Publications by authors named "Yuying Zhang"

236 Publications

KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge.

Cell Discov 2022 Jan 25;8(1). Epub 2022 Jan 25.

School of Pharmaceutical Science, Tsinghua-Peking Center for Life Sciences, Tsinghua University; Beijing Advanced Innovation Center for Human Brain Protection, Beijing, China.

KRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS(G12D) variant still lacks inhibitors. Herein, we designed a series of potent inhibitors that can form a salt bridge with KRAS's Asp12 residue. Our ITC results show that these inhibitors have similar binding affinity with both GDP-bound and GTP-bound KRAS(G12D), and our crystallographic studies reveal the structural basis of inhibitor binding-induced switch-II pocket in KRAS(G12D), experimentally confirming the formation of a salt bridge between the piperazine moiety of the inhibitors and the Asp12 residue of the mutant protein. Among KRAS family proteins and mutants, both ITC and enzymatic assays demonstrate the selectivity of the inhibitors for KRAS(G12D); and the inhibitors disrupt the KRAS-CRAF interaction. We also observed the inhibition of cancer cell proliferation as well as MAPK signaling by a representative inhibitor (TH-Z835). However, since the inhibition was not fully dependent on KRAS mutation status, it is possible that our inhibitors may have off-target effects via targeting non-KRAS small GTPases. Experiments with mouse xenograft models of pancreatic cancer showed that TH-Z835 significantly reduced tumor volume and synergized with an anti-PD-1 antibody. Collectively, our study demonstrates proof-of-concept for a strategy based on salt-bridge and induced-fit pocket formation for KRAS(G12D) targeting, which warrants future medicinal chemistry efforts for optimal efficacy and minimized off-target effects.
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http://dx.doi.org/10.1038/s41421-021-00368-wDOI Listing
January 2022

Multi-Omics Characterization of Circular RNA-Encoded Novel Proteins Associated With Bladder Outlet Obstruction.

Front Cell Dev Biol 2021 7;9:772534. Epub 2022 Jan 7.

Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.

Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Totally 3,051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1,414 up-regulated, and 1,637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression levels of five protein-encoding circRNAs were further validated by quantitative RT-PCR and mass spectrometry. The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.
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http://dx.doi.org/10.3389/fcell.2021.772534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8777291PMC
January 2022

Asparagine endopeptidase-targeted Ultrasound-responsive Nanobubbles Alleviate Tau Cleavage and Amyloid-β Deposition in an Alzheimer's Disease Model.

Acta Biomater 2022 Jan 16. Epub 2022 Jan 16.

School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China. Electronic address:

Inhibition of asparagine endopeptidase (AEP) has been implied to be effective for treating tau- and amyloid-beta-mediated neurodegenerative diseases, although a method for targeted intracerebral delivery of AEP inhibitors has not yet been achieved. Here, we fabricated ultrasound-responsive nanobubbles (NBs) to load AEP inhibitor RR-11a, and modified the NB surface with either AEP recognizable peptide AAN or pro-transendothelial transversal motif RGD, i.e. NB(11a)-A and NB(11a)-R, for AEP-targeted treatment of Alzheimer's disease (AD). The developed NBs were uniform, small in size (50.1 ± 1.5 nm), with strong echogenicity and high drug loading efficiency (∼91.97%). When intravenously co-injected in the APP/PS1 mouse model, NB(11a)-R could adhere to endothelial cells and enhance transient opening of the blood-brain barrier (BBB) upon focused ultrasound oscillations, allowing the rest NBs/localized released RR-11a molecules to enter the brain, and then NB(11a)-A could selectively bind with the impaired neurons and deposit RR-11a molecules at the AD lesion. As a result, co-administration of NB(11a)-A and NB(11a)-R significantly promoted accumulation of RR-11a in the mouse brain, and substantially alleviated both tau cleavage and amyloid plaques deposition in the hippocampus. Most strikingly, the cognitive ability of the AD model mice was dramatically improved, achieving a level close to the normal mice. Overall, this unique AEP-targeted nanobubble design provides an efficient intracerebral drug delivery strategy and significantly enhances treatment efficacy of AD. STATEMENT OF SIGNIFICANCE: Asparagine endopeptidase (AEP) is an innovative therapeutic target simultaneously involved in Aβ and tau-mediated Alzheimer's disease (AD) pathology, but targeted delivery of AEP inhibitors has not been achieved yet. Here we developed an efficient strategy to deliver AEP inhibitor RR-11a towards impaired neurons. We fabricated RR-11a-loaded ultrasound-responsive nanobubbles (NBs) and modified the NB surface with RGD peptide to promote BBB crossing upon focused ultrasound oscillations, or with AAN peptide to increase binding of NBs on the neurons. Our results indicated that, co-administration of the NB(11a)-A and NB(11a)-R significantly enhanced accumulation of RR-11a molecules at the AD lesion, alleviated both tau cleavage and amyloid plaques deposition in the hippocampus, and consequently restored cognitive function of the AD model mice.
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http://dx.doi.org/10.1016/j.actbio.2022.01.023DOI Listing
January 2022

Alteration in glycolytic/cholesterogenic gene expression is associated with bladder cancer prognosis and immune cell infiltration.

BMC Cancer 2022 Jan 3;22(1). Epub 2022 Jan 3.

Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China.

Background: Oncogenic metabolic reprogramming contributes to tumor growth and immune evasion. The intertumoral metabolic heterogeneity and interaction of distinct metabolic pathways may determine patient outcomes. In this study, we aim to determine the clinical and immunological significance of metabolic subtypes according to the expression levels of genes related to glycolysis and cholesterol-synthesis in bladder cancer (BCa).

Methods: Based on the median expression levels of glycolytic and cholesterogenic genes, patients were stratified into 4 subtypes (mixed, cholesterogenic, glycolytic, and quiescent) in an integrated cohort including TCGA, GSE13507, and IMvigor210. Clinical, genomic, transcriptomic, and tumor microenvironment characteristics were compared between the 4 subtypes.

Results: The 4 metabolic subtypes exhibited distinct clinical, molecular, and genomic patterns. Compared to quiescent subtype, mixed subtype was more likely to be basal tumors and was significantly associated with poorer prognosis even after controlling for age, gender, histological grade, clinical stage, and molecular phenotypes. Additionally, mixed tumors harbored a higher frequency of RB1 and LRP1B copy number deletion compared to quiescent tumors (25.7% vs. 12.7 and 27.9% vs. 10.2%, respectively, both adjusted P value< 0.05). Furthermore, aberrant PIK3CA expression level was significantly correlated with those of glycolytic and cholesterogenic genes. The quiescent subtype was associated with lower stemness indices and lower signature scores for gene sets involved in genomic instability, including DNA replication, DNA damage repair, mismatch repair, and homologous recombination genes. Moreover, quiescent tumors exhibited lower expression levels of pyruvate dehydrogenase kinases 1-3 (PDK1-3) than the other subtypes. In addition, distinct immune cell infiltration patterns were observed across the 4 metabolic subtypes, with greater infiltration of M0/M2 macrophages observed in glycolytic and mixed subtypes. However, no significant difference in immunotherapy response was observed across the 4 metabolic subtypes.

Conclusion: This study proposed a new metabolic subtyping method for BCa based on genes involved in glycolysis and cholesterol synthesis pathways. Our findings may provide novel insight for the development of personalized subtype-specific treatment strategies targeting metabolic vulnerabilities.
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http://dx.doi.org/10.1186/s12885-021-09064-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8722165PMC
January 2022

Improving the texture properties and protein thermal stability of Antarctic krill (Euphausia superba) by L-lysine marination.

J Sci Food Agric 2021 Dec 25. Epub 2021 Dec 25.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, China.

Background: The quality deterioration of Antarctic krill (Euphausia superba) after thermal processing limits its industrial application. This study sought to improve the texture characteristics of Antarctic krill after heat treatment through pre-soaking using l-lysine (Lys) solution and sodium tripolyphosphate (STPP). Moreover, the effects of Lys on heat-treated Antarctic krill were explored.

Results: Lys significantly reduced the cooking loss and improved the texture characteristics of Antarctic krill during heat treatment. The low-field nuclear magnetic resonance results showed that Lys reduced the water loss of Antarctic krill during heat treatment. Additionally, the surface hydrophobicity, Fourier transform infrared spectroscopy, and endogenous fluorescence spectroscopy results showed that Lys could inhibit the structural damage of Antarctic krill protein under the thermal denaturation condition and enhance the thermal stability of the protein. The scanning electron microscopy results showed that Lys could protect the structural integrity of Antarctic krill muscle fibers during heat treatment.

Conclusion: The cooking loss in the Lys added groups was better than the sodium tripolyphosphate added group, and 2.0% Lys solution could minimize the cooking loss of Antarctic krill. The secondary and tertiary structures of the Antarctic krill protein were actively protected by Lys during heat treatment. Overall, the study will provide insights into the application of Lys in the food industry as a natural additive and an alternative to phosphate. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11741DOI Listing
December 2021

Clinical Experience in Patients with Ocular Burns Treated with Boston Type I Keratoprosthesis Implantation with or Without Prophylactic Ahmed Glaucoma Valve Implantation.

Ophthalmol Ther 2022 Feb 23;11(1):421-434. Epub 2021 Dec 23.

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

Introduction: To compare outcomes in eyes with ocular burns following Boston Type I keratoprosthesis (KPro) implantation with and without prophylactic pars plana tube surgery.

Methods: A retrospective review of patients with ocular burns who underwent KPro surgery at Zhongshan Ophthalmic Center was performed. Twenty-six eyes of 26 patients without a preoperative diagnosis of glaucoma before KPro surgery met the inclusion criteria. Preoperative glaucoma was defined as a history of a durable elevated intraocular pressure (IOP) ≥ 25 mmHg at different time points, which resulted in the introduction of anti-glaucoma medication or surgical intervention. Sixteen eyes underwent KPro alone (Group 1), and 10 eyes received KPro with prophylactic pars plana tube surgery (Group 2).

Results: Group 1 and Group 2 were similar in the proportions of the ocular burn type and preoperative clock hours of peripheral anterior synechiae by ultrasound biomicroscopy (1.88 ± 1.63 vs. 2.30 ± 1.83; P = 0.54). Before KPro surgery, 62.5% of eyes in Group 1 and 50.0% of eyes in Group 2 had intraocular surgeries (P = 0.53). The follow-up time was 18 months. At the final follow-up time, the two groups had similar visual acuity (1.34 ± 0.87 logMAR, 1.03 ± 0.71 logMAR; P = 0.35) and eyes with a C/D ratio ≥ 0.8 (7/16, 2/10; P = 0.21), but more eyes in Group 1 developed glaucoma de novo than eyes in Group 2 (62.5%, 20%; P = 0.04) and had undergone secondary glaucoma surgery after KPro implantation (7/16 vs. 0/10; P = 0.02).

Conclusion: In eyes injured with ocular burns, KPro implantation with prophylactic pars plana tube surgery may be a feasible option to rehabilitate visual acuity and decrease the incidence of glaucoma de novo.
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http://dx.doi.org/10.1007/s40123-021-00446-yDOI Listing
February 2022

Letter to the Editor Regarding "Effectiveness of Continuous Hypertonic Saline in Acute Ischemic Infarcts: A Radiographic and Clinical Evaluation".

World Neurosurg 2022 01;157:242

Department of Neurosurgery, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2021.09.010DOI Listing
January 2022

Characterization of a sulfated fucan-specific carbohydrate-binding module: A promising tool for investigating sulfated fucans.

Carbohydr Polym 2022 Feb 16;277:118748. Epub 2021 Oct 16.

College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China.

Sulfated fucans are important polysaccharides with diverse biological and biomedical activities. Carbohydrate-binding modules (CBMs) could serve as beneficial tools for the investigation of polysaccharides. Nevertheless, no sulfated fucan-binding CBM has been hitherto discovered. In the present study, a novel CBM47 domain was cloned from the marine bacterium Wenyingzhuangia fucanilytica, and heterologously expressed in Escherichia coli. The expressed protein WfCBM47 exhibited a specific binding capacity to sulfated fucans with the backbone composed of 1,3-α-l-fucopyranose residues. Furthermore, a fluorescent probe was successfully constructed by fusing WfCBM47 with a green fluorescent protein, based on which the in situ visualization of sulfated fucan in the sea cucumber (Apostichopus japonicus) body wall was implemented for the first time. The discovery of WfCBM47 provided a promising tool for future investigations on sulfated fucans.
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http://dx.doi.org/10.1016/j.carbpol.2021.118748DOI Listing
February 2022

Cytotoxicity of stabilized/solidified municipal solid waste incineration fly ash.

J Hazard Mater 2022 02 29;424(Pt A):127369. Epub 2021 Sep 29.

Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China. Electronic address:

Low-carbon stabilization/solidification (S/S) is of increasing importance as an option for the treatment of municipal solid waste incineration fly ash (MIFA). This study tailored four binders (e.g., ordinary Portland cement (OPC), calcium aluminate cement (CAC), phosphate-modified OPC, and phosphate-modified CAC) for S/S of MIFA and evaluated the cytotoxicity of treated MIFA by using A549 cell-based in-vitro assay. After S/S treatment, the leachability of Cr, Cu, Zn and Pb from MIFA decreased by 76.1%, 93.4%, 69.6%, and 85.5%, respectively. Spectroscopic analysis indicated that the hydration products determined the immobilization efficiencies of various binders, and strong bonding between metallic cations and phosphate enhanced the immobilization efficiency. The treated MIFA showed significantly lower cellular reactive oxygen species (ROS)-inducing abilities than original MIFA, in which with phosphate-modified OPC treated MIFA showed the lowest ROS levels. Intracellular ROS and multicytotoxicity results also revealed that the treated MIFA not only decreased the cytotoxicity-inducing capability but also enhanced the tolerant dosage of cytotoxicity, in which phosphate-modified S/S treatments showed more effective mitigation (25% less cytotoxicity) than plain cement treatments due to the high-efficiency immobilization of potentially toxic elements. This study develops a pioneering assessment protocol to measure the success of sustainable treatment of MIFA in human health perspective.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127369DOI Listing
February 2022

Structure of cytochrome in complex with Q203 and TB47, two anti-TB drug candidates.

Elife 2021 11 25;10. Epub 2021 Nov 25.

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.

Pathogenic mycobacteria pose a sustained threat to global human health. Recently, cytochrome complexes have gained interest as targets for antibiotic drug development. However, there is currently no structural information for the cytochrome complex from these pathogenic mycobacteria. Here, we report the structures of cytochrome alone (2.68 Å resolution) and in complex with clinical drug candidates Q203 (2.67 Å resolution) and TB47 (2.93 Å resolution) determined by single-particle cryo-electron microscopy. cytochrome forms a dimeric assembly with endogenous menaquinone/menaquinol bound at the quinone/quinol-binding pockets. We observe Q203 and TB47 bound at the quinol-binding site and stabilized by hydrogen bonds with the side chains of Thr and Glu, residues that are conserved across pathogenic mycobacteria. These high-resolution images provide a basis for the design of new mycobacterial cytochrome inhibitors that could be developed into broad-spectrum drugs to treat mycobacterial infections.
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http://dx.doi.org/10.7554/eLife.69418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616580PMC
November 2021

Real-Time Image-Guided Navigation in the Management of Alveolar Cleft Repair.

Cleft Palate Craniofac J 2021 Nov 17:10556656211057744. Epub 2021 Nov 17.

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, 12390Wuhan University, Wuhan, China.

To present the use of dynamic navigation system in the repair of alveolar cleft. A total of three non-syndromic patients with unilateral alveolar cleft were involved in this study. Real-time computer-aided navigation were used to achieve restoration and reconstruction with standardized surgical technique. With the individual virtual 3-dimensional (3-D) modeling based on computed tomography (CT) data, preoperative planning and surgical simulation were carried out with the navigation system. During preoperative virtual planning, the defect volume or the quantity of graft is directly assessed at the surgical region. With the use of this system, the gingival periosteum flap incision can be tracked in real-time, and the bone graft can be navigated under the guidance of the 3-D views until it matches the preoperatively planned position. Three patients with alveolar cleft were successfully performed under navigation guidance. Through the model alignment procedure, accurate matches between the actual intraoperative position and the CT images were achieved within the systematic error of 0.3 mm. The grafted bone was implanted according to the preoperative plan with the aid of instrument- and probe-based navigation. All the patients were healed well without serious complications. These findings suggest that image-guided surgical navigation, including preoperative planning, surgical simulation, postoperative assessment, and computer-assisted navigation was feasible and yielded good clinical outcomes. This dynamic navigation could be proved to be a valuable option for this complicated surgical procedure in the management of alveolar cleft repair.
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http://dx.doi.org/10.1177/10556656211057744DOI Listing
November 2021

Synthetic liver fibrotic niche extracts achieve hepatoblasts phenotype enhancement and expansion.

iScience 2021 Nov 19;24(11):103303. Epub 2021 Oct 19.

Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing 100084, China.

It is still a challenge for synthesizing 'cellular niche-mimics' with satisfactory reproducibility and fidelity to recreate the natural niche components (e.g., extracellular matrices and soluble factors) for stem cell cultivation. Inspired by the massive amplification of hepatic progenitor cells during liver fibrosis , here we optimized the liver fibrotic niches and subsequently harvested their bioactive ingredients as niche extracts (NEs). The fibrosis-relevant NE marginally outperformed Matrigel for phenotype maintenance of human embryonic stem cell (hESC)-derived hepatoblasts (HBs) and recapitulation of the pathological angiogenesis of hESC-derived endothelial cells both in 2D culture and 3D liver organoids. Finally, defined NE components (i.e., collagen III, IV, IL-17, IL-18 and M-CSF) were resolved by the quantitative proteomics which exhibited advantage over Matrigel for multi-passaged HB expansion. The pathology-relevant and tissue-specific NEs provide innovative and generalizable strategies for the discovery of optimal cellular niche and bioactive niche compositions.
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http://dx.doi.org/10.1016/j.isci.2021.103303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571728PMC
November 2021

YTHDF1 promotes the proliferation, migration, and invasion of prostate cancer cells by regulating TRIM44.

Genes Genomics 2021 12 22;43(12):1413-1421. Epub 2021 Oct 22.

Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University (Qingyuan People's Hospital), Qingyuan, 511518, Guangdong, China.

Background: Prostate cancer (PCa) is one of the most common malignancies in men. YTHDF1 may play an important role in promoting PCa progression, but there is no reports to date on YTHDF1 function in PCa.

Objective: This study explored whether YTHDF1 could regulate TRIM44 in PCa cells.

Methods: By querying the TCGA database, we evaluated YTHDF1 expression in PCa, the OS and DFS of YTHDF1, and the correlation between YTHDF1 and TRIM44 in PCa. We constructed vectors to interfere with YTHDF1 expression and overexpress TRIM44 to examine the role of YTHDF1 and TRIM44 in PCa cells. Differentially expressed mRNAs were identified by mRNA sequencing. The levels of YTHDF1, TRIM44, LGR4, SGTA, DDX20, and FZD8 were measured by qRT-PCR and WB was used to determine YTHDF1 and TRIM44 expression. A CCK-8 assay was used to assess cell proliferation. A Transwell chamber assay was used measure cell migration and invasion ability.

Results: YTHDF1 was highly expressed in both Pca tissues and cells. PCa patient prognosis with high YTHDF1 expression was relatively poor. Cell function experiments showed that inhibiting YTHDF1 expression decreased cell proliferation, migration, and invasion. RNA sequencing analysis revealed that YTHDF1 may promote PCa cell proliferation, migration, and invasion by modulating TRIM44 expression. Cell function experiments further verified that YTHDF1 promoted PCa cell proliferation, migration, and invasion by regulating TRIM44.

Conclusions: YTHDF1 enhances PCa cell proliferation, migration, and invasion by regulating TRIM44.
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http://dx.doi.org/10.1007/s13258-021-01175-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606387PMC
December 2021

Brief introduction of machine learning on cSDH patients.

Clin Neurol Neurosurg 2021 Oct 7:106982. Epub 2021 Oct 7.

Department of Neurosurgery, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China. Electronic address:

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http://dx.doi.org/10.1016/j.clineuro.2021.106982DOI Listing
October 2021

Hair follicle-derived mesenchymal stem cells decrease alopecia areata mouse hair loss and reduce inflammation around the hair follicle.

Stem Cell Res Ther 2021 10 21;12(1):548. Epub 2021 Oct 21.

Department of Anatomy and Neurobiology, Xiangya School of Medicine, Central South University, Changsha, China.

Background: Alopecia areata (AA) is a common autoimmune hair loss disease with increasing incidence. Corticosteroids are the most widely used for hair loss treatment; however, long-term usage of hormonal drugs is associated with various side effects. Mesenchymal stem cells (MSCs) therapy has been studied extensively to curb autoimmune diseases without affecting immunity against diseases.

Methods: Hair follicle-derived MSCs (HF-MSCs) were harvested from the waste material of hair transplants, isolated and expanded. The therapeutic effect of HF-MSCs for AA treatment was investigated in vitro AA-like hair follicle organ model and in vivo C3H/HeJ AA mice model.

Results: AA-like hair follicle organ in vitro model was successfully established by pre-treatment of mouse vibrissa follicles by interferon-γ (IFN-γ). The AA-like symptoms were relieved when IFN-γ induced AA in vitro model was co-cultured with HF-MSC for 2 days. In addition, when skin grafted C3H/HeJ AA mice models were injected with 10 HF-MSCs once a week for 3 weeks, the transcription profiling and immunofluorescence analysis depicted that HF-MSCs treatment significantly decreased mouse hair loss and reduced inflammation around HF both in vitro and in vivo.

Conclusions: This study provides a new therapeutic approach for alopecia areata based on HF-MSCs toward its future clinical application.
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http://dx.doi.org/10.1186/s13287-021-02614-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532319PMC
October 2021

Solidification/Stabilization of Arsenic-Containing Tailings by Steel Slag-Based Binders with High Efficiency and Low Carbon Footprint.

Materials (Basel) 2021 Oct 7;14(19). Epub 2021 Oct 7.

Key Laboratory of High-Efficient Mining and Safety of Metal Mines, Ministry of Education, Beijing 100083, China.

The disposal of nonferrous metal tailings poses a global economic and environmental problem. After employing a clinker-free steel slag-based binder (SSB) for the solidification/stabilization (S/S) of arsenic-containing tailings (AT), the effectiveness, leaching risk, and leaching mechanism of the SSB S/S treated AT (SST) were investigated via the Chinese leaching tests HJ/T299-2007 and HJ557-2010 and the leaching tests series of the multi-process Leaching Environmental Assessment Framework (LEAF). The test results were compared with those of ordinary Portland cement S/S treated AT (PST) and showed that the arsenic (As) curing rates for SST and PST samples were in the range of 96.80-98.89% and 99.52-99.2%, respectively, whereby the leached-As concentration was strongly dependent on the pH of the leachate. The LEAF test results showed that the liquid-solid partitioning limit of As leaching from AT, SST, and PST was controlled by solubility, and the highest concentrations of leached As were 7.56, 0.34, and 0.33 mg/L, respectively. The As leaching mechanism of monolithic SST was controlled by diffusion, and the mean observed diffusion coefficient of 9.35 × 10 cm/s was higher than that of PST (1.55 × 10 cm/s). The findings of this study could facilitate the utilization of SSB in S/S processes, replacing cement to reduce CO emissions.
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http://dx.doi.org/10.3390/ma14195864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510415PMC
October 2021

Comparison of clinical-computed tomography model with 2D and 3D radiomics models to predict occult peritoneal metastases in advanced gastric cancer.

Abdom Radiol (NY) 2022 Jan 12;47(1):66-75. Epub 2021 Oct 12.

Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China.

Purpose: To compare the ability of a clinical-computed tomography (CT) model vs. 2D and 3D radiomics models for predicting occult peritoneal metastasis (PM) in patients with advanced gastric cancer (AGC).

Methods: In this retrospective study, we included 49 patients with occult PM and 49 control patients (without PM) who underwent preoperative CT and subsequent surgery between January 2016 and December 2018. Clinical information and CT semantic features were collected, and CT radiomics features were extracted. A predictive clinical-CT model was created using multivariate logistic regression. The least absolute shrinkage and selection operator algorithm and logistic regression were used for constructing 2D and 3D radiomics models. These models were validated with an external cohort (n = 30). Receiver operating characteristics curve with area under the curve (AUC), sensitivity, and specificity were used to evaluate predictive performance.

Results: Tumor size, mild ascites, and serum CA125 were independent factors predictive of occult PM. The clinical-CT model of these independent factors showed better diagnostic performance than 2D and 3D radiomics models. In the external validation cohort, the AUCs of different models were as follows-clinical-CT model: 0.853 (sensitivity, 66.7%; specificity, 93.3%); 2D radiomics model: 0.622 (sensitivity, 80.0%; specificity, 46.7%); and 3D radiomics model: 0.676 (sensitivity, 60.0%; specificity, 86.0%). The clinical-CT model nomogram showed good clinical predictive efficiency to assess occult PM.

Conclusion: The clinical-CT model was better than the radiomics models in predicting occult PM in AGC.
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http://dx.doi.org/10.1007/s00261-021-03287-2DOI Listing
January 2022

Effects of Transcutaneous Electrical Acupoint Stimulation on Stress Response during Intubation and Extubation in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Prospective, Randomized Controlled Trial.

Evid Based Complement Alternat Med 2021 30;2021:1098915. Epub 2021 Sep 30.

Department of Anesthesiology, North China University of Science and Technology Affiliated Hospital, Tangshan 063000, China.

Objective: The study aimed to evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on the stress response during intubation and extubation in patients undergoing video-assisted thoracoscopic surgery (VATS).

Methods: 122 patients undergoing VATS lobectomy were randomly divided into two groups: the TEAS group ( = 62) and the control group ( = 60). Patients in the TEAS group underwent electroacupuncture stimulation of bilateral Neiguan (PC6), Hegu (L14), Lieque (LU7), and Chize (LU5) acupoints from 30 min before anesthesia to the end of surgery. The patients in the control group did not undergo stimulation. The primary endpoints were the hemodynamic parameters and plasma concentrations of epinephrine, norepinephrine, and cortisol. The secondary endpoints were the consumption of remifentanil and propofol, Ramsay sedation score and arousal time, extubation quality score, and postoperative complications.

Results: The hemodynamic variables and plasma concentrations of epinephrine, norepinephrine, and cortisol during intubation and extubation were lower in the TEAS group at T1, T3, and T4 compared with the control group. TEAS led to a reduction in the consumption of remifentanil ( < 0.01), as well as a reduction in the incidence of postoperative complications. The extubation quality score was lower ( < 0.01) while the Ramsay sedation score was higher ( < 0.01) in the TEAS group than in the control group. However, the arousal time and consumption of propofol were not significantly different between the two groups.

Conclusion: TEAS can maintain hemodynamic stability, reduce the stress response during intubation and extubation, improve the quality of anesthesia recovery, and decrease the incidence of postoperative complications in patients undergoing VATS.
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http://dx.doi.org/10.1155/2021/1098915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497099PMC
September 2021

An integrated strategy using LC-MS/MS combined with microdialysis for the simultaneous determination of lignans of (Turcz.) Baill. Fructus and endogenous neurotransmitters: application in pharmacokinetic and pharmacodynamic studies.

Food Funct 2021 Oct 4;12(19):8932-8945. Epub 2021 Oct 4.

School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.

(Turcz.) Baill Fructus (SCF) is the ripe fruit of (Turcz.) Baill, and is often used as a neuroprotective drink. Modern pharmacological studies have shown that lignans are the main bioactive components responsible for neuroprotection and have potential in the treatment of Alzheimer's disease (AD). However, the mechanism of action of SCF in the treatment of AD from the pharmacokinetics-pharmacodynamics (PK-PD) perspective remains not well established. The purpose of this study is to investigate and compare the pharmacokinetic differences of lignans in normal and AD rats, as well as to investigate their effects on neurotransmitters and their role in the treatment of AD. To achieve this goal, an integrated strategy using LC-MS/MS combined with microdialysis for the simultaneous determination of lignans of SCF and endogenous neurotransmitters has been developed and validated. The results show that the pharmacokinetic behaviors of ten lignans in the AD group were significantly different from those in the normal group. The AD group had better absorption and slower elimination than the normal group. In addition, the pharmacodynamic results of the Morris water maze (MWM) test, biochemical tests, histopathological examination, as well as immunohistochemistry analysis showed that lignans could improve the learning and memory of AD rats. The oral administration of SCF could restore the levels of the neurotransmitter parameters; seven neurotransmitters showed clockwise or counterclockwise changes with the four lignans in the hippocampal region. Taken together, the PK and PD studies based on microdialysis sampling might offer novel insights into the mechanisms of action of SCF against AD.
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http://dx.doi.org/10.1039/d1fo01682bDOI Listing
October 2021

Designing novel magnesium oxysulfate cement for stabilization/solidification of municipal solid waste incineration fly ash.

J Hazard Mater 2022 Feb 25;423(Pt A):127025. Epub 2021 Aug 25.

Department of Civil and Environmental Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.

Municipal solid waste incineration (MSWI) fly ash is a typical hazardous waste worldwide. In this study, an innovative magnesium oxysulfate cement (MOSC) binder was designed for stabilization/solidification (S/S) of MSWI fly ash, focusing on the interactions between MOSC binder and typical metallic cations (Pb)/oxyanions (AsO). Experimental results showed that Pb and As slightly inhibited the reaction of high-sulfate 5MS system but significantly suppressed the reaction process of low-sulfate 10MS system. The 5MS binder system exhibited excellent immobilization efficiencies (99.8%) for both Pb and As. The extended X-ray absorption fine structure spectra suggested that Pb coordinated with SO/OH in the MOSC system and substituted Mg ion sites in the internal structure of 5Mg(OH)·MgSO.7HO (5-1-7) phase. In contrast, the AsO substituted SO sites with the formation of inner-sphere complexes with Mg in the large interlayer space of the 5-1-7 structure. Subsequent MSWI fly ash S/S experiments showed that a small amount of reactive Si in MSWI fly ash interfered with the MOSC reaction and adversely influenced the immobilization efficiencies of Pb, As, and other elements. Through the use of 33 wt% tailored MOSC binder for MSWI fly ash treatment, a satisfying S/S performance could be achieved.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127025DOI Listing
February 2022

Knockdown of LINC01123 inhibits cell viability, migration and invasion via miR-361-3p/TSPAN1 targeting in cervical cancer.

Exp Ther Med 2021 Oct 16;22(4):1184. Epub 2021 Aug 16.

Department of Gynecology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China.

Cervical cancer (CC) is a type of gynecological malignancy that poses a significant threat to females. The aim of the present study was to examine the role of long intergenic non-protein coding RNA 1123 (LINC01123) and its underlying molecular mechanism in the development of CC. mRNA expression levels of LINC01123 and microRNA (miR)-361-3p in CC tissue samples and cell lines were evaluated using reverse transcription-quantitative PCR. Cell viability, migration and invasion were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing and Transwell assays. Moreover, a xenograft tumor model was established for elucidating the influence of LINC01123 knockdown on tumor growth . A dual-luciferase reporter assay was used to confirm the association between LINC01123 and miR-361-3p, and miR-361-3p and tetraspanin 1 (TSPAN1). Western blot analysis was used to determine TSPAN1 protein expression. LINC01123 expression was upregulated and miR-361-3p expression was reduced in CC tissue samples and cell lines. Knockdown of LINC01123 inhibited cell viability, migration and invasion , and suppressed tumor growth . Furthermore, LINC01123 targeted miR-361-3p and negatively regulated miR-361-3p expression. Overexpression of miR-361-3p inhibited cell viability, migration and invasion in HeLa and CaSki cells. Additionally, miR-361-3p targeted TSPAN1 and negatively regulated TSPAN1 expression. Inhibition of miR-361-3p and overexpression of TSPAN1 reversed the effect of LINC01123 knockdown on cell proliferation, migration and invasion in HeLa cells. Knockdown of LINC01123 inhibited cell proliferation, migration and invasion via miR-361-3p/TSPAN1 regulation in CC, which may present an effective target for treatment of CC.
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http://dx.doi.org/10.3892/etm.2021.10618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406679PMC
October 2021

Association between FGF19, FGF21 and lipocalin-2, and diabetes progression in PCOS.

Endocr Connect 2021 Sep 28;10(10):1243-1252. Epub 2021 Sep 28.

Department of Medicine and Therapeutics The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Women with polycystic ovary syndrome (PCOS) have an increased risk of developing type 2 diabetes. FGF19, FGF21 and lipocalin-2 have emerged as important markers of metabolic risk. This study aims to compare the levels of FGF19, FGF21 and lipocalin-2 between subjects with or without PCOS, and to investigate the relationship between proteins and diabetes progression. In this nested case-control cohort study, 128 Chinese PCOS women and 128 controls were recruited and followed-up. All subjects underwent the oral glucose tolerance test for the evaluation of glycaemic status. Baseline serum protein levels were measured using ELISA. Compared with controls, PCOS subjects had higher levels of FGF19 (P < 0.001) and FGF21 (P = 0.022), but had lower lipocalin-2 (P < 0.001). In total, 20.8% of PCOS and 9.2% of controls developed diabetes over a mean duration of 10.4 ± 1.2 and 11.3 ± 0.5 years, respectively. Logistic regression analyses suggested FGF19 was positively associated with diabetes progression in controls, after adjusting for age, follow-up duration, waist and fasting glucose (P = 0.026, odds ratio (OR) (95% CI): 7.4 (1.3-43.6)), and the positive relationship between FGF21 and diabetes progression in controls was attenuated by adjusting for age and follow-up duration (P = 0.183). Lipocalin-2 was positively correlated with diabetes progression in PCOS group (P = 0.026, OR (95% CI)): 2.5 (1.1-5.6)); however, this became attenuated after adjusting for waist and fasting glucose (P = 0.081). In conclusion, there is differential expression of FGF19, FGF21, and lipocalin-2 in PCOS. The serum level of FGF19, and FGF21 is associated with diabetes progression in women without PCOS, while lipocalin-2 was related to diabetes progression in PCOS women.
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http://dx.doi.org/10.1530/EC-21-0082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494400PMC
September 2021

N6-Methylandenosine-Related lncRNAs Predict Prognosis and Immunotherapy Response in Bladder Cancer.

Front Oncol 2021 11;11:710767. Epub 2021 Aug 11.

Department of Urology, The Sixth Affiliated Hospital of Guangzhou Medical University (Qingyuan People's Hospital), Qingyuan, China.

Both lncRNAs and the N6-methyladenosine (m6A) modification are key regulators of tumorigenesis and innate immunity. However, little is known about the m6A modification of lncRNAs and their clinical and immune relevance in bladder cancer. In this study, we identified m6A-related lncRNAs using Pearson correlation analysis in The Cancer Genome Atlas (TCGA) and the IMvigor210 datasets. Next, univariate Cox regression was performed using the TCGA dataset to filter prognostic m6A-related lncRNAs, which were further subjected to the least absolute shrinkage and selection operator (LASSO) Cox regression to establish a 12 m6A-related lncRNA prognostic score (m6A-LRS). The m6A-LRS was validated in the IMvigor210 dataset. In addition, high m6A-LRS tumors, characterized by decreased tumor mutation load and neoantigen load, showed poorer response to immunotherapy than those with low m6A-LRS in the IMvigor210 dataset. Further, we constructed an m6A-LRS-based nomogram that demonstrated a strong ability to predict overall survival in patients with bladder cancer. Moreover, enrichment analysis revealed that tumor-associated biological processes, oncogenic signaling, and tumor hallmarks were commonly associated with a high m6A-LRS. Gene set variation analysis also indicated that high m6A-LRS was associated with activation of canonical oncogenic signatures, such as the epithelial-to-mesenchymal transition, cell cycle regulators, and DNA replication, as well as activation of immunosuppressive signatures, such as the T-cell exhaustion and pan-fibroblast-TGF-β response signatures. Furthermore, we observed distinct tumor microenvironment cell infiltration characteristics between high- and low-risk tumors. High m6A-LRS tumors showed reduced infiltration of CD8+ T-cells and enhanced infiltration of macrophages and fibroblasts. Additionally, we established a competing endogenous RNA network based on the12 m6A-related lncRNAs. Finally, three lncRNAs (SNHG16, SBF2-AS1, and BDNF-AS) were selected for further validation. The qualitative PCR assay on 10 pairs of bladder cancer and adjacent normal control samples validated the differential expression, and methylated RNA immunoprecipitation (MeRIP) analysis demonstrated a robust m6A enrichment in T24 bladder cancer cells compared with normal uroepithelial cells (SVHUC-1). In conclusion, this study introduced an m6A-related lncRNA signature that identified a subgroup of patients with poor prognoses and suboptimal immune responses, thus providing novel approaches for treatment response prediction and patient stratification in bladder cancer.
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http://dx.doi.org/10.3389/fonc.2021.710767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387102PMC
August 2021

Cloning, Heterologous Expression, and Characterization of a βκ-Carrageenase From Marine Bacterium : A Specific Enzyme for the Hybrid Carrageenan-Furcellaran.

Front Microbiol 2021 4;12:697218. Epub 2021 Aug 4.

College of Food Science and Engineering, Ocean University of China, Qingdao, China.

Carrageenan is a group of important food polysaccharides with high structural heterogeneity. Furcellaran is a typical hybrid carrageenan, which contains the structure consisted of alternative β-carrageenan and κ-carrageenan motifs. Although several furcellaran-hydrolyzing enzymes have been characterized, their specificity for the glycosidic linkage was still unclear. In this study, we cloned, expressed, and characterized a novel GH16_13 furcellaran-hydrolyzing enzyme Cgbk16A_Wf from the marine bacterium CZ1127. Cgbk16A_Wf exhibited its maximum activity at 50°C and pH 6.0 and showed high thermal stability. The oligosaccharides in enzymatic products were identified by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. It was confirmed that Cgbk16A_Wf specifically cleaves the β-1,4 linkages between β-carrageenan and κ-carrageenan motifs from non-reducing end to reducing end. Considering the structural heterogeneity of carrageenan and for the unambiguous indication of the specificity, we recommended to name the furcellaran-hydrolyzing activity represented by Cgbk16A as "βκ-carrageenase" instead of "furcellaranase".
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http://dx.doi.org/10.3389/fmicb.2021.697218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371452PMC
August 2021

Utilizing heterologously overexpressed endo-1,3-fucanase to investigate the structure of sulfated fucan from sea cucumber (Holothuria hilla).

Carbohydr Polym 2021 Nov 24;272:118480. Epub 2021 Jul 24.

College of Food Science and Engineering, Ocean University of China, 5 Yushan Road, Qingdao 266003, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.

Sea cucumber sulfated fucan (SC-FUC) attracted increasing interests in the recent decades. Endo-1,3-fucanase has been employed in the structural clarification and structure-function relationship investigations of SC-FUC. Nevertheless, the preparation of wild-type endo-1,3-fucanase is costly and time-consuming, which hinders its further utilization. In this study, a heterologously overexpressed endo-1,3-fucanase (FunA) was introduced into structural identification of SC-FUC. FunA was efficiently prepared within one day and utilized in the investigation of sulfated fucan from sea cucumber Holothuria hilla (Hh-FUC). By using enzymatic degradation, glycomics and NMR analysis, the major structure of Hh-FUC was identified to be composed of a tetrasaccharide repeating unit →3-α-l-Fucp-1 → 3-α-l-Fucp2,4(OSO)-1 → 3-α-l-Fucp2(OSO)-1 → 3-α-l-Fucp2(OSO)-1→. Due to the efficient acquisition of enzyme and the superior oligosaccharide recovery, 0.6 mL of E. coli broth and 10 mg of Hh-FUC were sufficient for the structural identification. The results demonstrated the superiority of heterologously overexpressed fucanase over its wild-type enzyme in structural investigation of sulfated fucan.
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http://dx.doi.org/10.1016/j.carbpol.2021.118480DOI Listing
November 2021

Status of antibiotic residues and detection techniques used in Chinese milk: A systematic review based on cross-sectional surveillance data.

Food Res Int 2021 09 31;147:110450. Epub 2021 May 31.

Department of Neurosurgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.

Antibiotic residues (ARs) in food of animal origin are of worldwide concern, particularly in China, the world's largest producer and consumer of antibiotics. Aiming to provide a reference for the use of antibiotics in dairy cows, for supervision and management departments in the detection of related antibiotics, and for guiding the safe use of antibiotics in food, this systematic review was carried out to determine the prevalence of ARs and antibiotic detection techniques in Chinese milk over the past three decades. The systematic review follows the PRSIMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Both English (Cochrane, Embase, MEDLINE, PubMed, and Web of Science) and Chinese databases (Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, and WanFang Database) were systematically searched, from inception to 31 July 2020. Among the 3131 citations screened, 46 active surveillance cross-sectional studies published between 1988 and 2020 in 26 Chinese provinces were eligible, providing antibiotic levels for a total of 8788 milk samples. Although the AR rates in fresh and sterilized milk fluctuate, they have largely declined in recent years. Among the 18 evaluated antibiotics, sulfamethoxazole, chloramphenicol, and trimethoprim are primary antibiotics with high residual rates. The most frequently used technique to monitor antibiotic levels in milk is 2,3,5-Triphenyltetrazolium chloride (TTC) staining. This review confirmed the importance of food safety monitoring and surveillance systems in preventing antibiotic exceedances in food. Several lessons learned from antibiotic surveillance and supervision in China were revealed. The provision of education to rural farmers should be strengthened to enhance their knowledge on antibiotic use in animal agriculture. Moreover, a standard operational protocol for screening and targeting antibiotics in dairy products should be considered to increase the comparability between cross-sectional active surveillance studies of AR in milk.
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http://dx.doi.org/10.1016/j.foodres.2021.110450DOI Listing
September 2021

Based on urine metabolomics to study the mechanism of Qi-deficiency affecting type 2 diabetes rats using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Aug 7;1179:122850. Epub 2021 Jul 7.

School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China. Electronic address:

Qi-deficiency also called energy deficiency, which approximates to the term of sub-health in contemporary medical theory. Diabetes is similar to the symptoms of "xiaoke" in traditional Chinese medicine (TCM) which is linked with Qi-deficiency. However, the mechanism of Qi-deficiency on type 2 diabetes (T2D) has not been completely elucidated. In this study, a model on Qi-deficiency T2D rat was established by using diet with high fat and high sugar and small-dose STZ induction combined with exhaustive swimming, and the model was evaluated by pathological section, hematological index and serum biochemical parameters. Applying urine metabolomics based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to explore the underlying molecular mechanism of Qi-deficiency on T2D and 32 urinary metabolites were identified as prospective biomarkers for Qi-deficiency T2D rats. Metabolic pathway analysis indicated that synthesis and degradation of ketone bodies, starch and sucrose metabolism, phenylalanine metabolism, arachidonic acid metabolism, butanoate metabolism and TCA cycle, etc., were closely related to potential mechanisms of Qi-deficiency on T2D. The metabolomics results can provide reliable data support for complex TCM syndrome diagnosis.
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http://dx.doi.org/10.1016/j.jchromb.2021.122850DOI Listing
August 2021

Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels.

Nat Commun 2021 07 30;12(1):4621. Epub 2021 Jul 30.

State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, China.

Cytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we have determined the 2.8 Å structure of Mycobacterium smegmatis cytochrome bd by single-particle cryo-electron microscopy. This bd oxidase consists of two subunits CydA and CydB, that adopt a pseudo two-fold symmetrical arrangement. The structural topology of its Q-loop domain, whose function is to bind the substrate, quinol, is significantly different compared to the C-terminal region reported for cytochromes bd from Geobacillus thermodenitrificans (G. th) and Escherichia coli (E. coli). In addition, we have identified two potential oxygen access channels in the structure and shown that similar tunnels also exist in G. th and E. coli cytochromes bd. This study provides insights to develop a framework for the rational design of antituberculosis compounds that block the oxygen access channels of this oxidase.
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http://dx.doi.org/10.1038/s41467-021-24924-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324918PMC
July 2021

MiR-29ab1 Cluster Resists Muscle Atrophy Through Inhibiting MuRF1.

DNA Cell Biol 2021 Sep 13;40(9):1167-1176. Epub 2021 Jul 13.

The State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, China.

Skeletal muscle has great plasticity. An increase in protein degradation can cause muscle atrophy. Atrogin-1 and muscle ring finger-1 (MuRF1) are dramatically upregulated in various muscle atrophy. Inhibition of Atrogin-1 and MuRF1 protects against muscle atrophy. MiR-29 plays an important regulatory role in skeletal muscle development. However, the function of miR-29 in skeletal muscle protein metabolism is not clear. To investigate the function of miR-29, we generated miR-29 knockout mice and the miR-29ab1 cluster overexpression mice. The disruption of miR-29 led to severe atrophy of skeletal muscle during puberty, and the muscle-specific overexpression of the miR-29ab1 cluster protected against denervation-induced and fasting-induced muscle atrophy. Furthermore, the overexpression of miR-29a, b mimics in myotubes resisted the muscle atrophy. MuRF1 was the direct target gene of miR-29a, b. These results demonstrate that miR-29ab1 cluster plays a critical role in the maintenance of skeletal muscle. MiR-29ab1 cluster is the excellent inhibitor of MuRF1, ultimately indicating that miR-29ab1 cluster is good therapeutic molecule candidate for adulthood.
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http://dx.doi.org/10.1089/dna.2021.0267DOI Listing
September 2021

The clinical value of blood flow parameters of the umbilical artery and middle cerebral artery for assessing fetal distress.

Am J Transl Res 2021 15;13(5):5280-5286. Epub 2021 May 15.

Department of Ultrasound, Qinghai Provincial People's Hospital Xining, Qinghai, P. R. China.

Objective: To explore the clinical value of blood flow parameters of the umbilical artery (UA) and middle cerebral artery (MCA) for gauging fetal distress.

Methods: This study was conducted among 256 pregnant women who presented for routine prenatal checkups and successfully gave birth in our hospital from January 2018 to February 2020. These pregnant women were examined with the Color Doppler Ultrasound, and the color Doppler flow imaging (CDFI) showed the blood flow of the UA and MCA. In accordance with the diagnostic criteria of fetal distress, they were divided into a fetal distress group (n=67) and a control group (n=189). The receiver operator characteristic (ROC) curve analysis was performed on the diagnostic value of the flow in the UA and MCA. According to their pregnancy outcomes, they were divided into a good pregnancy outcome group (n=209) and an adverse pregnancy outcome group (n=47), and their blood flow parameters of the UA and MCA were compared.

Results: The S/D, PI, and RI values of the UA in the fetal distress group exceeded those in the control group, and the S/D, PI, and RI values of the MCA were lower than those in the control group (P<0.05). The good pregnancy outcome group had lower S/D, PI, and RI values of the UA. The good pregnancy outcome group had higher S/D, PI, and RI values of the MCA (P<0.05). ROC curves revealed that the areas under curve of S/D, PI, and RI of the UA were 0.81, 0.76 and 0.74, respectively; the areas under curve of S/D, PI, and RI of the MCA were 0.82, 0.78 and 0.71, respectively.

Conclusion: The hemodynamic indexes of the UA and MCA can be used as a basis for evaluating fetal distress, which shows important clinical indications for gauging pregnancy outcome.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205796PMC
May 2021
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