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Rare variants contribute significantly to the 'missing heritability' of quantitative traits. The genome-wide characteristics of rare variants and their roles in environmental adaptation of woody plants remain unexplored. Utilizing genome-wide rare variant association study (RVAS), expression quantitative trait loci (eQTL) mapping, genetic transformation, and molecular experiments, we explored the impact of rare variants on stomatal morphology and drought adaptation in Populus. Through comparative analysis of five world-wide Populus species, we observed the influence of mutational bias and adaptive selection on the distribution of rare variants. RVAS identified 75 candidate genes correlated with stomatal size (SS)/stomatal density (SD), and a rare haplotype in the promoter of serine/arginine-rich splicing factor PtoRSZ21 emerged as the foremost association signal governing SS. As a positive regulator of drought tolerance, PtoRSZ21 can recruit the core splicing factor PtoU1-70K to regulate alternative splicing (AS) of PtoATG2b (autophagy-related 2). The rare haplotype PtoRSZ21hap2 weakens binding affinity to PtoMYB61, consequently affecting PtoRSZ21 expression and SS, ultimately resulting in differential distribution of Populus accessions in arid and humid climates. This study enhances the understanding of regulatory mechanisms that underlie AS induced by rare variants and might provide targets for drought-tolerant varieties breeding in Populus.
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Adaptação Fisiológica , Secas , Regulação da Expressão Gênica de Plantas , Haplótipos , Proteínas de Plantas , Estômatos de Plantas , Populus , Populus/genética , Populus/fisiologia , Populus/anatomia & histologia , Estômatos de Plantas/fisiologia , Estômatos de Plantas/genética , Haplótipos/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Adaptação Fisiológica/genética , Locos de Características Quantitativas/genética , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Estudo de Associação Genômica Ampla , Processamento Alternativo/genética , Variação Genética , Resistência à SecaRESUMO
The cause for at least 50% of recurrent miscarriages is unclear, which is defined as unexplained recurrent miscarriages. The B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in unexplained recurrent miscarriages. We found reduced levels of B7-H3 in the villus tissue of unexplained recurrent miscarriage patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts. Further, the HTR-8/SVneo and JEG-3 cells were selected to explore the role of B7-H3 in proliferation, apoptosis, tube formation, migration, and invasion. We found that B7-H3 regulated trophoblast migration and invasion via RhoA/ROCK2 signaling pathway. Inflammatory cytokines were detected through enzyme-linked immunosorbent assay after co-culturing with decidual natural killer cells and B7-H3-knockout JEG-3. Results showed that B7-H3 inhibited IL-8 and IP-10 secretion from the decidual natural killer cells. In a CBA/J × DBA/2 abortion-prone mice model, treatment with B7-H3-Fc protein successfully reduced the rate of embryo resorption. In conclusion, our results revealed a possible mechanism by which decreased B7-H3 on trophoblasts of unexplained recurrent miscarriages inhibited trophoblast migration and invasion and increased IL-8 and IP-10 secretion from the decidual natural killer cells. Furthermore, B7-H3 may be a promising new therapeutic target in unexplained recurrent miscarriage patients.
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Aborto Habitual , Interleucina-8 , Animais , Feminino , Humanos , Camundongos , Gravidez , Aborto Habitual/metabolismo , Linhagem Celular Tumoral , Quimiocina CXCL10/metabolismo , Decídua/metabolismo , Interleucina-8/metabolismo , Células Matadoras Naturais/metabolismo , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Transdução de Sinais , Trofoblastos/metabolismoRESUMO
Coordinated cell proliferation and differentiation result in the complex structure of the inflorescence in wheat. It exhibits unique differentiation patterns and structural changes at different stages, which have attracted the attention of botanists studying the dynamic regulation of its genes. Our research aims to understand the molecular mechanisms underlying the regulation of spike development genes at different growth stages. We conducted RNA-Seq and qRT-PCR evaluations on spikes at three stages. Our findings revealed that genes associated with the cell wall and carbohydrate metabolism showed high expression levels between any two stages throughout the entire process, suggesting their regulatory role in early spike development. Furthermore, through transgenic experiments, we elucidated the role of the cell wall regulator gene in spike development regulation. These research results contribute to identifying essential genes associated with the morphology and development of wheat spike tissue.
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Perfilação da Expressão Gênica , Transcriptoma , Triticum , Inflorescência/genética , Parede Celular/genética , Regulação da Expressão Gênica de PlantasRESUMO
Recurrent miscarriage (RM) seriously affects the physical and mental health of women of childbearing age, and 50% of the causes are unknown. Thus, it is valuable to investigate the causes of unexplained recurrent miscarriage (uRM). Similarities between tumor development and embryo implantation make us realize that tumor studies are informative for uRM. The non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1) is highly expressed in some tumors, and can promote tumor growth, invasion and migration. In this present paper, we firstly explore the role of NCK1 in uRM. We find that the NCK1 and PD-L1 are greatly reduced in peripheral blood mononuclear cells (PBMC) and decidua from patients with uRM. Next, we construct NCK1-knockdown HTR-8/SVneo cells, and find that NCK1-knockdown HTR-8/SVneo cells exhibit reduced proliferation and migration ability. Then we demonstrate that the expression of PD-L1 protein is decreased when the NCK1 is knocked down. In co-culture experiments with THP-1 and differently treated HTR-8/SVneo cells, we observe significantly increased proliferation of THP-1 in NCK1-knockdown group. In conclusion, NCK1 may be involved in RM by regulating trophoblast proliferation, migration, and regulating PD-L1-mediated macrophage proliferation at the maternal-fetal interface. Moreover, NCK1 has the potential to be a new predictor and therapeutic target.
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The joint landscape ecological risk as well as ecological corridors for ecological restoration area identification is of great significance to the past evolution and future development of landscapes. Ecological risks were assessed based on the landscape pattern and functional changes in Pengyang County in 2000, 2010, and 2020; ecological restoration areas were divided based on ecological risks and security pattern. Results showed that the ecological risk types in Pengyang County were mainly low risk from 2000 to 2010 and distributed in the central region, while the high-risk areas increased from 2010 to 2020 and were concentrated in the southern residential area. According to a comprehensive assessment of the landscape ecological risks, an ecological security pattern consisting of 17 ecological source points and 34 potential ecological corridors with an average length of 6.57 km was identified. Three ecological restoration areas were eventually identified: mining restoration areas, mountain restoration area, and urban restoration area. Our results would provide an important perspective for the sustainable development of regional natural landscape resources.
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Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental , Medição de Risco , Desenvolvimento Sustentável , China , EcologiaRESUMO
Lactobacillus has been reported to inhibit acute lung injury (ALI). However, the molecular mechanism of Lactobacillus casei (L. casei) in preventing ALI has not been identified, so we investigated whether L. casei pretreatment could inhibit the activation of TLR4/MyD88/NF-κB signaling pathway following ALI. ALI model was established by intraperitoneal injection of 2 mg/kg lipopolysaccharide (LPS) to female BALB/c mice. In L. casei LC2W group, mice were intragastrically administrated L. casei LC2W for a week, before the ALI modeling. The serum of normal BALB/c mice after intragastric administration of L. casei LC2W was used for in vitro cell assays. The serum was pre-incubated with mouse macrophage cell line (RAW264.7) and human lung cell line (HLF-A), then LPS was added to co-incubate. Compared with ALI model group, L. casei LC2W pretreatment significantly reduced lung pathological damage, the number of neutrophils and total cells in bronchoalveolar lavage fluid. Besides, L. casei LC2W pretreatment could significantly reverse the abnormal expression of ICAM-1, IL-6, TNF-α and IL-10 in lung tissue and serum, plus, L. casei LC2W significantly reduced the phosphorylation levels of IRAK-1 and NF-κB p65. In vitro, the serum decreased the up-regulation of IL-6 and TNF-α in cell lines induced by LPS. In conclusion, L. casei LC2W intragastric administration pretreatment could significantly improve LPS-induced ALI in mice, probably through circulation to reach the lungs so as to inhibit the inflammatory response induced by activation of TLR4/MyD88/NF-κB signaling pathway.
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The start of thermal growing season (STGS) is an important indicator for climate change effects on regional plant growth and development. This study comprehensively investigated and compared the spatiotemporal variations in STGS at 0 °C (STGS_0), 5 °C (STGS_5), and 10 °C (STGS_10) thresholds for grassland on the Qinghai-Tibetan Plateau (QTP) during 1961-2014. Although elevation was the predominant influencing factor of the spatial variations of STGSs, the effect of latitude should not be ignored at the low-elevation regions, especially for the STGS with a low-temperature threshold (e.g., STGS_0). With the decrease of temperature thresholds, the effect of elevation became weaker, while the effect of latitude became stronger. Significant advancing trends were observed in all the three STGSs, with greater advancing rate for STGS_0 (0.23 days·year-1) than that of STGS_5 (0.15 days·year-1) and STGS_10 (0.16 days·year-1). More obvious advancing trends were found after 1980, which coincided with more rapid climate warming. The advancing trends weakened after 1998 when climate warming hiatus occurred. Since positive and negative impacts may be simultaneously induced by the advanced STGSs, more observations are still needed to analyze their impacts on the growth and development of alpine grassland on the QTP.
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Mudança Climática/história , Pradaria , Estações do Ano , História do Século XX , História do Século XXI , Temperatura , TibetRESUMO
BACKGROUND AND PURPOSE: The anterior communicating artery (Acom) aneurysm is the most complex in all cerebral aneurysms, and wider vascular bifurcation angles are considered to be associated with aneurysm formation. The objective of this study was to investigate association of the Acom aneurysm formation with patient age and vascular bifurcation morphology. METHODS: Three-dimensional angiographic data of 665 patients were used in this study, including 160 patients with Acom aneurysms, 66 with non-Acom aneurysms, and 439 control subjects with no aneurysms. The anterior cerebral artery bifurcation angle (Acom/A2 angle), arterial diameters, and Acom aneurysm geometric characters were examined. RESULTS: Women of 50 to 70 years were more vulnerable to Acom aneurysm formation than men. The Acom/A2 bifurcation angle was significantly increased (P<0.0001) with increase of patient age. The size of the Acom aneurysm dome and neck was statistically positively correlated with the diameter of the Acom, A1 and A2 segments (P<0.0001). The Acom/A2 bifurcation angle was significantly (P<0.0001) wider in patients with than without Acom aneurysms, whereas the A1/A2 angle was significantly smaller in patients with than without Acom aneurysms (P<0.0001). The Acom aneurysms at the bifurcation apex mostly deviated toward the smaller angle formed between the parent A1 and branches and toward the daughter artery with a smaller diameter. The Acom aneurysms were located mostly on the dominant anterior cerebral artery. CONCLUSIONS: The presence of Acom aneurysm is significantly associated with patient age, wider angles of the anterior cerebral artery bifurcation, and smaller vascular diameter of the anterior communicating complex.
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Artéria Cerebral Anterior/diagnóstico por imagem , Aneurisma Intracraniano/etiologia , Fatores Etários , Idoso , Aneurisma Roto , Angiografia Cerebral/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND PURPOSE: Basilar artery (BA) bifurcation aneurysms are common, but the correlation between BA bifurcation morphology and aneurysm formation remains to be established. Our purpose was to determine the association of BA bifurcation aneurysms with patient age, sex, bifurcation angle, and branch diameter. METHODS: Three-dimensional angiographic data of 195 patients were used, including 59 patients with BA bifurcation aneurysms and 136 control subjects. The angles formed between left and right posterior cerebral arteries (φ1) and between posterior cerebral artery and BA (the smaller angle defined as φ2 and the larger one as φ3), arterial diameters, and BA bifurcation aneurysm geometric characters were examined. RESULTS: Women of 40 to 70 years of age are more vulnerable to BA bifurcation aneurysm formation than men. The φ1 bifurcation angle significantly increased (P<0.0001), whereas both φ2 and φ3 angles significantly decreased (P<0.0001 and P=0.09, respectively) with increase of patients' age. Statistically significant (P<0.0001 and P=0.0002, respectively) positive correlations were observed between BA bifurcation branch diameter and aneurysm size. The φ1 angle was significantly (P<0.0001) wider in patients harboring BA bifurcation aneurysms than the control, whereas φ2 and φ3 angles in aneurysm group were significantly smaller than those in the control group (P<0.0001). The BA bifurcation aneurysms were mostly deviated toward the smaller φ2 angle side between φ2 and φ3 angles and deviated toward the smaller-diameter daughter posterior cerebral artery branch. CONCLUSIONS: BA bifurcation aneurysms are significantly associated with patients' age, female sex, wider bifurcation angles, and smaller vascular diameter at the BA bifurcation.
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Fatores Etários , Imageamento Tridimensional , Aneurisma Intracraniano/epidemiologia , Fatores Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Artéria Basilar/diagnóstico por imagem , Angiografia Cerebral/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Posterior/diagnóstico por imagemRESUMO
Water is important resource for human survival and development. Coal mine wastewater (CMW) is a byproduct of the process of coal mining, which is about 7.0 × 1010 m3 in China in 2016. Considering coal mine wastewater includes different ingredients, a new bubble column humidification and dehumidification system is proposed for CMW treatment. The system is mainly composed of a bubble column humidification and dehumidification unit, solar collector, fan and water tank, in which air is used as a circulating medium. The system can avoid water treatment component blocking for reverse osmosis (RO) and multi effect distillation (MED) dealing with CMW, and produce water greenly. By analysis of heat and mass transfer, the effects of solar radiation, air bubble velocity and mine water temperature on water treatment production characteristics are studied. Compared with other methods, thermal energy consumption (TEC) of bubble column humidification and dehumidification (BCHD) is moderate, which is about 700 kJ/kg (powered by solar energy). The results would provide a new method for CMW treatment and insights into the efficient coal wastewater treatment, besides, it helps to identify the parameters for the technology development in mine water treatment.
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Minas de Carvão , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/análise , Poluentes Químicos da Água/química , China , Eliminação de Resíduos Líquidos/instrumentaçãoRESUMO
OBJECTIVE: To observe the therapeutic effects of exogenous pulmonary surfactant (PS) on acute lung injury induced by severe burn-blast combined injury in a rat model. METHODS: A total of 180 adult male SD rats were randomly divided into 3 groups of sham, treatment and control (n=60 each). Severe burn-blast combined injury was induced by inflicting rats with a moderate blast injury and a full-thickness burn injury of 25% total body surface area. The treatment and control groups received exogenous PS (2 ml/kg) and saline (2 ml/kg) by trachea respectively. At the time points of 0, 6, 24, 48 and 72 h, 12 rats per timepoint in each group underwent PaO2, PaCO2 and pulmonary function tests respectively. And they were then sacrificed for other analyses. Lung tissues were harvested for histological studies. Their arterial blood samples were collected for blood gas analysis. All data were expressed as mean ± standard deviation and analyzed with SPSS 20.0 (SPSS Inc., Chicago, IL, USA). The differences were considered to be statistically significant at P < 0.05. RESULTS: After removing death drain during the experiment, 8 rats were put equally into five phase points of the last three groups, the results were analyzed statistically. PaO2: At each timepoint of 6, 24, 48, 72 h, the control group PaO2 were obviously lower than the sham group ((69.55 ± 5.11), (62.05 ± 6.54), (53.24 ± 7.65), (50.00 ± 7.45) vs (93.75 ± 3.41), (94.25 ± 2.19), (93.63 ± 2.33), (93.25 ± 1.83) mmHg (1 mmHg = 0.133 kPa), all P < 0.01); at 6 h treatment group was close to sham group ((92.63 ± 3.74) vs (93.75 ± 3.41) mmHg, P=0.594); at 6 h control group PaO2 decreased to 70 mmHg and then gradually declined. And at each timepoint the treatment group PaO2 was significantly higher than the control group ((92.63 ± 3.74), (87.50 ± 3.34), (78.75 ± 3.11), (71.38 ± 3.74) vs (69.55 ± 5.11), (62.05 ± 6.54), (53.24 ± 7.65), (50.00 ± 7.45) mmHg, all P < 0.01); PaCO2: treatment group PaCO2 was lower than that of control group at 6, 24, 48 h ((45.50 ± 6.79), (49.38 ± 7.52), (54.13 ± 4.82) vs (53.25 ± 2.76), (59.50 ± 6.61), (63.60 ± 7.33) mmHg, all P < 0.01), both treatment and control groups were significantly higher than those in the sham group ((59.63 ± 6.87), (68.88 ± 6.85) vs (36.38 ± 1.85) mmHg, all P < 0.01). No difference existed between the control and treatment groups (P = 0.051). Deep inspiratory capacity, central airway resistance, lung compliance and tissue elasticity, treatment group was significantly better than control group at 24 h (P < 0.05). And it was close to sham group (P > 0.05). The treatment group alveolar structural damage and pulmonary hemorrhage and edema were better than those in the control group. CONCLUSION: Exogenous pulmonary surfactant (PS) can improve oxygenation and alleviate pulmonary edema and pulmonary capillary membrane permeability of rats with severe burn blast combined injury.
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Lesão Pulmonar Aguda , Traumatismos por Explosões , Queimaduras , Animais , Gasometria , Leucócitos , Complacência Pulmonar , Masculino , Surfactantes Pulmonares , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To explore the efficacies of resuscitation fluid volume after combined burn-blast injury versus a simple burn. METHODS: A total of 24 beagle dogs were randomly assigned into 3 groups of normal volume (N), decreased volume (D) and increased volume (I). Fluid volume for group N was calculated with the Parkland formula while groups D and I decreased or increased by 20% respectively. Urinary output (UOP), hemoglobin concentration (HB), cardiac output (CO), intrathoracic blood volume (ITBV), extravascular lung water index (ELWI), oxygen delivery (DO(2)) and oxygen consumption (VO(2)) were determined before and 4, 8, 24, 48 h after injury to evaluate the sufficiency of resuscitation in each group and examine the superiority. RESULTS: UOP were [(0.41 ± 0.13), (0.77 ± 0.17), (0.30 ± 0.13)] ml · kg(-1) · h(-1) at 4 h post-injury in groups N, I and D respectively. Group I was significantly higher than groups N and D (P < 0.001).It were [(0.59 ± 0.05), (0.88 ± 0.05), (0.53 ± 0.06)] ml · kg(-1) · h(-1) at 24 h post-injury in groups N, I and D respectively. Group I was significantly higher than groups N and D (P < 0.001). CO in group I was remarkably higher than those in groups N and D at 4 h and 8 h post-injury [(1.57 ± 0.19) vs (1.25 ± 0.17), (1.05 ± 0.17) L/min; (1.87 ± 0.20) vs (1.57 ± 0.24), (1.20 ± 0.19) L/min respectively] (P < 0.05); ITBV also significantly increased in group I than two other groups at 4 h and 8 h post-injury [(169 ± 16) vs (140 ± 12), (121 ± 12) ml; (161 ± 14) vs (135 ± 22), (112 ± 12) ml] (P < 0.05). VO2 in group I was significantly higher than that in group N at 24 h post-injury [(129 ± 10) vs (106 ± 12) ml · min(-1) · m(-2)] (P < 0.05). No differences were detected among 3 group in ELWI (P > 0.05). CONCLUSION: Larger fluid volume may compensate circulatory volume loss sooner, alleviate declining cardiac output better, maintain adequate organ perfusion, promote tissue oxygenation and improve anti-hypervolemia and anti-hypoxia.
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Traumatismos por Explosões , Queimaduras , Hidratação , Animais , Pressão Sanguínea , Débito Cardíaco , Cães , Água Extravascular Pulmonar , Ressuscitação , ChoqueRESUMO
Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.
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The purpose of the current investigation was to evaluate the effect of pinch span on the perception of pinch force in typical participants. The healthy participants (10 males and 10 females) conducted an ipsilateral force reproduction test with three distinct pinch spans (2, 4, and 6 cm) at three distinct forces of 10%, 30%, and 50% maximum voluntary isometric contraction. The findings revealed a significantly greater consistency (lower variable error (VE)) of 4 cm compared with 2 and 6 cm pinch spans. Our study also showed that the participants might use a larger force (more overestimated) output for larger pinch spans (4 and 6 cm) than small pinch spans (2 cm). These results may offer significant insights into the higher rates of musculoskeletal disorders among females, enabling researchers and clinicians to design novel interventions and tools to improve pinch force perception and reduce hand injury rates in males and females.
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Força da Mão , Contração Isométrica , Masculino , Feminino , Humanos , Voluntários SaudáveisRESUMO
The aim of this study was to identify the exact origin of force sense and identify whether it arises centrally or peripherally. The present study was designed to analyze the effects of short-term fatigue on pinch force sense and the duration of these effects. During the fatigue protocol, twenty (10 men and 10 women; Mage = 22.0 years old) young Chinese participants were asked to squeeze maximally until the pinch grip force decreased to 50% of its maximal due to fatigue. Participants were instructed to produce the target force (10% of maximal voluntary isometric contraction) using the same hand before and after fatigue (immediately, 10, 30, 60, 180, 300 s). The results showed significantly higher absolute error immediately after fatigue (1.22 ± 1.06 N) than before fatigue (0.68 ± 0.34 N), and 60 s (0.76 ± 0.69 N), 180 s (0.67 ± 0.42 N), and 300 s (0.75 ± 0.37 N) after fatigue (all P < 0.05) but with no effect on the variable error (P > 0.05). It was also revealed that there was a significant overestimate of the constant error values before (0.32 ± 0.61 N) and immediately after fatigue (0.80 ± 1.38 N, all P < 0.05), while no significant overestimation or underestimation exceeded 300 s after fatigue (P > 0.05). Our study results revealed that short-term fatigue resulted in a significant decrease in force sense accuracy, but it did not affect force sense consistently; however, force sense accuracy recovered to a certain extent within 10 s and 30 s, whereas it recovered fully within 60 s, and force sense directivity improvement exceeded 300 s after fatigue. The present study shows that the sense of tension (peripherally) is also an important factor affecting force sense. Our study supports the view that the periphery is part of the origin of force sense.
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Força da Mão , Mãos , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Contração Isométrica , Fadiga Muscular , Músculo EsqueléticoRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care.
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Thermally activated delayed fluorescence (TADF) materials with both high photoluminescence quantum yield (PLQY) and fast reverse intersystem crossing (RISC) are strongly desired to realize efficient and stable organic light-emitting diodes (OLEDs). Control of excited-state dynamics via molecular design plays a central role in optimizing the PLQY and RISC rate of TADF materials but remains challenging. Here, 3 TADF emitters possessing similar molecular structures, similar high PLQYs (89.5% to 96.3%), and approximate energy levels of the lowest excited singlet states (S1), but significantly different spin-flipping RISC rates (0.03 × 106 s-1 vs. 2.26 × 106 s-1) and exciton lifetime (297.1 to 332.8 µs vs. 6.0 µs) were systematically synthesized to deeply investigate the feasibility of spin-flip between charge-transfer excited states (3CT-1CT) transition. Experimental and theoretical studies reveal that the small singlet-triplet energy gap together with low RISC reorganization energy between the 3CT and 1CT states could provide an efficient RISC through fast spin-flip 3CT-1CT transition, without the participation of an intermediate locally excited state, which has previously been recognized as being necessary for realizing fast RISC. Finally, the OLED based on the champion TADF emitter achieves a maximum external quantum efficiency of 27.1%, a tiny efficiency roll-off of 4.1% at 1,000 cd/m2, and a high luminance of 28,150 cd/m2, which are markedly superior to those of the OLEDs employing the other 2 TADF emitters.
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Intrauterine adhesions (IUA) caused by endometrial injury are one of the main causes of female infertility. The current treatments for endometrial injury offer limited clinical benefits and cannot improve endometrial receptivity and pregnancy outcomes. Tissue engineering and regenerative medicine are considered potential solutions to address this concern and may offer effective treatment methods for the regeneration of injured human endometrium. Herein, we prepared an injectable hydrogel based on oxidized hyaluronic acid (HA-CHO) and hydrazide-grafted gelatin (Gel-ADH). The injectable hydrogel showed satisfactory biocompatibility when mixed with human umbilical cord mesenchymal stem cells (hUCMSCs). In an endometrial injury rat model, the treatment with hUCMSCs-loaded injectable hydrogel significantly enhanced the thickness of the endometrium and increased the abundance of blood vessels and glands in the injured endometrium compared to the control group. The hUCMSCs-loaded injectable hydrogel treatment significantly reduced endometrial fibrosis, decreased the expression of the pro-inflammatory factors (IL-1ß and IL-6) and increased the expression of the anti-inflammatory factor (IL-10). This treatment induced endometrial VEGF expression by activating the MEK/ERK1/2 signaling pathway. Moreover, this treatment improved endometrial receptivity to the embryo and restored the embryo implantation rate similar to the sham group (48% in the sham group vs 46% in the treatment group), and this treatment achieved pregnancy and live birth in rats with endometrial injury. In addition, we also preliminarily validated the safety of this treatment in the maternal rats and fetuses. Collectively, our study showed that the hUCMSCs-loaded injectable hydrogel hold potential as an effective treatment strategy promoting rapid recovery of endometrial injury, and this hydrogel is a promising biomaterial for regenerative medicine applications. STATEMENT OF SIGNIFICANCE: 1. Oxidized hyaluronic acid (HA-CHO)/hydrazide-grafted gelatin (Gel-ADH) hydrogel combined with human umbilical cord mesenchymal stem cells (hUCMSCs) are effective in improving the regeneration of endometrium in the endometrial injury rat model. 2. The hUCMSCs-loaded hydrogel treatment promotes the expression of endometrial VEGF through MEK/ERK1/2 signaling pathway and regulates the balance of inflammatory factors. 3. The embryo implantation and live birth rates restore to normal level in the endometrial injury rat model, and the hydrogel has no adverse effects on maternal rats, fetuses, and offspring development after the treatments.
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Hidrogéis , Células-Tronco Mesenquimais , Gravidez , Humanos , Ratos , Feminino , Animais , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Gelatina/farmacologia , Ácido Hialurônico/farmacologia , Ácido Hialurônico/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Endométrio/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical , Fertilidade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologiaRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care.
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The development of orange-red/red thermally activated delayed fluorescence (TADF) materials with both high emission efficiencies and short lifetimes is highly desirable for electroluminescence (EL) applications, but remains a formidable challenge owing to the strict molecular design principles. Herein, two new orange-red/red TADF emitters, namely AC-PCNCF3 and TAC-PCNCF3, composed of pyridine-3,5-dicarbonitrile-derived electron-acceptor (PCNCF3) and acridine electron-donors (AC/TAC) are developed. These emitters in doped films exhibit excellent photophysical properties, including high photoluminescence quantum yields of up to 0.91, tiny singlet-triplet energy gaps of 0.01 eV, and ultrashort TADF lifetimes of less than 1 µs. The TADF-organic light-emitting diodes employing the AC-PCNCF3 as emitter achieve orange-red and red EL with high external quantum efficiencies of up to 25.0% and nearly 20% at doping concentrations of 5 and 40 wt%, respectively, both accompanied by well-suppressed efficiency roll-offs. This work provides an efficient molecular design strategy for developing high-performance red TADF materials.