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1.
J Neurosci ; 43(24): 4525-4540, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37188517

RESUMO

Our recent study demonstrated the critical role of the mesolimbic dopamine (DA) circuit and its brain-derived neurotropic factor (BDNF) signaling in mediating neuropathic pain. The present study aims to investigate the functional role of GABAergic inputs from the lateral hypothalamus (LH) to the ventral tegmental area (VTA; LHGABA→VTA) in regulating the mesolimbic DA circuit and its BDNF signaling underlying physiological and pathologic pain. We demonstrated that optogenetic manipulation of the LHGABA→VTA projection bidirectionally regulated pain sensation in naive male mice. Optogenetic inhibition of this projection generated an analgesic effect in mice with pathologic pain induced by chronic constrictive injury (CCI) of the sciatic nerve and persistent inflammatory pain by complete Freund's adjuvant (CFA). Trans-synaptic viral tracing revealed a monosynaptic connection between LH GABAergic neurons and VTA GABAergic neurons. Functionally, in vivo calcium/neurotransmitter imaging showed an increased DA neuronal activity, decreased GABAergic neuronal activity in the VTA, and increased dopamine release in the NAc, in response to optogenetic activation of the LHGABA→VTA projection. Furthermore, repeated activation of the LHGABA→VTA projection was sufficient to increase the expression of mesolimbic BDNF protein, an effect seen in mice with neuropathic pain. Inhibition of this circuit induced a decrease in mesolimbic BDNF expression in CCI mice. Interestingly, the pain behaviors induced by activation of the LHGABA→VTA projection could be prevented by pretreatment with intra-NAc administration of ANA-12, a TrkB receptor antagonist. These results demonstrated that LHGABA→VTA projection regulated pain sensation by targeting local GABAergic interneurons to disinhibit the mesolimbic DA circuit and regulating accumbal BDNF release.SIGNIFICANCE STATEMENT The mesolimbic dopamine (DA) system and its brain-derived neurotropic factor (BDNF) signaling have been implicated in pain regulation, however, underlying mechanisms remain poorly understood. The lateral hypothalamus (LH) sends different afferent fibers into and strongly influences the function of mesolimbic DA system. Here, utilizing cell type- and projection-specific viral tracing, optogenetics, in vivo calcium and neurotransmitter imaging, our current study identified the LHGABA→VTA projection as a novel neural circuit for pain regulation, possibly by targeting the VTA GABA-ergic neurons to disinhibit mesolimbic pathway-specific DA release and BDNF signaling. This study provides a better understanding of the role of the LH and mesolimbic DA system in physiological and pathological pain.


Assuntos
Dopamina , Neuralgia , Camundongos , Masculino , Animais , Dopamina/metabolismo , Região Hipotalâmica Lateral/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cálcio/metabolismo , Área Tegmentar Ventral/fisiologia , Neurônios GABAérgicos/fisiologia , Ácido gama-Aminobutírico/metabolismo , Neuralgia/metabolismo , Sensação , Núcleo Accumbens/fisiologia
2.
Mol Pain ; 20: 17448069241252654, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38658141

RESUMO

Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. Mitochondrial-derived peptide (MOTS-c), a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate the putative underlying mechanisms. We found that endogenous MOTS-c levels in plasma and spinal dorsal horn were significantly lower in STZ-treated mice than in control animals. Accordingly, MOTS-c treatment significantly improves STZ-induced weight loss, elevation of blood glucose, mechanical allodynia, and thermal hyperalgesia; however, these effects were blocked by dorsomorphin, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, MOTS-c treatment significantly enhanced AMPKα1/2 phosphorylation and PGC-1α expression in the lumbar spinal cord of PDN mice. Mechanistic studies indicated that MOTS-c significantly restored mitochondrial biogenesis, inhibited microglia activation, and decreased the production of pro-inflammatory factors, which contributed to the alleviation of pain. Moreover, MOTS-c decreased STZ-induced pain hypersensitivity in PDN mice by activating AMPK/PGC-1α signaling pathway. This provides the pharmacological and biological evidence for developing mitochondrial peptide-based therapeutic agents for PDN.


Assuntos
Neuropatias Diabéticas , Hiperalgesia , Mitocôndrias , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Estreptozocina , Animais , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/patologia , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Peptídeos/farmacologia , Camundongos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Microglia/efeitos dos fármacos , Microglia/metabolismo
3.
Expert Rev Mol Med ; 26: e7, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602081

RESUMO

Trauma is a significant health issue that not only leads to immediate death in many cases but also causes severe complications, such as sepsis, thrombosis, haemorrhage, acute respiratory distress syndrome and traumatic brain injury, among trauma patients. Target protein identification technology is a vital technique in the field of biomedical research, enabling the study of biomolecular interactions, drug discovery and disease treatment. It plays a crucial role in identifying key protein targets associated with specific diseases or biological processes, facilitating further research, drug design and the development of treatment strategies. The application of target protein technology in biomarker detection enables the timely identification of newly emerging infections and complications in trauma patients, facilitating expeditious medical interventions and leading to reduced post-trauma mortality rates and improved patient prognoses. This review provides an overview of the current applications of target protein identification technology in trauma-related complications and provides a brief overview of the current target protein identification technology, with the aim of reducing post-trauma mortality, improving diagnostic efficiency and prognostic outcomes for patients.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/diagnóstico , Lesões Encefálicas Traumáticas/terapia , Hemorragia
4.
J Med Genet ; 60(10): 933-938, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37012053

RESUMO

BACKGROUND: Low-pass genome sequencing (LP GS) is an alternative to chromosomal microarray analysis (CMA). However, validations of LP GS as a prenatal diagnostic test for amniotic fluid are rare. Moreover, sequencing depth of LP GS in prenatal diagnosis has not been evaluated. OBJECTIVE: The diagnostic performance of LP GS was compared with CMA using 375 amniotic fluid samples. Then, sequencing depth was evaluated by downsampling. RESULTS: CMA and LP GS had the same diagnostic yield (8.3%, 31/375). LP GS showed all copy number variations (CNVs) detected by CMA and six additional variant of uncertain significance CNVs (>100 kb) in samples with negative CMA results; CNV size influenced LP GS detection sensitivity. CNV detection was greatly influenced by sequencing depth when the CNV size was small or the CNV was located in the azoospermia factor c (AZFc) region of the Y chromosome. Large CNVs were less affected by sequencing depth and more stably detected. There were 155 CNVs detected by LP GS with at least a 50% reciprocal overlap with CNVs detected by CMA. With 25 M uniquely aligned high-quality reads (UAHRs), the detection sensitivity for the 155 CNVs was 99.14%. LP GS using samples with 25 M UAHRs showed the same performance as LP GS using total UAHRs. Considering the detection sensitivity, cost and interpretation workload, 25 M UAHRs are optimal for detecting most aneuploidies and microdeletions/microduplications. CONCLUSION: LP GS is a promising, robust alternative to CMA in clinical settings. A total of 25 M UAHRs are sufficient for detecting aneuploidies and most microdeletions/microduplications.


Assuntos
Líquido Amniótico , Variações do Número de Cópias de DNA , Gravidez , Feminino , Humanos , Variações do Número de Cópias de DNA/genética , Diagnóstico Pré-Natal/métodos , Aneuploidia , Análise em Microsséries
5.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731974

RESUMO

Tomato (Solanum lycopersicum) breeding for improved fruit quality emphasizes selecting for desirable taste and characteristics, as well as enhancing disease resistance and yield. Seed germination is the initial step in the plant life cycle and directly affects crop productivity and yield. ERECTA (ER) is a receptor-like kinase (RLK) family protein known for its involvement in diverse developmental processes. We characterized a Micro-Tom EMS mutant designated as a knock-out mutant of sler. Our research reveals that SlER plays a central role in controlling critical traits such as inflorescence development, seed number, and seed germination. The elevation in auxin levels and alterations in the expression of ABSCISIC ACID INSENSITIVE 3 (ABI3) and ABI5 in sler seeds compared to the WT indicate that SlER modulates seed germination via auxin and abscisic acid (ABA) signaling. Additionally, we detected an increase in auxin content in the sler ovary and changes in the expression of auxin synthesis genes YUCCA flavin monooxygenases 1 (YUC1), YUC4, YUC5, and YUC6 as well as auxin response genes AUXIN RESPONSE FACTOR 5 (ARF5) and ARF7, suggesting that SlER regulates fruit development via auxin signaling.


Assuntos
Frutas , Germinação , Ácidos Indolacéticos , Proteínas de Plantas , Transdução de Sinais , Solanum lycopersicum , Ácido Abscísico/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Frutas/genética , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Sementes/genética , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/metabolismo
6.
Circulation ; 146(2): 125-139, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35616010

RESUMO

BACKGROUND: Early neonates of both large and small mammals are able to regenerate the myocardium through cardiomyocyte proliferation for only a short period after birth. This myocardial regenerative capacity declines in parallel with withdrawal of cardiomyocytes from the cell cycle in the first few postnatal days. No mammalian species examined to date has been found capable of a meaningful regenerative response to myocardial injury later than 1 week after birth. METHODS: We examined cardiomyocyte proliferation in neonates of the marsupial opossum (Monodelphis domestica) by immunostaining at various times after birth. The regenerative capacity of the postnatal opossum myocardium was assessed after either apex resection or induction of myocardial infarction at postnatal day 14 or 29, whereas that of the postnatal mouse myocardium was assessed after myocardial infarction at postnatal day 7. Bioinformatics data analysis, immunofluorescence staining, and pharmacological and genetic intervention were applied to determine the role of AMPK (5'-AMP-activated protein kinase) signaling in regulation of the mammalian cardiomyocyte cell cycle. RESULTS: Opossum neonates were found to manifest cardiomyocyte proliferation for at least 2 weeks after birth at a frequency similar to that apparent in early neonatal mice. Moreover, the opossum heart at postnatal day 14 showed substantial regenerative capacity both after apex resection and after myocardial infarction injury, whereas this capacity had diminished by postnatal day 29. Transcriptomic and immunofluorescence analyses indicated that AMPK signaling is activated in postnatal cardiomyocytes of both opossum and mouse. Pharmacological or genetic inhibition of AMPK signaling was sufficient to extend the postnatal window of cardiomyocyte proliferation in both mouse and opossum neonates as well as of cardiac regeneration in neonatal mice. CONCLUSIONS: The marsupial opossum maintains cardiomyocyte proliferation and a capacity for myocardial regeneration for at least 2 weeks after birth. As far as we are aware, this is the longest postnatal duration of such a capacity among mammals examined to date. AMPK signaling was implicated as an evolutionarily conserved regulator of mammalian postnatal cardiomyocyte proliferation.


Assuntos
Proteínas Quinases Ativadas por AMP , Coração , Monodelphis , Infarto do Miocárdio , Regeneração , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Animais Recém-Nascidos , Proliferação de Células , Coração/fisiologia , Camundongos , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo
7.
Mol Pain ; 19: 17448069231161031, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36938611

RESUMO

Bone cancer pain (BCP) is severe chronic pain caused by tumor metastasis to the bones, often resulting in significant skeletal remodeling and fractures. Currently, there is no curative treatment. Therefore, insight into the underlying mechanisms could guide the development of mechanism-based therapeutic strategies for BCP. We speculated that Rac1/PAK1 signaling plays a critical role in the development of BCP. Tumor cells implantation (TCI) into the tibial cavity resulted in bone cancer-associated mechanical allodynia. Golgi staining revealed changes in the excitatory synaptic structure of WDR (Wide-dynamic range) neurons in the spinal cord, including increased postsynaptic density (PSD) length and thickness, and width of the cleft. Behavioral and western blotting test revealed that the development and persistence of pain correlated with Rac1/PAK1 signaling activation in primary sensory neurons. Intrathecal injection of NSC23766, a Rac1 inhibitor, reduced the persistence of BCP as well as reversed the remodeling of dendrites. Therefore, we concluded that activation of the Rac1/PAK1 signaling pathway in the spinal cord plays an important role in the development of BCP through remodeling of dendritic spines. Modulation of the Rac1/PAK1 pathway may be a potential strategy for BCP treatment.


Assuntos
Neoplasias Ósseas , Dor do Câncer , Ratos , Animais , Dor do Câncer/patologia , Espinhas Dendríticas/metabolismo , Ratos Sprague-Dawley , Dor/patologia , Neoplasias Ósseas/complicações , Neoplasias Ósseas/patologia , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/metabolismo
8.
Chemistry ; 29(65): e202301294, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37589330

RESUMO

Organic molecular field-effect transistors (FETs) are promising building components for future electronic circuits. Efficient control of charge transport properties is one key issue in the design of organic molecular FETs. In this study, we propose a redesign of a naphthalene-based FET by introducing two azulene components in opposite dipole moment directions. Using density functional theory combined with non-equilibrium Green's function, the simulated electronic transport characteristics reveal that the introduction of polar azulene components effectively narrows the frontier molecular orbitals gap, leading to an increase in the ON-state current. Meanwhile, the OFF-state current is significantly suppressed by highly localizing the dominant electronic transport channel. As a result, improved gate controllability is achieved with a higher ON-OFF current ratio, which is nearly seven times higher than that of the naphthalene-based FET device. These findings provide theoretical directions for future design of organic molecular FET devices with enhanced gating regulation efficiency.

9.
Chemphyschem ; 24(6): e202200571, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36409197

RESUMO

Kinetic isotope effect values on the decarboxylation of 3-carboxybenzisoxazole have been computed using the second-order Kleinert's variational perturbation theory in the framework of Feynman's path integrals along with the potential energy surface obtained at the MP2/6-31+G(d) level. Good agreement with the experimental data was obtained, demonstrating that this novel computational approach for computing KIE values of organic reaction is a viable alternative to the traditional method employing the Bigeleisen equation and harmonic vibrational frequencies. Compared with the experimental measurements, consideration of anharmonicity and tunneling effects can significantly improve the calculated KIE values, reducing the root-mean-square deviation from 1.19 % for traditional method to 0.20 % for path-integral method.

10.
Cell Commun Signal ; 21(1): 205, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587494

RESUMO

BACKGROUND: Endothelial glycocalyx (EG) is an active player and treatment target in inflammatory-related vascular leakage. The bone marrow mesenchymal stem cells (bMSCs) are promising potential treatments for leakage; however, the therapeutic effect and mechanism of bMSC on EG degradation needs to be elucidated. METHODS: EG degradation and leakage were evaluated in both lipopolysaccharide (LPS)-induced mice ear vascular leakage model and LPS-stimulated human umbilical vein endothelial cells (HUVECs) model treated with bMSCs. Extracellular vesicles (EVs) were extracted from bMSCs and the containing microRNA profile was analyzed. EV and miR let-7-5p were inhibited to determine their function in the therapeutic process. The ABL2 gene was knockdown in HUVECs to verify its role as a therapeutic target in EG degradation. RESULTS: bMSCs treatment could alleviate LPS-induced EG degradation and leakage in vivo and in vitro, whereas EVs/let-7-5p-deficient bMSCs were insufficient to reduce EG degradation. LPS down-regulated the expression of let-7-5p while upregulated endothelial expression of ABL2 in HUVECs and induced EG degradation and leakage. bMSC-EVs uptaken by HUVECs could deliver let-7-5p targeting endothelial ABL2, which suppressed the activation of downstream p38MAPK and IL-6, IL-1ß levels, and thus reversed LPS-induced EG degradation and leakage. CONCLUSION: bMCSs alleviate LPS-induced EG degradation and leakage through EV delivery of miR let-7-5p targeting endothelial ABL2.


Background Inflammation-related Endothelial vascular leakage (EVL) is associated with poor clinical prognosis. Endothelial glycocalyx (EG) is a novel therapeutic target for EVL. bMSCs (Bone Mesenchymal Stem Cells) are potential therapies for EVL, but the effect of bMSCs on EG has not been investigated.Significance bMSCs alleviating EG degradation and leakage was firstly clarified in our LPS-induced vascular leakage mice model. Histology and electrophysiology experiments validated that bMSCs achieve therapeutic effects through paracrine extracellular vesicles (EVs). EV-delivered MicroRNA sequencing revealed that miR let-7-5p down-regulated endothelial ABL2/p38MAPK-related inflammation activation. The bMSC-EV delivered let-7-5p was proved as an effective element in alleviating inflammation-related EG degradation and leakage, providing an executable approach for bMSCs to treat EVL. Video Abstract.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Animais , Camundongos , Glicocálix , Lipopolissacarídeos/farmacologia , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana , MicroRNAs/genética
11.
Langmuir ; 39(25): 8769-8778, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37307594

RESUMO

Incorporating inorganic components into organic molecular devices offers one novel alternative to address challenges existing in the fabrication and integration of nanoscale devices. In this study, using a theoretical method of density functional theory combined with the nonequilibrium Green's function, a series of benzene-based molecules with group III and V substitutions, including borazine molecule and XnB3-nN3H6 (X = Al or Ga, n = 1-3) molecules/clusters, are constructed and investigated. An analysis of electronic structures reveals that the introduction of inorganic components effectively reduces the energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital, albeit at the cost of reduced aromaticity in these molecules/clusters. Simulated electronic transport characteristics demonstrate that XnB3-nN3H6 molecules/clusters coupled between metal electrodes exhibit lower conductance compared to prototypical benzene molecule. Additionally, the choice of metal electrode materials significantly impacts the electronic transport properties, with platinum electrode devices displaying distinct behavior compared to silver, copper, and gold electrode devices. This distinction arises from the amount of transferred charge, which modulates the alignment between molecular orbitals and the Fermi level of the metal electrodes by shifting the molecular orbitals in energy. These findings provide valuable theoretical insights for the future design of molecular devices incorporating inorganic substitutions.

12.
Phys Chem Chem Phys ; 25(25): 16896-16907, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37318781

RESUMO

van der Waals heterostructures (vdWHs) open the possibility of creating novel semiconductor materials at the atomic scale that demonstrate totally new physics and enable unique functionalities, and have therefore attracted great interest in the fields of advanced electronic and optoelectronic devices. However, the interactions between metals and vdWHs semiconductors require further investigation as they directly affect or limit the advancement of high-performance electronic devices. Here we study the contact behavior of MoS2/WSe2 vdWHs in contact with a series of bulk metals using ab initio electronic structure calculations and quantum transport simulations. Our study shows that dual transmission paths for electrons and holes exist at the metal-MoS2/WSe2 hetero-bilayer interfaces. In addition, the metal-induced bandgap state (MIGS) of the original monolayer disappears due to the creation of the heterolayer, which weakens the Fermi level pinning (FLP) effect. We also find that the creation of the heterolayer causes a change in the Schottky barrier height (SBH) of the non-ohmic contact systems, whilst this does not occur so easily in the ohmic contact systems. In addition, our results indicate that when Al, Ag and Au are in contact with a MoS2/WSe2 hetero-bilayer semiconductor, a low contact barrier exists throughout the whole transmission process causing the charge to tunnel to the MoS2 layer, irrespective of whether the MoS2 is in contact with the metals as the nearest layer or as the next-nearest layer. Our work not only offers new insights into electrical contact issues between metals and hetero-bilayer semiconductors, but also provides guidance for the design of high-performance vdWHs semiconductor devices.

13.
Phys Chem Chem Phys ; 25(37): 25458-25464, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37712287

RESUMO

Improving the solar-to-hydrogen efficiency has always been a significant topic in the field of photocatalysis. Based on first-principles calculations, herein, we propose multiple strategies to improve the photocatalytic properties of 2D arsenic sesquichalcogenides for full water splitting. The new configurations As2STe2 and As2SeTe2 monolayers, derived from the As2Te3 monolayers by surface modification, are manifested to be typical infrared-light driven photocatalysts. Notably, under the built-in electric field, As2STe2 and As2SeTe2 monolayers can fulfil overall water splitting and the predicted solar-to-hydrogen efficiencies even reach up to 36.19% and 29.36%, respectively. The Gibbs free energy calculations indicate that the OER can be successfully driven under light irradiation. In addition, the overpotentials can provide most of the energy for HER when illuminated, especially for As2STe2 with the . In addition, both As2S3 and As2Se3 monolayers are capable of satisfying the conditions for photocatalytic water splitting. Furthermore, the band gaps of As2Se3 and As2S3 can dramatically be narrowed by increasing the number of layers and doping, respectively. These findings provide a theoretical basis for As2X3 monolayers to achieve efficient photocatalytic water splitting.

14.
Appl Microbiol Biotechnol ; 107(7-8): 2561-2576, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36843198

RESUMO

Diabetic nephropathy (DN), the principal pathogeny of end-stage renal disease (ESRD), is related to metabolic disorders, chronic inflammation, and oxidative stress. It was reported that high expression of interleukin-17A (IL-17A) was intimately related to the progression of DN, and targeting IL-17A exhibited regulating effects on inflammation and autoimmunity but had only limited impact on the oxidative stress damage in DN. Recent studies showed that interleukin-22 (IL-22) could inhibit mitochondrial damage and inflammatory response. Thus, the cytokine IL-22 was first fused to anti-IL-17A antibody for endowing the antibody with the anti-hyperglycemia and anti-inflammation activity. Our study demonstrated that the fusion molecule, anti-IL17A/IL22 fusion protein, could not only lead to the increase of M1 macrophages and the decrease of M2 macrophages, further improving the immune microenvironment, but also prevent the loss of mitochondrial membrane potential by reducing the production of ROS in murine DN model. In addition, the fusion protein could block TRAF6/NF-κB and AKT/ROS/TXNIP signaling pathways, further synergistically restraining the production of NLRP3, thus suppressing the inflammatory response and playing beneficial effect on slowing down the progression of DN. In conclusion, our findings demonstrated that the bifunctional IL-17A antibody and IL-22 fusion protein were of great benefit to DN, which highlighted a potential therapeutic strategy. KEY POINTS: • Anti-IL17A/IL22 fusion protein could improve the immune microenvironment and reduce the production of ROS. • Anti-IL17A/IL22 fusion protein could block TRAF6/NF-κB and AKT/ROS/TXNIP signaling pathways and then restrain the activation of NLRP3.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Camundongos , Animais , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inflamação/patologia
15.
Compr Rev Food Sci Food Saf ; 22(4): 3105-3129, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37199492

RESUMO

Food preservation is a critical issue in ensuring food safety and quality. Growing concern around industrial pollution of food and demand for environmentally sustainable food has led to increased interest in developing effective and eco-friendly preservation techniques. Gaseous ClO2 has gained attention for its strong oxidizing properties, high efficacy in microorganism inactivation, and potential for preserving the attributes and nutritional quality of fresh food while avoiding the formation of toxic byproducts or unacceptable levels of residues. However, the widespread use of gaseous ClO2 in the food industry is limited by several challenges. These include large-scale generation, high cost and environmental considerations, a lack of understanding of its mechanism of action, and the need for mathematical models to predict inactivation kinetics. This review aims to provide an overview of the up-to-date research and application of gaseous ClO2 . It covers preparation methods, preservation mechanisms, and kinetic models that predict the sterilizing efficacy of gaseous ClO2 under different conditions. The impacts of gaseous ClO2 on the quality attributes of fresh produce and low-moisture foods, such as seeds, sprouts, and spices, are also summarized. Overall, gaseous ClO2 is a promising preservation approach, and future studies are needed to address the challenges in large-scale generation and environmental considerations and to develop standardized protocols and databases for safe and effective use in the food industry.


Assuntos
Desinfetantes , Gases , Gases/farmacologia , Contagem de Colônia Microbiana , Desinfetantes/química , Cinética , Conservação de Alimentos/métodos , Sementes
16.
J Gene Med ; 24(5): e3417, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35338537

RESUMO

BACKGROUND: Congenital hydrocephalus is one of the symptoms of Walker-Warburg syndrome that is attributed to the disruptions of the genes, among which the B3GALNT2 gene is rarely reported. A diagnosis of the Walker-Warburg syndrome depends on the clinical manifestations and the whole-exome sequencing after birth, which is unfavorable for an early diagnosis. METHODS: Walker-Warburg Syndrome was suspected in two families with severe fetal congenital hydrocephalus. Whole-exome sequencing and Sanger sequencing were performed on the affected fetuses. RESULTS: The compound heterozygous variants c.1A>G p.(Met1Val) and c.1151+1G>A, and c.1068dupT p.(D357*) and c.1052 T>A p.(L351*) in the B3GALNT2 gene were identified, which were predicted to be pathogenic and likely pathogenic, respectively. Walker-Warburg syndrome was prenatally diagnosed on the basis of fetal imaging and whole-exome sequencing. CONCLUSIONS: Our findings expand the spectrum of pathogenic mutations in Walker-Warburg syndrome and provide new insights into the prenatal diagnosis of the disease.


Assuntos
Hidrocefalia , N-Acetilgalactosaminiltransferases , Síndrome de Walker-Warburg , Feminino , Humanos , Mutação , N-Acetilgalactosaminiltransferases/genética , Gravidez , Diagnóstico Pré-Natal , Síndrome de Walker-Warburg/diagnóstico , Síndrome de Walker-Warburg/genética , Síndrome de Walker-Warburg/patologia , Sequenciamento do Exoma
17.
Phys Chem Chem Phys ; 24(17): 10095-10100, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35416191

RESUMO

Two-dimensional (2D) Dirac materials have been a research hotspot due to their intriguing properties, such as high carrier mobility and ballistic charge transport. Here, we demonstrate that the B2S3 monolayer with a hexagonal structure, which has been reported as a photocatalyst, can be tuned to new 2D Dirac materials by doping atoms. The Young's modulus can reach 65.23 N m-1, indicating that the monolayer can be used as a buffer materials. The electronic structures of the pristine B2S3 monolayer show that some Dirac points appear but do not occur exactly on the Fermi level (EF). Fortunately, we find that the Dirac cone can be tuned to the EF by doping C, N, or Sn atoms. The C-doped B2S3 monolayer can be a half-metallic Dirac material, which has significant potential application in spintronics. For N- and Sn-doped B2S3 monolayers, the typical kagome bands are formed near the EF, which arise from three molecular orbitals hybridized by B, S, and N (Sn) atoms. These outstanding properties render the doped B2S3 monolayers promising 2D Dirac materials for future nanoelectronic devices.

18.
Nanotechnology ; 32(22)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33601348

RESUMO

Metal-free semiconductors with desirable characteristics have recently gained great attention in the field of hydrogen generation. The non-metal material B2S3has two phases, hexagonal B2S3(h-B2S3) and orthorhombic B2S3(o-B2S3), which compose a novel class of 2D materials. Bothh-B2S3ando-B2S3monolayers are direct semiconductors with bandgaps of 2.89 and 3.77 eV by the Heyd-Scuserria-Ernzerhof (HSE) function, respectively. Under appropriate uniaxial strain (1%), the bandgap ofh-B2S3can be decreased to 2.8 eV. The carrier mobility can reach 1160 cm2V-1s-1, supporting the fast migration of photo-induced carriers. Most importantly, the band edges of bothh-B2S3ando-B2S3cover the reduction and oxidation levels for water splitting. We explore the process of photocatalytic water splitting onh-B2S3monolayers by analyzing the feasibility of the decomposition of H2O and the generation of H2. The results indicate that the special mesoporous structure of B2S3is helpful for photocatalytic hydrogen production. The new nanomaterial, B2S3, offers great promise as a metal-free photocatalyst due to its tunable bandgaps, its useful band edges, and its other excellent electronic properties.

19.
BMC Pregnancy Childbirth ; 21(1): 86, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499806

RESUMO

BACKGROUND: Non-invasive prenatal screening (NIPS) is widely used as the alternative choice for pregnant women at high-risk of fetal aneuploidy. However, whether NIPS has a good detective efficiency for pregnant women at advanced maternal age (AMA) has not been fully studied especially in Chinese women. METHODS: Twenty-nine thousand three hundred forty-three pregnant women at AMA with singleton pregnancy who received NIPS and followed-up were recruited. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), receiver operating characteristic (ROC) curves and the Youden Index for detecting fetal chromosomal aneuploidies were analyzed. The relationship between maternal age and common fetal chromosomal aneuploidy was observed. RESULTS: The sensitivity, specificity, PPV, NPV of NIPS for detecting fetal trisomy 21 were 99.11, 99.96, 90.98, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100, 99.94, 67.92, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100, 99.96, 27.78, and 100%, respectively. The prevalence of fetal trisomy 21 increased exponentially with maternal age. The high-risk percentage incidence rate of fetal trisomy 21 was significantly higher in the pregnant women at 37 years old or above than that in pregnant women at 35 to 37 years old. (Youden index = 37). CONCLUSION: It is indicated that NIPS is an effective prenatal screening method for pregnant women at AMA.


Assuntos
Idade Materna , Teste Pré-Natal não Invasivo/estatística & dados numéricos , Gravidez de Alto Risco , Adulto , Aneuploidia , China , Anormalidades Congênitas/diagnóstico , DNA/sangue , Síndrome de Down/diagnóstico , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Cariotipagem , Pessoa de Meia-Idade , Teste Pré-Natal não Invasivo/métodos , Gravidez , Sensibilidade e Especificidade , Trissomia/diagnóstico
20.
Phys Chem Chem Phys ; 22(34): 19202-19212, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32812593

RESUMO

Large Schottky barrier at the electric contact interface drastically hinders the performance of two-dimensional (2D) semiconductor devices, because of which it is crucial to develop better methods to achieve the ohmic contact. Recently, a new field effect transistor (FET) device was constructed by the popular 2D channel material MoS2 and an electrode material borophene was detected theoretically, but the large Schottky barrier still existed. Hence, we used surface functional groups modification on the borophene surface to regulate this Schottky barrier, based on ab initio electronic structure calculations and quantum transport simulations. Our study shows that this method makes it possible to obtain tunable metal work functions in a wide range, and the ohmic contact can still be realized. Although van der Waals (vdW) contacts were observed at all the interfaces between the 2D borophene-based metals and the monolayer MoS2, the Fermi level pinning (FLP) effect was still obvious, and existed in our proposed system with the ohmic contact. Moreover, we also discuss the origin of the FLP with varying degrees. It was found that the interface dipole and metal-induced gap states (MIGS) would be responsible for the FLP of vertical and lateral directions, respectively. More precisely, we find that the size of MIGS is dependent on the relative orientation between the functional group and metal-MoS2 interface. This work not only suggests that surface functional group modification is effective in forming ohmic contact with MoS2, but also holds some implication in the fundamental research on metal-semiconductor contacts with the vdW type.

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