Publications by authors named "Yao Zhang"

1,741 Publications

  • Page 1 of 1

Upregulation of KLHL17 promotes the proliferation and migration of non-small cell lung cancer by activating the Ras/MAPK signaling pathway.

Lab Invest 2022 Aug 17. Epub 2022 Aug 17.

Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, China.

Analysis of the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed that Kelch-like 17 (KLHL17) is overexpressed in non-small cell lung cancer (NSCLC) including adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We therefore explored the role of KLHL17 in the development and progression of NSCLC. Immunohistochemistry and western blotting showed that KLHL17 expression was significantly higher in the tumor tissues from 173 patients with NSCLC, compared with the corresponding non-neoplastic tissue. In addition, upregulated KLHL17 expression was positively correlated with tumor size, lymph node metastasis and tumor node metastasis (TNM) stage, and affected the overall survival (OS) of patients with NSCLC. Consistent with clinical samples, in vitro studies demonstrated that KLHL17 expression was higher in various cell lines of NSCLC (A549, H1299, H460 and SK cells) as compared to normal human bronchial epithelial cells (HBE cells). Overexpression of KLHL17 in the cell lines of NSCLC with KLHL17-Flag plasmid promoted the proliferation and migration of tumor cells, which was associated with elevated activation of Rat sarcoma/Mitogen-activated protein kinases (Ras/MAPK) signaling and increased expression of cyclin D1, cyclin D-dependent kinases 4 (CDK4), matrix metalloproteinase 2 (MMP2) and Ras homolog gene family member A (RhoA). In contrast, knockdown of KLHL17 in the cell lines of NSCLC using KLHL17 small interfering RNA suppressed the proliferation and migration of tumor cells, in association with reduced activation of Ras/MAPK signaling and decreased expression of cyclin D1, CDK4, MMP2 and RhoA. Moreover, treatment of tumor cells with Ras inhibitor salirasib prevented KLHL17-induced Ras/MAPK activity as well as tumor proliferation and migration. These results suggest that upregulated KLHL17 in NSCLC promotes the proliferation and migration of tumor by activating Ras/MAPK signaling pathway. Therefore, KLHL17 may be a novel therapeutic target for the treatment of NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41374-022-00806-7DOI Listing
August 2022

Characteristics of OGTT and Correlation Between the Insulin to C-Peptide Molar Ratio, HOMA-IR, and Insulin Antibodies in T2DM Patients.

Diabetes Metab Syndr Obes 2022 9;15:2417-2425. Epub 2022 Aug 9.

Department of Endocrinology, Xiang' an Hospital of Xiamen University, Xiamen, Fujian, People' s Republic of China.

Purpose: The purpose of our study was to analyze the characteristics of OGTT and the correlation between the insulin to C-peptide molar ratio (ICPR), HOMA-IR and insulin antibodies (IAs) in T2DM patients.

Patients And Methods: A total of 77 T2DM patients were included and divided into the IA+ group (25 patients) and IA- group (52 patients). The values of serum glucose, insulin, and C-peptide testing during 2-h OGTT were summarized comparatively, and ROC was made to analyze the predictive value of ICPR for IAs.

Results: At each time point of OGTT, there was no significant difference in serum glucose and C-peptide changes (p>0.05). Serum insulin levels in positive patients were elevated or not at different time points of the OGTT but ICPR was significantly different (P<0.05) in the two groups. Spearman correlation coefficient analysis showed that the presence of insulin antibodies was correlated with ICPR, but not with HOMA-IR, and ICPR-2h had a better prediction capacity (AUC=0.735, the optimal cutoff-point=0.11, Se=0.760, Sp=0.635).

Conclusion: T2DM patients with IAs showed no difference in serum glucose and serum C-peptide changes, but elevated or not insulin levels on the OGTTs, compared with negative patients. ICPR-2h can be a preliminary diagnostic index to timely predict IAs in T2DM patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/DMSO.S373475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9375563PMC
August 2022

Adaptation process of engineered cell line FCHO/IL-24 stably secreted rhIL-24 in serum-free suspension culture.

Protein Expr Purif 2022 Aug 12;199:106154. Epub 2022 Aug 12.

College of Life Science and Bioengineering, Beijing Jiaotong University, No 3 Shangyuancun, Beijing, 100044, PR China. Electronic address:

Interleukin-24 (IL-24) displays tumor cell-specific proliferation inhibition in vitro and in vivo. Recombinant human IL-24 (rhIL-24) has significantly higher activity, yet significantly lower expression level in mammalian cells than in bacteria. To further realize therapeutic potential of IL-24, we enhanced rhIL-24 expression in mammalian cell systems by adapting engineered Flp-InCHO/IL-24 (FCHO/IL-24) cells (adherent cultured in Ham's F12 medium with 10% serum) to serum-free suspension culture. First, MTT assay showed that among four different media (F12, DMEM/F12, 1640 and DMEM), DMEM/F12 medium was the most suitable media for lower-serum adherent culture. Then, cells were adherently cultured in DMEM/F12 with serum concentration reduced from 10% to 0.5% in a gradient manner. Compared to cells in 10% serum, cells in 0.5% serum displayed significantly lower relative cell viability by 40%, increased G0/G1 phase arrest (8.5 ± 2.4%, p < 0.05), decreased supernatant rhIL-24 concentration by 73%, and altered metabolite profiles, such as glucose, lactate and ammonia concentration. Next, the cells were directly adapted to 0.5% serum suspension culture in 125 mL shake flask at 119 rpm with the optimal cell seeding density of 5 × 10 cells/mL (3.3 times higher than that of adherent culture), under which the concentration of rhIL-24 in culture medium was stable at 3.5 ng/mL. Finally, cells adapted to 0.5% serum proliferated better in serum-free medium Eden™-B300S with higher rhIL-24 expression level compared to CDM4CHO. The successful adaptation of engineered cells FCHO/IL-24 laid foundation for adapting cells from adherent culture to suspension serum-free culture to mass produce rhIL-24 protein for therapeutic purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pep.2022.106154DOI Listing
August 2022

Associations of exposure to multiple metals with blood pressure and hypertension: A cross-sectional study in Chinese preschool children.

Chemosphere 2022 Aug 11;307(Pt 3):135985. Epub 2022 Aug 11.

Department of Endocrinology, Renmin Hospital, Hubei University of Medicine, Shiyan, 44200, China; Center for Environment and Health in Water Source Area of South-to-North Water Diversion, Hubei University of Medicine, 30 Renmin South Road, Shiyan, 442000, Hubei, China. Electronic address:

Exposure to metals might be a risk factor for hypertension, which contributes largely to the global burden of disease and mortality. However, relevant epidemiological studies of associations between metals exposure with hypertension among preschoolers are limited. This study aimed to explore the associations of urine metals with blood pressure and hypertension among Chinese preschoolers. A total of 1220 eligible participants who had urine metals measurement, blood pressure measurements, and relevant covariates were included in this cross-sectional study. Urine concentrations of metals were measured by inductively coupled plasma mass spectrometer. The single and multiple metals regression models were used to investigate the associations of urine metal with blood pressure and the risk of hypertension after adjusting for potential confounders. We observed urine concentrations of chromium, iron, and barium were negatively associated with levels of systolic blood pressure, diastolic blood pressure and the risk of hypertension in the single metal model (all P-FDR adjustment <0.05). Significant associations of urine chromium concentrations with systolic blood pressure, diastolic blood pressure and the risk of hypertension were found in the multi-metal model (β or OR (95% confidence interval) was -3.07 (-5.12, -1.02), -2.25 (-4.29, -0.22), and 0.51 (0.26, 0.97) for 3rd quartile, compared with 1st quartile, respectively). The same association was found for barium concentrations in the multi-metal model, while none of the associations among iron quartiles was significant. In addition, urine chromium, iron and barium may have joint effects on systolic blood pressure, diastolic blood pressure and hypertension. Children's age and body mass index could modify the associations of chromium, iron, and barium concentrations with blood pressure. Our findings suggested that exposure to chromium, iron, and barium was inversely associated with blood pressure and hypertension among preschool children. These findings need further validation in prospective studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2022.135985DOI Listing
August 2022

Copper functionalized poly (acrylic acid-co-itaconic acid) nanohydrogel: Its antibacterial properties on oral pathogens and biocompatibility.

Colloids Surf B Biointerfaces 2022 Jul 30;218:112741. Epub 2022 Jul 30.

Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China. Electronic address:

Although extensive efforts have been made to explore effective antibiotics, the development of antibiotics lags far behind the emergence of drug-resistant bacteria. Antimicrobial materials as an alternative strategy provide effective functions in aiding in relieving the dose of antibiotics. Herein, we report a novel antibacterial agent with high antibacterial effectivity and low toxicity, which is simply composed of a trace amount of Cu ion and nanoscale biocompatible polymer poly (acrylic acid-co-itaconic acid) (PAI-Cu). The polymer shows greatly enhanced antibacterial activity against various Gram-positive and Gram-negative pathogens compared with equal concentrations of copper ion solution, yet shows nearly no toxicity towards human cells. The antibacterial performance and mechanism of copper ionized polymer hydrogel are evaluated in terms of multiple methods, towards various oral bacteria including Streptococcus mutans, Enterococcus faecalis, Lactobacillus acidophilus, Actinomycetes viscosus, Porphyromonas gingivalis, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, and Prevotella intermedia. Bacterial cell membrane and wall damage caused by PAI-Cu nanohydrogel should be regarded as an important antibacterial mechanism. Moreover, PAI-Cu nanohydrogel, as the role of catalytic active center, can activate the surrounding oxygen, and generate hydroxyl radical (·OH), which can destroy the proliferation ability of microbial cells. We suggest that PAI-Cu nanohydrogel is a promising antibacterial agent against dental pathogens and beyond.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2022.112741DOI Listing
July 2022

Efficacy and safety of nasal intermittent positive pressure ventilation and nasal continuous positive airway pressure ventilation in neonatal respiratory distress syndrome: a systematic review and meta-analysis.

Transl Pediatr 2022 Jul;11(7):1242-1250

Neonatal Department, Haikou Maternal and Child Health Hospital, Haikou, China.

Background: The efficacies of nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV) in neonatal respiratory distress syndrome (RDS) are controversial. The reasons for controversy may be the selection bias of research objects and the small sample size.

Methods: Literature retrieval was performed in PubMed, EMBASE, Medline, Central, China National Knowledge Infrastructure (CNKI), Wanfang and China Science Digital Library (CSDL) databases. Inclusion criteria: (I) literatures involving subjects who were newborns with RDS; (II) studies that had established both experimental and control groups; (III) the intervention measures of the experimental and control groups were NIPPV and NCPAP, respectively; (IV) the results included the incidence of intubation, bronchopulmonary dysplasia (BPD), or mortality; and (V) randomized controlled trials (RCTs). The chi-square test was applied for heterogeneity test. Publication bias assessment was conducted by funnel plot and Egger's test. The revised Cochrane risk of bias tool for individually randomized, parallel group trials (RoB2.0) was used to evaluate the risk of bias of the included RCT research.

Results: A total of 10 literatures were included for analysis, including 1,104 patients, 557 in the NIPPV group and 547 in the NCPAP group. Among the literatures, 2 literatures had low risk of bias, 2 literatures had high risk of bias, and the rest had uncertain risk of bias. Compared to NCPAP, NIPPV reduced the incidence of neonatal intubation in RDS [risk ratio (RR) =0.57, 95% confidence interval (CI): 0.46-0.71, Z=5.11, P<0.00001]. There was no statistically significant heterogeneity (P=0.13, I=36%) or publication bias (P<0.05) among the studies. Compared with NCPAP, NIPPV reduced the incidence of BPD in RDS (RR =0.72, 95% CI: 0.57-0.91, Z=2.70, P=0.007). There was no statistically significant heterogeneity (P=0.10, I=41%) or publication bias (P>0.05) among the studies. NIPPV reduced the neonatal mortality rate of RDS (RR =0.55, 95% CI: 0.31-0.97, Z=2.08, P=0.04). There was no statistically significant heterogeneity (P=0.20, I=38%) or publication bias (P>0.05) among the studies.

Discussion: Compared with NCPAP, NIPPV can reduce the incidence of intubation, BPD, and mortality. The conclusions need to be confirmed via high-quality RCTs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tp-22-288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360829PMC
July 2022

Inferior and Coordinate Distillation for Object Detectors.

Sensors (Basel) 2022 Jul 30;22(15). Epub 2022 Jul 30.

School of Command and Control Engineering, Army Engineering University of PLA, Nanjing 210007, China.

Current distillation methods only distill between corresponding layers, and do not consider the knowledge contained in preceding layers. To solve this problem, we analyzed the guiding effect of the inferior features of a teacher model on the coordinate feature of a student model, and proposed inferior and coordinate distillation for object detectors. The proposed method utilizes the rich information contained in different layers of the teacher model; such that the student model can review the old information and learn the new information, in addition to the dark knowledge in the teacher model. Moreover, the refine module is used to align the features of different layers, distinguish the spatial and channel to extract attention, strengthen the correlation between the features of different stages, and prevent the disorder caused by merging. Exclusive experiments were conducted on different object detectors. The results for the mean average precision (mAP) obtained using Faster R-CNN, RetinaNet, and fully convolutional one-stage object detector (FCOS) with ResNet-50 as its backbone were 40.5%, 39.8%, and 42.8% with regard to the COCO dataset, respectively; which are 2.1%, 2.4%, and 4.3% higher than the benchmark, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s22155719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9370902PMC
July 2022

Identification of Estradiol Benzoate as an Inhibitor of HBx Using Inducible Stably Transfected HepG2 Cells Expressing HiBiT Tagged HBx.

Molecules 2022 Aug 6;27(15). Epub 2022 Aug 6.

Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Department of Infectious Diseases, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.

HBx plays a significant role in the cccDNA epigenetic modification regulating the hepatitis B virus (HBV) life cycle and in hepatocyte proliferation and carcinogenesis. By using the sleeping-beauty transposon system, we constructed a tetracycline-induced HBx-expressing stable cell line, SBHX21. HBx with a HiBiT tag can be quickly detected utilizing a NanoLuc-based HiBiT detection system. By screening a drug library using SBHX21 cells, we identified estradiol benzoate as a novel anti-HBx agent. Estradiol benzoate also markedly reduced the production of HBeAg, HBsAg, HBV pgRNA, and HBV DNA in a dose-dependent manner, suggesting that estradiol benzoate could be an anti-HBV agent. Docking model results revealed that estradiol benzoate binds to HBx at TRP87 and TRP107. Collectively, our results suggest that estradiol benzoate inhibits the HBx protein and HBV transcription and replication, which may serve as a novel anti-HBV molecular compound for investigating new treatment strategies for HBV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules27155000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9370419PMC
August 2022

Gga-miR-146b-3p promotes apoptosis and attenuate autophagy by targeting AKT1 in chicken granulosa cells.

Theriogenology 2022 Aug 3;190:52-64. Epub 2022 Aug 3.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China.

The normal development of follicles determines the reproductive performance of females. Granulosa cells (GC) play crucial roles in follicular maturation. Numerous studies have shown that miRNAs are involved in the regulation of GC. According to our previous sequencing data, gga-miR-146b-3p was differentially expressed in normal and atretic chicken follicles. In this study, we verified that gga-miR-146b-3p attenuated proliferation and autophagy but promoted apoptosis in chicken GC. Threonine kinase1 (AKT1), a key member of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, was predicted to be a target gene of gga-miR-146b-3p via bioinformatic analysis. Dual-luciferase reporter gene assays were used to determine target relationships. Moreover, knockout of AKT1 decelerated proliferation and autophagy while accelerating the apoptosis of GC. However, overexpression of AKT1 reversed these results. In summary, our results demonstrated that gga-miR-146b-3p repressed the proliferation and autophagy of chicken GC while up-regulating apoptosis by targeting AKT1 through the PI3K/AKT signaling pathway. These findings may provide great insights for further exploration of the molecular regulation of gga-miR-146b-3p and AKT1 on the functions of GC during folliculogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.theriogenology.2022.07.019DOI Listing
August 2022

Observation of a State X(2600) in the π^{+}π^{-}η' System in the Process J/ψ→γπ^{+}π^{-}η'.

Phys Rev Lett 2022 Jul;129(4):042001

Institute of High Energy Physics, Beijing 100049, People's Republic of China.

Based on (10087±44)×10^{6}  J/ψ events collected with the BESIII detector, the process J/ψ→γπ^{+}π^{-}η^{'} is studied using two largest decay channels of the η^{'} meson, η^{'}→γπ^{+}π^{-} and η^{'}→ηπ^{+}π^{-}, η→γγ. A new resonance, which we denote as the X(2600), is observed with a statistical significance larger than 20σ in the π^{+}π^{-}η^{'} invariant mass spectrum, and it has a connection to a structure around 1.5  GeV/c^{2} in the π^{+}π^{-} invariant mass spectrum. A simultaneous fit on the π^{+}π^{-}η^{'} and π^{+}π^{-} invariant mass spectra with the two η^{'} decay modes indicates that the mass and width of the X(2600) state are 2618.3±2.0_{-1.4}^{+16.3}  MeV/c^{2} and 195±5_{-17}^{+26}  MeV, where the first uncertainties are statistical, and the second systematic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevLett.129.042001DOI Listing
July 2022

The CRTC-CREB axis functions as a transcriptional sensor to protect against proteotoxic stress in Drosophila.

Cell Death Dis 2022 Aug 6;13(8):688. Epub 2022 Aug 6.

Yangzhi Rehabilitation Hospital, Sunshine Rehabilitation Center, School of Life Sciences and Technology, Tongji University, Shanghai, 20092, China.

cAMP Responsible Element Binding Protein (CREB) is an evolutionarily conserved transcriptional factor that regulates cell growth, synaptic plasticity and so on. In this study, we unexpectedly found proteasome inhibitors, such as MLN2238, robustly increase CREB activity in adult flies through a large-scale compound screening. Mechanistically, reactive oxidative species (ROS) generated by proteasome inhibition are required and sufficient to promote CREB activity through c-Jun N-terminal kinase (JNK). In 293 T cells, JNK activation by MLN2238 is also required for increase of CREB phosphorylation at Ser. Meanwhile, transcriptome analysis in fly intestine identified a group of genes involved in redox and proteostatic regulation are augmented by overexpressing CRTC (CREB-regulated transcriptional coactivator). Intriguingly, CRTC overexpression in muscles robustly restores protein folding and proteasomal activity in a fly Huntington's disease (HD) model, and ameliorates HD related pathogenesis, such as protein aggregates, motility, and lifespan. Moreover, CREB activity increases during aging, and further enhances its activity can suppress protein aggregates in aged muscles. Together, our results identified CRTC/CREB downstream ROS/JNK signaling as a conserved sensor to tackle oxidative and proteotoxic stresses. Boosting CRTC/CREB activity is a potential therapeutic strategy to treat aging related protein aggregation diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-022-05122-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357022PMC
August 2022

Dietary supplementation of salidroside alleviates liver lipid metabolism disorder and inflammatory response to promote hepatocyte regeneration via PI3K/AKT/Gsk3-β pathway.

Poult Sci 2022 Jun 28;101(9):102034. Epub 2022 Jun 28.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, P. R. China. Electronic address:

Fatty liver hemorrhagic syndrome (FLHS) is a chronic hepatic disease which occurs when there is a disorder in lipid metabolism. FLHS is often observed in caged laying hens and characterized by a decrease in egg production and dramatic increase of mortality. Salidroside (SDS) is an herbal drug which has shown numerous pharmacological activities, such as protecting mitochondrial function, attenuating cell apoptosis and inflammation, and promoting antioxidant defense system. We aimed to determine the therapeutic effects of SDS on FLHS in laying hens and investigate the underlying mechanisms through which SDS operates these functions. We constructed oleic acid (OA)-induced fatty liver model in vitro and high-fat diet-induced FLHS of laying hens in vivo. The results indicated that SDS inhibited OA-induced lipid accumulation in chicken primary hepatocytes, increased hepatocyte activity, elevated the mRNA expression of proliferation related genes PCNA, CDK2, and cyclinD1 and increased the protein levels of PCNA and CDK2 (P < 0.05), as well as decreased the cleavage levels of Caspase-9, Caspase-8, and Caspase-3 and apoptosis in hepatocytes (P < 0.05). Moreover, SDS promoted the phosphorylation levels of PDK1, AKT, and Gsk3-β, while inhibited the PI3K inhibitor (P < 0.05). Additionally, we found that high-fat diet-induced FLHS hens had heavier body weight, liver weight, and abdominal fat weight, and severe steatosis in histology, compared with the control group (Con). However, hens fed with SDS maintained lighter body weight, liver weight, and abdominal fat weight, as well as normal liver without hepatic steatosis. In addition, high-fat diet-induced FLHS hens had high levels of serum total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), and aspartate aminotransferase (AST) compared to the Con group, however, in the Model+SDS group, the levels of TC, TG, ALT, and AST decreased significantly, whereas the level of superoxide dismutase (SOD) increased significantly (P < 0.05). We also found that SDS significantly decreased the mRNA expression abundance of PPARγ, SCD, and FAS in the liver, as well as increased levels of PPARα and MTTP, and decreased the mRNA expression of TNF-α, IL-1β, IL-6, and IL-8 in the Model+SDS group (P < 0.05). In summary, this study showed that 0.3 mg/mL SDS attenuated ROS generation, inhibited lipid accumulation and hepatocyte apoptosis, and promoted hepatocyte proliferation by targeting the PI3K/AKT/Gsk3-β pathway in OA-induced fatty liver model in vitro, and 20 mg/kg SDS alleviated high-fat-diet-induced hepatic steatosis, oxidative stress, and inflammatory response in laying hens in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2022.102034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356167PMC
June 2022

Optothermally Programmable Liquids with Spatiotemporal Precision and Functional Complexity.

Adv Mater 2022 Aug 2:e2205563. Epub 2022 Aug 2.

South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou, 510640, China.

Due to the intrinsic lack of spatial order and self-supported shape, liquids are often incompatible with precision manufacturing/processing and are potentially limited for advanced functionality. Herein, we develop an optothermal strategy to fully command phase-separated liquids with unprecedent spatiotemporal addressability. Specifically, we focus a laser onto an Au film to create a hot spot that locally demixes a temperature-responsive solution to produce a single optothermal droplet. Spatial precision (∼ 1 micron) is assured by the well-defined thermal field and temporal accuracy (∼ 0.1 s) guaranteed by the fast heating and response rate. Time-multiplexed laser foci are deployed to engineer the thermal landscape as desired, which in turn dictates the formation/dissolution, positioning, shaping, and dynamic reconfiguration of the phase-separated liquids. We further program laser foci to orchestrate the liquid patterns in a time-continuous manner to produce liquid animations on the microscale with high fidelity. While focused laser has been routinely used to manipulate solid particles or to microfabricate solid materials, the current strategy embraces the merits of liquid and features functional complexity in information encryption, payload transportation, and reaction localization. We expect it to be further applicable in scenarios such as subcellular organization of biomolecular condensates and programmable modulation of nonequilibrium systems. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202205563DOI Listing
August 2022

P301S-hTau acetylates KEAP1 to trigger synaptic toxicity via inhibiting NRF2/ARE pathway: A novel mechanism underlying hTau-induced synaptic toxicities.

Clin Transl Med 2022 Aug;12(8):e1003

Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Human Tau (hTau) accumulation and synapse loss are two pathological hallmarks of tauopathies. However, whether and how hTau exerts toxic effects on synapses remain elusive.

Methods: Mutated hTau (P301S) was overexpressed in the N2a cell line, primary hippocampal neurons and hippocampal CA3. Western blotting and quantitative polymerase chain reaction were applied to examine the protein and mRNA levels of synaptic proteins. The protein interaction was tested by co-immunoprecipitation and proximity ligation assays. Memory and emotion status were evaluated by a series of behavioural tests. The transcriptional activity of nuclear factor-erythroid 2-related factor 2 (NRF2) was detected by dual luciferase reporter assay. Electrophoresis mobility shift assay and chromosome immunoprecipitation were conducted to examine the combination of NRF2 to specific anti-oxidative response element (ARE) sequences. Neuronal morphology was analysed after Golgi staining.

Results: Overexpressing P301S decreased the protein levels of post-synaptic density protein 93 (PSD93), PSD95 and synapsin 1 (SYN1). Simultaneously, NRF2 was decreased, whereas Kelch-like ECH-associated protein 1 (KEAP1) was elevated. Further, we found that NRF2 could bind to the specific AREs of DLG2, DLG4 and SYN1 genes, which encode PSD93, PSD95 and SYN1, respectively, to promote their expression. Overexpressing NRF2 ameliorated P301S-reduced synaptic proteins and synapse. By means of acetylation at K312, P301S increased the protein level of KEAP1 via inhibiting KEAP1 degradation from ubiquitin-proteasome pathway, thereby decreasing NRF2 and reducing synapse. Blocking the P301S-KEAP1 interaction at K312 rescued the P301S-suppressed expression of synaptic proteins and memory deficits with anxiety efficiently.

Conclusions: P301S-hTau could acetylate KEAP1 to trigger synaptic toxicity via inhibiting the NRF2/ARE pathway. These findings provide a novel and potential target for the therapeutic intervention of tauopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ctm2.1003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345400PMC
August 2022

Identification of OSCA gene family in Solanum habrochaites and its function analysis under stress.

BMC Genomics 2022 Aug 1;23(1):547. Epub 2022 Aug 1.

College of Horticulture and Landscape Architecture, Northeast Agricultural University, Harbin, 150030, China.

Background: OSCA (hyperosmolality-gated calcium-permeable channel) is a calcium permeable cation channel protein that plays an important role in regulating plant signal transduction. It is involved in sensing changes in extracellular osmotic potential and an increase in Ca concentration. S. habrochaites is a good genetic material for crop improvement against cold, late blight, planthopper and other diseases. Till date, there is no report on OSCA in S. habrochaites. Thus, in this study, we performed a genome-wide screen to identify OSCA genes in S. habrochaites and characterized their responses to biotic and abiotic stresses.

Results: A total of 11 ShOSCA genes distributed on 8 chromosomes were identified. Subcellular localization analysis showed that all members of ShOSCA localized on the plasma membrane and contained multiple stress-related cis acting elements. We observed that genome-wide duplication (WGD) occurred in the genetic evolution of ShOSCA5 (Solhab04g250600) and ShOSCA11 (Solhab12g051500). In addition, repeat events play an important role in the expansion of OSCA gene family. OSCA gene family of S. habrochaites used the time lines of expression studies by qRT-PCR, do indicate OSCAs responded to biotic stress (Botrytis cinerea) and abiotic stress (drought, low temperature and abscisic acid (ABA)). Among them, the expression of ShOSCAs changed significantly under four stresses. The resistance of silencing ShOSCA3 plants to the four stresses was reduced.

Conclusion: This study identified the OSCA gene family of S. habrochaites for the first time and analyzed ShOSCA3 has stronger resistance to low temperature, ABA and Botrytis cinerea stress. This study provides a theoretical basis for clarifying the biological function of OSCA, and lays a foundation for tomato crop improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-022-08675-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341080PMC
August 2022

Comprehensive analysis of differently expression mRNA and non-coding RNAs, and their regulatory mechanisms on relationship in thiram-induced tibial dyschondroplasia in chicken.

Ecotoxicol Environ Saf 2022 Jul 28;242:113924. Epub 2022 Jul 28.

Key Laboratory of Livestock and Poultry Multi-omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology (Institute of Animal Genetics and Breeding), Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China. Electronic address:

Thiram pollution is one of the main causes of tibial dyschondroplasia (TD) induced by feed sources. Several studies have speculated that miRNA, circRNA and lncRNA may have significant impact on the development of TD, however, the specific mRNAs and noncoding RNAs and their respective regulatory mechanisms and functions in the development of TD have not been explored. Therefore, in this present study, we screened the differentially expressed mRNA, miRNA, circRNA and lncRNA by whole-transcriptome sequencing (RNA-seq) and differentially expressed genes (DEGs) enrichment, as well as constructed the interaction network among the mRNA-miRNA, mRNA-lncRNA and mRNA-miRNA-circRNA. The sequencing results were verified by fluorescence real-time quantitative PCR (RT-qPCR). The results obtained in this study, revealed that the cells were atrophied and disordered in the TD group, and the expression of BMP6, TGF-β and VEGF were significantly reduced. A total of 141 mRNAs, 10 miRNAs, 23 lncRNAs and 35 circRNAs of DEGs were obtained (p<0.05) Theses DEGs were enriched in the adhere junction and insulin signaling pathways. In addition, the mRNA-miRNA-circRNA network suggested that several pivotal ceRNA showed a regulatory relationship between the transcripts with miRNA, circRNA or lncRNA. Taken together, the results in the present study, represent an insight for further functional research on the ceRNA regulatory mechanism of TD in broilers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2022.113924DOI Listing
July 2022

The interplay between small vessel disease and Parkinson disease pathology: A longitudinal study.

Eur J Radiol 2022 Jul 21;154:110441. Epub 2022 Jul 21.

Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Background: Cerebral small vessel disease (SVD) related brain changes have been found associated with various clinical symptoms of Parkinson disease (PD). On the other hand, PD pathology and treatment may also accelerate SVD progression.

Objective: The aim of this study is to explore the interplay between SVD and PD pathology using longitudinal dataset.

Methods: We screened 66 healthy controls (HCs) and 114 patients from the Parkinson Progression Markers Initiative (PPMI) database. The peak width of skeletonized mean diffusivity (PSMD) was quantified from diffusion tensor images to reflect vascular pathologies at baseline and 24 months follow-up, and dopamine transporter (DAT) imaging data was used to represent the extent of dopaminergic neuronal degeneration at the same point time. We compared the PSMD between PD patients and HCs, and analyzed whether PSMD and DAT availability could predict each other's progression using multiple regression analyses in PD patients.

Results: PSMD at baseline had no significant difference between the HCs and patients with PD (P = 0.169). Higher baseline PSMD was associated with less DAT reduction in the caudate (β = 0.216, P = 0.029), but not the putamen (β = 0.058, P = 0.552) in PD patients. Baseline caudate and putamen DAT availability had no significant association with PSMD progression (β = -0.006, P = 0.950; β = 0.017, P = 0.860, respectively).

Conclusions: Mild SVD might slow down PD pathology progression, while the effect of PD pathology on the progression of SVD was not significant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2022.110441DOI Listing
July 2022

Associations of Serum Vitamin B6 Status and Catabolism With All-Cause Mortality in Patients With T2DM.

J Clin Endocrinol Metab 2022 Jul 30. Epub 2022 Jul 30.

Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Nangang, 150001, China.

Context: There is little evidence regarding the association between serum vitamin B6 status and catabolism and all-cause mortality in patients with type-2 diabetes mellitus (T2DM).

Objective: We aimed to ascertain if the serum level of vitamin B6 and catabolism, including pyridoxal 5'-phosphate (PLP) and 4-pyridoxic acid (4-PA), were associated with risk of all-cause mortality in T2DM patients.

Methods: This prospective cohort study involved 2574 patients with T2DM who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The serum concentrations of PLP and 4-PA were used to assess the serum level of vitamin B6. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015.

Results: Over a median follow-up of 85 months, there were 588 deaths. The fully adjusted Cox model indicated that the highest serum PLP concentrations (> 63.6 nmol/L) were associated with a decrease in all-cause mortality (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99, P trend = .035). The risk for all-cause mortality was 59% higher for participants with the highest quartile of 4-PA level compared with the lowest quartile (HR, 1.62; 95% CI, 1.12-2.35; P trend = .003). The sensitivity and specificity of the combination of PLP and 4-PA levels for the prediction of all-cause mortality were 59.5% and 60.9%, respectively (area under the receiver operating characteristic curve = 0.632). The Kaplan-Meier method was used to estimate overall survival for patients based on different combinations of PLP level and 4-PA level. Patients with PLP less than 24.3 nmol/L and 4-PA greater than or equal to 25.4 nmol/L had the worst outcomes (log-rank P < .001).

Conclusion: Overall, our data suggest that a low serum level of PLP and high serum level of 4-PA, which represent the serum level of vitamin B6, increases the risk of all-cause mortality significantly in patients with T2DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgac429DOI Listing
July 2022

GPR12 Inhibits Apoptosis in Epithelial Ovarian Cancer the Activation of ERK1/2 Signaling.

Front Oncol 2022 12;12:932689. Epub 2022 Jul 12.

Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, China.

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological malignancies in women worldwide. G protein-coupled receptor 12 (GPR12) is a member of G protein-coupled receptors (GPCRs) and plays an important role in the regulation of cell proliferation and survival. However, its role in EOC is underappreciated. In this study, we found that GPR12 is highly expressed in the EOC tissues and can be an ideal biomarker to predict the prognosis of patients with EOC. GPR12 knockdown obviously inhibits the proliferation of EOC cells by inducing cellular apoptosis and . Meanwhile, bioinformatic analysis showed that the inhibitory effect of GPR12 knockdown on the cell viability is closely related with Extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, which has been confirmed by the fact that the activity of ERK1/2 pathway has been significantly blocked in the GPR12 knockdown cells. LM22B-10, ERK1/2 pathway activator, could reverse the inhibited proliferation caused by GPR12 knockdown in the EOC cells. Our findings suggest that GPR12 is involved in the EOC process and is a potential therapeutic target for EOC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2022.932689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316591PMC
July 2022

MiR-128-3p inhibits high-glucose-induced peritoneal mesothelial cells fibrosis via PAK2/SyK/TGF-β1 axis.

Ther Apher Dial 2022 Jul 28. Epub 2022 Jul 28.

Department of Nephrology and Laboratory of Kidney Disease, Hunan Provincial People' s Hospital, First Affiliated Hospital of Hunan Normal University, Changsha Clinical Research Center for Kidney Disease, Hunan Clinical Research Center for Chronic Kidney Disease, Changsha, Hunan Province, China.

Aim: To elucidate the mechanism of miR-128-3p in peritoneal fibrosis (PF).

Methods: Peritoneal mesothelial cells (PMCs) were dealt with high-glucose for three days. The expressions of miR-128-3p, PAK2, SyK and TGF-β1 were detected with qRT-PCR. The levels of IL-1β, TNF-α, IL-6, and MCP-1 in supernatant were measured by ELISA. Proteins of TGF-β1, SyK, PAK2, α-SMA, Collagen I, vimentin, ERK/AP-1, and IκBα/NF-κB pathway related proteins were measured by Western blot. The correlation between miR-128-3p and PAK2 was found by bioinformatics analysis and luciferase reporter gene analysis.

Results: miR-128-3p was decreased while PAK2, SyK and TGF-β1 were increased in high-glucose-induced PMCs. Moreover, miR-128-3p inhibited high-glucose-induced fibrosis and inflammation in PMCs by targeting PAK2. PAK2 activated SyK, which induced TGF-β1 expression through ERK/AP-1 and IκBα/NF-κB pathways to promote high-glucose-induced fibrosis of PMCs.

Conclusion: miR-128-3p inhibited high-glucose-induced PMCs fibrosis via PAK2/SyK/TGF-β1 axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1744-9987.13912DOI Listing
July 2022

Vonoprazan vs. lansoprazole for the treatment of endoscopic submucosal dissection induced gastric ulcer: a systematic review and meta-analysis.

Rev Esp Enferm Dig 2022 Jul 28. Epub 2022 Jul 28.

Shaanxi Hospital of Traditional Chinese Medicine, China.

Background: Vonoprazan is a potassium competitive acid blocker (P-CAB) approved in Japan in 2014 to treat endoscopic submucosal dissection (ESD)-induced ulcer and bleeding perforation, and this meta-analysis is to compare whether Vonoprazan is more effective than lansoprazole in the treatment of ESD-induced ulcers (including ulcer healing , shrinking rate and so on).

Methods: Collected randomized controlled trials (RCT) and retrospective studies from the PubMed (Medline), Embase, Web of science, and Cochrane Library databases that discussed the effectiveness of Vonoprazan and lansoprazole on ESD-induced ulcers. Studies were selected according to predetermined qualification criteria and data were extracted by two researchers. We evaluated the quality of the methods for published papers using the modified Jadad scale.

Results: There were five studies included in this meta-analysis, the ulcer healing rate effect was not significantly higher in the intervention groups than in the control groups at 4 weeks, [OR:1.07 (0.51, 2.22), 95% CI, I2=2%, Z=0.18, P=0.86]. The ulcer shrinkage rate was not significantly higher than the control group at 4 weeks, [MD:0.20 (-1.51, 1.92), 95% CI, I2=0%, P=0.82]. The ulcer shrinkage rate was not significantly higher than the control group at 8 weeks, [MD: -0.09 (-0.30, 0.12), 95% CI, I2=0%, P=0.39].

Conclusion: There were no significant difference between Vonoprazan and lansoprazole in the ulcers induced by treatment at 4 weeks and 8 weeks after treatment with ESD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17235/reed.2022.8863/2022DOI Listing
July 2022

New insights into fibrosis from the ECM degradation perspective: the macrophage-MMP-ECM interaction.

Cell Biosci 2022 Jul 27;12(1):117. Epub 2022 Jul 27.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Fibrosis is a pathological feature of a variety of chronic inflammatory diseases that can affect almost all organs, which can cause severe consequences and even lead to death. Fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) due to disruption of the balance between ECM production and degradation. Although overabundance of ECM proteins has long been the focus of studies on fibrosis, another facet of the problem-impaired degradation of the ECM-is gaining increasing attention. Matrix metalloproteinase (MMP) and the tissue inhibitor of metalloproteinase (TIMP) system is the main molecular system contributing to ECM degradation, and macrophages are the major regulators of ECM. However, the relationship among macrophages, the MMP/TIMP system and the ECM is not fully understood in the context of fibrosis. Here, we discuss in detail the role played by the ECM in the development of fibrosis and highlight the macrophage-MMP-ECM interaction that is involved in fibrogenesis and may be a potential therapeutic target for fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13578-022-00856-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9327238PMC
July 2022

An emerging role of vitamin D in amino acid absorption in different intestinal segments of on-growing grass carp ().

Anim Nutr 2022 Sep 28;10:305-318. Epub 2022 May 28.

Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China.

Vitamin D (VD), an essential nutrient for animals, has been demonstrated to stimulate the uptake of certain amino acids. However, the role of VD in the intestine, the primary site for digestion and absorption of nutrients, remains poorly characterized. Here, the grass carp () was studied to assess the influence of different doses of VD (15.2, 364.3, 782.5, 1,167.9, 1,573.8, and 1,980.1 IU/kg) on growth performance, intestinal morphology, digestive absorption, amino acid transport, and potential signaling molecule levels in a feeding experiment. As a result, dietary VD improved growth performance, intestinal structure, and digestive and brush border enzyme activities. Additionally, most intestinal free amino acids and their transporters were upregulated after VD intake, except for Ala, Lys, Asp, Leu, solute carrier () , , and mRNA in different segments, Leu and 4 mRNA in the proximal intestine, and mRNA in the mid and distal intestine. In the crucial target of rapamycin (TOR) signal pathway of amino acid transport, the gene and protein expression of TOR, S6 kinase 1, and activating transcription factor 4 were elevated, whereas 4E-binding protein 1 was decreased, further suggesting an advanced amino acid absorption capacity in the fish due to VD supplementation. Based on percentage weight gain, feed efficiency, and trypsin activity, the VD requirements of on-growing grass carp were estimated to be 968.33, 1,005.00, and 1,166.67 IU/kg, respectively. Our findings provide novel recommendations for VD supplementation to promote digestion and absorption capacities of fish, contributing to the overall productivity of aquaculture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aninu.2022.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293741PMC
September 2022

Effects of Small Peptide Supplementation on Growth Performance, Intestinal Barrier of Laying Hens During the Brooding and Growing Periods.

Front Immunol 2022 7;13:925256. Epub 2022 Jul 7.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.

The growing period is a critical period for growth and development in laying hens. During this period, chicks grow rapidly, but are accompanied by unstable digestive function, incomplete organ development, and high mortality. Small peptide, a feed additive, which has been proved to promote intestinal development and immunity in poultry. In order to elucidate the effects of small peptides on growth performance, immunity, antioxidant capacity, and intestinal health of growing laying hens, a total of 900 Tianfu green shell laying hens (1-day-old) were randomly divided into 5 treatments with 6 replicates of 30 birds each in this 18-week trial. Dietary treatments included a corn-soybean meal-based diet supplemented with 0 g/kg, 1.5 g/kg, 3.0 g/kg, 4.5 g/kg and 6.0 g/kg small peptide, respectively. The results showed that the supplementation of small peptides significantly increased growth rate (<0.05) in laying hens, as well as elevated the serum immunoglobulins (<0.05) and antioxidant indices (<0.05), however, it decreased inflammation parameters (<0.05). The supplementation of small peptides enhanced the intestinal function by promoting gut development (<0.05) and improving gut integrity (<0.05), barrier function (<0.05) and the diversity of gut microbiota (<0.05) in the growing hens. The best performance was recorded among the hens fed 4.5 g/kg level of small peptide. Taken together, these results showed that small peptide supplementation could improve the economic value of growing hens by promoting growth rate, disease resistance, and the optimal amount of addition for Tianfu green shell laying hens was 4.5 g/kg.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.925256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301363PMC
July 2022

Genetic correlation of crizotinib efficacy and resistance in ALK- rearranged non-small-cell lung cancer.

Lung Cancer 2022 Sep 19;171:18-25. Epub 2022 Jul 19.

Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address:

Objectives: Crizotinib remains one of the most commonly used targeted therapies for ALK fusion-positive patients. However, the mutational profiles and mechanisms of resistance to first-line crizotinib treatment remain to be thoroughly examined.

Materials And Methods: We retrospectively reviewed 125 ALK-positive patients with histological and/or cytological diagnosis of NSCLC. Of these, baseline samples were available from 62 patients and 63 had resistance samples following first-line crizotinib treatment, with 18 patients having paired baseline and resistance samples. All patients were genetically profiled by NGS using a 139 lung cancer gene panel (Pulmocan®, Nanjing Geneseeq Technology Inc.). Survival associations of progression-free survival (PFS) and resistance mechanisms were evaluated in relation to ALK fusion variants and background genetic alterations.

Results: The median age of the cohort was 53 years old (range 26-78; 46.4 % females). Three novel ALK fusion partners were identified, including PSME4, cullin3 (CUL3) and coiled-coil domain containing 85A (CCDC85A). Among the different ALK fusion genes, patients carrying the v3 variant experienced worse PFS outcome compared with other non-v3 fusions (P = 0.01) in response to first-line crizotinib. Profiling of the genetic landscape revealed TP53 as the most frequently co-mutated gene, alterations of which were associated with unfavorable outcome (P = 0.024) and were among the secondary acquired mutations in the resistance samples. Examinations of the resistance mechanisms showed that the v3 variant was more likely to acquire ALK activating mutations (P = 0.04). Off-target resistance mechanisms included mutations in genes in the RAS/MAPK and its parallel pathway genes, such as ERBB2, BRAF, KRAS, FGFR3, NF1 and CREBBP.

Conclusion: In this study, through profiling of the mutational landscape of ALK-positive advanced NSCLCs both at baseline and disease progression, we characterized resistance mechanisms and molecular correlations of PFS in response to first-line crizotinib. Our findings may facilitate rational selection of subsequent ALK TKIs in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lungcan.2022.07.011DOI Listing
September 2022

Observation of J/ψ Electromagnetic Dalitz Decays to X(1835), X(2120), and X(2370).

Phys Rev Lett 2022 Jul;129(2):022002

Turkish Accelerator Center Particle Factory Group, Istanbul Bilgi University, 34060 Eyup, Istanbul, Turkey.

Using a sample of about 10^{10}  J/ψ events collected at a center-of-mass energy sqrt[s]=3.097  GeV with the BESIII detector, the electromagnetic Dalitz decays J/ψ→e^{+}e^{-}π^{+}π^{-}η^{'}, with η^{'}→γπ^{+}π^{-} and η^{'}→π^{+}π^{-}η, have been studied. The decay J/ψ→e^{+}e^{-}X(1835) is observed with a significance of 15σ, and also an e^{+}e^{-} invariant-mass dependent transition form factor of J/ψ→e^{+}e^{-}X(1835) is presented for the first time. The intermediate states X(2120) and X(2370) are also observed in the π^{+}π^{-}η^{'} invariant-mass spectrum with significances of 5.3σ and 7.3σ. The corresponding product branching fractions for J/ψ→e^{+}e^{-}X, X→π^{+}π^{-}η^{'} [X=X(1835), X(2120), and X(2370)] are reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevLett.129.022002DOI Listing
July 2022

Gastric cancer incidence, mortality and burden in adolescents and young adults: a time-trend analysis and comparison among China, South Korea, Japan and the USA.

BMJ Open 2022 07 21;12(7):e061038. Epub 2022 Jul 21.

Department of Pharmacy, The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, China.

Objectives: To evaluate and compare the burden of gastric cancer in adolescents and young adults (GCAYA) among China, South Korea, Japan and the USA, four countries with similar or different rates of gastric cancer (GC) incidence, development levels and cancer control strategies.

Design: This population-based observational study collected the epidemiological data of GCAYA from the Global Burden of Diseases Study 2019. The trend magnitude and directions over time for incidence and mortality of GCAYA were analysed and compared among four countries.

Main Outcomes And Measures: Outcomes included new cases, deaths, mortality-to-incidence ratios (MIRs), disability-adjusted life years, and their age-standardised rates and estimated annual percentage changes (AAPCs).

Results: There were 49 008 new cases and 27 895 deaths from GCAYA in 2019, nearly half of which occurred in China. The AAPCs for the age-standardised incidence and mortality rate were 0.3 (-0.1 to 0.7), -3.6 (-3.7 to -3.4), -3.2 (-3.8 to -2.6), -0.1 (-0.6 to 0.5) and -2.0 (-2.3 to -1.6), -5.6 (-6.2 to -5.0), -4.4 (-4.7 to -4.1), -0.7 (-1.0 to -0.3) in China, South Korea, Japan and the USA, respectively. The incidence rate for females in the USA rose by 0.4% annually. GC ranks fifth, first, fourth and ninth in China, South Korea, Japan and the USA regarding burdens caused by cancer in adolescents and young adults. The MIRs declined constantly in South Korea and China, and the MIR in the USA became the highest in 2019.

Conclusions: Although not covered by prevention and screening programmes, variations in disease burden and time trends may reflect variations in risk factors, cancer control strategies and treatment accessibility of GC among the four countries. Investigating the reasons behind the varying disease burden and changing trends of GCAYA across countries will inform recommendations for prevention measures and timely diagnosis specific to this underserved population to further decrease the GC burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2022-061038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310161PMC
July 2022

Recurrent hypoglycemic coma and diabetic ketoacidosis caused by insulin antibody. A rare case of type 1 diabetes mellitus.

Rev Med Chil 2022 Jan;150(1):115-119

Department of Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: < 5%), and the concentrations of insulin and C-peptide were > 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4067/S0034-98872022000100115DOI Listing
January 2022

[Optimization of extraction process of Congrong Shujing Granules based on AHP-CRITIC analysis].

Zhongguo Zhong Yao Za Zhi 2022 Jul;47(13):3481-3487

Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.

The index weight coefficients were determined by comparing the analytic hierarchy process(AHP), the criteria importance through inter-criteria correlation(CRITIC), and the AHP-CRITIC mixed weighting method. The comprehensive scores of index components(echinacoside, salvianolic acid B, paeoniflorin, and ointment yield) of each group in the orthogonal test were compared to optimize the extraction process of Congrong Shujing Granules. The results showed that the AHP-CRITIC mixed weighting method scientifically optimized the extraction process. To be specific, the decoction pieces should be added with the 6-fold amount of water and extracted twice, 1 h each time. After three verification tests, the average mass fractions of echinacoside, salvianolic acid B, and paeoniflorin were 0.72, 9.34, and 5.92 mg·g~(-1), respectively, and the average ointment yield was 47.18%. As verified by the AHP-CRITIC mixed weighting method and the orthogonal test, the optimized extraction process of Congrong Shujing Granules was stable and feasible and could be applied to industrial production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.19540/j.cnki.cjcmm.20211125.303DOI Listing
July 2022

Evaluation of the Acute and Sub-Acute Oral Toxicity of Jaranol in Kunming Mice.

Front Pharmacol 2022 30;13:903232. Epub 2022 Jun 30.

Department of Natural Medicinal Chemistry, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China.

Jaranol has shown a wide range of pharmacological activities; however, no study has yet examined toxicity. The study aimed to investigate the oral acute and sub-acute toxicity of jaranol in mice. The acute toxicity was determined by a single oral dose of jaranol (2000 mg/kg). Therein animal behaviour and mortality rate were observed for 14 days. The jaranol (50, 100 and 200 mg/kg BW·d) was given by gavage for 28 days daily in the sub-acute study. The mouse body weight (BW), organ weight, food, water intake, biochemical, haematological parameters, and histopathology were studied in acute and sub-acute toxicity. During the acute toxicity test, a single oral dose (2000 mg/kg) jaranol did not cause significant alteration in majority of the hematological indices. However, jaranol decreased the level of serum alanine aminotransferase and aspartate aminotransferase. Those results showed that the oral lethal dose 50 (LD) of jaranol was higher than 2000 mg/kg BW, regardless of sex. In repeated daily oral doses (50, 100 and 200 mg/kg BW·d), no mortality was recorded in the various experimental groups. The jaranol reduced body weight gain (200 mg/kg BW·d), the relative spleen weight (all doses) and serum alanine aminotransferase activity (200 mg/kg BW·d). On the other hand, jaranol significantly elevated red blood cell count (100 and 200 mg/kg BW·d) and serum creatinine levels (200 mg/kg BW·d). Histological study revealed that spleen bleeding was identified in 200 mg/kg jaranol-treated mice. Jaranol was relatively safe in Kunming Mice when repetitively administered orally in small doses for a prolonged period of time. We recommend more chronic toxicity studies and clinical trials on jaranol to ensure that its use is free of potential toxicity to humans.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.903232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280858PMC
June 2022
-->