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1.
Genome Med ; 16(1): 52, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566104

RESUMO

BACKGROUND: Prostate cancer is a significant health concern, particularly among African American (AA) men who exhibit higher incidence and mortality compared to European American (EA) men. Understanding the molecular mechanisms underlying these disparities is imperative for enhancing clinical management and achieving better outcomes. METHODS: Employing a multi-omics approach, we analyzed prostate cancer in both AA and EA men. Using Illumina methylation arrays and RNA sequencing, we investigated DNA methylation and gene expression in tumor and non-tumor prostate tissues. Additionally, Boolean analysis was utilized to unravel complex networks contributing to racial disparities in prostate cancer. RESULTS: When comparing tumor and adjacent non-tumor prostate tissues, we found that DNA hypermethylated regions are enriched for PRC2/H3K27me3 pathways and EZH2/SUZ12 cofactors. Olfactory/ribosomal pathways and distinct cofactors, including CTCF and KMT2A, were enriched in DNA hypomethylated regions in prostate tumors from AA men. We identified race-specific inverse associations of DNA methylation with expression of several androgen receptor (AR) associated genes, including the GATA family of transcription factors and TRIM63. This suggests that race-specific dysregulation of the AR signaling pathway exists in prostate cancer. To investigate the effect of AR inhibition on race-specific gene expression changes, we generated in-silico patient-specific prostate cancer Boolean networks. Our simulations revealed prolonged AR inhibition causes significant dysregulation of TGF-ß, IDH1, and cell cycle pathways specifically in AA prostate cancer. We further quantified global gene expression changes, which revealed differential expression of genes related to microtubules, immune function, and TMPRSS2-fusion pathways, specifically in prostate tumors of AA men. Enrichment of these pathways significantly correlated with an altered risk of disease progression in a race-specific manner. CONCLUSIONS: Our study reveals unique signaling networks underlying prostate cancer biology in AA and EA men, offering potential insights for clinical management strategies tailored to specific racial groups. Targeting AR and associated pathways could be particularly beneficial in addressing the disparities observed in prostate cancer outcomes in the context of AA and EA men. Further investigation into these identified pathways may lead to the development of personalized therapeutic approaches to improve outcomes for prostate cancer patients across different racial backgrounds.


Assuntos
Neoplasias da Próstata , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/genética , Metilação de DNA , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Perfilação da Expressão Gênica , DNA/metabolismo
3.
Materials (Basel) ; 17(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38591525

RESUMO

Tb3+-activated LTA zeolite-derived boro-aluminosilicate glass samples with a composition of xTb2O3-68(Na2O-Al2O3-SiO2)-32B2O3 (x = 0.2, 1.0 and 10 extra wt%) were prepared using the melt-quenching method. The emission spectra recorded upon ultraviolet (UV) excitation with two different wavelengths of 193 and 378 nm showed blue light (5D3 to 7FJ=6,5,4 and 5D4 to 7F6 transitions of Tb3+) and green light (5D4 to 7F5 transition of Tb3+) emissions with comparable intensities up to a Tb3+ concentration of 10 extra wt%. Of note, the mean decay times of the green luminescence of the glass samples were relatively fast (<20 µs). The synthesized glass has potential in applications concerning UV imaging, UV detection, and plasma display panels.

4.
Front Psychiatry ; 15: 1336118, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577403

RESUMO

Introduction: While the attention to personality disorders (PD) and childhood maltreatment (CM) has grown in recent years, there remains limited understanding of the prevalence and distinctions of PD and CM in clinical populations of Chinese adolescents in comparison to adults. Methods: A total of 1,417 participants were consecutively sampled from patients diagnosed with either psychotic or non-psychotic disorders in the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. The participants were categorized into two groups based on their age: adolescents (aged 15-21 years) and adults (aged 22-35 years). PDs were evaluated using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were assessed using the Chinese version of the Child Trauma Questionnaire Short Form. Results: When comparing self-reported PD traits and CM between adolescents and adults, differences emerge. Adolescents, particularly in the psychotic disorder group, exhibit more pronounced schizotypal PD traits (p=0.029), and this pattern extends to non-psychotic disorders (p<0.001). Adolescents in the non-psychotic disorder group also report higher levels of emotional abuse (p=0.014), with a notable trend in physical abuse experiences compared to adults (p=0.057). Furthermore, the most prevalent PDs in the clinical sample are avoidant, borderline, and obsessive-compulsive PDs. Among patients with psychotic disorders, adolescents exhibit higher rates of schizoid, schizotypal, and obsessive-compulsive PDs compared to adults. Logistic regression analyses highlight distinct predictors for psychotic and non-psychotic disorders in adolescents and adults. Discussion: The findings emphasize distinct differences in PDs and CMs between adolescent and adult groups, shedding light on their potential roles in psychotic and non-psychotic disorders.

5.
Environ Pollut ; 349: 123966, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38621451

RESUMO

Polybrominated diphenyl ethers (PBDEs) are widely present in water ecosystems where they pose a significant threat to aquatic life, but our knowledge about how PBDEs affect feeding is limited. Therefore, this study explored the effects of continuous dietary exposure to 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) (40 and 4000 ng/g) on the feeding in common carp (Cyprinus carpio) and the underlying mechanism. BDE-47 significantly decreased the food intake of carp. Transcriptome analysis of brain tissue showed that BDE-47 mainly affected the nervous, immune, and endocrine systems. Further examination of the expression levels of appetite factors in the brain revealed that BDE-47 caused dysregulation of appetite factors expressions such as agrp, pomc, cart, etc. In addition, the JAK-STAT signaling pathway was activated under BDE-47 exposure. It can be concluded from these findings that BDE-47 activated the JAK-STAT signaling pathway, causing imbalanced expression of appetite factors, leading to disordered feeding behavior and decreased food intake in carp. These results provide an important reference for a more comprehensive understanding of the hazards posed by BDE-47 on animal feeding and the associated mechanisms.

6.
Water Res ; 255: 121496, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38564898

RESUMO

The evolution of riverine aquatic ecosystems typically exhibits notable characteristic with cumulative, enduring, and hysteresis. Exploring the non-linear response of riverine ecology to long-term hydrological fluctuations become a major challenge in contemporary interdisciplinary research. In response to the critical issue of frequent river algal blooms in the lower Han River, which is impacted by Asian largest inter-basin water diversion project. We identified the non-linear response of eco-hydrology across various time scales through the integration of Continuous Wavelet Transform (CWT) and Inverse Wavelet Transform (IWT). Our study revealed that: 1) Over the past half century, the hydrological regime in the lower Han river showed a significant downward trend, and existed three significant hydrological oscillation periods (HOPs), including the short-scale Intra-AC (180 days), the medium-scale AC (365 days, the first major period), and the long-scale Inter-AC (2500 days), the variation of Inter-AC changed most dramatically. 2) We further found that the Inter-AC variation of hydrology is more closely related to the formation of river algal blooms in the Han River, and when the hydrological Inter-AC shows steady state or downward trend, the frequency of algal blooms in the lower Han River increases significantly. 3) The river algal blooms in the lower Han River is a cumulative consequence to the long-term hydrological influences. Weakened hydrological Inter-AC is more likely to increase the frequency of river algal blooms, and 10-years Inter-AC cumulation increased the frequency by 60%. Therefore, the weaken of long-scale HOP will significantly increase the frequency of river algal blooms in the future. This study received a critical scientific insight and aimed at provide guidance for the optimization of ecological management within the framework of national large-scale water conservation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38657896

RESUMO

OBJECTIVE: Negative symptoms and neurocognitive impairments in psychosis correlate with their severity. Currently, there is no satisfactory treatment. We aimed to evaluate and compare the effects of repetitive transcranial magnetic stimulation(rTMS) on negative symptoms and neurocognitive impairments in patients in first-episode of psychosis(FEP) in a randomized controlled trial(RCT). METHOD: This is a single-site RCT of 85 patients with FEP. Patients were randomized to receive a 4-week course of active(n = 45) or sham rTMS(n = 40). Factor analysis was applied to a cross-sectional dataset of 744 FEP patients who completed negative symptom evaluation and neurocognitive battery tests. Two independent dimensions were generated and used for the K-means cluster analysis to produce sub-clusters. rTMS of 1-Hz was delivered to the right orbitofrontal(OFC) cortex. RESULTS: Two distinct dimensional factors of neurocognitive functions(factor-1) and negative symptoms(factor-2), and three clusters with distinctive features were generated. Significant improvements in factor-1 and factor-2 were observed after 4-weeks of rTMS treatment in both the active and sham rTMS groups. The repeated-measures analysis of variance revealed a significant effect of time×group(F = 5.594, p = 0.021, η2 = 0.073) on factor-2, but no effect of time×group on factor-1. Only improvements in negative symptoms were significantly different between the active and sham rTMS groups(p = 0.028). Patients in cluster-3 characterized by extensive negative symptoms, showed greater improvement in the active rTMS group than in the sham rTMS group. CONCLUSIONS: The 1-Hz right OFC cortex rTMS is more effective in reducing negative symptoms than neurocognitive impairments. It is especially effective in patients with dominantly negative symptoms in FEP.

8.
PLoS One ; 19(3): e0299945, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547197

RESUMO

To reduce financial pressure and operational risk, and improve match between supply and demand, an increasing number of enterprises are adopting presales to launch new products. In this context, this paper investigates three presale models for innovative products, namely, the no-presale model, the manufacturer presale model and the retailer presale model. A Hotelling model is used to describe the impact of channel preferences and valuation differences on the two-stage competition between innovative products. Aiming at evaluating the purchase behavior of consumers under three presale modes, a game optimization model is established to analyze the presale decision problem for innovative products under different presale entities. The research shows that: (1) Compared with no-presale, presales can help enterprises obtain more profits. The overall profit of the supply chain is optimal under the retailer presale mode. (2) When the difference in channel preferences is small, the manufacturer obtains the greatest profit by choosing the direct presale model. In contrast, the selection of different presale entities has a significant impact on product sales and supply chain enterprise profits. At this point, the manufacturer should choose the retailer presale model. (3) When the product valuation discount is high, the manufacturer can increase the spot and wholesale prices to induce consumers to choose the presale method to purchase the product. In the opposite situation, the manufacturer should lower the presale price to improve the presale utility of consumers and encourage them to participate in the presale. These conclusions provide more targeted suggestions for enterprises to formulate presale strategies, which can help them grasp market demand and improve market competitiveness.


Assuntos
Comércio , Comportamento do Consumidor , Custos e Análise de Custo
9.
Int J Biol Macromol ; 264(Pt 2): 130702, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38471607

RESUMO

Pretreatment is a key process restricting the development of biorefinery. This work developed a pretreatment process based on an ethanolamine/acetamide alkaline deep eutectic solvent (ADES). Under microwave assistance, pure ADES pretreatment at 100 °C for 10 min achieved 95.9 % delignification and 95.2 % hemicellulose removal of bamboo shoot shells (BSS). Further, when 75 % water was added to pure DES to prepare hydrated DES (75 %-HADES), impressive delignification (93.2 %), hemicellulose removal (92.2 %) and cellulose recovery (94.8 %) were still achieved. The cellulose digestibility of the 75 %-HADES pretreated solid residue was significantly increased from 12.2 % (the control) to 91.2 %. Meanwhile, the structural features of hemicellulose and lignin macromolecules fractionated by 75 %-HADES pretreatment were well preserved, offering opportunities for downstream utilization. Overall, this work proposes an effective pretreatment strategy with the potential to enable the utilization of all major components of bamboo shoot shells.


Assuntos
Celulose , Solventes Eutéticos Profundos , Solventes/química , Biomassa , Hidrólise , Lignina/química
10.
Inflammation ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436811

RESUMO

Diabetic retinopathy (DR) is a diabetes-associated complication that poses a threat to vision, distinguished by persistent and mild inflammation of the retinal microvasculature. The activation of microglia plays a crucial role in driving this pathological progression. Previous investigations have demonstrated that ubiquitin-specific peptidase 25 (USP25), a deubiquitinating enzyme, is involved in the regulation of immune cell activity. Nevertheless, the precise mechanisms through which USP25 contributes to the development of DR remain incompletely elucidated. Firstly, we have demonstrated the potential mechanism by which ROCKs can facilitate microglial activation and augment the synthesis of inflammatory mediators through the modulation of NF-κB signaling pathways in a high-glucose milieu. Furthermore, our study has provided novel insights by demonstrating that the regulatory role of USP25 in the secretion of proinflammatory factors is mediated through the involvement of ROCK in modulating the expression of NF-κB and facilitating the nuclear translocation of the phosphatase NF-κB. This regulatory mechanism plays a crucial role in modulating the activation of microglial cells within a high-glycemic environment. Hence, USP25 emerges as a pivotal determinant for the inflammatory activation of microglial cells, and its inhibition exhibits a dual effect of promoting retinal neuron survival while suppressing the inflammatory response in the retina. In conclusion, the promotion of diabetic retinopathy (DR) progression by USP25 is attributed to its facilitation of microglial activation induced by high glucose levels, a process mediated by the ROCK pathway. These findings highlight the importance of considering USP25 as a potential therapeutic target for the management of diabetic neuroinflammation.

11.
Anal Methods ; 16(14): 2051-2062, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38505936

RESUMO

A sensitive and recyclable substrate was fabricated through in situ reduction of silver nanoparticles (NPs) on zinc oxide nanorods (NRs). The prepared silver nanoparticles/zinc oxide nanorods/polyamide mesh (Ag/ZnO/PM) substrate exhibited not only excellent surface-enhanced Raman scattering (SERS) performance to R6G with a limit of detection (LOD) of 10-12 M, mainly attributed to the synergistic effect of the suitable size and the nanoscale gaps of the Ag NPs to produce local surface plasmon resonance (LSPR), but also outstanding self-cleaning property via UV irradiation due to its significant photocatalytic property based on the non-equilibrium carriers generated by ZnO and the presence of Schottky junctions between Ag and ZnO. The substrate showed good recycling stability even after five cycles. Furthermore, the successful recyclable application of Ag/ZnO/PM for tetracycline hydrochloride (TC) detection with high sensitivity further suggested that it is a promising candidate for constructing a portable SERS platform to detect organic pollutants.

12.
BMC Complement Med Ther ; 24(1): 114, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454410

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose-effect relationship of acupuncture. METHODS/DESIGN: This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. DISCUSSION: This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.


Assuntos
Terapia por Acupuntura , Doença Pulmonar Obstrutiva Crônica , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Acta Biochim Biophys Sin (Shanghai) ; 56(4): 645-656, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38529553

RESUMO

Spontaneous subarachnoid hemorrhage (SAH) is a kind of hemorrhagic stroke which causes neurological deficits in survivors. Huperzine A has a neuroprotective effect, but its role in SAH is unclear. Therefore, we explore the effect of Huperzine A on neurological deficits induced by SAH and the related mechanism. In this study, Evans blue assay, TUNEL staining, immunofluorescence, western blot analysis, and ELISA are conducted. We find that Huperzine A can improve neurological deficits and inhibit the apoptosis of nerve cells in SAH rats. Huperzine A treatment can improve the upregulation of brain water content, damage of blood-brain barrier, fibrinogen and matrix metalloprotein 9 expressions and the downregulation of ZO-1 and occludin expressions induced by SAH. Huperzine A inhibit the expressions of proteins involved in pyroptosis in endothelial cells in SAH rats. The increase in MDA content and decrease in SOD activity in SAH rats can be partly reversed by Huperzine A. The ROS inducer H 2O 2 can induce pyroptosis and inhibit the expressions of ZO-1 and occludin in endothelial cells, which can be blocked by Huperzine A. In addition, the increase in the entry of p65 into the nucleus in endothelial cells can be partly reversed by Huperzine A. Huperzine A may delay the damage of blood-brain barrier in SAH rats by inhibiting oxidative stress-mediated pyroptosis and tight junction protein expression downregulation through the NF-κB pathway. Overall, Huperzine A may have clinical value for treating SAH.


Assuntos
Alcaloides , Fármacos Neuroprotetores , Sesquiterpenos , Hemorragia Subaracnóidea , Ratos , Animais , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Ratos Sprague-Dawley , Piroptose , Ocludina , Células Endoteliais/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
14.
Risk Manag Healthc Policy ; 17: 435-453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449512

RESUMO

Background: Despite great achievements in clinical medicine, the in-hospital mortality of older patients remains high. How to reduce the in-hospital mortality of older inpatients is of great clinical value in clinical practice. This study is to analyze the leading causes of in-hospital death of older inpatients of different ages in Shanghai. Methods: An observational study was conducted in Shanghai. A total of 3894 older inpatients (≥60 years old) were investigated. According to the age stratification standard of World Health Organization, they were divided into young older patients group (aged 60 to 74), old older patients group (aged 75 to 89) and very old patients group (aged ≥90). Diseases of in-hospital death of older inpatients in different age groups were classified according to the 10th edition of the International Classification of Diseases. Constituent ratio of causes of in-hospital death in each group was analyzed. Results: The constituent ratio of pulmonary infection had the highest rate of in-hospital death in older patients. The constituent ratio of lung malignant tumors had the highest rate of in-hospital death in young older patients. The constituent ratio of pulmonary infection had the highest rate of in-hospital death in old older patients. The constituent ratio of pulmonary infection had the highest rate of in-hospital death in very old patients. Conclusion: The leading cause of in-hospital death of young older patients group was lung malignant tumor. The leading cause of in-hospital death of old older patients group and very older patients group was pulmonary infection. Great importance should be attached to the prevention of lung tumor and lung infection in the elderly. Results of this study will provide a basis for health administrative departments to formulate corresponding health-care policies for older patients.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38470538

RESUMO

OBJECTIVE: Indicators of heart rate variability (HRV) have been used to assess the autonomic activity. However, the influence of obesity on HRV in these patients remains to be determined. This study aimed to examine how obesity (measured with the body mass index [BMI]) affects HRV and determine whether the effect varies among different psychiatric disorders. We recruited 3159 consecutive patients, including 1744 with schizophrenia, 966 with mood disorders, and 449 with anxiety disorders. Patients were divided into four groups based on BMI: underweight (< 18.5), normal weight (18.5-23.9), overweight (24-27.9), and obese (≥ 28). The cardiovascular status was assessed using several time- and frequency-based HRV indicators, measured via electrocardiogram signals recorded for 5 min. The mean BMI of the participants was 23.6 ± 4.0. The patients in the overweight and obese groups were 29.4% and 13.6% of the total, respectively. The HRV indicators were higher in underweight and normal-weight patients than in the overweight and obese ones. After stratification based on the psychiatric diagnosis, the patients with mood disorders showed lower HRV than those with schizophrenia or anxiety disorder in the normal-weight group. In contrast, in the overweight and obese groups the patients with mood disorders showed higher HRV than those with the other disorders. The HRV variables were significantly associated with BMI, and higher BMI was associated with higher heart rates and lower HRV. These results indicate that weight gain in psychiatric disorders is associated with an imbalance in autonomic nerve activity. However, the relationship between autonomic activity, weight gain, and psychiatric disorders warrants further investigation.

16.
Materials (Basel) ; 17(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473558

RESUMO

The microstructures and mechanical properties of a γ'-strengthened nickel-based superalloy, GH4099, produced by laser powder bed fusion, at room temperature and 900 °C are investigated, followed by three various heat treatments. The as-built (AB) alloy consists of cellular/dendrite substructures within columnar grains aligning in <100> crystal orientation. No γ' phase is observed in the AB sample due to the relatively low content of Al +Ti. Following the standard solid solution treatment, the molten pool boundaries and cellular/dendrite substructures disappear, whilst the columnar grains remain. The transformation of columnar grains to equiaxed grains occurs through the primary solid solution treatment due to the recovery and recrystallization process. After aging at 850 °C for 480 min, the carbides in the three samples distributed at grain boundaries and within grains and the spherical γ' phase whose size is about 43 nm ± 16 nm develop in the standard solid solution + aging and primary solid solution + aging samples (SA and PA samples) while the bimodal size of cubic (181 nm ± 85 nm) and spherical (43 nm ± 16 nm) γ' precipitates is presented in the primary solid solution + secondary solid solution + aging sample (PSA samples). The uniaxial tensile tests are carried out at room temperature (RT) and 900 °C. The AB sample has the best RT ductility (~51% of elongation and ~67% of area reduction). Following the three heat treatments, the samples all acquire excellent RT tensile properties (>750 MPa of yield strengths and >32% of elongations). However, clear ductility dips and intergranular fracture modes occur during the 900 °C tensile tests, which could be related to carbide distribution and a change in the deformation mechanism.

17.
J Natl Cancer Inst ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466935

RESUMO

BACKGROUND: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, which lead to high microsatellite instability (MSI-H) and frameshift mutations (FSMs) at coding mononucleotide repeats (cMNRs) in the genome. Recurrent FSMs in these regions are thought to play a central role in the increased risk of various cancers. However, there are no biomarkers currently available for the surveillance of MSI-H-associated cancers. METHODS: An FSM-based biomarker panel was developed and validated by targeted next generation sequencing of supernatant DNA from cultured MSI-H colorectal cancer cells. This supported selection of 122-FSM targets as potential biomarkers. This biomarker panel was then tested using matched tumor, adjacent normal tissue, and buffy coat (53 samples), and blood-derived cell-free DNA (cfDNA; 38 samples) obtained from 45 cases of MSI-H/MMR deficient (MMRd) patients/carriers. cfDNA from 84 healthy individuals was also sequenced to assess background noise. RESULTS: Recurrent FSMs at cMNRs were detectable not only in tumors, but also in cfDNA from MSI-H/MMRd cases including a LS carrier with a varying range of target detection (up to 85.2%), whereas they were virtually undetectable in healthy individuals. ROC analysis showed high sensitivity and specificity (AUC = 0.94) of the investigated panel. CONCLUSIONS: We demonstrated that FSMs can be detected in cfDNA from MSI-H/MMRd cases and asymptomatic carriers. The 122-target FSM panel described here has promise as a tool for improved surveillance of MSI-H/MMRd carriers with the potential to reduce the frequency of invasive screening methods for this high-cancer-risk cohort.

18.
Org Lett ; 26(8): 1550-1555, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38364868

RESUMO

We report a three-component Nozaki-Hiyama-Kishi type reaction of 1,3-dioxolane, 1,3-butadienes, and aldehydes to access masked aldehyde-incorporated homoallylic alcohols, facilitated by photo-hydrogen atom transfer (HAT)/chromium dual catalysis. The diaryl ketone serves dual roles both in the HAT process and in facilitating the turnover of the chromium catalyst. A range of functional groups are tolerated owing to the mild conditions. Both aromatic and aliphatic aldehydes are suitable substrates for coupling with several 1,3-butadienes and 1,3-dioxolane.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38386573

RESUMO

Dynamic functional connectivity (FC) analyses have provided ample information on the disturbances of global functional brain organization in patients with schizophrenia. However, our understanding about the dynamics of local FC in never-treated first episode schizophrenia (FES) patients is still rudimentary. Dynamic Regional Phase Synchrony (DRePS), a newly developed dynamic local FC analysis method that could quantify the instantaneous phase synchronization in local spatial scale, overcomes the limitations of commonly used sliding-window methods. The current study performed a comprehensive examination on both the static and dynamic local FC alterations in FES patients (N = 74) from healthy controls (HCs, N = 41) with resting-state functional magnetic resonance imaging using DRePS, and compared the static local FC metrics derived from DRePS with those calculated from two commonly used regional homogeneity (ReHo) analysis methods that are defined based on Kendall's coefficient of concordance (KCC-ReHo) and frequency coherence (Cohe-ReHo). Symptom severities of FES patients were assessed with a set of clinical scales. Cognitive functions of FES patients and HCs were assessed with the MATRICS consensus cognitive battery. Group-level analysis revealed that compared with HCs, FES patients exhibited increased static local FC in right superior, middle temporal gyri, hippocampus, parahippocampal gyrus, putamen, and bilateral caudate nucleus. Nonetheless, the dynamic local FC metrics did not show any significant differences between the two groups. The associations between all local FC metrics and clinical characteristics manifested scores were explored using a relevance vector machine. Results showed that the Global Assessment of Functioning score highest in past year and the Brief Visuospatial Memory Test-Revised task score were statistically significantly predicted by a combination of all static and dynamic features. The diagnostic abilities of different local FC metrics and their combinations were compared by the classification performance of linear support vector machine classifiers. Results showed that the inclusion of zero crossing ratio of DRePS, one of the dynamic local FC metrics, alongside static local FC metrics improved the classification accuracy compared to using static metrics alone. These results enrich our understanding of the neurocognitive mechanisms underlying schizophrenia, and demonstrate the potential of developing diagnostic biomarker for schizophrenia based on DRePS.


Assuntos
Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Benchmarking , Encéfalo/diagnóstico por imagem , Cognição
20.
Nanoscale Adv ; 6(4): 1135-1144, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38356627

RESUMO

High-purity, monodisperse, and low-oxygen submicron copper powder particles with particle sizes in the range of 100-600 nm were synthesized under alkaline conditions using ascorbic acid (C6H8O6) as a reductant and copper chloride (CuCl2·2H2O) as a copper source. The redox potential of the Cu-Cl-H2O system was obtained by calculations and plotted on pH-E diagrams, and a one-step secondary reduction process (Cu(ii) → CuCl(i) → Cu2O(i) → Cu(0)) was proposed to slow down the reaction rate. The commonalities and differences in the nucleation and growth process of copper powders under methionine (Met), hexadecyl trimethyl ammonium bromide (CTAB), and sodium citrate dihydrate (SSC) as protectants and without the addition of protectants are compared, and the reaction mechanism is discussed. Among them, methionine (Met) showed excellent properties and the Cu2O(i) → Cu(0) process was further observed by in situ XRD. The synthesized copper powder particles have higher particle size controllability, dispersibility, antioxidant properties, and stability, and can be decomposed at lower temperatures (<280 °C). The resistivity can reach 21.4 µΩ cm when sintered at a temperature of 325 °C for 30 min. This green and simple synthesis process facilitates industrialization and storage, and the performance meets the requirements of electronic pastes.

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