RESUMEN
In great contrast to the numerous discoveries of superconductivity in layer-stacked graphene systems, the absence of superconductivity in the simplest monolayer graphene remains quite puzzling. Here, through realistic computation of the electronic structure, we identify a systematic trend that superconductivity emerges only upon alteration of the low-energy electronic lattice from the underlying honeycomb atomic structure. We then demonstrate that this inhibition can result from geometric frustration of the bond lattice that disables the quantum phase coherence of the order parameter residing on it. In comparison, upon deviation from the honeycomb lattice, relief of geometric frustration allows robust superfluidity with nontrivial spatial structures. For the specific examples of bilayer and trilayer graphene under an external electric field, such a bond-centered order parameter would develop superfluidity with staggered flux that breaks the time-reversal symmetry. Our study also suggests the possible realization of the long-sought superconductivity in single-layer graphene via the application of unidirectional strain.
RESUMEN
Hyperexcitability of neuronal networks is central to the pathogenesis of Alzheimer's disease (AD). Pharmacological activation of Kv7 channels is an effective way to reduce neuronal firing. Our results showed that that pharmacologically activating the Kv7 channel with Retigabine (RTG) can alleviate cognitive impairment in mice without affecting spontaneous activity. RTG could also ameliorate damage to the Nissl bodies in cortex and hippocampal CA and DG regions in 9-month-old APP/PS1 mice. Additionally, RTG could reduce the Aß plaque number in the hippocampus and cortex of both 6-month-old and 9-month-old mice. By recordings of electroencephalogram, we showed that a decrease in the number of abnormal discharges in the brains of the AD model mice when the Kv7 channel was opened. Moreover, Western blot analysis revealed a reduction in the expression of the p-Tau protein in both the hippocampus and cortex upon Kv7 channel opening. These findings suggest that Kv7 channel opener RTG may ameliorate cognitive impairment in AD, most likely by reducing brain excitability.
Asunto(s)
Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Carbamatos , Disfunción Cognitiva , Modelos Animales de Enfermedad , Hipocampo , Ratones Transgénicos , Fenilendiaminas , Animales , Fenilendiaminas/farmacología , Carbamatos/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Ratones , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Presenilina-1/genética , Masculino , Placa Amiloide/tratamiento farmacológico , Placa Amiloide/patología , Placa Amiloide/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Proteínas tau/metabolismo , Conducta Animal/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Objective: We performed this pooled analysis for the first time to comprehensively explore the prognostic value of tumor-associated high endothelial venules (TA-HEVs) and determine their relationships with clinicopathological features in solid tumors. Methods: Four online databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched to identify studies assessing the effect of TA-HEVs on prognosis or clinicopathological features. Hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate survival outcomes, including overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and cancer-specific survival (CSS). The association between TA-HEV status and clinicopathological characteristics was assessed by odds ratios (ORs) combined with 95% CIs. Subgroup analysis was conducted to explore sources of heterogeneity. The sensitivity analysis was performed to evaluate the stability of our findings. Meanwhile, Funnel plots were employed to visually evaluate potential publication bias, and both Begg's and Egger's tests were adopted to quantitatively determine publication bias. Results: A total of 13 retrospective cohort studies, involving 1,933 patients were finally included in this meta-analysis. Effect-size pooling analysis showed that the positivity of TA-HEVs was related to improved OS (pooled HR: 0.75, 95% CI: 0.62-0.93, P<0.01), and DFS (pooled HR = 0.54, 95% CI = 0.41-0.72, P< 0.01). However, TA-HEV positivity in solid tumors was not linked to PFS (pooled HR = 0.75, 95% CI 0.34-1.64, P = 0.47) or CSS (pooled HR: 0.58, 95% CI: 0.04-7.58, P= 0.68). Further subgroup analysis demonstrated that ethnicity and source of HR were the main factors contributing to heterogeneity. Moreover, TA-HEVs were inversely associated with lymph node metastasis and distant metastasis, but were positively related to worse tumor differentiation. However, TA-HEVs were not significantly correlated with sex, LVI, clinical stage, and depth of invasion. Sensitivity analysis suggested that the pooled results were stable and reliable, with no significant publication bias in all included articles. Conclusions: This is the first comprehensive analysis of the prognostic value of TA-HEVs in solid tumors using existing literature. Overall, our study demonstrated a significant correlation between TA-HEVs and prognosis as well as clinicopathological features. TA-HEVs may serve as novel immune-related biomarkers for clinical assessments and prognosis prediction in solid tumors. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php, identifier CRD42023394998.
Asunto(s)
Neoplasias , Humanos , Neoplasias/patología , Neoplasias/mortalidad , Vénulas/patología , Pronóstico , Microambiente Tumoral , Biomarcadores de TumorRESUMEN
As an important source of green cleaning flame retardants, bio-based materials have been widely studied by researchers. However, the development of efficient biobased flame retardants and convenient finishing methods was of great significance for the functional finishing of materials. Herein, a convenient and efficient flame retardant cotton fabric was prepared via layer by layer self-assembly (LbL) by alternating precipitation of a novel bio-based flame retardant phosphorylated sodium alginate (PSA) and alkylammonium functionalized siloxane (A-POSS). The effect of coating number on flame retardancy and thermal properties of coated cotton fabric was systematically studied. Thermogravimetric analysis (TGA) results showed that residual char contents of AP/PS-15BL under air and N2 atmospheres increased by 252.0% and 225.2%, respectively, compared with control cotton. In vertical flammability tests, both the AP/PS-10BL and AP/PS-15BL showed self-extinguishing behavior and successfully passed the UL-94 V-0 rating. More importantly, the LOI value of AP/PS-15BL was significantly increased to 35.0% from 20.0% of pure cotton fabric. Additionally, coated samples showed good mechanical properties and washable resistance. In CONE test, the peak heat release rate (PHRR) and total heat release rate (THR) of AP/PS-15BL decreased by 89.3% and 49.3% respectively, compared with control cotton. Therefore, this green and convenient flame-retardant finishing method has great application potential in the multi-functional finishing of cotton fabrics.
Asunto(s)
Alginatos , Fibra de Algodón , Retardadores de Llama , Alginatos/química , Fosforilación , Compuestos de Organosilicio/química , Textiles , Termogravimetría , Compuestos de Amonio Cuaternario/químicaRESUMEN
Background: Mobile phone addiction has adverse influences on the physical and mental health of college students. However, few studies shed light on the effect of fear of missing out on mobile phone addiction and the underlying mechanisms among college students. Methods: To explore their associations, the present study used the Fear of Missing Out Scales (FoMOS), Loneliness Scale (USL-8), Mobile Phone Addiction Index Scale (MPAI), and Depression-Anxiety-Stress Questionnaire (DASS-21) to investigate 750 college students. Results: The results suggested that fear of missing out significantly positively predicted mobile phone addiction. This direct effect could be mediated by depression, and the indirect effect of fear of missing out on mobile phone addiction could be moderated by loneliness. Specifically, the indirect effect was stronger for students with high levels of loneliness. Conclusion: This study provides a theoretical basis for developing future interventions for mobile phone addiction in higher education students.
Asunto(s)
Depresión , Soledad , Humanos , Miedo , Estudiantes , Adicción a la TecnologíaRESUMEN
Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme. In vivo and in vitro validations demonstrate that truncating just 6 key residues in GATA3 disrupts phase separation, enhancing tumor cell migration and inhibiting growth. Glycine and its motifs are enriched in spacer and key residues, as revealed by our comprehensive analysis. PSPHunter identifies nearly 80% of disease-associated phase-separating proteins, with frequent mutated pathological residues like glycine and proline often residing in these key residues. PSPHunter thus emerges as a crucial tool to uncover key residues, facilitating insights into phase separation mechanisms governing transcriptional control, cell fate transitions, and disease development.
Asunto(s)
Aprendizaje Automático , Proteínas , GlicinaRESUMEN
BACKGROUND: Depressive disorder is a severe global public health problem. It is crucial to evaluate the global incidence trends of depressive disorder. METHODS: The incidence data were drawn from the Global Burden of Disease Study (GBD) 2019. Estimates were presented by global and sociodemographic index (SDI) quintiles, and the age-period-cohort (APC) model was used to estimate the incidence trends. RESULTS: APC analysis indicated a decline in depressive disorder incidence globally (net drift = -0.24%, 95%CI: -0.29, -0.18), except for an increase in SDI regions (net drift = 0.07, 95%CI:0, 0.14). In high SDI regions, depressive disorder incidence increased among the younger and declined among the elder population, whereas the opposite trend was observed in middle and low-middle SDI regions. The depressive disorder incidence increased significantly among people aged 15 to 24 years after adjusting for age effects, decreased since 2000 after adjusting for period effects and increased rapidly in the birth cohort after 1990 in high SDI by adjusting for cohort effects. CONCLUSION: Globally, there was a declining trend of depressive disorder incidence in 1990-2019. Specifically, the incidence was declining globally in younger populations, while increasing in older populations. However, this trend differed depending on the SDI of the region.
Asunto(s)
Trastorno Depresivo , Carga Global de Enfermedades , Humanos , Anciano , Incidencia , Factores Socioeconómicos , Estudios de Cohortes , Trastorno Depresivo/epidemiología , Años de Vida Ajustados por Calidad de VidaRESUMEN
Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds' physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds' mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay for cytokine secretion levels.In vitroosteogenic capacity was determined through alkaline phosphatase and alizarin red staining. Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds' immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells, exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization.
Asunto(s)
Osteogénesis , Andamios del Tejido , Porosidad , Andamios del Tejido/química , Ingeniería de Tejidos/métodos , Regeneración Ósea , Diferenciación Celular , Macrófagos/metabolismo , Impresión TridimensionalRESUMEN
Increased acid phosphatase (APase) activity is a prominent feature of tomato (Solanum lycopersicum) responses to inorganic phosphate (Pi) restriction. SlPHL1, a phosphate starvation response (PHR) transcription factor, has been identified as a positive regulator of low Pi (LP)-induced APase activity in tomato. However, the molecular mechanism underlying this regulation remains to be elucidated. Here, SlPHL1 was found to positively regulate the LP-induced expression of five potential purple acid phosphatase (PAP) genes, namely SlPAP7, SlPAP10b, SlPAP12, SlPAP15, and SlPAP17b. Furthermore, we provide evidence that SlPHL1 can stimulate transcription of these five genes by binding directly to the PHR1 binding sequence (P1BS) located on their promoters. The P1BS mutation notably weakened SlPHL1 binding to the promoters of SlPAP7, SlPAP12, and SlPAP17b but almost completely abolished SlPHL1 binding to the promoters of SlPAP10b and SlPAP15. As a result, the transcriptional activation of SlPHL1 on SlPAP10b and SlPAP15 was substantially diminished. In addition, not only did transient overexpression of either SlPAP10b or SlPAP15 in tobacco leaves increase APase activity, but overexpression of SlPAP15 in Arabidopsis and tomato also increased APase activity and promoted plant growth. Subsequently, two SPX proteins, SlSPX1 and SlSPX4, were shown to physically interact with SlPHL1. Moreover, SlSPX1 inhibited the transcriptional activation of SlPHL1 on SlPAP10b and SlPAP15 and negatively regulated the activity of APase. Taken together, these results demonstrate that SlPHL1-mediated LP signaling promotes APase activity by activating the transcription of SlPAP10b and SlPAP15, which may provide valuable insights into the mechanisms of tomato response to Pi-limited stress.
Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Solanum lycopersicum , Fosfatos , Solanum lycopersicum/genética , Factores de Transcripción/metabolismo , Arabidopsis/metabolismo , Fosfatasa Ácida/genética , Fosfatasa Ácida/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Arabidopsis/metabolismoRESUMEN
Due to its invaluable potential in discrete mechanical energy collection, TENG (triboelectric nanogenerator) is considered to satisfy the power requirements of intelligent electronic devices and drive the development of the Internet of Things (IoT). Nowadays, the promotion of TENGs has been hindered due to the limitation of their output performance and service life. Herein, a brand new triboelectric nanogenerator based on a multi-material stacking structure is proposed. By stacking various triboelectric materials in a specific order, a special charge balance state could be achieved inside the system such that the conductive layer generates more induced charges, and the output performance is significantly enhanced. Besides, due to the usage of the electropositive elastomer PU (polyurethane sponge), the design also effectively alleviates abrasion on the contact surface and adjusts its own output according to different compression environments. The experimental results show that the stacked PTFE/FKM/PU TENG (PFP-TENG) presents a more than 50% increase in transferred charge and almost 5 times the current output compared with the general contact-separation type TENG. When connected to the application circuit, the maximum output power reached 10.2 W m-2 and 145.2 W m-3, and more than 1400 LEDs could be easily lit. Finally, the PFP-TENG was also used to collect mechanical energy from simple motion and realize considerable power generation. This study not only provides new ideas for the design of TENGs by reasoning the theoretical model but also presents improved output performance, thus exemplifying the strong potential of this design in developing a power-generation device that can collect discrete mechanical energy.
RESUMEN
OBJECTIVES: Research indicates adverse childhood experiences (ACEs) were associated with subjective cognitive decline (SCD), with higher ACEs reported by sexual minoritized individuals (i.e. lesbian, gay, and bisexual; LGB). This study aimed to explore the relationships between ACEs and SCD based on sexual orientation in middle-aged and older adults. METHODS: The study included 76,592 participants from the 2019-2020 Behavioral Risk Factor Surveillance Survey (BRFSS). Multivariate logistic regressions analyzed ACEs status, score, and type associations with SCD. RESULTS: 2.18% of the participants identified as sexual minoritized individuals. More sexual minoritized individuals reported SCD compared to heterosexual individuals (10.70% for heterosexuals; 17.27% for sexual minoritized individuals). Positive association between SCD and ACEs status (OR = 2.18, 95%CI: 1.09-4.40) was identified among sexual minoritized individuals. CONCLUSIONS: The association between ACEs and SCD was strong in both heterosexual and sexual minoritized populations. Given the higher experience of ACEs among sexual minoritized adults, the subsequent frequency of SCD among these adults also may be higher. CLINICAL IMPLICATIONS: Sexual minoritized older adults may have a history of numerous ACEs, which could contribute to a greater burden of SCD. Clinicians and other stakeholders may wish to consider relationships between ACEs and SCD based on sexual orientation.
RESUMEN
BACKGROUND: It has been demonstrated that circularRNA (circRNAs) plays a critical role in various cancers. While the potential molecular mechanism of circRNAs in the progression of colorectal cancer (CRC) remains uncertain. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. RT-qPCR detected the expression of circ_0009092, miR-665, and NLK in CRC tissues and cells. Functions of circ_0009092 on tumor cell proliferation, migration, and invasion were investigated by a series of in vitro assays. The underlying mechanism of circ_0009092 was explored by bioinformatics analysis, RNA immunoprecipitation (RIP) and luciferase assays. A co-culture assay in vitro was performed to detect the affection of circ_0009092 on macrophage recruitment in the tumor microenvironment (TME). A xenograft mouse model was used to explore the effect of circ_0009092 on tumor growth. RESULTS: Circ_0009092 was downregulated in CRCand predicted a good prognosis. Overexpression of circ_0009092 reduced tumor cell EMT, proliferation, migration, and invasion in vitro and in vivo. Mechanistically, circ_0009092 elevated the NLK expression via sponging miR-665 and suppressed the Wnt/ß-catenin signaling pathway. EIF4EA3 induced circ_0009092 expression in CRC cells. In addition, NLK regulates phosphorylation and O-GlcNAcylation of STAT3 by binding to STAT3, thereby inhibiting CCL2 expression, in which it inhibits macrophage recruitment in the tumor microenvironment (TME). CONCLUSION: EIF4A3 suppressed circ_0009092 biogenesis, whichinhibits CRC progression by sponging miR-665 to downregulate NLK. Circ_0009092/miR-665/NLK suppressed tumor EMT, proliferation, migration, and invasion by acting on the Wnt/ß-catenin signaling pathway. NLK directly interacted with STAT3 and decreased the CCL2 expression, inhibiting the recruitment of tumor-associated macrophages (TAMs) in the TME. Our study provided novel insights into the roles of circ_0009092 as a novel promising prognostic and therapeutic target in CRC.
Asunto(s)
Neoplasias Colorrectales , MicroARNs , Humanos , Animales , Ratones , ARN Circular/genética , ARN Circular/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Microambiente Tumoral/genética , Línea Celular Tumoral , Neoplasias Colorrectales/patología , MicroARNs/genética , MicroARNs/metabolismo , Vía de Señalización Wnt , Proliferación Celular/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Factor 4A Eucariótico de Iniciación/metabolismo , ARN Helicasas DEAD-box/metabolismoRESUMEN
Leiomyosarcoma occurring in the bone as primary tumor localization is extremely scarce with limited cases described in the literature, accounting for less than 0.7% of all primary bone malignancies. Once distant metastasis occurs, patients have limited treatments and often a somber prognosis, which underscore the need for innovative and effective treatment approaches. The emerging evidence suggests that anti-angiogenic therapy could inhibit angiogenesis and normalize vascular permeability in the tumor microenvironment, which, in turn, would increase immune effector cell infiltration into tumors. Immunotherapy depends on the accumulation and activity of immune effector cells within the tumor microenvironment, and immune responses and vascular normalization seem to be reciprocally regulated. Immunotherapy combined with anti-angiogenic therapy has recently made great progress in the treatment of various types of tumors. However, the effectiveness of the combination treatment in metastatic leiomyosarcoma is undetermined. In this study, we presented a rare case of primary leiomyosarcoma of the bone located in the trochanteric region of the femur, accompanied by multiple distant metastases. After the failure of multi-line therapies including AI regiments as the adjuvant chemotherapy, anlotinib as the first-line therapy, GT regiment as the second-line therapy, and eribulin as the third-line therapy, the patient received combinational therapy with penpulimab plus lenvatinib. The best efficacy for this regimen was a partial response, with a progression-free survival of 8.4 months according to the iRECIST criteria. After a dissociated response was detected without severe toxicities, the patient received local radiotherapy and continued treatment on penpulimab plus lenvatinib and eventually achieved long-term survival benefits with a total of over 60 months of overall survival with good quality of life and ongoing treatment. As our previous retrospective study found that one-third of advanced STS patients could still achieve clinical benefits from rechallenge with multi-targeted tyrosine kinase inhibitors (TKIs), after the failure of previous TKI therapy, this case provided the potential clinical activity of immunotherapy combined with anti-angiogenic TKI rechallenge in metastatic leiomyosarcoma.
RESUMEN
This multicenter study aimed to investigate the relationship between varicella incidence and meteorological factors including mean temperature, relative humidity, sunshine duration, diurnal temperature difference, wind speed, and rainfall, as previous studies have produced varying results. Our study also sought to identify potential sources of heterogeneity. Data on reported daily varicella numbers and meteorological factors were collected for 14 cities in Yunnan Province from 2017 to 2021. A distribution-lagged nonlinear model was constructed to explore the relationship between meteorological conditions and varicella incidence in each included city. We then used multiple meta-regression to explore sources of heterogeneity using demographic economics indicators, air pollutants, and geographic location as potential modifiers. The cumulative hazard effect plot showed an inverted S-shape for the relationship between temperature and varicella, with the smallest RR (relative risk) (0.533, 95% CI: 0.401-0.708) at temperatures up to 27.2 °C. The maximum RR (1.171, 95% CI: 1.001-1.371) was obtained when the relative humidity was equal to 98.5%. The RR (1.164, 95% CI: 1.002-1.352) was greatest at a diurnal temperature range of 2 °C (1.164, 95% CI: 1.002-1.352) and least (0.913, 95% CI: 0.834-0.999) at a diurnal temperature range of 16.1 °C. The maximum RR (1.214, 95% CI: 1.089-1.354) was obtained at 0 h of sunshine, and the minimum RR (0.808, 95% CI: 0.675-0.968) was obtained at 12.4 h of sunshine. The RR (0.792, 95% CI: 0.633-0.992) was minimum at a wind velocity of 4.8 m/s. Residual heterogeneity ranged from 1 to 42.7%, with PM10 (particles with an aerodynamic diameter less than 10 µm), GDP (gross domestic product), and population density explaining some of this heterogeneity. The temperature has a dual effect on varicella incidence. Varicella cases are negatively correlated with diurnal temperature range, sunshine duration, and wind speed, and positively correlated with relative humidity. GDP and PM10 may have a significant role in altering the association between temperature and varicella, while PM10 and population density may alter the association between wind velocity and varicella.
Asunto(s)
Varicela , Humanos , China/epidemiología , Conceptos Meteorológicos , Temperatura , IncidenciaRESUMEN
Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4+ T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to LAG3 promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4+ T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4+ T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.
Asunto(s)
Neoplasias de la Próstata , Linfocitos T , Masculino , Humanos , Linfocitos T/metabolismo , Transducción de Señal , Regulación hacia Arriba , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismoRESUMEN
For NiTi alloys prepared by the Laser Powder Bed Fusion (LPBF), changes in the building directions will directly change the preferred orientation and thus directly affect the smart properties, such as superelasticity, as well as change the distribution state of defects and impurity elements to affect the phase transformation behaviour, which in turn affects the smart properties at different temperatures. In this study, the relationship between impurity elements, the building directions, and functional properties; the effects of building directions on the crystallographic anisotropy; phase composition; superelastic properties; microhardness; geometrically necessary dislocation (GND) density; and impurity element content of NiTi SMAs fabricated by LPBF were systematically studied. Three building directions measured from the substrate, namely, 0°, 45° and 90°, were selected, and three sets of cylindrical samples were fabricated with the same process parameters. Along the building direction, a strong <100>//vertical direction (VD) texture was formed for all the samples. Because of the difference in transformation temperature, when tested at 15 °C, the sample with the 45° orientation possessed the highest strain recovery of 3.2%. When tested at the austenite phase transformation finish temperature (Af)+10 °C, the 90° sample had the highest strain recovery of 5.83% and a strain recovery rate of 83.3%. The sample with the 90° orientation presented the highest microhardness, which was attributed to its high dislocation density. Meanwhile, different building directions had an effect on the contents of O, C, and N impurity elements, which affected the transformation temperature by changing the Ni/Ti ratio. This study innovatively studied the impurity element content and GND densities of compressive samples with three building directions, providing theoretical guidance for LPBFed NiTi SMA structural parts.
RESUMEN
BACKGROUND: The prognosis of tumor patients can be assessed by measuring the levels of lncRNAs (long non-coding RNAs), which play a role in controlling the methylation of the RNA. Prognosis in individuals with colorectal adenocarcinoma (CRC) is strongly linked to lncRNA expression, making it imperative to find lncRNAs that are associated with RNA methylation with strong prognostic value. METHODS: In this study, by analyzing TCGA dataset, we were able to develop a risk model for lncRNAs that are associated with m5C with prognostic significance by employing LASSO regression and univariate Cox proportional analysis. There were a number of methods employed to ensure the model was accurate, including multivariate and univariate Cox regression analysis, Kaplan analysis, and receiver operating characteristic curve analysis. The principal component analysis, GSEA and GSVA analysis were used for risk model analysis. The CIBERSORT instrument and the TIMER database were used to evaluate the link between the immune cells that infiltrate tumors and the risk model. In vitro experiments were also performed to validate the predicted m5C-related significant lncRNAs. RESULTS: The m5c regulators were differentially expressed in colorectal cancer and normal tissue. Based on the screening criteria and LASSO regression, 11 m5c-related lncRNAs were identified for developing the prognostic risk model. Multivariate and univariate Cox regression analysis showed the risk score is a crucial prognostic factor in CRC patients. The 1-year, 3-year, and 5-year AUC curves showed the risk score was higher than those identified for other clinicopathological characteristics. A nomogram using the risk score as a quantitative tool was developed for predicting patients' outcomes in clinical settings. In addition, the risk profile of m5C-associated lncRNAs can discriminate between tumor immune cells' characteristics in CRC. Mutation patterns and chemotherapy were analyzed between high- and low- risk groups of CRC patients. Moreover, TNFRSF10A-AS1 was chosen for the in vitro verification of the m5C-connected lncRNA to demonstrate impressive effects on the proliferation, migration and invasion of CRC cells. CONCLUSION: A risk model including the prognostic value of 11 m5C-associated lncRNAs proves to be a useful prognostic tool for CRC and improves the care of patients suffering from CRC based on these findings.
RESUMEN
BACKGROUND: The treatment of brucellosis suffers from a high recurrence rate and drug resistance. Our study researched the differences in efficacy and side effects between triple antibiotics therapy and dual antibiotics therapy in the treatment of brucellosis through a systematic review and meta-analysis. METHODS: We searched 4 English electronic databases and 2 Chinese electronic databases for randomized controlled trials and cohort studies published through September 2022 on the use of triple antibiotics versus dual antibiotics in the treatment of brucellosis. Overall outcome indicators were therapeutic failure rate, relapse rate, overall therapeutic failure rate, and side effect rate. Relative risk (RR) and 95% confidence intervals (95% CIs) were used as summary statistics. A fixed-effects model was used to combine the overall effect sizes. RESULTS: The meta-analysis included 15 studies consisting of 11 randomized controlled trials and 4 cohort studies. Triple antibiotics showed better efficacy than dual antibiotics in a comparison of 3 overall outcome indicators (therapeutic failure rate (RR 0.42; 95% CI 0.30 to 0.59 heterogeneity P = 0.29, I2 = 15%), relapse rate (RR 0.29; 95% CI 0.18 to 0.45 heterogeneity P = 0.88, I2 = 0%), and overall therapeutic failure rate (RR 0.37; 95% CI 0.28 to 0.48 heterogeneity P = 0.35, I2 = 9%)). The incidence of side effects in patients with brucellosis treated with triple antibiotics was not significantly different from that in brucellosis patients treated with dual antibiotics (RR 0.85; 95% CI 0.67 to 1.06 heterogeneity P = 0.1, I2 = 35%). Sensitivity analyses showed robust results and Peter's test showed no publication bias. The results of subgroup analyses for the research type, drugs, and type of brucellosis were largely consistent with the overall outcome indicators, indicating the reliability and robustness of the overall results. CONCLUSIONS: In the treatment of brucellosis, triple antibiotics have better efficacy than dual antibiotics and do not increase the incidence of side effects.
Asunto(s)
Brucelosis , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Reproducibilidad de los Resultados , Antibacterianos/efectos adversos , Polimixina B , Brucelosis/tratamiento farmacológicoRESUMEN
Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.
Asunto(s)
Disfunción Cognitiva , Microbioma Gastrointestinal , Masculino , Femenino , Ratas , Animales , Eje Cerebro-Intestino , Enfermedades Neuroinflamatorias , Microbioma Gastrointestinal/fisiología , Ácidos Grasos Volátiles/metabolismo , Ácidos Grasos Volátiles/farmacología , HomeostasisRESUMEN
Indocyanine green (ICG) is an important kind of near infrared (NIR) photosensitive molecules for PTT/PDT therapy as well as imaging. When exposed to NIR light, ICG can produce reactive oxygen species (ROS), which can kill cancer cells and pathogenic bacteria. Moreover, the absorbed light can also be converted into heat by ICG molecules to eliminate cancer cells. In addition, it performs exceptionally well in optical imaging-guided tumor therapy and antimicrobial therapy due to its deeper tissue penetration and low photobleaching properties in the near-infrared region compared to other dyes. In order to solve the problems of water and optical stability and multi-function problem of ICG molecules, composite nanomaterials based on ICG have been designed and widely used, especially in the fields of tumors and sterilization. So far, ICG molecules and their composite materials have become one of the most famous infrared sensitive materials. However, there have been no corresponding review articles focused on ICG molecules. In this review, the molecular structure and properties of ICG, composite material design, and near-infrared light- triggered anti-tumor, and antibacterial, and clinical applications are reviewed in detail, which of great significance for related research.