GC patients. Besides, we found that ASPN expression was upregulated in GC cells. The knockdown of ASPN expression suppressed GC cell proliferation, migration, and invasion by deactivating the PI3K/AKT/mTOR and EMT pathways, respectively. Conclusions: Our findings indicated that ASPN participates in the biological process of GC as an oncogene and may be a promising biomarker in GC.

20.
PeerJ ; 10: e14366, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405023

RESUMO

In Prunus sibirica, the phenomenon of pistil abortion is very common and seriously affects its fruit quality and yield; however, the molecular mechanisms of pistil abortion remains unclear. In this study, we identified differentially expressed genes (DEGs) and pathways associated with pistil abortion using transcriptome sequencing. After comparative analysis, a total of 1,950 DEGs were identified, of which 1,000 were upregulated, and 950 were downregulated. Gene Ontology (GO) functional enrichment analysis of DEGs showed that metabolic process, cellular process, single-organism process, membrane, membrane part, cell, binding, catalytic activity, and transporter activity contained the largest number of DEGs. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the plant-pathogen interaction, starch and sucrose metabolism, and plant hormone signal transduction pathways contained the largest number of DEGs. The NAC, bHLH, and B3 transcription factor families contained the largest number of DEGs. qRT-PCR detection confirmed that the gene expression levels were consistent with the transcriptome sequencing results. This study provides a theoretical basis and scientific basis for further research on the molecular mechanisms of P. sibirica pistil abortion.


Assuntos
Prunus , Transcriptoma , Transcriptoma/genética , Perfilação da Expressão Gênica/métodos , Prunus/genética , Regulação da Expressão Gênica de Plantas/genética , Flores/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA