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1.
Noncoding RNA Res ; 8(1): 75-82, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36380817

RESUMO

Introduction: Hemorrhagic fever with renal syndrome (HFRS), caused by Orthohantaviruses, occupies one of the leading places among natural focal human diseases, for which there are no modern accurate and highly sensitive diagnostic methods. To improve this situation, a better understanding of the Hantavirus pathogenesis of HFRS is required. Determination of the expression level of exosomal microRNAs (miRNAs) in the serum/plasma of patients makes them potential biomarkers for diagnosing and predicting HFRS. The purpose of this study was to analyze the expression level of miRNA-146a, miRNA-126, miRNA-218, miRNA-410, miRNA-503 and miRNA-155 in patients with HFRS at different stages (fever stage, polyuric stage and convalescence stage) and with different severity of the course this disease. Materials and methods: The moderate group of patients with HFRS included 105 patients, the severe group included 99 patients, and the severe group with complications included 84 patients. Blood samples from patients with HFRS for molecular genetic analysis were collected three times: during the initial febrile period (days 1-4 of illness), the polyuric period (days 15-22 of the disease), and during convalescence. Total RNA isolation was performed using the exoRNeasy Midi Kit (Qiagen, Germany). Quantitative real-time PCR (qRT-PCR) was performed using the miRCURY LNA SYBR Green PCR Kit (Qiagen, Germany) and the LightCycler96 real-time PCR product detection system (Roche, Switzerland). Results: When comparing the expression level of exosomal miRNAs in groups of patients with different severity of the disease, a statistically significant increase in the expression level of miRNA-146a was revealed in patients with severe HFRS with complications (Fold change 2.694; p = 0.0022) compared to the group with a moderate disease form, as well as an increase in miRNA-155 expression in patients with severe and severe HFRS with complications compared to the moderate form (Fold change 1.861; p = 0.0492; Fold change 1.976; p = 0.001, respectively). Comparative analysis of the expression level of other miRNAs in patients with HFRS at various stages and with different severity of HFRS did not reveal any statistically significant results (P > 0.05). Conclusions: MiRNA-155 and miRNA-146a may be promising prognostic biomarkers in HFRS. However, further investigations are needed to evaluate the changes in the expression of miRNAs and the network of genes that can be potential targets for the studied miRNAs in order to elucidate the molecular mechanisms that can influence the occurrence and development of HFRS.

2.
Sci Total Environ ; 855: 158934, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36152865

RESUMO

As a class of persistent organic pollutant, polybrominated diphenyl ethers (PBDEs) and their hydroxylated and methoxylated derivatives (OH-PBDEs and MeO-PBDEs) have been widely detected in soil environments. However, studies on the bioavailability and transformation of PBDEs and their derivatives in soil organisms remain scarce. In this study, a detailed kinetic investigation on the accumulation and biotransformations of BDE-47, 6-MeO-BDE-47 and 6-OH-BDE-47 in earthworms (Eisenia fetida) exposed to artificially contaminated soils was conducted. The uptake and elimination kinetics of BDE-47, 6-MeO-BDE-47 and 6-OH-BDE-47 by earthworms were in accordance with a one-compartment first-order kinetic model. The bioaccumulation factors (BAFs) followed the order 6-MeO-BDE-47 > 6-OH-BDE-47 > BDE-47. All three compounds could undergo step-by-step debromination to produce lower brominated analogs in earthworms. Both BDE-47 and 6-OH-BDE-47 could be transformed to MeO-PBDEs, whereas no transformation from 6-OH-BDE-47 or 6-MeO-BDE-47 to PBDEs or from BDE-47 and 6-MeO-BDE-47 to OH-PBDEs took place in the earthworms. Methoxylation was proposed as a potential metabolic pathway to form MeO-PBDEs in earthworms, with the metabolic rates for the methoxylation of BDE-47 and 6-OH-BDE-47 being 27.7 and 5.1 times greater, respectively, than that of the debromination metabolism. The isomers of 6-MeO-BDE-47 and 6-OH-BDE-47 were formed via the addition of methoxy/hydroxy groups or via bromine shifts on benzene ring in the earthworms. This study provides comprehensive information for a better understanding of the accumulation and biotransformation of PBDEs and their derivatives in earthworms.


Assuntos
Éteres Difenil Halogenados , Oligoquetos , Animais , Éteres Difenil Halogenados/análise , Oligoquetos/metabolismo , Éter , Hidroxilação , Biotransformação , Etil-Éteres , Solo
3.
Sensors (Basel) ; 22(21)2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36366231

RESUMO

This paper presented a new kind of salinity and temperature dual-parameter sensor based on a fiber ring laser (FRL) with tapered side-hole fiber (SHF) embedded in a Sagnac interferometer. The sensing structure is majorly composed of tapered SHF located in the middle of SHF inside the Sagnac interferometer loop structure. The influences of the SHF's diameters of different tapered in the Sagnac interferometer loop on the FRL sensing system are studied. The presence of air holes in the SHF makes the cladding mode easier to excite, and the interaction between the cladding mode with its surroundings is enhanced, thus having higher salinity sensitivity. Besides, the unique advantages of high resolution, narrower linewidth, and high signal-to-noise ratio (SNR) of fiber laser make the measurement results more accurate. In this experiment, the SHF with different taper diameters was made, and it was found that reducing the diameter of the taper waist diameter could further improve the salinity sensitivity. When the waist diameter was 9.70 µm, the maximum salinity sensitivity of 0.2867 nm/‱ was achieved. Temperature sensing experiments were also carried out. The maximum temperature sensitivity of the FRL sensing system was -0.3041 nm/°C at the temperature range from 20 to 30 °C. The sensor has the characteristics of easy manufacture, good selectivity, and high sensitivity, proving the feasibility of simultaneous measurement of seawater salinity and temperature.

4.
Biomaterials ; 291: 121908, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36384085

RESUMO

Uncontrolled hemorrhage caused by trauma to internal organs or major arteries poses critical threats to lives. However, rapid hemostasis followed by tissue repair remains an intractable challenge in surgery owing to the lack of ideal internal-use adhesives that can achieve fast and robust wet adhesion and accelerate wound healing. Herein, we develop a robust hemostatic bioadhesive (CAGA) from novel highly-branched aminoethyl gelatin with end-grafted abundant catechol (Gel-AE-Ca). The unique chemical structure of Gel-AE-Ca makes CAGA capable of gelling on wet tissues via synergetic cross-linking of catechol-Fe3+ chelation and horseradish peroxidase (HRP)/H2O2-triggered covalent bonds using a dual-channel needle, meeting the key demands of internal medical applications (e.g., instant and strong wet adhesion, injectability, biocompatibility, self-healing, stretching flexibility, infection resistance, and proper biodegradability). It exhibits rapid gelation within 10 s and robust wet tissue adhesion up to 115.0 ± 13.1 kPa of shear strength and 245.0 ± 33.8 mm Hg of sealing strength. In vivo trials demonstrate that CAGA can not only effectively seal anastomosis of the carotid artery, but achieve rapid hemostasis on the sites of liver incisions and penetrating cardiac wounds within 10 s. The wound closure by CAGA and its timely biodegradation promote wound healing of the vital organs.

5.
Clin Immunol ; 245: 109178, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36368642

RESUMO

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma.


Assuntos
Antígeno B7-H1 , Glioma , Humanos , Antígenos B7/genética , Antígenos B7/metabolismo , Proteômica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Glioma/genética , Microambiente Tumoral
6.
Mol Biomed ; 3(1): 35, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36418786

RESUMO

Since the first monoclonal antibody drug, muromonab-CD3, was approved for marketing in 1986, 165 antibody drugs have been approved or are under regulatory review worldwide. With the approval of new drugs for treating a wide range of diseases, including cancer and autoimmune and metabolic disorders, the therapeutic antibody drug market has experienced explosive growth. Monoclonal antibodies have been sought after by many biopharmaceutical companies and scientific research institutes due to their high specificity, strong targeting abilities, low toxicity, side effects, and high development success rate. The related industries and markets are growing rapidly, and therapeutic antibodies are one of the most important research and development areas in the field of biology and medicine. In recent years, great progress has been made in the key technologies and theoretical innovations provided by therapeutic antibodies, including antibody-drug conjugates, antibody-conjugated nuclides, bispecific antibodies, nanobodies, and other antibody analogs. Additionally, therapeutic antibodies can be combined with technologies used in other fields to create new cross-fields, such as chimeric antigen receptor T cells (CAR-T), CAR-natural killer cells (CAR-NK), and other cell therapy. This review summarizes the latest approved or in regulatory review therapeutic antibodies that have been approved or that are under regulatory review worldwide, as well as clinical research on these approaches and their development, and outlines antibody discovery strategies that have emerged during the development of therapeutic antibodies, such as hybridoma technology, phage display, preparation of fully human antibody from transgenic mice, single B-cell antibody technology, and artificial intelligence-assisted antibody discovery.

7.
Adv Mater ; : e2206793, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36267034

RESUMO

On-skin electronics that offer revolutionary capabilities in personalized diagnosis, therapeutics, and human-machine interfaces require seamless integration between the skin and electronics. A common question remains whether an ideal interface can be introduced to directly bridge thin-film electronics with the soft skin, allowing the skin to breathe freely and the skin-integrated electronics to function stably. Here, an ever-thinnest hydrogel is reported that is compliant to the glyphic lines and subtle minutiae on the skin without forming air gaps, produced by a facile cold-lamination method. The hydrogels exhibit high water-vapor permeability, allowing nearly unimpeded transepidermal water loss and free breathing of the skin underneath. Hydrogel-interfaced flexible (opto)electronics without causing skin irritation or accelerated device performance deterioration are demonstrated. The long-term applicability is recorded for over one week. With combined features of extreme mechanical compliance, high permeability, and biocompatibility, the ultrathin hydrogel interface promotes the general applicability of skin-integrated electronics.

8.
Front Microbiol ; 13: 999399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246223

RESUMO

Microbial decomposition plays a crucial role in the incorporation of straw and straw biochar (SSB) into soil. Lime concretion black soil (LCBS) is a typical low-medium crop yield soil, and it is also one of the main soil types for grain production in China. However, the link between SSB additions and soil bacterial communities in LCBS remains unclear. This study explored the effects of SSB incorporation on bacterial community composition, structure and co-occurrence network patterns at different soil depths and maize growth stages. The results showed that soil PH, soil organic matter and total nitrogen significantly affected the seasonality and stratification of the soil bacterial community. The composition and diversity of bacterial communities were significantly affected by growth period and treatment rather than soil depth. Specifically, the bacterial community diversity increased significantly with crop growth at 0-20 cm, decreased the relative abundance of Actinobacteria, and increased the relative abundance of Proteobacteria and Acidobacteria. SF (straw with fertilizer) and BF (straw biochar with fertilizer) treatments decreased bacterial community diversity. Co-occurrence networks are more complex in BF, S (straw), and SF treatments, and the number of edge network patterns is increased by 92.5, 40, and 60% at the maturity stage compared with F (fertilizer) treatment, respectively. Moreover, the positive effect of straw biochar on the bacterial network pattern increased with time, while the effect of straw weakened. Notably, we found that rare species inside keystone taxa (Gemmatimonadetes and Nitrospirae) play an indispensable role in maintaining bacterial network construction in LCBS. This study offers a comprehensive understanding of the response of soil bacterial communities to SSB addition in LCBS areas, and provides a reference for further improvement of LCBS productivity.

9.
Neurol Res ; : 1-8, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36215435

RESUMO

OBJECTIVES: Medulloblastoma is the most common malignant brain tumor in childhood. Although metastasis constitutes one of the poorest prognostic indicators in this disease, the mechanisms that drive metastasis have received less attention. The aim of our study is to provide valid biological information for the metastasis mechanism of medulloblastoma. METHODS: Gene expression profile of GSE468 was downloaded from GEO database and was analyzed using limma R package. Function and enrichment analyses of DEGs were performed based on PANTHER database. PPI network construction, hub gene selection and module analysis were conducted in Cytoscape software. RESULTS: Nine upregulated genes and 34 downregulated genes were selected as DEGs. The upregulated genes were mainly enriched in molecular function and cell component, which mainly included protein binding and nucleus respectively. A total of 120 enriched GO terms and 40 KEGG pathways were identified. The main enriched GO terms were the biological process such as apoptosis and MAPK activity. Besides, the enriched KEGG pathways also included MAPK signaling pathway. A PPI network was obtained, and JUN was identified as a hub gene. Also, we firstly investigated the role and regulatory mechanism of JUN in the metastasis of medulloblastoma. CONCLUSIONS: Through the bioinformatics analysis of the gene microarray in GEO, we found some crucial genes and pathways associated with the metastasis of medulloblastoma.

10.
J Ophthalmol ; 2022: 4922616, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237559

RESUMO

Objective: This meta-analysis was performed to evaluate the anatomical efficacy and functional improvement of the conventional inverted internal limiting membrane (ILM), flap covering technique, and ILM flap filling technique for patients with idiopathic macular hole (MH). Methods: Literature from Pubmed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were comprehensively retrieved. The primary outcomes included the MH closure rate and postoperative best-corrected visual acuity (BCVA). The secondary outcomes were the proportion of external limiting membrane (ELM) and ellipsoid zone (EZ) defect recovery. Pooled odds ratios (ORs), weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated using STATA 17.0 software. Results: 7 studies that contained 139 eyes in the inverted ILM flap covering group and 121 eyes in the ILM flap filling group were selected. Pooled data suggested that the surgical treatment resulted in an overall MH closure rate of up to 97.12% (135/139 eyes) in the inverted ILM flap covering group and 99.17% (120/121 eyes) in the filling group, with no significant difference between the 2 groups (OR = 1.98, 95% CI: 0.55 to 7.09, and P=0.29). Similarly, the 2 techniques demonstrated equal effectiveness on the anatomical closure in MH with the average diameter smaller than 650 µm (OR = 2.17, 95% CI: 0.48 to 9.77, and P=0.31) and larger than 650 µm (OR = 1.58, 95% CI: 0.14 to 17.37, and P=0.71). However, compared with the filling technique, the inverted ILM flap covering technique was superior in postoperative BCVA (WMD = 0.11, 95% CI: 0.04 to 0.18, and P=0.0017) and presented a significantly higher proportion of reconstitution of ELM (OR = 0.02, 95% CI: 0.00 to 0.08, and P < 0.0001) and EZ (OR = 0.11, 95% CI: 0.04 to 0.32, and P=0.0001). Conclusion: The inverted ILM flap covering technique was associated with the superior reconstitution of outer layers of the retina, including ELM and EZ, and more improvement in postoperative BCVA than the ILM flap filling technique.

11.
Org Lett ; 24(43): 8025-8030, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36282514

RESUMO

Conventional glycosylation with galactosyl donors having C-2 benzyl (Bn) ether-type functionality often leads to anomeric mixtures, due to the anomeric and steric effects that stabilize the 1,2-cis-α- and 1,2-trans-ß-glycosides, respectively. Herein we report a versatile ZnI2-directed ß-galactosylation approach employing a 4,6-O-tethered and 2-O-Bn galactosyl donor for the stereoselective and efficient synthesis of ß-O-galactosides. With a broad substrate scope, the reaction tolerates a wide range of functional groups and complex molecular architectures, providing stereocontrolled ß-galactosides in moderate to excellent yields. The practicality of this transformation is demonstrated through the synthesis of a tetrasaccharide arabinogalactan fragment with high stereoselectivity.


Assuntos
Éter , Glicosídeos , Glicosilação , Glicosídeos/química , Éteres , Etil-Éteres , Galactosídeos , Estereoisomerismo
12.
BMJ Open ; 12(10): e063781, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36302575

RESUMO

OBJECTIVE: With advances in mobile technology, smartphone-based point-of-care testing (POCT) urinalysis hold great potential for disease screening and health management for clinicians and individual users. The purpose of this study is to evaluate the analytical performance of Hipee S2 POCT urine dipstick analyser. DESIGN: A multicentre, hospital-based, cross-sectional study. SETTING: Analytical performance of the POCT analyser was conducted at a clinical laboratory, and method comparison was performed at three clinical laboratories in China. PARTICIPANTS: Urine samples were collected from 1603 outpatients and inpatients at three hospitals, and 5 health check-up population at one of the hospitals. OUTCOME MEASURES: All tests were performed by clinical laboratory technicians. Precision, drift, carry-over, interference and method comparison of Hipee S2 were evaluated. Diagnostic accuracy of semiquantitative albumin-to-creatinine ratio (ACR) for albuminuria was carried out using quantitative ACR as the standard. RESULTS: The precision for each parameter, assessed by control materials, was acceptable. No sample carry-over or drift was observed. Ascorbate solution with 1 g/L had an inhibitory effect for the haemoglobin test. Agreement for specific gravity (SG) varied between moderate to substantial (κ values 0.496-0.687), for pH was moderate (κ values 0.423-0.569) and for other parameters varied between substantial to excellent (κ values 0.669-0.991), on comparing the Hipee S2 with laboratory analysers. The semiquantitative microalbumin and creatinine were highly correlated with the quantitative results. The sensitivity of semiquantitative ACR to detect albuminuria was 87.2%-90.7%, specificity was 70.7%-78.4%, negative predictive value was 85.3%-87.9% and positive predictive value was 73.9%-83%. CONCLUSIONS: Hipee S2 POCT urine analyser showed acceptable analytical performance as a semiquantitative method. It serves as a convenient alternate device for clinicians and individual users for urinalysis and health management. In addition, the POCT semiquantitative ACR would be useful in screening for albuminuria.


Assuntos
Albuminúria , Urinálise , Humanos , Albuminúria/diagnóstico , Creatinina , Estudos Transversais , Urinálise/métodos , Testes Imediatos , Sistemas Automatizados de Assistência Junto ao Leito
13.
Sensors (Basel) ; 22(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36080934

RESUMO

Accidents occur frequently in urban gas pipelines, and pipeline damage detection is an important means of ensuring pipeline safety. Aiming at the problem that the small diameter pipeline is difficult to detect, this paper proposes a detection method for the inner wall damage of a small-diameter pipeline based on the TE01 mode microwave and uses the TE01 mode to detect the inner wall damage of the pipeline by the terminal short-circuit reflection method. By analyzing the transition of microwave propagation mode at the defect, based on the Maxwell equation and the field distribution equation of the TE01 mode microwave in the pipe and the pipe wall current equation, the microwave reflection coefficient at the defect is established when the microwave distortion modes at the defect are TE and TM modes. A small-diameter pipeline simulation model is established, and the influence of the electric field, magnetic field, wall current distribution, and reflected wave reflection coefficient in the pipeline when inner wall defects of different widths are analyzed using the finite integral theory during microwave detection of the TE01 mode. An experimental platform for the microwave detection of small-diameter pipes was built to detect defects on the inner walls of pipes with different widths. The results show that the inner wall defect causes the electric field, magnetic field, current propagation period, and energy distribution of the TE01 mode microwave propagated in the pipe to be distorted, and the microwave reflection coefficient and return loss exhibit a significant frequency shift with the change in the defect width. The experimental and simulation results had a good consistency.

14.
J Gastrointest Oncol ; 13(4): 1640-1655, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092333

RESUMO

Background: The onset and progression of many cancers, including gastric cancer (GC), are strongly influenced by cell senescence. Numerous studies have demonstrated that long non-coding RNA (lncRNA) impacts cell senescence, thus affecting cancer progression. However, it is not possible to develop a relevant predictive model for GC owing to the absence of a cell senescence-linked lncRNA. Since lncRNAs are linked to cellular senescence, the goal of this work was to create a prognostic signature for stomach adenocarcinoma (STAD) patients utilizing these lncRNAs. Methods: Through the Pearson correlation, variance, and univariate Cox regression analyses, the cellular senescence lncRNAs that were related to the disease prognosis could be successfully identified. Using the least absolute shrinkage and selection operator (LASSO) regression algorithm, a predictive model that utilized the 11 cellular senescence-linked lncRNAs was constructed. Kaplan-Meier (KM) survival and the receiver operating characteristic (ROC) curve analyses, were employed for assessing the prognostic performance of the proposed model. In addition, ESTIMATE analysis of the low- and high-risk subtypes for the infiltration of various immune cells was carried out. Additionally, the CIBERSORT algorithm was utilized for investigating the infiltration status of numerous immune cells in both groups, while the expression of the immune checkpoint genes in the two groups, was also determined. Results: In this study, a new prognostic model was constructed using 11 cellular senescence-related lncRNAs. The findings revealed that the OS status of the patients in the low-risk group (category) was significantly higher compared to the high-risk category (P<0.001). The 1-year ROC-area under the curve (AUC) values for the risk score in the training group was 0.714, while the AUC value for the test and comprehensive groups were recorded to be 0.666 and 0.695, respectively, which were obviously due to stage, grade, age, etc. And based on univariate [hazard ratio (HR): 1.435; P<0.001; 95% confidence interval (CI): 1.295-1.589] and multivariate analyses (P<0.001; 95% CI: HR: 1.387; 1.247-1.543), it was noted that risk scores were effectively employed as a patient-independent prognostic factor. Conclusions: Taken together, these results suggest that cellular senescence-related lncRNAs are likely to be valuable prognostic markers for GC. They also reflect the situation of the STAD immune microenvironment and may provide direction for future GC treatment.

15.
Mol Ther ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056553

RESUMO

Glioblastoma (GBM) is the most aggressive primary malignant brain cancer and urgently requires effective treatments. Chimeric antigen receptor T (CAR-T) cell therapy offers a potential treatment method, but it is often hindered by poor infiltration of CAR-T cells in tumors and highly immunosuppressive tumor microenvironment (TME). Here, we armed an oncolytic adenovirus (oAds) with a chemokine CXCL11 to increase the infiltration of CAR-T cells and reprogram the immunosuppressive TME, thus improving its therapeutic efficacy. In both immunodeficient and immunocompetent orthotopic GBM mice models, we showed that B7H3-targeted CAR-T cells alone failed to inhibit GBM growth but, when combined with the intratumoral administration of CXCL11-armed oAd, it achieved a durable antitumor response. Besides, oAd-CXCL11 had a potent antitumor effect and reprogramed the immunosuppressive TME in GL261 GBM models, in which increased infiltration of CD8+ T lymphocytes, natural killer (NK) cells, and M1-polarized macrophages, while decreased proportions of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and M2-polarized macrophages were observed. Furthermore, the antitumor effect of the oAd-CXCL11 was CD8+ T cell dependent. Our findings thus revealed that CXCL11-armed oAd can improve immune-virotherapy and can be a promising adjuvant of CAR-T therapy for GBM.

16.
Sheng Wu Gong Cheng Xue Bao ; 38(9): 3489-3500, 2022 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-36151816

RESUMO

Eukaryotic translation initiation factor 4B (eIF4B) plays an important role in mRNA translation initiation, cell survival and proliferation in vitro, but the in vivo function is poorly understood. In this study, via various experimental techniques such as hematoxylin-eosin (HE) staining, flow cytometry, Western blotting, and immunohistochemistry, we investigated the role of eIF4B in mouse embryo development using an eIF4B knockout (KO) mouse model and explored the mechanism. We found that the livers, but not lungs, brain, stomach, or pancreas, derived from eIF4B KO mouse embryos displayed severe pathological changes characterized by enhanced apoptosis and necrosis. Accordingly, high expression of cleaved-caspase 3, and excessive activation of mTOR signaling as evidenced by increased expression and phosphorylation of p70S6K and enhanced phosphorylation of 4EBP1, were observed in mouse embryonic fibroblasts and fetal livers from eIF4B KO mice. These results uncover a critical role of eIF4B in mouse embryo development and provide important insights into the biological functions of eIF4B in vivo.


Assuntos
Fibroblastos , Proteínas Quinases S6 Ribossômicas 70-kDa , Animais , Apoptose/genética , Caspase 3 , Amarelo de Eosina-(YS) , Fatores de Iniciação em Eucariotos/genética , Fatores de Iniciação em Eucariotos/metabolismo , Hematoxilina , Fígado/metabolismo , Camundongos , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Serina-Treonina Quinases TOR
17.
J Am Chem Soc ; 144(40): 18485-18493, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36161870

RESUMO

The atomically dispersed metal catalyst or single-atom catalyst (SAC) with the utmost metal utilization efficiency shows excellent selectivity toward ethylene compared to the metal nanoparticles catalyst in the acetylene semi-hydrogenation reaction. However, these catalysts normally work at relatively high temperatures. Achieving low-temperature reactivity while preserving high selectivity remains a challenge. To improve the intrinsic reactivity of SACs, rationally tailoring the coordination environments of the first metal atom by coordinating it with a second neighboring metal atom affords an opportunity. Here, we report the fabrication of a dual-atom catalyst (DAC) that features a bonded Pd1-Cu1 atomic pair anchoring on nanodiamond graphene (ND@G). Compared to the single-atom Pd or Cu catalyst, it exhibits increased reactivity at a lower temperature, with 100% acetylene conversion and 92% ethylene selectivity at 110 °C. This work provides a strategy for designing DACs for low-temperature hydrogenation by manipulating the coordination environment of catalytic sites at the atomic level.

18.
Dis Markers ; 2022: 4822964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36164370

RESUMO

Background: IQGAP3 has important function in cancer progression and has become a potential therapeutic target as a transmembrane protein. But its role in tumor immunity and pan-cancer was not systematically investigated. This study evaluated the potential role of IQGAP3 and clinical significance in pan-cancer through combined multiomics analysis. Methods: From Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases, transcriptomic datasets were first obtained, and from Gene Expression Omnibus (GEO), expression profiling microarray data were acquired and integrated to systematically assess the expression differences and prognostic relevance of IQGAP3 in pancreatic cancer. Immunohistochemical data were obtained from Human Protein Atlas (HPA) to assess IQGAP3 protein expression differences, and exome data from TCGA were used to analyze IQGAP3 expression in relation to tumor mutational burden (TMB), microsatellite instability (MSI), and mutation. Additionally, we also analyzed the relationship between IQGAP3 expression and immune checkpoints, mismatch repair (MMR), and IQGAP3 relationship with methylation and copy number variation based on expression profiles. Results: Microsatellite instability (MSI), immune checkpoints, mismatch repair (MMR), and tumor mutational burden (TMB) all closely interacted with IQGAP3 mRNA. In addition, detailed relationships between the immune microenvironment and IQGAP3 mRNA as well as immune cell CD4+ Th2 and myeloid-derived suppressor cells (MDSCs) were determined. Mechanistically, IQGAP3 was involved in cytoskeleton formation, T cell receptor signaling pathways, DNA damage, cell cycle, P53 pathway, Fc gamma R-mediated phagocytosis, and apoptosis. Conclusion: IQGAP3 could serve as an effective prognostic biomarker for pan-cancer immune-related therapy.


Assuntos
Instabilidade de Microssatélites , Neoplasias , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Variações do Número de Cópias de DNA , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/uso terapêutico , Humanos , Neoplasias/patologia , Prognóstico , RNA Mensageiro , Receptores de Antígenos de Linfócitos T/genética , Microambiente Tumoral/genética , Proteína Supressora de Tumor p53/genética
19.
Water Res ; 225: 119076, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36155004

RESUMO

Ceramic membranes for energy conversion and storage devices are essential for becoming carbon neutral due to low cost and high stability, but limited by slow proton and water transport. Meanwhile magic-angle graphene with unconventional superconductivity ushers in a new era, properties research of which are in infant stage, urgently longing for specific applications. Herein, we investigate the ionic-conductivity and water-transport properties of ceramic membrane-based magic-angle graphene by choosing proton and water as a proof-of-concept for the first time, discover the twist-angle tuned proton conduction and water transport in ceramic membrane-based magic-angle graphene, demonstrate the faster proton and water transport in magic-angle graphene than that in graphene, and construct an efficient device of protonic ceramic membrane fuel cell based upon the new fast proton-conducting materials of magic-angle graphene. The proton conduction and water transport in magic-angle graphene can be easily tuned by the twist angle, explained by the corresponding potential energy surface. The smaller the twist angle is, and the faster the proton transport is. The protonic migration energy barrier in magic-angle graphene is lower by about 50% than that in graphene. Additionally, the water transport properties in magic-angle graphene can be improved by tuning twist angles. The electrode with magic-angle graphene can provide higher performance of protonic ceramic membrane fuel cells. The present work opens the specific application of ceramic membrane-based magic-angle graphene as new proton-conducting and water-transport materials in energy and environment.

20.
Adv Mater ; 34(40): e2205679, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35986669

RESUMO

Bioinspired artificial visual perception devices with the optical environment-adaptable function have attracted significant attention for their promising potential in applications like robotics and machine vision. In this regard, a photodetector with in-sensor adaptability is longed for in terms of complexity, efficiency, and cost. Here, a near-infrared phototransistor with a benign light irradiance-adaptability is presented. The phototransistor uses a vertically stacking graphene/lead sulfide quantum dots/graphene heterojunction as the conductive channel. Compared with ordinary lead sulfide quantum dots-decorated graphene phototransistors, the present device demonstrates a faster photoresponse speed and an abnormal transfer characteristic. The latter characteristic is induced by the gate voltage-tunable Fermi level in the heterojunction and the abundant electron trap states in the quantum dot film, which jointly results in an intense dependence of the photoresponse on the gate voltage. The dynamic trapping and de-trapping processes in the quantum dot film enable the inhibition or potentiation of the photoresponse, based on which the photopic or scotopic adaptation behavior of the human retina is successfully mimicked, respectively. By providing an irradiance-adaptable photodetector with a spectral response beyond visible light, this work should inspire future research on artificial environment-adaptable perception devices.

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