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1.
PLoS Genet ; 19(4): e1010698, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37053298

RESUMEN

Rice axillary meristems (AMs) are essential to the formation of tillers and panicle branches in rice, and therefore play a determining role in rice yield. However, the regulation of inflorescence AM development in rice remains elusive. In this study, we identified no spikelet 1-Dominant (nsp1-D), a sparse spikelet mutant, with obvious reduction of panicle branches and spikelets. Inflorescence AM deficiency in nsp1-D could be ascribed to the overexpression of OsbHLH069. OsbHLH069 functions redundantly with OsbHLH067 and OsbHLH068 in panicle AM formation. The Osbhlh067 Osbhlh068 Osbhlh069 triple mutant had smaller panicles and fewer branches and spikelets. OsbHLH067, OsbHLH068, and OsbHLH069 were preferentially expressed in the developing inflorescence AMs and their proteins could physically interact with LAX1. Both nsp1-D and lax1 showed sparse panicles. Transcriptomic data indicated that OsbHLH067/068/069 may be involved in the metabolic pathway during panicle AM formation. Quantitative RT-PCR results demonstrated that the expression of genes involved in meristem development and starch/sucrose metabolism was down-regulated in the triple mutant. Collectively, our study demonstrates that OsbHLH067, OsbHLH068, and OsbHLH069 have redundant functions in regulating the formation of inflorescence AMs during panicle development in rice.


Asunto(s)
Oryza , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Oryza/genética , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Inflorescencia/genética , Inflorescencia/metabolismo , Meristema/genética , Meristema/metabolismo , Regulación de la Expresión Génica de las Plantas
2.
J Cell Mol Med ; 28(10): e18390, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38801402

RESUMEN

T cells are crucial for adaptive immunity to regulate proper immune response and immune homeostasis. T cell development occurs in the thymus and mainly differentiates into CD4+ and CD8+ T cell subsets. Upon stimulation, naive T cells differentiate into distinct CD4+ helper and CD8+ cytotoxic T cells, which mediate immunity homeostasis and defend against pathogens or tumours. Trace elements are minimal yet essential components of human body that cannot be overlooked, and they participate in enzyme activation, DNA synthesis, antioxidant defence, hormone production, etc. Moreover, trace elements are particularly involved in immune regulations. Here, we have summarized the roles of eight essential trace elements (iron, zinc, selenium, copper, iodine, chromium, molybdenum, cobalt) in T cell development, activation and differentiation, and immune response, which provides significant insights into developing novel approaches to modulate immunoregulation and immunotherapy.


Asunto(s)
Oligoelementos , Humanos , Oligoelementos/metabolismo , Animales , Linfocitos T/inmunología , Linfocitos T/metabolismo , Diferenciación Celular , Selenio/metabolismo , Activación de Linfocitos/inmunología
3.
J Cell Mol Med ; 28(10): e18363, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38770891

RESUMEN

The spleen is a vital organ for the immune system, while splenectomy may be necessary for various reasons. However, there is limited research on the impact of splenectomy on T cell function in peripheral lymph nodes as a compensatory mechanism in preventing infections. This study aimed to investigate the characteristics and function of CD8+ and CD4+ T cells in different peripheral lymph nodes during viral infection using a well-established splenectomy model. The results revealed that splenectomy caused an increase in CD8+GP33+ T cells in the mesenteric lymph nodes (MLN). Moreover, we demonstrated that splenectomy resulted in an increase of effector KLRG1+ T cells in the MLN. Additionally, the number of CD4+ cytotoxic T cells (CD4 CTLs) was also elevated in the peripheral lymph nodes of mice with splenectomy. Surprisingly, aged mice exhibited a stronger compensatory ability than adult mice, as evidenced by an increase in effector CD8+ T cells in all peripheral lymph nodes. These findings provide compelling evidence that T cells in MLN play a crucial role in protecting individuals with splenectomy against viral infections. The study offers new insights into understanding the changes in the immune system of individuals with splenectomy and highlights the potential compensatory mechanisms involved by T cells in peripheral lymph nodes.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Ganglios Linfáticos , Esplenectomía , Animales , Ganglios Linfáticos/inmunología , Ratones , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , Ratones Endogámicos C57BL , Bazo/inmunología
4.
Plant Mol Biol ; 114(1): 6, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38265739

RESUMEN

tRNA-derived small RNAs (tsRNAs), a new category of regulatory small non-coding RNA existing in almost all branches of life, have recently attracted broad attention. Increasing evidence has shown that tsRNAs are not random degradation debris of tRNAs, but products cleaved by specific endoribonucleases, with versatile functions in response to various developmental and environmental cues. However, it is still unclear about the diversity, biogenesis and function of tsRNAs in plants. In this study, we comprehensively profiled 10-60 nts small RNAs in Arabidopsis thaliana leaf with or without wounding stress and identified four 16 nts tiny tRFs (tRNA-derived fragments) sharply increased after wounding, namely tRF5'Ala. Notably, genetic, biochemical and bioinformatic data indicated that RNS2, a member of class II RNase T2 enzymes, was the main endoribonuclease responsible for the biogenesis of tRF5'Ala. Moreover, tRF5'Ala was highly abundant and conserved in Arabidopsis and rice pollen. However, tRF5'Ala did not associate with AGO 1 in vivo or display any inhibitory effect on the translation of a luciferase mRNA in vitro. Altogether, our study highlights the discovery of a novel class of tiny tsRNAs drastically increased under wounding stress as well as their generation by RNS2, which provides a new insight into tsRNAs research in plants.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Ribonucleasas , Biología Computacional , ARN , ARN de Transferencia , Proteínas de Arabidopsis/genética , Ribonucleasas/genética
5.
Small ; 20(8): e2306159, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37840442

RESUMEN

2D metal-organic frameworks (2D MOFs) with π conjugation have attracted widespread attention in the field of lithium storage due to their unique electron transfer units and structural characteristics. However, the periodic 2D planar extension structure hides some active sites, which is not conducive to the utilization of its structural advantages. In this work, a series of triptycene-based 2D conductive MOFs (M-DBH, M = Ni, Mn, and Co) with 3D extension structures are constructed by coordinating 9,10-dihydro-9,10-[1,2]benzenoanthracene-2,3,6,7,14,15-hexaol with metal ions to explore their potential applications in lithium-ion and lithium-sulfur batteries. This is the first study in which 2D conductive MOFs with the 3D extended molecule are used as electrode materials for lithium storage. The designed material generates rich active sites through staggered stacking layers and shows excellent performance in lithium-ion and lithium-sulfur batteries. The capacity retention rate of Ni-DBH can reach over 70% after 500 cycles at 0.2 C in lithium-ion batteries, while the capacity of S@Mn-DBH exceeds 305 mAh g-1 after 480 cycles at 0.5 C in lithium-sulfur batteries. Compared with the materials with 2D planar extended structures, the M-DBH electrodes with 3D extended structures in this work exhibit better performance in terms of cycle time and lithium storage capacity.

6.
Nurs Crit Care ; 29(5): 962-973, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38639246

RESUMEN

BACKGROUND: Pneumonia has a high incidence in traumatic brain injury (TBI) patients and lacks effective treatments. Early mobilization (EM) may be a potentially effective treatment. AIM: To explore the impact of EM on TBI-related pneumonia in the neurosurgical intensive care unit (NICU). STUDY DESIGN: This study was a historical control study. 100 TBI patients who received EM intervention were prospectively included as the experimental group (EM cohort), and 250 TBI patients were retrospectively included as the control group. The propensity score matching (PSM) method was employed to balance baseline and minimize potential bias. The relationship between EM and TBI-related pneumonia was investigated by univariate and multivariate logistic regression, then further determined by subgroup analysis. The influence of other variables was excluded by interaction analyses. Finally, the effect of EM on the prognosis of TBI patients was analysed by comparing the Glasgow Coma Scale (GCS) and the hospital stay. RESULTS: After screening, 86 patients were included in the EM cohort and 199 patients were included in the control cohort. There were obvious differences between the two cohorts at baseline, and these differences were eliminated after PSM, when the incidence of pneumonia was significantly lower in the EM cohort than in the control cohort (35.0% vs. 61.9%, p < .001). Multivariate logistic regression showed that EM was an independent risk factor for TBI-related pneumonia and was significantly associated with a decreased incidence of pneumonia. This correlation was present in most subgroups and was not affected by other variables (p for interaction >.05). Patients in the EM cohort had shorter length of ICU stay (6 vs. 7 days, p = .017) and higher GCS at discharge (12 vs. 11, p = .010). CONCLUSION: EM is a safe and effective treatment for TBI patients in NICU, which can reduce the incidence of pneumonia, help to improve prognosis and shorten the length of ICU stay. RELEVANCE TO CLINICAL PRACTICE: Although the utilization rate of EM is low in TBI patients for various reasons, EM is still an effective method to prevent complications. Our study confirms that a scientific and detailed EM strategy can effectively reduce the incidence of pneumonia while ensuring the safety of TBI patients, which is worthy of further research and clinical application.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Ambulación Precoz , Unidades de Cuidados Intensivos , Neumonía , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Neumonía/prevención & control , Adulto , Estudios Retrospectivos , Escala de Coma de Glasgow , Tiempo de Internación/estadística & datos numéricos , Puntaje de Propensión , Incidencia , Estudio Históricamente Controlado , Estudios Prospectivos
7.
Angew Chem Int Ed Engl ; 63(6): e202316319, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38095848

RESUMEN

Recently, hydrogen spillover based binary (HSBB) catalysts have received widespread attention due to the sufficiently utilized reaction sites. However, the specific regulation mechanism of spillover intensity is still unclear. Herein, we have fabricated oxygen vacancies enriched Ru/NiMoO4-x to investigate the internal relationship between electron supply and mechanism of hydrogen spillover enhancement. The DFT calculations cooperate with in situ Raman spectrum to uncover that the H* spillover from NiMoO4-x to Ru. Meanwhile, oxygen vacancies weakened the electron supply from Ru to NiMoO4-x , which contributes to dilute the resistance of built-in electric field (BEF) for hydrogen spillover. In addition, the higher ion concentration in electrolyte will promote the H* adsorption step obviously, which is demonstrated by in situ EIS tests. As a result, the Ru/NiMoO4-x exhibits a low overpotential of 206 mV at 3.0 A cm-2 , a small Tafel slope of 28.8 mV dec-1 , and an excellent durability of 550 h at the current density of 0.5 A cm-2 for HER in 1.0 M KOH seawater.

8.
Angew Chem Int Ed Engl ; : e202414721, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39392202

RESUMEN

The development of materials for hydrogen production via seawater electrolysis at high current densities plays a crucial role in producing renewable hydrogen energy. However, during the seawater electrolysis process, the anode inevitably undergoes chloride oxidation reaction (ClOR) due to Cl- adsorption, making the seawater electrolysis process difficult to sustain. Inspired by the selective permeability of cell membranes, we propose a biomimetic design of frustrated Lewis pairs (FLPs) layers. Combining experimental results and molecular dynamics simulations, it has been demonstrated that cerium dioxide layers with FLPs sites can decompose water molecules, capture hydroxyl anions, and repel chloride ions simultaneously. DFT theoretical analysis indicates that the FLP sites regulate the Ce 4f-O 2p-Ni 3d gradient orbital coupling, providing additional oxygen non-bonding (ONB) to stabilize the Ni-O bond and optimize the adsorption strength of intermediates, thereby breaking the *OH and *OOH scaling relationship. Assembled anion exchange membrane electrolyzers exhibit an efficiency of 95.7% at a current density of 0.1 A cm-2 and can stably operate for 250 hours at a current density of 0.2 A cm-2.

9.
Small ; : e2308613, 2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38072783

RESUMEN

Due to the shortage of pure water resources, seawater electrolysis is a promising strategy to produce green hydrogen energy. To avoid chlorine oxidation reactions (ClOR) and the production of more corrosive hypochlorite, enhancing OER electrocatalyst activity is the key to solving the above problem. Considering that transition metal phosphides (TMPs) are promising OER eletrocatalysts for seawater splitting, a method to regulate the electronic structure of FeP by introducing Mn heteroatoms and phosphorus vacancy on it (Mn-FePV ) is developed. As an OER electrocatalyst in seawater solution, the synthesized Mn-FePV achieves extremely low overpotentials (η500  = 376, η1000  = 395 mV). In addition, the Pt/C||Mn-FePV couple only requires the voltage of 1.81 V to drive the current density of 1000 mA cm-2 for overall seawater splitting. The density functional theory (DFT) calculation shows that Mn-FePV (0.21 e- ) has more charge transfer number compared with FeP (0.17 e- ). In-situ Raman analysis shows that phosphorus vacancy and Mn doping can synergistically regulate the electronic structure of FeP to induce rapid phase reconstruction, further improving the OER performance of Mn-FePV . The new phase species of FeOOH is confirmed to can enhance the adsorption kinetics of OER intermediates.

10.
Am J Pathol ; 192(8): 1186-1198, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35640677

RESUMEN

This study reports that hairy and enhancer of split homolog-1 (HES1), known to repress gene transcription in progenitor cells of several cell lineages, was strongly expressed in cells and tissues of T-cell lymphoma expressing the oncogenic chimeric tyrosine kinase nucleophosmin (NPM)-anaplastic lymphoma kinase [ALK; ALK+ T-cell lymphoma (TCL)]. The structural analysis of the Orange domain of HES1 indicated that HES1 formed a highly stable homodimer. Of note, repression of HES1 expression led to inhibition of ALK+ TCL cell growth in vivo. The expression of the HES1 gene was induced by NPM-ALK through activation of STAT3, which bound to the gene's promoter and induced the gene's transcription. NPM-ALK also directly phosphorylated HES1 protein. In turn, HES1 up-regulated and down-regulated in ALK+ TCL cells, the expression of numerous genes, protein products of which are involved in key cell functions, such as cell proliferation and viability. Among the genes inhibited by HES1 was thioredoxin-interacting protein (TXNIP), encoding a protein implicated in promotion of cell death in various types of cells. Accordingly, ALK+ TCL cells and tissues lacked expression of TXNIP, and its transcription was co-inhibited by HES1 and STAT3 in an NPM-ALK-dependent manner. Finally, the induced expression of TXNIP induced massive apoptotic cell death of ALK+ TCL cells. The results reveal a novel NPM-ALK-controlled pro-oncogenic regulatory network and document an important role of HES and TXNIP in the NPM-ALK-driven oncogenesis, with the former protein displaying oncogenic and the latter tumor suppressor properties.


Asunto(s)
Quinasa de Linfoma Anaplásico , Proteínas Portadoras , Linfoma de Células T , Factor de Transcripción HES-1 , Quinasa de Linfoma Anaplásico/genética , Carcinogénesis/genética , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Humanos , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Linfoma de Células T/patología , Oncogenes , Fosforilación , Factor de Transcripción HES-1/genética , Factor de Transcripción HES-1/metabolismo
11.
Opt Lett ; 48(7): 1846-1849, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37221781

RESUMEN

In this Letter, we report a bridge-connected three-electrode germanium-on-silicon (Ge-on-Si) avalanche photodiode (APD) array compatible with the complementary metal-oxide semiconductor (CMOS) process. In addition to the two electrodes on the Si substrate, a third electrode is designed for Ge. A single three-electrode APD was tested and analyzed. By applying a positive voltage on the Ge electrode, the dark current of the device can be reduced, and yet the response of the device can be increased. Under a dark current of 100 nA, as the voltage on Ge increases from 0 V to 15 V, the light responsivity is increased from 0.6 A/W to 1.17 A/W. We report, for the first time to the best of our knowledge, the near-infrared imaging properties of an array of three-electrode Ge-on-Si APDs. Experiments show that the device can be used for LiDAR imaging and low-light detection.

12.
Cancer Cell Int ; 23(1): 244, 2023 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-37848941

RESUMEN

BACKGROUND: Primary hepatocellular carcinoma (HCC) is a malignancy with high morbidity and mortality. KH domain-containing, RNA-binding signal transduction-associated protein 3 (KHDRBS3) is an RNA-binding protein that is aberrantly expressed in multiple tumors; however, its expression and biological function in HCC have not been reported. METHODS: KHDRBS3 knockdown and overexpression were performed using the lentiviral vector system to investigate the effects of KHDRBS3 on cell proliferation, apoptosis, chemoresistance, and glycolysis. Murine xenograft tumor models were constructed to study the role of KHDRBS3 on tumor growth in vivo. Furthermore, RNA-Pull Down and RNA immunoprecipitation were utilized to explore the interaction between KHDRBS3 and 14-3-3ζ, a phosphopeptide-binding molecule encoded by YWHAZ. RESULTS: KHDRBS3 was highly expressed in human HCC tissues and predicted the poor prognosis of patients with HCC. Knockdown of KHDRBS3 exhibited a carcinostatic effect in HCC and impeded proliferation and tumor growth, reduced glycolysis, enhanced cell sensitivity to doxorubicin, and induced apoptosis. On the contrary, forced expression of KHDRBS3 expedited the malignant biological behaviors of HCC cells. The expression of KHDRBS3 was positively correlated with the expression of 14-3-3ζ. RNA immunoprecipitation and RNA pull-down assays demonstrated that KHDRBS3 bound to YWHAZ. We further confirmed that 14-3-3ζ silencing significantly reversed the promotion of proliferation and glycolysis and the inhibition of apoptosis caused by KHDRBS3 overexpression. CONCLUSIONS: Our findings suggest that KHDRBS3 promotes glycolysis and malignant progression of HCC through upregulating 14-3-3ζ expression, providing a possible target for HCC therapy.

13.
Chem Rec ; 23(12): e202300231, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37665225

RESUMEN

Geminal-difluoroalkanes featuring intriguing steric and electronic properties are of great significance in medicinal chemistry, and great progresses have been achieved for their synthesis. In recent years, iodine(III) reagent-mediated migratory gem-difluorination of alkenes has proved to be an efficient and powerful strategy to access to diverse gem-difluoroalkanes, especially those bearing a readily transformable functionality (TF), which are important for rapid assembly of complex gem-difluorinated molecules in a modular and diverse manner. In this review, we systematically summarize the recent development of iodine(III)-mediated migratory gem-difluorination reactions for the synthesis of gem-difluoroalkanes bearing a synthetically versatile TF at the ß position. The reaction mechanism and the utilities of the products are also discussed. This review is presented and grouped basically according to the types of transformable functionalities within the products.

14.
Clin Chem Lab Med ; 61(2): 251-259, 2023 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-36351699

RESUMEN

OBJECTIVES: This study aimed to establish time-resolved fluorescence immunoassays to quantitatively detect the autoantibodies targeting different epitopes of M-type phospholipase A2 receptor (PLA2R) and evaluate its clinical application in primary membranous nephropathy (PMN). METHODS: PLA2R and its reactive epitope-specific IgG/IgG4 time-resolved fluorescence immunoassays (TRFIAs) were established using europium-labeled anti-human IgG/IgG4 antibodies, recombinant proteins, and patient serum. The levels of IgG/IgG4 targeting PLA2R and its epitopes in PMN patient serum were detected, and the relationship between epitope spreading of PLA2R and the severity of patients with PMN was evaluated. RESULTS: The TRFIAs established in this study could quantitatively detect PLA2R and its epitope-specific IgG and IgG4. Sera from 59 patients with PMN were subjected to detection using anti-PLA2R IgG and anti-PLA2R IgG4. Among them, 46 and 54 patients were found positive for PLA2R antibodies, respectively. Moreover, the levels of PLA2R antibodies were strongly correlated with the severity of patients with PMN. Patients who were detected to have two or more epitopes had more serious renal injury. CONCLUSIONS: PLA2R domain-specific IgG/IgG4 TRFIAs were established in this study, and detection with anti-PLA2R IgG4 could more sensitively screen the reactivity of patients to the PLA2R domain. Moreover, detection epitope spreading of PLA2R was confirmed which is related to the severity of patients with PMN.


Asunto(s)
Glomerulonefritis Membranosa , Receptores de Fosfolipasa A2 , Humanos , Receptores de Fosfolipasa A2/metabolismo , Glomerulonefritis Membranosa/diagnóstico , Epítopos , Autoanticuerpos , Inmunoglobulina G
15.
Eur Arch Otorhinolaryngol ; 280(6): 2885-2896, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36695908

RESUMEN

PURPOSE: To developed a model to screen distant metastatic laryngeal carcinoma (DMLC) patients who would benefit from the primary tumor resection. METHODS: The propensity score matching (PSM) was utilized to avoid disproportionate distributions of the confounding factors. We hypothesized that patients who underwent surgery would benefit from surgery by having a longer median cancer-specific survival (CSS) than patients without surgery. Multivariable Cox model was used to explore the independent factors of CSS and overall survival (OS) among PSM population. We used these factors to construct a nomogram to identify surgery benefit patients. The predictive performance and clinical practicability of the nomogram were determined by area under the curve (AUC), calibration curve, and decision curve. RESULTS: The CSS and OS for patients who received primary tumor resection were significantly longer than those without resection (median CSS: 19 months vs. 10 months, P = 0.009; median OS: 21 months vs. 10 months, P = 0.001). The nomogram displayed a good degree of discrimination and calibration. The mean AUC of the nomogram was 0.70 (95% confidence interval [CI] 0.66-0.76) through threefold cross-validation. CONCLUSIONS: A predictive model was established and might be used to screen the optimal candidates for primary tumor surgery in DMLC patients.


Asunto(s)
Carcinoma , Neoplasias Laríngeas , Humanos , Neoplasias Laríngeas/cirugía , Área Bajo la Curva , Nomogramas , Puntaje de Propensión
16.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5278-5284, 2023 Oct.
Artículo en Zh | MEDLINE | ID: mdl-38114117

RESUMEN

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.


Asunto(s)
Neoplasias Pancreáticas , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/genética , Caspasa 3 , Proteína X Asociada a bcl-2 , Beclina-1/farmacología , Línea Celular Tumoral , Serina-Treonina Quinasas TOR/genética , Apoptosis , Neoplasias Pancreáticas/tratamiento farmacológico , Caspasas , Autofagia
17.
Appl Environ Microbiol ; 88(23): e0094022, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36374019

RESUMEN

Cre1 is an important transcription factor that regulates carbon catabolite repression (CCR) and is widely conserved across fungi. The cre1 gene has been extensively studied in several Ascomycota species, whereas its role in gene expression regulation in the Basidiomycota species remains poorly understood. Here, we identified and investigated the role of cre1 in Coprinopsis cinerea, a basidiomycete model mushroom that can efficiently degrade lignocellulosic plant wastes. We used a rapid and efficient gene deletion approach based on PCR-amplified split-marker DNA cassettes together with in vitro assembled Cas9-guide RNA ribonucleoproteins (Cas9 RNPs) to generate C. cinerea cre1 gene deletion strains. Gene expression profiling of two independent C. cinerea cre1 mutants showed significant deregulation of carbohydrate metabolism, plant cell wall degrading enzymes (PCWDEs), plasma membrane transporter-related and several transcription factor-encoding genes, among others. Our results support the notion that, like reports in the ascomycetes, Cre1 of C. cinerea orchestrates CCR through a combined regulation of diverse genes, including PCWDEs, transcription factors that positively regulate PCWDEs, and membrane transporters which could import simple sugars that can induce the expression of PWCDEs. Somewhat paradoxically, though in accordance with other Agaricomycetes, genes related to lignin degradation were mostly downregulated in cre1 mutants, indicating they fall under different regulation than other PCWDEs. The gene deletion approach and the data presented here will expand our knowledge of CCR in the Basidiomycota and provide functional hypotheses on genes related to plant biomass degradation. IMPORTANCE Mushroom-forming fungi include some of the most efficient lignocellulosic plant biomass degraders. They degrade dead plant materials by a battery of lignin-, cellulose-, hemicellulose-, and pectin-degrading enzymes, the encoding genes of which are under tight transcriptional control. One of the highest-level regulations of these metabolic enzymes is known as carbon catabolite repression, which is orchestrated by the transcription factor Cre1, and ensures that costly lignocellulose-degrading enzyme genes are expressed only when simple carbon sources (e.g., glucose) are not available. Here, we identified the Cre1 ortholog in a litter decomposer Agaricomycete, Coprinopsis cinerea, knocked it out, and characterized transcriptional changes in the mutants. We identified several dozen lignocellulolytic enzyme genes as well as membrane transporters and other transcription factors as putative target genes of C. cinerea cre1. These results extend knowledge on carbon catabolite repression to litter decomposer Basidiomycota.


Asunto(s)
Agaricales , Ascomicetos , Basidiomycota , Represión Catabólica , Lignina/metabolismo , Eliminación de Gen , Carbono/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Sistemas CRISPR-Cas , Agaricales/metabolismo , Basidiomycota/metabolismo , Ascomicetos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas de Transporte de Membrana/genética , Regulación Fúngica de la Expresión Génica
18.
Opt Express ; 30(4): 5008-5018, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35209472

RESUMEN

Silicon based optoelectronic integrated optical phased array is attractive owing to large-dense integration, large scanning range and CMOS compatibility. In this paper, we design and fabricate a SiN-on-SOI two-dimensional optical phased array chip. We demonstrate a two-dimensional scanning range of 96°×14.4° and 690 mW peak power of the main lobe. Additionally, we set up the time of flight (ToF) and frequency-modulated continuous-wave (FMCW) ranging systems by using this optical phased array chip, and achieve the objects detection at the range of 20 m in the ToF system and 109 m in the FMCW system, respectively.

19.
Eur Radiol ; 32(11): 7755-7766, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35608663

RESUMEN

OBJECTIVES: To establish and validate a CT radiomics model for prediction of induction chemotherapy (IC) response and progression-free survival (PFS) among patients with locally advanced hypopharyngeal carcinoma (LAHC). METHODS: One hundred twelve patients with LAHC (78 in training cohort and 34 in validation cohort) who underwent contrast-enhanced CT (CECT) scans prior to IC were enrolled. Least absolute shrinkage and selection operator (LASSO) was used to select the crucial radiomic features in the training cohort. Radiomics signature and clinical data were used to build a radiomics nomogram to predict individual response to IC. Kaplan-Meier analysis and log-rank test were used to evaluate ability of radiomics signature in progression-free survival risk stratification. RESULTS: The radiomics signature consisted of 6 selected features from the arterial and venous phases of CECT images and demonstrated good performance in predicting the IC response in both two cohorts. The radiomics nomogram showed good discriminative performance, and the C-index of nomogram was 0.899 (95% confidence interval (CI), 0.831-0.967) and 0.775 (95% CI, 0.591-0.959) in the training and validation cohorts, respectively. Survival analysis indicated that low-risk and high-risk groups defined by the value of radiomics signature had significant difference in PFS (3-year PFS 66.4% vs 29.7%, p < 0.001). CONCLUSIONS: Multiparametric CT-based radiomics model could be useful for predicting treatment response and PFS in patients with LAHC who underwent IC. KEY POINTS: • CT radiomics can predict IC response and progression-free survival in hypopharyngeal carcinoma. • We combined significant radiomics signature with clinical predictors to establish a nomogram to predict individual response to IC. • Radiomics signature could divide patients into the high-risk and low-risk groups based on the PFS.


Asunto(s)
Carcinoma , Quimioterapia de Inducción , Humanos , Quimioterapia de Inducción/métodos , Supervivencia sin Progresión , Pronóstico , Nomogramas , Tomografía Computarizada por Rayos X/métodos
20.
J Fluoresc ; 32(2): 629-636, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35025017

RESUMEN

The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum Galectin-3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated with Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85-1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P < 0.0001). In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu3+) chelates for the detection of Gal-3 concentrations in serum. Gal-3 concentration is elevated in patients with IMN.


Asunto(s)
Fluoroinmunoensayo/métodos , Galectina 3/sangre , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/diagnóstico , Anticuerpos/sangre , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Galectina 3/inmunología , Humanos , Estudios Prospectivos , Sensibilidad y Especificidad , Factores de Tiempo
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