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1.
Proc Natl Acad Sci U S A ; 121(20): e2318384121, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38713627

RESUMO

The reaction kinetics of photocatalytic CO2 reduction is highly dependent on the transfer rate of electrons and protons to the CO2 molecules adsorbed on catalytic centers. Studies on uncovering the proton effect in catalysts on photocatalytic activity of CO2 reduction are significant but rarely reported. In this paper, we, from the molecular level, revealed that the photocatalytic activity of CO2 reduction is closely related to the proton availability in catalysts. Specifically, four dinuclear Co(II) complexes based on Robson-type ligands with different number of carboxylic groups (-nCOOH; n = 0, 2, 4, 6) were designed and synthesized. All these complexes show photocatalytic activity for CO2 reduction to CO in a water-containing system upon visible-light illumination. Interestingly, the CO yields increase positively with the increase of the carboxylic-group number in dinuclear Co(II) complexes. The one containing -6COOH shows the best photocatalytic activity for CO2 reduction to CO, with the TON value reaching as high as 10,294. The value is 1.8, 3.4, and 7.8 times higher than those containing -4COOH, -2COOH, and -0COOH, respectively. The high TON value also makes the dinuclear Co(II) complex with -6COOH outstanding among reported homogeneous molecular catalysts for photocatalytic CO2 reduction. Control experiments and density functional theory calculation indicated that more carboxylic groups in the catalyst endow the catalyst with more proton relays, thus accelerating the proton transfer and boosting the photocatalytic CO2 reduction. This study, at a molecular level, elucidates that more carboxylic groups in catalysts are beneficial for boosting the reaction kinetics of photocatalytic CO2 reduction.

2.
Invest Ophthalmol Vis Sci ; 65(5): 8, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38700874

RESUMO

Purpose: In the present study, we aim to elucidate the underlying molecular mechanism of endoplasmic reticulum (ER) stress induced delayed corneal epithelial wound healing and nerve regeneration. Methods: Human limbal epithelial cells (HLECs) were treated with thapsigargin to induce excessive ER stress and then RNA sequencing was performed. Immunofluorescence, qPCR, Western blot, and ELISA were used to detect the expression changes of SLIT3 and its receptors ROBO1-4. The role of recombinant SLIT3 protein in corneal epithelial proliferation and migration were assessed by CCK8 and cell scratch assay, respectively. Thapsigargin, exogenous SLIT3 protein, SLIT3-specific siRNA, and ROBO4-specific siRNA was injected subconjunctivally to evaluate the effects of different intervention on corneal epithelial and nerve regeneration. In addition, Ki67 staining was performed to evaluate the proliferation ability of epithelial cells. Results: Thapsigargin suppressed normal corneal epithelial and nerve regeneration significantly. RNA sequencing genes related to development and regeneration revealed that thapsigargin induced ER stress significantly upregulated the expression of SLIT3 and ROBO4 in corneal epithelial cells. Exogenous SLIT3 inhibited normal corneal epithelial injury repair and nerve regeneration, and significantly suppressed the proliferation and migration ability of cultured mouse corneal epithelial cells. SLIT3 siRNA inhibited ROBO4 expression and promoted epithelial wound healing under thapsigargin treatment. ROBO4 siRNA significantly attenuated the delayed corneal epithelial injury repair and nerve regeneration induced by SLIT3 treatment or thapsigargin treatment. Conclusions: ER stress inhibits corneal epithelial injury repair and nerve regeneration may be related with the upregulation of SLIT3-ROBO4 pathway.


Assuntos
Proliferação de Células , Estresse do Retículo Endoplasmático , Epitélio Corneano , Regeneração Nervosa , Receptores Imunológicos , Proteínas Roundabout , Transdução de Sinais , Cicatrização , Animais , Humanos , Camundongos , Western Blotting , Movimento Celular/fisiologia , Células Cultivadas , Estresse do Retículo Endoplasmático/fisiologia , Ensaio de Imunoadsorção Enzimática , Epitélio Corneano/metabolismo , Limbo da Córnea/citologia , Regeneração Nervosa/fisiologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Transdução de Sinais/fisiologia , Cicatrização/fisiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38653931

RESUMO

PURPOSE: The absence of clinically applicable imaging techniques for continuous monitoring of transplanted cells poses a significant obstacle to the clinical translation of stem cell-based therapies for vascular regeneration. This study aims to optimize a clinically applicable, non-invasive imaging technique to longitudinally monitor vascular endothelial cells (ECs) for vascular regeneration in peripheral artery disease (PAD). METHODS: Human induced pluripotent stem cells (HiPSCs) were employed to generate ECs (HiPSC-ECs). Lentiviral vectors encoding human sodium iodide symporter (hNIS) and enhanced green fluorescent protein (eGFP) genes were introduced to HiPSCs and HiPSC-ECs at varying multiplicities of infection (MOI). Through a combination of fluorescence microscopy and flow cytometry, an optimized transduction technique for introducing hNIS-eGFP into HiPSC-ECs was established. Subsequently, single-photon emission computed tomography (SPECT) was utilized for imaging of the transduced cells in vitro and in vivo after transplantation into the gastrocnemius muscle of nude mice. RESULTS: Lentiviral transduction resulted in sustained co-expression of hNIS and eGFP in HiPSC-ECs when transduced post-endothelial differentiation. An optimal MOI of five yielded over 90% hNIS-eGFP expression efficiency without compromising cell viability. hNIS-eGFP+ HiPSC-ECs exhibited 99mTc uptake and were detectable through SPECT in vitro. Additionally, intramuscular injection of hNIS-eGFP+ HiPSC-ECs with MatrigelTM into the hindlimbs of nude mice enabled real-time SPECT/CT tracking, from which a reduction in signal exceeding 80% was observed within 7 days. CONCLUSIONS: This study establishes an optimized cell modification and imaging protocol for tracking transplanted cells. Future efforts will focus on enhancing cell survival and integration via improved delivery systems, thereby advancing the potential of cell-based therapies for PAD.

4.
Cancer Rep (Hoboken) ; 7(3): e1991, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38441306

RESUMO

BACKGROUND: Surgical resection remains the primary treatment option for gallbladder carcinoma (GBC). However, there is a pressing demand for prognostic tools that can refine patients' treatment choices and tailor personalized therapies accordingly. AIMS: The nomograms were constructed using the data of a training cohort (n = 378) of GBC patients at Eastern Hepatobiliary Surgery Hospital (EHBH) between 2008 and 2018. The model's performance was validated in GBC patients (n = 108) at Guangzhou Centre from 2007 to 2018. METHODS AND RESULTS: The 5-year overall survival (OS) rate in the training cohort was 24.4%. Multivariate analyses were performed using preoperative and postoperative data to identify independent predictors of OS. These predictors were then incorporated into preoperative and postoperative nomograms, respectively. The C-index of the preoperative nomogram was 0.661 (95% CI, 0.627 to 0.694) for OS prediction and correctly delineated four subgroups (5-year OS rates: 48.1%, 19.0%, 15.6%, and 8.1%, p < 0.001). The C-index of the postoperative nomogram was 0.778 (95%CI, 0.756 -0.800). Furthermore, this nomogram was superior to the 8th TNM system in both C-index and the net benefit on decision curve analysis. The results were externally validated. CONCLUSION: The two nomograms showed an optimally prognostic prediction in GBC patients after curative-intent resection.


Assuntos
Neoplasias da Vesícula Biliar , Nomogramas , Humanos , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/cirurgia , Período Pós-Operatório
5.
Anal Chem ; 96(14): 5499-5508, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38547315

RESUMO

Characterizing the profiles of proteome and metabolome at the single-cell level is of great significance in single-cell multiomic studies. Herein, we proposed a novel strategy called one-shot single-cell proteome and metabolome analysis (scPMA) to acquire the proteome and metabolome information in a single-cell individual in one injection of LC-MS/MS analysis. Based on the scPMA strategy, a total workflow was developed to achieve the single-cell capture, nanoliter-scale sample pretreatment, one-shot LC injection and separation of the enzyme-digested peptides and metabolites, and dual-zone MS/MS detection for proteome and metabolome profiling. Benefiting from the scPMA strategy, we realized dual-omic analysis of single tumor cells, including A549, HeLa, and HepG2 cells with 816, 578, and 293 protein groups and 72, 91, and 148 metabolites quantified on average. A single-cell perspective experiment for investigating the doxorubicin-induced antitumor effects in both the proteome and metabolome aspects was also performed.


Assuntos
Proteoma , Espectrometria de Massas em Tandem , Humanos , Proteoma/metabolismo , Cromatografia Líquida , Metaboloma , Células HeLa
6.
Nat Commun ; 15(1): 1279, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341466

RESUMO

The shotgun proteomic analysis is currently the most promising single-cell protein sequencing technology, however its identification level of ~1000 proteins per cell is still insufficient for practical applications. Here, we develop a pick-up single-cell proteomic analysis (PiSPA) workflow to achieve a deep identification capable of quantifying up to 3000 protein groups in a mammalian cell using the label-free quantitative method. The PiSPA workflow is specially established for single-cell samples mainly based on a nanoliter-scale microfluidic liquid handling robot, capable of achieving single-cell capture, pretreatment and injection under the pick-up operation strategy. Using this customized workflow with remarkable improvement in protein identification, 2449-3500, 2278-3257 and 1621-2904 protein groups are quantified in single A549 cells (n = 37), HeLa cells (n = 44) and U2OS cells (n = 27) under the DIA (MBR) mode, respectively. Benefiting from the flexible cell picking-up ability, we study HeLa cell migration at the single cell proteome level, demonstrating the potential in practical biological research from single-cell insight.


Assuntos
Proteoma , Proteômica , Animais , Humanos , Células HeLa , Proteômica/métodos , Proteoma/metabolismo , Análise de Célula Única , Fluxo de Trabalho , Mamíferos/metabolismo
7.
Chem Biol Drug Des ; 103(1): e14410, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38230794

RESUMO

Triptolide (TPL), the main active ingredient of Tripterygium wilfordii, has anti-inflammatory, immunomodulatory, and antitumor actions. It can also inhibit cell proliferation and metastasis while promoting apoptosis of several tumors, such as colorectal cancer (CRC). However, the mechanism of TPL against CRC is not clear. This study was designed to investigate the effects and molecular mechanisms of TPL on the proliferation and invasion ability of CRC cells. A human CRC cell line (HT29 cell line) cultured in vitro was treated with different concentrations of TPL (0, 25, 50, and 100 nmol/L). The proliferation of cells was detected by MTT, the invasion ability of cells by Transwell, and the apoptosis level by flow cytometry. The protein expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), matrix metalloproteinase (MMP)-2, and MMP-9 were detected by western blotting. After transfection with sh-Nrf2, HT29 cells were divided into NC group, NC + TPL group and sh-Nrf2 + TPL group, and the above assays were repeated for each group. TPL significantly inhibited the proliferation and invasion ability of HT29 cells and promoted apoptosis (p < .05). Notably, its inhibitory or promotional effects were concentration-dependent, which were enhanced with increasing drug concentration (p < .05). After silencing Nrf2 expression, the proliferation, and invasion ability of HT29 cells were further significantly inhibited while cells apoptosis was further promoted (p < .05). Besides, the decreased Nrf2 expression reduced the protein expression levels of MMP-2 and MMP-9 (p < .05). TPL can effectively inhibit the proliferation and invasion while promoting apoptosis of HT29 cells. And its mechanism of action may be related to the inhibition of Nrf2 signaling expression.


Assuntos
Neoplasias Colorretais , Diterpenos , Fenantrenos , Humanos , Metaloproteinase 9 da Matriz/genética , Fator 2 Relacionado a NF-E2 , Proliferação de Células , Diterpenos/farmacologia , Apoptose , Compostos de Epóxi/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico
8.
Adv Mater ; 36(6): e2306326, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38043945

RESUMO

Regenerative medicine aims to restore tissue and organ function without the use of prosthetics and permanent implants. However, achieving this goal has been elusive, and the field remains mostly an academic discipline with few products widely used in clinical practice. From a materials science perspective, barriers include the lack of proregenerative biomaterials, a complex regulatory process to demonstrate safety and efficacy, and user adoption challenges. Although biomaterials, particularly biodegradable polymers, can play a major role in regenerative medicine, their suboptimal mechanical and degradation properties often limit their use, and they do not support inherent biological processes that facilitate tissue regeneration. As of 2020, nine synthetic biodegradable polymers used in medical devices are cleared or approved for use in the United States of America. Despite the limitations in the design, production, and marketing of these devices, this small number of biodegradable polymers has dominated the resorbable medical device market for the past 50 years. This perspective will review the history and applications of biodegradable polymers used in medical devices, highlight the need and requirements for regenerative biomaterials, and discuss the path behind the recent successful introduction of citrate-based biomaterials for manufacturing innovative medical products aimed at improving the outcome of musculoskeletal surgeries.


Assuntos
Materiais Biocompatíveis , Engenharia Tecidual , Materiais Biocompatíveis/farmacologia , Ácido Cítrico , Medicina Regenerativa , Polímeros , Citratos
9.
Cell Rep ; 42(11): 113455, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37976159

RESUMO

Although single-cell multi-omics technologies are undergoing rapid development, simultaneous transcriptome and proteome analysis of a single-cell individual still faces great challenges. Here, we developed a single-cell simultaneous transcriptome and proteome (scSTAP) analysis platform based on microfluidics, high-throughput sequencing, and mass spectrometry technology to achieve deep and joint quantitative analysis of transcriptome and proteome at the single-cell level, providing an important resource for understanding the relationship between transcription and translation in cells. This platform was applied to analyze single mouse oocytes at different meiotic maturation stages, reaching an average quantification depth of 19,948 genes and 2,663 protein groups in single mouse oocytes. In particular, we analyzed the correlation of individual RNA and protein pairs, as well as the meiosis regulatory network with unprecedented depth, and identified 30 transcript-protein pairs as specific oocyte maturational signatures, which could be productive for exploring transcriptional and translational regulatory features during oocyte meiosis.


Assuntos
Proteoma , Transcriptoma , Animais , Camundongos , Transcriptoma/genética , Proteoma/metabolismo , Oócitos/metabolismo , Oogênese/genética , Perfilação da Expressão Gênica , Meiose
10.
Gynecol Endocrinol ; 39(1): 2264983, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37857342

RESUMO

OBJECTIVE: This study aimed to collect, organize, and conduct a meta-analysis of the literature on the expression of silent information regulator two homolog 1 (SIRT1) in the placental tissue and plasma of patients with pre-eclampsia. METHODS: The enrolled patients were divided into two groups: the pre-eclampsia group and the healthy group. This study summarized and analyzed the demographic characteristics of the two groups, including pregnancy age, gestational weeks, parity, gravidity, blood pressure, Body Mass Index, newborn weight, placental weight, and SIRT1 expression in placental tissue and maternal plasma. RESULTS: Eleven studies were included in this research, with 586 cases in the pre-eclampsia group and 479 cases in the control group. Three research studies are reporting immunohistochemistry tests, among which the pre-eclampsia group had a positivity rate of 30.24% (62/205), while the control group had 58.02% (76/131); the two groups have a significant difference (p < 0.05). Two research studies reported the results of ELISA tests, with 107 cases in the pre-eclampsia group and 125 cases in the control group. A comparison of the SIRT1 test results showed a statistically significant difference between the two groups (p < 0.05). Pre-eclampsia group patients had lower gestational weeks, newborn birth weight, and placental weight compared to the healthy control group (all p < 0.05). However, systolic and diastolic blood pressures were higher in the pre-eclampsia group than in the control group (p < 0.05). CONCLUSION: SIRT1 expression is downregulated in pre-eclampsia patients' plasma and placental tissue. Further research is needed to validate this conclusion.


Assuntos
Placenta , Pré-Eclâmpsia , Sirtuína 1 , Feminino , Humanos , Recém-Nascido , Gravidez , Peso ao Nascer , Idade Materna , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/metabolismo , Sirtuína 1/biossíntese , Sirtuína 1/sangue
11.
Cell Div ; 18(1): 17, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872600

RESUMO

BACKGROUND: LncRNAs have been shown to be involved in and control the biological processes of multiple diseases, including preeclampsia (PE). The impairment of trophoblast cell proliferation is recognized as a significant anomaly contributing to the development of PE. LncRNA FEZF1-AS1 was found downregulated in placental tissues of PE patients. However, the precise regulatory mechanism of FEZF1-AS1 in placental trophoblast proliferation and apoptosis remains unclear. RESULTS: In this study, we conducted an investigation into the expression levels of FEZF1-AS1 and NOC2L in placental tissues obtained from patients diagnosed with PE. Subsequently, we employed CCK-8 and EdU assays to quantify cell proliferation, while TUNEL staining and western blot for apoptosis-related protein detection to assess apoptosis. Furthermore, the interactions between FEZF1-AS1 and ELAVL1, as well as NOC2L and ELAVL1, were confirmed through the implementation of RIP and RNA pull-down assays. We found a downregulation of lncRNA FEZF1-AS1 and NOC2L in placental tissues of PE patients. Overexpression of FEZF1-AS1 or NOC2L resulted in increased cell proliferation and inhibition of apoptosis, whereas knockdown of FEZF1-AS1 or NOC2L had the opposite effect. In addition, lncRNA FEZF1-AS1 stabilized NOC2L mRNA expression by interacting with ELAVL1. Moreover, partial reversal of the effects of FEZF1-AS1 overexpression on cell proliferation and apoptosis was observed upon suppression of ELAVL1 or NOC2L. CONCLUSIONS: PE related lncRNA FEZF1-AS1 could regulate apoptosis and proliferation of placental trophoblast cells through the ELAVL1/NOC2L axis.

12.
Biosensors (Basel) ; 13(10)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37887107

RESUMO

Free-floating electrochemical sensors are promising for in situ bioprocess monitoring with the advantages of movability, a lowered risk of contamination, and a simplified structure of the bioreactor. Although floating sensors were developed for the measurement of physical and chemical indicators such as temperature, velocity of flow, pH, and dissolved oxygen, it is the lack of available electrochemical sensors for the determination of the inorganic ions in bioreactors that has a significant influence on cell culture. In this study, a capsule-shaped electrochemical system (iCapsuleEC) is developed to monitor ions including K+, NH4+, Na+, Ca2+, and Mg2+ based on solid-contact ion-selective electrodes (SC-ISEs). It consists of a disposable electrochemical sensor and signal-processing device with features including multichannel measurement, self-calibration, and wireless data transmission. The capacities of the iCapsuleEC were demonstrated not only for in situ measurement of ion concentrations but also for the optimization of the sensing electrodes. We also explored the possibility of the system for use in detection in simulated cell culture media.


Assuntos
Reatores Biológicos , Eletrodos Seletivos de Íons , Íons , Calibragem , Técnicas de Cultura de Células
13.
J Refract Surg ; 39(7): 482-490, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37449507

RESUMO

PURPOSE: To investigate the impact of corneal toricity on the distribution characteristics of corneal epithelial thickness (CET). METHODS: A total of 330 eyes in 330 healthy participants were included in this study. They were divided into two groups based on the median of the corneal toricity value: low-toricity group (corneal toricity < 1.50 diopters) and high-toricity group (corneal toricity ≥ 1.50 diopters). The CET within a 9-mm-diameter area of the central cornea was obtained using optical coherence tomography. The difference of CET value between flat and steep meridians (F-S CET) was defined to evaluate the CET distribution. The F-S CET between the two groups was compared, and the correlations between F-S CET and the corneal toricity were analyzed. RESULTS: The CET was thinner in the superior-peripheral area than in other areas. A slight intergroup difference was noted in terms of the F-S CET at the paracentral (0.11 ± 0.93 vs 0.32 ± 0.92, P = .038), midperipheral (0.45 ± 0.78 vs 0.77 ± 0.89, P = .001), and peripheral (3.11 ± 2.18 vs 4.10 ± 2.38, P < .001) zone. In each zone, the difference in F-S CET between the two groups was less than 1 µm. As the area expanded, the F-S CET continued to increase (F = 850.303, P < .001). A weak correlation was observed between F-S CET and corneal toricity (r = 0.103 to 0.240); however, this correlation was not significant in the paracentral zone. Covariance analysis demonstrated that F-S CET was slightly correlated with age, refractive state, and intraocular pressure. CONCLUSIONS: The corneal toricity did not significantly affect the distribution of the corneal epithelium in normal corneas. [J Refract Surg. 2023;39(7):482-490.].


Assuntos
Córnea , Epitélio Corneano , Humanos , Refração Ocular , Tomografia de Coerência Óptica/métodos , Pressão Intraocular
14.
Adv Sci (Weinh) ; 10(27): e2303429, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37518771

RESUMO

Myocardial infarction (MI) is one of the leading causes of death and disability. Recently developed cardiac patches provide mechanical support and additional conductive paths to promote electrical signal propagation in the MI area to synchronize cardiac excitation and contraction. Cardiac patches based on conductive polymers offer attractive features; however, the modest levels of elasticity and high impedance interfaces limit their mechanical and electrical performance. These structures also operate as permanent implants, even in cases where their utility is limited to the healing period of tissue damaged by the MI. The work presented here introduces a highly conductive cardiac patch that combines bioresorbable metals and polymers together in a hybrid material structure configured in a thin serpentine geometry that yields elastic mechanical properties. Finite element analysis guides optimized choices of layouts in these systems. Regular and synchronous contraction of human induced pluripotent stem cell-derived cardiomyocytes on the cardiac patch and ex vivo studies offer insights into the essential properties and the bio-interface. These results provide additional options in the design of cardiac patches to treat MI and other cardiac disorders.


Assuntos
Células-Tronco Pluripotentes Induzidas , Infarto do Miocárdio , Humanos , Implantes Absorvíveis , Miócitos Cardíacos , Polímeros/química , Tecnologia
15.
Shock ; 60(3): 410-418, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37493583

RESUMO

ABSTRACT: Background: Aberrant expression of circular RNAs (circRNAs) has been revealed to have crucial roles in the pathological processes of cardiovascular disease. Here, this study aimed to investigate the role and mechanism of circ_0001379 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury to explore the potential action of circ_0001379 in acute myocardial infarction (AMI). Methods: Levels of genes and proteins were examined by quantitative real-time polymerase chain reaction and western blot. Cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry were used to detect cardiomyocyte proliferation and apoptosis, respectively. The activity of IL-1ß, IL-6, and TNF-α was determined by ELISA analysis. The target relationship between miR-98-5p and circ_0001379 or SOX6 (SRY-Box Transcription Factor 6) was verified by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0001379 was highly expressed in AMI mouse model and H/R-induced cardiomyocytes. Functionally, circ_0001379 silencing attenuated H/R-evoked cardiomyocyte apoptosis and inflammatory response. Mechanistically, circ_0001379 functioned as a sponge for miR-98-5p, which directly targeted SOX6. Moreover, circ_0001379 could regulate SOX6 expression via sponging miR-98-5p. Further rescue experiments showed that inhibition of miR-98-5p reversed the protective effects of circ_0001379 silencing on H/R-induced cardiomyocytes. Besides that, miR-98-5p overexpression abolished H/R-evoked cardiomyocyte apoptosis and inflammatory response, while this condition was abated by SOX6. Conclusion: Circ_0001379 silencing protects cardiomyocytes from H/R-induced apoptosis and inflammatory response by miR-98-5p/SOX6 axis, suggesting a novel therapeutic strategy for AMI prevention.


Assuntos
MicroRNAs , Miócitos Cardíacos , Animais , Camundongos , Apoptose/genética , Proliferação de Células , Hipóxia , MicroRNAs/genética , Fator de Necrose Tumoral alfa , RNA Circular/genética
16.
Adv Healthc Mater ; 12(31): e2301683, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37327023

RESUMO

Impaired wound healing is a common complication for diabetic patients and effective diabetic wound management remains a clinical challenge. Furthermore, a significant problem that contributes to patient morbidity is the suboptimal quality of healed skin, which often leads to reoccurring chronic skin wounds. Herein, a novel compound and biomaterial building block, panthenol citrate (PC), is developed. It has interesting fluorescence and absorbance properties, and it is shown that PC can be used in soluble form as a wash solution and as a hydrogel dressing to address impaired wound healing in diabetes. PC exhibits antioxidant, antibacterial, anti-inflammatory, and pro-angiogenic properties, and promotes keratinocyte and dermal fibroblast migration and proliferation. When applied in a splinted excisional wound diabetic rodent model, PC improves re-epithelialization, granulation tissue formation, and neovascularization. It also reduces inflammation and oxidative stress in the wound environment. Most importantly, it improves the regenerated tissue quality with enhanced mechanical strength and electrical properties. Therefore, PC could potentially improve wound care management for diabetic patients and play a beneficial role in other tissue regeneration applications.


Assuntos
Materiais Biocompatíveis , Diabetes Mellitus Experimental , Animais , Humanos , Materiais Biocompatíveis/farmacologia , Ácido Cítrico/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Cicatrização , Citratos
17.
Materials (Basel) ; 16(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36903232

RESUMO

Herein, we present the synthesis and electrochemical performance of a comb-like polycaprolactone-based gel electrolyte from acrylate terminated polycaprolactone oligomers and liquid electrolyte for high-voltage lithium metal batteries. The ionic conductivity of this gel electrolyte at room temperature was measured to be 8.8 × 10-3 S cm-1, which is an exceptionally high value that is more than sufficient for the stable cycling of solid-state lithium metal batteries. The Li+ transference number was detected to be 0.45, facilitating the prohibition of concentration gradients and polarization, thereby prohibiting lithium dendrite formation. In addition, the gel electrolyte exhibits high oxidation voltage up to 5.0 V vs. Li+/Li and perfect compatibility against metallic lithium electrodes. The superior electrochemical properties provide the LiFePO4-based solid-state lithium metal batteries with excellent cycling stability, displaying a high initial discharge capacity of 141 mAh g-1 and an extraordinary capacity retention exceeding 74% of its initial specific capacity after being cycled for 280 cycles at 0.5C at room temperature. This paper presents a simple and effective in situ preparation process yielding an excellent gel electrolyte for high-performance lithium metal battery applications.

18.
Open Forum Infect Dis ; 10(2): ofad016, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36751650

RESUMO

Background: The prevalence of human immunodeficiency type 1 (HIV-1) pretreatment drug resistance (PDR) in men who have sex with men (MSM) in Guangxi remains unclear, and its effect on antiretroviral therapy (ART) needs to be further studied. Methods: Individuals newly diagnosed with HIV in Guangxi from 2016 to 2020, which mainly included MSM and the heterosexual (HES) population, were recruited in this study. Pol sequences were sequenced to analyze PDR and construct a genetic network. The risk factors for PDR and the effect on ART were respectively analyzed. Results: The PDR of MSM in Guangxi was 4.7% (34/716), consisting of nonnucleoside reverse transcriptase inhibitors (3.5%), protease inhibitors (0.8%), integrase strand transfer inhibitors (0.7%), and nucleoside reverse transcriptase inhibitors (0.4%), and lower than that of HES (9.3% [77/827]). The subtype was associated with PDR, and MSM was lower than HES (CRF01_AE: 3.0% vs 8.0%; CRF07_BC: 4.1% vs 7.2%). CRF55_01B (adjusted odds ratio [aOR], 3.35) was a risk factor for PDR in MSM, while CRF08_BC (aOR, 2.34) and older (aOR, 2.75) were risk factors for PDR in HES. Six of 18 (33.3%) PDR of MSM in the network connected to each other, lower than that of HES (61.1% [22/36]). CRF55_01B (aOR, 5.69) was a risk factor for PDR transmission in MSM, while CRF08_BC (aOR, 4.08) was a risk factor in HES. Pretreatment CD4+ T-cell count, age, infection route, and subtype were associated with recovery of CD4+ count and suppression of viral load. Conclusions: The prevalence of PDR was different between MSM and HES, which may be associated with subtype. Thus, the monitoring of subtype and PDR should be strengthened.

19.
Sci Adv ; 9(8): eade4687, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36812305

RESUMO

Chronic wounds, particularly those associated with diabetes mellitus, represent a growing threat to public health, with additional notable economic impacts. Inflammation associated with these wounds leads to abnormalities in endogenous electrical signals that impede the migration of keratinocytes needed to support the healing process. This observation motivates the treatment of chronic wounds with electrical stimulation therapy, but practical engineering challenges, difficulties in removing stimulation hardware from the wound site, and absence of means to monitor the healing process create barriers to widespread clinical use. Here, we demonstrate a miniaturized wireless, battery-free bioresorbable electrotherapy system that overcomes these challenges. Studies based on a splinted diabetic mouse wound model confirm the efficacy for accelerated wound closure by guiding epithelial migration, modulating inflammation, and promoting vasculogenesis. Changes in the impedance provide means for tracking the healing process. The results demonstrate a simple and effective platform for wound site electrotherapy.


Assuntos
Diabetes Mellitus , Terapia por Estimulação Elétrica , Camundongos , Animais , Implantes Absorvíveis , Impedância Elétrica , Cicatrização , Modelos Animais de Doenças , Inflamação
20.
Anal Chim Acta ; 1239: 340698, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628766

RESUMO

On-site nucleic acid testing (NAT) plays an important role for disease monitoring and pathogen diagnosis. In this work, we developed an automated and fully-integrated nucleic acid analyzer by combining the automated liquid handling robot technique with the microfluidic droplet-based real-time PCR assay technique. The present analyzer could achieve multiple operations including sample introduction, nucleic acid extraction based on magnetic solid-phase extraction, reverse transcription and, sample droplet generation, PCR amplification, real-time and dual fluorescence detection of droplet array. A strategy of constructing an integrated compact and low-cost system was adopted to minimize the analyzer size to 50 × 45 × 45 cm (length × width × height), and reduce the instrument cost to ca. $900 with a single analysis cost less than $5. A simple chip was also designed to pre-load reagents and carry oil-covered PCR reaction droplets. We applied the analyzer to identify eight types of influenza pathogens in human throat swabs, and the results were consistent with the colloidal gold method.


Assuntos
Técnicas Analíticas Microfluídicas , Ácidos Nucleicos , Robótica , Humanos , Microfluídica/métodos , Ácidos Nucleicos/análise , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Técnicas Analíticas Microfluídicas/métodos
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