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1.
Nano Lett ; 24(5): 1579-1586, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38284987

RESUMEN

Engineering room-temperature strong coupling of few-exciton in transition-metal dichalcogenides (TMDCs) with plasmons promises to construct compact and high-performance quantum optical devices. But it remains unimplemented due to their in-plane excitons. Here, we demonstrate the strong coupling of few-exciton within 10 in monolayer WS2 with the plasmonic mode with a large tangential component of the electric field tightly trapped around the sharp corners of an Au@Ag nanocuboid, the fewest number of excitons observed in the TMDC family so far. Furthermore, we for the first time report a significant deviation with a relative difference of up to 100.6% between the spectrum and eigenlevel splitting dispersions, which increases with decreasing coupling strength. It is also shown that the coupling strength obtained by the conventional concept of both being equal to the measured spectrum splitting is markedly overestimated. Our work enriches the understanding of strong light-matter interactions at room temperature.

2.
Blood ; 140(10): 1145-1155, 2022 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-35820059

RESUMEN

Developing erythroblasts acquire massive amounts of iron through the transferrin (Tf) cycle, which involves endocytosis, sorting, and recycling of the Tf-Tf receptor (Tfrc) complex. Previous studies on the hemoglobin-deficit (hbd) mouse have shown that the exocyst complex is indispensable for the Tfrc recycling; however, the precise mechanism underlying the efficient exocytosis and recycling of Tfrc in erythroblasts remains unclear. Here, we identify the guanine nucleotide exchange factor Grab as a critical regulator of the Tf cycle and iron metabolism during erythropoiesis. Grab is highly expressed in differentiating erythroblasts. Loss of Grab diminishes the Tfrc recycling and iron uptake, leading to hemoglobinization defects in mouse primary erythroblasts, mammalian erythroleukemia cells, and zebrafish embryos. These defects can be alleviated by supplementing iron together with hinokitiol, a small-molecule natural compound that can mediate iron transport independent of the Tf cycle. Mechanistically, Grab regulates the exocytosis of Tfrc-associated vesicles by activating the GTPase Rab8, which subsequently promotes the recruitment of the exocyst complex and vesicle exocytosis. Our results reveal a critical role for Grab in regulating the Tf cycle and provide new insights into iron homeostasis and erythropoiesis.


Asunto(s)
Eritroblastos , Factores de Intercambio de Guanina Nucleótido , Hierro , Receptores de Transferrina , Animales , Eritroblastos/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Hierro/metabolismo , Mamíferos/metabolismo , Ratones , Receptores de Transferrina/genética , Receptores de Transferrina/metabolismo , Transferrina/metabolismo , Pez Cebra/metabolismo
3.
J Asian Nat Prod Res ; 26(3): 353-371, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37589480

RESUMEN

The organic anion transporter 3 (OAT3), an important renal uptake transporter, is associated with drug-induced acute kidney injury (AKI). Screening and identifying potent OAT3 inhibitors with little toxicity in natural products, especially flavonoids, in reducing OAT3-mediated AKI is of great value. The five strongest OAT3 inhibitors from the 97 flavonoids markedly decreased aristolochic acid I-induced cytotoxicity and alleviated methotrexate-induced nephrotoxicity. The pharmacophore model clarified hydrogen bond acceptors and hydrophobic groups are the critical pharmacophores. These findings would provide valuable information in predicting the potential risks of flavonoid-containing food/herb-drug interactions and optimizing flavonoid structure to alleviate OAT3-related AKI.


Asunto(s)
Lesión Renal Aguda , Flavonoides , Transportadores de Anión Orgánico Sodio-Independiente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Transporte Biológico , Flavonoides/farmacología , Flavonoides/química , Transportadores de Anión Orgánico/efectos de los fármacos , Transportadores de Anión Orgánico/metabolismo , Relación Estructura-Actividad , Transportadores de Anión Orgánico Sodio-Independiente/efectos de los fármacos , Transportadores de Anión Orgánico Sodio-Independiente/metabolismo
4.
Environ Sci Technol ; 57(1): 674-684, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36576943

RESUMEN

Microbial extracellular electron transfer (EET) is the basis for many microbial processes involved in element geochemical recycling, bioenergy harvesting, and bioremediation, including the technique for remediating U(VI)-contaminated environments. However, the low EET rate hinders its full potential from being fulfilled. The main challenge for engineering microbial EET is the difficulty in optimizing cell resource allocation for EET investment and basic metabolism and the optimal coordination of the different EET pathways. Here, we report a novel combinatorial optimization strategy with a physiologically adapted regulatory platform. Through exploring the physiologically adapted regulatory elements, a 271.97-fold strength range, autonomous, and dynamic regulatory platform was established for Shewanella oneidensis, a prominent electrochemically active bacterium. Both direct and mediated EET pathways are modularly reconfigured and tuned at various intensities with the regulatory platform, which were further assembled combinatorically. The optimal combinations exhibit up to 16.12-, 4.51-, and 8.40-fold improvements over the control in the maximum current density (1009.2 mA/m2) of microbial electrolysis cells and the voltage output (413.8 mV) and power density (229.1 mW/m2) of microbial fuel cells. In addition, the optimal strains exhibited up to 6.53-fold improvement in the radionuclide U(VI) removal efficiency. This work provides an effective and feasible approach to boost microbial EET performance for environmental applications.


Asunto(s)
Fuentes de Energía Bioeléctrica , Shewanella , Electrones , Transporte de Electrón , Biodegradación Ambiental , Shewanella/metabolismo
5.
Proc Natl Acad Sci U S A ; 117(37): 23001-23010, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32855303

RESUMEN

The unique extracellular electron transfer (EET) ability has positioned electroactive bacteria (EAB) as a major class of cellular chassis for genetic engineering aimed at favorable environmental, energy, and geoscience applications. However, previous efforts to genetically enhance EET ability have often impaired the basal metabolism and cellular growth due to the competition for the limited cellular resource. Here, we design a quorum sensing-based population-state decision (PSD) system for intelligently reprogramming the EET regulation system, which allows the rebalanced allocation of the cellular resource upon the bacterial growth state. We demonstrate that the electron output from Shewanella oneidensis MR-1 could be greatly enhanced by the PSD system via shifting the dominant metabolic flux from initial bacterial growth to subsequent EET enhancement (i.e., after reaching a certain population-state threshold). The strain engineered with this system achieved up to 4.8-fold EET enhancement and exhibited a substantially improved pollutant reduction ability, increasing the reduction efficiencies of methyl orange and hexavalent chromium by 18.8- and 5.5-fold, respectively. Moreover, the PSD system outcompeted the constant expression system in managing EET enhancement, resulting in considerably enhanced electron output and pollutant bioreduction capability. The PSD system provides a powerful tool for intelligently managing extracellular electron transfer and may inspire the development of new-generation smart bioelectrical devices for various applications.


Asunto(s)
Transporte de Electrón/fisiología , Shewanella/fisiología , Respiración de la Célula/fisiología , Cromo/metabolismo , Electrones , Percepción de Quorum/fisiología , Shewanella/metabolismo
6.
Plant Biotechnol J ; 20(8): 1561-1577, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35514032

RESUMEN

Adventitious rooting is an essential biological process in the vegetative propagation of economically important horticultural and forest tree species. It enables utilization of the elite genotypes in breeding programmes and production. Promotion of adventitious root (AR) formation has been associated with starvation of inorganic phosphate and some factors involved in low phosphorus (LP) signalling. However, the regulatory mechanism underlying LP-mediated AR formation remains largely elusive. We established an efficient experimental system that guaranteed AR formation through short-term LP treatment in Populus ussuriensis. We then generated a time-course RNA-seq data set to recognize key regulatory genes and regulatory cascades positively regulating AR formation through data analysis and gene network construction, which were followed by experimental validation and characterization. We constructed a multilayered hierarchical gene regulatory network, from which PuMYB40, a typical R2R3-type MYB transcription factor (TF), and its interactive partner, PuWRKY75, as well as their direct targets, PuLRP1 and PuERF003, were identified to function upstream of the known adventitious rooting genes. These regulatory genes were functionally characterized and proved their roles in promoting AR formation in P. ussuriensis. In conclusion, our study unveiled a new hierarchical regulatory network that promoted AR formation in P. ussuriensis, which was activated by short-term LP stimulus and primarily governed by PuMYB40 and PuWRKY75.


Asunto(s)
Populus , Regulación de la Expresión Génica de las Plantas/genética , Fósforo , Fitomejoramiento , Raíces de Plantas/genética , Populus/genética
7.
J Transl Med ; 20(1): 416, 2022 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-36085041

RESUMEN

BACKGROUND: Bowen's disease is a cutaneous squamous cell carcinoma (CSCC) in situ. If left untreated, BD may progress to invasive CSCC. CSCC is one of the most common cutaneous carcinoma in the elderly and the advanced, metastasis CSCC usually have a poor outcomes. However, the mechanisms of invasion and metastasis from Bowen's disease to CSCC is complicated and still unclear. OBJECTIVES: The aim of this study was to explore the biomarkers and molecular alterations in Bowen's disease development process via analyzing the proteomics changes in tissues of CSCC, Bowen disease and healthy skin. METHODS: A total of 7 individuals with CSCC (5 for proteomics study and 2 for validation), 7 individuals with Bowen disease (5 for proteomics study and 2 for validation) and 7 healthy controls (5 for proteomics study and 2 for validation) presented to the Department of Dermatology, Yijishan Hospital, the First Affiliated Hospital of Wannan Medical College between January 2021 and December 2021 were enrolled. The proteomics analysis was performed to screen differentially expressed proteins/gens (DEPs/DEGs) in the lesions of CSCC, Bowen disease and healthy skin tissues. The transcriptomic data (GSE32628) of CSCC was selected and downloaded from the GEO database. The common DEGs in our proteomics results and GSE32628 between CSCC and healthy skin tissues were selected. And then, the common DEGs which significantly up or down-regulated between CSCC and Bowen disease in our proteomics results were further screened to identify using Western blot methods in the validation group. CSCC A431 cells were transfected with SERPINB1 small interfering RNA (si-SERPINB1) or small interfering RNA negative control (si-NC). To explore the effect of SERPINB1 silencing on migration and invasion ability of A431 cells. RESULTS: A total of 501 proteins were differentially expressed between the CSCC and healthy skin tissues, with 332 up-regulated and 169 down-regulated at least 1.5-fold with a P value < 0.05. These DEPs involved multiple biological functions such as protein binding process, immune, inflammation, ribosome, protein digestion and absorption, ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway and others. A total of 20 common DEGs (COL3A1, LUM, TNC, COL1A1, ALDH3A2, FSCN1, SERPINB4, SERPINB1, CD36, COL4A1, CSTB, GPX3, S100A7, ACTN1, SERPINB3, S100A8, RAB31, STAT1, SPRR1B, S100A9) between CSCC and healthy skin tissues in GSE32628 and our proteomics results were found. Besides, the proteins of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in CSCC were significantly up-regulated, while COL3A1, COL1A1 and CD36 were significantly down-regulated relative to Bowen disease in proteomics results. These proteins were mainly involved in multiple pathways, including Focal adhesion, ECM-receptor interaction, Human papillomavirus infection, PI3K-Akt signaling pathway, PPAR signaling pathway, AMPK signaling pathway and others. These eight proteins were selected for further validation. According to the Western blotting analysis, when compared with the Bowen disease and healthy skin tissues, we found that the relative expression levels of TNC, FSCN1, SERPINB1, ACTN1 and RAB31 in the CSCC were significantly increased, while COL1A1 and CD36 were significantly decreased, and the differences were statistically significant (P < 0.05). Furthermore, the relative expression levels of TNC, FSCN1, SERPINB1 in the Bowen disease were also significantly increased, while the COL3A1 were also significantly decreased relative to the healthy control. SERPINB1 siRNA inhibited the expression of SERPINB1 at mRNA and protein levels in the A431 cells. After interfering with the expression of SERPINB1, the migration and invasion ability in the A431 cells were significantly decreased (P < 0.05). CONCLUSIONS: This study highlights that eight proteins, TNC, FSCN1, SERPINB1, ACTN1, RAB31, COL3A1, COL1A1, CD36, were significantly associated with the mechanisms of invasion and metastasis in Bowen's disease.


Asunto(s)
Enfermedad de Bowen , Carcinoma de Células Escamosas , Serpinas , Neoplasias Cutáneas , Anciano , Biomarcadores , Enfermedad de Bowen/genética , Carcinoma de Células Escamosas/genética , Proteínas Portadoras , Humanos , Proteínas de Microfilamentos , Fosfatidilinositol 3-Quinasas , Proteómica , Proteínas Proto-Oncogénicas c-akt , ARN Interferente Pequeño , Neoplasias Cutáneas/genética , Transcriptoma/genética
8.
Blood ; 135(3): 208-219, 2020 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-31945154

RESUMEN

Mammalian red blood cells lack nuclei. The molecular mechanisms underlying erythroblast nuclear condensation and enucleation, however, remain poorly understood. Here we show that Wdr26, a gene upregulated during terminal erythropoiesis, plays an essential role in regulating nuclear condensation in differentiating erythroblasts. Loss of Wdr26 induces anemia in zebrafish and enucleation defects in mouse erythroblasts because of impaired erythroblast nuclear condensation. As part of the glucose-induced degradation-deficient ubiquitin ligase complex, Wdr26 regulates the ubiquitination and degradation of nuclear proteins, including lamin B. Failure of lamin B degradation blocks nuclear opening formation leading to impaired clearance of nuclear proteins and delayed nuclear condensation. Collectively, our study reveals an unprecedented role of an E3 ubiquitin ligase in regulating nuclear condensation and enucleation during terminal erythropoiesis. Our results provide mechanistic insights into nuclear protein homeostasis and vertebrate red blood cell development.


Asunto(s)
Diferenciación Celular , Núcleo Celular/metabolismo , Eritroblastos/fisiología , Eritropoyesis , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de Pez Cebra/metabolismo , Pez Cebra/metabolismo , Animales , Núcleo Celular/genética , Eritroblastos/citología , Péptidos y Proteínas de Señalización Intracelular/genética , Ratones , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Pez Cebra/genética , Pez Cebra/crecimiento & desarrollo , Proteínas de Pez Cebra/genética
9.
Opt Express ; 30(17): 30832-30844, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-36242180

RESUMEN

This paper proposes a vanadium dioxide metamaterial-based tunable, polarization-independent coherent perfect absorber (CPA) in the terahertz frequency range. The designed CPA demonstrates intelligent reconfigurable switch modulation from an ultra-broadband absorber mode to a dual-band absorber mode via the thermally controlled of VO2. The mode of ultra-broadband absorber is realized when the conductivity of VO2 reaches 11850 S/m via controlling its temperature around T = 328 K. In this mode, the CPA demonstrates more than 90% absorption efficiency within the ultra-wide frequency band that extends from 0.1 THz to 10.8 THz. As the conductivity of VO2 reaches 2×105 S/m (T = 340 K), the CPA switches to a dual-band absorber mode where a relatively high absorption efficiency of 98% and 99.7% is detected at frequencies of 4.5 THz and 9.8 THz, respectively. Additionally, using phase modulation of the incident light, the proposed CPA can regulate the absorption efficiency, which can be intelligently controlled from perfect absorption to high pass-through transmission. Owing to the ability of the proposed CPA to intelligently control the performance of light, this study can contribute towards enhancing the performance of stealth devices, all-optical switches and coherent photodetectors.

10.
Int J Mol Sci ; 23(7)2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-35409200

RESUMEN

In this study, we characterized the gene expression profile in the roots of Populus ussuriensis at 0, 6, 12, 24, 48 and 120 h after the start of polyethylene glycol (PEG)-induced drought stress using PacBio single-molecule real-time sequencing (SMRT-seq) and Illumina RNA sequencing. Compared to the control, 2244 differentially expressed genes (DEGs) were identified, and many of these DEGs were associated with the signal transduction, antioxidant system, ion accumulation and drought-inducing proteins. Changes in certain physiological and biochemical indexes, such as antioxidant activity and the contents of Ca2+, proline, and total soluble sugars, were further confirmed in P. ussuriensis roots. Furthermore, most of the differentially expressed transcription factors were members of the AP2/ERF, C2H2, MYB, NAC, C2C2 and WRKY families. Additionally, based on PacBio SMRT-seq results, 5955 long non-coding RNAs and 700 alternative splicing events were identified. Our results provide a global view of the gene expression profile that contributes to drought resistance in P. ussuriensis and meaningful information for genetic engineering research in the future.


Asunto(s)
Populus , Sequías , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Populus/genética , Populus/metabolismo , Estrés Fisiológico/genética , Transcriptoma
11.
Molecules ; 27(23)2022 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-36500657

RESUMEN

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.


Asunto(s)
Gentamicinas , Factor 2 Relacionado con NF-E2 , Ratas , Animales , Gentamicinas/efectos adversos , Factor 2 Relacionado con NF-E2/metabolismo , Apoptosis , Riñón , Malondialdehído/metabolismo , Glutatión/metabolismo
12.
Environ Microbiol ; 23(2): 1238-1255, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33369000

RESUMEN

The advances in synthetic biology bring exciting new opportunities to reprogram microorganisms with novel functionalities for environmental applications. For real-world applications, a genetic tool that enables genetic engineering in a stably genomic inherited manner is greatly desired. In this work, we design a novel genetic device for rapid and efficient genome engineering based on the intron-encoded homing-endonuclease empowered genome editing (iEditing). The iEditing device enables rapid and efficient genome engineering in Shewanella oneidensis MR-1, the representative strain of the electroactive bacteria group. Moreover, combining with the Red or RecET recombination system, the genome-editing efficiency was greatly improved, up to approximately 100%. Significantly, the iEditing device itself is eliminated simultaneously when genome editing occurs, thereby requiring no follow-up to remove the encoding system. Then, we develop a new extracellular electron transfer (EET) engineering strategy by programming the parallel EET systems to enhance versatile EET. The engineered strains exhibit sufficiently enhanced electron output and pollutant reduction ability. Furthermore, this device has demonstrated its great potential to be extended for genome editing in other important microbes. This work provides a useful and efficient tool for the rapid generation of synthetic microorganisms for various environmental applications.


Asunto(s)
Fuentes de Energía Bioeléctrica/microbiología , Electrones , Ingeniería Genética/métodos , Genoma Bacteriano/genética , Biodegradación Ambiental , Transporte de Electrón/genética , Contaminantes Ambientales/metabolismo , Edición Génica/instrumentación , Ingeniería Genética/instrumentación , Recombinación Genética , Shewanella/genética , Shewanella/metabolismo
13.
Opt Express ; 29(4): 6000-6010, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33726131

RESUMEN

In this paper, a metal-dielectric metamaterial absorber is proposed to achieve ultrabroadband absorption at frequencies from ultraviolet to near-infrared. Based on finite element method solutions, the average absorption of the absorber is 97.75% from 382 nm to 1100 nm, with a maximum of 99.92%, resulting from multiple resonance coupling. The influences of geometric parameters and incident conditions on absorption are investigated. Broadband and narrowband absorption changes are realized by changing incident light polarization. Polarization-independent properties can be realized by changing the dielectric structure to centrosymmetric. The average absorption of the polarization-independent structure is 97.11% from 250 nm to 1115 nm, with a maximum of 99.98%. The proposed absorber structure has wide optical applications including solar energy harvesting and light-emitting devices.

14.
Opt Express ; 29(5): 7158-7167, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33726222

RESUMEN

In this paper, we design a polarization-independent and angle-insensitive broadband THz graphene metamaterial absorber based on the surface plasmon-polaritons resonance. Full-wave simulation is conducted, and the results show that the designed metamaterial absorber has an absorption above 99% in the frequency range from 1.23 THz to 1.68 THz, which refers to a very high standard. Furthermore, the absorber has the properties of tunability, and the absorption can be nearly adjusted from 1% to 99% by varying the Fermi energy level of the graphene from 0 eV to 0.7 eV. In the simulation, when the incident angles of TE and TM waves change from 0° to 60°, the average absorption keeps greater than 80%. The proposed absorber shows promising performance, which has potential applications in developing graphene-based terahertz energy harvesting and thermal emission.

15.
Environ Sci Technol ; 55(17): 11997-12008, 2021 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-34378391

RESUMEN

Dissimilatory metal-reducing bacteria (DMRB) with extracellular electron transfer (EET) capability show great potential in bioremediating the subsurface environments contaminated by uranium through bioreduction and precipitation of hexavalent uranium [U(VI)]. However, the low EET efficiency of DMRB remains a bottleneck for their applications. Herein, we develop an engineered CRISPR platform to drive the extracellular electron pumping of Shewanella oneidensis, a representative DMRB species widely present in aquatic environments. The CRISPR platform allows for highly efficient and multiplex genome editing and rapid platform elimination post-editing in S. oneidensis. Enabled by such a platform, a genomic promoter engineering strategy (GPS) for genome-widely engineering the EET-encoding gene network was established. The production of electron conductive Mtr complex, synthesis of electron shuttle flavin, and generation of NADH as intracellular electron carrier are globally optimized and promoted, leading to a significantly enhanced EET ability. Applied to U(VI) bioreduction, the edited strains achieve up to 3.62-fold higher reduction capacity over the control. Our work endows DMRB with an enhanced ability to remediate the radionuclides-contaminated environments and provides a gene editing approach to handle the growing environmental challenges of radionuclide contaminations.


Asunto(s)
Shewanella , Uranio , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Transporte de Electrón , Electrones , Shewanella/genética
16.
J Anesth ; 35(5): 654-662, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34279702

RESUMEN

OBJECTIVE: This study explored the effects of sevoflurane exposure during different stages of pregnancy on the brain development of offspring. METHODS: Thirty-six pregnant SD rats were randomly divided into 4 groups: control, sevoflurane exposure in early (S1) pregnancy, sevoflurane exposure in middle (S2) pregnancy, and sevoflurane exposure in late (S3) pregnancy. After natural birth, the learning and memory capacity of offspring rats was analyzed using the Morris water maze experiment. The hippocampi of offspring rats were collected. The levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus were measured by ELISA. Additionally, the Nissl bodies in the hippocampus were analyzed using Nissl staining. Immunohistochemistry was used to examine the expression of BDNF and CPEB2 in the hippocampus of offspring. Proteins related to the NR4A1/NF-κB pathway were analyzed using western blotting. RESULTS: The memory and learning capacity of offspring rats was significantly reduced in the S1 and S2 groups compared to the control group (p < 0.05), while there was no obvious difference between the control and S3 groups (p > 0.05). The level of IL-1ß was significantly increased (p < 0.05) in the S1 group compared with the control group. Sevoflurane anesthesia received in early and middle pregnancy could significantly affect the formation of Nissl bodies in the hippocampi of offspring rats. In addition, the expression of BDNF and CPEB2 in the hippocampi of offspring rats was greatly decreased in the S1 group compared with the control group (p < 0.05). The expression of NR4A1 in the hippocampi of rat offspring was significantly decreased in the S1 and S2 groups compared with the control group (p < 0.05). The expression of proteins related to the NF-κB pathway was increased in the S1 group compared to the control group (p < 0.05). CONCLUSIONS: The neurotoxic effect of maternal sevoflurane anesthesia on the brain development of offspring is higher when the exposure occurs in early pregnancy than in late pregnancy, and its mechanism might involve the NR4A1/NF-κB pathway to increase the secretion of inflammatory cytokines.


Asunto(s)
Hipocampo , Aprendizaje , Animales , Femenino , Hipocampo/metabolismo , FN-kappa B/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Sevoflurano/toxicidad
17.
Oncologist ; 25(10): e1464-e1472, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32342599

RESUMEN

LESSONS LEARNED: Patient compliance with the oral dosage treatment was good, with no need for hospitalization. Patients with tracheal and esophageal fistulas can take crushed apatinib by nutrient tube, with the same bioavailability and efficacy. Apatinib may be an effective and safe second- or further-line treatment for advanced esophageal cancer. BACKGROUND: Apatinib is an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2), which is thought to play a role in esophageal cancer progression. Our goal was to evaluate the efficacy and safety of apatinib in patients with unresectable esophageal cancer and to examine whether VEGFR2 expression influenced the clinical response. METHODS: This single-arm, open-label, investigator-initiated phase II study enrolled patients with advanced squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or esophagogastric junction who were admitted to Tianjin Medical University Cancer Institute and Hospital between August 2017 and January 2019. Apatinib monotherapy (500 mg/day) was given orally or via an enteral tube until disease progression, unacceptable toxicity, withdrawal, or death. Patients were followed until treatment was discontinued or death. The main endpoints were tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: Among 32 patients screened for inclusion, 30 were included in the safety and survival analyses (i.e., received apatinib), and 26 were included in the efficacy analysis (at least one imaging follow-up). Median follow-up time and exposure to apatinib were 5.34 months and 72 days, respectively. Among 26 patients included in the efficacy analysis, 2 had a partial response (PR; 7.7%) and 14 had stable disease (SD; 53.8%). The overall response rate (ORR) was 7.7%, and the disease control rate (DCR) was 61.5%. Median PFS and OS were 4.63 months (95% confidence interval, 2.11-7.16 months) and 6.57 months (4.90 months to not estimable), respectively. Fifteen patients (50.0%) experienced treatment-related AEs, most commonly hypertension (26.7%), diarrhea (20.0%), and hand-foot-skin reaction (10.0%). No patients had grade ≥4 treatment-related AEs. CONCLUSION: Apatinib was effective as second- or further-line treatment for advanced esophageal cancer.


Asunto(s)
Antineoplásicos , Neoplasias Esofágicas , Neoplasias Esofágicas/tratamiento farmacológico , Humanos , Piridinas , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular
18.
Biochem Biophys Res Commun ; 527(3): 785-790, 2020 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-32423826

RESUMEN

Diabetic neuropathic pain is one of the most common complications of diabetes. Mechanisms underlying the central modulation are still unclear. Here, we investigated the role of the neuron-restricted silencing factor (NRSF/REST) in diabetic-related neuropathic pain. Mechanical allodynia and thermal hyperalgesia were assessed to evaluate painful behaviors. Our results found that in the anterior cingulate cortex (ACC) of db/db mice, NRSF/REST levels increased significantly. Reduction of NRSF/REST improved the painful sensation. Meanwhile, in vitro study found that high glucose and high palmitic acid treatment induced elevation of NRSF/REST and its cofactors (mSin3A, CoREST and HDAC1), whereas downregulation of GluR2 and NMDAR2B. Knockdown of NRSF/REST could attenuate the LDH release and partially reversed the expression changes of HDAC1 and NMDAR2B. Our results suggested that the elevation of NRSF/REST in the ACC area of db/db mice is one of the key mediators of diabetic neuropathic pain.


Asunto(s)
Neuropatías Diabéticas/fisiopatología , Giro del Cíngulo/fisiopatología , Hiperalgesia/fisiopatología , Proteínas Represoras/metabolismo , Animales , Neuropatías Diabéticas/complicaciones , Neuropatías Diabéticas/genética , Neuropatías Diabéticas/metabolismo , Técnicas de Silenciamiento del Gen , Giro del Cíngulo/metabolismo , Hiperalgesia/complicaciones , Hiperalgesia/genética , Hiperalgesia/metabolismo , Masculino , Ratones , Células PC12 , Ratas , Proteínas Represoras/genética , Regulación hacia Arriba
19.
Opt Express ; 28(21): 31781-31795, 2020 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-33115144

RESUMEN

In this paper, tunable dual plasmon-induced transparency (PIT) is achieved by using a monolayer graphene metamaterial in the terahertz region, which consists of two graphene strips of different sizes and a graphene ring. As the dual PIT effect is induced by the destructive interference between the two quasi-dark modes and the bright mode, we propose a four-level plasmonic system based on the linearly coupled Lorentzian oscillators to explain the mechanism behind the dual PIT. It is proved that the theoretical results agree well with the simulation results. Most importantly, the sensing properties of the designed device have been investigated in detail and we found that it can exhibit high sensitivities and figure of merit (FOM). Furthermore, the dual PIT windows can be effectively modulated by changing the Fermi energy of the graphene layer and the angle of incidence. Thus, the proposed graphene-based metamaterial can hold wide applications for switches, modulators, and multi-band refractive index sensors in the terahertz region.

20.
Environ Sci Technol ; 54(6): 3599-3608, 2020 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-32062962

RESUMEN

Pursuing efficient approaches to promote the extracellular electron transfer (EET) of extracellular respiratory bacteria is essential to their application in environmental remediation and waste treatment. Here, we report a new strategy of tuning electron flux by clustered regularly interspaced short palindromic repeat (CRISPR)-ddAsCpf1-based rediverting (namely STAR) to enhance the EET capacity of Shewanella oneidensis MR-1, a model extracellular respiratory bacterium widely present in the environment. The developed CRISPR-ddAsCpf1 system enabled approximately 100% gene repression with the green fluorescent protein (GFP) as a reporter. Using a WO3 probe, 10 representative genes encoding for putative competitive electron transfer proteins were screened, among which 7 genes were identified as valid targets for EET enhancement. Repressing the valid genes not only increased the transcription level of the l-lactate metabolism genes but also affected the genes involved in direct and indirect EET. Increased riboflavin production was also observed. The feasibility of this strategy to enhance the bioreduction of methyl orange, an organic pollutant, and chromium, a typical heavy metal, was demonstrated. This work implies a great potential of the STAR strategy with the CIRPSR-ddAsCpf1 system for enhancing bacterial EET to favor more efficient environmental remediation applications.


Asunto(s)
Contaminantes Ambientales , Shewanella , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Transporte de Electrón , Electrones
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