Publications by authors named "Yong Wu"

962 Publications

A Novel Metabolic Reprogramming Strategy for the Treatment of Diabetes-Associated Breast Cancer.

Adv Sci (Weinh) 2022 Jan 12:e2102303. Epub 2022 Jan 12.

Division of Cancer Research and Training, Department of Internal Medicine, Charles Drew University of Medicine and Science, David Geffen UCLA School of Medicine and UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, 90095, USA.

Diabetes is directly related to the risk of breast cancer (BC) occurrence and worsened BC prognosis. Currently, there are no specific treatments for diabetes-associated BC. This paper aims to understand the fundamental mechanisms of diabetes-induced BC progression and to develop personalized treatments. It reports a metabolic reprogramming strategy (MRS) that pharmaceutical induction of glucose import and glycolysis with metformin and NF-κB inhibitor (NF-κBi) while blocking the export of excessive lactate via inhibiting monocarboxylate transporter 4 (MCT4) leads to a metabolic crisis within the cancer cells. It demonstrates that the MRS shifts the metabolism of BC cells toward higher production of lactate, blocks lactate secretion, prompts intracellular acidification and induces significant cytotoxicity. Moreover, a novel MCT4 inhibitor CB-2 has been identified by structure-based virtual screening. A triple combination of metformin, CB-2, and trabectedin, a drug that impedes NF-κB signaling, strongly inhibits BC cells. Compared to normal glucose condition, MRS elicits more potent cancer cell-killing effects under high glucose condition. Animal model studies show that diabetic conditions promote the proliferation and progression of BC xenografts in nude mice and that MRS treatment significantly inhibits HG-induced BC progression. Therefore, inhibition of MCT4 combined with metformin/NF-κBi is a promising cancer therapy, especially for diabetes-associated BC.
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http://dx.doi.org/10.1002/advs.202102303DOI Listing
January 2022

Multiple targeted doxorubicin-lonidamine liposomes modified with p-hydroxybenzoic acid and triphenylphosphonium to synergistically treat glioma.

Eur J Med Chem 2021 Dec 30;230:114093. Epub 2021 Dec 30.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China. Electronic address:

A type of pH-sensitive multi-targeted brain tumor site-specific liposomes (Lip-CTPP) co-modified with p-hydroxybenzoic acid (p-HA) and triphenylphosphonium (TPP) were designed and prepared to co-load doxorubicin (DOX) and lonidamine (LND). Lip-CTPP are promising potential carriers to exert the anti-glioma effect of DOX and LND collaboratively given the following features: 1) Lip-CTPP have a good pharmacokinetic behavior; 2) Lip-CTPP can cross the blood-brain barrier (BBB) and recognize tumor cells through the affinity of p-HA and dopamine/sigma receptors; 3) Lip-CTPP are highly positive charged once the acid-sensitive amide bonds are cleaved in endo/lysosomes to expose TPP and protonate amine groups; 4) the positive charged Lip-CTPP escape from endo/lysosomes and accumulate in mitochondria through electrostatic adsorption; 5) DOX and LND are released and synergistically increase anti-tumor efficacy. Our in vitro and in vivo results confirmed that Lip-CTPP could greatly elevate the inhibition rate of tumor cell proliferation, migration and invasion, promote apoptosis and necrosis, and interfere with mitochondrial function. In addition, Lip-CTPP could significantly prolong the survival time of glioma bearing mice, narrow the tumor region and inhibit the infiltration and metastasis capability of glioma cells. Collectively, Lip-CTPP are promising nano formulations to enhance the synergistic effect of DOX and LND in glioma treatment.
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http://dx.doi.org/10.1016/j.ejmech.2021.114093DOI Listing
December 2021

Case Report: First Case of Cefotaxime-Sulbactam-Induced Acute Intravascular Hemolysis in a Newborn With ABO Blood Type Incompatibility by the Mechanism of Non-Immunologic Protein Adsorption.

Front Immunol 2021 22;12:698541. Epub 2021 Dec 22.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

Background: ABO blood type incompatibility hemolytic disease of newborn (ABO-HDN) and drug-induced immune hemolytic anemia (DIIHA) due to non-immunologic protein adsorption (NIPA) mainly cause extravascular hemolysis. All the reported severe DIIHA were caused by drug-induced antibodies, and rare report of acute intravascular hemolysis was caused by the NIPA mechanism or ABO-HDN.

Case Presentation: We report the first case of acute intravascular hemolysis induced by cefotaxime sodium - sulbactam sodium (CTX - SBT) in a case of ABO-HDN which resulted in death at 55 h after birth. The mother's blood type was O and RhD-positive, and the newborn's blood type was B and RhD-positive. No irregular red blood cell (RBC) antibodies or drug-dependent antibodies related to CTX or SBT was detected in the mother's plasma and the plasma or the RBC acid eluent of the newborn. Before the newborn received CTX - SBT treatment, the result of direct antiglobulin test (DAT) was negative while anti-B was positive (2 +) in both plasma and acid eluent. After the newborn received CTX - SBT treatment, the results of DAT for anti-IgG and anti-C3d were both positive, while anti-B was not detected in plasma, but stronger anti-B (3 +) was detected in acid eluent. experiments confirmed that NIPA of SBT promoted the specific binding of maternal-derived IgG anti-B to B antigen on RBCs of the newborn, thereby inducing acute intravascular hemolysis.

Conclusion: The NIPA effect of SBT promoted the specific binding of mother-derived IgG anti-B in newborn's plasma to the newborn's RBC B antigens and formed an immune complex, and then activated complement, which led to acute intravascular hemolysis. Drugs such as SBT with NIPA effect should not be used for newborns with HDN.
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http://dx.doi.org/10.3389/fimmu.2021.698541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727536PMC
December 2021

Identification of hub genes and construction of an mRNA-miRNA-lncRNA network of gastric carcinoma using integrated bioinformatics analysis.

PLoS One 2021 30;16(12):e0261728. Epub 2021 Dec 30.

Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Gastric carcinoma (GC) is one of the most common cancer globally. Despite its worldwide decline in incidence and mortality over the past decades, gastric cancer still has a poor prognosis. However, the key regulators driving this process and their exact mechanisms have not been thoroughly studied. This study aimed to identify hub genes to improve the prognostic prediction of GC and construct a messenger RNA-microRNA-long non-coding RNA(mRNA-miRNA-lncRNA) regulatory network.

Methods: The GSE66229 dataset, from the Gene Expression Omnibus (GEO) database, and The Cancer Genome Atlas (TCGA) database were used for the bioinformatic analysis. Differential gene expression analysis methods and Weighted Gene Co-expression Network Analysis (WGCNA) were used to identify a common set of differentially co-expressed genes in GC. The genes were validated using samples from TCGA database and further validation using the online tools GEPIA database and Kaplan-Meier(KM) plotter database. Gene set enrichment analysis(GSEA) was used to identify hub genes related to signaling pathways in GC. The RNAInter database and Cytoscape software were used to construct an mRNA-miRNA-lncRNA network.

Results: A total of 12 genes were identified as the common set of differentially co-expressed genes in GC. After verification of these genes, 3 hub genes, namely CTHRC1, FNDC1, and INHBA, were found to be upregulated in tumor and associated with poor GC patient survival. In addition, an mRNA-miRNA-lncRNA regulatory network was established, which included 12 lncRNAs, 5 miRNAs, and the 3 hub genes.

Conclusions: In summary, the identification of these hub genes and the establishment of the mRNA-miRNA-lncRNA regulatory network provide new insights into the underlying mechanisms of gastric carcinogenesis. In addition, the identified hub genes, CTHRC1, FNDC1, and INHBA, may serve as novel prognostic biomarkers and therapeutic targets.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261728PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718005PMC
January 2022

Wild-Type TP53 Predicts Poor Prognosis in Patients with Gastric Cancer.

J Cancer Sci Clin Ther 2021 Mar;5(1):134-153

Division of Cancer Research and Training, Department of Internal Medicine, Charles Drew University of Medicine and Science, CA, USA.

TP53 gene is often mutated in gastric cancer (GC), nonetheless its relationship with clinicopathological characteristics and prognosis is still unclear. Here, we sought to ascertain the difference in clinical phenotypes between TP53 wild-type and mutant tumors in confirmed gastric cancer patients. To this end, we analyzed TP53 mutation status of 415 TCGA GC patients in relation to their clinical and pathological features as well as prognosis. Longrank Test showed that the survival rate of gastric cancer patients with TP53 WT was significantly lower than that of TP53 mut. Compared with TP53 mut gastric cancer patients with low mRNA expression, TP53 WT patients with low mRNA expression have lower overall survival rate. The death risk of TP53 WT gastric cancer patients is 1.395 times that of TP53 mut gastric cancer patients. The death risk of TP53 mut gastric cancer patients is not related to age, and advanced age is not a risk factor. However, the death risk of TP53 WT patients with gastric cancer increases with age, and the death risk of patients over 70 years old is 1.899 times that of patients under 60 years old. These results suggest that the prognosis of elderly gastric cancer patients with TP53 WT is worse.

Conclusion: our results indicate that the status of TP53 mutation in GC is significantly correlated with clinical or molecular categories and that the prognosis of GC patients with WT TP53 is worse than that of patients with mutant TP53. Therefore, our data emphasize the importance of distinguishing TP53 WT to predict poor overall survival and relapse-free survival in patients with GC.
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http://dx.doi.org/10.26502/jcsct.50790107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694034PMC
March 2021

AIM2 inflammasome contributes to aldosterone-induced renal injury via endoplasmic reticulum stress.

Clin Sci (Lond) 2022 Jan;136(1):103-120

Department of Nephrology, Huashan Hospital and Nephrology Institute, Fudan University, Shanghai, China.

Inflammatory response and renal fibrosis are the hallmarks of chronic kidney disease (CKD). However, the specific mechanism of aldosterone-induced renal injury in the progress of CKD requires elucidation. Emerging evidence has demonstrated that absent in melanoma 2 (AIM2)-mediated inflammasome activation and endoplasmic reticulum stress (ERS) play a pivotal role in the renal fibrosis. Here, we investigated whether overexpression or deficiency of AIM2 affects ERS and fibrosis in aldosterone-infused renal injury. Interestingly, we found that AIM2 was markedly expressed in the diseased proximal tubules from human and experimental CKD. Mechanically, overactivation of AIM2 aggravated aldosterone-induced ERS and fibrotic changes in vitro while knockdown of AIM2 blunted these effects in vivo and in vitro. By contrast, AIM2 deficiency ameliorated renal structure and function deterioration, decreased proteinuria levels and lowered systolic blood pressure in vivo; silencing of AIM2 blocked inflammasome-mediated signaling pathway, relieved ERS and fibrotic changes in vivo. Furthermore, mineralocorticoid receptor (MR) antagonist eplerenone and ERS inhibitor tauroursodeoxycholic acid (TUDCA) had nephroprotective effects on the basis of AIM2 overactivation in vitro, while they failed to produce a more remarkable renoprotective effect on the treatment of AIM2 silence in vitro. Notably, the combination of TUDCA with AIM2 knockdown significantly reduced proteinuria levels in vivo. Additionally, immunofluorescence assay identified that apoptosis-associated speck-like protein (ASC) recruitment and Gasdermin-D (GSDMD) cleavage respectively occurred in the glomeruli and tubules in vivo. These findings establish a crucial role for AIM2 inflammasome in aldosterone-induced renal injury, which may provide a novel therapeutic target for the pathogenesis of CKD.
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http://dx.doi.org/10.1042/CS20211075DOI Listing
January 2022

In Situ Synthesis of CuN /Mesoporous N-Doped Carbon for Selective Oxidative Crosscoupling of Terminal Alkynes under Mild Conditions.

Small 2021 Dec 18:e2105178. Epub 2021 Dec 18.

The Institute for Advanced Studies, Wuhan University, Wuhan, Hubei, 430072, P. R. China.

The 1,3-conjugated diynes are an important class of chemical intermediates, and the selective crosscoupling of terminal alkynes is an efficient chemical process for manufacturing asymmetrical 1,3-conjugated diynes. However, it often occurs in homogenous conditions and costs a lot for reaction treatment. Herein, a copper catalyzed strategy is used to synthesize highly ordered mesoporous nitrogen-doped carbon material (OMNC), and the copper species is in situ transformed into the copper single-atom site with four nitrogen coordination (CuN ). These features make the CuN /OMNC catalyst efficient for selective oxidative crosscoupling of terminal alkynes, and a wide range of asymmetrical and symmetrical 1,3-diynes (26 examples) under mild conditions (40 °C) and low substrates ratio (1.3). Density functional theory (DFT) calculations reveal that the aryl-alkyl crosscoupling has the lowest energy barrier on the CuN site, which can explain the high selectivity. In addition, the catalyst can be separated and reused by simply centrifugation or filtration. This work can open a facile avenue for constructing single-atom loaded mesoporous materials to bridge homogeneous and heterogeneous catalysis.
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http://dx.doi.org/10.1002/smll.202105178DOI Listing
December 2021

Microbial keystone taxa drive crop productivity through shifting aboveground-belowground mineral element flows.

Sci Total Environ 2022 Mar 15;811:152342. Epub 2021 Dec 15.

State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Unbalanced fertilization of nutritional elements is a potential threat to environmental quality and agricultural productivity in acid soil. Harnessing keystone taxa in soil microbiome represents a promising strategy to enhance crop productivity as well as reducing the adverse environmental effects of fertilizers, with the goal of agricultural sustainability. However, there is a lack of information on which and how soil microbial keystone taxa contribute to sustainable crop productivity in acid soil. Here, we examined soil microbial communities (including bacteria, fungi, and archaea) and soil nutrients, and the mineral nutrition and yield of maize subjected to different inorganic and organic fertilization treatments over 35 years in acid soil. The application of organic fertilizer alone or in combination with inorganic fertilizers sustained high maize yield when compared with the other fertilization treatments. Microbial abundances and community structures rather than their alpha diversities explained the main variation in maize yield among different treatments. Sixteen soil keystone taxa (a fungal operational taxonomic unit and 15 bacterial operational taxonomic units) were identified from the microbial co-occurrence network. Among them, five keystone taxa (in Hypocreales, Bryobacter, Solirubrobacterales, Thermomicrobiales, and Roseiflexaceae) contributed to high maize yield through increasing phosphorus flow and inhibiting toxic aluminum and manganese flow from soils to plants. However, the remaining eleven keystone taxa (in Conexibacter, Acidothermus, Ktedonobacteraceae, Deltaproteobacteria, Actinobacteria, Elsterales, Ktedonobacterales, and WPS-2) exerted the opposite effects. As a result, maize productivity varied among different fertilization treatments because of the altered maize mineral element flows by microbial keystone taxa. We conclude that microbial keystone taxa drive crop productivity through shifting aboveground-belowground mineral element flows in acid soil. This study highlights the importance of microbial keystone taxa for sustainable crop productivity in acid soil and provides deep insights into the relationships between soil microbial keystone taxa, crop mineral nutrition, and productivity.
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http://dx.doi.org/10.1016/j.scitotenv.2021.152342DOI Listing
March 2022

Repurposing Sitafloxacin, Prulifloxacin, Tosufloxacin, and Sisomicin as Antimicrobials Against Biofilm and Persister Cells of Pseudomonas aeruginosa.

Curr Microbiol 2021 Dec 14;79(1):12. Epub 2021 Dec 14.

Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, 138 Tong Zipo Road, Changsha, 410013, Hunan, People's Republic of China.

Pseudomonas aeruginosa is a ubiquitous bacterium found in hospitals and the surrounding environment. The ability of P. aeruginosa to form biofilms confers high-level resistance to antibiotics, and the persister cells formed in the presence of high antibacterial drug concentrations make P. aeruginosa-related infections more refractory. Further, there rarely is an effective antimicrobial alternative when biofilm- and persister cell-targeting treatment fails. Using a high-throughput screening assay, we previously identified fluoroquinolones sitafloxacin, prulifloxacin, and tosufloxacin as well as aminoglycoside sisomicin among FDA-approved drugs with significant bactericidal activity against P. aeruginosa. In addition, in our current study, these antibiotics exhibited an effective time- and dose-dependent eradication effects against the preformed biofilms of P. aeruginosa at the concentrations of 2-4 μM. These agents also exhibited bactericidal efficacy against CCCP-induced P. aeruginosa persister cells with the viable cell count decreased from 9.14 log10 CFU/mL to 6.15 (sitafloxacin), 7.59 (prulifloxacin), 4.27 (tosufloxacin), and 6.17 (sisomicin) log10 CFU/mL, respectively, following 4 h of treatment. Furthermore, sisomicin was also effective against conventional antibiotics induced persister cells in a time-dependent manner within 24 h. In addition, we confirmed the in vivo anti-biofilm efficacy of the identified antibiotics in a subcutaneous implantation biofilm-related infection model. Tosufloxacin exhibited the greatest in vivo bactericidal activity against P. aeruginosa biofilms with a reduction of 4.54 ΔLog10 CFU/mL compared to the vehicle group, followed by prulifloxacin, sitafloxacin, and sisomicin. Taken together, our results indicate that sitafloxacin, prulifloxacin, tosufloxacin, and sisomicin have great potential as alternatives for the treatment of refractory infections caused by P. aeruginosa biofilms and persister cells.
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http://dx.doi.org/10.1007/s00284-021-02729-wDOI Listing
December 2021

Fructose and biotin co-modified liposomes for dual-targeting breast cancer.

J Liposome Res 2021 Dec 13:1-10. Epub 2021 Dec 13.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China.

Chemotherapy, as the main treatment for breast cancer, inevitably damages normal tissues due to the lack of targeting. Various nano targeting drug delivery systems (TDDS) have the potential to be developed as anticancer therapeutics. Although mono-ligand-directed liposomes have been used with some success, dual-ligand-directed liposomes exhibit promising advantages. In current work, we synthesized a Y-shaped ligand covalently linking fructose and biotin (Fru-Bio-Chol) to prepare a dual-targeting liposome Fru-Bio-Lip for breast cancer. The targeting ability was evaluated by comparing the Fru-Bio-Lip with the non-modified liposome (Lip), fructose or biotin mono modified liposomes (Fru-Lip and Bio-Lip), and another dual-targeting liposome (Fru + Bio-Lip) physically mixing fructose and biotin mono modified ligands (Fru-Chol and Bio-Chol). The cellular uptake of Fru-Bio-Lip is 3.27-, 1.81-, 2.19-, 1.15-times that of Lip, Fru-Lip, Bio-Lip and Fru + Bio-Lip on 4T1 cells, and 3.11-, 1.80-, 1.89-, 1.15-times on MCF-7 cells. Additionally, the uptake mechanism indicates the uptake of Fru-Bio-Lip is energy-dependently achieved through multiple endocytosis pathway with a dual recognition of fructose and biotin by GLUT and SMVT. The cytotoxicity and apoptosis assay show PTX-Fru-Bio-Lip among liposomes have the strongest proliferation inhibitory effect on breast cancer cells, and the apoptosis rate is 1.7-times that of PTX-Lip. images indicate Fru-Bio-Lip have the strongest tumour enrichment ability, which is 2.76-, 1.60-, 1.96-, 1.40-times that of Lip, Fru-Lip, Bio-Lip and Fru + Bio-Lip, respectively. Overall, the fructose and biotin covalently modified liposomes improved breast cancer targeting ability, demonstrating great potential as a drug delivery system for breast cancer.
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http://dx.doi.org/10.1080/08982104.2021.1894171DOI Listing
December 2021

Is Long Noncoding a Reliable Diagnostic Tool for Metastasis Diagnosis of Cancer: A Meta-Analysis.

Genet Test Mol Biomarkers 2021 Dec 10;25(12):765-771. Epub 2021 Dec 10.

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

The small nucleolar RNA host gene 7 (SNHG7) has been suggested as a biomarker of metastatic cancer; however, its reliability is controversial. Therefore, the goal of this study was to conduct a meta-analysis to assess the reliability of SNHG7 as a comprehensive cancer metastasis diagnostic biomarker. A comprehensive literature search was conducted using PubMed, Cochrane Library, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) to identify articles which examined the role of in cancers. Random-effects models and fixed-effects models were conducted to estimate the pooled odds ratios (ORs) for the associations of with distant metastases and lymph node metastases. Hierarchical summary receiver operating characteristic (ROC) models were used to estimate the sensitivity and specificity of as a biomarker for cancer metastasis diagnoses. Nineteen studies comprised 1491 patients were included in this meta-analysis. We found that both distant metastasis (OR = 4.19, 95% confidence interval [CI] = 2.93-5.99,  = 34%) and lymph node metastasis (OR = 3.07, 95% CI = 1.65-5.68,  = 79.03%) were significantly associated with a higher expression of . We also showed a pooled sensitivity and specificity of 74% (95% CI = 66-82) and 57% (95% CI = 53-61) for distant metastasis; as well as 72% (95% CI = 63-80) and 54% (95% CI = 46-63) for lymph node metastasis, respectively. Our findings suggest that is a potential diagnostic biomarker for metastasis of cancer; however, its clinical application requires stronger evidence due to the low sensitivity and specificity. Further larger-scale studies from diverse settings and cancer types will be necessary to reveal novel insights into as a biomarker for cancer metastasis diagnoses.
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http://dx.doi.org/10.1089/gtmb.2021.0099DOI Listing
December 2021

A proteomics study of the subacute toxicity of rat brain after long-term exposure of Gelsemium elegans.

Curr Mol Pharmacol 2021 Dec 9. Epub 2021 Dec 9.

College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, Hunan. China.

Background: Gelsemium elegans (G. elegans) has been shown to have strong pharmacological and pharmacodynamic effects in relevant studies both in China and USA. G. elegans has been used as a traditional medicine to treat a variety of diseases and even has the potential to be an alternative to laboratory synthesized drugs. However, its toxicity severely limited its application and development. At present, there is little attention paid to protein changes in toxicity.

Aim: This study investigated the toxicity effects after long-term exposure of G. elegans of the rat brain through proteomic.

Method: 11 differential abundance proteins were detected, among which 8 proteins were higher in the G. elegans- exposure group than in the control group, including Ig-like domain-containing protein (N/A), receptor-type tyrosine-protein phosphatase C (Ptprc), disheveled segment polarity protein 3 (Dvl3), trafficking protein particle complex 12 (Trappc12), seizure-related 6 homolog-like (Sez6l), transmembrane 9 superfamily member 4 (Tm9sf4), DENN domain-containing protein 5A (Dennd5a) and Tle4, whereas the other 3 proteins do the opposite including Golgi to ER traffic protein 4 (Get4), vacuolar protein sorting 4 homolog B (Vps4b) and cadherin-related 23 (CDH23). Furthermore, we performed validation of WB analysis on the key protein CDH23.

Result: Finally, only fewer proteins and related metabolic pathways were affected, indicating that there was no accumulative toxicity of G. elegans. G. elegans has the potential to develop and utilize of its pharmacological activity. CHD23, however, is a protein associated with hearing.

Conclusion: Whether the hearing impairment is a sequela after G. elegans exposure remains to be further studied.
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http://dx.doi.org/10.2174/1874467214666211209144139DOI Listing
December 2021

Spatial distribution and main controlling factor of cadmium accumulation in agricultural soils in Guizhou, China.

J Hazard Mater 2022 02 22;424(Pt A):127308. Epub 2021 Sep 22.

College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541006, PR China.

A large-scale investigation was conducted on the cadmium (Cd) content in the farmland soils of Guizhou to explore the spatial variation in soil Cd content, identify the main factors responsible for causing Cd pollution, and determine the zonation of Cd pollution. Multivariate statistical analysis, geographic information system (GIS) analysis, and decision tree methods were used to study the distribution, spatial variation, and pollution partitioning of Cd and the factors influencing the Cd accumulation in agricultural soils of the Guizhou province. Areas with high Cd content in agricultural soil were found to be concentrated in the high-altitude areas in the western region of Guizhou province. The results of the single factor pollution index showed that the proportion of sample sites with Cd class I (priority protection), II (security utilization), and III (strict control) in the agricultural soils of Guizhou province were 65.96%, 31.27%, and 2.77%, respectively. In high-altitude areas, the Cd content in the agricultural soils was mainly derived from the soil parent material. In contrast, mining activities and road traffic were the main factors Cd accumulation in agricultural soils in lower altitude areas.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127308DOI Listing
February 2022

Prognostic Value of the Distribution of Lymph Node Metastasis in Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy.

Front Surg 2021 17;8:749575. Epub 2021 Nov 17.

Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

The objective of this study is to assess the prognostic value of lymph node metastasis distribution (LND) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT). This study included 179 patients with pathological stage III LARC who underwent nCRT followed by radical surgery. LND was classified into three groups: LND1, lymph node metastasis at the mesorectum (140/179, 78.2%); LND2, lymph node metastasis along the inferior mesenteric artery trunk nodes (26/179, 14.5%); LND3, lymph node metastasis at the origin of the IMA (13/179, 7.3%). Clinicopathologic characteristics were analyzed to identify independent prognostic factors. LND showed better stratification for 3-year DFS (LND1 66.8, LND2 50, and LND3 15.4%, < 0.01) compared to the ypN (3-year DFS: N1 59.9 and N2 60.3%, = 0.34) and ypTNM (3-year DFS: IIIA 68.6%, IIIB 57.5%, and IIIC 53.5, = 0.19) staging systems. Similar results were found for 3-year LRFS and DMFS. According to multivariate survival analysis, LND was shown to be an independent prognostic factor for DFS, LRFS, and DMFS in patients with positive lymph nodes ( < 0.01, in all cases). LND is an independent prognostic factor in stage III rectal cancer after nCRT. LND can be used as a supplementary indicator for the ypTNM staging system in patients with LARC after nCRT.
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http://dx.doi.org/10.3389/fsurg.2021.749575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635484PMC
November 2021

LncRNAs Associated with Chemoradiotherapy Response and Prognosis in Locally Advanced Rectal Cancer.

J Inflamm Res 2021 27;14:6275-6292. Epub 2021 Nov 27.

Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.

Background: There are only limited studies on the long non-coding RNAs (lncRNAs) associated with neoadjuvant chemoradiotherapy (NCRT) response and prognosis of locally advanced rectal cancer (LARC) patients. This study identified lncRNAs associated with NCRT response and prognosis in CRC patients and explored their potential predictive mechanisms.

Methods: The study subjected the LncRNA expression profiles from our previous gene chip data to LASSO and identified a four-lncRNA signature that predicted NCRT response and prognosis. A Cox regression model was subsequently performed to identify the prognostic risk factors. The function of LINC00909, the lncRNA with the most powerful predictive ability, was finally identified in vivo and in vitro using CRC cell lines.

Results: A comparison of the relative lncRNA expression of NCRT-responsive and non-responsive patients revealed four hub lncRNAs: DBET, LINC00909, FLJ33534, and HSD52 with AUC = 0.68, 0.73, 0.73, and 0.70, respectively (all p < 0.05). COX regression analysis further demonstrated that DBET, LINC00909 and FLJ33534 were associated with the DFS in CRC patients. The expression of the four lncRNAs was also significant in LARC patients who had not undergone NCRT (all p < 0.05). A risk score model was subsequently constructed based on the results of the multivariate COX analysis and used to predict NCRT response and prognosis in the CRC and LARC patients. The expression and prognosis of DBET, LINC00909 and FLJ33534 in the CRC tissues were further validated in the R2 platform and Oncomine database. Notably, overexpression of the LINC00909 increased the cell line resistance to the 5-FU and radiotherapy in vivo and in vitro.

Conclusion: DBET, LINC00909, and FLJ33534 are potential novel biomarkers for predicting NCRT response and prognosis in CRC patients. In particular, LINC00909 is an effective oncogene in CRC that could be used as a novel therapeutic target to enhance NCRT response.
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http://dx.doi.org/10.2147/JIR.S334096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636753PMC
November 2021

Development and Validation of a Robust Pyroptosis-Related Signature for Predicting Prognosis and Immune Status in Patients with Colon Cancer.

J Oncol 2021 18;2021:5818512. Epub 2021 Nov 18.

Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

Background: Pyroptosis has been confirmed as a type of inflammatory programmed cell death in recent years. However, the prognostic role of pyroptosis in colon cancer (CC) remains unclear.

Methods: Dataset TCGA-COAD which came from the TCGA portal was taken as the training cohort. GSE17538 from the GEO database was treated as validation cohorts. Differential expression genes (DEGs) between normal and tumor tissues were confirmed. Patients were classified into two subgroups according to the expression characteristics of pyroptosis-related DEGs. The LASSO regression analysis was used to build the best prognostic signature, and its reliability was validated using Kaplan-Meier, ROC, PCA, and t-SNE analyses. And a nomogram based on the multivariate Cox analysis was developed. The enrichment analysis was performed in the GO and KEGG to investigate the potential mechanism. In addition, we explored the difference in the abundance of infiltrating immune cells and immune microenvironment between high- and low-risk groups. And we also predicted the association of common immune checkpoints with risk scores. Finally, we verified the expression of the pyroptosis-related hub gene at the protein level by immunohistochemistry.

Results: A total of 23 pyroptosis-related DEGs were identified in the TCGA cohort. Patients were classified into two molecular clusters (MC) based on DEGs. Kaplan-Meier survival analysis indicated that patients with MC1 represented significantly poorer OS than patients with MC2. 13 overall survival- (OS-) related DEGs in MCs were used to construct the prognostic signature. Patients in the high-risk group exhibited poorer OS compared to those in the low-risk group. Combined with the clinical features, the risk score was found to be an independent prognostic factor of CC patients. The above results are verified in the external dataset GSE17538. A nomogram was established and showed excellent performance. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the varied prognostic performance between high- and low-risk groups may be related to the immune response mediated by local inflammation. Further analysis showed that the high-risk group has stronger immune cell infiltration and lower tumor purity than the low-risk group. Through the correlation between risk score and immune checkpoint expression, T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) was predicted as a potential therapeutic target for the high-risk group.

Conclusion: The 13-gene signature was associated with OS, immune cells, tumor purity, and immune checkpoints in CC patients, and it could provide the basis for immunotherapy and predicting prognosis and help clinicians make decisions for individualized treatment.
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http://dx.doi.org/10.1155/2021/5818512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616665PMC
November 2021

A Multiparametric MR-Based RadioFusionOmics Model with Robust Capabilities of Differentiating Glioblastoma Multiforme from Solitary Brain Metastasis.

Cancers (Basel) 2021 Nov 18;13(22). Epub 2021 Nov 18.

Department of Radiology, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China.

This study aimed to evaluate the diagnostic potential of a novel RFO model in differentiating GBM and SBM with multiparametric MR sequences collected from 244 (131 GBM and 113 SBM) patients. Three basic volume of interests (VOIs) were delineated on the conventional axial MR images (TWI, TWI, T_FLAIR, and CE_TWI), including volumetric non-enhanced tumor (nET), enhanced tumor (ET), and peritumoral edema (pTE). Using the RFO model, radiomics features extracted from different multiparametric MRI sequence(s) and VOI(s) were fused and the best sequence and VOI, or possible combinations, were determined. A multi-disciplinary team (MDT)-like fusion was performed to integrate predictions from the high-performing models for the final discrimination of GBM vs. SBM. Image features extracted from the volumetric ET (VOI) had dominant predictive performances over features from other VOI combinations. Fusion of VOI features from the TWI and T_FLAIR sequences via the RFO model achieved a discrimination accuracy of AUC = 0.925, accuracy = 0.855, sensitivity = 0.856, and specificity = 0.853, on the independent testing cohort 1, and AUC = 0.859, accuracy = 0.836, sensitivity = 0.708, and specificity = 0.919 on the independent testing cohort 2, which significantly outperformed three experienced radiologists ( = 0.03, 0.01, 0.02, and 0.01, and = 0.02, 0.01, 0.45, and 0.02, respectively) and the MDT-decision result of three experienced experts ( = 0.03, 0.02, 0.03, and 0.02, and = 0.03, 0.02, 0.44, and 0.03, respectively).
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http://dx.doi.org/10.3390/cancers13225793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616314PMC
November 2021

Selenium-Enriched Soy Protein Has Antioxidant Potential via Modulation of the NRF2-HO1 Signaling Pathway.

Foods 2021 Oct 22;10(11). Epub 2021 Oct 22.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.

Selenium (Se)-enriched proteins are an important dietary source of Se for humans; however, only a few Se-enriched proteins have been identified. In the present study, we tested for potential antioxidant activity by Se-enriched soy protein, both in vitro and in vivo. Se-enriched soy protein isolate (S-SPI) was shown to have a higher free radical scavenging ability compared to ordinary soy protein isolate (O-SPI). Furthermore, Caco-2 cell viability was improved by S-SPI at low doses, whereas O-SPI did not. In addition, S-SPI was shown to inhibit oxidative stress via modulation of the NRF2-HO1 signaling pathway, upregulating the expression of downstream antioxidant enzymes (GPx, SOD). To further study the antioxidant capacity of S-SPI, BALB/c female mice were given oral gavages with 0.8 mL of S-SPI or O-SPI (5 g/kg/d, 20 g/kg/d and 40 g/kg/d) or saline as control. Hepatic GPx and SOD activity increased with increasing S-SPI dosage, but not with O-SPI. Taken together, our results suggest that Se-enriched soy protein has a high antioxidant ability and may be used as a dietary supplement for people with oxidative dam-age-mediated diseases.
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http://dx.doi.org/10.3390/foods10112542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623322PMC
October 2021

Angiotensin(1-7) activates MAS-1 and upregulates CFTR to promote insulin secretion in pancreatic β-cells: the association with type 2 diabetes.

Endocr Connect 2022 01 11;11(1). Epub 2022 Jan 11.

Department of Physiology, School of Medicine, Jinan University, Guangzhou, China.

Objective: The beneficial effect of angiotensin(1-7) (Ang(1-7)), via the activation of its receptor, MAS-1, has been noted in diabetes treatment; however, how Ang(1-7) or MAS-1 affects insulin secretion remains elusive and whether the endogenous level of Ang(1-7) or MAS-1 is altered in diabetic individuals remains unexplored. We recently identified an important role of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl- channel, in the regulation of insulin secretion. Here, we tested the possible involvement of CFTR in mediating Ang(1-7)'s effect on insulin secretion and measured the level of Ang(1-7), MAS-1 as well as CFTR in the blood of individuals with or without type 2 diabetes.

Methods: Ang(1-7)/MAS-1/CFTR pathway was determined by specific inhibitors, gene manipulation, Western blotting as well as insulin ELISA in a pancreatic β-cell line, RINm5F. Human blood samples were collected from 333 individuals with (n = 197) and without (n = 136) type 2 diabetes. Ang(1-7), MAS-1 and CFTR levels in the human blood were determined by ELISA.

Results: In RINm5F cells, Ang(1-7) induced intracellular cAMP increase, cAMP-response element binding protein (CREB) activation, enhanced CFTR expression and potentiated glucose-stimulated insulin secretion, which were abolished by a selective CFTR inhibitor, RNAi-knockdown of CFTR, or inhibition of MAS-1. In human subjects, the blood levels of MAS-1 and CFTR, but not Ang(1-7), were significantly higher in individuals with type 2 diabetes as compared to those in non-diabetic healthy subjects. In addition, blood levels of MAS-1 and CFTR were in significant positive correlation in type-2 diabetic but not non-diabetic subjects.

Conclusion: These results suggested that MAS-1 and CFTR as key players in mediating Ang(1-7)-promoted insulin secretion in pancreatic β-cells; MAS-1 and CFTR are positively correlated and both upregulated in type 2 diabetes.
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http://dx.doi.org/10.1530/EC-21-0357DOI Listing
January 2022

Barriers to seeking psychosocial support among adult patients with hematologic neoplasms: a qualitative study.

Support Care Cancer 2021 Nov 23. Epub 2021 Nov 23.

School of Nursing, Fujian Medical University, No. 1 Xueyuan Road, Shangjie, Minhou, Fuzhou, Fujian, China.

Purpose: This study aims to explore the barriers that adult patients with hematologic neoplasms experience when seeking psychosocial support.

Methods: A descriptive qualitative approach was used to investigate the experiences of patients with hematologic neoplasms. Face-to-face, semi-structured, in-depth individual interviews were conducted between June and October 2020 with 17 patients diagnosed with hematologic neoplasms. The interviews were audio-recorded and transcribed verbatim. A thematic analysis was performed to identify the essential themes.

Results: Seventeen patients aged 28-67 years completed the interviews. Two themes and six subthemes were identified that describe barriers to seeking psychosocial support. Internal barriers included limited communication, negative emotions, social avoidance, and focusing on treatment rather than psychosocial needs; external barriers included traditional cultural influences and lack of professional support.

Conclusions: Significant others were the key source for psychosocial support for patients with hematologic neoplasms. Tackling diverse barriers to accessing psychosocial support remains a challenge for these patients. Healthcare providers should continually assess and provide effective support.
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http://dx.doi.org/10.1007/s00520-021-06699-4DOI Listing
November 2021

Genomic Identification and Functional Analysis of JHAMTs in the Pond Wolf Spider, .

Int J Mol Sci 2021 Oct 29;22(21). Epub 2021 Oct 29.

Key Laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education), College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China.

Juvenile hormone (JH) plays a critical role in many physiological activities of Arthropoda. Juvenile hormone acid methyltransferase (JHAMT) is involved in the last steps of JH biosynthesis as an important rate-limiting enzyme. In recent studies, an increasing number of JHAMTs were identified in arthropods, but no JHAMT was reported in spiders. Herein, eight JHAMTs were identified in the pond wolf spider, , all containing the well conserved S-adenosyl-L-methionine binding motif. and the other seven were located at chromosome 13 and chromosome 1, respectively. Multiple alignment and phylogenetic analysis showed that JHAMT-1 was grouped together with insect JHAMTs independently and shared high similarities with insect JHAMTs compared to the other seven JHAMTs. In addition, , , and were highly expressed in the abdomen of spiderlings and could respond to the stimulation of exogenous farnesoic acid. Meanwhile, knockdown of these three caused the overweight and accelerated molting of spiderlings. These results demonstrated the cooperation of multi-JHAMTs in spider development and provided a new evolutionary perspective of the expansion of in Arachnida.
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http://dx.doi.org/10.3390/ijms222111721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584100PMC
October 2021

Riociguat therapy for pulmonary hypertension: a systematic review and meta-analysis.

Ann Palliat Med 2021 10;10(10):11117-11128

Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China; NHC Key Laboratory of Chronobiology (Sichuan University), West China Second University Hospital, Sichuan University, Chengdu, China; The Joint Laboratory for Lung Development and Related Diseases, West China Second University Hospital, Sichuan University, Chengdu, China.

Background: Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic significance for other types of pulmonary hypertension (PH). Our purpose was to evaluate the specific impact of riociguat on all types of PH.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of riociguat treatment for PH through databases of the Cochrane Library, PubMed, Embase, and Web of Science from inception to the present. Duplicate publications, studies with no full text, incomplete information or inability to extract data, animal experiments and reviews, and systematic reviews were excluded. The software RevMan 5.4 was used for data synthesis.

Results: There were 8 RCTs included in our study, involving 1,606 participants. For PAH and CTEPH patients, riociguat treatment extended 6-minute walk distance (6MWD) by 39.84 meters, decreased mean pulmonary arterial pressure (PAP) by 4.20 mmHg, lowered pulmonary vascular resistance (PVR) by 218.76 dynes/sec/cm-5, cut down right atrial pressure (RAP) by 0.9 mmHg, increased cardiac index (CI) by 0.49 L/min/m2, improved cardiac output (CO) by 0.89 L/min, reduced N-terminal pro-type B natriuretic peptide (NT-proBNP) by 436.21 pg/mL, and decreased adverse events and clinical worsening as compared with placebo. For other types of PH including PH due to left heart disease and PH due to lung disease, riociguat was reported as having improved CI by 0.42 L/min/m2 and CO was increased by 0.92 L/min compared with placebo. Other efficacy outcomes and safety outcomes did not attain statistical difference in other types of PH.

Conclusions: For PAH and CTEPH, riociguat treatment is safe and effective, but for other types of PH, it can only improve some hemodynamic parameters.
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http://dx.doi.org/10.21037/apm-21-2656DOI Listing
October 2021

Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein.

Signal Transduct Target Ther 2021 11 10;6(1):389. Epub 2021 Nov 10.

State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.

SARS-CoV-2 and SARS-CoV are genetically related coronavirus and share the same cellular receptor ACE2. By replacing the VSV glycoprotein with the spikes (S) of SARS-CoV-2 and SARS-CoV, we generated two replication-competent recombinant viruses, rVSV-SARS-CoV-2 and rVSV-SARS-CoV. Using wild-type and human ACE2 (hACE2) knock-in mouse models, we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal (i.n.) and intramuscular (i.m.) routes. Despite the high genetic similarity between SARS-CoV-2 and SARS-CoV, no obvious cross-neutralizing activity was observed in the immunized mice sera. In macaques, neutralizing antibody (NAb) titers induced by one i.n. dose of rVSV-SARS-CoV-2 were eight-fold higher than those by a single i.m. dose. Thus, our data indicates that rVSV-SARS-CoV-2 might be suitable for i.n. administration instead of the traditional i.m. immunization in human. Because rVSV-SARS-CoV elicited significantly stronger NAb responses than rVSV-SARS-CoV-2 in a route-independent manner, we generated a chimeric antigen by replacing the receptor binding domain (RBD) of SARS-CoV S with that from the SARS-CoV-2. rVSV expressing the chimera (rVSV-SARS-CoV/2-RBD) induced significantly increased NAbs against SARS-CoV-2 in mice and macaques than rVSV-SARS-CoV-2, with a safe Th1-biased response. Serum immunized with rVSV-SARS-CoV/2-RBD showed no cross-reactivity with SARS-CoV. hACE2 mice receiving a single i.m. dose of either rVSV-SARS-CoV-2 or rVSV-SARS-CoV/2-RBD were fully protected against SARS-CoV-2 challenge without obvious lesions in the lungs. Our results suggest that transplantation of SARS-CoV-2 RBD into the S protein of SARS-CoV might be a promising antigen design for COVID-19 vaccines.
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http://dx.doi.org/10.1038/s41392-021-00797-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578532PMC
November 2021

TCP1 increases drug resistance in acute myeloid leukemia by suppressing autophagy via activating AKT/mTOR signaling.

Cell Death Dis 2021 11 8;12(11):1058. Epub 2021 Nov 8.

Fujian Provincial Key Laboratory on Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.

T-complex protein 1 (TCP1) is one of the subunits of chaperonin-containing T complex (CCT), which is involved in protein folding, cell proliferation, apoptosis, cell cycle regulation, and drug resistance. Investigations have demonstrated that TCP1 is a factor being responsible for drug resistance in breast and ovarian cancer. However, the TCP1 role in acute myeloid leukemia (AML) remains elusive. In the present study, we discovered that the TCP1 expression was elevated in AML patients and high TCP1 expression was associated with low complete response rate along with poor overall survival. TCP1 showed higher expression in the adriamycin-resistant leukemia cell line HL60/A and K562/A, comparing to their respective parent cells HL60 and K562 cells. TCP1 inhibition suppressed drug resistance in HL60/A and K562/A cells, whereas TCP1 overexpression in HL60 cells incremented drug resistance, both in vitro and in vivo. Mechanistic investigations revealed that TCP1 inhibited autophagy and adriamycin-induced cell apoptosis, and TCP1-mediated autophagy inhibition conferred resistance to adriamycin-induced cell apoptosis. Furthermore, TCP1 interacted with AKT and mTOR to activate AKT/mTOR signaling, which negatively regulates apoptosis and autophagy. Pharmacological inhibition of AKT/mTOR signal particularly activated autophagy and resensitized TCP1-overexpressing HL60 cells to adriamycin. These findings identify a novel role of TCP1 regarding drug resistance in AML, which advise a new strategy for overcoming drug resistance in AML through targeting TCP1/AKT/mTOR signaling pathway.
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http://dx.doi.org/10.1038/s41419-021-04336-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575913PMC
November 2021

An overlapping peaks separation algorithm for ion mobility spectrometry based on second-order differentiation and dynamic inertia weight particle swarm optimization algorithm.

Rapid Commun Mass Spectrom 2022 Jan;36(2):e9220

Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, 315211, China.

Rationale: Ion mobility spectrometry (IMS) is a powerful analytical tool extensively applied in numerous domains. However, there still exists the phenomenon of peaks overlapping in the analysis of isomers with similar structures due to the limited resolution of IMS. In this paper, a dynamic inertia weight particle swarm optimization (DIWPSO) algorithm combined with second-order differentiation is proposed to separate the IMS overlapping peaks efficiently and precisely.

Methods: It can identify the component number of overlapping peaks and limit those parameters (ion mobility, intensity, and full-width at half maximum of each single peak) of the peak model in a small range using second-order differentiation. Based on this, DIWPSO that has been set the best operating parameters is capable of accurately separating IMS overlapping peaks to identify the compound within a short time.

Results: A comparison between the performance of DIWPSO and the improved particle swarm optimization (IPSO) found that DIWPSO with separation errors less than 2.34% overall outperforms IPSO whose maximum error is up to 5.58%. Moreover, the running time of DIWPSO is 30-80 times less than that of IPSO, and DIWPSO exhibits stronger robustness.

Conclusions: This method can automatically identify the component number of IMS overlapping peaks and resolve them with muticomponents and different overlapped degrees rapidly and accurately, which further improves the structural resolution of IMS.
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http://dx.doi.org/10.1002/rcm.9220DOI Listing
January 2022

Polymorphisms in the interleukin 4 promoter -589C/T gene and the risk of asthma: a systematic review and meta-analysis.

Transl Pediatr 2021 Sep;10(9):2355-2365

Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Background: To identify the association between polymorphisms in the interleukin 4 (IL-4) promoter -589C/T gene and the risk of asthma.

Methods: The databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, Chongqing VIP (CQVIP), and Chinese Biomedical Literature (CBM) were searched and appropriate journal articles on the association between polymorphisms in the IL-4 promoter -589C/T gene and the risk of asthma were retrieved from establishment of the database to April 2021. All relevant randomized controlled trials (RCTs) were included, to the exclusion of duplicate publications, studies with no whole composition, imperfect information or inability to extract data, animal experiments and reviews, and systematic reviews. The software Review manager 5.3 was used to analyze the data.

Results: Literature search led to retrieving of 16 publications containing 3181 cases and 3786 controls. The results show that CT, CC, and T gene polymorphisms were risk factors for asthma [odds ratio (OR) =1.05, 95% confidence interval (CI): 0.89-1.24; OR =1.04, 95% CI: 0.85-1.27; OR =1.98, 95% CI: 1.54-2.53]. Ethnic subgroup analysis showed that genotype CT was associated with the risk of asthma in the Asian population (OR =1.75, 95% CI: 1.01-3.05).

Discussion: Through the study of IL-4 (C-590T) gene polymorphism, it was found that CT, TT, and T gene polymorphism were risk factors for asthma, and the results suggested that this locus polymorphism was related to the risk of asthma. The results of subgroup analysis showed that CC and T gene polymorphisms were risk factors for asthma. Thus, IL-4(C-590T) may be the susceptibility gene of asthma.
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http://dx.doi.org/10.21037/tp-21-419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506068PMC
September 2021

Inhibitory effects of 1,3-diaminopropane on the biofilm formation of via interaction with quorum sensing system.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Sept 28;46(9):942-948

Department of Laboratory Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, China.

Objectives: To study the inhibitory effects of 1,3-diaminopropane on the biofilm formation of and the underlying mechanisms.

Methods: The experiment was divided into an experimental group and a control group. Crystal violet staining was used to examine the inhibitory effects of 1,3-diaminopropane on the biofilm formation of , and the biofilm formation was compared between the 2 groups.Initial adherence inhibition assay and swimming plate assay were used to determine the inhibitory effects of 1,3-diaminopropane on the initial adherence and swimming motility of ,and the quantification of adhered cells and swimming diameter were compared between the 2 groups. Meanwhile, Western blotting was used to detect the Flagellin production of ; real-time RT-PCR was used to detect the quorum sensing system relative genes and flagellum regulative related genes expression in the 2 groups. Finally, molecular docking assay was used to calculate the interaction between 1,3-diaminopropane and LasI.

Results: Compared with the control group, the biofilm formation of was significantly inhibited in the experimental group in a dose-dependent manner (=6.07, <0.01).Compared with the control group, the initial adherence of could significantly inhibit from (0.890±0.389)×10 to (0.245±0.076)×10 CFU/mL (=3.257, <0.05) in the experimental group (2.0 mmol/L).Compared with the control group, the swimming motility of flagellar mediation could also inhibit in the experimental group (2.0 mmol/L). The swimming motility diameter was from (1.840±0.144) to (0.756±0.222) cm (=7.099, <0.01). Compared with the control group, the Flagellin production was inhibited in the experimental group. Finally, the molecular docking assay showed that the potential target of 1,3-diaminopropane was LasI.

Conclusions: 1,3-diaminopropane can significantly inhibit the biofilm formation of , which potentially targets LasI protein.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200810DOI Listing
October 2021

Effects of a WeChat-based multimodal psychoeducational intervention on psychological well-being and quality of life in acute leukaemia patients in China: a randomised controlled trial.

J Cancer Surviv 2021 Oct 27. Epub 2021 Oct 27.

The School of Nursing, Fujian Province, Fujian Medical University, No.1 Xueyuan Road, Shangjie Town, Minhou County, Fuzhou City, 350108, China.

Purpose: The treatment and side effects of chemotherapy for acute leukaemia (AL) may cause both physical and psychological symptoms in patients. This study evaluated the effects of a WeChat-based multimodal psychoeducational intervention (ICARE programme) on fatigue, distress, anxiety, depression, and quality of life (QoL) among adult AL patients.

Methods: In total, 72 participants were randomly assigned either to an intervention or control group (n = 36), respectively, from two large tertiary hospitals in Fuzhou, China (from April to December 2019). Data were collected at baseline, post-intervention, and after a 4-week follow-up using the Brief Fatigue Inventory, Distress Thermometer, Hospital Anxiety and Depression Scale, and Functional Assessment of Cancer Therapy-leukaemia. Descriptive statistics was used to summarise the sociodemographic and clinical characteristics of the participants and a linear mixed model was used to analyse the score changes.

Results: Between the two groups, there were statistically significant improvements in fatigue, distress, anxiety, depression, physical well-being, social/family well-being, emotional well-being, functional well-being (all p < 0.001), and leukaemia-specific subscale (p = 0.001). The difference over time was significant for leukaemia-specific subscale and fatigue, both (p < 0.001), anxiety (p = 0.001), and social/family well-being (p = 0.005). The interaction effects were significant for fatigue, distress, anxiety, physical well-being, social/family well-being, and emotional well-being, all (p < 0.001), depression (p = 0.019), leukaemia-specific subscale (p = 0.008), and total QoL score (p = 0.004).

Conclusion: WeChat-based multimodal psychoeducational intervention demonstrated a significant effect in reducing fatigue, distress, anxiety, depression, and QoL in AL patients. This ICARE programme contributed to continuing care to support AL patients.

Implications For Cancer Survivors: The ICARE programme can improve the mental health and QoL of AL patients. The application of WeChat-based psychoeducational interventions have significant potential to benefit cancer patients due to their reach and can be an added value to routine care.
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http://dx.doi.org/10.1007/s11764-021-01124-5DOI Listing
October 2021

He . 2018 is a later heterotypic synonym of Park . 2018.

Int J Syst Evol Microbiol 2021 Oct;71(10)

Shanghai Engineering Research Center of Hadal Science and Technology, College of Marine Sciences, Shanghai Ocean University, Shanghai 201306, PR China.

L53 was compared with MM-14 to examine the taxonomic relationship between the two type strains. The 16S rRNA gene sequence of L53 had complete similarity (100.0%) to that of MM-14. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the two strains formed a tight cluster within the genus . Draft genomic comparison between the two strains revealed an average nucleotide identity of 96.9 % and a digital DNA-DNA hybridization estimate of 75.3±2.8 %, strongly indicating that the two strains represented a single species. In addition, neither strain displayed any striking difference in metabolic, physiological or chemotaxonomic features. Therefore, we propose that is a later heterotypic synonym of .
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http://dx.doi.org/10.1099/ijsem.0.005074DOI Listing
October 2021

Full-coverage regulations of autophagy by ROS: from induction to maturation.

Autophagy 2021 Oct 18:1-16. Epub 2021 Oct 18.

Department of Physiology, School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi Province, China.

Macroautophagy/autophagy is an evolutionarily well-conserved recycling process in response to stress conditions, including a burst of reactive oxygen species (ROS) production. High level of ROS attack key cellular macromolecules. Protein cysteinyl thiols or non-protein thiols as the major redox-sensitive targets thus constitute the first-line defense. Autophagy is unique, because it removes not only oxidized/damaged proteins but also bulky ROS-generating organelles (such as mitochondria and peroxisome) to restrict further ROS production. The oxidative regulations of autophagy occur in all processes of autophagy, from induction, phagophore nucleation, phagophore expansion, autophagosome maturation, cargo delivery to the lysosome, and finally to degradation of the cargo and recycling of the products, as well as autophagy gene transcription. Mechanically, these regulations are achieved through direct or indirect manners. Direct thiol oxidation of key proteins such as ATG4, ATM and TFEB are responsible for specific regulations in phagophore expansion, cargo recognition and autophagy gene transcription, respectively. Meanwhile, oxidation of certain redox-sensitive chaperone-like proteins (. PRDX family members and PARK7) may impair a nonspecifically local reducing environment in the phagophore membrane, and influence BECN1-involved phagophore nucleation and mitophagy recognition. However, ROS do exhibit some inhibitory effects on autophagy through direct oxidation of key autophagy regulators such as ATG3, ATG7 and SENP3 proteins. SQSTM1 provides an alternative antioxidant mechanism when autophagy is unavailable or impaired. However, it is yet to be unraveled how cells evolve to equip proteins with different redox susceptibility and in their correct subcellular positions, and how cells fine-tune autophagy machinery in response to different levels of ROS. AKT1/PKB: AKT serine/threonine kinase 1; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATM: ATM serine/threonine kinase; BAX: BCL2 associated X, apoptosis regulator; BECN1: beclin 1; BH3: BCL2-homology-3; CAV1: caveolin 1; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CTSB: cathepsin B; CTSL: cathepsin L; DAPK: death associated protein kinase; ER: endoplasmic reticulum; ETC: electron transport chain; GSH: glutathione; GSTP1: glutathione S-transferase pi 1; HO: hydrogen peroxide; HK2: hexokinase 2; KEAP1: kelch like ECH associated protein 1; MAMs: mitochondria-associated ER membranes; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MAPK8/JNK1: mitogen-activated protein kinase 8; MAP3K5/ASK1: mitogen-activated protein kinase kinase kinase 5; MCOLN1: mucolipin 1; MMP: mitochondrial membrane potential; MTOR: mechanistic target of rapamycin kinase; NFE2L2/NRF2: nuclear factor, erythroid 2 like 2; NFKB1: nuclear factor kappa B subunit 1; NOX: NADPH oxidase; O: superoxide radical anion; p-Ub: phosphorylated Ub; PARK7/DJ-1: Parkinsonism associated deglycase; PE: phosphatidylethanolamine; PEX5: peroxisomal biogenesis factor 5; PINK1: PTEN induced kinase 1; PPP3CA/calcineurin: protein phosphatase 3 catalytic subunit beta; PRDX: peroxiredoxin; PRKAA1: protein kinase AMP-activated catalytic subunit alpha 1; PRKD/PKD: protein kinase D; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PTEN: phosphatase and tensin homolog; ROS: reactive oxygen species; SENP3: SUMO specific peptidase 3; SIRT1: sirtuin 1; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; SUMO: small ubiquitin like modifier; TFEB: transcription factor EB; TRAF6: TNF receptor associated factor 6; TSC2: TSC complex subunit 2; TXN: thioredoxin; TXNRD1: thioredoxin reductase 1; TXNIP: thioredoxin interacting protein; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1.
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http://dx.doi.org/10.1080/15548627.2021.1984656DOI Listing
October 2021
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