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1.
Open Biol ; 12(1): 210335, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35042406

RESUMO

YAP protein is a critical regulator of mammalian embryonic development. By generating a near-infrared fusion YAP reporter mouse line, we have achieved high-resolution live imaging of YAP localization during mouse embryonic development. We have validated the reporter by demonstrating its predicted responses to blocking LATS kinase activity or blocking cell polarity. By time lapse imaging preimplantation embryos, we revealed a mitotic reset behaviour of YAP nuclear localization. We also demonstrated deep tissue live imaging in post-implantation embryos and revealed an intriguing nuclear YAP pattern in migrating cells. The YAP fusion reporter mice and imaging methods will open new opportunities for understanding dynamic YAP signalling in vivo in many different situations.

2.
Neuropharmacology ; 206: 108947, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35026286

RESUMO

Extracting relevant information and transforming it into appropriate behavior, is a fundamental brain function, and requires the coordination between the sensory and cognitive systems, however, the underlying mechanisms of interplay between sensory and cognition systems remain largely unknown. Here, we developed a mouse model for mimicking human auditory mismatch negativity (MMN), a well-characterized translational biomarker for schizophrenia, and an index of early auditory information processing. We found that a subanesthetic dose of ketamine decreased the amplitude of MMN in adult mice. Using pharmacological and chemogenetic approaches, we identified an auditory cortex-entorhinal cortex-hippocampus neural circuit loop that is required for the generation of MMN. In addition, we found that inhibition of dCA1→MEC circuit impaired the auditory related fear discrimination. Moreover, we found that ketamine induced MMN deficiency by inhibition of long-range GABAergic projection from the CA1 region of the dorsal hippocampus to the medial entorhinal cortex. These results provided circuit insights for ketamine effects and early auditory information processing. As the entorhinal cortex is the interface between the neocortex and hippocampus, and the hippocampus is critical for the formation, consolidation, and retrieval of episodic memories and other cognition, our results provide a neural mechanism for the interplay between the sensory and cognition systems.

3.
Clin Transl Sci ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34997701

RESUMO

Odronextamab is a fully-human IgG4-based CD20xCD3 bispecific antibody that binds to CD3 on T cells and CD20 on B cells, triggering T-cell-mediated cytotoxicity independent of T-cell-receptor recognition. Adequate safety, tolerability, and encouraging durable complete responses have been observed in an ongoing first-in-human (FIH) study of odronextamab in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL; NCT02290951). We retrospectively evaluated the pharmacokinetic, pharmacodynamic, and antitumor characteristics of odronextamab in a series of in vitro/in vivo preclinical experiments, to assess their translational value to inform dose escalation for the FIH study. Half-maximal effective concentration values from in vitro cytokine release assays (range: 0.05-0.08 mg/L) provided a reasonable estimate of odronextamab concentrations in patients associated with cytokine release at a 0.5 mg dose (maximum serum concentration: 0.081 mg/L) on week 1/day 1, which could therefore be used to determine the week 1 clinical dose. Odronextamab concentrations resulting in 100% inhibition of tumor growth in a Raji xenograft tumor mouse model (1-10 mg/L) were useful to predict efficacious concentrations in patients and inform dose-escalation strategy. Although predicted human pharmacokinetic parameters derived from monkey data overestimated projected odronextamab exposure, they provided a conservative estimate for FIH starting doses. With step-up dosing, the highest-tested weekly odronextamab dose in patients (320 mg) exceeded the 1 mg/kg single dose in monkeys without step-up dosing. In conclusion, combination of odronextamab in vitro cytokine data, efficacious concentration data from mouse tumor models, and pharmacokinetic evaluations in monkeys has translational value to inform odronextamab FIH study design in patients with R/R B-NHL.

4.
Brain Behav ; : e2469, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978387

RESUMO

INTRODUCTION: Mutations in the GFPT1 gene are associated with a particular subtype of congenital myasthenia syndrome (CMS) called limb-girdle myasthenia with tubular aggregates. However, not all patients show tubular aggregates in muscle biopsy, suggesting the diversity of myopathology should be further investigated. METHODS: In this study, we reported two unrelated patients clinically characterized by easy fatigability, limb-girdle muscle weakness, positive decrements of repetitive stimulation, and response to pyridostigmine. The routine examinations of myopathology were conducted. The causative gene was explored by whole-exome screening. In addition, we summarized all GFPT1-related CMS patients with muscle biopsy in the literature. RESULTS: Pathogenic biallelic GFPT1 mutations were identified in the two patients. In patient one, muscle biopsy indicated vacuolar myopathic changes and atypical pathological changes of myofibrillar myopathy characterized by desmin deposits, Z-disc disorganization, and electronic dense granulofilamentous aggregation. In patient two, muscle biopsy showed typical myopathy with tubular aggregates. Among the 51 reported GFPT1-related CMS patients with muscle biopsy, most of them showed tubular aggregates myopathy, while rimmed vacuolar myopathy, autophagic vacuolar myopathy, mitochondria-like myopathy, neurogenic myopathy, and unspecific myopathic changes were also observed in some patients. These extra-synaptic pathological changes might be associated with GFPT1-deficiency hypoglycosylation and altered function of muscle-specific glycoproteins, as well as partly responsible for the permanent muscle weakness and resistance to acetylcholinesterase inhibitor therapy. CONCLUSIONS: Most patients with GFPT1-related CMS had tubular aggregates in the muscle biopsy, but some patients could show great diversities of the pathological change. The myopathological findings might be a biomarker to predict the prognosis of the disease.

5.
Chem Commun (Camb) ; 58(3): 451-454, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34904975

RESUMO

We unprecedentedly report spatially separated CoNx nanodots on carbon nanotubes (CNTs) via a facile formamide condensation reaction. To our knowledge, CoNx-CNTs outperform the activities of current catalysts in peroxymonosulfate activation. CoNx-CNT-oriented radical-free degradation of contaminants shows robust anti-interference capacity toward environmental conditions. Our work will stimulate general interest in designing cost-effective and versatile quantum-/atom-sized catalysts with fully exposed active sites for water purification and beyond.

6.
Dev Comp Immunol ; 126: 104244, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34450127

RESUMO

The mechanism by which infection by Bombyx mori cytoplasmic nucleopolyhedrosis virus (BmCPV) causes autophagy has not been studied in detail. Herein we have observed by electron microscopy that infection with BmCPV causes autophagosome and mitochondrial structure damage in Bombyx mori midgut. In BmN cells infected with BmCPV and expressing eGFP-LC3, fluorescence spots and LC3-II levels increased, suggesting that BmCPV infection causes autophagy. Autophagy inducer rapamycin (Rap) and autophagy inhibitor 3-methyladenine (3-MA) were used to monitor the effects of mitophagy on BmCPV proliferation. It was found BmCPV proliferation to be promoted by mitophagy. Transient transfection experiments in cultured BmN cells showed that mitophagy can be triggered by expression of BmCPV structural protein VP4. Moreover, VP4 caused upregulation of p-Drp1, PINK1 and Parkin proteins in the mitophagy pathway and downregulation of mitochondrial membrane protein Tom20. Furthermore, interaction between VP4 with Tom40 was confirmed by Co-IP, western blot and colocalization experiment, and overexpression of Tom40 reduce the level of mitochondrial autophagy induced by VP4. These results suggested that VP4 induced PINK1-Parkin-mediated mitophagy interacting with Tom40. These findings deepen our understanding of the interaction between BmCPV and silkworm and also provide a molecular target for screening anti-BmCPV drugs.

7.
Talanta ; 237: 122954, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736679

RESUMO

Herein, a simple microfluidic paper-based analytical device (µPAD) by using platinum nanoparticles (Pt NPs) as highly active peroxidase mimic for simultaneous determination of glucose and uric acid was fabricated. The µPAD consisted of one sample transportation layer, four paper-based detection chips, and two layers of hydrophobic polyethylene terephthalate (PET) films. The four detection chips were immobilized with various chromogenic reagents, Pt NPs, and specific oxidase (glucose oxidase or uricase). H2O2 generated by specific enzymatic reactions could oxidize co-immobilized chromogenic reagents to produce colored products by using Pt NPs as efficient catalyst. The multi-layered structure of µPAD could effectively improve the color uniformity and color intensity. Total color intensity from each two detection chips modified with distinct chromogenic reagents were used for quantitative analysis of glucose and uric acid, respectively, resulting in significantly improved sensitivity. The linear range for glucose and uric acid detection was 0.01-5.0 mM and 0.01-2.5 mM, respectively. Satisfied results were obtained for glucose and uric acid detection in real serum samples. An easy-to-use smartphone APP was developed for convenient and intelligent detection. The developed µPAD integrated with smartphone as detector holds great applicability for simple and portable on-site analysis.


Assuntos
Nanopartículas Metálicas , Técnicas Analíticas Microfluídicas , Colorimetria , Glucose , Peróxido de Hidrogênio , Microfluídica , Papel , Peroxidase , Peroxidases , Platina , Smartphone , Ácido Úrico
8.
J Colloid Interface Sci ; 608(Pt 1): 922-930, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34785467

RESUMO

It is important to develop novel energy to solve energy shortage and environmental problems. Hydrogen evolution reaction (HER) is envisaged as a viable technology that can be used to develop sustainable clean energy. Herein, we report a catalyst with CoSe2-MoSe2 heterostructure grown on reduced graphene oxide with an optimum Co/Mo proportion of 1:1 (CoSe2-MoSe2(1-1)/rGO). It exhibits good HER activities in both acidic and alkaline conditions. The CoSe2-MoSe2(1-1)/rGO shows an overpotential of 107 mV at 10 mA cm-2 with a Tafel slope of 56 mV dec-1 under acidic condition. Meanwhile, CoSe2-MoSe2(1-1)/rGO also presents an overpotential of 182 mV at 10 mA cm-2 and with a Tafel slope of 89 mV dec-1 under alkaline condition. These impressive performances of the catalyst are mainly due to the excellent electronic transmission capability of rGO and the abundant active sites of CoSe2-MoSe2 heterostructure as well as the optimized hydrogen adsorption energy of CoSe2-MoSe2 interface. The design of CoSe2-MoSe2(1-1)/rGO provides a meaningful guide for manufacturing electrode in energy storage and conversion.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34847670

RESUMO

Ag2Se is a narrow band gap n-type semiconductor with high carrier mobility and low lattice thermal conductivity. It has high thermoelectric performance near room temperature. However, there is a noticeable data discrepancy for thermoelectric performance in the reported literature studies, which greatly hinders the rational understanding and potential application of this material. In this work, we comprehensively studied the homogeneity, reproducibility, and thermal stability of bulk Ag2Se prepared by melting and mechanical alloying methods followed by spark plasma sintering. By virtue of the atom probe topology technique, we revealed nanosized Ag- or Se-rich precipitates and micropores with Se-aggregated interfaces that have not been detected previously. The samples prepared by melting and spark plasma sintering exhibit the best homogeneity and repeatability in thermoelectric properties despite abundant nanoprecipitates. Moreover, the thermoelectric performance of Ag2Se is greatly improved by introducing a slight amount of excess selenium. The average zT can steadily reach 0.8-0.9 in the range of 300-380 K, which is among the highest values reported for Ag2Se-based materials. This work will rationalize the evaluation of the thermoelectric performance of Ag2Se.

10.
Andrologia ; : e14343, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34866220

RESUMO

Circular RNAs (circRNAs) participate in the progression of various cancers. However, the function of circ_0062019 in prostate cancer (PCa) remains unclear. In this study, CCK-8, colony formation, transwell, tube formation and flow cytometry assays were applied to assess cell proliferation, motility, angiogenesis, cell cycle distribution and apoptosis. The binding association between miR-1253 and circ_0062019 or NRBP1 was verified through dual-luciferase reporter assay and RIP assay. Xenograft assay was conducted to evaluate tumour formation in vivo. As a result, circ_0062019 and NRBP1 were increased, but miR-1253 was decreased in PCa. Depletion of circ_0062019 curbed cell proliferation, migration, invasion, angiogenesis and EMT and induced apoptosis in PCa cells. Circ_0062019 facilitated the malignancy of PCa cells via sequestering miR-1253. Simultaneously, miR-1253 hindered PCa cell progression via regulating NRBP1. Ccirc_0062019 silencing suppressed tumour growth in vivo. Taken together, circ_0062019 expedited PCa progression through mediating miR-1253/NRBP1 pathway.

11.
Int J Biol Macromol ; 194: 223-232, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34875309

RESUMO

Bombyx mori cypovirus (BmCPV), a member of the family Reoviridae, is a model of Cypovirus, has a 10 segmented double-stranded RNA genome. However, so far, only one viral small peptide vSP27 with negative regulation on viral infection was identified; the mechanisms underlying host-BmCPV interaction are still unknown. Here, we identified that vSP27 was translated from a BmCPV derived circular RNA (circRNA-vSP27). Subsequently, results showed that vSP27 induced generation of ROS activated the NF-κB signaling pathway, induced the expression of antimicrobial peptides, and suppressed BmCPV infection. On the other hand, we identified a nuclear protein Akirin that could hijack vSP27, positively regulate the NF-κB pathway, and lead to inhibiting the viral infection. Altogether, our data suggested that BmCPV derived circRNA-vSP27 with small peptide translation activity may be employed by the host immunity in defense against the BmCPV infection.

13.
Thorac Cancer ; 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862856

RESUMO

BACKGROUND: Patients with primary lung adenocarcinoma are at increased risk of venous thromboembolism (VTE). However, lung adenocarcinoma characteristics differ across histological subtypes. Therefore, we performed comprehensive analyses on the clinicopathological characteristics of lung adenocarcinoma and risk of VTE. METHODS: A total of 952 surgically resected lung adenocarcinoma cases were reviewed and classified according to criteria of the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS) /European Respiratory Society (ERS). The correlation between this classification and VTE risk was retrospectively analyzed. The risks of other clinicopathological features including pleural invasion, vascular invasion and associated surgical intervention risks were also assessed. RESULTS: Of the 952 patients, 100 (10.4%) cases experienced VTE events during the follow-up period. Among those with VTE, 28 (28%) were found before surgery, 47 (47%) were found within 1 month after surgery, and 91 (91%) were found in hospital. Univariate analysis revealed that ages, extent of resection and presence of micropapillary features were predictive of VTE risk. Furthermore, multivariable analysis demonstrated that the presence of micropapillary features (subdistribution hazard ratio [SHR] 1.560, 95% CI: 1.043-2.330) and age >60 (SHR: 2.270, 95% CI:1.491-3.470) were associated with increased risk of VTE. After one year, the probability of developing VTE was 13.1% and 8.3% in patients with micropapillary features and those without, respectively. CONCLUSIONS: VTE is a common complication for lung adenocarcinoma patients who undergo surgery, especially during the perioperative process and hospitalization. Presence of micropapillary subtype and age are positively associated with VTE risk.

14.
J Biol Chem ; 298(1): 101516, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34942145

RESUMO

The thymus is the central immune organ, but it is known to progressively degenerate with age. As thymus degeneration is paralleled by the wasting of aging skeletal muscle, we speculated that the thymus may play a role in muscle wasting. Here, using thymectomized mice, we show that the thymus is necessary for skeletal muscle regeneration, a process tightly associated with muscle aging. Compared to control mice, the thymectomized mice displayed comparable growth of muscle mass, but decreased muscle regeneration in response to injury, as evidenced by small and sparse regenerative myofibers along with inhibited expression of regeneration-associated genes myh3, myod, and myogenin. Using paired box 7 (Pax7)-immunofluorescence staining and 5-Bromo-2'-deoxyuridine-incorporation assay, we determined that the decreased regeneration capacity was caused by a limited satellite cell pool. Interestingly, the conditioned culture medium of isolated thymocytes had a potent capacity to directly stimulate satellite cell expansion in vitro. These expanded cells were enriched in subpopulations of quiescent satellite cells (Pax7highMyoDlowEdUpos) and activated satellite cells (Pax7highMyoDhighEdUpos), which were efficiently incorporated into the regenerative myofibers. We thus propose that the thymus plays an essential role in muscle regeneration by directly promoting satellite cell expansion and may function profoundly in the muscle aging process.

15.
J Biol Chem ; 298(1): 101536, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34954140

RESUMO

SEC23B is one of two vertebrate paralogs of SEC23, a key component of the coat protein complex II vesicles. Complete deficiency of SEC23B in mice leads to perinatal death caused by massive degeneration of professional secretory tissues. However, functions of SEC23B in postnatal mice and outside professional secretory tissues are unclear. In this study, we generated a Sec23b KO mouse and a knockin (KI) mouse with the E109K mutation, the most common human mutation in congenital dyserythropoietic anemia type II patients. We found that E109K mutation led to decreases in SEC23B levels and protein mislocalization. However, Sec23bki/ki mice showed no obvious abnormalities. Sec23b hemizygosity (Sec23bki/ko) was partially lethal, with only half of expected hemizygous mice surviving past weaning. Surviving Sec23bki/ko mice exhibited exocrine insufficiency, increased endoplasmic reticulum stress and apoptosis in the pancreas, and phenotypes consistent with chronic pancreatitis. Sec23bki/ko mice had mild to moderate anemia without other typical congenital dyserythropoietic anemia type II features, likely resulting from exocrine insufficiency. Moreover, Sec23bki/ko mice exhibited severe growth restriction accompanied by growth hormone (GH) insensitivity, reminiscent of Laron syndrome. Growth restriction is not associated with hepatocyte-specific Sec23b deletion, suggesting a nonliver origin of this phenotype. We propose that inflammation associated with chronic pancreatic deficiency may explain GH insensitivity in Sec23bki/ko mice. Our results reveal a genotype-phenotype correlation in SEC23B deficiency and indicate that pancreatic acinar is most sensitive to SEC23B deficiency in adult mice. The Sec23bki/ko mice provide a novel model of chronic pancreatitis and growth retardation with GH insensitivity.

16.
J Am Dent Assoc ; 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34952683

RESUMO

BACKGROUND: Aerosols are generated routinely during patient care in dentistry. Managing exposure risk requires understanding characteristics of aerosols created during procedures such as those performed using high-speed drills that operate at 200,000 revolutions per minute. METHODS: A trained dentist performed drilling procedures on a manikin's incisors (teeth nos. 8 and 9) using a high-speed drill and high-volume evacuator. The authors used high-speed imaging to visualize the formation and transport of aerosol clouds and particle sampling to measure aerosol concentration and size distribution at several locations. The authors studied several aerosol mitigation strategies. RESULTS: Aerosols produced during high-speed drilling were erratic and yielded high concentrations that were at least an order of magnitude above baseline. High-speed imaging showed aerosols initially travelled at 1 m per second. Owing to erratic behavior of aerosols, supplemental suction was not effective at collecting all aerosols; however, barriers were effective. CONCLUSIONS: Barriers are the most effective mitigation strategy. Other methods studied have limitations and risks. To the authors' knowledge, this article presents the first characterization of aerosols generated during high-speed drilling by a dentist. PRACTICAL IMPLICATIONS: With thorough preoperative planning and the use of this investigation's findings about effectiveness of mitigation strategies as a guide, dental offices may be able to return to prepandemic productivity.

17.
Sensors (Basel) ; 21(24)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34960290

RESUMO

The high-precision characterization of the intra-pixel sensitivity (IPS) for infrared focal plane array (FPA) photodetector is of great significance to high-precision photometry and astrometry in astronomy, as well as target tracking in under-sampled remote sensing images. The discrete sub-pixel response (DSPR) model and fill factor model have been used for IPS characterization in some studies. However, these models are incomplete and lack the description of physical process of charge diffusion and capacitance coupling, leading to the inaccuracy of IPS characterization. In this paper, we propose an improved IPS characterization method based on the diffusion and coupling physical (DCP) model for infrared FPA photodetector, which considering the processes of generation and collection of the charge, can improve the accuracy of IPS characterization. The IPS model can be obtained by convolving the ideal rectangular response function with the charge diffusion function and the capacitive coupling function. Then, the IPS model is convolved with the beam spot profile to obtain the beam spot scanning response model. Finally, we calculate the parameters of IPS by fitting the beam spot scanning response map with the proposed DCP model based on the Trust-Region-Reflective algorithm. Simulated results show that when using a 3 µm beam spot to scan, the error of IPS characterization based on DCP model is 0.63%, which is better than that of DSPR model's 3.70%. Experimental results show that the fitting error of the beam spot scan response model based on DCP model is 4.29%, which is better than that of DSPR model's 8.31%.

18.
Front Oncol ; 11: 768035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900717

RESUMO

Objectives: A new patient assistance program (PAP) for pembrolizumab was started in China in 2021. The researchers aimed to evaluate the economic outcomes of pembrolizumab plus pemetrexed and platinum versus chemotherapy alone in the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer, based on the pricing mechanism of PAP. Material and Methods: Survival analysis and partitioned survival model were performed to evaluate the incremental cost-effectiveness ratio (ICER) in the pembrolizumab group compared with the chemotherapy group. Survival probabilities were extracted from the data of the KEYNOTE-189 trial. Cost and utility data were gathered from published literature. The pricing mechanism of PAP was set in each cycle in the partitioned survival model, according to the progression-free survival (PFS) data of the KEYNOTE-189 trial, which included PFS-1 and PFS-2. Deterministic sensitivity analysis and probabilistic sensitivity analysis were conducted. Results: The ICER of the pembrolizumab group versus chemotherapy group was $65,272/quality-adjusted life year (QALY), which still exceeded the willingness-to-pay threshold of three times per capita gross domestic product (GDP) of China ($33,581.22), although PAP was calculated. Sensitivity analysis implied that the price of chemotherapeutic drugs combined with pembrolizumab was one of the main influencing factors of ICER. Conclusions: Due to various prices set by PAP and the payment for combined chemotherapy, the economic advantage of pembrolizumab plus chemotherapy in the first-line treatment of non-small cell lung cancer (NSCLC) is still not achieved in China.

19.
Mol Plant Pathol ; 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34962031

RESUMO

Sw-5b is an effective resistance gene used widely in tomato to control tomato spotted wilt virus (TSWV), which causes severe losses in crops worldwide. Sw-5b confers resistance by recognizing a 21-amino-acid peptide region of the viral movement protein NSm (NSm21, amino acids 115-135). However, C118Y or T120N mutation within this peptide region of NSm has given rise to field resistance-breaking (RB) TSWV isolates. To investigate the potential ability of TSWV to break Sw-5b-mediated resistance, we mutagenized each amino acid on NSm21 and determined which amino acid mutations would evade Sw-5b recognition. Among all alanine-scan mutants, NSmP119A , NSmW121A , NSmD122A , NSmR124A , and NSmQ126A failed to induce a hypersensitive response (HR) when coexpressed with Sw-5b in Nicotiana benthamiana leaves. TSWV with the NSmP119A , NSmW121A , or NSmQ126A mutation was defective in viral cell-to-cell movement and systemic infection, while TSWV carrying the NSmD122A or NSmR124A mutation was not only able to infect wild-type N. benthamiana plants systemically but also able to break Sw-5b-mediated resistance and establish systemic infection on Sw-5b-transgenic N. benthamiana plants. Two improved mutants, Sw-5bL33P/K319E/R927A and Sw-5bL33P/K319E/R927Q , which we recently engineered and which provide effective resistance against field RB isolates carrying NSmC118Y or NSmT120N mutations, recognized all NSm21 alanine-substitution mutants and conferred effective resistance against new experimental RB TSWV with the NSmD122A or NSmR124A mutation. Collectively, we determined the key residues of NSm for Sw-5b recognition, investigated their potential RB ability, and demonstrated that the improved Sw-5b mutants could provide effective resistance to both field and potential RB TSWV isolates.

20.
Front Oncol ; 11: 767116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926270

RESUMO

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients. Chemical Compounds Studied in this Article: Rutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).

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