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1.
Nat Immunol ; 17(1): 95-103, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26523864

RESUMO

Aerobic glycolysis regulates T cell function. However, whether and how primary cancer alters T cell glycolytic metabolism and affects tumor immunity in cancer patients remains a question. Here we found that ovarian cancers imposed glucose restriction on T cells and dampened their function via maintaining high expression of microRNAs miR-101 and miR-26a, which constrained expression of the methyltransferase EZH2. EZH2 activated the Notch pathway by suppressing Notch repressors Numb and Fbxw7 via trimethylation of histone H3 at Lys27 and, consequently, stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling. Moreover, small hairpin RNA-mediated knockdown of human EZH2 in T cells elicited poor antitumor immunity. EZH2(+)CD8(+) T cells were associated with improved survival in patients. Together, these data unveil a metabolic target and mechanism of cancer immune evasion.


Assuntos
Regulação Neoplásica da Expressão Gênica/imunologia , MicroRNAs , Neoplasias/imunologia , Complexo Repressor Polycomb 2/imunologia , Linfócitos T/imunologia , Evasão Tumoral/imunologia , Animais , Separação Celular , Imunoprecipitação da Cromatina , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Citometria de Fluxo , Imunofluorescência , Glicólise , Humanos , Immunoblotting , Melanoma Experimental/imunologia , Camundongos Endogâmicos C57BL , Neoplasias Ovarianas/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Análise Serial de Tecidos , Transfecção
2.
Nat Methods ; 20(12): 1887-1899, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37857907

RESUMO

RNA deaminases are powerful tools for base editing and RNA molecular recording. However, the enzymes used in currently available RNA molecular recorders such as TRIBE, DART or STAMP have limitations due to RNA structure and sequence dependence. We designed a platform for directed evolution of RNA molecular recorders. We engineered an RNA A-to-I deaminase (an RNA adenosine base editor, rABE) that has high activity, low bias and low background. Using rABE, we present REMORA (RNA-encoded molecular recording in adenosines), wherein deamination by rABE writes a molecular record of RNA-protein interactions. By combining rABE with the C-to-U deaminase APOBEC1 and long-read RNA sequencing, we measured binding by two RNA-binding proteins on single messenger RNAs. Orthogonal RNA molecular recording of mammalian Pumilio proteins PUM1 and PUM2 shows that PUM1 competes with PUM2 for a subset of sites in cells. Furthermore, we identify transcript isoform-specific RNA-protein interactions driven by isoform changes distal to the binding site. The genetically encodable RNA deaminase rABE enables single-molecule identification of RNA-protein interactions with cell type specificity.


Assuntos
Citidina Desaminase , RNA , Animais , RNA/genética , Sequência de Bases , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/genética , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
3.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38282455

RESUMO

Individual variability in functional connectivity underlies individual differences in cognition and behaviors, yet its association with functional specialization in the auditory cortex remains elusive. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, this study was designed to investigate the spatial distribution of auditory cortex individual variability in its whole-brain functional network architecture. An inherent hierarchical axis of the variability was discerned, which radiates from the medial to lateral orientation, with the left auditory cortex demonstrating more pronounced variations than the right. This variability exhibited a significant correlation with the variations in structural and functional metrics in the auditory cortex. Four auditory cortex subregions, which were identified from a clustering analysis based on this variability, exhibited unique connectional fingerprints and cognitive maps, with certain subregions showing specificity to speech perception functional activation. Moreover, the lateralization of the connectional fingerprint exhibited a U-shaped trajectory across the subregions. These findings emphasize the role of individual variability in functional connectivity in understanding cortical functional organization, as well as in revealing its association with functional specialization from the activation, connectome, and cognition perspectives.


Assuntos
Córtex Auditivo , Conectoma , Humanos , Córtex Auditivo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Conectoma/métodos , Encéfalo , Cognição
4.
Small ; 20(4): e2306516, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37715101

RESUMO

Antimony selenide (Sb2 Se3 ) is a highly promising photovoltaic material thanks to its outstanding optoelectronic properties, as well as its cost-effective and eco-friendly merits. However, toxic CdS is widely used as an electron transport layer (ETL) in efficient Sb2 Se3 solar cells, which largely limit their development toward market commercialization. Herein, an effective green Cd-free ETL of SnOx is introduced and deposited by atomic layer deposition method. Additionally, an important post-annealing treatment is designed to further optimize the functional layers and the heterojunction interface properties. Such engineering strategy can optimize SnOx ETL with higher nano-crystallinity, higher carrier density, and less defect groups, modify Sb2 Se3 /SnOx heterojunction with better interface performance and much desirable "spike-like" band alignment, and also improve the Sb2 Se3 light absorber layer quality with passivated bulk defects and prolonged carrier lifetime, and therefore to enhance carrier separation and transport while suppressing non-radiative recombination. Finally, the as-fabricated Cd-free Mo/Sb2 Se3 /SnOx /ITO/Ag thin-film solar cell exhibits a stimulating efficiency of 7.39%, contributing a record value for Cd-free substrate structured Sb2 Se3 solar cells reported to date. This work provides a viable strategy for developing and broadening practical applications of environmental-friendly Sb2 Se3 photovoltaic devices.

5.
J Med Virol ; 96(1): e29338, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38163280

RESUMO

Monkeypox (mpox), a viral zoonotic disease, is spreading worldwide. However, evidence that informs prevention and control strategies in the Asia Pacific Region is very limited. Our study aims to investigate the experiences of mpox patients from infection to treatment to provide scientific basis for the prevention and control. A multicenter qualitative design was used. A total of 15 mpox patients were recruited between July 6 and July 25, 2023, from six cities in China. Semistructured interviews were conducted by telephone and analyzed using the thematic analysis. The interview was divided into two sections: patients' experiences (prediagnosis experience, treatment-seeking experience, and quarantine experience) and advice. Prediagnosis experience was summarized into three themes: symptoms, possible routes of infection, and knowledge of mpox. Treatment-seeking experience was summarized into three themes: time of visit to hospital, diagnostic difficulties, and attitude toward diagnosis. Quarantine experience was summarized into three themes: body and mind reactions, reluctance to self-disclose infection status, and factors facilitating recovery. Themes identified from patients' advice were as follows: (1) Increase in testing channels and methods, (2) Development and introduction of vaccines, (3) Adjustment of quarantine program, (4) Improvement of treatment measures, and (5) Improvement of publicity and education. To effectively curb the mpox epidemic, structured measures are urgently needed to address the mpox-related stigma and discrimination. Targeted health education should be provided to MSM, focusing on the prevention, detection, and treatment services. Hospitals should enhance the training of clinicians in key departments including infectious disease and dermatology, to improve diagnostic capability and sensitivity. Furthermore, given the absence of specific antiviral medications, supervised home quarantine may be a good option.


Assuntos
Mpox , Humanos , China/epidemiologia , Ásia , Antivirais , Cidades
6.
Cancer Cell Int ; 24(1): 113, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528591

RESUMO

BACKGROUND: Long non-coding RNAs (lncRNAs) are key regulators of the 6-methyladenosine (m6A) epigenetic modification, playing a role in the initiation and progression of tumors. However, the regulatory mechanisms in head and neck squamous cell carcinoma (HNSCC) remain elusive. In this study, we investigated the molecular regulatory mechanisms of the lncRNA RASAL2-AS1 in the occurrence and development of HNSCC tumors. METHODS: A bioinformatics analysis was conducted to analyze the expression level of RASAL2-AS1 in HNSCC and normal tissues. RASAL2-AS1 mRNA and protein levels were detected using RT-PCR and Western blotting. Wound healing, transwell assays, flow cytometry, M6A dot blot, and RNA immunoprecipitation experiments were conducted to explore the regulatory role of the RASAL2-AS1 and downstream targets METTL14/LIS1 signaling pathway in HNSCC. Immunohistochemical examination was conducted to evaluate the expression of METTL14 and LIS1 in HNSCC and normal tissues. A tumor xenograft model of BALB/c nude mice was established to assess the impact of RASAL2-AS1 on cell proliferation and growth. RESULTS: RASAL2-AS1 high expression in HNSCC and cells deteriorated with survival rates of HNSCC. RASAL2-AS1 overexpression in HNSCC accelerated cell migration, colony formation, cell proliferation, cell cycle in S stage, while RASAL2-AS1 knockdown in HNSC cells inhibited cell cycle in G1 stage. After silencing METTL14, the above effects induced by overexpression of the RASAL2-AS1 were reversed. RASAL2-AS1 overexpression prompted LIS1 expression, whereas RASAL2-AS1 silencing reduced LIS1 levels in HNSCC cells, which was confirmed by immunohistological staining. Results demonstrated elevated expression of METTL14 or LIS1 in tongue cancer tissues. Overexpression of RASAL2-AS1 promoted tumor weight and tumor volume, which was counteracted by pcDNA3.1 RASAL2-AS1 plus silencing METTL14 and METTL14 and LIS1 were significantly decreased. CONCLUSION: Our study highlights the functional importance of the LncRNA RASAL2-AS1 in HNSCC and might assist in the development of a prognostic stratification and therapeutic approach. Which regulates HNSCC with the dependence of m6a manner.

7.
BMC Nephrol ; 25(1): 190, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831279

RESUMO

PURPOSE: Some studies have found that the pathological formation of kidney stones is closely related to injury and inflammatory response. Behaviors such as dietary composition, physical activity, obesity and smoking can all affect the body's oxidative stress levels. In order to evaluate the effects of various diets and lifestyles on the body's oxidative and antioxidant systems, an oxidative balance score was developed. To investigate whether the OBS is associated with the development of kidney stones. METHODS: Data were taken from the National Health and Nutrition Examination Survey (NHANES) from 2007-2018, followed by retrospective observational studies. The association between kidney stones and OBS was analyzed using survey-weighted logistic regression by adjusting for demographics, laboratory tests, and medical comorbidity covariates. The oxidative balance score is calculated by screening 16 nutrients and 4 lifestyle factors, including 5 prooxidants and 15 antioxidants, based on prior information about the relationship between oxidation levels in the body and nutrients or lifestyle factors. RESULTS: A total of 26,786 adult participants were included in the study, of which 2,578, or 9.62%, had a history of nephrolithiasis. Weighted logistic regression analysis found an association between OBS and kidney stones. In the fully tuned model, i.e., model 3, the highest quartile array of OBS was associated with the lowest quartile array of OBS (OR = 0.73 (0.57, 0.92)) with the risk of kidney stone (p = 0.01), and was statistically significant and remained relatively stable in each model. At the same time, the trend test in the model is also statistically significant. With the increase of OBS, the OR value of kidney stones generally tends to decrease. CONCLUSIONS: There is an inverse correlation between OBS and kidney stone disease. At the same time, higher OBS suggests that antioxidant exposure is greater than pro-oxidative exposure in diet and lifestyle, and is associated with a lower risk of kidney stones.


Assuntos
Cálculos Renais , Inquéritos Nutricionais , Estresse Oxidativo , Humanos , Cálculos Renais/epidemiologia , Cálculos Renais/metabolismo , Cálculos Renais/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Antioxidantes/metabolismo , Estilo de Vida , Dieta , Idoso
8.
BMC Pulm Med ; 24(1): 264, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824531

RESUMO

BACKGROUND: Smoking induces and modifies the airway immune response, accelerating the decline of asthmatics' lung function and severely affecting asthma symptoms' control level. To assess the prognosis of asthmatics who smoke and to provide reasonable recommendations for treatment, we constructed a nomogram prediction model. METHODS: General and clinical data were collected from April to September 2021 from smoking asthmatics aged ≥14 years attending the People's Hospital of Zhengzhou University. Patients were followed up regularly by telephone or outpatient visits, and their medication and follow-up visits were recorded during the 6-months follow-up visit, as well as their asthma control levels after 6 months (asthma control questionnaire-5, ACQ-5). The study employed R4.2.2 software to conduct univariate and multivariate logistic regression analyses to identify independent risk factors for 'poorly controlled asthma' (ACQ>0.75) as the outcome variable. Subsequently, a nomogram prediction model was constructed. Internal validation was used to test the reproducibility of the model. The model efficacy was evaluated using the consistency index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve. RESULTS: Invitations were sent to 231 asthmatics who smoked. A total of 202 participants responded, resulting in a final total of 190 participants included in the model development. The nomogram established five independent risk factors (P<0.05): FEV1%pred, smoking index (100), comorbidities situations, medication regimen, and good or poor medication adherence. The area under curve (AUC) of the modeling set was 0.824(95%CI 0.765-0.884), suggesting that the nomogram has a high ability to distinguish poor asthma control in smoking asthmatics after 6 months. The calibration curve showed a C-index of 0.824 for the modeling set and a C-index of 0.792 for the self-validation set formed by 1000 bootstrap sampling, which means that the prediction probability of the model was consistent with reality. Decision curve analysis (DCA) of the nomogram revealed that the net benefit was higher when the risk threshold probability for poor asthma control was 4.5 - 93.9%. CONCLUSIONS: FEV1%pred, smoking index (100), comorbidities situations, medication regimen, and medication adherence were identified as independent risk factors for poor asthma control after 6 months in smoking asthmatics. The nomogram established based on these findings can effectively predict relevant risk and provide clinicians with a reference to identify the poorly controlled population with smoking asthma as early as possible, and to select a better therapeutic regimen. Meanwhile, it can effectively improve the medication adherence and the degree of attention to complications in smoking asthma patients.


Assuntos
Asma , Nomogramas , Fumar , Humanos , Asma/tratamento farmacológico , Asma/fisiopatologia , Masculino , Feminino , Fatores de Risco , Adulto , Pessoa de Meia-Idade , Fumar/epidemiologia , Fumar/efeitos adversos , Curva ROC , Modelos Logísticos , China/epidemiologia , Inquéritos e Questionários , Prognóstico , Reprodutibilidade dos Testes
9.
Gen Physiol Biophys ; 43(2): 153-162, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38477605

RESUMO

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARß antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARß. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors.


Assuntos
Isoflavonas , PPAR alfa , PPAR gama , Humanos , PPAR alfa/metabolismo , Células Endoteliais , Glucose
10.
Int J Mol Sci ; 25(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732022

RESUMO

The molecular weight (MW) of an enzyme is a critical parameter in enzyme-constrained models (ecModels). It is determined by two factors: the presence of subunits and the abundance of each subunit. Although the number of subunits (NS) can potentially be obtained from UniProt, this information is not readily available for most proteins. In this study, we addressed this gap by extracting and curating subunit information from the UniProt database to establish a robust benchmark dataset. Subsequently, we propose a novel model named DeepSub, which leverages the protein language model and Bi-directional Gated Recurrent Unit (GRU), to predict NS in homo-oligomers solely based on protein sequences. DeepSub demonstrates remarkable accuracy, achieving an accuracy rate as high as 0.967, surpassing the performance of QUEEN. To validate the effectiveness of DeepSub, we performed predictions for protein homo-oligomers that have been reported in the literature but are not documented in the UniProt database. Examples include homoserine dehydrogenase from Corynebacterium glutamicum, Matrilin-4 from Mus musculus and Homo sapiens, and the Multimerins protein family from M. musculus and H. sapiens. The predicted results align closely with the reported findings in the literature, underscoring the reliability and utility of DeepSub.


Assuntos
Bases de Dados de Proteínas , Aprendizado Profundo , Subunidades Proteicas , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Animais , Humanos , Multimerização Proteica , Camundongos , Biologia Computacional/métodos
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(5): 586-590, 2024 May 10.
Artigo em Zh | MEDLINE | ID: mdl-38684306

RESUMO

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene. METHODS: A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c.548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4). CONCLUSION: Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.


Assuntos
Proteínas Ribossômicas , Humanos , Feminino , Adulto , Proteínas Ribossômicas/genética , Gravidez , Sequenciamento do Exoma , Fenótipo , Osteocondrodisplasias/genética , Nanismo/genética , Mutação de Sentido Incorreto , Testes Genéticos
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 762-768, 2024 May 20.
Artigo em Zh | MEDLINE | ID: mdl-38948302

RESUMO

Objective: Ultrasound diagnosis and treatment is easy to perform and takes little time. It is widely used in clinical practice thanks to its non-invasive, real-time, and dynamic characteristics. In the process of ultrasound diagnosis and treatment, the probe may come into contact with the skin, the mucous membranes, and even the sterile parts of the body. However, it is difficult to achieve effective real-time disinfection of the probes after use and the probes are often reused, leading to the possibility of the probes carrying multiple pathogenic bacteria. At present, the processing methods for probes at home and abroad mainly include probe cleaning, probe disinfection, and physical isolation (using probe covers or sheaths). Yet, each approach has its limitations and cannot completely prevent probe contamination and infections caused by ultrasound diagnosis and treatment. For example, when condoms are used as the probe sheath, the rate of condom breakage is relatively high. The cutting and fixing of cling film or freezer bags involves complicated procedures and is difficult to perform. Disposable plastic gloves are prone to falling off and causing contamination and are hence not in compliance with the principles of sterility. Furthermore, the imaging effect of disposable plastic gloves is poor. Therefore, there is an urgent need to explore new materials to make probe covers that can not only wrap tightly around the ultrasound probe, but also help achieve effective protection and rapid reuse. Based on the concept of physical barriers, we developed in this study a heat sealing system for the rapid reuse of ultrasound probes. The system uses a heat sealing device to shrink the protective film so that it wraps tightly against the surface of the ultrasound probe, allowing for the rapid reuse of the probe while reducing the risk of nosocomial infections. The purpose of this study is to design a heat sealing system for the rapid reuse of ultrasound probes and to verify its application effect on the rapid reuse of ultrasound probes. Methods: 1) The heat sealing system for the rapid reuse of ultrasound probes was designed and tested by integrating medical and engineering methods. The system included a protective film (a multilayer co-extruded polyolefin thermal shrinkable film) and a heat sealing device, which included heating wire components, a blower, a photoelectric switch, temperature sensors, a control and drive circuit board, etc. According to the principle of thermal shrinkage, the ultrasound probe equipped with thermal shrinkable film was rapidly heated and the film would wrap closely around the ultrasound probe placed on the top of the heat sealing machine. The ultrasound probe was ready for use after the thermal shrinkage process finished. Temperature sensors were installed on the surface of the probe to test the thermal insulation performance of the system. The operation procedures of the system are as follows: placing the ultrasound probe covered with the protective film in a certain space above the protective air vent, which is detected by the photoelectric switch; the heating device heats the thermal shrinkable film with a constant flow of hot air at a set temperature value. Then, the probe is rotated so that the thermal shrinkable film will quickly wrap around the ultrasound probe. After the heat shrinking is completed, the probe can be used directly. 2) Using the convenience sampling method, 90 patients from the Department of Anesthesiology and Perioperative Medicine, the First Affiliated Hospital of Xi'an Jiaotong University were included as the research subjects. All patients were going to undergo arterial puncture under ultrasound guidance. The subjects were divided into 3 groups, with 30 patients in each group. Three measures commonly applied in clinical practice were used to process the probes in the three groups and water-soluble fluorescent labeling was applied around the puncture site before use. In the experimental group, the probes were processed with the heat sealing system. The standard operating procedures of the heat sealing system for rapid reuse of ultrasonic probes were performed to cover the ultrasonic probe and form a physical barrier to prevent probe contamination. There were two control groups. In control group 1, disinfection wipes containing double-chain quaternary ammonium salt were used to repeatedly wipe the surface of the probe for 10-15 times, and then the probe was ready for use once it dried up. In the control group 2, a disposable protective sheath was used to cover the front end of the probe and the handle end of the sheath was tied up with threads. Comparison of the water-soluble fluorescent labeling on the surface of the probe (which reflected the colony residues on the surface of the probe) before and after use and the reuse time (i.e., the lapse of time from the end of the first use to the beginning of the second use) were made between the experimental group and the two control groups. Results: 1) The temperature inside the ultrasound probe was below 40 ℃ and the heat sealing system for rapid reuse did not affect the performance of the ultrasound probe. 2) The reuse time in the heat sealing system group, as represented by (median [P25, P75]), was (8.00 [7.00, 10.00]) s, which was significantly lower than those of the disinfection wipe group at (95.50 [8.00, 214.00]) s and the protective sleeve group at (25.00 [8.00, 51.00]) s, with the differences being statistically significant (P<0.05). No fluorescence residue was found on the probe in either the heat sealing system group or the protective sheath group after use. The fluorescence residue in the heat sealing system group was significantly lower than that in the disinfection wipes group, showing statistically significant differences (χ 2=45.882, P<0.05). Conclusion: The thermal shrinkable film designed and developed in this study can be cut and trimmed according to the size of the equipment. When the film is heated, it shrinks and wraps tightly around the equipment, forming a sturdy protective layer. With the heat sealing system for rapid reuse of ultrasonic probes, we have realized the semi-automatic connection between the thermal shrinkable film and the heating device, reducing the amount of time-consuming and complicated manual operation. Furthermore, the average reuse time is shortened and the system is easy to use, which contributes to improvements in the reuse and operation efficiency of ultrasound probes. The heat sealing system reduces colony residues on the surface of the probe and forms an effective physical barrier on the probe. No probes were damaged in the study. The heat sealing system for rapid reuse of ultrasonic probes can be used as a new method to process the ultrasonic probes.


Assuntos
Ultrassonografia , Ultrassonografia/instrumentação , Ultrassonografia/métodos , Temperatura Alta , Reutilização de Equipamento , Humanos , Desinfecção/métodos , Desinfecção/instrumentação , Desenho de Equipamento , Contaminação de Equipamentos/prevenção & controle
13.
Angew Chem Int Ed Engl ; : e202409541, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935325

RESUMO

Sulfur-containing functional groups have garnered considerable attention owing to their frequent occurrence in ligands, pharmaceuticals and insecticides. However, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging and long-standing goal. Herein we report a highly enantio- and chemoselective cross-coupling of sulfenamides with aryl electrophiles to construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide groups were crucial for attaining high reactivity and selectivity. This strategy offers a general, modular and divergent platform for rapid synthesis of chiral sulfilimines and sulfoximines that are otherwise difficult to access. Furthermore, the origins of the high chemoselectivity and enantioselectivity were extensively investigated using density functional theory calculations.

14.
Neuroimage ; 281: 120374, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37729795

RESUMO

The study of neural circuits, which underlies perception, cognition, emotion, and behavior, is essential for understanding the mammalian brain, a complex organ consisting of billions of neurons. To study the structure and function of the brain, in vivo neuronal labeling and imaging techniques are crucial as they provide true physiological information that ex vivo methods cannot offer. In this paper, we present a new strategy for in vivo neuronal labeling and quantification using MRI. We demonstrate the efficacy of this method by delivering the oatp1a1 gene to the target neurons using rAAV2-retro virus. OATP1A1 protein expression on the neuronal membrane increased the uptake of a specific MRI contrast agent (Gd-EOB-DTPA), leading to hyperintense signals on T1W images of labeled neuronal populations. We also used dynamic contrast enhancement-based methods to obtain quantitative information on labeled neuronal populations in vivo.

15.
Anal Chem ; 95(33): 12240-12246, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37556358

RESUMO

Ferroptosis is an iron-regulated, caspase-mediated pathway of cell death that is associated with the excessive aggregation of lipid-reactive oxygen species and is extensively involved in the evolution of many diseases, including epilepsy. The superoxide anion (O2•-), as the primary precursor of ROS, is closely related to ferroptosis-mediated epilepsy. Therefore, it is crucial to establish a highly effective and convenient method for the real-time dynamic monitoring of O2•- during the ferroptosis process in epilepsy for the diagnosis and therapy of ferroptosis-mediated epilepsy. Nevertheless, no probes for detecting O2•- in ferroptosis-mediated epilepsy have been reported. Herein, we systematically conceptualized and developed a novel near-infrared (NIR) fluorescence probe, NIR-FP, for accurately tracking the fluctuation of O2•- in ferroptosis-mediated epilepsy. The probe showed exceptional sensitivity and outstanding selectivity toward O2•-. In addition, the probe has been utilized effectively to bioimage and evaluate endogenous O2•- variations in three types of ferroptosis-mediated epilepsy models (the kainic acid-induced chronic epilepsy model, the pentylenetetrazole-induced acute epilepsy model, and the pilocarpine-induced status epilepticus model). The above applications illustrated that NIR-FP could serve as a reliable and suitable tool for guiding the accurate diagnosis and therapy of ferroptosis-mediated epilepsy.


Assuntos
Epilepsia , Ferroptose , Humanos , Superóxidos/metabolismo , Fluorescência , Epilepsia/diagnóstico por imagem , Epilepsia/metabolismo , Espécies Reativas de Oxigênio
16.
Small ; 19(44): e2303251, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37376823

RESUMO

In this paper, strong hydrophilic poly(ionic liquid)s (PILs) are selectively grafted on different positions (mesoporous channels and outer surface) of mesoporous silica via thiol-ene click chemical reaction. The purposes of selective grafting are on the one hand, to explore the differences of adsorption and transportation of water molecules in mesoporous channels and on the outer surface, and on the other hand, to combine the two approaches (intra-pore grafting and external surface grafting) to reasonably design SiO2 @PILs low humidity sensing film with synergetic function to achieve high sensitivity. The results of low relativehumidity (RH) sensing test show that the sensing performance of humidity sensor based on mesoporous silica grafted with PILs in the channels is better than that of humidity sensor based on mesoporous silica grafted with PILs on the outer surface. Compared with water molecules transport single channel, the construction of dual-channel water transport significantly improves the sensitivity of the low humidity sensor, and the response of the sensor is up to 4112% in the range of 7-33% RH. Moreover, the existence of micropores and the formation of dual-channel water transport affect the adsorption/desorption behaviors of the sensor under different humidity ranges, especially below 11% RH.

17.
J Med Virol ; 95(10): e29198, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37881113

RESUMO

Human mpox is occurring worldwide, however, evidence from the Asian Pacific Region is limited. In this multicenter cross-sectional study, information of confirmed mpox cases diagnosed between June 1 and July 31, 2023 in China. Information included demographic and epidemiological characteristics, and clinical manifestations, laboratory results, and mental health status of mpox cases. A total of 115 confirmed mpox cases were enrolled. All cases were men. A total of 102 (90.3%) identified as homosexual. The median age was 31.0 years (interquartile range 27.0-36.5). A total of 65 (56.5%) were HIV-positive, of whom 92.3% were receiving antiretroviral therapy (ART). A total of 19/39 (40.4%) had a CD4 cell count <500 cells/µL. Systemic features such as fever (73.0%), lymphadenopathies (49.6%), and myalgia (28.7%) were commonly observed. Skin lesions were present in all participants: 49.6% in the genital area and 27.0% in the perianal area. Vesicular rash (78.3%) and papular rash (44.3%) were the most common lesion morphologies. People living with HIV were more likely to have anxiety than those living without HIV. The majority of mpox cases had primary genital lesions and sexual activities before diagnosis, which supports the likelihood of sexual contact transmission. Guidelines on hospitalization and isolation protocols for mpox patients necessitate further confirmation.


Assuntos
Exantema , Infecções por HIV , Mpox , Adulto , Humanos , Masculino , China/epidemiologia , Estudos Transversais , Nível de Saúde , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia
18.
Plant Physiol ; 190(4): 2122-2136, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-35947689

RESUMO

Linarin (acacetin-7-O-rutinoside), isorhoifolin (apigenin-7-O-rutinoside), and diosmin (diosmetin-7-O-rutinoside) are chemically and structurally similar flavone rutinoside (FR) compounds found in Chrysanthemum L. (Anthemideae, Asteraceae) plants. However, their biosynthetic pathways remain largely unknown. In this study, we cloned and compared FRs and genes encoding rhamnosyltransferases (RhaTs) among eight accessions of Chrysanthemum polyploids. We also biochemically characterized RhaTs of Chrysanthemum plants and Citrus (Citrus sinensis and Citrus maxima). RhaTs from these two genera are substrate-promiscuous enzymes catalyzing the rhamnosylation of flavones, flavanones, and flavonols. Substrate specificity analysis revealed that Chrysanthemum 1,6RhaTs preferred flavone glucosides (e.g. acacetin-7-O-glucoside), whereas Cs1,6RhaT preferred flavanone glucosides. The nonsynonymous substitutions of RhaTs found in some cytotypes of diploids resulted in the loss of catalytic function. Phylogenetic analysis and specialized pathways responsible for the biosynthesis of major flavonoids in Chrysanthemum and Citrus revealed that rhamnosylation activity might share a common evolutionary origin. Overexpression of RhaT in hairy roots resulted in 13-, 2-, and 5-fold increases in linarin, isorhoifolin, and diosmin contents, respectively, indicating that RhaT is mainly involved in the biosynthesis of linarin. Our findings not only suggest that the substrate promiscuity of RhaTs contributes to the diversity of FRs in Chrysanthemum species but also shed light on the evolution of flavone and flavanone rutinosides in distant taxa.


Assuntos
Chrysanthemum , Citrus , Diosmina , Flavonas , Chrysanthemum/genética , Chrysanthemum/química , Filogenia , Flavonoides , Flavonas/química , Glucosídeos/química
19.
Microvasc Res ; 148: 104531, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36963481

RESUMO

In diabetes mellitus (DM), high glucose can result in endothelial cell injury, and then lead to diabetic vascular complications. Gastrodin, as the mainly components of Chinese traditional herb Tianma (Gastrodia elata Bl.), has been widely used for cardiovascular diseases. However, the known of the effect of gastrodin on endothelial cell injury is still limited. In this study, we aimed to investigate the effect and possible mechanism of gastrodin on high glucose-injured human umbilical vein endothelial cells (HUVEC). High glucose (30 mmol/L) treatment caused HUVEC injury. After gastrodin (0.1, 1, 10 µmol/L) treatment, compared with the high glucose group, the cell proliferation ability increased in a dose-dependent manner. Meanwhile, gastrodin (10 µmol/L) up-regulated the mRNA and protein expressions of PPARß and eNOS, decreased the expressions of iNOS, also reduced the protein expression of 3-nitrotyrosine, and lowed the level of ONOO-, increased NO content. Both the PPARß antagonist GSK0660 (1 µmol/L) and the eNOS inhibitor L-NAME (10 µmol/L) were able to block the above effects of gastrodin. In conclusion, gastrodin protectes vascular endothelial cells from high glucose injury, which may be, at least partly, mediated by up-regulating the expression of PPARß and negatively regulating nitrative stress.


Assuntos
PPAR beta , Humanos , PPAR beta/metabolismo , Regulação para Cima , Células Endoteliais da Veia Umbilical Humana/metabolismo , Glucose/toxicidade , Glucose/metabolismo
20.
Opt Lett ; 48(12): 3179-3182, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37319056

RESUMO

A simple polarization-insensitive coherent radio-over-fiber (RoF) link with increased spectrum efficiency and transmission capacity is proposed and demonstrated. Instead of using two polarization splitters (PBSs), two 90° hybrids, and four pairs of balanced photodetectors (PDs) in a conventional polarization-diversity coherent receiver (PDCR), a simplified PDCR with only one PBS, one optical coupler (OC), and two PDs is employed in the coherent RoF link. At the simplified receiver, a novel, to the best of our knowledge, digital signal processing (DSP) algorithm is proposed to achieve polarization-insensitive detection and demultiplexing of two spectrally overlapping microwave vector signals as well as the elimination of the joint phase noise originating from the transmitter and the local oscillator (LO) laser sources. An experiment is performed. The transmission and detection of two independent 16QAM microwave vector signals at identical microwave carrier frequencies of 3 GHz with a symbol rate of 0.5 GSym/s over a 25-km single-mode fiber (SMF) is demonstrated. Thanks to the spectrum superposition of the two microwave vector signals, the spectral efficiency as well as the data transmission capacity is increased.


Assuntos
Telecomunicações , Desenho de Equipamento , Análise de Falha de Equipamento , Processamento de Sinais Assistido por Computador
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