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1.
Front Neurosci ; 18: 1429019, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170677

RESUMEN

Objective: The aim of our study was to explore the relationship between changes in neural oscillatory power in the EEG, the severity of depressive-anxiety symptoms, and the risk of suicide in MDD. Methods: 350 MDD patients' demographic and clinical data were collected, and their depressive and anxious symptoms were evaluated using HDRS-17 and HAMA-14, along with a suicide risk assessment using the Nurses' Global Assessment of Suicide Risk (NGASR). EEG data were captured, processed, and analyzed to study brain activity patterns related to MDD. The participants were divided based on suicide risk levels, and statistical analyses, including chi-square, t-tests, Pearson's correlations were used to explore the associations between brain activity, symptom severity, and suicide risk. Closely related variables were identified and ultimately the optimal model was screened using stepwise regression analysis with a forward strategy, and mediation effects were further used to determine the possible interactions between the variables in the regression model. Results: The regression model showed a significant effect of HDRS-17 and alpha power of Medial Occipital Cortex (MOC) on suicide risk, with elevated HDRS-17 increasing suicide risk and elevated alpha power decreasing suicide risk. Mediation effect analyses showed that MOC alpha power partially mediated the effect of depression level on suicide risk, and that an increase in depression severity may lead to a decrease in MOC alpha power, while a decrease in MOC alpha power may lead to an increase in suicide risk. Conclusion: The severity of depression directly increases suicide risk, whereas higher alpha power in the MOC serves as a protective factor, reducing this risk. Notably, MOC alpha power not only directly impacts suicide risk but also mediates the effects of both depression severity and anxiety levels on this risk. Limitations: The relatively small sample size of this study may limit the representativeness of the overall MDD patient population and the detailed analysis of different subgroups. This study did not delve into the relationship between the severity of cognitive symptoms in MDD patients and suicide risk.

2.
Front Neurosci ; 18: 1412591, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055996

RESUMEN

Background: Major depressive disorder (MDD) is the leading cause of disability among all mental illnesses with increasing prevalence. The diagnosis of MDD is susceptible to interference by several factors, which has led to a trend of exploring objective biomarkers. Electroencephalography (EEG) is a non-invasive procedure that is being gradually applied to detect and diagnose MDD through some features such as functional connectivity (FC). Methods: In this research, we analyzed the resting-state EEG of patients with MDD and healthy controls (HCs) in both eyes-open (EO) and eyes-closed (EC) conditions. The phase locking value (PLV) method was utilized to explore the connection and synchronization of neuronal activities spatiotemporally between different brain regions. We compared the PLV between participants with MDD and HCs in five frequency bands (theta, 4-8 Hz; alpha, 8-12 Hz; beta1, 12-16 Hz; beta2, 16-24 Hz; and beta3, 24-40 Hz) and further analyzed the correlation between the PLV of connections with significant differences and the severity of depression (via the scores of 17-item Hamilton Depression Rating Scale, HDRS-17). Results: During the EO period, lower PLVs were found in the right temporal-left midline occipital cortex (RT-LMOC; theta, alpha, beta1, and beta2) and posterior parietal-right temporal cortex (PP-RT; beta1 and beta2) in the MDD group compared with the HC group, while PLVs were higher in the MDD group in LT-LMOC (beta2). During the EC period, for the MDD group, lower theta and beta (beta1, beta2, and beta3) PLVs were found in PP-RT, as well as lower theta, alpha, and beta (beta1, beta2, and beta3) PLVs in RT-LMOC. Additionally, in the left midline frontal cortex-right temporal cortex (LMFC-RT) and posterior parietal cortex-right temporal cortex (PP-RMOC), higher PLVs were observed in beta2. There were no significant correlations between PLVs and HDRS-17 scores when connections with significantly different PLVs (all p > 0.05) were checked. Conclusion: Our study confirmed the presence of differences in FC between patients with MDD and healthy individuals. Lower PLVs in the connection of the right temporal-left occipital cortex were mostly observed, whereas an increase in PLVs was observed in patients with MDD in the connections of the left temporal with occipital lobe (EO), the circuits of the frontal-temporal lobe, and the parietal-occipital lobe. The trends in FC involved in this study were not correlated with the level of depression. Limitations: The study was limited due to the lack of further analysis of confounding factors and follow-up data. Future studies with large-sampled and long-term designs are needed to further explore the distinguishable features of EEG FC in individuals with MDD.

3.
ACS Synth Biol ; 13(6): 1589-1599, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38820348

RESUMEN

Glycosylation is a ubiquitous modification present across all of biology, affecting many things such as physicochemical properties, cellular recognition, subcellular localization, and immunogenicity. Nucleotide sugars are important precursors needed to study glycosylation and produce glycosylated products. Saccharomyces cerevisiae is a potentially powerful platform for producing glycosylated biomolecules, but it lacks nucleotide sugar diversity. Nucleotide sugar metabolism is complex, and understanding how to engineer it will be necessary to both access and study heterologous glycosylations found across biology. This review overviews the potential challenges with engineering nucleotide sugar metabolism in yeast from the salvage pathways that convert free sugars to their associated UDP-sugars to de novo synthesis where nucleotide sugars are interconverted through a complex metabolic network with governing feedback mechanisms. Finally, recent examples of engineering complex glycosylation of small molecules in S. cerevisiae are explored and assessed.


Asunto(s)
Ingeniería Metabólica , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Glicosilación , Ingeniería Metabólica/métodos , Productos Biológicos/metabolismo , Nucleótidos/metabolismo , Redes y Vías Metabólicas
4.
Nature ; 629(8013): 937-944, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38720067

RESUMEN

QS-21 is a potent vaccine adjuvant and remains the only saponin-based adjuvant that has been clinically approved for use in humans1,2. However, owing to the complex structure of QS-21, its availability is limited. Today, the supply depends on laborious extraction from the Chilean soapbark tree or on low-yielding total chemical synthesis3,4. Here we demonstrate the complete biosynthesis of QS-21 and its precursors, as well as structural derivatives, in engineered yeast strains. The successful biosynthesis in yeast requires fine-tuning of the host's native pathway fluxes, as well as the functional and balanced expression of 38 heterologous enzymes. The required biosynthetic pathway spans seven enzyme families-a terpene synthase, P450s, nucleotide sugar synthases, glycosyltransferases, a coenzyme A ligase, acyl transferases and polyketide synthases-from six organisms, and mimics in yeast the subcellular compartmentalization of plants from the endoplasmic reticulum membrane to the cytosol. Finally, by taking advantage of the promiscuity of certain pathway enzymes, we produced structural analogues of QS-21 using this biosynthetic platform. This microbial production scheme will allow for the future establishment of a structure-activity relationship, and will thus enable the rational design of potent vaccine adjuvants.


Asunto(s)
Adyuvantes Inmunológicos , Ingeniería Metabólica , Saccharomyces cerevisiae , Saponinas , Adyuvantes Inmunológicos/biosíntesis , Adyuvantes Inmunológicos/química , Adyuvantes Inmunológicos/genética , Adyuvantes Inmunológicos/metabolismo , Vías Biosintéticas/genética , Diseño de Fármacos , Enzimas/genética , Enzimas/metabolismo , Ingeniería Metabólica/métodos , Plantas/enzimología , Plantas/genética , Plantas/metabolismo , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saponinas/biosíntesis , Saponinas/química , Saponinas/genética , Saponinas/metabolismo , Relación Estructura-Actividad
5.
J Affect Disord ; 355: 254-264, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38561155

RESUMEN

BACKGROUND: The diagnosis of major depressive disorder (MDD) is commonly based on the subjective evaluation by experienced psychiatrists using clinical scales. Hence, it is particularly important to find more objective biomarkers to aid in diagnosis and further treatment. Alpha-band activity (7-13 Hz) is the most prominent component in resting electroencephalogram (EEG), which is also thought to be a potential biomarker. Recent studies have shown the existence of multiple sub-oscillations within the alpha band, with distinct neural underpinnings. However, the specific contribution of these alpha sub-oscillations to the diagnosis and treatment of MDD remains unclear. METHODS: In this study, we recorded the resting-state EEG from MDD and HC populations in both open and closed-eye state conditions. We also assessed cognitive processing using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: We found that the MDD group showed significantly higher power in the high alpha range (10.5-11.5 Hz) and lower power in the low alpha range (7-8.5 Hz) compared to the HC group. Notably, high alpha power in the MDD group is negatively correlated with working memory performance in MCCB, whereas no such correlation was found in the HC group. Furthermore, using five established classification algorithms, we discovered that combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy compared to using EEG or MCCB scores alone. CONCLUSIONS: Our results demonstrate the potential of sub-oscillations within the alpha frequency band as a potential distinct biomarker. When combined with psychological scales, they may provide guidance relevant for the diagnosis and treatment of MDD.


Asunto(s)
Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Consenso , Electroencefalografía , Cognición , Biomarcadores
6.
BMC Pulm Med ; 24(1): 201, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658897

RESUMEN

PURPOSE: To summarize and analyze the safety and efficacy of a Y-shape Sigma stent loaded with I125 in patients with inoperable malignant main airway obstruction. METHODS: This study was approved by the Institutional Ethics Committee, and a written informed consent was obtained from each participant. A Y-shape Sigma stent loaded with I125 was placed under vision from rigid bronchoscopy. The primary endpoint was alleviation of symptoms and improvement of Karnofsky Performance Status (KPS) score, and the secondary endpoint was complications and technical success. RESULTS: From November 2018 through June 2023, total 33 patients with malignant airway obstruction were palliatively treated by installing Y-shape Sigma stents loaded with I125. The airway lumen was immediately restored and the average airway opening significantly increased to 70 ± 9.4% after the procedure from baseline 30.2 ± 10.5% (p < 0.05). Average KPS score was improved from baseline 30.0 ± 10.0 to 70.0 ± 10.0 (p < 0.05) as well as PaO2 from baseline 50.1 ± 15.4 mmHg to 89.3 ± 8.6 mmHg (p < 0.05). The technical success rate of placing the stent in this study was 73%, and adverse events or complications including bleeding, I125 loss, and airway infection occurred during or after the procedure. CONCLUSION: Placement of Y-shape Sigma stents under vision from rigid bronchoscopy in the patients with malignant airway obstruction is feasible and it immediately alleviates dyspnea and significantly improves quality of life.


Asunto(s)
Obstrucción de las Vías Aéreas , Broncoscopía , Radioisótopos de Yodo , Cuidados Paliativos , Stents , Humanos , Broncoscopía/métodos , Obstrucción de las Vías Aéreas/terapia , Masculino , Femenino , Anciano , Persona de Mediana Edad , Cuidados Paliativos/métodos , Neoplasias Pulmonares/complicaciones , Estado de Ejecución de Karnofsky , Anciano de 80 o más Años , Resultado del Tratamiento , Braquiterapia/métodos , Braquiterapia/efectos adversos , Adulto
7.
Clin Neurophysiol ; 161: 147-156, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38484486

RESUMEN

OBJECTIVE: We leveraged microstate characteristics and power features to examine temporal and spectral deviations underlying persistent and remittent attention-deficit/hyperactivity disorder (ADHD). METHODS: 50 young adults with childhood ADHD (28 persisters, 22 remitters) and 28 demographically similar healthy controls (HC) were compared on microstates features and frequency principal components (f-PCs) of eye-closed resting state. Support vector machine model with sequential forward selection (SVM-SFS) was utilized to discriminate three groups. RESULTS: Four microstates and four comparable f-PCs were identified. Compared to HC, ADHD persisters showed prolonged duration in microstate C, elevated power of the delta component (D), and compromised amplitude of the two alpha components (A1 and A2). Remitters showed increased duration and coverage of microstate C, together with decreased activity of D, relatively intact amplitude of A1, and amplitude reduction in A2. The SVM-SFS algorithm achieved an accuracy of 93.59% in classifying persisters, remitters and controls. The most discriminative features selected were those exhibiting group differences. CONCLUSIONS: We found widespread anomalies in ADHD persisters in brain dynamics and intrinsic EEG components. Meanwhile, the neural features in remitters exhibited multiple patterns. SIGNIFICANCE: This study underlines the use of microstate dynamics and spectral components as potential markers of persistent and remittent ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Electroencefalografía , Humanos , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Masculino , Femenino , Adulto Joven , Adulto , Electroencefalografía/métodos , Máquina de Vectores de Soporte , Adolescente
8.
ACS Synth Biol ; 13(4): 1215-1224, 2024 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-38467016

RESUMEN

Glycosylation of biomolecules can greatly alter their physicochemical properties, cellular recognition, subcellular localization, and immunogenicity. Glycosylation reactions rely on the stepwise addition of sugars using nucleotide diphosphate (NDP)-sugars. Making these substrates readily available will greatly accelerate the characterization of new glycosylation reactions, elucidation of their underlying regulation mechanisms, and production of glycosylated molecules. In this work, we engineered Saccharomyces cerevisiae to heterologously express nucleotide sugar synthases to access a wide variety of uridine diphosphate (UDP)-sugars from simple starting materials (i.e., glucose and galactose). Specifically, activated glucose, uridine diphosphate d-glucose (UDP-d-Glc), can be converted to UDP-d-glucuronic acid (UDP-d-GlcA), UDP-d-xylose (UDP-d-Xyl), UDP-d-apiose (UDP-d-Api), UDP-d-fucose (UDP-d-Fuc), UDP-l-rhamnose (UDP-l-Rha), UDP-l-arabinopyranose (UDP-l-Arap), and UDP-l-arabinofuranose (UDP-l-Araf) using the corresponding nucleotide sugar synthases of plant and microbial origins. We also expressed genes encoding the salvage pathway to directly activate free sugars to achieve the biosynthesis of UDP-l-Arap and UDP-l-Araf. We observed strong inhibition of UDP-d-Glc 6-dehydrogenase (UGD) by the downstream product UDP-d-Xyl, which we circumvented using an induction system (Tet-On) to delay the production of UDP-d-Xyl to maintain the upstream UDP-sugar pool. Finally, we performed a time-course study using strains containing the biosynthetic pathways to produce five non-native UDP-sugars to elucidate their time-dependent interconversion and the role of UDP-d-Xyl in regulating UDP-sugar metabolism. These engineered yeast strains are a robust platform to (i) functionally characterize sugar synthases in vivo, (ii) biosynthesize a diverse selection of UDP-sugars, (iii) examine the regulation of intracellular UDP-sugar interconversions, and (iv) produce glycosylated secondary metabolites and proteins.


Asunto(s)
Nucleótidos , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Azúcares , Azúcares de Uridina Difosfato/genética , Azúcares de Uridina Difosfato/metabolismo , Xilosa
9.
Trauma Violence Abuse ; : 15248380241227538, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347760

RESUMEN

Peer victimization during adolescence has a detrimental impact on the mental health of victims throughout their lives. However, it remains unclear whether these effects are gender-specific. The present study conducted a systematic review to examine the effects of peer victimization on depression status, explore potential sources of heterogeneity, and investigate gender differences in these effects. We systematically searched four electronic databases (Web of Science, PubMed, Embase, and CNKI) for relevant articles that published as far as July 2022. We then extracted odds ratios (OR) and 95% confidence intervals (CI) to assess the association between peer victimization during adolescence and depression, and potential gender differences in the relation. Meta-analysis was performed, using fixed effects models and random effects models, to evaluate the association between each exposure and the outcome. A meta-analysis of 27 studies revealed that peer victimization during adolescence was significantly associated with higher risks of depression (OR = 2.79, 95% CI [2.43, 3.21], p < .001). This finding was consistent across subgroup analyses. In particular, the effect of peer victimization during adolescence on depression was found to be more pronounced in studies conducted in Asia (OR = 3.06, 95% CI [2.38, 3.92], p < .001). Furthermore, five studies focused on gender differences demonstrated that peer victimization has a stronger association with the risk of depression in women (OR = 2.84, 95% CI [2.49, 3.26], p < .001). Peer victimization during adolescence is a significant risk factor for depression, with a greater impact on women and individuals residing in Asia. Further prospective studies are needed to investigate the relationship between peer victimization and depression.

10.
Kidney Med ; 6(2): 100773, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38317757

RESUMEN

Rationale & Objective: Intradialytic hypotension (IDH) is associated with mortality in adults with kidney failure requiring hemodialysis (HD); however, large-scale pediatric studies are lacking. Moreover, there is no evidence-based consensus definition of IDH in pediatric literature. We aimed to examine the association of commonly used definitions of IDH with mortality in adolescents and young adults. Study Design: This was a retrospective observational cohort study. Setting & Participants: In total, 1,199 adolescents and young adults (N = 320, aged 10-18 years and N = 879, aged 19-21 years) who initiated HD in a large dialysis organization were included. Exposures: This study used different definitions of IDH. Outcome: The study outcome was 2-year all-cause mortality. Analytical Approach: Several definitions of IDH were selected a priori based on a literature review. Patients were classified as having IDH if it was present in at least 30% of HD treatments during the first 90 days after dialysis initiation. Cox proportional hazards regression was used to test whether IDH associated with 2-year all-cause mortality. Results: Over a 2-year follow-up period, 54 (4.5%) patients died. Dependent on its definition, IDH was present in 2.9%-61.1% of patients. After the multivariable adjustment for sociodemographic and clinical characteristics, we found no association of IDH with mortality. Results were consistent across subgroups stratified by age (aged <18 and 19-21 years) and predialysis systolic blood pressure (<120, 120-150, and >150 mm Hg). We also examined IDH as occurring in <5%, 5%-29%, 30%-50%, and >50% of baseline treatments, and did not find a dose-response association with mortality (P > 0.05). Limitations: Owing to low event rates, our current sample size may have been too small to detect a difference in mortality. Conclusions: Our study found that IDH was not associated with mortality in adolescents and young adults.


Intradialytic hypotension (IDH), or hypotension experienced during dialysis, is common among children and young adults with kidney failure requiring hemodialysis. We examined the association of commonly used definitions of IDH with death in adolescents and young adults with kidney failure receiving hemodialysis. Intradialytic hypotension was present in 2.9%-61.1% of patients, depending on the definition, and over a 2-year follow-up period, 4.5% of the patients died. We found no association of IDH with mortality.

11.
Front Neurosci ; 18: 1362111, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38419668

RESUMEN

Background: Major Depressive Disorder (MDD) is a pervasive mental health issue with significant diagnostic challenges. Electroencephalography (EEG) offers a non-invasive window into the neural dynamics associated with MDD, yet the diagnostic efficacy is contingent upon the appropriate selection of EEG features and brain regions. Methods: In this study, resting-state EEG signals from both eyes-closed and eyes-open conditions were analyzed. We examined band power across various brain regions, assessed the asymmetry of band power between the hemispheres, and integrated these features with clinical characteristics of MDD into a diagnostic regression model. Results: Regression analysis found significant predictors of MDD to be beta2 (16-24 Hz) power in the Prefrontal Cortex (PFC) with eyes open (B = 20.092, p = 0.011), beta3 (24-40 Hz) power in the Medial Occipital Cortex (MOC) (B = -12.050, p < 0.001), and beta2 power in the Right Medial Frontal Cortex (RMFC) with eyes closed (B = 24.227, p < 0.001). Asymmetries in beta1 (12-16 Hz) power with eyes open (B = 28.047, p = 0.018), and in alpha (8-12 Hz, B = 9.004, p = 0.013) and theta (4-8 Hz, B = -13.582, p = 0.008) with eyes closed were also significant predictors. Conclusion: The study confirms the potential of multi-region EEG analysis in improving the diagnostic precision for MDD. By including both neurophysiological and clinical data, we present a more robust approach to understanding and identifying this complex disorder. Limitations: The research is limited by the sample size and the inherent variability in EEG signal interpretation. Future studies with larger cohorts and advanced analytical techniques are warranted to validate and refine these findings.

12.
J Clin Nurs ; 33(3): 1076-1083, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38041239

RESUMEN

AIMS AND OBJECTIVES: The aim of this study was to investigate the relationship between burnout and post-traumatic stress disorder (PTSD) among frontline nurses who went to assist the epidemic situation in Wuhan, China, during the outbreak in 2020. The study also explored the mediating role of depression and the moderating role of age in the main relationship. BACKGROUND: The relationship between burnout and PTSD in nurse has rarely been investigated in the context of the COVID-19 pandemic. Understand the relationship between these variables can provide empirical evidence for developing interventions and protocols that improve the health of nurses in future public health emergencies. DESIGN: An online cross-sectional survey of targeted local 327 nurses who went to assist the COVID-19 epidemic situation in Wuhan during the initial outbreak. METHODS: This study was conducted in August 2020, the burnout scale, the PTSD scale and the depression scale were used to survey participants. The moderated mediation model was used to test research hypotheses. RESULTS: Burnout could affect the PTSD symptoms in nursing staffs and depression could mediate this relationship. Age moderated the relationship between burnout/depression and PTSD, and the effects was strong and significant among younger participants in the relationship between burnout and PTSD. CONCLUSIONS: Burnout was identified as a core risk factor of PTSD in nurses. Depression and age played significant roles in the relationship between burnout and PTSD. RELEVANCE TO CLINICAL PRACTICE: PTSD, as a symptom that manifests after experiencing a stressful event, should be a key concern among frontline healthcare professionals. This study suggests that PTSD in nurses can be further reduced by reducing burnout. Attention should also be paid to the PTSD status of nurses of different age groups. PATIENT OR PUBLIC CONTRIBUTION: Patients and the public were not involved in the design and implementation of this study. Frontline nurses completed an online questionnaire for this study.


Asunto(s)
Agotamiento Profesional , COVID-19 , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/epidemiología , Estudios Transversales , Análisis de Mediación , Pandemias , COVID-19/epidemiología , Agotamiento Psicológico , Agotamiento Profesional/epidemiología
13.
Int Immunopharmacol ; 126: 111321, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38041955

RESUMEN

Vitamin C (VitC) presents excellent anti-tumor effect for long time. Recently, high dose VitC achieved by intravenous administration manifests superior anti-tumor effect. However, the functions and detailed mechanisms of high dose VitC's role in cancer immunity are not fully understood. This study investigates the effect of high dose VitC on PD-L1 expression in triple negative breast cancer (TNBC) and the potential mechanism. Results showed VitC inhibited PD-L1 expression in breast cancer cell lines and enhanced anti-tumor effects of T cells. Furthermore, we found VitC inhibited PD-L1 transcription through ROS-pSTAT3 signal pathways. Consistent with in vitro results, in vivo study showed VitC suppressed tumor growth in immunocompetent mice and enhanced CD8+ T cells infiltration and function in tumor microenvironment. Our findings identify the effects of high dose VitC on PD-L1 expression and provide a rationale for the use of high dose VitC as immunomodulator for cancer therapy.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Antígeno B7-H1/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Antineoplásicos/uso terapéutico , Transducción de Señal , Ácido Ascórbico/uso terapéutico , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Microambiente Tumoral
14.
Genome Biol ; 24(1): 277, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049885

RESUMEN

BACKGROUND: Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking datasets. Herein, we sequence a Chinese Quartet, comprising two monozygotic twin daughters and their biological parents, using four short and long sequencing platforms (Illumina, BGI, PacBio, and Oxford Nanopore Technology). RESULTS: The long reads from the monozygotic twin daughters are phased into paternal and maternal haplotypes using the parent-child genetic map and for each haplotype. We also use long reads to generate haplotype-resolved whole-genome assemblies with completeness and continuity exceeding that of GRCh38. Using this Quartet, we comprehensively catalogue the human variant landscape, generating a dataset of 3,962,453 SNVs, 886,648 indels (< 50 bp), 9726 large deletions (≥ 50 bp), 15,600 large insertions (≥ 50 bp), 40 inversions, 31 complex structural variants, and 68 de novo mutations which are shared between the monozygotic twin daughters. Variants underrepresented in previous benchmarks owing to their complexity-including those located at long repeat regions, complex structural variants, and de novo mutations-are systematically examined in this study. CONCLUSIONS: In summary, this study provides high-quality haplotype-resolved assemblies and a comprehensive set of benchmarking resources for two Chinese monozygotic twin samples which, relative to existing benchmarks, offers expanded genomic coverage and insight into complex variant categories.


Asunto(s)
Benchmarking , Pueblos del Este de Asia , Gemelos Monocigóticos , Humanos , Pueblos del Este de Asia/genética , Genómica , Haplotipos , Secuenciación de Nucleótidos de Alto Rendimiento , Análisis de Secuencia de ADN , Gemelos Monocigóticos/genética , Estudios en Gemelos como Asunto
15.
Am J Cancer Res ; 13(10): 4508-4530, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37970339

RESUMEN

Paget's disease (PD) of the breast is a rare underlying malignant tumor. Approximately 50% to 60% of patients with mammary PD are concurrently diagnosed with invasive ductal carcinoma (PD-IDC), a condition associated with a worse prognosis than IDC without PD. Thus far, there has been a lack of an accurate and efficient prognostic model for PD-IDC, and the factors influencing the effectiveness of chemotherapy and radiotherapy for these patients remain unknown. In this study, we developed a web-based nomogram based on the data from the Surveillance Epidemiology and End Results (SEER) database. We subjected the model to a series of validation methods, including area under the curve (AUC) values, receiver operating characteristic curve (ROC) analysis, calibration curves, and decision curve analysis (DCA). Our results demonstrated that our model exhibited high discrimination, accuracy, and clinical applicability in predicting the overall survival (OS) of patients with PD-IDC (testing set: three- and five-year AUCs, 0.831 and 0.841, respectively). To further validate our nomogram, we used external data from both our institution and sister hospitals (external data: three- and five-year AUCs, 0.892 and 0.914, respectively). Multivariable Cox regression analysis identified several independent unfavorable prognostic factors for the OS of patients with PD-IDC, including increasing age, high grade, widowed status, higher T stages, and the presence of bone metastases. Furthermore, propensity score matching (PSM)-adjusted analysis was conducted, revealing that chemotherapy did not significantly improve the survival of patients with PD-IDC across molecular subtypes, except for those in the grade III/IV group, where it improved both OS and breast cancer-specific survival (BCSS). Additionally, our findings indicated that only patients with PD-IDC with T4 and N3 stages benefited from radiotherapy, leading to improvements in both OS and BCSS. In conclusion, we have comprehensively analyzed the clinical characteristics and prognosis of patients with PD-IDC, culminating in the development of a user-friendly web-based nomogram for predicting their survival. Our predictive model is not only highly accurate but also offers simplicity, making it accessible for healthcare providers and patients. Furthermore, our stratified analysis highlights that the pathological grade, rather than the molecular subtype, plays a pivotal role in determining the efficacy of chemotherapy in improving the prognosis for patients with PD-IDC, while radiotherapy confers survival benefits to patients with PD-IDC in T4 and N3 stages.

16.
Nat Commun ; 14(1): 7569, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37989746

RESUMEN

Micro-light-emitting diode displays are generating considerable interest as a promising technology for augmented-reality glasses. However, the fabrication of highly efficient and ultra-small ( <3 µm) micro-light-emitting diodes, which are required for augmented-reality applications, remains a major technical challenge due to the presence of strong sidewall nonradiative recombination. In this study, we demonstrate a 3.5 × 3.5 µm2 blue GaN micro-light-emitting diode with negligible sidewall nonradiative recombination compared with bulk nonradiative recombination. We achieve this by using an ultralow-damage dry etching technique, known as neutral beam etching, to create the micro-light-emitting diode mesa. Our 3.5 × 3.5 µm2 micro-light-emitting diode exhibits a low decrease in external quantum efficiency of only 26% at a current density of 0.01 A/cm2, compared with the maximum external quantum efficiency that is reached at the current density of ∼3 A/cm2. Our findings represent a significant step towards realizing micro-light-emitting diode displays for augmented-reality glasses.

17.
Crit Rev Biotechnol ; : 1-17, 2023 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-37455417

RESUMEN

Fungi-mediated synthesis of Gold nanoparticles (AuNPs) has advantages in: high efficiency, low energy consumption, no need for extra capping and stabilizing agents, simple operation, and easy isolation and purification. Many fungi have been found to synthesize AuNPs inside cells or outside cells, providing different composition and properties of particles when different fungi species or reaction conditions are used. This is good to produce AuNPs with different properties, but may cause challenges to precisely control the particle shape, size, and activities. Besides, low concentrations of substrate and fungal biomass are needed to synthesize small-size particles, limiting the yield of AuNPs in a large scale. To find clues for the development methods to solve these challenges, the reported mechanisms of the fungi-mediated synthesis of AuNPs were summarized. The mechanisms of intracellular AuNPs synthesis are dependent on gold ions absorption by the fungal cell wall via proteins, polysaccharides, or electric absorption, and the reduction of gold ions via enzymes, proteins, and other cytoplasmic redox mediators in the cytoplasm or cell wall. The extracellular synthesis of AuNPs is mainly due to the metabolites outside fungal cells, including proteins, peptides, enzymes, and phenolic metabolites. These mechanisms cause the great diversity of the produced AuNPs in functional groups, element composition, shapes, sizes, and properties. Many methods have been developed to improve the synthesis efficiency by changing: chloroauric acid concentrations, reaction temperature, pH, fungal mass, and reaction time. However, future studies are still required to precisely control the: shape, size, composition, and properties of fungal AuNPs.

18.
Front Psychiatry ; 14: 1212579, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37484676

RESUMEN

Introduction: This study aims to explore the risk factors associated with suicidal behavior and establish predictive models in female patients with mood disorders, specifically using a nomogram of the least absolute shrinkage and selection operator (LASSO) regression. Methods: A cross-sectional survey was conducted among 396 female individuals diagnosed with mood disorders (F30-F39) according to the International Classification of Diseases and Related Health Problems 10th Revision (ICD-10). The study utilized the Chi-Squared Test, t-test, and the Wilcoxon Rank-Sum Test to assess differences in demographic information and clinical characteristics between the two groups. Logistic LASSO Regression Analyses were utilized to identify the risk factors associated with suicidal behavior. A nomogram was constructed to develop a prediction model. The accuracy of the prediction model was evaluated using a Receiver Operating Characteristic (ROC) curve. Result: The LASSO regression analysis showed that psychotic symptoms at first-episode (ß = 0.27), social dysfunction (ß = 1.82), and somatic disease (ß = 1.03) increased the risk of suicidal behavior. Conversely, BMI (ß = -0.03), age of onset (ß = -0.02), polarity at onset (ß = -1.21), and number of hospitalizations (ß = -0.18) decreased the risk of suicidal behavior. The area under ROC curve (AUC) of the nomogram predicting SB was 0.778 (95%CI: 0.730-0.827, p < 0.001). Conclusion: The nomogram based on demographic and clinical characteristics can predict suicidal behavior risk in Chinese female patients with mood disorders.

19.
ACS Appl Mater Interfaces ; 15(30): 36866-36876, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37486017

RESUMEN

A low-temperature Al2O3 deposition process provides a simplified method to form a conductive two-dimensional electron gas (2DEG) at the metal oxide/Al2O3 heterointerface. However, the impact of key factors of the interface defects and cation interdiffusion on the interface is still not well understood. Furthermore, there is still a blank space in terms of applications that go beyond the understanding of the interface's electrical conductivity. In this work, we carried out a systematic experimental study by oxygen plasma pretreatment and thermal annealing post-treatment to study the impact of interface defects and cation interdiffusion at the In2O3/Al2O3 interface on the electrical conductance, respectively. Combining the trends in electrical conductance with the structural characteristics, we found that building a sharp interface with a high concentration of interface defects provides a reliable approach to producing such a conductive interface. After applying this conductive interface as electrodes for fabricating a field-effect transistor (FET) device, we found that this interface electrode exhibited ultrastability in phosphate-buffered saline (PBS), a commonly used biological saline solution. This study provides new insights into the formation of conductive 2DEGs at metal oxide/Al2O3 interfaces and lays the foundation for further applications as electrodes in bioelectronic devices.

20.
Cancer Sci ; 114(10): 3834-3847, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37489486

RESUMEN

Triple-negative breast cancer (TNBC) is a special pathological type of breast cancer (BC) with poor prognosis. Obesity is shown to be involved in TNBC tumor progression. The interaction between obesity and BC has generated great attention in recent years, however, the mechanism is still unclear. Here, we showed that leptin secreted by adipocytes upregulated PD-L1 expression in TNBC through the p-STAT3 signaling pathway and that baicalein inhibited PD-L1 expression in tumor microenvironment by suppressing leptin transcription of adipocytes. Collectively, our findings suggest that leptin may be the key factor participating in obesity-related tumor progression and that baicalein can break through the dilemma to boost the anti-tumor immune response.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Leptina , Antígeno B7-H1/metabolismo , Adipocitos/patología , Obesidad , Inmunidad , Línea Celular Tumoral , Microambiente Tumoral
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