Publications by authors named "Juan Feng"

432 Publications

Biochemical, metabolic, and immune responses of mud crab (Scylla paramamosain) after mud crab reovirus infection.

Fish Shellfish Immunol 2022 Jun 29. Epub 2022 Jun 29.

Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, Guangdong, 510300, PR China. Electronic address:

Mud crab reovirus (MCRV) is a serious pathogen that leads to large economic losses in the mud crab farming. However, the molecular mechanism of the immune response after MCRV infection is unclear. In the present study, physiological, transcriptomic, and metabolomic responses after MCRV infection were investigated. The results showed that MCRV infection could increase lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities. MCRV infection decreased antioxidant enzyme activity levels, induced oxidative stress, and caused severe histological damage. Transcriptome analysis identified 416 differentially expressed genes, including 354 up-regulated and 62 down-regulated genes. The detoxification, immune response, and metabolic processes-related genes were found. The results showed that two key pathways including phagocytosis and apoptosis played important roles in response to MCRV infection. The combination of transcriptomic and metabolomic analyses showed that related metabolic pathways, such as glycolysis, citrate cycle, lipid, and amino acid metabolism were also significantly disrupted. Moreover, the biosynthesis of unsaturated fatty acids was activated in response to MCRV infection. This study provided a novel insight into the understanding of cellular mechanisms in crustaceans against viral invasion.
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http://dx.doi.org/10.1016/j.fsi.2022.06.058DOI Listing
June 2022

Mammary Leukocyte-Assisted Nanoparticle Transport Enhances Targeted Milk Trace Mineral Delivery.

Adv Sci (Weinh) 2022 Jun 30:e2200841. Epub 2022 Jun 30.

Institute of Dairy Science, College of Animal Sciences, MOE Key Laboratory of Molecular Animal Nutrition, Zhejiang University, Hangzhou, 310029, P. R. China.

Nanoparticles are applied as versatile platforms for drug/gene delivery in many applications owing to their long-retention and specific targeting properties in living bodies. However, the delivery mechanism and the beneficial effect of nanoparticle-retention in many organisms remain largely uncertain. Here, the transport and metabolism of mineral nanoparticles in mammary gland during lactation are explored. It is shown that maternal intravenous administration of iron oxide nanoparticles (IONPs; diameter: ≈11.0 nm, surface charge: -29.1 mV, surface area: 1.05 m g ) provides elevated iron delivery to mammary gland and increased iron secretion into breast milk, which is inaccessible by classical iron-ion transport approaches such as the transferrin receptor-mediated endocytic pathway. Mammary macrophages and neutrophils are found to play dominant roles in uptake and delivery of IONPs through an unconventional leukocyte-assisted iron secretion pathway. This pathway bypasses the tight iron concentration regulation of liver hepcidin-ferroportin axis and mammary epithelial cells to increase milk iron-ion content derived from IONPs. This work provides keen insight into the metabolic pathway of nanoparticles in mammary gland while offering a new scheme of nutrient delivery for neonate metabolism regulation by using nanosized nutrients.
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http://dx.doi.org/10.1002/advs.202200841DOI Listing
June 2022

A clinical prediction model to estimate the risk for coarctation of the aorta: From fetal to newborn life.

J Obstet Gynaecol Res 2022 Jun 26. Epub 2022 Jun 26.

Department of Cardiovascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Aim: A prenatal diagnosis of coarctation of the aorta (CoA) is challenging. This study aimed to develop a coarctation probability model incorporating prenatal cardiac sonographic markers to estimate the probability of an antenatal diagnosis of CoA.

Methods: We reviewed 89 fetuses as an investigation cohort with prenatal suspicion for CoA and categorized them into three subgroups: severe CoA: symptomatic CoA and surgery within the first 3 months; mild CoA: surgery within 4 months to 1 year (29); and false-positive CoA: not requiring surgery (45). Logistic regression was used to create a multiparametric model, and a validation cohort of 86 fetuses with suspected CoA was used to validate the model.

Results: The prediction model had an optimal criterion >0.25 (sensitivity of 97.7%; specificity of 59.1%), and the area under the receiver operator curve was 0.85. The parameters and their cut-off values were as follows: left common carotid artery to left subclavian artery distance/distal transverse arch (LCCA-LSCA)/DT Index >1.77 (sensitivity 62%, specificity 88%, 95% confidence interval [CI]: 0.6-0.8), and z-score of AAo peak Doppler > -1.7 (sensitivity 77%, specificity 56%, 95% CI: 0.6-0.8). The risk assessment demonstrated that fetuses with a model probability >60% should have inpatient observation for a high risk of CoA, whereas fetuses with a model probability <15% should not undergo clinical follow-up.

Conclusion: The probability model performs well in predicting CoA outcomes postnatally and can also improve the accuracy of risk assessment. The objectivity of its parameters may allow its implementation in multicenter studies of fetal cardiology.
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http://dx.doi.org/10.1111/jog.15341DOI Listing
June 2022

Multiple-Vessel-Based Blood Gas Profiles Analysis Revealed the Potential of Blood Oxygen in Mammary Vein as Indicator of Mammary Gland Health Risk of High-Yielding Dairy Cows.

Animals (Basel) 2022 Jun 8;12(12). Epub 2022 Jun 8.

MoE Key Laboratory of Molecular Animal Nutrition, Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.

The blood gas profile is a routine method in the rapid disease diagnosis of farm animals, yet its potential in evaluating mammary health status of dairy cows remains to be investigated. This study was conducted to learn the potential of the blood gas parameter regarding the mammary gland health status in lactating dairy cows. Twenty animals were divided into two groups, the H-SCC group (milk SCC > 122 k/mL) and L-SCC group (milk SCC < 73.8 k/mL), to compare blood gas profiles from different blood vessels and to identify the key parameters associated with milk somatic cell count. H-SCC cows are higher in malondialdehyde content, but lower in SOD and T-AOC activities in the milk, compared to the L-SCC group. In terms of blood gas parameters, most differ across the three vessels, including K, CO pressure, O pressure, HCO, base excess in the extracellular fluid compartment, and saturation of O. The Pearson correlation analysis showed that oxygen-related variables in the mammary vein, including oxygen concentrations, O pressure, and saturation of O, are negatively correlated with levels of malondialdehyde, lactate dehydrogenase, and plasmin in the milk. Our study revealed that oxygen-related variables in the mammary vein can be a marker in suggesting mammary-gland health status in high-yielding cows.
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http://dx.doi.org/10.3390/ani12121484DOI Listing
June 2022

Addition of Mercury Causes Quenching of NIR Fluorescence Emission Spectra of a Photoactivatable PAiRFP1 Protein.

Curr Protein Pept Sci 2022 Jun 20. Epub 2022 Jun 20.

School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China.

Background: Biliverdin (BV) containing far-red light photoactivatable near-infrared fluorescent protein (NIR-FP) named PAiRFP1 has been developed by directed molecular evolution from one bathy bacteriophytochrome of Agrobacterium tumefaciens C58 called Agp2 or AtBphP2. Usually, the fluorescence intensity of the NIR emission spectra of PAiRFP1 tends to increase upon repeated excitation by far-red light.

Objective: To explore the role of PAiRFP1 and its mutants such as V386A, V480A, and Y498H as NIR biosensors for the detection of Hg2+ ions in the buffer solutions.

Methods: In this study, we used PCR-based site-directed reverse mutagenesis, fluorescence spectroscopy, and molecular modeling approaches on PAiRFP1 and its mutants.

Results: It was found that PAiRFP1 and its mutants experienced strong quenching of NIR fluorescence emission spectra upon the addition of different concentrations (0-3μM) of mercuric chloride (HgCl2).

Conclusion: We hypothesized that PAiRFP1 and its variants have some potential to use them as NIR biosensors for the in vitro detection of Hg2+ ions in biological media. Moreover, we also hypothesized that PAiRFP1 will be the best tool to use as a NIR biosensor to detect Hg2+ ions in living organisms because of its higher signal-to-noise (SNR) ratio than other infra-red fluorescent proteins.
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http://dx.doi.org/10.2174/1389203723666220620162926DOI Listing
June 2022

Focus on the Role of the NLRP3 Inflammasome in Multiple Sclerosis: Pathogenesis, Diagnosis, and Therapeutics.

Front Mol Neurosci 2022 25;15:894298. Epub 2022 May 25.

Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.

Neuroinflammation is initiated with an aberrant innate immune response in the central nervous system (CNS) and is involved in many neurological diseases. Inflammasomes are intracellular multiprotein complexes that can be used as platforms to induce the maturation and secretion of proinflammatory cytokines and pyroptosis, thus playing a pivotal role in neuroinflammation. Among the inflammasomes, the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome is well-characterized and contributes to many neurological diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), and ischemic stroke. MS is a chronic autoimmune disease of the CNS, and its hallmarks include chronic inflammation, demyelination, and neurodegeneration. Studies have demonstrated a relationship between MS and the NLRP3 inflammasome. To date, the pathogenesis of MS is not fully understood, and clinical studies on novel therapies are still underway. Here, we review the activation mechanism of the NLRP3 inflammasome, its role in MS, and therapies targeting related molecules, which may be beneficial in MS.
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http://dx.doi.org/10.3389/fnmol.2022.894298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9175009PMC
May 2022

Performance of PROPELLER FSE TWI in reducing metal artifacts of material porcelain fused to metal crown: a clinical preliminary study.

Sci Rep 2022 May 19;12(1):8442. Epub 2022 May 19.

Department of Radiology, The Second Hospital of Shanxi Medical University, NO.382 Wuyi Road, Taiyuan, 030001, Shanxi, China.

This study aimed to compare MRI quality between conventional fast spin echo T weighted imaging (FSE TWI) with periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) FSE TWI for patients with various porcelain fused to metal (PFM) crown and analyze the value of PROPELLER technique in reducing metal artifacts. Conventional FSE TWI and PROPELLER FSE TWI sequences for axial imaging of head were applied in participants with different PFM crowns: cobalt-chromium (Co-Cr) alloy, pure titanium (Ti), gold-palladium (Au-Pd) alloy. Two radiologists evaluated overall image quality of section in PFM using a 5-point scale qualitatively and measured the maximum artifact area and artifact signal-to-noise ratio (SNR) quantitatively. Fifty-nine participants were evaluated. The metal crown with the least artifacts and the optimum image quality shown in conventional FSE TWI and PROPELLER FSE TWI were in Au-Pd alloy, Ti, and Co-Cr alloy order. PROPELLER FSE TWI was superior to conventional FSE TWI in improving image quality and reducing artifact area for Co-Cr alloy (17.0 ± 0.2% smaller artifact area, p < 0.001) and Ti (11.6 ± 0.7% smaller artifact area, p = 0.005), but had similar performance compared to FSE TWI for Au-Pd alloy. The SNRs of the tongue and masseter muscle were significantly higher on PROPELLER FSE TWI compared with conventional FSE TWI (tongue: 29.76 ± 8.45 vs. 21.54 ± 9.31, p = 0.007; masseter muscle: 19.11 ± 8.24 vs. 15.26 ± 6.08, p = 0.016). Therefore, the different PFM crown generate varying degrees of metal artifacts in MRI, and the PROPELLER can effectively reduce metal artifacts especially in the PFM crown of Co-Cr alloy.
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http://dx.doi.org/10.1038/s41598-022-12402-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120134PMC
May 2022

Overexpression and kinetic analysis of Ideonella sakaiensis PETase for polyethylene terephthalate (PET) degradation.

Environ Res 2022 Sep 14;212(Pt D):113472. Epub 2022 May 14.

School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, China; Center for Informational Biology, University of Electronic Science and Technology of China, Chengdu, 610054, China. Electronic address:

Ideonella sakaiensis PET hydrolase (IsPETase) is a well-characterized enzyme for effective PET biodegradation. However, the low soluble expression level of the enzyme hampers its practical implementation in the biodegradation of PET. Herein, the expression of IsPETase, one of the most active mutants of IsPETase obtained so far, was systematically explored in E. coli by adopting a series of strategies. A notable improvement of soluble IsPETase was observed by using chaperon co-expression and fusion expression systems. Under the optimized conditions, GroEL/ES co-expression system yielded 75 ± 3.4 mg·L purified soluble IsPETase (GroEL/ES), and NusA fusion expression system yielded 80 ± 3.7 mg·L purified soluble NusA-IsPETase, which are 12.5- and 4.6-fold, respectively, higher than its commonly expression in E. coli. The two purified enzymes were further characterized. The results showed that IsPETase (GroEL/ES) displayed the same catalytic behavior as IsPETase, while the fusion of NusA conferred new enzymatic properties to IsPETase. Although NusA-IsPETase displayed a lower initial hydrolysis capacity than IsPETase, it showed a 1.4-fold higher adsorption constant toward PET. Moreover, the product inhibition effect of terephthalic acid (TPA) on IsPETase was reduced with NusA-IsPETase. Taken together, the latter two catalytic properties of NusA-IsPETase are more likely to contribute to the enhanced product release by NusA-IsPETase PET degradation for two weeks.
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http://dx.doi.org/10.1016/j.envres.2022.113472DOI Listing
September 2022

Comparison of neutrophil-to-lymphocyte ratio between myelin oligodendrocyte glycoprotein antibody-associated disease and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders in adults.

J Clin Neurosci 2022 Jul 12;101:89-93. Epub 2022 May 12.

Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address:

The neutrophil-to-lymphocyte ratio (NLR) is a biomarker for evaluating disease activity in systemic autoimmune diseases. However, few studies have discussed NLR changes in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This study aimed to explore the NLR difference between MOGAD, aquaporin-4 antibody (AQP4-Ab)-positive neuromyelitis optica spectrum disorders (NMOSD), and healthy controls (HCs) and evaluate the clinical value of NLR in the differential diagnosis. We included 15 patients with MOGAD, 28 patients with AQP4-Ab-positive NMOSD, and 68 HCs. Their NLRs were calculated, and statistical analysis was performed, with statistical significance set at P < 0.05. In pairwise comparisons between three groups, P < 0.017 was considered statistically significant under Bonferroni correction. NLR was higher during the acute attack in MOGAD patients than HCs but lower than in AQP4-Ab-positive NMOSD patients. NLR was correlated with Expanded Disability Status Scale (EDSS) in MOGAD and AQP4-Ab-positive NMOSD patients. Also, there were no statistical differences in intracranial pressure between MOGAD and AQP4-Ab-positive NMOSD patients and HCs. The cut-off value was 2.86, and the sensitivity and specificity were 0.750 and 0.867, respectively. In conclusion, our results suggest that NLR may be a helpful marker to evaluate disease severity and differentiate between both diseases at a cut-off value of > 2.86 when patients have clinical symptoms like optic neuritis or myelitis.
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http://dx.doi.org/10.1016/j.jocn.2022.05.002DOI Listing
July 2022

Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetyl-CoA metabolism.

Nat Commun 2022 05 3;13(1):2412. Epub 2022 May 3.

State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Human neurodegenerative disorders often exhibit similar pathologies, suggesting a shared aetiology. Key pathological features of Parkinson's disease (PD) are also observed in other neurodegenerative diseases. Pantothenate Kinase-Associated Neurodegeneration (PKAN) is caused by mutations in the human PANK2 gene, which catalyzes the initial step of de novo CoA synthesis. Here, we show that fumble (fbl), the human PANK2 homolog in Drosophila, interacts with PINK1 genetically. fbl and PINK1 mutants display similar mitochondrial abnormalities, and overexpression of mitochondrial Fbl rescues PINK1 loss-of-function (LOF) defects. Dietary vitamin B5 derivatives effectively rescue CoA/acetyl-CoA levels and mitochondrial function, reversing the PINK1 deficiency phenotype. Mechanistically, Fbl regulates Ref(2)P (p62/SQSTM1 homolog) by acetylation to promote mitophagy, whereas PINK1 regulates fbl translation by anchoring mRNA molecules to the outer mitochondrial membrane. In conclusion, Fbl (or PANK2) acts downstream of PINK1, regulating CoA/acetyl-CoA metabolism to promote mitophagy, uncovering a potential therapeutic intervention strategy in PD treatment.
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http://dx.doi.org/10.1038/s41467-022-30178-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065001PMC
May 2022

Automatic video analysis framework for exposure region recognition in X-ray imaging automation.

IEEE J Biomed Health Inform 2022 May 3;PP. Epub 2022 May 3.

The deep learning-based automatic recognition of the scanning or exposing region in medical imaging automation is a promising new technique, which can decrease the heavy workload of the radiographers, optimize imaging workflow and improve image quality. However, there is little related research and practice in X-ray imaging. In this paper, we focus on two key problems in X-ray imaging automation: automatic recognition of the exposure moment and the exposure region. Consequently, we propose an automatic video analysis framework based on the hybrid model, approaching real-time performance. The framework consists of three interdependent components: Body Structure Detection, Motion State Tracing, and Body Modeling. Body Structure Detection disassembles the patient to obtain the corresponding body keypoints and body Bboxes. Combining and analyzing the two different types of body structure representations is to obtain rich spatial location information about the patient body structure. Motion State Tracing focuses on the motion state analysis of the exposure region to recognize the appropriate exposure moment. The exposure region is calculated by Body Modeling when the exposure moment appears. A large-scale dataset for X-ray examination scene is built to validate the performance of the proposed method. Extensive experiments demonstrate the superiority of the proposed method in automatically recognizing the exposure moment and exposure region. This paradigm provides the first method that can enable automatically and accurately recognize the exposure region in X-ray imaging without the help of the radiographer.
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http://dx.doi.org/10.1109/JBHI.2022.3172369DOI Listing
May 2022

Advances in the Role of Endothelial Cells in Cerebral Small Vessel Disease.

Front Neurol 2022 11;13:861714. Epub 2022 Apr 11.

Department of Neurology, Shengjing Hospital of China Medical University, China Medical University, Shen yang, China.

Cerebral small vessel disease (CSVD) poses a serious socio-economic burden due to its high prevalence and severe impact on the quality of life of elderly patients. Pathological changes in CSVD mainly influence small cerebral arteries, microarteries, capillaries, and small veins, which are usually caused by multiple vascular risk factors. CSVD is often identified on brain magnetic resonance imaging (MRI) by recent small subcortical infarcts, white matter hyperintensities, lacune, cerebral microbleeds (CMBs), enlarged perivascular spaces (ePVSs), and brain atrophy. Endothelial cell (EC) dysfunction is earlier than clinical symptoms. Immune activation, inflammation, and oxidative stress may be potential mechanisms of EC injury. ECs of the blood-brain-barrier (BBB) are the most important part of the neurovascular unit (NVU) that ensures constant blood flow to the brain. Impaired cerebral vascular autoregulation and disrupted BBB cause cumulative brain damage. This review will focus on the role of EC injury in CSVD. Furthermore, several specific biomarkers will be discussed, which may be useful for us to assess the endothelial dysfunction and explore new therapeutic directions.
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http://dx.doi.org/10.3389/fneur.2022.861714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035937PMC
April 2022

The PARP1 Inhibitor Niraparib Represses DNA Damage Repair and Synergizes with Temozolomide for Antimyeloma Effects.

J Oncol 2022 5;2022:2800488. Epub 2022 Apr 5.

Department of Hematology, Xijing Hospital, Air Force Medical University, Xi'an, 710032 Shaanxi, China.

Purpose: Poly(ADP-ribose) polymerase 1 (PARP1) is necessary for single-strand break (SSB) repair by sensing DNA breaks and facilitating DNA repair through poly ADP-ribosylation of several DNA-binding and repair proteins. Inhibition of PARP1 results in collapsed DNA replication fork and double-strand breaks (DSBs). Accumulation of DSBs goes beyond the capacity of DNA repair response, ultimately resulting in cell death. This work is aimed at assessing the synergistic effects of the DNA-damaging agent temozolomide (TMZ) and the PARP inhibitor niraparib (Nira) in human multiple myeloma (MM) cells.

Materials And Methods: MM RPMI8226 and NCI-H929 cells were administered TMZ and/or Nira for 48 hours. CCK-8 was utilized for cell viability assessment. Cell proliferation and apoptosis were detected flow-cytometrically. Immunofluorescence was performed for detecting H2A.X expression. Soft-agar colony formation assay was applied to evaluate the antiproliferative effect. The amounts of related proteins were obtained by immunoblot. The combination index was calculated with the CompuSyn software. A human plasmacytoma xenograft model was established to assess the anti-MM effects . The anti-MM activities of TMZ and/or Nira were evaluated by H&E staining, IHC, and the TUNEL assay.

Results: The results demonstrated that cotreatment with TMZ and Nira promoted DNA damage, cell cycle arrest, and apoptotic death in cultured cells but also reduced MM xenograft growth in nude mice, yielding highly synergistic effects. Immunoblot revealed that TMZ and Nira cotreatment markedly increased the expression of p-ATM, p-CHK2, RAD51, and H2A.X, indicating the suppression of DNA damage response (DDR) and elevated DSB accumulation.

Conclusion: Inhibition of PARP1 sensitizes genotoxic agents and represents an important therapeutic approach for MM. These findings provide preliminary evidence for combining PARP1 inhibitors with TMZ for MM treatment.
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http://dx.doi.org/10.1155/2022/2800488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005285PMC
April 2022

Base-Promoted Formal [3 + 2] Cycloaddition of α-Halohydroxamates with Carbon Disulfide to Synthesize Polysubstituted Rhodanines.

Org Lett 2022 04 8;24(15):2837-2841. Epub 2022 Apr 8.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.

A concise and practical strategy via potassium-carbonate-mediated [3 + 2]-cycloaddition reaction of α-halohydroxamates with the common solvent carbon disulfide for the synthesis of functionalized rhodanine derivatives in good to excellent yields is developed. The present methodology features a wide substrate scope as well as good functional group tolerance. The potential synthetic utility of this protocol is demonstrated by synthesis of a series of natural product derivatives containing rhodamine skeletons.
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http://dx.doi.org/10.1021/acs.orglett.2c00736DOI Listing
April 2022

Development and Validation of a Novel Prognostic Model for Overall Survival in Newly Diagnosed Multiple Myeloma Integrating Tumor Burden and Comorbidities.

Front Oncol 2022 17;12:805702. Epub 2022 Mar 17.

Department of Hematology, Xijing Hospital, Air Force Medical University, Xi'an, China.

Background: Multiple myeloma (MM) is a highly heterogeneous disease with enormously variable outcomes. It remains to be a major challenge to conduct a more precise estimation of the survival of MM patients. The existing stratifications attached less importance to the prognostic significance of comorbidities. In the present study, we aimed to develop and validate a novel and simple prognostic stratification integrating tumor burden and comorbidities measured by HCT-CI.

Method: We retrospectively enrolled 385 consecutive newly diagnosed multiple myeloma (NDMM) patients in Xijing Hospital from January 2013 to December 2020. The cohort between January 2016 and December 2020 was selected as development cohort ( = 233), and the cohort between January 2013 and December 2015 was determined as validation cohort ( = 152). By using LASSO analysis and univariate and multivariable Cox regression analyses, we developed the MM-BHAP model in the way of nomogram composed of β2-MG, HCT-CI, ALB, and PBPC. We internally and externally validated the MM-BHAP model and compared it with ISS stage and R-ISS stage.

Results: The MM-BHAP model was superior to the ISS stage and partially better than the R-ISS stage according to time-dependent AUC, time-dependent C-index, DCA, IDI, and continuous NRI analyses. In predicting OS, only the MM-BHAP stratification clearly divided patients into three groups while both the ISS stage and R-ISS stage had poor classifications in patients with stage I and stage II. Moreover, the MM-BHAP stratification and the R-ISS stage performed well in predicting PFS, but not for the ISS stage. Besides, the MM-BHAP model was also applied to the patients with age ≤65 or age >65 and with or without HRCA and could enhance R-ISS or ISS classifications.

Conclusions: Our study offered a novel simple MM-BHAP stratification containing tumor burden and comorbidities to predict outcomes in the real-world unselected NDMM population.
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http://dx.doi.org/10.3389/fonc.2022.805702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968003PMC
March 2022

Acute septicemia and immune response of spotted sea bass (Lateolabrax maculatus) to Aeromonas veronii infection.

Fish Shellfish Immunol 2022 May 31;124:47-55. Epub 2022 Mar 31.

Innovative Institute of Animal Healthy Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, 510225, China. Electronic address:

A previous study confirmed that spotted sea bass (Lateolabrax maculatus), an economically important cultured species in East Asia, is a new host of Aeromonas veronii, which can cause acute death in these fish, but there is little in-depth understanding of this disease. In the present study, the virulence of 10 isolates of A. veronii derived from spotted sea bass was determined. It was found that the 18BJ181 isolate was a virulent strain and led to the fastest death of spotted sea bass. Death was determined to be within in 2-12 h, and resulted in abdominal effusion and varying degrees of hemorrhage in internal organs. Bacterial colonization analysis showed that the bacterial load in the spleen was highest, and was up to 3.1 × 10 cfu g. In addition, the bacteria proliferated massively in the blood and reached 2.4 × 10 cfu mL at 12 h after 18BJ181 strain infection, which was also a typical feature of acute septicemia. Histopathology of the spleen revealed edema in interstitial tissue, degeneration, and necrosis in lymphoid tissue, and hemorrhage in the capillary network. Transcriptome analysis of the spleen showed that the expression level of HSP70, CCL19, and IL-1β was extremely significantly up-regulated at 8 h after infection (P < 0.01), and the expression of these genes was normal at 24 h. These results revealed that A. veronii infection could rapidly activate the chemokine signal pathway and stimulate the acute inflammatory response in the host. The bacterial colonization, pathological features, and gene expression patterns in immune pathways will help us to better understand acute septicemia in spotted sea bass caused by A. veronii.
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http://dx.doi.org/10.1016/j.fsi.2022.03.030DOI Listing
May 2022

Characterization of phosphofructokinase (PFK) from mud crab Scylla paramamosain and its role in mud crab dicistrovirus-1 proliferation.

Fish Shellfish Immunol 2022 May 31;124:39-46. Epub 2022 Mar 31.

Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, Guangdong, 510300, PR China. Electronic address:

Phosphofructokinase (PFK), the key enzyme of glycolysis, can catalyze the irreversible transphosphorylation of fructose-6-phosphate forming fructose-1, 6-biphosphate. In the present study, a PFK gene from the mud crab Scylla paramamosain, named SpPFK, was cloned and characterized. The full length of SpPFK contained a 5'untranslated region (UTR) of 249 bp, an open reading frame of 2,859 bp, and a 3'UTR of 1,248 bp. The mRNA of SpPFK was highly expressed in the gill, followed by the hemocytes and muscle. The expression of SpPFK was significantly up-regulated after mud crab dicistrovirus-1 (MCDV-1) infection. Knocking down SpPFK in vivo by RNA interference significantly reduced the expression of lactate dehydrogenase after MCDV-1 infection. Furthermore, silencing of SpPFK in vivo increased the survival rate of mud crabs and decreased the MCDV-1 copies in the gill and hepatopancreas after MCDV-1 infection. All these results suggested that SpPFK could play an important role in the process of MCDV-1 proliferation in mud crab.
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http://dx.doi.org/10.1016/j.fsi.2022.03.042DOI Listing
May 2022

Generation of an avian influenza DIVA vaccine with a H3-peptide replacement located at HA2 against both highly and low pathogenic H7N9 virus.

Virulence 2022 12;13(1):530-541

College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

A differentiating infected from vaccinated animals (DIVA) vaccine is an ideal strategy for viral eradication in poultry. Here, according to the emerging highly pathogenic H7N9 avian influenza virus (AIV), a DIVA vaccine strain, named rGD4-TX, was successfully developed, based on a substituted 12 peptide of H3 virus located at HA2. In order to meet with the safety requirement of vaccine production, the multi-basic amino acid located at the HA cleavage site was modified. Meanwhile, six inner viral genes from a H9N2 AIV TX strainwere introduced for increasing viral production. The rGD4-TX strain displayed a similar reproductive ability with rGD4 and low pathogenicity in chickens, suggesting a good productivity and safety. In immuned chickens, rGD4-TX induced a similar antibody level with rGD4 and provided 100% clinical protection and 90% shedding protection against highly pathogenic virus challenge. rGD4-TX strain also produced a good cross-protection against low pathogenic AIV JD/17. Moreover, serological DIVA characteristics were evaluated by a successfully established competitive inhibition ELISA based on a 3G10 monoclonal antibody, and the result showed a strong reactivity with antisera of chickens vaccinated with H7 subtype strains but not rGD4-TX. Collectedly, rGD4-TX is a promising DIVA vaccine candidate against both high and low pathogenic H7N9 subtype AIV.
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http://dx.doi.org/10.1080/21505594.2022.2040190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928850PMC
December 2022

Single-cell RNA sequencing reveals B cell-T cell interactions in vascular adventitia of hyperhomocysteinemia-accelerated atherosclerosis.

Protein Cell 2022 Jul;13(7):540-547

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University, Beijing, 100191, China.

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http://dx.doi.org/10.1007/s13238-021-00904-0DOI Listing
July 2022

T lymphocyte-derived extracellular vesicles aggravate abdominal aortic aneurysm by promoting macrophage lipid peroxidation and migration via pyruvate kinase muscle isozyme 2.

Redox Biol 2022 04 4;50:102257. Epub 2022 Feb 4.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China; Department of Interventional Radiology and Vascular Surgery, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing 100191, China; Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address:

T lymphocyte and macrophage infiltration in the aortic wall is critical for abdominal aortic aneurysm (AAA). However, how T lymphocytes interact with macrophages in the pathogenesis of AAA remains largely uncharacterized. In an elastase-induced murine AAA model, we first found that the expression of pyruvate kinase muscle isozyme 2 (PKM2), the last rate-limiting enzyme in glycolysis, was increased in infiltrated T lymphocytes of vascular lesions. T lymphocyte-specific PKM2 deficiency in mice (LckCrePKM2) or intraperitoneal administration of the sphingomyelinase inhibitor GW4869 caused a significant attenuation of the elastase-increased aortic diameter, AAA incidence, elastic fiber disruption, matrix metalloproteinases (MMPs) expression, and macrophage infiltration in the vascular adventitia compared with those in PKM2 mice. Mechanistically, extracellular vesicles (EVs) derived from PKM2-activated T lymphocytes elevated macrophage iron accumulation, lipid peroxidation, and migration in vitro, while macrophages treated with EVs from PKM2-null T lymphocytes or pretreated with the lipid peroxidation inhibitors ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1), or the iron chelating agent deferoxamine mesylate (DFOM) reversed these effects. In vascular lesions of elastase-induced LckCrePKM2 mice with AAA, the oxidant system weakened, with downregulated 4-hydroxynonenal (4-HNE) levels and strengthened antioxidant defense systems with upregulated glutathione peroxidase 4 (GPX4) and cystine/glutamate antiporter solute carrier family 7 member 11 (Slc7a11) expressions in macrophages. High-throughput metabolomics showed that EVs derived from PKM2-activated T lymphocytes contained increased levels of polyunsaturated fatty acid (PUFA)-containing phospholipids, which may provide abundant substrates for lipid peroxidation in target macrophages. More importantly, upregulated T lymphocyte PKM2 expression was also found in clinical AAA subjects, and EVs isolated from AAA patient plasma enhanced macrophage iron accumulation, lipid peroxidation, and migration ex vivo. Therefore, from cell-cell crosstalk and metabolic perspectives, the present study shows that PKM2-activated T lymphocyte-derived EVs may drive AAA progression by promoting macrophage redox imbalance and migration, and targeting the T lymphocyte-EV-macrophage axis may be a potential strategy for early warning and treating AAA.
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http://dx.doi.org/10.1016/j.redox.2022.102257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842084PMC
April 2022

Repair of Breast Defect by Transfer of a Contralateral Internal Mammary Artery Perforator Flap.

Plast Reconstr Surg Glob Open 2022 Jan 12;10(1):e4014. Epub 2022 Jan 12.

Department of Breast Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

This is a case report of a patient with a borderline phyllodes tumor in the left breast. Seventeen months after the resection of the phyllodes tumor from the patient's left breast, the tumor occurred again 5 months ago in the surgical region. A large defect was generated after the extended resection of the left breast mass, and it was repaired with a contralateral internal mammary artery perforator flap. After the operation, bilateral breast symmetry was good, and the patient was satisfied with the shape of the breast. Postoperative follow-up was performed for 15 months, and no local recurrence was observed.
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http://dx.doi.org/10.1097/GOX.0000000000004014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8754181PMC
January 2022

Trojan-Horse Diameter-Reducible Nanotheranostics for Macroscopic/Microscopic Imaging-Monitored Chemo-Antiangiogenic Therapy.

ACS Appl Mater Interfaces 2022 Feb 19;14(4):5033-5052. Epub 2022 Jan 19.

Department of biomaterials, College of Materials, The higher educational key laboratory for biomedical engineering of Fujian Province Research center of biomedical engineering of xiamen & Research Center of Biomedical Engineering of Xiamen, Xiamen University, Xiamen 361005, China.

Although nanotheranostics have displayed striking potential toward precise nanomedicine, their targeting delivery and tumor penetration capacities are still impeded by several biological barriers. Besides, the current antitumor strategies mainly focus on killing tumor cells rather than antiangiogenesis. Enlightened by the fact that the smart transformable self-targeting nanotheranostics can enhance their targeting efficiency, tumor penetration, and cellular uptake, we herein report carrier-free Trojan-horse diameter-reducible metal-organic nanotheranostics by the coordination-driven supramolecular sequential co-assembly of the chemo-drug pemetrexed (PEM), transition-metal ions (Fe), and antiangiogenesis pseudolaric acid B. Such nanotheranostics with both a high dual-drug payload efficiency and outstanding physiological stability are responsively decomposed into numerous ultra-small-diameter nanotheranostics under stimuli of the moderate acidic tumor microenvironment and then internalized into tumor cells through tumor-receptor-mediated self-targeting, synergistically enhancing tumor penetration and cellular uptake. Besides, such nanotheranostics enable visualization of self-targeting capacity under the macroscopic monitor of computed tomography/magnetic resonance imaging, thereby realizing efficient oncotherapy. Moreover, tumor microvessels are precisely monitored by optical coherence tomography angiography/laser speckle imaging during chemo-antiangiogenic therapy , visually verifying that such nanotheranostics possess an excellent antiangiogenic effect. Our work will provide a promising strategy for further tumor diagnosis and targeted therapy.
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http://dx.doi.org/10.1021/acsami.1c22350DOI Listing
February 2022

Nutrients, temperature, and oxygen mediate microbial antibiotic resistance in sea bass (Lateolabrax maculatus) ponds.

Sci Total Environ 2022 May 15;819:153120. Epub 2022 Jan 15.

Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, China. Electronic address:

Antibiotic resistance genes (ARGs) have drawn increasing attention as novel environmental pollutants because of the threat they impose on human and animal health. The sea bass (Lateolabrax maculatus) is the third most cultured marine fish in China. Therefore, a study of ARG pollution in the sea bass culture environment is of great significance for the healthy and sustainable development of the sea bass industry. Here, we systematic investigated the contents of 23 antibiotic resistance-related genes (ARRGs), including 19 ARGs and four mobile genetic elements, and analyzed bacterial community composition and environmental parameters in sea bass ponds. The relative abundance (ARRG copies/16S ribosomal RNA gene copies) of ARRGs was up to 3.83 × 10. Sul1 was the most abundant ARRG, followed by ereA, intI-1, sul2, dfrA1, and aadA. Both the ARRG changes and aquatic microbiota succession were mainly driven by water temperature (WT), dissolved oxygen (DO), and NO. WT is positively correlated with the most ARGs and some of the top 38 Operational Taxonomic Units (OTUs) belonging to the orders of Frankiales, Micrococcales, Chitinophagales, and Sphingomonadales. Furthermore, WT is negatively related with some other OTUs of the orders Frankiales, Xanthomonadales, Micrococcales, and Rhizobiales. However, DO and NO have the opposite function with WT on specific taxa and ARGs. These results indicate that sea bass ponds are reservoirs of ARGs, and are driven mainly by the nutrient, temperature, and oxygen with inducing specific microbial taxa. The regulation of environmental factors (increasing DO and NO) can be conducted to reduce drug resistance risk in aquaculture ponds. Therefore, environmental factors and specific taxa could be the indicators of ARG contamination and can be used to establish an antibiotic elimination system and consequently realize a sustainable aquaculture industry.
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http://dx.doi.org/10.1016/j.scitotenv.2022.153120DOI Listing
May 2022

Adenine base-editing-mediated exon skipping induces gene knockout in cultured pig cells.

Biotechnol Lett 2022 Jan 8;44(1):59-76. Epub 2022 Jan 8.

Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Gene Editing Technology Center of Guangdong Province, Foshan University, Foshan, 528225, China.

Gene-knockout pigs have important applications in agriculture and medicine. Compared with CRISPR/Cas9, Adenine base editor (ABE) convert single A·T pairs to G·C pairs in the genome without generating DNA double-strand breaks, and this method has higher accuracy and biosafety in pig genetic modification. However, the application of ABE in pig gene knockout is limited by protospacer-adjacent motif sequences and the base-editing window. Alternative mRNA splicing is an important mechanism underlying the formation of proteins with diverse functions in eukaryotes. Spliceosome recognizes the conservative sequences of splice donors and acceptors in a precursor mRNA. Mutations in these conservative sequences induce exon skipping, leading to proteins with novel functions or to gene inactivation due to frameshift mutations. In this study, adenine base-editing-mediated exon skipping was used to expand the application of ABE in the generation of gene knockout pigs. We first constructed a modified "all-in-one" ABE vector suitable for porcine somatic cell transfection that contained an ABE for single-base editing and an sgRNA expression cassette. The "all-in-one" ABE vector induced efficient sgRNA-dependent A-to-G conversions in porcine cells during single base-editing of multiple endogenous gene loci. Subsequently, an ABE system was designed for single adenine editing of the conservative splice acceptor site (AG sequence at the 3' end of the intron 5) and splice donor site (GT sequence at the 5' end of the intron 6) in the porcine gene GHR; this method achieved highly efficient A-to-G conversion at the cellular level. Then, porcine single-cell colonies carrying a biallelic A-to-G conversion in the splice acceptor site in the intron 5 of GHR were generated. RT-PCR indicated exon 6 skipped at the mRNA level. Western blotting revealed GHR protein loss, and gene sequencing showed no sgRNA-dependent off-target effects. These results demonstrate accurate adenine base-editing-mediated exon skipping and gene knockout in porcine cells. This is the first proof-of-concept study of adenine base-editing-mediated exon skipping for gene regulation in pigs, and this work provides a new strategy for accurate and safe genetic modification of pigs for agricultural and medical applications.
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http://dx.doi.org/10.1007/s10529-021-03214-xDOI Listing
January 2022

Association between Caffeine Intake and All-Cause and Cause-Specific Mortality: An Analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014 Database.

Nurs Rep 2021 Nov 10;11(4):901-912. Epub 2021 Nov 10.

Department of Natural Sciences/Nursing, University of Houston Downtown, Houston, TX 77002, USA.

Sixty-four percent of adults in America drink coffee daily, and caffeine is the main reason people tend to drink coffee habitually. Few studies have examined the association between caffeine and all-cause and cause-specific mortality. The objective of this study was to examine the association between caffeine and all-cause and cause-specific mortality using the National Health and Nutrition Examination Survey (NHANES) 1999-2014 database. The multivariate Cox proportional hazards regression model was used to examine 23,878 individuals 20 years and older. Daily caffeine intake was measured once at baseline. A total of 2206 deaths occurred, including 394 cardiovascular (CVD) deaths and 525 cancer deaths. Compared to those with a caffeine intake of <100 mg/day, the hazard ratios (HRs) for CVD mortality were significantly lower in the participants with a caffeine intake of 100-200 mg/day (HR, 0.63; 95% confidence interval [CI], 0.45-0.88), and those with a caffeine intake of >200 mg/day (HR, 0.67; 95% CI, 0.50-0.88) after adjusting for potential confounders. The HRs for all-cause mortality were significantly lower in the participants with a caffeine intake of 100-200 mg/day (HR, 0.78; 95% CI, 0.67-0.91), and those with a caffeine intake of >200 mg/day (HR, 0.68; 95% CI, 0.60-0.78). Subgroup analyses showed that caffeine may have different effects on all-cause mortality among different age and body mass index (BMI) groups. In conclusion, higher caffeine intake was associated with lower all-cause and CVD mortality.
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http://dx.doi.org/10.3390/nursrep11040083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715461PMC
November 2021

Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2.

Elife 2021 12 23;10. Epub 2021 Dec 23.

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States.

HAP2 is a transmembrane gamete fusogen found in multiple eukaryotic kingdoms and is structurally homologous to viral class II fusogens. Studies in have suggested that HAP2 is an attractive target for vaccines that block transmission of malaria. HAP2 has three extracellular domains, arranged in the order D2, D1, and D3. Here, we report monoclonal antibodies against the D3 fragment of HAP2 and crystal structures of D3 in complex with Fab fragments of two of these antibodies, one of which blocks fertilization of in vitro and transmission of malaria in mosquitoes. We also show how this Fab binds the complete HAP2 ectodomain with electron microscopy. The two antibodies cross-react with HAP2 among multiple plasmodial species. Our characterization of the D3 structure, HAP2 ectodomain architecture, and mechanism of inhibition provide insights for the development of a vaccine to block malaria transmission.
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http://dx.doi.org/10.7554/eLife.74707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806182PMC
December 2021

Biological Response Profiling Reveals the Functional Differences of Main Alkaloids in Rhizoma Coptidis.

Molecules 2021 Dec 6;26(23). Epub 2021 Dec 6.

Medical Systems Biology Research Center, School of Medicine, Tsinghua University, Beijing 100084, China.

Rhizoma Coptidis (RC) is a widely used traditional Chinese medicine. Although modern research has found that some alkaloids from RC are the pharmacologically active constituents, the differences in their biological effects are not completely clear. This study analyzed the differences in the typical alkaloids in RC at a systematic level and provided comprehensive information on the pharmaceutical mechanisms of the different alkaloids. The ethanol RC extract (RCE) was characterized using HPLC assay. HepG2, 3T3-L1, and RAW264.7 cells were used to detect the cytotoxicity of alkaloids. Transcriptome analyses were performed to elucidate the cellular pathways affected by RCE and alkaloids. HPLC analysis revealed that the typical alkaloids of RCE were berberine, coptisine, and palmatine. Coptisine and berberine displayed a stronger inhibitory effect on cell proliferation than palmatine. The overlapping ratios of differentially expressed genes between RCE and berberine, coptisine, and palmatine were 70.8%, 52.6%, and 42.1%, respectively. Pathway clustering analysis indicated that berberine and coptisine possessed a certain similarity to RCE, and both compounds affected the cell cycle pathway; moreover, some pathways were uniquely enriched by berberine or coptisine. Berberine and coptisine had different regulatory effects on genes involved in lipid metabolism. These results provide comprehensive information on the pharmaceutical mechanisms of the different RC alkaloids and insights into their better combinatory use for the treatment of diseases.
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http://dx.doi.org/10.3390/molecules26237389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658997PMC
December 2021

LuxS modulates motility and secretion of extracellular protease in fish pathogen .

Can J Microbiol 2022 Mar 2;68(3):215-226. Epub 2021 Dec 2.

Key Laboratory of South China Sea Fishery Resources Exploitation & Utilization, Ministry of Agriculture and Rural Affairs, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510300, China.

can cause infections and diseases in a variety of marine vertebrates and invertebrates, which are harmful to the aquaculture industry. The LuxS quorum-sensing system regulates the expression of virulence factors in a wide variety of pathogenic bacteria. In this study, an in-frame deletion of the gene was constructed to reveal the role of LuxS in the physiology and virulence of . Statistical analysis showed no significant differences in the growth ability, biofilm formation, antibiotic susceptibility, virulence by intraperitoneal injection, and ability of to colonize the spleen and liver of the pearl gentian grouper between the wild-type (WT) and mutant. However, deletion of decreased the secretion of extracellular protease, while increasing swimming and swarming abilities. Simultaneously, a -deleted mutant showed overproduction of lateral flagella, and an intact complemented this defect. Since motility is flagella dependent, 16 flagella biogenesis related genes were selected for further analysis. Based on quantitative real-time reverse transcription-PCR (qRT-PCR), the expression levels of these genes, including the polar flagella genes , , , , , , and and the lateral flagella genes , , , , , , and , were significantly upregulated in the Δ: pMMB207 (Δ) strain as compared with the 345: pMMB207 (WT) and C-Δ strains during the early, mid-exponential, and stationary growth phases. Our results indicate that LuxS plays an important role in controlling motility, flagella biogenesis, and extracellular protease secretion in .
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http://dx.doi.org/10.1139/cjm-2021-0311DOI Listing
March 2022

Novel Quinic Acid Glycerates from Tussilago farfara Inhibit Polypeptide GalNAc-Transferase.

Chembiochem 2022 02 9;23(3):e202100539. Epub 2021 Dec 9.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China.

The discovery of a bioactive inhibitor tool for human polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts), the initiating enzyme for mucin-type O-glycosylation, remains challenging. In the present study, we identified an array of quinic acid derivatives, including four new glycerates (1-4) from Tussilago farfara, a traditional Chinese medicinal plant, as active inhibitors of GalNAc-T2 using a combined screening approach with a cell-based T2-specific sensor and purified enzyme assay. These inhibitors dose-dependently inhibited human GalNAc-T2 but did not affect O-linked N-acetylglucosamine transferase (OGT), the other type of glycosyltransferase. Importantly, they are not cytotoxic and retain inhibitory activity in cells lacking elongated O-glycans, which are eliminated by the CRISPR/Cas9 gene editing tool. A structure-activity relationship study unveiled a novel quinic acid-caffeic acid conjugate pharmacophore that directs inhibition. Overall, these new natural product inhibitors could serve as a basis for developing an inhibitor tool for GalNAc-T2.
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http://dx.doi.org/10.1002/cbic.202100539DOI Listing
February 2022

Risk factors of decompensated tinnitus and the interaction effect of anxiety and poor sleep on decompensated tinnitus: a multicenter study.

Acta Otolaryngol 2021 Dec 13;141(12):1049-1054. Epub 2021 Nov 13.

Department of Otorhinolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Decompensated tinnitus substantially degrades quality of life. Anxiety and poor sleep are comorbidities in decompensated tinnitus.

Objective: This multicenter study was designed to investigate the risk factors of decompensated tinnitus and to analyze the interaction effect of anxiety and poor sleep on decompensated tinnitus by conducting a multicenter study.

Material And Methods: We retrospectively analyzed patients with subjective chronic tinnitus who presented to five Chinese hospitals in China from September 2019 to November 2020. Demographic characteristics, pure tone audiometry, tinnitus-related tests, psychometric and sleep questionnaires were applied.

Results: A total of 338 patients were included, and 99 (29.3%) patients were in the decompensated group. Poor sleep and anxiety were possible risk factors of decompensated tinnitus by a forced-entry binary logistic analysis. Sleep disturbances and anxiety had an additive interaction that accounted for 87% of the decompensated tinnitus cases in our study population (RERI = 10.96,  = 18.22, AP = 0.87).

Conclusions And Significance: Anxiety and sleep disturbances are possible risk factors of decompensated tinnitus. The combination of poor sleep and anxiety exerts a greater impact on tinnitus severity than either risk factor alone.
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http://dx.doi.org/10.1080/00016489.2021.1922754DOI Listing
December 2021
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