Publications by authors named "Juan Liu"

2,071 Publications

  • Page 1 of 1

Transmembrane Protein ANTXR1 Regulates -Globin Expression by Targeting the Wnt/-Catenin Signaling Pathway.

J Immunol Res 2022 30;2022:8440422. Epub 2022 Jul 30.

School of Medicine, Guizhou University, Guiyang, Guizhou 550025, China.

Reactivation of fetal hemoglobin (HbF, 22) alleviates clinical symptoms in patients with -thalassemia and sickle cell disease, although the regulatory mechanisms of -globin expression have not yet been fully elucidated. Recent studies found that interfering with the expression of the membrane protein ANTXR1 gene upregulated -globin levels. However, the exact mechanism by which ANTXR1 regulates -globin levels remains unclear. Our study showed that overexpression and knockdown of ANTXR1 in K562, cord blood CD34, and HUDEP-2 cells decreased and increased -globin expression, respectively. ANTXR1 regulates the reactivation of fetal hemoglobin (HbF, 22) in K562, cord blood CD34, and adult peripheral blood CD34 cells through interaction with LRP6 to promote the nuclear entry of -catenin and activate the Wnt/-catenin signaling pathway. The overexpression or knockdown of ANTXR1 on -globin and Wnt/-catenin signaling in K562 cells was reversed by the inhibitor XAV939 and the activator LiCl, respectively, where XAV939 inhibits the transcription of -catenin in the Wnt pathway, but LiCl inhibits GSK3-. We also showed that the binding ability of the rank4 site in the transcriptional regulatory region of the SOX6 gene to c-Jun was significantly increased after overexpression of ANTXR1 in K562 cells. SOX6 protein expression was increased significantly after overexpression of the c-Jun gene, indicating that the transcription factor c-Jun initiated the transcription of SOX6, thereby silencing -globin. Our findings may provide a new intervention target for the treatment of -hemoglobinopathies.
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http://dx.doi.org/10.1155/2022/8440422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356848PMC
August 2022

Effects of Electroacupuncture with Different Waveforms on Chronic Prostatitis/Chronic Pelvic Pain Syndromes: A Randomized Controlled Trial.

Contrast Media Mol Imaging 2022 13;2022:6866000. Epub 2022 Jul 13.

The Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 358 Daotong Road, Pudong New Area, Shanghai 200137, China.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in adult men. Evidence has demonstrated that acupuncture is effective for treating CP/CPPS. Electroacupuncture (EA) is a combination of traditional acupuncture and electrical stimulation, and the waveform is one of the key factors influencing EA effects. Different waveforms contain different stimulating parameters, thus generating different effects. However, the effects of different waveforms of EA on CP/CPPS remain unclear and there is no recommended standard for the application of EA waveforms. At the same time, the waveform prescription of CP/CPPS is also different, so exploring the influence of different waveforms on CP/CPPS patients will also provide a certain treatment basis for clinical treatment. A total of 108 eligible patients were recruited from the Seventh People's Hospital affiliated to the Shanghai University of Traditional Chinese Medicine from March 18, 2021, to January 31, 2022, according to inclusion and exclusion criteria. All subjects were randomly divided into three groups (continuous wave 4 Hz, continuous wave 20 Hz, and extended wave 4/20 Hz) in a ratio of 1 : 1 : 1. Patients in all three groups were treated for the same duration of 20 minutes, with intervention twice a week for 4 weeks. The changes in chronic prostatitis index (NIH-CPSI), erectile function index 5 (IIEF-5), Hospital Anxiety and Depression Scale (HADS), and NIH-CPSI response rate in three groups were compared after the intervention, and the occurrence of adverse events in patients during treatment was observed. After 4 weeks of treatment, the CP/CPPS response rates were 66.7%, 62.5%, and 88.2% in the 4 Hz, 20 Hz, and 4/20 Hz groups, respectively. The reaction rate of CP / CPPS in 4 / 20 Hz group was higher than that in 4 Hz group and 20 Hz group. ( < 0.05). During treatment, the difference between NIH-CPSI scores between 4 Hz and 4/20 Hz was insignificant ( > 0.05). NIH-CPSI scores were lower in the 4/20 Hz group than in the 4 Hz and 20 Hz groups ( < 0.05). After treatment, there was no significant difference in the pain and discomfort subscales ( > 0.05) between the 4 Hz and 20 Hz groups and there were significantly lower pain and discomfort scores in the 4/20 Hz group ( < 0.05) compared to the 4 Hz and 20 Hz groups. There was no significant difference in the reduction of urination symptoms and quality of life among the three groups ( > 0.05). Compared with before treatment, IIEF-5 scores of the three groups were improved ( < 0.05). After treatment, there was no significant difference between the IIEF-5 scores in 4 Hz and 20 Hz ( > 0.05), while the IIEF-5 score in 4/20 Hz was significantly higher than that in 4 Hz and 20 Hz, and the change was significant ( < 0.05). The HADS scores decreased in all the three groups ( < 0.05), but there was no significant difference in HADS scores between the three groups ( > 0.05). Adverse events were mild and transient, and no serious adverse events occurred in each group. Both the expansive and continuous waveforms of EA can effectively alleviate symptoms such as prostatitis, erectile dysfunction, anxiety, and depression in patients with CP/CPPS. Expansion waves are superior to continuous waves in improving erectile function and pain symptoms in chronic prostatitis and can be used as a preferred waveform for the treatment of CP/CPPS. This trial is registered with Chinese Clinical Trial Registry, ChiCTR2100044418.
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http://dx.doi.org/10.1155/2022/6866000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300282PMC
August 2022

Attitudes and opinions about ecopharmacovigilance from multi-disciplinary perspectives: a cross-sectional survey among academic researchers in China.

Environ Sci Pollut Res Int 2022 Aug 5. Epub 2022 Aug 5.

Hubei Province Woman and Child Hospital, Wuhan, China.

As a promising upstream strategy to reduce the environmental loads of pharmaceutical emerging contaminants (PECs) through source control, ecopharmacovigilance (EPV) is concerned with the set of activities to identify, evaluate, understand, and prevent against diverse PEC-related problems, and has been accepted as a multi-disciplinary and multi-stakeholder system. This cross-sectional observational survey aimed to assess the attitudes and opinions about EPV from multi-disciplinary perspectives among Chinese academic professors from four main EPV-related disciplines including pharmacy, management, clinical medicine, and environmental and ecological science based on a self-developed questionnaire. Forty-two usable survey instruments were acquired. Results showed that the responding Chinese academic researchers from different disciplines expressed consistently positive attitudes and strong intentions for EPV, in spite of several disparities existing among disciplinary groups showing that pharmacy and medical researchers felt more certain of the environmental adverse effects of PECs, and researchers in pharmacy and environmental and ecological science were more interested in EPV. A multi-disciplinary consensus was achieved in regard to the types of key stakeholders in EPV practices including the pharmaceutical manufacturers, the public, the drug safety authority, hospitals, and the environmental protection agency. The main roles and responsibilities of each stakeholder identity in EPV practices were summarized based on the expert opinions.
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http://dx.doi.org/10.1007/s11356-022-22406-0DOI Listing
August 2022

lncRNA-GM targets Foxo1 to promote T cell-mediated autoimmunity.

Sci Adv 2022 Aug 5;8(31):eabn9181. Epub 2022 Aug 5.

Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.

RNA-RBP interaction is important in immune regulation and implicated in various immune disorders. The differentiation of proinflammatory T cell subset T17 and its balance with regulatory T cell (T) generation is closely related to autoimmune pathogenesis. The roles of RNA-RBP interaction in regulation of T17/T differentiation and autoinflammation remain in need of further investigation. Here we report that lncRNA-GM polarizes T17 differentiation but inhibits iT differentiation by reducing activity of Foxo1, a transcriptional factor that is important in inhibiting T17 differentiation but promoting T generation. -deficient mice were protected from experimental autoimmune encephalomyelitis. Mechanistically, lncRNA-GM directly binds to cytoplasmic Foxo1, thus inhibiting its activity through blocking dephosphorylation of Foxo1 by phosphatase PP2A to promote transcription. The human homolog of lncRNA-GM (AK026392.1) also polarizes human T17 differentiation. Our study provides mechanistic insight into the interaction of lncRNA and transcriptional factor in determining T cell subset differentiation during T cell-mediated autoimmune diseases.
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http://dx.doi.org/10.1126/sciadv.abn9181DOI Listing
August 2022

[Association of polymorphisms of VEGF and VEGFR1 pathways related genes and risk of pre-eclampsia].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Aug;39(8):893-897

Department of Gynecology and Oncology, Xinxiang Central Hospital, Xinxiang, Henan 453000, China.

Objective: To assess the association of single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 1 (VEGFR1) pathways-related genes and the risk of pre-eclampsia.

Methods: In total 178 pregnant women with pre-eclampsia (case group) and 100 healthy pregnant women (control group) during the third trimester were enrolled. The SNPs of VEGF rs3025039, rs2010963 and VEGFR1 rs3812867, rs55875014 and rs722503 loci were determined by PCR-restriction fragment length polymorphism (PCR-RFLP) assay. The levels of serum VEGF and sVEGFR1 were also determined. And their association with pre-eclampsia was analyzed.

Results: The systolic blood pressure, diastolic blood pressure and sVEGFR1 of the case group were significantly higher than those of the control group, while the VEGF level was significantly lower than that in the control group (P<0.05). Allelic frequencies of the VEGF (rs3025039, rs2010963) and VEGFR1 (rs3812867, rs55875014, rs722503) have fit the Hardy-Weinberg equilibrium (P>0.05). The frequency of T allele of VEGF at rs3025039 locus in the case group was higher than that in the control group (P<0.05). There were significant differences in VEGF at rs3025039 locus under dominant and co-dominant models in case group (P<0.05). Compared with those with CC, the risk was higher in patients with CT or TT genotypes (P<0.05). The systolic and diastolic blood pressure and sVEGFR1 in pre-eclampsia pregnant women with CT or TT genotypes were significantly higher than those with the CC genotype, while their VEGF level was significantly lower (P<0.05). No significant difference was found in allelic frequencies of other four loci between the two groups (P>0.05).

Conclusion: Polymorphisms of rs3025039 locus of VEGF gene is associated with the occurrence of pre-eclampsia. The variant at this locus may affect the activity of VEGF and influence the development of pre-eclampsia.
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http://dx.doi.org/10.3760/cma.j.cn511374-20210623-00534DOI Listing
August 2022

Dietary compounds in modulation of gut microbiota-derived metabolites.

Front Nutr 2022 19;9:939571. Epub 2022 Jul 19.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Gut microbiota, a group of microorganisms that live in the gastrointestinal tract, plays important roles in health and disease. One mechanism that gut microbiota in modulation of the functions of hosts is achieved through synthesizing and releasing a series of metabolites such as short-chain fatty acids. In recent years, increasing evidence has indicated that dietary compounds can interact with gut microbiota. On one hand, dietary compounds can modulate the composition and function of gut microbiota; on the other hand, gut microbiota can metabolize the dietary compounds. Although there are several reviews on gut microbiota and diets, there is no focused review on the effects of dietary compounds on gut microbiota-derived metabolites. In this review, we first briefly discussed the types of gut microbiota metabolites, their origins, and the reasons that dietary compounds can interact with gut microbiota. Then, focusing on gut microbiota-derived compounds, we discussed the effects of dietary compounds on gut microbiota-derived compounds and the following effects on health. Furthermore, we give our perspectives on the research direction of the related research fields. Understanding the roles of dietary compounds on gut microbiota-derived metabolites will expand our knowledge of how diets affect the host health and disease, thus eventually enable the personalized diets and nutrients.
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http://dx.doi.org/10.3389/fnut.2022.939571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343712PMC
July 2022

Overexpression of miR-651-5p inhibits ultraviolet radiation-induced malignant biological behaviors of sebaceous gland carcinoma cells by targeting .

Ann Transl Med 2022 May;10(9):517

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, China.

Background: Ultraviolet (UV) exposure is the most essential etiological factor in sebaceous gland carcinoma (SGC). The abnormal expression of microRNAs (miRNAs) is also involved in SGC. However, the function of miRNAs in UV-induced SGC is still unclear.

Methods: In this study, the expression levels of miR-651-5p and zinc finger E-box binding homeobox 2 () in SGC tissues and cells were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. Then, the effects of miR-651-5p on the apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) of UV-induced SGC cells were determined. The interactions between miR-651-5p and were verified by a dual-luciferase reporter assay. An tumor growth assay was performed to assess tumorigenicity.

Results: The results showed that there was abnormal expression of miR-651-5p and in SGC tissues and cells compared with the control tissues and cells. Overexpression of miR-651-5p and knockdown of inhibited the malignant biological behaviors of SGC cells. Moreover, is one of the target genes of miR-651-5p, and the expression of was negatively regulated by miR-651-5p in SGC cells. Further studies showed that overexpression of miR-651-5p promoted cell apoptosis and inhibited the cell invasion and migration ability and EMT of UV-induced SGC cells by downregulating the expression of ZEB2 and .

Conclusions: This study revealed that overexpression of miR-651-5p inhibited UV-induced SGC growth and metastasis by suppressing , which may be a potential target for SGC prevention and therapy.
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http://dx.doi.org/10.21037/atm-21-3897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347044PMC
May 2022

LIM Mineralization Protein-1 Enhances the Committed Differentiation of Dental Pulp Stem Cells through the ERK1/2 and p38 MAPK Pathways and BMP Signaling.

Int J Med Sci 2022 18;19(8):1307-1319. Epub 2022 Jul 18.

Department of Stomatology, Jinling Hospital, Medical School of Nanjing University, School of Stomatology of Southern Medical University, Clinical Medical School of Nanjing Medical University, Nanjing 210002, China.

Tissue regeneration is the preferred treatment for dentin and bone tissue defects. Dental pulp stem cells (DPSCs) have been extensively studied for their use in tissue regeneration, including the regeneration of dentin and bone tissue. LIM mineralization protein-1 (LMP-1) is an intracellular non-secretory protein that plays a positive regulatory role in the mineralization process. In this study, an LMP-1-induced DPSCs model was used to explore the effect of LMP-1 on the proliferation and odonto/osteogenic differentiation of DPSCs, as well as the underlying mechanisms. As indicated by the cell counting kit-8 assay, the results showed that LMP-1 did not affect the proliferation of DPSCs. Overexpression of LMP-1 significantly promoted the committed differentiation of DPSCs and vice versa, as shown by alkaline phosphatase activity assay, alizarin red staining, western blot assay, quantitative real-time polymerase chain reaction assay, and mineralized tissue formation assay. Furthermore, inhibiting the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways using specific pathway inhibitors showed that the ERK1/2 and p38 MAPK pathways attenuated the differentiation of DPSCs. Besides, the expression of BMP signaling pathway components were also determined, which suggested that LMP-1 could activate BMP-2/Smad1/5 signaling pathway. Our results not only indicated the underlying mechanism of LMP-1 treated DPSCs but also provided valuable insight into therapeutic strategies in regenerative medicine.
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http://dx.doi.org/10.7150/ijms.70411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346378PMC
August 2022

The Herbal Combination of , , and Regulates the Functions of Type 2 Innate Lymphocytes and Macrophages Contributing to the Resolution of Collagen-Induced Arthritis.

Front Pharmacol 2022 19;13:964559. Epub 2022 Jul 19.

Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Type 2 innate lymphocytes (ILC2s), promoting inflammation resolution, was a potential target for rheumatoid arthritis (RA) treatment. Our previous studies confirmed that . and . could intervene in immunologic balance of T lymphocytes. . also have anti-inflammatory therapeutic effects. In this study, the possible molecular mechanisms of the combination of these three herbs for the functions of ILC2s and macrophages contributing to the resolution of collagen-induced arthritis (CIA) were studied. Therefore, we used . , . , and . as treatment. The synovial inflammation and articular cartilage destruction were alleviated after herbal treatment. The percentages of ILC2s and Tregs increased significantly. The differentiation of Th17 cells and the secretion of IL-17 and IFN-γ significantly decreased. In addition, treatment by the combination of these three herbs could increase the level of anti-inflammatory cytokine IL-4 secreted, active the STAT6 signaling pathway, and then contribute to the transformation of M1 macrophages to M2 phenotype. The combination of the three herbs could promote inflammation resolution of synovial tissue by regulating ILC2s immune response network. The synergistic effects of three drugs were superior to the combination of . and . or . alone.
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http://dx.doi.org/10.3389/fphar.2022.964559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343953PMC
July 2022

The Efficacy and Safety of Diyushengbai Tablet on Preventing and Treating Leukopenia Caused by Radiotherapy and Chemotherapy Against Tumor: A Systematic Review and Meta-Analysis.

Front Pharmacol 2022 19;13:827710. Epub 2022 Jul 19.

Department of TCM Pharmacy, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu, China.

Leukopenia is one of the side effects of radiotherapy and chemotherapy. Diyushengbai tablet (DYT) is used to prevent and treat leukopenia caused by various reasons. A meta-analysis was performed to systematically analyze the therapeutic effects of DYT on preventing and treating leukopenia caused by radiotherapy and chemotherapy. This study aimed to systematically evaluate the efficacy and safety of DYT in preventing and treating leukopenia caused by radiotherapy and chemotherapy. We performed a comprehensive literature search of electronic databases such as PubMed, The Cochrane Library, China Knowledge Network (CNKI), China Biomedical Literature Database (CBM), Wanfang Data Knowledge Service Platform, and VIP, through November of 2021. The scanning reports deadline is until November 2021. The bias risk evaluation criteria developed by the Cochrane collaborative organization were used to evaluate the literature quality of the included studies. The RevMan5.4 software was used to analyze the data, and the Stata16.0 was used to perform the Egger test. After selecting all the databases, a total of 41 reports which involved 3,793 cases were analyzed. Meta-analysis showed that DYT could significantly reduce the white blood cell (WBC) suppression caused by radiotherapy and chemotherapy and improve the patients' WBC counts and neutrophils, compared with the efficacy of other oral WBC-elevating drugs such as Leucogen tablets and Batilol tablets and additional utilization of granulocyte colony-stimulating factor (G-CSF). The results of meta-analysis showed that for preventive medication purpose, the overall incidence of leukocyte suppression was [RR = 0.74, 95%CI (0.59, 0.92), = 0.006], and the white blood cell count was [MD = 1.12, 95%CI (0.95, 1.29), < 0.00001]; while for therapeutic purpose, the incidence of overall leukocyte suppression was [RR = 0.61, 95%CI (0.38, 0.95), = 0.03], and the white blood cell count was [MD = 1.20, 95%CI (0.77, 1.62), < 0.00001]. More importantly, the additional use of DYT can reduce the application amount of G-CSF. The results showed that the application of G-CSF can be reduced by an average of 1.57 from the beginning of treatment to return normal white blood cells around 2.23 in two cycles of chemotherapy. DYT is more effective in preventing and treating leukopenia caused by radiotherapy and chemotherapy than other oral WBC-elevating drugs, which have a high clinical value.
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http://dx.doi.org/10.3389/fphar.2022.827710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343950PMC
July 2022

High-content imaging of human hepatic spheroids for researching the mechanism of duloxetine-induced hepatotoxicity.

Cell Death Dis 2022 Aug 1;13(8):669. Epub 2022 Aug 1.

Hepato-pancreato-biliary Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, 102218, Beijing, China.

Duloxetine (DLX) has been approved for the successful treatment of psychiatric diseases, including major depressive disorder, diabetic neuropathy, fibromyalgia and generalized anxiety disorder. However, since the usage of DLX carries a manufacturer warning of hepatotoxicity given its implication in numerous cases of drug-induced liver injuries (DILI), it is not recommended for patients with chronic liver diseases. In our previous study, we developed an enhanced human-simulated hepatic spheroid (EHS) imaging model system for performing drug hepatotoxicity evaluation using the human hepatoma cell line HepaRG and the support of a pulverized liver biomatrix scaffold, which demonstrated much improved hepatic-specific functions. In the current study, we were able to use this robust model to demonstrate that the DLX-DILI is a human CYP450 specific, metabolism-dependent, oxidative stress triggered complex hepatic injury. High-content imaging analysis (HCA) of organoids exposed to DLX showed that the potential toxicophore, naphthyl ring in DLX initiated oxidative stress which ultimately led to mitochondrial dysfunction in the hepatic organoids, and vice versa. Furthermore, DLX-induced hepatic steatosis and cholestasis was also detected in the exposed EHSs. We also discovered that a novel compound S-071031B, which replaced DLX's naphthyl ring with benzodioxole, showed dramatically lower hepatotoxicities through reducing oxidative stress. Thus, we conclusively present the human-relevant EHS model as an ideal, highly competent system for evaluating DLX induced hepatotoxicity and exploring related mechanisms in vitro. Moreover, HCA use on functional hepatic organoids has promising application prospects for guiding compound structural modifications and optimization in order to improve drug development by reducing hepatotoxicity.
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http://dx.doi.org/10.1038/s41419-022-05042-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343405PMC
August 2022

Changes in Rat Scleral Collagen Structure Induced by UVA-Riboflavin Crosslinking at Various Tissue Depths in Whole Globe Versus Scleral Patch.

Transl Vis Sci Technol 2022 Aug;11(8)

Aier School of Ophthalmology, Central South University, Changsha, Hunan, China.

Purpose: To investigate structural changes in scleral collagen fibers at various tissue depths before and after photosensitized crosslinking (CXL) both isolated scleral patch versus whole globe using second-harmonic generation (SHG) imaging.

Methods: Scleral tissues were harvested from Sprague-Dawley rats and separated into three groups: untreated sclera (control), full-thickness scleral patch for CXL (Free Scleral CXL group), and sclera in intact globe for CXL (Globe CXL group). The CXL groups were soaked in 0.1% riboflavin and irradiated with 365 nm ultraviolet-A light (power, 0.45 mW/cm2) for 30 minutes. SHG images were acquired every 5 µm between 10 and 60 µm from the outer scleral surface. Collagen fiber waviness was calculated as the ratio of the total length of a traced fiber and the length of a straight path between the fiber ends.

Results: In the Free Scleral CXL group, collagen waviness was significantly increased compared to the control group at 35 to 50 µm (P < 0.05). In the Globe CXL group, collagen waviness was decreased compared to control at all depths with statistical significance (P < 0.05) achieved from 10 to 45 µm.

Conclusions: Depending upon its initial state (i.e., free scleral patch versus mechanically loaded intact globe under pressure), collagen may experience different structural changes after CXL. In addition, the extent of the CXL effects may vary at different depths away from the surface.

Translational Relevance: Understanding the CXL effects on collagen structure may be important in optimizing the scleral crosslinking protocol for future clinical applications such as preventing myopic progression.
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http://dx.doi.org/10.1167/tvst.11.8.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351595PMC
August 2022

COQ10B Knockdown Modulates Cell Proliferation, Invasion, Migration, and Apoptosis in Esophageal Squamous Cell Carcinoma.

Evid Based Complement Alternat Med 2022 21;2022:6247824. Epub 2022 Jul 21.

Department 4 of Comprehensive Internal Medicine of Healthy Care Center for Cadres, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.

Objective: Esophageal squamous-cell carcinoma (ESCC) is an aggressive malignant tumor, accounting for more than 90% of esophageal cancers. However, treatments such as surgical resection, radiotherapy, and chemotherapy are unable to achieve ideal clinical outcomes. The purpose of this study was to explore the effects of COQ10B on proliferation, apoptosis, migration, and invasion of esophageal squamous-cell carcinoma (ESCC) cells.

Methods: Quantitative real-time PCR (qRT-PCR) was used to detect the expression of COQ10B in ESCC and normal tissues and in ESCC cell lines (KYSE-15 and TE-1). MTT assay and flow cytometry were applied to investigate the effects of COQ10B shRNA lentivirus (LV-shCOQ10B) on ESCC cell proliferation and apoptosis, respectively. The effect of COQ10B silencing on ESCC cell migration and invasion was determined by wound healing assay and transwell invasion assay, respectively.

Results: The expression of COQ10B mRNA in ESCC tissues was higher than that in surrounding tissues. The decreased COQ10B level in KYSE-15 and TE-1 cells by LV-shCOQ10B could inhibit cell proliferation, promote cell apoptosis, and reduce the ability of invasion and migration (all < 0.05).

Conclusion: COQ10B was highly expressed in human ESCC tissues. COQ10B silencing contributed to the inhibition of proliferation, invasion, and migration of ESCC cells and the promotion of cell apoptosis, suggesting COQ10B may be a potential molecular target for the diagnosis and treatment of ESCC.
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http://dx.doi.org/10.1155/2022/6247824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334081PMC
July 2022

Erratum: Local administration of liposomal-based Srpx2 gene therapy reverses pulmonary fibrosis by blockading fibroblast-to-myofibroblast transition: Erratum.

Theranostics 2022 8;12(12):5330-5331. Epub 2022 Jul 8.

Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of National Health Commission, Key Site of National Clinical Research Center for Respiratory Disease, Wuhan Clinical Medical Research Center for Chronic Airway Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, 1095 Jiefang Ave, Wuhan 430030, China.

[This corrects the article DOI: 10.7150/thno.61085.].
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http://dx.doi.org/10.7150/thno.74512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330520PMC
July 2022

Superficial myofibroblastoma of the lower female genital tract: A clinicopathological analysis of 15 cases.

Ann Diagn Pathol 2022 Jul 22;60:152010. Epub 2022 Jul 22.

Department of Pathology, West China Second University Hospital, Sichuan University/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Chengdu 610041, Sichuan Province, China. Electronic address:

Objective: To describe the clinicopathological features and differential diagnoses of 15 cases of superficial myofibroblastoma, a rare mesenchymal tumor involving the lower female genital tract.

Methods: The clinicopathological data and immunohistochemical findings were retrospectively analyzed in 15 cases of superficial myofibroblastoma. Meanwhile, a systematic literature review was conducted.

Results: The age of patients ranged from 34 to 73 years (median, 49 years). Most patients presented with nodular or polypoid masses ranging in size from 0.4 cm to 6.5 cm. Twelve tumors were located in the vagina, two in the vulva, and one in the cervix. Microscopically, the tumor was located in the subepithelial tissue, with a clear boundary and without capsule on the surface. The tumor cells were spindle, oval, stellate or wavy, and arranged in various architectural patterns of reticular, fascicular, wavy and disorderly patterns. There were no obvious cellular atypia and mitotic figures. Thin collagen fibers and thin-walled vessels could be observed in all cases. Most cases were diffusely and strongly reactive to Vimentin (12/12), Desmin (14/15), ER (15/15) and PR (13/14). Variable immunoreactivity for CD34 (8/15), Caldesmon (2/8), SMA (4/14) and CD99 (4/5) were observed. The tumors showed a low Ki67 proliferative index (≤5 %). Follow-up information was available in 10 patients and there was no evidence of recurrence or metastasis.

Conclusions: Superficial myofibroblastoma is a rare benign tumor that originates from the hormone-sensitive, subepithelial mesenchymal tissue of the lower female genital tract, and should be differentiated from other mesenchymal tumors.
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http://dx.doi.org/10.1016/j.anndiagpath.2022.152010DOI Listing
July 2022

Metal-Chelatable Porphyrinic Frameworks for Single-Cell Multiplexing with Mass Cytometry.

Angew Chem Int Ed Engl 2022 Jul 27. Epub 2022 Jul 27.

Zhejiang University, State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, CHINA.

Single-cell multiplexing is key to exploration of the heterogeneous cell populations in biological systems. Although the state-of-the-art mass cytometry (CyTOF) possesses high resolution and multiple dimensions, the lack of suitable marker materials prohibits fully exploiting the available CyTOF detection channels. Here we report a new design strategy for CyTOF markers using functionalized mesoporous porphyrinic frameworks (MPFs) as scaffolds for chelating metals that have been unachievable by conventional approaches. We developed surface modification for stably dispersing the MPF nanoparticles (<40 nm) during the metalation and antibody conjugation processes. Our markers exhibit higher sensitivity and comparable specificity compared with a polymer-based commercial benchmark. Compatibility with commercial markers during co-staining was also confirmed. Furthermore, our markers show promising performance for immunophenotyping and potential implementation in CyTOF systems.
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http://dx.doi.org/10.1002/anie.202208640DOI Listing
July 2022

Virtual high-count PET image generation using a deep-learning method.

Med Phys 2022 Jul 26. Epub 2022 Jul 26.

Department of Radiology and Biomedical Imaging, Yale University, New Haven, 06520, USA.

Purpose: Recently, deep learning-based methods have been established to denoise the low-count PET images and predict their standard-count image counterparts, which could achieve reduction of injected dosage and scan time, and improve image quality for equivalent lesion detectability and clinical diagnosis. In clinical settings, the majority scans are still acquired using standard injection dose with standard scan time. In this work, we applied a 3D U-Net network to reduce the noise of standard-count PET images to obtain the virtual-high-count (VHC) PET images for identifying the potential benefits of the obtained VHC PET images.

Methods: The training datasets, including down-sampled standard-count PET images as the network input and high-count images as the desired network output, were derived from 27 whole-body PET datasets, which were acquired using 90-minute dynamic scan. The down-sampled standard-count PET images were rebinned with matched noise level of 195 clinical static PET datasets, by matching the normalized standard derivation (NSTD) inside 3D liver region of interests (ROIs). Cross-validation was performed on 27 PET datasets. Normalized mean square error (NMSE), peak signal to noise ratio (PSNR), structural similarity index (SSIM), and standard uptake value (SUV) bias of lessons were used for evaluation on standard-count and VHC PET images, with real-high-count PET image of 90 minutes as the gold standard. In addition, the network trained with 27 dynamic PET datasets was applied to 195 clinical static datasets to obtain VHC PET images. The NSTD and mean/max SUV of hypermetabolic lesions in standard-count and virtual high-count PET images were evaluated. Three experienced nuclear medicine physicians evaluated the overall image quality of randomly selected 50 out of 195 patients' standard-count and VHC images and conducted 5-score ranking. A Wilcoxon signed-rank test was used to compare differences in the grading of standard-count and VHC images.

Results: The cross-validation results showed that VHC PET images had improved quantitative metrics scores than the standard-count PET images. The mean/max SUVs of 35 lesions in the standard-count and true-high-count PET images did not show significantly statistical difference. Similarly, the mean/max SUVs of VHC and true-high-count PET images did not show significantly statistical difference. For the 195 clinical data, the VHC PET images had a significantly lower NSTD than the standard-count images. The mean/max SUVs of 215 hypermetabolic lesions in the VHC and standard-count images showed no statistically significant difference. In the image quality evaluation by three experienced nuclear radiologists, standard-count images and VHC images received scores with mean and standard deviation of 3.34±0.80 and 4.26±0.72 from Physician 1, 3.02±0.87 and 3.96±0.73 from Physician 2, and 3.74±1.10 and 4.58±0.57 from Physician 3, respectively. The VHC images were consistently ranked higher than the standard-count images. The Wilcoxon signed-rank test also indicated that the image quality evaluation between standard-count and VHC images had significant difference.

Conclusions: A deep learning method is proposed to convert the standard-count images to the VHC images. The VHC images have reduced noise level. No significant difference in mean/max SUV to the standard-count images is observed. VHC images improve image quality for better lesion detectability and clinical diagnosis. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mp.15867DOI Listing
July 2022

Review of computer-generated hologram algorithms for color dynamic holographic three-dimensional display.

Light Sci Appl 2022 Jul 26;11(1):231. Epub 2022 Jul 26.

Beijing Engineering Research Center for Mixed Reality and Advanced Display, School of Optics and Photonics, Beijing Institute of Technology, Beijing, 100081, China.

Holographic three-dimensional display is an important display technique because it can provide all depth information of a real or virtual scene without any special eyewear. In recent years, with the development of computer and optoelectronic technology, computer-generated holograms have attracted extensive attention and developed as the most promising method to realize holographic display. However, some bottlenecks still restrict the development of computer-generated holograms, such as heavy computation burden, low image quality, and the complicated system of color holographic display. To overcome these problems, numerous algorithms have been investigated with the aim of color dynamic holographic three-dimensional display. In this review, we will explain the essence of various computer-generated hologram algorithms and provide some insights for future research.
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http://dx.doi.org/10.1038/s41377-022-00916-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314381PMC
July 2022

VEGF promotes tendon regeneration of aged rats by inhibiting adipogenic differentiation of tendon stem/progenitor cells and promoting vascularization.

FASEB J 2022 Aug;36(8):e22433

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, China.

Studies have shown that the stem cell microenvironment is a key factor for stem cell maintenance or differentiation. In this study, we compared the expression of 23 cytokines such as IL-6, IL-10, and TNFα between young and aged rats during patellar tendon repair by cytokine microarray, and found that significant difference between IL-10, G-CSF, and VEGF at 3, 7, or 14 days post-operatively. The effects of these factors on adipogenic differentiation of TPSCs were examined through western blot and oil red O experiments. It was shown that VEGF had an inhibitive effect on the adipogenic differentiation of TPSCs. SPP-1 was figured out as our target by RNA sequencing and confirmed by western blot in vitro. Further in vivo studies showed that adipocyte accumulation was also decreased in the tendons of aged rats after injection of VEGF and the histological score and biomechanical property were also improved via targeting SPP-1. Furthermore, histochemical results showed that vascularization of the injury sites was significantly elevated. In conclusion, VEGF not only plays an important role in decreasing adipocyte accumulation but also improves vascularization of the tendon during aged tendon healing. We believe active regulation of VEGF may improve the treatment of age-related tendon diseases and tendon injuries.
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http://dx.doi.org/10.1096/fj.202200213RDOI Listing
August 2022

Diagnose earlier, live longer? The impact of cervical and breast cancer screening on life span.

PLoS One 2022 20;17(7):e0270347. Epub 2022 Jul 20.

School of Public Health, Shandong University, Jinan, People's Republic of China.

Cancer has become a leading cause of death and aroused the cancer scare. Breast and cervical cancer are two main health threats for women. In order to reduce mortality through early detection and early treatment, cancer screening has been widely recommended and applied for breast and cervical cancer detection and prevention. However, the benefit of cancer screening has been a controversial issue for the recent decades. The Chinese government has launched a free screening program on breast and cervical cancer for women since 2009. There is lack of strong data and sufficient information, however, to examine the effect of breast and cervical cancer screening. A Difference-in-Difference model estimated by Cox proportional hazard estimation was applied to evaluate the effects of breast and cervical cancer screening using data from Nown County Cancer Registry between the year 2009 and 2013. Based on the case study in a county of central China, this study found that the screening program reduced the risk of death, but found the lion's share for the benefit has been mainly due to the cervical cancer screening rather breast cancer screening, which may be related to the difference between early detection screening and preventive screening. Our results suggest sufficient funding and better education of related cancer knowledge will be meaningful measures for the prevention and treatment of breast and cervical cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270347PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299384PMC
July 2022

Functions of Gut Microbiota Metabolites, Current Status and Future Perspectives.

Aging Dis 2022 Jul 11;13(4):1106-1126. Epub 2022 Jul 11.

1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological of hosts. In healthy state, gut microbiota metabolites are helpful for maintaining the basic functions of hosts, whereas disturbed production of these metabolites can lead to numerous diseases such as metabolic diseases, cardiovascular diseases, gastrointestinal diseases, neurodegenerative diseases, and cancer. Although there are many reviews about the specific mechanisms of gut microbiota metabolites on specific diseases, there is no comprehensive summarization of the functions of these metabolites. In this Opinion, we discuss the knowledge of gut microbiota metabolites including the types of gut microbiota metabolites and their ways acting on targets. In addition, we summarize their physiological and pathologic functions in health and diseases, such as shaping the composition of gut microbiota and acting as nutrition. This paper can be helpful for understanding the roles of gut microbiota metabolites and thus provide guidance for developing suitable therapeutic strategies to combat microbial-driven diseases and improve health.
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http://dx.doi.org/10.14336/AD.2022.0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286904PMC
July 2022

RNA-binding protein ZCCHC4 promotes human cancer chemoresistance by disrupting DNA-damage-induced apoptosis.

Signal Transduct Target Ther 2022 07 20;7(1):240. Epub 2022 Jul 20.

National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 200433, Shanghai, China.

RNA-binding proteins (RBPs) play important roles in cancer development and treatment. However, the tumor-promoting RBPs and their partners, which may potentially serve as the cancer therapeutic targets, need to be further identified. Here, we report that zinc finger CCHC domain-containing protein 4 (ZCCHC4) is of aberrantly high expression in multiple human cancer tissues and is associated with poor prognosis and chemoresistance in patients of hepatocellular carcinoma (HCC), pancreatic cancer and colon cancer. ZCCHC4 promotes chemoresistance of HCC cells to DNA-damage agent (DDA) both in vitro and in vivo. HCC cell deficiency of ZCCHC4 reduces tumor growth in vivo and intratumoral interference of ZCCHC4 expression obviously enhances the DDA-induced antitumor effect. Mechanistically, ZCCHC4 inhibits DNA-damage-induced apoptosis in HCC cells by interacting with a new long noncoding RNA (lncRNA) AL133467.2 to hamper its pro-apoptotic function. Also, ZCCHC4 blocks the interaction between AL133467.2 and γH2AX upon DDA treatment to inhibit apoptotic signaling and promote chemoresistance to DDAs. Knockout of ZCCHC4 promotes AL133467.2 and γH2AX interaction for enhancing chemosensitivity in HCC cells. Together, our study identifies ZCCHC4 as a new predictor of cancer poor prognosis and a potential target for improving chemotherapy effects, providing mechanistic insights to the roles of RBPs and their partners in cancer progression and chemoresistance.
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http://dx.doi.org/10.1038/s41392-022-01033-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296561PMC
July 2022

PTHrP promotes subchondral bone formation in TMJ-OA.

Int J Oral Sci 2022 Jul 19;14(1):37. Epub 2022 Jul 19.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.

PTH-related peptide (PTHrP) improves the bone marrow micro-environment to activate the bone-remodelling, but the coordinated regulation of PTHrP and transforming growth factor-β (TGFβ) signalling in TMJ-OA remains incompletely understood. We used disordered occlusion to establish model animals that recapitulate the ordinary clinical aetiology of TMJ-OA. Immunohistochemical and histological analyses revealed condylar fibrocartilage degeneration in model animals following disordered occlusion. TMJ-OA model animals administered intermittent PTHrP (iPTH) exhibited significantly decreased condylar cartilage degeneration. Micro-CT, histomorphometry, and Western Blot analyses disclosed that iPTH promoted subchondral bone formation in the TMJ-OA model animals. In addition, iPTH increased the number of osterix (OSX)-positive cells and osteocalcin (OCN)-positive cells in the subchondral bone marrow cavity. However, the number of osteoclasts was also increased by iPTH, indicating that subchondral bone volume increase was mainly due to the iPTH-mediated increase in the bone-formation ability of condylar subchondral bone. In vitro, PTHrP treatment increased condylar subchondral bone marrow-derived mesenchymal stem cell (SMSC) osteoblastic differentiation potential and upregulated the gene and protein expression of key regulators of osteogenesis. Furthermore, we found that PTHrP-PTH1R signalling inhibits TGFβ signalling during osteoblastic differentiation. Collectively, these data suggested that iPTH improves OA lesions by enhancing osteoblastic differentiation in subchondral bone and suppressing aberrant active TGFβ signalling. These findings indicated that PTHrP, which targets the TGFβ signalling pathway, may be an effective biological reagent to prevent and treat TMJ-OA in the clinic.
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http://dx.doi.org/10.1038/s41368-022-00189-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296483PMC
July 2022

EEG signal classification of tinnitus based on SVM and sample entropy.

Comput Methods Biomech Biomed Engin 2022 Jul 19:1-15. Epub 2022 Jul 19.

School of Electromechanical Engineering, Guangdong University of Technology, Guangzhou, Guangdong, China.

The prevalence of tinnitus is high and seriously affects the daily life of patients. As the pathogenesis of tinnitus is not yet clear, there is a lack of rapid and objective diagnostic modalities. In order to provide clinicians with an objective diagnostic approach, this paper combines time-frequency domain and non-linear power analysis to investigate the differences in the specificity of the EEG signal in tinnitus patients compared to healthy subjects. In this paper, resting-state electroencephalograms (EEG) were collected from 10 cases each of tinnitus patients and healthy subjects, and the data from the two groups were compared in the δ (0.5 - 3 .5 Hz), θ (4 - 7.5 Hz), α1 (8 - 10 Hz), α2 (10 - 12 Hz), β1 (13 - 18 Hz), β2 (18.5 - 21 Hz), β3 (21.5 - 30 Hz), and γ (30.5 - 44 Hz) bands for the differences in sample entropy values. The results of the resting state experiment revealed that the δ, α2 and β1 band samples of tinnitus patients all had greater entropy values than healthy subjects, with extremely significant differences compared to healthy subjects (p < 0.01). It is mainly concentrated in the δ band in the right parietal region of the cerebral cortex, the α2 band in the central region, and the γ band in the left prefrontal region. Finally, support vector machines combined with optimal feature combinations were used to achieve objective recognition of tinnitus disorders, with an 8.58% increase in accuracy compared to other features. Through the above study, entropy reflects the degree of chaos in the brain and the chaotic characteristics of the resting state EEG signal can characterise the onset of tinnitus, the results of which can help clinicians in the early diagnosis of tinnitus.
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http://dx.doi.org/10.1080/10255842.2022.2075698DOI Listing
July 2022

Facile synthesizing Z-scheme BiOCl/InVO heterojunction to effectively degrade pollutants and antibacterial under light-emitting diode light.

J Colloid Interface Sci 2022 Jul 6;627:224-237. Epub 2022 Jul 6.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, P. R. China.

The design of a photocatalytic system with Z-scheme heterojunction is the key to charge separation. In this paper, a simple synthesis method was used to prepare BiOCl/InVO photocatalyst. The synthesized photocatalyst can effectively degrade pollutants, and inactivate bacteria under LED light irradiation. The optimal ratio of 30% BiOCl/InVO material effectively degraded 78.85% of TC and 97.83% of RhB within 90 min and inactivated Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in 40 min. This improvement in photocatalytic performance is mainly due to the formation of a Z-scheme heterojunction between BiOCl and InVO, which produces effective charge separation and improves photocatalytic degradation and antibacterial activity. The capture experiment revealed the main active substances. The effects of catalyst dosage and pollutant concentration were investigated in details. The intermediates of TC degradation were identified by mass spectrometry (MS), and the possible photocatalytic degradation pathway was proposed. Capture experiment and related measurements proposed the Z-scheme mechanism. This work emphasizes the importance of heterogeneous structure construction and proposes feasible solutions for the rational design of catalysts with photodegradation and antibacterial properties under LED light.
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http://dx.doi.org/10.1016/j.jcis.2022.07.026DOI Listing
July 2022

Molecular Epidemiology of New Delhi Metallo--Lactamase-Producing in Food-Producing Animals in China.

Front Microbiol 2022 1;13:912260. Epub 2022 Jul 1.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou, China.

We conducted a molecular surveillance study for carbapenem-resistant (CRE) colonization in food-producing animals in China that included primarily swine and poultry for three consecutive years. A total of 2,771 samples from food-producing animals and their surrounding environments were collected from different regions in China from 2015 to 2017. Enrichment cultures supplemented with meropenem were used to isolate carbapenem non-susceptible isolates and these were subsequently identified by MALDI-TOF MS. Resistance phenotypes and genotypes were confirmed using antimicrobial susceptibility testing and molecular biological techniques. Genomic characteristics of the carbapenemase-producing isolates were investigated using whole genome sequencing (WGS) and bioinformatic analysis. In total, 88 NDM-positive were identified from 2,771 samples and 96.6% were . The New Delhi metallo--lactamase (NDM)-positive displayed a diversity of sequence types (ST), and ST48 and ST165 were the most prevalent. Three variants of ( , , and ) were detected and WGS indicated that predominated and was carried primarily on IncX3 plasmids. All these isolates were also multiply-drug resistant. These results revealed that food-producing animals in China are an important reservoir for NDM-positive and pose a potential threat to public health.
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http://dx.doi.org/10.3389/fmicb.2022.912260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284025PMC
July 2022

Whole-Blood MicroRNA Sequence Profiling and Identification of Specific miR-21 for Adolescents With Postural Tachycardia Syndrome.

Front Neurosci 2022 30;16:920477. Epub 2022 Jun 30.

Department of Pediatrics, The Third Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.

Objective: The aim of the study was to establish whether whole-blood microRNA (miRNA) profiles differ between postural tachycardia syndrome (POTS) sufferers and control subjects and to identify the miRNA that regulates plasma HS.

Study Design: High-throughput sequencing was used to obtain whole-blood miRNA expression profiles for 20 POTS sufferers and 20 normal children.The thresholds for defining differentially expressed miRNAs (DEmiRNAs) were an adjusted DESeq of <0.05 and a log2 fold variation of ≥3. The DEmiRNA target genes were identified using RNAhybrid and miRanda, and only those identified by both were considered. The combined effects of the DEmiRNAs were determined using KEGG pathway analysis. Another 40 POTS and 20 normal patients were used as validation subjects. Plasma HS was determined with a sulfide electrode, and flow-mediated vasodilation (FMD) was performed with a color Doppler ultrasound system. miRNAs were analyzed using qRT-PCR.

Results: Totally, 13 DEmiRNAs were identified through high-throughput sequencing. In the 60-member validation group, the 13 miRNAs were verified again, and it turned out that miR-21 was significantly elevated and could diagnose POTS with a 100% specificity and 92.5% sensitivity. Overall, 198 and 481 genes, respectively, were shown to be targeted by the 13 DEmiRNAs when values of 0.01 and 0.05 were used. The target gene of hsa-miR-21-5p was SP1 when the -value is <0.01. DEmiRNAs were significantly enriched in 36 pathways ( < 0.05), in which PI3K/Akt signaling was closely related to vascular function. In the validation subjects, the plasma HS and FMD were higher in the POTS sufferers ( < 0.05).

Conclusion: Elevated whole-blood miR-21 levels serve as an indicator for POTS and may explain the increased plasma HS observed in POTS sufferers.
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http://dx.doi.org/10.3389/fnins.2022.920477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281551PMC
June 2022

Accurate classification of white blood cells by coupling pre-trained ResNet and DenseNet with SCAM mechanism.

BMC Bioinformatics 2022 Jul 15;23(1):282. Epub 2022 Jul 15.

Landing Artificial Intelligence Center for Pathological Diagnosis, Wuhan, 430072, China.

Background: Via counting the different kinds of white blood cells (WBCs), a good quantitative description of a person's health status is obtained, thus forming the critical aspects for the early treatment of several diseases. Thereby, correct classification of WBCs is crucial. Unfortunately, the manual microscopic evaluation is complicated, time-consuming, and subjective, so its statistical reliability becomes limited. Hence, the automatic and accurate identification of WBCs is of great benefit. However, the similarity between WBC samples and the imbalance and insufficiency of samples in the field of medical computer vision bring challenges to intelligent and accurate classification of WBCs. To tackle these challenges, this study proposes a deep learning framework by coupling the pre-trained ResNet and DenseNet with SCAM (spatial and channel attention module) for accurately classifying WBCs.

Results: In the proposed network, ResNet and DenseNet enables information reusage and new information exploration, respectively, which are both important and compatible for learning good representations. Meanwhile, the SCAM module sequentially infers attention maps from two separate dimensions of space and channel to emphasize important information or suppress unnecessary information, further enhancing the representation power of our model for WBCs to overcome the limitation of sample similarity. Moreover, the data augmentation and transfer learning techniques are used to handle the data of imbalance and insufficiency. In addition, the mixup approach is adopted for modeling the vicinity relation across training samples of different categories to increase the generalizability of the model. By comparing with five representative networks on our developed LDWBC dataset and the publicly available LISC, BCCD, and Raabin WBC datasets, our model achieves the best overall performance. We also implement the occlusion testing by the gradient-weighted class activation mapping (Grad-CAM) algorithm to improve the interpretability of our model.

Conclusion: The proposed method has great potential for application in intelligent and accurate classification of WBCs.
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http://dx.doi.org/10.1186/s12859-022-04824-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287918PMC
July 2022

Corrigendum: Endoscope-Assisted Retrosigmoid Approach for Vestibular Schwannomas with Intracanalicular Extensions: Facial Nerve Outcomes.

Front Oncol 2022 22;12:963829. Epub 2022 Jun 22.

Department of Neurosurgery, Shanghai General Hospital of Nanjing Medical University, Shanghai, China.

[This corrects the article DOI: 10.3389/fonc.2021.774462.].
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http://dx.doi.org/10.3389/fonc.2022.963829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257275PMC
June 2022

Identification of Small-Molecule Inhibitors for Osteosarcoma Targeted Therapy: Synchronizing , , and Analyses.

Front Bioeng Biotechnol 2022 23;10:921107. Epub 2022 Jun 23.

School of Basic Medical Sciences, Affiliated Hospital, School of Mechanical Engineering, Chengdu University, Chengdu, China.

The study aimed to explore a new approach for the treatment of osteosarcoma through combining biomaterials with next-generation small molecule-based targeted therapy. The model of osteosarcoma was established by 4-hydroxyaminoquinoline 1-oxide (4-HAQO) in mice while the collagen-thermosensitive hydrogel-calcium phosphate (CTC) biocomposites were prepared, and the small molecule inhibitors were virtually screened and synthesized. Then, for the osteosarcoma cell line, MG-63 cells were used to validate our bioinformatic findings , and the mouse osteosarcoma models were treated by combing CTC composites and small-molecule inhibitors after debridement. Five compounds, namely, ZINC150338698, ZINC14768621, ZINC4217203, ZINC169291448, and ZINC85537017, were found in the ZINK database. Finally, ZINC150338698 was selected for chemical synthesis and experimental verification. The results of the MTT assay and Hoechst staining showed that the small-molecule inhibitor ZINC150338698 could significantly induce MG-63 cell death. Furthermore, CTC composites and ZINC150338698 could repair the bone defects well after the debridement of osteosarcoma. In addition, the biomaterials and small-molecule inhibitors have good biocompatibility and biosafety. Our findings not only offer systems biology approach-based drug target identification but also provide new clues for developing novel treatment methods for future osteosarcoma research.
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http://dx.doi.org/10.3389/fbioe.2022.921107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260275PMC
June 2022
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