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1.
Opt Lett ; 49(10): 2641-2644, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748125

RESUMEN

Mid-infrared (MIR) Si-based optoelectronics has wide potential applications, and its design requires simultaneous consideration of device performance optimization and the feasibility of heterogeneous integration. The emerging interest in all-dielectric metasurfaces for optoelectronic applications stems from their exceptional ability to manipulate light. In this Letter, we present our research on an InSb all-dielectric metasurface designed to achieve ultrahigh absorptivity within the 5-5.5 µm wavelength range. By integrating an InSb nanodisk array layer on a Si platform using wafer bonding and heteroepitaxial growth, we demonstrate three kinds of metasurface with high absorptivity of 98.36%, 99.28%, and 99.18%. The enhanced absorption is mainly contributed by the Kerker effect and the anapole state and the peak, with the added flexibility of tuning both the peak and bandwidth of absorption by altering the metasurface parameters. Our findings provide an alternative scheme to develop high-performance detectors and absorbers for MIR silicon photonics.

2.
Redox Biol ; 73: 103176, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38705094

RESUMEN

Excitotoxicity is a prevalent pathological event in neurodegenerative diseases. The involvement of ferroptosis in the pathogenesis of excitotoxicity remains elusive. Transcriptome analysis has revealed that cytoplasmic reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels are associated with susceptibility to ferroptosis-inducing compounds. Here we show that exogenous NADPH, besides being reductant, interacts with N-myristoyltransferase 2 (NMT2) and upregulates the N-myristoylated ferroptosis suppressor protein 1 (FSP1). NADPH increases membrane-localized FSP1 and strengthens resistance to ferroptosis. Arg-291 of NMT2 is critical for the NADPH-NMT2-FSP1 axis-mediated suppression of ferroptosis. This study suggests that NMT2 plays a pivotal role by bridging NADPH levels and neuronal susceptibility to ferroptosis. We propose a mechanism by which the NADPH regulates N-myristoylation, which has important implications for ferroptosis and disease treatment.

3.
Chem Soc Rev ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712843

RESUMEN

Transition metal-containing materials with aggregation-induced emission (AIE) have brought new opportunities for the development of biological probes, optoelectronic materials, stimuli-responsive materials, sensors, and detectors. Coordination compounds containing the platinum metal have emerged as a promising option for constructing effective AIE platinum complexes. In this review, we classified AIE platinum complexes based on the number of ligands. We focused on the development and performance of AIE platinum complexes with different numbers of ligands and discussed the impact of platinum ion coordination and ligand structure variation on the optoelectronic properties. Furthermore, this review analyzes and summarizes the influence of molecular geometries, stacking models, and aggregation environments on the optoelectronic performance of these complexes. We provided a comprehensive overview of the AIE mechanisms exhibited by various AIE platinum complexes. Based on the unique properties of AIE platinum complexes with different numbers of ligands, we systematically summarized their applications in electronics, biological fields, etc. Finally, we illustrated the challenges and opportunities for future research on AIE platinum complexes, aiming at giving a comprehensive summary and outlook on the latest developments of functional AIE platinum complexes and also encouraging more researchers to contribute to this promising field.

4.
Neurophotonics ; 11(2): 024207, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38577628

RESUMEN

Significance: Genetically encoded calcium ion (Ca2+) indicators (GECIs) are powerful tools for monitoring intracellular Ca2+ concentration changes in living cells and model organisms. In particular, GECIs have found particular utility for monitoring the transient increase of Ca2+ concentration that is associated with the neuronal action potential. However, the palette of highly optimized GECIs for imaging of neuronal activity remains relatively limited. Expanding the selection of available GECIs to include new colors and distinct photophysical properties could create new opportunities for in vitro and in vivo fluorescence imaging of neuronal activity. In particular, blue-shifted variants of GECIs are expected to have enhanced two-photon brightness, which would facilitate multiphoton microscopy. Aim: We describe the development and applications of T-GECO1-a high-performance blue-shifted GECI based on the Clavularia sp.-derived mTFP1. Approach: We use protein engineering and extensive directed evolution to develop T-GECO1. We characterize the purified protein and assess its performance in vitro using one-photon excitation in cultured rat hippocampal neurons, in vivo using one-photon excitation fiber photometry in mice, and ex vivo using two-photon Ca2+ imaging in hippocampal slices. Results: The Ca2+-bound state of T-GECO1 has an excitation peak maximum of 468 nm, an emission peak maximum of 500 nm, an extinction coefficient of 49,300 M-1 cm-1, a quantum yield of 0.83, and two-photon brightness approximately double that of EGFP. The Ca2+-dependent fluorescence increase is 15-fold, and the apparent Kd for Ca2+ is 82 nM. With two-photon excitation conditions at 850 nm, T-GECO1 consistently enabled the detection of action potentials with higher signal-to-noise (SNR) than a late generation GCaMP variant. Conclusions: T-GECO1 is a high-performance blue-shifted GECI that, under two-photon excitation conditions, provides advantages relative to late generation GCaMP variants.

5.
J Agric Food Chem ; 72(18): 10406-10419, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38659208

RESUMEN

The impact of leptin resistance on intestinal mucosal barrier integrity, appetite regulation, and hepatic lipid metabolism through the microbiota-gut-brain-liver axis has yet to be determined. Water extract of Phyllanthus emblica L. fruit (WEPE) and its bioactive compound gallic acid (GA) effectively alleviated methylglyoxal (MG)-triggered leptin resistance in vitro. Therefore, this study investigated how WEPE and GA intervention relieve leptin resistance-associated dysfunction in the intestinal mucosa, appetite, and lipid accumulation through the microbiota-gut-brain-liver axis in high-fat diet (HFD)-fed rats. The results showed that WEPE and GA significantly reduced tissues (jejunum, brain, and liver) MG-evoked leptin resistance, malondialdehyde (MDA), proinflammatory cytokines, SOCS3, orexigenic neuropeptides, and lipid accumulation through increasing leptin receptor, tight junction proteins, antimicrobial peptides, anorexigenic neuropeptides, excretion of fecal triglyceride (TG), and short-chain fatty acids (SCFAs) via a positive correlation with the Allobaculum and Bifidobacterium microbiota. These novel findings suggest that WEPE holds the potential as a functional food ingredient for alleviating obesity and its complications.


Asunto(s)
Encéfalo , Dieta Alta en Grasa , Frutas , Microbioma Gastrointestinal , Homeostasis , Leptina , Hígado , Obesidad , Phyllanthus emblica , Extractos Vegetales , Ratas Sprague-Dawley , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Masculino , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/microbiología , Frutas/química , Hígado/metabolismo , Hígado/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Leptina/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Phyllanthus emblica/química , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Homeostasis/efectos de los fármacos , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Apetito/efectos de los fármacos , Eje Cerebro-Intestino/efectos de los fármacos , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación
6.
bioRxiv ; 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38585797

RESUMEN

Mitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons in Caenorhabditis elegans ( C. elegans ) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism.

7.
J Am Chem Soc ; 146(11): 7506-7514, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38457476

RESUMEN

Very recently, a new superconductor with Tc = 80 K has been reported in nickelate (La3Ni2O7) at around 15-40 GPa conditions (Nature, 621, 493, 2023), which is the second type of unconventional superconductor, besides cuprates, with Tc above liquid nitrogen temperature. However, the phase diagram plotted in this report was mostly based on the transport measurement under low-temperature and high-pressure conditions, and the assumed corresponding X-ray diffraction (XRD) results were carried out at room temperature. This encouraged us to carry out in situ high-pressure and low-temperature synchrotron XRD experiments to determine which phase is responsible for the high Tc state. In addition to the phase transition from the orthorhombic Amam structure to the orthorhombic Fmmm structure, a tetragonal phase with the space group of I4/mmm was discovered when the sample was compressed to around 19 GPa at 40 K where the superconductivity takes place in La3Ni2O7. The calculations based on this tetragonal structure reveal that the electronic states that approached the Fermi energy were mainly dominated by the eg orbitals (3dz2 and 3dx2-y2) of Ni atoms, which are located in the oxygen octahedral crystal field. The correlation between Tc and this structural evolution, especially Ni-O octahedra regularity and the in-plane Ni-O-Ni bonding angles, is analyzed. This work sheds new light to identify what is the most likely phase responsible for superconductivity in double-layered nickelate.

8.
Adv Sci (Weinh) ; : e2309068, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38477060

RESUMEN

To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2 W cm-2 ). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.

9.
Org Lett ; 26(10): 2007-2012, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38442042

RESUMEN

Here, we present a versatile modular strategy for crafting novel covalent organic cages (para-cage[n]arenes and meta-cage[n]arenes, n = 3,4) and bimacrocycles (meta-bimacrocyclic-arenes) with stable backbones and modifiable rims. These structures can be synthesized from commercially available aromatic multialdehydes in a three-step process: quantitative bromination, Suzuki-Miyaura reaction (yielding over 60%), and a rapid one-pot Friedel-Crafts reaction with paraformaldehyde. Notably, the cage[n]arenes exhibit a well-defined prismatic shape, and the bimacrocyclic-arenes display both dimeric and monomeric configurations.

10.
J Food Drug Anal ; 32(1): 54-64, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38526590

RESUMEN

Increased leptin resistance and methylglyoxal (MG) levels are observed in obese patients. However, whether MG deposits contribute to leptin resistance, oxidative stress, and inflammation in peripheral tissues remains unclear. In addition, the edible fruit of Indian gooseberry (Phyllanthus emblica L.) contains abundant bioactive components such as vitamin C, ß-glucogallin (ß-glu), gallic acid (GA), and ellagic acid (EA). Water extract of Indian gooseberry fruit (WEIG) and GA has been shown to improve cognitive decline by suppressing brain MG-induced insulin resistance in rats administered a high-fat diet (HFD). Accordingly, this study investigated the functions of WEIG and GA in inhibiting MG-induced leptin resistance, oxidative stress, and inflammation in the peripheral tissues of HFD-fed rats. The results showed that MG, advanced glycation end products (AGEs), and leptin resistance accumulation in the liver, kidney, and perinephric fat were effectively restored by elevated glyoxalase-1 (Glo-1) activity after WEIG and GA administration comparable to that of alagebrium chloride (positive control) treatment in HFD-fed rats. Furthermore, WEIG and GA supplementation increased adiponectin and antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase) and decreased inflammatory cytokines (IL-6, IL-1ß, TNF-α) in the peripheral tissues of HFD-fed rats. In conclusion, these findings demonstrated that MG may trigger leptin resistance, oxidative stress, and inflammation in peripheral tissues, which could be abolished by WEIG and GA treatment. These results show the potential of P. emblica for functional food development and improving obesity-associated metabolic disorders.


Asunto(s)
Phyllanthus emblica , Ribes , Humanos , Animales , Ratas , Leptina , Dieta Alta en Grasa/efectos adversos , Piruvaldehído , Ácido Gálico , Inflamación
11.
Eur J Pharmacol ; 967: 176393, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38325792

RESUMEN

Sunitinib (SUN) is the first-line targeted therapeutic drug for advanced renal cell carcinoma (RCC). However, SUN resistance is frequently observed to result in tumor metastasis, with a poor survival rate. Therefore, finding an effective and safe adjuvant to reduce drug resistance is important for RCC treatment. Pterostilbene (PTE) and 6-shogaol (6-S) are natural phytochemicals found in edible sources and have potential applications against various cancers. However, the biological mechanisms of PTE and 6-S in SUN-resistant RCC are still unclear. Accordingly, this study investigated the regulatory effects of PTE and 6-S on cell survival, drug resistance, and cell invasion in 786-O and SUN-resistant 786-O (786-O SUNR) cells, respectively. The results demonstrated that PTE and 6-S induced apoptosis in both cell lines by upregulating the Bax/Bcl-2 ratio. Additionally, PTE and 6-S increased SUN sensitivity by inhibiting the expression of the RLIP76 transport protein, reduced cell invasion and downregulated MMP expression in both 786-O and 786-O SUNR cells. Mechanistically, PTE, and 6-S significantly and dose-dependently suppressed the RLIP76-initiated Ras/ERK and Akt/mTOR pathways. In summary, PTE and 6-S induce apoptosis, enhance SUN sensitivity, and inhibit migration in both 786-O and 786-O SUNR cells. These novel findings demonstrate the potential of PTE and 6-S as target therapeutic adjuvants for RCC treatment.


Asunto(s)
Carcinoma de Células Renales , Catecoles , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Sunitinib/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias Renales/patología , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular Tumoral
12.
J Med Chem ; 67(3): 2176-2187, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38284525

RESUMEN

Long-acting neuromuscular blocks followed by rapid reversal may provide prolonged surgeries with improved conditions by omitting repetitive or continuous administration of the neuromuscular blocking agent (NMBA), eliminating residual neuromuscular block and minimizing postoperative recovery, which, however, is not clinically available. Here, we demonstrate that imidazolium-based macrocycles (IMCs) and acyclic cucurbit[n]urils (ACBs) can form such partners by functioning as long-acting NMBAs and rapid reversal agents through a pseudo[2]catenation mechanism based on stable complexation with Ka values of over 109 M-1. In vivo experiments with rats reveal that, at the dose of 2- and 3-fold ED90, one IMC attains a duration of action corresponding to 158 or 442 min for human adults, covering most of prolonged surgeries. The block can be reversed by one ACB with recovery time significantly shorter than that achieved by sugammadex for reversing the block of rocuronium, the clinically most widely used intermediate-acting NMBA.


Asunto(s)
Catenanos , Bloqueo Neuromuscular , gamma-Ciclodextrinas , Adulto , Humanos , Animales , Ratas , Sugammadex/farmacología , Rocuronio
13.
Clin Nurs Res ; 33(1): 19-26, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37596863

RESUMEN

This study sought to evaluate the impact of the subcutaneous tunneling technique on peripherally inserted central catheter (PICC) placement. We randomized 694 patients who needed PICC placement to either the tunneled PICCs (experimental group) or the non-tunneled PICCs (control group) from August to December 2021. The cumulative frequency of complications was assessed as the primary outcome. Secondary outcomes comprised of the amount of bleeding, catheter insertion time, self-reported pain score, and one-puncture success rate. After 6 months of follow-up, the tunneled PICCs group showed a significant decrease in the frequency of total complications, especially in infection (3.0% vs. 7.1%, p = .021) and catheter-related thrombosis (3.3% vs. 8.3%, p = .008), although approximately 0.5 ml bleeding and 3.5 min time were increased. This randomized multicenter study supports the efficacy of subcutaneous tunneling technology in reducing PICC-related complications, enhancing patient comfort, and encouraging using subcutaneous tunneling technology for PICC placement.


Asunto(s)
Cateterismo Venoso Central , Cateterismo Periférico , Neoplasias , Humanos , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Factores de Riesgo , Neoplasias/terapia , Cateterismo Periférico/métodos , Catéteres , Estudios Retrospectivos
14.
Int J Biol Macromol ; 258(Pt 2): 129043, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38158054

RESUMEN

Pharmacological treatments for colitis have limited efficacy and side effects. Plant polysaccharides improve colitis by modulating the gut microbiota. However, the specific benefits of Phyllanthus emblica L. polysaccharides (PEPs) in colitis remain unclear. Therefore, this study aimed to assess the physical characteristics and health advantages of PEP in rats subjected to 2,4,6-trinitrobenzene sulfonic acid (TNBS) treatment. The results showed that PEP (1.226 × 103 kDa) was an α-acidic pyran heteropolysaccharide rich in galactose and galacturonic acid. Prefeeding rats with PEP significantly decreased the levels of NO, MDA, proinflammatory cytokines (IL-6, IL-1ß, TNF-α), apoptosis, and the activities of mucinase and ß-glucuronidase. These changes were accompanied by increases in the levels of anti-inflammatory cytokines (IL-4, IL-10) and antioxidant enzymes (SOD, catalase, GPx) in colitis rats. Mechanistically, PEP suppressed the abundance of inflammatory-related bacteria (Bacteroides, Intestinimonas, and Parabacteroides) while promoting the growth of short-chain fatty acid (SCFA)-producing bacteria (Romboutsia, Clostridium_sensu_stricto_1, and Lactobacillus), along with an increase in SCFA secretion. SCFAs may engage with the GPR43 receptor and inhibit downstream HDAC3, consequently downregulating the activation of the RAGE/NF-κB and MAPK pathways. In conclusion, PEP demonstrated preventive effects through its antioxidant, anti-inflammatory, and microbiota modulation properties, thereby ameliorating TNBS-induced colitis in rats.


Asunto(s)
Colitis , Microbioma Gastrointestinal , Phyllanthus emblica , Ratas , Animales , FN-kappa B/metabolismo , Phyllanthus emblica/metabolismo , Antioxidantes/farmacología , Colitis/tratamiento farmacológico , Transducción de Señal , Citocinas/metabolismo , Polisacáridos/farmacología , Antiinflamatorios/farmacología , Ácido Trinitrobencenosulfónico/efectos adversos , Ácido Trinitrobencenosulfónico/metabolismo , Colon/metabolismo
15.
Phys Chem Chem Phys ; 26(1): 412-420, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38078489

RESUMEN

Recently, MXenes, an emerging family of two-dimensional (2D) materials, have attracted increasing interest for photocatalytic water splitting due to their various excellent physical and chemical properties, such as large specific surface area, good hydrophilicity, and remarkable light absorption ability. However, the photocatalysts of MXenes with symmetric structures are limited by rapid recombination of photo-generated carriers and the prerequisite of a large band gap no less than 1.23 eV. Differently, Janus MXenes with different surface functional groups facilitate the separation of photo-generated electrons and holes with the help of the intrinsic electric field. And, at the same time, there is no prerequisite for the band gap of Janus MXene photocatalysts as long as they possess appropriate band edge positions. Here, we explored the structural, electronic and photocatalytic water splitting properties of symmetric Y2CT2 and Janus Y2CTT' MXenes (T, T' = H, F, Cl, OH) using the density functional theory (DFT) method. Our calculations show that all the investigated Y2CT2 are not suitable photocatalysts for photocatalytic water splitting at all pH values (pH = 0, 7, and 14). In contrast, all the investigated Janus Y2CTT' MXenes are good water splitting photocatalysts with high optical absorption coefficients and remarkable solar-to-hydrogen (STH) efficiencies larger than 18% at pH = 14. Moreover, the STH efficiencies are larger than 18% even at all investigated pH values for Y2CHCl (18.5-22.6%), Y2 CFCl (∼18.7%), and Y2 C(OH)Cl (∼19.4%). Based on the first-principles calculations, we here for the first time propose an easy strategy to design Janus MXene photocatalyst candidates with possible high STH efficiency according to the electronic properties of their symmetric counterparts. Our study is helpful for the future design of Janus MXenes and more generally Janus 2D photocatalysts for water splitting with high STH efficiency.

16.
Rev Sci Instrum ; 94(12)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38117197

RESUMEN

The utilization of a low-frequency (<200 MHz) RF system in storage facilitates the attainment of ultra-low emittances in synchrotron light sources through on-axis injection. This paper focuses on the development of a low-frequency normal conducting (NC) cavity with higher-order mode (HOM) damping for fourth-generation synchrotron light sources. We propose a novel approach to achieve efficient HOM damping in a NC cavity by optimizing the lowest frequency HOM and implementing a beam-line absorber. Notably, unlike conventional NC cavities, the presence of a large beam tube for the beam-line absorber does not compromise the accelerating performance in a coaxial resonant cavity, enabling effective HOM damping while maintaining a high shunt impedance. Through simulations, the prototype design of a 166.6 MHz HOM-damped cavity demonstrates a fundamental mode impedance of ∼8 MΩ, with longitudinal and transverse HOM impedances below 2.0 and 50 kΩ/m, respectively.

17.
Cells ; 12(24)2023 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-38132176

RESUMEN

In the skin, repeated incidents of ischemia followed by reperfusion can result in the breakdown of the skin and the formation of a pressure ulcer. Here we gently applied paired magnets to the backs of mice to cause ischemia for 1.5 h and then removed them to allow reperfusion. The sterile inflammatory response generated within 4 h causes a stage 1 pressure ulcer with an elevation of the gap junction protein Cx43 in the epidermis. If this process is repeated the insult will result in a more severe stage 2 pressure ulcer with a breakdown of the epidermis 2-3 days later. After a single pinch, the elevation of Cx43 in the epidermis is associated with the inflammatory response with an increased number of neutrophils, HMGB1 (marker of necrosis) and RIP3 (responsible for necroptosis). Delivering Cx43 specific antisense oligonucleotides sub-dermally after a single insult, was able to significantly reduce the elevation of epidermal Cx43 protein expression and reduce the number of neutrophils and prevent the elevation of HMGB1 and RIP3. In a double pinch model, the Cx43 antisense treatment was able to reduce the level of inflammation, necroptosis, and the extent of tissue damage and progression to an open wound. This approach may be useful in reducing the progression of stage 1 pressure ulcers to stage 2.


Asunto(s)
Proteína HMGB1 , Úlcera por Presión , Ratones , Animales , Conexina 43/metabolismo , Conexinas/metabolismo , Isquemia
18.
J Orthop Surg Res ; 18(1): 870, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37968686

RESUMEN

OBJECTIVES: This study aimed to explore the value of the Charlson comorbidity index (CCI) in predicting ICU admission in patients with aortic aneurysm (AA). METHODS: The clinical data of patients were obtained from the Medical Information Mart for Intensive Care-IV database. The association between CCI and ICU admission was explored by restricted cubic spline (RCS), threshold effect analysis, generalized linear model, logistic regression, interaction, and mediation analyses. Its clinical value was evaluated by decision curve analysis (DCA), receiver operating characteristic curve (ROC), DeLong's test, and net reclassification index (NRI) analyses. RESULTS: The ICU admission was significantly associated with the thoracic AA (TAA), unruptured status, and surgery status. Therefore, 288 candidate patients with unruptured TAA who received surgery were enrolled in the further analysis. We found that CCI was independently associated with the ICU admission of candidates (P = 0.005). Further, their nonlinear relationship was observed (adjusted P = 0.008), and a significant turning point of 6 was identified. The CCI had a favorable performance in predicting ICU admission (area under curve = 0.728) and achieved a better clinical net benefit. New models based on CCI significantly improved the accuracy of prediction. Besides the importance of CCI in ICU admission, CCI also exerted important interaction effect (rather than mediating effects) on the association of other variables (such as age and blood variables) with ICU admission requirements (all P < 0.05). CONCLUSIONS: The CCI is an important predictor of ICU admission after surgery in patients with unruptured TAA.


Asunto(s)
Aneurisma de la Aorta Torácica , Hospitalización , Humanos , Curva ROC , Comorbilidad , Aneurisma de la Aorta Torácica/epidemiología , Aneurisma de la Aorta Torácica/cirugía , Unidades de Cuidados Intensivos , Estudios Retrospectivos
19.
bioRxiv ; 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37905143

RESUMEN

Significance: Genetically encoded calcium ion (Ca2+) indicators (GECIs) are powerful tools for monitoring intracellular Ca2+ concentration changes in living cells and model organisms. In particular, GECIs have found particular utility for monitoring the transient increase of Ca2+ concentration that is associated with the neuronal action potential. However, the palette of highly optimized GECIs for imaging of neuronal activity remains relatively limited. Expanding the selection of available GECIs to include new colors and distinct photophysical properties could create new opportunities for in vitro and in vivo fluorescence imaging of neuronal activity. In particular, blue-shifted variants of GECIs are expected to have enhanced two-photon brightness, which would facilitate multiphoton microscopy. Aim: We describe the development and applications of T-GECO1 - a high-performance blue-shifted GECI based on the Clavularia sp.-derived mTFP1. Approach: We used protein engineering and extensive directed evolution to develop T-GECO1. We characterize the purified protein and assess its performance in vitro using one-photon excitation in cultured rat hippocampal neurons, in vivo using one-photon excitation fiber photometry in mice, and ex vivo using two-photon Ca2+ imaging in hippocampal slices. Results: The Ca2+-bound state of T-GECO1 has an excitation peak maximum of 468 nm, an emission peak maximum of 500 nm, an extinction coefficient of 49,300 M-1cm-1, a quantum yield of 0.83, and two-photon brightness approximately double that of EGFP. The Ca2+-dependent fluorescence increase is 15-fold and the apparent Kd for Ca2+ is 82 nM. With two-photon excitation conditions at 850 nm, T-GECO1 consistently enabled detection of action potentials with higher signal-to-noise (SNR) than a late generation GCaMP variant. Conclusion: T-GECO1 is a high performance blue-shifted GECI that, under two-photon excitation conditions, provides advantages relative to late generation GCaMP variants.

20.
Nanoscale ; 15(39): 16188-16198, 2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37772909

RESUMEN

Fe-N-C catalysts with highly dispersed metal active centers were developed as promising non-precious metal materials for acidic oxygen reduction reaction (ORR) electrocatalysis. However, such kind of novel catalysts still suffer from major challenges in the manipulation of dispersion, utilization, and stability of the Fe-based metal centers. Herein, a N-rich molecular dual-guided pyrolysis strategy was proposed to develop an efficient yolk-shelled Fe-N-C ORR electrocatalyst. A unique yolk-shelled nanostructure with a relatively ordered shell and disordered yolk of a carbon skeleton was controllably constructed via this guided-pyrolysis route from the precursor of Fe-doped zeolitic imidazolate framework-8 (Fe-ZIF-8). Moreover, the atomic-level dispersion of Fe element in the carbon skeleton could be achieved via the dual guidance from phenanthroline and melamine molecules. The optimized Fe-N-C catalyst demonstrated a half-wave potential of 0.78 V vs. RHE in acid media, close to commercial 30% Pt/C, along with a small negative shift of 19 mV after an accelerated durability test. These enhanced electrocatalytic properties could be attributed to the preferred transformation of the Fe precursors to atomically dispersed Fe-Nx active configurations, as well as the enhanced three-phased interfacial reaction kinetics.

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