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1.
Cell ; 150(5): 1055-67, 2012 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-22939628

RESUMO

The type 2 ryanodine receptor/calcium release channel (RyR2), required for excitation-contraction coupling in the heart, is abundant in the brain. Chronic stress induces catecholamine biosynthesis and release, stimulating ß-adrenergic receptors and activating cAMP signaling pathways in neurons. In a murine chronic restraint stress model, neuronal RyR2 were phosphorylated by protein kinase A (PKA), oxidized, and nitrosylated, resulting in depletion of the stabilizing subunit calstabin2 (FKBP12.6) from the channel complex and intracellular calcium leak. Stress-induced cognitive dysfunction, including deficits in learning and memory, and reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection were rescued by oral administration of S107, a compound developed in our laboratory that stabilizes RyR2-calstabin2 interaction, or by genetic ablation of the RyR2 PKA phosphorylation site at serine 2808. Thus, neuronal RyR2 remodeling contributes to stress-induced cognitive dysfunction. Leaky RyR2 could be a therapeutic target for treatment of stress-induced cognitive dysfunction.


Assuntos
Transtornos Cognitivos/metabolismo , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Animais , Cálcio/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos de Estresse Traumático/metabolismo
2.
Circulation ; 149(17): 1375-1390, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38214189

RESUMO

BACKGROUND: Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear. METHODS: Given the known role of Ptpn23 (protein tyrosine phosphatase, nonreceptor type 23) in regulating membrane deformation, its expression in patients with dilated cardiomyopathy was determined. Taking advantage of Cre/Loxp, CRISPR/Cas9, and adeno-associated virus 9 (AAV9)-mediated in vivo gene editing, we generated cardiomyocyte-specific Ptpn23 and Actn2 (α-actinin-2, a major component of Z-discs) knockout mice. We also perturbed the DGC by using dystrophin global knockout mice (DmdE4*). MM 4-64 and Di-8-ANEPPS staining, Cav3 immunofluorescence, and transmission electron microscopy were performed to determine T-tubule structure in isolated cells and intact hearts. In addition, the assembly of the DGC with Ptpn23 and dystrophin loss of function was determined by glycerol-gradient fractionation and SDS-PAGE analysis. RESULTS: The expression level of Ptpn23 was reduced in failing hearts from dilated cardiomyopathy patients and mice. Genetic deletion of Ptpn23 resulted in disorganized T-tubules with enlarged diameters and progressive dilated cardiomyopathy without affecting sarcomere organization. AAV9-mediated mosaic somatic mutagenesis further indicated a cell-autonomous role of Ptpn23 in regulating T-tubule formation. Genetic and biochemical analyses showed that Ptpn23 was essential for the integrity of costameres, which anchor the T-tubule membrane to Z-discs, through interactions with α-actinin and dystrophin. Deletion of α-actinin altered the subcellular localization of Ptpn23 and DGCs. In addition, genetic inactivation of dystrophin caused similar T-tubule defects to Ptpn23 loss-of-function without affecting Ptpn23 localization at Z-discs. Last, inducible Ptpn23 knockout at 1 month of age showed Ptpn23 is also required for the maintenance of T-tubules in adult cardiomyocytes. CONCLUSIONS: Ptpn23 is essential for cardiac T-tubule formation and maintenance along Z-discs. During postnatal heart development, Ptpn23 interacts with sarcomeric α-actinin and coordinates the assembly of the DGC at costameres to sculpt T-tubule spatial patterning and morphology.

3.
Arterioscler Thromb Vasc Biol ; 43(5): 726-738, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36951065

RESUMO

BACKGROUND: S1P (sphingosine-1-phosphate) has been reported to possess vasodilatory properties, but the underlying pathways are largely unknown. METHODS: Isolated mouse mesenteric artery and endothelial cell models were used to determine S1P-induced vasodilation, intracellular calcium, membrane potentials, and calcium-activated potassium channels (KCa2.3 and KCa3.1 [endothelial small- and intermediate-conductance calcium-activated potassium channels]). Effect of deletion of endothelial S1PR1 (type 1 S1P receptor) on vasodilation and blood pressure was evaluated. RESULTS: Mesenteric arteries subjected to acute S1P stimulation displayed a dose-dependent vasodilation response, which was attenuated by blocking endothelial KCa2.3 or KCa3.1 channels. In cultured human umbilical vein endothelial cells, S1P stimulated immediate membrane potential hyperpolarization following activation of KCa2.3/KCa3.1 with elevated cytosolic Ca2+. Further, chronic S1P stimulation enhanced expression of KCa2.3 and KCa3.1 in human umbilical vein endothelial cells in dose- and time-dependent manners, which was abolished by disrupting either S1PR1-Ca2+ signaling or downstream Ca2+-activated calcineurin/NFAT (nuclear factor of activated T-cells) signaling. By combination of bioinformatics-based binding site prediction and chromatin immunoprecipitation assay, we revealed in human umbilical vein endothelial cells that chronic activation of S1P/S1PR1 promoted NFATc2 nuclear translocation and binding to promoter regions of KCa2.3 and KCa3.1 genes thus to upregulate transcription of these channels. Deletion of endothelial S1PR1 reduced expression of KCa2.3 and KCa3.1 in mesenteric arteries and exacerbated hypertension in mice with angiotensin II infusion. CONCLUSIONS: This study provides evidence for the mechanistic role of KCa2.3/KCa3.1-activated endothelium-dependent hyperpolarization in vasodilation and blood pressure homeostasis in response to S1P. This mechanistic demonstration would facilitate the development of new therapies for cardiovascular diseases associated with hypertension.


Assuntos
Hipertensão , Vasodilatação , Camundongos , Humanos , Animais , Pressão Sanguínea , Endotélio/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Homeostase , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismo
4.
Angew Chem Int Ed Engl ; 63(15): e202400312, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38306324

RESUMO

The metastable liquid properties and chemical bonds beyond 2000 K remain a huge challenge for ground-based research on liquid materials chemistry. We show the strong undercooling capability, metastable liquid properties and surface wave patterns of refractory Nb-Si and Zr-V binary alloys explored in space environment. The floating droplet of Nb82.7Si17.3 eutectic alloy superheated up to 2338 K exhibited an extreme undercooling of 437 K, approaching the 0.2TE threshold for homogeneous nucleation of liquid-solid reaction. The microgravity state endowed alloy droplets with nearly perfect sphericity and thus ensured the high accuracy to determine metastable undercooled liquid properties. A special kind of swirling flow was induced for liquid alloy owing to Marangoni convection, which resulted in the spiral microstructures on Zr64V36 alloy surface during liquid-solid phase transition. The coupled impacts of surface nucleation and surface flow brought in a novel olivary shape for these binary alloys. Furthermore, the chemical bonds and atomic structures of high temperature liquids were revealed to understand the liquid properties in outer space circumstances.

5.
Anal Chem ; 95(2): 1599-1607, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36580626

RESUMO

SARS-CoV-2, especially the variant strains, is rapidly spreading around the world. Rapid detection methods for the virus are crucial for controlling the COVID-19 epidemic. Herein, a localized surface plasmonic resonance (LSPR) biosensor based on Ω-shaped fiber optic (Ω-FO) was developed for dual assays of SARS-CoV-2 monitoring. Due to its strong ability to control the orientation and density, a new T-shaped aptamer exhibits enhanced binding affinity toward N proteins. After being combined on the fiber optic surface, the T-shaped aptamer sensitively captured N proteins of SARS-CoV-2 for a direct assay. Further, core-shell structured gold/silver nanoparticles functionalized with a T-shaped aptamer (apt-Ag@AuNPs) can amplify the signal of N protein detection for a sandwich assay. The real-time analytical feature of the dual assays endows time-dependent sensitivity enhancement behavior, which provides a guideline to save analytical time. With those characteristics, the LSPR biosensor has been successfully used to rapidly identify 39 healthy volunteers and 39 COVID-19 patients infected with the ancestral or variant SARS-CoV-2. With the help of simple pretreatment, we obtain a true negative rate of 100% and a true positive rate of 92.3% with a short analysis time of 45 min using the direct assay. Further, the LSPR biosensor could also broaden the detection application range to the surface of cold-chain foods using a sandwich assay. Thus, the LSPR biosensor based on Ω-FO was demonstrated to have broad application potential to detect SARS-CoV-2 rapidly.


Assuntos
Técnicas Biossensoriais , COVID-19 , Nanopartículas Metálicas , Humanos , Ressonância de Plasmônio de Superfície/métodos , SARS-CoV-2 , Ouro , COVID-19/diagnóstico , Prata , Técnicas Biossensoriais/métodos , Oligonucleotídeos
6.
J Exp Bot ; 74(1): 118-129, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36227010

RESUMO

Encasements formed around haustoria and biotrophic hyphae as well as hypersensitive reaction (HR) cell death are essential plant immune responses to filamentous pathogens. In this study we examine the components that may contribute to the absence of these responses in susceptible barley attacked by the powdery mildew fungus. We find that the effector CSEP0162 from this pathogen targets plant MONENSIN SENSITIVITY1 (MON1), which is important for the fusion of multivesicular bodies to their target membranes. Overexpression of CSEP0162 and silencing of barley MON1 both inhibit encasement formation. We find that the Arabidopsis ecotype No-0 has resistance to powdery mildew, and that this is partially dependent on MON1. Surprisingly, we find the MON1-dependent resistance in No-0 not only includes an encasement response, but also an effective HR. Similarly, silencing of MON1 in barley also blocks Mla3-mediated HR-based powdery mildew resistance. Our results indicate that MON1 is a vital plant immunity component, and we speculate that the barley powdery mildew fungus introduces the effector CSEP0162 to target MON1 and hence reduce encasement formation and HR.


Assuntos
Arabidopsis , Ascomicetos , Hordeum , Ascomicetos/fisiologia , Hordeum/genética , Hordeum/metabolismo , Monensin/metabolismo , Imunidade Vegetal , Arabidopsis/metabolismo , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
7.
J Bone Miner Metab ; 41(5): 606-620, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37418073

RESUMO

INTRODUCTION: The increase of ATP concentration in the extracellular space represents one of the effective signals that stimulate the physiological activities of cells when the bone is exposed to external mechanical stimulation such as stretching and shear stress force throughout life. However, the effects of ATP on osteoblast differentiation and related mechanisms are not well understood. MATERIALS AND METHODS: In this study, the roles of extracellular ATP on osteoblast differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. RESULTS: Our results showed that 100 µM extracellular ATP initiated intracellular calcium ([Ca2+]i) oscillations via the calcium-sensing receptor (P2R) and promoted the differentiation of MC3T3-E1 cells. Metabolomics analysis showed that the differentiation of MC3T3-E1 cells depended on aerobic oxidation, but little glycolysis. Moreover, the differentiation of MC3T3-E1 cells and aerobic oxidation were suppressed with the inhibition of AMP-activated protein kinase (AMPK). CONCLUSION: These results indicate that calcium oscillations triggered by extracellular ATP can activate aerobic oxidation through AMPK-related signaling pathways and thus promote osteoblast differentiation.


Assuntos
Sinalização do Cálcio , Cálcio , Cálcio/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Diferenciação Celular , Osteoblastos/metabolismo , Trifosfato de Adenosina/metabolismo
8.
BMC Musculoskelet Disord ; 24(1): 880, 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37951888

RESUMO

PURPOSE: Ankle fracture-dislocations are among the most severe injuries, and the use of an external fixator as a recommended fixation method has some disadvantages. The aim of this study was to compare the clinical outcomes and complication rates of external and K-wire fixations in the treatment of ankle fracture dislocations. METHODS: A total of 67 patients with ankle fracture-dislocations requiring temporary external or percutaneous K-wire fixation were included. The exclusion criteria were pilon fractures, open fractures, and those who required acute open reduction internal fixation (ORIF). The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, a 10-point visual analog scale (VAS) score (range 0-10), and complications before and after the definitive surgery were recorded. RESULTS: A significant difference between the two groups was not observed for age, sex, affected side, fracture type, smoking status, or diabetes. The average AOFAS scores were 83.2 and 83.3, the median VAS scores were 3 and 3, and the complication rates were 32.4% and 6.7% in the external and K-wire fixation groups, respectively (p = 0.010). However, skin necrosis, re-dislocation of the ankle, surgical wound infection, and posttraumatic ankle osteoarthritis frequency were not significantly different between the groups, except for pin-sites infection (p = 0.036). CONCLUSION: Ankle fracture-dislocations using percutaneous k-wire fixation showed a low rate of complications and favorable clinical outcomes. This method could be a good alternative treatment option for ankle fracture-dislocations.


Assuntos
Fraturas do Tornozelo , Fratura-Luxação , Humanos , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Fraturas do Tornozelo/etiologia , Tornozelo , Resultado do Tratamento , Fixação de Fratura/efeitos adversos , Fixação de Fratura/métodos , Fixadores Externos/efeitos adversos , Fratura-Luxação/diagnóstico por imagem , Fratura-Luxação/cirurgia , Fratura-Luxação/etiologia , Fixação Interna de Fraturas/efeitos adversos , Estudos Retrospectivos
9.
Proc Natl Acad Sci U S A ; 117(48): 30465-30475, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33208532

RESUMO

Polycomb repressive complex 2 (PRC2) installs and spreads repressive histone methylation marks on eukaryotic chromosomes. Because of the key roles that PRC2 plays in development and disease, how this epigenetic machinery interacts with DNA and nucleosomes is of major interest. Nonetheless, the mechanism by which PRC2 engages with native-like chromatin remains incompletely understood. In this work, we employ single-molecule force spectroscopy and molecular dynamics simulations to dissect the behavior of PRC2 on polynucleosome arrays. Our results reveal an unexpectedly diverse repertoire of PRC2 binding configurations on chromatin. Besides reproducing known binding modes in which PRC2 interacts with bare DNA, mononucleosomes, and adjacent nucleosome pairs, our data also provide direct evidence that PRC2 can bridge pairs of distal nucleosomes. In particular, the "1-3" bridging mode, in which PRC2 engages two nucleosomes separated by one spacer nucleosome, is a preferred low-energy configuration. Moreover, we show that the distribution and stability of different PRC2-chromatin interaction modes are modulated by accessory subunits, oncogenic histone mutations, and the methylation state of chromatin. Overall, these findings have implications for the mechanism by which PRC2 spreads histone modifications and compacts chromatin. The experimental and computational platforms developed here provide a framework for understanding the molecular basis of epigenetic maintenance mediated by Polycomb-group proteins.


Assuntos
Cromatina/química , Cromatina/metabolismo , Modelos Moleculares , Complexo Repressor Polycomb 2/química , Complexo Repressor Polycomb 2/metabolismo , Cromatina/genética , Epigênese Genética , Heterocromatina/genética , Histonas/metabolismo , Humanos , Metilação , Modelos Biológicos , Simulação de Dinâmica Molecular , Mutação , Nucleossomos , Ligação Proteica , Conformação Proteica , Imagem Individual de Molécula/métodos , Análise Espectral , Relação Estrutura-Atividade
10.
Int J Mol Sci ; 24(5)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36902420

RESUMO

During bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium concentrations on osteoblast proliferation and differentiation, intracellular calcium ([Ca2+]i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca2+]i transient via the calcium-sensing receptor (CaSR) and promoted the proliferation of MC3T3-E1 cells. Metabolomics analysis showed that the proliferation of MC3T3-E1 cells was dependent on aerobic glycolysis, but not the tricarboxylic acid cycle. Moreover, the proliferation and glycolysis of MC3T3-E1 cells were suppressed following the inhibition of AKT. These results indicate that calcium transient triggered by high extracellular calcium levels activated glycolysis via AKT-related signaling pathways and ultimately promoted the proliferation of osteoblasts.


Assuntos
Cálcio , Osteoblastos , Proteínas Proto-Oncogênicas c-akt , Cálcio/metabolismo , Cálcio da Dieta/farmacologia , Diferenciação Celular , Proliferação de Células , Osteoblastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Camundongos , Linhagem Celular
11.
Sheng Li Xue Bao ; 75(6): 799-816, 2023 Dec 25.
Artigo em Zh | MEDLINE | ID: mdl-38151345

RESUMO

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are the physical connection sites between mitochondria and endoplasmic reticulum (ER). As the compartments controlling substance and information communications between ER and mitochondria, MAMs were involved in the regulation of various pathophysiological processes, such as calcium homeostasis, mitochondrial morphology and function, lipid metabolism and autophagy. In the past decades, accumulating lines of evidence have revealed the pivotal role of MAMs in diverse cardiovascular diseases (CVD). Aging is one of the major independent risk factors for CVD, which causes progressive degeneration of the cardiovascular system, leading to increased morbidity and mortality of CVD. This review aims to summarize the research progress of MAMs in age-related CVD, and explore new targets for its prevention and treatment.


Assuntos
Doenças Cardiovasculares , Membranas Mitocondriais , Humanos , Doenças Cardiovasculares/metabolismo , Sinalização do Cálcio/fisiologia , Mitocôndrias/fisiologia , Retículo Endoplasmático/metabolismo
12.
Int Wound J ; 20(7): 2673-2678, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36872305

RESUMO

The physiological phenomenon of wound contraction in mice cannot completely imitate the process of human skin regeneration, which is primarily attributed to reepithelialisation. As such, excisional wound models in mice are considered to be imperfect comparisons. This study aimed to enhance the correlation of mouse excisional wound models with that of humans, and to offer more practical and accurate ways to record and measure wound areas. We present evidence that simple excisional wounds produce a robust and stable wound model by comparing splint-free and splint groups. We monitored reepithelialisation and contraction in the C57BL/6J mouse excision wound model at different time points and prove that excisional wounds heal by both contraction and reepithelialisation. Some parameters were measured and a formula was used to calculate the area of wound reepithelialisation and contraction. In our results, reepithelialisation accounted for 46% of the wound closure of full-thickness excisional wounds. In conclusion, excisional wound models can be used as wound-healing models and a straightforward formula may be used to determine the process of reepithelialisation over a wound bed created by a simple excisional rodent wound model.


Assuntos
Pele , Cicatrização , Humanos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Cicatrização/fisiologia , Reepitelização
13.
J Proteome Res ; 21(3): 822-832, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-34319108

RESUMO

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.


Assuntos
Sangue Fetal , Hemangioma , Biomarcadores , Cromatografia Líquida , Hemangioma/complicações , Hemangioma/diagnóstico , Hemangioma/tratamento farmacológico , Humanos , Lactente , Estudos Prospectivos
14.
Plant Biotechnol J ; 20(3): 454-467, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34651397

RESUMO

The biotrophic fungal pathogen Blumeria graminis f. sp. tritici (Bgt) is a crucial factor causing reduction in global wheat production. Wild wheat relatives, for example Thinopyrum intermedium, is one of the wild-used parents in wheat disease-resistant breeding. From T. intermedium line, we identified the aspartic protease gene, TiAP1, which is involved in resistance against Bgt. TiAP1 is a secreted protein that accumulates in large amounts at the infection sites of Bgt and extends to the intercellular space. Yeast two-hybrid, luciferase complementation imaging and bimolecular florescent complimentary analysis showed that TiAP1 interacted with the chitin deacetylase (BgtCDA1) of Bgt. The yeast expression, purification and in vitro test confirmed the chitin deacetylase activity of BgtCDA1. The bombardment and VIGS-mediated host-induced gene silencing showed that BgtCDA1 promotes the invasion of Bgt. Transcriptome analysis showed the cell wall xylan metabolism, lignin biosynthesis-related and defence genes involved in the signal transduction were up-regulated in the transgenic TiAP1 wheat induced by Bgt. The TiAP1 in wheat may inactivate the deacetylation function of BgtCDA1, cause chitin oligomers expose to wheat chitin receptor, then trigger the wheat immune response to inhibit the growth and penetration of Bgt, and thereby enhance the resistance of wheat to pathogens.


Assuntos
Doenças das Plantas , Triticum , Amidoidrolases , Ascomicetos , Quitina/metabolismo , Resistência à Doença/genética , Melhoramento Vegetal , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Saccharomyces cerevisiae , Triticum/metabolismo
15.
J Transl Med ; 20(1): 596, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517908

RESUMO

BACKGROUND: It has been well-documented that haplo-identical hematopoietic stem cell transplantation (HID-HSCT) can provide outcomes comparable to conventional matched sibling donor (MSD) HSCT, however, little is known about the effects on quality of life (QoL) in long-term survivors. This study is to investigate the differences in longitudinal performance of QoL between HID and MSD HSCT using a comprehensive assessment system. METHODS: This prospective study enrolled consecutive patients who had received allogenic-HSCT (allo-HSCT) between January 2018 and December 2019 in our center. All patients were informed to complete QoL questionnaires including the Mos 36-Item Short-Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, version 4), using an online applet, before transplantation and at scheduled time points after transplantation. The linear mixed-effects model was used to analyze the variation trend of different dimensions of both SF-36 and FACT-BMT with different follow-up times. RESULTS: Of the 425 participants, recipients of HID and MSD who survived more than 1 year (n = 230) were included in the final analysis of QoL (median age [range]: 36, [15, 66]). The 3 year overall survival (OS) of HID and MSD was 82.42% and 86.46%, respectively. QoL was assessed using both SF-36 and FACT-BMT and there was longitudinal recovery with clinical significance in the cohort. Compared to MSD-HSCT patients, HID-HSCT recipients demonstrated superior QoL performance in some subscales describing physical and mental wellness. Specifically, the difference in physical performance is more remarkable using FACT-BMT whereas that in mental wellness is more significant using SF36. In the subsequent stratified analysis, patients with a history of aGVHD or CMV reactivation demonstrated inferior QoL. CONCLUSIONS: Long-term survivors of HID HSCT achieved better QoL in some sub-scales compared to MSD HSCT. In addition, SF-36 and FACT-BMT demonstrated different performance thus combination of both improved capacity of the evaluation system.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Irmãos , Qualidade de Vida , Estudos Prospectivos , Estudos Retrospectivos , Sobreviventes
16.
Proc Natl Acad Sci U S A ; 116(10): 4238-4243, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30770441

RESUMO

Trimeric intracellular cation (TRIC) channels are thought to provide counter-ion currents that facilitate the active release of Ca2+ from intracellular stores. TRIC activity is controlled by voltage and Ca2+ modulation, but underlying mechanisms have remained unknown. Here we describe high-resolution crystal structures of vertebrate TRIC-A and TRIC-B channels, both in Ca2+-bound and Ca2+-free states, and we analyze conductance properties in structure-inspired mutagenesis experiments. The TRIC channels are symmetric trimers, wherein we find a pore in each protomer that is gated by a highly conserved lysine residue. In the resting state, Ca2+ binding at the luminal surface of TRIC-A, on its threefold axis, stabilizes lysine blockage of the pores. During active Ca2+ release, luminal Ca2+ depletion removes inhibition to permit the lysine-bearing and voltage-sensing helix to move in response to consequent membrane hyperpolarization. Diacylglycerol is found at interprotomer interfaces, suggesting a role in metabolic control.


Assuntos
Cálcio/metabolismo , Cátions/metabolismo , Citoplasma/metabolismo , Canais Iônicos/química , Canais Iônicos/metabolismo , Animais , Sinalização do Cálcio/fisiologia , Cristalografia por Raios X , Modelos Moleculares , Mutagênese , Conformação Proteica , Análise de Sequência de Proteína
17.
Foot Ankle Surg ; 28(7): 872-878, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34916143

RESUMO

BACKGROUND: We compared the effectiveness of the extensile lateral approach (ELA) and modified sinus tarsi approach (MSTA) with a variable-angle locking anterolateral plate in treating Sanders type II and III calcaneal fractures. METHODS: We reviewed 45 DIACFs treated by a single surgeon from 2017 to 2020. Open reduction using ELA and MSTA was performed in 25 and 20 patients, respectively. Follow-up evaluations included radiological assessments and clinical evaluations. RESULTS: Pre- and postoperative radiologic parameters for the calcaneus were significantly different. The average American Orthopaedic Foot and Ankle Society scores were 81.24 and 85.00, the mean visual analogue scale scores were 2.28 and 1.65, and the wound-related complication rates were 64.0% and 15.0% in the ELA and MSTA groups, respectively. Bony union was achieved in all cases. CONCLUSIONS: For Sanders type II and III fractures, MSTA seems to be a safer and more satisfactory method, with fewer postoperative complications.


Assuntos
Traumatismos do Tornozelo , Calcâneo , Traumatismos do Pé , Fraturas Ósseas , Fraturas Intra-Articulares , Placas Ósseas , Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Traumatismos do Pé/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Calcanhar , Humanos , Fraturas Intra-Articulares/diagnóstico por imagem , Fraturas Intra-Articulares/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
18.
J Minim Access Surg ; 18(4): 585-590, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204938

RESUMO

Background: Over the last two decades, several endoscopic thyroidectomy methods have been developed. However, there are some limitations in these procedures. To date, the optimal surgical approach for thyroid cancer has not yet been developed. This study reported the surgical operation steps, clinical outcomes, and experience of 30 patients who underwent trans-cervico-mental angle single-port endoscopic thyroidectomy (TCMASPET) at our centre. Patients and Methods: A total of 30 patients were enrolled in the present study. Patients underwent unilateral or bilateral thyroidectomy through a cervico-mental angle incision of 2.48 ± 0.31 cm, after which the lymphoid adipose tissues in the central region were dissected. Results: All surgeries were successfully completed. Two patients underwent bilateral thyroid carcinoma resection with bilateral central region lymph node dissection, 23 patients received unilateral thyroid cancer resection with unilateral central region lymph node dissection, four patients underwent unilateral thyroid resection, and one patient received bilateral thyroid resection with unilateral central region lymph node dissection. No permanent post-operative complications were observed. Conclusions: TCMASPET was a safe and feasible approach that was relatively easy to perform. This approach may expand the indications for endoscopic thyroidectomy while maintaining excellent cosmetic outcomes.

19.
Angew Chem Int Ed Engl ; 61(44): e202205301, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-35866885

RESUMO

The electrocatalytic CO2 reduction reaction (ECO2 RR) is one promising method for storing intermittent clean energy in chemical bonds and producing fuels. Among various kinds of catalysts for ECO2 RR, molecular metal complexes with well-defined structures are convenient for studies of their rational design, structure-reactivity relationships, and mechanisms. In this Review, we summarize the molecular engineering of several N-based metal complexes including Re/Mn bipyridine compounds and metal macrocycles, concluding with general modification strategies to devise novel molecular catalysts with high intrinsic activity. Through physical adsorption, covalent linking, and formation of a periodic backbone, these active molecules can be heterogenized into immobilized catalysts with more practical prospects. Finally, significant challenges and opportunities based on molecular catalysts are discussed.

20.
Ecotoxicol Environ Saf ; 213: 111941, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33567358

RESUMO

Cloudy weather with low light is more common during rice growing season of South China which often leads reduced yield and aroma formations in fragrant rice. However, exogenous γ-aminobutyric acid (GABA) application could enhance the 2-acetyl-1-pyrroline (2AP) accumulations and yield of fragrant rice under low light conditions. Field and pot experiments were conducted with three fragrant rice cultivars i.e., Basmati and Yuxiangyouzhan (indica), and Yungengyou 14 (japonica) that were grown under three different treatments i.e., normal light + GABA 0 mg L-1 (CK), low light + GABA 0 mg L-1 (T1), and low light + GABA 250 mg L-1 (T2). The results revealed that the grain 2AP contents were increased by 14.67-34.83% and up to 29.34% under T1 and T2 treatments in pot and field experiments, respectively, as compared with CK. The T1 and T2 treatments improved aroma owing to regulation in the accumulation of micronutrients i.e., Na, Mn, and Fe and enzyme activities involved in 2AP biosynthesis. The grain yield was substantially reduced in T1 as compared with T2 treatment for all rice cultivars. On the other hand, GABA application improved the grain yield under low light conditions by regulating the plant growth, and related physiological and biochemical attributes in all rice cultivars. Thus, GABA could balance low light-induced 2AP content and grain yield by modulating morphological and yield related attributes as well as physio-biochemical responses of fragrant rice.


Assuntos
Oryza/crescimento & desenvolvimento , Ácido gama-Aminobutírico/metabolismo , China , Grão Comestível/química , Odorantes , Perfumes/análise , Proteínas de Plantas/análise , Pirróis
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