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1.
Angew Chem Int Ed Engl ; : e202413769, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313757

RESUMEN

Growing interest in p-block metal single-atom catalysts (PM-SACs) is driven by their low toxicity, economic viability, and transition metal-like catalytic properties. However, selection criteria for p-block single-atom species and catalytic mechanisms of PM-SACs remain unclear. This study explores the catalytic abilities of PM-SACs and their transition metal counterparts (TM-SACs) based on polymetric carbon nitride (PCN) for photocatalytic hydrogen peroxide (H2O2) production. Using thermodynamic barriers as a key descriptor, it was found that PM-SACs can surpass TM-SACs in H2O2 production due to a lower energy barrier for *OOH intermediate formation resulting from optimized p-p hybridization. Specifically, Sb-SAC based on PCN shows the highest apparent quantum yield of 35.3% at 400 nm. This study offers a rationale for the utilization of p-block SACs in the context of sustainable chemical synthesis.

2.
bioRxiv ; 2024 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-39229158

RESUMEN

A fundamental challenge in biomedicine is understanding the mechanisms predisposing individuals to disease. While previous research has suggested that switch-like gene expression is crucial in driving biological variation and disease susceptibility, a systematic analysis across multiple tissues is still lacking. By analyzing transcriptomes from 943 individuals across 27 tissues, we identified 1,013 switch-like genes. We found that only 31 (3.1%) of these genes exhibit switch-like behavior across all tissues. These universally switch-like genes appear to be genetically driven, with large exonic genomic structural variants explaining five (~18%) of them. The remaining switch-like genes exhibit tissue-specific expression patterns. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, likely under the influence of tissue-specific master regulators, including hormonal signals. Among our most significant findings, we identified hundreds of concordantly switched-off genes in the stomach and vagina that are linked to gastric cancer (41-fold, p<10-4) and vaginal atrophy (44-fold, p<10-4), respectively. Experimental analysis of vaginal tissues revealed that low systemic levels of estrogen lead to a significant reduction in both the epithelial thickness and the expression of the switch-like gene ALOX12. We propose a model wherein the switching off of driver genes in basal and parabasal epithelium suppresses cell proliferation therein, leading to epithelial thinning and, therefore, vaginal atrophy. Our findings underscore the significant biomedical implications of switch-like gene expression and lay the groundwork for potential diagnostic and therapeutic applications.

3.
PLoS One ; 19(9): e0308943, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39231188

RESUMEN

Complex steerable pyramid (CSP) performs well when applied to magnify subtle motions of structures for observing the dynamic characteristics of facilities. However, the impact of the types and parameters of CSP filters upon the performance of phase-based optical flow (PBOF) in measuring motion parameters has not been systematically studied. The purpose of this study is to comprehensively evaluate the impact of different CSP filter types (Octave, HalfOctave, SmoothHalfOctave, and QuarterOctave) and parameters on the performance of PBOF in measuring motion parameters. Firstly, by measuring simulated translational motion, the influence of the CSP's down-sampling rates on the displacement measurement accuracy of PBOF is analyzed to determine appropriate settings. Subsequently, the effective displacement measurement interval and accuracy of PBOF using the CSP are studied through simulated and experimental translational motion measurements. Further, the vibration parameter's accuracy is analyzed through simulated periodic vibration measurements. Finally, the characteristics of PBOF using the four kinds of CSP and practical considerations are discussed. Simulation and experimental results demonstrate that when using middle-level filters within the effective level range of HalfOctave, PBOF achieves the best overall displacement measurement performance. Additionally, this method can easily integrate with signal processing techniques in analyzing structural dynamic characteristics under field conditions.


Asunto(s)
Flujo Optico , Movimiento (Física) , Simulación por Computador , Vibración
4.
Res Sq ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39315271

RESUMEN

A fundamental challenge in biomedicine is understanding the mechanisms predisposing individuals to disease. While previous research has suggested that switch-like gene expression is crucial in driving biological variation and disease susceptibility, a systematic analysis across multiple tissues is still lacking. By analyzing transcriptomes from 943 individuals across 27 tissues, we identified 1,013 switch-like genes. We found that only 31 (3.1%) of these genes exhibit switch-like behavior across all tissues. These universally switch-like genes appear to be genetically driven, with large exonic genomic structural variants explaining five (~18%) of them. The remaining switch-like genes exhibit tissue-specific expression patterns. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, likely under the influence of tissue-specific master regulators, including hormonal signals. Among our most significant findings, we identified hundreds of concordantly switched-off genes in the stomach and vagina that are linked to gastric cancer (41-fold, p<10-4) and vaginal atrophy (44-fold, p<10-4), respectively. Experimental analysis of vaginal tissues revealed that low systemic levels of estrogen lead to a significant reduction in both the epithelial thickness and the expression of the switch-like gene ALOX12. We propose a model wherein the switching off of driver genes in basal and parabasal epithelium suppresses cell proliferation therein, leading to epithelial thinning and, therefore, vaginal atrophy. Our findings underscore the significant biomedical implications of switch-like gene expression and lay the groundwork for potential diagnostic and therapeutic applications.

5.
Sci Rep ; 14(1): 15482, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969688

RESUMEN

With the progression of many shale gas wells in the Sichuan-Chongqing region of China into the middle and late stages of exploitation, the problem of sand production in these wells is a primary factor influencing production. Failure to implement measures to remove sand from the gas wells will lead to a sharp decline in production after a certain period of exploitation. Moreover, As the amount of sand produced in the well increases, the production layer will be potentially buried by sand. To boost the production of shale gas wells in the Sichuan-Chongqing region and improve production efficiency, a novel downhole jet sand-washing device has been developed. Upon analyzing the device's overall structure, it is revealed that the device adopts a structural design integrating a jet pump with an efficient sand- washing nozzle, providing dual capabilities for jet sand- washing and sand conveying via negative pressure. To enhance the sand- washing and unblocking performance of the device, various sand- washing fluids and the structures of different sand- washing nozzles are compared for selection, aiming to elevate the device's sand- washing and unblocking performance from a macro perspective. Subsequently, drawing on simulation and internal flow field analysis of the device's sand- washing and unblocking process through CFD and the control variable method, it is ultimately found that the length diameter ratio of the cylindrical segment of the nozzle outlet, the outlet diameter, and the contraction angle of the nozzle greatly influence the device's sand- washing and unblocking performance. And the optimum ranges for the length-diameter ratio of the cylindrical segment of the nozzle outlet, the outlet diameter, the contraction angle of the nozzle, and the inlet diameter are 2 to 4, 6 mm to 10 mm, 12° to 16°, and 18 mm and 22 mm, respectively. The findings of the research not only provide new insights into existing sand removal processes but also offer a novel structure for current downhole sand removal devices and a specific range for the optimal size of the nozzle.

6.
World J Clin Cases ; 12(20): 4365-4371, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39015900

RESUMEN

BACKGROUND: Anti-contactin-associated protein-like 2 (CASPR2) antibody encephalitis is an autoimmune disorder characterized by the presence of antibodies against the voltage-gated potassium channel. This leads to neurological symptoms, such as seizures, cognitive decline, and neuropathic pain, primarily affecting the limbic system. The prognosis of this disorder varies among individuals. CASE SUMMARY: The patient, a girl aged nine years and nine months, underwent treatment for 14 to 21 d. The main clinical manifestations were vomiting and unclear consciousness, positive pathological signs, normal cranial computed tomography and magnetic resonance imaging, and abnormal electroencephalogram. The child was discharged after receiving immunoglobulin and hormone treatment. Subsequent follow-up over a period of 15 months after discharge, conducted through telephone and outpatient visits, showed no recurrence of symptoms. CONCLUSION: Anti-CASPR2 antibody autoimmune encephalitis in children is rare, mainly manifested as convulsions, mental abnormalities, cognitive impairment, and neuropathic pain, among others. Timely evaluation for autoimmune encephalitis antibodies is crucial, especially in cases of recurrent central nervous system involvement in children.

7.
Vaccine ; 42(25): 126052, 2024 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38906762

RESUMEN

African swine fever (ASF) is a contagious and fatal disease caused by the African swine fever virus (ASFV), which can infect pigs of all breeds and ages. Most infected pigs have poor prognosis, leading to substantial economic losses for the global pig industry. Therefore, it is imperative to develop a safe and efficient commercial vaccine against ASF. The development of ASF vaccine can be traced back to 1960. However, because of its large genome, numerous encoded proteins, and complex virus particle structure, currently, no effective commercial vaccine is available. Several strategies have been applied in vaccine design, some of which are potential candidates for vaccine development. This review provides a comprehensive analysis on the safety and effectiveness, suboptimal immunization effects at high doses, absence of standardized evaluation criteria, notable variations among strains of the same genotype, and the substantial impact of animal health on the protective efficacy against viral challenge. All the information will be helpful to the ASF vaccine development.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Vacunas Atenuadas , Vacunas Virales , Animales , Fiebre Porcina Africana/prevención & control , Fiebre Porcina Africana/inmunología , Vacunas Atenuadas/inmunología , Porcinos , Virus de la Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/genética , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Desarrollo de Vacunas
8.
J Virol Methods ; 329: 114971, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38876255

RESUMEN

Peste des petis ruminants (PPR) is an acute, highly contagious fatal disease affecting both domestic and wild small ruminants, caused by Morbillivirus caprinae (also known as peste des petis ruminants virus (PPRV)). Herein, a rapid method based on recombinase aided amplification-clustered regularly interspaced short palindromic repeats-Cas12a (RAA-CRISPR Cas12a) to detect PPRV was developed. CRISPR RNAs and RAA primers for PPRV-N (nucleocapsid) and PPRV-M (matrix) fragments were designed. The reaction system was constructed following screening and optimization. Detection could be completed within in 50 minutes at 37°C. Detection of gradient dilutions of plasmids carrying of PPRV N and M gene fragments indicated a minimum limit of detection of 10 copies/µL. There were no cross-reactions with related viruses and all tested lineages of PPRV were detected successfully. The method also showed good repeatability. The detection of clinical samples (previously detected using reverse transcription polymerase chain reaction (RT-PCR)) indicated good consistency between the RAA-CRISPR Cas12a method and RT-PCR. Thus, the RAA-CRISPR Cas12a method for rapid PPRV diagnosis has strong specificity, high sensitivity, and stable repeatability. Moreover, the results can be observed visually under blue or UV light or using lateral flow strips without complex instruments.


Asunto(s)
Sistemas CRISPR-Cas , Cabras , Peste de los Pequeños Rumiantes , Virus de la Peste de los Pequeños Rumiantes , Sensibilidad y Especificidad , Virus de la Peste de los Pequeños Rumiantes/genética , Virus de la Peste de los Pequeños Rumiantes/aislamiento & purificación , Animales , Peste de los Pequeños Rumiantes/diagnóstico , Peste de los Pequeños Rumiantes/virología , Proteínas de la Nucleocápside/genética , Proteínas de la Matriz Viral/genética , Enfermedades de las Cabras/diagnóstico , Enfermedades de las Cabras/virología , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , ARN Viral/genética , Ovinos , Proteínas Bacterianas , Endodesoxirribonucleasas , Proteínas Asociadas a CRISPR
9.
ChemSusChem ; : e202400946, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38899379

RESUMEN

Oxygen vacancy (VO) has been recognized to possess an effect to promote the charge separation and transfer (CST) in various n-type semiconductor based photoelectrodes. But how external stimulus will change this VO effect has not been investigated. In this work, external polarization is applied to investigate the effect of VO on the CST process of a typical ferroelectric BiFeO3 photoelectrode. It is found that negative poling treatment can significantly boost VO effect, while positive poling treatment will deteriorate the CST capability in BiFeO3 photoelectrodes. This poling history determined VO effect is rooted in the VO induced defect dipoles, wherein their alignment produces a depolarization electric field to modulate the CST driving force. This finding highlights the significance of poling history in functionalizing the VO in a photoelectrode.

10.
Front Microbiol ; 15: 1393127, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38690369

RESUMEN

Bovine respiratory syncytial virus (BRSV) is an RNA virus with envelope that causes acute, febrile, and highly infectious respiratory diseases in cattle. However, the manner and mechanism of BRSV entry into cells remain unclear. In this study, we aimed to explore the entry manner of BRSV into MDBK cells and its regulatory mechanism. Our findings, based on virus titer, virus copies, western blot and IFA analysis, indicate that BRSV enters MDBK cells through endocytosis, relying on dynamin, specifically via clathrin-mediated endocytosis rather than caveolin-mediated endocytosis and micropinocytosis. We observed that the entered BRSV initially localizes in early endosomes and subsequently localizes in late endosomes. Additionally, our results of western blot, virus titer and virus copies demonstrate that BRSV entry through clathrin-mediated endocytosis is regulated by PI3K-Akt and Src-JNK signaling pathways. Overall, our study suggests that BRSV enters MDBK cells through clathrin-mediated endocytosis, entered BRSV is trafficked to late endosome via early endosome, BRSV entry through clathrin-mediated endocytosis is regulated by PI3K-Akt and Src-JNK signaling pathways.

11.
Exp Cell Res ; 439(1): 114074, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38710403

RESUMEN

Ferroptosis inhibits tumor progression in pancreatic cancer cells, while PITX2 is known to function as a pro-oncogenic factor in various tumor types, protecting them from ferroptosis and thereby promoting tumor progression. In this study, we sought to investigate the regulatory role of PITX2 in tumor cell ferroptosis within the context of pancreatic cancer. We conducted PITX2 knockdown experiments using lentiviral infection in two pancreatic cancer cell lines, namely PANC-1 and BxPC-3. We assessed protein expression through immunoblotting and mRNA expression through RT-PCR. To confirm PITX2 as a transcription factor for GPX4, we employed Chromatin Immunoprecipitation (ChIP) and Dual-luciferase assays. Furthermore, we used flow cytometry to measure reactive oxygen species (ROS), lipid peroxidation, and apoptosis and employed confocal microscopy to assess mitochondrial membrane potential. Additionally, electron microscopy was used to observe mitochondrial structural changes and evaluate PITX2's regulation of ferroptosis in pancreatic cancer cells. Our findings demonstrated that PITX2, functioning as a transcription factor for GPX4, promoted GPX4 expression, thereby exerting an inhibitory effect on ferroptosis in pancreatic cancer cells and consequently promoting tumor progression. Moreover, PITX2 enhanced the invasive and migratory capabilities of pancreatic cancer cells by activating the WNT signaling pathway. Knockdown of PITX2 increased ferroptosis and inhibited the proliferation of PANC-1 and BxPC-3 cells. Notably, the inhibitory effect on ferroptosis resulting from PITX2 overexpression in these cells could be countered using RSL3, an inhibitor of GPX4. Overall, our study established PITX2 as a transcriptional regulator of GPX4 that could promote tumor progression in pancreatic cancer by reducing ferroptosis. These findings suggest that PITX2 may serve as a potential therapeutic target for combating ferroptosis in pancreatic cancer.


Asunto(s)
Ferroptosis , Regulación Neoplásica de la Expresión Génica , Proteína del Homeodomínio PITX2 , Proteínas de Homeodominio , Neoplasias Pancreáticas , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Especies Reactivas de Oxígeno , Factores de Transcripción , Animales , Humanos , Ratones , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Ferroptosis/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Peroxidación de Lípido , Potencial de la Membrana Mitocondrial/genética , Ratones Desnudos , Mitocondrias/metabolismo , Mitocondrias/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Especies Reactivas de Oxígeno/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Vía de Señalización Wnt/genética
12.
Heliyon ; 10(8): e29305, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38655359

RESUMEN

Background: To investigate the correlation between retinal vessel density (VD) parameters with serum B-type natriuretic peptide (BNP) in patients with coronary heart disease (CHD) using novel optical coherence tomography angiography (OCTA) denoising images based on artificial intelligence (AI). Methods: OCTA images of the optic nerve and macular area were obtained using a Canon-HS100 OCT device in 176 patients with CHD. Baseline information and blood test results were recorded. Results: Retinal VD parameters of the macular and optic nerves on OCTA were significantly decreased in patients with CHD after denoising. Retinal VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC) was strongly correlated with serum BNP levels in patients with CHD. Significant differences were noted in retinal thickness and retinal VD (SCP, DCP and RPC) between the increased BNP and normal BNP groups in patients with CHD. Conclusion: Deep learning denoising can remove background noise and smooth rough vessel surfaces. SCP,DCP and RPC may be potential clinical markers of cardiac function in patients with CHD. Denoising shows great potential for improving the sensitivity of OCTA images as a biomarker for CHD progression.

13.
J Cell Mol Med ; 28(8): e18208, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38613347

RESUMEN

Increasing evidences have found that the interactions between hypoxia, immune response and metabolism status in tumour microenvironment (TME) have clinical importance of predicting clinical outcomes and therapeutic efficacy. This study aimed to develop a reliable molecular stratification based on these key components of TME. The TCGA data set (training cohort) and two independent cohorts from CGGA database (validation cohort) were enrolled in this study. First, the enrichment score of 277 TME-related signalling pathways was calculated by gene set variation analysis (GSVA). Then, consensus clustering identified four stable and reproducible subtypes (AFM, CSS, HIS and GLU) based on TME-related signalling pathways, which were characterized by differences in hypoxia and immune responses, metabolism status, somatic alterations and clinical outcomes. Among the four subtypes, HIS subtype had features of immunosuppression, oxygen deprivation and active energy metabolism, resulting in a worst prognosis. Thus, for better clinical application of this acquired stratification, we constructed a risk signature by using the LASSO regression model to identify patients in HIS subtype accurately. We found that the risk signature could accurately screen out the patients in HIS subtype and had important reference value for individualized treatment of glioma patients. In brief, the definition of the TME-related subtypes was a valuable tool for risk stratification in gliomas. It might serve as a reliable prognostic classifier and provide rational design of individualized treatment, and follow-up scheduling for patients with gliomas.


Asunto(s)
Glioma , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Metabolismo Energético , Análisis por Conglomerados , Glioma/diagnóstico , Glioma/genética , Hipoxia
14.
Heliyon ; 10(7): e29107, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38623223

RESUMEN

Background: To investigate the associations between retinal/choroidal microvasculature and carotid plaque in patients with CAD assessed by optical coherence tomography angiography (OCTA). Methods: This study included 127 CAD patients with and 79 without carotid plaque. Each patient had both OCTA taken and digitized to determine retinal/choroidal thickness, vessel density and flow area and carotid ultrasound for carotid plaque size and stability measurement. The superficial capillary plexus (SCP), deep capillary plexus (DCP), out retina and choriocapillaris vessel density, out retina and choriocapillaris flow area, and full retina thickness were analyzed in the fovea centered 6 × 6 mm area. The association between OCTA measurements and carotid plaque characteristics in patients with CAD were evaluated. Results: The duration of hypertension and diabetes mellitus (DM) was significantly longer in CAD patients with carotid plaque than that without (p < 0.001). The mean values for vessel density SCP and DCP (except fovea zone), and choriocapillaris nasal zone were significantly lower in plaque group (p < 0.05). Negative correlations between the carotid plaque width and vessel density SCP and DCP (except fovea zone) (p < 0.05) were also found in this study. Conclusions: In patients with CAD, carotid plaque, a risk factor and marker of atherosclerosis and stenosis, is significantly and independently associated with retinal and choroidal microvascular changes by OCTA.

15.
AIDS ; 38(6): 779-789, 2024 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-38578957

RESUMEN

OBJECTIVE: This study aims to investigate the functions and mechanistic pathways of Astrocyte Elevated Gene-1 (AEG-1) in the disruption of the blood-retinal barrier (BRB) caused by the HIV-1 envelope glycoprotein gp120. DESIGN: We utilized ARPE-19 cells challenged with gp120 as our model system. METHODS: Several analytical techniques were employed to decipher the intricate interactions at play. These included PCR, Western blot, and immunofluorescence assays for the molecular characterization, and transendothelial electrical resistance (TEER) measurements to evaluate barrier integrity. RESULTS: We observed that AEG-1 expression was elevated, whereas the expression levels of tight junction proteins ZO-1, Occludin, and Claudin5 were downregulated in gp120-challenged cells. TEER measurements corroborated these findings, indicating barrier dysfunction. Additional mechanistic studies revealed that the activation of NFκB and MMP2/9 pathways mediated the AEG-1-induced barrier destabilization. Through the use of lentiviral vectors, we engineered cell lines with modulated AEG-1 expression levels. Silencing AEG-1 alleviated gp120-induced downregulation of tight junction proteins and barrier impairment while concurrently inhibiting the NFκB and MMP2/9 pathways. Conversely, overexpression of AEG-1 exacerbated these pathological changes, further compromising the integrity of the BRB. CONCLUSION: Gp120 upregulates the expression of AEG-1 and activates the NFκB and MMP2/9 pathways. This in turn leads to the downregulation of tight junction proteins, resulting in the disruption of barrier function.


Asunto(s)
Barrera Hematorretinal , Proteína gp120 de Envoltorio del VIH , Infecciones por VIH , VIH-1 , Proteínas de la Membrana , Proteínas de Unión al ARN , Humanos , Barrera Hematorretinal/metabolismo , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Proteína gp120 de Envoltorio del VIH/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Unión al ARN/metabolismo
16.
Int J Ophthalmol ; 17(4): 707-712, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38638269

RESUMEN

AIM: To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography (SS-OCT). METHODS: According to the body mass index (BMI) results, the adults enrolled in the cross-sectional study were divided into the normal group (18.50≤BMI<25.00 kg/m2), the overweight group (25.00≤BMI<30.00 kg/m2), and the obesity group (BMI≥30.00 kg/m2). The one-way ANOVA and the Chi-square test were used for comparisons. Pearson's correlation analysis was used to evaluate the relationships between the measured variables. RESULTS: This research covered the left eyes of 3 groups of 434 age- and sex-matched subjects each: normal, overweight, and obesity. The mean BMI was 22.20±1.67, 26.82±1.38, and 32.21±2.35 kg/m2 in normal, overweight and obesity groups, respectively. The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group (P<0.05 for all), while the retinal thickness of the three groups did not differ significantly. Pearson's correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness, but no significant correlation was observed between BMI and retinal thickness. CONCLUSION: Choroidal thickness is decreased in people with overweight or obesity. Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.

17.
J Acquir Immune Defic Syndr ; 96(3): 299-303, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38534141

RESUMEN

OBJECTIVE: Efavirenz (EFV) is commonly used in combination antiretroviral therapy. However, in our previous study, many persons living with HIV exhibited ocular complications despite undergoing effective combination antiretroviral therapy. Here, we aimed to determine the intraocular EFV concentrations in the vitreous and analyze the factors affecting viral load in the vitreous in patients with HIV-associated retinopathies. DESIGN: Observational, retrospective study. METHODS: Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy were enrolled between January 2019 and August 2022. The patients were divided into 2 groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during pars plana vitrectomy. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using ultra-high-performance liquid chromatography/tandem mass spectrometry. RESULTS: The median age of the enrolled patients was 48 years (interquartile range, 32.25-53.25), including 12 men and 2 women. Median vitreous and plasma EFV concentrations were 141.5 (interquartile range, 69.63-323.75) and 2620 ng/mL (1680-4207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0.04 vs 0.12, P = 0.042). CONCLUSIONS: The vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be because of poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with RD, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit HIV-1 replication in ocular tissues.


Asunto(s)
Alquinos , Fármacos Anti-VIH , Benzoxazinas , Ciclopropanos , Infecciones por VIH , VIH-1 , Carga Viral , Humanos , Benzoxazinas/uso terapéutico , Benzoxazinas/farmacocinética , Masculino , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/farmacocinética , Cuerpo Vítreo/metabolismo , Cuerpo Vítreo/virología , ARN Viral/sangre , Vitrectomía
18.
Surg Endosc ; 38(5): 2622-2631, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38499780

RESUMEN

BACKGROUND: Postoperative pancreatic fistula (POPF) is the most prevalent complications following minimally invasive pancreaticoduodenectomy (MIPD). Only one model related to MIPD exists, and previous POPF scoring prediction methods are based on open pancreaticoduodenectomy patients. Our objectives are to determine the variables that may increase the probability of pancreatic fistula following MIPD and to develop and validate a POPF predictive risk model. METHODS: Data from 432 patients who underwent MIPD between July 2015 and May 2022 were retrospectively collected. A nomogram prediction model was created using multivariate logistic regression analysis to evaluate independent factors for POPF in patients undergoing MIPD in the modeling cohort. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) and the calibration curve were used to verify the nomogram prediction model internally and externally within the modeling cohort and the verification cohort. RESULTS: Multivariate logistic regression analysis showed that body mass index (BMI), albumin, triglycerides, pancreatic duct diameter, pathological diagnosis and intraoperative bleeding were independent variables for POPF. On the basis of this information, a model for the prediction of risks associated with POPF was developed. In accordance with the ROC analysis, the modeling cohort's AUC was 0.819 (95% CI 0.747-0.891), the internal validation cohort's AUC was 0.830 (95% CI 0.747-0.912), and the external validation cohort's AUC was 0.793 (95% CI 0.671-0.915). Based on the calibration curve, the estimated values of POPF have a high degree of concordance with the actual values that were measured. CONCLUSIONS: This model for predicting the probability of pancreatic fistula following MIPD has strong predictive capacity and can provide a trustworthy predictive method for the early screening of high-risk patients with pancreatic fistula after MIPD and timely clinical intervention.


Asunto(s)
Nomogramas , Fístula Pancreática , Pancreaticoduodenectomía , Complicaciones Posoperatorias , Humanos , Fístula Pancreática/etiología , Fístula Pancreática/epidemiología , Pancreaticoduodenectomía/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Anciano , Factores de Riesgo , Curva ROC , Adulto , Medición de Riesgo/métodos
19.
Biomimetics (Basel) ; 9(3)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38534807

RESUMEN

The facial expressions of humanoid robots play a crucial role in human-computer information interactions. However, there is a lack of quantitative evaluation methods for the anthropomorphism of robot facial expressions. In this study, we designed and manufactured a humanoid robot head that was capable of successfully realizing six basic facial expressions. The driving force behind the mechanism was efficiently transmitted to the silicone skin through a rigid linkage drive and snap button connection, which improves both the driving efficiency and the lifespan of the silicone skin. We used human facial expressions as a basis for simulating and acquiring the movement parameters. Subsequently, we designed a control system for the humanoid robot head in order to achieve these facial expressions. Moreover, we used a flexible vertical graphene sensor to measure strain on both the human face and the silicone skin of the humanoid robot head. We then proposed a method to evaluate the anthropomorphic degree of the robot's facial expressions by using the difference rate of strain. The feasibility of this method was confirmed through experiments in facial expression recognition. The evaluation results indicated a high degree of anthropomorphism for the six basic facial expressions which were achieved by the humanoid robot head. Moreover, this study also investigates factors affecting the reproduction of expressions. Finally, the impulse was calculated based on the strain curves of the energy consumption of the humanoid robot head to complete different facial expressions. This offers a reference for fellow researchers when designing humanoid robot heads, based on energy consumption ratios. To conclude, this paper offers data references for optimizing the mechanisms and selecting the drive components of the humanoid robot head. This was realized by considering the anthropomorphic degree and energy consumption of each part. Additionally, a new method for evaluating robot facial expressions is proposed.

20.
Phys Chem Chem Phys ; 26(12): 9295-9308, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38469695

RESUMEN

Understanding selectivity mechanisms of inhibitors towards highly homologous proteins is of paramount importance in the design of selective candidates. Human aldo-keto reductases (AKRs) pertain to a superfamily of monomeric oxidoreductases, which serve as NADPH-dependent cytosolic enzymes to catalyze the reduction of carbonyl groups to primary and secondary alcohols using electrons from NADPH. Among AKRs, AKR1B1 is emerging as a promising target for cancer treatment and diabetes, despite its high structural similarity with AKR1B10, which leads to severe adverse events. Therefore, it is crucial to understand the selectivity mechanisms of AKR1B1 and AKR1B10 to discover safe anticancer candidates with optimal therapeutic efficacy. In this study, multiple computational strategies, including sequence alignment, structural comparison, Protein Contacts Atlas analysis, molecular docking, molecular dynamics simulation, MM-GBSA calculation, alanine scanning mutagenesis and pharmacophore modeling analysis were employed to comprehensively understand the selectivity mechanisms of AKR1B1/10 inhibition based on selective inhibitor lidorestat and HAHE. This study would provide substantial evidence in the design of potent and highly selective AKR1B1/10 inhibitors in future.


Asunto(s)
Inhibidores Enzimáticos , Simulación de Dinámica Molecular , Humanos , Simulación del Acoplamiento Molecular , NADP/metabolismo , Aldo-Ceto Reductasas/metabolismo , Inhibidores Enzimáticos/farmacología , Aldehído Reductasa/metabolismo
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