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Objective: To observe the relationship between the expression of human matricellular protein 3 (MATN3) and the pathological features, drug resistance, and prognosis of gastric cancer based on immunohistochemical method. Methods: A total of 100 gastric cancer patients treated at the First Affiliated Hospital of Bengbu Medical College from January 2022 to December 2022 were included. MATN3 expression in gastric cancer tissues and paracancerous tissues was assessed by immunohistochemistry. The expression of MATN3 was compared across pathological features. Patients were divided into sensitive and resistant groups based on chemotherapy resistance, and MATN3 expression was compared between these groups. The relationship between MATN3 and recurrence-free survival (RFS) and overall survival (OS) of gastric cancer patients was analyzed using Kaplan-Meier survival curves. Univariate and multifactorial Cox regression analyses were used to analyze the factors affecting the prognosis of gastric cancer patients. Human gastric cancer cells MGC803 were transfected with MATN3. The cells were divided into a high expression group (LV-MATN3 group) and its control group (LV-NC group) and a low expression group (sh-MATN3 group) and its control group (sh-NC group). Cell proliferation was assessed using the CCK8 assay, cell migration and invasion were assessed using the Transwell assay, and MATN3 mRNA expression levels were measured using RT-qPCR. A nude mouse xenograft model was constructed by hypodermic injection of MGC-803 cells transfected with MATN3, and MATN3 mRNA expression levels in tumor tissues were measured using RT-qPCR. Results: Immunohistochemical results showed a significantly higher rate of high MATN3 expression in gastric cancer tissues (64.00%, 64/100) compared to adjacent non-cancerous tissues (31.00%, 31/100) (P<0.05). High MATN3 expression was associated with age ≥60 years old, tumor location in the gastric body, tumor size ≥5 cm, lymph node metastasis (N1-N3), histological differentiation (moderate to high), tumor invasion depth (T3-T4), TNM stage (â ¢-â £), distant organ metastasis, recurrence, and mortality (P<0.05). Among patients with chemotherapy resistance, the high MATN3 expression rate was 79.49% (31/39) in the resistant group compared to 54.10% (33/61) in the sensitive group (P<0.05). Follow-up duration ranged from 11 to 22 months, with a 97.00% follow-up rate and 3 cases lost to follow-up. Kaplan-Meier survival curve analysis showed that patients with high MATN3 expression had significantly lower RFS and OS compared to those with low MATN3 expression (RFS: log-rank=17.291, P<0.001; OS: log-rank=21.719, P<0.001). Multivariate Cox analysis identified high MATN3 expression (hazard ratio [HR]=2.291, 95% confidence interval [CI]: 1.268-5.392), tumor location in the gastric body (HR=2.057, 95% CI: 1.441-5.666), lymph node metastasis (N1-N3) (HR=2.011, 95% CI: 1.010-2.274), tumor invasion depth (T3-T4) (H=2.977, 95% CI: 1.032-7.853), TNM stage â ¢-â £ (HR=2.008, 95% CI: 1.049-3.902), and distant organ metastasis (HR=2.505, 95% CI: 1.529-5.000) as independent risk factors affecting RFS and OS (P<0.05). Cell and animal experiments demonstrated that compared to the LV-NC group, the LV-MATN3 group exhibited significantly higher cell proliferation, migration, and invasion (P<0.05), as well as increased tumor volume and MATN3 mRNA expression in tumor tissues (P<0.05). Conversely, the sh-MATN3 group showed significantly reduced cell proliferation, migration, and invasion, along with decreased tumor volume and MATN3 mRNA levels compared to the sh-NC group (P<0.05). Conclusion: MATN3 is highly expressed in gastric cancer tissues and is associated with various pathological features, drug resistance and poor prognosis. MATN3 holds potential as a diagnostic marker for poor prognosis and may play a role in the malignant behaviors of gastric cancer cells, including proliferation, migration, and invasion.
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Resistencia a Medicamentos Antineoplásicos , Imuno-Histoquímica , Camundongos Nus , Neoplasias Gástricas , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Prognóstico , Animais , Camundongos , Linhagem Celular Tumoral , Masculino , Feminino , Pessoa de Meia-Idade , Proliferação de CélulasRESUMO
Background: Paternal antenatal depression and postpartum depression are associated with adverse health outcomes in mothers and infants; however, their prevalence among Chinese fathers remains controversial. This meta-analysis aimed to summarize the prevalence of antenatal depression and postpartum depression in Chinese fathers. Methods: We conducted a systematic meta-analysis on the prevalence of antenatal depression and postpartum depression among Chinese fathers by searching 11 databases. Pooled estimates and 95 % confidence intervals were calculated. The choice between a random-effects model and a fixed-effects model was based on an assessment of heterogeneity among the studies as well as assumptions regarding the similarity of the studies in terms of clinical characteristics, quality, design, and conduct. Subgroup and meta-regression analyses were conducted based on the scale used to measure antenatal depression and postpartum depression, the region where the study was completed, the time of the study, the study design, the number of children, publication language, the study site, and quality assessment. Results: This meta-analysis included 28 studies with 8795 participants. The prevalence of antenatal depression among Chinese fathers was 11 % (95 % CI: 5%-17 %, P < 0.01) using a random-effects model. Heterogeneity was I2 = 91 %. Publication language moderated the prevalence of paternal antenatal depression (the amount of heterogeneity accounted for was 92.13 %). The prevalence of postpartum depression among Chinese fathers was 16 % (95 % CI: 13%-18 %, P < 0.01), using a random-effects model. The heterogeneity was I2 = 94 %. The prevalence of paternal postpartum depression was moderated by the scale used to measure postpartum depression (39.17 % heterogeneity) and the region where the study was completed (33.15 % heterogeneity). Moreover, Egger's test (t = 4.542, P < 0.001) indicated publication bias in studies on postpartum depression among Chinese fathers. However, after applying the trimming correction, the pooled prevalence of postpartum depression had a P value of <0.05, indicating that despite the publication bias, the results remain reliable and unaffected in terms of effect size. Conclusion: The prevalence of antenatal depression and postpartum depression among Chinese fathers was similar to those reported in low- and middle-income countries. Fathers should receive regular screening, effective prevention, and appropriate treatment. However, interpreting these results requires consideration of the limitations of the study.
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Mesenchymal stem cells (MSCs) hold significant promise for regenerative medicine and tissue engineering due to their unique multipotent differentiation ability and immunomodulatory properties. MSC therapy is widely discussed and utilized in clinical treatment. However, during both in vitro expansion and in vivo transplantation, MSCs are prone to senescence, an irreversible growth arrest characterized by morphological, gene expression, and functional changes in genomic regulation. The microenvironment surrounding MSCs plays a crucial role in modulating their senescence phenotype, influenced by factors such as hypoxia, inflammation, and aging status. Numerous strategies targeting MSC senescence have been developed, including senolytics and senomorphic agents, antioxidant and exosome therapies, mitochondrial transfer, and niche modulation. Novel approaches addressing replicative senescence have also emerged. This paper comprehensively reviews the current molecular manifestations of MSC senescence, addresses the environmental impact on senescence, and highlights potential therapeutic strategies to mitigate senescence in MSC-based therapies. These insights aim to enhance the efficacy and understanding of MSC therapies.
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The hydrocarbon reserves in carbonate rocks account for about half of the global hydrocarbon reserves and are an important reservoir type. The Ordovician Majiagou Formation in the central Ordos Basin is a representative weathering crust reservoir. The Caledonian movement uplifted the stratum as a whole, and subsequently, 120 million years of exposed weathering, denudation, and leaching created this unique karst paleomorphology. Dolomite reservoirs have developed dissolved pores and microfractures, which are the best reserved spaces for natural gas and good hydrocarbon migration channels. This paper takes the Ma5Member (hereinafter referred to as Ma51+2) carbonate reservoir in Gaoqiao Gas Field as the research target, based on the core, thin section, cathodoluminescence, logging data, etc., and systematically study the effect of karstification on the reservoir and the genesis of the dolomite reservoir. The results show that the depositional period of the Ordovician Majiagou strata is a regression cycle and the depositional environment is a limited evaporative tidal flat. The reservoir lithology of Ma51+2 is mainly gypsiferous dolomite and micrite dolomite. The reservoir space types consist of intergranular pores, gypsum mold pore, intragranular dissolution pores, intercrystalline pores, and microfractures. The porosity has values from 0.3 to 11.2% (mostly less than 5.0%) with an average of 3.3%, and the permeability ranges from 0.003 to 13.2 mD (mostly less than 1 mD) with an average of 0.36 mD. Karstification is divided into three periods, including syngenetic karst, eogenetic karst, and burial karst. The sedimentary microfacies determine the material basis of the reservoir, and multistage karstification finally modifies the physical properties. By deeply exploring the formation mechanism and influencing factors of the carbonate reservoir in the Ordovician Majiagou Formation, it provides an important theoretical basis and practical guidance for oil and gas exploration and development. At the same time, it also has important reference value for understanding and predicting the development law and distribution characteristics of carbonate reservoirs under similar geological background.
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The unique features of two-dimensional (2D) materials provide significant opportunities for the development of transparent and flexible electronics. Recently, ambipolar 2D semiconductors have advanced innovative applications such as CMOS-like circuits, reconfigurable circuits, and ultrafast neuromorphic image sensors. Here, we report on the fabrication of full 2D ambipolar field-effect transistors (FETs), in which graphene serves as the source/drain/gate electrodes, WSe2 is for the channel, and h-BN is for the dielectric. The produced ambipolar FETs exhibit comparable on-currents in the n-branch and p-branch with on/off ratios up to 108. By using two ambipolar FETs in series, a CMOS-like inverter is demonstrated with a maximum gain of up to 147, which can work in both the first and third quadrants by controlling the supply voltages and input voltages. The full 2D ambipolar FETs yield a transmittance of over 70% for visible light on transparent glass and achieve a curvature radius of less than 0.5 cm for bending on polyethylene terephthalate (PET) substrate. The work is helpful for the application of ambipolar 2D materials-based devices in transparent and flexible electronics.
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The karst area has become a high-risk area for Cadmium (Cd) exposure. Interestingly, the high levels of Cd in soils do not result in an excessive bioaccumulation of Cd in rice. Carbonate rock dissolution ions (CRIs) could limit the accumulation and translocation of Cd in rice. CRIs can become a major bottleneck in the remediation and management of farmlands in karst areas. However, there is limited research on the effects of CRIs in soils on Cd accumulation in rice. The karst area of lime soil (LS) and the non-karst areas of yellow soil (YS) were collected, and an external Cd was added to conduct rice cultivation experiments. Cd and CRIs (Ca2+, Mg2+, CO32-/HCO3-, and OH-) in the rice-soil system were investigated from the grain-filling to maturity periods. The results showed that CRIs of LS were significantly higher than that of YS in different treatments. CRIs of LS were 2.05 mg·kg-1 for Ca2+, 0.90 mg·kg-1 for Mg2+, and 42.29 mg·kg-1 for CO32- in LS. CRIs could influence DTPA Cd, resulting in DTPA Cd of LS being lower than that of YS. DTPA Cd of YS was one to three times larger than that of YS. Cd content in different parts of rice in YS was higher than that of LS. Cd in rice grains of YS was one to six times larger than that of LS. The uptake of Cd from the soil during Filling III was critical in determining rice Cd accumulation. CRIs in the soil could affect Cd accumulation in rice. Ca2+ and Mg2+ had significant negative effects on Cd accumulation of rice at maturity and filling, respectively. CO32-/HCO3- and OH- had significant negative effects on DTPA Cd in soil.
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This study is centered around the dynamic behaviors observed in a class of fractional-order generalized reaction-diffusion inertial neural networks (FGRDINNs) with time delays. These networks are characterized by differential equations involving two distinct fractional derivatives of the state. The global uniform stability of FGRDINNs with time delays is explored utilizing Lyapunov comparison principles. Furthermore, global synchronization conditions for FGRDINNs with time delays are derived through the Lyapunov direct method, with consideration given to various feedback control strategies and parameter perturbations. The effectiveness of the theoretical findings is demonstrated through three numerical examples, and the impact of controller parameters on the error system is further investigated.
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Ewing sarcoma is a cancer of bone and soft tissue in children and young adults primarily driven by the EWS-FLI1 fusion oncoprotein, which has been undruggable. Here, we report that Ewing sarcoma depends on secreted sphingomyelin phosphodiesterase 1 (SMPD1), a ceramide-generating enzyme, and ceramide. We find that G-protein-coupled receptor 64 (GPR64)/adhesion G-protein-coupled receptor G2 (ADGRG2) responds to ceramide and mediates critical growth signaling in Ewing sarcoma. We show that ceramide induces the cleavage of the C-terminal intracellular domain of GPR64, which translocates to the nucleus and restrains the protein levels of RIF1 in a manner dependent on SPOP, a substrate adaptor of the Cullin3-RING E3 ubiquitin ligase. We demonstrate that both SMPD1 and GPR64 are transcriptional targets of EWS-FLI1, indicating that SMPD1 and GPR64 are EWS-FLI1-induced cytokine-receptor dependencies. These results reveal the SMPD1-ceramide-GPR64 pathway, which drives Ewing sarcoma growth and is amenable to therapeutic intervention.
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OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.
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Experiências Adversas da Infância , Dor , Humanos , Masculino , Feminino , China/epidemiologia , Estudos Longitudinais , Experiências Adversas da Infância/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Dor/epidemiologia , Exercício Físico , Fatores Socioeconômicos , Fatores de RiscoRESUMO
Objective: This study aimed to investigate the biomechanical characteristics of the tandem spinal external fixation (TSEF) for treating multilevel noncontiguous spinal fracture (MNSF) using finite element analysis and provide a theoretical basis for clinical application. Methods: We constructed two models of L2 and L4 vertebral fractures that were fixed with the TSEF and the long-segment spinal inner fixation (LSIF). The range of motion (ROM), maximum stresses at L2 and L4 vertebrae, the screws and rods, and the intervertebral discs of the two models were recorded under load control. Subsequently, the required torque, the maximum stress at L2 and L4 vertebrae, the screws and rods, and the intervertebral discs were analyzed under displacement control. Results: Under load control, the TSEF model reserved more ROM than the LSIF model. The maximum stresses of screws in the TSEF model were increased, while the maximum stresses of rods were reduced compared to the LSIF model. Moreover, the maximum stresses of L2 and L4 vertebrae and discs in the TSEF model were increased compared to the LSIF model. Under displacement control, the TSEF model required fewer moments (N·mm) than the LSIF model. Compared to the LSIF model, the maximum stresses of screws and rods in the TSEF model have decreased; the maximum stresses at L2 and L4 in the TSEF model were increased. In the flexion condition, the maximum stresses of discs in the TSEF model were less than the LSIF model, while the maximum stresses of discs in the TSEF model were higher in the extension condition. Conclusion: Compared to LSIF, the TSEF has a better stress distribution with higher overall mobility. Theoretically, it reduces the stress concentration of the connecting rods and the stress shielding of the fractured vertebral bodies.
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Pipelines are an important transportation form in industry. However, pipeline corrosion, particularly that occurring internally, poses a significant threat to safe operations. To detect the internal corrosion of a pipeline, a method utilizing piezoelectric sensors alongside singular spectrum analysis is proposed. Two piezoelectric patches are affixed to the exterior surface of the pipeline, serving the roles of an actuator and a sensor, respectively. During the detection, the signals excited by the actuator are transmitted through the pipeline's wall and are received by PZT2 through different paths, and the corresponding piezoelectric sensor captures the signals. Then, the response signals are denoised by singular spectrum analysis, and the first several wave packets in the response signals are selected to establish a feature for pipeline corrosion detection. At last, the envelope area of the selected packets is calculated as a feature to detect corrosion. To validate the proposed method, corrosion monitoring experiments are performed. The experimental results indicate that the envelope area of the first several wave packets from the response signals, following singular spectrum analysis, can serve as a feature to assess the degree of pipeline corrosion, and the index has a monotonic relationship with the corrosion depth of the pipeline. This method provides an effective way for pipeline corrosion monitoring.
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Optical encryption is receiving much attention with the rapid growth of information technology. Conventional optical encryption usually relies on specific configurations, such as metasurface-based holograms and structure colors, not meeting the requirements of increasing dynamic and programmable encryption. Here, we report a programmable optical encryption approach using WS2/SiO2/Au metal-oxide-semiconductor (MOS) devices, which is based on the electrical-field-controlled exciton-trion transitions in monolayer WS2. The modulation depth of the MOS device reflection amplitude up to 25% related to the excitons ensures the fidelity of information, and the decryption based on the near excitonic resonance assures security. With such devices, we successfully demonstrate their applications in real-time encryption of ASCII codes and visual images. For the latter, it can be implemented at the pixel level. The strategy shows significant potential for low-cost, low-energy-consumption, easily integrated, and high-security programmable optical encryptions.
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To explore the effect of Hei Xiaoyaosan on autophagy levels in Alzheimer's disease(AD). A total of 100 4-month-old Wistar male rats were randomly selected as a blank group, and 10 rats were taken as a sham operation group and injected with 1 µL of normal saline on both sides of the hippocampus. The other rats were injected with Aß_(1-42) solution in the hippocampus to replicate the AD model. Fifty successfully modeled rats were selected and randomly divided into the model group, Aricatio group(0.5 mg·kg~(-1)), and high, medium, and low dose groups of Hei Xiaoyaosan(15.30, 7.65, and 3.82 g·kg~(-1)), with 10 rats in each group. The rats were administered by continuous gavage for 42 days. Morris water maze was used to detect the learning and memory ability of rats, and Hoechst staining was used to observe the pathological changes of nerve cells in the hippocampal CA1 region. The mRNA expression of p38MAPK, Beclin-1, and Bcl-2 was detected by RT-qPCR.Western blot was used to detect the expressions of p38MAPK, Beclin-1, Bcl-2, APP, and related proteins. The level of Aß_(1-42) in the hippocampus was detected by ELISA, and the expression level of LC3â ¡ in the hippocampus was detected by immunohistochemistry. The experimental results showed that compared with the blank group, the learning and memory ability of rats in the model group decreased(P<0.01). The nuclei in the CA1 region of the hippocampus showed blue bright spots and were closely arranged. The mRNA expression of p38MAPK was up-regulated, and the mRNA expressions of Beclin-1 and Bcl-2 were down-regulated(P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were increased, while those of Beclin-1, Bcl-2, and p-Bcl-2 were decreased(P<0.01). The expression of Aß_(1-42) was increased(P<0.01). The relative expression of LC3â ¡ decreased(P<0.01). Compared with the model group, the learning and memory ability of rats in each administration group was improved(P<0.05 or P<0.01). The nuclei in the CA1 region of the hippocampus gradually became clear, showing light blue. The mRNA expression of p38MAPK was down-regulated(P<0.01), and that of Beclin-1 and Bcl-2 was increased(P<0.05 or P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were down-regulated, while those of Beclin-1, Bcl-2, and p-Bcl-2 were up-regulated(P<0.05 or P<0.01). The expression of Aß_(1-42) was decreased(P<0.01). The relative expression of LC3â ¡ was increased(P<0.01). It can be concluded that Hei Xiaoyaosan can improve the cognitive ability of AD model rats, and its potential mechanism may be related to regulating the p38MAPK/Beclin-1/Bcl-2 signaling pathway, increasing the level of autophagy, and reducing the accumulation of Aß_(1-42).
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Doença de Alzheimer , Autofagia , Proteína Beclina-1 , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Proteínas Proto-Oncogênicas c-bcl-2 , Ratos Wistar , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Masculino , Ratos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Autofagia/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteína Beclina-1/metabolismo , Proteína Beclina-1/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Humanos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To compare the range of endoscopic and microscopic exposure of the petroclival core area through the middle skull base and to observe the corresponding anatomical structures. METHODS: Ten intact adult cadaveric head specimens fixed with formaldehyde were craniotomized through an expanded middle skull base epidural approach on 20 sides. The distance from the greater superficial petrosal nerve to the petrous ridge was measured. When different degrees (1-3 degrees) of the Kawase triangle bone were removed, the exposed anatomical structure was observed, and the exposed core area of the rock slope was measured under an endoscope and microscope. RESULTS: The average distance from the greater superficial petrosal nerve to the petrous ridge was 14.26 mm. During 1 to 2 degrees of bone removal, the petrous segment of the internal carotid artery (ICA) was not exposed, whereas during 3 degrees of bone removal, the petrous segment of the ICA was exposed. At 1 degree of bone removal, 400.62 ± 15.73 mm2 of the area was exposed by endoscopy and 170.87 ± 8.93 mm2 by microscopy, and the abducens nerve was not exposed. However, there was a significant difference between the two areas (P < 0.001). During 2 degrees of bone removal, 689.30 ± 32.06 mm2 of the abducens nerve was exposed by endoscopy, but 366.84 ± 30.30 mm2 of the abducens nerve could not be exposed by microscopy; moreover, there was a significant difference in the area of exposure between the two (P < 0.001). At 3 degrees of bone removal, the endoscopic exposure area was 875.92 ± 31.87 mm2, the microscopic exposure area was 699.26 ± 48.00 mm2, and the abducens nerves were exposed. There were significant differences between the two areas (P < 0.001). However, the difference between the 2-degree endoscopic exposure area and the 3-degree microscopic exposure area was studied by using paired t tests, and there was no difference (P > 0.05). CONCLUSION: When the same degree of the Kawase triangle bone was removed, the extent of endoscopic exposure of the petroclival core area was significantly greater than the extent of microscopic exposure. At 2 degrees of bone removal, an endoscopic application can maximally expose the petroclival core area, thus reducing the probability of exposure damage to the ICA and abductor nerve.
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Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease lacking effective treatments without adverse effects. Dimethyloxallyl glycine (DMOG) enhanced mesenchymal stem cells (MSC) capabilities, but it remains unclear how DMOG-pretreatment of MSCs augments their SLE treatment. Here, we explore the therapeutic potential of DMOG-pretreated human umbilical cord MSCs (hUC-MSCs) in a mouse lupus nephritis (LN) model. In vitro experiments showed that DMOG could alleviate the mRNA levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-6 and increase the mRNA level of IL-13 in lipopolysaccharide (LPS)-induced inflammation in hUC-MSCs. DMOG enhanced the migratory and invasive abilities of the hUC-MSCs. In vivo animal studies revealed that DMOG-pretreated hUC-MSCs exhibited more pronounced inhibition of lymphadenectasis and reduced kidney weight and urinary protein content than MSCs alone. DMOG-pretreated hUC-MSCs improved renal morphological structure and alleviated inflammatory cell infiltration and renal fibrosis, evidenced by the reduced mRNA levels of fibrosis markers, including fibronectin (Fn), collagen alpha-1 chain (Colα1), collagen alpha-3 chain (Colα3), and TNF-α, IFN-γ, and IL-6 cytokines. Further investigation revealed that DMOG-pretreated hUC-MSCs down-regulated the expressions of transforming growth factor (Tgf)-ß1 and its downstream effectors Smad2 and Smad3, recognized as central mediators in renal fibrosis (P < 0.05). The findings suggest that DMOG-pretreated hUC-MSCs can augment the therapeutic efficacy of hUC-MSCs in LN by enhancing their anti-inflammatory and antifibrotic effects, and the TGF-ß/Smad signaling pathway may be involved in this process.
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Haematopoietic stem cells (HSCs) possess unique physiological adaptations to sustain blood cell production and cope with stress responses throughout life. To maintain these adaptations, HSCs rely on maintaining a tightly controlled protein translation rate. However, the mechanism of how HSCs regulate protein translation remains to be fully elucidated. In this study, we investigate the role of transfer RNA (tRNA) m1A58 'writer' proteins TRMT6 and TRMT61A in regulating HSCs function. Trmt6 deletion promoted HSC proliferation through aberrant activation of mTORC1 signaling. TRMT6-deficient HSCs exhibited an impaired self-renewal ability in competitive transplantation assay. Mechanistically, single cell RNA-seq analysis reveals that the mTORC1 signaling pathway is highly upregulated in HSC-enriched cell populations after Trmt6 deletion. m1A-tRNA-seq and Western blot analysis suggest that TRMT6 promotes methylation modification of specific tRNA and expression of TSC1, fine-tuning mTORC1 signaling levels. Furthermore, Pharmacological inhibition of the mTORC1 pathway rescued functional defect in TRMT6-deficient HSCs. To our knowledge, this study is the first to elucidate a mechanism by which TRMT6-TRMT61A complex-mediated tRNA-m1A58 modification regulates HSC homeostasis.
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Proliferação de Células , Células-Tronco Hematopoéticas , Alvo Mecanístico do Complexo 1 de Rapamicina , RNA de Transferência , Transdução de Sinais , Proteína 1 do Complexo Esclerose Tuberosa , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Animais , RNA de Transferência/metabolismo , RNA de Transferência/genética , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Camundongos , Proteína 1 do Complexo Esclerose Tuberosa/metabolismo , Proteína 1 do Complexo Esclerose Tuberosa/genética , Autorrenovação Celular/genética , Camundongos Knockout , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos Endogâmicos C57BL , MetilaçãoRESUMO
Gasoline compression ignition characterized by partially premixed and long ignition delays typically features complex flame structures such as deflagration or spontaneous ignition fronts. In this study, the flame structure and propagation characteristics of PRF90/air mixtures under compression ignition engine-relevant conditions are investigated numerically. Similar to other types of fuels, under such conditions, the propagation speed of PRF90 laminar premixed flames depends not only on the unburnt mixture properties but also on the residence time, and the transition of the flame regime depends only on the residence time. Nevertheless, due to the temperature-dependent autoignition chemistry of PRF90, flames with excessively high unburnt temperatures show different combustion behaviors after the transition from deflagration to autoignition-assisted flames. Sensitivity analysis showed that, the dominant chain branching reactions in the deflagration mode are H + O2 = OH + O and CO + OH = CO2 + H, and that in the autoignition-assisted flames with lower unburnt temperature are H2O2(+M) = 2OH(+M) and IC8H18 + HO2 = AC8H17 + H2O2, while for higher unburnt temperatures, the reactions C3H5 + HO2 = C2H3 + CH2O + OH and IC8H18 = IC4H9 + TC4H9 are more important than the fuel low-temperature oxidation reactions. In addition, a criterion based on chemical explosive mode analysis is used to analyze the local combustion mode. The results show that the difference in diffusion/chemical structure at the crossover progress variables C 0 and crossover temperature allows both C 0 and to be used as a flame location for distinguishing propagation modes in premixed flame. However, the effects of the equivalence ratio on C 0 are different from that on , which means that the selection of C 0 and may lead to different discriminant results for stratified mixtures. Comparing the applicability of C 0-based and -based locations in three-dimensional gasoline compression ignition flame, it is found that the flame location based on the value of C 0 at Ï = 1.0 can more completely reflect the flame development characteristics in stratified premixed combustion.
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Based on the disaster-pregnant environment and development characteristics of landslide disasters in the western region of Henan Province, a generalized model was established by taking the "oblique-cut" locking rock slope in the layered rock slope as the research object. The numerical simulation method was used to analyze the deformation and failure mechanism and stability influence law of the oblique-cut locking rock slope in western Henan under rainfall conditions. The results show that the inclination angle of the weak interlayer directly affects the deformation and failure characteristics of the slope rock mass. With the increase of the geometric parameters of the slope and the inclination angle of the weak interlayer, the failure mechanism is manifested as the slip shear failure along the level at the foot of the slope â the slip shear failure along the level at the foot of the slope (the sliding surface moves upward) â the shear failure in the middle of the slope surface â the slip shear failure along the level at the foot of the slope (the sliding surface moves downward) â the uplift shear failure at the lower edge of the rock layer. When the dip angle of the weak interlayer is constant, the slope stability decreases gradually with the increase in slope gradient and slope height, and the geometric factors of the slope control the overall change trend of the slope stability coefficient. When the slope is greater than 55° and the slope height is greater than 55 m, the shear stress of the slope locking section exceeds its shear strength, and the probability of landslide instability is greatly increased.
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BACKGROUND: Body weight has been recognized as a driving factor of osteoarthritis. Few studies had investigated the association between weight status across adulthood and risk of osteoarthritis (OA). This study investigates the association of weight change patterns across adulthood (lasting at least 25 years) with the risk of OA from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. METHODS: The study assessed the relationship between weight change across adulthood and OA in 7392 individuals aged > 50 spanning a minimum of 25 years. Multivariate linear regression analyses were utilized to detect the association between weight change patterns and self-reported OA. Restricted cubic splines (RCS) were used to examine the nonlinear relationship between absolute weight change and OA risk. RESULTS: From 10 years ago to survey, the risk of OA was 1.34-fold (95% CI 1.07-1.68) in people changed from obese to non-obese, 1.61-fold (95% CI 1.29-2.00) in people change from non-obese to obese, and 1.82-fold (95% CI 1.49-2.22) in stable obese people compared with people who were at stable normal weight. Similar patterns were also observed at age 25 years to baseline and age 25 years to 10 years before the baseline. The dose-response association of RCS found a U-shaped relationship between absolute weight change and OA risk. CONCLUSIONS: The study suggests that weight patterns across adulthood are associated with the risk of OA. These findings stressed important to maintain a normal weight throughout adulthood, especially to prevent ignored weight gain in early adulthood to reduce OA risk later.
Assuntos
Inquéritos Nutricionais , Obesidade , Osteoartrite , Humanos , Masculino , Osteoartrite/epidemiologia , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Obesidade/epidemiologia , Obesidade/complicações , Idoso , Aumento de Peso/fisiologia , Adulto , Peso CorporalRESUMO
Efficient separation of CH4 from N2 is essential for the purification of methane from nitrogen. In order to address this problem, composite materials consisting of rod-shaped SBA-15-based UiO-66-Br2 were synthesized for the purpose of separating a CH4/N2 mixture. The materials were characterized via PXRD, N2 adsorption-desorption, SEM, TEM, FT-IR, and TGA. The adsorption isotherms of CH4 and N2 under standard pressure conditions for the composites were determined and subsequently compared. The study revealed that the composites were formed through the growth of MOF nanocrystals on the surfaces of the SBA-15 matrix. The enhancements in surface area and adsorption capacity of hybrid materials were attributed to the structural modifications resulting from the interactions between surface silanol groups and metal centers. The selectivity of the composites towards a gas mixture of CH4 and N2 was assessed utilizing the Langmuir adsorption equation. The results of the analysis revealed that the U6B2S5/SBA-15 sample exhibited the greatest selectivity for CH4/N2 adsorption compared to the other samples, with an adsorption selectivity parameter (S) of 20.06. Additional research is necessary to enhance the enrichment of methane from CH4/N2 mixtures using SBA-15-based metal-organic framework materials.