Publications by authors named "Xiaoyu Cai"

48 Publications

Gut cytokines modulate olfaction through metabolic reprogramming of glia.

Nature 2021 Jul 21. Epub 2021 Jul 21.

Immunology Discovery, Genentech, Inc., South San Francisco, CA, USA.

Infection-induced aversion against enteropathogens is a conserved sickness behaviour that can promote host survival. The aetiology of this behaviour remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviours against toxic microorganisms. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviours remains unknown. Here we show that enteropathogen infection in Drosophila can modulate olfaction through metabolic reprogramming of ensheathing glia of the antennal lobe. Infection-induced unpaired cytokine expression in the intestine activates JAK-STAT signalling in ensheathing glia, inducing the expression of glial monocarboxylate transporters and the apolipoprotein glial lazarillo (GLaz), and affecting metabolic coupling of glia and neurons at the antennal lobe. This modulates olfactory discrimination, promotes the avoidance of bacteria-laced food and increases fly survival. Although transient in young flies, gut-induced metabolic reprogramming of ensheathing glia becomes constitutive in old flies owing to age-related intestinal inflammation, which contributes to an age-related decline in olfactory discrimination. Our findings identify adaptive glial metabolic reprogramming by gut-derived cytokines as a mechanism that causes lasting changes in a sensory system in ageing flies.
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http://dx.doi.org/10.1038/s41586-021-03756-0DOI Listing
July 2021

Diagnosis and Surgical Treatment of Human Brucellar Spondylodiscitis.

J Vis Exp 2021 May 23(171). Epub 2021 May 23.

Department of Spine Surgery, First Affiliated Hospital of Xinjiang Medical University;

Brucellar spondylodiscitis (BS) is the most prevalent and significant osteoarticular presentation of human Brucellosis, which is commonly manifested in pastoral communities. It is difficult to differentially diagnose and usually leads to irreversible neurologic deficits and spinal deformities. The initial diagnosis of BS is based on clinical findings and radiographic assessments, and the confirmed diagnosis should be established by the isolation of Brucella species from the blood and/or the standard tube agglutination test. Differential diagnosis of multifocal BS from either degenerative disc diseases or tuberculosis is especially highlighted. The surgical approach, either endoscopic or open, is demonstrated in detail, accompanied by radiographic evidence of structural compression or severe instability. Further, the crucial surgical steps, including single-stage transforaminal decompression, debridement, interbody fusion, and internal fixation, are explained. Moreover, perioperative care and postoperative rehabilitation are also addressed. Taken together, this clinical algorithm presents a practical guide that has yielded substantially satisfactory outcomes in the past decades, which can also be introduced for large-scale application to manage human BS, especially in endemic regions.
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http://dx.doi.org/10.3791/61840DOI Listing
May 2021

A new type of nanoscale reference grating manufactured by combined laser-focused atomic deposition and x-ray interference lithography and its use for calibrating a scanning electron microscope.

Ultramicroscopy 2021 Jul 3;226:113293. Epub 2021 May 3.

School of Physics Science and Engineering, Tongji University, Shanghai, China. Electronic address:

Calibration of magnification and nonlinearity of scanning electron microscopy (SEM) is an essential task. In this paper, we proposed a new type of 1D grating sample fabricated by combining laser-focused atomic deposition and x-ray interference lithography as a lateral standard for calibrating SEMs. The calibrations of the grating pattern by a metrological large-range atomic force microscope indicate that the grating sample exhibits outstanding pattern uniformity that surpasses conventional samples fabricated by e-beam lithography: (1) the nonlinear deviation of the grating structures is below +/- 0.5 nm over a measurement range of 5 µm; (2) the maximal variation of the calibrated mean pitch values is lower than 0.01 nm at different locations randomly selected all over the pattern area. The proposed new sample is applied for accurately calibrating the magnification and nonlinearity of a commercial SEM, showing its advantages of easy-of-use and high accuracy. The influence of the defocus level of SEM on the calibration result is also demonstrated. This research offers a feasible solution for highly accurate SEM calibration needed for 3D nanometrology and hybrid metrology demanded in metrology of modern nanoelectronics devices and systems.
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http://dx.doi.org/10.1016/j.ultramic.2021.113293DOI Listing
July 2021

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases.

Front Immunol 2021 31;12:664871. Epub 2021 Mar 31.

Department of Pharmacy, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China.

Osteoimmunity is involved in regulating the balance of bone remodeling and resorption, and is essential for maintaining normal bone morphology. The interaction between immune cells and osteoclasts in the bone marrow or joint cavity is the basis of osteoimmunity, in which the macrophage-osteoclast axis plays a vital role. Monocytes or tissue-specific macrophages (macrophages resident in tissues) are an important origin of osteoclasts in inflammatory and immune environment. Although there are many reports on macrophages and osteoclasts, there is still a lack of systematic reviews on the macrophage-osteoclast axis in osteoimmunity. Elucidating the role of the macrophage-osteoclast axis in osteoimmunity is of great significance for the research or treatment of bone damage caused by inflammation and immune diseases. In this article, we introduced in detail the concept of osteoimmunity and the mechanism and regulators of the differentiation of macrophages into osteoclasts. Furthermore, we described the role of the macrophage-osteoclast axis in typical bone damage caused by inflammation and immune diseases. These provide a clear knowledge framework for studying macrophages and osteoclasts in inflammatory and immune environments. And targeting the macrophage-osteoclast axis may be an effective strategy to treat bone damage caused by inflammation and immune diseases.
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http://dx.doi.org/10.3389/fimmu.2021.664871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044404PMC
March 2021

Ectopic models recapitulating morphological and functional features of articular cartilage.

Ann Anat 2021 Sep 19;237:151721. Epub 2021 Mar 19.

Center of Experimental Orthopaedics, Saarland University, Homburg, Germany. Electronic address:

Background: Articular cartilage is an extremely specialized connective tissue which covers all diarthrodial joints. Implantation of chondrogenic cells without or with additional biomaterial scaffolds in ectopic locationsin vivo generates substitutes of cartilage with structural and functional characteristics that are used in fundamental investigations while also serving as a basis for translational studies.

Methods: Literature search in Pubmed.

Results And Discussion: This narrative review summarizes the most relevant ectopic models, among which subcutaneous, intramuscular, and kidney capsule transplantation and elaborates on implanted cells and biomaterial scaffolds and on their use to recapitulate morphological and functional features of articular cartilage. Although the absence of a physiological joint environment and biomechanical stimuli is the major limiting factor, ectopic models are an established component for articular cartilage research aiming to generate a bridge between in vitro data and the clinically more relevant translational orthotopic in vivo models when their limitations are considered.
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http://dx.doi.org/10.1016/j.aanat.2021.151721DOI Listing
September 2021

Hydrogel-Guided, rAAV-Mediated IGF-I Overexpression Enables Long-Term Cartilage Repair and Protection against Perifocal Osteoarthritis in a Large-Animal Full-Thickness Chondral Defect Model at One Year In Vivo.

Adv Mater 2021 Apr 18;33(16):e2008451. Epub 2021 Mar 18.

Center of Experimental Orthopaedics, Saarland University and Saarland University Medical Center, D-66421, Homburg/Saar, Germany.

The regeneration of focal articular cartilage defects is complicated by the reduced quality of the repair tissue and the potential development of perifocal osteoarthritis (OA). Biomaterial-guided gene therapy may enhance cartilage repair by controlling the release of therapeutic sequences in a spatiotemporal manner. Here, the benefits of delivering a recombinant adeno-associated virus (rAAV) vector coding for the human insulin-like growth factor I (IGF-I) via an alginate hydrogel (IGF-I/AlgPH155) to enhance repair of full-thickness chondral defects following microfracture surgery after one year in minipigs versus control (lacZ/AlgPH155) treatment are reported. Sustained IGF-I overexpression is significantly achieved in the repair tissue of defects treated with IGF-I/AlgPH155 versus those receiving lacZ/AlgPH155 for one year and in the cartilage surrounding the defects. Administration of IGF-I/AlgPH155 significantly improves parameters of cartilage repair at one year relative to lacZ/AlgPH155 (semiquantitative total histological score, cell densities, matrix deposition) without deleterious or immune reactions. Remarkably, delivery of IGF-I/AlgPH155 also significantly reduces perifocal OA and inflammation after one year versus lacZ/AlgPH155 treatment. Biomaterial-guided rAAV gene transfer represents a valuable clinical approach to promote cartilage repair and to protect against OA.
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http://dx.doi.org/10.1002/adma.202008451DOI Listing
April 2021

pNaSS-Grafted PCL Film-Guided rAAV TGF-β Gene Therapy Activates the Chondrogenic Activities in Human Bone Marrow Aspirates.

Hum Gene Ther 2021 Apr 26. Epub 2021 Apr 26.

Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg/Saar, Germany.

Scaffold-guided viral gene therapy is a novel, powerful tool to enhance the processes of tissue repair in articular cartilage lesions by the delivery and overexpression of therapeutic genes in a noninvasive, controlled release manner based on a procedure that may protect the gene vehicles from undesirable host immune responses. In this study, we examined the potential of transferring a recombinant adeno-associated virus (rAAV) vector carrying a sequence for the highly chondroregenerative transforming growth factor beta (TGF-β), using poly(ɛ-caprolactone) (PCL) films functionalized by the grafting of poly(sodium styrene sulfonate) (pNaSS) in chondrogenically competent bone marrow aspirates as future targets for therapy in cartilage lesions. Effective overexpression of TGF-β in the aspirates by rAAV was achieved upon delivery using pNaSS-grafted and ungrafted PCL films for up to 21 days (the longest time point evaluated), with superior levels using the grafted films, compared with respective conditions without vector coating. The production of rAAV-mediated TGF-β by pNaSS-grafted and ungrafted PCL films significantly triggered the biological activities and chondrogenic processes in the samples (proteoglycan and type-II collagen deposition and cell proliferation), while containing premature mineralization and hypertrophy relative to the other conditions, with overall superior effects supported by the pNaSS-grafted films. These observations demonstrate the potential of PCL film-assisted rAAV TGF-β gene transfer as a convenient, off-the-shelf technique to enhance the reparative potential of the bone marrow in patients in future approaches for improved cartilage repair.
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http://dx.doi.org/10.1089/hum.2020.329DOI Listing
April 2021

Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part I: Large animals.

Ann Anat 2021 May 3;235:151680. Epub 2021 Feb 3.

Center of Experimental Orthopaedics, Saarland University, Homburg, Germany; Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg, Germany. Electronic address:

Background: The human knee is a complex joint, and affected by a variety of articular cartilage disorders. Large animal models are critical to model the complex disease mechanisms affecting a functional joint. Species-dependent differences highly affect the results of a pre-clinical study and need to be considered, necessitating specific knowledge not only of macroscopic and microscopic anatomical and pathological aspects, but also characteristics of their individual gait and joint movements.

Methods: Literature search in Pubmed.

Results And Discussion: This narrative review summarizes the most relevant anatomical structural and functional characteristics of the knee (stifle) joints of the major translational large animal species, comprising dogs, (mini)pigs, sheep, goats, and horses in comparison with humans. Specific characteristics of each species, including kinematical gait parameters are provided. Considering these multifactorial dimensions will allow to select the appropriate model for answering the research questions in a clinically relevant fashion.
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http://dx.doi.org/10.1016/j.aanat.2021.151680DOI Listing
May 2021

Regulating Gut Microbiome: Therapeutic Strategy for Rheumatoid Arthritis During Pregnancy and Lactation.

Front Pharmacol 2020 11;11:594042. Epub 2020 Nov 11.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and bone destruction. Microbial infection is considered to be the most important inducement of RA. The pregnancy planning of women in childbearing age is seriously affected by the disease activity of RA. Gut microbiome, related to immunity and inflammatory response of the host. At present, emerging evidence suggested there are significant differences in the diversity and abundance of gut microbiome during pregnancy and lactation, which may be associated with the fluctuation of RA disease activity. Based on these research foundations, we pioneer the idea of regulating gut microbiome for the treatment of RA during pregnancy and lactation. In this review, we mainly introduce the potential treatment strategies for controlling the disease activity of RA based on gut microbiome during pregnancy and lactation. Besides, we also briefly generalize the effects of conventional anti-rheumatic drugs on gut microbiome, the effects of metabolic changes during pregnancy on gut microbiome, alteration of gut microbiome during pregnancy and lactation, and the effects of anti-rheumatic drugs commonly used during pregnancy and lactation on gut microbiome. These will provide a clear knowledge framework for researchers in immune-related diseases during pregnancy. Regulating gut microbiome may be a potential and effective treatment to control the disease activity of RA during pregnancy and lactation.
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http://dx.doi.org/10.3389/fphar.2020.594042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748111PMC
November 2020

The role of short-chain fatty acids in immunity, inflammation and metabolism.

Crit Rev Food Sci Nutr 2020 Dec 1:1-12. Epub 2020 Dec 1.

Department of Pharmacy, Women's Hospital School of Medicine Zhejiang University, Hangzhou, China.

Short-chain fatty acids (SCFAs) are carboxylic acids with carbon atom numbers less than 6, which are important metabolites of gut microbiome. Existing research shows that SCFAs play a vital role in the health and disease of the host. First, SCFAs are the key energy source for colon and ileum cells, and affect the intestinal epithelial barrier and defense functions by regulating related gene expression. Second, SCFAs regulate the function of innate immune cells to participate in the immune system, such as macrophages, neutrophils and dendritic cells. Third, SCFAs can also regulate the differentiation of T cells and B cells and the antigen-specific adaptive immunity mediated by them. Besides, SCFAs are raw materials for sugar and lipid synthesis, which provides a theoretical basis for studying the potential role of SCFAs in regulating energy homeostasis and metabolism. There are also studies showing that SCFAs inhibit tumor cell proliferation and promote apoptosis. In this article, we summarized in detail the role of SCFAs in immunity, inflammation and metabolism, and briefly introduced the role of SCFAs in tumor cell survival. It provides a systematic theoretical basis for the study of SCFAs as potential drugs to promote human health.
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http://dx.doi.org/10.1080/10408398.2020.1854675DOI Listing
December 2020

Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part II: Small animals.

Ann Anat 2021 Mar 29;234:151630. Epub 2020 Oct 29.

Center of Experimental Orthopaedics, Saarland University, Homburg, Germany; Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg, Germany. Electronic address:

Background: Small animal models are critical to model the complex disease mechanisms affecting a functional joint leading to articular cartilage disorders. They are advantageous for several reasons and significantly contributed to the understanding of the mechanisms of cartilage diseases among which osteoarthritis.

Methods: Literature search in Pubmed.

Results And Discussion: This narrative review summarizes the most relevant anatomical structural and functional characteristics of the knee (stifle) joints of the major small animal species, including mice, rats, guinea pigs, and rabbits compared with humans. Specific characteristics of each species, including kinematical gait parameters are provided and compared with the human situation. When placed in a proper context respecting their challenges and limitations, small animal models are important and appropriate models for articular cartilage disorders.
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http://dx.doi.org/10.1016/j.aanat.2020.151630DOI Listing
March 2021

Application of a microfluidic paper-based bioimmunosensor with laser-induced fluorescence detection in the determination of alpha-fetoprotein from serum of hepatopaths.

Talanta 2021 Jan 14;221:121660. Epub 2020 Sep 14.

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Research Institute of Photocatalysis, School of Chemistry, Fuzhou University, Fuzhou, 350116, PR China.

As a common plasma protein, alpha-fetoprotein (AFP) is widely applied as the tumor biomarker for the diagnosis of many cancers. To develop a low cost, high sensitive and high-throughput method for the determination of AFP is significant for the disease diagnosis. In this work, an immunoassay with sandwich-type structures was performed on a paper-based chip for the analysis of AFP. AFP could be captured by the primary antibodies which were immobilized on the paper by chitosan. On the secondary antibodies, the modified initiator DNAs could trigger the hybridization chain reaction to amplify the fluorescence signals for AFP. A laser-induced fluorescence detector coupled with an interface was applied to detect the targets on the paper-based chip. Under the optimized conditions, the detection limit for AFP was 1.0 pg/mL. For every test, the sample solution consumption only was 10 μL. Finally, the method was applied to determine the AFP in serum of normal person and hepatopaths with hepatic malignant tumor, chronic hepatitis B and other suspected liver diseases. The AFP could be found from all of the samples and the results were similar to that obtained by chemiluminescence immunoassay. The recoveries for AFP ranged from 93.8% to 106%, which indicated the method was reliable. The method based on paper chip had great potential in the application of AFP determination.
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http://dx.doi.org/10.1016/j.talanta.2020.121660DOI Listing
January 2021

The Role of Microbiomes in Pregnant Women and Offspring: Research Progress of Recent Years.

Front Pharmacol 2020 8;11:643. Epub 2020 May 8.

Department of Pharmacy, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Pregnancy is a complicated and delicate process, the maternal body undergoes changes on hormones, immunity, and metabolism during pregnancy to support fetal development. Microbiomes in the human body mainly live in the intestine, and the human gut microbiomes are complex, which composed of more than 500 to 1500 different bacteria, archaea, fungi, and viruses. Studies have shown that these microbiomes are not only involved in the digestion and absorption of food but also indispensable in regulating host health. In recent years, there has been increasing evidence that microbiomes are important for pregnant women and fetuses. During pregnancy, there will be great changes in gut microbiomes. Regulating gut microbiomes is beneficial to the health of the mother and the fetus. In addition, many complications during pregnancy are related to gut microbiomes, such as gestational diabetes, obesity, preeclampsia, digestive disorders, and autoimmune diseases. Moreover, the microbiomes in mother's milk and vagina are closely related to the colonization of microbiomes in the early life of infants. In this review, we systematically review the role of maternal microbiomes in different gestational complications, and elucidate the function and mechanism of maternal microbiomes in the neural development and immune system of offspring. These will provide a clear knowledge framework or potential research direction for researchers in related fields.
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http://dx.doi.org/10.3389/fphar.2020.00643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225329PMC
May 2020

A microfluidic paper-based laser-induced fluorescence sensor based on duplex-specific nuclease amplification for selective and sensitive detection of miRNAs in cancer cells.

Talanta 2020 Aug 8;216:120996. Epub 2020 Apr 8.

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Research Institute of Photocatalysis, School of Chemistry, Fuzhou University, Fuzhou, 350116, PR China. Electronic address:

MicroRNAs (miRNAs) are considered as the potential biomarkers for many cancers. To determine miRNAs in cancer cells is significant for realizing these diseases. In this work, a microfluidic paper-based laser-induced fluorescence sensor based on duplex-specific nuclease (DSN) amplification was developed and applied to selectively and sensitively determine miRNAs in cancer cells. An interface for laser-induced fluorescence detection was firstly applied to perform the sample detection on the paper-based chip. Under the optimal conditions, DSN (3 μL 0.10 U) and Taqman probes (2 μL 2.5 × 10 M) were preserved on the circles (Diameter 4 mm) of the folded paper chip. When miRNA solution was added, the mixed solution could trigger fluorescence signal amplification by cyclically digesting hybrids of miRNAs and Taqman probes by DSN. The whole determination, including sample heating process, could be accomplished within 40 min. The detection limits for miRNA-21 and miRNA-31 were 0.20 and 0.50 fM respectively, corresponding to only 1.0 and 1.5 zmol consumption of miRNAs. The testing of mismatched miRNAs showed that the method had good specificity. Finally, the method was applied to determine miRNA-21 and miRNA-31 in lysates of cancer cells of A549 and HeLa, and hepatocyte LO2. MiRNA-21 and miRNA-31 could be successfully found from the two cancer cells. The concentrations for miRNA-21 and miRNA-31 were 1.74 × 10 M and 6.29 × 10 M in HeLa cell lysate (3.75 × 10 cells/mL), 3.07 × 10 M and 3.28 × 10 M in A549 cell lysate (8.33 × 10 cells/mL) respectively. The recoveries ranged from 87.30% to 111.83%, indicating the results were reliable. The developed method was effective, selective and sensitive in the determination of miRNAs in cancer cells.
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http://dx.doi.org/10.1016/j.talanta.2020.120996DOI Listing
August 2020

Accelerating nutrient release and pathogen inactivation from human waste by different pretreatment methods.

Sci Total Environ 2020 Sep 4;733:139105. Epub 2020 May 4.

State Key Laboratory of Urban Water Resource and Environment, School of Environment, Harbin Institute of Technology, Harbin 150090, China. Electronic address:

The limitation of hydrolysis and the health risks from pathogenic microorganisms are challenges in the treatment of human waste for volume reduction and nutrient recovery. In this study, potassium ferrate (PF), peroxymonosulfate (PMS), and PF combined with peroxymonosulfate (PMS+ PF) were used as pretreatment or co-treatment methods to enhance nutrient release and control pathogenic microorganisms in human waste. The PF pretreatment was the most effective regarding hydrolysis and organic matter release. The largest difference (D-value) in the soluble chemical oxygen demand (3117.0 mg/L) between the control and the treatment after 120 min was observed for the PF pretreatment, followed by the alkaline (ALK) pretreatment (1525.0 mg/L), the PF + PMS pretreatment (1169.3 mg/L), and the PMS pretreatment (1020.6 mg/L). The PF pre-treated waste exhibited the highest volatile solids reduction of 79.2% after 120 min compared with 15.0% reduction of the untreated waste, as well as the highest polysaccharide release, with a D-value of 198.5 mg/L. All pretreatments exhibited inactivation of pathogenic bacteria and helminths eggs; however, the PF pretreatment was the most efficient method to suppress pathogenic micrograms, with a 3.5 log (N/N) decrease in the number of total coliforms. The PF pretreatment and PMS + PF co-treatment both exhibited the good performance regarding nitrogen release, including soluble protein and ammonium. The maximum D-value of the total soluble nitrogen was 372.8 mg/L for the PF + PMS co-treatment. The maximum D-value of soluble protein was 156.2 mg/L for the ALK pretreatment. The results indicated that the PF pretreatment was the most effective method for disintegrating human waste, thus providing a new method for safe and rapid reduction of human waste, as well as nutrient release.
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http://dx.doi.org/10.1016/j.scitotenv.2020.139105DOI Listing
September 2020

Adaptive Fisher method detects dense and sparse signals in association analysis of SNV sets.

BMC Med Genomics 2020 04 3;13(Suppl 5):46. Epub 2020 Apr 3.

College of Public Health, Division of Biostatistics, The Ohio State University, 1841 Neil Ave., 208E Cunz Hall, Columbus, OH 43210, US.

Background: With the development of next generation sequencing (NGS) technology and genotype imputation methods, statistical methods have been proposed to test a set of genomic variants together to detect if any of them is associated with the phenotype or disease. In practice, within the set, there is an unknown proportion of variants truly causal or associated with the disease. There is a demand for statistical methods with high power in both dense and sparse scenarios, where the proportion of causal or associated variants is large or small respectively.

Results: We propose a new association test - weighted Adaptive Fisher (wAF) that can adapt to both dense and sparse scenarios by adding weights to the Adaptive Fisher (AF) method we developed before. Using simulation, we show that wAF enjoys comparable or better power to popular methods such as sequence kernel association tests (SKAT and SKAT-O) and adaptive SPU (aSPU) test. We apply wAF to a publicly available schizophrenia dataset, and successfully detect thirteen genes. Among them, three genes are supported by existing literature; six are plausible as they either relate to other neurological diseases or have relevant biological functions.

Conclusions: The proposed wAF method is a powerful disease-variants association test in both dense and sparse scenarios. Both simulation studies and real data analysis indicate the potential of wAF for new biological findings.
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http://dx.doi.org/10.1186/s12920-020-0684-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118831PMC
April 2020

A Machine Learning-Based Model to Predict Acute Traumatic Coagulopathy in Trauma Patients Upon Emergency Hospitalization.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029619897827

Department of Emergency, The First Medical Center to Chinese People's Liberation Army General Hospital, Beijing, China.

Acute traumatic coagulopathy (ATC) is an extremely common but silent murderer; this condition presents early after trauma and impacts approximately 30% of severely injured patients who are admitted to emergency departments (EDs). Given that conventional coagulation indicators usually require more than 1 hour after admission to yield results-a limitation that frequently prevents the ability for clinicians to make appropriate interventions during the optimal therapeutic window-it is clearly of vital importance to develop prediction models that can rapidly identify ATC; such models would also facilitate ancillary resource management and clinical decision support. Using the critical care Emergency Rescue Database and further collected data in ED, a total of 1385 patients were analyzed and cases with initial international normalized ratio (INR) values >1.5 upon admission to the ED met the defined diagnostic criteria for ATC; nontraumatic conditions with potentially disordered coagulation systems were excluded. A total of 818 individuals were collected from Emergency Rescue Database as derivation cohorts, then were split 7:3 into training and test data sets. A Pearson correlation matrix was used to initially identify likely key clinical features associated with ATC, and analysis of data distributions was undertaken prior to the selection of suitable modeling tools. Both machine learning (random forest) and traditional logistic regression were deployed for prediction modeling of ATC. After the model was built, another 587 patients were further collected in ED as validation cohorts. The ATC prediction models incorporated red blood cell count, Shock Index, base excess, lactate, diastolic blood pressure, and potential of hydrogen. Of 818 trauma patients filtered from the database, 747 (91.3%) patients did not present ATC (INR ≤ 1.5) and 71 (8.7%) patients had ATC (INR > 1.5) upon admission to the ED. Compared to the logistic regression model, the model based on the random forest algorithm showed better accuracy (94.0%, 95% confidence interval [CI]: 0.922-0.954 to 93.5%, 95% CI: 0.916-0.95), precision (93.3%, 95% CI: 0.914-0.948 to 93.1%, 95% CI: 0.912-0.946), F1 score (93.4%, 95% CI: 0.915-0.949 to 92%, 95% CI: 0.9-0.937), and recall score (94.0%, 95% CI: 0.922-0.954 to 93.5%, 95% CI: 0.916-0.95) but yielded lower area under the receiver operating characteristic curve (AU-ROC) (0.810, 95% CI: 0.673-0.918 to 0.849, 95% CI: 0.732-0.944) for predicting ATC in the trauma patients. The result is similar in the validation cohort. The values for classification accuracy, precision, F1 score, and recall score of random forest model were 0.916, 0.907, 0.901, and 0.917, while the AU-ROC was 0.830. The values for classification accuracy, precision, F1 score, and recall score of logistic regression model were 0.905, 0.887, 0.883, and 0.905, while the AU-ROC was 0.858. We developed and validated a prediction model based on objective and rapidly accessible clinical data that very confidently identify trauma patients at risk for ATC upon their arrival to the ED. Beyond highlighting the value of ED initial laboratory tests and vital signs when used in combination with data analysis and modeling, our study illustrates a practical method that should greatly facilitates both warning and guided target intervention for ATC.
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http://dx.doi.org/10.1177/1076029619897827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098202PMC
July 2020

Characteristics of Periodic Ultrasonic Assisted TIG Welding for 2219 Aluminum Alloys.

Materials (Basel) 2019 Dec 6;12(24). Epub 2019 Dec 6.

State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China.

Tungsten inert gas (TIG) arc welding of 2219 aluminum alloy was assisted with a trailing periodic ultrasonic vibration, which was output from a trailing roller behind the welding torch. It was found that the weld appearance was periodically convex due to the periodic input of ultrasonic vibration. With the addition of ultrasonic vibration, the columnar grains in the weld zone transformed to equiaxed grains, so along the longitudinal direction, the equiaxed grains and the columnar grains were alternately distributed due to the periodic ultrasonic vibration. The effects of different ultrasonic powers were investigated. The penetration depth and the amount of the melting metal both increased as the ultrasonic power increased. The coarse precipitated phases in the weld zone tended to disperse uniformly under ultrasonic vibration. Compared with conventional TIG welded joints, the hardness of the weld zone of the ultrasonic assisted TIG welding increased by 8.43%, and the tensile strength increased by 29.02%. The ultrasonic cavitation could decrease the nucleation radius and break the dendrites, which led to the grains' refinement and the final mechanical properties' improvement.
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http://dx.doi.org/10.3390/ma12244081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947573PMC
December 2019

Thermosensitive Hydrogel Based on PEO-PPO-PEO Poloxamers for a Controlled In Situ Release of Recombinant Adeno-Associated Viral Vectors for Effective Gene Therapy of Cartilage Defects.

Adv Mater 2020 Jan 25;32(2):e1906508. Epub 2019 Nov 25.

Center of Experimental Orthopaedics, Saarland University Medical Center and Saarland University, D-66421, Homburg, Saarland, Germany.

Advanced biomaterial-guided delivery of gene vectors is an emerging and highly attractive therapeutic solution for targeted articular cartilage repair, allowing for a controlled and minimally invasive delivery of gene vectors in a spatiotemporally precise manner, reducing intra-articular vector spread and possible loss of the therapeutic gene product. As far as it is known, the very first successful in vivo application of such a biomaterial-guided delivery of a potent gene vector in an orthotopic large animal model of cartilage damage is reported here. In detail, an injectable and thermosensitive hydrogel based on poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO poloxamers, capable of controlled release of a therapeutic recombinant adeno-associated virus (rAAV) vector overexpressing the chondrogenic sox9 transcription factor in full-thickness chondral defects, is applied in a clinically relevant minipig model in vivo. These comprehensive analyses of the entire osteochondral unit with multiple standardized evaluation methods indicate that rAAV-FLAG-hsox9/PEO-PPO-PEO hydrogel-augmented microfracture significantly improves cartilage repair with a collagen fiber orientation more similar to the normal cartilage and protects the subchondral bone plate from early bone loss.
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http://dx.doi.org/10.1002/adma.201906508DOI Listing
January 2020

Establishment and Initial Testing of a Medium-Sized, Surgically Feasible Animal Model for Brucellar Spondylodiscitis: A Preliminary Study.

Biomed Res Int 2019 30;2019:7368627. Epub 2019 Sep 30.

Department of Spine Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

Brucellar spondylodiscitis, the most prevalent and significant osteoarticular presentation of human Brucellosis, is difficult to diagnose and usually yields irreversible neurologic deficits and spinal deformities. However, no animal models of Brucellar spondylodiscitis exist, allowing for preclinical investigations. The present study investigated whether intraosseous injection of attenuated vaccine into rabbits' lumbar vertebrae imitates the radiographic and histopathological characteristics of human Brucellar spondylodiscitis. Radiographic and histopathological analyses at 8 weeks postoperatively revealed radiographic changes within vertebral bodies and intervertebral discs, abscesses formation within the paravertebral soft tissue, and typical prominent inflammation response without caseous necrosis, which were largely comparable to human Brucellar spondylodiscitis. Such a medium-sized, surgically feasible rabbit model provides a promising setting for further preclinical investigation of Brucellar spondylodiscitis.
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http://dx.doi.org/10.1155/2019/7368627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791230PMC
March 2020

Association of Nicotine with Osteochondrogenesis and Osteoarthritis Development: The State of the Art of Preclinical Research.

J Clin Med 2019 Oct 16;8(10). Epub 2019 Oct 16.

Center of Experimental Orthopaedics, Saarland University Medical Center and Saarland University, 66421 Homburg/Saar, Germany.

The deleterious effects of nicotine on various health conditions have been well documented. Although many orthopedic diseases are adversely affected by nicotine, little is known about its preclinical effects on chondrogenesis or osteogenesis, cartilage formation, osteoarthritis (OA), and osteochondral repair. A systematic review was conducted examining the current scientific evidence on the effects of nicotine on chondrogenesis or osteogenesis in vitro, possible consequences of prenatal nicotine exposure (PNE) on cartilage and OA susceptibility in the offspring, and whether nicotine affects OA development and osteochondral repair in vivo, always focusing on their underlying mechanisms. The data reveal dose-dependent effects on articular chondrocytes and on the chondrogenesis and osteogenesis of medicinal signaling cells in vitro, with lower doses often resulting in positive effects and higher doses causing negative effects. PNE negatively affects articular cartilage development and induces OA in the offspring without or with nicotine exposure. In contrast, protective effects on OA development were only reported in monosodium iodoacetate-induced small animal models. Finally, nicotine repressed MSC-based osteochondral repair in vivo. Future studies need to investigate dose-dependent clinical effects of smoking on cartilage quality in offspring, OA susceptibility and progression, and osteochondral repair more in detail, thus identifying possible thresholds for its pathological effects.
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http://dx.doi.org/10.3390/jcm8101699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832988PMC
October 2019

Improved Optical Waveguide Microcantilever for Integrated Nanomechanical Sensor.

Sensors (Basel) 2019 Oct 8;19(19). Epub 2019 Oct 8.

Shanghai Institute of Measurement and Testing Technology, National Center of Measurement and Testing for East China, National Center of Testing Technology, Shanghai 201203, China.

This paper reports on an improved optical waveguide microcantilever sensor with high sensitivity. To improve the sensitivity, a buffer was introduced into the connection of the input waveguide and optical waveguide cantilever by extending the input waveguide to reduce the coupling loss of the junction. The buffer-associated optical losses were examined for different cantilever thicknesses. The optimum length of the buffer was found to be 0.97 μm for a cantilever thickness of 300 nm. With this configuration, the optical loss was reduced to about 40%, and the maximum sensitivity was more than twice that of the conventional structure.
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http://dx.doi.org/10.3390/s19194346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806205PMC
October 2019

PSTPIP2 attenuates joint damage and suppresses inflammation in adjuvant-induced arthritis.

Eur J Pharmacol 2019 Sep 17;859:172558. Epub 2019 Jul 17.

Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, 230032, China. Electronic address:

Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is related to inflammation. In this study, we investigated the function of PSTPIP2 in adjuvant-induced arthritis (AIA) by using adeno-associated virus (AAV) to overexpress PSTPIP2 in rat. AIA rats were developed by injecting Lewis rats with complete Freund's adjuvant (CFA) on day 0. AAV-empty or AAV-PSTPIP2, or PBS was administered intraarticularly into each knee joint on day 8 postinduction. All animals were killed at day 18 after adjuvant injection. WB was used to detect the expression of PSTPIP2 in rat synovial tissues. Fluorescence microscopy showed the transduction efficiency in synovial tissue. The morphology of arthritic joints was examined by HE, safranin O/fast green, or Toluidine blue staining. The bone destruction was examined via X-ray and micro-CT analysis. Immunohistochemical analysis or TRAP staining were used to investigate the role of PSTPIP2 in osteoclasts and the expression of PSTPIP2 in synovial tissue. RT-qPCR and ELISA were used to examine the expression of pro-inflammatory cytokines in synovial tissue or serum. AIA rats were found to have decreased PSTPIP2 expression and AIA-associated bone loss and inflammatory infiltration. We showed that administration of AAV-PSTPIP2 before arthritis onset significantly reduces the severity of AIA. PSTPIP2 was highly expressed in synovial cells. In addition, inflammatory responses and the number of osteoclasts were reduced with AAV-PSTPIP2 treatment. These findings demonstrate that PSTPIP2 may improve the severity of AIA by inhibiting the function of fibroblast-like synoviocytes, suppressing inflammation and reducing the number of osteoclasts.
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http://dx.doi.org/10.1016/j.ejphar.2019.172558DOI Listing
September 2019

Study of the effect of culture mediums on the amino acid metabolites for Corynebacterium glutamicum using high-speed micellar electrokinetic chromatography.

Electrophoresis 2019 10 4;40(20):2665-2671. Epub 2019 Jun 4.

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, School of Chemistry, Fuzhou University, Fuzhou, P. R. China.

Corynebacterium glutamicum (C. glutamicum) is a well-known workhorse for the industrial production of amino acids. Different carbon, nitrogen, and sulfur source may force the bacterium to produce specific metabolites. In this work, a method of high-speed MEKC with LIF detection was developed to rapidly analyze the amino acid metabolites released by C. glutamicum, which is fed with different culture mediums. Corynebacterium glutamicum was cultured in microbial fuel cells to monitor its metabolism process and collect its metabolites. In the CE system, a microliter-scale sample reservoir was designed and applied to perform tiny volume sample injection. With the assistance of microwave, the derivatization time for amino acids with FITC was greatly shortened to 6 min. Under the optimized condition, the eight candidate amino acids of metabolites could be rapidly separated within 2 min. The whole analysis process for real samples, from sampling to determination, could be shortened to less than 10 min. The results showed that C. glutamicum could produce additional l-lysine and l-valine as the metabolites when fed with glucose and l-methionine, respectively. The method proved that culture mediums used to feed C. glutamicum had great effect on the bacterium's metabolites.
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http://dx.doi.org/10.1002/elps.201900010DOI Listing
October 2019

Heat Source Characteristics of Ternary-Gas-Shielded Tandem Narrow-Gap GMAW.

Materials (Basel) 2019 Apr 29;12(9). Epub 2019 Apr 29.

State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, Harbin 150001, China.

The characteristics of the welding heat source for tandem narrow-gap gas metal arc welding are examined for different ternary shielding gas (Ar-CO-He) compositions. Results of previous calculations of arc properties for bead-on-plate geometry are adapted to the narrow-gap geometry to predict these characteristics. The heat source concentration factor decreases and the maximum heat flux density increases as the helium content increases, which leads to an increased welding heat efficiency. Addition of CO up to around 10% also increases the heat efficiency. When the CO content exceeds 10%, the heat source concentration factor increases significantly and the heat efficiency decreases. The shielding gas composition also affects the heat source distribution. The heat source characteristics are applied to a computational fluid dynamic model of the weld pool to predict the weld shape, and the predictions are verified by experiment. The results indicate that the appropriate addition of helium to the shielding gas can increase the heat transferred to the peripheral regions of the arc and increase the sidewall penetration.
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http://dx.doi.org/10.3390/ma12091397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539640PMC
April 2019

Distribution Pattern of Atherosclerotic Stenosis in Chinese Patients with Stroke: A Multicenter Registry Study.

Aging Dis 2019 Feb 1;10(1):62-70. Epub 2019 Feb 1.

20Department of Ultrasonography, Brain Hospital of Hunan Province, China.

The aim of this multicenter study was to demonstrate the distribution pattern of atherosclerotic stenosis and its trend with aging between extracranial and intracranial arteries and its distribution between the anterior and posterior circulations in Chinese patients hospitalized with ischemic stroke. In addition, the risk factors for the distribution pattern were illustrated. From June 2015 to May 2016, 9,346 patients with ischemic stroke from 20 hospitals were enrolled. Carotid artery ultrasonography and transcranial color-coded sonography/transcranial Doppler were used to evaluate the extracranial and intracranial arteries. The distribution pattern of atherosclerotic stenosis and its trend with aging were analyzed. Logistic regression was used to analyze the risk factors for the distribution pattern. Among the 9,346 patients, 2,882 patients (30.8%) had at least one artery with a degree of stenosis ≥50%. Among patients with arterial stenosis, the proportion of patients with intracranial artery stenosis was higher than those with extracranial artery stenosis (52.6% 27.6%), and the proportion of anterior circulation artery stenosis was higher than that in the posterior circulation (52.2% 26.2%). With aging, the proportion of intracranial artery stenosis alone decreased; at the same time, the proportion of extracranial artery stenosis and extracranial plus intracranial artery stenosis increased (trend χ=6.698, =0.001). Hypertension (OR 1.416, =0.008) and family history of stroke (OR 1.479, =0.014) were risk factors for intracranial artery stenosis. Male, aging, and smoking were factors more related to extracranial artery stenosis. Aging (OR 1.022, <0.001) and hypertension (OR 1.392, =0.019) were related to posterior circulation artery stenosis. Intracranial arteries and anterior circulation arteries were susceptible to stenosis in Chinese patients with ischemic stroke. However, the distribution pattern of atherosclerotic stenosis was dynamic and varied with aging. Aging and different risk factors contribute to this distribution pattern.
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http://dx.doi.org/10.14336/AD.2018.0602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345329PMC
February 2019

Regulatory B cells in inflammatory diseases and tumor.

Int Immunopharmacol 2019 Feb 17;67:281-286. Epub 2018 Dec 17.

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation, China; Center of Anti-inflammatory and Immune Medicine, Hefei 230032, Anhui Province, China. Electronic address:

As antigen-presenting cells (APC), B cells exert a variety of immune regulatory functions mainly by presenting antigens, triggering immune response, and producing antibodies for immune regulation. Regulatory B cells (Bregs) are special subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Bregs suppress immune response through inhibiting the differentiation of dendritic cells (DCs), suppressing the proliferation of helper T1(TH1) cells and helper T17 (TH17) cells, inducing the differentiation of fork head transcription factor p3 positive regulatory T cells (FoxP3 Tregs). Different subsets of Bregs have distinct phenotypes and markers. Different subsets of Bregs participate in immune modulation by different ways. The absence or loss of Bregs exacerbates the severity of many disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and graft-versus-host-disease (GVHD). Bregs are also involved in tumor immunosuppressive effect and inhibit the antitumor immune process. In this article, we review the research advances of Bregs in autoimmune diseases, GVHD and tumor.
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http://dx.doi.org/10.1016/j.intimp.2018.12.007DOI Listing
February 2019

Separation and determination of microRNAs by high-speed capillary sieving electrophoresis.

J Sep Sci 2018 Oct 5;41(20):3925-3931. Epub 2018 Sep 5.

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, School of Chemistry, Fuzhou University, Fuzhou, Fujian, P. R. China.

In this work, high-speed capillary sieving electrophoresis with laser-induced fluorescence detection was applied to simultaneously determine three microRNAs. A developed manual sample introduction device for the high-speed capillary electrophoresis system was applied to perform sample injection. Strategies, including field-amplified sample injection and electrokinetic injection, were studied to improve the detection sensitivity. Under the optimal conditions, the limit of detection for DNA-159 could be lowered to 5.10 × 10  mol/L. In order to achieve enough separation resolution, two DNA probes were designed to have extra sequences that acted as the drag tails. Under the optimized conditions, the three DNA probes and the complexes of microRNA-156, microRNA-159, and microRNA-166 could be completely separated within 3.2 min in background electrolyte (pH 8.7) containing 2.0% m/m polyvinyl pyrrolidone and 0.4% m/m hydroxyethyl cellulose. The limits of detection for the three microRNAs were 0.051, 0.11, and 0.25 nmol/L, respectively. Then the method was applied to analyze the microRNAs spiked in the samples extracted from banana leaves. The recoveries ranged from 114.3 to 121.1% (n = 3). The results showed that the method developed in this work was an effective means for microRNA assay.
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http://dx.doi.org/10.1002/jssc.201800635DOI Listing
October 2018

Ocular Biometry in Primary Angle-Closure Glaucoma Associated with Retinitis Pigmentosa.

J Ophthalmol 2017 31;2017:9164846. Epub 2017 Dec 31.

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

Background: Retinitis pigmentosa (RP) comprises a group of inherited disorders in which patients typically lose night vision in adolescence and then lose peripheral vision in young adulthood before eventually losing central vision later in life. A retrospective case-control study was performed to evaluate differences in ocular biometric parameters in primary angle-closure glaucoma (PACG) patients with and without concomitant RP to determine whether a relationship exists between PACG and RP.

Methods: We used ultrasound biomicroscopy (UBM) to measure anterior chamber depth (ACD). A-scan biometry was carried out to measure lens thickness (LT) and axial length (AL). Propensity score matching and mixed linear regression model analysis were conducted. 23 patients with chronic primary angle-closure glaucoma (CPACG) associated with RP, 21 patients with acute primary angle-closure glaucoma (APACG) associated with RP, 270 patients with CPACG, and 269 patients with APACG were recruited for this study.

Results: There were no significant differences on ACDs, ALs, and relative lens position (RLP) ( > 0.05) between patients with PACG associated with RP and patients with PACG; however, patients with APACG associated with RP had a significantly greater LT than patients with APACG ( < 0.05).

Conclusion: Patients with PACG associated with RP had the same biometric parameter characteristic as the patients with CPACG and APACG. This may suggest that RP is a coincidental relationship with angle-closure glaucoma.
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http://dx.doi.org/10.1155/2017/9164846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5804412PMC
December 2017

Separation and determination of peptide metabolite of Bacillus licheniformis in a microbial fuel cell by high-speed capillary micellar electrokinetic chromatography.

J Sep Sci 2017 Nov 27;40(22):4446-4452. Epub 2017 Sep 27.

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, School of Chemistry, Fuzhou University, Fuzhou, P. R. China.

A method using high-speed capillary micellar electrokinetic chromatography and a microbial fuel cell was applied to determine the metabolite of the peptides released by Bacillus licheniformis. Two peptides, l-carnosine and l-alanyl-l-glutamine were used as the substrate to feed Bacillus licheniformis in a microbial fuel cell. The metabolism process of the bacterium was monitored by analyzing the voltage outputs of the microbial fuel cell. A home-made spontaneous injection device was applied to perform high-speed capillary micellar electrokinetic chromatography. Under the optimized conditions, tryptophan, glycine, valine, tyrosine and the two peptides could be rapidly separated within 2.5 min with micellar electrokinetic chromatography mode. Then the method was applied to analyze the solutions sampled from the microbial fuel cell. After 92 h running, valine, as the metabolite, was successfully detected with concentration 3.90 × 10 M. The results demonstrated that Bacillus licheniformis could convert l-carnosine and l-alanyl-l-glutamine into valine. The method employed in this work was proved to have great potential in analysis of metabolites, such as amino acids, for microorganisms.
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http://dx.doi.org/10.1002/jssc.201700656DOI Listing
November 2017
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