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Mouse FOXA1 and GATA4 are prototypes of pioneer factors, initiating liver cell development by binding to the N1 nucleosome in the enhancer of the ALB1 gene. Using cryoelectron microscopy (cryo-EM), we determined the structures of the free N1 nucleosome and its complexes with FOXA1 and GATA4, both individually and in combination. We found that the DNA-binding domains of FOXA1 and GATA4 mainly recognize the linker DNA and an internal site in the nucleosome, respectively, whereas their intrinsically disordered regions interact with the acidic patch on histone H2A-H2B. FOXA1 efficiently enhances GATA4 binding by repositioning the N1 nucleosome. In vivo DNA editing and bioinformatics analyses suggest that the co-binding mode of FOXA1 and GATA4 plays important roles in regulating genes involved in liver cell functions. Our results reveal the mechanism whereby FOXA1 and GATA4 cooperatively bind to the nucleosome through nucleosome repositioning, opening chromatin by bending linker DNA and obstructing nucleosome packing.
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SLC30A9 (ZnT9) is a mitochondria-resident zinc transporter. Mutations in SLC30A9 have been reported in human patients with a novel cerebro-renal syndrome. Here, we show that ZnT9 is an evolutionarily highly conserved protein, with many regions extremely preserved among evolutionarily distant organisms. In Drosophila melanogaster (the fly), ZnT9 (ZnT49B) knockdown results in acutely impaired movement and drastic mitochondrial deformation. Severe Drosophila ZnT9 (dZnT9) reduction and ZnT9-null mutant flies are pupal lethal. The phenotype of dZnT9 knockdown can be partially rescued by mouse ZnT9 expression or zinc chelator TPEN, indicating the defect of dZnT9 loss is indeed a result of zinc dyshomeostasis. Interestingly, in the mouse, germline loss of Znt9 produces even more extreme phenotypes: the mutant embryos exhibit midgestational lethality with severe development abnormalities. Targeted mutagenesis of Znt9 in the mouse brain leads to serious dwarfism and physical incapacitation, followed by death shortly. Strikingly, the GH/IGF-1 signals are almost non-existent in these tissue-specific knockout mice, consistent with the medical finding in some human patients with severe mitochondrial deficiecny. ZnT9 mutations cause mitochondrial zinc dyshomeostasis, and we demonstrate mechanistically that mitochondrial zinc elevation quickly and potently inhibits the activities of respiration complexes. These results reveal the critical role of ZnT9 and mitochondrial zinc homeostasis in mammalian development. Based on our functional analyses, we finally discussed the possible nature of the so far identified human SLC30A9 mutations.
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Proteínas de Transporte de Catión , Desarrollo Embrionario , Mitocondrias , Zinc , Animales , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Humanos , Zinc/metabolismo , Ratones , Mitocondrias/metabolismo , Desarrollo Embrionario/genética , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/embriología , Evolución Molecular , Ratones Noqueados , Secuencia de Aminoácidos , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Factores de Transcripción , Proteínas de Ciclo CelularRESUMEN
Cervical cancer (CxCa) is the fourth most frequent cancer in women. This study aimed to determine the role and underlying mechanism of fibronectin type III domain-containing protein 5 (FNDC5) in inhibiting CxCa growth. Experiments were performed in human CxCa tissues, human CxCa cell lines (HeLa and SiHa), and xenograft mouse model established by subcutaneous injection of SiHa cells in nude mice. Bioinformatics analysis showed that CxCa patients with high FNDC5 levels have a longer overall survival period. FNDC5 expression was increased in human CxCa tissues, HeLa and SiHa cells. FNDC5 overexpression or FNDC5 protein not only inhibited proliferation, but also restrained invasion and migration of HeLa and SiHa cells. The effects of FNDC5 were prevented by inhibiting integrin with cilengitide, activating PI3K with recilisib or activating Akt with SC79. FNDC5 inhibited the phosphorylation of PI3K and Akt, which was attenuated by recilisib. PI3K inhibitor LY294002 showed similar effects to FNDC5 in HeLa and SiHa cells. Intravenous injection of FNDC5 (20 µg/day) for 14 days inhibited the tumor growth, and reduced the proliferation marker Ki67 expression and the Akt phosphorylation in the CxCa xenograft mouse model. These results indicate that FNDC5 inhibits the malignant phenotype of CxCa cells through restraining PI3K/Akt signaling. Upregulation of FNDC5 may play a beneficial role in retarding the tumor growth of CxCa.
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Proliferación Celular , Fibronectinas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Neoplasias del Cuello Uterino , Animales , Femenino , Humanos , Ratones , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fibronectinas/metabolismo , Fibronectinas/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HeLa , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto , Integrinas/metabolismo , Progresión de la EnfermedadRESUMEN
BACKGROUND: The mitochondrial unfolded protein response (UPRmt) is an evolutionarily conserved mitochondrial response that is critical for maintaining mitochondrial and energetic homeostasis under cellular stress after tissue injury and disease. Here, we ask whether UPRmt may be a potential therapeutic target for ischemic stroke. METHODS: We performed the middle cerebral artery occlusion and oxygen-glucose deprivation models to mimic ischemic stroke in vivo and in vitro, respectively. Oligomycin and meclizine were used to trigger the UPRmt. We used 2,3,5-triphenyltetrazolium chloride staining, behavioral tests, and Nissl staining to evaluate cerebral injury in vivo. The Cell Counting Kit-8 assay and the Calcein AM Assay Kit were conducted to test cerebral injury in vitro. RESULTS: Inducing UPRmt with oligomycin protected neuronal cultures against oxygen-glucose deprivation. UPRmt could also be triggered with meclizine, and this Food and Drug Administration-approved drug also protected neurons against oxygen-glucose deprivation. Blocking UPRmt with siRNA against activating transcription factor 5 eliminated the neuroprotective effects of meclizine. In a mouse model of focal cerebral ischemia, pretreatment with meclizine was able to induce UPRmt in vivo, which reduced infarction and improved neurological outcomes. CONCLUSIONS: These findings suggest that the UPRmt is important in maintaining the survival of neurons facing ischemic/hypoxic stress. The UPRmt mechanism may provide a new therapeutic avenue for ischemic stroke.
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Isquemia Encefálica , Glucosa , Mitocondrias , Neuronas , Respuesta de Proteína Desplegada , Animales , Masculino , Ratones , Isquemia Encefálica/metabolismo , Células Cultivadas , Glucosa/deficiencia , Infarto de la Arteria Cerebral Media/metabolismo , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Oxígeno/metabolismo , Respuesta de Proteína Desplegada/efectos de los fármacosRESUMEN
MAIN CONCLUSION: The expression peak of VcAP1.4, VcAP1.6, VcAP3.1, VcAP3.2, VcAG3, VcFLC2, and VcSVP9 coincided with the endo-dormancy release of flower buds. Additionally, GA4+7 not only increased the expression of these genes but also promoted flower bud endo-dormancy release. The MIKCC-type MADS-box gene family is involved in the regulation of flower development. A total of 109 members of the MIKCC-type MADS-box gene family were identified in blueberry. According to the phylogenetic tree, these 109 MIKCC-type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scaffolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional differentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have significant roles in the endo-dormancy release of flower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate flower bud dormancy release. VcSEP11 might promote flowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of flower buds. The effect of gibberellin (GA4+7) treatment on the expression pattern of MIKCC-type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote flower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry flower buds.
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Arándanos Azules (Planta) , Arándanos Azules (Planta)/genética , Filogenia , Reproducción , Flores/genética , Duplicación de GenRESUMEN
Posttreatment of pristine metal-organic frameworks (MOFs) with suitable vapor may be an effective way to regulate their structures and properties but has been less explored. Herein, we report an interesting example in which a crystalline nonporous Eu(III)-MOF was transferred to a porous amorphous MOF (aMOF) via iodine vapor adsorption-desorption posttreatment, and the resulting aMOF showed improved turn-on sensing properties with respect to Ag+ ions. The crystalline Eu-MOF, namely, Eu-IPDA, was assembled from Eu(III) and 4,4'-{4-[4-(1H-imidazol-1-yl)phenyl]pyridine-2,6-diyl}dibenzoic acid (H2IPDA) and exhibited a two-dimensional (2D) coordination network based on one-dimensional secondary building blocks. The close packing of the 2D networks gives rise to a three-dimensional supramolecular framework without any significant pores. Interestingly, the nonporous Eu-IPDA could absorb iodine molecules when Eu-IPDA crystals were placed in iodine vapor at 85 °C, and the adsorption capacity was 1.90 g/g, which is comparable to those of many MOFs with large BET surfaces. The adsorption of iodine is attributed to the strong interactions among the iodine molecule, the carboxy group, and the N-containing group and leads to the amorphization of the framework. After immersion of the iodine-loaded Eu-IPDA in EtOH, approximately 89.7% of the iodine was removed, resulting in a porous amorphous MOF, denoted as a-Eu-IPDA. In addition, the remaining iodine in the a-Eu-IPDA framework causes strong luminescent quenching in the fluorescence emission region of the Eu(III) center when compared with that in Eu-IPDA. The luminescence intensity of a-Eu-IPDA in water suspensions was significantly enhanced when Ag+ ions were added, with a detection limit of 4.76 × 10-6 M, which is 1000 times that of pristine Eu-IPDA. It also showed strong anti-interference ability over many common competitive metal ions and has the potential to sense Ag+ in natural water bodies and traditional Chinese medicine preparations. A mechanistic study showed that the interactions between Ag+ and the absorbed iodine, the carboxylate group, and the N atoms all contribute to the sensing performance of a-Eu-IPDA.
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Gestational diabetes (GD) is a condition characterized by elevated blood sugar levels during pregnancy. GD poses various health risks, such as serious birth injuries, the need for cesarean delivery, and the necessity of newborn care. Monitoring glucose levels is essential for ensuring safe delivery and reducing the risks to both the mother and fetus. Various sensors are readily available for monitoring glucose levels, and researchers are continually working to develop highly sensitive glucose sensors. This research aimed to develop a gold nanourchin (AuNU)-hybrid biosensor for quantifying glucose on a multi-point electrode sensor. Glucose oxidase (GOx) was attached to the AuNU and seeded on the sensing surface using an amine linker. The current-potential (1-2 V at 0.1 V sweep) was recorded for the GOx-glucose interaction, with a limit of detection of 560 µM and a regression coefficient (R2) of 0.9743 [y = 0.9106x - 0.9953] on the linear curve. The sensitivity was estimated to be 3.5 mAcm-2M-1. Furthermore, control experiments with galactose, sucrose, and fructose did not yield an increase in current-potential, confirming specific glucose detection. This experiment helps in monitoring glucose levels to manage conditions associated with GD.
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OBJECTIVES: To assess the ability of left atrial (LA) strain parameters to discriminate patients with elevated left atrial pressure (LAP) from patients with atrial fibrillation (AF). METHODS AND RESULTS: A total of 142 patients with non-valvular AF who underwent first catheter ablation (CA) between November 2022 and November 2023 were enrolled in the study. Conventional and speckle-tracking echocardiography (STE) were performed in all patients within 24 h before CA, and LAP was invasively measured during the ablation procedure. According to mean LAP, the study population was classified into two groups of normal LAP (LAP < 15 mmHg, n = 101) and elevated LAP (LAP ≥ 15 mmHg, n = 41). Compared with the normal LAP group, elevated LAP group showed significantly reduced LA reservoir strain (LASr) [9.14 (7.97-11.80) vs. 20 (13.59-26.96), p < .001], and increased LA filling index [9.60 (7.15-12.20) vs. 3.72 (2.17-5.82), p < .001], LA stiffness index [1.13 (.82-1.46) vs. .47 (.30-.70), p < .001]. LASr, LA filling index and LA stiffness index were independent predictors of elevated LAP after adjusted by the type of AF, EDT, E/e', mitral E, and peak acceleration rate of mitral E velocity. The receiver-operating characteristic curve (ROC) analysis showed LA strain parameters (area under curve [AUC] .794-.819) could provide similar or greater diagnostic accuracy for elevated LAP, as compared to conventional echocardiographic parameters. Furthermore, the novel algorithms built by LASr, LA stiffness index, LA filling index, and left atrial emptying fraction (LAEF), was used to discriminate elevated LAP in AF with good accuracy (AUC .880, accuracy of 81.69%, sensitivity of 80.49%, and specificity of 82.18%), and much better than 2016 ASE/EACVI algorithms in AF. CONCLUSION: In patients with AF, LA strain parameters could be useful to predict elevated LAP and non-inferior to conventional echocardiographic parameters. Besides, the novel algorithm built by LA strain parameters combined with conventional parameters would improve the diagnostic efficiency.
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Fibrilación Atrial , Función del Atrio Izquierdo , Presión Atrial , Ecocardiografía , Atrios Cardíacos , Humanos , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Femenino , Masculino , Persona de Mediana Edad , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Ecocardiografía/métodos , Presión Atrial/fisiología , Función del Atrio Izquierdo/fisiología , Valor Predictivo de las Pruebas , Ablación por Catéter/métodos , Reproducibilidad de los Resultados , AncianoRESUMEN
PURPOSE: This large retrospective, single-center, follow-up study investigated the endoscopic prelacrimal recess approach (PLRA) for treating maxillary sinus inverted papilloma (MSIP). METHODS: Between January 2007 and November 2022, patients with MSIP treated with PLRA were enrolled. Data on clinical manifestations, imaging, and surgical procedures were collected. The visual analog scale (VAS) scores for maxillofacial numbness and nasal symptoms and the SNOT-22 nasal symptom scores were statistically analyzed. RESULT: Of 122 patients (68 males and 54 females) enrolled in the study, with a mean age of 50.75 ± 12.84 years (26-80 years), 111 patients underwent PLRA, nine underwent modified PLRA, one converted to an endoscopic medial maxillectomy (EMM), and one to an endoscopic modified Denker's approach. The average follow-up was 86.60 (13-192) months, the recurrence rate was 3.28%, and 29 patients (23.77%) complained of maxillofacial numbness one month postoperatively, which disappeared in most cases one year after surgery. Five patients (4.10%) experienced mild numbness at the end of the follow-up period. Maxillary sinus ostium contracture or atresia occurred in two cases (1.64%). After surgery, the VAS nasal symptom scores improved significantly (P < 0.001). SNOT-22 indicated that the most common postoperative symptom was thick nasal discharge. CONCLUSION: PLRA is a flexible first-choice surgical treatment for maxillary sinus inverted papilloma and can be modified according to the extent of the lesion, the surgeon's experience and technique, and surgical instruments. That can help achieve complete resection and reduce recurrence and surgical complications. Upper teeth numbness, the most common postoperative complication, tends to disappear after 1 year.
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Recurrence of breast cancer may be due to the presence of breast cancer stem cells (BCSC). Abnormal tumor cell growth is closely associated with increased reactive oxygen species (ROS) and disruption of redox homeostasis, and BCSCs exhibit low levels of ROS. The detailed mechanism between the low levels of ROS in BCSCs and their maintenance of stemness characteristics has not been reported. A growing number of studies have shown that tumor development is often accompanied by metabolic reprogramming, which is an important hallmark of tumor cells. As the first rate-limiting enzyme of pentose phosphate pathway (PPP), the expression of G6PD is precisely regulated in tumor cells, and there is a certain correlation between PPP and BCSCs. MiR-375 has been shown to inhibit stem cell-like properties in breast cancer, but the exact mechanism is not clear. Here, KLF5, as a transcription factor, was identified to bind to the promoter of G6PD to promote its expression, whereas miR-375 inhibited the expression of KLF5 by binding to the 3'UTR region of KLF5 mRNA and thus reduced the expression of G6PD expression, inhibits PPP to reduce NADPH, and increases ROS levels in breast cancer cells, thereby weakening breast cancer cell stemness. Our study reveals the specific mechanism by which miR-375 targets the KLF5/G6PD signaling axis to diminish the stemness of breast cancer cells, providing a therapeutic strategy against BCSCs.
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BACKGROUND: Creatine supplementation is ubiquitously consumed by fitness enthusiasts due to its perceived advantages in enhancing athletic performance. Although there is an increasing concern within this demographic regarding its possible impact on renal function, there is still a lack of rigorous scientific investigations into this alleged association. METHODS: Data were collected through an online survey on the participants' demographics, creatine usage and concerns related to renal function. The reliability and validity of the survey were assessed using SPSS software. A total of 1129 participants responded to the survey, and chi-square tests were utilized for data analysis. To explore the potential association between creatine levels (as the exposure) and renal function (as the outcome), we utilized open-access genetic databases, and Mendelian randomization (MR) techniques were used to confirm this correlation. RESULTS: Chi-square analysis revealed no significant association between creatine usage and renal function among the participants. Our MR analysis further supported this finding, demonstrating no significant association between creatine levels and six indicators assessing renal function (IVW, all with p values exceeding 0.05). Similar p values were consistently observed across other MR methods, confirming the absence of a statistical correlation. CONCLUSIONS: This MR study offers compelling evidence indicating that creatine levels are not statistically associated with renal function, suggesting the potential to alleviate concerns within the fitness community and emphasizing the significance of evidence-based decision-making when considering nutritional supplementation.
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Creatina , Suplementos Dietéticos , Análisis de la Aleatorización Mendeliana , Humanos , Creatina/administración & dosificación , Masculino , Femenino , Adulto , Riñón/fisiopatología , Persona de Mediana Edad , Adulto Joven , Encuestas y Cuestionarios , Reproducibilidad de los ResultadosRESUMEN
The escalating frequency, duration, and intensity of extreme heat events have posed a significant threat to human society in recent decades. Understanding the dynamic patterns of human mobility under extreme heat will contribute to accurately assessing the risk of extreme heat exposure. This study leverages an emerging geospatial data source, anonymous cell phone location data, to investigate how people in different communities adapt travel behaviors responding to extreme heat events. Taking the Greater Houston Metropolitan Area as an example, we develop two indices, the Mobility Disruption Index (MDI) and the Activity Time Shift Index (ATSI), to quantify diurnal mobility changes and activity time shift patterns at the city and intra-urban scales. The results reveal that human mobility decreases significantly in the daytime of extreme heat events in Houston while the proportion of activity after 8 p.m. is increased, accompanied with a delay in travel time in the evening. Moreover, these mobility-decreasing and activity-delaying effects exhibited substantial spatial heterogeneity across census block groups. Causality analysis using the Geographical Convergent Cross Mapping (GCCM) model combined with correlation analyses indicates that people in areas with a high proportion of minorities and poverty are less able to adopt heat adaptation strategies to avoid the risk of heat exposure. These findings highlight the fact that besides the physical aspect of environmental justice on heat exposure, the inequity lies in the population's capacity and knowledge to adapt to extreme heat. This research is the first of the kind that quantifies multi-level mobility for extreme heat responses, and sheds light on a new facade to plan and implement heat mitigations and adaptation strategies beyond the traditional approaches.
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Teléfono Celular , Calor Extremo , HumanosRESUMEN
BACKGROUND: The caregiver contribution to self-care plays an important role in improving the health outcomes of chronic patients, which needs urgent attention. However, it has been hindered by the lack of a tailored instrument that assesses the caregiver contribution to self-care of stroke. OBJECTIVES: To test the psychometric characteristics of the caregiver contribution to self-care of stroke Inventory (CC-SCSI) in health care practice. METHODS: Participants were recruited in Henan Province from March 2021 to October 2022, utilizing a multicenter stratified sampling approach. A 23-item self-report CC-SCSI with 3 separate scales measuring caregiver contribution to self-care maintenance of stroke, caregiver contribution to self-care monitoring of stroke and caregiver contribution to self-care management of stroke was tested for validity through discriminant validity, confirmatory factor analysis, concurrent validity and convergent validity. The reliability was tested by Cronbach's α coefficient and test-retest reliability. Qualitative data were analysed using thematic analysis. A STROBE checklist was used. RESULTS: The three scales of the CC-SCSI exhibited good discriminant validity. Confirmatory factor analysis supported the three-factor structure of the Caregiver Contribution to Stroke Self-Care Maintenance and Management scales and the one-factor structure of the Caregiver Contribution to Stroke Self-Care Monitoring scale. The moderate correlation between the CC-SCSI and the Self-Care of Stroke Inventory indicated acceptable concurrent validity. The moderate correlation between the CC-SCSI and the Caregiver Contribution to Self-Care of Chronic Illness Inventory indicated acceptable convergent validity. Cronbach's αs for the Caregiver Contribution to Self-Care Maintenance, Self-Care Monitoring, and Self-Care Management scales ranged from 0.876 to 0.974. Test-retest reliability showed average ICC values ranging from 0.828 to 0.903 (P < 0.001). CONCLUSIONS: The 23-item CC-SCSI presents good psychometric properties and could be used to explore the caregiver contribution to stroke self-care in health care practice and research.
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This study aims to investigate the mechanism of Mailuo Shutong Pills(MLST) on posterior limb muscle swelling caused by femoral fracture(SCFF) through network pharmacology and animal experiments. The plasma components of MLST were analyzed by LC-MS, and the target and signal pathway of SCFF were predicted by network pharmacology and verified by molecular docking. SCFF model rats were established through animal experiments, and different doses of MLST were administered to detect the degree of limb swelling. Hematoxylin-eosin(HE) staining was used to observe pathological changes in muscle tissue, and interleukin-6(IL-6), interleukin-1ß(interleukin-1ß), and tumor necrosis factor-α(TNF-α) in peripheral blood were determined by enzyme-linked immunosorbent assay(ELISA). The expression of relevant signaling pathways was measured by Western blot. Network pharmacological results showed that MLST and SCFF had a total of 153 disease targets, and the key targets were IL-6, TNF, etc., involving mitogen-activated protein kinase(MAPK) signaling pathway, phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, etc. The binding energies of the main components and key targets were lower than-7.0 kcal·mol~(-1), indicating that the network analysis results were reliable. The results of animal experiments showed that MLST could reduce the swelling degree and pathological damage of the posterior limb muscles of SCFF rats compared with the model group. ELISA results showed that MLST could reduce the levels of IL-6, IL-1ß, and TNF-α in the serum of SCFF rats. Western blot results showed that MLST can reduce the expression of p-AKT, p-PI3K, p-NF-κB, p-p38 MAPK, and p-ERK in SCFF rats. MLST may reduce the content of inflammatory factors in serum by regulating the expression of PI3K/AKT and MAPK-related signaling pathway protein and improving posterior limb muscle SCFF in rats.
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Medicamentos Herbarios Chinos , Fracturas del Fémur , Farmacología en Red , Animales , Ratas , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Masculino , Fracturas del Fémur/tratamiento farmacológico , Fracturas del Fémur/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Simulación del Acoplamiento Molecular , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genéticaRESUMEN
OBJECTIVES: To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder (IMD) among neonates in Gansu Province of China. METHODS: A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021. A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination. RESULTS: A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates, and the overall prevalence rate of IMD was 0.63 (1/1 593), among which phenylketonuria showed the highest prevalence rate of 0.32 (1/3 083), followed by methylmalonic acidemia (0.11, 1/8 959) and tetrahydrobiopterin deficiency (0.06, 1/15 927). In this study, 166 variants were identified in the 28 pathogenic genes, with 13 novel variants found in 9 genes. According to American College of Medical Genetics and Genomics guidelines, 5 novel variants were classified as pathogenic variants, 7 were classified as likely pathogenic variants, and 1 was classified as the variant of uncertain significance. CONCLUSIONS: This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.
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Errores Innatos del Metabolismo de los Aminoácidos , Enfermedades Metabólicas , Niño , Recién Nacido , Humanos , Estudios Retrospectivos , Enfermedades Metabólicas/genética , Errores Innatos del Metabolismo de los Aminoácidos/genética , China , Salud InfantilRESUMEN
The coordinated development of green finance and technological innovation is a key driver of China's high-quality economic growth and therefore deserves close attention. But are green finance and technological innovation really coordinated? This study establishes a coordinating coupling system to link green finance and technological innovation. 2010-2021 is chosen as the observation period, and 31 provinces in China are selected for study. This paper uses the coupling coordination model to investigate the development of the coupling coordination of technological innovation and green finance, and discusses its spatial distribution by the Moran index. The results show that, overall, the degree of coupling coordination between green finance and technological innovation shows a consistent upward trend. The trend is particularly strong in the East. Moreover, the coordination coupling between green finance and technological innovation has the spatial effect. And it shows a binary characteristic, with a decreasing trend observed from coastal to inland regions. These results remained valid after replacing weight matrix and sample size.The above findings have important policy implications for optimising the synergistic development of green finance and technological innovation and achieving high-quality economic development.
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It is of critical importance to address energy poverty in rural areas if inclusive prosperity is to be achieved. Digital finance offers new opportunities to alleviate energy poverty in these regions. However, previous studies have mainly focused on the impact of digital finance on poverty, neglecting research on its impact in rural areas and on specific forms of poverty. This study aims to fill this gap by investigating the impact of digital finance on rural energy poverty. The period 2011-2021 was selected as the observation period, with 31 provinces serving as the study objects. The fixed effects model was employed to investigate the impact of digital finance on rural energy poverty, while exploring the mediating effect. The results indicate that digital finance alleviates the level of rural energy poverty, and this conclusion remains valid following a series of robustness tests. Furthermore, digital finance can indirectly alleviate rural energy poverty through technological innovation and agricultural entrepreneurship activities. Further research indicates that the impact of digital finance on rural energy poverty is more pronounced in regions with abundant human capital, robust government intervention, and minimal urban-rural disparities. This study extends the theoretical support for digital finance to indirectly support rural energy to alleviate poverty. Likewise, this finding provides a new perspective for the government and relevant departments to improve the welfare of residents and alleviate rural energy poverty.
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BACKGROUND: In Chinese culture, the concept of Mianzi holds significant importance in interpersonal interactions. Mianzi represents one's social standing, dignity, and reputation, influencing behaviors and decisions within various contexts. Mianzi consciousness manifests in two primary forms: proactive and defensive. Proactive Mianzi consciousness involves efforts to enhance one's social image, while defensive Mianzi consciousness focuses on protecting one's existing reputation. Analyzing the impact of the two Mianzi consciousness dimensions on individuals' attitudes and behaviors is effective for understanding interpersonal dynamics in China. This study specifically examined the relationship between high Mianzi consciousness congruence and unethical pro-organizational behavior (UPB). UPB refers to actions taken by employees that are intended to benefit their organization but are unethical or morally questionable. By investigating how congruence in proactive and defensive Mianzi consciousness influences the likelihood of engaging in UPB, this research aimed to uncover the underlying social and psychological mechanisms driving such behavior. METHODS: Employing polynomial regression and response surface analysis method, this study developed a model that combines the proactive Mianzi consciousness and the defensive Mianzi consciousness into different Mianzi management strategies and tested the relationship between high Mianzi consciousness congruence and UPB. RESULTS: Sample data collected at two time points one month apart supported all hypotheses. Specifically, the findings revealed that high levels of Mianzi consciousness congruence (i.e., all-around type in Mianzi management strategies) positively relate to UPB, and verified the mediation effect of external work locus of control and the moderation effect of relational psychological contract. CONCLUSION: This research advanced a novel, synergistic perspective on the role of social Mianzi and contributed to the localized UPB research, thus helping to find a path to prevent UPB from occurring in the Chinese sociocultural context.
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Estado de Conciencia , Humanos , China , Femenino , Adulto , Masculino , Cultura Organizacional , Principios Morales , Conducta Social , Dinámica de GrupoRESUMEN
Axon regeneration requires the mobilization of intracellular resources, including proteins, lipids, and nucleotides. After injury, neurons need to adapt their metabolism to meet the biosynthetic demands needed to achieve axonal regeneration. However, the exact contribution of cellular metabolism to this process remains elusive. Insights into the metabolic characteristics of proliferative cells may illuminate similar mechanisms operating in axon regeneration; therefore, unraveling previously unappreciated roles of metabolic adaptation is critical to achieving neuron regrowth, which is connected to the therapeutic strategies for neurological conditions necessitating nerve repairs, such as spinal cord injury and stroke. Here, we outline the metabolic role in axon regeneration and discuss factors enhancing nerve regrowth, highlighting potential novel metabolic treatments for restoring nerve function.
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The impact of macroeconomic policy uncertainty (EPU) on micro-level entities has garnered increasing attention in economic circles. This study examines the influence of EPU on the efficiency of investments made by China's A-share listed companies between 2016 and 2021. Using a panel fixed effect model for analysis, the research reveals that EPU has a notable adverse effect on the investment efficiency of enterprises. Furthermore, it suggests that advancements in digital finance, strong ESG performance, and enhanced entrepreneurial confidence can mitigate this negative impact effectively. The study also highlights that enterprises with lower valuation, shareholder control, limited audit reputation, and no bank connections are more vulnerable to the impact of EPU on investment efficiency compared to those with higher valuation, manager control, strong audit reputation, and bank connections. Consequently, future efforts should be directed towards enhancing the stability and relevance of economic policies, promoting digital finance, and enhancing corporate governance structures.