Publications by authors named "Kun Liu"

1,532 Publications

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Shelf-Life Prediction and Critical Value of Quality Index of Sichuan Sauerkraut Based on Kinetic Model and Principal Component Analysis.

Foods 2022 Jun 15;11(12). Epub 2022 Jun 15.

Sichuan Tianwei Food Group Co., Ltd., Chengdu 610207, China.

Kinetic models and accelerated shelf-life testing were employed to estimate the shelf-life of Sichuan sauerkraut. The texture, color, total acid, microbe, near-infrared analysis, volatile components, taste, and sensory evaluation of Sichuan sauerkraut stored at 25, 35, and 45 °C were determined. Principal component analysis (PCA) and Fisher discriminant analysis (FDA) were used to analyze the e-tongue data. According to the above analysis, Sichuan sauerkraut with different storage times can be divided into three types: completely acceptable period, acceptable period, and unacceptable period. The model was found to be useful to determine the critical values of various quality indicators. Furthermore, the zero-order kinetic reaction model (R, 0.8699-0.9895) was fitted better than the first-order kinetic reaction model. The Arrhenius model ( value was 47.23-72.09 kJ/mol, value was 1.076 × 10-9.220 × 10 d) exhibited a higher fitting degree than the Eyring model. Based on the analysis of physical properties, the shelf-life of Sichuan sauerkraut was more accurately predicted by the combination of the zero-order kinetic reaction model and the Arrhenius model, while the error back propagation artificial neural network (BP-ANN) model could better predict the chemical properties. It is a better choice for dealers and consumers to judge the shelf life and edibility of food by shelf-life model.
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http://dx.doi.org/10.3390/foods11121762DOI Listing
June 2022

Indole-3-Carbinol (I3C) Protects the Heart From Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress, Inflammation, and Cellular Apoptosis in Mice.

Front Pharmacol 2022 6;13:924174. Epub 2022 Jun 6.

Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.

Strategies for treating myocardial ischemia in the clinic usually include re-canalization of the coronary arteries to restore blood supply to the myocardium. However, myocardial reperfusion insult often leads to oxidative stress and inflammation, which in turn leads to apoptosis and necrosis of myocardial cells, for which there are no standard treatment methods. The aim of this study was to determine the pharmacological effect of indole-3-carbinol (I3C), a phytochemical found in most cruciferous vegetables, in a mouse model of myocardial ischemia/reperfusion injury (MIRI). Our results showed that I3C pretreatment (100 mg/kg, once daily, i. p.) prevented the MIRI-induced increase in infarct size and serum creatine kinase (CK) and lactate dehydrogenase (LDH) in mice. I3C pretreatment also suppressed cardiac apoptosis in MIRI mice by increasing the expression levels of the anti-apoptotic protein Bcl-2 and decreasing the expression levels of several apoptotic proteins, including Bax, caspase-3, and caspase-9. In addition, I3C pretreatment was found to reduce the levels of parameters reflecting oxidative stress, such as dihydroethidium (DHE), malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO), while increasing the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC) and glutathione (GSH), in MIRI-induced ischemic heart tissue. I3C pretreatment was also able to remarkably decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) mRNA in ischemic heart tissue. These results demonstrate that administration of I3C protects the heart from MIRI through its anti-apoptotic, antioxidant, and anti-inflammatory effects.
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http://dx.doi.org/10.3389/fphar.2022.924174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208008PMC
June 2022

Green Polymer Electrolytes based on Polycaprolactones for Solid-State High-Voltage Lithium Metal Batteries.

Macromol Rapid Commun 2022 Jun 20:e2200335. Epub 2022 Jun 20.

Forschungszentrum Jülich GmbH, Helmholtz Institute Münster, IEK-12, Corrensstraße 46, 48149, Münster, Germany.

Solid polymer electrolytes (SPEs) have attracted considerable attention for high energy solid-state lithium metal batteries (LMBs). In this work, potentially ecofriendly, solid-state poly(ε-caprolactone) (PCL)-based star polymer electrolytes with cross-linked structures (xBt-PCL) are introduced that robustly cycle against NMC622 composite cathodes, affording long-term stability even at higher current densities. Their superior features allow for sufficient suppression of dendritic lithium deposits, as monitored by Li solid-state NMR. Advantageous electrolyte|electrode interfacial properties derived from cathode impregnation with 1.5wt% PCL enable decent cell performance until up to 500 cycles at rates of 1C (60°C), illustrating the high potential of PCL-based SPEs for application in high-voltage LMBs. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/marc.202200335DOI Listing
June 2022

The prognostic value of chemotherapy or/and radiotherapy in adenoid cystic carcinoma and adenoid basal carcinoma of the uterine cervix.

Ann Transl Med 2022 May;10(10):554

Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, China.

Background: Cervical adenoid cystic carcinoma (ACC) and adenoid basal carcinoma (ABC) are rare cervical cancer types and have unclarified clinicopathological features and survival outcomes. This retrospective study focused on predicting the value of radiotherapy or/and chemotherapy for cervical ACC and ABC patients.

Methods: The clinical data of cervical ACC and ABC patients in the Surveillance, Epidemiology, and End Results (SEER) database from 1973 and 2013 were included. The clinicopathological features, Kaplan-Meier curves, and overall survival (OS) of patients were evaluated. The prognostic nomogram was established based on the multivariate Cox models. To validate the nomogram prediction, Harrell's Concordance index (C-index) was calculated and receiver operating characteristic (ROC) curves were generated.

Results: A total of 84 cervical ACC and 82 ABC patients were identified, and ABC patients had better 10-year OS than ACC patients (60.81% 36.94%, P=0.001). Age, ACC, surgery, radiotherapy, chemotherapy, and regional node involvement were significantly correlated with patient prognosis. In the multivariate analysis, only age >80 years (HR =5.945, 95% CI: 1.912-18.485, P=0.002) and age 70-80 years (HR =4.803, 95% CI: 1.626-14.188, P=0.005) were independent predictors of patient prognosis. In subgroup analysis, patients who underwent surgery (HR =2.199, 95% CI: 1.085-4.455, P=0.029) and the ABC subgroup (HR =4.233, 95% CI: 1.532-11.696, P=0.005) received radiotherapy, chemotherapy, or chemoradiotherapy with a poor prognosis. Patients received radiotherapy (HR =1.936, 95% CI: 1.208-3.105, P=0.006) was associated with a poor prognosis, while surgical patients had a better prognosis (HR =0.535, 95% CI: 0.344-0.832, P=0.006).

Conclusions: Cervical ABC patients had a better survival time than cervical ACC patients. We found that increased age was potentially an independent risk factor for poor prognosis, surgical patients had a better prognosis, and radiotherapy, or chemotherapy combination treatment had an unfavorable tendency to prognosis.
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http://dx.doi.org/10.21037/atm-22-1584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201134PMC
May 2022

Integrated analysis of tRNA-derived small RNAs in proliferative human aortic smooth muscle cells.

Cell Mol Biol Lett 2022 Jun 15;27(1):47. Epub 2022 Jun 15.

Department of Biochemistry and Molecular Biology, Key Laboratory of Medical Biotechnology of Hebei Province, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang, China.

Background: Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling diseases. Recently, it has been discovered that tRNA-derived small RNAs (tsRNAs), a new type of noncoding RNAs, are related to the proliferation and migration of VSMCs. tsRNAs regulate target gene expression through miRNA-like functions. This study aims to explore the potential of tsRNAs in human aortic smooth muscle cell (HASMC) proliferation.

Methods: High-throughput sequencing was performed to analyze the tsRNA expression profile of proliferative and quiescent HASMCs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the sequence results and subcellular distribution of AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076. Based on the microRNA-like functions of tsRNAs, we predicted target promoters and mRNAs and constructed tsRNA-promoter and tsRNA-mRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the function of target genes. EdU incorporation assay, Western blot, and dual-luciferase reporter gene assay were utilized to detect the effects of tsRNAs on HASMC proliferation.

Results: Compared with quiescent HASMCs, there were 1838 differentially expressed tsRNAs in proliferative HASMCs, including 887 with increased expression (fold change > 2, p < 0.05) and 951 with decreased expression (fold change < ½, p < 0.05). AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076 were increased in proliferative HASMCs and were mainly located in the nucleus. Bioinformatics analysis suggested that the four tsRNAs involved a variety of GO terms and pathways related to VSMC proliferation. AS-tDR-000067 promoted HASMC proliferation by suppressing p53 transcription in a promoter-targeted manner. AS-tDR-000076 accelerated HASMC proliferation by attenuating mitofusin 2 (MFN2) levels in a 3'-untranslated region (UTR)-targeted manner.

Conclusions: During HASMC proliferation, the expression levels of many tsRNAs are altered. AS-tDR-000067 and AS-tDR-000076 act as new factors promoting VSMC proliferation.
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http://dx.doi.org/10.1186/s11658-022-00346-4DOI Listing
June 2022

A multifunctional chitosan hydrogel dressing for liver hemostasis and infected wound healing.

Carbohydr Polym 2022 Sep 18;291:119631. Epub 2022 May 18.

State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China; Foshan Xianhu Laboratory of the Advanced Energy Science and Technology Guangdong Laboratory, Xianhu Hydrogen Valley, Foshan 528200, China; Shenzhen Research Institute of Wuhan University of Technology, Shenzhen 518000, China. Electronic address:

For the treatment of infected bleeding wounds, we compounded methacrylate anhydride dopamine (DAMA) and Zn-doped whitlockite nanoparticles (Zn-nWH) into methacrylate anhydride quaternized chitosan (QCSMA) to obtain a multifunctional hydrogel dressing (QCSMA/DAMA/Zn-nWH) with hemostasis, disinfection and wound healing promotion. QCSMA/DAMA/Zn-nWH exhibited good adhesion (0.031 MPa) and DPPH scavenging ability (94%), favorable biocompatibility (hemolysis ratio < 2%, no cytotoxicity), and showed a low BCI value (< 13%) in vitro coagulation test and could activate coagulation pathway. In addition, QCSMA/DAMA/Zn-nWH had excellent hemostatic effect (129 ± 22 s, 27 ± 5 mg) in vivo compared with the control (571 ± 15 s, 147 ± 31 mg) and CCS (354 ± 27 s, 110 ± 46 mg). Meanwhile, QCSMA/DAMA/Zn-nWH showed excellent antibacterial properties (> 90% against S. aureus and E. coli) and could promote collagen deposition, reduce inflammatory expression and promote wound healing. All results indicate that these multifunctional hydrogel dressings have great potential in clinical hemostasis and anti-infection healing.
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http://dx.doi.org/10.1016/j.carbpol.2022.119631DOI Listing
September 2022

Diurnal rhythm of human semen quality: analysis of large-scale human sperm bank data and timing-controlled laboratory study.

Hum Reprod 2022 Jun 12. Epub 2022 Jun 12.

Key Lab of Medical Protection for Electromagnetic Radiation, Ministry of Education of China, Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China.

Study Question: Can we identify diurnal oscillations in human semen parameters as well as peak times of semen quality?

Summary Answer: Human semen parameters show substantial diurnal oscillation, with most parameters reaching a peak between 1100 and 1500 h.

What Is Known Already: A circadian clock appears to regulate different physiological functions in various organs, but it remains controversial whether diurnal rhythms occur in human semen parameters.

Study Design, Size, Duration: The medical record of a provincial human sperm bank (HSB) with 33 430 semen samples collected between 0800 and 1700 h from 1 March 2010 to 8 July 2015 was used to analyze variation in semen parameters among time points. A laboratory study was conducted to collect semen samples (n = 36) from six volunteers at six time points with identical time intervals (2 days plus 4 h) between 6 June and 8 July in 2019, in order to investigate the diurnal oscillation of semen parameters in vivo, with a strictly controlled abstinence period. Therefore, the sperm bank study with a large sample size and the in vivo study with a strictly controlled abstinence period in a 24-h time window could be compared to describe the diurnal rhythms in human semen parameters.

Participants/materials, Setting, Methods: Samples were obtained from potential HSB donors and from participants in the laboratory study who were volunteers, recruited by flyers distributed in the community. Total sperm count, sperm concentration, semen volume, progressive motility and total motility were assessed using computer-aided sperm analysis. In addition, sperm chromatin integrity parameters (DNA fragmentation index and high DNA stainability) were assessed by the sperm chromatin structure assay, and sperm viability was measured with flow cytometry in the laboratory study.

Main Results And The Role Of Chance: The 33 430 samples from the HSB showed a temporal variation in total sperm count, sperm concentration, semen volume, progressive motility and total motility (all P < 0.001) between 0800 and 1700 h. Consequently, the eligibility of semen samples for use in ART, based on bank standards, fluctuated with time point. Each hour earlier/later than 1100 h was associated with 1.14-fold risk of ineligibility. Similarly, the 36 samples taken during the 24-h time window showed diurnal oscillation. With the pre-collection abstinence period strictly controlled, most semen parameters reached the most favorable level between 1100 and 1500 h.

Limitations, Reasons For Caution: Some of the possible confounding factors, such as energy intake, which might influence semen quality or diurnal rhythms, were not adjusted for in the analyses. In addition, the findings should be considered with caution because the study was conducted in a specific population, time and place, while the timing of oscillations could differ with changing conditions.

Wider Implications Of The Findings: The findings could help us to estimate semen quality more precisely and to obtain higher quality sperm for use in ART and in natural conception.

Study Funding/competing Interest(s): This study was supported by the National Natural Science Foundation of China (81871208) and National Key R&D Program of China (2017YFC1002001). There are no conflicts of interest to declare.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deac135DOI Listing
June 2022

Effect of grazing and nitrogen addition on the occurrence of species with different seed masses in alpine meadows on the Tibet Plateau.

Sci Total Environ 2022 Sep 8;838(Pt 4):156531. Epub 2022 Jun 8.

State Key Laboratory of Grassland and Agro-ecosystems, College of Ecology, Lanzhou University, Lanzhou, PR China. Electronic address:

Seed mass (SM) is a core functional trait of plant species. Thus, information of the effect of grazing and nitrogen addition on the occurrence of species with different SMs can help us understand the influence of grazing and fertilization on survival of species and community assembly. In alpine meadows with different grazing and nitrogen addition treatments on the eastern Tibet Plateau, we measured SM and plant height (H) of the most common plants and conducted a series of quadrat surveys. Overall, grazing promoted survival of small-seeded species, while fertilization suppressed their survival. At the community level, moderate grazing reduced the average community weighted mean (CWM) of SM and increased the coefficient of variation (CV) of SM. However, there was no significant difference between the functional diversity (FDrao, calculated as Rao's index) of SM in grazed and nongrazed meadows. Nitrogen addition significantly increased the CWM of SM, had a marginally significant effect on FDrao of SM, but had no significant effect on CV of SM. The impact of gazing and fertilization on occurrence of species with different SMs can be explained by their effect on vegetation height. From the perspective of SM selection, our study helps clarify the mechanism of species diversity loss due to fertilization, and that of species diversity increase by moderate grazing.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156531DOI Listing
September 2022

Regulating the Physicochemical Properties of Chitosan Films through Concentration and Neutralization.

Foods 2022 Jun 5;11(11). Epub 2022 Jun 5.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

Chitosan offers real potential for use in food preservation, biomedicine, and environmental applications due to its excellent functional properties, such as ease in the fabrication of large films, biocompatibility, and antibacterial properties. However, the production and application of chitosan films were limited by their strong residual acetic acid taste, weak mechanical properties, and poor water vapor barrier properties. In this study, the effects of the chitosan concentration in the film-forming solutions and the neutralization treatment on the physicochemical properties of chitosan films were examined. The results demonstrated that the chitosan concentration affected the mechanical and barrier properties of chitosan films without the neutralization treatment. This was mainly due to the low acetic acid contents in chitosan films after drying. Acetic acid acted as a plasticizer within chitosan films resulting in a looser network structure. After neutralization, the chitosan films showed improvements in properties, with little effect on the chitosan concentration in the film-forming solutions. Moreover, chitosan films after neutralization showed no residual acetic acid. Therefore, neutralization could effectively improve the performance of chitosan films.
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http://dx.doi.org/10.3390/foods11111657DOI Listing
June 2022

Astragalus polysaccharides protects against acute leptospirosis by glycolysis-depended priming effect.

Biomed Pharmacother 2022 Jul 28;151:113198. Epub 2022 May 28.

Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, People's Republic of China. Electronic address:

Leptospirosis, caused by pathogenic leptospira, is a neglected infectious disease that causes acute kidney injury, bleeding disorders, and even death. People can become infected with leptospirosis when they travel into epidemic areas. Except for vaccines and antibiotics, there are few reports of other drugs about prevention of leptospirosis. In this study, we show that the natural molecular compound, astragalus polysaccharides (APS), prevents against acute leptospirosis in hamsters. Pretreatment with APS improved the survival rate of hamsters with more minor organ damage and lower leptospira burden. After pretreatment with APS, the expression levels of leptospira-induced TLR2, TLR4, and TNF-α were enhanced. The priming effect of APS was studied in vitro. The data showed that leptospira-induced expressions of TNF-α and IL-1β were higher in APS-primed peritoneal macrophage, with enhanced glucose consumption and lactate production. Transcriptomic analysis revealed that pretreatment with APS down regulated respiratory chain and mitochondrial function, up regulated glycolysis related gene expressions. After pretreatment with glycolysis inhibitor (2-DG), the priming effect of APS in leptospira infection was inhibited. Our results indicated that pretreatment with natural molecular compound, APS, protected against acute leptospirosis in hamsters by priming effect through enhanced glycolysis.
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http://dx.doi.org/10.1016/j.biopha.2022.113198DOI Listing
July 2022

Chemo-Immunotherapy Regimes for Recurrent or Metastatic Nasopharyngeal Carcinoma: A Network Meta-Analysis and Cost-Effectiveness Analysis.

Front Pharmacol 2022 20;13:858207. Epub 2022 May 20.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.

In 2021, two phase III clinical trials confirmed that toripalimab or camrelizumab combined with gemcitabine and cisplatin (TGP or CGP) provide more benefits in the first-line treatment of R/M NPC than GP. Fortunately, TGP and CGP were recently approved as first-line treatments for cases experiencing R/M NPC by the China National Medical Products Administration in 2021. However, due to the high cost and variety of treatment options, the promotion of chemo-immunotherapeutics in the treatment of R/M NPC remains controversial. Therefore, we performed a cost-effectiveness assessment of the two newly approved treatment strategies to assess which treatments provide the greatest clinical benefits at a reasonable cost. A cost-effectiveness analysis and network meta-analysis network meta-analysis was conducted based on the JUPITER-02 and CAPTAIN-first Phase 3 randomized clinical trials. A Markov model was expanded for the evaluation of the effectiveness and cost of TGP, CGP, and GP chemotherapy with a 10-years horizon and measured the health achievements in quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and life-years (LYs). We constructed a treatment strategy and other parameters based on two clinical trials and performed one-way and probabilistic sensitivity experiments for the evaluation of the uncertainty in the model. For the model of patients with treatment-R/M NPC, TGP was associated with a total cost of $48,525 and 2.778 QALYs (4.991 LYs), leading to an ICER of $15,103 per QALY ($10,321 per LY) compared to CGP. On comparing the GP chemotherapy, we found TGP and CGP incurred substantial health costs, resulting in ICERs of $19,726 per QALY and $20,438 per QALY, respectively. The risk of adverse events (AEs) and the price of the drugs had significant impacts on the ICER. At the assumed willingness-to-pay (WTP) threshold of $35,673 per QALY, there were approximately 75.8 and 68.5% simulations in which cost-effectiveness was achieved for TGP and CGP, respectively. From the Chinese payer's perspective, TGP is more possible to be a cost-effective regimen compared with CGP and GP for first-line treatment of patients with R/M NPC at a WTP threshold of $35,673 per QALY.
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http://dx.doi.org/10.3389/fphar.2022.858207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163401PMC
May 2022

Application of Diffusion Kurtosis Imaging in Evaluating Acute Xerostomia in Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy.

Front Oncol 2022 19;12:870315. Epub 2022 May 19.

Department of Radiation Oncology, First Medical Center of PLA General Hospital, Beijing, China.

Purpose: The aim of this study was to identify the efficacy of diffusion kurtosis imaging (DKI) in tracking and monitoring the dynamic change of parotid glands (PGs), submandibular glands (SMGs), sublingual glands (SLGs), and acute xerostomia in nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT).

Methods: The prospective study recruited 42 participants treated with IC+CCRT. All patients underwent DKI scanning six times: before IC, before RT, in the middle of the RT course, immediately after RT, and 1 and 3 months post-RT. Mean diffusion coefficient (MD) and mean kurtosis (MK) of PG, SMG, SLG, saliva flow rate measured under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire (XQ) scores were recorded.

Results: At each time point, sSFR was significantly higher than uSFR ( < 0.05 for all). MD of the salivary glands and XQ scores increased over time while MK, uSFR, and sSFR decreased. After IC, the significant differences were detected in MD and MK of bilateral SMG and MK of the left SLG ( < 0.05 for all), but not in MD and MK of PG, uSFR, sSFR, and XQ scores. After RT, sSFR at 1m-RT decreased significantly ( = 0.03) while no significant differences were detected in uSFR and XQ scores. Moderate-strong correlations were detected in ΔMD-PG-R%, ΔMK-PG-R%, ΔMD-PG-L%, ΔMK-PG-L%, ΔMD-SMG-R%, ΔMK-SMG-R%, ΔMD-SMG-L%, ΔMK-SMG-L%, and ΔMD-SLG-R%, with correlation coefficients ( < 0.05 for all) ranging from 0.401 to 0.714. ΔuSFR% was correlated with ΔMD-SMG% ( = 0.01, = -0.39), ΔMD-SLG% ( < 0.001, = -0.532), and ΔMK-SMG% ( < 0.001, = -0.493). ΔsSFR% correlated with ΔMD-PG% ( = 0.001, = -0.509), ΔMD-SMG% ( = 0.015, = -0.221), and ΔMK-PG% ( < 0.001, = 0.524). ΔXQ% was only correlated with ΔMK-PG% ( = 0.004, = 0.433).

Conclusion: DKI is a promising tool for tracking and monitoring the acute damage of PG, SMG, and SLG induced by IC+CCRT in NPC patients.
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http://dx.doi.org/10.3389/fonc.2022.870315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162117PMC
May 2022

The effects of weathering of coal-bearing stratum on the transport and transformation of DIC in karst watershed.

Sci Total Environ 2022 Sep 3;838(Pt 4):156436. Epub 2022 Jun 3.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550081, China. Electronic address:

The mining of medium- to high‑sulfur coal in karst areas has led to serious acidification problems in surface water, thus encouraging a re-evaluation of DIC transformation and CO source-sink relationships in karst watersheds. The weathering of limestone and sulfide-rich coal measures jointly influence the pH of the Huatan River in karst areas in Southwest China, which is lower in the rainy season and higher in the dry season. Due to CO degassing, DIC concentration tends to decrease along the flow direction, while δC-DIC gradually becomes heavier. In general, DIC transformation in the Huatan River is controlled by AMD input, CO degassing, organic matter (OM) degradation, and the dissolution and precipitation balance of carbonate minerals in different seasons. In spring, the mineralization of OM from terrestrial and domestic sewage gradually enhances and replenishes DIC in the water. As the pH increases in this season, the capacity for buffering CO increases. Meanwhile, OM degradation generates a large amount of CO in summer, and carbonic acid begins to dissolve limestone. In autumn, the pH decreases due to the enhanced weathering of sulfide-rich coal measures and the mass input of AMD. Thus, the river shows the ability to drive CO outgassing. In winter, CO degassing gradually weakens, DIC concentration is at its lowest, and δC-DIC reaches the heaviest value.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156436DOI Listing
September 2022

Noncanonical amino acid mutagenesis in response to recoding signal-enhanced quadruplet codons.

Nucleic Acids Res 2022 Jun 3. Epub 2022 Jun 3.

Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.

While amber suppression is the most common approach to introduce noncanonical amino acids into proteins in live cells, quadruplet codon decoding has potential to enable a greatly expanded genetic code with up to 256 new codons for protein biosynthesis. Since triplet codons are the predominant form of genetic code in nature, quadruplet codon decoding often displays limited efficiency. In this work, we exploited a new approach to significantly improve quadruplet UAGN and AGGN (N = A, U, G, C) codon decoding efficiency by using recoding signals imbedded in mRNA. With representative recoding signals, the expression level of mutant proteins containing UAGN and AGGN codons reached 48% and 98% of that of the wild-type protein, respectively. Furthermore, this strategy mitigates a common concern of reading-through endogenous stop codons with amber suppression-based system. Since synthetic recoding signals are rarely found near the endogenous UAGN and AGGN sequences, a low level of undesirable suppression is expected. Our strategy will greatly enhance the utility of noncanonical amino acid mutagenesis in live-cell studies.
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http://dx.doi.org/10.1093/nar/gkac474DOI Listing
June 2022

Formal β-C-H Arylation of Aldehydes and Ketones by Cooperative Nickel and Photoredox Catalysis.

Angew Chem Int Ed Engl 2022 Jun 3:e202206533. Epub 2022 Jun 3.

Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstraße 40, 48149, Münster, Germany.

α-C-H-functionalization of ketones and aldehydes has been intensively explored in organic synthesis. The functionalization of unactivated β-C-H bonds in such carbonyl compounds is less well investigated and developing a general method for their β-C-H arylation remains challenging. Herein we report a method that uses cooperative nickel and photoredox catalysis for the formal β-C-H arylation of aldehydes and ketones with (hetero)aryl bromides. The method features mild conditions, remarkable scope and wide functional group tolerance. Importantly, the introduced synthetic strategy also allows the β-alkenylation, β-alkynylation and β-acylation of aldehydes under similar conditions. Mechanistic studies revealed that this transformation proceeds through a single electron oxidation/Ni-mediated coupling/reductive elimination cascade.
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http://dx.doi.org/10.1002/anie.202206533DOI Listing
June 2022

The causal relationships between obstructive sleep apnea and elevated CRP and TNF-α protein levels.

Ann Med 2022 12;54(1):1578-1589

Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.

Background: Obstructive sleep apnea (OSA) and inflammation are closely related. This study aimed to evaluate the associations and causal effect between C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-α) levels andOSA.

Methods: Pooled analysis was conducted to compare the expression differences of CRP and TNF-α between OSA patients with different severity and controls, and between continuous positive airway pressure (CPAP) and non-CPAP interventions for OSA patients. Using published GWAS summary statistics, we conducted a bidirectional two-sample Mendelian Randomization (MR) to estimate the causal relationships between CRP and TNF-α levels and OSA risk. Effect estimates were evaluated using inverse-variance weighted (IVW) as primary method, and several other MR methods as sensitivity analysis.

Results: Both TNF-α (WMD [95%CI] = 5.86 [4.80-6.93] pg/ml,  < .00001) and CRP (WMD [95%CI] = 2.66 [2.15-3.17] mg/L,  < .00001), showed a significant increase in OSA patients compared with controls and this increasing trend was associated with OSA severity. Besides, compared to blank control (non-CPAP), CPAP treatment can reduce high TNF-α (WMD [95%CI]= -4.44 [-4.81, -4.07]pg/ml,  < .00001) and CRP (WMD [95%CI]= -0.91 [-1.65, -0.17] mg/l,  = .02) in OSA. Moreover, the primary MR analysis by IVW showed that OSA was the genetically predicted cause of elevated CRP (estimate: 0.095; 95% CI, [0.010-0.179];  = .029) using six SNPs as the instrument variable, which were repeated by weighted median (estimate: 0.053; 95% CI, [0.007, 0.100];  =.024) and MR RAPS (estimate: 0.109; 95% CI, [0.079, 0.140];  = 1.98x10). Besides, the causal effect from elevated CRP on increased OSA risk was almost significant by IVW (OR:1.053; 95% CI, [1.000, 1.111];  = .053). However, there were no causal associations between TNF-α and OSA from both directions.

Conclusions: Increased CRP and TNF-α were associated with OSA severity and sensible to CPAP treatment. Also, OSA had a suggestive causal effect on elevated CRP.
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http://dx.doi.org/10.1080/07853890.2022.2081873DOI Listing
December 2022

CircPVT1 promotes the tumorigenesis and metastasis of osteosarcoma via mediation of miR-26b-5p/CCNB1 axis.

J Bone Miner Metab 2022 Jun 1. Epub 2022 Jun 1.

Department of Pediatric Orthopedics, Hunan Children's Hospital, No. 86, Ziyuan Road, Changsha, 410007, Hunan, People's Republic of China.

Introduction: Osteosarcoma (OS) is the most aggressive malignancy among the bone tumors in the world. Circular RNAs (circRNAs) have been reported to be participated in multiple cancers, including OS. Meanwhile, circPVT1 has been proved to be upregulated in OS. However, the mechanism by which circPVT1 mediates the tumorigenesis of OS remains to be further explored.

Materials And Methods: Protein and gene expressions in OS cells were measured by western blot and RT-qPCR, respectively. Cell growth was assessed by flow cytometry and colony formation, respectively. In addition, cell migration was assessed by wound healing, and invasion was evaluated by Transwell assay. Meanwhile, the correlation among circPVT1, miR-26b-5p and CCNB1 was explored by RNA pull-down and dual luciferase assay. Finally, in vivo model was established to explore the role of circPVT1 in OS in vivo.

Results: CircPVT1 and CCNB1 were significantly upregulated in OS cells, while miR-26b-5p was downregulated. Knockdown of circPVT1 notably inhibited proliferation and induced apoptosis of OS cells. CircPVT1 shRNA significantly suppressed the OS cell invasion and migration. Meanwhile, circPVT1 sponged miR-26b-5p and CCNB1 was found to be the direct target of miR-26b-5p. Furthermore, silencing of circPVT1 inhibited the growth and metastasis of OS in vivo.

Conclusion: Silencing of circPVT1 notably suppressed the tumorigenesis and metastasis of OS via miR-26b-5p/CCNB1 axis. Therefore, circPVT1 might be used as a target for OS treatment.
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http://dx.doi.org/10.1007/s00774-022-01326-6DOI Listing
June 2022

Relationship between urinary dichlorophenols and cognitive function among people over 60 years old from NHANES.

Environ Sci Pollut Res Int 2022 May 27. Epub 2022 May 27.

Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No.601 Huangpu Ave West, Guangzhou, 510632, Guangdong, China.

Studies have shown that exposure to dichlorophenols (DCPs) and their precursors might have potential neurotoxicity, which may be related to low cognitive function, but there are few large-scale, representative population data to explore the association between DCP exposure and cognitive function. We aimed to examine the relationship between urinary DCPs and cognitive function in the US older people. A total of 952 participants ≥ 60 years old from the National Health and Nutrition Examination Survey (NHANES) in two cycles (2011-2014) were enrolled. The Consortium to Establish a Registry for Alzheimer's disease Word Learning subtest (CERAD W-L), the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST) were used to assess cognition. Multivariate logistic regression and restricted cubic spline (RCS) were used to evaluate the relationship between DCP exposure and cognitive function. A positive association between 2,5-DCP and the risk of bad performance of DSST was observed (P for trend = 0.024) after adjusting for the covariates. Compared to the lowest quartile, OR of DSST for the highest quartile of 2,5-DCP was 1.72 (95%CI:1.03-2.87, P = 0.039). There were no significant associations between DCPs and the other tests. The RCS plot showed an inverted J-shaped relationship between 2,5-DCP, 2,4-DCP, and the DSST score. The inflection points for the curves were found at 1.531 μg/L and 0.230 μg/L, respectively. On the right side of the inflection points, the DSST score dropped sharply. In subgroup analysis, those under 70 years old, smokers, and alcohol drinkers had a higher risk of bad performance in DSST when exposed to 2,5-DCP. The higher concentration of urinary DCPs is associated with a lower score of DSST in the US older people.
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http://dx.doi.org/10.1007/s11356-022-20840-8DOI Listing
May 2022

Advancing the Understanding of Acupoint Sensitization and Plasticity Through Cutaneous C-Nociceptors.

Front Neurosci 2022 10;16:822436. Epub 2022 May 10.

Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.

Acupoint is the key area for needling treatment, but its physiology is not yet understood. Nociceptors, one of the responders in acupoints, are responsible for acupuncture manipulation and delivering acupuncture signals to the spinal or supraspinal level. Recent evidence has shown that various diseases led to sensory hypersensitivity and functional plasticity in sensitized acupoints, namely, acupoint sensitization. Neurogenic inflammation is the predominant pathological characteristic for sensitized acupoints; however, the underlying mechanism in acupoint sensitization remains unclear. Recent studies have reported that silent C-nociceptors (SNs), a subtype of C nociceptors, can be "awakened" by inflammatory substances released by sensory terminals and immune cells under tissue injury or visceral dysfunction. SNs can transform from mechano-insensitive nociceptors in a healthy state to mechanosensitive nociceptors. Activated SNs play a vital role in sensory and pain modulation and can amplify sensory inputs from the injured tissue and then mediate sensory hyperalgesia. Whether activated SNs is involved in the mechanism of acupoint sensitization and contributes to the delivery of mechanical signals from needling manipulation remains unclear? In this review, we discuss the known functions of cutaneous C nociceptors and SNs and focus on recent studies highlighting the role of activated SNs in acupoint functional plasticity.
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http://dx.doi.org/10.3389/fnins.2022.822436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127573PMC
May 2022

Corrigendum to "Berberine Reduces Renal Cell Pyroptosis in Golden Hamsters with Diabetic Nephropathy through the Nrf2-NLRP3-Caspase-1-GSDMD Pathway".

Evid Based Complement Alternat Med 2022 14;2022:9828973. Epub 2022 May 14.

The First Hospital, Hebei Medical University, Shijiazhuang 050031, Hebei, China.

[This corrects the article DOI: 10.1155/2021/5545193.].
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http://dx.doi.org/10.1155/2022/9828973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124113PMC
May 2022

Synthesis and macrocyclization-induced emission enhancement of benzothiadiazole-based macrocycle.

Nat Commun 2022 May 23;13(1):2850. Epub 2022 May 23.

College of Sciences, Center for Supramolecular Chemistry and Catalysis, Shanghai University, Shanghai, 200444, People's Republic of China.

We presented an effective and universal strategy for the improvement of luminophore's solid-state emission, i.e., macrocyclization-induced emission enhancement (MIEE), by linking luminophores through C(sp) bridges to give a macrocycle. Benzothiadiazole-based macrocycle (BT-LC) has been synthesized by a one-step condensation of the monomer 4,7-bis(2,4-dimethoxyphenyl)-2,1,3-benzothiadiazole (BT-M) with paraformaldehyde, catalyzed by Lewis acid. In comparison with the monomer, macrocycle BT-LC produces much more intense fluorescence in the solid state (Φ = 99%) and exhibits better device performance in the application of OLEDs. Single-crystal analysis and theoretical simulations reveal that the monomer can return to the ground state through a minimum energy crossing point (MECP), resulting in the decrease of fluorescence efficiency. For the macrocycle, its inherent structural rigidity prohibits this non-radiative relaxation process and promotes the radiative relaxation, therefore emitting intense fluorescence. More significantly, MIEE strategy has good universality that several macrocycles with different luminophores also display emission improvement.
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http://dx.doi.org/10.1038/s41467-022-30121-0DOI Listing
May 2022

Genome-wide identification and expression profile of gene family in

PeerJ 2022 13;10:e13372. Epub 2022 May 13.

State Key Laboratory of Cotton Biology, Institute of Cotton Research, Chinese Academy of Agricultural Sciences, Anyang, Henan, China.

Background: Cotton is the primary source of renewable natural fiber in the textile industry and an important biodiesel crop. Growth regulating factors () are involved in regulating plant growth and development.

Methods: Using genome-wide analysis, we identified 35 genes in .

Results: Chromosomal location information revealed an uneven distribution of GhGRF genes, with maximum genes on chromosomes A02, A05, and A12 from the At sub-genome and their corresponding D05 and D12 from the Dt sub-genome. In the phylogenetic tree, 35 genes were divided into five groups, including G1, G2, G3, G4, and G5. The majority of genes have two to three introns and three to four exons, and their deduced proteins contained conserved QLQ and WRC domains in the N-terminal end of in and rice. Sequence logos revealed that genes were highly conserved during the long-term evolutionary process. The CDS of the gene can complement MiRNA396a. Moreover, most genes transcripts developed high levels of ovules and fibers. Analyses of promoter cis-elements and expression patterns indicated that GhGRF genes play an essential role in regulating plant growth and development by coordinating the internal and external environment and multiple hormone signaling pathways. Our analysis indicated that are ideal target genes with significant potential for improving the molecular structure of cotton.
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http://dx.doi.org/10.7717/peerj.13372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109687PMC
May 2022

Protective effect of pentraxin 3 on pathological retinal angiogenesis in an in vitro model of diabetic retinopathy.

Arch Biochem Biophys 2022 Aug 13;725:109283. Epub 2022 May 13.

Department of Ophthalmology, Shanghai General Hospital, National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. Electronic address:

Background: Diabetic retinopathy (DR) is the most common retinal microvascular disease caused by diabetes. Previous studies indicated that Pentraxin 3 (PTX3), an acute phase reactant, was closely related to the development of DR. But the exact effect of PTX3 in diabetic retinopathy needs more investigations.

Methods: Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) analysis and western blot (WB) were used to detect the expression of PTX3 in vitro. The Ki67 immunofluorescent staining, scratch-wound migration assay, and tube formation experiments were performed to detect the effect of PTX3 knockdown and overexpression on the fibroblast growth factor (FGF)-induced proliferation, migration and tube-forming ability of human retinal microvascular endothelial cells (HRMECs). The phosphorylation levels of extracellular regulated protein kinases (ERK) and fibroblast growth factor receptor (FGFR) in HRMECs were detected by WB.

Results: In vitro, the mRNA and protein expressions of PTX3 in the high-concentration glucose condition group were upregulated compared with the normal group (p < 0.05). The proliferation, migration and tube-forming abilities of HRMECs exposed to high-concentration glucose were enhanced (p < 0.01, p < 0.01, p < 0.05 respectively), and the phosphorylation of FGFR and ERK1/2 were increased (p < 0.01, p < 0.05 respectively) compared with the normal condition group. Compared with the high glucose condition group, the proliferation, migration and tube-forming abilities of HRMECs in the high glucose + PTX3 siRNA condition group were further strengthened (p < 0.001, p < 0.0001, p < 0.05 respectively), and the phosphorylation of FGFR and ERK1/2 were increased (p < 0.001, p < 0.01 respectively).
 Compared with the high glucose condition group, the proliferation, migration and tube-forming abilities of HRMECs in the high glucose + PTX3 overexpression condition group were compromised (p < 0.001, p < 0.05, p < 0.01 respectively), and the phosphorylation of FGFR and ERK1/2 were inhibited (p < 0.001, p < 0.0001 respectively). Neither the scramble siRNA condition group nor the blank plasmid condition group showed significant difference on the proliferation, migration and tube-forming abilities of HRMECs compared with the high glucose condition group (p > 0.05).

Conclusions: The upregulated expression of PTX3 may play a protective role on pathological angiogenesis in DR. PTX3 may serve as a new target for the treatment of DR.
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http://dx.doi.org/10.1016/j.abb.2022.109283DOI Listing
August 2022

Polymer-Tethered Nanoparticles: From Surface Engineering to Directional Self-Assembly.

Acc Chem Res 2022 Jun 16;55(11):1503-1513. Epub 2022 May 16.

Department of Chemistry, University of Toronto, Toronto, M5S3H6 ON, Canada.

ConspectusCurrent interest in nanoparticle ensembles is motivated by their collective synergetic properties that are distinct from or better than those of individual nanoparticles and their bulk counterparts. These new advanced optical, electronic, magnetic, and catalytic properties can find applications in advanced nanomaterials and functional devices, if control is achieved over nanoparticle organization. Self-assembly offers a cost-efficient approach to produce ensembles of nanoparticles with well-defined and predictable structures. Nanoparticles functionalized with polymer molecules are promising building blocks for self-assembled nanostructures, due to the comparable dimensions of macromolecules and nanoparticles, the ability to synthesize polymers with various compositions, degrees of polymerization, and structures, and the ability of polymers to self-assemble in their own right. Moreover, polymer ligands can endow additional functionalities to nanoparticle assemblies, thus broadening the range of their applications.In this Account, we describe recent progress of our research groups in the development of new strategies for the self-assembly of nanoparticles tethered to macromolecules. At the beginning of our journey, we developed a new approach to patchy nanoparticles and their self-assembly. In a thermodynamically driven strategy, we used poor solvency conditions to induce homopolymer surface segregation in pinned micelles (patches). Patchy nanoparticles underwent self-assembly in a well-defined and controlled manner. Following this work, we overcame the limitation of low yield of the generation of patchy nanoparticles, by using block copolymer ligands. For block copolymer-capped nanoparticles, patch formation and self-assembly were "staged" by using distinct stimuli for each process. We expanded this work to the generation of patchy nanoparticles via dynamic exchange of block copolymer molecules between the nanoparticle surface and micelles in the solution. The scope of our work was further extended to a series of strategies that utilized the change in the configuration of block copolymer ligands during nanoparticle interactions. To this end, we explored the amphiphilicity of block copolymer-tethered nanoparticles and complementary interactions between reactive block copolymer ligands. Both approaches enabled exquisite control over directional and self-limiting self-assembly of complex hierarchical nanostructures. Next, we focused on the self-assembly of chiral nanostructures. To enable this goal, we attached chiral molecules to the surface of nanoparticles and organized these hybrid building blocks in ensembles with excellent chiroptical properties. In summary, our work enables surface engineering of polymer-capped nanoparticles and their controllable and predictable self-assembly. Future research in the field of nanoparticle self-assembly will include the development of effective characterization techniques, the synthesis of new functional polymers, and the development of environmentally responsive self-assembly of polymer-capped nanoparticles for the fabrication of nanomaterials with tailored functionalities.
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http://dx.doi.org/10.1021/acs.accounts.2c00066DOI Listing
June 2022

Construction of an individualized clinical prognostic index based on ubiquitination-associated lncRNA in clear cell renal cell carcinoma patients.

World J Surg Oncol 2022 May 10;20(1):148. Epub 2022 May 10.

Department of Urology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, China.

Background: ccRCC is considered as the main subtype of RCC, which accounted for sixth deadliest cancer worldwide. Recently, ubiquitination has been reported to be closely involved in the progression of tumore. The purpose of this study was to identify the ubiquitination-associated genes and co-expressed lncRNAs on the prognosis of clear cell renal cell carcinoma (ccRCC) patients.

Methods And Patients: We downloaded 530 cases and the corresponding transcriptome profiling from The Cancer Genome Atlas (TCGA) database. We distinguished mRNA and lncRNA expression data from the transcriptome profiling and then extracted the expression of mRNAs that regulate protein ubiquitination. We obtained lncRNAs associated with protein ubiquitination regulation from the lncRNA data by gene co-expression analysis. Cox regression analysis of survival time, survival status, and lncRNA expression level was carried out, and a prognostic index (PI) was constructed.

Results: The PI was established based on 8 prognostic lncRNAs that regulate protein ubiquitination and distinguish the high-risk group patients from all patients. Multivariate analysis indicated that this PI was an individualized clinical prognostic factor for patients with ccRCC. Regarding clinical characteristics, a ubiquitination-associated clinical-prognostic index (UCPI), containing 8 ubiquitination-related lncRNAs and age, was established and tested with AUC of 0.80.

Conclusion: We established a UCPI containing 8 lncRNAs related to protein ubiquitination. This UCPI may become an appropriate model to predict the prognosis in ccRCC patients and guide clinicians to adjust the follow-up regimen.
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http://dx.doi.org/10.1186/s12957-022-02618-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087998PMC
May 2022

RUNX1 is a promising prognostic biomarker and related to immune infiltrates of cancer-associated fibroblasts in human cancers.

BMC Cancer 2022 May 9;22(1):523. Epub 2022 May 9.

Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: Runt-related transcription factor 1 (RUNX1) is a vital regulator of mammalian expression. Despite multiple pieces of evidence indicating that dysregulation of RUNX1 is a common phenomenon in human cancers, there is no evidence from pan-cancer analysis.

Methods: We comprehensively investigated the effect of RUNX1 expression on tumor prognosis across human malignancies by analyzing multiple cancer-related databases, including Gent2, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), the Human Protein Atlas (HPA), UALCAN, PrognoScan, cBioPortal, STRING, and Metascape.

Results: Bioinformatics data indicated that RUNX1 was overexpressed in most of these human malignancies and was significantly associated with the prognosis of patients with cancer. Immunohistochemical results showed that most cancer tissues were moderately positive for granular cytoplasm, and RUNX1 was expressed at a medium level in four types of tumors, including cervical cancer, colorectal cancer, glioma, and renal cancer. RUNX1 expression was positively correlated with infiltrating levels of cancer-associated fibroblasts (CAFs) in 33 different cancers. Moreover, RUNX1 expression may influence patient prognosis by activating oncogenic signaling pathways in human cancers.

Conclusion: Our findings suggest that RUNX1 expression correlates with patient outcomes and immune infiltrate levels of CAFs in multiple tumors. Additionally, the increased level of RUNX1 was linked to the activation of oncogenic signaling pathways in human cancers, suggesting a potential role of RUNX1 among cancer therapeutic targets. These findings suggest that RUNX1 can function as a potential prognostic biomarker and reflect the levels of immune infiltrates of CAFs in human cancers.
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http://dx.doi.org/10.1186/s12885-022-09632-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088136PMC
May 2022

Evolving Insights Into the Biological Function and Clinical Significance of Long Noncoding RNA in Glioblastoma.

Front Cell Dev Biol 2022 21;10:846864. Epub 2022 Apr 21.

Department of Oncology, 920th Hospital of Joint Logistics Support Force, Teaching Hospital of Kunming Medical University, Kunming, China.

Glioblastoma (GBM) is one of the most prevalent and aggressive cancers worldwide. The overall survival period of GBM patients is only 15 months even with standard combination therapy. The absence of validated biomarkers for early diagnosis mainly accounts for worse clinical outcomes of GBM patients. Thus, there is an urgent requirement to characterize more biomarkers for the early diagnosis of GBM patients. In addition, the detailed molecular basis during GBM pathogenesis and oncogenesis is not fully understood, highlighting that it is of great significance to elucidate the molecular mechanisms of GBM initiation and development. Recently, accumulated pieces of evidence have revealed the central roles of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of GBM by binding with DNA, RNA, or protein. Targeting those oncogenic lncRNAs in GBM may be promising to develop more effective therapeutics. Furthermore, a better understanding of the biological function and underlying molecular basis of dysregulated lncRNAs in GBM initiation and development will offer new insights into GBM early diagnosis and develop novel treatments for GBM patients. Herein, this review builds on previous studies to summarize the dysregulated lncRNAs in GBM and their unique biological functions during GBM tumorigenesis and progression. In addition, new insights and challenges of lncRNA-based diagnostic and therapeutic potentials for GBM patients were also introduced.
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http://dx.doi.org/10.3389/fcell.2022.846864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068894PMC
April 2022

Degradation-Kinetics-Controllable and Tissue-Regeneration-Matchable Photocross-linked Alginate Hydrogels for Bone Repair.

ACS Appl Mater Interfaces 2022 May 4;14(19):21886-21905. Epub 2022 May 4.

Center of Stomatology, Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China.

Photocross-linked alginate hydrogels, due to their biodegradability, biocompatibility, strong control for gelling kinetics in space and time, and admirable adaptability for in situ polymerization with a minimally invasive approach in surgical procedures, have created great expectations in bone regeneration. However, hydrogels with suitable degradation kinetics that can match the tissue regeneration process have not been designed, which limits their further application in bone tissue engineering. Herein, we finely developed an oxidation strategy for alginate to obtain hydrogels with more suitable degradation rates and comprehensively explored their physical and biological performances in vitro and in vivo to further advance the clinical application for the hydrogels in bone repair. The physical properties of the gels can be tuned via tailoring the degree of alginate oxidation. In particular, in vivo degradation studies showed that the degradation rates of the gels were significantly increased by oxidizing alginate. The activity, proliferation, initial adhesion, and osteogenic differentiation of rat and rabbit bone marrow stromal cells (BMSCs) cultured with/in the hydrogels were explored, and the results demonstrated that the gels possessed excellent biocompatibility and that the encapsulated BMSCs were capable of osteogenic differentiation. Furthermore, in vivo implantation of rabbit BMSC-loaded gels into tibial plateau defects of rabbits demonstrated the feasibility of hydrogels with appropriate degradation rates for bone repair. This study indicated that hydrogels with increasingly controllable and matchable degradation kinetics and satisfactory bioproperties demonstrate great clinical potential in bone tissue engineering and regenerative medicine and could also provide references for drug/growth-factor delivery therapeutic strategies for diseases requiring specific drug/growth-factor durations of action.
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http://dx.doi.org/10.1021/acsami.2c01739DOI Listing
May 2022

Abnormal Cyclic Nucleotide Signaling at the Outer Mitochondrial Membrane In Sympathetic Neurons During the Early Stages of Hypertension.

Hypertension 2022 Jul 4;79(7):1374-1384. Epub 2022 May 4.

Burdon Sanderson Cardiac Science Centre and BHF Centre of Research Excellence, Department of Physiology, Anatomy and Genetics (D.L., K.L., H.D., C.R., O.C.N., A.T., N.L., M.Z., D.J.P.), University of Oxford, United Kingdom.

Background: Disruption of cyclic nucleotide signaling in sympathetic postganglionic neurons contributes to impaired intracellular calcium handling (Ca) and the development of dysautonomia during the early stages of hypertension, although how this occurs is poorly understood. Emerging evidence supports the uncoupling of signalosomes in distinct cellular compartments involving cyclic nucleotide-sensitive PDEs (phosphodiesterases), which may underpin the autonomic phenotype in stellate neurons.

Methods: Using a combination of single-cell RNA sequencing together with Forster resonance energy transfer-based sensors to monitor cyclic adenosine 3',5'-monophosphate, PKA (protein kinase A)-dependent phosphorylation and cGMP (cyclic guanosine 3',5'-monophosphate), we tested the hypothesis that dysregulation occurs in a sub-family of PDEs in the cytosol and outer mitochondrial membrane of neurons from the stellate ganglion.

Results: PDE2A, 6D, 7A, 9A genes were highly expressed in young Wistar neurons and also conserved in neurons from spontaneously hypertensive rats (SHRs). In stellate neurons from prehypertensive SHRs, we found the levels of cyclic adenosine 3',5'-monophosphate and cGMP at the outer mitochondrial membrane were decreased compared with normal neurons. The reduced cyclic adenosine 3',5'-monophosphate response was due to the hydrolytic activity of overexpressed PDE2A2 located at the mitochondria. Normal cyclic adenosine 3',5'-monophosphate levels were re-established by inhibition of PDE2A. There was also a greater PKA-dependent phosphorylation in the cytosol and at the outer mitochondrial membrane in spontaneously hypertensive rat neurons, where this response was regulated by protein phosphatases. The cGMP response was only restored by inhibition of PDE6.

Conclusions: When taken together, these results suggest that site-specific inhibition of PDE2A and PDE6D at the outer mitochondrial membrane may provide a therapeutic target to ameliorate cardiac sympathetic impairment during the onset of hypertension.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18882DOI Listing
July 2022

Dual-Cross-linked Liquid Crystal Hydrogels with Controllable Viscoelasticity for Regulating Cell Behaviors.

ACS Appl Mater Interfaces 2022 May 3;14(19):21966-21977. Epub 2022 May 3.

Biomaterial Research Laboratory, Department of Material Science and Engineering, College of Chemistry and Materials, Jinan University, Guangzhou 510632, P. R. China.

The liquid crystal properties and viscoelasticity of the natural bone extracellular matrix (ECM) play a decisive role in guiding cell behavior, conducting cell signals, and regulating mineralization. Here, we develop a facile approach for preparing a novel polysaccharide hydrogel with liquid crystal properties and viscoelasticity similar to those of natural bone ECM. First, a series of chitin whisker/chitosan (CHW/CS) hydrogels were prepared by chemical cross-linking with genipin, in which CHW can self-assemble to form cholesteric liquid crystals under ultrasonic treatment and CS chains can enter into the gaps between the helical layers of the CHW cholesteric liquid crystal phase to endow morphological stability and good mechanical properties. Subsequently, the obtained chemically cross-linked liquid crystal hydrogels were immersed into the desired concentration of the NaCl solution to form physical cross-linking. Due to the Hofmeister effect, the as-prepared dual-cross-linked liquid crystal hydrogels showed an enhanced modulus, viscoelasticity similar to that of natural ECM with relatively fast stress relaxation behavior, and fold surface morphology. Compared to both CHW/CS hydrogels without liquid crystal properties and CHW/CS liquid crystal hydrogels without further physical cross-linking, the dual-cross-linked CHW/CS liquid crystal hydrogels are more favorable for the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells. This approach could inspire the design of hydrogels mimicking the liquid crystal properties and viscoelasticity of natural bone ECM for bone repair.
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http://dx.doi.org/10.1021/acsami.2c02689DOI Listing
May 2022
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