Publications by authors named "Qing Xia"

554 Publications

Suppression of mitochondrial ROS by prohibitin drives glioblastoma progression and therapeutic resistance.

Nat Commun 2021 06 17;12(1):3720. Epub 2021 Jun 17.

State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China.

Low levels of reactive oxygen species (ROS) are crucial for maintaining cancer stem cells (CSCs) and their ability to resist therapy, but the ROS regulatory mechanisms in CSCs remains to be explored. Here, we discover that prohibitin (PHB) specifically regulates mitochondrial ROS production in glioma stem-like cells (GSCs) and facilitates GSC radiotherapeutic resistance. We find that PHB is upregulated in GSCs and is associated with malignant gliomas progression and poor prognosis. PHB binds to peroxiredoxin3 (PRDX3), a mitochondrion-specific peroxidase, and stabilizes PRDX3 protein through the ubiquitin-proteasome pathway. Knockout of PHB dramatically elevates ROS levels, thereby inhibiting GSC self-renewal. Importantly, deletion or pharmacological inhibition of PHB potently slows tumor growth and sensitizes tumors to radiotherapy, thus providing significant survival benefits in GSC-derived orthotopic tumors and glioblastoma patient-derived xenografts. These results reveal a selective role of PHB in mitochondrial ROS regulation in GSCs and suggest that targeting PHB improves radiotherapeutic efficacy in glioblastoma.
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http://dx.doi.org/10.1038/s41467-021-24108-6DOI Listing
June 2021

Layered Double Oxides for Sensing Reducing Volatile Organic Compounds: The Effect of Local Charge Region Modulation.

Chempluschem 2021 Jun;86(6):904-912

School of Microelectronics, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, P. R. China.

Multi-metal oxides with uniform distribution of various metal elements have potential for an enhanced gas-sensing response due to the strong heterogeneous and synergistic effects involved. In this study, three layered double oxides, labeled as CuCr-, ZnCr-, and ZnTi-LDOs, respectively, were prepared with corresponding LDHs (layered double hydroxides) as precursors and self-sacrificial templates. The elemental mapping confirms the uniform distribution of hetero-metal elements in whole LDOs. The CuCr-LDOs exhibits a much larger sensing response towards reducing VOCs at room temperature, which is 3.5 or 13.3 times that of ZnCr- or ZnTi-LDOs, respectively. The response differences are analyzed in terms of the local charge region modulation associated with heterojunction formation, and it is further demonstrated based on first-principles calculations and valence electron theory. The present work suggests a possible strategy for developing highly sensitive oxide-based gas sensors for VOCs detection.
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http://dx.doi.org/10.1002/cplu.202100161DOI Listing
June 2021

Interactive Effects of Glucocorticoids and Cytochrome P450 Polymorphisms on the Plasma Trough Concentrations of Voriconazole.

Front Pharmacol 2021 25;12:666296. Epub 2021 May 25.

Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, China.

To explore the interactive influence of glucocorticoids and cytochrome P450 (CYP450) polymorphisms on voriconazole (VRC) plasma trough concentrations (C) and provide a reliable basis for reasonable application of VRC. A total of 918 VRC C from 231 patients was collected and quantified using high-performance liquid chromatography in this study. The genotypes of , , and were detected by DNA sequencing assay. The effects of different genotypes and the coadministration of glucocorticoids on VRC C were investigated. Furthermore, the interactive effects of glucocorticoids with CYP450s on VRC C were also analyzed. The median C of oral administration was lower than that of intravenous administration (1.51 vs. 4.0 mg l). Coadministration of glucocorticoids (including dexamethasone, prednisone, prednisolone, and methylprednisolone) reduced the VRC C/dose, respectively, among which dexamethasone make the median of the VRC C/dose ratio lower. As a result, when VRC was coadministrated with glucocorticoids, the proportion of VRC C/dose in the subtherapeutic window was increased. Different CYP450 genotypes have different effects on the C/dose of VRC. Mutations of and increased C/dose of VRC, while and rs4646437 polymorphisms decreased C/dose of VRC. The mutation of has no significant effect. Furthermore, mutants could strengthen the effects of glucocorticoids and decrease VRC C/dose to a larger extent. Our study revealed that glucocorticoids reduced the C/dose levels of VRC and different SNPs of CYP450 have different effects on the C/dose ratio of VRC. Glucocorticoids and mutants had a synergistic effect on reducing VRC C/dose. The present results suggested that when VRC is combined with glucocorticoids, we should pay more attention to the clinical efficacy of VRC, especially when mutants exist.
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http://dx.doi.org/10.3389/fphar.2021.666296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185288PMC
May 2021

Factors Associated with Malignancy in Patients with Maximal Thyroid Nodules ≥2 Cm.

Cancer Manag Res 2021 4;13:4473-4482. Epub 2021 Jun 4.

Department of Thyroid Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China.

Purpose: The relationship between large thyroid nodules and the risk of malignancy is controversial. This study aimed to examine the relationship between thyroid nodule size and the risk of malignancy of maximal thyroid nodules ≥2 cm and the risk of accompanied by occult thyroid carcinoma.

Methods: This was a retrospective study of patients who underwent near-total or total thyroidectomy for thyroid nodules from January 2016 to January 2019 at the First Affiliated Hospital,Zhejiang University School of Medicine. Clinical, biochemical, and pathological characteristics were examined for association with malignancy using univariable, multivariable, and receiver operating characteristic curve analyses.

Results: Finally, 367 patients (277 females (75.5%) and 90 males (24.5%)) with a mean age of 49.0±13.5 years were included. Multivariable logistic regression analysis showed that age (OR=0.959, 95% CI: 0.939-0.979, <0.001), Hashimoto's thyroiditis (OR=2.437, 95% CI: 1.162-5.112, =0.018), the diameter of maximal nodule (small) (OR=0.706, 95% CI: 0.541-0.919, =0.010), and punctate echogenic foci (OR=2.837, 95% CI: 1.598-5.286, <0.001) were independently associated with malignancy. Of 223 patients who had non-suspicious malignant nodules (TI-RADS <4), 12.7% (n=29) patients showed malignancy at postoperative pathology. Only age was associated with occult PTC in the univariable analyses (OR=0.962, 95% CI: 0.934-0.991, =0.011). When TPOAb was used as a continuous variable for statistical analysis, it showed a significant difference in the ROC curve, and the results showed TPOAb >31.4 mIU/L was more associated with occult PTC (=0.006). A predictive model including four independent risk factors of malignancy showed an optimal discriminatory accuracy (area under the curve, AUC) of 0.783 (95% CI=0.732-0.833).

Conclusion: Relatively young age (<54.5 years), Hashimoto's thyroiditis, the diameter of the maximal nodule, and punctate echogenic foci were independently associated with thyroid malignancy in patients with maximal thyroid nodules ≥2 cm. Young age (<54.5 years) and TPOAb >31.4 mIU/L were associated with occult PTC.
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http://dx.doi.org/10.2147/CMAR.S303715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186937PMC
June 2021

Genetic diversity and phylogenetic relationship of nine sheep populations based on microsatellite markers.

Arch Anim Breed 2021 6;64(1):7-16. Epub 2021 Jan 6.

Key Laboratory of Animal Genetics and Breeding and Reproduction of the Ministry of Agriculture and Rural Affairs, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China.

The objective of this study was to assess the genetic diversity and phylogenetic relationship of nine sheep populations, including two famous high prolific populations and seven popular mutton populations raised in China. Overall, these sheep populations in this study exhibited a rich genetic diversity. Both the expected heterozygosity and Nei's unbiased gene diversity ranged from 0.64 to 0.75, with the lowest value found in Dorset sheep (DST) and the highest in Hu sheep (HUS) and Ba Han sheep (BAS). The polymorphic information content (PIC) varied between 0.59 in DST and 0.71 in HUS and BAS. Specifically, for individual breeds, the small-tail Han sheep (STH) and the four introduced populations did not display the expected diversity; therefore more attention should be paid to the maintenance of diversity during management of these populations. The results of un-weighted pair-group method (UPGMA) phylogenetic tree and structure analysis indicated that the nine investigated populations can be divided into two groups. Suffolk (SUF) and DST were clustered in one group, and the other group can be further divided into three clusters: German Mutton Merino (GMM)-BAS-Bamei Mutton sheep (BAM), HUS-STH and Du Han (DOS)-Dorper (DOP). This clustering result is consistent with sheep breeding history. TreeMix analysis also hinted at the possible gene flow from GMM to SUF. Together, an in-depth view of genetic diversity and genetic relationship will have important implications for breed-specific management.
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http://dx.doi.org/10.5194/aab-64-7-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160997PMC
January 2021

Profiling of Volatile Compounds and Associated Gene Expression in Two Cultivars and Their F1 Hybrid Progenies.

Molecules 2021 May 13;26(10). Epub 2021 May 13.

Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou 510642, China.

is an important ornamental crop in the world market and its floral scent can enhance its ornamental value. To date, studies of the components and formation mechanism of the floral scent of are relatively few. In this study, the scent profiles of two varieties were measured by gas chromatograph-mass spectrometer (GC-MS). There were 32 volatile organic compounds (VOCs) identified in  ', and the most abundant compound was eucalyptol (57.5%). Extremely small amounts of VOCs were detected in 'Alabama'. Compared with 'Alabama', most genes related to floral scent synthesis exhibited a higher expression in , including , ,  , , and In order to produce new varieties of with fragrance, 454 progenies of two crossbred combinations of  '' and 'Alabama' were obtained. Four F1 generation plants with different floral scent intensities were selected for further study. The major components of floral scent in the progenies were similar to that of the parental plant. The expression patterns of genes related to floral scent synthesis were consistent with the relative contents of different types of VOCs. This study revealed the profiles of volatile compounds and associated gene expression in two cultivars and their F1 hybrids, which provided a basis for the floral scent inheritance of .
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http://dx.doi.org/10.3390/molecules26102902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153298PMC
May 2021

Lateral rectus muscle differentiation potential in paralytic esotropia patients.

BMC Ophthalmol 2021 May 27;21(1):235. Epub 2021 May 27.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou, 510060, China.

Purpose And Background: Recently, we found that maximal medial rectus recession and lateral rectus resection in patients with complete lateral rectus paralysis resulted in a partial restoration of abduction. In an attempt to understand some of the mechanisms involved with this effect we examined gene expression profiles of lateral recti from these patients, with our focus being directed to genes related to myogenesis.

Materials And Methods: Lateral recti resected from patients with complete lateral rectus paralysis and those from concomitant esotropia (controls) were collected. Differences in gene expression profiles between these two groups were examined using microarray analysis and quantitative Reverse-transcription PCR (qRT-PCR).

Results: A total of 3056 differentially expressed genes (DEGs) were identified between these two groups. Within the paralytic esotropia group, 2081 genes were up-regulated and 975 down-regulated. The results of RT-PCR revealed that PAX7, MYOG, PITX1, SIX1 and SIX4 showed higher levels of expression, while that of MYOD a lower level of expression within the paralytic esotropia group as compared with that in the control group (p < 0.05).

Conclusion: The decreased expression of MYOD in the paralytic esotropia group suggested that extraocular muscle satellite cell (EOMSCs) differentiation processes were inhibited. Whereas the high expression levels of PAX7, SIX1/4 and MYOG, suggested that the EOMSCs were showing an effective potential for differentiation. The stimulation resulting from muscle surgery may induce EOMSCs to differentiate and thus restore abduction function.
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http://dx.doi.org/10.1186/s12886-021-01994-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161593PMC
May 2021

Single-cell analysis of pancreatic ductal adenocarcinoma identifies a novel fibroblast subtype associated with poor prognosis but better immunotherapy response.

Cell Discov 2021 May 25;7(1):36. Epub 2021 May 25.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

The current pathological and molecular classification of pancreatic ductal adenocarcinoma (PDAC) provides limited guidance for treatment options, especially for immunotherapy. Cancer-associated fibroblasts (CAFs) are major players of desmoplastic stroma in PDAC, modulating tumor progression and therapeutic response. Using single-cell RNA sequencing, we explored the intertumoral heterogeneity among PDAC patients with different degrees of desmoplasia. We found substantial intertumoral heterogeneity in CAFs, ductal cancer cells, and immune cells between the extremely dense and loose types of PDACs (dense-type, high desmoplasia; loose-type, low desmoplasia). Notably, no difference in CAF abundance was detected, but a novel subtype of CAFs with a highly activated metabolic state (meCAFs) was found in loose-type PDAC compared to dense-type PDAC. MeCAFs had highly active glycolysis, whereas the corresponding cancer cells used oxidative phosphorylation as a major metabolic mode rather than glycolysis. We found that the proportion and activity of immune cells were much higher in loose-type PDAC than in dense-type PDAC. Then, the clinical significance of the CAF subtypes was further validated in our PDAC cohort and a public database. PDAC patients with abundant meCAFs had a higher risk of metastasis and a poor prognosis but showed a dramatically better response to immunotherapy (64.71% objective response rate, one complete response). We characterized the intertumoral heterogeneity of cellular components, immune activity, and metabolic status between dense- and loose-type PDACs and identified meCAFs as a novel CAF subtype critical for PDAC progression and the susceptibility to immunotherapy.
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http://dx.doi.org/10.1038/s41421-021-00271-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149399PMC
May 2021

Intravenous Dexmedetomidine Administration Prior Anesthesia Induction With Propofol at 4°C Attenuates Propofol Injection Pain: A Double-Blind, Randomized, Placebo-Controlled Trial.

Front Med (Lausanne) 2021 7;8:590465. Epub 2021 May 7.

Center of Gastrointestinal Endoscopy, Huadong Sanatorium, Wuxi, China.

Propofol injection pain, despite various interventions, still occurs during the anesthesia induction and causes intense discomfort and anxiety in patients. This study aimed to explore the effect of intravenous dexmedetomidine on propofol injection pain prior to anesthesia induction with propofol at 4°C. A total of 251 patients (American Society of Anesthesiologists I-II) who underwent oral and maxillofacial surgery were randomly assigned to a combination group ( = 63), lidocaine group ( = 62), dexmedetomidine group ( = 63), and placebo-control group ( = 63); they received 0.5 ug/kg dexmedetomidine prior to anesthesia induction with propofol at 4°C, 40 mg lidocaine, 0.5 ug/kg dexmedetomidine prior to anesthesia induction, and normal saline, respectively. Incidence of pain, pain intensity, and reaction to the pain stimulus were evaluated by using verbal categorial scoring (VCS), a numerical rating scale (NRS), and the Surgical Pleth Index (SPI), respectively. In addition, hemodynamic parameters such as heart rate (HR) and mean arterial pressure (MAP) were also measured. The VCS and NRS were evaluated at 5 s after propofol injection. In addition, SPI, HR, and MAP were evaluated at three time points (before anesthesia induction and 5 and 30 s after propofol injection). The incidence of pain in the combination group (51%) was significantly lower than that in the lidocaine group (71%), dexmedetomidine group (67%), or placebo-control group (94%) ( < 0.001). VCS and NRS scores in the combination group were also lower compared with the other three groups ( < 0.001), with no statistically significant differences between the lidocaine group and dexmedetomidine group ( > 0.05). The SPI of the combination group decreased significantly in comparison with the other three groups at 5 s after propofol injection ( = 96.23, < 0.001) and 30 s after propofol injection ( = 4.46, = 0.005). Further comparisons between HR and MAP revealed no significant differences across the groups ( > 0.05). Because of the sedative nature of dexmedetomidine and analgesic effect of low temperature, this study showed that intravenous dexmedetomidine prior to anesthesia induction with propofol at 4°C is highly effective in attenuating the incidence and severity of pain during injection compared with lidocaine (40 mg), dexmedetomidine 0.5 ug/kg) and placebo. This approach was not associated with any anesthesia complications. ClinicalTrials.gov, identifier: ChiCTR-2000034663.
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http://dx.doi.org/10.3389/fmed.2021.590465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137828PMC
May 2021

Alleviation of acute pancreatitis-associated lung injury by inhibiting the p38 mitogen-activated protein kinase pathway in pulmonary microvascular endothelial cells.

World J Gastroenterol 2021 May;27(18):2141-2159

Department of Integrated Traditional Chinese and Western Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.

Background: Previous reports have suggested that the p38 mitogen-activated protein kinase signaling pathway is involved in the development of severe acute pancreatitis (SAP)-related acute lung injury (ALI). Inhibition of p38 by SB203580 blocked the inflammatory responses in SAP-ALI. However, the precise mechanism associated with p38 is unclear, particularly in pulmonary microvascular endothelial cell (PMVEC) injury.

Aim: To determine its role in the tumor necrosis factor-alpha (TNF-α)-induced inflammation and apoptosis of PMVECs . We then conducted experiments to confirm the effect of SB203580-mediated p38 inhibition on SAP-ALI.

Methods: , PMVEC were transfected with mitogen-activated protein kinase kinase 6 (Glu), which constitutively activates p38, and then stimulated with TNF-α. Flow cytometry and western blotting were performed to detect the cell apoptosis and inflammatory cytokine levels, respectively. , SAP-ALI was induced by 5% sodium taurocholate and three different doses of SB203580 (2.5, 5.0 or 10.0 mg/kg) were intraperitoneally injected prior to SAP induction. SAP-ALI was assessed by performing pulmonary histopathology assays, measuring myeloperoxidase activity, conducting arterial blood gas analyses and measuring TNF-α, interleukin (IL)-1β and IL-6 levels. Lung microvascular permeability was measured by determining bronchoalveolar lavage fluid protein concentration, Evans blue extravasation and ultrastructural changes in PMVECs. The apoptotic death of pulmonary cells was confirmed by performing a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis and examining the Bcl2, Bax, Bim and cle-caspase3 levels. The proteins levels of P-p38, NFκB, IκB, P-signal transducer and activator of transcription-3, nuclear factor erythroid 2-related factor 2, HO-1 and Myd88 were detected in the lungs to further evaluate the potential mechanism underlying the protective effect of SB203580.

Results: , mitogen-activated protein kinase (Glu) transfection resulted in higher apoptotic rates and cytokine (IL-1β and IL-6) levels in TNF-α-treated PMVECs. , SB2035080 attenuated lung histopathological injury, decreased inflammatory activity (TNF-α, IL-1β, IL-6 and myeloperoxidase) and preserved pulmonary function. Furthermore, SB203580 significantly reversed changes in the bronchoalveolar lavage fluid protein concentration, Evans blue accumulation, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cell numbers, apoptosis-related proteins (cle-caspase3, Bim and Bax) and endothelial microstructure. Moreover, SB203580 significantly reduced the pulmonary P-p38, NFκB, P-signal transducer and activator of transcription-3 and Myd88 levels but increased the IκB and HO-1 levels.

Conclusion: p38 inhibition may protect against SAP-ALI by alleviating inflammation and the apoptotic death of PMVECs.
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http://dx.doi.org/10.3748/wjg.v27.i18.2141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117735PMC
May 2021

Evaluation of the individual and combined toxicity of perfluoroalkyl substances to human liver cells using biomarkers of oxidative stress.

Chemosphere 2021 May 5;281:130808. Epub 2021 May 5.

The University of Queensland, Queensland Alliance for Environmental Health Sciences (QAEHS), 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia. Electronic address:

Although human exposure is to mixtures of per- and polyfluoroalkyl substances (PFAS), their combined effects and underlying mechanisms remain largely unknown. In this study, the combined effects of PFAS was investigated by treating human liver cells (HepG2) with various concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluorohexanoic acid (PFHxS) individually or in binary combinations (PFOS + PFOA, PFOS + PFDA, PFOS + PFNA, PFOS + PFHxS, PFOA + PFDA, PFOA + PFNA, and PFOA + PFHxS) for 24 h using an orthogonal design. The individual and binary combination effects of PFAS on the cytotoxicity, intracellular reactive oxygen species (ROS) production, and glutathione (GSH) levels were determined by MTS assay, dichlorofluorescein diacetate assay, and GSH-Glo™ Glutathione assay, respectively. The results showed that exposure to PFOA, PFOS, PFDA, PFNA, and PFHxS individually and in binary combinations caused concentration-dependent cytotoxicity to HepG2 cells. Also, intracellular ROS production was not significantly induced in both the individual and co-treatment groups, indicating that ROS production may not be likely influencing the combined cytotoxicity of PFAS to HepG2 cells. However, the depletion of the intracellular glutathione levels was correlated with cytotoxicity. Moreover, the factorial analysis results showed no significant interactive effects between PFOS + PFOA, PFOS + PFDA, PFOS + PFNA, PFOS + PFHxS, PFOA + PFDA, PFOA + PFNA, and PFOA + PFHxS. Taken together, the results showed that both individual and combined PFAS could induce concentration-dependent cytotoxicity and depletion of GSH levels, but could not induce significant increases in ROS production at the concentration range tested. Overall, these results provided valuable toxicological data on the combined effects of mixed PFAS that may help to better assess their human health risk.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130808DOI Listing
May 2021

Recovering chemical sludge from the zero liquid discharge system of flue gas desulfurization wastewater as flame retardants by a stepwise precipitation process.

J Hazard Mater 2021 May 7;417:126054. Epub 2021 May 7.

Shanghai Engineering Research Center of Energy - Saving in Heat Exchange Systems, College of Environmental and Chemical Engineering, Shanghai University of Electric Power, Shanghai 200090, China.

In this study, a five-stage stepwise precipitation process, including pre-sedimentation, magnesium removal, gypsum precipitation, ettringite precipitation and calcium removal, was proposed as a softening pretreatment for zero liquid discharge system for flue gas desulfurization wastewater. Batch tests and long-term bench-scale experiment showed that magnesium, sulfate and calcium were efficiently removed with efficiencies all above 98.0%, leaving a clean effluent majorly containing NaCl and NaOH. The precipitated CaSO, CaCO, Mg(OH) and ettringite were completely separated by stepwise precipitation, and the purity of Mg(OH) and ettringite were further enhanced by washing and soaking treatment. CaSO and CaCO can be directly recycled as gypsum product and desulfurizing agent within the power plant, while Mg(OH) and ettringite presented proper particle size and excellent thermal properties as a synergistic flame retardant. The flame retardancy of ethylene vinyl acetate copolymer were greatly improved when blended with recovered Mg(OH) and ettringite, and possessed better performance by blending them together because ettringite could act as a dispersing and compatible agent of Mg(OH), and relieve the intensity of smoke releasing. Chemical sludge recovery compensates the total cost of the five-stage process by 45.0%, and makes the process technically versatile, economically beneficial and environmentally friendly without solid waste production.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126054DOI Listing
May 2021

Photoperiod induced the pituitary differential regulation of lncRNAs and mRNAs related to reproduction in sheep.

PeerJ 2021 21;9:e10953. Epub 2021 Apr 21.

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.

The pituitary is a vital endocrine organ that regulates animal seasonal reproduction by controlling the synthesis and secretion of the hormone. The change of photoperiod is the key factor affecting the function of the pituitary in animals, but the mechanism is unclear. Here, we studied the transcriptomic variation in pars distalis (PD) of the pituitary between short photoperiod (SP) and long photoperiod (LP) using RNA sequencing based on the OVX+E sheep. 346 differentially expressed (DE) lncRNAs and 186 DE-mRNA were found in the PD. Moreover, function annotation analysis indicated that the reproductive hormones and photoperiod response-related pathways including aldosterone synthesis and secretion, insulin secretion, thyroid hormone synthesis, and circadian entrainment were enriched. The interaction analysis of mRNA-lncRNA suggested that MSTRG.240648, MSTRG.85500, MSTRG.32448, and MSTRG.304959 targeted and , which may be involved in the photoperiodic regulation of the PD. These findings provide resources for further study on the seasonal reproductive in ewes.
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http://dx.doi.org/10.7717/peerj.10953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067910PMC
April 2021

Involvement of Nrf2-HO-1/JNK-Erk Signaling Pathways in Aconitine-Induced Developmental Toxicity, Oxidative Stress, and ROS-Mitochondrial Apoptosis in Zebrafish Embryos.

Front Pharmacol 2021 21;12:642480. Epub 2021 Apr 21.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.

Aconitine (AC), one of the bioactive diterpenoid alkaloids extracted from plants, is widely used in traditional herbal medicine to treat various diseases. Emerging evidence indicates that AC has attracted great interest for its wide cardiotoxicity and neurotoxicity. However, the toxic effects of AC on embryonic development and its underlying mechanisms remain unclear. Here, a developmental toxicity assay of AC was performed on zebrafish embryos from 4 to 96 h post fertilization (hpf), and its underlying mechanisms were discussed. AC exposure impaired the cardiac, liver, and neurodevelopment. Especially, a high dose of AC (7.27 and 8.23 μM) exposure resulted in malformations at 72 and 96 hpf, including reduced body length, curved body shape, pericardial edema, yolk retention, swim bladder and brain developmental deficiency, and degeneration of dopaminergic neurons. High-concentration AC exposure caused a deficient cardiovascular system with cardiac dysfunctions, increased heart rates at 72 and 96 hpf, and reduced locomotor behavior at 120 hpf. AC treatment significantly increased the ROS level and triggered cell apoptosis in the heart and brain regions of embryos at 96 hpf in 7.27 and 8.23 μM AC treatment zebrafish. Oxidative stress was confirmed by reduced levels of T-SOD activity associated with accumulation of lipid peroxidation in larvae. The expression levels of oxidative stress-related genes (, , , and ) and were significantly downregulated at 96 hpf. The expression pattern of JNK and mitochondrial apoptosis-related genes (, , , , and ) was significantly upregulated. Taken together, all these parameters collectively provide the first evidence of AC-induced developmental toxicity in zebrafish embryo/larvae through ROS-medicated mitochondrial apoptosis involving Nrf2/HO-1 and JNK/Erk pathways.
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http://dx.doi.org/10.3389/fphar.2021.642480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097150PMC
April 2021

Stress Hyperglycemia Is Independently Associated with Persistent Organ Failure in Acute Pancreatitis.

Dig Dis Sci 2021 May 3. Epub 2021 May 3.

Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, No. 37 Wannan Guoxue Alley, Chengdu, 610041, Sichuan Province, China.

Background/aims: Stress hyperglycemia is common in critical illness but it has not been clearly studied in patients with acute pancreatitis (AP). This study aimed to investigate the specific blood glucose (BG) level that defines stress hyperglycemia and to determine the impact of stress hyperglycemia on clinical outcomes in AP patients.

Methods: AP patients admitted ≤ 48 h after abdominal pain onset were retrospectively analyzed. Patients were stratified by pre-existing diabetes and stress hyperglycemia was defined using stratified BG levels for non-diabetes and diabetes with clinical outcomes compared.

Results: There were 967 non-diabetic and 114 diabetic (10.5%) patients met the inclusion criteria and the clinical outcomes between these two groups were not significantly different. In non-diabetes, the cut-off BG level of ≥ 180 mg/dl was selected to define stress hyperglycemia with an 8.8-fold higher odds ratio for persistent organ failure (POF) (95% CI 5.4-14.3; P < 0.001). For diabetes, ≥ 300 mg/dl was selected with a 7.5-fold higher odds ratio for POF (95% CI 1.7-34.3; P = 0.009). In multivariable logistic regression, stress hyperglycemia was independently associated with POF, acute necrotic collection, major infection and mortality. The combination of BG and systemic inflammatory response syndrome (SIRS) score in predicting POF was better than SIRS or Glasgow score alone.

Conclusions: This study identifies a cut-off BG level of ≥ 180 mg/dl and ≥ 300 mg/dl was optimal to define stress hyperglycemia for non-diabetic and diabetic AP patients, respectively. There was a significant relationship between stress hyperglycemia and adverse clinical outcomes.
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http://dx.doi.org/10.1007/s10620-021-06982-8DOI Listing
May 2021

The Protective A673T Mutation of Amyloid Precursor Protein (APP) in Alzheimer's Disease.

Mol Neurobiol 2021 Apr 29. Epub 2021 Apr 29.

Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by extracellular amyloid beta peptides and neurofibrillary tangles consisted of intracellular hyperphosphorylated Tau in the hippocampus and cerebral cortex. Most of the mutations in key genes that code for amyloid precursor protein can lead to significant accumulation of these peptides in the brain and cause Alzheimer's disease. Moreover, some point mutations in amyloid precursor protein can cause familial Alzheimer's disease, such as Swedish mutation (KM670/671NL) and A673V mutation. However, recent studies have found that the A673T mutation in amyloid precursor protein gene can protect against Alzheimer's disease, even if it is located next to the Swedish mutation (KM670/671NL) and at the same site as A673V mutation, which are pathogenic. It makes us curious about the protective A673T mutation. Here, we summarize the most recent insights of A673T mutation, focus on their roles in protective mechanisms against Alzheimer's disease, and discuss their involvement in future treatment.
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http://dx.doi.org/10.1007/s12035-021-02385-yDOI Listing
April 2021

Upconversion nanoparticles modified by CuS for photothermal therapy along with real-time optical thermometry.

Nanoscale 2021 Apr 7;13(15):7161-7168. Epub 2021 Apr 7.

Department of Mathematics and Physics, Chongqing University of Posts and Telecommunications, 2 Chongwen Road, Chongqing 400065, China.

Highly effective photothermal conversion performance coupled with high resolution temperature detection in real time is urgently needed for photothermal therapy (PTT). Herein, ultra-small CuS nanoparticles (NPs) were designed to absorb on the surface of NaScF: Yb/Er/[email protected]@SiO NPs to form a central-satellite system, in which the CuS NPs play the role of providing significant light-to-heat conversion ability and the Er ions in the NaScF: Yb/Er/Mn cores act as a thermometric probe based on the fluorescence intensity ratio (FIR) technology operating in the biological windows. A wavelength of 915 nm is used instead of the conventional 980 nm excitation wavelength to eliminate the laser induced overheating effect for the bio-tissues, by which Yb can also be effectively excited. The temperature resolution of the FIR-based optical thermometer is determined to be better than 0.08 K over the biophysical temperature range with a minimal value of 0.06 K at 298 K, perfectly satisfying the requirements of biomedicine. Under the radiation of 915 nm light, the CuS NPs exhibit remarkable light-to-heat conversion capacity, which is proved by photothermal ablation testing of E. coli. The results reveal the enormous potential of the present NPs for PTT integrated with real-time temperature sensing with high resolution.
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http://dx.doi.org/10.1039/d0nr09115dDOI Listing
April 2021

Radiofrequency ablation stereotactic body radiotherapy for stage IA non-small cell lung cancer in nonsurgical patients.

J Cancer 2021 19;12(10):3057-3066. Epub 2021 Mar 19.

Department of Respiratory Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Approximately 20% resectable non-small cell lung cancer (NSCLC) patients are treated non-surgically due to various reasons. The aim of the present study was to compare the effectiveness of radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) in patients with stage IA NSCLC who were ineligible for surgery using the surveillance, epidemiology and end-results (SEER) Database. Using the SEER registry, we identified a total of 6,195 IA NSCLC patients who received SBRT or RFA between 2004 and 2015 because of ineligibility for surgical resection due to various reasons. Complete clinical information was available in all these patients. Overall survival (OS) and cancer-specific survival (CSS) were compared between RFA and SBRT groups by using propensity score matching (PSM), inverse probability of treatment weight (IPTW), and overlap weighting analysis. Additionally, an exploratory analysis was conducted to determine the effectiveness of RFA treatment based on the subsets of clinically relevant patients. Of the 6,195 nonsurgical IA NSCLC patients, 191 patients (3.1%) received RFA and the other 6,004 patients (96.9%) received SBRT. The one-, three- and five-year OS in the unmatched RFA and SBRT groups were 83.3%, 48.5%and 29.1% 83.8%, 48.3% and 27.4%, respectively, there was similar results in the PSM, IPTW, overlap weighing analysis. Nonsurgical IA NSCLC patients receiving RFA seemed to have better five-year survival than those receiving SBRT, though the difference was not statistically significant (OS, HR; 0.986; 95% CI, 0.827-1.175, =0.8738; CSS, HR; 0.965; 95% CI, 0.765-1.219, =0.7663). We found that the odds of receiving RFA decreased with larger tumor size (>2, <3 cm, OR; 0.303; 95% CI, 0.191-0.479; >3 cm, OR; 0.153; 95% CI, 0.093-0.251) compared with tumor size <1 cm. In subgroup analysis, patients receiving RFA seemed to have better OS than those receiving SBRT, though the difference was not statistically significant. This specific trend was even more obvious in patients with tumors <1cm in diameter (=0.1577). In comparison with SBRT, RFA did not seem to adversely affect CSS and OS of IA NSCLC patients who were not suitable for surgical treatment. In addition, RFA seemed to offer better survival to IA NSCLC patients, especially those with tumors <1 cm.
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http://dx.doi.org/10.7150/jca.51413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040894PMC
March 2021

Predominant Microbial Colonizers in the Root Endosphere and Rhizosphere of Turfgrass Systems: , , and spp.

Front Microbiol 2021 23;12:643904. Epub 2021 Mar 23.

Department of Crop and Soil Sciences, North Carolina State University, Raleigh, NC, United States.

Microbes can colonize plant roots to modulate plant health and environmental fitness. Thus, using microbes to improve plant adaptation to biotic and abiotic stresses will be promising to abate the heavy reliance of management systems on synthetic chemicals and limited resource. This is particularly important for turfgrass systems because intensive management for plant available nutrients (e.g., nitrogen), water, and pest control is necessary to maintain a healthy and aesthetic landscape. However, little is known on microbial species and host compatibility in turfgrass root endosphere and rhizosphere. Here, by using marker gene high throughput sequencing approaches we demonstrated that a few bacterial and fungal species prevailed the root endosphere and rhizosphere and were of a broad host spectrum. Irrespective of turfgrass species (bermudagrass, ultradwarf bermudagrass, creeping bentgrass, and tall fescue), defoliation intensities (i.e., mowing height and frequency), turfgrass sites, and sampling time, was predominant in the root endosphere, constituting ∼38% of the total bacterial community, which was much higher than its presence in the bulk soil (∼0.5%) and rhizosphere (∼4.6%). By contrast, and fungal species of the genus were more abundant in the rhizosphere, constituting ∼15 and ∼ 39% of the total bacterial and fungal community, respectively, compared to their respective presence in the bulk soil (∼ 0.1 and 5%) and root endosphere (∼ 0.8 and 0.3%). Such stark contrasts in the microbiome composition between the root endosphere, rhizosphere, and bulk soil were little influenced by turfgrass species, suggesting the broad turfgrass host compatibility of these bacterial and fungal species. Further, their dominance in respective niches were mutually unaffected, implying the possibility of developing a multiple species formula for coping turfgrass with environmental stresses. These species were likely involved in controlling pests, such as infectious nematodes and fungi, decomposing root debris, and helping turfgrass water and nutrient uptake; yet these possibilities need to be further examined.
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http://dx.doi.org/10.3389/fmicb.2021.643904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021697PMC
March 2021

Targeting Macrophage Migration Inhibitory Factor in Acute Pancreatitis and Pancreatic Cancer.

Front Pharmacol 2021 11;12:638950. Epub 2021 Mar 11.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital of Sichuan University, Chengdu, China.

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in the pathogenesis of inflammation and cancer. It is produced by various cells and circulating MIF has been identified as a biomarker for a range of diseases. Extracellular MIF mainly binds to the cluster of differentiation 74 (CD74)/CD44 to activate downstream signaling pathways. These in turn activate immune responses, enhance inflammation and can promote cancer cell proliferation and invasion. Extracellular MIF also binds to the C-X-C chemokine receptors cooperating with or without CD74 to activate chemokine response. Intracellular MIF is involved in Toll-like receptor and inflammasome-mediated inflammatory response. Pharmacological inhibition of MIF has been shown to hold great promise in treating inflammatory diseases and cancer, including small molecule MIF inhibitors targeting the tautomerase active site of MIF and antibodies that neutralize MIF. In the current review, we discuss the role of MIF signaling pathways in inflammation and cancer and summarize the recent advances of the role of MIF in experimental and clinical exocrine pancreatic diseases. We expect to provide insights into clinical translation of MIF antagonism as a strategy for treating acute pancreatitis and pancreatic cancer.
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http://dx.doi.org/10.3389/fphar.2021.638950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992011PMC
March 2021

A multi-strategy platform for quality control and Q-markers screen of Chaiqin chengqi decoction.

Phytomedicine 2021 May 20;85:153525. Epub 2021 Feb 20.

Department and Laboratory of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

Background: Acute pancreatitis (AP) is an inflammatory disorder of the pancreas that is associated with substantial morbidity and mortality. Chaiqin chengqi decoction (CQCQD) has been proven clinically to be an effective treatment for AP for decades in West China Hospital. Quality control for CQCQD containing many hundreds of characteristic phytochemicals poses a challenge for developing robust quality assessment metrics.

Purpose: To evaluate quality consistency of CQCQD with a multi-strategy based analytical method, identify potential quality-markers (Q-markers) based on drug properties and effect characteristics, and endeavor to establish CQCQD as a globally-accepted medicine.

Methods: A typical analysis of constitutive medicinal plant materials was performed following the Chinese Pharmacopoeia. The extraction process was optimized through an orthogonal array (L(3)) to evaluate three levels of liquid to solid ratio, soaking time, duration of extraction, and the number of extractions. An ultra-high-performance liquid chromatography (UHPLC) fingerprinting combined with absolute quantitation of multi chemical marker compounds, coupled with similarity, hierarchical clustering analysis (HCA), and principal component analyses (PCA) were performed to evaluate 10 batches of CQCQD. On the basis of systematic analysis of fundamental features of CQCQD in treating AP, the potential Q-marker screen was proposed through detection of quality transfer and efficacy for chemical markers. UHPLC coupled with quadrupole orbitrap mass spectrometry were used to determine compounds in medicinal materials, decoctions and plasma. Network pharmacology and taurolithocholic acid 3-sulfate induced pancreatic acinar cell death were used to evaluate the correlation between chemical markers and anti-pancreatitis activity. A cerulein induced AP murine model was used to validate quality assessed CQCQD batches at clinically-equivalent dose. The effective content of chemical markers was predicted using linear regression analysis on quantitative information between validated batches and the other batches.

Results: The chemical markers and other physical and chemical indices in the original materials met Chinese Pharmacopoeia standards. A total of 22 co-existing fingerprint peaks were selected and the similarity varied between 0.946 and 0.990. Batch D10 possessed the highest similarity index. HCA classified the 10 batches into 2 main groups: 7 batches represented by D10 and 3 batches represented by D1. During the initial Q-marker screen stage, 22 compounds were detected in both plant materials and decoctions, while 13 compounds were identified in plasma. Network pharmacology predicted the potential targets and pathway of AP related to the 22 compounds. All 10 batches showed reduced necrosis below 60% with the best effect achieved by D10 (~40%). The spectrum-efficacy relationship analyzed by Pearson correlation analysis indicated that emodin, rhein, aloe emodin, geniposide, hesperridin, chrysin, syringin, synephrine, geniposidic acid, magnolol, physcion, sinensetin, and baicalein showed positive correlation with pancreatic acinar cell death protection. Similar to the in vitro evaluation, batch D10 significantly reduced total histopathological scores and biochemical severity indices at a clinically-equivalent dose but batch D1 did not. The content of naringin, narirutin and baicalin in batches D1, D5 and D9 consistently exceeds the upper limit of the predicted value. Eight markers whose lower limit is predicted to be close to 0 contributed less to the material basis for AP protection.

Conclusion: Despite qualified materials used for CQCQD preparation, the clinical effect depends on appropriate content range of Q-markers. Emodin, rhein, aloe emodin, magnolol, hesperidin, synephrine, baicalein, and geniposide are considered as vital Q-markers in the primary screen. This study proposed a feasible platform for producing highly consistent batches of CQCQD in future study.
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http://dx.doi.org/10.1016/j.phymed.2021.153525DOI Listing
May 2021

Chaiqin chengqi decoction ameliorates acute pancreatitis in mice via inhibition of neuron activation-mediated acinar cell SP/NK1R signaling pathways.

J Ethnopharmacol 2021 Jun 14;274:114029. Epub 2021 Mar 14.

Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Ethnopharmacological Relevance: Chaiqin chengqi decoction (CQCQD) and its derivatives have been widely used in China for the early management of patients with acute pancreatitis (AP). Numerous studies demonstrate the anti-inflammatory and anti-oxidative effects of CQCQD and derivatives, but whether these effects can be attributed to suppressing neurogenic inflammation, has never been studied.

Aim Of The Study: To investigate the effects of CQCQD on substance P (SP)-neurokinin 1 receptor (NK1R) based neurogenic inflammation in an experimental AP model.

Material And Methods: For AP patients on admission, pain score was accessed by visual analog scale (VAS); the levels of serum SP and expressions of pancreatic SP and NK1R were also determined. For in vivo study, mice received 7 intraperitoneal injections of cerulein (50 μg/kg) at hourly intervals to induce AP, whilst controls received normal saline injections. In the treatment groups, CQCQD (10 g/kg, 200 μl) was intragastrically given at the third, fifth, and seventh of the cerulein injection or the NK1R antagonist CP96345 (5 mg/kg) was intraperitoneally injected 30 min before the first cerulein administration. The von Frey test was performed to evaluate pain behavior. Animals were sacrificed at 12 h from the first cerulein/saline injection for severity assessment. Pharmacology network analysis was used to identify active ingredients of CQCQD for AP and pain. In vitro, freshly isolated pancreatic acinar cells were pre-treated with CQCQD (5 mg/ml), CP96345 (1 μM), or selected active compounds of CQCQD (12.5, 25, and 50 μM) for 30 min, followed by SP incubation for another 30 min.

Results: The VAS score as well as the levels of serum SP and expressions of pancreatic SP-NK1R were up-regulated in moderately severe and severe patients compared with those with mild disease. CQCQD, but not CP96345, consistently and significantly ameliorated pain, pancreatic necrosis, and systemic inflammation in cerulein-induced AP as well as inhibited NK1R internalization of pancreatic acinar cells. These effects of CQCQD were associated with reduction of pancreatic SP-NK1R and neuron activity in pancreas, dorsal root ganglia, and spinal cord. Baicalin, emodin, and magnolol, the top 3 active components of CQCQD identified via pharmacology network analysis, suppressed NK1R internalization and NF-κB signal pathway activation in isolated pancreatic acinar cells.

Conclusions: CQCQD ameliorated cerulein-induced AP and its associated pain via inhibiting neuron activation-mediated pancreatic acinar cell SP-NK1R signaling pathways and its active compounds baicalin, emodin, and magnolol contributed to this effect.
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http://dx.doi.org/10.1016/j.jep.2021.114029DOI Listing
June 2021

Metabolomic-based clinical studies and murine models for acute pancreatitis disease: A review.

Biochim Biophys Acta Mol Basis Dis 2021 Jul 11;1867(7):166123. Epub 2021 Mar 11.

West China-Washington Mitochondria and Metabolism Centre, Frontiers Science Center for Disease-related Molecular Network, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address:

Acute pancreatitis (AP) is one of the most common gastroenterological disorders requiring hospitalization and is associated with substantial morbidity and mortality. Metabolomics nowadays not only help us to understand cellular metabolism to a degree that was not previously obtainable, but also to reveal the importance of the metabolites in physiological control, disease onset and development. An in-depth understanding of metabolic phenotyping would be therefore crucial for accurate diagnosis, prognosis and precise treatment of AP. In this review, we summarized and addressed the metabolomics design and workflow in AP studies, as well as the results and analysis of the in-depth of research. Based on the metabolic profiling work in both clinical populations and experimental AP models, we described the metabolites with potential utility as biomarkers and the correlation between the altered metabolites and AP status. Moreover, the disturbed metabolic pathways correlated with biological function were discussed in the end. A practical understanding of current and emerging metabolomic approaches applicable to AP and use of the metabolite information presented will aid in designing robust metabolomics and biological experiments that result in identification of unique biomarkers and mechanisms, and ultimately enhanced clinical decision-making.
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http://dx.doi.org/10.1016/j.bbadis.2021.166123DOI Listing
July 2021

Lidocaine Inhibits Myoblast Cell Migration and Myogenic Differentiation Through Activation of the Notch Pathway.

Drug Des Devel Ther 2021 2;15:927-936. Epub 2021 Mar 2.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China.

Purpose: To assess the cellular and molecular effects of lidocaine on muscles/myoblasts.

Methods: Cultured myogenic precursor (C2C12) cells were treated with varying concentrations of lidocaine.

Results: Cell viability of C2C12 cells was inhibited by lidocaine in a concentration-dependent manner, with concentrations ≥0.08%, producing a dramatic reduction in cell viability. These ≥0.08% concentrations of lidocaine arrested cell cycles of C2C12 cells in the G0/G1 phase. Moreover, lidocaine inhibited cell migration and myogenic processes in C2C12 cells at low concentrations. Results from QRT-PCR assays revealed that following treatment with lidocaine, Notch1, Notch2, Hes1, Csl and Dll4 all showed higher levels of expression, while no changes were observed in Mmal1, Hey1, Dll1 and Jag1.

Conclusion: This work provides the first description of the effects of lidocaine upon the regeneration of muscles and maintenance of satellite cells at the cellular and molecular levels. In specific, we found that the Dll4-Notch-Csl-Hes1 axis was up-regulated suggesting that the Notch signaling pathway was involved in producing these effects of lidocaine. These findings provide a new and important foundation for future investigations into the effects of drug therapies in muscle diseases.
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http://dx.doi.org/10.2147/DDDT.S290002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936691PMC
March 2021

A flexible hybrid capacitor based an NiCoS nanowire electrode with an ultrahigh capacitance.

Dalton Trans 2021 Mar 5;50(11):4045-4052. Epub 2021 Mar 5.

School of Materials Science and Engineering, Shenyang University of Technology, Shenyang 110870, P. R. China.

It is well-known that the excellent cycling stability and high energy density of electrode materials is very important for supercapacitors. However, their actual performance falls far behind and does not satisfy the practical demand. In this study, we synthesized NiCoS nanowire bundles on a nickel foam via facile hydrothermal routes. The as-obtained product as an electrode material possesses excellent specific surface area, which suggests that numerous active sites on the electrode surface can shorten the diffusion channel of ions. The assembled asymmetric supercapacitor delivers an energy density of 57.36 W h kg at 1412.92 W kg. Also, it exhibits excellent mechanical stability even at different bending angles.
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http://dx.doi.org/10.1039/d0dt04381hDOI Listing
March 2021

RNA helicase DDX5 acts as a critical regulator for survival of neonatal mouse gonocytes.

Cell Prolif 2021 May 5;54(5):e13000. Epub 2021 Mar 5.

CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.

Objectives: Mammalian spermatogenesis is a biological process of male gamete formation. Gonocytes are the only precursors of spermatogonial stem cells (SSCs) which develop into mature spermatozoa. DDX5 is one of DEAD-box RNA helicases and expresses in male germ cells, suggesting that Ddx5 plays important functions during spermatogenesis. Here, we explore the functions of Ddx5 in regulating the specification of gonocytes.

Materials And Methods: Germ cell-specific Ddx5 knockout (Ddx5 ) mice were generated. The morphology of testes and epididymides and fertility in both wild-type and Ddx5 mice were analysed. Single-cell RNA sequencing (scRNA-seq) was used to profile the transcriptome in testes from wild-type and Ddx5 mice at postnatal day (P) 2. Dysregulated genes were validated by single-cell qRT-PCR and immunofluorescent staining.

Results: In male mice, Ddx5 was expressed in germ cells at different stages of development. Germ cell-specific Ddx5 knockout adult male mice were sterile due to completely devoid of germ cells. Male germ cells gradually disappeared in Ddx5 mice from E18.5 to P6. Single-cell transcriptome analysis showed that genes involved in cell cycle and glial cell line-derived neurotrophic factor (GDNF) pathway were significantly decreased in Ddx5-deficient gonocytes. Notably, Ddx5 ablation impeded the proliferation of gonocytes.

Conclusions: Our study reveals the critical roles of Ddx5 in fate determination of gonocytes, offering a novel insight into the pathogenesis of male sterility.
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http://dx.doi.org/10.1111/cpr.13000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088469PMC
May 2021

Direct Visualization of Chiral Amplification of Chiral Aggregation Induced Emission Molecules in Nematic Liquid Crystals.

ACS Nano 2021 Mar 4;15(3):4956-4966. Epub 2021 Mar 4.

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.

Chiral amplification in liquid crystals (LCs) is a well-known strategy. However, current knowledge about the underlying mechanism was still lacking; in particular, how it was realized at the nano scale still remained to be revealed. Here, we provide systematical exploration of chiral amplification of chiral aggregation induced emission (AIE) molecules in LCs from direct visualization of their co-assemblies at the nano scale to theoretical calculation of the molecular packing modes on a single molecular level. Using AFM imaging,we directly visualized the co-assembly formed by chiral AIE molecules/LCs at the nano scale: the chiral AIE molecules self-assembled into helical fibers to serve as the helical template for LCs to bind, while the LCs helically bound to the helical fibers to form the co-assembly, giving the morphology of pearled necklaces or thick rods. Theoretical calculation suggested that chiral AIE molecules were packed into left-handed helical fibers with a large volume of empty space between neighboring molecules, which provided the binding cites for LCs. Structural analysis showed that the π-π stacking between aromatic groups from LCs and TPE groups and the σ-π hyperconjugation between LC aromatic groups and cholesterol aliphatic groups play an important role in stabilizing the binding of LCs in the confined space on the surface of the helical assemblies.
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http://dx.doi.org/10.1021/acsnano.0c09802DOI Listing
March 2021

Quantitative assessment of U.S. bulk power systems and market operations during the COVID-19 pandemic.

Appl Energy 2021 Mar 30;286:116354. Epub 2021 Jan 30.

Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.

Starting in early 2020, the novel coronavirus disease (COVID-19) severely attached the U.S., causing substantial changes in the operations of bulk power systems and electricity markets. In this paper, we develop a data-driven analysis to substantiate the pandemic's impacts from the perspectives of power system security, electric power generation, electric power demand and electricity prices. Our results suggest that both electric power demand and electricity prices have discernibly dropped during the COVID-19 pandemic. Geographically diverse impacts are observed and quantified, while the bulk power systems and markets in the northeast region are most severely affected. All the data sources, assessment criteria, and analysis codes reported in this paper are available on a GitHub repository.
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http://dx.doi.org/10.1016/j.apenergy.2020.116354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846474PMC
March 2021

Tumor cell membrane-derived nano-Trojan horses encapsulating phototherapy and chemotherapy are accepted by homologous tumor cells.

Mater Sci Eng C Mater Biol Appl 2021 Jan 22;120:111670. Epub 2020 Oct 22.

Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Tumor cell membrane-derived nanostructures targeting homologous tumors are promising biomimetic drugs. Herein, curcumin (Cur) and chlorin e6 (Ce6) were co-loaded into PLGA nanoparticles (NPs), and then the NPs were coated with MCF-7 cell membranes (MCNPs). Cell membrane coating sharply increased the uptake of MCNPs by homologous cells, as compared to that with naked NPs. The NPs co-loaded with Cur and Ce6 (Cur/Ce6-NPs) showed a stronger proliferation-inhibitory effect on MCF-7 cells than the NP groups loaded with Cur and Ce6 alone. Cytotoxicity and apoptosis rates of MCF-7 cells in the Cur/Ce6-MCNPs group were significantly higher than those in the uncoated Cur/Ce6-NPs group. Both Cur/Ce6-NPs and Cur/Ce6-MCNPs significantly inhibited the migration of MCF-7cells, although Cur/Ce6-MCNPs showed a stronger effect. Compared to that of Cur/Ce6-NPs, the elimination of Cur/Ce6-MCNPs was both decreased and retarded, prolonging their in vivo systemic circulation and resulting in improved bioavailability. After intravenous administration for 24 h, the fluorescence intensity of drugs in the liver and spleen of the Cur/Ce6-MCNPs group was significantly weaker than that in the Cur/Ce6-NPs group, but that in tumor tissue was enhanced. Further, Cur/Ce6-MCNPs treatment achieved significantly better tumor-suppressive effects in vivo than Cur/Ce6-NPs, resulting in smaller tumor weights, increased apoptosis rates, and the down regulation of Ki67 protein in the tumor tissue. Thus, the tumor cell membrane-camouflaged nanocomposites have potential for homologous tumor-targeted therapy. Furthermore, photodynamic therapy combined with chemotherapy has promising future prospects.
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http://dx.doi.org/10.1016/j.msec.2020.111670DOI Listing
January 2021

The effects of m A modification in central nervous system function and disease.

Yi Chuan 2020 Dec;42(12):1156-1167

Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, China.

N -methyladenosine (m A) is an important RNA modification, which is highly active in brain tissues, participates in global intracellular mRNA metabolism, and regulates gene expression and a variety of biological processes. Stable m A modification contributes to the normal embryonic brain development and memory formation and plays an important role in maintaining the functions of the central nervous system. However, changes in the level of m A modification and the expression of its related proteins cause abnormal nervous system functions, including brain tissue development retardation, axon regeneration disorders, memory changes, and stem cell renewal and differentiation disorders. Recent studies have also found that m A modification and its related proteins play key roles in the development of various nervous system diseases, such as Alzheimer's disease, Parkinson's disease, fragile X-chromosome syndrome, depression and glioblastoma. In this review, we summarize the research progresses of m A modification regulation mechanism in the central nervous system in recent years, and discusses the effects of gene expression regulation mediated by m A modification on the biological functions of the central nervous system and related diseases, thereby providing some insights on the new research targets and treatment directions for the central nervous system diseases.
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http://dx.doi.org/10.16288/j.yczz.20-233DOI Listing
December 2020