Publications by authors named "Jing Guo"

1,966 Publications

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Amidoxime functionalized PVDF-based chelating membranes enable synchronous elimination of heavy metals and organic contaminants from wastewater.

J Environ Manage 2022 Sep 2;318:115643. Epub 2022 Jul 2.

School of Textile and Material Engineering, Dalian Polytechnic University, Dalian, China.

Aiming at the synchronous elimination of heavy metals and organic contaminants from wastewater, the amidoxime functionalized PVDF-based chelating membrane was fabricated in this study. The structure and morphology of the chelating membrane were characterized using infrared spectroscopy (FT-IR), nuclear magnetic resonance spectrometer (NMR) and scanning electron microscopy (SEM). The SEM results show that the chemical modification with amidoxime groups did not damage the structure of the PVDF-based membrane. The chelating membrane has a high removal efficiency for Cu (77.33%) and Pb (79.23%) owing to the chemisorption through coordination bonds. However, the chelating membrane exhibits a low removal efficiency for Cd (29.88%) due to the physical adsorption. The chelating membrane has a high rejection efficiency of BSA (95.17%) and lysozyme (70.09%), which is attributed to the sieving effect and increased hydrophobicity. Furthermore, the membrane performance for simultaneously removing metals and proteins from simulated wastewater was examined. The interaction of metal ions with proteins (BSA and lysozyme) can enhance the ion removal efficiency of the chelated membrane, but decrease the protein rejection efficiency due to the destructive effect. The amidoxime functionalized PVDF-based chelating membrane has a high potential for application in wastewater treatment.
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http://dx.doi.org/10.1016/j.jenvman.2022.115643DOI Listing
September 2022

An LC-MS-based metabolomic approach provides insights into the metabolite profiles of Ginkgo biloba L. at different developmental stages and in various organs.

Food Res Int 2022 Sep 9;159:111644. Epub 2022 Jul 9.

Nanjing Forestry University, Co-Innovation Center for Sustainable Forestry in Southern China, 159 Longpan Road, Nanjing 210037, China. Electronic address:

Ginkgo (Ginkgo biloba L.) is a tree valued for the high medicinal and nutritional value of its leaves and seeds. However, the metabolite profiles of ginkgo leaves and seeds and their changes during development have not been comprehensively analyzed, which hinders improvements in the utilization of ginkgo. A comprehensive and systematic untargeted LC-MS metabolomics analysis of the metabolites in ginkgo leaves (male and female) and seeds at two developmental stages identified 8146 known metabolites, which mainly included lipids and lipid-like molecules, phenylpropanoids and polyketides, organoheterocyclic compounds, organic acids and derivatives, organic oxygen compounds, and benzenoids. Some of the identified metabolites have known healthcare and food value, and some of the others are newly discovered metabolites with potential for new drug development. The small number of differential Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between leaves of male and female gingko trees indicated that the developmental stage affected the metabolic pathways more significantly than sex. Among the flavonoid constituents of ginkgo, 653 flavonoid metabolites were identified, and these included some new flavonoid components, which confirmed that the developmental stage is a critical factor in secondary metabolite variations. This study illuminated the metabolites and medicinal and edible values of ginkgo leaves and seeds at different developmental stages and thus supports further effective utilization of ginkgo leaves and seeds.
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http://dx.doi.org/10.1016/j.foodres.2022.111644DOI Listing
September 2022

Robustness of Bilayer Hexagonal Ice against Surface Symmetry and Corrugation.

Phys Rev Lett 2022 Jul;129(4):046001

International Center for Quantum Materials, School of Physics, Peking University, Beijing 100871, China.

Two-dimensional (2D) bilayer hexagonal ice (BHI) is regarded as the first intrinsic 2D ice crystal. However, the robustness of such a structure or its derivatives against surface symmetry and corrugation is still unclear. Here, we report the formation of 2D BHI on gold surfaces with 1D corrugation, using noncontact atomic force microscopy. The hexagonal arrangement of the first wetting layer was visualized on the Au(110)-1×2 surface. Upon depositing more water molecules, the first layer would rearrange and shrink, resulting in the formation of buckled BHI. Such a buckled BHI is hydrophobic despite the appearance of dangling OH, due to the strong interlayer bonding. Furthermore, the BHI is also stable on the Au(100)-5×28 surface. This work reveals the unexpected generality of the BHI on corrugated surfaces with nonhexagonal symmetry, thus shedding new light on the microscopic understandings of the low-dimensional ice formation on solid surfaces or under confinement.
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http://dx.doi.org/10.1103/PhysRevLett.129.046001DOI Listing
July 2022

The potential application of natural products in cutaneous wound healing: A review of preclinical evidence.

Front Pharmacol 2022 22;13:900439. Epub 2022 Jul 22.

Dermatological Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Under normal circumstances, wound healing can be summarized as three processes. These include inflammation, proliferation, and remodeling. The vast majority of wounds heal rapidly; however, a large percentage of nonhealing wounds have still not been studied significantly. The factors affecting wound nonhealing are complex and diverse, and identifying an effective solution from nature becomes a key goal of research. This study aimed to highlight and review the mechanisms and targets of natural products (NPs) for treating nonhealing wounds. The results of relevant studies have shown that the effects of NPs are associated with PI3K-AKT, P38MAPK, fibroblast growth factor, MAPK, and ERK signaling pathways and involve tumor growth factor (TNF), vascular endothelial growth factor, TNF-α, interleukin-1β, and expression of other cytokines and proteins. The 25 NPs that contribute to wound healing were systematically summarized by an inductive collation of the six major classes of compounds, including saponins, polyphenols, flavonoids, anthraquinones, polysaccharides, and others, which will further direct the attention to the active components of NPs and provide research ideas for further development of new products for wound healing.
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http://dx.doi.org/10.3389/fphar.2022.900439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354992PMC
July 2022

Application of fluoride disturbs plaque microecology and promotes remineralization of enamel initial caries.

J Oral Microbiol 2022 27;14(1):2105022. Epub 2022 Jul 27.

Department of Operative Dentistry & Endodontics, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, School of Stomatology, the Fourth Military Medical University, Xi'an, PR China.

Background: The caries-preventive effect of topical fluoride application has been corroborated by a number of clinical studies. However, the effect of fluoride on oral microecology remains unclear.

Objective: To monitor the effect of fluoride on dental plaque microecology and demineralization/remineralization balance of enamel initial caries.

Methods: Three-year-old children were enrolled and treated with fluoride at baseline and 6 months. International Caries Detection and Assessment System II indices of 52 subjects were measured at baseline, 3, 6, and 12 months. Supragingival plaque samples of 12 subjects were collected at baseline, 3 and 14 days for 16S rRNA sequencing.

Results: Changes in microbial community structure were observed at 3 days after fluoridation. Significant changes in the relative abundance of microorganisms were observed after fluoride application, especially , unidentified and . Functional prediction revealed that cell movement, carbohydrate and energy metabolism were affected significantly after fluoride application. Fluoride significantly inhibited enamel demineralization and promoted remineralization of early demineralized caries enamel at 3 months.

Conclusion: Fluoride application significantly inhibited the progression of enamel initial caries and reversed the demineralization process, possibly by disturbing dental plaque microecology and modulating the physicochemical action of demineralization/remineralization. This deepened our understanding of caries-preventive effects and mechanisms of fluoride.
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http://dx.doi.org/10.1080/20002297.2022.2105022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341347PMC
July 2022

DFNA5 inhibits colorectal cancer proliferation by suppressing the mTORC1/2 signaling pathways via upregulation of DEPTOR.

Cell Cycle 2022 Aug 3:1-14. Epub 2022 Aug 3.

Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

The human deafness, autosomal dominant 5 gene (DFNA5), a newly discovered executor of pyroptosis, has been strongly implicated in the tumorigenesis of several human cancers. However, an understanding of the functional role of DFNA5 in the development and progression of colorectal cancer (CRC) is limited. In this study, we demonstrated that DFNA5 was downregulated in CRC tissues. Ectopic expression of DFNA5 inhibited tumor cell growth in vitro, retarded tumor formation in vivo, and blocked a cell-cycle transition from the G0/G1 to the S phase, whereas a DFNA5 knockdown promoted cell proliferation. Western blotting showed that the levels of cell cycle-related proteins, including cyclin D1, cyclin E, CDK2, and p21, were accordingly altered upon DFNA5 overexpression or DFNA5 knockdown. Mechanistic studies indicated that DFNA5 exerted its tumor suppressor functions by antagonizing mTORC1/2 signaling via upregulation of DEPTOR. In addition, blockage of mTORC1/2 signaling by Torin-1 abolished the accelerative proliferation by DFNA5 knockdown. In conclusion, these results indicated that DFNA5 inhibits the proliferation and tumor formation of colon cancer cells by suppressing mTORC1/2 signaling.
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http://dx.doi.org/10.1080/15384101.2022.2088570DOI Listing
August 2022

Use of folic acid supplementation to halt and even reverse the progression of gastric precancerous conditions: a meta-analysis.

BMC Gastroenterol 2022 Aug 2;22(1):370. Epub 2022 Aug 2.

Geriatric Department, Hospital of Chengdu University of Traditional Chinese Medicine, 39 Shi-er-qiao Road, Chengdu, Sichuan, 610072, People's Republic of China.

Background: Current data indicate that supplements such as folic acid and vitamin B may be beneficial in halting and even reversing atrophic gastritis, intestinal metaplasia and intraepithelial neoplasia, generally referred to as gastric precancerous conditions(GPC). However, there is no Meta-analysis article to evaluate the prevention and treatment of folic acid in the gastric precancerous conditions. We therefore conducted a meta-analysis to confirm the efficacy of folic acid in treating GPC.

Methods: Using a systematic review method, consider randomized controlled trials (RCT), including clinical trial reports, unpublished clinical trial data, and conference papers. The search time was been set from the database's establishment to June 2, 2021. The language was not limited, using PubMed, SinoMed, Lancet, Web of Science, CNKI, Cochrane, Ovid, Science Direct, Embase, and EBSCO databases. Data were extracted using a pre-designed extraction tool and analysis was undertaken using RevMan5.2.Besides,we use Origin software to construct the Time-dose interval analysis.

Results: Of the 225 records identified, 13 studies involving 1252 patients (including 11 clinical controlled trials, 1 conference paper report and 1 unpublished research report) met the inclusion conditions. Folic acid dose maintained at 20-30 mg / d for 3-6 months may be beneficial to pathological changes of GPC. Moreover, in the 3 month treatment of 5 trials, the effect was more obvious when the folic acid dose was maintained at 30 mg / d. In the 7 trials, the symptom ineffective rate of GPC treated with folic acid was 32% (RR:0.32, 95% confidence interval CI:0.21-0.48), which was combined using a fixed analysis model; The effect of folic acid on gastric mucosal atrophy in 5 trials (RR: 1.61, 95%CI 1.07-2.41). The changes of folic acid on intestinal metaplasia in the 2 experiments (RR: 1.77, 95% CI: 1.32-2.37).The 2 results are combined using a fixed analytical model. However, the subgroup analysis of 9 trials revealed no significant effectiveness of symptom.

Conclusions: Our research showed that folic acid supplementation brings benefits in preventing and even reversing the progression of GPC in the stomach, and provided evidence for its potential clinical use in management of GPC.

Registration: The logn number of our Meta-anlysis on PROSPERO is CRD420223062.
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http://dx.doi.org/10.1186/s12876-022-02390-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344768PMC
August 2022

Causal Structural Covariance Network Suggesting Structural Alterations Progression in Type 2 Diabetes Patients.

Front Hum Neurosci 2022 15;16:936943. Epub 2022 Jul 15.

The Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States.

Background And Purpose: According to reports, type 2 diabetes (T2D) is a progressive disease. However, no known research has examined the progressive brain structural changes associated with T2D. The purpose of this study was to determine whether T2D patients exhibit progressive brain structural alterations and, if so, how the alterations progress.

Materials And Methods: Structural magnetic resonance imaging scans were collected for 81 T2D patients and 48 sex-and age-matched healthy controls (HCs). Voxel-based morphometry (VBM) and causal structural covariance network (CaSCN) analyses were applied to investigate gray matter volume (GMV) alterations and the likely chronological processes underlying them in T2D. Two sample -tests were performed to compare group differences, and the differences were corrected using Gaussian random field (GRF) correction (voxel-level < 0.001, cluster-level < 0.01).

Results: Our findings demonstrated that GMV alterations progressed in T2D patients as disease duration increased. In the early stages of the disease, the right temporal pole of T2D patients had GMV atrophy. As the diseases duration prolonged, the limbic system, cerebellum, subcortical structures, parietal cortex, frontal cortex, and occipital cortex progressively exhibited GMV alterations. The patients also exhibited a GMV alterations sequence exerting from the right temporal pole to the limbic-cerebellum-striatal-cortical network areas.

Conclusion: Our results indicate that the progressive GMV alterations of T2D patients manifested a limbic-cerebellum-striatal-cortical sequence. These findings may contribute to a better understanding of the progression and an improvement of current diagnosis and intervention strategies for T2D.
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http://dx.doi.org/10.3389/fnhum.2022.936943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336220PMC
July 2022

An Assay Combining Droplet Digital PCR With Propidium Monoazide Treatment for the Accurate Detection of Live Cells of in Plasma Samples.

Front Microbiol 2022 15;13:927285. Epub 2022 Jul 15.

Hangzhou Medical College, Hangzhou, China.

() is one of the most common pathogenic species to humans; therefore, the establishment of timely and credible detection methods has become an urgent requirement for illness surveillance. In this study, an assay combining droplet digital PCR (ddPCR) with propidium monoazide (PMA) treatment was developed for detecting The primers/probes targeting the hemolysin A () gene, amplification procedures, and PMA processing conditions involved in the assay were optimized. Then, we analyzed the specificity, sensitivity, and ability to detect live cell DNA while testing the performance of PMA-ddPCR in clinical samples. The optimal concentrations of primers and probes were 1.0 and 0.3 μM, respectively. The annealing temperature achieving the highest accuracy in ddPCR assay was 60°C. With an initial cell concentration of 10 CFU/mL (colony-forming units per milliliter), the optimal strategy to distinguish live cells from dead cells was to treat samples with 100 μM PMA for 15 min in the dark and expose them to LED light with an output wavelength of 465 nm for 10 min. The specificity of the PMA-ddPCR assay was tested on 27 strains, including seven strains and 20 other bacterial strains. Only the seven strains were observed with positive signals in specificity analysis. Comparative experiments on the detection ability of PMA-ddPCR and PMA-qPCR in pure cultures and plasma samples were performed. The limit of detection (LOD) and the limit of quantitation (LOQ) in pure culture solutions of were 29.33 and 53.64 CFU/mL in PMA-ddPCR, respectively. For artificially clinical sample tests in PMA-ddPCR, could be detected at concentrations as low as 65.20 CFU/mL. The sensitivity of the PMA-ddPCR assay was 15- to 40-fold more sensitive than the PMA-qPCR in this study. The PMA-ddPCR assay we developed provides a new insight to accurately detect live cells of in clinical samples, which is of great significance to enhance public health safety and security capability and improve the emergency response level for infection.
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http://dx.doi.org/10.3389/fmicb.2022.927285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335127PMC
July 2022

Effect of shiitake mushrooms polysaccharide and chitosan coating on softening and browning of shiitake mushrooms (Lentinus edodes) during postharvest storage.

Int J Biol Macromol 2022 Jul 27;218:816-827. Epub 2022 Jul 27.

School of Chemistry and Chemical Engineering, Xi'an University of Science and Technology, Xi'an 710054, China.

We investigated the browning and softening of fresh Lentinula edodes (LE) coated with polysaccharides (LEP) isolated from LE stalks and stored at 4 °C for 15 days. The results showed that compared to the chitosan-coated and uncoated LE, the LEP-treated mushrooms showed significant improvements in several qualities during storage, such as reduced weight loss, retention of hardness and springiness, improved soluble protein content, and reduced browning, malondialdehyde content, and electrolyte leakage rate. The best results were obtained with 1.5 % LEP. LEP improved the activities of peroxidase, catalase, superoxide dismutase, ascorbate peroxidase, and phenylalanine ammonialyase and significantly reduced the accumulation of hydrogen peroxide during storage compared to the control samples. In addition, the LEP treatment maintained the high antioxidant activity of LE during storage. Notably, LEP inhibited browning-related enzymes (polyphenol oxidase and tyrosinase) to reduce browning. It also maintained high levels of cellulase, chitinase, and β-1,3 glucanase to improve softening during storage. These findings suggest the potential of LEP to improve the post-harvest quality of mushrooms, allowing a storage period of up to 15 days (extending the shelf life by six days) and indirectly suggesting that the polysaccharide component of LEP can act as a self-defense additive to protect against spoilage during storage.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.193DOI Listing
July 2022

Lineage-specific rearrangement of chromatin loops and epigenomic features during adipocytes and osteoblasts commitment.

Cell Death Differ 2022 Jul 29. Epub 2022 Jul 29.

Biomedical Informatics & Genomics Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, P. R. China.

Human mesenchymal stem cells (hMSCs) can be differentiated into adipocytes and osteoblasts. The processes are driven by the rewiring of chromatin architectures and transcriptomic/epigenomic changes. Here, we induced hMSCs to adipogenic and osteogenic differentiation, and performed 2 kb resolution Hi-C experiments for chromatin loops detection. We also generated matched RNA-seq, ChIP-seq and ATAC-seq data for integrative analysis. After comprehensively comparing adipogenesis and osteogenesis, we quantitatively identified lineage-specific loops and screened out lineage-specific enhancers and open chromatin. We reveal that lineage-specific loops can activate gene expression and facilitate cell commitment through combining enhancers and accessible chromatin in a lineage-specific manner. We finally proposed loop-mediated regulatory networks and identified the controlling factors for adipocytes and osteoblasts determination. Functional experiments validated the lineage-specific regulation networks towards IRS2 and RUNX2 that are associated with adipogenesis and osteogenesis, respectively. These results are expected to help better understand the chromatin conformation determinants of hMSCs fate commitment.
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http://dx.doi.org/10.1038/s41418-022-01035-7DOI Listing
July 2022

New Insights into TRP Ion Channels in Stem Cells.

Int J Mol Sci 2022 Jul 14;23(14). Epub 2022 Jul 14.

Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.

Transient receptor potential (TRP) ion channels are cationic permeable proteins located on the plasma membrane. TRPs are cellular sensors for perceiving diverse physical and/or chemical stimuli; thus, serving various critical physiological functions, including chemo-sensation, hearing, homeostasis, mechano-sensation, pain, taste, thermoregulation, vision, and even carcinogenesis. Dysregulated TRPs are found to be linked to many human hereditary diseases. Recent studies indicate that TRP ion channels are not only involved in sensory functions but are also implicated in regulating the biological characteristics of stem cells. In the present review, we summarize the expressions and functions of TRP ion channels in stem cells, including cancer stem cells. It offers an overview of the current understanding of TRP ion channels in stem cells.
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http://dx.doi.org/10.3390/ijms23147766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318110PMC
July 2022

A nonconjugated radical polymer with stable red luminescence in the solid state.

Mater Horiz 2022 Jul 26. Epub 2022 Jul 26.

School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong, Shenzhen, Guangdong, 518172, China.

Organic radicals are unstable and stable radicals usually display non-luminescent properties. Luminescent radicals possess the all-in-one properties of optoelectronics, electronics, and magnetics. To date, the reported structures of luminescent radicals are limited to triphenylmethyl radical derivatives and their analogues, which are stabilized with extended π-conjugation. Here, we demonstrate the first example of a nonconjugated luminescent radical. In spite of the lack of delocalized π-stabilization, the radical polymer readily emits red luminescence in the solid state. A traditional luminescent quencher, 2,2,6,6-tetramethylpiperidin-1-yl turned into a red chromophore when grafted onto a polymer backbone. Experimental data confirm that the emission is associated with the nitroxide radicals and is also affected by the packing of the polymer. This work discloses a novel class of luminescent radicals and a distinctive pathway for luminescence from open-shell materials.
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http://dx.doi.org/10.1039/d2mh00808dDOI Listing
July 2022

Amyloid-Mediated Remineralization in Pit and Fissure for Caries Preventive Therapy.

Adv Healthc Mater 2022 Jul 22:e2200872. Epub 2022 Jul 22.

Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, 710119, China.

The pits and fissures of teeth have high caries susceptibility, and sealing these areas is considered as an effective method to prevent caries. However, long-term caries prophylaxis cannot be maintained because of the negative effects derived from the technical sensitivity and disadvantages of sealing materials. Herein, a new strategy is proposed to occlude fossae by amyloid-mediated biomimetic remineralization. In contrast to conventional inward blocking from the outside of fossae, amyloid-mediated biomimetic mineralization delivers an amyloid-like protein nanofilm into the deepest zone of the fossae and induces the formation of remineralized enamel inside. Such assembly from lysozyme conjugated with poly (ethylene glycol) enriches the interface with strongly bonded ionsand directs in situ nucleation to achieve enamel epitaxial growth. Not only is the structure of the enamel-like crystalline hydroxyapatite layer but also its mechanical stability is similar to that of natural enamel. Furthermore, the layer shows good biocompatibility and antibacterial properties. On the basis of the findings, it is demonstrated that amyloid-like protein aggregation may provide an enamel remineralization strategy to modify the current clinically available methods of pit and fissure sealing and shows great promise in preventing caries.
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http://dx.doi.org/10.1002/adhm.202200872DOI Listing
July 2022

Electroacupuncture Attenuates Post-Inflammatory IBS-Associated Visceral and Somatic Hypersensitivity and Correlates With the Regulatory Mechanism of Epac1-Piezo2 Axis.

Front Endocrinol (Lausanne) 2022 5;13:918652. Epub 2022 Jul 5.

Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity the reduction of the level of 5-hydroxytryptamine (5-HT) and 5-HT receptors (5-HTR). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HTR from the mouse distal colon/L5-S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HTR expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5-S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1-Piezo2 axis.
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http://dx.doi.org/10.3389/fendo.2022.918652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294163PMC
July 2022

Visualizing Eigen/Zundel cations and their interconversion in monolayer water on metal surfaces.

Science 2022 07 14;377(6603):315-319. Epub 2022 Jul 14.

International Center for Quantum Materials, School of Physics, Peking University, Beijing 100871, China.

The nature of hydrated proton on solid surfaces is of vital importance in electrochemistry, proton channels, and hydrogen fuel cells but remains unclear because of the lack of atomic-scale characterization. We directly visualized Eigen- and Zundel-type hydrated protons within the hydrogen bonding water network on Au(111) and Pt(111) surfaces, using cryogenic qPlus-based atomic force microscopy under ultrahigh vacuum. We found that the Eigen cations self-assembled into monolayer structures with local order, and the Zundel cations formed long-range ordered structures stabilized by nuclear quantum effects. Two Eigen cations could combine into one Zundel cation accompanied with a simultaneous proton transfer to the surface. Moreover, we revealed that the Zundel configuration was preferred over the Eigen on Pt(111), and such a preference was absent on Au(111).
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http://dx.doi.org/10.1126/science.abo0823DOI Listing
July 2022

Bidirectional two-sample Mendelian randomization analysis identifies causal associations between relative carbohydrate intake and depression.

Nat Hum Behav 2022 Jul 18. Epub 2022 Jul 18.

National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, P. R. China.

Growing evidence suggests that relative carbohydrate intake affects depression; however, the association between carbohydrates and depression remains controversial. To test this, we performed a two-sample bidirectional Mendelian randomization (MR) analysis using genetic variants associated with relative carbohydrate intake (N = 268,922) and major depressive disorder (N = 143,265) from the largest available genome-wide association studies. MR evidence suggested a causal relationship between higher relative carbohydrate intake and lower depression risk (odds ratio, 0.42 for depression per one-standard-deviation increment in relative carbohydrate intake; 95% confidence interval, 0.28 to 0.62; P = 1.49 × 10). Multivariable MR indicated that the protective effect of relative carbohydrate intake on depression persisted after conditioning on other diet compositions. The mediation analysis via two-step MR showed that this effect was partly mediated by body mass index, with a mediated proportion of 15.4% (95% confidence interval, 6.7% to 24.1%). These findings may inform prevention strategies and interventions directed towards relative carbohydrate intake and depression.
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http://dx.doi.org/10.1038/s41562-022-01412-9DOI Listing
July 2022

Expression and Mechanism of TXNIP/NLRP3 Inflammasome in Sciatic Nerve of Type 2 Diabetic Rats.

Dis Markers 2022 8;2022:9696303. Epub 2022 Jul 8.

Department of Endocrinology for Senior Citizens, Second Hospital of Shanxi Medical University, Taiyuan, 030001 Shanxi, China.

Objective: To determine the expression profiling and mechanism of thioredoxin-interacting protein (TXNIP)/nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome pathway in sciatic nerve (SN) of type 2 diabetes mellitus (T2DM) rats.

Methods: Ten out of the 35 healthy SD rats (specific pathogen free) purchased were randomized into the control group, while the others were established a T2DM model by feeding a high-fat and high-sugar diet plus laparoscopic injection of 1% streptozotocin (STZ). The successfully modeled rats were subgrouped into two arms: a DM group with 10 rats and a resveratrol- (RES-) treated DM intervention group with 11 rats. Normal saline to control and DM groups. Alterations in fasting blood glucose (FBG) and body weight (BW) at different time points after administration were observed. Sciatic nerve conduction velocity (SNCV) and mechanical pain threshold (MPT) were measured. TXNIP, NLRP3, caspase-1, and interleukin- (IL-) 1 levels in rat SN tissue were determined.

Results: DM group rats showed higher FBG and lower BW than control rats at different time points ( < 0.05). The FBG of DM intervention group at 2, 4, and 6 weeks after administration was lower, and the BW at 4 and 6 weeks after dosing was higher than DM group. Higher MPT and SNCV were determined in DM intervention group versus DM group ( < 0.05). DM group rats had disordered, swollen, and dissolved SN myelin sheath structure; TXNIP inhibition led to a small amount of nerve myelin fragments and mild pathological changes. Lower TXNIP, NLRP3, caspase-1, and IL-1 protein levels were found in DM intervention group versus DM group ( < 0.05).

Conclusion: The pathogenesis of peripheral neuropathy in T2DM rats may be linked to TXNIP/NLRP3 inflammasome pathway activation, indicating the potential of this pathway as a therapeutic target for diabetic peripheral neuropathy (DPN).
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http://dx.doi.org/10.1155/2022/9696303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286945PMC
July 2022

Treatment paradigms and survival outcomes in esophageal adenocarcinoma with liver metastasis: a retrospective cohort study using the SEER database.

J Gastrointest Oncol 2022 Jun;13(3):935-948

Department of Thoracic Surgery, Ningbo First Hospital, Ningbo, China.

Background: Esophageal adenocarcinoma with liver metastasis (EACLM) at the time of diagnosis has a poor prognosis and few therapeutic options. The best treatment options and prognostic factors for EACLM patients are unclear. The present study sought to explore the optimal treatment modalities for and the prognosis of these patients.

Methods: Patients diagnosed with EACLM at the time of diagnosis were identified from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015. The last follow-up date was December 31, 2018. Treatment patterns were divided into four groups: local therapy (surgery/radiation), systemic therapy [chemotherapy (CT)], combination therapy (surgery/radiation + CT), and no treatment. The Kaplan-Meier (K-M) method and log-rank test were used for overall survival (OS) and disease-specific survival (DSS). Univariable and multivariable Cox regression were performed to identify the prognostic factors. Propensity score-matching (PSM) analyses were performed for sensitive analyses.

Results: A total of 925 patients diagnosed with EACLM were included in the study. The median OS was 12, 10, 3, and 2 months for combination therapy, systemic therapy, local therapy, and no treatment, respectively (P<0.001). After PSM, the patients who received systemic treatment had a better OS (median 9 2 months; P<0.001) and DSS (median 9 3 months; P<0.001) than those who received no treatment. Compared to systemic therapy, combination therapy did not increase patients' OS (median 13 12 months, P=0.069) but did improve their DSS (median 19 13 months, P=0.048).

Conclusions: EACLM patients might benefit the most from systemic therapy and combination therapy. For patients who are well-tolerated, combination therapy should be considered as a preferable option.
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http://dx.doi.org/10.21037/jgo-22-420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274064PMC
June 2022

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial.

Front Immunol 2022 24;13:898151. Epub 2022 Jun 24.

National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co Ltd, Wuhan, China.

Safe and effective vaccines against SARS-CoV-2 for children are urgently needed. Here we aimed to assess the safety and immunogenicity of an inactivated COVID-19 vaccine candidate, WIBP-CorV, in participants aged 3-17 years. A randomized, double-blind, placebo-controlled, phase 1/2 clinical trial was conducted in Henan Province, China, in healthy children aged 3-17 years. 240 participants in phase 1 trial and 576 participants in phase 2 trial were randomly assigned to vaccine or control with an age de-escalation in three cohorts (3-5, 6-12 and 13-17 years) and dose-escalation in three groups (2.5, 5.0 and 10.0μg/dose), and received 3 intramuscular injections at day 0, 28, and 56. WIBP-CorV showed a promising safety profile with approximately 17% adverse reactions within 30 days after injection and no grade 3 or worse adverse events. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting. The geometric mean titers of neutralizing antibody ranged from 102.2 to 1065.5 in vaccinated participants at 28 days after the third vaccination, and maintained at a range of 14.3 to 218.2 at day 180 after the third vaccination. WIBP-CorV elicited significantly higher titers of neutralizing antibody in the cohort aged 3-5 years than the other two cohorts. There were no detectable antibody responses in all alum-only groups. Taken together, our data demonstrate that WIBP-CorV is safe and well tolerated at all tested doses in participants aged 3-17 years, and elicited robust humoral responses against SARS-CoV-2 lasted for at least 6 months after the third vaccination. This study is ongoing and is registered with www.chictr.org.cn, ChiCTR2000031809.
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http://dx.doi.org/10.3389/fimmu.2022.898151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265248PMC
June 2022

Identification of Novel Variants of Thyroid Hormone Receptor Interaction Protein 13 That Cause Female Infertility Characterized by Zygotic Cleavage Failure.

Front Physiol 2022 23;13:899149. Epub 2022 Jun 23.

Laboratory of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, China.

Zygotic cleavage failure (ZCF) is a severe, early type of embryonic arrest in which zygotes cannot complete the first cleavage. Although mutations in and have been identified as genetic causes of ZCF, these genes only explain a small population of ZCF cases. Thus, the underlying genetic causes for other affected individuals need to be identified. Here, we identified three missense variants responsible for ZCF in two patients and showed that they followed a recessive inheritance pattern. All three variants resulted in obvious changes in hydrogen bonding and consistent increase in DNA damage. Additionally, transcriptomic sequencing of oocytes and arrested embryos containing these variants suggested a greater number of differentially expressed transcripts in germinal vesicle (GV) oocytes than in 1-cell embryos. Vital genes for energy metabolism and cell cycle procession were widely and markedly downregulated, while DNA repair-related genes were significantly upregulated in both GV oocytes and 1-cell embryos of patients. These findings highlight a critical role of in meiosis and mitosis, as well as expand the genetic and phenotypic spectra of variants with respect to female infertility, especially in relation to ZCF.
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http://dx.doi.org/10.3389/fphys.2022.899149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259851PMC
June 2022

Insight into Point Defects and Complex Defects in β-MoC and Carbide Evolution from First Principles.

Materials (Basel) 2022 Jul 5;15(13). Epub 2022 Jul 5.

School of Engineering, Faculty of Engineering and Technology, Liverpool John Moores University, Liverpool L3 3AF, UK.

In this paper, first principles method was adopted to investigate the point defects, Vanadium-related defects and defect combinations (vacancy (V), substitutional (S) and/or interstitial (I)) in molybdenum β-MoC and explore the use of first principles calculation data in analysing the link between different carbides and the effects of doping elements. Supercell models with different defect types were established and optimized, and the formation energy data of defects was developed. The structure evolution during the optimization process is analysed in detail to establish the main characteristics of changes and the relevant electronic properties. The data for different types of intrinsic defects and combined defects complexes was developed and key results is analysed. The results show that carbon vacancy (V) is stable but does not inevitably exist in pure β-MoC. Interstitial site II is a very unstable position for any type of atoms (Mo, V and C), and analysis of the structure evolution shows that the atom always moves to the interface area near the interstitial site I between two layers. In particular, a C atom can expand the lattice structure when it exists between the layer interfaces. One type of the defects studied, the substitution of Mo with V (designated as 'S'), is the most stable defect among all single point defects. The data for defect complexes shows that the combination of multiple S defects in the super cell being more stable than the combination of other defects (e.g., 'V+I', 'S+V'). The data with increasing S in (Mo, V)C system is developed, and typical data (e.g., formation energy) for Mo-rich carbides and V carbides are correlated and the potential of the data in analysing transition of different carbides is highlighted. The relevance of using first principles calculation data in the studying of V-doping and the complex carbides (V- and Mo-rich carbides) evolution in different materials systems and future focus of continuous work is also discussed.
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http://dx.doi.org/10.3390/ma15134719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9267726PMC
July 2022

Iron Chelator VLX600 Inhibits Mitochondrial Respiration and Promotes Sensitization of Neuroblastoma Cells in Nutrition-Restricted Conditions.

Cancers (Basel) 2022 Jun 30;14(13). Epub 2022 Jun 30.

Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.

Neuroblastoma, the most common solid tumor in children, is characterized by amplification of the proto-oncogene, a high-risk aggressive clinical marker associated with treatment failure. MYCN plays an important role in cell growth, proliferation, metabolism, and chemoresistance. Here, we show for the first time that in neuroblastoma, iron chelator VLX600 inhibits mitochondrial respiration, decreases expression levels of MYCN/LMO1, and induces an efficient cell death regardless of MYCN status in both 2D and 3D culture conditions. Moreover, insufficient induction of autophagy was observed in cells treated with VLX600, which is essential as a protective response in the event of ATP synthesis disruption. Further inhibition of glucose uptake using DRB18, a pan-GLUT (glucose transporter) inhibitor, synergized the effect of VLX600 and no significant cell death was found in immortalized epithelial cells under this combination treatment. Our results demonstrate that inhibition of mitochondrial respiration by iron chelator VLX600 accompanied by autophagy deficiency promotes sensitivity of neuroblastoma cells in a nutrition-restricted microenvironment regardless of MYCN status, indicating that MYCN expression level is an essential clinical marker but might not be a necessary target for the treatment of neuroblastoma which warrants further investigation. VLX600 has been studied in Phase I clinical trials; combining VLX600 with conventional chemotherapy could be an innovative therapeutic strategy for neuroblastoma.
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http://dx.doi.org/10.3390/cancers14133225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264775PMC
June 2022

The Relationship Between Admission Blood Pressure and Clinical Outcomes for Acute Basilar Artery Occlusion.

Front Neurosci 2022 21;16:900868. Epub 2022 Jun 21.

Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Background And Purpose: Optimal blood pressure management of patients with basilar artery occlusion (BAO) remains uncertain. This study aimed to investigate the relationship between admission blood pressure and clinical outcomes following acute BAO.

Materials And Methods: We analyzed data from a prospective, nationwide cohort study of 829 patients with acute BAO and posterior circulation stroke. Baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded on admission. The primary outcome was neurological functional disability based on the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included successful reperfusion, mortality within 90 days, and National Institutes of Health Stroke Scale (NIHSS) score change. Multivariable logistic regression was used to assess the associations of SBP and DBP with outcomes.

Results: We include 829 patients with posterior circulation stroke and BAO between January 2014 and May 2019. Multivariate logistic regression showed high SBP and DBP correlated with unfavorable outcomes. The favorable prognosis (mRS ≤ 3) rates of the low-to-normal and the hypertension groups were 34.8 and 23.9%, respectively. After adjusting for covariates, multivariate regression analysis demonstrated that an SBP > 140 mm Hg was associated with a poor functional outcome [adjusted OR (aOR), 1.509; 95% CI, 1.130-2.015] and mortality at 90 days (aOR, 1.447; 95% CI, 1.055-1.985), and predicted a lower probability of successful reperfusion (aOR, 0.550; 95% CI, 0.389-0.778). The risk of symptomatic intracranial hemorrhage and the NIHSS score at 24 h were not significantly different between the high SBP group and the low-to-normal blood pressure group. And the results for DBP were similar.

Conclusion: Among patients with acute BAO, higher systolic or DBP at admission was associated with poor stroke outcomes and had a lower probability of successful reperfusion, with an increased risk of mortality. [http://www.chictr.org.cn], [ChiCTR1800014759].
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http://dx.doi.org/10.3389/fnins.2022.900868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253464PMC
June 2022

Low expression of PRDM5 predicts poor prognosis of esophageal squamous cell carcinoma.

BMC Cancer 2022 Jul 7;22(1):745. Epub 2022 Jul 7.

Department of Radiation Oncology, Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu, China.

Background: The role of the PRDM5 in esophageal squamous cell carcinoma (ESCC) has not been revealed. This study investigated the relationship between PRDM5 expression and survival outcome in esophageal squamous cell carcinoma and explored the mechanism in tumor development.

Methods: In present study, expression of PRDM5 mRNA in esophageal squamous cell carcinoma patients was conducted using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The expression of PRDM5 was assessed by immunohistochemical staining. Kaplan-Meier curve and Cox regression analysis was performed to analyze the survival outcome and independent predictive factors. qRT-PCR and Methylation-specific PCR were performed to identify the mRNA level of PRDM5 and Methylation rate. Cibersort algorithm to analyze the relationship between PRDM5 expression and immune cell invasion. Western-blot was performed to confirm the expression of esophageal tumor tissues and adjacent tissues.

Results: The TCGA database and GEO database show that PRDM5 mRNA level in esophageal squamous cell carcinoma adjacent tissues was higher than that of cancer tissues, and ESCC patients with high expression of PRDM5 mRNA had better overall survival. Tissue microarray showed that the protein level of PRDM5 in the adjacent tissues of patients with ESCC was higher than that in cancer tissues, and the expression level of PRDM5 was significantly correlated with the grade of clinicopathological characteristics (P < 0.001). Patients with high expression of PRDM5 displayed a better OS and DFS. Cox regression analysis showed that PRDM5 was an independent risk factor and prognostic factor for ESCC patients (HR: 2.626, 95%CI: 1.824-3.781; P < 0.001). The protein level of PRDM5 matched with the transcriptional level, whereas the DNA methylation affected the transcriptional level. Cibersort showed that T cells CD4 memory resting, mast cells resting, eosinophils, M2 macrophages and mast cells activated were significantly positively correlated with PRDM5 expression (P < 0.05), while regulatory T cells, monocytes and dendritic cells negatively correlated with PRDM5 expression (P < 0.05).

Conclusion: PRDM5 can be used as a biomarker to predict the survival of ESCC patients. Furthermore, PRDM5 expression in ESCC cells may affect WNT/β-catenin signaling pathways, thus further affect the ESCC cell proliferation, migration, and invasion capacity.
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http://dx.doi.org/10.1186/s12885-022-09787-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264607PMC
July 2022

The Molecular Mechanism of Yellow Mushroom () Response to Strong Ultraviolet Radiation on the Qinghai-Tibet Plateau.

Front Microbiol 2022 20;13:918491. Epub 2022 Jun 20.

Test Station for Grassland Improvement, Xining, China.

The Qinghai-Tibet Plateau (QTP) is the highest plateau in the world, and its ultraviolet (UV) radiation is much greater than that of other regions in the world. Yellow mushroom () is a unique and widely distributed edible fungus on the QTP. However, the molecular mechanism of response to strong UV radiation remains unclear. Herein, we reported the 205 environmental adaptation and information processing genes from genome of . In addition, we assembled the RNA sequence of UV-affected at different growth stages. The results showed that in response to strong UV radiation, a total of 11,871 significantly different genes were identified, of which 4,444 genes in the vegetative mycelium (VM) stage were significantly different from the young fruiting bodies (YFB) stage, and only 2,431 genes in the YFB stage were significantly different from fruiting bodies (FB) stage. A total of 225 differentially expressed genes (DEGs) were found to be involved in environmental signal transduction, biochemical reaction preparation and stress response pathway, pigment metabolism pathway, and growth cycle regulation, so as to sense UV radiation, promote repair damage, regulate intracellular homeostasis, and reduce oxidative damage of UV radiation. On the basis of these results, a molecular regulation model was proposed for the response of to strong UV radiation. These results revealed the molecular mechanism of adaptation of adapting to strong UV radiation, and provided novel insights into mechanisms of fungi adapting to extreme environmental conditions on the QTP; the production the riboflavin pigment of the endemic fungi (Yellow mushroom) in the QTP was one of the response to extreme environment of the strong UV radiation.
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http://dx.doi.org/10.3389/fmicb.2022.918491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251379PMC
June 2022

Catalyst-dependent chemoselective insertion of diazoalkanes into the N-H/C-H/O-H/C-O bonds of 2-hydroxybenzothiazoles.

Org Biomol Chem 2022 Jul 6. Epub 2022 Jul 6.

Department of Chemistry, University of Toronto, 80 St George Street, Toronto, Ontario M5S 3H6, Canada.

The control of chemoselective insertions of diazoalkanes into 2-hydroxybenzothiazoles is challenging. Herein, the chemoselective N-H, O-H, C-O or C-H bond insertions of diazoalkanes into 2-hydroxybenzothiazoles are achieved using B(CF), Rh(OAc) or TfOH as the catalyst. This affords routes to 54 benzothiazole derivatives. These protocols are scalable and demonstrate the complementary nature of Lewis acid, transition metal and Brønsted acid catalyses.
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http://dx.doi.org/10.1039/d2ob01048hDOI Listing
July 2022

Correlation between Platelet miRNA Expression and Coagulation Function in Children with Severe Pneumonia.

Evid Based Complement Alternat Med 2022 22;2022:2826115. Epub 2022 Jun 22.

Department of Pediatrics, Hengshui People's Hospital, Hengshui, Hebei, China.

Objective: To investigate the relationship between expression levels of platelet miRNAs and severe pneumonia (SP) in children.

Methods: A randomized controlled trial was conducted in 129 children with SP hospitalized from May 2018 to May 2020. All children joined the study group and were divided into the mild infection group, moderate infection group, and severe infection group according to the diagnostic criteria, 43 cases in each group. Besides, 129 healthy children were selected as the control group. The expression levels of platelet miR-223 and miR-192 were detected by real-time quantitative polymerase chain reaction (qPCR). The prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were detected by the Sysmex CA-1500 System (Sysmex Corporation, Japan). The Pearson analysis was conducted to evaluate the correlation between coagulation function and the levels of miR-223 and miR-192.

Results: Compared with the control group, miR-223 in the study group was significantly higher and miR-192 was significantly lower ( < 0.05). Compared with the mild infection group, miR-223 was significantly higher and miR-192 was significantly lower in the moderate infection group and severe infection group ( < 0.05). Compared with the control group, PT and APTT were significantly lower and FIB was significantly higher in the study group ( < 0.05). Pearson correlation analysis revealed that miR-223 was positively correlated with PT and APTT ( < 0.05) and negatively correlated with FIB ( < 0.05); miR-192 was negatively correlated with PT and APTT ( < 0.05) and positively correlated with FIB ( < 0.05).

Conclusion: miR-223 and miR-192 can reflect coagulation function in children with SP, which can provide a certain reference basis for clinical guidance and treatment and prognosis.
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http://dx.doi.org/10.1155/2022/2826115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242775PMC
June 2022

Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug.

J Adv Res 2022 07 18;39:319-332. Epub 2021 Oct 18.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China; Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. Electronic address:

Introduction: Pharmacokinetic variability in disease state is common in clinical practice, but its underlying mechanism remains unclear. Recently, gut microbiota has been considered to be pharmacokinetically equivalent to the host liver. Although some studies have explored the roles of gut microbiota and host Cyp450s in drug pharmacokinetics, few have explored their effects on pharmacokinetic variability, especially in disease states.

Objectives: In this study, we aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH), and to elucidate the contribution of gut microbiota and host Cyp450s to pharmacokinetic variability in this setting.

Methods: The pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administrations of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol, after which the results were compared with those obtained from the control group. Thereafter, the pharmacokinetic variabilities of all drugs and their relations to the changes in gut microbiota and host Cyp450s were compared and analyzed.

Results: The exposures of all drugs, except metoprolol, significantly increased in the NASH group under intragastric administration. However, no significant increase in the exposure of all drugs, except tolbutamide, was observed in the NASH group under intravenous administration. The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity in the gut microbiota. By contrast, the pharmacokinetic variability of tolbutamide was mainly related to the change in the host Cyp2c65. Notably, gut microbiota and host Cyp450s exerted minimal effects on the pharmacokinetic variability of metoprolol.

Conclusion: Gut microbiota and host Cyp450s co-contribute to the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug. The present findings provide new insights into the explanation of pharmacokinetic variability in disease states.
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http://dx.doi.org/10.1016/j.jare.2021.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263650PMC
July 2022

The Association Between Family Environment and Adolescent Alcohol Drinking Behavior: A Cross-Sectional Study of Six Chinese Cities.

Front Nutr 2022 14;9:903216. Epub 2022 Jun 14.

Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China.

Objective: Adolescents' alcohol consumption has lifetime adverse physical and mental health effects. Family environment factors have a significant influence in shaping adolescents' beliefs and habits. We conducted the multicenter cross-sectional study aiming to investigate the association between family environment factors and adolescent drinking behavior in China.

Methods: The study investigated 27,762 middle school students from Beijing, Shanghai, Guangzhou, Jinan, Chengdu, and Harbin. A logistic regression model was used to explore the association between family environmental factors and adolescent drinking behavior. Participants were asked to self-report previous experiences of drinking and getting drunk to access their drinking status. Factors of family environment related to alcohol consumption included: parents' educational level, family economic status, family composition, the number of times parents drank alcohol in the past 30 days, and parents' attitudes toward their drinking behavior. The logistic regression model was used to adjust the demographic confounders, including gender, age, city, location, and smoking status, and to explore the association between family environmental factors and adolescent alcohol drinking behaviors.

Results: Compared with students whose parents prohibited drinking, students who were approved drinking were more likely to drink in this year ( = < ; Full adjustment: = < ), drink in this month ( = < ; Full adjustment: = < ). In addition, Low family economic status, not living with the mother, parents' ambivalent attitudes toward their children's drinking and parental drinking were risk factors for drinking among middle school students.

Conclusion: The family environment, especially parents' attitudes, is associated with students' drinking and drunken behavior. Mobilizing the power of parents may play a positive role in the effective prevention and control of adolescent drinking.
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http://dx.doi.org/10.3389/fnut.2022.903216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237503PMC
June 2022
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