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1.
Proc Natl Acad Sci U S A ; 120(6): e2216933120, 2023 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-36716361

RESUMEN

Sluggish CO2 reduction reaction (CO2RR) and evolution reaction (CO2ER) kinetics at cathodes seriously hamper the applications of Li-CO2 batteries, which have attracted vast attention as one kind of promising carbon-neutral technology. Two-dimensional transition metal dichalcogenides (TMDs) have shown great potential as the bidirectional catalysts for CO2 redox, but how to achieve a high exposure of dual active sites of TMDs with CO2RR/CO2ER activities remains a challenge. Herein, a bidirectional catalyst that vertically growing MoS2 on Co9S8 supported by carbon paper (V-MoS2/Co9S8@CP) has been designed with abundant edge as active sites for both CO2RR and CO2ER, improves the interfacial conductivity, and modulates the electron transportation pathway along the basal planes. As evidenced by the outstanding energy efficiency of 81.2% and ultra-small voltage gap of 0.68 V at 20 µA cm-2, Li-CO2 batteries with V-MoS2/Co9S8@CP show superior performance compared with horizontally growing MoS2 on Co9S8 (H-MoS2/Co9S8@CP), MoS2@CP, and Co9S8@CP. Density functional theory calculations help reveal the relationship between performance and structure and demonstrate the synergistic effect between MoS2 edge sites and Co9S8. This work provides an avenue to understand and realize rationally designed electronic contact of TMDs with specified crystal facets, but more importantly, provides a feasible guide for the design of high-performance cathodic catalyst materials in Li-CO2 batteries.

2.
J Biol Chem ; : 107556, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39002683

RESUMEN

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin (TK) signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their post-translational modifications were observed in extracts of CNS ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (TKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C-termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

3.
Cereb Cortex ; 34(1)2024 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-38102971

RESUMEN

Individuals inherently seek social consensus when making decisions or judgments. Previous studies have consistently indicated that dissenting group opinions are perceived as social conflict that demands attitude adjustment. However, the neurocognitive processes of attitude adjustment are unclear. In this electrophysiological study, participants were recruited to perform a face attractiveness judgment task. After forming their own judgment of a face, participants were informed of a purported group judgment (either consistent or inconsistent with their judgment), and then, critically, the same face was presented again. The neural responses to the second presented faces were measured. The second presented faces evoked a larger late positive potential after conflict with group opinions than those that did not conflict, suggesting that more motivated attention was allocated to stimulus. Moreover, faces elicited greater midfrontal theta (4-7 Hz) power after conflict with group opinions than after consistency with group opinions, suggesting that cognitive control was initiated to support attitude adjustment. Furthermore, the mixed-effects model revealed that single-trial theta power predicted behavioral change in the Conflict condition, but not in the No-Conflict condition. These findings provide novel insights into the neurocognitive processes underlying attitude adjustment, which is crucial to behavioral change during conformity.


Asunto(s)
Toma de Decisiones , Conformidad Social , Humanos , Conflicto Psicológico , Conducta Social , Juicio/fisiología , Electrofisiología , Electroencefalografía
4.
Gut ; 73(7): 1169-1182, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38395437

RESUMEN

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.


Asunto(s)
Carcinoma Hepatocelular , Virus de la Hepatitis B , Neoplasias Hepáticas , Integración Viral , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/patología , Virus de la Hepatitis B/genética , Humanos , Integración Viral/genética , Animales , Ratones , Masculino , Persona de Mediana Edad , Femenino , Adulto , Secuenciación Completa del Genoma , Variaciones en el Número de Copia de ADN , Anciano
5.
J Am Chem Soc ; 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39031086

RESUMEN

The sluggish CO2 reduction and evolution reaction kinetics are thorny problems for developing high-performance Li-CO2 batteries. For the complicated multiphase reactions and multielectron transfer processes in Li-CO2 batteries, exploring efficient cathode catalysts and understanding the interplay between structure and activity are crucial to couple with these pendent challenges. In this work, we applied the CoS as a model catalyst and adjusted its electronic structure by introducing sulfur vacancies to optimize the d-band and p-band centers, which steer the orbital hybridization and boost the redox kinetics between Li and CO2, thus improving the discharge platform of Li-CO2 batteries and altering the deposition behavior of discharge products. As a result, a highly efficient bidirectional catalyst exhibits an ultrasmall overpotential of 0.62 V and a high energy efficiency of 82.8% and circulates stably for nearly 600 h. Meanwhile, density functional theory calculations and multiphysics simulations further elucidate the mechanism of bidirectional activity. This work not only provides a proof of concept to design a remarkably efficient catalyst but also sheds light on promoting the reversible Li-CO2 reaction by tailoring the electronic structure.

6.
Int J Cancer ; 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38733360

RESUMEN

Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.

7.
Biochem Biophys Res Commun ; 703: 149687, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38368674

RESUMEN

BACKGROUND: ZNF468 is a relatively unexplored gene that has been implicated in potential oncogenic properties in various cancer types. However, the exact role of ZNF468 in radiotherapy resistance of esophageal squamous cell carcinomas (ESCCs) is not well understood. METHODS: Bioinformatic analysis was performed using the TCGA database to assess ZNF468 expression and prognostic significance in pan-cancer and ESCC. Functional experiments were conducted using ZNF468 overexpressing and knockdown cell lines to assess its impact on cell survival, DNA damage response, cell cycle, and apoptosis upon radiation. A luciferase reporter assay was utilized to validate ZNF468 binding to the AURKA promoter. RESULTS: ZNF468 was significantly upregulated in diverse cancer types, including ESCC, and its high expression correlated with adverse prognosis in specific tumors. In the ESCC cohort, ZNF468 exhibited substantial upregulation in post-radiotherapy tissues, indicating its potential role in conferring radiotherapy resistance. Functional experiments revealed that ZNF468 enhances cell viability and facilitates DNA damage repair in radiotherapy-treated ESCC cells, while dampening the G2/M cell cycle arrest and apoptosis induced by radiation. Moreover, ZNF468 facilitated AURKA transcription, resulting in upregulated Aurora A expression, and subsequently inhibited P53 expression, unveiling key molecular mechanisms underlying radiotherapy resistance in ESCC. CONCLUSION: ZNF468 plays an oncogenic role in ESCC and contributes to radiotherapy resistance. It enhances cell survival while dampening radiation-induced G2/M cell cycle arrest and apoptosis. By modulating AURKA and P53 expression, ZNF468 represents a promising therapeutic target for enhancing radiotherapy efficacy in ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Apoptosis/genética , Aurora Quinasa A/genética , Aurora Quinasa A/metabolismo , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/radioterapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Tolerancia a Radiación/genética , Proteína p53 Supresora de Tumor
8.
Opt Express ; 32(3): 2929-2941, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38297529

RESUMEN

Developing from transient absorption (TA) spectroscopy, two-dimensional (2D) spectroscopy with pump-probe geometry has emerged as a versatile approach for alleviating the difficulty in implementing 2D spectroscopy with other geometries. However, the presence of cross-phase modulation (XPM) in TA spectroscopy introduces significant spectral distortions, particularly when the pump and probe pulses overlap. We demonstrate that this phenomenon is extended to the 2D spectroscopy with pump-probe geometry and the XPM is induced by the interference of the two pump pulses. We present the oscillatory behavior of XPM in the 2D spectrum and its displacement with respect to the waiting time delay through both experimental measurements and numerical simulations. Additionally, we explore the influence of probe pulse chirp on XPM and discover that by compressing the chirp, the impact of XPM on the desired signal can be reduced.

9.
Exp Dermatol ; 33(1): e14812, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37086043

RESUMEN

Rosacea is a complex chronic inflammatory skin disorder with high morbidity. Pyroptosis is known as a regulated inflammatory cell death. While its association with immune response to various inflammatory disorders is well established, little is known about its functional relevance of rosacea. So, we aimed to explore and enrich the pathogenesis involved in pyroptosis-related rosacea aggravations. In this study, we evaluated the pyroptosis-related patterns of rosacea by consensus clustering analysis of 45 ferroptosis-related genes (FRGs), with multiple immune cell infiltration analysis to identify the pyroptosis-mediated immune response in rosacea using GSE65914 dataset. The co-co-work between PRGs and WGCNA-revealed hub genes has established using PPI network. FRG signature was highlighted in rosacea using multi-transcriptomic and experiment analysis. Based on this, three distinct pyroptosis-related rosacea patterns (non/moderate/high) were identified, and the notably enriched pathways have revealed through GO, KEGG and GSEA analysis, especially immune-related pathways. Also, the XCell/MCPcount/ssGSEA/Cibersort underlined the immune-related signalling (NK cells, Monocyte, Neutrophil, Th2 cells, Macrophage), whose hub genes were identified through WGCNA (NOD2, MYD88, STAT1, HSPA4, CXCL8). Finally, we established a pyroptosis-immune co-work during the rosacea aggravations. FRGs may affect the progression of rosacea by regulating the immune cell infiltrations. In all, pyroptosis with its mediated immune cell infiltration is a critical factor during the development of rosacea.


Asunto(s)
Piroptosis , Rosácea , Humanos , Piroptosis/genética , Rosácea/genética , Piel , Proteínas Adaptadoras Transductoras de Señales , Perfilación de la Expresión Génica
10.
Exp Dermatol ; 33(6): e15120, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38886965

RESUMEN

Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.


Asunto(s)
Biomarcadores , Senescencia Celular , Biología Computacional , Fibroblastos , Envejecimiento de la Piel , Humanos , Envejecimiento de la Piel/genética , Fibroblastos/metabolismo , Biomarcadores/metabolismo , Aprendizaje Automático , Transcriptoma , Colágeno/metabolismo , Regulación hacia Abajo , Piel/metabolismo , Rayos Ultravioleta , Peróxido de Hidrógeno/metabolismo
11.
Cell Commun Signal ; 22(1): 147, 2024 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388921

RESUMEN

BACKGROUND: Patients with Alzheimer's disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial. METHODS: Four-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated. RESULTS: APP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV+ Ins) and decreased levels of GABA synthesis and transport. We also found impaired NRG1-ErbB4 signaling which mediated by PV+ Ins loss. And NRG1 administration could effectively reduce seizures and improve cognition in four-month-old APP mice. CONCLUSION: Our results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.


Asunto(s)
Enfermedad de Alzheimer , Epilepsia , Humanos , Ratones , Animales , Lactante , Receptor ErbB-4/metabolismo , Enfermedad de Alzheimer/complicaciones , Hipocampo/metabolismo , Ácido gamma-Aminobutírico , Convulsiones , Neurregulina-1/metabolismo
12.
Clin Exp Dermatol ; 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38648509

RESUMEN

BACKGROUND: Elderly-onset seborrheic dermatitis (SD) seriously affects the quality of life. However, associations between air pollution exposures and elderly-onset SD incidence have not been elucidated. OBJECTIVES: Investigate air pollution's role in the incidence of elderly-onset SD. METHODS: We engaged a prospective cohort analysis utilizing the UK Biobank database. Exposure data for specific air pollutants (PM2.5, PM2.5-10, NOX, NO2, and PM10) spanning various years was incorporated. Through a composite air pollution score constructed from five pollutants and employing Cox proportional hazards models, the relationship between pollution and SD was delineated. RESULTS: Our examination of 193,995 participants identified 3,363 SD cases. Higher concentrations of specific pollutants, particularly in the upper quartile (Q4), were significantly linked to an elevated SD risk. Notably, PM2.5, PM10, NO2, and NOX exhibited hazard ratios of 1.11, 1.15, 1.22, and 1.15, respectively. The correlation was further solidified with a positive association between air pollution score increments and SD onset. Intriguingly, this association was accentuated in certain demographics, including younger males, the socioeconomically deprived, smokers, daily alcohol consumers, and those engaging in regular physical activity. CONCLUSIONS: Our findings revealed that air pollution exposures were associated with elderly-onset SD incidence. These results emphasize the importance of preventing environmental exposures to the risk of SD development.

13.
J Transl Med ; 21(1): 57, 2023 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-36717900

RESUMEN

Immunotherapy is a vital treatment for patients with cutaneous melanoma (CM), but effective predictors to guide clinical immunotherapy are lacking. Cuproptosis is a newly discovered mode of cell death related to tumorigenesis. Exploring the relationship between the mode of cuproptosis and the effect of immunotherapy on CM could better guide clinical management. We clustered all patients with CM in the Cancer Genome Atlas (TCGA) database based on cuproptosis-related genes (CRGs). Prognosis, immunotherapeutic effect, tumor microenvironment score, expression of CD274, CTLA4, and PDCD1, and abundance of CD8 + T infiltration in group A were higher than in group B. Using a combination of LASSO and COX regression analysis, we identified 10 molecules significant to prognosis from differentially expressed genes between the two groups and constructed a cuproptosis-related scoring system (CRSS). Compared with the American Joint Committee on Cancer (AJCC) staging system, CRSS more accurately stratified CM patient risk and guided immunotherapy. CRSS successfully stratified risk and predicted the effect of immunotherapy in 869 patients with eight CM immunotherapy datasets and multiple other tumor immunotherapy cohorts. The nomogram model, which combined AJCC stage and CRSS, greatly improved the ability and accuracy of prognosis prediction. In general, our cuproptosis-related scoring system and nomogram model accurately stratified risk in CM patients and effectively predicted prognosis and the effect of immunotherapy in CM patients.


Asunto(s)
Apoptosis , Melanoma , Neoplasias Cutáneas , Humanos , Melanoma/genética , Nomogramas , Pronóstico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Microambiente Tumoral , Cobre , Melanoma Cutáneo Maligno
14.
Hepatology ; 76(2): 330-344, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34897774

RESUMEN

BACKGROUND AND AIMS: Chimeric antigen receptor engineered T cells (CARTs) for HCC and other solid tumors are not as effective as they are for blood cancers. CARTs may lose function inside tumors due to persistent antigen engagement. The aims of this study are to develop low-affinity monoclonal antibodies (mAbs) and low-avidity CARTs for HCC and to test the hypothesis that low-avidity CARTs can resist exhaustion and maintain functions in solid tumors, generating durable antitumor effects. METHODS AND RESULTS: New human glypican-3 (hGPC3) mAbs were developed from immunized mice. We obtained three hGPC3-specific mAbs that stained HCC tumors, but not the adjacent normal liver tissues. One of them, 8F8, bound an epitope close to that of GC33, the frequently used high-affinity mAb, but with approximately 17-fold lower affinity. We then compared the 8F8 CARTs to GC33 CARTs for their in vitro function and in vivo antitumor effects. In vitro, low-avidity 8F8 CARTs killed both hGPC3high and hGPC3low HCC tumor cells to the same extent as high-avidity GC33 CARTs. 8F8 CARTs expanded and persisted to a greater extent than GC33 CARTs, resulting in durable responses against HCC xenografts. Importantly, compared with GC33 CARTs, there were 5-fold more of 8F8-BBz CARTs in the tumor mass for a longer period of time. Remarkably, the tumor-infiltrating 8F8 CARTs were less exhausted and apoptotic, and more functional than GC33 CARTs. CONCLUSION: The low-avidity 8F8-BBz CART resists exhaustion and apoptosis inside tumor lesions, demonstrating a greater therapeutic potential than high-avidity CARTs.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Glipicanos , Humanos , Neoplasias Hepáticas/patología , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Synapse ; 77(3): e22261, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36633502

RESUMEN

Triptolide is an epoxidized diterpene lactone isolated from Tripterygium wilfordii. Studies have shown that triptolide exerts organ-protective effects. However, it remains unknown whether triptolide improves Alzheimer's disease (AD)-like presentations. Thirty healthy 8-week-old male C57BL/6J mice were randomly divided into control (n = 10), model (n = 10), and triptolide (n = 10) groups. Amyloid-ß (Aß)42 was injected bilaterally into the ventricles of mice in the model group. Triptolide was injected intraperitoneally daily after injecting Aß42 (a total of 30 days) in the triptolide group. Learning and memory were tested using the Morris water maze test. The deposition of Aß42 in the hippocampus was detected using immunohistochemical staining. In the hippocampus, three synaptic-associated proteins-gephyrin, collybistin, and GABRA1 -were detected by western blotting. Furthermore, we used ELISA to detect proinflammatory cytokines, including TNF-α and IL-1ß, in the blood and hippocampus. Moreover, superoxide dismutase (SOD), malondialdehyde (MDA), and GSH levels were measured using the corresponding kits. We found that triptolide improved spatial learning and memory in AD-like mice. Additionally, triptolide maintained the expression of gephyrin, collybistin, and GABRA1 and reduced Aß in these mice. Additionally, triptolide reduced the expression of inflammatory cytokines and decreased oxidative damage in AD-like mice. Our study suggests that triptolide attenuates AD-like changes in the mouse brain.


Asunto(s)
Enfermedad de Alzheimer , Diterpenos , Ratones , Masculino , Animales , Enfermedad de Alzheimer/metabolismo , Ratones Endogámicos C57BL , Péptidos beta-Amiloides/metabolismo , Diterpenos/farmacología , Diterpenos/uso terapéutico , Diterpenos/metabolismo , Hipocampo/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad
16.
J Surg Res ; 283: 817-823, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36915008

RESUMEN

INTRODUCTION: Objective measurements for applicant ranking are becoming increasingly important, not only to help address the growing number of general surgery applicants each year but also to minimize bias and ensure consistency. We assessed if our general surgery applicant scoring system was an effective tool for accurately predicting the results of the resident match. METHODS: A retrospective review of applicant rank lists from 2017 to 2020 was conducted. Applicants were ranked based on the sum of preinterview and interview scores. The preinterview score is an objective metric related to the applicant's academic portfolio. The interview score is a standardized score based on interview performance. We reviewed match results from ranked candidates and categorized them as academic categorical (AC), community categorical (CC), preliminary surgical (PS), nonsurgical specialty (NS), or unmatched (UM) positions. RESULTS: A total of 378 applicants were interviewed. Forty-nine percent matched into AC, 22% into CC, 11% into PS, and 5% into NS positions, while 13% of the interviewees were UM. Applicants who matched into AC positions had significantly higher preinterview and interview scores than applicants in other categories. Applicants who matched into CC positions had significantly higher interview scores than those categorized as UM, but their preinterview scores did not differ significantly from the UM group. Applicants who did not match into a categorical position (PS, NS, or UM) did not have significantly different preinterview or interview scores from one another. CONCLUSIONS: Our standardized scoring system was effective in stratifying which applicants would match into categorical general surgery residency programs.


Asunto(s)
Cirugía General , Internado y Residencia , Estudios Retrospectivos , Cirugía General/educación
17.
J Intensive Care Med ; 38(4): 391-398, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36128776

RESUMEN

Background: Extracorporeal membrane oxygenation (ECMO) is widely utilized for severe cardiopulmonary insufficiency, but its application to the oncologic population has been debated given concern for increased risk of infection. This study aims to analyze the implications of infections acquired during ECMO runs in patients with malignancy. Methods: The Extracorporeal Life Support Organization (ELSO) database was queried for patients with an International Classification of Diseases code of neoplasms over the last two decades (2000-2019). Culture-proven infections during ECMO runs were analyzed and compared to previously reported data for all ECMO runs. Results: Two thousand, seven hundred and fifty-seven patients met inclusion criteria. Infection acquired during ECMO run was found in 687 patients, a significantly greater proportion compared to all ECMO runs (24.9% vs 11.7%; P = .001). Adult patients had a significantly higher rate of infection (27.0%; P < .001) compared to neonatal (11.0%) and pediatric (21.4%) patients. Prevalence of infection was highest in pulmonary ECMO (29.0%), while the infection rate standardized with ECMO duration was highest in extracorporeal cardiopulmonary resuscitation (55.03/1000-day ECMO run). Compared with ECMO for all diagnoses, the prevalence of Candida and Klebsiella infection was significantly higher in adult and pediatric oncologic patients. Regardless of the pathogen, the presence of infection was not associated with lower survival (38.6% vs 40.0%; P = .522). Conclusions: Oncologic patients had a significantly higher infection rate while on ECMO compared with the general ECMO population. However, the prognostic impact of these infections was minimal, thus ECMO should not be withheld in oncologic patients solely with concern for infection.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Recién Nacido , Adulto , Humanos , Niño , Estudios Retrospectivos , Oxigenación por Membrana Extracorpórea/efectos adversos , Prevalencia , Pronóstico , Sistema de Registros
18.
Gen Physiol Biophys ; 42(5): 403-415, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37702446

RESUMEN

This study was designed to investigate the correlation of microsatellite status (MS) and Epstein-Barr virus (EBV) infection with the clinical characteristics of gastric cancer (GC) patients. MS was detected by immunohistochemistry. EBV was detected by in situ hybridization. There were 31.3% cases showed mismatch repair-deficient (dMMR)/ microsatellite instability (MSI) and 68.7% cases showed mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). The dMMR/MSI was more common in the elderly, in patients with cardia GC, smaller tumor diameter or non-poorly differentiated carcinoma. The survival in dMMR/MSI patients tended to be longer than that in pMMR/MSS patients. Total 7.6% cases showed EBV-positive (EBV(+)) among 198 GC patients. EBV(+) was more common in patients with advanced GC or poorly differentiated adenocarcinoma. MSI was more common in EBV-negative (EBV(-)) patients than in EBV(+) patients. The dMMR/MSI patients with stage II GC benefited from chemotherapy. The survival of EBV(+) patients tended to be longer than that of EBV(-) patients.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Neoplasias Gástricas , Anciano , Humanos , Neoplasias Gástricas/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Herpesvirus Humano 4/genética , Repeticiones de Microsatélite
19.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(1): 66-69, 2023 Jan 30.
Artículo en Zh | MEDLINE | ID: mdl-36752009

RESUMEN

OBJECTIVE: In order to solve the problem of inadequate CT screening ability in emergency medical rescue in remote mountainous areas, high-altitude areas, other public health events and sudden natural disasters, a vehicle-mounted mobile CT suitable for emergency medical rescue is studied. METHODS: A vehicle chassis system suitable for long-distance transportation and a cabin system suitable for epidemic prevention and control was designed. A domestic 32-slice CT with small volume, light weight and high stability was selected to design a vehicle-mounted mobile CT suitable for emergency medical rescue. RESULTS: The high-performance vehicle-mounted mobile CT can provide rapid support, and provide large-scale screening, emergency medical rescue, a supplement to daily CT scanning in peacetime and wartime. CONCLUSIONS: The vehicle CT has high stability, fast scanning speed and high social and economic value.

20.
BMC Bioinformatics ; 23(1): 549, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36536280

RESUMEN

Extracting knowledge from heterogeneous data sources is fundamental for the construction of structured biomedical knowledge graphs (BKGs), where entities and relations are represented as nodes and edges in the graphs, respectively. Previous biomedical knowledge extraction methods simply considered limited entity types and relations by using a task-specific training set, which is insufficient for large-scale BKGs development and downstream task applications in different scenarios. To alleviate this issue, we propose a joint continual learning biomedical information extraction (JCBIE) network to extract entities and relations from different biomedical information datasets. By empirically studying different joint learning and continual learning strategies, the proposed JCBIE can learn and expand different types of entities and relations from different datasets. JCBIE uses two separated encoders in joint-feature extraction, hence can effectively avoid the feature confusion problem comparing with using one hard-parameter sharing encoder. Specifically, it allows us to adopt entity augmented inputs to establish the interaction between named entity recognition and relation extraction. Finally, a novel evaluation mechanism is proposed for measuring cross-corpus generalization errors, which was ignored by traditional evaluation methods. Our empirical studies show that JCBIE achieves promising performance when continual learning strategy is adopted with multiple corpora.


Asunto(s)
Investigación Biomédica , Minería de Datos , Minería de Datos/métodos , Redes Neurales de la Computación , Conocimiento , Estudios Longitudinales
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