Publications by authors named "Mengya Wang"

57 Publications

Ruminal Microbiota Determines the High-Fiber Utilization of Ruminants: Evidence from the Ruminal Microbiota Transplant.

Microbiol Spectr 2022 Aug 4:e0044622. Epub 2022 Aug 4.

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.

The rumen, which contains a series of prokaryotes and eukaryotes with high abundance, determines the high ability to degrade complex carbohydrates in ruminants. Using 16S rRNA gene sequencing, we compared the ruminal microbiota of dairy goats with that in the foregut and colon of mice and found more identified in the rumen, which helps ruminants to utilize plant-derived polysaccharides, cellulose, and other structural carbohydrates. Furthermore, high-fiber diets did not significantly increase intestinal fiber-degrading bacteria in mice, but did produce higher levels of ruminal fiber-degrading bacteria in dairy goats. Through rumen microbe transplantation (RMT), we found that rumen-derived fiber-degrading bacteria can colonize the intestines of mice to exert their fiber-degrading function, but their colonization efficiency is affected by diet. Additionally, the colonization of these fiber-degrading bacteria in the colon may involve higher content of butyrate in the colon, protecting the colonic epithelial barrier and promoting energy metabolism. Overall, the fiber degradation function of rumen bacteria through RMT was verified, and our results provide new insights into isolating the functional and beneficial fiber-degrading bacteria in the rumen, providing a theoretical basis for the role of dietary fiber in intestinal health. Ruminants have a powerful progastric digestive system that converts structural carbohydrates into nutrients useful to humans. It is well known that this phenomenon is due to the fact that the rumen of ruminants is a natural microbial fermenter, which can ferment structural carbohydrates such as cellulose and hemicellulose and transform them into volatile fatty acids to supply energy for host. However, monogastric animals have an inherent disadvantage in utilizing fiber, so screening rumen-derived fiber-degrading bacteria as a fermentation strain for biological feed is needed in an attempt at improving the fiber digestibility of monogastric animals. In this study, a ruminal microbiota transplant experiment from goats to mice proves that ruminal microbiota could serve as a key factor in utilization of high-fiber diets and provides a new perspective for the development of probiotics with fiber degradation function from the rumen and the importance of the use of prebiotics during the intake of probiotics.
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http://dx.doi.org/10.1128/spectrum.00446-22DOI Listing
August 2022

Stimulation of CGRP-expressing neurons in the medial cerebellar nucleus induces light and touch sensitivity in mice.

Neurobiol Pain 2022 Aug-Dec;12:100098. Epub 2022 Jun 23.

Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.

Calcitonin gene-related peptide (CGRP) is considered a major player in migraine pathophysiology. However, the location and mechanisms of CGRP actions in migraine are not clearly elucidated. One important question yet to be answered is: Does central CGRP signaling play a role in migraine? One candidate site is the cerebellum, which serves as a sensory and motor integration center and is activated in migraine patients. The cerebellum has the most CGRP binding sites in the central nervous system and a deep cerebellar nucleus, the medial nucleus (MN), expresses CGRP (MN). A previous study demonstrated that CGRP delivery into the cerebellum induced migraine-like behaviors. We hypothesized that stimulation of MN neurons might induce migraine-like behaviors. To test the hypothesis, we used an optogenetic strategy using mice to drive Cre-dependent expression of channelrhodopsin-2 selectively in CGRP neurons in the cerebellar MN. A battery of behavioral tests was done to assess preclinical behaviors that are surrogates of migraine symptoms, including light aversion, cutaneous allodynia, and spontaneous pain when MN neurons were optically stimulated. Motor functions were also assessed. Optical stimulation of MN neurons decreased the time spent in the light, which was coupled to increased time spent resting in the dark, but not the light. These changes were only significant in female mice. Plantar tactile sensitivity was increased in the ipsilateral paws of both sexes, but contralateral paw data were less clear. There was no significant increase in anxiety-like behavior, spontaneous pain (squint), or changes in gait. These discoveries reveal that MN neurons may contribute to migraine-like sensory hypersensitivity to light and touch.
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http://dx.doi.org/10.1016/j.ynpai.2022.100098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240374PMC
June 2022

Vasa Is a Potential Germ Cell Marker in Leopard Coral Grouper ().

Genes (Basel) 2022 Jun 16;13(6). Epub 2022 Jun 16.

Key Laboratory of Marine Genetics and Breeding (Ministry of Education), College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.

Vasa (, DEAD box polypeptide 4), an extremely specific marker of germ cells in vivo, is an ATP-dependent RNA helicase that plays an essential role in germ cell development and gametogenesis. However, the expression and function information about this gene in groupers remains lacking. Here, homolog termed was isolated and identified as a putative germ cell marker in the leopard coral grouper, (). Results indicated that contained 17 exons in the genomic sequence and 9 conserved motifs of the DEAD-box protein by sequence analysis. The sequence comparison, phylogenetic analyses and synteny analyses showed that was homologous with other teleosts. Additionally, the expression of was significantly higher in gonads than in other tissues in adult individuals ( < 0.05). Further, the distribution of revealed that it was only expressed in the germ cells, such as spermatids, germline stem cells and oocytes at different stages, and could not be detected in the somatic cells of gonads. The current study verified that the gene is a valuable molecular marker of germ cells in leopard coral grouper, which potentially plays an important role in investigating the genesis and development of teleost germ cells.
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http://dx.doi.org/10.3390/genes13061077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222667PMC
June 2022

CGRP Administration Into the Cerebellum Evokes Light Aversion, Tactile Hypersensitivity, and Nociceptive Squint in Mice.

Front Pain Res (Lausanne) 2022 25;3:861598. Epub 2022 Apr 25.

Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, United States.

The neuropeptide calcitonin gene-related peptide (CGRP) is a major player in migraine pathophysiology. Previous preclinical studies demonstrated that intracerebroventricular administration of CGRP caused migraine-like behaviors in mice, but the sites of action in the brain remain unidentified. The cerebellum has the most CGRP binding sites in the central nervous system and is increasingly recognized as both a sensory and motor integration center. The objective of this study was to test whether the cerebellum, particularly the medial cerebellar nuclei (MN), might be a site of CGRP action. In this study, CGRP was directly injected into the right MN of C57BL/6J mice via a cannula. A battery of tests was done to assess preclinical behaviors that are surrogates of migraine-like symptoms. CGRP caused light aversion measured as decreased time in the light zone even with dim light. The mice also spent more time resting in the dark zone, but not the light, along with decreased rearing and transitions between zones. These behaviors were similar for both sexes. Moreover, significant responses to CGRP were seen in the open field assay, von Frey test, and automated squint assay, indicating anxiety, tactile hypersensitivity, and spontaneous pain, respectively. Interestingly, CGRP injection caused significant anxiety and spontaneous pain responses only in female mice, and a more robust tactile hypersensitivity in female mice. No detectable effect of CGRP on gait was observed in either sex. These results suggest that CGRP injection in the MN causes light aversion accompanied by increased anxiety, tactile hypersensitivity, and spontaneous pain. A caveat is that we cannot exclude contributions from other cerebellar regions in addition to the MN due to diffusion of the injected peptide. These results reveal the cerebellum as a new site of CGRP actions that may contribute to migraine-like hypersensitivity.
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http://dx.doi.org/10.3389/fpain.2022.861598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9082264PMC
April 2022

A Comparative Review of Pyroptosis in Mammals and Fish.

J Inflamm Res 2022 11;15:2323-2331. Epub 2022 Apr 11.

Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Pyroptosis is a form of programmed cell death, which is executed by gasdermin family proteins. Under the stimulation of pathogen- and/or damage-associated molecular patterns, pattern recognition receptors (PRRs) such as Nod like receptors could recruit apoptosis-associated speck-like protein containing a CARD (ASC) and pro-caspases to form inflammasomes and then activate caspases through various pathways. The activated caspases then cleave gasdermin family proteins, and N-terminal (NT) domains of gasdermins were released to form oligomeric pores, resulting in the increased membrane permeability, cell swelling, and final pyroptosis. During this process, caspases also promote the maturation and release of inflammatory cytokines such as IL-1β and IL-18, thus pyroptosis is also named inflammatory cell death. Unlike numerous gasdermin family proteins in mammals, only gasdermin E (GSDME) has been identified in fish. GSDME in fish can be cleaved by caspase-a/-b to release its NT domain and induce pyroptosis. Studies indicated that pyroptosis in fish mainly depends on NLR family pyrin domain-containing 3 (NLRP3) inflammasome. ASC and different caspase proteins also were identified in different fish species. The influences of pathogenic microorganism infection and environmental pollutants on fish pyroptosis were studied in recent years. Considering that fish living environment is affected by multiple factors such as water salinity, temperature, oxygen supply, and highly fluctuating food supply, the in-depth research about fish pyroptosis will contribute to revealing the mechanism of pyroptosis during evolution.
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http://dx.doi.org/10.2147/JIR.S361266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9012342PMC
April 2022

FNDC5 Causes Resistance to Sorafenib by Activating the PI3K/Akt/Nrf2 Pathway in Hepatocellular Carcinoma Cells.

Front Oncol 2022 22;12:852095. Epub 2022 Mar 22.

Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China.

In this study, we aimed to reveal the resistance mechanism of hepatocellular carcinoma (HCC) cells to sorafenib by exploring the effect of FNDC5 on sorafenib-induced ferroptosis in HCC cells. We compared the expression level of FNDC5 between sorafenib-resistant and sorafenib-sensitive HCC cell lines and the level of ferroptosis between the groups after treatment with sorafenib. We knocked down FNDC5 in drug-resistant cell lines and overexpressed it in sorafenib-sensitive HCC cell lines to further demonstrate the role of FNDC5 in sorafenib-induced ferroptosis. Using PI3K inhibitors, we revealed the specific mechanism by which FNDC5 functions. In addition, we verified our findings obtained in experiments using a subcutaneous tumorigenic nude mouse model. The findings revealed that FNDC5 inhibits sorafenib-induced ferroptosis in HCC cells. In addition, FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib.
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http://dx.doi.org/10.3389/fonc.2022.852095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980859PMC
March 2022

Roles of the Cannabinoid System in the Basal Ganglia in Parkinson's Disease.

Front Cell Neurosci 2022 21;16:832854. Epub 2022 Feb 21.

Department of Physiology, School of Basic Medicine, Institute of Brain Science and Disorders, Qingdao University, Qingdao, China.

Parkinson's disease (PD) is a neurodegenerative disease usually caused by neuroinflammation, oxidative stress and other etiologies. Recent studies have found that the cannabinoid system present in the basal ganglia has a strong influence on the progression of PD. Altering the cannabinoid receptor activation status by modulating endogenous cannabinoid (eCB) levels can exert an anti-movement disorder effect. Therefore, the development of drugs that modulate the endocannabinoid system may be a novel strategy for the treatment of PD. However, eCB regulation is complex, with diverse cannabinoid receptor functions and the presence of dopaminergic, glutamatergic, and γ-aminobutyric signals interacting with cannabinoid signaling in the basal ganglia region. Therefore, the study of eCB is challenging. Here, we have described the function of the cannabinoid system in the basal ganglia and its association with PD in three parts (eCBs, cannabinoid receptors, and factors regulating the cannabinoid metabolism) and summarized the mechanisms of action related to the cannabinoid analogs currently aimed at treating PD. The shortcomings identified from previous studies and the directions that should be explored in the future will provide insights into new approaches and ideas for the future development of cannabinoid-based drugs and the treatment of PD.
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http://dx.doi.org/10.3389/fncel.2022.832854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900732PMC
February 2022

Regulation of Serotonin 1A Receptor SUMOylation by SENP2 and PIASxα.

Int J Mol Sci 2021 Dec 7;22(24). Epub 2021 Dec 7.

Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA.

Serotonin 1A receptors (5-HT1ARs) are implicated in the control of mood, cognition, and memory and in various neuropsychiatric disorders such as depression and anxiety. As such, understanding the regulation of 5-HT1ARs will inform the development of better treatment approaches. We previously demonstrated 5-HT1ARs are SUMOylated by SUMO1 in the rat brain. Agonist stimulation increased SUMOylation and was further enhanced when combined with 17β-estradiol-3-benzoate (EB), which are treatments that cause the transient and prolonged desensitization of 5-HT1AR signaling, respectively. In the current study, we identified the protein inhibitor of activated STAT (PIAS)xα as the enzyme that facilitates SUMOylation, and SENP2 as the protein that catalyzes the deSUMOylation of 5-HT1ARs. We demonstrated that PIASxα significantly increased in the membrane fraction of rats co-treated with EB and an agonist, compared to either the EB-treated or vehicle-treated groups. The acute treatment with an agonist alone shifted the location of SENP2 from the membrane to the cytoplasmic fraction, but it has little effect on PIASxα. Hence, two separate mechanisms regulate SUMOylation and the activity of 5-HT1ARs by an agonist and EB. The effects of EB on 5-HT1AR SUMOylation and signaling may be related to the higher incidence of mood disorders in women during times with large fluctuations in estrogens. Targeting the SUMOylation of 5-HT1ARs could have important clinical relevance for the therapy for several neuropsychiatric disorders in which 5-HT1ARs are implicated.
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http://dx.doi.org/10.3390/ijms222413176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706138PMC
December 2021

A Robust Hierarchical MXene/Ni/Aluminosilicate Glass Composite for High-Performance Microwave Absorption.

Adv Sci (Weinh) 2022 Feb 13;9(4):e2104163. Epub 2021 Dec 13.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, China.

The 2D titanium carbide MXene with both extraordinary electromagnetic attenuation and elastic properties has shown great potential as the building block for constructing mechanically robust microwave absorbing composites (MACs). However, the weak thermal stability has inhibited the successful incorporation of MXene into the inorganic MACs matrix so far. Herein, an ultralow temperature sintering strategy to fabricate a hierarchical aluminosilicate glass composite is demonstrated by using EMT zeolite as starting powder, which can not only endow the composites with high sinterability, but also facilitate the alignment of MXene in the glass matrix. Accordingly, the highly oriented MXene and mesoporous structure can effectively reduce the conduction loss in the out-of-plane direction while maintaining its large polarization loss. Meanwhile, the in situ formed Ni nanoparticles via ion exchange serve as a synergistic modulator to further improve the attenuation capability and impedance matching of composite, resulting in a low reflection loss of -59.5 dB in X band and general values below -20 dB with a low fitting thickness from 4 to 18 GHz. More attractively, such a delicate structure also gives the composite a remarkable fracture strength and contact-damage-resistance, which qualifies the mesoporous glass composite as a structural MACs with a superior comprehensive performance.
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http://dx.doi.org/10.1002/advs.202104163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811826PMC
February 2022

Chrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways.

Innate Immun 2021 10 20;27(7-8):514-524. Epub 2021 Nov 20.

232830Henan University of Chinese Medicine, Zhengzhou, China.

This study investigated the effect and mechanism of chrysosplenol D (CD) on LPS-induced acute lung injury in mice. Histological changes in the lungs were measured by hematoxylin-eosin staining. The levels of IL-6, IL-1β, and TNF-α in the bronchoalveolar lavage fluid were detected by ELISA. The levels of oxidative stress were detected by the cuvette assay. Immune cells in peripheral blood, the levels of reactive oxygen species, and apoptosis of primary lung cells were detected by flow cytometry. The mRNA levels of TLR4, MyD88, IL-1β, and NLRP3 were measured by quantitative real-time polymerase chain reaction. The levels of proteins in apoptosis and the TLR4-MAPKs/NF-κB signaling pathways were detected by Western blot. Hematoxylin-eosin staining showed that CD could improve lung injury; decrease the levels of inflammatory factors, oxidative stress, reactive oxygen species, and cell apoptosis; and regulate the immune system. Moreover, CD could down-regulate the mRNA levels of TLR4, MyD88, NLRP3, and IL-1β in lung, and the protein levels of Keap-1, Cleaved-Caspase-3/Caspase-3, Cleaved-Caspase-9/Caspase-9, TLR4, MyD88, p-ERK/ERK, p-JNK/JNK, p-p38/p38, p-p65/p65, NLRP3, and IL-1β, and up-regulated the levels of Bcl-2/Bax, p-Nrf2/Nrf2, and HO-1. The results suggested that CD could protect mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via the TLR4-MAPKs/NF-κB signaling pathways.
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http://dx.doi.org/10.1177/17534259211051069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762090PMC
October 2021

The Programming of Antioxidant Capacity, Immunity, and Lipid Metabolism in Dojo Loach () Larvae Linked to Sodium Chloride and Hydrogen Peroxide Pre-treatment During Egg Hatching.

Front Physiol 2021 28;12:768907. Epub 2021 Oct 28.

Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, China.

Non-nutritional stress during early life period has been reported to promote the metabolic programming in fish induced by nutritional stimulus. Sodium chloride (NaCl) and hydrogen peroxide (HO) have been widely applied during fish egg hatching, but the influences on health and metabolism of fish in their later life remain unknown. In the present study, HO treatment at 400mg/L but not 200mg/L significantly increased the loach hatchability and decreased the egg mortality, while NaCl treatment at 1,000 and 3,000mg/L showed no significant influences on the loach hatchability nor egg mortality. Further studies indicated that 400mg/L HO pre-treatment significantly enhanced the antioxidant capacity and the mRNA expression of genes involved in immune response of loach larvae, accompanied by the increased expression of genes involved in fish early development. However, the expression of most genes involved in lipid metabolism, including catabolism and anabolism of loach larvae, was significantly upregulated after 200mg/L HO pre-treatment. NaCl pre-treatment also increased the expression of antioxidant enzymes; however, only the expression of C1q within the detected immune-related genes was upregulated in loach larvae. One thousand milligram per liter NaCl pre-treatment significantly increased the expression of LPL and genes involved in fish early development. Thus, our results suggested the programming roles of 400mg/L HO pre-treatment during egg hatching in enhancing antioxidant capacity and immune response of fish larvae promoting fish early development.
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http://dx.doi.org/10.3389/fphys.2021.768907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581469PMC
October 2021

Psychopathic dispositions and emotion dysregulation: A dual-disposition model perspective.

J Clin Psychol 2022 06 4;78(6):1170-1183. Epub 2021 Nov 4.

Department of Social Psychology, Zhou Enlai School of Government, Nankai University, Tianjin, China.

The Dual-Disposition Model proposes to understand psychopathy through two dispositions (i.e., threat sensitivity and poor inhibitory control) with distinct etiological substrates. In the current study, we examined the predictive contributions of threat sensitivity, poor inhibitory control, and their interaction to emotion dysregulation in 694 Chinese undergraduates based on the Disinhibition subscale of Triarchic Psychopathy Measure, Behavioral Inhibition System Scale, and Difficulties in Emotion Regulation Scale. Our results suggested that two dispositions have independent contributions to emotion dysregulation. Additionally, interactive effects of two dispositions were found for emotion awareness, impulse control, emotional acceptance, and limited emotion regulation strategies when upset. These provide evidence that deficits associated with poor inhibitory control can be selectively suppressed by low threat sensitivity or exacerbated by high threat sensitivity. Training individuals with high psychopathic dispositions to focus on their emotional state might be able to enhance their ability of emotion regulation.
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http://dx.doi.org/10.1002/jclp.23274DOI Listing
June 2022

FNDC5 induces M2 macrophage polarization and promotes hepatocellular carcinoma cell growth by affecting the PPARγ/NF-κB/NLRP3 pathway.

Biochem Biophys Res Commun 2021 12 19;582:77-85. Epub 2021 Oct 19.

Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, China. Electronic address:

Purpose: The purpose of this study was to investigate the effect of FNDC5 expression levels in hepatocellular carcinoma on the phenotypic changes of macrophages in tumor tissues.

Methods: In this study, we established an in vitro co-culture system of hepatocellular carcinoma cells and macrophages. Then we performed overexpression or knockdown of FNDC5 gene in hepatocellular carcinoma cells to observe the effect of changes in FNDC5 expression level on the phenotypic changes of THP-1 macrophages. And the conclusions obtained in the in vitro assay were further validated by a subcutaneous tumorigenic nude mice model.

Results: Our findings suggest that elevated FNDC5 expression in hepatocellular carcinoma cells lead to an increased M2 phenotype and decreased M1 phenotype in macrophages. This effect may be achieved by elevating PPARγ levels in macrophages while decreasing NF-κB and NLRP3 levels. These changes could be reversed by using PPARγ inhibitors.

Conclusion: We preliminarily demonstrated that FNDC5 in hepatocellular carcinoma cells promotes the polarization of M2 macrophages by affecting the PPARγ/NF-κB/NLRP3 pathway.
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http://dx.doi.org/10.1016/j.bbrc.2021.10.041DOI Listing
December 2021

Effect of alkali-treated birch sawdust on the lignocellulase secretion and exo-polysaccharide production by Inonotus obliquus under submerged fermentation and its lignocellulose degradation patterns.

J Biosci Bioeng 2022 Jan 21;133(1):33-38. Epub 2021 Oct 21.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

The objectives of this study were to investigate the medicinal mushroom Inonotus obliquus on the production of polysaccharides and changes of extracellular lignocellulolytic enzymes during submerged fermentation using alkali-treated birch sawdust as substrate. Meanwhile, in order to explore the degradation mode of lignocellulose in alkali-treated birch sawdust, degradation analysis of three components of lignocellulose was carried out. The fungus process in alkali-treated birch sawdust medium resulted in a higher degradation rate of cellulose, hemicellulose, and lignin of 39.24%, 51.00% and 31.3% after 11 days of submerged fermentation by the mycelium of I. obliquus, respectively. Maximal polysaccharide production and α-glucosidase inhibition rate determined in the alkali-treated birch sawdust medium were 6.93 mg/mL and 55.80%, while they were 4.98 mg/mL and 27.89% in the control. Moreover, high activities of laccase (51.95 IU/mL), CMCase (1.35 IU/mL), filter paper activity (0.50 IU/mL) and β-glucosidase (0.55 IU/mL) were observed in alkali-treated birch sawdust medium, respectively. The results demonstrated that the addition of alkali-treated birch sawdust could promote the yield and α-glucosidase inhibition activity of polysaccharides and induce the production of cellulase and xylanase, indicating that alkali pretreatment was conducive to utilization of birch sawdust by I. obliquus.
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http://dx.doi.org/10.1016/j.jbiosc.2021.09.013DOI Listing
January 2022

Tanshinone IIA affects the malignant growth of Cholangiocarcinoma cells by inhibiting the PI3K-Akt-mTOR pathway.

Sci Rep 2021 09 29;11(1):19268. Epub 2021 Sep 29.

Department of Hepatobiliary Surgery, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China.

In the present study, we aimed to find the target of Tanshinone IIA (Tan-IIA) in Cholangiocarcinoma by network pharmacology-based prediction and investigate the possible mechanism through experimental verification. In this study, we combined Tan-IIA-specific and Cholangiocarcinoma-specific targets with protein-protein interactions (PPI) to construct a Tan-IIA targets-Cholangiocarcinoma network, and network pharmacology approach was applied to identify potential targets and mechanisms of Tan-IIA in the treatment of Cholangiocarcinoma. The anti-cancer effects of Tan-IIA were investigated by using subcutaneous tumorigenic model in nude mice and in the human Cholangiocarcinoma cell lines in vitro. Our results showed that Tan-IIA treatment considerably suppressed the proliferation and migration of Cholangiocarcinoma cells while inducing apoptosis of Cholangiocarcinoma cells. Western blot results demonstrated that the expression of PI3K, p-Akt, p-mTOR, and mTOR were inhibited by Tan-IIA. Meanwhile, After treatment with Tan-IIA, the level of Bcl2 was downregulated and cleaved caspase-3 expression increased. Further studies revealed that the anticancer effects of Tan-IIA were severely mitigated by pretreatment with a PI3K agonist. Our research provides a new anticancer strategy and strengthens support for the use of Tan-IIA as an anticancer drug for the treatment of CCA.
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http://dx.doi.org/10.1038/s41598-021-98948-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481305PMC
September 2021

Investigating Migraine-Like Behavior using Light Aversion in Mice.

J Vis Exp 2021 08 11(174). Epub 2021 Aug 11.

Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health Center, Iowa City, IA; Department of Molecular Physiology and Biophysics, University of Iowa; Department of Neurology, University of Iowa;

Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as photophobia. Whilst it is impossible to confirm that a mouse is experiencing migraine, light aversion can be used as a behavioral surrogate for the migraine symptom of photophobia. To test for light aversion, we utilize the light/dark assay to measure the time mice freely choose to spend in either a light or dark environment. The assay has been refined by introducing two critical modifications: pre-exposures to the chamber prior to running the test procedure and adjustable chamber lighting, permitting the use of a range of light intensities from 55 lux to 27,000 lux. Because the choice to spend more time in the dark is also indicative of anxiety, we also utilize a light-independent anxiety test, the open field assay, to distinguish anxiety from light-aversive behavior. Here, we describe a modified test paradigm for the light/dark and open field assays. The application of these assays is described for intraperitoneal injection of calcitonin gene-related peptide (CGRP) in two mouse strains and for optogenetic brain stimulation studies.
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http://dx.doi.org/10.3791/62839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428768PMC
August 2021

A new approach for health-oriented ozone control strategy: Adjoint-based optimization of NO emission reductions using metaheuristic algorithms.

J Clean Prod 2021 Aug;312(20):127533

Department of Geography and Resource Management, The Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong, China.

While levels of particulate matters in the Pearl River Delta Region (PRD) show a significant reduction, ozone (O) has an opposite increasing trend, becoming the critical air quality target in this decade. Emission control strategies are typically formulated sector by sector, spatial variability in emissions reductions and health impacts of air pollutants may not be taken into account, affecting the overall effectiveness of control strategies. This study proposes an adjoint-based optimization framework to facilitate health-oriented O control over PRD. The location-specific adjoint sensitivity coefficients, which reflect the spatiotemporal influences from emissions of nitrogen dioxide (NO) on O health impacts, are combined with metaheuristic algorithms to minimize the O-related premature mortalities over receptor regions. Using the proposed optimization methodology, the regional O health benefits under current emission reduction policy can be increased by 16-27%. The results show that relatively larger NO emissions reductions occurred at highly developed and populated areas. Particularly, significant reductions in NO emissions are observed at Shenzhen and urban Guangzhou. Furthermore, implementing regional NO emissions abatement has advantages to achieve an overall O health benefits for all cities. The interregional influences of NO emissions abatement between cities indicate a promising strategy of health-oriented O control in PRD.
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http://dx.doi.org/10.1016/j.jclepro.2021.127533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262626PMC
August 2021

Fabrication of Highly Textured 2D SnSe Layers with Tunable Electronic Properties for Hydrogen Evolution.

Molecules 2021 Jun 1;26(11). Epub 2021 Jun 1.

Department of Physics, and Innovation center of Materials for Energy and Environment Technologies, College of Science, Tibet University, Lhasa 850000, China.

Hydrogen is regarded to be one of the most promising renewable and clean energy sources. Finding a highly efficient and cost-effective catalyst to generate hydrogen via water splitting has become a research hotspot. Two-dimensional materials with exotic structural and electronic properties have been considered as economical alternatives. In this work, 2D SnSe films with high quality of crystallinity were grown on a mica substrate via molecular beam epitaxy. The electronic property of the prepared SnSe thin films can be easily and accurately tuned in situ by three orders of magnitude through the controllable compensation of Sn atoms. The prepared film normally exhibited p-type conduction due to the deficiency of Sn in the film during its growth. First-principle calculations explained that Sn vacancies can introduce additional reactive sites for the hydrogen evolution reaction (HER) and enhance the HER performance by accelerating electron migration and promoting continuous hydrogen generation, which was mirrored by the reduced Gibbs free energy by a factor of 2.3 as compared with the pure SnSe film. The results pave the way for synthesized 2D SnSe thin films in the applications of hydrogen production.
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http://dx.doi.org/10.3390/molecules26113319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199299PMC
June 2021

CGRP induces migraine-like symptoms in mice during both the active and inactive phases.

J Headache Pain 2021 Jun 30;22(1):62. Epub 2021 Jun 30.

Department of Molecular Physiology and Biophysics, University of Iowa, 51 Newton Rd, Iowa City, IA, 52242, USA.

Background: Circadian patterns of migraine attacks have been reported by patients but remain understudied. In animal models, circadian phases are generally not taken into consideration. In particular, rodents are nocturnal animals, yet they are most often tested during their inactive phase during the day. This study aims to test the validity of CGRP-induced behavioral changes in mice by comparing responses during the active and inactive phases.

Methods: Male and female mice of the outbred CD1 strain were administered vehicle (PBS) or CGRP (0.1 mg/kg, i.p.) to induce migraine-like symptoms. Animals were tested for activity (homecage movement and voluntary wheel running), light aversive behavior, and spontaneous pain at different times of the day and night.

Results: Peripheral administration of CGRP decreased the activity of mice during the first hour after administration, induced light aversive behavior, and spontaneous pain during that same period of time. Both phenotypes were observed no matter what time of the day or night they were assessed.

Conclusions: A decrease in wheel activity is an additional clinically relevant phenotype observed in this model, which is reminiscent of the reduction in normal physical activity observed in migraine patients. The ability of peripheral CGRP to induce migraine-like symptoms in mice is independent of the phase of the circadian cycle. Therefore, preclinical assessment of migraine-like phenotypes can likely be done during the more convenient inactive phase of mice.
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http://dx.doi.org/10.1186/s10194-021-01277-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243868PMC
June 2021

Genome-Wide Identification, Characterization and Expression Profiling of Family Genes in .

Genes (Basel) 2021 05 25;12(6). Epub 2021 May 25.

MOE Key Laboratory of Molecular Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.

Myosins are important eukaryotic motor proteins that bind actin and utilize the energy of ATP hydrolysis to perform a broad range of functions such as muscle contraction, cell migration, cytokinesis, and intracellular trafficking. However, the characterization and function of is poorly studied in teleost fish. In this study, we identified 60 family genes in a marine teleost, black rockfish (), and further characterized their expression patterns. showed divergent expression patterns in adult tissues, indicating they are involved in different types and compositions of muscle fibers. Among 12 subfamilies, subfamily was significantly expanded, which was driven by tandem duplication events. The up-regulation of five representative genes of in the skeletal muscle during fast-growth stages of juvenile and adult revealed their active role in skeletal muscle fiber synthesis. Moreover, the expression regulation of during the process of myoblast differentiation suggested that they contribute to skeletal muscle growth by involvement of both myoblast proliferation and differentiation. Taken together, our work characterized genes systemically and demonstrated their diverse functions in a marine teleost species. This lays foundation for the further studies of muscle growth regulation and molecular mechanisms of indeterminate skeletal muscle growth of large teleost fishes.
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http://dx.doi.org/10.3390/genes12060808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228858PMC
May 2021

and Exhibit Distinct and Overlapping Functions in Marking Muscle Satellite Cells and Muscle Repair in a Marine Teleost, .

Int J Mol Sci 2021 Apr 5;22(7). Epub 2021 Apr 5.

MOE Key Laboratory of Molecular Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.

and are members of the gene family which are essential for embryo and organ development. Both genes have been proved to be markers of muscle satellite cells and play key roles in the process of muscle growth and repair. Here, we identified two genes ( and ) and two genes ( and ) in a marine teleost, black rockfish (). Our results showed and marked distinct populations of muscle satellite cells, which originated from the multi-cell stage and somite stage, respectively. In addition, we constructed a muscle injury model to explore the function of these four genes during muscle repair. Hematoxylin-eosin (H-E) of injured muscle sections showed new-formed myofibers occurred at 16 days post-injury (dpi). ISH (in situ hybridization) analysis demonstrated that the expression level of and two genes increased gradually during 0-16 dpi and peaked at 16 dpi. Interestingly, showed no significant differences during the injury repair process, indicating that the satellite cells labeled by were not involved in muscle repair. These results imply that the muscle stem cell populations in teleosts are more complicated than in mammals. This lays the foundation for future studies on the molecular mechanism of indeterminant growth and muscle repair of large fish species.
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http://dx.doi.org/10.3390/ijms22073769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038590PMC
April 2021

Shengma Biejia Decoction Inhibits Cell Growth in Multiple Myeloma by Inducing Autophagy-Mediated Apoptosis Through the ERK/mTOR Pathway.

Front Pharmacol 2021 29;12:585286. Epub 2021 Mar 29.

Department of Hematology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Shengma Biejia decoction (SMBJD), a traditional Chinese formula recorded in the , has been widely used for the treatment of malignant tumors. However, its underlying molecular targets and mechanisms are still unclear. This study showed that SMBJD inhibited tumor growth and stimulated hemogram recovery significantly in a multiple myeloma xenograft model. Western blot and immunohistochemistry assays of tumor tissues showed that SMBJD reduced the ratio of autophagy-related proteins LC3-II/LC3-I, while P62 and apoptosis-related proteins cleaved caspase-3/caspase-3 and Bax/Bcl-2 were upregulated. experiments demonstrated the time-dependent and dose-dependent cytotoxicity of SMBJD on multiple myeloma cell lines H929 and U266 through MTT assays. The LC3-II/LC3-I ratio and number of GFP-LC3 puncta showed that SMBJD inhibited the autophagy process of H929 and U266 cells. Moreover, both SMBJD and 3-methyladenine (3-MA) caused a decrease in LC3-II/LC3-I, and SMBJD could not reverse the upregulation of LC3-II/LC3-I caused by bafilomycin A1 (Baf-A1). Furthermore, the results of annexin V-FITC and propidium iodide double staining demonstrated that SMBJD treatment induced the apoptosis of H929 and U266 cells. These data prove that SMBJD inhibits autophagy and promotes apoptosis in H929 and U266 cells. The results also show that rapamycin could reduce the rate of SMBJD-induced apoptosis in H929 and U266 cells, at a concentration which had no effect on apoptosis but activated autophagy. In addition, analysis of the mechanism indicated that levels of phosphorylated ERK and phosphorylated mTOR were increased by treatment with SMBJD and . These results indicate that SMBJD, an old and effective herbal compound, could inhibit the viability of H929 and U266 cells and induce autophagy-mediated apoptosis through the ERK/mTOR pathway. Thus, it represents a potential therapy strategy for multiple myeloma.
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http://dx.doi.org/10.3389/fphar.2021.585286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039907PMC
March 2021

The expression characteristics and prognostic roles of autophagy-related genes in gastric cancer.

PeerJ 2021 3;9:e10814. Epub 2021 Feb 3.

Tumor Etiology and Screening Department of Cancer Institute, and Key Laboratory of Cancer Etiology and Prevention in Liaoning Education Department, the First Hospital of China Medical University, Shenyang, China.

Background: Autophagy is an evolutionally highly conserved process, accompanied by the dynamic changes of various molecules, which is necessary for the orderly degradation and recycling of cellular components. The aim of the study was to identify the role of autophagy-related () genes in the occurrence and development of gastric cancer (GC).

Methods: Data from Oncomine dataset was used for the differential expression analysis between cancer and normal tissues. The association of genes expression with clinicopathologic indicators was evaluated by The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Moreover, using the TCGA datasets, the prognostic role of genes was assessed. A nomogram was further built to assess the independent prognostic factors.

Results: The expression of autophagy-related genes , , , , , , , , and showed differences between cancer and normal tissues. After verification, and were significantly associated with TNM stage. , , and were associated with T stage. and were low-expressed in patients without lymph node metastasis. No gene in autophagy pathway was associated with M stage. Further multivariate analysis suggested that and were independent prognostic factors for GC. The C-index of nomogram was 0.676 and the 95% CI was 0.628 to 0.724.

Conclusion: Our study provided a comprehensive illustration of genes expression characteristics in GC. Abnormal expressions of the ubiquitin-like conjugated system in genes plays a key role in the occurrence of GC. sub-system may play an important role in development and clinical outcome of GC. In the future, it is necessary to further elucidate the alterations of specific forms in order to provide insights for the discovery, diagnosis, or targeting for GC.
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http://dx.doi.org/10.7717/peerj.10814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866901PMC
February 2021

Solasonine Suppresses the Proliferation of Acute Monocytic Leukemia Through the Activation of the AMPK/FOXO3A Axis.

Front Oncol 2020 29;10:614067. Epub 2021 Jan 29.

Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Solasonine, the main active ingredient of ., has been reported to exert extensive antitumor activity. However, the antitumor effects in acute monocytic leukemia and the exact mechanisms involved are unknown. In this study, we investigated the role of solasonine on inhibiting the progression of acute monocytic leukemia. Our findings showed that solasonine inhibited the proliferation of acute monocytic leukemic cell lines (THP-1 and MV4-11) . Solasonine promoted apoptosis and induced cell cycle arrest in the G2/M phase. Analysis of RNA-seq data suggested that solasonine correlated with increased expression of genes in the AMPK/FOXO3A pathway. Inhibition of AMPK with compound C followed by treatment with solasonine showed that solasonine reduced apoptosis, caused less cell cycle arrest, and inactivated the AMPK/FOXO3A axis in THP-1 and MV4-11 cells. Solasonine also inhibited tumor growth by the activation of the AMPK/FOXO3A axis. In conclusion, solasonine inhibited the progress of acute monocytic leukemia and and triggered the apoptosis and cell cycle arrest in the G2/M phase by upregulating the AMPK/FOXO3A pathway.
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http://dx.doi.org/10.3389/fonc.2020.614067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879981PMC
January 2021

Effect of Different Pretreatment of Birch Sawdust on the Production of Active Polysaccharides by Inonotus obliquus Under Submerged Fermentation and Its Structural Mechanism.

Appl Biochem Biotechnol 2021 May 23;193(5):1545-1557. Epub 2021 Jan 23.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.

This study examined the effects of different pretreatments of birch sawdust on the production and activity of polysaccharides by Inonotus obliquus, and in order to explore the mechanism, structural characterization and analysis were carried out. The result clearly indicated that alkali treatment, ozone treatment, and alkali combined with ozone treatment of birch sawdust could be all helpful for the production of active polysaccharide by I. obliquus. Among four pretreatment groups, birch sawdust treated with alkali showed the highest increase in the exo-polysaccharide content (39.90%) and the inhibition rate of α-glucosidase (80.78%) within 11 days by the mycelium of I. obliquus through deep fermentation, in comparison to water-washed birch sawdust. Through a single-factor analysis and orthogonal experimental design, the optimum alkali treatment condition was as follows: NaOH concentration 1%, temperature 60 °C, and time 3 h. Moreover, the structural characteristics of pretreated birch sawdust with the optimum alkali treatment condition before and after fermentation by the mycelium of I. obliquus was performed by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electronic microscopy. The results showed that alkali treatment destroyed the lignin structure of birch sawdust, exposed the cellulose in the amorphous area, reduced the crystallinity of lignocellulose, and damaged the surface structure of birch sawdust, which had a further damage and a greater degradation degree of birch sawdust after fermentation, indicating that alkali pretreatment was beneficial for utilization of birch sawdust by I. obliquus.
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http://dx.doi.org/10.1007/s12010-021-03508-wDOI Listing
May 2021

Heavy-Atom-Modulated Supramolecular Assembly Increases Antitumor Potency against Malignant Breast Tumors via Tunable Cooperativity.

Adv Mater 2021 Jan 3;33(2):e2004225. Epub 2020 Dec 3.

State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China.

Triple-negative breast cancer (TNBC) remains with highest incidence and mortality rates among females, and a critical bottleneck lies in rationally establishing potent therapeutics against TNBC. Here, the self-assembled micellar nanoarchitecture of heavy-atom-modulated supramolecules with efficient cytoplasmic translocation and tunable photoconversion is shown, for potent suppression against primary, metastatic, and recurrent TNBC. Multi-iodinated boron dipyrromethene micelles yield tunable photoconversion into singlet oxygen and a thermal effect, together with deep penetration and subsequent cytoplasmic translocation at the tumor. Tetra-iodinated boron dipyrromethene micelles (4-IBMs) particularly show a distinctly enhanced cooperativity of antitumor efficiency through considerable expressions of apoptotic proteins, potently suppressing subcutaneous, and orthotopic TNBC models, together with reduced oxygen dependence. Furthermore, 4-IBMs yield preferable anti-metastatic and anti-recurrent efficacies through the inhibition of metastasis-relevant proteins, distinct immunogenic cell death, and re-education of M2 macrophages into tumoricidal M1 phenotype as compared to chemotherapy and surgical resection. These results offer insights into the cooperativity of supramolecular nanoarchitectures for potent phototherapy against TNBC.
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http://dx.doi.org/10.1002/adma.202004225DOI Listing
January 2021

Undecanoic Acid, Lauric Acid, and N-Tridecanoic Acid Inhibit Persistence and Biofilm Formation.

J Microbiol Biotechnol 2021 Jan;31(1):130-136

Department of Chemical and Biological Engineering, Illinois Institute of Technology, Chicago, IL 60616, USA.

Persister cell formation and biofilms of pathogens are extensively involved in the development of chronic infectious diseases. Eradicating persister cells is challenging, owing to their tolerance to conventional antibiotics, which cannot kill cells in a metabolically dormant state. A high frequency of persisters in biofilms makes inactivating biofilm cells more difficult, because the biofilm matrix inhibits antibiotic penetration. Fatty acids may be promising candidates as antipersister or antibiofilm agents, because some fatty acids exhibit antimicrobial effects. We previously reported that fatty acid ethyl esters effectively inhibit persister formation by regulating an antitoxin. In this study, we screened a fatty acid library consisting of 65 different fatty acid molecules for altered persister formation. We found that undecanoic acid, lauric acid, and N-tridecanoic acid inhibited BW25113 persister cell formation by 25-, 58-, and 44-fold, respectively. Similarly, these fatty acids repressed persisters of enterohemorrhagic EDL933. These fatty acids were all medium-chain saturated forms. Furthermore, the fatty acids repressed Enterohemorrhagic (EHEC) biofilm formation (for example, by 8-fold for lauric acid) without having antimicrobial activity. This study demonstrates that medium-chain saturated fatty acids can serve as antipersister and antibiofilm agents that may be applied to treat bacterial infections.
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http://dx.doi.org/10.4014/jmb.2008.08027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513074PMC
January 2021

Ultrastable Near-Infrared Nonlinear Organic Chromophore Nanoparticles with Intramolecular Charge Transfer for Dually Photoinduced Tumor Ablation.

Adv Healthc Mater 2020 10 16;9(20):e2001042. Epub 2020 Sep 16.

State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School of Radiation Medicine and Protection, Soochow University, Suzhou, 215123, China.

Near-infrared (NIR) light-responsive nanoparticles (NPs) of organic photosensitizers (PS) hold great promise as phototherapeutic agents for precision photoinduced cancer therapy. However, highly photostable PS nanoparticles with extraordinary photoconversion capacities are urgently desired to fully realize potent phototherapy. Here, NIR nonlinear organic chromophore nanoparticles (NOC-NPs) are shown as single-component PS for dually cooperative phototherapy. Upon 785 nm irradiation, excited NOC-NPs pass through intrinsic intramolecular charge transfer (ICT) channel to generate both abundant singlet oxygen and local hyperthermia, affording synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) for tumor ablation. Furthermore, NOC-NPs exhibit dramatic photostability, enhanced cellular uptake, effective cytoplasmic translocation, as well as preferable tumor accumulation, further ensuring favorable in vivo singlet oxygen generation and hyperthermia for photoinduced tumor ablation. Thus, NOC-NPs may represent novel high-performance PS for synergistic photoinduced cancer therapy, providing new insights into the development of potent PS for clinical translation.
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http://dx.doi.org/10.1002/adhm.202001042DOI Listing
October 2020

[Etomidate reduces excitability of the neurons and suppresses the function of nAChR ventral horn in the spinal cord of neonatal rats].

Nan Fang Yi Ke Da Xue Xue Bao 2020 May;40(5):676-682

Psychophysiology Laboratory, Institute of Physiological Sciences, Wannan Medical College, Wuhu 241002, China.

Objective: To investigate the effects of etomidate on electrophysiological properties and nicotinic acetylcholine receptors (nAChRs) of ventral horn neurons in the spinal cord.

Methods: The spinal cord containing lumbosacral enlargement was isolated from 19 neonatal SD rats aged 7-12 days. The spinal cord were sliced and digested with papain (0.18 g/30 mL artificial cerebrospinal fluid) and incubated for 40 min. At the ventral horn, acute mechanical separation of neurons was performed with fire-polished Pasteur pipettes, and perforated patch-clamp recordings combined with pharmacological methods were employed on the adherent healthy neurons. In current-clamp mode, the spontaneous action potential (AP) of the ventral horn neurons in the spinal cord was recorded. The effects of pretreatment with different concentrations of etomidate on AP recorded in the ventral horn neurons were examined. In the voltage-clamp mode, nicotine was applied to induce inward currents in the ventral horn neurons, and the effect of pretreatment with etomidate on the inward currents induced by nicotine were examined with different etomidate concentrations, different holding potentials and different use time.

Results: The isolated ventral horn neurons were in good condition with large diverse somata and intact processes. The isolated spinal ventral horn neurons (=21) had spontaneous action potentials, and were continuously perfused for 2 min with 0.3, 3.0 and 30.0 μmol/L etomidate. Compared with those before administration, the AP amplitude, spike potential amplitude and overshoot were concentration-dependently suppressed ( < 0.01), and spontaneous discharge frequency was obviously reduced ( < 0.01, =12). The APs of the other 9 neurons were completely abolished by etomidate at 3.0 or 30 μmol/L. At the same holding potential (VH=-70 mV), pretreatment with 0.3, 3.0 or 30.0 μmol/L etomidate for 2 min concentration-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =7). At the holding potentials of - 30, - 50, and - 70 mV, pretreatment with 30.0 μmol/L etomidate for 2 min voltage-dependently suppressed the current amplitude induced by 0.4 mmol/L nicotine ( < 0.01, =6 for each holding potential). During the 6 min of 30.0 μmol/L etomidate pretreatment, the clamped cells were exposed to 0.4 mmol/L nicotine for 4 times at 0, 2, 4, and 6 min (each exposure time was 2 s), and the nicotinic current amplitude decreased gradually as the number of exposures increased. But at the same concentration, two nicotine exposures (one at the beginning and the other at the end of the 6 min pretreatment) resulted in a significantly lower inhibition rate compared with 4 nicotine exposures ( < 0.01, =6).

Conclusions: etomidate reduces the excitability of the spinal ventral neurons in a concentration-dependent manner and suppresses the function of nAChR in a concentration-, voltage-, and use-dependent manner.
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http://dx.doi.org/10.12122/j.issn.1673-4254.2020.05.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277324PMC
May 2020
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