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1.
J Agric Food Chem ; 72(22): 12434-12444, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38775141

ABSTRACT

A series of novel isoindoline-1-one derivatives containing piperidine moiety were designed and synthesized using natural compounds as raw materials, and their biological activities were tested for three bacterial and three fungal pathogens. These derivatives exhibited good against phytopathogenic bacteria activities against Pseudomonas syringae pv actinidiae (Psa) and Xanthomonas axonopodis pv.citri (Xac). Some compounds exhibited excellent antibacterial activities against Xanthomonas oryzae pv oryzae (Xoo). The dose of Y8 against Xoo (the maximum half lethal effective concentration (EC50) = 21.3 µg/mL) was better than that of the thiediazole copper dose (EC50 = 53.3 µg/mL). Excitingly, further studies have shown that the molecular docking of Y8 with 2FBW indicates that it can fully locate the interior of the binding pocket through hydrogen bonding and hydrophobic interactions, thereby enhancing its anti-Xoo activity. Scanning electron microscopy (SEM) studies revealed that Y8 induced the Xoo cell membrane collapse. Moreover, the proteomic results also indicate that Y8 may be a multifunctional candidate as it affects the formation of bacterial Xoo biofilms, thereby exerting antibacterial effects.


Subject(s)
Anti-Bacterial Agents , Drug Design , Molecular Docking Simulation , Piperidines , Xanthomonas , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Xanthomonas/drug effects , Xanthomonas/growth & development , Piperidines/pharmacology , Piperidines/chemistry , Piperidines/chemical synthesis , Structure-Activity Relationship , Microbial Sensitivity Tests , Pseudomonas syringae/drug effects , Indoles/chemistry , Indoles/pharmacology , Indoles/chemical synthesis , Molecular Structure
2.
Int J Nanomedicine ; 19: 4081-4101, 2024.
Article in English | MEDLINE | ID: mdl-38736654

ABSTRACT

Purpose: Spinal cord injury (SCI) is an incurable and disabling event that is accompanied by complex inflammation-related pathological processes, such as the production of excessive reactive oxygen species (ROS) by infiltrating inflammatory immune cells and their release into the extracellular microenvironment, resulting in extensive apoptosis of endogenous neural stem cells. In this study, we noticed the neuroregeneration-promoting effect as well as the ability of the innovative treatment method of FTY720-CDs@GelMA paired with NSCs to increase motor function recovery in a rat spinal cord injury model. Methods: Carbon dots (CDs) and fingolimod (FTY720) were added to a hydrogel created by chemical cross-linking GelMA (FTY720-CDs@GelMA). The basic properties of FTY720-CDs@GelMA hydrogels were investigated using TEM, SEM, XPS, and FTIR. The swelling and degradation rates of FTY720-CDs@GelMA hydrogels were measured, and each group's ability to scavenge reactive oxygen species was investigated. The in vitro biocompatibility of FTY720-CDs@GelMA hydrogels was assessed using neural stem cells. The regeneration of the spinal cord and recovery of motor function in rats were studied following co-treatment of spinal cord injury using FTY720-CDs@GelMA hydrogel in combination with NSCs, utilising rats with spinal cord injuries as a model. Histological and immunofluorescence labelling were used to determine the regeneration of axons and neurons. The recovery of motor function in rats was assessed using the BBB score. Results: The hydrogel boosted neurogenesis and axonal regeneration by eliminating excess ROS and restoring the regenerative environment. The hydrogel efficiently contained brain stem cells and demonstrated strong neuroprotective effects in vivo by lowering endogenous ROS generation and mitigating ROS-mediated oxidative stress. In a follow-up investigation, we discovered that FTY720-CDs@GelMA hydrogel could dramatically boost NSC proliferation while also promoting neuronal regeneration and synaptic formation, hence lowering cavity area. Conclusion: Our findings suggest that the innovative treatment of FTY720-CDs@GelMA paired with NSCs can effectively improve functional recovery in SCI patients, making it a promising therapeutic alternative for SCI.


Subject(s)
Fingolimod Hydrochloride , Hydrogels , Neural Stem Cells , Rats, Sprague-Dawley , Spinal Cord Injuries , Animals , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/therapy , Fingolimod Hydrochloride/pharmacology , Fingolimod Hydrochloride/chemistry , Fingolimod Hydrochloride/administration & dosage , Neural Stem Cells/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/administration & dosage , Rats , Recovery of Function/drug effects , Reactive Oxygen Species/metabolism , Quantum Dots/chemistry , Disease Models, Animal , Female , Spinal Cord/drug effects
3.
Article in English | MEDLINE | ID: mdl-38498765

ABSTRACT

COVID-19, caused by the highly contagious SARS-CoV-2 virus, is distinguished by its positive-sense, single-stranded RNA genome. A thorough understanding of SARS-CoV-2 pathogenesis is crucial for halting its proliferation. Notably, the 3C- like protease of the coronavirus (denoted as 3CLpro) is instrumental in the viral replication process. Precise delineation of 3CLpro cleavage sites is imperative for elucidating the transmission dynamics of SARS-CoV-2. While machine learning tools have been deployed to identify potential 3CLpro cleavage sites, these existing methods often fall short in terms of accuracy. To improve the performances of these predictions, we propose a novel analytical framework, the Transformer and Deep Forest Fusion Model (TDFFM). Within TDFFM, we utilize the AAindex and the BLOSUM62 matrix to encode protein sequences. These encoded features are subsequently input into two distinct components: a Deep Forest, which is an effective decision tree ensemble methodology, and a Transformer equipped with a Multi-Level Attention Model (TMLAM). The integration of the attention mechanism allows our model to more accurately identify positive samples, thus enhancing the overall predictive performance. Evaluation on a test set demonstrates that our TDFFM achieves an accuracy of 0.955, an AUC of 0.980, and an F1-score of 0.367, substantiating the model's superior prediction capabilities.

4.
Int J Nanomedicine ; 18: 7305-7333, 2023.
Article in English | MEDLINE | ID: mdl-38084124

ABSTRACT

Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies.


Subject(s)
Spinal Cord Injuries , Spinal Cord Regeneration , Humans , Hydrogels/therapeutic use , Spinal Cord Injuries/drug therapy , Biocompatible Materials/therapeutic use , Tissue Engineering , Nerve Regeneration/physiology , Spinal Cord
5.
Thorac Cancer ; 14(31): 3089-3096, 2023 11.
Article in English | MEDLINE | ID: mdl-37772424

ABSTRACT

BACKGROUND: The aim of this study was to analyze the effect of paclitaxel on the apoptosis of esophageal cancer cells in relation to MUC20. METHODS: RT-qPCR analysis, a CCK-8 assay, western blotting, and flow cytometry were used to analyze the anticancer effects of paclitaxel treatment or OE-MUC20 in vitro and in vivo. RESULTS: The in vitro results showed that paclitaxel significantly induced MUC20 upregulation and that paclitaxel treatment or OE-MUC20 significantly decreased esophageal cancer cell viability and increased mTOR signaling activation and apoptosis. In addition, PKM2, a key downstream molecule of mTOR signaling, similarly showed significant upregulation after paclitaxel treatment in cells with OE-MUC20, and its expression was attenuated after treatment with mTOR inhibitors. In a nude mouse model, tumor growth was slow in the OE-MUC20 group and accelerated after inhibition of mTOR signaling. CONCLUSION: These data suggest that MUC20 is an important target of paclitaxel in esophageal cancer and promotes apoptosis through activation of mTOR signaling.


Subject(s)
Esophageal Neoplasms , Humans , Animals , Mice , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics , Apoptosis , Cell Survival , Mice, Nude , Paclitaxel/pharmacology , TOR Serine-Threonine Kinases , Cell Line, Tumor , Cell Proliferation , Mucins
6.
Front Bioeng Biotechnol ; 11: 1154301, 2023.
Article in English | MEDLINE | ID: mdl-36994359

ABSTRACT

The rapid healing and repair of skin wounds has been receiving much clinical attention. Covering the wound with wound dressing to promote wound healing is currently the main treatment for skin wound repair. However, the performance of wound dressing prepared by a single material is limited and cannot meet the requirements of complex conditions for wound healing. MXene is a new two-dimensional material with electrical conductivity, antibacterial and photothermal properties and other physical and biological properties, which has a wide range of applications in the field of biomedicine. Based on the pathophysiological process of wound healing and the properties of ideal wound dressing, this review will introduce the preparation and modification methods of MXene, systematically summarize and review the application status and mechanism of MXene in skin wound healing, and provide guidance for subsequent researchers to further apply MXene in the design of skin wound dressing.

7.
Sci Total Environ ; 857(Pt 1): 159384, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36240921

ABSTRACT

Phytoremediation assisted by endophytic bacteria is promising to efficiently remediate cadmium (Cd) contaminated soil. Bacillus cereus BL4, isolated from Miscanthus floridulus growing around a pyrite mine, exhibited high Cd tolerance and plant growth-promoting traits and could improve Cd bioavailability in soil. As a result of the pot experiment, after inoculation with strain BL4, the fresh weight, height, and Cd accumulation of Miscanthus floridulus shoots increased by 19.08-32.26 %, 6.02-16.60 %, and 23.67 %-24.88 %, respectively, and roots increased by 49.38-56.41 %, 22.87-33.93 %, and 28.51 %-42.37 %, respectively. Under Cd stress, the chlorophyll content, photosynthetic rate, and root activity of Miscanthus floridulus increased, while the membrane permeability and malonaldehyde (MDA) content significantly decreased after the inoculation of BL4, which indicated the alleviation of the cytotoxicity of Cd. Accordingly, the glutathione (GSH) content increased, and the activities of antioxidant enzymes presented downward trends after BL4 inoculation. Cd bioavailability in soil increased after BL4 inoculation, accompanied by increases in the activities of soil enzymes (invertase, urease, alkaline phosphatase, dehydrogenase, FDA hydrolase, and catalase) as well as the richness and diversity of soil bacteria. Our findings revealed that strain BL4 might strengthen the phytoremediation of Cd by Miscanthus floridulus through its effects on plant physio-biochemistry and soil microecology, which provided a basis for the relative application to Cd-contaminated soil.


Subject(s)
Cadmium , Soil Pollutants , Cadmium/toxicity , Cadmium/analysis , Soil/chemistry , Bacillus cereus , Soil Pollutants/toxicity , Soil Pollutants/analysis , Biodegradation, Environmental , Poaceae , Plant Roots/chemistry
8.
J Environ Manage ; 326(Pt A): 116725, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36375431

ABSTRACT

Although the contamination situation of chromium (Cr) and vanadium (V) have been revealed, the effects of their re-release on ecological risk in contaminated acidic paddy soil are unclear. To evaluate the effects, we assigned soil microcosms across three different concentration (100, 200, 300 mg/L) and introduced Cr and V alone or combination into an already slightly contaminated acidic soil. We found that Cr and V alone or interacted to increased soil bioavailable-metals, changed soil properties and nutrients to varying degrees. Meanwhile, soil ammoniacal nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) contents, nitrogen (N) -cycling enzyme activities, microbial mass N were significantly influenced by Cr addition. Which demonstrated that Cr re-release may disturb soil N cycle. However, V alone significantly improved soil NO3--N contents, cellulase and dehydrogenase activities, soil respiration intensity and microbial mass carbon: nitrogen. Meanwhile, V addition also decreased bacterial diversity while Cr addition increased bacterial diversity and shaped new bacterial community, some V(V) and Cr (VI) reducing bacteria were identified. Heatmap of Pearson correlation and Redundancy analysis showed that NH4+-N, NO3--N, Potassium, Phosphorus, and Cr played an important role in bacterial community structure. These findings suggested that re-release of Cr and V disturbed soil function and raised ecological risks, and the power to destroy the ecosystem stability originated from Cr was much stronger than V. This study was contributed to understand the effects of Cr and V re-release on microecology in contaminated acidic agricultural soil.


Subject(s)
Soil Pollutants , Soil , Soil/chemistry , Chromium/analysis , Vanadium/pharmacology , Soil Microbiology , Soil Pollutants/analysis , Ecosystem , Bacteria , Nitrogen/analysis , Nutrients
9.
J Biol Eng ; 16(1): 32, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36419160

ABSTRACT

Bone defect repair is a continual and complicated process driven by a variety of variables. Because of its bright multicolor luminescence, superior biocompatibility, water dispersibility, and simplicity of synthesis from diverse carbon sources, carbon dots (CDs) have received a lot of interest. It has a broad variety of potential biological uses, including bone defect repair, spinal cord injury, and wound healing. Materials including CDs as the matrix or major component have shown considerable benefits in enabling bone defect healing in recent years. By altering the carbon dots or mixing them with other wound healing-promoting agents or materials, the repair effect may be boosted even further. The report also shows and discusses the use of CDs to heal bone abnormalities. The study first presents the fundamental features of CDs in bone defect healing, then provides CDs manufacturing techniques that should be employed in bone defect repair, and lastly examines their development in the area of bioengineering, particularly in bone defect repair. In this work, we look at how carbon dots and their alteration products may help with bone defect healing by being antibacterial, anti-infective, osteogenic differentiation-promoting, and gene-regulating.

10.
J Environ Manage ; 319: 115683, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-35853307

ABSTRACT

Soil ecosystem functions and microbial community structure were severely impaired with long-term cadmium (Cd) contamination and acidification. To investigate the effect of amendments on soil physiochemical parameters and soil micro-ecology in acidic Cd contaminated soil, this study was conducted in a pot experiment with the application of calcium amendments, oyster shell powders (OS) and limestone (LM). Each amendment applied at ratios of 1.0%, 3.0%, and 5.0% (w/w), respectively. The results showed that the application of amendments increased the soil pH by 2.10-2.88, the bioavailable Cd decreased by 12.49%-19.48%, and un-bioavailable Cd increased by 96.57%-200.7%. The OS increased the richness index (Chao and Ace increased by 13.23%-16.20% and 7.13%-47.63%), and LM increased the microbial diversity index (Shannon increased by 1.14%-8.72% and Simpson indexes decreased by 28.00%-63.61%). In LM groups, soil microbial communities were significantly altered with increasing application concentrations, the relative abundance of phylum Proteobacteria, Bacteroidota and Gemmatimonadota increased, while Firmicute, Actinobacteria, Chloroflexi decreased. In OS treatments, the soil microbial community structure was basically unchanged. The correlation analysis showed that pH, TN, TP, CEC, OM were the dominant factors affecting the microbial community. This study has shown that application of amendments could effectively reduce the Cd bioavailability in soil, but LM altered the soil microbial community structure, while OS maintained the soil microbiological structure.


Subject(s)
Metals, Heavy , Microbiota , Oryza , Ostreidae , Soil Pollutants , Acids , Animals , Bacteria , Biomass , Cadmium/chemistry , Calcium Carbonate , Metals, Heavy/analysis , Soil/chemistry , Soil Pollutants/analysis
11.
Environ Pollut ; 308: 119585, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35728693

ABSTRACT

Microbially induced carbonate precipitation (MICP) is a technique used extensively to address heavy metal pollution but its micro-dynamic process remains rarely explored. In this study, A novel Cd-tolerant ureolytic bacterium DL-1 (Pseudochrobactrum sp.) was used to study the micro-dynamic process. With conditions optimized by response surface methodology, the removal efficiency of Cd2+ could achieve 99.89%. Three components were separated and characterized in the reaction mixture of Cd2+ removal by MICP. The quantitative-dynamic distribution of Cd2+ in different components was revealed. Five synergistic effects for Cd2+ removal were found, including co-precipitation, adsorption by precipitation, crystal precipitation on the cell surface, intracellular accumulation and extracellular chemisorption. Importantly, during Cd2+ removal by MICP, the phenomenon that crystalline nanoparticles adhere to the cell surface, but without any micrometer-sized precipitation encapsulated bacterial cells was observed. This indicated that the previously studied model of bacterial cells as nucleation sites for metal cation precipitation and crystal growth is oversimplified. Our findings provided valuable insights into the mechanism of heavy metals removal by MICP, and a more straightforward method for studying biomineralization-related dynamic process.


Subject(s)
Cadmium , Metals, Heavy , Bacteria/metabolism , Cadmium/metabolism , Calcium Carbonate/chemistry , Carbonates/chemistry , Metals, Heavy/metabolism
12.
Front Genet ; 13: 884589, 2022.
Article in English | MEDLINE | ID: mdl-35571057

ABSTRACT

Parasites can cause enormous damage to their hosts. Studies have shown that antiparasitic peptides can inhibit the growth and development of parasites and even kill them. Because traditional biological methods to determine the activity of antiparasitic peptides are time-consuming and costly, a method for large-scale prediction of antiparasitic peptides is urgently needed. We propose a computational approach called i2APP that can efficiently identify APPs using a two-step machine learning (ML) framework. First, in order to solve the imbalance of positive and negative samples in the training set, a random under sampling method is used to generate a balanced training data set. Then, the physical and chemical features and terminus-based features are extracted, and the first classification is performed by Light Gradient Boosting Machine (LGBM) and Support Vector Machine (SVM) to obtain 264-dimensional higher level features. These features are selected by Maximal Information Coefficient (MIC) and the features with the big MIC values are retained. Finally, the SVM algorithm is used for the second classification in the optimized feature space. Thus the prediction model i2APP is fully constructed. On independent datasets, the accuracy and AUC of i2APP are 0.913 and 0.935, respectively, which are better than the state-of-arts methods. The key idea of the proposed method is that multi-level features are extracted from peptide sequences and the higher-level features can distinguish well the APPs and non-APPs.

13.
ACS Omega ; 6(41): 27561-27567, 2021 Oct 19.
Article in English | MEDLINE | ID: mdl-34693177

ABSTRACT

A total of 34 novel ferulic amide Ac5c derivatives were designed and synthesized and their antipest activities were investigated. The results showed that some compounds exhibited excellent in vitro antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo) and X. oryzae pv. oryzicola (Xoc), such as compounds 4q and 5n demonstrated excellent in vitro activity against Xoo, with EC50 values of 4.0, and 1.9 µg/mL, respectively. Compounds 4c, 4h, 4m, 4p, 4q, and 5a had significant in vitro activities against Xoc, with EC50 values of 12.5, 13.9, 9.8 15.0, 9.2, and 19.8 µg/mL, respectively. Moreover, the antibacterial activity in vivo against rice bacterial leaf blight was also evaluated. Scanning electron microscopy (SEM) showed that compound 5n significantly reduced the cell membrane of Xoo, and resulted in cell surface wilting, deformation, breakage, and increased porous attributes. In addition, some of the target compounds also showed moderate biological activity against fungi and acted as potential insecticides.

14.
Bioorg Chem ; 115: 105248, 2021 10.
Article in English | MEDLINE | ID: mdl-34392177

ABSTRACT

A series of new ferulic acid derivatives bearing an oxadiazole ether was synthesized by introducing a structure of oxadiazole into trans-ferulic acid via an ether linkage. The synthesized target compounds were evaluated in vivo for their anti-TMV (tobacco mosaic virus) activity, which indicated that some synthesized compounds displayed strong activity for controlling TMV. For protective activity, compounds 6f and 6h had the most activities of 65% and 69.8% at 500 mg L-1, respectively. Compounds 6a, 6b, 6e, 6f and 6h showed > 60% curative activities at 500 mg L-1. Preliminary proteomics analysis showed that compound 6h could regulate the phenylpropanoid biosynthesis pathway and chloroplast function. These results indicated that synthesized novel ferulic acid derivatives could be used for controlling TMV.


Subject(s)
Antiviral Agents/pharmacology , Caffeic Acids/pharmacology , Ethers/pharmacology , Oxadiazoles/pharmacology , Tobacco Mosaic Virus/drug effects , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Caffeic Acids/chemical synthesis , Caffeic Acids/chemistry , Dose-Response Relationship, Drug , Ethers/chemistry , Microbial Sensitivity Tests , Molecular Structure , Oxadiazoles/chemistry , Structure-Activity Relationship
15.
J Agric Food Chem ; 69(35): 10082-10092, 2021 Sep 08.
Article in English | MEDLINE | ID: mdl-34432441

ABSTRACT

Thirty-eight novel ferulic amide 1-aminocyclohexane carboxylic acid (Ac6c) derivatives D1-D19 and E1-E19 were designed and synthesized, and their antibacterial, antifungal, and insecticidal activities were tested. Most of the synthesized compounds displayed excellent activity againstXanthomonas oryzae pv. oryzae (Xoo), with EC50 values ranging from 11.6 to 83.1 µg/mL better than that of commercial bismerthiazol (BMT, EC50 = 84.3 µg/mL), as well as much better performance compared to that of thiediazole copper (TDC, EC50 = 137.8 µg/mL). D6 (EC50 = 17.3 µg/mL), D19 (EC50 = 29.4 µg/mL), E3 (EC50 = 29.7 µg/mL), E9 (EC50 = 27.0 µg/mL), E10 (EC50 = 18.6 µg/mL), and E18 (EC50 = 20.8 µg/mL) showed much higher activity on Xanthomonas oryzae pv. oryzicola compared with BMT (EC50 = 80.1 µg/mL) and TDC (EC50 = 124.7 µg/mL). In relation to controlling the fungus, Rhizoctonia solani, E1, E10, and E13 had much lower EC50 values of 0.005, 0.140, and 0.159 µg/mL compared to hymexazol at 74.8 µg/mL. Further in vivo experiments demonstrated that E6 and E12 controlled rice bacterial leaf blight disease better than BMT and TDC did. Scanning electron microscopy (SEM) studies revealed that E12 induced the Xoo cell membrane collapse. Moreover, D13 (73.7%), E5 (80.6%), and E10 (73.4%) also showed moderate activity against Plutella xylostella. These results indicated that the synthesized ferulic amide Ac6c derivatives showed promise as candidates for treating crop diseases.


Subject(s)
Oryza , Xanthomonas , Amides/pharmacology , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Oxadiazoles , Plant Diseases , Rhizoctonia
16.
Eur J Med Genet ; 64(6): 104228, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33878481

ABSTRACT

Hermansky-Pudlak syndrome is a rare, autosomal, recessive syndromic form of albinism characterized by oculocutaneous albinism, bleeding diathesis, and a series of clinical complications. It is rarely reported in China, even with its large population base. In this study, we describe the clinical phenotypes and genotypes of five unrelated Chinese Hermansky-Pudlak syndrome pedigrees following clinical observation and next-generation sequencing. We identified three HPS-1 and two HPS-6 cases among 548 Chinese patients with oculocutaneous albinism. Five novel variants [c.1279_1280insGGAG p.(Asp427Glyfs*27) and c.875_878delACAG p.(Asp292Alafs*38) in HPS1 and c.1999C>T p.(Arg667*), c.335G>A p.(W112*), and c.1732C>T p.(R578*) in HPS6] were identified by next-generation sequencing. Our findings expand the spectrum of known variants and the genetic background of Hermansky-Pudlak syndrome, which may help in investigating phenotype-genotype relationships and aid in genetic counselling of patients with Hermansky-Pudlak syndrome.


Subject(s)
Hermanski-Pudlak Syndrome/genetics , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Child , Child, Preschool , Female , Hermanski-Pudlak Syndrome/pathology , Humans , Male , Mutation , Phenotype
17.
J Microbiol Immunol Infect ; 54(6): 1179-1183, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33563561

ABSTRACT

BACKGROUND: The rapid spread of C. difficile 027 has become one of the leading threats of healthcare-associated infections wordwild. However, C. difficile 027 infections have rarely been reported in China. The objective of this study was to strengthen the understanding of the molecular characterizations of C. difficile 027 in China. METHODS: In this study, stool specimens from 176 suspected CDI cases were collected from 1 Jan 2018 to 30 Jun 2019. These specimens were measured by GeneXpert test and C.difficile colonies were identified and analyzed. RESULTS: There were five samples positive for tcdA, tcdB, binary toxin genes and had deletions in tcdC gene. These five Clostridioides difficile isolates belonged to ST1 and confirmed as Clostridioides difficile 027 strains by PCR ribotyping. Through using whole genome sequencing, , we found that these five strains were closely clustered into the same predominant evolutionary branch and were highly similar to C. difficile 027 strain R20291. Antimicrobial susceptibility testing result showed they were highly resistant to fluoroquinolones. CONCLUSIONS: In Our study, five C. difficile 027 isolates were identified and characterized using MLST, PCR ribotyping and whole genome sequencing. We proposed that C. difficile 027 infections are probably neglected in China. Further epidemiological studies across the country together with the introduction of routine diagnostic testing and multi-center or national level surveillance are needed to ascertain the size of this potentially significant problem.


Subject(s)
Clostridioides difficile/genetics , Clostridium Infections/microbiology , Anti-Bacterial Agents/pharmacology , China/epidemiology , Clostridioides difficile/classification , Clostridioides difficile/drug effects , Clostridioides difficile/isolation & purification , Clostridium Infections/epidemiology , Drug Resistance, Bacterial , Genome, Bacterial/genetics , Genotype , Hospitals , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , Retrospective Studies , Ribotyping
18.
Front Genet ; 11: 760, 2020.
Article in English | MEDLINE | ID: mdl-32903636

ABSTRACT

As cancer remains one of the main threats of human life, developing efficient cancer treatments is urgent. Anticancer peptides, which could overcome the significant side effects and poor results of traditional cancer treatments, have become a new potential alternative these years. However, identifying anticancer peptides by experimental methods is time consuming and resource consuming, it is of great significance to develop effective computational tools to quickly and accurately identify potential anticancer peptides from amino acid sequences. For most current computational methods, feature representation plays a key role in their final successes. This study proposes a novel fast and accurate approach to identify anticancer peptides using diversified feature representations and ensemble learning method. For the feature representations, the information is encoded from multidimensional feature spaces, including sequence composition, sequence-order, physicochemical properties, etc. In order to better model the potential relationships of peptides, multiple ensemble classifiers, LightGBMs, are applied to detect the different feature sets at first. Then the obtained multiple outputs are used as inputs of the support vector machine classifier, which effectively identifies anticancer peptides. Experimental results on cross validation and independent test sets demonstrate that our method can achieve better or comparable performances compared with other state-of-the-art methods.

19.
J Agric Food Chem ; 68(27): 7226-7234, 2020 Jul 08.
Article in English | MEDLINE | ID: mdl-32530620

ABSTRACT

A series of novel α-ketoamide derivatives bearing a vanillin skeleton were designed and synthesized. Bioactivity tests on virus and bacteria were performed. The results indicated that some compounds exhibited excellent antitobacco mosaic virus (TMV) activities, such as compound 34 exhibited an inactivation activity of 90.1% and curative activity of 51.8% and compound 28 exhibited a curative activity of 54.8% at 500 µg mL-1, which is equivalent to that of the commercial ningnanmycin (inactivation of 91.9% and curative of 51.9%). Moreover, the in vitro antibacterial activity test illustrated that compounds 2, 22, and 33 showed much higher activities than commercial thiodiazole copper, which could be used as lead compounds or potential candidates. The findings of transmission electron microscopy and molecular docking indicated that the synthesized compounds exhibited strong and significant binding affinity to the TMV coat protein and could obstruct the self-assembly and increment of TMV particles. This study revealed that α-ketoamide derivatives bearing a vanillin skeleton could be used as a novel potential pesticide for controlling the plant diseases.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Benzaldehydes/chemistry , Anti-Bacterial Agents/chemistry , Antiviral Agents/chemistry , Bacteria/drug effects , Bacteria/growth & development , Benzaldehydes/pharmacology , Drug Design , Microbial Sensitivity Tests , Molecular Docking Simulation , Plant Diseases/microbiology , Plant Diseases/virology , Tobacco Mosaic Virus/drug effects , Tobacco Mosaic Virus/growth & development
20.
Int Immunopharmacol ; 83: 106478, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32278132

ABSTRACT

BACKGROUND: CMTM6 was identified as an important regulator of the PD-L1 protein. The role of CMTM6 in lung adenocarcinoma (LUAD) has so far remained unclear. We aimed at investigating the role of CMTM6 in LUAD at transcriptome and genomic levels and its relationship with tumor-infiltrating immune cells (TIICs). METHODS: We downloaded the data sets of LUAD from TCGA. The genomic profiles containing somatic mutations were analyzed and the transcriptome level of CMTM6 was also obtained. Gene set variation analysis (GSVA) was used to predict the pathway change. In addition, we explored the association between CMTM6 and LUAD immune infiltrates by means of CIBERSORT. The association between CMTM6 and PD-L1 mRNA was analyzed using an integrated repository portal for tumor-immune system interactions (TISIDB) and was further validated in 80 LUAD patients. Kaplan-Meier survival curve and the log-rank test was used to analyze the survival significance of CMTM6. RESULTS: We found that CMTM6 was downregulated in LUAD. Patients with low CMTM6 expression were more likely to be frequent with somatic mutations. Moreover, GSVA analysis exhibited that CMTM6 was associated with immune responses and inflammatory activities. Specifically, a positive correlation between increased CMTM6 expression and immune infiltrating level of Dendritic cells resting, Eosinophils, Macrophages M1, Macrophages M2, Neutrophils, T cells CD4 memory activated and T cells CD4 memory resting was established. The CMTM6 expression was positively correlated with PD-L1 in both mRNA and protein level. Clinically, patients with high expression of CMTM6 tended to have a better survival. CONCLUSION: CMTM6 expression likely had an important effect on TIICs composition and prognosis in LUAD patients. The CMTM6 expression was positively correlated with PD-L1 in LUAD. These findings establish CMTM6 as a promising target for immunotherapeutic prospects.


Subject(s)
Adenocarcinoma/immunology , Biomarkers, Tumor/metabolism , CD4-Positive T-Lymphocytes/immunology , Lung Neoplasms/immunology , Lymphocytes, Tumor-Infiltrating/immunology , MARVEL Domain-Containing Proteins/metabolism , Myelin Proteins/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/mortality , B7-H1 Antigen/genetics , B7-H1 Antigen/metabolism , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Immunologic Memory , Lung Neoplasms/genetics , Lung Neoplasms/mortality , MARVEL Domain-Containing Proteins/genetics , Myelin Proteins/genetics , Survival Analysis , Up-Regulation
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