Publications by authors named "Tai Wang"

123 Publications

Hexyl-aminolevulinate ethosome-mediated photodynamic therapy against acne: in vitro and in vivo analyses.

Drug Deliv Transl Res 2021 Mar 17. Epub 2021 Mar 17.

Department of Dermatology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou Guangdong, 510515, China.

Biofilm formation by Propionibacterium acnes is known to cause failure of anti-acne treatment. Conventional therapies for acne are typically inadequate. Accordingly, in this study, we evaluated the therapeutic potential of photodynamic therapy (PDT) using hexyl-aminolevulinate (HAL)-loaded ethosomes (ESs) against the biofilms of P. acnes in vitro and P. acnes-induced inflammatory acne model in vivo. The antibacterial effects of HAL ESs were evaluated using XTT colorimetric assays and scanning electron microscopic observations of morphological changes. P. acnes was intradermally injected into the ears of Sprague-Dawley rats, and the anti-inflammatory effects of HAL ESs were measured by determining changes in appearance, histology, and the antibacterial effects by P. acnes abundance in ear tissues compared with blank control ESs, HAL alone, and 5-aminolevulinic acid (ALA) alone. The highest reduction in viability in P. acnes biofilms was observed after treatment with 5 mg/mL HAL ESs. Notably, blank control ESs also showed significant inhibitory effects. Furthermore, HAL ESs had superior therapeutic effects in the rat model compared with HAL or ALA solutions. The observed therapeutic effects of HAL ESs against P. acnes biofilms and P. acnes-induced inflammation suggest that PDT with HAL-loaded ESs may have potential applications in the treatment of acne.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13346-021-00942-5DOI Listing
March 2021

Need for anticoagulation and use of direct oral anticoagulants in lung transplant recipients.

J Thromb Thrombolysis 2021 Mar 4. Epub 2021 Mar 4.

Section of Pulmonary, Critical Care, and Sleep, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.

Limited information is available about use of direct oral anticoagulants (DOACs) in lung transplant recipients (LTRs). The purpose of this study is to describe the indications and use of long-term anticoagulation, including the safety and tolerability of DOACs, in LTRs. This was a single-center retrospective study. LTRs who received therapeutic anticoagulation were identified. Patient characteristics, indications for treatment, and complications of therapy were obtained. A total of 203 patients underwent lung transplantation of which 118 patients (58.1%) had an indication for anticoagulation. Patients with an indication for anticoagulation were older than those without (59 ± 14 years versus 48 ± 17 years, p < 0.001) and were more likely to be male (72.0% versus 50.6%, p = 0.002). Of the patients with indication for anticoagulation, 74 (62.7%) received it. Fifty-one (68.9%) of patients receiving anticoagulation were treated with DOACs. In the patients receiving anticoagulation, there were 14 major bleeding events in 13 patients, of which 3 were receiving DOACs and the remainder were receiving heparin or warfarin. The need for anticoagulation is common in LTRs for both atrial arrhythmias and venous thromboembolism. However, many patients with atrial arrhythmias do not receive anticoagulation. The use of DOACs is well tolerated and safe in LTRs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-021-02399-2DOI Listing
March 2021

Neuroinflammation in Parkinson's Disease: Triggers, Mechanisms, and Immunotherapies.

Neuroscientist 2021 Feb 12:1073858421991066. Epub 2021 Feb 12.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.

Parkinson's disease (PD) is a heterogeneous neurodegenerative disease involving multiple etiologies and pathogenesis, in which neuroinflammation is a common factor. Both preclinical experiments and clinical studies provide evidence for the involvement of neuroinflammation in the pathophysiology of PD, although there are a number of key issues related to neuroinflammatory processes in PD that remain to be addressed. In this review, we highlight the relationship between the common pathological mechanisms of PD and neuroinflammation, including aggregation of α-synuclein, genetic factors, mitochondrial dysfunction, and gut microbiome dysbiosis. We also describe the two positive feedback loops initiated in PD after the immune system is activated, and their role in the pathogenesis of PD. In addition, the interconnections and differences between the central and peripheral immune systems are discussed. Finally, we review the latest progress in immunotherapy research for PD patients, and propose future directions for clinical research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1073858421991066DOI Listing
February 2021

Male gametophyte development in flowering plants: A story of quarantine and sacrifice.

J Plant Physiol 2021 Mar-Apr;258-259:153365. Epub 2021 Jan 21.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China; College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China; Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing 100093, China. Electronic address:

Over 160 years ago, scientists made the first microscopic observations of angiosperm pollen. Unlike in animals, male meiosis in angiosperms produces a haploid microspore that undergoes one asymmetric division to form a vegetative cell and a generative cell. These two cells have distinct fates: the vegetative cell exits the cell cycle and elongates to form a tip-growing pollen tube; the generative cell divides once more in the pollen grain or within the growing pollen tube to form a pair of sperm cells. The concept that male germ cells are less active than the vegetative cell came from biochemical analyses and pollen structure anatomy early in the last century and is supported by the pollen transcriptome data of the last decade. However, the mechanism of how and when the transcriptional repression in male germ cells occurs is still not fully understood. In this review, we provide a brief account of the cytological and metabolic differentiation between the vegetative cell and male germ cells, with emphasis on the role of temporary callose walls, dynamic nuclear pore density, transcription repression, and histone variants. We further discuss the intercellular movement of small interfering RNA (siRNA) derived from transposable elements (TEs) and reexamine the function of TE expression in male germ cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jplph.2021.153365DOI Listing
January 2021

The complete mitochondrial genome sequence and phylogenetic position of .

Mitochondrial DNA B Resour 2020 Jan 24;5(1):808-809. Epub 2020 Jan 24.

Gansu Fisheries Research Institute, Lanzhou, China.

In this paper, we determined the complete mitochondrial DNA (mtDNA) sequence of and analyzed its phylogenetic position. The complete mitogenome is 16,604 bp in length. It consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and 1 control region. Among the 37 genes, 28 were encoded on the heavy strand, while 9 were encoded on the light strand. The overall base composition was 28.97% for A, 18.06% for G, 26.54% for T, and 26.43% for C, with a higher A + T content (55.51%). There are some overlaps existing in mitochondrial genome. The neighbor-joining (NJ) phylogenetic tree based on whole mitogenome sequences supported that is the closest to . This result will provide a basic reference for understanding the genetic structure, molecular evolution, and phylogeny of and related species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/23802359.2020.1715864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748591PMC
January 2020

DNA methylation dynamics of sperm cell lineage development in tomato.

Plant J 2021 Feb 26;105(3):565-579. Epub 2020 Dec 26.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China.

During the sexual reproduction of higher plants, DNA methylation and transcription are broadly changed to reshape a microspore into two sperm cells (SCs) and a vegetative cell (VC). However, when and how the DNA methylation of SCs is established remains not fully understood. Here we investigate the DNA methylation (5 mC) dynamics of SC lineage and the VC in tomato using whole-genome bisulfite sequencing. We find the asymmetric division of the microspore gives its two daughter cells differential methylome. Compared with the generative cell (GC), the VC is hypomethylated at CG sites while hypermethylated at CHG and CHH sites, with the majority of differentially methylation regions targeted to transposable elements (TEs). SCs have a nearly identical DNA methylome to the GC, suggesting that the methylation landscape in SCs may be pre-established following the asymmetric division or inherited from the GC. The random forest classifier for predicting gene and TE expression shows that methylation within the gene body is a more powerful predictor for gene expression. Among all tested samples, gene and TE expression in the microspore may be more predictable by DNA methylation. Our results depict an intact DNA methylome landscape of SC lineage in higher plants, and reveal that the impact of DNA methylation on transcription is variant in different cell types.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tpj.15098DOI Listing
February 2021

DNA barcoding reveals cryptic diversity in the underestimated genus Triplophysa (Cypriniformes: Cobitidae, Nemacheilinae) from the northeastern Qinghai-Tibet Plateau.

BMC Evol Biol 2020 11 12;20(1):151. Epub 2020 Nov 12.

Gansu Key Laboratory of Cold Water Fishes Germplasm Resources and Genetics Breeding, Gansu Fisheries Research Institute, Lanzhou, China.

Background: The northeastern part of the Qinghai-Tibet Plateau (QTP) presents a high number of plateau loach species. As one of the three major groups of fishes distributed on the QTP, plateau loach has high ecological value. However, the taxonomy and systematics of these fish are still controversial, and a large number of new species have been reported. The reason for this phenomenon is that the degree of morphological variation is low, the phylogenetic information provided by morphological and anatomical features used for species identification is relatively poor, and many cryptic species are observed. Based on the high-density sampling points from the biodiversity hotspots surveyed, this study aims to evaluate the biodiversity of plateau loach in the northeastern part of the QTP and reveal the hidden diversity by comparing morphological species with molecular operational taxonomic units (MOTUs).

Results: After careful identification and comparison of the morphology and DNA barcoding of 1630 specimens, 22 species were identified, with 20 considered valid local species and two identified as new species that had not been previously described. Based on the combination of morphological and molecular methods, a total of 24 native species were found, two of which were cryptic species: Triplophysa robusta sp1 and Triplophysa minxianensis sp1. Fourteen of the 24 species form clusters of barcodes that allow them to be reliably identified. The remaining cases involved 10 closely related species, including rapidly differentiated species and species that seemed to have experienced incomplete lineage sorting or showed introgressions.

Conclusions: The results highlight the need to combine traditional taxonomies with molecular methods to correctly identify species, especially closely related species, such as the plateau loach. This study provides a basis for protecting the biodiversity of plateau loach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12862-020-01718-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663858PMC
November 2020

Three-Dimensional Accuracy of Bone Contouring Surgery for Zygomaticomaxillary Fibrous Dysplasia Using Virtual Planning and Surgical Navigation.

J Oral Maxillofac Surg 2020 12 31;78(12):2328-2338. Epub 2020 Jul 31.

Professor, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China. Electronic address:

Purpose: Fibrous dysplasia (FD) is a benign condition in which normal cancellous bone is replaced by immature woven bone and fibrous tissue. The present study aimed to estimate and compare the 3-dimensional (3D) accuracy of bone contouring surgery for zygomaticomaxillary FD performed using virtual planning and surgical navigation versus surgeon's intraoperative assessment.

Patients And Methods: This is a retrospective cross-sectional study. Patients with zygomaticomaxillary FD who underwent bone contouring surgery between 2012 and 2019 were reviewed. They were divided into 2 groups: group A underwent bone contouring surgery using virtual planning and surgical navigation, and group B underwent bone contouring surgery by surgeon's intraoperative assessment. The predictor variable was surgical technique. The other variables were gender, age, and operative region. The primary outcome variable was 3D accuracy, which was indicated by root mean square, calculated as a measure of the deviation of the postoperative computed tomography from the preoperative virtual plan. The other outcome variables were patient satisfaction with the outcome by self-evaluation score and operative times. Correlation analysis between the predictor variables and outcome variables was performed.

Results: The sample comprised 24 patients (17 males and 7 females, mean age, 25.7 ± 10.45 years), 13 patients in group A and 11 patients in group B. The mean root mean square was significantly lower in group A than in group B (P = .007). Patient satisfaction with facial symmetry was significantly better in group A (P = .015). Mean operative time was comparable between the 2 groups (P = .918). Surgical technique (P = .011) and operative region (P = .01) were significant influence factors in 3D accuracy of surgery.

Conclusions: Virtual planning and surgical navigation can significantly improve the 3D accuracy and patient satisfaction of bone contouring surgery for zygomaticomaxillary FD, without prolonging operative time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joms.2020.07.208DOI Listing
December 2020

Multicenter prospective study to validate a new transient elastography device for staging liver fibrosis in patients with chronic hepatitis B.

J Dig Dis 2020 Sep;21(9):519-525

Liver Research Center, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Objectives: To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB).

Methods: In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis.

Results: In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to < 0.0001). Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively.

Conclusion: FibroTouch has a high success rate and good reliability in staging liver fibrosis in patients with CHB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1751-2980.12924DOI Listing
September 2020

NaCO-responsive Photosynthetic and ROS Scavenging Mechanisms in Chloroplasts of Alkaligrass Revealed by Phosphoproteomics.

Genomics Proteomics Bioinformatics 2020 06 16;18(3):271-288. Epub 2020 Jul 16.

Development Center of Plant Germplasm Resources, College of Life and Environmental Sciences, Shanghai Normal University, Shanghai 200234, China; Alkali Soil Natural Environmental Science Center, Northeast Forestry University, Key Laboratory of Saline-alkali Vegetation Ecology Restoration in Oil Field, Ministry of Education, Harbin 150040, China. Electronic address:

Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To understand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under NaCO stress were conducted. In addition, Western blot, real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the NaCO-responsive proteins. A total of 104 and 102 NaCO-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 NaCO-responsive phosphoproteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloroplasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced NaCO tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of photosystem (PS) II, PSI activity, and ROS homeostasis were altered in response to NaCO stress, which help to improve our understanding of the NaCO-responsive mechanisms in halophytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gpb.2018.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801222PMC
June 2020

Gold/alpha-lactalbumin nanoprobes for the imaging and treatment of breast cancer.

Nat Biomed Eng 2020 07 13;4(7):686-703. Epub 2020 Jul 13.

Center for Molecular Imaging and Nanotechnology (CMINT), Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Theranostic agents should ideally be renally cleared and biodegradable. Here, we report the synthesis, characterization and theranostic applications of fluorescent ultrasmall gold quantum clusters that are stabilized by the milk metalloprotein alpha-lactalbumin. We synthesized three types of these nanoprobes that together display fluorescence across the visible and near-infrared spectra when excited at a single wavelength through optical colour coding. In live tumour-bearing mice, the near-infrared nanoprobe generates contrast for fluorescence, X-ray computed tomography and magnetic resonance imaging, and exhibits long circulation times, low accumulation in the reticuloendothelial system, sustained tumour retention, insignificant toxicity and renal clearance. An intravenously administrated near-infrared nanoprobe with a large Stokes shift facilitated the detection and image-guided resection of breast tumours in vivo using a smartphone with modified optics. Moreover, the partially unfolded structure of alpha-lactalbumin in the nanoprobe helps with the formation of an anti-cancer lipoprotein complex with oleic acid that triggers the inhibition of the MAPK and PI3K-AKT pathways, immunogenic cell death and the recruitment of infiltrating macrophages. The biodegradability and safety profile of the nanoprobes make them suitable for the systemic detection and localized treatment of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41551-020-0584-zDOI Listing
July 2020

Factors Affecting Volume Change of Anterolateral Thigh Flap in Head and Neck Defect Reconstruction.

J Oral Maxillofac Surg 2020 11 15;78(11):2090-2098. Epub 2020 Jun 15.

Professor, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China. Electronic address:

Purpose: The anterolateral thigh flap (ALTF) volume will decrease over time after surgery. We measured and identified the risk factors for postoperative volume changes in the ALTF.

Materials And Methods: We designed and performed a retrospective cohort study of patients who had undergone reconstruction of oral and maxillofacial defects using ALTFs at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from June 2012 to December 2018. We measured the volume of the ALTFs at 1, 3, 6, 12, and 24 months postoperatively; the flap volume at 1 month postoperatively was taken as the baseline. The primary outcome variables were the residual ALTF rates at 3, 6, 12, and 24 months postoperatively, defined as the ratio between the present volume at each month and at baseline. The primary predictor variables were the clinical variables that might be associated with ALTF volume loss. Descriptive and bivariate statistics were computed, and the P value for statistical significance was set at ≤ .05.

Results: The sample included 70 subjects with a mean age of 53.8 years (46 men and 24 women). The postoperative residual rates at 3, 6, 12, and 24 months were 72.3, 69.0, 67.9, and 68.7%, respectively, of the baseline volume. The use of postoperative radiotherapy (P < .01) and low body mass index (BMI; P = .006) were significantly associated with postoperative ALTF volume loss.

Conclusions: The results of the present study suggest that ALTF volume shrinkage mainly occurs within 6 months postoperatively and that postoperative radiotherapy and a low BMI are risk factors for volume loss. Overcorrection should be performed to account for the shrinkage of ALTFs, and postoperative nutrition management is important to avoid ALTF volume loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joms.2020.06.017DOI Listing
November 2020

Molecular Stressors Engender Protein Connectivity Dysfunction through Aberrant N-Glycosylation of a Chaperone.

Cell Rep 2020 06;31(13):107840

Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Stresses associated with disease may pathologically remodel the proteome by both increasing interaction strength and altering interaction partners, resulting in proteome-wide connectivity dysfunctions. Chaperones play an important role in these alterations, but how these changes are executed remains largely unknown. Our study unveils a specific N-glycosylation pattern used by a chaperone, Glucose-regulated protein 94 (GRP94), to alter its conformational fitness and stabilize a state most permissive for stable interactions with proteins at the plasma membrane. This "protein assembly mutation' remodels protein networks and properties of the cell. We show in cells, human specimens, and mouse xenografts that proteome connectivity is restorable by inhibition of the N-glycosylated GRP94 variant. In summary, we provide biochemical evidence for stressor-induced chaperone-mediated protein mis-assemblies and demonstrate how these alterations are actionable in disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2020.107840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372946PMC
June 2020

ARSA gene variants and Parkinson's disease.

Brain 2020 06;143(6):e47

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awaa134DOI Listing
June 2020

Chaperome Networks - Redundancy and Implications for Cancer Treatment.

Adv Exp Med Biol 2020 ;1243:87-99

Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

The chaperome is a large family of proteins composed of chaperones, co-chaperones and a multitude of other factors. Elegant studies in yeast and other organisms have paved the road to how we currently understand the complex organization of this large family into protein networks. The goal of this chapter is to provide an overview of chaperome networks in cancer cells, with a focus on two cellular states defined by chaperome network organization. One state characterized by chaperome networks working in isolation and with little overlap, contains global chaperome networks resembling those of normal, non-transformed, cells. We propose that in this state, redundancy in chaperome networks results in a tumor type unamenable for single-agent chaperome therapy. The second state comprises chaperome networks interconnected in response to cellular stress, such as MYC hyperactivation. This is a state where no redundant pathways can be deployed, and is a state of vulnerability, amenable for chaperome therapy. We conclude by proposing a change in how we discover and implement chaperome inhibitor strategies, and suggest an approach to chaperome therapy where the properties of chaperome networks, rather than genetics or client proteins, are used in chaperome inhibitor implementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-40204-4_6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279512PMC
June 2020

Pollen germination is impaired by disruption of a Shaker K channel OsAKT1.2 in rice.

J Plant Physiol 2020 May 22;248:153140. Epub 2020 Feb 22.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China. Electronic address:

Potassium homeostasis is essential for pollen development and pollen-pistil interactions during the sexual reproduction of flowering plants. Here, we described the role of a Shaker K channel, OsAKT1.2, in rice pollen germination and growth. OsAKT1.2 is specifically expressed in the tricellular pollen, mature pollen grains and growing pollen tubes. Using CRISPR gene editing, we found that knockout lines did not differ from wildtype in vegetative growth, but showed decreased pollen germination rate both in the germination medium and in vivo. OsAKT1.2-GFP fusion protein was localized in the plasma membrane and enriched at the pollen tube tip. OsAKT1.2 could complement the yeast strain which is deficient in K intake. These findings suggest that OsAKT1.2 is associated with pollen germination and tube elongation in rice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jplph.2020.153140DOI Listing
May 2020

The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction.

Nat Commun 2020 01 16;11(1):319. Epub 2020 Jan 16.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-14082-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965647PMC
January 2020

A Chromosome-Scale Reference Assembly of a Tibetan Loach, .

Front Genet 2019 16;10:991. Epub 2019 Oct 16.

The Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Cobitoidea is one of the two superfamilies in Cypriniformes; however, few genomes have been sequenced for Cobitoidea fishes. Here, we obtained a total of 252.90 Gb of short Illumina reads and 31.60 Gb of long PacBio Sequel reads, representing approximate genome coverage of 256× and 50×, respectively. The final assembled genome is about 583.47 Mb with contig N50 sizes of 2.87 Mb, which accounts for 91.44% of the estimated genome size of 638.07 Mb. Using Hi-C-based chromatin contact maps, 99.31% of the genome assembly was placed into 25 chromosomes, and the N50 is 22.3 Mb. The gene annotation completeness was evaluated by BUSCO, and 2,470 of the 2,586 conserved genes (95.5%) could be found in our assembly. Repetitive elements were calculated to reach 33.08% of the whole genome. Moreover, we identified 25,406 protein-coding genes, of which 92.59% have been functionally annotated. This genome assembly will be a valuable genomic resource to understand the biology of the Tibetan loaches and will also set a stage for comparative analysis of the classification, diversification, and adaptation of fishes in Cobitoidea.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2019.00991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6807559PMC
October 2019

Paradigms for Precision Medicine in Epichaperome Cancer Therapy.

Cancer Cell 2019 11 24;36(5):559-573.e7. Epub 2019 Oct 24.

Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Program in Molecular Pharmacology, Sloan Kettering Institute, New York, NY 10065, USA.

Alterations in protein-protein interaction networks are at the core of malignant transformation but have yet to be translated into appropriate diagnostic tools. We make use of the kinetic selectivity properties of an imaging probe to visualize and measure the epichaperome, a pathologic protein-protein interaction network. We are able to assay and image epichaperome networks in cancer and their engagement by inhibitor in patients' tumors at single-lesion resolution in real time, and demonstrate that quantitative evaluation at the level of individual tumors can be used to optimize dose and schedule selection. We thus provide preclinical and clinical evidence in the use of this theranostic platform for precision medicine targeting of the aberrant properties of protein networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ccell.2019.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996250PMC
November 2019

Microstructure and Properties of Surface-Modified Plates and Their Welded Joints.

Materials (Basel) 2019 Sep 6;12(18). Epub 2019 Sep 6.

School of Material Science and Engineering, Tianjin University, Tianjin 300072, China.

The surface of Q235 low carbon steel was modified by the metal inert-gas welding (MIG) method; a 304 stainless steel surfacing layer was fabricated to improve the properties of Q235 low carbon steel. For practical industry application, keyhole tungsten inter gas (K-TIG) welding was used to weld the surface-modified plates. The microstructure, elemental distribution, micro-hardness, and corrosion resistance of the surface-modified plates and the welded joints were analyzed. The corrosion tests of welded joints and surface-modified plates were carried out with the electrochemical method and hydrochloric acid immersion method, respectively, and surface morphology after corrosion was studied. The results show that the surface-modified plates and their welded joints were defect-free. The microstructure of the surfacing layer consisted of austenite, martensite, and ferrite; and the microstructure of the weld consisted mainly of martensite. The hardness and corrosion resistance of the surfacing layer was superior to that that of low carbon steel. The micro-hardness of the weld is higher than that of the stainless steel surfacing layer and the base material. The corrosion resistance of the surfacing layer is the best, and the corrosion resistance of the welding seam is better than that of the base material.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma12182883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766005PMC
September 2019

Semi-preparative separation of dihydromyricetin enantiomers by supercritical fluid chromatography and determination of anti-inflammatory activities.

J Chromatogr A 2019 Nov 19;1606:460386. Epub 2019 Jul 19.

School of Chemistry and Environment, South China Normal University, Guangzhou 510006, China. Electronic address:

Dihydromyricetin, extracted from Ampelopsis grossedentata, has been widely used as one of Chinese health products in recent years. However, limited chiral separation method hinders the studies of pharmacological and pharmacokinetic activity differences of (+)-dihydromyricetin, (-)-dihydromyricetin, and (±)-dihydromyricetin. Herein, we developed a supercritical fluid chromatography approach for chiral separation of dihydromyricetin. Firstly, effects of chiral stationary phase, co-solvent, and flow rate of mobile phase have been investigated in detail. The resolution of 5.11 was achieved for dihydromyricetin enantiomers on amylose tris(3, 5-dimethylphenylcarbamate)-coated chiral stationary phase with the CO-methanol mixture (60:40, v/v). With respect to the enantiomeric purity, production rate and solvent consumption of 15 stacked injections, sample loading for semi-preparative separation of dihydromyricetin was optimized in three given equivalents set by volume overloading. Along with increase of sample loading per injection from 40 mg to 120 mg, the productivity of dihydromyricetin increased from 0.07 g (racemate)/g (chiral stationary phase) /24 h to 0.27 g (racemate) /g (chiral stationary phase)/24 h, and the consumption of methanol significantly reduced from 5.86 L/g (racemate) to 1.76 L/g (racemate). Moreover, (-)-dihydromyricetin exhibited better anti-inflammatory activity in TLR 2-related Raw 264.7 cells than (+)-dihydromyricetin and (±)-dihydromyricetin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2019.460386DOI Listing
November 2019

Deficiency of very long chain alkanes biosynthesis causes humidity-sensitive male sterility via affecting pollen adhesion and hydration in rice.

Plant Cell Environ 2019 12 14;42(12):3340-3354. Epub 2019 Aug 14.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing, China.

Pollen adhesion and hydration are the earliest events of the pollen-stigma interactions, which allow compatible pollen to fertilize egg cells, but the underlying mechanisms are still poorly understood. Rice pollen are wind dispersed, and its pollen coat contains less abundant lipids than that of insect-pollinated plants. Here, we characterized the role of OsGL1-4, a rice member of the Glossy family, in pollen adhesion and hydration. OsGL1-4 is preferentially expressed in pollen and tapetal cells and is required for the synthesis of very long chain alkanes. osgl1-4 mutant generated apparently normal pollen but displayed excessively fast dehydration at anthesis and defective adhesion and hydration under normal condition, but the defective adhesion and hydration were rescued by high humidity. Gas chromatography-mass spectrometry analysis suggested that the humidity-sensitive male sterility of osgl1-4 was probably due to a significant reduction in C25 and C27 alkanes. These results indicate that very long chain alkanes are components of rice pollen coat and control male fertility via affecting pollen adhesion and hydration in response to environmental humidity. Moreover, we proposed that a critical point of water content in mature pollen is required for the initiation of pollen adhesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pce.13637DOI Listing
December 2019

A Chemical Biology Approach to the Chaperome in Cancer-HSP90 and Beyond.

Cold Spring Harb Perspect Biol 2020 04 1;12(4). Epub 2020 Apr 1.

Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065.

Cancer is often associated with alterations in the chaperome, a collection of chaperones, cochaperones, and other cofactors. Changes in the expression levels of components of the chaperome, in the interaction strength among chaperome components, alterations in chaperome constituency, and in the cellular location of chaperome members, are all hallmarks of cancer. Here we aim to provide an overview on how chemical biology has played a role in deciphering such complexity in the biology of the chaperome in cancer and in other diseases. The focus here is narrow and on pathologic changes in the chaperome executed by enhancing the interaction strength between components of distinct chaperome pathways, specifically between those of HSP90 and HSP70 pathways. We will review chemical tools and chemical probe-based assays, with a focus on HSP90. We will discuss how kinetic binding, not classical equilibrium binding, is most appropriate in the development of drugs and probes for the chaperome in disease. We will then present our view on how chaperome inhibitors may become potential drugs and diagnostics in cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/cshperspect.a034116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773535PMC
April 2020

The sensitivity to Hsp90 inhibitors of both normal and oncogenically transformed cells is determined by the equilibrium between cellular quiescence and activity.

PLoS One 2019 6;14(2):e0208287. Epub 2019 Feb 6.

Département de Biologie Cellulaire, Université de Genève, Sciences III, Genève, Switzerland.

The molecular chaperone Hsp90 is an essential and highly abundant central node in the interactome of eukaryotic cells. Many of its large number of client proteins are relevant to cancer. A hallmark of Hsp90-dependent proteins is that their accumulation is compromised by Hsp90 inhibitors. Combined with the anecdotal observation that cancer cells may be more sensitive to Hsp90 inhibitors, this has led to clinical trials aiming to develop Hsp90 inhibitors as anti-cancer agents. However, the sensitivity to Hsp90 inhibitors has not been studied in rigorously matched normal versus cancer cells, and despite the discovery of important regulators of Hsp90 activity and inhibitor sensitivity, it has remained unclear, why cancer cells might be more sensitive. To revisit this issue more systematically, we have generated an isogenic pair of normal and oncogenically transformed NIH-3T3 cell lines. Our proteomic analysis of the impact of three chemically different Hsp90 inhibitors shows that these affect a substantial portion of the oncogenic program and that indeed, transformed cells are hypersensitive. Targeting the oncogenic signaling pathway reverses the hypersensitivity, and so do inhibitors of DNA replication, cell growth, translation and energy metabolism. Conversely, stimulating normal cells with growth factors or challenging their proteostasis by overexpressing an aggregation-prone sensitizes them to Hsp90 inhibitors. Thus, the differential sensitivity to Hsp90 inhibitors may not stem from any particular intrinsic difference between normal and cancer cells, but rather from a shift in the balance between cellular quiescence and activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208287PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364869PMC
October 2019

Assembly of a miRNA-modified QCM sensor for miRNA recognition through response patterns.

J Mol Recognit 2019 05 6;32(5):e2772. Epub 2018 Dec 6.

School of Chemistry and Environment, South China Normal University, Guangzhou, China.

In this paper, a miRNA-based quartz crystal microbalance (QCM) biosensor was fabricated and used to the rapid and effective sensing of miRNA. The specific hybridization between probe miRNA and different selected miRNAs (miR-27a, miR-27b, and Let-7a) cause a different interaction mode, thus display different frequency change and response patterns in the QCM sensor, which were used to detect miR-27a and miR-27b. The selective sensing of miR-27a in mixed miRNA solution was also achieved. This miRNA-based QCM biosensor has the advantages of real-time, label-free, and short cycle detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmr.2772DOI Listing
May 2019

Chaperome heterogeneity and its implications for cancer study and treatment.

J Biol Chem 2019 02 8;294(6):2162-2179. Epub 2018 Nov 8.

From the Chemical Biology Program and

The chaperome is the collection of proteins in the cell that carry out molecular chaperoning functions. Changes in the interaction strength between chaperome proteins lead to an assembly that is functionally and structurally distinct from each constituent member. In this review, we discuss the epichaperome, the cellular network that forms when the chaperome components of distinct chaperome machineries come together as stable, functionally integrated, multimeric complexes. In tumors, maintenance of the epichaperome network is vital for tumor survival, rendering them vulnerable to therapeutic interventions that target critical epichaperome network components. We discuss how the epichaperome empowers an approach for precision medicine cancer trials where a new target, biomarker, and relevant drug candidates can be correlated and integrated. We introduce chemical biology methods to investigate the heterogeneity of the chaperome in a given cellular context. Lastly, we discuss how ligand-protein binding kinetics are more appropriate than equilibrium binding parameters to characterize and unravel chaperome targeting in cancer and to gauge the selectivity of ligands for specific tumor-associated chaperome pools.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.REV118.002811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369301PMC
February 2019

HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons.

Nat Commun 2018 10 19;9(1):4345. Epub 2018 Oct 19.

The Center for Stem Cell Biology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 256, New York, NY, 10065, USA.

Environmental and genetic risk factors contribute to Parkinson's Disease (PD) pathogenesis and the associated midbrain dopamine (mDA) neuron loss. Here, we identify early PD pathogenic events by developing methodology that utilizes recent innovations in human pluripotent stem cells (hPSC) and chemical sensors of HSP90-incorporating chaperome networks. We show that events triggered by PD-related genetic or toxic stimuli alter the neuronal proteome, thereby altering the stress-specific chaperome networks, which produce changes detected by chemical sensors. Through this method we identify STAT3 and NF-κB signaling activation as examples of genetic stress, and phospho-tyrosine hydroxylase (TH) activation as an example of toxic stress-induced pathways in PD neurons. Importantly, pharmacological inhibition of the stress chaperome network reversed abnormal phospho-STAT3 signaling and phospho-TH-related dopamine levels and rescued PD neuron viability. The use of chemical sensors of chaperome networks on hPSC-derived lineages may present a general strategy to identify molecular events associated with neurodegenerative diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-06486-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195591PMC
October 2018

Lenalidomide, a blockbuster drug for the treatment of multiple myeloma: Semipreparative separation through supercritical fluid chromatography and vibrational circular dichroism spectroscopy.

J Sep Sci 2018 Oct 12;41(20):3840-3847. Epub 2018 Sep 12.

School of Chemistry and Environment, South China Normal University, Guangzhou, P. R. China.

Semipreparative separation of lenalidomide has been performed through supercritical fluid chromatography. In regard to retention and resolution of lenalidomide, effects of chromatographic conditions, such as chiral stationary phases, organic co-solvents, mobile phases, and column temperature, have been studied in detail. Amylose tris(3, 5-dimethylphenylcarbamate)-coated and the single-urea-bound β-cyclodextrin chiral stationary phases exhibited good separation performances for lenalidomide in the CO /methanol mixture. Then, a comparative study of semipreparative separation of lenalidomide has been carried out on these two chiral stationary phases. As indicated, separation of lenalidomide on the β-cyclodextrin-bound column was much better than the other. Under the optimized conditions, the loading per injection was 30 mg, the cycle time was 5 min, and the recoveries of two enantiomers were about 81.7 and 79.5%, respectively. Moreover, the vibrational circular dichroism spectrum of the first-eluted enantiomer in d -dimethylsulfoxide solution was consistent with the calculated pattern based on the S configuration, revealing that it should be (S)-(-)-lenalidomide. Briefly, this separation method through supercritical fluid chromatography might provide favorable information for rapid separation, enantioselective assessment, and absolute configurations of chiral pharmaceuticals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jssc.201800519DOI Listing
October 2018

Transcriptomics analyses reveal the molecular roadmap and long non-coding RNA landscape of sperm cell lineage development.

Plant J 2018 10 27;96(2):421-437. Epub 2018 Aug 27.

Key Laboratory of Plant Molecular Physiology, Institute of Botany, Chinese Academy of Sciences, Beijing, 100093, China.

Sperm cell (SC) lineage development from the haploid microspore to SCs represents a unique biological process in which the microspore generates a larger vegetative cell (VC) and a smaller generative cell (GC) enclosed in the VC, then the GC further develops to functionally specified SCs in the VC for double fertilization. Understanding the mechanisms of SC lineage development remains a critical goal in plant biology. We isolated individual cells of the three cell types, and characterized the genome-wide atlas of long non-coding (lnc) RNAs and mRNAs of haploid SC lineage cells. Sperm cell lineage development involves global repression of genes for pluripotency, somatic development and metabolism following asymmetric microspore division and coordinated upregulation of GC/SC preferential genes. This process is accompanied by progressive loss of the active marks H3K4me3 and H3K9ac, and accumulation of the repressive methylation mark H3K9. The SC lineage has a higher ratio of lncRNAs to mRNAs and preferentially expresses a larger percentage of lncRNAs than does the non-SC lineage. A co-expression network showed that the largest set of lncRNAs in these nodes, with more than 100 links, are GC-preferential, and a small proportion of lncRNAs co-express with their neighboring genes. Single molecular fluorescence in situ hybridization showed that several candidate genes may be markers distinguishing the three cell types of the SC lineage. Our findings reveal the molecular programming and potential roles of lncRNAs in SC lineage development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tpj.14041DOI Listing
October 2018

Proteomic discovery of HO response in roots and functional characterization of PutGLP gene from alkaligrass.

Planta 2018 Nov 23;248(5):1079-1099. Epub 2018 Jul 23.

Alkali Soil Natural Environmental Science Center, Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, Northeast Forestry University, Harbin, 150040, China.

Main Conclusion: Hydrogen peroxide-responsive pathways in roots of alkaligrass analyzed by proteomic studies and PutGLP enhance the plant tolerance to saline-, alkali- and cadmium-induced oxidative stresses. Oxidative stress adaptation is critical for plants in response to various stress environments. The halophyte alkaligrass (Puccinellia tenuiflora) is an outstanding pasture with strong tolerance to salt and alkali stresses. In this study, iTRAQ- and 2DE-based proteomics approaches, as well as qRT-PCR and molecular genetics, were employed to investigate HO-responsive mechanisms in alkaligrass roots. The evaluation of membrane integrity and reactive oxygen species (ROS)-scavenging systems, as well as abundance patterns of HO-responsive proteins/genes indicated that Ca-mediated kinase signaling pathways, ROS homeostasis, osmotic modulation, and transcriptional regulation were pivotal for oxidative adaptation in alkaligrass roots. Overexpressing a P. tenuiflora germin-like protein (PutGLP) gene in Arabidopsis seedlings revealed that the apoplastic PutGLP with activities of oxalate oxidase and superoxide dismutase was predominantly expressed in roots and played important roles in ROS scavenging in response to salinity-, alkali-, and CdCl-induced oxidative stresses. The results provide insights into the fine-tuned redox-responsive networks in halophyte roots.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00425-018-2940-8DOI Listing
November 2018