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Multi-component composite materials with a magnetic-dielectric synergistic effect exhibit satisfactory electromagnetic wave absorption performance. However, the effective construction of the structure for these multi-component materials to fully exploit the advantages of each component remains a challenge. Inspired by natural biomass, this study utilizes wood as the raw material and successfully prepares high-performance MoS2@Gd2O3/Mxene loaded porous carbon aerogel (MGMCA) composite material through a one-pot hydrothermal method and carbonization treatment process. With a delicate structural design, the MGMCA is endowed with abundant heterogeneous interface structures, favorable impedance matching characteristics, and a magnetic-dielectric synergistic system, thus demonstrating multiple electromagnetic wave loss mechanisms. Benefiting from these advantages, the obtained MGMCA exhibits outstanding electromagnetic wave absorption performance, with a minimum reflection loss of -57.5 dB at an ultra-thin thickness of only 1.9 mm. This research proposes a reliable strategy for the design of multi-component composite materials, providing valuable insight for the design of biomass-based materials as electromagnetic wave absorbers.
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OBJECTIVES: To study the features of catheter-related bloodstream infection (CRBSI) or central line-associated bloodstream infection (CLABSI) after peripherally inserted central catheterization (PICC) in neonates admitted to the neonatal intensive care unit (NICU) and the risk factors for CRBSI or CLABSI. METHODS: A retrospective analysis was performed on the medical data of the neonates who were treated and required PICC in the NICU of the Children's Hospital, Zhejiang University School of Medicine from June 1, 2018 to May 1, 2020. The catheterization-related data were collected, including placement time, insertion site, removal time, and antimicrobial lock of PICC. The multivariate logistic regression model was used to investigate the risk factors for CRBSI or CLABSI in the neonates. RESULTS: A total of 446 neonates were enrolled, with a mean gestational age of (30.8±4.0) weeks, a mean birth weight of (1 580±810) g, a median age of 9 days, and a median duration of PICC of 18 days. The incidence rates of CLABSI and CRBSI were 5.6 and 1.46 per 1 000 catheter days, respectively. Common pathogens for CLABSI caused by PICC included Staphylococcus epidermidis (n=19) and Klebsiella pneumoniae (n=11), and those for CRBSI caused by PICC included Klebsiella pneumoniae (n=6). The risk of CLABSI caused by PICC increased significantly with prolonged durations of PICC and antibiotic use, and the PICC-related infection probability at head and neck was significantly lower than that in the upper and low limbs (P<0.05), while the above conditions were more obvious in neonates with a birth weight of <1 500 g. The risk of CRBSI caused by PICC decreased with the increase in gestational age (P<0.05). CONCLUSIONS: CRBSI and CLABSI remain serious issues in NICU nosocomial infection. The identification of the risk factors for CRBSI and CLABSI provides a basis for improving the quality of clinical care and management.
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Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Cateterismo Periférico , Catéteres Venosos Centrales , Sepsis , Infecciones Relacionadas con Catéteres/complicaciones , Infecciones Relacionadas con Catéteres/etiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Niño , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Factores de Riesgo , Sepsis/etiologíaRESUMEN
Glucocorticoids (GC) are used as the first-line treatment of immune thrombocytopenia (ITP), but 10-20% of patients are insensitive to them. Regulatory T cells (Tregs) can maintain immune tolerance in autoimmune diseases. The present research pooled 55 patients with newly diagnosed ITP and 44 healthy volunteers from seven hospitals. All patients received GC treatment and were divided into GC-sensitive and GC-insensitive groups according to the curative effect after 2 weeks of treatment. The levels of lymphocyte subgroups and Tregs were recorded. As the results indicated, the levels of CD8+ CD25str+ Tregs in the GC-sensitive group were significantly higher than that of the GC-insensitive group (P = 0·005). The optimal critical value of CD8+ CD25str+ Tregs to distinguish GC sensitivity was 0·09%. With GC therapy the level of CD45RO+ /CD8+ CD25str+ Tregs (activated type) decreased after treatment (P = 0·02) and the level of CD45RO- /CD8+ CD25str+ Tregs (initial type) increased slightly (P = 0·11). There were no obvious changes in the level of CD4+ Tregs. These findings support that the level of CD8+ CD25str+ Tregs and its subgroups have a predictive value in judging the sensitivity to GC among patients with ITP. Trial registration: www.chictr.org.cn; ChiCTR-OON-17014165.
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Linfocitos T CD8-positivos/metabolismo , Glucocorticoides/administración & dosificación , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Linfocitos T Reguladores/metabolismo , Adulto , Femenino , Estudios de Seguimiento , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Acute myeloid leukemia (AML) is a highly heterogeneous disease featured by a clonal proliferation derived from primitive hematopoietic stem/progenitor cells. Circular RNAs (circRNAs) have been identified as crucial regulators in the progression of various cancers, including AML. However, the molecular mechanism of AML is still not definite. This study aimed to explore the influences of circ_0012152 on cell development in AML cells and the underlying regulatory mechanism. The expression of circ_0012152, microRNA-625-5p (miR-625-5p) and sex-determining region Y-related high mobility group box 12 (SOX12) was detected by quantitative real-time polymerase chain reaction. The proliferation of AML cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for cell viability, 5-ethynyl-2'-deoxyuridine incorporation assay for DNA biosynthesis and flow cytometry for cell cycle distribution, respectively. The death of AML cells was detected by flow cytometry. The protein expression was assessed by Western blot assay. Dual-luciferase reporter and RNA immunoprecipitation assays were carried out to examine the relationships among circ_0012152, miR-625-5p and SOX12. The expression of circ_0012152 was increased in AML tissues and cells and circ_0012152 knockdown suppressed proliferation and promoted death in AML cells. Further exploration revealed that circ_0012152 inhibited miR-625-5p expression and downregulation of miR-625-5p overturned the effects of circ_0012152 knockdown on proliferation and death in AML cells. Moreover, miR-625-5p targeted SOX12 and circ_0012152 facilitated the expression of SOX12 by relieving miR-625-5p-mediated inhibitory effect on SOX12 in AML cells. Circ_0012152 knockdown suppressed cell proliferation and promoted death by targeting SOX12 mediated by miR-625-5p in AML cells.
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Leucemia Mieloide Aguda/genética , MicroARNs/metabolismo , Apoptosis , Estudios de Casos y Controles , Proliferación Celular , Regulación hacia Abajo , Humanos , Persona de Mediana Edad , TransfecciónRESUMEN
In this study, the in vitro biotransformation of nobiletin by human intestinal microbiota, which is a bioactive polymethoxyflavone widely presented in Citrus plants, has been investigated via utilizing an anaerobic incubation protocol. The incubation samples were detected using high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. A background subtraction strategy incorporated in Microsoft Office was employed to eliminate the interferences in medium and feces. The parent and three metabolites sinensetin, 5-hydroxy-6,7,3',4'-tetramethoxyflavone, and 5-demethylnobiletin were detected and identified based on the characteristics of their protonated molecules. The proposed metabolic pathway revealed that nobiletin went through phase I metabolism including demethylation and demethoxylation in human intestinal microbiota. The characterization of nobiletin metabolic profile transformed by human intestinal bacteria would be helpful for understanding its efficacy and action mechanism.
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Bacterias/metabolismo , Flavonas/química , Flavonas/metabolismo , Microbioma Gastrointestinal , Biotransformación , Cromatografía Líquida de Alta Presión/métodos , Citrus/metabolismo , Heces/química , Heces/microbiología , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Espectrometría de Masas/métodosRESUMEN
Zinc (Zn) is an essential trace element that modulate innate and acquired immune responses, and its deficiency triggers lymphopenia. However, the precise mechanisms underlying zinc-mediated lymphocyte maintenance have not been well clarified. Here, we have successfully generated a zip6-null mutant zebrafish line using TALENs. The Zip6-null mutant zebrafish developed normally during gastrulation. Loss of zip6 in zebrafish resulted in significant T lymphocyte reduction and a decrease in intracellular Zn levels. And the zip6 deficiency increases caspase-related cell apoptosis in both zebrafish cells and human T cells. Our results suggest that ZIP6 plays a critical part in T cell development, and enhance our understanding of Zn homeostasis and immune system maintenance.
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Proteínas de Transporte de Catión/genética , Eliminación de Gen , Linfocitos T/metabolismo , Proteínas de Pez Cebra/genética , Pez Cebra/genética , Zinc/metabolismo , Animales , Apoptosis , Proteínas de Transporte de Catión/metabolismo , Células Cultivadas , Regulación del Desarrollo de la Expresión Génica , Homeostasis , Linfocitos T/citología , Pez Cebra/embriología , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismoRESUMEN
PAX5 mutations have important role in leukemogenesis and leukemia relapse, cancer cell dormancy participates in cancer relapse, but there was no report about PAX5 mutation inducing cancer cell dormancy. we constructed the PAX5 deletion Raji cell lines using gene editing technology, evaluated dormancy biological characteristics of cell lines. Our results showed PAX5 haploinsufficiency restrained the proliferation of Raji cells, induced G0/G1 arrest of Raji cells, reduced chemotherapy sensitivity. The tumor formation rate reduced in PAX5 mutation Raji cells. Our results showed PAX5 insufficiency induced cancer cell dormancy in Raji cell.
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Linfoma de Burkitt/genética , Ciclo Celular/genética , Haploinsuficiencia/genética , Factor de Transcripción PAX5/genética , Línea Celular Tumoral , Proliferación Celular/genética , Edición Génica , Humanos , Masculino , RecurrenciaRESUMEN
BACKGROUND/AIMS: Bortezomib (BTZ) is largely used as a chemotherapeutic agent for the treatment of multiple myeloma. However, one of the significant limiting complications of BTZ is painful peripheral neuropathy during BTZ therapy. The purpose of this study was to examine the underlying mechanisms leading to neuropathic pain induced by BTZ. METHODS: ELISA and western blot analysis were used to examine the levels of tumor necrosis factor alpha (TNF-α) and its receptor, transient receptor potential ankyrin 1 (TRPA1) and intracellular p38-MAPK and JNK signal in the lumbar dorsal root ganglion. Behavioral test was performed to determine mechanical pain and cold sensitivity in a rat model. RESULTS: Systemic injection of BTZ significantly increased mechanical pain and cold sensitivity as compared with control animals (P< 0.05 vs. control rats). Our data also showed that protein expression of TRPA1 was upregulated in the dorsal root ganglion of BTZ rats and blocking TRPA1 attenuated mechanical pain and cold sensitivity in control rats and BTZ rats (P< 0.05 vs. vehicle control). Notably, the inhibitory effect of blocking TRPA1 on mechanical pain and cold sensitivity was smaller in BTZ rats than that in control rats. In addition, a blockade of TNF-α attenuated intracellular p38-MAPK and JNK signal in the dorsal root ganglion. This also decreased TRPA1 expression and alleviated mechanical hyperalgesia and cold hypersensitivity in BTZ rats. CONCLUSION: We revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ. The data also suggest that blocking TRPA1 and tumor necrosis factor alpha is beneficial to alleviate neuropathic pain during BTZ intervention.
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Antineoplásicos/efectos adversos , Bortezomib/efectos adversos , Neuralgia/inducido químicamente , Transducción de Señal/efectos de los fármacos , Canal Catiónico TRPA1/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Síndromes Periódicos Asociados a Criopirina/inducido químicamente , Síndromes Periódicos Asociados a Criopirina/tratamiento farmacológico , Síndromes Periódicos Asociados a Criopirina/metabolismo , Femenino , Humanos , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Masculino , Mieloma Múltiple/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Ratas Wistar , Canal Catiónico TRPA1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
We report the surface cladding-like waveguide fabricated by the cooperation of the ultrafast laser writing and the ion irradiation. The ultrafast laser writes tracks near the surface of the Nd:YAG crystal, constructing a semi-circle columnar structure with a decreased refractive index of - 0.00208. Then, the Nd:YAG crystal is irradiated by the Carbon ion beam, forming an enhanced-well in the semi-circle columnar with an increased refractive index of + 0.0024. Tracks and the enhanced-well consisted a surface cladding-like waveguide. Utilizing this cladding-like waveguide as the gain medium for the waveguide lasing, optimized characterizations were observed compared with the monolayer waveguide. This work demonstrates the refractive index of the Nd:YAG crystal can be well tailored by the cooperation of the ultrafast laser writing and the ion irradiation, which provides an convenient way to fabricate the complex and multilayered photonics devices.
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Ardisiae Japonicae Herba is a well-known traditional Chinese medicine for the treatment of bronchitis conjunctivitis, pneumonia, and trauma. In this work, a high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was first established for the separation and structural identification of the chemical constituents in Ardisiae Japonicae Herba. A total of 15 compounds including coumarins, flavonoid glycosides, and catechins were identified or tentatively characterized based on their chromatographic behaviors and mass spectral fragmentation and by comparisons with the reference standards. Furthermore, a simple high-performance liquid chromatography with diode array detection method was developed for the simultaneous determination of five major constituents. Results obtained from method validation, including linearity, precision, repeatability, stability, and recovery, showed that the established method was reliable and accurate. Bergenin and quercitrin were found to be the most abundant constituents and could be served as chemical markers for quality control of Ardisiae Japonicae Herba.
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Ardisia/química , Catequina/aislamiento & purificación , Cumarinas/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Flavonoides/aislamiento & purificación , Glicósidos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Espectrometría de Masas , Medicina Tradicional ChinaRESUMEN
We report on the fabrication of ridge waveguides in KTiOPO4 nonlinear optical crystals through carbon ion irradiation followed by precise diamond blade dicing. The diced side-walls have low roughness, which allows for low propagation loss of ~1dB/cm in fabricated of ridges. The waveguide property investigation has been performed at 1064 nm as well as 532 nm, showing good guidance at both TE and TM polarizations. Based on type II phase matching configuration, efficient second harmonic generation of green light at room temperature has been realized. High conversion efficiencies of ~1.12%W-1 and ~12.4% have been obtained for frequency doubling under the pump of continuous-wave (CW) and pulsed fundamental waves at 1064 nm, respectively.
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Due to the existence of the aerosol, the traditional method of measuring atmospheric temperature by using Rayleigh scattering technique has limitations in the low altitude. A pure rotational Raman lidar to get tropospheric temperature profiles is built. We carried out the atmospheric temperature observation in Beijing for two months. The atmospheric temperature profile was retrieved using the observed rotational Raman scattering signals. The effect of smooth window, calibration range and calibration constant on the retrieval precision of the atmospheric temperature was evaluated and analyzed. The results show that with the increase of smooth window, the mean absolute deviation between the lidar and radiosonde firstly decreases and then increases; in order to remove effectively the effect of random error in the return signals, while maintaining the fine vertical structure of temperature profile, it is better to choose the range between 600 and 1 200 m for smooth window. When calibration range is different, the mean absolute deviation between the lidar and radiosonde is varied, the relative variation of the deviation is about 0.07 K. When both calibration constant a and b increase or decrease, the mean deviation between the lidar and radiosonde increases; when one increases and another decreases, the mean deviation has a tendency to cancel each other out. The variance probability of a or b is not equal, and the variance of a and b is always contrary in the sign; the mean deviation is not sensitive to variance of a or b, and it is sensitive to the whole variance of a and b, about 91.7% of the mean deviation is in the range between -3 and 3 K. These results provide the theoretical basis for the selection of smooth window and calibration range in pure rotational Raman lidar data retrieval, and the reference for the error of actual temperature inversion result caused by lidar calibration constant.
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Recombinant adeno-associated virus (rAAV) vectors encoding human factor VIII (hFVIII) were systematically evaluated for hemophilia A (HA) gene therapy. A 5.7-kb rAAV-expression cassette (rAAV-HLP-codop-hFVIII-N6) containing a codon-optimized hFVIII cDNA in which a 226 amino acid (aa) B-domain spacer replaced the entire B domain and a hybrid liver-specific promoter (HLP) mediated 10-fold higher hFVIII levels in mice compared with non-codon-optimized variants. A further twofold improvement in potency was achieved by replacing the 226-aa N6 spacer with a novel 17-aa peptide (V3) in which 6 glycosylation triplets from the B domain were juxtaposed. The resulting 5.2-kb rAAV-HLP-codop-hFVIII-V3 cassette was more efficiently packaged within AAV virions and mediated supraphysiologic hFVIII expression (732 ± 162% of normal) in HA knock-out mice following administration of 2 × 10(12) vector genomes/kg, a vector dose shown to be safe in subjects with hemophilia B. Stable hFVIII expression at 15 ± 4% of normal was observed at this dose in a nonhuman primate. hFVIII expression above 100% was observed in 3 macaques that received a higher dose of either this vector or the N6 variant. These animals developed neutralizing anti-FVIII antibodies that were abrogated with transient immunosuppression. Therefore, rAAV-HLP-codop-hFVIII-V3 substantially improves the prospects of effective HA gene therapy.
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Dependovirus/genética , Factor VIII/farmacología , Terapia Genética , Variación Genética/genética , Vectores Genéticos/administración & dosificación , Hemofilia A/terapia , Animales , Western Blotting , Factor VIII/genética , Factor VIII/inmunología , Glicosilación , Hemofilia A/genética , Humanos , Tolerancia Inmunológica , Hígado/metabolismo , Macaca mulatta , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Regiones Promotoras Genéticas/genéticaRESUMEN
We report on a cladding-like waveguide structure in Nd:YAG crystal fabricated by the multiple carbon ion beam irradiation. After the designed multiple irradiation process, the cladding-like waveguide with triple refractive-index layers were constructed in the region near the surface of the crystal. With such a structure, the waveguiding core was compressed and refractive index profile was modified, resulting in a higher light intensity than that of the single ion-beam-irradiated monolayer waveguide. The waveguide lasing at wavelength of 1064 nm was achieved with enhanced performance in the cladding-like structures with both planar and ridge configurations by the optical pump at 810 nm.
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We report on an optical amplifier based on a Nd:YAG channel waveguide, which was fabricated by proton beam writing. Under the pumping of a continuous wave laser, the high-gain optical amplifications at single wavelength of 1064 nm and wavelength band of 1300 nm -1360 nm were obtained. The maximum gain was 24 dB/cm at 1064 nm and 6 dB/cm at 1319 nm, respectively. This work paves a way to apply proton beam written Nd:YAG waveguides as integrated optical amplifiers for the efficient amplification.
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Why are linear (E)-enones such challenging substrates in the Rh-catalyzed asymmetric arylation with boronic acids, which is one of the most important asymmetric catalysis methods? DFT computations show that these substrates adopt a specific conformation in which the largest substituent is antiperiplanar to Rh(I) π-complexed with the C = C bond within the enantioselectivity-determining carborhodation transition state. Additionally, for such structures, there is a strong, but not exclusive, preference for s-cis enone conformation. This folding minimizes steric interactions between the substrate and the ligand, and hence reduces the enantioselectivity. This idea is further confirmed by investigating three computation-only substrate "probes", one of which is capable of double asymmetric induction, and a recent computationally designed 1,5-diene ligand. On average, excellent agreement between predicted and experimental enantioselectivity was attained by a three-pronged approach: 1)â thorough conformational search within ligand and substrate subunits to locate the most preferred carborhodation transition state; 2)â including dispersion interaction and long-range corrections by SMD/ωB97xD/DGDZVP level of theory; and 3)â full substrate and ligand modeling. Based on the results, a theory-enhanced enantioselectivity model that is applicable to both chiral diene and diphosphane ligands is proposed.
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Ácidos Borónicos/química , Rodio/química , Catálisis , Modelos Moleculares , Conformación Molecular , Estructura Molecular , EstereoisomerismoRESUMEN
Fetal alcohol spectrum disorder (FASD) can cause severe mental retardation in children who are prenatally exposed to ethanol. The effects of prenatal and early postnatal ethanol exposure on adult hippocampal neurogenesis have been investigated; however, the effects of prenatal ethanol exposure on the subventricular zone (SVZ) have not. Gypenosides (GPs) have been reported to have neuroprotective effects in addition to other bioactivities. The effects of GPs on neural stem cells (NSCs) in the FASD model are unknown. Here, we test the effect of prenatal ethanol exposure on the neonatal SVZ, and the protection potential of GPs on NSCs in FASD rats. Our results show that prenatal ethanol exposure can suppress the cell proliferation and differentiation of neural stem cells in the neonatal SVZ and that GPs (400 mg/kg/day) can significantly increase the cell proliferation and differentiation of neural stem cells inhibited by ethanol. Our data indicate that GPs have neuroprotective effects on the NSCs and can enhance the neurogenesis inhibited by ethanol within the SVZ of neonatal rats. These findings provide new evidence for a potential therapy involving GPs for the treatment of FASD.
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Etanol/toxicidad , Ventrículos Laterales/patología , Células-Madre Neurales/patología , Fármacos Neuroprotectores/farmacología , Efectos Tardíos de la Exposición Prenatal/patología , Animales , Animales Recién Nacidos , Recuento de Células , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Citoprotección/efectos de los fármacos , Proteínas de Dominio Doblecortina , Embrión de Mamíferos/efectos de los fármacos , Embrión de Mamíferos/patología , Etanol/sangre , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Gynostemma , Proteínas Asociadas a Microtúbulos/metabolismo , Nestina/metabolismo , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Neuropéptidos/metabolismo , Extractos Vegetales/farmacología , Embarazo , Ratas WistarRESUMEN
Background: The prognostic significance of the ratio of activated CD4 T cells to Tregs infiltrating tumor tissues in gastric cancer (GC) remains unknown. Materials and methods: For the quantification of infiltration of immune cells, the ssGSEA algorithm, which is a single sample gene set enrichment analysis, was utilized. Group A was defined as having activated CD4 T cells/Tregs >1, while group B was defined as having activated CD4 T cells/Tregs <1. To compare the overall survival (OS) of the two groups, the Kaplan-Meier survival analysis was employed. The R package 'limma' was used to identify the immune and metabolism related genes that were expressed differentially between the two groups, with a false discovery rate (FDR) less than 0.05. The risk score (RS) was constructed by combining univariate Cox regression analysis, LASSO penalized Cox regression analysis, and multivariate Cox regression analysis. The median RS was used to classify high-risk (HR) and low-risk (LR) groups. Results: A predicted unfavorable outcome of GC was observed when the ratio of activated CD4 T cells to Tregs was less than 1. Our proposed RS was utilized for prognostic risk categorization in ten distinct independent cohorts (TCGA-STAD, n = 371; GSE84437, n = 433; GSE26253, n = 432; GSE13861, n = 65; GSE15459, n = 192; GSE26899, n = 93; GSE26901, n = 109; GSE28541, n = 40; GSE34942, n = 56; GSE62254, n = 300) and exhibited exceptional precision. In terms of tumor microenvironment (TME) and treatment strategies, compared to the LR group, the HR group was characterized by a higher infiltration levels of stromal cells, Tregs, macrophages, Tfh, mast cells, and NK cells, inclined to activated CD4 T cells/Tregs <1, and exhibited insensitivity to immunotherapy and multiple chemotherapy drugs. In relation to the potential molecular mechanism, the excessive activation of oncogenic pathways such as MAPK, hedgehog, WNT, calcium, and TGF-ß signaling pathways may accelerate the malignant progression of GC by stimulating angiogenesis, promoting EMT, and altering ECM. Conversely, the overactivation of the P53 pathway is likely to inhibit tumor proliferation by regulating the cell cycle. Conclusion: The immune-metabolism signature associated with the ratio of activated CD4 T cells and Tregs could be used to assess prognosis, TME, and treatment strategies in GC patients.
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Spinal cord injury (SCI) can cause a range of functional impairments, and patients with SCI have limited potential for functional recovery. Previous studies have demonstrated that autophagy plays a role in the pathological process of SCI, but the specific mechanism of autophagy in this context remains unclear. Therefore, we explored the role of autophagy in SCI by identifying key autophagy-related genes and pathways. This study utilized the GSE132242 expression profile dataset, which consists of four control samples and four SCI samples; autophagy-related genes were sourced from GeneCards. R software was used to screen differentially expressed genes (DEGs) in the GSE132242 dataset, which were then intersected with autophagy-related genes to identify autophagy-related DEGs in SCI. Subsequently, the expression levels of these genes were confirmed and analyzed with gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) analysis was conducted to identify interaction genes, and the resulting network was visualized with Cytoscape. The MCODE plug-in was used to build gene cluster modules, and the cytoHubba plug-in was applied to screen for hub genes. Finally, the GSE5296 dataset was used to verify the reliability of the hub genes. We screened 129 autophagy-related DEGs, including 126 up-regulated and 3 down-regulated genes. GO and KEGG pathway enrichment analysis showed that these 129 genes were mainly involved in the process of cell apoptosis, angiogenesis, IL-1 production, and inflammatory reactions, the TNF signaling pathway and the p53 signaling pathway. PPI identified 10 hub genes, including CCL2, TGFB1, PTGS2, FN1, HGF, MYC, IGF1, CD44, CXCR4, and SERPINEL1. The GSE5296 dataset revealed that the control group exhibited lower expression levels than the SCI group, although only CD44 and TGFB1 showed significant differences. This study identified 129 autophagy-related genes that might play a role in SCI. CD44 and TGFB1 were identified as potentially important genes in the autophagy process after SCI. These findings provide new targets for future research and offer new perspectives on the pathogenesis of SCI.
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Perfilación de la Expresión Génica , Traumatismos de la Médula Espinal , Humanos , Perfilación de la Expresión Génica/métodos , Mapas de Interacción de Proteínas/genética , Reproducibilidad de los Resultados , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/metabolismo , Autofagia/genética , Biología Computacional/métodosRESUMEN
Methods: Herein, we obtained and characterized deltaN p63- and adenosine triphosphate-binding cassette subfamily G member 2-expressing limbal stem cells (LSCs). Chitosan and carboxymethyl chitosan (CTH) were cross-linked to be an in situ thermosensitive hydrogel (ACH), which was printed through four-dimensional (4D) printing to obtain a porous carrier with uniform pore diameter (4D-CTH). Rabbits were injected with alloxan to induce diabetes mellitus (DM). Following this, the LSC-carrying hydrogel was spread on the surface of the cornea of the diabetic rabbits to cure corneal epithelium injury. Results: Compared with the control group (LSCs only), rapid wound healing was observed in rabbits treated with LSC-carrying 4D-CTH. Furthermore, the test group also showed better corneal nerve repair ability. The results indicated the potential of LSC-carrying 4D-CTH in curing corneal epithelium injury. Conclusion: 4D-CTH holds potential as a useful tool for studying regenerative processes occurring during the treatment of various diabetic corneal epithelium pathologies with the use of stem cell-based technologies.