Publications by authors named "Yong-Xin Li"

122 Publications

Predicting mortality in acute ischaemic stroke treated with mechanical thrombectomy: analysis of a multicentre prospective registry.

BMJ Open 2021 04 1;11(4):e043415. Epub 2021 Apr 1.

Department of Neurology, Jinan University First Affiliated Hospital, Guangzhou, China

Objectives: We aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT).

Design: Analysis of a multicentre prospective registry.

Setting: In six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively.

Participants: 224 patients with AIS were treated by MT.

Results: Of 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality.

Conclusions: We developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated.

Trial Registration Number: Chinese Clinical Trial Registry (ChiCTR-OOC-17013052).
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http://dx.doi.org/10.1136/bmjopen-2020-043415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021751PMC
April 2021

Discovery of Antibiofilm Activity of Elasnin against Marine Biofilms and Its Application in the Marine Antifouling Coatings.

Mar Drugs 2021 Jan 5;19(1). Epub 2021 Jan 5.

Department of Ocean Science and Hong Kong Branch of Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China.

Biofilms are surface-attached multicellular communities that play critical roles in inducing biofouling and biocorrosion in the marine environment. Given the serious economic losses and problems caused by biofouling and biocorrosion, effective biofilm control strategies are highly sought after. In a screening program of antibiofilm compounds against marine biofilms, we discovered the potent biofilm inhibitory activity of elasnin. Elasnin effectively inhibited the biofilm formation of seven strains of bacteria isolated from marine biofilms. With high productivity, elasnin-based coatings were prepared in an easy and cost-effective way, which exhibited great performance in inhibiting the formation of multi-species biofilms and the attachment of large biofouling organisms in the marine environment. The 16S amplicon analysis and anti-larvae assay revealed that elasnin could prevent biofouling by the indirect impact of changed microbial composition of biofilms and direct inhibitory effect on larval settlement with low toxic effects. These findings indicated the potential application of elasnin in biofilm and biofouling control in the marine environment.
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http://dx.doi.org/10.3390/md19010019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824865PMC
January 2021

Two-stage enrichment of hydrogen-oxidizing bacteria as biofertilizers.

Chemosphere 2021 Mar 10;266:128932. Epub 2020 Nov 10.

Centre of Wastewater Resource Recovery, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian, 350002, China; CAS Key Laboratory for Urban Pollutant Conversion, Department of Applied Chemistry, University of Science and Technology of China, Hefei, 230026, China. Electronic address:

Biofertilizers can replace chemical fertilizers to promote the plant growth without causing any pollution. The study of hydrogen-oxidizing bacteria (HOB) enrichment as biofertilizers from mixed culture is scarce. Our recent study shows that biofertilizing HOB are successfully enriched in a short hydraulic retention time of 10 h. While, the mechanism is unknown. This study intentionally used a two-stage method to enrich biofertilizing HOB specifically with nitrate as nitrogen source in Stage 1 and then 1-aminocyclopropane-1-carboxylate (ACC) as nitrogen source in Stage 2. It was found Pseudomonas (34.46%, reported HOB) predominated in Stage 1, while Azospirillum (59.35%), Azoarcus (36%) were dominant genera and Azospirillum lipoferum strain DSM 1691 (50%), Azoarcus olearius strain DQS-4 (50%) were dominant species in Stage 2. The enriched HOB of Stage 2 showed ACC deaminase activity. Furthermore, they could also fix N and consume Ca(PO). Thus, the two-stage method can be used as a specific enrichment for HOB as biofertilizers, which extends the application of HOB in agriculture.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128932DOI Listing
March 2021

Perillaldehyde: A promising antifungal agent to treat oropharyngeal candidiasis.

Biochem Pharmacol 2020 10 18;180:114201. Epub 2020 Aug 18.

College of Life Science, Jiangsu Normal University, Xuzhou 221116, Jiangsu Province, PR China. Electronic address:

Perillaldehyde (PAE), a natural monoterpenoid agent extracted from Perilla frutescence, PAE has been reported to present various physiological capabilities, such as anti-inflammation, anti-oxidative and anti-fungal. In this study, we show that PAE exhibits strong antifungal activity against Candida albicans (C. albicans). C. albicans, a fungal pathogen with high incidence of antifungal resistance in clinical settings, is the major cause of oropharyngeal candidiasis (OPC). OPC is characterized by inflammatory immunological responses to fungal infections. Our in vitro results show PAE inhibited several virulence attributes of C. albicans including biofilm formation, yeast-to-hyphal transition and secreted aspartic proteinases (SAPs) gene expression. Using an experimental murine model of OPC, we found that PAE inhibited NLRP3 inflammasome assembly, reduced the excessive accumulation of ROS and prevented the p65 transfer in nuclear; processes all leading to reduced inflammation burden in the host. Together, this supports use PAE as a promising new agent to improve OPC.
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http://dx.doi.org/10.1016/j.bcp.2020.114201DOI Listing
October 2020

Stereoselective Synthesis of Vinylcyclopropa[]indolines via a Rh-Migration Strategy.

Org Lett 2020 Aug 16;22(15):5978-5983. Epub 2020 Jul 16.

Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.

A mild rhodium catalytic system has been developed to synthesize vinylcyclopropa[]indolines through cyclopropanation of indoles with vinyl carbenoids generated from ring opening of cyclopropenes . By employing a Rh-migration strategy, the products can be obtained with good to excellent : ratios (≤99:1) and complete diastereoselectivity (≤99:1). This method is easy, has a low catalyst loading, and works for a broad range of functionalities.
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http://dx.doi.org/10.1021/acs.orglett.0c02071DOI Listing
August 2020

Challenges and advances in genome mining of ribosomally synthesized and post-translationally modified peptides (RiPPs).

Synth Syst Biotechnol 2020 Sep 24;5(3):155-172. Epub 2020 Jun 24.

Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong, Hong Kong SAR, China.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a class of cyclic or linear peptidic natural products with remarkable structural and functional diversity. Recent advances in genomics and synthetic biology, are facilitating us to discover a large number of new ribosomal natural products, including lanthipeptides, lasso peptides, sactipeptides, thiopeptides, microviridins, cyanobactins, linear thiazole/oxazole-containing peptides and so on. In this review, we summarize bioinformatic strategies that have been developed to identify and prioritize biosynthetic gene clusters (BGCs) encoding RiPPs, and the genome mining-guided discovery of novel RiPPs. We also prospectively provide a vision of what genomics-guided discovery of RiPPs may look like in the future, especially the discovery of RiPPs from dominant but uncultivated microbes, which will be promoted by the combinational use of synthetic biology and metagenome mining strategies.
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http://dx.doi.org/10.1016/j.synbio.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327761PMC
September 2020

[Mechanism of Urban Black Odorous Water Based on Continuous Monitoring: A Case Study of the Erkeng Stream in Nanning].

Huan Jing Ke Xue 2020 May;41(5):2257-2263

College of Environmental Science and Engineering, Guilin University of Technology, Guilin 541004, China.

Black odorous water seriously endangers urban ecological functions. The "Water Pollution Prevention Action Plan" promulgated by the State Council has attached great importance to this issue and set a timetable for achieving the goal of pollution remediation of the urban black odorous water problem. However, in the process of managing the city's black odorous water, we found that the apparent governance effect is not sustainable. Many of the urban waters that have been treated to become clear have returned to a black odorous state. This problem has constrained the completion of the black odorous water control plan, and urgently needs to be resolved. To explain the reason for this phenomenon, we chose the Erkeng Stream in Nanning as the research object, which is a water body that returns to a black odorous state after treatment. We used a multi-parameter water quality tester and chemical analysis method to carry out daily continuous monitoring for 24 h and monthly dynamic monitoring of the water body. The results showed that the rainfall process was significantly correlated with the ammonia nitrogen concentration in the water (<0.01), and the temperature was positively correlated with the trend of ammonia nitrogen concentration in the water (=0.23, <0.05), which in turn was negatively correlated with the change trend of water transparency (=-0.33, <0.01). The above results show that the return of the black odorous state may be related to the microbial degradation of endogenous pollutants and the input of external pollutants. The reason may be:① The microorganisms are driven by light and temperature to promote the development of water in the direction of the black odorous state; ② Contaminants carried by rainfall promote the formation of black odor in water bodies. In short, in the context that internal pollution cannot be completely eradicated and external pollutants are difficult to control effectively, to prevent the treated urban water body from returning to a black odorous state, attention should be paid to endogenous pollutants such as river sediment and its control technology. Moreover, ecological control measures should be comprehensively adopted to reduce the input of external source indicators.
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http://dx.doi.org/10.13227/j.hjkx.201909259DOI Listing
May 2020

Enrichment of hydrogen-oxidizing bacteria with nitrate recovery as biofertilizers in the mixed culture.

Bioresour Technol 2020 Oct 8;313:123645. Epub 2020 Jun 8.

CAS Key Laboratory for Urban Pollutant Conversion, Department of Applied Chemistry, University of Science and Technology of China, Hefei 230026, China; Centre of Wastewater Resource Recovery, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China. Electronic address:

Hydrogen-oxidizing bacteria (HOB) can utilize hydrogen and oxygen to produce valuable products in biomass, including polyhydroxyalkanoates, microbial proteins, and biofertilizers. However, the method of enriching HOB as biofertilizers from mixed culture remains unknown. In this study HOB were enriched with nitrate as nitrogen source at a hydraulic retention time of 10 h. The nitrate consumption rate was 120 mgN/L/d or 16 mg N/g VSS/h, which was comparable to those of denitrification using organic carbon or hydrogen. The percentage of Azospirillum (dominated genus, reported biofertilizing HOB) was 84.89% and the dominated species was Azospirillum lipoferum strain DSM 1691. Furthermore, the enriched HOB had the abilities of 1-aminocyclopropane-1-carboxylate conversion and phosphate solubilization, the functions of biofertilizers. This is the first report on the enrichment of biofertilizing HOB from mixed culture. Meanwhile, the enriched HOB can recover nitrate from wastewater without any secondary nitrogen pollution, extending HOB application for resource recovery from wastewater.
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http://dx.doi.org/10.1016/j.biortech.2020.123645DOI Listing
October 2020

Toxoplasma gondii infection in patients with lung diseases in Shandong province, eastern China.

Acta Trop 2020 Nov 3;211:105554. Epub 2020 Jun 3.

Department of Urinary Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China. Electronic address:

Toxoplasma gondii, an intracellular protozoan parasite, can induce various clinical symptoms. T. gondii has been considered to play an important role in the pathogenesis of lung diseases. This survey was conducted to explore the correlation between T. gondii infection and lung diseases through a case-control study carried out in Shandong province, eastern China. In the present survey, T. gondii IgG antibodies were found in 76/398 (19.10%) of patients with lung diseases, which was significantly higher (P < 0.001) than the level found in the control subjects (35/398; 8.79%) through serological diagnosis. Patients with lung cancer have the highest T. gondii seroprevalence (26.19%), followed by Pulmonary cyst (25.00%), Tuberculosis (17.07%), Pneumonia (16.33%) and chronic obstructive pulmonary disease (COPD) (16.05%). Moreover, a semi-nest PCR targeted T. gondii B1 gene was employed to detect the T. gondii DNA in the blood samples. T. gondii DNA was detected in 5.53% blood samples of patients with lung diseases and 2.51% control subjects, respectively. The present study firstly shows that T. gondii has a high probability to infect the patients with lung diseases. Thus, the potential presence of T. gondii in patients with lung diseases should be appreciated during in the course of treatment and safeguard procedures should be implemented to protect vulnerable patients with lung diseases.
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http://dx.doi.org/10.1016/j.actatropica.2020.105554DOI Listing
November 2020

Activities of Nerol, a natural plant active ingredient, against Candida albicans in vitro and in vivo.

Appl Microbiol Biotechnol 2020 Jun 4;104(11):5039-5052. Epub 2020 Apr 4.

School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.

Candida albicans invasion is one of the most serious fungal infections in clinical history. In recent years, because of the widespread use of immunosuppressive drugs, chemotherapy drugs, glucocorticoids, and broad-spectrum antibiotics, serious drug resistance has been reported; therefore, a new type of antifungal drug needs to be developed. In this study, we found that Nerol (NEL) had strong antimicrobial activity and 0.77 μL/mL NEL was the minimum inhibitory concentration (MIC) effective against C. albicans. We determined the change of the growth curve of NEL for C. albicans, to identify the trend of NEL activity against C. albicans. Through the determination of the ergosterol content and glucose-induced extracellular fluid acidification of NEL on C. albicans, we found that NEL inhibits the growth of C. albicans by destroying cell membranes. This finding was also supported by the expression of SAP (secreted aspartyl proteinase) involved in cell membrane synthesis. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and PAS (periodic acid-Schiff) staining were conducted to prove that NEL had the ability to treated mouse oral C. albicans infection and vaginal C. albicans infection. This research may help us to investigate new antimicrobial agents for treating C. albicans infections. KEY POINTS: • NEL can inhibit the growth of C. albicans. • NEL destroys the cell membrane formation and permeability of C. albicans. • NEL can treat vulvovaginal candidiasis and oropharyngeal candidiasis in mice. • NEL could be used as a possible antifungal agent.
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http://dx.doi.org/10.1007/s00253-020-10559-2DOI Listing
June 2020

The Molecular Mechanism of Perillaldehyde Inducing Cell Death in by Inhibiting Energy Metabolism Revealed by Transcriptome Sequencing.

Int J Mol Sci 2020 Feb 23;21(4). Epub 2020 Feb 23.

College of Life Science, Jiangsu Normal University, Xuzhou 221116, China.

Perillaldehyde (PAE), an essential oil in Perilla plants, serves as a safe flavor ingredient in foods, and shows an effectively antifungal activity. Reactive oxygen species (ROS) accumulation in plays a critical role in initiating a metacaspase-dependent apoptosis. However, the reason for ROS accumulation in is not yet clear. Using transcriptome sequencing of treated with different concentrations of PAE, our data showed that the ROS accumulation might have been as a result of an inhibition of energy metabolism with less production of reducing power. By means of GO and KEGG enrichment analysis, we screened four key pathways, which were divided into two distinct groups: a downregulated group that was made up of the glycolysis and pentose phosphate pathway, and an upregulated group that consisted of MAPK signaling pathway and GSH metabolism pathway. The inhibition of dehydrogenase gene expression in two glycometabolism pathways might play a crucial role in antifungal mechanism of PAE. Also, in our present study, we systematically showed a gene interaction network of how genes of four subsets are effected by PAE stress on glycometabolism, oxidant damage repair, and cell cycle control. This research may contribute to explaining an intrinsic antifungal mechanism of PAE against .
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http://dx.doi.org/10.3390/ijms21041518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073185PMC
February 2020

No difference in inhibition among free acids of acetate, propionate and butyrate on hydrogenotrophic methanogen of Methanobacterium formicicum.

Bioresour Technol 2019 Dec 3;294:122237. Epub 2019 Oct 3.

Centre of Wastewater Resource Recovery, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; CAS Key Laboratory for Urban Pollutant Conversion, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address:

Free volatile fatty acids such as free acetic acid (FAA) and free butyrate acid (FBA) are true inhibitors of hydrogenotrophic methanogens (HM) in mixed culture. However, their inhibitory effects on pure culture of HM remain unclear. In this study, a typical HM of Methanobacterium formicicum demonstrated no difference in toxicity conferred by FAA, free propionate acid (FPA), or FBA in regard to the specific methanogenic activity (SMA) based on the C (0.19, 0.17, and 0.23 g/L, respectively) and recoverable concentration values (0.97, 0.69, and 0.61 g/L, respectively). These results were within the same order of magnitude. The concentrations of FAA, FBA, and FPA all correlated well with the SMA values according to the inhibition model. Additionally, changes in the activity of the electron transport system also agreed well with the trend in the SMA variation. Together, the results of this study provide a benchmark to control methanogenesis during industrial applications.
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http://dx.doi.org/10.1016/j.biortech.2019.122237DOI Listing
December 2019

Cinnamaldehyde inhibits Candida albicans growth by causing apoptosis and its treatment on vulvovaginal candidiasis and oropharyngeal candidiasis.

Appl Microbiol Biotechnol 2019 Nov 28;103(21-22):9037-9055. Epub 2019 Oct 28.

College of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, People's Republic of China.

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti-C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans. Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed that C. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discovered that when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid-Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.
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http://dx.doi.org/10.1007/s00253-019-10119-3DOI Listing
November 2019

A Chemical-Intervention Strategy To Circumvent Peptide Hydrolysis by d-Stereoselective Peptidases.

J Med Chem 2019 11 8;62(22):10466-10472. Epub 2019 Nov 8.

School of Chemistry and Chemical Engineering, Stranmillis Road , Queen's University Belfast , Belfast BT9 5AG , U.K.

d-Stereoselective peptidases that degrade nonribosomal peptides (NRPs) were recently discovered and could have serious implications for the future of NRPs as antibiotics. Herein, we report chemical modifications that can be used to impart resistance to the d-peptidases BogQ and TriF. New tridecaptin A analogues were synthesized that retain strong antimicrobial activity and have significantly enhanced d-peptidase stability. assays confirmed that synthetic analogues retain the ability to bind to their cellular receptor, peptidoglycan intermediate lipid II.
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http://dx.doi.org/10.1021/acs.jmedchem.9b01078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887851PMC
November 2019

Long-term follow-up of auditory performance and speech perception and effects of age on cochlear implantation in children with pre-lingual deafness.

Chin Med J (Engl) 2019 Aug;132(16):1925-1934

Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Otolaryngology, Beijing 100005, China.

Background: The development of auditory and speech perception ability of children with hearing loss is affected by many factors after they undergo cochlear implantation (CI). Age at CI (CI age) appears to play an important role among these factors. This study aimed to evaluate the development of auditory and speech perception ability and explore the impact of CI age on children with pre-lingual deafness present before 3 years of age.

Methods: Two hundred and seventy-eight children with pre-lingual deafness (176 boys and 102 girls) were included in this study, and the CI age ranged from 6 to 36 months (mean age, 19 months). Categorical auditory performance (CAP) was assessed to evaluate auditory ability, and the speech intelligibility rating was used to evaluate speech intelligibility. The evaluations were performed before CI and 1, 3, 6, 12, 18, 24, 36, 48, and 60 months after CI.

Results: The auditory ability of the pre-lingually hearing-impaired children showed the fastest development within 6 months after CI (k = 0.524, t = 30.992, P < 0.05); then, the progress started to decelerate (k = 0.14, t = 3.704, P < 0.05) and entered a plateau at the 24th month (k = 0.03, t = 1.908, P < 0.05). Speech intelligibility showed the fastest improvement between the 12th and 24th months after CI (k = 0.138, t = 5.365, P < 0.05); then, the progress started to decelerate (k = 0.026, t = 1.465, P < 0.05) and entered a plateau at the 48th month (k = 0.012, t = 1.542, P < 0.05). The CI age had no statistical significant effect on the auditory and speech abilities starting at 2 years after CI (P > 0.05). The optimal cutoff age for CI was 15 months.

Conclusions: Within 5 years after CI, the auditory and speech ability of young hearing-impaired children continuously improved, although speech development lagged behind that of hearing. An earlier CI age is recommended; the optimal cutoff age for CI is at 15 months.
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http://dx.doi.org/10.1097/CM9.0000000000000370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708680PMC
August 2019

Marine biofilms constitute a bank of hidden microbial diversity and functional potential.

Nat Commun 2019 01 31;10(1):517. Epub 2019 Jan 31.

Department of Ocean Science and Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China.

Recent big data analyses have illuminated marine microbial diversity from a global perspective, focusing on planktonic microorganisms. Here, we analyze 2.5 terabases of newly sequenced datasets and the Tara Oceans metagenomes to study the diversity of biofilm-forming marine microorganisms. We identify more than 7,300 biofilm-forming 'species' that are undetected in seawater analyses, increasing the known microbial diversity in the oceans by more than 20%, and provide evidence for differentiation across oceanic niches. Generation of a gene distribution profile reveals a functional core across the biofilms, comprised of genes from a variety of microbial phyla that may play roles in stress responses and microbe-microbe interactions. Analysis of 479 genomes reconstructed from the biofilm metagenomes reveals novel biosynthetic gene clusters and CRISPR-Cas systems. Our data highlight the previously underestimated ocean microbial diversity, and allow mining novel microbial lineages and gene resources.
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http://dx.doi.org/10.1038/s41467-019-08463-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355793PMC
January 2019

Infection in Diabetes Mellitus Patients in China: Seroprevalence, Risk Factors, and Case-Control Studies.

Biomed Res Int 2018 18;2018:4723739. Epub 2018 Dec 18.

Department of Urinary Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.

The association between () infection and diabetes mellitus remains controversial. With the improvement of living standards, the prevalence rate of diabetes is steadily increasing in China. Thus, it is necessary to explore the possible association between toxoplasmosis and diabetes mellitus in China. Hence, case-control studies were conducted to explore the seroprevalence and identify the risk factors and possible transmission routes of infection in different types of diabetes, including type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM) patients in China. Four hundred serum samples for each type of diabetes mellitus, matched with 400 control subjects for each group, were collected and examined for anti- IgG and IgM antibodies using commercially available enzyme immunoassay kits. The total seroprevalence in T1DM, T2DM, and GDM patients was 16.50%, 23.50%, and 21.25%, respectively. Each type of diabetes mellitus patients had a significantly higher seroprevalence than the control subjects. Multivariate regression identified three variables as risk factors for infection in diabetes patients, including keeping cats at home and consumption of raw oysters for T1DM patients and consumption of raw/undercooked meat and raw oysters for T2DM patients, which may help to guide future research and control policies in diabetes mellitus patients.
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http://dx.doi.org/10.1155/2018/4723739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312584PMC
May 2019

[Research progress on auditory neuropathy spectrum disorder and cochlear implantation in infants and young children].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018 07;32(14):1120-1124

Auditory neuropathy is a disorder characterized by absent or severely abnormal auditory brainstem response (ABR) with intact outer hair cell function, as evidenced by the presence of evoked otoacoustic emissions and/or cochlear microphonics. Unlike patients with sensory hearing loss who show clinical evidence of impaired outer hair cell function. For ANSD patients, clinical rehabilitation is mainly limited to hearing aid wearing and cochlear implantation. However, the effect of cochlear implantation for ANSD patients may be difference. The outcome of cochlear implantation is related to the lesion location, the age of implantation and the diameter of cochlear nerve.
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http://dx.doi.org/10.13201/j.issn.1001-1781.2018.14.020DOI Listing
July 2018

Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects.

Int J Neuropsychopharmacol 2019 03;22(3):247-259

Falk Center for Molecular Therapeutics, Department of Biomedical Engineering, McCormick School of Engineering and Applied Sciences, Northwestern University, Evanston, Illinois.

Background: Modulation of glutamatergic synaptic transmission by N-methyl-D-aspartate receptors can produce rapid and sustained antidepressant effects. Rapastinel (GLYX-13), initially described as a N-methyl-D-aspartate receptor partial glycine site agonist, exhibits rapid antidepressant effect in rodents without the accompanying dissociative effects of N-methyl-D-aspartate receptor antagonists.

Methods: The relationship between rapastinel's in vitro N-methyl-D-aspartate receptor pharmacology and antidepressant efficacy was determined by brain microdialysis and subsequent pharmacological characterization of therapeutic rapastinel concentrations in N-methyl-D-aspartate receptor-specific radioligand displacement, calcium mobilization, and medial prefrontal cortex electrophysiology assays.

Results: Brain rapastinel concentrations of 30 to 100 nM were associated with its antidepressant-like efficacy and enhancement of N-methyl-D-aspartate receptor-dependent neuronal intracellular calcium mobilization. Modulation of N-methyl-D-aspartate receptors by rapastinel was independent of D-serine concentrations, and glycine site antagonists did not block rapastinel's effect. In rat medial prefrontal cortex slices, 100 nM rapastinel increased N-methyl-D-aspartate receptor-mediated excitatory postsynaptic currents and enhanced the magnitude of long-term potentiation without any effect on miniature EPSCs or paired-pulse facilitation responses, indicating postsynaptic action of rapastinel. A critical amino acid within the NR2 subunit was identified as necessary for rapastinel's modulatory effect.

Conclusion: Rapastinel brain concentrations associated with antidepressant-like activity directly enhance medial prefrontal cortex N-methyl-D-aspartate receptor activity and N-methyl-D-aspartate receptor-mediated synaptic plasticity in vitro. At therapeutic concentrations, rapastinel directly enhances N-methyl-D-aspartate receptor activity through a novel site independent of the glycine coagonist site. While both rapastinel and ketamine physically target N-methyl-D-aspartate receptors, the 2 molecules have opposing actions on N-methyl-D-aspartate receptors. Modest positive modulation of N-methyl-D-aspartate receptors by rapastinel represents a novel pharmacological approach to promote well-tolerated, rapid, and sustained improvements in mood disorders.
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http://dx.doi.org/10.1093/ijnp/pyy101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403082PMC
March 2019

Inhibitory effects of free propionic and butyric acids on the activities of hydrogenotrophic methanogens in mesophilic mixed culture fermentation.

Bioresour Technol 2019 Jan 28;272:458-464. Epub 2018 Oct 28.

Fujian Provincial Key Laboratory of Soil Environmental Health and Regulation, College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China; CAS Key Laboratory for Urban Pollutant Conversion, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address:

The aim of this work was to study the inhibitory of free propionic acid (FPA) and free butyric acid (FBA) on enriched hydrogenotrophic methanogens. It demonstrated that concentrations of FPA and FBA were correlated well with the specific methanogenic activity. Coenzyme M concentrations also agreed well with the trends of FPA and FBA. Two fators of C (concentration at 50% inhibition) and C (recoverable concentration from inhibition) were used to quantitively analyze the inhibitory order using the former result of free acetic acid (FAA) and the results of FBA and FPA. The order according to C was FAA (5.2 mM) > FBA (8.3 mM) > FPA (8.5 mM), while for C it was FPA (9.3 mM) > FAA = FBA (13.5 mM). After comparing with literatue, it suggests that the toxicities of these three organic acids are similar. Thus, accumulating free organic acid offers a cost-effective method to inhibit methanogenesis.
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http://dx.doi.org/10.1016/j.biortech.2018.10.076DOI Listing
January 2019

Rational design of new cyclic analogues of the antimicrobial lipopeptide tridecaptin A.

Chem Commun (Camb) 2018 Sep 4;54(75):10634-10637. Epub 2018 Sep 4.

School of Chemistry and Chemical Engineering, David Keir Building, Stranmillis Road, Queen's University Belfast, Belfast BT9 5AG, UK.

Non-ribosomal peptides (NRPs) are a rich source of antibiotic candidates. However, it was recently discovered that resistance to NRPs can be mediated by d-stereoselective peptidases. The tridecaptins, a class of NRPs that selectively target Gram-negative bacteria, are degraded by the d-peptidase TriF. Through analysis of a solution NMR structure of tridecaptin A, we have rationally synthesized new cyclic tridecaptin analogues that retain strong antimicrobial activity and are resistant to TriF.
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http://dx.doi.org/10.1039/c8cc05790gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146376PMC
September 2018

Inhibitors of the Neutral Amino Acid Transporters ASCT1 and ASCT2 Are Effective in In Vivo Models of Schizophrenia and Visual Dysfunction.

J Pharmacol Exp Ther 2018 11 31;367(2):292-301. Epub 2018 Aug 31.

Department of Biological Sciences, Allergan, Inc., Irvine, California

The -methyl-d-aspartate receptor coagonist d-serine is a substrate for the neutral amino acid transporters ASCT1 and ASCT2, which may regulate its extracellular levels in the central nervous system (CNS). We tested inhibitors of ASCT1 and ASCT2 for their effects in rodent models of schizophrenia and visual dysfunction, which had previously been shown to be responsive to d-serine. L-4-fluorophenylglycine (L-4FPG), L-4-hydroxyPG (L-4OHPG), and L-4-chloroPG (L-4ClPG) all showed high plasma bioavailability when administered systemically to rats and mice. L-4FPG showed good brain penetration with brain/plasma ratios of 0.7-1.4; however, values for L-4OHPG and L-4ClPG were lower. Systemically administered L-4FPG potently reduced amphetamine-induced hyperlocomotion in mice, whereas L-4OHPG was 100-fold less effective and L-4ClPG inactive at the doses tested. L-4FPG and L-4OHPG did not impair visual acuity in naive rats, and acute systemic administration of L-4FPG significantly improved the deficit in contrast sensitivity in blue light-treated rats caused by retinal degeneration. The ability of L-4FPG to penetrate the brain makes this compound a useful tool to further evaluate the function of ASCT1 and ASCT2 transporters in the CNS.
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http://dx.doi.org/10.1124/jpet.118.251116DOI Listing
November 2018

Discovery of cationic nonribosomal peptides as Gram-negative antibiotics through global genome mining.

Nat Commun 2018 08 16;9(1):3273. Epub 2018 Aug 16.

Department of Ocean Science and Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

The worldwide prevalence of infections caused by antibiotic-resistant Gram-negative bacteria poses a serious threat to public health due to the limited therapeutic alternatives. Cationic peptides represent a large family of antibiotics and have attracted interest due to their diverse chemical structures and potential for combating drug-resistant Gram-negative pathogens. Here, we analyze 7395 bacterial genomes to investigate their capacity for biosynthesis of cationic nonribosomal peptides with activity against Gram-negative bacteria. Applying this approach, we identify two novel compounds (brevicidine and laterocidine) showing bactericidal activities against antibiotic-resistant Gram-negative pathogens, such as Pseudomonas aeruginosa and colistin-resistant Escherichia coli, and an apparently low risk of resistance. The two peptides show efficacy against E. coli in a mouse thigh infection model. These findings may contribute to the discovery and development of Gram-negative antibiotics.
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http://dx.doi.org/10.1038/s41467-018-05781-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095874PMC
August 2018

Structural Changes Induced by Acupuncture in the Recovering Brain after Ischemic Stroke.

Evid Based Complement Alternat Med 2018 23;2018:5179689. Epub 2018 May 23.

Acupuncture and Tuina School/Third Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.

The aim of this study was to observe the grey matter (GM) tissue changes of ischemic stroke patients, to explore the therapy responses and possible mechanism of acupuncture. 21 stroke patients were randomly assigned to receive either acupuncture plus conventional (Group A) or only conventional (Group B) treatments for 4 weeks. All patients in both groups accepted resting-state functional magnetic resonance (fMRI) scan before and after treatment, and the voxel-based morphometry (VBM) analysis was performed to detect the cerebral grey structure changes. The modified Barthel index (MBI) was used to evaluate the therapeutic effect. Compared with the patients in Group B, the patients in Group A exhibited a more significant enhancement of the changes degree of MBI from pre- to post-treatment intervention. VBM analyses found that after treatment the patients in Group A showed extensive changes in GMV. In Group A, the left frontal lobe, precentral gyrus, superior parietal gyrus, anterior cingulate cortex, and middle temporal gyrus significantly increased, and the right frontal gyrus, inferior parietal gyrus, and middle cingulate cortex decreased ( < 0.05, corrected). In addition, left anterior cingulate cortex and left middle temporal gyrus are positively related to the increase in MBI score ( < 0.05, corrected). In Group B, right precentral gyrus and right inferior frontal gyrus increased ( < 0.05, corrected). In conclusion, acupuncture can evoke pronounced structural reorganization in the frontal areas and the network of DMN areas, which may be the potential therapy target and the potential mechanism where acupuncture improved the motor and cognition recovery.
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http://dx.doi.org/10.1155/2018/5179689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989285PMC
May 2018

Tarps differentially affect the pharmacology of ampakines.

Biochem Pharmacol 2018 08 12;154:446-451. Epub 2018 Jun 12.

RespireRx Pharmaceuticals Inc., 126 Valley Road, Glen Rock, NJ 07452,United States.

Transmembrane AMPA receptor regulatory proteins (TARPs) govern AMPA receptor cell surface expression and distinct physiological properties including agonist affinity, desensitization and deactivation kinetics. The prototypical TARP, STG or γ2 and TARPs γ3, γ4, γ7 and γ8 are all expressed to varying degrees in the mammalian brain and differentially regulate AMPAR gating parameters. Positive allosteric AMPA receptor modulators or ampakines alter receptor rates of agonist binding/unbinding, channel opening and can offset receptor desensitization and deactivation. The effects of the two ampakines, CX614 and cyclothiazide (CTZ) were evaluated on homomeric GluR1-flip receptors and GluR2-flop receptors expressed on HEK293 cells by transient transfection with or without different TARPs γ2, γ3, γ4 or γ8 genes. γ4 was the most robust TARP in increasing the affinities of CX614 and CTZ on GluR1-flip receptors, but had no such effect on GluR2-flop receptors. However, γ8 gave the most significant increases in affinities of CX614 and CTZ on GluR2-flop. These data show that TARPs differentially affect the surface expression and kinetics of the AMPA receptor, as well as the pharmacology of ampakines for the AMPA receptor. The modulatory effects of TARPs on ampakine pharmacology are complex, being dependent on both the TARP subtype and the AMPA receptor subtypes/isoforms.
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http://dx.doi.org/10.1016/j.bcp.2018.06.013DOI Listing
August 2018

Selection and environmental adaptation along a path to speciation in the Tibetan frog .

Proc Natl Acad Sci U S A 2018 05 14;115(22):E5056-E5065. Epub 2018 May 14.

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China;

Tibetan frogs, , are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including in the brain, and in the heart, and in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation.
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http://dx.doi.org/10.1073/pnas.1716257115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5984489PMC
May 2018

[Long-term results of endolymphatic sac mastoid drainage for Ménière disease].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018 Jan;32(2):138-142

Department of Otolaryngology Head and Neck Surgery,Beijing Tongren Hospital,Capital Medical University,Key Laboratory of Otolaryngology Head and Neck Surgery,Ministry of Education Beijing,100730,China.

To investigate the long-term efficacy of endolymphatic sac mastoid drainage for Ménière disease.Data from 26 patients diagnosed with MD strictly meeting the criteria issued by " Guideline of diagnosis and treatment of Meniere disease(2017)" from 2006 to 2015 were analyzed in this study.Endolymphatic sac mastoid shunt surgery was performed for each patient.The therapeutic effect was evaluated against the " Guideline of diagnosis and treatment of Meniere disease(2017)".Vertigo control and auditory function were measured after at least two years follow up.In 26 cases,16 cases were male and 10 cases were femaleThe age ranged from 24 to 71 years old,with an average of 52.04 years.The disease duration ranged from 1 to 32 years.22 cases were diagnosed as unilateral Ménière disease,and bilateral involvement was identified in 4 cases,thus a total of 30 ears were included.According to the preoperative staging of hearing,there were 0 cases in stage one,5 cases in stage two,16 in stage three and 9 cases in stage four.15 cases(57.7%)achieved class A vertigo conrol(complete control),9 cases(34.6%)class B(substantial control)and 2 cases(7.7%)class D(no control).The severity of vertigo and its impact on daily life were improved in 24 cases(92.3%)with a score of 0 point,and 2 cases(7.7%)scored 2 points.Post-operative hearing was improved in 3 cases(11.5%),unchanged in 16 cases(61.6%)and worsened in 7 cases(26.9%).After operation,tinnitus disappeared in 5 cases(19.2%),reduced in 13 case(50%)and unchanged in 8 cases(30.8%).Endolymphatic sac mastoid drainage was an effective and safe management for intractable Ménière disease patients with pre-operative residual hearing.The occurrence of complication was unsual.The patients who are in stage four could gain benifits from the surgery.
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http://dx.doi.org/10.13201/j.issn.1001-1781.2018.02.015DOI Listing
January 2018

[Clinical analysis of otogenic Mouret abscess: a case report].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2018 Mar;32(6):472-473

Mouret abscess is a rare extracranial complication of suppurative otitis media. It is generally believed to be a deep neck abscess caused by inflammation leading to the rupture of the bony tip of the mastoid tip. The location of Mouret abscess is deep. The symptoms are insidious at the onset, but may eventually spread to the surrounding tissue, and even lead to mediastinal abscess, cavernous sinus thrombosis, meningitis, dyspnea and other serious complications. At present, with the popularization of antibiotics, the occurrence rate of Mouret abscess is very low, and only sporadic cases have been reported.In this paper, a case of Mouret abscess caused by cholesteatoma was analyzed to explore Mouret abscess in terms of the route of infection, clinical manifestations, imaging features, diagnosis and treatment.
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http://dx.doi.org/10.13201/j.issn.1001-1781.2018.06.018DOI Listing
March 2018

[The Detection of Micro RNA346 Gene Polymorphism by Capillary Electrophoresis].

Sichuan Da Xue Xue Bao Yi Xue Ban 2018 Mar;49(2):280-284

Department of Laboratory Science in Public Health,West China School of Public Health,Sichuan University,Chengdu 610041,China.

Objective: To develop a method for the detection of micro RNA346 gene polymorphism by capillary electrophoresis (CE).

Methods: The genome DNA was extracted with the kit of blood/cell/tissue genome DNA extraction,then micro RNA346 gene was amplified by PCR,digested by BciT130Ⅰrestriction enzyme and detected by CE. The conditions for CE separation were optimized. Samples from rheumatoid arthritis patients and healthy persons were detected under the optimal conditions.

Results: Under the optimized experimental conditions of CE (sieving medium mass concentration was 10 g/L and the separation voltage was 12 kV),the detection of the digested products of microRNA346 gene could be completed within 25 min. The intra-day relative standard deviation (RSD) of the method was 0.43%-0.63% and inter-day RSD was 1.49%-1.56%.Samples from 96 rheumatoid arthritis patients and 43 healthy persons were analyzed by the proposed method. The results showed that only micro RNA346Ⅰtype was detected but micro RNA346 Ⅱ type wasn't.

Conclusion: This method is easy to operate,and has the advantages of high efficiency,fast speed,less sample consumption and high automation level. This method is suitable for the determination of RNA gene polymorphism of mirco RNA.
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March 2018

Publisher Correction: Resistance to nonribosomal peptide antibiotics mediated by D-stereospecific peptidases.

Nat Chem Biol 2018 Sep;14(9):901

Department of Ocean Science and Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

In the version of this article originally published, the links and files for the Supplementary Information, including Supplementary Tables 1-5, Supplementary Figures 1-25, Supplementary Note, Supplementary Datasets 1-4 and the Life Sciences Reporting Summary, were missing in the HTML. The error has been corrected in the HTML version of this article.
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http://dx.doi.org/10.1038/s41589-018-0022-7DOI Listing
September 2018
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