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1.
Plant J ; 114(2): 338-354, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36789486

RESUMO

Cytidine diphosphate diacylglycerol (CDP-DAG), an important intermediate for glycerolipid biosynthesis, is synthesized under the catalytic activity of CDP-DAG synthase (CDS) to produce anionic phosphoglycerolipids such as phosphatidylglycerol (PG) and cardiolipin (CL). Previous studies showed that Arabidopsis CDSs are encoded by a small gene family, termed CDS1-CDS5, the members of which are integral membrane proteins in endoplasmic reticulum (ER) and in plastids. However, the details on how CDP-DAG is provided for mitochondrial membrane-specific phosphoglycerolipids are missing. Here we present the identification of a mitochondrion-specific CDS, designated CDS6. Enzymatic activity of CDS6 was demonstrated by the complementation of CL synthesis in the yeast CDS-deficient tam41Δ mutant. The Arabidopsis cds6 mutant lacking CDS6 activity showed decreased mitochondrial PG and CL biosynthesis capacity, a severe growth deficiency finally leading to plant death. These defects were rescued partly by complementation with CDS6 or supplementation with PG and CL. The ultrastructure of mitochondria in cds6 was abnormal, missing the structures of cristae. The degradation of triacylglycerol (TAG) in lipid droplets and starch in chloroplasts in the cds6 mutant was impaired. The expression of most differentially expressed genes involved in the mitochondrial electron transport chain was upregulated, suggesting an energy-demanding stage in cds6. Furthermore, the contents of polar glycerolipids in cds6 were dramatically altered. In addition, cds6 seedlings lost the capacity for cell proliferation and showed a higher oxidase activity. Thus, CDS6 is indispensable for the biosynthesis of PG and CL in mitochondria, which is critical for establishing mitochondrial structure, TAG degradation, energy production and seedling development.


Assuntos
Arabidopsis , Arabidopsis/metabolismo , Glicogênio Sintase/metabolismo , Cistina Difosfato/metabolismo , Diglicerídeos/metabolismo , Diacilglicerol Colinofosfotransferase/metabolismo , Mitocôndrias/metabolismo , Fosfatidilgliceróis/metabolismo , Saccharomyces cerevisiae/metabolismo
2.
Cladistics ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016633

RESUMO

Tooth attachment and replacement play significant roles in the feeding ecology of polyphyodont vertebrates, yet these aspects have remained largely unexplored in non-avialan paravians including troodontids. Here, we describe a new troodontid species, Urbacodon norelli sp.n., recovered from the Upper Cretaceous Iren Dabasu Formation of Inner Mongolia, China, based on an incomplete right dentary and 12 associated replacement teeth. Urbacodon norelli is distinguished from all other known troodontids, including its relative U. itemirensis from Uzbekistan, by several features: the presence of paired dentary symphyseal foramina, the presence of a relatively steep anterior margin of the dentary, the absence of a dentary chin, the presence of a common groove hosting the anterior 12 dentary teeth, and the presence of relatively larger dentary teeth. Phylogenetic analysis places both species of Urbacodon as sister taxa to Zanabazar junior, confirming their status as later-diverging troodontids. Radiographs revealed an alternating tooth replacement pattern in U. norelli, with a maximum Zahnreihen-spacing estimated to be 3. During tooth replacement, the anteriorly inclined interdental septa, which wedge between anterior dentary teeth, underwent frequent remodelling as the developing tooth moved upwards, particularly anterolabially. This rapid turnover left insufficient time for an interdental plate to form, resulting in the absence of such structures in this specimen. The frequent remodelling of periodontal tissues accompanying tooth replacement is likely to account for the absence of interdental plates. The discovery of this new troodontid expands our understanding of paravian theropods from the Upper Cretaceous Iren Dabasu Formation and provides valuable insights into troodontid tooth biology.

3.
BMC Med Res Methodol ; 24(1): 147, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003440

RESUMO

BACKGROUND: Decision analytic models and meta-analyses often rely on survival probabilities that are digitized from published Kaplan-Meier (KM) curves. However, manually extracting these probabilities from KM curves is time-consuming, expensive, and error-prone. We developed an efficient and accurate algorithm that automates extraction of survival probabilities from KM curves. METHODS: The automated digitization algorithm processes images from a JPG or PNG format, converts them in their hue, saturation, and lightness scale and uses optical character recognition to detect axis location and labels. It also uses a k-medoids clustering algorithm to separate multiple overlapping curves on the same figure. To validate performance, we generated survival plots form random time-to-event data from a sample size of 25, 50, 150, and 250, 1000 individuals split into 1,2, or 3 treatment arms. We assumed an exponential distribution and applied random censoring. We compared automated digitization and manual digitization performed by well-trained researchers. We calculated the root mean squared error (RMSE) at 100-time points for both methods. The algorithm's performance was also evaluated by Bland-Altman analysis for the agreement between automated and manual digitization on a real-world set of published KM curves. RESULTS: The automated digitizer accurately identified survival probabilities over time in the simulated KM curves. The average RMSE for automated digitization was 0.012, while manual digitization had an average RMSE of 0.014. Its performance was negatively correlated with the number of curves in a figure and the presence of censoring markers. In real-world scenarios, automated digitization and manual digitization showed very close agreement. CONCLUSIONS: The algorithm streamlines the digitization process and requires minimal user input. It effectively digitized KM curves in simulated and real-world scenarios, demonstrating accuracy comparable to conventional manual digitization. The algorithm has been developed as an open-source R package and as a Shiny application and is available on GitHub: https://github.com/Pechli-Lab/SurvdigitizeR and https://pechlilab.shinyapps.io/SurvdigitizeR/ .


Assuntos
Algoritmos , Humanos , Estimativa de Kaplan-Meier , Análise de Sobrevida , Probabilidade
4.
Nanotechnology ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134022

RESUMO

Although enhanced performances of photovoltaic devices by embedding metal nanoparticals in charge transport layer, doping into active layer bulk, decorating the active layer surface, and inserting at the interface between semiconductor and the electrode were reported, the effect of incorporating metal NPs at the interface of single crystal semiconductor and perovskite is rarely tackled. Herein the effects of incorporating Ag nanoparticals (AgNPs) at p-Si/MAPbI3 perovskite interface on the photodiode performances were investigated. The results showed that compared with reference device (without AgNPs) the photoresponsivity of the device incorporating AgNPs is greatly improved with the exception for light with wavelengths fall in the spectral range where AgNPs have strong optical absorption. This effect is extremely significant for relatively shorter wavelengths in visible region, and a maximal improvement of around 10.6 times in photoresponsivity was achieved. The physical origin of the exception for spectral range that AgNPs have strong optical absorption is the cancelation of scatter resulted enhancement through AgNPs by band-to-band absorption resulted reduction of photocurrent, in which the generated electron has energy near the fermi level and the hole has large effective mass, which relax by nonradiative recombination, thus making not contribution to the photocurrent. More importantly, the AgNP decorated device showed much faster photo response speed than reference device, and a maximal improvement of around 7.9 times in rise and fall time was achieved. These findings provide a novel approach for high responsive and high speed detection for weak light.

5.
J Chem Phys ; 160(9)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38441265

RESUMO

In order to prepare highly heat-resistant packaging insulation materials, in this paper, bismaleimide/epoxy resin (BMI/EP55) composites with different contents of BMI were prepared by melt blending BMI into amino tetrafunctional and phenolic epoxy resin (at a ratio of 5:5). The microstructures and thermal and electrical properties of the composites were tested. The electrostatic potential distribution, energy level distribution, and molecular orbitals of BMI were calculated using Gaussian. The results showed that the carbonyl group in BMI is highly electronegative, implying that the carbonyl group has a strong electron trapping ability. The thermal decomposition temperature of the composites gradually increased with the increase of BMI content, and the 20% BMI/EP55 composites had the highest heat-resistance index, along with a glass transition temperature (Tg) of >250 °C. At different test temperatures, with increase in the BMI content, the conductivity of epoxy resin composites showed a tendency to first decrease and then increase, the breakdown field strength showed a tendency to first increase and then decrease, and the dielectric constant was gradually decreased. Two trap centers were present simultaneously in the composites, where the shallow trap energy level is the deepest in 20% BMI/EP composites and the deep trap energy level is the deepest in 10% BMI/EP55 composites. Correspondingly, the 10% BMI/EP55 composite had a slower charge decay rate, while the 20% BMI/EP55 had a faster charge decay rate. In summary, the BMI/EP55 composites with high heat resistance and insulating properties were prepared in this study, which provided ideas for preparing high-temperature packaging insulating materials.

6.
BMC Oral Health ; 24(1): 1096, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285382

RESUMO

BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease (AIBD). Some reports suggest that it has a drug-related pathogenesis especially anti-hypertensive drug. CASE PRESENTATION: A 67-year-old man with a 7-year history of essential hypertension was prescribed enalapril maleate for 5 months. He presented at our department with pain, ulcers, and blisters on the oral mucosa. We performed clinical, histopathology, and direct immunofluorescence examinations, and findings were consistent with the diagnostic criteria for MMP. Consequently, we consulted with the cardiovascular physician and agreed to discontinue the enalapril maleate replacing it with irbesartan/hydrochlorothiazide tablets and topical corticosteroid therapies instead. The lesions healed without recurrence. CONCLUSIONS: ABID induced by antihypertensive drugs have been reported, and enalapril maleate has been implicated as an antihypertensive agent that may trigger AIBDs, such as MMP. This case highlights the potential relationship between antihypertensive drugs and MMP, of which clinicians should be aware to accurately diagnose and promptly relieve patients' pain.


Assuntos
Anti-Hipertensivos , Enalapril , Penfigoide Mucomembranoso Benigno , Humanos , Enalapril/efeitos adversos , Enalapril/uso terapêutico , Masculino , Idoso , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Penfigoide Mucomembranoso Benigno/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Irbesartana/uso terapêutico , Hidroclorotiazida/efeitos adversos , Hidroclorotiazida/uso terapêutico
7.
Opt Lett ; 48(13): 3579-3582, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37390185

RESUMO

Employing a photosensitive donor/acceptor planar heterojunction (DA-PHJ) with complementary optical absorption as the active layer is one of the key strategies for realizing broad spectral organic photodiodes (BS-OPDs). To achieve superior optoelectronic performance, it is vital to optimize the thickness ratio of the donor layer to acceptor layer (the DA thickness ratio) in addition to the optoelectronic properties of the DA-PHJ materials. In this study, we realized a BS-OPD exploiting tin(II) phthalocyanine (SnPc)/3,4,9,10-perylenete-acarboxylic dianhydride (PTCDA) as the active layer and investigated the effect of the DA thickness ratio on the device performance. The results showed that the DA thickness ratio has a significant impact on the device performance, and an optimized DA thickness ratio of 30:20 was found. Upon the optimization of the DA thickness ratio, improvements of 187% in photoresponsivity and 144% in specific detectivity were achieved on average. Trap-free space-charge-limited photocarrier transport and balanced optical absorption over the wavelength range can be ascribed to the improved performance at the optimized DA thickness ratio. These results establish a solid photophysical foundation for improving the performance of BS-OPDs via thickness ratio optimization.


Assuntos
Isoindóis , Estanho
8.
Health Commun ; 38(10): 1994-2001, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35282726

RESUMO

Using panel data from mainland China, this study incorporates uncertainty, information seeking, and social support into the goal disruption theoretical model to examine the indirect influence of goal disruption on psychological disequilibrium through uncertainty and the moderating roles of information seeking and social support in this relationship. The results demonstrate that goal disruption causes uncertainty and then leads to psychological disequilibrium. Information seeking can reduce uncertainty and social support can attenuate psychological disequilibrium as well. Limitations and further directions are discussed.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Comportamento de Busca de Informação , Incerteza , Objetivos , China/epidemiologia , Surtos de Doenças , Apoio Social
9.
Cladistics ; 38(1): 59-82, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35049080

RESUMO

A new troodontid (LH PV39) recovered from the Upper Cretaceous Wulansuhai Formation, Inner Mongolia, China, is described, highlighting the dorsoventrally compressed sacral centra. The completely fused neurocentral junctions indicate that LH PV39 had reached adulthood at the time of death, but its size is nevertheless 20% smaller than that of the sympatric Philovenator, demonstrating that it is the second small-bodied troodontid recovered from the Wulansuhai Formation. Phylogenetic analyses scoring LH PV39 using different strategies and performed with different algorithms unambiguously recovered it as a troodontid. While the parsimony-based analysis scoring LH PV39 as an independent OTU with all of its available characteristics included recovered it as a basal troodontid, the Bayesian analysis suggests a closer relationship of LH PV39 to Almas and an unnamed troodontid from Ukhaa Tolgod, Mongolia (MPC-D100/1126+D100/3500). Body size analysis confirmed a single trend of gigantism throughout the evolution of troodontids, and suggests that the Late Cretaceous troodontids evolved in two directions: (i) several size-independent characteristics evolved while retaining the small sizes that are typical of the Early Cretaceous relatives, resulting in the Late Cretaceous small-bodied troodontids; and (ii) size-dependent characteristics (e.g., the elongation of the rostrum) evolved accompanying the size increase, resulting in large-bodied derived troodontids. The mosaic features of the Late Cretaceous small-bodied troodontids place them intermediate between their Early Cretaceous basal relatives and the Late Cretaceous large-bodied taxa in a well-resolved phylogeny, which is crucial for understanding the size and morphological evolution of troodontids.


Assuntos
Dinossauros , Animais , Teorema de Bayes , Tamanho Corporal , China , Dinossauros/anatomia & histologia , Filogenia
10.
Oral Dis ; 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36260219

RESUMO

OBJECTIVE: Manganese ion (Mn2+ ) is reported to promote the antitumor immune response by activating the cGAS-STING pathway, but it is unknown whether Mn2+ can prevent the malignant transformation of precancerous lesions. The effects of Mn2+ in treating oral leukoplakia (OLK) were explored in this work. METHODS: Peripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP-AES). A coculture model of dendritic cells (DCs)/macrophages, CD8+ T cells, and dysplastic oral keratinocytes (DOKs) was employed to analyze the role and mechanism of Mn2+ in a simulated OLK immune microenvironment. Western blot, RT-PCR, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and lactate dehydrogenase (LDH) assays were adopted to detect the mechanism of Mn2+ in this model. 4-nitroquinoline oxide (4NQO)-induced OLK mice were used to assess the role of Mn2+ in suppressing OLK progression, and a novel Mn2+ -loaded guanosine-tannic acid hydrogel (G-TA@Mn2+ hydrogel) was fabricated and evaluated for its advantages in OLK therapy. RESULTS: The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. Mn2+ promoted the maturation and antigen presentation of DCs and macrophages and enhanced the activation of CD8+ T cells in the coculture model, resulting in effective killing of DOKs. Mechanistic analysis found that Mn2+ enhanced the anti-OLK immune response by activating the cGAS-STING pathway. Moreover, Mn2+ suppressed the development of 4NQO-induced carcinogenesis in the mouse model. In addition, the G-TA@Mn2+ hydrogel had better anti-OLK effects. CONCLUSIONS: Mn2+ enhanced the anti-OLK immune response by activating the cGAS-STING pathway, and the G-TA@Mn2+ hydrogel is a potential novel therapeutic approach for OLK treatment.

11.
J Cell Biochem ; 120(11): 18751-18761, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31218742

RESUMO

Skeletal muscle is an important and complex organ with multiple biological functions in humans and animals. Proliferation and differentiation of myoblasts are the key steps during the development of skeletal muscle. MicroRNA (miRNA) is a class of 21-nucleotide noncoding RNAs regulating gene expression by combining with the 3'-untranslated region of target messenger RNA. Many studies in recent years have suggested that miRNAs play a critical role in myogenesis. Through high-throughput sequencing, we found that miR-323-3p showed significant changes in the longissimus dorsi muscle of Rongchang pigs in different age groups. In this study, we discovered that overexpression of miR-323-3p repressed myoblast proliferation and promoted differentiation, whereas the inhibitor of miR-323-3p displayed the opposite results. Furthermore, we predicted Smad2 as the target gene of miR-323-3p and found that miR-323-3p directly modulated the expression level of Smad2. Then luciferase reporter assays verified that Smad2 was a target gene of miR-323-3p during the differentiation of myoblasts. These findings reveal that miR-323-3p is a positive regulator of myogenesis by targeting Smad2. This provides a novel mechanism of miRNAs in myogenesis.


Assuntos
Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/genética , Desenvolvimento Muscular/genética , Mioblastos/metabolismo , Proteína Smad2/genética , Animais , Sequência de Bases , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/genética , Células HEK293 , Humanos , Camundongos , Mioblastos/citologia , Homologia de Sequência do Ácido Nucleico , Proteína Smad2/metabolismo , Suínos
12.
Mol Genet Genomics ; 294(1): 47-56, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30167790

RESUMO

The ACTN3 gene locates on 11q13-q14 and encodes the α-actinin-3 protein, which is only expressed in human skeletal muscle and influenced muscle function and metabolism. The previous studies reported that SNP rs1815739 is associated with elite power athletes' performance. In this study, we investigated the association between five SNPs within the ACTN3 gene and Chinese children physical fitness. We recruited 2244 Han Chinese children participants, and measured their 25-m run, stand broad jump, 10-m shuttle run, handgrip, BMI (calculated by weight and height) data. SNPs rs1671064, rs2275998, rs2290463, rs10791881, and rs1815739 of ACTN3 gene were genotyped and analyzed in five physical fitness data. QTL analysis on genotype and physical fitness data was carried out in all samples. Furthermore, a dichotomous division of samples into an overweight group (543) and a normal group (1701) was used for an association study of overweight. In the QTL analysis, we found rs2290463 was significantly associated with stand broad jump (corrected P value = 0.009, beta = 2.692). After added age and gender as covariates in the regression test, the association became more significant (P value = 5.80 × 10- 5, corrected P value = 4.06 × 10- 4); when we used BMI as a covariate, the association still existed (P value = 4.65 × 10- 4, corrected P value = 0.001). In the association study of overweight, rs2275998 was found to be significant (OR, 95% CI = 0.733 [0.6-0.895]; Pallele = 0.011, Pgenotype = 0.024) after the Bonferroni correction, and the association did not change much after a further correction for gender, age, and stand broad jump performance. Our results showed that common variants in ACTN3 are significantly associated with both stand broad jump performance and overweight in Han Chinese children.


Assuntos
Actinina/genética , Povo Asiático/etnologia , Sobrepeso/genética , Aptidão Física , Polimorfismo de Nucleotídeo Único , Povo Asiático/genética , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Genótipo , Força da Mão , Humanos , Masculino , Locos de Características Quantitativas
13.
Lipids Health Dis ; 18(1): 183, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647014

RESUMO

OBJECTIVES: The aim of the current study was to evaluate influence of serum triglyceride levels on the course of acute pancreatitis (AP). METHODS: Rats models of hypertriglyceridemic were used in animal experiments. Following induction of acute pancreatitis, amylase, and pancreas histological scores were all compared. In addition, in a clinical study, clinical data were collected from 1681 AP patients admitted from 2003 to 2016 who were divided into 4 groups based on their serum triglyceride (TG) levels. The clinical features among these 4 groups were compared, and a receiver operating characteristic (ROC) curve analysis was also performed on TG values to estimate their relationship with severity. RESULTS: In animal experiments, the hypertriglyceridemic pancreatitis (HTGP) group had markedly higher serum amylase, and histological scores relative to the other animal groups. In the clinical study, we identified significant differences in gender, age, body mass index (BMI), cost, and incidence of partial complications among the 4 TG-based groups. Importantly, the TG levels on day 3-4 after admission could be used to accurately predict disease severity. CONCLUSIONS: Hypertriglyceridemia (HTG) can aggravate pancreatic injury, and hypertriglyceridemia patients are more likely to suffer from severe pancreatic injury with a higher possibility of complications. In addition, triglyceride levels are correlated with the severity of AP positively.


Assuntos
Amilases/sangue , Hipertrigliceridemia/sangue , Pâncreas/metabolismo , Doença Aguda , Animais , Índice de Massa Corporal , Modelos Animais de Doenças , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ratos , Estudos Retrospectivos , Índice de Gravidade de Doença , Triglicerídeos/sangue
14.
Hereditas ; 156: 15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31148953

RESUMO

BACKGROUND: Athletic performances are complex traits with heritability of ~66%. Dynamic balance is one of the most important athletic performances, and there has been little studies for it in sports genomics. The candidate PPARD gene was reported to be able to affect muscle development for balance predisposition and influence the athletic performance including skiing triumph in the Caucasian population. This study aims to investigate whether the PPARD gene is a susceptibility gene for dynamic balance performance in Han Chinese children. RESULTS: A total 2244 children were recruited and their balance beam performances were measured. Five polymorphisms in the PPARD gene were genotyped through the MassARRAY Sequenom platform. Rs2016520 exerted significant association with dynamic balance performance (minor allele C, P = 0.015, Pcorrected < 0.05) and was affirmed in a meta-analysis by combining previously reported Caucasian cohorts (OR = 1.57, 95% CI = [1.30, 1.91], P < 10 -5) . Another polymorphism, rs2267668, was also significantly associated with dynamic balance performance (minor allele G, P = 0.015, Pcorrected < 0.05). In the dichotomous study, 321 cases (61% boys and 39% girls) and 370 controls (49% boys and 51% girls) in our samples were selected as representatives, and the thresholds were the mean velocity (0.737 m/s) ± standard deviation (0.264 m/s), in which rs2016520-C and rs2267668-G still remained significant (CI =1.41 [1.11~1.79], P = 0.004, Pcorrected < 0.016; CI =1.45 [1.14~1.86], P = 0.002, Pcorrected < 0.016). In different genders, consistent OR direction was observed for each variant. CONCLUSIONS: Our results suggested that the PPARD gene is associated with dynamic balance performance of human being, and further studies to reveal its etiology is strongly suggested.


Assuntos
Genótipo , PPAR delta/genética , Polimorfismo de Nucleotídeo Único , Equilíbrio Postural/genética , Alelos , Povo Asiático/genética , Criança , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Ligação Genética , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , Razão de Chances , Locos de Características Quantitativas
15.
J Transl Med ; 16(1): 171, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925382

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) have been suggested as potential prognostic indicators for multiple tumors, including gastric cancer; however, pre- and post-operative CTC changes in resectable gastric cancer and possible correlations to post-operative recurrence have not been evaluated. METHODS: Subjects (n = 93) with resectable gastric cancer were prospectively reviewed from July 2013 to December 2014 at Peking University Cancer Hospital. The proportion of CTCs were evaluated before (n = 93) and after (n = 63) radical operation using a standardized CellSearch system. RESULTS: CTCs ≥ 1 were measured in the pre-operative blood of 31 (33.3%) patients and in the post-operative blood of 21 patients (33.3%). Patients with relatively poor clinicopathological features had more pre- and post-operative CTCs. The 3-year disease-free survival (DFS) rate for patients with CTCs ≥ 5/7.5 ml was significantly lower than for patients with CTCs < 5/7.5 ml (40.0% vs 66.4%, p < 0.001 for pre-surgery; 25.0% vs 62.2%, p < 0.001 for post-surgery). Patients with CTCs ≥ 5/7.5 ml in post-operative blood had significantly shorter mean DFS (1.28 vs 31.6 months; p = 0.002) and overall survival (OS; 10.0 vs 34.9 months; p = 0.001) than other patients. Among the 10 patients with hematogenous recurrence, 3 had post-operative CTCs ≥ 2/7.5 ml and had early recurrence (DFS 1.1, 1.1, 1.4 months). Moreover, DFS for the seven patients was 20.2, 11.9, 20.0, 6.0, 15.5, 25.9, 30.0 months, respectively. DFS for the three patients with increased CTCs after surgery was shorter than for patients with mildly increased, stable, or decreased CTCs. CONCLUSIONS: Pre- and post-operative CTCs are promising prognostic markers for resectable gastric cancer. Our study further suggests that increased post-operative CTCs may be correlated with hematogenous recurrence. Trial registration (ClinicalTrials.gov Identifier: NCT01848015). Registered 7 May 2013. https://clinicaltrials.gov/ct2/show/NCT01848015.


Assuntos
Células Neoplásicas Circulantes/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos
17.
Br J Cancer ; 114(2): 138-45, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26784122

RESUMO

BACKGROUND: This study was intended to determine the clinical significance of circulating tumour cells (CTCs) in patients with advanced gastric cancer (AGC), particularly the potential role of CTCs for dynamic monitoring of the therapeutic response. METHODS: A single-centre, prospective study was undertaken in 136 patients with newly diagnosed AGC. The patients' CTCs were enumerated using CellSearch at baseline and at the first response evaluation. In 15 patients whose clinical condition permitted longitudinal study, CTCs were longitudinally enumerated during treatment. RESULTS: Following 6 weeks of chemotherapy, an unfavourable post-therapy CTC level (⩾3 CTCs per 7.5 ml) was closely correlated with the objective response rate (P=0.016) and the disease control rate (P=0.013), and it also independently predicted a shorter progression-free survival and overall survival. Particularly, conversion to a favourable CTC level following therapy improved the prognosis, but patients who changed to an unfavourable CTC level fared significantly worse. Elevated CTCs during therapy may be associated with a poor prognosis. CONCLUSIONS: Post-therapy CTC level may help in evaluating therapeutic response in patients with AGC and predicting their prognosis. In addition, changes in CTCs following therapy may be useful in rapidly identifying ineffective treatments and poor prognosis.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Células Neoplásicas Circulantes , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/metabolismo , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina/administração & dosagem , Cisplatino/administração & dosagem , Estudos de Coortes , Junção Esofagogástrica/patologia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/sangue , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Trastuzumab/administração & dosagem , Resultado do Tratamento
18.
Chin J Cancer Res ; 28(6): 579-588, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28174486

RESUMO

OBJECTIVE: Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells (CTCs) correlated with therapeutic efficacy for advanced gastric cancer (AGC) patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients' clinical prognosis. METHODS: The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment (SE) and immunostaining-fluorescence in situ hybridization (iFISH) platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy. RESULTS: CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 mL and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival (PFS) and overall survival (OS). In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS. CONCLUSIONS: Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.

19.
Heliyon ; 10(3): e24111, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38333880

RESUMO

Many countries attract international students to higher education programs to invest in human resources. However, living abroad can be stressful and adversely affect international students' mental and physical health. This study, conducted during the COVID-19 pandemic, investigated stress-related factors affecting the socio-psychological health of Chinese students, the greatest proportion of international students in Korea. The path coefficients and mediating effects of COVID-19-related stress factors were analyzed via a transaction-based stress model for 307 students using partial least squares structural equation modeling. Cultural adaptive stress had the greatest impact on mental health. Perceived financial stress was not statistically significant. Additionally, because the COVID-19 situation in Korea is relatively mild, anxiety regarding the pandemic did not lead to stress. However, excessive COVID-19-related information on social networking services negatively impacted mental health. Understanding the causes of stress and taking preemptive measures to prevent it will result in positive educational and social impacts for both international students and host countries. This study's results have implications for the formulation of international student policies.

20.
mBio ; 15(6): e0044524, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38682948

RESUMO

Histone deacetylation affects Candida albicans (C. albicans) pathogenicity by modulating virulence factor expression and DNA damage. The histone deacetylase Sir2 is associated with C. albicans plasticity and maintains genome stability to help C. albicans adapt to various environmental niches. However, whether Sir2-mediated chromatin modification affects C. albicans virulence is unclear. The purpose of our study was to investigate the effect of Sir2 on C. albicans pathogenicity and regulation. Here, we report that Sir2 is required for C. albicans pathogenicity, as its deletion affects the survival rate, fungal burden in different organs and the extent of tissue damage in a mouse model of disseminated candidiasis. We evaluated the impact of Sir2 on C. albicans virulence factors and revealed that the Sir2 null mutant had an impaired ability to adhere to host cells and was more easily recognized by the innate immune system. Comprehensive analysis revealed that the disruption of C. albicans adhesion was due to a decrease in cell surface hydrophobicity rather than the differential expression of adhesion genes on the cell wall. In addition, Sir2 affects the distribution and exposure of mannan and ß-glucan on the cell wall, indicating that Sir2 plays a role in preventing the immune system from recognizing C. albicans. Interestingly, our results also indicated that Sir2 helps C. albicans maintain metabolic activity under hypoxic conditions, suggesting that Sir2 contributes to C. albicans colonization at hypoxic sites. In conclusion, our findings provide detailed insights into antifungal targets and a useful foundation for the development of antifungal drugs. IMPORTANCE: Candida albicans (C. albicans) is the most common opportunistic fungal pathogen and can cause various superficial infections and even life-threatening systemic infections. To successfully propagate infection, this organism relies on the ability to express virulence-associated factors and escape host immunity. In this study, we demonstrated that the histone deacetylase Sir2 helps C. albicans adhere to host cells and escape host immunity by mediating cell wall remodeling; as a result, C. albicans successfully colonized and invaded the host in vivo. In addition, we found that Sir2 contributes to carbon utilization under hypoxic conditions, suggesting that Sir2 is important for C. albicans survival and the establishment of infection in hypoxic environments. In summary, we investigated the role of Sir2 in regulating C. albicans pathogenicity in detail; these findings provide a potential target for the development of antifungal drugs.


Assuntos
Candida albicans , Candidíase , Parede Celular , Evasão da Resposta Imune , Sirtuína 2 , Candida albicans/genética , Candida albicans/patogenicidade , Candida albicans/imunologia , Parede Celular/metabolismo , Animais , Candidíase/microbiologia , Candidíase/imunologia , Camundongos , Sirtuína 2/metabolismo , Sirtuína 2/genética , Fatores de Virulência/metabolismo , Fatores de Virulência/genética , Virulência , Modelos Animais de Doenças , Deleção de Genes , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Camundongos Endogâmicos BALB C , Feminino
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