Publications by authors named "Juan Wang"

3,367 Publications

  • Page 1 of 1

Three-dimensional quantitative structural-activity relationship and molecular dynamics study of multivariate substituted 4-oxyquinazoline HDAC6 inhibitors.

Mol Divers 2022 Jun 29. Epub 2022 Jun 29.

School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China.

3D-QSAR models were established by collecting 46 multivariate-substituted 4-oxyquinazoline HDAC6 inhibitors. The relationship of molecular structure and inhibitory activity was studied by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). The results showed the models established by CoMFA (q = 0.590, r = 0.965) and CoMSIA (q = 0.594, r = 0.931) had good prediction ability. At the same time, 3D-QSAR models met the internal verification, external verification and AD test. Ten new compounds were designed based on CoMFA and CoMSIA contour maps and their pharmacokinetic/toxic properties (ADME/T) were evaluated. It was found that most compounds have well safety profile and pharmacokinetic property. Then, we explored the interaction between HDAC6 and compounds by molecular docking. The results showed that the binding mode of the new compounds with HDAC6 was the same as the template compound 46, and the hydrogen bond and hydrophobic bond played a vital role in the binding process. Molecular dynamics simulation results showed that residues Ser531, His574 and Tyr745 played key roles in the binding process. All newly designed compounds had lower energy gap and binding energy than compound 46 according to DFT analysis and free energy analysis. This study provided a theoretical reference for designing compounds of higher activity and a new idea for the development of novel HDAC6 inhibitors.
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http://dx.doi.org/10.1007/s11030-022-10474-wDOI Listing
June 2022

Suppression of phosphodiesterase IV enzyme by Roflumilast ameliorates cognitive dysfunction in aged rats after sevoflurane anesthesia via PKA-CREB and MEK/ERK pathways.

Eur J Neurosci 2022 Jun 29. Epub 2022 Jun 29.

Department of Anesthesiology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, P.R. China.

Postoperative cognitive dysfunction (POCD) is a prevalent disorder after anesthesia in the elderly patients. Roflumilast (RF), a phosphodiesterase 4 (PDE-4) inhibitor, could improve cognition with no side effects. Here, we sought to explore the efficacy of RF in the improvement of cognitive dysfunction caused by sevoflurane (Sev). Sprague-Dawley rats were anesthetized and the hippocampal neurons were treated with Sev to develop in vivo and in vitro POCD models, followed by RF administration. The mechanism of the PKA-CREB and MEK/ERK pathways in the pathogenesis of POCD were explored. Sev impaired the cognitive functions of rats, significantly reduced cyclic adenosine monophosphate (cAMP) concentrations and blocked the PKA-CREB and MEK/ERK pathways. Moreover, the Sev-treated rats and neurons exhibited enhanced apoptosis and reactive oxygen species (ROS). After treatment with RF, rats had better learning and memory function, and the activity of neurons in hippocampus and cortex was improved. Loss-of-function assay indicated that PKA-CREB and MEK/ERK signaling impairment reduced cAMP levels and promoted apoptosis and ROS in rat hippocampus and neurons. Generally, RF promotes neuronal activity in rats after Sev treatment by maintaining cAMP levels and sustaining the activation of PKA-CREB and MEK/ERK pathways. This might offer novel sights for POCD therapy.
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http://dx.doi.org/10.1111/ejn.15751DOI Listing
June 2022

miR-338-3p Plays a Significant Role in Casticin-Induced Suppression of Acute Myeloid Leukemia via Targeting PI3K/Akt Pathway.

Biomed Res Int 2022 18;2022:9214130. Epub 2022 Jun 18.

Department of Hematology, Qingdao Women and Children's Hospital, Qingdao 266034, China.

Objective: Casticin is generally used in traditional herbal medicine for its anti-inflammatory and anticarcinogenic pharmacological properties. Also, microRNAs are indispensable oncogenes or cancer suppressors being dysregulated in various diseases. In this study, we aimed to elucidate the mechanisms underlying effects of casticin on the progression of acute myeloid leukemia (AML).

Methods: CCK-8 and flow cytometry were utilized to measure the proliferation and apoptosis of AML cell lines, respectively, after treatment with different concentrations of casticin. The alteration of several microRNA expressions in response to casticin treatment was detected by performing qRT-PCR, and the activity of PI3K/Akt pathways was evaluated through immunoblotting. Afterwards, the potential target gene of miR-338-3p was investigated by dual-luciferase reporter assay. In order to evaluate the role of miR-338-3p in the casticin-induced cellular phenotype changes, AML cells were transfected with miR-338-3p mimics or inhibitor and then subjected to proliferation and apoptosis analysis. Finally, a mouse xenograft model system was employed to investigate the role of casticin in AML progression in vivo.

Results: Suppressed cellular proliferation and enhanced apoptosis were observed in HL-60 and THP-1 cells after exposure to casticin, accompanied by remarkable upregulation of the miR-338-3p expression as well as a decline in the phosphorylation of PI3K and Akt proteins. RUNX2 was identified as a direct target molecular of miR-338-3p, which might account for the findings that miR-338-3p knockdown enhanced the PI3K/Akt pathway activity, whereas the miR-338-3p overexpression inactivated this signaling pathway. In addition, the inhibition of the miR-338-3p expression attenuated severe cell apoptosis and suppressions of PI3K/Akt pathway induced by casticin. Furthermore, casticin treatment retarded tumor growth rate in mouse models, whilst elevating miR-338 expression and repressing the activity of PI3K/Akt pathway in vivo. However, miR-338-3p depletion could also abolish the phenotypic alterations caused by casticin treatment.

Conclusion: Casticin promotes AML cell apoptosis but inhibits AML cell proliferation in vitro and tumor growth in vivo by upregulating miR-338-3p, which targets RUNX2 and thereafter inactivates PI3K-Akt signaling pathway. Our results provide insights into the mechanisms underlying the action of casticin in the control of AML progression.
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http://dx.doi.org/10.1155/2022/9214130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233736PMC
June 2022

Deep Orbital Hyaluronic Acid Gel Filler for Volume Augmentation in Orbital Dysplasia.

J Craniofac Surg 2022 Jun 29. Epub 2022 Jun 29.

Department of Eye Plastic Surgery, Hebei Provincial Key Laboratory of Ophthalmology, Hebei Provincial Eye Institute, Hebei Provincial Eye Hospital, Xingtai, Hebei 054001, China.

Purpose: Orbital dysplasia is caused by congenital microphthalmos, anophthalmos, or eye atrophy. Orbital volume growth is known to parallel ocular growth and the absence of an eye results in noticeable hemifacial deformity that affects patients' lives. The aim of this study was to observe the effects of injections of hyaluronic acid gel into the orbit combined with ocular prosthesis to treat orbital dysplasia.

Methods: Three patients with orbital dysplasia who were 3 to 7 years old treated in our department. Each year, the hyaluronic acid gel was injected into each patient intraconal and extraconal posterior orbit and each wore an ocular prosthesis. The length of the palpebral fissure and orbital volume were measured before and after the injections.

Results: A total of 9 injections were performed on 3 patients ages 7, 5, and 4 years old, respectively. The follow-up periods were 5, 5, and 2 years. The authors observed significant improvements in patient appearance. The length of the palpebral fissure and the volume of the orbit increased linearly with the increasing age, and there were no complications, such as intraorbital hemorrhage or local hyperplastic stimulation.

Conclusions: Orbital hyaluronic acid gel injection and combined with an ocular prosthesis is a safe, convenient, and effective treatment for orbital dysplasia.
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http://dx.doi.org/10.1097/SCS.0000000000008393DOI Listing
June 2022

Interactions between tannins allelochemicals and extracellular polymeric substance (EPS) of Microcystis aeruginosa.

Environ Sci Pollut Res Int 2022 Jun 28. Epub 2022 Jun 28.

School of Environment, Nanjing Normal University, Nanjing, 210023, China.

The protective mechanism of extracellular polymeric substance (EPS) secreted by a harmful cyanobacteria against tannins allelochemicals was explored in this study. The binding properties of soluble EPS (SEPS) and bound EPS (BEPS) of Microcystis aeruginosa to tannic acid (TA) were investigated via fluorescence spectroscopy. The results suggested that TA interacted with the proteins in SEPS and BEPS mainly with binding constants of 5.26 and 7.93 L/mol, respectively; TA interacted with the humic acids in SEPS and BEPS mainly with binding constants of 5.12 and 5.24 L/mol, respectively. Thermodynamic experiments confirmed that the binding was mainly controlled by the hydrophobic force. Combined with Fourier transform infrared spectroscopy, it was found that the amine, carbonyl, carboxyl, and hydroxyl groups in EPS were the main functional groups contributing to the interaction of TA with EPS. The existence of EPS reduced the toxicity of TA to algal cells, with the 96 h inhibition rate of 40 mg L TA on algal cells decreasing by 48.95%. The results of this study may improve our understanding of the protective mechanism of cyanobacteria against tannins allelochemicals.
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http://dx.doi.org/10.1007/s11356-022-21661-5DOI Listing
June 2022

Self-Regulating Solar Steam Generators Enable Volatile Organic Compound Removal through In Situ HO Generation.

Environ Sci Technol 2022 Jun 28. Epub 2022 Jun 28.

Institute of Environmental Health, MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental & Resource Sciences, Zhejiang University, Hangzhou 310058, China.

Interfacial solar steam generation for clean water production suffers from volatile organic compound (VOC) contamination during solar-to-steam conversion. Here, we present a solar steam generator based on the integration of melamine foam (MF), polydopamine (PDA), and Ag/AgCl particles. Together with the high photothermal conversion efficiency (ca. 87.8%, 1 kW/m) achieved by the PDA thin film, the Ag/AgCl particles can efficiently activate the localized generation of HO and OH in situ, thus degrading the VOCs during the rapid vapor generation. The generation of HO and OH in situ also facilitates the creation of a buffer zone containing HO and OH for the rapid removal of organic pollutants in the surrounding water attracted to the solar vapor generator, demonstrating a self-cleaning steam generator toward various volatile compounds such as phenol, aniline, 2,4-dichlorophenol, and -dimethylformamide in a wide range of concentrations.
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http://dx.doi.org/10.1021/acs.est.2c02067DOI Listing
June 2022

Effect of prenatal and postnatal exposure to home renovation on the risk of common cold in preschool children.

Indoor Air 2022 Jun;32(6):e13063

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Common cold is usually considered to be associated with outdoor climate, but the evidence linking with indoor environmental factors is lacking. The role of indoor renovations during which critical timing window on childhood common cold remains unclear. Therefore, we investigated the effect of exposure to new furniture and/or redecoration during prenatal and postnatal periods on the occurrence and duration of common cold in preschool children. We conducted a retrospective cohort study of 39 782 children aged 3-6 years in seven cities of China. The occurrence and duration of common cold in children, and their lifetime exposures to indoor new furniture and redecoration (including pregnancy, the first year of life, and after one year old) were assessed using a questionnaire administered by the parents. Associations between high frequency (>5 colds) and long duration (≥2 weeks per cold) of common cold during past 12 months and exposure to indoor new furniture/redecoration were examined by logistic regression models in terms of odds ratio (OR) and 95% confidence interval (CI). We found that the prevalence of high frequency and long duration of common cold in preschool children in China were, respectively, 9.2% and 11.9%. Frequent common cold was significantly associated with exposure to indoor new furniture/redecoration during pregnancy, first year, and after 1 year old, respectively, with the ORs (95% CI) = 1.25 (1.12-1.39), 1.11 (1.00-1.25), and 1.09 (1.01-1.18). Furthermore, childhood long duration per cold was associated with exposure to indoor new furniture/redecoration during pregnancy with OR (95% CI) of 1.14 (1.03-1.25) but not with postnatal exposure. We identified that prenatal exposure to home renovation was more critical than postnatal exposure for an increased risk of high frequency and long duration of common cold. Sensitivity analysis showed that the association between prenatal exposure to indoor renovations and the risk of childhood common cold was consistent and robust, and the associations were modified by some personal and indoor environmental factors. Our findings indicated that prenatal and postnatal exposure to home renovation played an important role in the risk of childhood common cold, supporting the hypothesis of "fetal origin of childhood infection."
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http://dx.doi.org/10.1111/ina.13063DOI Listing
June 2022

Polysaccharides from Cordyceps militaris prevent obesity in association with modulating gut microbiota and metabolites in high-fat diet-fed mice.

Food Res Int 2022 Jul 1;157:111197. Epub 2022 Apr 1.

Department of Food Science and Engineering, Institute of Food Safety and Nutrition, College of Science & Engineering, Jinan University, Guangzhou 510632, China. Electronic address:

Improved gut microbes and nutritious metabolites have been considered as the mediators of health benefits from indigestible polysaccharides, but their role in the anti-obesity effect of polysaccharides from Cordyceps militaris (CMP) remains elusive. This study aims to explore the potential mediators of the anti-obesity effects of CMP in high-fat diet (HFD)-fed mice using 16S rRNA sequencing and untargeted metabolomics analysis. The results showed that CMP supplementation in HFD-fed mice reduced body weight, fat accumulation, pro-inflammatory cytokine levels, and impaired glucose tolerance as well as gut barrier. Moreover, the CMP reversed the HFD-induced gut microbiota dysbiosis, as indicated by the elevated population of Alloprevotella, Parabacteroides, Butyricimonas, and Alistipes; and decreased population of Negativebacillus, in addition to altered levels of metabolites, such as brassicasterol and 4'-O-methylkanzonol W. Notably, CMP prevented obesity in association with the altered gut microbes and metabolites. These findings suggest that CMP may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play a critical role in its preventing obesity-related diseases.
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http://dx.doi.org/10.1016/j.foodres.2022.111197DOI Listing
July 2022

IDO1 plays a tumor-promoting role via MDM2-mediated suppression of the p53 pathway in diffuse large B-cell lymphoma.

Cell Death Dis 2022 Jun 27;13(6):572. Epub 2022 Jun 27.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, China.

With the intensive therapeutic strategies, diffuse large B-cell lymphoma (DLBCL) is still a fatal disease due to its progressive characteristics. Indoleamine 2,3-dioxygenase 1 (IDO1) is a key regulator that catalyzes the commitment step of the kynurenine pathway in the immune system, its aberrant activation may contribute to malignant cell escape eradication. However, the role of IDO1 in DLBCL progression remains elusive. Our study showed IDO1 expression was upregulated in DLBCL and was associated with a poor prognosis and low overall survival. Inhibition of IDO1 suppressed DLBCL cell proliferation in vitro and impeded xenograft tumorigenesis in vivo. RNA-seq analyses revealed MDM2 was downregulated while TP53 was upregulated in IDO1 inhibition OCI-Ly10 cells. Mechanistically, IDO1 inhibition decreased the expression of MDM2, a major negative regulator of p53, and restored p53 expression in OCI-Ly3 and OCI-Ly10 cells, resulting in cell cycle arrest and apoptosis. IDO1 inhibition induced cell apoptosis coupled with PUMA and BAX upregulation, as well as BCL2 and BCL-XL downregulation. In addition, p21, a p53 transcriptional target, was upregulated in cell cycle arrest. Taken together, this study revealed IDO1 is essential for the proliferation of DLBCL cells and may be a potential therapeutic target for the treatment of DLBCL.
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http://dx.doi.org/10.1038/s41419-022-05021-2DOI Listing
June 2022

Predictive value of serum bile acids as metabolite biomarkers for liver cirrhosis: a systematic review and meta-analysis.

Metabolomics 2022 Jun 27;18(7):43. Epub 2022 Jun 27.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing, 100700, China.

Introduction: A large number of studies have explored the potential biomarkers for detecting liver cirrhosis in an early stage, yet consistent conclusions are still warranted.

Objectives: To conduct a review and a meta-analysis of the existing studies that test the serum level of bile acids in cirrhosis as the potential biomarkers to predict cirrhosis.

Methods: Six databases had been searched from inception date to April 12, 2021. Screening and selection of the records were based on the inclusion criteria. The risk of bias was assessed with the Newcastle-Ottawa quality assessment scale (NOS). Mean difference (MD) and confidence intervals 95% (95% CI) were calculated by using the random effect model for the concentrations of bile acids in the meta-analysis, and I statistic was used to measure studies heterogeneity. This study was registered on PROSPERO.

Results: A total of 1583 records were identified and 31 studies with 2679 participants (1263 in the cirrhosis group, 1416 in the healthy control group) were included. The quality of included studies was generally high, with 25 studies (80.6%) rated over 7 stars. A total of 45 bile acids or their ratios in included studies were extracted. 36 increased in the cirrhosis group compared with those of the healthy controls by a qualitative summary, 5 decreased and 4 presented with mixing results. The result of meta-analysis among 12 studies showed that 13 bile acids increased, among which four primary conjugated bile acids showed the most significant elevation in the cirrhosis group: GCDCA (MD = 11.38 μmol/L, 95% CI 8.21-14.55, P < 0.0001), GCA (MD = 5.72 μmol/L, 95% CI 3.47-7.97, P < 0.0001), TCDCA (MD = 3.57 μmol/L, 95% CI 2.64-4.49, P < 0.0001) and TCA (MD = 2.14 μmol/L, 95% CI 1.56-2.72, P < 0.0001). No significant differences were found between the two groups in terms of DCA (MD = - 0.1 μmol/L, 95% CI - 0.18 to - 0.01, P < 0.0001) and LCA (MD = - 0.01 μmol/L, 95% CI - 0.01 to - 0.02, P < 0.0001), UDCA (MD = - 0.14 μmol/L, 95% CI - 0.04 to - 0.32, P < 0.0001), and TLCA (MD = 0 μmol/L, 95% CI 0-0.01, P < 0.0001). Subgroup analysis in patients with hepatitis B cirrhosis showed similar results.

Conclusion: Altered serum bile acids profile seems to be associated with cirrhosis. Some specific bile acids (GCA, GCDCA, TCA, and TCDCA) may increase with the development of cirrhosis, which possibly underlay their potential role as predictive biomarkers for cirrhosis. Yet this predictive value still needs further investigation and validation in larger prospective cohort studies.
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http://dx.doi.org/10.1007/s11306-022-01890-yDOI Listing
June 2022

Pesticide Residues in Commonly Consumed Vegetables in Henan Province of China in 2020.

Front Public Health 2022 10;10:901485. Epub 2022 Jun 10.

Department of Social Medicine, College of Public Health, Zhengzhou University, Zhengzhou, China.

Background: Pesticides are widely used in agricultural production to control insect pests and regulate plant growth in China, which may result in the presence of some pesticide residues in the vegetables. However, few studies of monitoring pesticides have been conducted in Henan Province. The aim of this study was to evaluate the level of pesticide residues in commonly consumed vegetables in the regions of Henan Province.

Methods: In this study, we collected 5,576 samples of 15 different vegetables in 17 areas from Henan Province during 2020. Eight kinds of pesticides were analyzed by gas chromatography-mass spectrometry (GC-MS), including procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin, isocarbophos, isazophos, fenthion and deltamethrin. The chi-square test was used to compare the detection rates of pesticide residues in different regions.

Results: Of all the pesticides above, procymidone, lambda-cyhalothrin, cypermethrin, pendimethalin and isocarbophos were detected in vegetables, the detection rates were 27.0%, 16.2%, 11.4%, 3.5%, and 1.9%, respectively. However, isazophos, fenthion, and deltamethrin were not detected. In addition, procymidone, lambda-cyhalothrin, and cypermethrin were detected in urban areas, while pendimethalin was detected in rural areas. The detection rates of cypermethrin and pendimethalin in rural were 19.8% and 5.4%, respectively, which in urban were at relatively lower levels (13.7% and 1.9%, respectively) ( < 0.05). Compared the differences of pesticide detection rates among five areas of Henan province, we found that there were statistical differences in the detection rates of procymidone, cypermethrin and lambda-cyhalothrin in different regions (all < 0.05).

Conclusion: The results have revealed that the pesticide residues are present. Higher detection rates and more types of pesticides were found in rural areas than urban areas. In addition, there were higher detection rates in Eastern Henan. The findings provided valuable information on the current pesticide residues status, which can be a reference of pesticide supervision and management.
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http://dx.doi.org/10.3389/fpubh.2022.901485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226416PMC
June 2022

Immune-Related LncRNAs as Prognostic Factors for Pediatric Rhabdoid Tumor of the Kidney.

Dis Markers 2022 15;2022:4752184. Epub 2022 Jun 15.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.

Background: Immune-related long noncoding RNAs (IrlncRNAs) are recognized as important prognostic factors in a variety of cancers, but thus far, their prognostic value in pediatric rhabdoid tumor of the kidney (pRTK) has not been reported. Here, we clarified the associations between IrlncRNAs and overall survival (OS) of pRTK patients and constructed a model to predict their prognosis.

Methods: We accessed RNA sequencing data and corresponding clinical data of pRTK from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. An expression profile of immune-related genes (Irgenes) and lncRNAs of pRTK was extracted from the RNA sequencing data. IrlncRNAs were defined by co-expression analysis of lncRNAs and Irgenes. The limma R package was used to identify differential expression IrlncRNAs. Univariate and multivariate Cox regression analyses were conducted to build a prognostic IrlncRNAs model. The performance of this prognostic model was validated by multimethods, like ROC curve analysis.

Results: A total of 1097 IrlncRNAs were defined. Univariate Cox regression analysis identified 7 IrlncRNAs (AC004791.2, AP003068.23, RP11-54O7.14, RP11-680F8.1, TBC1D3P1-DHX40P1, TUNAR, and XXbac-BPG308K3.5) and were significantly associated with OS. Multivariate regression analysis constructed the best prognostic model based on the expression of AC004791.2, AP003068.23, RP11-54O7.14, TBC1D3P1-DHX40P1, and TUNAR. According to the prognostic model, a risk score of each patient was calculated, and patients were divided into high-risk and low-risk groups accordingly. The survival time of low-risk patients was significantly better than high-risk patients ( < 0.001). Univariate (hazard ratio 1.098, 95% confidence interval 1.048-1.149, value <0.001) and multivariate (hazard ratio 1.095, 95% confidence interval 1.043-1.150, value <0.001) analyses confirmed that the prognostic model was reliable and independent in prediction of OS. Time-dependent ROC analysis showed that 1-year survival AUC of prognostic model, stage, age, and sex was 0.824, 0.673, 0.531, and 0.495, respectively, which suggested that the prognostic model was the best predictor of survival in pRTK patients.

Conclusions: The prognostic model based on 5 IrlncRNAs was robust and could better predict the survival of pRTK than other clinical factors. Additionally, the mechanism of regulation and action of prognosis-associated lncRNAs could provide new avenues for basic research to explore the mechanism of tumor initiation and development in order to prevent and treat pRTK.
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http://dx.doi.org/10.1155/2022/4752184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217527PMC
June 2022

A Flagella Hook Coding Gene Positively Affects Biofilm Formation and Cereulide Production in Emetic .

Front Microbiol 2022 10;13:897836. Epub 2022 Jun 10.

Department of Food Science and Technology, Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China.

, an important foodborne pathogen, poses a risk to food safety and quality. Robust biofilm formation ability is one of the key properties that is responsible for the food contamination and food poisoning caused by , especially the emetic strains. To investigate the mechanism of biofilm formation in emetic . strains, we screened for the mutants that fail to form biofilms by using random mutagenesis toward 892-1, an emetic strain with strong biofilm formation ability. When knocking out , a flagellar hook encoding gene, the mutant showed disappearance of flagellar structure and swimming ability. Further analysis revealed that both pellicle and ring presented defects in the null mutant compared with the wild-type and complementary strains. Compared with the flagellar paralytic strains and , the inhibition of biofilm formation by is not only caused by the inhibition of motility. Interestingly, also decreased the synthesis of cereulide. To our knowledge, this is the first report showing that a flagellar component can both affect the biofilm formation and cereulide production in emetic , which can be used as the target to control the biohazard of emetic .
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http://dx.doi.org/10.3389/fmicb.2022.897836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226606PMC
June 2022

Research of Synergistic Substances on Tobacco Beetle [ (Fabricius) (Coleoptera: Anobiidae)] Adults Attractants.

Front Chem 2022 8;10:921113. Epub 2022 Jun 8.

Guizhou Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region, Institute of Entomology, Scientific Observing and Experimental Station of Crop Pest in Guiyang, Ministry of Agriculture, Guizhou University, Guiyang, China.

In this study, four kinds of chemical substances (2,3,5,6-tetramethylpyrazine, -ionone, citronellal, and paeonol), three kinds of plant essential oils (tea tree essential oil, lavender essential oil, and myrrh essential oil), and their combinations were selected to explore their synergistic effects on tobacco beetle [ (Fabricius) (Coleoptera: Anobiidae)] adults by the behavioral test and laboratory simulation test. Behavioral test results showed that some of the combinations revealed a synergistic effect on tobacco beetle adults, especially the sexual attractant +2,3,5,6-tetramethylpyrazine + -ionone + citronellal + paeonol (SABCD, one portion of sexual attractant, and 1 mg/L synergistic substances) combination and the food attractant +2,3,5,6-tetramethylpyrazine + paeonol (FAD, 1 ml of food attractant and 1 mg/L synergistic substances) combination showed the best behavioral effect on tobacco beetle adults with average dwell times of 120.97 and 126.74 s, respectively, compared to those of other combinations. Meanwhile, SABCD had the highest selection rate [89.47%, about 1.5 times that of the sexual attractant (S)] on tobacco beetle adults compared with those of other combinations. In addition, laboratory simulation test results showed that the SABCD combination had the highest average selection rate (37.31%, about 2 times that of S) on tobacco beetle adults at 1 mg/L. However, our results showed that there was no significant difference in the indoor simulation results of food attractant synergistic substances. Our results will provide guidance for the development of new pesticides for tobacco beetle adults.
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http://dx.doi.org/10.3389/fchem.2022.921113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213786PMC
June 2022

LncRNA Pnky Positively Regulates Neural Stem Cell Migration by Modulating mRNA Splicing and Export of Target Genes.

Cell Mol Neurobiol 2022 Jun 24. Epub 2022 Jun 24.

College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei, 430065, People's Republic of China.

Directed migration of neural stem cells (NSCs) is critical for embryonic neurogenesis and the healing of neurological injuries. The long noncoding RNA (lncRNA) Pnky has been reported to regulate neuronal differentiation of NSCs by interacting with PTBP1. However, its regulatory effect on NSC migration remains to be determined. Herein, we identified that Pnky is also a key regulator of NSC migration in mice, as underscored by the finding that Pnky silencing suppressed but Pnky overexpression promoted the in vitro migration of both C17.2 and NE4C murine NSCs. Additionally, in vivo cell tracking demonstrated that Pnky depletion attenuated but Pnky overexpression facilitated the migration of NE4C cells in the spinal canal after transplantation via injection into the spinal canal. Mechanistically, Pnky regulated the expression of a core set of critical regulators that direct NSC migration, including MMP2, MMP9, Connexin43, Paxillin, AKT, ERK, and P38MAPK. Using catRAPID, a web server for large-scale prediction of protein-RNA interactions, the splicing factors U2AF1 and U2AF1L4, as well as the mRNA export adaptors SARNP, Aly/Ref, and THOC7, were predicted to interact strongly with Pnky. Further investigations using colocalization and RNA immunoprecipitation (RIP) assays confirmed the direct binding of Pnky to U2AF1, SARNP, Aly/Ref, and THOC7. Transcriptomic profiling revealed that as many as 5319 differential splicing events of 3848 genes, which were highly enriched in focal adhesion, PI3K-Akt and MAPK signaling pathways, were affected by Pnky depletion. The predominant subtype of differential splicing by Pnky depletion is intron retention, followed by alternative 5' and 3' splice sites and mutually exclusive exons. Moreover, Pnky knockdown substantially blocked but Pnky overexpression facilitated the export of MMP2, Paxillin, AKT, p38MAPK, and other mRNAs to the cytosol. Collectively, our data showed that through interacting with U2AF1, SARNP, Aly/Ref, and THOC7, Pnky couples and modulates the splicing and export of target mRNAs, which consequently controlling NSC migration. These findings provide a possible theoretical basis of NSC migration regulation.
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http://dx.doi.org/10.1007/s10571-022-01241-4DOI Listing
June 2022

A Systematic Review of Associations between Energy Use, Fuel Poverty, Energy Efficiency Improvements and Health.

Int J Environ Res Public Health 2022 Jun 16;19(12). Epub 2022 Jun 16.

Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, 75185 Uppsala, Sweden.

Energy use in buildings can influence the indoor environment. Studies on green buildings, energy saving measures, energy use, fuel poverty, and ventilation have been reviewed, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The database PubMed was searched for articles published up to 1 October 2020. In total, 68 relevant peer-reviewed epidemiological or exposure studies on radon, biological agents, and chemicals were included. The main aim was to assess current knowledge on how energy saving measures and energy use can influence health. The included studies concluded that buildings classified as green buildings can improve health. More efficient heating and increased thermal insulation can improve health in homes experiencing fuel poverty. However, energy-saving measures in airtight buildings and thermal insulation without installation of mechanical ventilation can impair health. Energy efficiency retrofits can increase indoor radon which can cause lung cancer. Installation of a mechanical ventilation systems can solve many of the negative effects linked to airtight buildings and energy efficiency retrofits. However, higher ventilation flow can increase the indoor exposure to outdoor air pollutants in areas with high levels of outdoor air pollution. Finally, future research needs concerning energy aspects of buildings and health were identified.
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http://dx.doi.org/10.3390/ijerph19127393DOI Listing
June 2022

Role of mTOR Signaling Cascade in Epidermal Morphogenesis and Skin Barrier Formation.

Biology (Basel) 2022 Jun 19;11(6). Epub 2022 Jun 19.

Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong 226011, China.

The skin epidermis, with its capacity for lifelong self-renewal and rapid repairing response upon injury, must maintain an active status in metabolism. Mechanistic target of rapamycin (mTOR) signaling is a central controller of cellular growth and metabolism that coordinates diverse physiological and pathological processes in a variety of tissues and organs. Recent evidence with genetic mouse models highlights an essential role of the mTOR signaling network in epidermal morphogenesis and barrier formation. In this review, we focus on the recent advances in understanding how mTOR signaling networks, including upstream inputs, kinases and downstream effectors, regulate epidermal morphogenesis and skin barrier formation. Understanding the details of the metabolic signaling will be critical for the development of novel pharmacological approaches to promote skin barrier regeneration and to treat epidermal barrier defect-associated diseases.
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http://dx.doi.org/10.3390/biology11060931DOI Listing
June 2022

Bioengineering Human Tissues and the Future of Vascular Replacement.

Circ Res 2022 Jun 23;131(1):109-126. Epub 2022 Jun 23.

Department of Anesthesiology and Biomedical Engineering, Yale University, New Haven, CT (L.E.N.).

Cardiovascular defects, injuries, and degenerative diseases often require surgical intervention and the use of implantable replacement material and conduits. Traditional vascular grafts made of synthetic polymers, animal and cadaveric tissues, or autologous vasculature have been utilized for almost a century with well-characterized outcomes, leaving areas of unmet need for the patients in terms of durability and long-term patency, susceptibility to infection, immunogenicity associated with the risk of rejection, and inflammation and mechanical failure. Research to address these limitations is exploring avenues as diverse as gene therapy, cell therapy, cell reprogramming, and bioengineering of human tissue and replacement organs. Tissue-engineered vascular conduits, either with viable autologous cells or decellularized, are the forefront of technology in cardiovascular reconstruction and offer many benefits over traditional graft materials, particularly in the potential for the implanted material to be adopted and remodeled into host tissue and thus offer safer, more durable performance. This review discusses the key advances and future directions in the field of surgical vascular repair, replacement, and reconstruction, with a focus on the challenges and expected benefits of bioengineering human tissues and blood vessels.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.319984DOI Listing
June 2022

Emergence of extensive multidrug resistant Staphylococcus aureus carrying novel Sa-MRR in retail food.

J Glob Antimicrob Resist 2022 Jun 19. Epub 2022 Jun 19.

Guangdong Provincial Key Laboratory of Microbial Safety and Health, state Key Laboratory of Applied Microbiology Southern China, Key Laboratory of Agricultural Microbiomics and Precision Application, Ministry of Agriculture and Rural Affairs, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, PR China. Electronic address:

Objectives: The aim of this study was to investigate the prevalence and genetic environment of the multidrug resistance gene lsa(E) in food-related S. aureus in China.

Methods: 1463 S. aureus from retail food products in 39 Chinese cities were investigated to determined the prevalence of lsa(E). Furthermore, antimicrobial susceptibility testing, whole-genome sequencing (WGS) and complete genetic analysis were performed in lsa(E)-positive isolates.

Results: As a result, thirty-five isolates (2.4%) were positive for the lsa(E) gene which had an extensive multidrug-resistance phenotype. ST9-t899 and ST1-t4792 were the common types in positive strains. The lsa(E) genes were located in two different types of novel multiresistance region (MRR) on the chromosome. The Sa-MRR-I were inserted into lctP gene. The Sa-MRR-II were inserted into crtP gene and they were comprised of 7 ARGs interspersed with varieties of ISs, transposons and DNA invertase genes, showing is a novel arrangement harboring lsa(E). Part of transposon Tn1546 was inserted into downstream of lnu(B) in the novel Sa-MRR-II. Both two types of Sa-MRR could be excised from chromosome, indicating the Sa-MRR may be transferable.

Conclusion: Our study is the first systematical investigation of lsa(E)-positive S. aureus in retail foods in China. It indicated that the origin of most food-related lsa(E)-positive S. aureus in China might be associated with livestock or poultry breeding farm and has been transmitted between animal and food. Moreover, the emergence of S. aureus carrying novel Sa-MRR, especially serve as a reservoir of antibiotic resistance traits, should warrants further attention.
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http://dx.doi.org/10.1016/j.jgar.2022.06.011DOI Listing
June 2022

Engineering of triterpene metabolism and overexpression of the lignin biosynthesis gene PAL promotes ginsenoside Rg accumulation in ginseng plant chassis.

J Integr Plant Biol 2022 Jun 22. Epub 2022 Jun 22.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China.

The ginsenoside Rg found in Panax species has extensive pharmacological properties, in particular anti-cancer effects. However, its natural yield in Panax plants is limited. Here, we report a multi-modular strategy to improve yields of Rg in a Panax ginseng chassis, combining engineering of triterpene metabolism and overexpression of a lignin biosynthesis gene, phenylalanine ammonia lyase (PAL). We first performed semi-rational design and site mutagenesis to improve the enzymatic efficiency of Pq3-O-UGT2, a glycosyltransferase that directly catalyzes the biosynthesis of Rg from Rh . Next, we used CRISPR/Cas9 gene editing to knock down the branch pathway of protopanaxatriol-type ginsenoside biosynthesis to enhance the metabolic flux of the protopanaxadiol-type ginsenoside Rg . Overexpression of PAL accelerated the formation of the xylem structure, significantly improving ginsenoside Rg accumulation (to 6.19-fold higher than in the control). We combined overexpression of the ginsenoside aglycon synthetic genes squalene epoxidase, Pq3-O-UGT2, and PAL with CRISPR/Cas9-based knockdown of CYP716A53v2 to improve ginsenoside Rg accumulation. Finally, we produced ginsenoside Rg at a yield of 83.6 mg/L in a shake flask (7.0 mg/g dry weight, 21.12-fold higher than with wild-type cultures). The high-production system established in this study could be a potential platform to produce the ginsenoside Rg commercially for pharmaceutical use. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jipb.13315DOI Listing
June 2022

Gamma knife radiosurgery versus transcatheter arterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a propensity score matching study.

Hepatol Int 2022 Jun 21. Epub 2022 Jun 21.

Department of Oncology and Hematology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, China.

Background: The optimal locoregional treatment for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is unclear. This study aimed to investigate the efficacy of Gamma knife radiosurgery (GKR) versus transcatheter arterial chemoembolization (TACE) in HCC patients with PVTT.

Methods: This retrospective study included 544 HCC patients with PVTT (GKR, 202; TACE, 342). Propensity score matching (PSM) analysis identified 171 matched pairs of patients. The primary endpoint was overall survival (OS).

Results: Before PSM, the GKR group exhibited longer median OS (mOS) than the TACE group (17.2 vs. 8.0 months, p < 0.001). We followed the Cheng's classification for PVTT. In the subgroup analysis, GKR was associated with significantly longer mOS for patients with PVTT II-IV (17.5 vs. 8.7 months, p < 0.001; 17.2 vs. 7.8 months, p = 0.001; 14.5 vs. 6.5 months, p = 0.001, respectively) and comparable OS for patients with PVTT I. After PSM, the GKR group had also a longer mOS than the TACE group (15.8 vs. 10.4 months, p < 0.001). In the subgroup analysis, the GKR group demonstrated superior mOS for patients with PVTT II-IV (all p < 0.05) and comparable OS for patients with PVTT I.

Conclusions: GKR was associated better OS than TACE in HCC patients with PVTT, especially for patients with PVTT II-IV.

Clinical Trials Registration: The study was registered in the Chinese Clinical Trials Registry under the registration number ChiCTR2100051057.
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http://dx.doi.org/10.1007/s12072-022-10339-2DOI Listing
June 2022

Uridylation: a vital way for cellular RNA surveillance.

Yi Chuan 2022 Jun;44(6):449-465

Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.

RNA uridylation is an efficient posttranscriptional regulator of gene expression conserved in almost all eukaryotes. Terminal uridylyltransferase (TUTase) are responsible for monouridylation and oligouridylation of various RNA substrates, including snRNA, miRNA, mRNA and other ncRNAs. Studies have demonstrated that monouridylation on ncRNA intermediates alters their ultimate products and processing rates, whereas oligouridylation is often employed to degrade particular RNAs with spatio-temporal specificity and responsible for clearance of the aberrant RNAs and viral RNAs. Uridylation regulates gene expression by these two ways, therefore affects several important biological processes including organismal reproduction and early development, apoptosis, tumorigenesis, as well as virus infection. In this review, we provide the summarization of current researches on uridylation, introduce several techniques widely used for RNA 3' terminus detection, put more emphases on describing the mechanisms of how uridylation controls gene expression, and summarize the key roles of uridylation in RNA surveillance and several biological processes. Furthermore, we discuss other unsolved issues and crucial aspects of future research as well, with the aim of providing new ideas for anti-tumor and anti-virus therapies.
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http://dx.doi.org/10.16288/j.yczz.22-094DOI Listing
June 2022

Function, quality-of-life and complications after sacrospinous ligament fixation using an antegrade reusable suturing device (ARSD-Ney) at 6 and 12 months: a retrospective cohort study.

Ann Transl Med 2022 May;10(10):582

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Background: Pelvic organ prolapse (POP) is a common pathology in the female population. Sacrospinous ligament fixation (SSLF) is one of the traditional transvaginal procedures for POP and high sacrospinous ligament fixation (h-SSLF) optimizes it using an antegrade reusable suturing device (ARSD-Ney). Previous studies on h-SSLF have focused on the correction of anatomical positions, with less assessment of patients' function, quality of life and complications. In this study, we evaluated post-operative complications, function, and quality-of-life after h-SSLF to confirm the safety and effectiveness of it.

Methods: This was a retrospective cohort study that included 71 patients between 2018 and 2021: 50 patients for h-SSLF and 21 patients for laparoscopic sacrocolpopexy (LSC) according to patient age and background, POP-Q stage, patient preference, and so on. A clinical evaluation took place before surgery and was repeated at 6 and 12 months postoperatively. Intra- and post-operative complications and anatomical results were recorded. Patients completed self-administered questionnaires for functional pelvic problems [Pelvic Floor Disability Index-20 (PFDI-20)], quality of life [Pelvic Floor Impact Questionnaire-7 (PFIQ-7)], and sexual function [Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12)] at each medical visit.

Results: Patients in both h-SSLF and LSC groups were similar in terms of demographic characteristics except for surgery time (86.04±28.70 153.19±54.88, P<0.05), postoperative indwelling catheter time (3.88±1.65 4.90±1.84, P<0.05), and hospital stay (8.94±2.38 10.57±2.06, P<0.05). There were no statistically significant differences between the 2 groups in scores of PFDI-20, PFIQ-7, and PISQ-12 at pre- and post-operative 6 and 12 months (P>0.05). Functional pelvic problems (PFDI-20 scores) and their impact on patients' quality of life (PFIQ-7 scores) significantly improved at 6 and 12 months postoperatively (P<0.05). Improvements in sexual activity were noted at 6 and 12 months postoperatively (P<0.05).

Conclusions: This retrospective cohort study confirmed the positive results of h-SSLF in terms of improvement in function and quality of life following treatment for pelvic organ prolapse.
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http://dx.doi.org/10.21037/atm-22-2150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201128PMC
May 2022

A Dual-Labeling Probe for Super-Resolution Imaging to Detect Mitochondrial Reactive Sulfur Species in Live Cells.

Front Pharmacol 2022 1;13:871059. Epub 2022 Jun 1.

Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, China.

Mitochondria are the main sites of reactive sulfur species (RSS) production in living cells. RSS in mitochondria play an important role in physiological and pathological processes of life. In this study, a dual-labeling probe that could simultaneously label the mitochondrial membrane and matrix was designed to quantitatively detect RSS of mitochondria in living cells using nano-level super-resolution imaging. A fluorescent probe CPE was designed and synthesized. The cytotoxicity of CPE was determined and co-localization of CPE with a commercial mitochondrial probe was analyzed in HeLa cells. Then, the uptake patterns of CPE in HeLa cells at different temperatures and endocytosis levels were investigated. The staining characteristics of CPE under different conditions were imaged and quantitated under structured illumination microscopy. A fluorescence probe CPE reacting to RSS was developed, which could simultaneously label the mitochondrial membrane with green fluorescence and the mitochondrial matrix with red fluorescence. CPE was able to demonstrate the mitochondrial morphology and detect the changes of RSS in mitochondria. With the increase of mitochondrial RSS concentration, the light of the red matrix will be quenched. CPE provides a strategy for the design of probes and an attractive tool for accurate examination to changes of mitochondrial morphology and RSS in mitochondria in living cells at the nanoscale.
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http://dx.doi.org/10.3389/fphar.2022.871059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198575PMC
June 2022

Osthole Induces Apoptosis and Caspase-3/GSDME-Dependent Pyroptosis via NQO1-Mediated ROS Generation in HeLa Cells.

Oxid Med Cell Longev 2022 8;2022:8585598. Epub 2022 Jun 8.

College of Pharmacy, Guilin Medical University, 541004 Guilin, China.

Osthole is a natural coumarin which has been proved to inhibit growth of cancer cells by inducing cell death, while its mechanism was considered to be just caused by apoptosis. In our study, we found that osthole activated not just apoptosis, but also pyroptosis which is a form of regulated cell death accompanied by loss of cell membrane integrity and lactate dehydrogenase (LDH) release. Caspase-3 is a key protein of apoptosis as well as pyroptosis. The apoptosis and pyroptosis induced by osthole were all inhibited by irreversible caspase-3 inhibitor Z-DEVD-FMK. Meanwhile, knockdown of gasdermin E (GSDME) only reduced the osthole-induced pyroptosis but did not affect the occurrence of apoptosis. Our proteomic analysis revealed that the expression of NAD(P)H: quinone oxidoreductase 1 (NQO1) was decreased in osthole-treated cells. Moreover, NQO1 inhibition by osthole induced the overproduction of reactive oxygen species (ROS), as well as apoptosis and pyroptosis. ROS inhibitor N-Acetyl-L-cysteine (NAC) not only reduced osthole-induced apoptosis but also reversed its effect on the pyroptosis. Meanwhile, knockdown of NQO1 by si-NQO1 or its inhibitor dicoumarol (DIC) not only enhanced ROS generation but also strengthened the GSDME-mediated pyroptosis. Finally, we demonstrated that osthole inhibited tumor growth and the expression of NQO1 in a HeLa xenograft mode. Similar to the results , osthole stimulated the activation of caspase-3, PARP, and GSDME . Taken together, all these data suggested that osthole induced apoptosis and caspase-3/GSDME-mediated pyroptosis via NQO1-mediated ROS accumulation.
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http://dx.doi.org/10.1155/2022/8585598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200556PMC
June 2022

Interventions of Advanced Lung Cancer Patient Receiving Chemotherapy by Computed Tomography Image Information Data Analysis-Based Soothing Care Plans.

Comput Math Methods Med 2022 9;2022:3585567. Epub 2022 Jun 9.

Department of Respiratory Medicine, First People's Hospital of Fuyang District, Hangzhou, 311400 Zhejiang, China.

The objective of this study was to investigate the intervention effect of computed tomography (CT) image information data on patients with advanced lung cancer treated with chemotherapy under palliative care program. The research subjects were 60 patients with advanced lung cancer who received palliative care in our hospital from January 1, 2019, to January 1, 2021. All patients were grouped according to the evaluation criteria of solid tumor efficacy, including 28 patients in the remission group and 32 patients in the nonremission group. Texture analysis was performed on the CT images of the two groups of patients. The gray-scale cooccurrence matrix parameters, the maximum diameter of the lesion, and the CT value of the CT images of the two groups of patients before and after palliative care were compared. The results showed that after the palliative care, the combined mean, combined energy, and inverse moment of the three gray cooccurrence matrix parameters of the two groups of patients were decreased, and the combined entropy and contrast were increased. The absolute value of the gray-scale cooccurrence matrix Δ parameter of the patients in the remission group was greater than that in the nonremission group. The Δ combined entropy, Δ contrast, and Δ correlation of the two groups of patients were significantly different, and the difference in Δ contrast was the largest. It suggested that the gray-scale cooccurrence matrix parameter can evaluate the effect of soothing care, and the contrast was the best evaluation parameter. The maximum diameter of the lesions in the remission group before and after palliative care was reduced by 1.23 cm, and the degree of reduction was significantly better. The CT value was reduced by 6.22 HU, and the degree of reduction was significantly higher than that in the nonremission group. There was a significant difference in the data between the two groups ( < 0.05). Therefore, the CT image information data had a better evaluation effect on patients with advanced lung cancer under the palliative care program and can be applied to the clinical evaluation of the palliative care effect, which had good clinical value.
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http://dx.doi.org/10.1155/2022/3585567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203179PMC
June 2022

Analysis of Gut Microbiota Signature and Microbe-Disease Progression Associations in Locally Advanced Non-Small Cell Lung Cancer Patients Treated With Concurrent Chemoradiotherapy.

Front Cell Infect Microbiol 2022 1;12:892401. Epub 2022 Jun 1.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Purpose: To evaluate the association of gut microbiome signature and disease progression in locally advanced non-small cell lung cancer (LA-NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) by fecal metagenome analysis.

Methods: Metagenome-wide association studies on baseline fecal samples from 18 LA-NSCLC patients before CCRT and 13 controls from healthy first-degree relatives were performed. Among the 18 LA-NSCLC patients, six patients were defined as the long progression-free survival (long-PFS) group (PFS≥11 months) while another 12 were in the short-PFS group (PFS<11 months). Alpha diversity, taxonomic composition, and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways were compared between groups.

Results: The Firmicutes/Bacteroidetes value of long-PFS group was higher than those of short-PFS (p=0.073) and healthy individual groups (p=0.009). Meanwhile, long-PFS group had significantly higher diversities in Fungi, Archaea, and Viruses than short-PFS group. The KEGG pathways overrepresented in short-PFS group included fructose and mannose metabolism (p=0.028), streptomycin biosynthesis (p=0.028), acarbose and validamycin biosynthesis (p=0.013), ribosome biogenesis in eukaryotes (p=0.035), biosynthesis of vancomycin group antibiotics (p=0.004), apoptosis-fly (p=0.044), and tetracycline biosynthesis (p=0.044), while those overrepresented in long-PFS group included fatty acid biosynthesis (p=0.035), fatty acid metabolism (p=0.008), vancomycin resistance (p=0.008), longevity regulating pathway-worm (p=0.028), type II diabetes mellitus (p=0.004), and viral carcinogenesis (p=0.003). Further analysis of antibiotic resistome demonstrated that the short-PFS group had a trend with more antibiotic resistance genes than healthy control (p=0.070) and long-PFS groups (p=0.218). The vancomycin resistance sequences were significantly enriched in the long-PFS group compared to the short-PFS group (p=0.006).

Conclusions: The baseline gut microbiome composition and functionality might be associated with PFS in LA-NSCLC treated with CCRT. The outcome of CCRT might be modulated through bacterial metabolic pathways. The antibiotic resistance genes might play a role in disease progression and provide potential information on the relationship between the use of antibiotics and treatment efficacy of CCRT in LA-NSCLC.
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http://dx.doi.org/10.3389/fcimb.2022.892401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200620PMC
June 2022

A cascade amplification strategy for ultrasensitive Salmonella typhimurium detection based on DNA walker coupling with CRISPR-Cas12a.

J Colloid Interface Sci 2022 Jun 7;625:257-263. Epub 2022 Jun 7.

School of Public Health, Jilin University, Changchun 130021, PR China. Electronic address:

Salmonella typhimurium (S. typhimurium) infection is one of leading causes of severe foodborne illness, which poses grievous threats to public health. Thus, the detection with ultra-sensitivity is highly demanded for timely prevention and diagnosis of S. typhimurium. In this study, we developed a novel detection machinery based on DNA walker and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas12a technologies. Mechanistically, the S. typhimurium specific sequence triggers Nt.AlwI nicking endonuclease and produces particular signaling nucleotide, which further activates Cas12a for strong fluorescence signal output. This cascade amplification strategy exhibits excellent specificity and successfully decreases the limit of detection (LOD) of DNA walker by 2,000 folds to 5 CFU/mL. Collectively, this combinatorial approach offers great promises to effectively reduce foodborne diseases by ultrasensitive detection of S. typhimurium. As a proof of concept, this innovative design also shows prominent potential in detections of other biomolecules, cells and pathogens.
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http://dx.doi.org/10.1016/j.jcis.2022.06.027DOI Listing
June 2022

Promising application of polyoxometalates in the treatment of cancer, infectious diseases and Alzheimer's disease.

J Biol Inorg Chem 2022 Jun 17. Epub 2022 Jun 17.

School of Public Health, Jilin University, Changchun, Jilin, China.

As shown in studies conducted in recent decades, polyoxometalates (POMs), as inorganic metal oxides, have promising biological activities, including antitumor, anti-infectious and anti-Alzheimer's activities, due to their special structures and properties. However, some side effects impede their clinical applications to a certain extent. Compared with unmodified POMs, POM-based inorganic-organic hybrids and POM-based nanocomposite structures show significantly enhanced bioactivity and reduced side effects. In this review, we introduce the biological activities of POMs and their derivatives and highlight the side effects of POMs on normal cells and organisms and their possible mechanisms of action. We then propose a development direction for overcoming their side effects. POMs are expected to constitute a new generation of inorganic metal drugs for the treatment of cancer, infectious diseases, and Alzheimer's disease.Graphical abstract.
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http://dx.doi.org/10.1007/s00775-022-01942-7DOI Listing
June 2022

A Nomogram for Predicting Survival in Patients With Colorectal Cancer Incorporating Cardiovascular Comorbidities.

Front Cardiovasc Med 2022 27;9:875560. Epub 2022 May 27.

Chinese Academy of Medical Sciences and Peking Union Medical College, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, China.

Background: Cardiovascular comorbidities (CVCs) affect the overall survival (OS) of patients with colorectal cancer (CRC). However, a prognostic evaluation system for these patients is currently lacking.

Objectives: This study aimed to develop and validate a nomogram, which takes CVCs into account, for predicting the survival of patients with CRC.

Methods: In total, 21,432 patients with CRC were recruited from four centers in China between January 2011 and December 2017. The nomogram was constructed, based on Cox regression, using a training cohort (19,102 patients), and validated using a validation cohort (2,330 patients). The discrimination and calibration of the model were assessed by the concordance index and calibration curve. The clinical utility of the model was measured by decision curve analysis (DCA). Based on the nomogram, we divided patients into three groups: low, middle, and high risk.

Results: Independent risk factors selected into our nomogram for OS included age, metastasis, malignant ascites, heart failure, and venous thromboembolism, whereas dyslipidemia was found to be a protective factor. The c-index of our nomogram was 0.714 (95% : 0.708-0.720) in the training cohort and 0.742 (95% : 0.725-0.759) in the validation cohort. The calibration curve and DCA showed the reliability of the model. The cutoff values of the three groups were 68.19 and 145.44, which were also significant in the validation cohort ( < 0.001).

Conclusion: Taking CVCs into account, an easy-to-use nomogram was provided to estimate OS for patients with CRC, improving the prognostic evaluation ability.
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http://dx.doi.org/10.3389/fcvm.2022.875560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196079PMC
May 2022
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