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1.
Nature ; 597(7878): 655-659, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34588672

RESUMO

In 1878, Lord Rayleigh observed the highly celebrated phenomenon of sound waves that creep around the curved gallery of St Paul's Cathedral in London1,2. These whispering-gallery waves scatter efficiently with little diffraction around an enclosure and have since found applications in ultrasonic fatigue and crack testing, and in the optical sensing of nanoparticles or molecules using silica microscale toroids. Recently, intense research efforts have focused on exploring non-Hermitian systems with cleverly matched gain and loss, facilitating unidirectional invisibility and exotic characteristics of exceptional points3,4. Likewise, the surge in physics using topological insulators comprising non-trivial symmetry-protected phases has laid the groundwork in reshaping highly unconventional avenues for robust and reflection-free guiding and steering of both sound and light5,6. Here we construct a topological gallery insulator using sonic crystals made of thermoplastic rods that are decorated with carbon nanotube films, which act as a sonic gain medium by virtue of electro-thermoacoustic coupling. By engineering specific non-Hermiticity textures to the activated rods, we are able to break the chiral symmetry of the whispering-gallery modes, which enables the out-coupling of topological 'audio lasing' modes with the desired handedness. We foresee that these findings will stimulate progress in non-destructive testing and acoustic sensing.

2.
FASEB J ; 38(15): e23880, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39132919

RESUMO

Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis.


Assuntos
Fígado , RNA Longo não Codificante , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Camundongos , Fígado/metabolismo , Camundongos Knockout , Glucose/metabolismo , Masculino , Hepatócitos/metabolismo , Camundongos Endogâmicos C57BL , Glicogênio Hepático/metabolismo
3.
Mol Ther ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39066479

RESUMO

Cardiac signaling pathways functionally important in the heart's response to exercise often protect the heart against pathological stress, potentially providing novel therapeutic targets. However, it is important to determine which of these pathways can be feasibly targeted in vivo. Transgenic overexpression of exercise-induced CITED4 has been shown to protect against adverse remodeling after ischemia/reperfusion injury (IRI). Here we investigated whether somatic gene transfer of CITED4 in a clinically relevant time frame could promote recovery after IRI. Cardiac CITED4 gene delivery via intravenous AAV9 injections in wild type mice led to an approximately 3-fold increase in cardiac CITED4 expression. After 4 weeks, CITED4-treated animals developed physiological cardiac hypertrophy without adverse remodeling. In IRI, delivery of AAV9-CITED4 after reperfusion resulted in a 6-fold increase in CITED4 expression 1 week after surgery, as well as decreased apoptosis, fibrosis, and inflammatory markers, culminating in a smaller scar and improved cardiac function 8 weeks after IRI, compared with control mice receiving AAV9-GFP. Somatic gene transfer of CITED4 induced a phenotype suggestive of physiological cardiac growth and mitigated adverse remodeling after ischemic injury. These studies support the feasibility of CITED4 gene therapy delivered in a clinically relevant time frame to mitigate adverse ventricular remodeling after ischemic injury.

4.
J Mol Cell Cardiol ; 195: 55-67, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39089571

RESUMO

Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.


Assuntos
Lesão Pulmonar Aguda , Vesículas Extracelulares , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ubiquitinação , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Animais , Masculino , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Camundongos , Inflamassomos/metabolismo , Proto-Oncogene Mas , Ponte Cardiopulmonar/efeitos adversos , Células Epiteliais/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/etiologia , Pulmão/metabolismo , Pulmão/patologia , Peptídeos e Proteínas de Sinalização Intracelular
5.
Small ; 20(27): e2307759, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38269473

RESUMO

Two types of functional surfaces with the same roughness but completely different surface topographies are prepared, namely positively skewed surfaces filled with micropillar arrays (Sa ≈4.4 µm, Ssk >0) and negatively skewed surfaces filled with microcavity arrays (Sa ≈4.4 µm, Ssk <0), demonstrating promoting droplet splashing. Remarkably, the critical Weber number for generating satellite droplets on the negatively skewed surfaces is significantly lower than that on the positively skewed surfaces, indicating that the negatively skewed surface with microcavity arrays is more likely to promote droplet splashing. It is mainly attributed to the fact that air on the negatively skewed surface can make the liquid film take on a Cassie-Baxter state on the surface so that the stabilizing capillary force of the liquid film exceeds the destabilizing stress of the air film. Moreover, the surface topography promoting droplet spreading and the mechanical properties of three-phase moving contact lines are analyzed from the perspective of microscopic interface mechanics. Finally, it is demonstrated the designed positively skewed surfaces can be employed for large-area heat dissipation by means of high-efficiency evaporation.

6.
BMC Microbiol ; 24(1): 93, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515035

RESUMO

Plant growth promoting microbe assisted phytoremediation is considered a more effective approach to rehabilitation than the single use of plants, but underlying mechanism is still unclear. In this study, we combined transcriptomic and physiological methods to explore the mechanism of plant growth promoting microbe Trichoderma citrinoviride HT-1 assisted phytoremediation of Cd contaminated water by Phragmites australis. The results show that the strain HT-1 significantly promoted P. australis growth, increased the photosynthetic rate, enhanced antioxidant enzyme activities. The chlorophyll content and the activity of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) were increased by 83.78%, 23.17%, 47.60%, 97.14% and 12.23% on average, and decreased the content of malondialdehyde (MDA) by 31.10%. At the same time, strain HT-1 improved the absorption and transport of Cd in P. australis, and the removal rate of Cd was increased by 7.56% on average. Transcriptome analysis showed that strain HT-1 induced significant up-regulated the expression of genes related to oxidative phosphorylation and ribosome pathways, and these upregulated genes promoted P. australis remediation efficiency and resistance to Cd stress. Our results provide a mechanistic understanding of plant growth promoting microbe assisted phytoremediation under Cd stress.


Assuntos
Cádmio , Hypocreales , Poluentes do Solo , Cádmio/análise , Biodegradação Ambiental , Água , Antioxidantes/metabolismo , Poaceae/metabolismo , Perfilação da Expressão Gênica , Poluentes do Solo/metabolismo
7.
Opt Express ; 32(12): 20682-20694, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38859444

RESUMO

Fiber-bundle-based endoscopy, with its ultrathin probe and micrometer-level resolution, has become a widely adopted imaging modality for in vivo imaging. However, the fiber bundles introduce a significant honeycomb effect, primarily due to the multi-core structure and crosstalk of adjacent fiber cores, which superposes the honeycomb pattern image on the original image. To tackle this issue, we propose an iterative-free spatial pixel shifting (SPS) algorithm, designed to suppress the honeycomb effect and enhance real-time imaging performance. The process involves the creation of three additional sub-images by shifting the original image by one pixel at 0, 45, and 90 degree angles. These four sub-images are then used to compute differential maps in the x and y directions. By performing spiral integration on these differential maps, we reconstruct a honeycomb-free image with improved details. Our simulations and experimental results, conducted on a self-built fiber bundle-based endoscopy system, demonstrate the effectiveness of the SPS algorithm. SPS significantly improves the image quality of reflective objects and unlabeled transparent scattered objects, laying a solid foundation for biomedical endoscopic applications.

8.
Opt Express ; 32(2): 1501-1511, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297700

RESUMO

In this study, we designed a self-focused ultrasonic transducer made of polyvinylidene fluoride (PVDF). This transducer involves a back-reflector, which is modeled after tapetum lucidum in the eyes of some nocturnal animals. The bionic structure reflects the ultrasound, which passes through the PVDF membrane, back to PVDF and provides a second chance for the PVDF to convert the ultrasound to electric signals. This design increases the amount of ultrasound absorbed by the PVDF, thereby improving the detection sensitivity. Both ultrasonic and photoacoustic (PA) experiments were conduct to characterize the performance of the transducer. The results show that the fabricated transducer has a center frequency of 13.07 MHz, and a bandwidth of 96% at -6 dB. With an acoustic numerical aperture (NA) of 0.64, the transducer provides a lateral resolution of 140µm. Importantly, the bionic design improves the detection sensitivity of the transducer about 30%. Finally, we apply the fabricated transducer to optical-resolution (OR) and acoustic-resolution photoacoustic microscopy (AR-PAM) to achieve multiscale-resolution PA imaging. Imaging of the bamboo leaf and the leaf skeleton demonstrates that the proposed transducer can provide high spatial resolution, better imaging intensity and contrast. Therefore, the proposed transducer design will be useful to enhance the performance of multiscale-resolution PAM.

9.
Hum Reprod ; 39(4): 658-673, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38335261

RESUMO

STUDY QUESTION: What is the significance and mechanism of human seminal plasma extracellular vesicles (EVs) in regulating human sperm functions? SUMMARY ANSWER: EV increases the intracellular Ca2+ concentrations [Ca2+]i via extracellular Ca2+ influx by activating CatSper channels, and subsequently modulate human sperm motility, especially hyperactivated motility, which is attributed to both protein and non-protein components in EV. WHAT IS KNOWN ALREADY: EVs are functional regulators of human sperm function, and EV cargoes from normal and asthenozoospermic seminal plasma are different. Pre-fusion of EV with sperm in the acidic and non-physiological sucrose buffer solution could elevate [Ca2+]i in human sperm. CatSper, a principle Ca2+ channel in human sperm, is responsible for the [Ca2+]i regulation when sperm respond to diverse extracellular stimuli. However, the role of CatSper in EV-evoked calcium signaling and its potential physiological significance remain unclear. STUDY DESIGN, SIZE, DURATION: EV isolated from the seminal plasma of normal and asthenozoospermic semen were utilized to investigate the mechanism by which EV regulates calcium signal in human sperm, including the involvement of CatSper and the responsible cargoes in EV. In addition, the clinical application potential of EV and EV protein-derived peptides were also evaluated. This is a laboratory study that went on for more than 5 years and involved more than 200 separate experiments. PARTICIPANTS/MATERIALS, SETTING, METHODS: Semen donors were recruited in accordance with the Institutional Ethics Committee on human subjects of the Affiliated Hospital of Nantong University and Jiangxi Maternal and Child Health Hospital. The Flow NanoAnalyzer, western blotting, and transmission electron microscope were used to systematically characterize seminal plasma EV. Sperm [Ca2+]i responses were examined by fluorimetric measurement. The whole-cell patch-clamp technique was performed to record CatSper currents. Sperm motility parameters were assessed by computer-assisted sperm analysis. Sperm hyperactivation was also evaluated by examining their penetration ability in viscous methylcellulose media. Protein and non-protein components in EV were analyzed by liquid chromatography-mass spectrum. The levels of prostaglandins, reactive oxygen species, malonaldehyde, and DNA integrity were detected by commercial kits. MAIN RESULTS AND THE ROLE OF CHANCE: EV increased [Ca2+]i via an extracellular Ca2+ influx, which could be suppressed by a CatSper inhibitor. Also, EV potentiated CatSper currents in human sperm. Furthermore, the EV-in [Ca2+]i increase and CatSper currents were absent in a CatSper-deficient sperm, confirming the crucial role of CatSper in EV induced Ca2+ signaling in human sperm. Both proteins and non-protein components of EV contributed to the increase of [Ca2+]i, which were important for the effects of EV on human sperm. Consequently, EV and its cargos promoted sperm hyperactivated motility. In addition, seminal plasma EV protein-derived peptides, such as NAT1-derived peptide (N-P) and THBS-1-derived peptide (T-P), could activate the sperm calcium signal and enhance sperm function. Interestingly, EV derived from asthenozoospermic semen caused a lower increase of [Ca2+]i than that isolated from normal seminal plasma (N-EV), and N-EV significantly improved sperm motility and function in both asthenozoospermic samples and frozen-thawed sperm. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This was an in vitro study and caution must be taken when extrapolating the physiological relevance to in vivo regulation of sperm. WIDER IMPLICATIONS OF THE FINDINGS: Our findings demonstrate that the CatSper-mediated-Ca2+ signaling is involved in EV-modulated sperm function under near physiological conditions, and EV and their derivates are a novel CatSper and sperm function regulators with potential for clinical application. They may be developed to improve sperm motility resulting from low [Ca2+]i response and/or freezing and thawing. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the National Natural Science Foundation of China (32271167), the Social Development Project of Jiangsu Province (BE2022765), the Nantong Social and People's Livelihood Science and Technology Plan (MS22022087), the Basic Science Research Program of Nantong (JC22022086), and the Jiangsu Innovation and Entrepreneurship Talent Plan (JSSCRC2021543). The authors declare no conflict of interest.


Assuntos
Astenozoospermia , Canais de Cálcio , Vesículas Extracelulares , Sêmen , Motilidade dos Espermatozoides , Humanos , Masculino , Astenozoospermia/metabolismo , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Peptídeos/metabolismo , Peptídeos/farmacologia , Sêmen/química , Sêmen/metabolismo , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/metabolismo , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo
10.
Opt Lett ; 49(2): 234-237, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38194536

RESUMO

Photoacoustic imaging is a powerful technique for obtaining high-resolution images of vascular distribution and physiological information about blood by utilizing the light absorption coefficient as an imaging contrast. However, visualizing weakly light-absorbing components without specific contrast agents or multi-wavelength techniques presents a challenge due to significant differences in light absorption between these components and blood. In this study, we propose a novel method that leverages the thermal effect of ultrasound to induce temperature differences and enhance the contrast of photoacoustic imaging. We conducted phantom experiments to verify the feasibility of our method. Our method effectively highlighted weakly light-absorbing components with strong acoustic absorption, even in the presence of highly light-absorbing components such as blood or melanin. Furthermore, it enabled the differentiation of components with similar light absorption but different acoustic absorption.


Assuntos
Acústica , Tomografia Computadorizada por Raios X , Ultrassonografia , Imagens de Fantasmas , Melaninas
11.
Opt Lett ; 49(6): 1445-1448, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489421

RESUMO

This study introduces the optical path-optimized dual-grating chromatic line confocal imaging (DG-LCI) technique for high-resolution and wide-range surface topography measurements. Chromatic line confocal imaging (LCI) finds extensive applications in high-speed 3D imaging of surface morphology, roughness analysis in industrial production, and quality inspection. A key advantage of LCI is its ability to achieve a large depth of focus, enabling the imaging system to measure a wide range in the Z direction. However, the challenge lies in the trade-off between the measurement range and resolution. Increasing the measurement range reduces the resolution, making it unsuitable for precise measurements required in industrial processing. Conversely, enhancing the resolution limits the measurement range, thereby sacrificing the advantage of LCI systems' broad measurement capabilities. Addressing this limitation, we propose a dual optical path dual-grating structure using a simplified and ingenious optical path optimization design. This design overcomes the challenge of sacrificing the millimeter-level measurement range while simultaneously improving the resolution. Rigorous simulations and experiments validate the effectiveness and validity of our proposed method.

12.
Opt Lett ; 49(13): 3757-3760, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950260

RESUMO

Optical frequency comb in the vacuum ultraviolet (VUV)/extreme ultraviolet (XUV) region has attracted a great deal of attention, as it provides coherent VUV/XUV radiation source with a rather narrow bandwidth, facilitating precise spectroscopic measurements in the short wavelength regime. In this study, we report on the linewidth measurement of a home-built VUV comb centered at 148 nm using direct frequency comb spectroscopy with NO2. The measurement reveals that the upper bound of our comb linewidth is less than 28 MHz. Fitting the whole trace with different repetition rates shows that the center frequency of the excitation is 2 021.25 ± 0.24 THz (∼148.32 nm). Thus, we assigned this excitation to the transition from the 6a1 orbital (ν1'=0, ν2'=0) to the 3pσu orbital (ν1'=3, ν2'=8) in NO2. Our work demonstrates that VUV combs are potentially powerful tools for precision spectroscopic measurements in the short wavelength regime.

13.
Phys Rev Lett ; 133(11): 113804, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39331978

RESUMO

The increasing interest in chiral light stems from its spiral trajectory along the propagation direction, facilitating the interaction between different polarization states of light and matter. Despite tremendous achievements in chiral light-related research, the generation and control of chiral pulses have presented enduring challenges, especially at the terahertz and ultraviolet spectral ranges, due to the lack of suitable optical elements for effective pulse manipulation. Conventionally, chiral light can be obtained from intricate optical systems, by an external magnetic field, or by metamaterials, which necessitate sophisticated optical configurations. Here, leveraging the high harmonic generation process, we propose a versatile tunable chiral emitter, composed of only two planar Weyl semimetals slabs, addressing the challenges in both spectral ranges. Our results open the way to a compact tunable chiral emitter platform in both terahertz and ultra-violet frequency ranges. This advancement holds the potential to serve as the cornerstone for integrated chiral photonics.

14.
Phys Rev Lett ; 132(22): 223202, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38877960

RESUMO

Attoclock provides a powerful tool for probing the ultrafast electron dynamics in strong laser fields. However, this technique has remained restricted to single electron or sequential double ionized electron dynamics. Here, we propose a novel attoclock scheme with a polarization-gated few-cycle laser pulse and demonstrate its application in timing the correlated-electron emission in strong field double ionization of argon. Our experimental measurements reveal that the correlated-electron emission occurs mainly through two channels with time differences of 234±22 as and 1043±73 as, respectively. Classical model calculations well reproduce the experimental results and deepen our understanding of ultrafast electron correlation dynamics.

15.
Arch Biochem Biophys ; 761: 110153, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39271097

RESUMO

Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.

16.
FASEB J ; 37(1): e22652, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36515690

RESUMO

FOXA factors are critical members of the developmental gene regulatory network (GRN) composed of master transcription factors (TF) which regulate murine cell fate and metabolism in the gut and liver. How FOXA factors dictate human liver cell fate, differentiation, and simultaneously regulate metabolic pathways is poorly understood. Here, we aimed to determine the role of FOXA2 (and FOXA1 which is believed to compensate for FOXA2) in controlling hepatic differentiation and cell metabolism in a human hepatic cell line (HepG2). siRNA mediated knockdown of FOXA1/2 in HepG2 cells significantly downregulated albumin (p < .05) and GRN TF gene expression (HNF4α, HEX, HNF1ß, TBX3) (p < .05) and significantly upregulated endoderm/gut/hepatic endoderm markers (goosecoid [GSC], FOXA3, and GATA4), gut TF (CDX2), pluripotent TF (NANOG), and neuroectodermal TF (PAX6) (p < .05), all consistent with partial/transient reprograming. shFOXA1/2 targeting resulted in similar findings and demonstrated evidence of reversibility of phenotype. RNA-seq followed by bioinformatic analysis of shFOXA1/2 knockdown HepG2 cells demonstrated 235 significant downregulated genes and 448 upregulated genes, including upregulation of markers for alternate germ layers lineages (cardiac, endothelial, muscle) and neurectoderm (eye, neural). We found widespread downregulation of glycolysis, citric acid cycle, mitochondrial genes, and alterations in lipid metabolism, pentose phosphate pathway, and ketogenesis. Functional metabolic analysis agreed with these findings, demonstrating significantly diminished glycolysis and mitochondrial respiration, with concomitant accumulation of lipid droplets. We hypothesized that FOXA1/2 inhibit the initiation of human liver differentiation in vitro. During human pluripotent stem cells (hPSC)-hepatic differentiation, siRNA knockdown demonstrated de-differentiation and unexpectedly, activation of pluripotency factors and neuroectoderm. shRNA knockdown demonstrated similar results and activation of SOX9 (hepatobiliary). These results demonstrate that FOXA1/2 controls hepatic and developmental GRN, and their knockdown leads to reprogramming of both differentiation and metabolism, with applications in studies of cancer, differentiation, and organogenesis.


Assuntos
Fígado , Células-Tronco Pluripotentes , Humanos , Camundongos , Animais , Diferenciação Celular/fisiologia , Fígado/metabolismo , Linhagem Celular , RNA Interferente Pequeno/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-alfa Nuclear de Hepatócito/metabolismo
17.
Neurochem Res ; 49(9): 2491-2504, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38862726

RESUMO

Idebenone, an antioxidant used in treating oxidative damage-related diseases, has unclear neuroprotective mechanisms. Oxidative stress affects cell and mitochondrial membranes, altering Adp-ribosyl cyclase (CD38) and Silent message regulator 3 (SIRT3) protein expression and possibly impacting SIRT3's ability to deacetylate Tumor protein p53 (P53). This study explores the relationship between CD38, SIRT3, and P53 in H2O2-injured HT22 cells treated with Idebenone. Apoptosis was detected using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after determining appropriate H2O2 and Idebenone concentrations.In this study, Idebenone was found to reduce apoptosis and decrease P53 and Caspase3 expression in H2O2-injured HT22 cells by detecting apoptosis-related protein expression. Through bioinformatics methods, CD38 was identified as the target of Idebenone, and it further demonstrated that Idebenone decreased the expression of CD38 and increased the level of SIRT3. An increased NAD+/NADH ratio was detected, suggesting Idebenone induces SIRT3 expression and protects HT22 cells by decreasing apoptosis-related proteins. Knocking down SIRT3 downregulated acetylated P53 (P53Ac), indicating SIRT3's importance in P53 deacetylation.These results supported that CD38 was used as a target of Idebenone to up-regulate SIRT3 to deacetylate activated P53, thereby protecting HT22 cells from oxidative stress injury. Thus, Idebenone is a drug that may show great potential in protecting against reactive oxygen species (ROS) induced diseases such as Parkinson's disease, and Alzheimer's disease. And it might be able to compensate for some of the defects associated with CD38-related diseases.


Assuntos
ADP-Ribosil Ciclase 1 , Apoptose , Estresse Oxidativo , Sirtuína 3 , Proteína Supressora de Tumor p53 , Ubiquinona , Proteína Supressora de Tumor p53/metabolismo , Estresse Oxidativo/efeitos dos fármacos , ADP-Ribosil Ciclase 1/metabolismo , Animais , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Camundongos , Sirtuína 3/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Peróxido de Hidrogênio/toxicidade , Antioxidantes/farmacologia , Glicoproteínas de Membrana/metabolismo , Fármacos Neuroprotetores/farmacologia
18.
Langmuir ; 40(29): 15263-15270, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39001857

RESUMO

In this study, we examined how surface topography and particle medium interact to affect the tribological performance of rubber sliding interfaces, uncovering the mechanisms of particle lubrication under various conditions. We found that microtextured surfaces, created using a mold transfer method, modestly reduced the friction coefficient of rubber under both dry and lubricated states, primarily by altering the real contact area. Additionally, the presence of different microconvex textures on the surface topography significantly influenced rubber's tribological properties. Our three-dimensional morphological analysis revealed that microtextured rubber surfaces with higher Sa, Sku, and Sal and lower Str values consistently showed lower friction coefficients during sliding. The friction mechanism was attributed to the combined effects of the material properties, surface topography, and contact area. With the addition of a particle medium, the dry friction coefficient of the rubber interface decreased but exhibited an initial increase, followed by a decrease with increasing particle diameter. When particles were mixed with a water-based cutting fluid, the concentration, diameter, and wettability of the particles significantly impacted the tribological properties due to the synergistic effects of surface topography and particle lubrication. This work enhances our understanding of tribological control for viscoelastic materials through surface design, providing a theoretical basis for the tribological optimization of rubber surfaces.

19.
Langmuir ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335533

RESUMO

Superhydrophobic surfaces (SHSs) have possibilities for achieving significantly reduced solid-liquid frictional drag in the marine sector due to their excellent water-repelling properties. Although the stability of SHSs plays a key role in drag reduction, little consideration was given to the effect of extreme environments on the ability of SHSs to achieve drag reduction underwater, particularly when subjected to acidic conditions. Here, we propose interconnected microstructures to protect superhydrophobic coatings with the aim of enhancing the stability of SHSs in extreme environments. The stability of armored SHSs (ASHSs) was demonstrated by the contact angle and bounce time of droplets on superhydrophobic surfaces treated by various methods, resulting in an ASHS surface with excellent stability under extreme environmental conditions. Additionally, inspired by microstructures protecting superhydrophobic nanomaterials from frictional wear, the armored superhydrophobic spheres (ASSPs) were designed to explain from theoretical and experimental perspectives why ASSPs can achieve sustainable drag reduction and demonstrate that the ASSPs can achieve drag reduction of over 90.4% at a Reynolds number of 6.25 × 104 by conducting water entry experiments on spheres treated in various solutions. These studies promote a fundamental understanding of what drives the application of SHSs under extreme environmental conditions and provide practical strategies to maximize frictional drag reduction.

20.
Langmuir ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39291359

RESUMO

This study explores the kinetic behavior of droplets impacting microtextured surfaces under a Leidenfrost temperature, employing high-speed photography and picosecond laser micromachining techniques. The investigation focuses on two types of microtextured surfaces with totally different surface peak-valley features: a negatively skewed surface with micropit arrays (Ssk < 0) and a positively skewed surface with micropillar arrays (Ssk > 0). The results indicate that both microtextured surfaces contribute to a higher Leidenfrost temperature compared with the original smooth surface, which is consistent with previous studies. However, it is worth noting that the Leidenfrost points of the micropit and micropillar surfaces showed opposite trends with the microtexture area occupancy. Specifically, the Leidenfrost temperature on micropit surfaces increases with greater micropit area occupancy, while it decreases on micropillar surfaces under similar conditions, which is mainly attributed to the differential impact of area occupancy on droplet heat transfer efficiency. When the microtexture area occupancy is 50%, it is worth noting that the micropit and micropillar surfaces have nearly same roughness (Sa), but the Leidenfrost temperature was notably higher on the micropit surface with negative skewness (Ssk < 0), which was related to differences in vapor flow dynamics. We further find that the Weber number (We) significantly influences the Leidenfrost point, with the droplet impact wall behavior going through the states of film bounce back, ejecting tiny droplets and bounce back, and ultimately droplet breakup as the We increases. The dynamic Leidenfrost point was found to be generally higher than the static point and increases with the We. Finally, we compare the cooling efficiency of these surfaces, and it is found that the micropit surfaces with a negative skewness exhibit superior heat dissipation performance under the same conditions, which proved that the negatively skewed surface may have great potential in high-density heat dissipation technology.

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