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1.
Luminescence ; 39(5): e4778, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38772865

RESUMEN

To establish a new method for detecting crystal violet (CV), a harmful dye, herein, a genre of novel biomass carbon dots (CDs) was synthesized via a microwave method and employed as a fluorescent probe, in which water spinach and polyethylene glycol (PEG) performed as raw materials. Based on the inner filter effect (IFE) between the luminescent CDs and CV, the blue emission of this probe at 430 nm could be quenched by CV. Hence, a new strategy was proposed to selectively determine CV in aquaculture ambient. Moreover, under the optimal experiment conditions, this method showed a good linearity between the concentration of CV (c) and fluorescence quenching rate (ΔF/F0) in the concentration range of 4-200 µmol/L with the corresponding correlation coefficient (r) and the detection limit of 0.997 and 710 nmol/L, respectively. With advantages of environmental protectivity, sensitivity, affordability, and user-friendliness, the facilely fabricated CDs could be successfully applied in detecting CV in aquaculture samples, providing a technical foundation for monitoring the pollution of CV and ensuring the quality and safety of aquatic products.


Asunto(s)
Biomasa , Carbono , Colorantes Fluorescentes , Violeta de Genciana , Microondas , Puntos Cuánticos , Violeta de Genciana/química , Carbono/química , Puntos Cuánticos/química , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Espectrometría de Fluorescencia , Fluorescencia , Polietilenglicoles/química
2.
Artículo en Inglés | MEDLINE | ID: mdl-38753528

RESUMEN

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

3.
Cell Rep ; 43(5): 114221, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38748877

RESUMEN

ZBP1 is an interferon (IFN)-induced nucleic acid (NA) sensor that senses unusual Z-form NA (Z-NA) to promote cell death and inflammation. However, the mechanisms that dampen ZBP1 activation to fine-tune inflammatory responses are unclear. Here, we characterize a short isoform of ZBP1 (referred to as ZBP1-S) as an intrinsic suppressor of the inflammatory signaling mediated by full-length ZBP1. Mechanistically, ZBP1-S depresses ZBP1-mediated cell death by competitive binding with Z-NA for Zα domains of ZBP1. Cells from mice (Ripk1D325A/D325A) with cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome are alive but sensitive to IFN-induced and ZBP1-dependent cell death. Intriguingly, Ripk1D325A/D325A cells die spontaneously when ZBP1-S is deleted, indicating that cell death driven by ZBP1 is under the control of ZBP1-S. Thus, our findings reveal that alternative splicing of Zbp1 represents autogenic inhibition for regulating ZBP1 signaling and indicate that uncoupling of Z-NA with ZBP1 could be an effective strategy against autoinflammations.

4.
Nat Commun ; 15(1): 4035, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740742

RESUMEN

Rapid and accurate detection of respiratory virus aerosols is highlighted for virus surveillance and infection control. Here, we report a wireless immunoassay technology for fast (within 10 min), on-site (wireless and battery-free), and sensitive (limit of detection down to fg/L) detection of virus antigens in aerosols. The wireless immunoassay leverages the immuno-responsive hydrogel-modulated radio frequency resonant sensor to capture and amplify the recognition of virus antigen, and flexible readout network to transduce the immuno bindings into electrical signals. The wireless immunoassay achieves simultaneous detection of respiratory viruses such as severe acute respiratory syndrome coronavirus 2, influenza A H1N1 virus, and respiratory syncytial virus for community infection surveillance. Direct detection of unpretreated clinical samples further demonstrates high accuracy for diagnosis of respiratory virus infection. This work provides a sensitive and accurate immunoassay technology for on-site virus detection and disease diagnosis compatible with wearable integration.


Asunto(s)
Hidrogeles , Subtipo H1N1 del Virus de la Influenza A , SARS-CoV-2 , Tecnología Inalámbrica , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Humanos , Hidrogeles/química , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Tecnología Inalámbrica/instrumentación , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Aerosoles , COVID-19/diagnóstico , COVID-19/virología , COVID-19/inmunología , Antígenos Virales/inmunología , Antígenos Virales/análisis , Virus Sincitiales Respiratorios/inmunología , Virus Sincitiales Respiratorios/aislamiento & purificación , Límite de Detección
5.
Pancreas ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38696448

RESUMEN

OBJECTIVES: Proximal migration is one of the complications after pancreatic duct stenting. This study aimed to determine the incidence of proximal migration and to analyze the rescue methods. METHODS: A search was performed in MEDLINE/EMBASE database. The literatures included were reviewed and analyzed. Retrieval tools were classified into 3 classes: Class A works by indirectly contacting the outer surface of the stent. Class B works by directly contacting the outer surface. Class C works by directly contacting the inner surface. RESULTS: 416 literatures were retrieved from 1983 to 2021. 15 literatures were included. The incidence of proximal migration of pancreatic stents was 4.7% (106/2246). The success rate of endotherapy was 86.6% (214/247), and the surgical conversion rate of it was 9.3%. Among the 214 cases in which the displaced stents were successfully removed under endoscopy, 49 cases (22.9%) used Class A methods, 154 cases (72.0%) used Class B methods and 11 cases (5.1%) used Class C methods. The overall rate of postoperative complication was 12.1%, including postprocedure pancreatitis (9.1%, 18/247), followed by bleeding (1.5%), perforation (1.0%) and biliary infection (0.5%). CONCLUSIONS: Endoscopy is an effective method for the treatment of proximal displacement of pancreatic stents with acceptable complication rate.

6.
BMC Public Health ; 24(1): 1333, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760740

RESUMEN

BACKGROUND: Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. METHOD: Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. RESULTS: A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507-0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116-1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425-0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135-0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322-0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells < 200 cells/µL subgroup, temperature, precipitation, and PM10 had a significant hysteretic effect on TB incidence, while temperature and precipitation had a significant cumulative lag effect. However, these effects were not observed in the CD4(+) T cells ≥ 200 cells/µL subgroup. CONCLUSION: For PLWHA in subtropical Guangxi, temperature and precipitation had a significant cumulative effect on TB incidence among PLWHA, while air pollutants had little effect. Moreover, the influence of meteorological factors on the incidence of TB also depends on the immune status of PLWHA.


Asunto(s)
Contaminantes Atmosféricos , Infecciones por VIH , Conceptos Meteorológicos , Tuberculosis , Humanos , China/epidemiología , Incidencia , Tuberculosis/epidemiología , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Infecciones por VIH/epidemiología , Femenino , Masculino , Adulto , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Persona de Mediana Edad
7.
Ecotoxicol Environ Saf ; 277: 116368, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38669874

RESUMEN

Perfluorooctane sulfonate (PFOS) is a persistent chemical that has long been a threat to human health. However, the molecular effects of PFOS on various organs are not well studied. In this study, male Sprague-Dawley rats were treated with various doses of PFOS through gavage for 21 days. Subsequently, the liver, lung, heart, kidney, pancreas, testis, and serum of the rats were harvested for lipid analysis. We applied a focusing lipidomic analytical strategy to identify key lipid responses of phosphorylcholine-containing lipids, including phosphatidylcholines and sphingomyelins. Partial least squares discriminant analysis revealed that the organs most influenced by PFOS exposure were the liver, kidney, and testis. Changes in the lipid profiles of the rats indicated that after exposure, levels of diacyl-phosphatidylcholines and 22:6-containing phosphatidylcholines in the liver, kidney, and testis of the rats decreased, whereas the level of 20:3-containing phosphatidylcholines increased. Furthermore, levels of polyunsaturated fatty acids-containing plasmenylcholines decreased. Changes in sphingomyelin levels indicated organ-dependent responses. Decreased levels of sphingomyelins in the liver, nonmonotonic dose responses in the kidney, and irregular responses in the testis after PFOS exposure are observed. These lipid responses may be associated with alterations pertaining to phosphatidylcholine synthesis, fatty acid metabolism, membrane properties, and oxidative stress in the liver, kidney, and testis. Lipid responses in the liver could have contributed to the observed increase in liver to body weight ratios. The findings suggest potential toxicity and possible mechanisms associated with PFOS in multiple organs.


Asunto(s)
Ácidos Alcanesulfónicos , Fluorocarburos , Riñón , Hígado , Ratas Sprague-Dawley , Testículo , Animales , Ácidos Alcanesulfónicos/toxicidad , Fluorocarburos/toxicidad , Masculino , Ratas , Hígado/efectos de los fármacos , Hígado/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Testículo/efectos de los fármacos , Testículo/metabolismo , Contaminantes Ambientales/toxicidad , Esfingomielinas , Fosfatidilcolinas , Metabolismo de los Lípidos/efectos de los fármacos , Lipidómica , Pulmón/efectos de los fármacos , Pulmón/metabolismo
8.
Spectrochim Acta A Mol Biomol Spectrosc ; 315: 124259, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38636428

RESUMEN

Soil is the basis of agricultural production and accessing accurate information on soil nutrients is essential. Traditional methods of soil composition detection, which are based on chemical analysis, are characterized by being costly and polluting. Spectroscopic analysis has proven to be a rapid, non-destructive and effective technique for predicting soil properties in general and potassium, phosphorus and organic matter in particular. However, previous research on soils has rarely combined optimization algorithms with machine learning techniques, which has led to suboptimal model accuracy and convergence speed. In this study, a total of 184 soil samples were collected from three cities of Linhai, Yueqing and Longyou County, Zhejiang Province, China. After measuring pH values, alkali-hydrolyzable nitrogen (SAN), available phosphorus (SAP), available potassium (SAK) and soil organic matter (SOM) contents, along with their corresponding spectroscopic measurements, nine pretreatment methods and their combinations are adopted. A novel assessment model, integrating support vector machine and dung beetle optimization algorithm (DBO-SVR), is proposed to predict pH values and SAN, SAP, SAK, SOM content. Meanwhile, the DBO algorithm is compared with three mainstream optimization algorithms (particle swarm optimization (PSO), whale optimization algorithm (WOA) and grey wolf optimizer (GWO)). Results showed that the DBO-SVR model was shown best performance with Rp, RMSEP and RPD of 0.9842, 0.1306, 5.6485 respectively for prediction of pH value, with Rp, RMSEP and RPD of 0.8802, 15.0574 mg/kg and 2.0508, respectively for assessment of SAN content, with Rp, RMSEP and RPD of 0.9790, 12.8298 mg/kg, and 4.5132, respectively for assessment of SAP content, with Rp, RMSEP and RPD of 0.8677, 22.5107 mg/kg, and 1.9546, respectively for assessment of SAK content, and with Rp, RMSEP and RPD of 0.9273, 2.6427g/kg , and 2.1821, respectively for assessment of SOM content. This study demonstrates that the combination of near-infrared (NIR) spectroscopy and the DBO-SVR algorithm is capable of predicting soil nutrient composition with greater accuracy and efficiency.

9.
ACS Nano ; 18(14): 10288-10301, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38556985

RESUMEN

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development of a biomaterial capable of activating ROS-induced apoptosis and ferroptosis is a potential strategy to enhance RT sensitivity. To achieve precision and high-efficiency RT, the theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, and inducing apoptosis-ferroptosis to sensitize RT. A large amount of ROS is derived from three aspects: (1) When exposed to ionizing radiation, Au/CuNDs effectively absorb photons and emit various electrons, which can interact with water to produce ROS. (2) Au/CuNDs act as a catalase-like to produce abundant ROS through Fenton reaction with hydrogen peroxide overexpressed of tumor cells. (3) Au/CuNDs deplete overexpressed glutathione, which causes the accumulation of ROS. Large amounts of ROS and ionizing radiation further lead to apoptosis by increasing DNA damage, and ferroptosis by enhancing lipid peroxidation, significantly improving the therapeutic efficiency of RT. Furthermore, Au/CuNDs serve as an excellent nanoprobe for high-resolution near-infrared fluorescence imaging and computed tomography of tumors. The promising dual-mode imaging performance shows their potential application in clinical cancer detection and imaging-guided precision RT, minimizing damage to adjacent normal tissues during RT. In summary, our developed theranostic nanoplatform integrates dual-mode imaging and sensitizes RT via ROS-activated apoptosis-ferroptosis, offering a promising prospect for clinical cancer diagnosis and treatment.


Asunto(s)
Ferroptosis , Neoplasias , Radioterapia Guiada por Imagen , Humanos , Especies Reactivas de Oxígeno , Neoplasias/diagnóstico por imagen , Neoplasias/radioterapia , Apoptosis , Peróxido de Hidrógeno , Línea Celular Tumoral
11.
ACS Appl Mater Interfaces ; 16(15): 18551-18563, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38564314

RESUMEN

High levels of reactive oxygen species (ROS) are known to play a critical role in the secondary cascade of spinal cord injury (SCI). The scavenging of ROS has emerged as a promising approach for alleviating acute SCI. Moreover, identifying the precise location of the SCI site remains challenging. Enhancing the visualization of the spinal cord and improving the ability to distinguish the lesion site are crucial for accurate and safe treatment. Therefore, there is an urgent clinical need to develop a biomaterial that integrates diagnosis and treatment for SCI. Herein, ultra-small-sized gold nanodots (AuNDs) were designed for dual-mode imaging-guided precision treatment of SCI. The designed AuNDs demonstrate two important functions. First, they effectively scavenge ROS, inhibit oxidative stress, reduce the infiltration of inflammatory cells, and prevent apoptosis. This leads to a significant improvement in SCI repair and promotes a functional recovery after injury. Second, leveraging their excellent dual-mode imaging capabilities, the AuNDs enable rapid and accurate identification of SCI sites. The high contrast observed between the injured and adjacent uninjured areas highlights the tremendous potential of AuNDs for SCI detection. Overall, by integrating ROS scavenging and dual-mode imaging in a single biomaterial, our work on functionalized AuNDs provides a promising strategy for the clinical diagnosis and treatment of SCI.


Asunto(s)
Oro , Traumatismos de la Médula Espinal , Humanos , Especies Reactivas de Oxígeno , Oro/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Estrés Oxidativo , Materiales Biocompatibles/uso terapéutico
12.
Artículo en Inglés | MEDLINE | ID: mdl-38668948

RESUMEN

During the COVID-19 pandemic, a substantial quantity of disposable face masks was discarded, consisting of three layers of nonwoven fabric. However, their improper disposal led to the release of microplastics (MPs) and nanoplastics (NPs) when they ended up in aquatic environments. To analyze the release kinetics and size characteristics of these masks, release experiments were performed on commercially available disposable masks over a period of 7 days and micro- and nanoplastic releases were detected using fiber counting and nanoparticle tracking analysis. The study's findings revealed that there was no significant difference (p > 0.05) in the quantity of MPs released among the layers of the masks. However, the quantity of NPs released from the middle layer of the mask was 25.9 ± 1.3 × 108 to 81.3 ± 5.3 × 108 particles/piece, significantly higher than the inner and outer layers (p < 0.05). The release process of micro/nanoplastics (M/NPs) from each layer of the mask followed the Elovich equation and the power function equation, indicating that the release was divided into two stages. MPs in the range of 1-500 µm and NPs in the range of 100-300 nm dominated the release from each layer of the mask, accounting for an average of 93.81% and 67.52%, respectively. Based on these findings, recommendations are proposed to reduce the release of M/NPs from masks during subsequent use.

13.
Natl Sci Rev ; 11(5): nwae055, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38577668

RESUMEN

Enhancing the quality of junctions is crucial for optimizing carrier extraction and suppressing recombination in semiconductor devices. In recent years, metal halide perovskite has emerged as the most promising next-generation material for optoelectronic devices. However, the construction of high-quality perovskite junctions, as well as characterization and understanding of their carrier polarity and density, remains a challenge. In this study, using combined electrical and spectroscopic characterization techniques, we investigate the doping characteristics of perovskite films by remote molecules, which is corroborated by our theoretical simulations indicating Schottky defects consisting of double ions as effective charge dopants. Through a post-treatment process involving a combination of biammonium and monoammonium molecules, we create a surface layer of n-type low-dimensional perovskite. This surface layer forms a heterojunction with the underlying 3D perovskite film, resulting in a favorable doping profile that enhances carrier extraction. The fabricated device exhibits an outstanding open-circuit voltage (VOC) up to 1.34 V and achieves a certified efficiency of 19.31% for single-junction wide-bandgap (1.77 eV) perovskite solar cells, together with significantly enhanced operational stability, thanks to the improved separation of carriers. Furthermore, we demonstrate the potential of this wide-bandgap device by achieving a certified efficiency of 27.04% and a VOC of 2.12 V in a perovskite/perovskite tandem solar cell configuration.

14.
Pathogens ; 13(4)2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38668227

RESUMEN

Since November 2021, Omicron has emerged as the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and its sublineages continue to appear one after another, significantly reducing the effectiveness of existing therapeutic neutralizing antibodies (NAbs). It is urgent to develop effective NAbs against circulating Omicron variants. Here, we isolated receptor binding domain (RBD)-specific single memory B cells via flow cytometry from a COVID-19 convalescent. The antibody variable region genes of the heavy chain (VHs) and light chain (VLs) were amplified and cloned into expression vectors. After antibody expression, ELISA screening and neutralizing activity detection, we obtained an IGHV3-53-encoded RBD-targeting cross-neutralizing antibody D6, whose VL originated from the IGKV1-9*01 germlines. D6 could potently neutralize circulating Omicron variants (BA.1, BA.2, BA.4/5 and BF.7), with IC50 values of less than 0.04 µg/mL, and the neutralizing ability against XBB was reduced but still effective. The KD values of D6 binding with RBD of the prototype and BA.1 were both less than 1.0 × 10-12 M. The protein structure of the D6-RBD model indicates that D6 interacts with the RBD external subdomain and belongs to the RBD-1 community. The sufficient contact and deep interaction of D6 HCDR3 and LCDR3 with RBD may be the crucial reason for its cross-neutralizing activity. The sorting and analysis of mAb D6 will provide important information for the development of anti-COVID-19 reagents.

15.
Front Pharmacol ; 15: 1197651, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38595918

RESUMEN

Primary membranous nephropathy (PMN) is the most common cause for adult nephrotic syndrome. Rituximab has demonstrated promising clinical efficacy by random controlled trials and the off-label use is widely adopted in PMN. However, the standard dosage is borrowed from B cell lymphoma treatment with far more antigens and is oversaturated for PMN treatment, accompanied with additional safety risk and unnecessary medical cost. More than 15% serious adverse events were observed under standard dosage and low dose therapies were explored recently. Dose optimization by clinical trials is extremely time- and cost-consuming and can be significantly accelerated with the aid of model-informed drug development. Here, we aim to establish the first population pharmacokinetic and pharmacodynamic (PPK/PD) model for rituximab in PMN to guide its dosage optimization. Rituximab pharmacokinetic and pharmacodynamic data from 41 PMN patients in a retrospective study under a newly proposed monthly mini-dose were used to construct quantitative dose-exposure-response relationship via mechanistic target-mediated drug disposition (TMDD) model followed by regression between the reduction of anti-PLA2R titer and time after the treatment. The final model, validated by goodness-of-fit plots, visual predictive checks and bootstrap, was used to recommend the optimized dosing regimen by simulations. The model was well validated for PK/PD prediction. The systemic clearance and half-life are 0.54 L/h and 14.7 days, respectively. Simulation of a novel regimen (6 monthly doses of 100 mg) indicated the comparable ability and superior duration time of CD20+ B cell depletion compared with standard dosage, while the cumulative dosage and safety risk was significantly decreased. We established the first PPK/PD model and provide evidence to support the dosage optimization based on monthly mini-dose. Our study can also efficiently accelerate dosage optimization of novel anti-CD20 antibodies in PMN and other indications.

16.
Science ; 383(6690): 1467-1470, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38547290

RESUMEN

Similar to the optical diffraction of light passing through a material grating, the Kapitza-Dirac effect occurs when an electron is diffracted by a standing light wave. In its original description, the effect is time independent. Here, we extended the Kapitza-Dirac effect to the time domain. By tracking the spatiotemporal evolution of a pulsed electron wave packet diffracted by a 60-femtosecond (where one femtosecond = 10-15 seconds) standing wave pulse in a pump-probe scheme, we observed time-dependent diffraction patterns. The fringe spacing in the observed pattern differs from that generated by the conventional Kapitza-Dirac effect. By exploiting this time-resolved diffraction scheme, we can access the time evolution of the phase properties of a free electron and potentially image ionic potentials and electronic decoherences.

17.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38543155

RESUMEN

The objectives of this study were to support dose selection of a novel FXR agonist XZP-5610 in first-in-human (FIH) trials and to predict its liver concentrations in Chinese healthy adults. Key parameters for extrapolation were measured using in vitro and in vivo models. Allometric scaling methods were employed to predict human pharmacokinetics (PK) parameters and doses for FIH clinical trials. To simulate the PK profiles, a physiologically based pharmacokinetic (PBPK) model was developed using animal data and subsequently validated with clinical data. The PBPK model was employed to simulate XZP-5610 concentrations in the human liver across different dose groups. XZP-5610 exhibited high permeability, poor solubility, and extensive binding to plasma proteins. After a single intravenous or oral administration of XZP-5610, the PK parameters obtained from rats and beagle dogs were used to extrapolate human parameters, resulting in a clearance of 138 mL/min and an apparent volume of distribution of 41.8 L. The predicted maximum recommended starting dose (MRSD), minimal anticipated biological effect level (MABEL), and maximum tolerated dose (MTD) were 0.15, 2, and 3 mg, respectively. The PK profiles and parameters of XZP-5610, predicted using the PBPK model, demonstrated good consistency with the clinical data. By using allometric scaling and PBPK models, the doses, PK profile, and especially the liver concentrations were successfully predicted in the FIH study.

18.
Sci Rep ; 14(1): 7048, 2024 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528047

RESUMEN

The close link between HIV-1 infection and the occurrence of pulmonary arterial hypertension (PAH). However, the underlying molecular mechanisms of their interrelation remain unclear. The microarray data of HIV-1 and PAH were downloaded from GEO database. We utilized WGCNA to identify shared genes between HIV-1 and PAH, followed by conducting GO and pathway enrichment analyses. Subsequently, differentially genes analysis was performed using external validation datasets to further filter hub genes. Immunoinfiltration analysis was performed using CIBERSORT. Finally, hub gene expression was validated using scRNA-seq data. We identified 109 shared genes through WGCNA, primarily enriched in type I interferon (IFN) pathways. By taking the intersection of WGCNA important module genes and DEGs, ISG15 and IFI27 were identified as pivotal hub genes. Immunoinfiltration analysis and scRNA-seq results indicated the significant role of monocytes in the shared molecular mechanisms of HIV-1 and PAH. In summary, our study illustrated the possible mechanism of PAH secondary to HIV-1 and showed that the heightened IFN response in HIV-1 might be a crucial susceptibility factor for PAH, with monocytes being pivotal cells involved in the type I IFN response pathway. This provides potential new insights for further investigating the molecular mechanisms connecting HIV-1 and PAH.


Asunto(s)
Seropositividad para VIH , VIH-1 , Interferón Tipo I , Hipertensión Arterial Pulmonar , Humanos , VIH-1/genética , Hipertensión Pulmonar Primaria Familiar , Bases de Datos Factuales , Interferón Tipo I/genética , Biología Computacional
19.
BMC Neurol ; 24(1): 104, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528480

RESUMEN

BACKGROUND: No uniform consensus has been achieved regarding the ambulation protocol after transfemoral cerebral angiography (TFA). Until now, in most hospitals patients are prescribed 8-12 h strict immobilization along with bed rest in the supine position after TFA in China, which causes great discomfort to patients. OBJECTIVE: To evaluate the effect of an evidence-based early ambulation protocol on the prevention of vascular complications and general discomfort in patients following transfemoral cerebral angiography (TFA). METHODS: A prospective quasi-experimental study was conducted on 214 patients undergoing TFA with manual compression. Patients in the experimental group were placed supine position for 2 h with a sandbag placed on the wound dressing, followed by a semi-seated position for another 2 h. After this period, patients took 2 h bed rest (move freely) with the sandbag removed, and were allowed to get out of bed 6 h after TFA. Patients in the control group were restricted to an 8 h bed rest in a supine position with the affected leg straight and immobilized. The vascular complications (bleeding, hematoma, ecchymosis) and levels of comfort (low back pain, leg pain, and blood pressure) were evaluated after the procedure. Numeric Rating Scale (NRS) pain scores, systolic blood pressure (SBP); diastolic blood pressure (DBP) were measured hourly for 8 h after TFA. RESULTS: There was no significant difference in the two groups with regard to vascular complications including bleeding events (P = 0.621), bleeding volume (P = 0.321), and area of hematoma (P = 0.156). The area of ecchymosis in the experimental group was significantly smaller than the control group (P = 0.031). Compared with the control group, the NRS score for low back pain in the 4th, 5th, 6th, 7th, and 8th hour after TFA were significantly lower (P < 0.05), and the NRS score for leg pain in the 5th, 6th, 7th, 8th hour after TFA were significantly lower (P < 0.05). The SBP and DBP in the 6th, 7th, and 8th hour after TFA were significantly lower than the control group (all P < 0.05). CONCLUSIONS: The evidence-based early ambulation protocol can effectively and safely increase comfort and decrease the pain level for patients undergoing TFA, without change in the incidence of vascular complications.


Asunto(s)
Dolor de la Región Lumbar , Humanos , Angiografía Cerebral , Estudios Prospectivos , Dolor de la Región Lumbar/complicaciones , Ambulación Precoz/efectos adversos , Equimosis , Hemorragia/complicaciones , Hematoma/etiología
20.
BMC Public Health ; 24(1): 831, 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493080

RESUMEN

BACKGROUND: The Guangxi government initiated two rounds of the Guangxi AIDS Conquering Project (GACP) in 2010 (Phase I) and 2015 (Phase II) to control human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemics. However, the effectiveness of GACP in HIV prevention and treatment has rarely been reported. This study aimed to assess the effectiveness of the GACP implemented in Guangxi, China and provide data for strategy and praxis improvements to achieve Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95 targets. METHODS: We used spatial approaches to trace the spatiotemporal distribution properties, epidemic trends, and correlation between macroscopic factors and HIV incidence using data from the Chinese HIV/AIDS case reporting system to explore the effects of the GACP. RESULTS: During the GACP era, the HIV epidemic stabilized in urban centers, showing a downward trend in the Hengzhou and Binyang Counties in the eastern region, whereas it continued to increase in rural areas of the northwest region, such as the Long'an, Mashan, Shanglin, and Wuming Districts. The linear directional mean (LDM) of HIV infection reported cases displayed a southeast-northwest direction, with an LDM value of 12.52°. Compared with that in Phase I, Hengzhou withdrew from the high-high clustering area, and the west-north suburban counties pulled out the low-low clustering area during Phase II. Significant HIV clusters were identified in the eastern region during Phase I, whereas these clusters emerged in the northwestern areas during Phase II. Regarding HIV, socioeconomic status, population mobility, and medical care levels were the key social drivers of heterogeneous spatial distribution. CONCLUSIONS: The GACP assisted in effectively managing the HIV epidemic in urban and eastern areas of Nanning City. However, prevention and control efforts in rural regions, particularly those located in the northwest, may not have yielded comparable outcomes. To address this disparity, allocating additional resources and implementing tailored intervention measures for these rural areas are imperative.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Humanos , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Síndrome de Inmunodeficiencia Adquirida/epidemiología , VIH , Prevalencia , China/epidemiología
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