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1.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Article in English | MEDLINE | ID: mdl-33372158

ABSTRACT

Macrophages are the principal immune cells of the epididymis and testis, but their origins, heterogeneity, development, and maintenance are not well understood. Here, we describe distinct populations of epididymal and testicular macrophages that display an organ-specific cellular identity. Combining in vivo fate-mapping, chimeric and parabiotic mouse models with in-depth cellular analyses, we found that CD64hiMHCIIlo and CD64loMHCIIhi macrophage populations of epididymis and testis arise sequentially from yolk sac erythro-myeloid progenitors, embryonic hematopoiesis, and nascent neonatal monocytes. While monocytes were the major developmental source of both epididymal and testicular macrophages, both populations self-maintain in the steady-state independent of bone marrow hematopoietic precursors. However, after radiation-induced macrophage ablation or during infection, bone marrow-derived circulating monocytes are recruited to the epididymis and testis, giving rise to inflammatory macrophages that promote tissue damage. These results define the layered ontogeny, maintenance and inflammatory response of macrophage populations in the male reproductive organs.


Subject(s)
Infertility, Male/immunology , Macrophages/immunology , Macrophages/metabolism , Animals , Cell Differentiation , Cell Lineage , Epididymis/immunology , Epididymis/metabolism , Infertility, Male/metabolism , Infertility, Male/physiopathology , Male , Mice , Mice, Inbred C57BL , Monocytes/immunology , Testis/immunology , Testis/metabolism
2.
Bioinformatics ; 2021 Jan 28.
Article in English | MEDLINE | ID: mdl-33508087

ABSTRACT

MOTIVATION: The analysis of gene co-expression network (GCN) is critical in examining the gene-gene interactions and learning the underlying complex yet highly organized gene regulatory mechanisms. Numerous clustering methods have been developed to detect communities of co-expressed genes in the large network. The assumed independent community structure, however, can be oversimplified and may not adequately characterize the complex biological processes. RESULTS: We develop a new computational package to extract interconnected communities from gene co-expression network. We consider a pair of communities be interconnected if a subset of genes from one community is correlated with a subset of genes from another community. The interconnected community structure is more flexible and provides a better fit to the empirical co-expression matrix. To overcome the computational challenges, we develop efficient algorithms by leveraging advanced graph norm shrinkage approach. We validate and show the advantage of our method by extensive simulation studies. We then apply our interconnected community detection method to an RNA-seq data from The Cancer Genome Atlas (TCGA) Acute Myeloid Leukemia (AML) study and identify essential interacting biological pathways related to the immune evasion mechanism of tumor cells. AVAILABILITY: The software is available at Github: https://github.com/qwu1221/ICN and Figshare: https://figshare.com/articles/software/ICN-package/13229093. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

3.
J Sep Sci ; 45(22): 4079-4098, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36200604

ABSTRACT

Citri Reticulatae Pericarpium Viride is used in traditional Chinese medicine as Geqingpi and Sihuaqingpi varieties. We used the ultra-high-performance liquid chromatography-quadrupole-Exactive Orbitrap-mass spectrometry method and high-performance liquid chromatography-triple quadrupole-tandem mass spectrometry to analyze the chemical compounds in these varieties. Principal components analysis and orthogonal partial least squares discriminant analysis were used to analyze the quantitative results. Network pharmacology and molecular docking technology were used to forecast Citri Reticulatae Pericarpium Viride treatment mechanisms in irritable bowel syndrome. We identified 44 main compounds in Citri Reticulatae Pericarpium Viride. Compared to Sihuaqingpi, Geqingpi had higher narirutin, didymin, naringenin, and hesperetin, and lower hesperidin, isosinensetin, nobiletin, 3,5,6,7,8,3',4'-hexamethoxyflavone, tangeretin. Tangeretin, nobiletin, narirutin, didymin, and isosinensetin were the main compounds distinguishing Geqingpi from Sihuaqingpi. We found that the MAPK signaling pathway, which is closely related to irritable bowel syndrome, was an important target pathway. TP53, HRAS, MAPK1, AKT1, and EGFR were important targets in this pathway. Eriodictyol-7-O-rutinoside, narirutin, limonin, and hesperidin showed a good binding ability to the five targets. Orientin, unique to Sihuaqingpi, bound well to TP53, MAPK1, AKT1, and EGFR, while rhoifolin bound well to TP53, HRAS, MAPK1, AKT1, and EGFR. Hesperetin, unique to Geqingpi, bound well to TP53, HRAS, and MAPK1, while naringenin bound well to HRAS. Hesperidin and didymin bound well to TP53, MAPK1, AKT1, and EGFR.


Subject(s)
Citrus , Drugs, Chinese Herbal , Hesperidin , Irritable Bowel Syndrome , Chromatography, High Pressure Liquid/methods , Hesperidin/analysis , Molecular Docking Simulation , Tandem Mass Spectrometry/methods , Citrus/chemistry , Network Pharmacology , Drugs, Chinese Herbal/chemistry , ErbB Receptors
4.
Molecules ; 27(10)2022 May 20.
Article in English | MEDLINE | ID: mdl-35630762

ABSTRACT

Citri Reticulatae Pericarpium Viride (CRPV) is the processed product of Citrus reticulata Blanco. We systematically analyzed two CRPV types, Geqingpi (GQP) and Sihuaqingpi (SHQP), based on powder color, microscopic characteristics, and chemical composition. In addition, we characterized their constituents via ultra-high-performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Both showed significant differences in their powder color and microscopic characteristics. Fourier-transform infrared (FT-IR) spectroscopic analysis results showed that the C=O peak absorption of carboxylic acids and their carbonyl esters in SHQP was higher than that of GQP, while the C-OH and C-H plane bending peaks of polysaccharides were lower than those of GQP. We analyzed these data via similarity analysis, PCA, and OPLS-DA. GQP and SHQP had large distinct differences. Based on the mass measurements for molecular and characteristic fragment ions, we identified 44 main constituents from CRPV, including different flavonoid glycosides and flavonoid aglycones in SHQP and GQP, respectively. We found luteolin-6-C-glucoside, orientin, rhoifolin, and pilloin solely in SHQP, and naringenin and hesperetin only in GQP. The peak area measurements showed GQP having a higher flavonoid glycoside (narirutin, hesperidin, etc.) content, whereas SHQP had a higher polymethoxyflavone (nobiletin, tangeretin, etc.) content. Since we holistically analyzed two CRPV types, the results can not only support future pharmacological research, but also provide a scientific basis for formulating more reasonable CRPV quality standards and guide its clinical potential as a precision medicine.


Subject(s)
Flavonoids , Chromatography, High Pressure Liquid/methods , Flavonoids/chemistry , Powders , Spectroscopy, Fourier Transform Infrared
5.
Zhongguo Zhong Yao Za Zhi ; 47(14): 3723-3737, 2022 Jul.
Article in Zh | MEDLINE | ID: mdl-35850829

ABSTRACT

Dictamni Cortex, the dried root bark of Dictamnus dasycarpus, has many chemical constituents, such as alkaloids, limonoids, flavonoids, sesquiterpenoids, glycosides, and steroids.It has the effects of anti-inflammation, anti-fungi, anti-arteriosclerosis, stopping bleeding, anti-cancer, neuroprotection, and antioxidation.The chemical constituents of Dictamni Cortex are the important material basis for its medicinal effects.This paper reviewed the chemical constituents and pharmacological activities of Dictamni Cortex and analyzed the research trend and present research progress on this medicinal, with a view to its further development and utilization.


Subject(s)
Alkaloids , Dictamnus , Drugs, Chinese Herbal , Limonins , Alkaloids/pharmacology , Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology
6.
Small ; 17(20): e2100762, 2021 May.
Article in English | MEDLINE | ID: mdl-33817965

ABSTRACT

In this work, by combining the superiority of polyoxometalates (POMs) and catalytic single-metal site Co of metalloporphyrin, a series of mixed-valence POM-based metal-organic frameworks (MOFs) composites is synthesized by a post-modification method. The electron-transfer property of POM@PCN-222(Co) composite is significantly enhanced owing to the directional electron-transfer from POM to single-metal site Co in PCN-222(Co). In particular, H-POM@PCN-222(Co) gives a high Faradaic efficiency of 96.2% for electroreduction of CO2 into CO and good stability over 10 h. DFT calculations confirm that the directional electron transfer, which accelerates the multi-electron transfer from the electrode to active single-metal site Co, enriches the electron density of the Co center, and ultimately reduces the energy of the rate-determining step, thus increasing the catalytic activity of CO2 reduction reaction (CO2 RR). This work therefore suggests some new insight for the design of efficient electrocatalysts for CO2 RR.

7.
Angew Chem Int Ed Engl ; 60(44): 23705-23712, 2021 10 25.
Article in English | MEDLINE | ID: mdl-34428857

ABSTRACT

Guided by a second-sphere interaction strategy, we fabricated a Tb(III)-based metal-organic framework (MMCF-4) for turn-on sensing of methyl amine with ultra-low detection limit and high turn-on efficiency. MMCF-4 features lanthanide nodes shielded in a nonacoordinate geometry along with secondary coordination spheres that are densely populated with H-bond interacting sites. Nonradiative routes were inhibited by binding-induced rigidification of the ligand on the second coordination sphere, resulting in luminescence amplification. Such remote interacting mechanism involved in the turn-on sensing event was confirmed by single-crystal X-ray diffraction and molecular dynamic simulation studies. The design of both primary and secondary coordination spheres of Tb(III) enabled the first turn-on sensing of organic amines in aqueous conditions. Our work suggests a promising strategy for high-performance turn-on sensing for Ln-MOFs and luminous materials driven by other metal chromophores.

8.
Nanotechnology ; 31(31): 315705, 2020 Jul 31.
Article in English | MEDLINE | ID: mdl-32419696

ABSTRACT

Carbon nanotube (CNT)-doped polyamide (PA) membranes have attracted much attention in reverse osmosis (RO) membranes due to their significant advantages of water flux and desalination. In this study, we synthesized multi-walled carbon nanotube (MWNT)/PA RO membrane by 12-oxodidodecanoic acid methyl ester group interior-modified MWNTs (MWNT-C14H25O4). Then, their mechanism of desalination behavior was successfully analyzed by combining dielectric relaxation spectrum (DRS) and molecular dynamics (MD) simulation. DRS analysis mainly focuses on two aspects: (1) the water volume fraction, average pore size and dielectric parameters of MWNT-C14H25O4/PA and PA membranes were obtained by model analysis of DRS data. These data of MWNT-C14H25O4/PA membrane are higher than PA membrane, which indicates that the water flux of the MWNT-C14H25O4/PA membrane was higher than that of the PA membrane. (2) Further analysis shows that the MWNT-C14H25O4/PA membranes have high average charge density, ion solvation barrier and reflection coefficient, which indicates that the added interior-modified MWNT can improve the salt rejection of PA membranes. In the microscopic aspect, the desalination behavior of the MWNT-C14H25O4/PA and PA membrane was analyzed from the aspects of free volume distribution, the dynamic diffusion process of water and ions. The results show that the microscopic data of dynamic simulation well support the conclusion of the DRS method. This study provides a convenient methodology to characterize the properties of the membrane from the aspect of membrane structure.

9.
J Nanosci Nanotechnol ; 19(9): 5591-5600, 2019 09 01.
Article in English | MEDLINE | ID: mdl-30961713

ABSTRACT

The tip and inner surface of large diameter multi-walled carbon nanotubes (MWCNTs) (4.9 nm diameter) were functionalized on the tip and inner surface to improve the rate of desalination and maintain high water flux. The modified MWCNTs-doped reverse osmosis membranes were fabricated by interfacial polymerization using trimesoyl chloride (TMC) solution in n-hexane and aqueous solutions of m-phenylenediamine (MPD) containing functionalized MWCNTs. The functionalized MWCNTs were analyzed by X-ray photoelectron spectroscopy (XPS), thermal gravity analysis (TGA), high resolution transmission electron microscopy (HRTEM), UV-Vis spectroscopy and other techniques. The obtained results showed that changes occurred in the structure of the carbon nanotubes with the inner diameter becoming smaller, and the dispersibility and stability were improved. Carboxyl, acyl chloride, amide and amino groups were successfully grafted on the tip and interior of MWCNTs. The surface characteristics of the prepared membranes were studied by scanning electron microscopy (SEM) and contact angle analysis. The desalination performance of the membranes was investigated in terms of water flux and salt rejection. The experimental results revealed that the incorporation of the modified MWCNTs (especially containing hydrophilic groups such as carboxyl groups) into the polyamide layer of RO membranes led to a significantly increase of the water flux and salt rejection.

10.
J Autoimmun ; 95: 47-57, 2018 12.
Article in English | MEDLINE | ID: mdl-30340822

ABSTRACT

Gut microbiota and bacterial translocation have been implicated as significant contributors to mucosal immune responses and tolerance; alteration of microbial molecules, termed pathogen-associated molecular patterns (PAMP) and bacterial translocation are associated with immune pathology. However, the mechanisms by which dysregulated gut microbiota promotes autoimmunity is unclear. We have taken advantage of a well-characterized murine model of primary biliary cholangitis, dnTGFßRII mice, and an additional unique construct, toll-like receptor 2 (TLR2)-deficient dnTGFßRII mice coined dnTGFßRIITLR2-/- mice to investigate the influences of gut microbiota on autoimmune cholangitis. Firstly, we report that dnTGFßRII mice manifest altered composition of gut microbiota and that alteration of this gut microbiota by administration of antibiotics significantly alleviates T-cell-mediated infiltration and bile duct damage. Second, toll-like receptor 2 (TLR2)-deficient dnTGFßRII mice demonstrate significant exacerbation of autoimmune cholangitis when their epithelial barrier integrity was disrupted. Further, TLR2-deficiency mediates downregulated expression of tight junction-associated protein ZO-1 leading to increased gut permeability and bacterial translocation from gut to liver; use of antibiotics reduces microbiota translocation to liver and also decreases biliary pathology. In conclusion, our data demonstrates the important role of gut microbiota and bacterial translocation in the pathogenesis of murine autoimmune cholangitis.


Subject(s)
Autoimmune Diseases/microbiology , Bacterial Translocation/immunology , Bile Ducts/immunology , Liver Cirrhosis, Biliary/immunology , Receptor, Transforming Growth Factor-beta Type II/immunology , Toll-Like Receptor 2/immunology , Ampicillin/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/pathology , Bacterial Translocation/drug effects , Bile Ducts/drug effects , Bile Ducts/microbiology , Bile Ducts/pathology , Colon/drug effects , Colon/immunology , Colon/microbiology , Colon/pathology , Feces/microbiology , Female , Gastrointestinal Microbiome/drug effects , Gastrointestinal Microbiome/immunology , Gene Expression Regulation , Immunity, Mucosal/drug effects , Liver/drug effects , Liver/immunology , Liver/microbiology , Liver/pathology , Liver Cirrhosis, Biliary/drug therapy , Liver Cirrhosis, Biliary/microbiology , Liver Cirrhosis, Biliary/pathology , Metronidazole/pharmacology , Mice , Mice, Inbred C57BL , Mice, Knockout , Neomycin/pharmacology , Receptor, Transforming Growth Factor-beta Type II/deficiency , Receptor, Transforming Growth Factor-beta Type II/genetics , Signal Transduction , Toll-Like Receptor 2/deficiency , Toll-Like Receptor 2/genetics , Zonula Occludens-1 Protein/genetics , Zonula Occludens-1 Protein/immunology
11.
J Autoimmun ; 78: 19-28, 2017 03.
Article in English | MEDLINE | ID: mdl-28129932

ABSTRACT

CXC Chemokine Receptor 3 (CXCR3) is functionally pleiotropic and not only plays an important role in chemotaxis, but also participates in T cell differentiation and may play a critical role in inducing and maintaining immune tolerance. These observations are particularly critical for autoimmune cholangitis in which CXCR3 positive T cells are found around the portal areas of both humans and mouse models of primary biliary cholangitis (PBC). Herein, we investigated the role of CXCR3 in the pathogenesis of autoimmune cholangitis. We have taken advantage of a unique CXCR3 knockout dnTGFßRII mouse to focus on the role of CXCR3, both by direct observation of its influence on the natural course of disease, as well as through adoptive transfer studies into Rag-/- mice. We report herein that not only do CXCR3 deficient mice develop an exacerbation of autoimmune cholangitis associated with an expanded effector memory T cell number, but also selective adoptive transfer of CXCR3 deficient CD8+ T cells induces autoimmune cholangitis. In addition, gene microarray analysis of CXCR3 deficient CD8+ T cells reveal an intense pro-inflammatory profile. Our data suggests that the altered gene profiles induced by CXCR3 deficiency promotes autoimmune cholangitis through pathogenic CD8+ T cells. These data have significance for human PBC and other autoimmune liver diseases in which therapeutic intervention might be directed to chemokines and/or their receptors.


Subject(s)
Autoimmunity/genetics , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Liver Cirrhosis, Biliary/genetics , Liver Cirrhosis, Biliary/immunology , Lymphocyte Activation/genetics , Lymphocyte Activation/immunology , Receptors, CXCR3/deficiency , Animals , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Cytokines/blood , Cytokines/metabolism , Disease Models, Animal , Gene Expression Profiling , Immunologic Memory , Ligands , Liver Cirrhosis, Biliary/metabolism , Liver Cirrhosis, Biliary/pathology , Mice , Mice, Knockout , Receptors, CXCR3/metabolism
12.
Zhongguo Zhong Yao Za Zhi ; 42(19): 3733-3738, 2017 Oct.
Article in Zh | MEDLINE | ID: mdl-29235288

ABSTRACT

Squalene synthase of Alisma orientale catalyzes farnesyl diphosphate (FPP) to form squalene, which is the key regulatory enzyme of the carbon source flow to protostane triterpenes biosynthesis. For further research on the function and expression of AoSS gene, the open reading frame (ORF) of squalene synthase gene (accession no. JX866770) from A. orientale was subcloned into a prokaryotic expression vector pCzn1 and induced the expression of AoSS gene in Escherichia coli BL21(Roseta). The fusion protein was mainly in the form of inclusion bodies and purified to obtain high purity protein. By verifying its functionality through vitro enzymatic reaction, the results showed that the catalytic protein had the catalytic activity of FPP into squalene. In order to research the expression of AoSS in A. orientale, the purified protein was used to immunized rabbits to prepare polyclonal antibody which was then purified, the titer of the antibody was greater than 1∶51 200 by ELISA detection, and displayed good specificity by Western blotting. The prepared antibody was used for immunoassay of AoSS in different organs of A. orientale, and the results showed that the AoSS expression level was the highest in tubers, followed by leaves, and lowest in root. Successful construction of prokaryotic expression vector, validation of gene functions and establishment of rapid immunoassay lay the foundation for further researches on the function and regulation of AoSS gene, and also provide scientific basis on the application of the protostane triterpenes of A. orientale in the field of synthetic biology.


Subject(s)
Alisma/enzymology , Farnesyl-Diphosphate Farnesyltransferase/metabolism , Amino Acid Sequence , Animals , Cloning, Molecular , Farnesyl-Diphosphate Farnesyltransferase/genetics , Plant Leaves/chemistry , Plant Roots/chemistry , Plant Tubers/chemistry , Rabbits , Recombinant Fusion Proteins/biosynthesis , Squalene
13.
J Pharm Pharmacol ; 76(6): 579-591, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38624082

ABSTRACT

OBJECTIVES: Ranunculus L. genus contains 413 species, and it is the biggest genus in the family Ranunculaceae Juss. This review is to provide botanical characteristics, traditional uses, phytochemistry, pharmacology, toxicity, and pharmaceutical preparations of the genus Ranunculus. KEY FINDINGS: The genus Ranunculus contains flavonoids, organic acids, coumarins, lactones, glycosides, sterols, polysaccharides, and trace elements. These chemical constituents complement the pharmacological actions and work together to exert anti-inflammatory, anticancer, antitubercular, antibacterial, antimalarial, etc. Those traditional Chinese medicine characteristics, like clearing away heat and detoxification, make this genus significant in ethnic medicine. The progress in research and the development of various pharmaceutical preparations made it appear in epidemiological and clinical studies. SUMMARY: The genus Ranunculus has attracted the attention of experts and scholars in many fields due to its unique advantages. However, there are many species that are not scientifically investigated. The toxicity issues are also a huge concern. Fortunately, the toxicity can be overcome via special processes like drying or heating and by choosing a safe extraction solvent, such as water thus ensuring the safety of medication. Pharmaceutical preparations containing the plants from Ranunculus have gratifying clinical value, but they are not promoted sufficiently. Therefore, further research should be carried out to promote the genus for its health benefits to humans.


Subject(s)
Ranunculus , Ranunculus/chemistry , Humans , Phytochemicals/pharmacology , Phytochemicals/toxicity , Phytochemicals/isolation & purification , Animals , Medicine, Chinese Traditional/methods , Asia , Phytotherapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/toxicity , Plant Extracts/pharmacology , Plant Extracts/toxicity , Plant Extracts/chemistry , Ethnopharmacology
14.
Clin Transl Med ; 14(3): e1594, 2024 03.
Article in English | MEDLINE | ID: mdl-38426403

ABSTRACT

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study. METHODS: In conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC-associated cells within the tissue sections. The spatial RNA-clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand-receptor analysis and Gene Ontology enrichment analysis. RESULTS: The spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse-free survival in PTC patients. We discovered key ligand-receptor interactions, including LAMB3-ITGA2, FN1-ITGA3 and FN1-SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse-free survival. In the tumour immune microenvironment, reduced interaction between myeloid-derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA-clinical analysis method developed here revealed prognosis-associated cellular heterogeneity in the PTC microenvironment. CONCLUSIONS: The occurrence of tumour foci No. 2 and three enhanced ligand-receptor interactions in the AFC area/tumour foci reduced the relapse-free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.


Subject(s)
Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Ligands , Tumor Microenvironment/genetics , Neoplasm Recurrence, Local , Gene Expression Profiling , Prognosis , RNA
15.
bioRxiv ; 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37873111

ABSTRACT

The pursuit of precision oncology heavily relies on large-scale genomic and pharmacological data garnered from preclinical cancer model systems such as cell lines. While cell lines are instrumental in understanding the interplay between genomic programs and drug response, it well-established that they are not fully representative of patient tumors. Development of integrative methods that can systematically assess the commonalities between patient tumors and cell-lines can help bridge this gap. To this end, we introduce the Integrative Principal Component Regression (iPCR) model which uncovers both joint and model-specific structured variations in the genomic data of cell lines and patient tumors through matrix decompositions. The extracted joint variation is then used to predict patient drug responses based on the pharmacological data from preclinical models. Moreover, the interpretability of our model allows for the identification of key driver genes and pathways associated with the treatment-specific response in patients across multiple cancers. We demonstrate that the outputs of the iPCR model can assist in inferring both model-specific and shared co-expression networks between cell lines and patients. We show that iPCR performs favorably compared to competing approaches in predicting patient drug responses, in both simulation studies and real-world applications, in addition to identifying key genomic drivers of cancer drug responses.

16.
Genes (Basel) ; 14(6)2023 05 23.
Article in English | MEDLINE | ID: mdl-37372306

ABSTRACT

Maize stalk strength is a crucial agronomic trait that affects lodging resistance. We used map-based cloning and allelic tests to identify a maize mutant associated with decreased stalk strength and confirmed that the mutated gene, ZmBK2, is a homolog of Arabidopsis AtCOBL4, which encodes a COBRA-like glycosylphosphatidylinositol (GPI)-anchored protein. The bk2 mutant exhibited lower cellulose content and whole-plant brittleness. Microscopic observations showed that sclerenchymatous cells were reduced in number and had thinner cell walls, suggesting that ZmBK2 affects the development of cell walls. Transcriptome sequencing of differentially expressed genes in the leaves and stalks revealed substantial changes in the genes associated with cell wall development. We constructed a cell wall regulatory network using these differentially expressed genes, which revealed that abnormal cellulose synthesis may be a reason for brittleness. These results reinforce our understanding of cell wall development and provide a foundation for studying the mechanisms underlying maize lodging resistance.


Subject(s)
Arabidopsis , Zea mays , Zea mays/metabolism , Cellulose/metabolism , Phenotype , Genes, Plant , Arabidopsis/genetics
17.
Am J Reprod Immunol ; 90(1): e13708, 2023 07.
Article in English | MEDLINE | ID: mdl-37095737

ABSTRACT

PROBLEM: The phenotypes and functions of B and CD4+ T-helper cell subsets during chronic inflammation of the endometria remain largely unexplored. This study aimed to investigate the characteristics and functions of follicular helper T (Tfh) cells to understand the pathological mechanisms of chronic endometritis (CE). METHOD OF STUDY: Eighty patients who underwent hysteroscopic and histopathological examinations for CE were divided into three groups-those with positive results for hysteroscopy and CD138 staining (DP), negative results for hysteroscopy but positive CD138 staining (SP), and negative results for hysteroscopy and CD138 staining (DN). The phenotypes of B cells and CD4+ T-cell subsets were analyzed using flow cytometry. RESULTS: CD38+ and CD138+ cells were mainly expressed in the non-leukocyte population of the endometria, and the endometrial CD19+ CD138+ B cells were fewer than the CD3+ CD138+ T cells. The percentage of Tfh cells increased with chronic inflammation in the endometria. Additionally, the elevated percentage of Tfh cells correlated with the number of miscarriages. CONCLUSIONS: CD4+ T cells, particularly Tfh cells, may be critical in chronic endometrial inflammation and affect its microenvironment, thereby regulating endometrial receptivity, compared to B cells.


Subject(s)
Pregnancy Outcome , T-Lymphocytes, Helper-Inducer , Humans , Pregnancy , Female , B-Lymphocytes , Endometrium , Inflammation
18.
J Health Popul Nutr ; 42(1): 63, 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37420277

ABSTRACT

BACKGROUND: The elevated circulating toxins secondary to the impairment of intestinal barrier integrity commonly elicit a chronic inflammatory response and finally contribute to multiple diseases. These toxins, including bacterial by-products and heavy metals, are the potent risk factors for the development of recurrent spontaneous abortion (RSA). Preclinical evidence suggests that several dietary fibers can restore intestinal barrier function and decrease the accumulation of heavy metals. However, it is uncertain whether treatment with a newly developed blend of dietary fibers product (Holofood) benefits patients with RSA. METHODS: In this trial, we enrolled 70 adult women with RSA, who were randomly assigned into the experiment group and the control group in a 2:1 ratio. Upon the basis of conventional therapy, subjects in the experiment group (n = 48) received 8 weeks oral administration with Holofood three times daily at a dose of 10 g each time. Subjects without Holofood consumption were set as the control (n = 22). Blood samples were collected for the determinations of metabolic parameters, heavy mental lead, and the indices related to intestinal barrier integrity (D-lactate, bacterial endotoxin, and diamine oxidase activity). RESULTS: The reduction amplitude in blood lead from baseline to week 8 was 40.50 ± 54.28 (µg/L) in the experiment group as compared with 13.35 ± 36.81 (µg/L) in the control group (P = 0.037). The decreased level of serum D-lactate from baseline to week 8 was 5.58 ± 6.09 (mg/L) in the experiment group as compared with - 2.38 ± 8.90 (mg/L, P < 0.0001) in the control group. The change in serum DAO activity from baseline to week 8 was 3.26 ± 2.23 (U/L) in the experiment group as compared with - 1.24 ± 2.22 (U/L, P < 0.0001) in the control group. Participants who received Holofood had a greater decline in blood endotoxin from baseline to week 8 than those in the control group. Moreover, by comparing with the self-baseline, Holofood consumption significantly decreased the blood levels of lead, D-lactate, bacterial endotoxin, and DAO activity. CONCLUSION: Our results suggest that Holofood affords a clinically relevant improvements in blood lead level and intestinal barrier dysfunction in patients with RSA.


Subject(s)
Abortion, Spontaneous , Lead , Humans , Adult , Female , Pregnancy , Lead/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Abortion, Spontaneous/metabolism , Endotoxins/metabolism , Dietary Fiber/therapeutic use , Dietary Fiber/metabolism , Lactic Acid/metabolism
19.
Article in English | MEDLINE | ID: mdl-35055471

ABSTRACT

This article uses the "Green Credit Guidelines" promulgated in 2012 as an example to construct a quasi-natural experiment and uses the double difference method to test the impact of the implementation of the "Green Credit Guidelines" on the green innovation activities of heavy-polluting enterprises. The study found that, in comparison to non-heavy polluting enterprises, the implementation of green credit policies inhibited the green innovation of all heavy-polluting enterprises. In the analysis of heterogeneity, this restraint effect did not differ significantly due to the nature of property rights and the company's size. The mechanism test showed that green credit policy limits the efficiency of business investment and increases the cost of financing business debt. Eliminating corporate credit financing, particularly long-term borrowing, negatively impacts the green innovation behavior of listed companies.


Subject(s)
Investments , Policy , China , Efficiency , Organizations
20.
Article in English | MEDLINE | ID: mdl-35055674

ABSTRACT

With the rise and popularization of the concept of green sustainable development, green income growth of agricultural insurance policies has attracted wide attention. Whether green income growth can be achieved has become an important criterion for measuring an agricultural insurance policy. In this context, this paper attempts to test whether the agricultural insurance policy achieves green income growth. Based on the panel data of 31 provinces (the research sample of this paper selects 31 provincial-level units (province for short) in China, including 22 provinces, 5 autonomous regions and 4 municipalities directly under the central government. Hong Kong Special Administrative Region, Macau Special Administrative Region and Taiwan Province are not included in the research sample) from 2009 to 2020 in China, this paper empirically evaluates the triple-effect of total cost insurance pilot program (TCI) on farmers' income, environment and public health by employing a difference-in-difference model (DID). The results show that TCI increases farmers' income, but deteriorates the environment and residents' health without achieving green income growth. In the analysis of heterogeneity, compared with central and western regions, farmers' income is more likely to increase in the eastern regions. However, environmental pollution is more severe, and residents' health deteriorates more, in eastern regions. In addition, the positive effect of TCI on farmers' income and the deterioration of residents' health is more obvious in areas with a higher degree of damage, while the negative effect of TCI on the environment is more obvious in areas with a lower degree of damage. Furthermore, the mechanism analysis shows that TCI not only promotes the increase in farmers' income through insurance density, but also affects the environment and residents' health through straw burning. Therefore, the government should raise the subsidy standard for farmers to use straw-processing equipment and also to implement differentiated subsidies in regions with different levels of economic development and areas with different degrees of damage.


Subject(s)
Farmers , Insurance , Agriculture , China , Humans , Pilot Projects , Policy
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