Publications by authors named "Yun Liu"

2,335 Publications

  • Page 1 of 1

α-Synuclein Interaction with Lipid Bilayer Discs.

Langmuir 2022 Aug 11. Epub 2022 Aug 11.

Physical Chemistry, Department of Chemistry, Lund University, SE-22100 Lund, Sweden.

α-Synuclein (aSyn) is a 140 residue long protein present in presynaptic termini of nerve cells. The protein is associated with Parkinson's disease, in which case it has been found to self-assemble into long amyloid fibrils forming intracellular inclusions that are also rich in lipids. Furthermore, its synaptic function is proposed to involve interaction with lipid membranes, and hence, it is of interest to understand aSyn-lipid membrane interactions in detail. In this paper we report on the interaction of aSyn with model membranes in the form of lipid bilayer discs. Using a combination of cryogenic transmission electron microscopy and small-angle neutron scattering, we show that circular discs undergo a significant shape transition after the adsorption of aSyn. When aSyn self-assembles into fibrils, aSyn molecules desorb from the bilayer discs, allowing them to recover to their original shape. Interestingly, the desorption process has an all-or-none character, resulting in a binary coexistence of circular bilayer discs with no adsorbed aSyn and deformed bilayer discs having a maximum amount of adsorbed protein. The observed coexistence is consistent with the recent finding of cooperative aSyn adsorption to anionic lipid bilayers.
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http://dx.doi.org/10.1021/acs.langmuir.2c01368DOI Listing
August 2022

An affordable approach to classifying type 2 diabetes based on fasting plasma glucose, TyG index and BMI: a retrospective cohort study of NHANES Data from 1988 to 2014.

Diabetol Metab Syndr 2022 Aug 10;14(1):113. Epub 2022 Aug 10.

College of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China.

Background: The β-cell function and insulin resistance required by existing methods of classifying type 2 diabetes are not routinely adopted in most medical institutions of developing countries and regions. This study aims to propose a novel, affordable classification approach and evaluate its predictive ability for several health and mortality outcomes, including cardiovascular health (CVH), retinopathy, chronic kidney disease (CKD), nonalcoholic fatty liver disease (NAFLD), advanced liver fibrosis, and mortality caused by all-cause, cardiovascular disease (CVD), cancer.

Methods: Based on 4060 participants with diabetes (aged ≥ 30 at the time of diagnosis) selected from the National Health and Nutrition Examination Survey III & 1999-2014, we proposed a novel, but simple classification approach based on the threshold of fasting plasma glucose (FPG), triglyceride-glucose (TyG) index and body mass index (BMI). We used logistic regression model to assess its predictability for diabetes complications, and Cox regression model to estimate the mortality risks.

Results: By utilizing this approach, we characterized the subjects into four subgroups: subgroup A (obesity-related), which accounts for 37% of the total, subgroup B (age-related), 38%, subgroup C (insulin resistance), 20%, and subgroup D (severe insulin deficiency), 5%. Subjects in subgroup D had a higher risk of retinopathy, in subgroup B had a lower risk of poor cardiovascular health, nonalcoholic fatty liver disease, and advanced liver fibrosis, in subgroup C had a higher risk of all-cause mortality.

Conclusions: This study proposes an affordable and practical method for classifying patients with type 2 diabetes into different subgroups, with a view to yield a high predictability of patient outcomes and to assist clinicians in providing better treatment.
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http://dx.doi.org/10.1186/s13098-022-00883-0DOI Listing
August 2022

Periodontal Ligament Stem Cells Reverse the High Glucose Level-Induced Inflammatory State of Macrophages.

Biomed Environ Sci 2022 Jul;35(7):674-679

School of Stomatology, Weifang Medical University, Weifang 261053, Shandong, China.

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http://dx.doi.org/10.3967/bes2022.089DOI Listing
July 2022

Artificial intelligence for phase recognition in complex laparoscopic cholecystectomy.

Surg Endosc 2022 Aug 8. Epub 2022 Aug 8.

Department of Surgery, The Hebrew University School of Medicine, Sharee Zedek Medical Center, Jerusalem, Israel.

Background: The potential role and benefits of AI in surgery has yet to be determined. This study is a first step in developing an AI system for minimizing adverse events and improving patient's safety. We developed an Artificial Intelligence (AI) algorithm and evaluated its performance in recognizing surgical phases of laparoscopic cholecystectomy (LC) videos spanning a range of complexities.

Methods: A set of 371 LC videos with various complexity levels and containing adverse events was collected from five hospitals. Two expert surgeons segmented each video into 10 phases including Calot's triangle dissection and clipping and cutting. For each video, adverse events were also annotated when present (major bleeding; gallbladder perforation; major bile leakage; and incidental finding) and complexity level (on a scale of 1-5) was also recorded. The dataset was then split in an 80:20 ratio (294 and 77 videos), stratified by complexity, hospital, and adverse events to train and test the AI model, respectively. The AI-surgeon agreement was then compared to the agreement between surgeons.

Results: The mean accuracy of the AI model for surgical phase recognition was 89% [95% CI 87.1%, 90.6%], comparable to the mean inter-annotator agreement of 90% [95% CI 89.4%, 90.5%]. The model's accuracy was inversely associated with procedure complexity, decreasing from 92% (complexity level 1) to 88% (complexity level 3) to 81% (complexity level 5).

Conclusion: The AI model successfully identified surgical phases in both simple and complex LC procedures. Further validation and system training is warranted to evaluate its potential applications such as to increase patient safety during surgery.
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http://dx.doi.org/10.1007/s00464-022-09405-5DOI Listing
August 2022

Isoliensinine Suppresses Osteoclast Formation Through NF-κB Signaling Pathways and Relieves Ovariectomy-Induced Bone Loss.

Front Pharmacol 2022 22;13:870553. Epub 2022 Jul 22.

Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Osteoporosis is among the major contributors of pathologic fracture in postmenopausal women, which is caused by the bone metabolic disorder owing to the over-activation of osteoclasts. Inhibition of osteoclast differentiation and maturation has become a mainstream research interest in the prevention of osteoporosis. Isoliensinine (Iso) is a dibenzyl isoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-cancer activities. However, whether it can be used as a potential treatment for osteoporosis remains undiscovered. Here, we investigated whether Iso might suppress the differentiation of osteoclasts and to play an anti-osteoporosis role. Our results showed that Iso inhibits the formation of mature multinuclear osteoclasts induced by RANKL, the bone resorption, and the osteoclast-specific genes expression by blocking the nuclear translocation of NF-κB p65, and the effect was in a dosage-dependent way. Furthermore, we investigated the therapeutic effect of Iso on osteoporosis in ovariectomized (OVX) mice. We found that Iso attenuated bone loss in the OVX mice and significantly promoted BS, Conn. DN, Tb.Th, TB.N, and BV/TV Index. All in all, Iso showed a prominent effect of osteoclast inhibition, with great promise for treating osteoporosis.
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http://dx.doi.org/10.3389/fphar.2022.870553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353689PMC
July 2022

Near-infrared probe for early diagnosis of diabetic complications-nephropathy and in vivo visualization fluorescence imaging research.

Anal Chim Acta 2022 Aug 9;1221:340147. Epub 2022 Jul 9.

Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China. Electronic address:

Diabetic nephropathy is one of the common complications of diabetes, which has high risk of renal function. Dipeptidyl peptidase 4 (DPP4) is considered to be one of the good dynamic monitoring indicators for early diabetic nephropathy. Therefore, real-time monitoring of changes in the activity of DPP4 in organisms is helpful to the diagnosis and treatment of diabetes and its complications-diabetic nephropathy. A near-infrared fluorescent probe GP-DCMNH is designed to detect the activity of DPP4. GP-DCMNH is catalyzed and hydrolyzed by DPP4 into the near-infrared fluorescent dye DCMNH, to achieve the purpose of detecting DPP4 in organisms. Based on the excellent near-infrared spectroscopy characteristics displayed by the probe GP-DCMNH in vitro, in living cells and diabetic mouse models, GP-DCMNH has been further applied in the visual fluorescence imaging of diabetic complications-diabetic nephropathy. Compared with the control group and the treatment group, GP-DCMNH showed a stronger near-infrared fluorescence signal in the kidney tissue and blood of diabetic nephropathy mice. Because GP-DCMNH shows high sensitivity in real-time dynamic monitoring of changes in the activity of DPP4 in organisms, and shows strong practicability in the spectral test of mouse models of diabetes and diabetic nephropathy. In clinical medicine, GP-DCMNH is expected to be used in the early diagnosis, prevention and treatment of diabetes and diabetic nephropathy.
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http://dx.doi.org/10.1016/j.aca.2022.340147DOI Listing
August 2022

Dioscin ameliorates cisplatin-induced intestinal toxicity by mitigating oxidative stress and inflammation.

Int Immunopharmacol 2022 Aug 4;111:109111. Epub 2022 Aug 4.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Cisplatin is the most widely prescribed drug in chemotherapy, but its gastrointestinal toxicity reduces therapeutic efficacy. Oxidative stress and inflammation are considered to be the main pathogenesis of cisplatin-induced intestinal toxicity. Dioscin is a steroidal saponin with potential anti-cancer, antioxidant, and anti-inflammatory activities. In this study, we established a rat model of intestinal injury by tail vein injection of cisplatin, and intragastrically administered dioscin to evaluate its effect on intestinal injury. Biochemical markers, western blotting, qRT-PCR and histopathological staining were used to analyze intestinal injury according to various molecular mechanisms. The results revealed that dioscin significantly inhibited cisplatin-induced intestinal mucosal damage and decreased DAO levels in rats. Furthermore, dioscin activated the Nrf2/HO-1 pathway to increase the level of antioxidant enzymes and reduce the levels of MDA and HO. In addition, dioscin pretreatment significantly reduced ileum epithelial NLRP3 inflammasome formation and decreased the levels of inflammatory factors compared with the cisplatin group. In parallel, Nrf2 inhibitor ML385 blocked the therapeutic effect of dioscin in rat with cisplatin-induced intestinal toxicity. In terms of mechanisms, dioscin reversed cisplatin-induced up-regulation of MAPKs and up-regulated p-PI3K and p-AKT levels. Meanwhile, dioscin potently promoted Wnt3A/β-catenin signaling to relieve cisplatin-induced proliferation inhibition. In conclusion, our study suggests that dioscin could ameliorate the cisplatin-induced intestinal toxicity by reducing oxidative stress and inflammation.
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http://dx.doi.org/10.1016/j.intimp.2022.109111DOI Listing
August 2022

Biophysical properties of hydrogels for mimicking tumor extracellular matrix.

Biomater Adv 2022 May 30;136:212782. Epub 2022 Mar 30.

Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address:

The extracellular matrix (ECM) is an essential component of the tumor microenvironment. It plays a critical role in regulating cell-cell and cell-matrix interactions. However, there is lack of systematic and comparative studies on different widely-used ECM mimicking hydrogels and their properties, making the selection of suitable hydrogels for mimicking different in vivo conditions quite random. This study systematically evaluates the biophysical attributes of three widely used natural hydrogels (Matrigel, collagen gel and agarose gel) including complex modulus, loss tangent, diffusive permeability and pore size. A new and facile method was developed combining Critical Point Drying, Scanning Electron Microscopy imaging and a MATLAB image processing program (CSM method) for the characterization of hydrogel microstructures. This CSM method allows accurate measurement of the hydrogel pore size down to nanometer resolution. Furthermore, a microfluidic device was implemented to measure the hydrogel permeability (P) as a function of particle size and gel concentration. Among the three gels, collagen gel has the lowest complex modulus, medium pore size, and the highest loss tangent. Agarose gel exhibits the highest complex modulus, the lowest loss tangent and the smallest pore size. Collagen gel and Matrigel produced complex moduli close to that estimated for cancer ECM. The P of these hydrogels decreases significantly with the increase of particle size. By assessing different hydrogels' biophysical characteristics, this study provides valuable insights for tailoring their properties for various three-dimensional cancer models.
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http://dx.doi.org/10.1016/j.bioadv.2022.212782DOI Listing
May 2022

α-FeO based nanotherapeutics for near-infrared/dihydroartemisinin dual-augmented chemodynamic antibacterial therapy.

Acta Biomater 2022 Jul 30. Epub 2022 Jul 30.

Guangdong Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Zhanjiang 524023, China; The Marine Biomedical Research Institute of Guangdong, Zhanjiang 524023, China. Electronic address:

Due to the negligible bacterial resistance, chemodynamic therapy (CDT) is a promising treatment for bacterial infection. However, it is severely impeded by the constant body temperature, shortage of Fe(Ⅱ) ions and insufficient HO level in infected tissue. To enhance the therapeutic efficiency of CDT, improved strategies are urgently needed to tackle these problems. Herein, we exploited an infection microenvironment-responsive nanotherapeutics for near-infrared (NIR)/dihydroartemisinin (DHA) dual-augmented antibacterial CDT. The convenient encapsulation of DHA-loaded α-FeO nanorods with metal-polyphenol networks (MPN) led to the generation of an antibacterial nanoagent [email protected]@MPN (FDM). Afterwards, its photothermal and peroxidase-like activities were intensively studied. Furthermore, the bactericidal efficacy of FDM was evaluated through both in vitro and in vivo antibacterial assays. Firstly, FDM showed both satisfactory photothermal and NIR/DHA dual-augmented peroxidase-like activities. Besides, it exhibited a pH-responsive release behavior of both Fe(Ⅱ) ions and DHA. Moreover, it presented tannic acid-mediated bacterial adhesion effect. In vitro experiments demonstrated that FDM could achieve a satisfactory efficiency against both planktonic bacteria and biofilms. In vivo assays illustrated both the extraordinary synergistic antibacterial effect and efficient anti-inflammatory ability of FDM. The outcomes indicated that the exploited antibacterial agent could offer new insight on developing intelligent nanotherapeutics for clinical use in the future. STATEMENT OF SIGNIFICANCE: The antibacterial efficiency of chemodynamic therapy (CDT) is seriously limited by the constant body temperature, shortage of Fe(Ⅱ) ions and insufficient HO level at the mildly acidic inflammatory microenvironment. To address these issues, we have developed a pH-responsive nanoagent ([email protected]@MPN) for near-infrared (NIR)/dihydroartemisinin (DHA) dual-augmented CDT. Through the NIR-induced photothermal effect of exterior Fe(Ⅲ)/tannic acid complex, the increased local temperature led to a photothermal enhanced CDT. Besides, a continuous supply of Fe(Ⅱ) ions could be achieved by tannic acid-mediated Fe(Ⅲ) reduction. Moreover, DHA was adopted as a substitute for HO to initiate DHA-mediated CDT. Both in vitro and in vivo assays demonstrated its outstanding bactericidal efficiency. Therefore, the developed nanotherapeutics could be a promising candidate for clinical trials.
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http://dx.doi.org/10.1016/j.actbio.2022.07.047DOI Listing
July 2022

Circ_0035381 Regulates Acute Myeloid Leukemia Development by Modulating YWHAZ Expression via Adsorbing miR-582-3p.

Biochem Genet 2022 Aug 2. Epub 2022 Aug 2.

Biological and Agricultural, Engineering College of Weifang University, No. 5147 Dongfeng East Street, Kuiwen District, Weifang, 261061, Shandong, China.

Acute myeloid leukemia (AML) is a common hematopoietic disorder. Many circular RNAs (circRNAs) are abnormally expressed in AML, including hsa_circ_0035381 (circ_0035381). Nevertheless, the function and mechanism of circ_0035381 in AML remain mostly unclear. Expression of circ_0035381 was determined by qRT-PCR. The impacts of circ_0035381 on AML cell proliferation, apoptosis, and mitochondrial damage were validated via performing loss-of-function experiments. Targeting relationship was predicted by bioinformatics analysis and verified via dual-luciferase reporter and RNA immunoprecipitation assays. Circ_0035381 was upregulated in AML bone marrow samples and cells. Circ_0035381 downregulation decreased AML cell growth in nude mice and restrained AML cell proliferation and contributed to AML apoptosis and mitochondrial damage in vitro. Circ_0035381 acted as a miR-582-3p sponge, and miR-582-3p downregulation mitigated the impacts of circ_0035381 interference on AML cell proliferation, apoptosis, and mitochondrial damage. MiR-582-3p targeted Tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ), and it restrained AML cell proliferation and facilitated AML cell apoptosis and mitochondrial damage by decreasing YWHAZ expression. Notably, circ_0035381 regulated YWHAZ expression via miR-582-3p. Circ_0035381 knockdown repressed cell proliferation and promoted cell apoptosis and mitochondrial damage via regulating the miR-582-3p/YWHAZ axis in AML.
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http://dx.doi.org/10.1007/s10528-022-10244-1DOI Listing
August 2022

Would you zoom with your doctor? A discrete choice experiment to identify patient preferences for video and in-clinic consultations in German primary care.

J Telemed Telecare 2022 Aug 2:1357633X221111975. Epub 2022 Aug 2.

Erasmus School of Health Policy and Management, 84857Erasmus University Rotterdam, The Netherlands.

Introduction: The popularity of video consultations in healthcare has accelerated during the COVID-19 pandemic. Despite increased availability and obvious benefits, many patients remain hesitant to use video consultations. This study investigates the relative importance of the consultation mode compared to other attributes in patients' appointment choices in Germany.

Methods: A discrete choice experiment was conducted to examine the influence of appointment attributes on preferences for video over in-clinic consultations. A total of 350 participants were included in the analysis.

Results: The level of continuity of care (46%) and the waiting time until the next available appointment (22%) were shown to have higher relative importance than consultation mode (18%) and other attributes. Participants with fewer data privacy concerns, higher technology proficiency, and more fear of COVID-19 tended to prefer video over in-clinic consultations. The predicted choice probability of a video over a typical in-clinic consultation and opting out increased from <1% to 40% when the video consultation was improved from the worst-case to the best-case scenario.

Conclusion: This study provides insight into the effect of the consultation mode on appointment choice at a time when telemedicine gains momentum. The results suggest that participants preferred in-clinic over video consultations. Policymakers and service providers should focus on increasing the level of continuity of care and decreasing the time until the next available appointment to prompt the adoption of video consultations. Although participants preferred to talk to their physician in person over consulting via video per se, the demand for video consultations can be increased significantly by improving the other appointment attributes of video consultations such as the level of continuity of care.
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http://dx.doi.org/10.1177/1357633X221111975DOI Listing
August 2022

S100a16 deficiency prevents hepatic stellate cells activation and liver fibrosis via inhibiting CXCR4 expression.

Metabolism 2022 Jul 29;135:155271. Epub 2022 Jul 29.

Department of Pharmacy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China; Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China. Electronic address:

Introduction: Liver fibrosis caused by hepatic stellate cells (HSCs) activation is implicated in the pathogenesis of liver diseases. To date, there has been no effective intervention means for this process. S100 proteins are calcium-binding proteins that regulate cell growth and differentiation. This study aimed to investigate whether S100A16 induces HSCs activation and participates in liver fibrosis progression.

Methods: HSCs were isolated, and the relationship between S100A16 expression and HSCs activation was studied. S100a16 knockdown and transgenic mice were generated and subjected to HSCs activation and liver fibrosis stimulated by different models. Clinical samples were collected for further confirmation. Alterations in gene expression in HSCs were investigated, using transcriptome sequencing to determine the underlying mechanisms.

Results: We observed increased S100A16 levels during HSCs activation. Genetic silencing of S100a16 prevented HSCs activation in vitro. Furthermore, S100a16 silencing exhibited obvious protective effects against HSCs activation and fibrosis progression in mice. In contrast, S100a16 transgenic mice exhibited spontaneous liver fibrosis. S100A16 was also upregulated in the HSCs of patients with fibrotic liver diseases. RNA sequencing revealed that C-X-C motif chemokine receptor 4 (Cxcr4) gene was a crucial regulator of S100A16 induction during HSCs activation. Mechanistically, S100A16 bound to P53 to induce its degradation; this augmented CXCR4 expression to activate ERK 1/2 and AKT signaling, which then promoted HSCs activation and liver fibrosis.

Conclusions: These data indicate that S100a16 deficiency prevents liver fibrosis by inhibiting Cxcr4 expression. Targeting S100A16 may provide insight into the pathogenesis of liver fibrosis and pave way for the design of novel clinical therapeutic strategies.
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http://dx.doi.org/10.1016/j.metabol.2022.155271DOI Listing
July 2022

NAFLD aggravates acute pancreatitis through bacterial translocation and cholesterol metabolic dysregulation in the liver and pancreas in mice.

Hepatobiliary Pancreat Dis Int 2022 Jul 20. Epub 2022 Jul 20.

Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China; Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing 100044, China. Electronic address:

Background: Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for severe acute pancreatitis (AP). The underlying mechanism remains unclear. We sought to determine how bacterial translocation and cholesterol metabolism in the liver and pancreas affect the severity of AP in NAFLD mice.

Methods: C57BL/6N mice were fed on a high-fat diet (HFD) to generate the NAFLD model, and mice in the control group were provided with a normal diet (ND). After being anesthetized with ketamine/xylazine, mice got a retrograde infusion of taurocholic acid sodium into the pancreatic duct to induce AP, and sham operation (SO) was used as control. Serum amylase and Schmidt's pathological score system were used to evaluate AP severity. Bacterial loads, total cholesterol level, and cholesterol metabolic-associated molecules [low-density lipoprotein receptor (LDLR) and ATP-binding cassette transporter A1 (ABCA1)] were analyzed in the liver and pancreas.

Results: Compared with the ND-AP group, mice in the HFD-AP group had severer pancreatitis, manifested with higher serum amylase levels and higher AP pathologic scores, especially the inflammation and hemorrhage scores. Compared with the HFD-SO group and ND-AP group, bacterial loads in the liver and pancreas were significantly higher in the HFD-AP group. Mice in the HFD-AP group showed a decreased LDLR expression and an increased ABCA1 expression in the pancreas, although there was no significant difference in pancreas total cholesterol between the HFD-AP group and the ND-AP group.

Conclusions: NAFLD aggravates AP via increasing bacterial translocation in the liver and pancreas and affecting pancreas cholesterol metabolism in mice.
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http://dx.doi.org/10.1016/j.hbpd.2022.07.004DOI Listing
July 2022

Microbial induced phosphate precipitation accelerate lead mineralization to alleviate nucleotide metabolism inhibition and alter Penicillium oxalicum's adaptive cellular machinery.

J Hazard Mater 2022 Jul 23;439:129675. Epub 2022 Jul 23.

College of New Energy and Environment, Jilin University, Changchun 130021, PR China; Key Laboratory of Groundwater Resources and Environment Ministry of Education, Jilin University, Changchun 130021, PR China. Electronic address:

Microbial-induced phosphate (P) precipitation (MIPP) based on P-solubilizing microorganisms (PSM) is regarded as a promising approach to bioimmobilize environmental lead (Pb). Nevertheless, the underlying changes of Pb biotoxicity in PSM during MIPP process were rarely discussed. The current study explored the Pb immobilization and metabolic changes in PSM Penicillium oxalicum postexposure to Pb and/or tricalcium phosphate (TCP). TCP addition significantly increased soluble P concentrations, accelerated extracellular Pb mineralization, and improved antioxidative enzyme activities in P. oxalicum during MIPP process. Secondary Pb biomineralization products were measured as hydroxypyromorphite [Pb(PO)(OH)]. Using untargeted metabolomic and transcriptomics, we found that Pb exposure stimulated the membrane integrity deterioration and nucleotide metabolism obstruction of P. oxalicum. Correspondingly, P. oxalicum could produce higher levels of gamma-aminobutyric acid (GABA) to enhance the adaptive cellular machineries under Pb stress. While the MIPP process improved extracellular Pb mineralization, consequently alleviating the nucleotide metabolism inhibition and membrane deterioration. Multi-omics results suggested that GABA degradation pathway was stimulated for arginine biosynthesis and TCA cycle after Pb mineralization. These results provided new biomolecular information underlying the Pb exposure biotoxicities to microorganisms in MIPP before the application of this approach in environmental Pb remediation.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129675DOI Listing
July 2022

A truncated derivative of FGFR1 kinase cooperates with FLT3 and KIT to transform hematopoietic stem cells in syndromic and de novo AML.

Mol Cancer 2022 07 29;21(1):156. Epub 2022 Jul 29.

Georgia Cancer Center, Augusta University, 1410 Laney Walker Blvd, Augusta, GA, 30912, USA.

Background: Myeloid and lymphoid malignancies associated with chimeric FGFR1 kinases are the hallmark of stem cell leukemia and lymphoma syndrome (SCLL). In all cases, FGFR1 kinase is constitutively phosphoactivated as a result of chromosome translocations, which lead to acquisition of dimerization motifs in the chimeric proteins. Recently, we demonstrated that these chimeric kinases could be cleaved by granzyme B to generate a truncated derivative, tnFGFR1, which localized exclusively into the nucleus and was not phosphorylated.

Methods: Stem cell transduction and transplantation in syngeneic mice was used to assess the transforming ability of tnFGFR1 in bone marrow stem cells, and RPPA and RNA-Seq was used to examine the related signaling pathways and regulated target genes.

Results: For the first time, we show that this non-classical truncated form of FGFR1 can independently lead to oncogenic transformation of hematopoietic stem cells in an animal model in vivo. These leukemia cells show a mixed immunophenotype with a B-cell B220 + Igm- profile in the majority of cells and Kit+ in virtually all cells, suggesting a stem cell disease. tnFGFR1, however, does not activate classic FGFR1 downstream signaling pathways but induces a distinct profile of altered gene expression with significant upregulation of transmembrane signaling receptors including FLT3 and KIT. We further show that de novo human AML also express tnFGFR1 which correlates with upregulation of FLT3 and KIT as in mouse leukemia cells. ChIP analysis demonstrates tnFGFR1 occupancy at the Flt3 and Kit promoters, suggesting a direct transcriptional regulation. Cells transformed with tnFGFR1 are insensitive to FGFR1 inhibitors but treatment of these cells with the Quizartinib (AC220) FLT3 inhibitor, suppresses in vitro growth and development of leukemia in vivo. Combined treatment with FGFR1 and FLT3 inhibitors provides increased survival compared to FGFR1 inhibition alone.

Conclusions: This study demonstrates a novel model for transformation of hematopoietic stem cells by chimeric FGFR1 kinases with the combined effects of direct protein activation by the full-length kinases and transcriptional regulation by the truncated nuclear tnFGFR1 derivative, which is associated with GZMB expression levels. Genes significantly upregulated by tnFGFR1 include Flt3 and Kit which promote a leukemia stem cell phenotype. In human AML, tnFGFR1 activation leads to increased FLT3 and KIT expression, and higher FLT3 and GZMB expression levels are associated with an inferior prognosis. These observations provide insights into the relative therapeutic value of targeting FGFR1 and FLT3 in treating AML with this characteristic gene expression profile.
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http://dx.doi.org/10.1186/s12943-022-01628-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336057PMC
July 2022

Trace determination of fifteen free amino acids in drinking source water via solid-phase extraction coupled with liquid chromatography tandem mass spectrometry.

Environ Sci Pollut Res Int 2022 Jul 29. Epub 2022 Jul 29.

Ministry of Ecology and Environment of the People's Republic of China, South China Institute of Environmental Sciences, Guangzhou, 510655, China.

Amino acids (AAs) are important nitrogen-containing organics in water, and a large number of reports have proven that they were the precursors of many nitrogen-containing disinfection by-products, some of which have cytotoxicity and carcinogenicity. However, little has been done on their occurrence in drinking source water. Therefore, a trace determination method via solid-phase extraction coupled with ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for 15 free AAs (FAAs) was developed, which was successfully applied for drinking source water samples. For sample preparation, strong cation-exchange stationary solid-phase extraction (SPE) cartridge showed better extraction performance to that of reverse phase stationary oasis HLB SPE cartridge. The optimal water pH was determined to be 2.8 before extraction. Strong matrix effects for most FAAs were observed in this work; thus, sample extraction with SPE was recommended to eliminate the matrix effects. The developed method showed excellent linearity (R > 0.991), low limits of detection (LODs, 0.01-0.27 nmol/L), and good recoveries of 69.8-117.9% in drinking source water with low relative standard deviations (RSDs, 0.3-13.2%). The developed method was finally applied to eight drinking source water samples, and the top five FAAs were found to be serine, glycine, leucine, alanine, and isoleucine.
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http://dx.doi.org/10.1007/s11356-022-22133-6DOI Listing
July 2022

PD-L1 and the Clinical Outcomes of Ovarian Cancer: Meta-Analysis and Bioinformatical Analysis.

Asian Pac J Cancer Prev 2022 07 1;23(7):2285-2290. Epub 2022 Jul 1.

Department of Toxicology, Guilin Medical University, Guilin 541004, China.

Objective: A meta-analysis was performed to analyze the association between PD-L1 expression and overall survival (OS) in various tumors and to identify potential targets through biological information analysis.

Methods: the data were collected from PubMed and Cochrane library, the all analysis of our study were conducted by STATA software and online website.

Results: Ten articles (including 11 studies) that met all inclusion criteria were obtained. The combined HR showed that high PD-L1 expression was significantly associated with poor overall survival (HR = 1.84, 95% CI: 1.15-2.93). Pathway analysis revealed that the upregulated genes were primarily involed in biological processes, including nucleic acid transcription, biosynthesis and negative regulation of cell metabolism. The downregulated genes were primarily involed in the regulation of cell cycle, including chromosome separation and DNA metabolism. The top ten genes that were identified were hub genes (CDK1, CCNB1, CCNA2, KIF11, CDC20, UBE2C, NCAPG, AURKA, AURKB, CHEK1), which had significant function in cell differentiation and virus infection. The Kaplan-Meier survival curve indicated that CCNB1, KIF11, UBE2C, NCAPG, AURKA and CHEK1 were statistically significant (P<0.05).

Conclusion: PD-L1 was found to be a latent biomarker for predicting the prognostic value of cancer and also a therapeutic target.
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http://dx.doi.org/10.31557/APJCP.2022.23.7.2285DOI Listing
July 2022

Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to let-7c-5p and miR-181b-5p.

Front Endocrinol (Lausanne) 2022 8;13:926769. Epub 2022 Jul 8.

Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

As carriers containing abundant biological information, exosomes could deliver the property of donor cells to recipient cells. Emerging studies have shown that tumor cells could secrete a mass of exosomes into the microenvironment to regulate bystander cells. However, the underlying mechanisms of such a phenomenon remain largely unexplored. In this research, we purified and identified the exosomes of A549 cells and found that A549-cell-derived exosomes promoted BEAS-2B cells migration, invasion, and epithelial-mesenchymal transition (EMT). Importantly, we observed that let-7c-5p and miR-181b-5p were attenuated in A549-cell-derived exosomes compared to BEAS-2B-cell-derived exosomes. The analysis of miRNA expression level in BEAS-2B cells indicated that incubation with A549-cell-derived exosomes reduced the expression levels of let-7c-5p and miR-181b-5p. In transient transfections assay, we found that downregulation of let-7c-5p and miR-181b-5p simultaneously showed stronger promotion of BEAS-2B cells migration and invasion than individually. Moreover, exosomes secreted from A549 cells with upregulated expression of let-7c-5p and miR-181b-5p significantly reduce their regulatory effect on BEAS-2B cells. Bioinformatics analyses revealed that let-7c-5p and miR-181b-5p inhibit the EMT process mainly by regulating focal adhesion and mitogen-activated protein kinase (MAPK) signaling pathway. Thus, our data demonstrated that A549-cell-derived exosomal let-7c-5p and miR-181b-5p could induce migration, invasion, and EMT in BEAS-2B cells, which might be regulated through focal adhesion and MAPK signaling pathway. The expression level of let-7c-5p and miR-181b-5p may show great significance for the early diagnosis of lung cancer.
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http://dx.doi.org/10.3389/fendo.2022.926769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309177PMC
July 2022

Telomere Length and Hearing Loss: A Two-Sample Mendelian Randomization.

Int J Environ Res Public Health 2022 Jul 22;19(15). Epub 2022 Jul 22.

School of Public Health, Hangzhou Normal University, Hangzhou 310000, China.

Background: Observational studies have suggested that there may be an association between telomere length (TL) and hearing loss (HL). However, inferring causality from observational studies is subject to residual confounding effects, reverse causation, and bias. This study adopted a two-sample Mendelian randomization (MR) approach to evaluate the causal relationship between TL and increased risk of HL.

Methods: A total of 16 single nucleotide polymorphisms (SNPs) associated with TL were identified from a genome-wide association study (GWAS) meta-analysis of 78,592 European participants and applied to our modeling as instrumental variables. Summary-level data for hearing loss (HL), age-related hearing loss (ARHL), and noise-induced hearing loss (NIHL) were obtained from the recent largest available GWAS and five MR analyses were used to investigate the potential causal association of genetically predicted TL with increased risk for HL, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode. In addition, sensitivity analysis, pleiotropy, and heterogeneity tests were also used to evaluate the robustness of our findings.

Results: There was no causal association between genetically predicted TL and HL or its subtypes (by the IVW method, HL: odds ratio (OR) = 1.216, = 0.382; ARHL: OR = 0.934, = 0.928; NIHL: OR = 1.003, = 0.776). Although heterogenous sites rs2736176, rs3219104, rs8105767, and rs2302588 were excluded for NIHL, the second MR analysis was consistent with the first analysis (OR = 1.003, = 0.572).

Conclusion: There was no clear causal relationship between shorter TLs and increased risk of HL or its subtypes in this dataset.
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http://dx.doi.org/10.3390/ijerph19158937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330868PMC
July 2022

Clinicopathological Analysis of Expression of Enhancer of Zeste Homologue 2 in Canine Mammary Carcinoma.

J Vet Res 2022 Jun 5;66(2):267-272. Epub 2022 Jul 5.

Department of Veterinary Clinic, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150000, PR China.

Introduction: Enhancer of zeste homologue 2 (EZH2) is the human homologue of gene enhancer. The aim of this study was to determine the expression of EZH2 in canine mammary carcinomas (CMCs) and its relationship with clinicopathological features.

Material And Methods: The expression of EZH2 mRNA and protein in 53 CMC tissue and 8 normal mammary gland tissue samples was measured by quantitative real-time PCR and immunohistochemical staining assay, respectively. The relationship between EZH2 protein expression and clinicopathological features was analysed by χ2 test to further explore the clinical significance of EZH2 in CMCs.

Results: Compared with normal mammary gland tissues, EZH2 mRNA expressions were significantly increased in CMC tissues (P < 0.01). Moreover, normal mammary glands did not express the EZH2 protein but carcinomic glands did, and expression increased in CMCs with high histological grades, especially in histological grade II (P < 0.05). However, EZH2 expression was not related to age, tumour size, or metastasis (P > 0.05). The expression of EZH2 in one type of CMC was not significantly different from the expression in any other type (P > 0.05).

Conclusion: EZH2 is highly expressed in CMCs, indicating that it can be used as a molecular marker for early diagnosis, prognosis, or therapy of CMCs.
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http://dx.doi.org/10.2478/jvetres-2022-0033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281528PMC
June 2022

Progressive Damage Behaviour Analysis and Comparison with 2D/3D Hashin Failure Models on Carbon Fibre-Reinforced Aluminium Laminates.

Polymers (Basel) 2022 Jul 20;14(14). Epub 2022 Jul 20.

School of Mechanical and Engineering, Tianjin Sino-German University of Applied Sciences, Tianjin 300350, China.

It is known that carbon fibre-reinforced aluminium laminate is the third generation of fibre metal materials. This study investigates the response of carbon fibre-reinforced aluminium laminates (CARALL) under tensile loading and three-point bending tests, which evaluate the damage initiation and propagation mechanism. The 2D Hashin and 3D Hashin VUMAT models are used to analyse and compare each composite layer for finite element modelling. A bilinear cohesive contact model is modelled for the interface failure, and the Johnson cook model describes the aluminium layer. The mechanical response and failure analysis of CARALL were evaluated using load versus deflection curves, and the scanning electron microscope was adopted. The results revealed that the failure modes of CARALL were mainly observed in the aluminium layer fracture, fibre pull-out, fracture, and matrix tensile fracture under tensile and flexural loading conditions. The 2D Hashin and 3D Hashin models were similar in predicting tensile properties, flexural properties, mechanical response before peak load points, and final failure modes. It is highlighted that the 3D Hashin model can accurately reveal the failure mechanism and failure propagation mechanism of CARALL.
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http://dx.doi.org/10.3390/polym14142946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324354PMC
July 2022

Aging endometrium in young women: molecular classification of endometrial aging-based markers in women younger than 35 years with recurrent implantation failure.

J Assist Reprod Genet 2022 Jul 26. Epub 2022 Jul 26.

Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510655, China.

Background: To explore the differences between a population with premature endometrial aging and a population with normal endometrial status in young women with recurrent implantation failure (< 35 years).

Methods: Systematic analysis of the endometrium transcriptome of 274 RIF women. The NMF algorithm was used for classification based on endometrial-specific aging markers in CellAge, and the endometrial receptivity, gene expression patterns, and clinical data were compared between the classifications.

Results: Two hundred forty-five young RIF women could be divided into two clusters, in which the aging gene expression pattern of cluster 2 was closer to the reference cluster. Cluster 1 was characterized by high immune activity, while cluster 2 was characterized by high metabolic activity. Combined with clinical data, cluster 2 was worse than cluster 1 in window of implantation deviation rate and endometrial receptivity.

Conclusion: Premature aging of the endometrium exists in young women with RIF, and premature aging of the endometrium was associated with poor reproductive outcomes.
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http://dx.doi.org/10.1007/s10815-022-02578-xDOI Listing
July 2022

Redox-Activatable Theranostic Co-Prodrug for Precise Tumor Diagnosis and Selective Combination Chemotherapy.

J Med Chem 2022 Aug 25;65(15):10393-10407. Epub 2022 Jul 25.

School of Pharmacy, Nantong University, Nantong 226001, P. R. China.

A novel theranostic co-prodrug has been designed by combining a co-prodrug from CDDO-Me and SAHA with a biotin-coupled near-infrared (NIR) probe hemicyanine via redox-responsive linker thiolactate to enhance the tumor theranostic efficacy and reduce the toxic side effects using both active and passive targeting strategies. displayed reactive oxygen species (ROS)- and glutathione (GSH)-dependent release of NIR fluorescence and two parent drugs. Furthermore, the administration of caused selective illumination of the tumor tissues for >24 h, thereby guiding precise removal of a tumor from intraoperative mice. Importantly, exhibited highly efficient tumor inhibition, exerted selective combination therapy through prodrug mode, and minimized the adverse effects. Finally, induced mitochondrial depolarization, DNA damage, and cell apoptosis through ROS generation and downregulation of HDAC6 protein, as verified by H2AX, Bax, cleaved-PARP, and Mcl-1 proteins. Thus, we suggest that can provide a new platform for both precise diagnosis-guided tumor removal and selective combination therapy with high safety.
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http://dx.doi.org/10.1021/acs.jmedchem.2c00130DOI Listing
August 2022

Construction of circRNA-Mediated Immune-Related ceRNA Network and Identification of Circulating circRNAs as Diagnostic Biomarkers in Acute Ischemic Stroke.

J Inflamm Res 2022 17;15:4087-4104. Epub 2022 Jul 17.

Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, People's Republic of China.

Background And Purpose: Accumulating evidence suggests that circular RNAs (circRNAs) are involved in immune and inflammatory processes after acute ischemic stroke (AIS). However, the roles of circRNA-mediated competing endogenous RNA (ceRNA) in modulating immune inflammation of AIS have not yet been determined. This study aimed to construct a circRNA-mediated immune-related ceRNA network and identify novel circRNAs in AIS.

Methods: Microarray data were downloaded from the GEO database and further analysed by R software. Then, we constructed a circRNA-mediated ceRNA network based on interaction information from the bioinformatics database. A topological property analysis of the ceRNA network was conducted to screen novel circRNAs. Finally, we further applied quantitative real-time polymerase chain reaction (qRT-PCR) to two independent sets.

Results: We constructed an AIS immune-related ceRNA (AISIRC) network containing immune-related genes (IRGs), miRNAs, and circRNAs. Additionally, we extracted the subnetwork from the AISIRC network and screened six immune-related circRNAs. After identification and validation, we finally confirmed that plasma levels of circPTP4A2 and circTLK2 were significantly increased in AIS patients compared with both healthy control subjects (HCs) and transient ischemic attack (TIA) patients. Logistic regression and receiver-operating characteristic (ROC) curve analyses demonstrated that these two circRNAs may function as predictive and discriminative biomarkers for AIS. We also confirmed that plasma levels of circPTP4A2 were elevated in TIA patients compared with HCs and might be an independent risk factor for predicting TIA. Longitudinal analysis of circRNA expression up to 90 days after AIS indicated that the ability of circPTP4A2 and circTLK2 to monitor AIS dynamics was highly desirable.

Conclusion: In summary, the circRNA-mediated immune-related ceRNA network was successfully constructed, and two circulating circRNAs (circPTP4A2 and circTLK2) improved sensitivity for the diagnosis of AIS and could be considered diagnostic biomarkers.
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http://dx.doi.org/10.2147/JIR.S368417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304636PMC
July 2022

Carotenoid extraction, detection, and analysis in citrus.

Methods Enzymol 2022 1;670:179-212. Epub 2022 Feb 1.

Key Laboratory of Horticultural Plant Biology of MOE (Ministry of Education), Huazhong Agricultural University, Wuhan, China. Electronic address:

Citrus is an important horticultural crop with global, economic and nutritional value. Carotenoids represent the main pigments in citrus fruits and contribute to the esthetic and nutritional value. The complexity of carotenoids in citrus poses a challenge for carotenoid analysis. In this chapter, we describe methods for carotenoid extraction, detection, and analysis that have been optimized for study of citrus fruits. High-performance liquid chromatography (HPLC) and Ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) strategies are used for carotenoid profiling of citrus fruit carotenoids and are explained in detail. We outline the applications, advantages, and disadvantages of using these methods to analyze carotenoids in the main citrus species including mandarin, orange, and pummelo.
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http://dx.doi.org/10.1016/bs.mie.2022.01.006DOI Listing
February 2022

Novel protein kinase inhibitor TT-00420 inhibits gallbladder cancer by inhibiting JNK/JUN-mediated signaling pathway.

Cell Oncol (Dordr) 2022 Jul 23. Epub 2022 Jul 23.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai, 200127, China.

Purpose: This study aimed to investigate the efficiency of our chemically synthesized TT-00420, a novel spectrum-selective multiple protein kinase inhibitor, in cultured cells and animal models of gallbladder cancer (GBC) and explore its potential mechanism.

Methods: Multiple GBC models were established to assess the anti-tumor efficiency, toxicity, and pharmacokinetics of TT-00420. Integrated transcriptomic, proteomic and phosphoproteomic analysis was conducted to identify potential downstream effectors of TT-00420. Western blotting, qRT-PCR, nuclear-cytoplasm separation, and immunofluorescence were performed to confirm the multi-omic results and explore the molecular mechanism of TT-00420. Immunohistochemistry was used to detect FGFR1 and p-FGFR1 expression levels in GBC samples. Autodock software was utilized to investigate the potential binding mode between the TT-00420 and the human FGFR1.

Results: We found that TT-00420 exerted potent growth inhibition of GBC cell lines and multiple xenograft models. Treatment of mice with 15 mg/kg TT-00420 via gavage displayed a half-life of 1.8 h in the blood and rapid distribution to the liver, kidneys, lungs, spleen, and tumors at 0.25 h, but no toxicity to these organs over 2 weeks. Multi-omic analysis revealed c-Jun as a potential downstream effector after TT-00420 treatment. Mechanistically, TT-00420 showed rigorous ability to block FGFR1 and its downstream JNK-JUN (S63/S73) signaling pathway, and induce c-Jun S243-dependent MEK/ERK reactivation, leading to FASLG-dependent tumor cell death. Finally, we found that FGFR1 and p-FGFR1 expression was elevated in GBC patients and these levels correlated with decreased patient survival.

Conclusions: TT-00420 shows potent antitumor efficacy and may serve as a novel agent to improve GBC prognosis.
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http://dx.doi.org/10.1007/s13402-022-00692-7DOI Listing
July 2022

2D MXene interfaces preserve the basal electrophysiology of targeted neural circuits.

Nanoscale 2022 Aug 4;14(30):10992-11002. Epub 2022 Aug 4.

Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, 215000, China.

Neural interfaces enable the monitoring of the state of the brain and its composite cell networks, as well as stimulate them to treat nervous disorders. In addition to their highly efficient charge transduction and stability during operation, the neural electrodes should avoid altering the physiological properties of targeted neuronal tissues. Two-dimensional (2D) MXene materials integrate the advantages of metallic conductivity, high specific-surface area and surface functionality in aqueous dispersions, showing promising potential in neural interface applications. Here, we apply uncoated TiCT MXene to interface neuronal development. The impacts of the uncoated TiCT MXene interface on neuronal development and neuronal microcircuit activity were tested for the first time. Compared to the standard neuronal culture with a poly-L-ornithine coated coverslip, uncoated TiCT MXene surfaces did not affect the cell morphology, density, neuron ratios, maturation or the compositions of the neuronal network. Moreover, calcium imaging, spontaneous postsynaptic currents (sPSCs) and also miniature postsynaptic currents (mPSCs) were recorded to demonstrate that TiCT MXene interfaces preserved the basal physiology of neuronal activity. The ability to interface neuronal circuit development without altering neuronal signaling properties enables the construction of MXene-based neural prosthetic devices for neuroscience research, diagnosis, and therapies.
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http://dx.doi.org/10.1039/d2nr01542kDOI Listing
August 2022

Effects of oral non-protein calorie supplements on nutritional status among maintenance hemodialysis patients with protein-energy wasting: a multi-center randomized controlled trial.

Food Funct 2022 Jul 21. Epub 2022 Jul 21.

Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China.

Protein-energy wasting (PEW) is prevalent in maintenance hemodialysis (MHD) patients, and is one of the major risk factors for poor outcomes and death. This study aimed to investigate the effects of non-protein calorie supplements on the nutritional status of MHD patients with PEW. MHD patients with PEW were enrolled in this multi-center, open-label, randomized controlled trial. Then, they were randomly assigned to the intervention group to receive the non-protein calorie supplements containing 280 kcal of energy every day for 6 months or the control group to complete all aspects of the study without receiving supplements. Patients in both groups received dietary counselling from dietitians. Data on nutritional assessments, anthropometric measurements, blood analysis and dietary recall were collected at the baseline and at six months from both groups. Statistical analyses were performed using analysis of covariance (ANCOVA) adjusted for sex and baseline values. Ninety-two MHD patients completed the study. A significant increase in the subjective global assessment (SGA) score was found in the intervention group compared with the control group (4.88 ± 1.41 4.40 ± 1.16, = 0.044). The ratio of PEW patients (diagnosed with SGA ≤5) in the intervention group (61.2%) was also significantly lower than that in the control group (83.7%) ( < 0.001). Moreover, significant improvements in body mass index (20.81 ± 2.46 kg m 19.51 ± 2.60 kg m, < 0.001), nutrition risk screening 2002 (2.45 ± 1.40 3.12 ± 1.37, = 0.038), mid-upper arm circumference (23.30 ± 2.78 cm 21.75 ± 2.87 cm, = 0.001), and mid-arm muscle circumference (20.51 ± 2.32 cm 19.06 ± 2.92 cm, = 0.005) were observed in the intervention group compared with the control group. Patients in the intervention group took in more dietary energy than the control group (26.96 ± 4.75 kcal per kg body weight per day 24.33 ± 2.68 kcal per kg body weight per day, < 0.001). In conclusion, non-protein calorie supplements may improve the nutritional status of MHD patients with PEW.
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http://dx.doi.org/10.1039/d1fo03791aDOI Listing
July 2022

Sensitivity Toward Gender and Sexually Diverse Populations: Development of a Scale.

J Nurs Educ 2022 Jul 1;61(7):383-389. Epub 2022 Jul 1.

Background: Individuals who are lesbian, gay, bisexual, transgender, queer, intersex, asexual, or nonbinary (LGBTQIA+) experience inequitable access to and utilization of health care services. Nurses' lack of awareness and sensitivity may contribute to this phenomenon.

Purpose: This article describes the development and validation of the Gender and Sexual Diversity Sensitivity Scale (GSDSS). A sample of 210 undergraduate nursing students from a large research-intensive university completed the scale online. An exploratory factor analysis was conducted.

Results: Factor analysis illustrated a three-factor construct of the scale (i.e., General Education Experience, Cognitive Awareness, and Comfort With Interactions); Cronbach's alpha coefficients ranged from .66 to .91, and the total scale alpha coefficient was .782.

Conclusion: The GSDSS has evidence of construct validity and reliability, and can be used in studies that include nursing and other health professional students. .
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http://dx.doi.org/10.3928/01484834-20220613-01DOI Listing
July 2022

Simplified Transfer Learning for Chest Radiography Models Using Less Data.

Radiology 2022 Jul 19:212482. Epub 2022 Jul 19.

From Google Health, Google, 3400 Hillview Ave, Palo Alto, CA 94304 (A.B.S., C.C., Z.N., Y. Liu, K.E., D.T., N.B., S.S.); Google Research, Cambridge, Mass (Y. Li, A.M., A.S., J.H., D.K.); Google via Advanced Clinical, Deerfield, Ill (C.L.); Apollo Radiology International, Hyderabad, India (S.R.K.); and Northwestern Medicine, Chicago, Ill (M.E., F.G.V., D.M.).

Background Developing deep learning models for radiology requires large data sets and substantial computational resources. Data set size limitations can be further exacerbated by distribution shifts, such as rapid changes in patient populations and standard of care during the COVID-19 pandemic. A common partial mitigation is transfer learning by pretraining a "generic network" on a large nonmedical data set and then fine-tuning on a task-specific radiology data set. Purpose To reduce data set size requirements for chest radiography deep learning models by using an advanced machine learning approach (supervised contrastive [SupCon] learning) to generate chest radiography networks. Materials and Methods SupCon helped generate chest radiography networks from 821 544 chest radiographs from India and the United States. The chest radiography networks were used as a starting point for further machine learning model development for 10 prediction tasks (eg, airspace opacity, fracture, tuberculosis, and COVID-19 outcomes) by using five data sets comprising 684 955 chest radiographs from India, the United States, and China. Three model development setups were tested (linear classifier, nonlinear classifier, and fine-tuning the full network) with different data set sizes from eight to 8. Results Across a majority of tasks, compared with transfer learning from a nonmedical data set, SupCon reduced label requirements up to 688-fold and improved the area under the receiver operating characteristic curve (AUC) at matching data set sizes. At the extreme low-data regimen, training small nonlinear models by using only 45 chest radiographs yielded an AUC of 0.95 (noninferior to radiologist performance) in classifying microbiology-confirmed tuberculosis in external validation. At a more moderate data regimen, training small nonlinear models by using only 528 chest radiographs yielded an AUC of 0.75 in predicting severe COVID-19 outcomes. Conclusion Supervised contrastive learning enabled performance comparable to state-of-the-art deep learning models in multiple clinical tasks by using as few as 45 images and is a promising method for predictive modeling with use of small data sets and for predicting outcomes in shifting patient populations. © RSNA, 2022
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http://dx.doi.org/10.1148/radiol.212482DOI Listing
July 2022
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