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1.
J Immunol Res ; 2022: 5254911, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35028320

RESUMO

Introduction: KLRB1 is a gene encoding CD161 expressed in NK cells and some T cell subsets. At present, KLRB1 is believed to affect tumorigenesis and development by regulating the cytotoxicity of NK cells in several cancers. However, there is a lack of systematic reviews of KLRB1 in a variety of malignancies. Objectives: Hence, our research is aimed at providing a relatively comprehensive understanding of the role of KLRB1 in different types of cancer, paving the way for further research on the molecular mechanism and immunotherapy potential of KLRB1. Methods: In this study, we used relevant public databases, including TCGA (The Cancer Genome Atlas), GEO (Gene Expression Omnibus), CCLE (Cancer Cell Line Encyclopedia), GTEx (Genotype Tissue-Expression), and HPA (Human Protein Atlas), to perform a pan-cancer analysis of KLRB1 across 33 types of cancer. We explored the potential molecular mechanism of KLRB1 in clinical prognosis and tumor immunity from the aspects of gene expression, survival status, clinical phenotype, immune infiltration, immunotherapy response, and chemotherapeutic drug sensitivity. Results: KLRB1 was downregulated in 13 cancers while upregulated in kidney cancer. Patients with high expression of KLRB1 have a better prognosis in most types of cancer. Moreover, the KLRB1 expression level is related to TMB and MSI and related to various immune signatures of tumor. The expression of KLRB1 can affect tumor immune cell infiltration. KLRB1 expression level can also affect the sensitivity of chemotherapy drugs. Conclusions: KLRB1 may be a prognostic and immunological biomarker across tumors. At the same time, KLRB1 expression can reflect the sensitivity of cancer patients to chemotherapy drugs. KLRB1 may become a new target for immunotherapy.

2.
Mol Biol Evol ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35038730

RESUMO

The spotted hyena (Crocuta crocuta) is a large and unique terrestrial carnivore. It is a particularly fascinating species due to its distinct phenotypic traits, especially its complex social structure and scavenging lifestyle, with associated high dietary exposure to microbial pathogens. However, the underlying molecular mechanisms related to these phenotypes remain elusive. Here, we sequenced and assembled a high-quality long-read genome of the spotted hyena, with a contig N50 length of ∼13.75 Mbp. Based on comparative genomics, immunoglobulin family members (e.g., IGKV4-1) showed significant adaptive duplications in the spotted hyena and striped hyena. Furthermore, immune-related genes (e.g., CD8A, LAG3, and TLR3) experienced species-specific positive selection in the spotted hyena lineage. These results suggest that immune tolerance between the spotted hyena and closely related striped hyena has undergone adaptive divergence to cope with prolonged dietary exposure to microbial pathogens from scavenging. Furthermore, we provided the potential genetic insights underlying social complexity, hinting at social behavior and cognition. Specifically, the RECNE-associated genes (e.g., UGP2 and ACTR2) in the spotted hyena genome are involved in regulation of social communication. Taken together, our genomic analyses provide molecular insights into the scavenging lifestyle and societal complexity of spotted hyenas.

3.
Brain Behav ; : e2488, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35041261

RESUMO

OBJECTIVE: To investigate the effects of eszopiclone on sleep quality and cognitive function in elderly patients with Alzheimer's disease (AD) and sleep disorders. METHODS: This study was a prospective study of 96 elderly patients with AD and sleep disturbance treated in our hospital from April 2019 to December 2020. All patients were divided into a control group (48 patients, given alprazolam tablets) and a study group (48 patients, given eszopiclone) according to the random number table method. RESULTS: After treatment, compared with the control group, the study group had lower sleep latency, daytime function, sleep disturbance, sleep efficiency, sleep quality, sleeping time, and hypnotic medication scores (p < .05). After treatment, sleep progression and sleep architecture improvement were more obvious in the study group compared with the control group (p < .05). After treatment, compared with the control group, the rhythm disturbance, psychotic disorder, hallucination, phobic anxiety, and disorder in the study group improved more significantly (p < .05). After treatment, compared with the control group, the scores of orientation, attention, memory, calculation, recall, and language ability in the study group improved more significantly (p < .05). After treatment, the scores of the physical life self-care scale and instrumental activities of daily living scale in the study group were improved more obviously compared with the control group, with significant differences (p < .05). CONCLUSION: Eszopiclone can effectively improve the quality of sleep and cognitive function in elderly patients with AD and sleep disorder.

4.
J Org Chem ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020395

RESUMO

The C-S activation and sulfur removal from native thiols is challenging, which limits their application as feedstock materials in organic synthesis despite their natural abundance. Herein, we introduce a per-/polyfluoroaryl moiety, which serves as a redox-active scaffold, into sp3-hybridized thiols to activate the C-S bond. Using a Ni catalyst with MgBr2 as an additive, the S group can be removed to yield an aliphatic radical that can react with an aryl halide in a reductive cross-coupling.

5.
Emerg Microbes Infect ; : 1-28, 2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35034586

RESUMO

AbstractThe extremely high transmission rate of SARS-CoV-2 and severe cases of COVID-19 pose the two critical challenges in the battle against COVID-19. Increasing evidence has shown that the viral spike (S) protein-driven syncytia may be responsible for these two events. Intensive attention has thus been devoted to seeking S-guided syncytium inhibitors. However, the current screening campaigns mainly rely on either live virus-based or plasmid-based method, which are always greatly limited by the shortage of high-level biosafety BSL-3 facilities or too much labor-intensive work. Here, we constructed a new hybrid VEEV-SARS-CoV-2-S-eGFP reporter vector through replacement of the structural genes of Venezuelan equine encephalitis virus (VEEV) with the S protein of SARS-CoV-2 as the single structural protein. VEEV-SARS-CoV-2-S-eGFP can propagate steadily through cell-to-cell transmission pathway in S- and ACE2-dependent manner, forming GFP positive syncytia. In addition, a significant dose-dependent decay in GFP signals was observed in VEEV-SARS-CoV-2-S-eGFP replicating cells upon treatment with SARS-CoV-2 antiserum or entry inhibitors, providing further evidence that VEEV-SARS-CoV-2-S-eGFP system is highly sensitive to characterize the anti-syncytium-formation activity of antiviral agents. More importantly, the assay is able to be performed in a BSL-2 laboratory without manipulation of live SARS-CoV-2. Taken together, our work establishes a more convenient and efficient VEEV-SARS-CoV-2-S-eGFP replicating cells-based method for rapid screening of inhibitors blocking syncytium formation.

6.
Virol J ; 19(1): 2, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983583

RESUMO

The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.


Assuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Camundongos , SARS-CoV-2/imunologia
7.
Trials ; 23(1): 6, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980197

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is a common degenerative disease that causes pain, functional impairment, and reduced quality of life. Resistance training is considered as an effective approach to reduce the risk of muscle weakness in patients with KOA. Blood flow restriction (BFR) with low-load resistance training has better clinical outcomes than low-load resistance training alone. However, the degree of BFR which works more effectively with low-load resistance training has not been determined. The purpose of this study is to evaluate the effectiveness of different degrees of BFR with low-load resistance training in patients with KOA on pain, self-reported function, physical function performance, muscle strength, muscle thickness, and quality of life. METHODS: This is a study protocol for a randomized, controlled trial with blinded participants. One hundred individuals will be indiscriminately assigned into the following groups: two training groups with a BFR at 40% and 80% limb occlusion pressure (LOP), a training group without BFR, and a health education group. The three intervention groups will perform strength training for the quadriceps muscles twice a week for 12 weeks, while the health education group will attend sessions once a week for 12 weeks. The primary outcome is pain. The secondary outcomes include self-reported function, physical function performance, muscle strength of the knee extensors, muscle mass of the quadriceps, quality of life, and adverse events. Intention-to-treat analysis will be conducted for individuals who withdraw during the trial. DISCUSSION: Previous studies have shown that BFR with low-load resistance training is more effective than low-load resistance training alone; however, a high degree of BFR may cause discomfort during training. If a 40% LOP for BFR could produce similar clinical outcomes as an 80% LOP for BFR, resistance training with a low degree of BFR can be chosen for patients with KOA who are unbearable for a high degree of BFR. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000037859 ( http://www.chictr.org.cn/edit.aspx?pid=59956&htm=4 ). Registered on 2 September 2020.


Assuntos
Osteoartrite do Joelho , Treinamento de Força , Humanos , Força Muscular , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/terapia , Músculo Quadríceps , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fluxo Sanguíneo Regional
8.
J Hazard Mater ; 425: 128007, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986569

RESUMO

Removal of radioactive 133Ba, 60Co and 63Ni and their nonradioactive isotopes through ion exchange method would be highly beneficial for the safe disposal of liquid industrial waste, and it also bears importance for the emergency response to nuclear accident. Herein, we report the employment of an indium sulfide [CH3CH2NH3]6In8S15 (InS-2) with exchangeable ethylammonium cations for efficient and selective uptake of Ba2+, Co2+ and Ni2+. The corner-sharing linkage of P1-{In8S17} clusters in InS-2 endow the layered structure with nanoscale windows, which facilitates both transfer and accommodation of the large hydrated divalent metal ions. This results in ultrafast exchange kinetics (10-20 min) and top-level exchange capacities of 211.73 mg g-1 for Ba2+, 103.57 mg g-1 for Co2+, and 111.78 mg g-1 for Ni2+. Particularly, InS-2 achieves ultrahigh Kd values of 2.3 × 105 mL g-1 for Ba2+, 2.0 × 105 mL g-1 for Co2+ and 1.6 × 105 mL g-1 for Ni2+, corresponding to remarkable removal efficiencies larger than 99.4% (C0 ~ 6 ppm). InS-2 shows high ß and γ irradiation resistance, wide pH durability (pH 3-13 for Ba2+, pH 3-11 for Co2+ and Ni2+), and outstanding selectivity against competitor ions (e.g. Na+, K+, Mg2+, Ca2+). The InS-2-filled ion exchange column exhibits a fantastic removal effect (R > 99%) for mixed Ba2+, Co2+, Ni2+, as well as Sr2+. The ultralong column-treatment on 20000 BVs of flow reveals an affinity order of Co2+ > Ni2+ > Ba2+ > Sr2+ for InS-2, which gives deep insights into the adsorption process and interaction between competitor ions. This excellent uptake of Ba2+ (Ra by analogy), Co2+ and Ni2+ ions by InS-2 highlights the great potential of metal chalcogenides as a type of promising materials for minimizing contamination in complex wastewater.

9.
Eur Thyroid J ; 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35060924

RESUMO

OBJECTIVE: Sorafenib and lenvatinib have been recommended as standard tyrosine kinase inhibitors (TKIs) for progressive radioiodine-refractory differentiated thyroid carcinoma (RR-DTC). However, their efficacy remains limited with unresolved drug resistance. Therefore, we conceived this open-label study based on real-world evidence to investigate the efficacy and safety of apatinib in patients with progressive RR-DTC. METHODS: Off-label use of apatinib as either initial treatment or salvage treatment for sorafenib resistance was investigated. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. RESULTS: For all the enrolled 28 patients, the median PFS was 15.1 months, with an ORR of 69.6%. The median OS was not reached at the data cut-off. In detail, the median PFS of 17.3 months and the ORR of 75% were determined in patients with TKI-naive RR-DTC (initial treatment group, n = 14). And in patients with first-line sorafenib-resistant RR-DTC (salvage treatment group, n = 14), a median PFS of 12.0 months was reached, with an ORR of 45.5%. In salvage treatment group, the median OS from the start of apatinib administration was 20.6 months, reaching to 89.1 months from sorafenib treatment initiation. Adverse events at grade 3 or higher occurred in 64.3% of all subjects treated with apatinib. CONCLUSIONS: This study demonstrated that apatinib shows promise against RR-DTC with tolerable toxicity, representing a novel initial treatment for progressive RR-DTC and effective salvage treatment for RR-DTC resistant to sorafenib.

10.
Oncol Lett ; 23(1): 8, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34820007

RESUMO

Isoliensinine is a bis-benzylisoquinoline alkaloid that can be isolated from the lotus Nelumbo nucifera Gaertn. It has been reported to exert a variety of anti-cancer properties. In the present study, the potential effects of isoliensinine on cervical cancer Siha, HeLa, Caski and C33A cell lines were investigated by using Cell Counting Kit-8 (CCK-8), flow cytometry, western blotting and reverse transcription-PCR (RT-PCR) to measure cell proliferation, the cell cycle and apoptosis, in addition to elucidating the underlying molecular mechanism. Protein levels of p21, CDK2, Cyclin E, Mcl-1, cleaved Caspase-9, AKT, phosphorylated-AKT, glycogen synthase kinase (Gsk)3α, PTEN, and mRNA levels of p21, p15, p27, CDK2, CDK4, Cyclin E, Cyclin D, Gsk3α, Gsk3ß and PTEN were measured. Molecular docking assays were used to calculate the strength of binding of isoliensinine to AKT using AutoDock 4.0. Isoliensinine was found to induce cell cycle arrest at the G0/G1 phase by upregulating p21 expression and downregulating CDK2 and cyclin E in breast cancer cells. In addition, in previous research, isoliensinine promoted cell apoptosis by downregulating myeloid-cell leukemia 1 expression and activating caspase-9. Upstream, isoliensinine significantly downregulated AKT (S473) phosphorylation and GSK3α expression in a dose- and time-dependent manner. The AKT inhibitor AKTi-1/2 enhanced the function of isoliensinine on cell cycle arrest and apoptosis through the AKT/GSK3α pathway. AutoDock analysis showed that isoliensinine can bind to the AKT protein. These findings suggest that isoliensinine can induce cervical cancer cell cycle arrest and apoptosis by inhibiting the AKT/GSK3α pathway, which represents a novel strategy for the treatment of cervical cancer.

11.
J Am Chem Soc ; 144(2): 872-882, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34932330

RESUMO

Mechanically interlocked networks (MINs) have emerged as an encouraging platform for the development of mechanically robust yet adaptive materials. However, the difficulty in reversibly breaking the mechanical bonds poses a real challenge to MINs as customizable and sustainable materials. Herein, we couple the vitrimer chemistry with mechanically interlocked structures to generate a new class of MINs─referred to as mechanically interlocked vitrimers (MIVs)─to address the challenge. Specifically, we have prepared the acetoacetate-decorated [2]rotaxane that undergoes catalyst-free condensation reaction with two commercially available multiamine monomers to furnish MIVs. Compared with the control whose wheels are nonslidable under applied force, our MIVs with slidable mechanically interlocked motifs showcase enhanced mechanical performance including Young's modulus (18.5 ± 0.9 vs 1.0 ± 0.1 MPa), toughness (3.7 ± 0.1 vs 0.9 ± 0.1 MJ/m3), and damping capacity (98% vs 72%). The structural basis behind unique property profiles is demonstrated to be the force-induced host-guest dissociation and consequential intramolecular sliding of the wheels along the axles. The peculiar behaviors represent a consecutive energy dissipation mechanism, which provides a complement to other pathways that mainly depend on the breaking of sacrificial bonds. Moreover, by virtue of the vitrimer chemistry of vinylogous urethanes, we impart reprocessability and chemical recyclability to the MINs, thereby empowering the reconfiguration of the networks without breaking of the mechanical bonds. Finally, it is disclosed that the intramolecular motions of [2]rotaxanes could accelerate the dynamic exchange of the vinylogous urethane bonds via loosening the network, suggestive of a synergistic effect between the dual dynamic entities.

12.
Emerg Microbes Infect ; : 1-31, 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34877923

RESUMO

AbstractJapanese encephalitis virus (JEV), an important neurotropic pathogen, belongs to the genus Flavivirus of the family Flaviviridae and has caused huge threat to public health. It is still obscure regarding the functions of stem loop (SL) and dumbbell (DB) domains of JEV 3' UTR in viral replication and virulence. In the current study, using the infectious clone of JEV SA14 strain as a backbone, we constructed a series of deletion mutants of 3' UTR to investigate their effects on virus replication. The results showed that partial deletions within SL or DB domain had no apparent effects on virus replication in both mammalian (BHK-21) and mosquito (C6/36) cells, suggesting that they were not involved in viral host-specific replication. However, the entire SL domain deletion (ΔVR) significantly reduced virus replication in both cell lines, indicating the important role of the complete SL domain in virus replication. The revertant of ΔVR mutant virus was obtained by serial passage in BHK-21 cells that acquired a duplication of DB domain (DB-dup) in the 3' UTR, which greatly restored virus replication as well as the capability to produce the subgenomic flavivirus RNAs (sfRNAs). Interestingly, the DB-dup mutant virus was highly attenuated in C57BL/6 mice despite replicating similar to WT JEV. These findings demonstrate the significant roles of the duplicated structures in 3' UTR in JEV replication and provide a novel strategy for the design of live attenuated vaccine.

13.
Sensors (Basel) ; 21(23)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34883804

RESUMO

The development of the smart grid requires the distribution switch to not be limited to the original breaking function. More functional requirements lead to more complex switch structures, especially the intelligent processing unit on the secondary side. A technology called primary and secondary integration optimizes the structure of the switch, which greatly increases the intelligence level of the switch, but also has disadvantages. The secondary intelligent unit is arranged close to the primary high-voltage electromagnetic environment, and the distribution switch is prone to failure due to electromagnetic interference. In order to explore the influence of electromagnetic interference on it, a transient electromagnetic interference simulation test platform was built for a 10 kV intelligent distribution switch based on the principle of spherical gap arc discharge, and the interference signal of the intelligent distribution switch was measured; the law of the spatial magnetic field near the electronic transformer is mainly studied in this paper. The shielding effectiveness of the distribution terminal of the switch was analyzed, and the interference of the power line of the sensor merging unit circuit board was calculated. The results show that the electronic transformer may have serious faults under continuous strong transient electromagnetic interference. The electromagnetic transient simulation test system studied in this paper can evaluate the anti strong electromagnetic interference ability of the electronic transformer.

14.
J Therm Biol ; 102: 103122, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34863485

RESUMO

Desaturase is one of the key enzymes in the unsaturated fatty acid synthesis pathway. Δ9 desaturase catalyzes the synthesis of oleic acid from stearic acid by introducing double bonds in the 9th and 10th carbon chains, thereby increasing the content of MUFAs in the body. In order to explore the main function of the Δ9 desaturase gene under low temperature stress, RACE-PCR technology was used in this study to clone the full-length sequence of the CqFAD9-like from the hepatopancreas of red claw crayfish, Cherax quadricarinatus. The full length of the sequence is 1236 bp, and the open reading frame is 1041 bp, encoding 346 amino acid residues. The 5 'UTR is 116 bp, the 3' UTR is 79 bp, and the 3 'UTR contains a PloyA tail. The predicted theoretical isoelectric point and molecular weight are 8.68 and 40.28 kDa, respectively. Homology analysis showed that the sequence had the highest similarity with FAD9 from crustaceans. The results of real-time PCR showed that the expression level of this gene was highest in the hepatopancreas, which was significantly higher than other tissues, followed by the ovaries, brain ganglion and stomach. At the same time, the expression of the CqFAD9-like in hepatopancreas of crayfish cultured at 25, 20, 15 and 9 °C for four weeks was detected. The results showed that expression of the FAD9 gene increased gradually with decreasing temperature, indicating that metabolic desaturation might play a regulatory role during cold stress.

15.
JTO Clin Res Rep ; 2(12): 100253, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34870249

RESUMO

Introduction: We compared the magnetic resonance imaging total tumor volume (TTV) and median apparent diffusion coefficient (ADC) of malignant pleural mesothelioma (MPM) before and at 4 weeks after chemotherapy, to evaluate whether these are potential early markers of treatment response. Methods: Diffusion-weighted magnetic resonance imaging was performed in 23 patients with MPM before and after 4 weeks of chemotherapy. The TTV was measured by semiautomatic segmentation (GrowCut) and transferred onto ADC maps to record the median ADC. Test-retest repeatability of TTV and ADC was evaluated in eight patients. TTV and median ADC changes were compared between responders and nonresponders, defined using modified Response Evaluation Criteria In Solid Tumors on computed tomography (CT) at 12 weeks after treatment. TTV and median ADC were also correlated with CT size measurement and disease survival. Results: The test-retest 95% limits of agreement for TTV were -13.9% to 16.2% and for median ADC -1.2% to 3.3%. A significant increase in median ADC in responders was observed at 4 weeks after treatment (p = 0.02). Correlation was found between CT tumor size change at 12 weeks and median ADC changes at 4 weeks post-treatment (r = -0.560, p = 0.006). An increase in median ADC greater than 5.1% at 4 weeks has 100% sensitivity and 90% specificity for responders (area under the curve = 0.933, p < 0.001). There was also moderate correlation between median tumor ADC at baseline and overall survival (r = 0.45, p = 0.03). Conclusions: Diffusion-weighted magnetic resonance imaging measurements of TTV and median ADC in MPM have good measurement repeatability. Increase in ADC at 4 weeks post-treatment has the potential to be an early response biomarker.

16.
J Exp Clin Cancer Res ; 40(1): 390, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893086

RESUMO

BACKGROUND: Centromere protein N (CENP-N) has been reported to be highly expressed in malignancies, but its role and mechanism in nasopharyngeal carcinoma (NPC) are unknown. METHODS: Abnormal CENP-N expression from NPC microarrays of GEO database was analyzed. CENP-N expression level was confirmed in NPC tissues and cell lines. Stable CENP-N knockdown and overexpression NPC cell lines were established, and transcriptome sequencing after CENP-N knockdown was performed. In vitro and in vivo experiments were performed to test the impact of CENP-N knockdown in NPC cells. ChIP and dual luciferase reporter assays were used to verify the combination of IRF2 and CENP-N. Western blot analysis, cellular immunofluorescence, immunoprecipitation and GST pulldown assays were used to verify the combination of CENP-N and AKT. RESULTS: CENP-N was confirmed to be aberrantly highly expressed in NPC tissues and cell lines and to be associated with high 18F-FDG uptake in cancer nests and poor patient prognosis. Transcriptome sequencing after CENP-N knockdown revealed that genes with altered expression were enriched in pathways related to glucose metabolism, cell cycle regulation. CENP-N knockdown inhibited glucose metabolism, cell proliferation, cell cycling and promoted apoptosis. IRF2 is a transcription factor for CENP-N and directly promotes CENP-N expression in NPC cells. CENP-N affects the glucose metabolism, proliferation, cell cycling and apoptosis of NPC cells in vitro and in vivo through the AKT pathway. CENP-N formed a complex with AKT in NPC cells. Both an AKT inhibitor (MK-2206) and a LDHA inhibitor (GSK2837808A) blocked the effect of CENP-N overexpression on NPC cells by promoting aerobic glycolysis, proliferation, cell cycling and apoptosis resistance. CONCLUSIONS: The IRF2/CENP-N/AKT axis promotes malignant biological behaviors in NPC cells by increasing aerobic glycolysis, and the IRF2/CENP-N/AKT signaling axis is expected to be a new target for NPC therapy.

17.
J Burn Care Res ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34850015

RESUMO

The incidence rate of electrical injury has remained stable, while the absolute case number has increased. Amputations, erosions, occlusions, and delayed blood vessel rupture are the common complications. Ectopic implantation salvage has been performed widely in mechanical trauma patients, to preserve viable or possibly viable tissues and organ, without application in the electrical injury patients to the best of our knowledge. Here, we present a case report involving ectopic implantation salvage of the left thumb before contralateral transplantation to the right hand after high-voltage electrical injury. The patient's left thumb remained viable despite necrosis of the left forearm at 3 weeks post-injury. After debridement, we implanted the left thumb to his thigh where it was anastomosed to the lateral circumflex femoral artery's descending branch and great saphenous vein. We replanted the left thumb on the right hand with fixation 6 weeks later. The reassembled right hand remained well-circulated 11 months post-reconstruction. We believe this case supports broadening the indication for ectopic implantation salvage surgeries to patients who sustain electrical injuries.

18.
Arch Microbiol ; 204(1): 19, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34910249

RESUMO

A novel actinobacterium, YIM 132084T, was isolated from Lepraria sp. lichen collected from Yunnan province, south-west PR China and identified by a polyphasic taxonomic approach. The strain was Gram-stain-positive, aerobic, catalase-positive, oxidase-negative, non-motile and coccus-shaped. Colonies were round, convex, smooth and light orange yellow in color. It grew at 10-40 °C (optimum 28 °C), at pH 6.0-11.0 (optimum pH 7.0) and in the presence of 0-4% NaCl (optimum 0%). Strain YIM 132084T comprised diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol as the major polar lipids, MK-8(H4) as the predominant menaquinone, and anteiso-C15:0, anteiso-C17:0, iso-C15:0 and iso-C16:0 as major fatty acids. Strain YIM 132084T had meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan, and mannose, ribose, glucose and rhamnose as whole-cell sugars. The 16S rRNA gene sequence showed high level of similarity with Nakamurella flavida KCTC 19127T (97.7%) and Nakamurella flava CGMCC 4.7524T (97.7%). The G + C content of the genomic DNA was 72.4 mol%. Based on draft genome sequences, strain YIM 132084T showed an average nucleotide identity value of 76.1% and 74.9%, a digital DNA-DNA hybridization value of 20.9% and 20.6% with the reference strains Nakamurella flavida and Nakamurella flava, respectively. The results of the phenotypic, chemotaxonomic and phylogenetic analyses showed that strain YIM 132084T represents a novel species of the genus Nakamurella, for which the name Nakamurella leprariae sp. nov. is proposed. The type strain is YIM 132084T (= CGMCC 4.7667T = NBRC 114280T = KCTC 49367T).


Assuntos
Líquens , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
19.
Medicine (Baltimore) ; 100(51): e27983, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34941037

RESUMO

INTRODUCTION: Pancreatic arteriovenous malformation (P-AVM) is a rare vascular malformation. Fewer than 200 cases have been reported. The clinical manifestations lack specificity. Common symptoms include abdominal pain, gastrointestinal hemorrhage, and jaundice, which is easily confused with other disorders. PATIENT CONCERNS: A 42-year-old man received TAE due to abdominal pain caused by P-AVM in a local hospital, melena and abdominal pain occurred in a short time after TAE. DIAGNOSIS: The patient was diagnosed as P-AVM which was confirmed by computed tomography and digital subtraction angiography. INTERVENTIONS: A pylorus-preserving pancreatoduodenectomy was successfully performed after diagnosis was made. OUTCOMES: The patient recovered with no complications two weeks after surgery, and no sign of recurrence was found during the 4-mo follow-up period. CONCLUSION: In our experience, TAE may have limitations in the treatment of P-AVM and surgical resection should be considered as the treatment of choice.

20.
Front Immunol ; 12: 766821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966387

RESUMO

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations-K417N, E484K, and N501Y-found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Neutralizantes/farmacologia , Anticorpos Antivirais/farmacologia , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Células HEK293 , Humanos , Imunização Passiva , Camundongos
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