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1.
J Hepatol ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38782118

ABSTRACT

BACKGROUND & AIMS: Hepatocellular Carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma (AHCC) trials group (NCT03267641), we recruited one of the largest prospective cohorts of HCC with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provided a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort) IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected HCC, reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of Hepatocellular Carcinoma (HCC). These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for developing personalized therapies tailored to specific tumor evolutionary and transcriptomic profiles. The co-existence of multiple sub-types within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making.

2.
BMC Cancer ; 23(1): 118, 2023 Feb 03.
Article in English | MEDLINE | ID: mdl-36737737

ABSTRACT

BACKGROUND: Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). METHODS: Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients' matched adjacent normal samples. RESULTS: Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. DISCUSSION/CONCLUSION: Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Gene Expression Regulation, Neoplastic
3.
J Environ Sci (China) ; 114: 503-513, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35459512

ABSTRACT

Air pollution in China is complex, and the formation mechanism of chemical components in particulate matter is still unclear. This study selected three consecutive heavy haze pollution episodes (HPEs) during winter in Beijing for continuous field observation, including an episode with heavy air pollution under red alert. Clean days during the observation period were selected for comparison. The HPE characteristics of Beijing in winter were: under the influence of adverse meteorological conditions such as high relative humidity, temperature inversion and low wind speed; and strengthening of secondary transformation reactions, which further intensified the accumulation of secondary aerosols and other pollutants, promoting the explosive growth of PM2.5. PM2.5/CO values, as indicators of the contribution of secondary transformation in PM2.5, were approximately 2 times higher in the HPEs than the average PM2.5/CO during the clean period. The secondary inorganic aerosols (sulfate nitrate and ammonium salt) were significantly enhanced during the HPEs, and the conversion coefficients were remarkably improved. In addition, it is interesting to observe that the production of sulfate tended to exceed that of nitrate in the late stage of all three HPEs. The existence of aqueous phase reactions led to the explosive growth sulfur oxidation ratio (SOR) and rapid generation of sulfate under high relative humidity (RH>70%).


Subject(s)
Air Pollutants , Air Pollution , Aerosols/analysis , Air Pollutants/analysis , Air Pollution/analysis , Beijing , China , Environmental Monitoring , Nitrates/analysis , Nitrogen Oxides/analysis , Particulate Matter/analysis , Seasons , Sulfates/analysis
4.
J Immunol ; 202(3): 991-1002, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30567728

ABSTRACT

Early detection of lung cancer offers an important opportunity to decrease mortality while it is still treatable and curable. Thirteen secretory proteins that are Stat3 downstream gene products were identified as a panel of biomarkers for lung cancer detection in human sera. This panel of biomarkers potentially differentiates different types of lung cancer for classification. Among them, the transthyretin (TTR) concentration was highly increased in human serum of lung cancer patients. TTR concentration was also induced in the serum, bronchoalveolar lavage fluid, alveolar type II epithelial cells, and alveolar myeloid cells of the CCSP-rtTA/(tetO)7-Stat3C lung tumor mouse model. Recombinant TTR stimulated lung tumor cell proliferation and growth, which were mediated by activation of mitogenic and oncogenic molecules. TTR possesses cytokine functions to stimulate myeloid cell differentiation, which are known to play roles in tumor environment. Further analyses showed that TTR treatment enhanced the reactive oxygen species production in myeloid cells and enabled them to become functional myeloid-derived suppressive cells. TTR demonstrated a great influence on a wide spectrum of endothelial cell functions to control tumor and immune cell migration and infiltration. TTR-treated endothelial cells suppressed T cell proliferation. Taken together, these 13 Stat3 downstream inducible secretory protein biomarkers potentially can be used for lung cancer diagnosis, classification, and as clinical targets for lung cancer personalized treatment if their expression levels are increased in a given lung cancer patient in the blood.


Subject(s)
Endothelial Cells/immunology , Gene Expression Regulation, Neoplastic , Lung Neoplasms/immunology , Prealbumin/immunology , Alveolar Epithelial Cells/immunology , Animals , Biomarkers, Tumor/blood , Bronchoalveolar Lavage Fluid/chemistry , Cell Movement , Cell Proliferation , Disease Models, Animal , Humans , Lung Neoplasms/classification , Melanoma, Experimental , Mice , Mice, Inbred C57BL , Mice, Transgenic , Myeloid Cells/immunology , Neoplasms, Experimental/immunology , Prealbumin/pharmacology , Recombinant Proteins/pharmacology , STAT3 Transcription Factor/genetics
5.
Nature ; 522(7555): 173-8, 2015 Jun 11.
Article in English | MEDLINE | ID: mdl-26040716

ABSTRACT

Stem cells of the gastrointestinal tract, pancreas, liver and other columnar epithelia collectively resist cloning in their elemental states. Here we demonstrate the cloning and propagation of highly clonogenic, 'ground state' stem cells of the human intestine and colon. We show that derived stem-cell pedigrees sustain limited copy number and sequence variation despite extensive serial passaging and display exquisitely precise, cell-autonomous commitment to epithelial differentiation consistent with their origins along the intestinal tract. This developmentally patterned and epigenetically maintained commitment of stem cells is likely to enforce the functional specificity of the adult intestinal tract. Using clonally derived colonic epithelia, we show that toxins A or B of the enteric pathogen Clostridium difficile recapitulate the salient features of pseudomembranous colitis. The stability of the epigenetic commitment programs of these stem cells, coupled with their unlimited replicative expansion and maintained clonogenicity, suggests certain advantages for their use in disease modelling and regenerative medicine.


Subject(s)
Intestines/cytology , Stem Cells/cytology , Stem Cells/metabolism , Bacterial Toxins/pharmacology , Cell Differentiation/drug effects , Cell Lineage , Cells, Cultured , Clone Cells/cytology , Clone Cells/metabolism , Clostridioides difficile/physiology , Colon/cytology , Colon/drug effects , Enterocolitis, Pseudomembranous/microbiology , Enterocolitis, Pseudomembranous/pathology , Epigenesis, Genetic/genetics , Epithelium/drug effects , Epithelium/metabolism , Fetus/cytology , Genomic Instability/genetics , Humans , Intestine, Small/cytology , Intestines/drug effects , Organoids/cytology , Organoids/growth & development
6.
J Environ Sci (China) ; 102: 185-197, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33637243

ABSTRACT

Understanding the formation mechanisms of secondary air pollution is very important for the formulation of air pollution control countermeasures in China. Thus, a large-scale outdoor atmospheric simulation smog chamber was constructed at Chinese Research Academy of Environmental Sciences (the CRAES Chamber), which was designed for simulating the atmospheric photochemical processes under the conditions close to the real atmospheric environment. The chamber consisted of a 56-m3 fluorinated ethylene propylene (FEP) Teflon film reactor, an electrically-driven stainless steel alloy shield, an auxiliary system, and multiple detection instrumentations. By performing a series of characterization experiments, we obtained basic parameters of the CRAES chamber, such as the mixing ability, the background reactivity, and the wall loss rates of gaseous compounds (propene, NO, NO2, ozone) and aerosols (ammonium sulfate). Oxidation experiments were also performed to study the formation of ozone and secondary organic aerosol (SOA), including α-pinene ozonolysis, propene and 1,3,5-trimethylbenzene photooxidation. Temperature and seed effects on the vapor wall loss and SOA yields were obtained in this work: higher temperature and the presence of seed could reduce the vapor wall loss; SOA yield was found to depend inversely on temperature, and the presence of seed could increase SOA yield. The seed was suggested to be used in the chamber to reduce the interaction between the gas phase and chamber walls. The results above showed that the CRAES chamber was reliable and could meet the demands for investigating tropospheric chemistry.


Subject(s)
Air Pollutants , Smog , Aerosols/analysis , Air Pollutants/analysis , China , Photochemical Processes , Smog/analysis
7.
Bioorg Med Chem ; 26(8): 2017-2027, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29545016

ABSTRACT

To discover more derivatives with better glucose-lowering efficacy compared with berberine, twenty-three novel compounds with 4,7,12,12a-tetrahydro-5H-thieno[3',2':3,4]pyrido[1,2-b]isoquinoline or 5,8,12,12a-tetrahydro-6H-thieno[2',3':4,5]pyrido[2,1-a]isoquinoline cores were designed, synthesized, and biologically evaluated in vitro in continuation of our previous work on indirect activators of adenosine 5'-monophosphate-activated protein kinase (AMPK). Nine compounds effectively stimulated glucose consumption (>2.3-fold at 10 µM) in L6 myotube cells, and two compounds (4d and 4s) exhibited superior inhibitory activity (<57.6% at 5 µM) compared with berberine on gluconeogenesis in rat primary hepatocytes. Additionally, these compounds significantly up-regulated the phosphorylation of AMPK and its substrate, acetyl-CoA carboxylase (ACC) and slightly decreased the mitochondrial membrane potential in L6 myotube cells.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Drug Design , Isoquinolines/chemistry , AMP-Activated Protein Kinases/chemistry , Animals , Cells, Cultured , Glucose/metabolism , Hepatocytes/cytology , Hepatocytes/drug effects , Hepatocytes/metabolism , Isoquinolines/chemical synthesis , Isoquinolines/pharmacology , Membrane Potential, Mitochondrial/drug effects , Muscle Fibers, Skeletal/cytology , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism , Phosphorylation/drug effects , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship
8.
J Pathol ; 238(4): 519-530, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26415052

ABSTRACT

High-grade serous cancer (HGSC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and Fallopian tubes in patients with BRCA1 or BRCA2 mutations have documented a pre-metastatic intramucosal neoplasm that is found almost exclusively in the Fallopian tube, termed 'serous tubal intraepithelial carcinoma' or STIC. Moreover, other proliferations, termed p53 signatures, secretory cell outgrowths (SCOUTs), and lower-grade serous tubal intraepithelial neoplasms (STINs) fall short of STIC but share similar alterations in expression, in keeping with an underpinning of genomic disturbances involved in, or occurring in parallel with, serous carcinogenesis. To gain insight into the cellular origins of this unique tubal pathway to high-grade serous cancer, we cloned and both immortalized and transformed Fallopian tube stem cells (FTSCs). We demonstrated that pedigrees of FTSCs were capable of multipotent differentiation and that the tumours derived from transformed FTSCs shared the histological and molecular features of HGSC. We also demonstrated that altered expression of some biomarkers seen in transformed FTSCs and HGSCs (stathmin, EZH2, CXCR4, CXCL12, and FOXM1) could be seen as well in immortalized cells and their in vivo counterparts SCOUTs and STINs. Thus, a whole-genome transcriptome analysis comparing FTSCs, immortalized FTSCs, and transformed FTSCs showed a clear molecular progression sequence that is recapitulated by the spectrum of accumulated perturbations characterizing the range of proliferations seen in vivo. Biomarkers unique to STIC relative to normal tubal epithelium provide a basis for novel detection approaches to early HGSC, but must be viewed critically given their potential expression in lesser proliferations. Perturbations shared by both immortalized and transformed FTSCs may provide unique early targets for prevention strategies. Central to these efforts has been the ability to clone and perpetuate multipotent FTSCs.


Subject(s)
Carcinoma in Situ/pathology , Cystadenocarcinoma, Serous/pathology , Fallopian Tube Neoplasms/pathology , Neoplasms, Cystic, Mucinous, and Serous/pathology , Neoplastic Stem Cells/pathology , Biomarkers, Tumor/metabolism , Cystadenocarcinoma, Serous/genetics , Fallopian Tube Neoplasms/genetics , Female , Humans , Neoplasms, Cystic, Mucinous, and Serous/diagnosis , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology
9.
J Environ Sci (China) ; 53: 107-112, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28372734

ABSTRACT

In this study, the temperature dependence of the heterogeneous uptake of acrylic acid on Arizona test dust (ATD) has been investigated within a temperature range of 255-315K using a Knudsen cell reactor. Combined with diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) experiment, it was found that acrylic acid could adsorb on ATD via surface OH groups and convert to carboxylate on the particle surface. The kinetics study suggests that the initial true uptake coefficient (γt) of acrylic acid on ATD decreases from (4.02±0.12)×10-5 to (1.73±0.05)×10-5 with a temperature increase from 255 to 315K. According to the temperature dependence of uptake coefficients, the enthalpy (ΔHobs) and entropy (ΔSobs) of uptake processes were determined to be -(9.60±0.38) KJ/mol and -(121.55±1.33) J·K/mol, respectively. The activation energy for desorption (Edes) was calculated to be (14.57±0.60) KJ/mol. These results indicated that the heterogeneous uptake of acrylic acid on ATD surface was sensitive to temperature. The heterogeneous uptake on ATD could affect the concentration of acrylic acid in the atmosphere, especially at low temperature.


Subject(s)
Acrylates/chemistry , Dust/analysis , Models, Chemical , Adsorption , Arizona , Kinetics , Temperature , Thermodynamics
10.
Chemphyschem ; 17(21): 3515-3523, 2016 Nov 04.
Article in English | MEDLINE | ID: mdl-27504908

ABSTRACT

Heterogeneous reactions have a vital role in the atmosphere due to their significant effects on the evolution of atmospheric aerosols, which in turn contribute to air pollution. However, the mechanism and kinetics of these processes involving unsaturated organic acids, important types of volatile organic compounds, are still unclear. In this work, the heterogeneous uptake of two representative atmospheric unsaturated organic acids (acrylic acid and methacrylic acid) on mineral aerosols including α-Al2 O3 and CaCO3 are investigated using a Knudsen cell reactor and an in situ diffuse reflectance infrared Fourier transform spectrometry (DRIFTS) reactor. The corresponding reaction pathways are proposed from the DRIFTS analysis. In addition, the initial uptake coefficients of unsaturated organic acids and their heterogeneous fate are obtained for the first time. Our results suggest that heterogeneous reactions on α-Al2 O3 and CaCO3 can be important sinks for acrylic acid and methacrylic acid, as well as possible contributors to the organic coating found on atmospheric aerosols, especially in high-pollution events.

11.
J Pathol ; 234(4): 478-87, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25130537

ABSTRACT

The oviducts contain high-grade serous cancer (HGSC) precursors (serous tubal intraepithelial neoplasia or STINs), which are γ-H2AX(p) - and TP53 mutation-positive. Although they express wild-type p53, secretory cell outgrowths (SCOUTs) are associated with older age and serous cancer; moreover, both STINs and SCOUTs share a loss of PAX2 expression (PAX2(n) ). We evaluated PAX2 expression in proliferating adult and embryonic oviductal cells, normal mucosa, SCOUTs, Walthard cell nests (WCNs), STINs, and HGSCs, and the expression of genes chosen empirically or from SCOUT expression arrays. Clones generated in vitro from embryonic gynaecological tract and adult Fallopian tube were Krt7(p) /PAX2(n) /EZH2(p) and underwent ciliated (PAX2(n) /EZH2(n) /FOXJ1(p) ) and basal (Krt7(n) /EZH2(n) /Krt5(p) ) differentiation. Similarly, non-ciliated cells in normal mucosa were PAX2(p) but became PAX2(n) in multi-layered epithelium undergoing ciliated or basal (WCN) cell differentiation. PAX2(n) SCOUTs fell into two groups: type 1 were secretory or secretory/ciliated with a 'tubal' phenotype and were ALDH1(n) and ß-catenin(mem) (membraneous only). Type 2 displayed a columnar to pseudostratified (endometrioid) phenotype, with an EZH2(p) , ALDH1(p) , ß-catenin(nc) (nuclear and cytoplasmic), stathmin(p) , LEF1(p) , RCN1(p) , and RUNX2(p) expression signature. STINs and HGSCs shared the type 1 immunophenotype of PAX2(n) , ALDH1(n) , ß-catenin(mem) , but highly expressed EZH2(p) , LEF1(p) , RCN1(p) , and stathmin(p) . This study, for the first time, links PAX2(n) with proliferating fetal and adult oviductal cells undergoing basal and ciliated differentiation and shows that this expression state is maintained in SCOUTs, STINs, and HGSCs. All three entities can demonstrate a consistent perturbation of genes involved in potential tumour suppressor gene silencing (EZH2), transcriptional regulation (LEF1), regulation of differentiation (RUNX2), calcium binding (RCN1), and oncogenesis (stathmin). This shared expression signature between benign and neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target for early prevention.


Subject(s)
Fallopian Tube Neoplasms/genetics , Neoplastic Stem Cells/pathology , PAX2 Transcription Factor/genetics , Cell Differentiation/genetics , Cell Lineage , Epithelium/pathology , Fallopian Tube Neoplasms/pathology , Fallopian Tubes/pathology , Female , Humans , Immunohistochemistry , Immunophenotyping , Oligonucleotide Array Sequence Analysis , Transcriptome
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 32(5): 651-6, 2015 Oct.
Article in Zh | MEDLINE | ID: mdl-26418984

ABSTRACT

OBJECTIVE To investigate the distribution of killer cell immunoglobulin-like receptors (KIR) and their specific ligands human leukocyte antigen-I (HLA-I) gene in northern China. METHODS One hundred and eighty-four unrelated northern Chinese Han individuals were recruited. Genotypes of the KIR and HLA-ABC genes were studied by sequence-specific primer polymerase chain reaction (SSP-PCR). RESULTS Sixteen KIR genes were detected among the 184 unrelated individuals. In all individuals, the four framework genes were present. The frequencies for those carrying the remaining 12 KIR genes have ranged from 16.3% to 99.5%. Twenty-four KIR genotypes were identified, for which half were detected in a single individual. A new genotype comprised of KIR2DL3, 3DL1, 2DP1 and the framework genes was detected in one subject. Respectively, 12, 27 and 11 specificities of HLA alleles were identified on the HLA-A, B, C loci. CONCLUSION The distribution of polymorphisms of KIR and its ligand HLA-ABC genes among northern Chinese Han population have been ascertained. The frequencies of 9 KIR/HLA combinations in the above population have been determined for the first time.


Subject(s)
Histocompatibility Antigens Class I/genetics , Receptors, KIR/genetics , Child , China/ethnology , Ethnicity , Female , Gene Frequency , Humans , Male
13.
Blood ; 119(1): 115-26, 2012 Jan 05.
Article in English | MEDLINE | ID: mdl-22053106

ABSTRACT

Peroxisome proliferator-activated receptor-γ (PPARγ) is an anti-inflammatory molecule. To study its biologic function in myeloid cells, dominant-negative PPARγ (dnPPARγ) was overexpressed in a myeloid-specific bitransgenic mouse model. In this bitransgenic system, overexpression of the dnPPARγ-Flag fusion protein in myeloid-lineage cells abnormally elevated frequencies and total numbers of IL-7Rα(-)Lin(-)c-Kit(+)Sca-1(-), Lin(-)/Scal(+)/c-Kit(+), common myeloid, and granulocyte-monocyte progenitor populations in the BM. dnPPARγ overexpression led to up-regulation of IL-1ß, IL-6, and TNFα in the blood plasma. As a result, CD11b(+)Ly6G(+) cells were systemically increased in association with activation of Stat3, NF-κB, Erk1/2, and p38 molecules. Myeloid-derived suppressor cells (MDSCs) inhibited the proliferation and lymphokine production of wild-type CD4+ T cells in vitro. CD4+ T cells from doxycycline-treated bitransgenic mice displayed reduced proliferation and lymphokine release. Both CD4+ and CD8+ T-cell populations were decreased in doxycycline-treated bitransgenic mice. Multiple forms of carcinoma and sarcoma in the lung, liver, spleen, and lymph nodes were observed in doxycycline-treated bitransgenic mice. BM transplantation revealed that a myeloid-autonomous defect was responsible for MDSC expansion, immunosuppression, and tumorigenesis in these mice. These studies suggest that anti-inflammatory PPARγ in myeloid-lineage cells plays a key role in controlling pro-inflammatory cytokine synthesis, MDSC expansion, immunosuppression, and the development of cancer.


Subject(s)
Adenocarcinoma/etiology , Genes, Dominant , Immunosuppression Therapy , Inflammation/etiology , Myeloid Cells/immunology , Myeloid Cells/pathology , PPAR gamma/physiology , Sarcoma/etiology , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Blotting, Western , Bone Marrow Transplantation , Cell Proliferation , Chromatin Immunoprecipitation , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Hematopoietic Stem Cells , Humans , Immunoenzyme Techniques , Inflammation/metabolism , Inflammation/pathology , Interleukin-1beta/blood , Interleukin-6/blood , Liver Neoplasms/etiology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Lung Neoplasms/etiology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lymph Nodes/metabolism , Lymph Nodes/pathology , Male , Mice , Mice, Transgenic , Myeloid Cells/metabolism , NF-kappa B/metabolism , PPAR gamma/antagonists & inhibitors , Proto-Oncogene Proteins c-kit/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Receptors, Interleukin-7/metabolism , STAT3 Transcription Factor/metabolism , Sarcoma/metabolism , Sarcoma/pathology , Signal Transduction , Splenic Neoplasms/etiology , Splenic Neoplasms/metabolism , Splenic Neoplasms/pathology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology , Tumor Necrosis Factor-alpha/blood , Up-Regulation
14.
Medicine (Baltimore) ; 103(20): e37893, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758882

ABSTRACT

RATIONALE: Leiomyoma is a benign smooth muscle tumor which is rarely found in urethra. We hereby report a case of a 44-year-old female who presented with complaints of dysuria. PATIENT CONCERNS: A 44-year-old female patient presented to the urology outpatient clinic with symptoms of dysuria. The patient described the presence of a protrusion from the urethra during urination. DIAGNOSIS: Urethral leiomyoma. INTERVENTIONS: Physical examination confirmed a solid urethral mass. CT scan and USG reports indicated that the mass originated from the mid-urethra with vascularity at the base. We performed a complete resection of the urethral mass. The patient was discharged after 3 days of observation. OUTCOME: During a follow-up after 1 month, the patient reported improved urinary flow and no occurrence of hematuria. The patient recovered well after discharge. LESSON: Urethral leiomyoma is a rare benign tumor that is often misdiagnosed in clinical practice. Diagnosis requires careful clinical examination. Surgical removal usually works well. It is important to remember that in some cases of acute urinary retention, it can be caused by a complete obstruction of a mass in the urethra. Urologists should be more cautious and experienced in handling such cases.


Subject(s)
Dysuria , Leiomyoma , Urethral Neoplasms , Humans , Female , Leiomyoma/surgery , Leiomyoma/diagnosis , Leiomyoma/complications , Leiomyoma/pathology , Leiomyoma/diagnostic imaging , Adult , Dysuria/etiology , Urethral Neoplasms/diagnosis , Urethral Neoplasms/surgery , Urethral Neoplasms/pathology , Tomography, X-Ray Computed
15.
Materials (Basel) ; 17(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38473548

ABSTRACT

Polyvinyl chloride (PVC) foam, valued for its mechanical and thermal properties along with cost-effectiveness, is extensively utilized across diverse industries. However, its high volatile organic compound (VOC) emissions hinder its adoption in eco-friendly synthetic leather. This study proposes a solution by optimizing the formulation design and foaming processes and achieving mechanical property enhancement via carbon-fiber-reinforced PVC composite foam (CF/PVC). The aim is to reduce PVC usage via enhancing its intrinsic properties. Systematic investigations were carried out on the impact of foaming raw materials, foaming processes, fiber content, and fiber length on the foaming performance, mechanical properties, and VOC emissions. The material formulation and process parameters were successfully optimized. Further assessment of various indicators such as the density, mechanical properties, and tear resistance of synthetic leather samples confirmed that the innovative CF/PVC foam developed in this study meets the requirements for automotive interior applications. Notably, the tensile strength and tear resistance of CF/PVC composite synthetic leather increased by 50% and 29%, respectively, compared to pure PVC, while VOC emissions decreased by 28%. It is anticipated that a more pronounced reduction in VOC emissions will be achieved in practical automotive interior leather applications when further considering the reinforcing effect of fibers, which leads to a reduction in PVC usage. The findings present a technical reference for innovative applications, aiming to enhance PVC foam performance and minimize emissions.

16.
Environ Pollut ; 345: 123563, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38355086

ABSTRACT

The pollution of heavy metals (HMs) in the environment is a significant global environmental issue, characterized by its extensive distribution, severe contamination, and profound ecological impacts. Excessive exposure to heavy metal pollutants can damage the nervous system. However, the mechanisms underlying the neurotoxicity of most heavy metals are not completely understood. Epigenetics is defined as a heritable change in gene function that can influence gene and subsequent protein expression levels without altering the DNA sequence. Growing evidence indicates that heavy metals can induce neurotoxic effects by triggering epigenetic changes and disrupting the epigenome. Compared with genetic changes, epigenetic alterations are more easily reversible. Epigenetic reprogramming techniques, drugs, and certain nutrients targeting specific epigenetic mechanisms involved in gene expression regulation are emerging as potential preventive or therapeutic tools for diseases. Therefore, this review provides a comprehensive overview of epigenetic modifications encompassing DNA/RNA methylation, histone modifications, and non-coding RNAs in the nervous system, elucidating their association with various heavy metal exposures. These primarily include manganese (Mn), mercury (Hg), lead (Pb), cobalt (Co), cadmium (Cd), nickel (Ni), sliver (Ag), toxic metalloids arsenic (As), and etc. The potential epigenetic mechanisms in the etiology, precision prevention, and target therapy of various neurodevelopmental disorders or different neurodegenerative diseases are emphasized. In addition, the current gaps in research and future areas of study are discussed. From a perspective on epigenetics, this review offers novel insights for prevention and treatment of neurotoxicity induced by heavy metal pollutants.


Subject(s)
Arsenic Poisoning , Environmental Pollutants , Mercury , Metals, Heavy , Humans , Environmental Pollutants/toxicity , Environmental Pollutants/analysis , Metals, Heavy/analysis , Mercury/analysis , Cadmium/analysis , Epigenesis, Genetic , Environmental Monitoring/methods , Risk Assessment
17.
J Phys Chem A ; 117(23): 4937-44, 2013 Jun 13.
Article in English | MEDLINE | ID: mdl-23682776

ABSTRACT

Although recent evidence suggests that the heterogeneous reaction of NO2 on the surface of mineral aerosol plays an important role in the atmospheric chemistry, a fundamental understanding of how temperature influences the rate and extent of nitrate formation processes remains unclear. This work presents the first laboratory study of the effect of temperature on heterogeneous reaction of NO2 on the surface of γ-Al2O3 in the temperature range of 250-318 K at ambient pressure. From the analysis of IR spectra, nitrite was found to be an intermediate product at temperatures between 250 and 318 K. It is proved by our experiments that nitrite would convert to the bidentate nitrate as the reaction proceeded. In addition, it is interesting to find that the rate of conversion increased with decreasing temperature. Along with nitrite decrease, the initial rate of nitrate formation increased while the rate of nitrate formation in the steady region decreased with decreasing temperature. The uptake coefficients at seasonal temperatures were determined for the first time and were found to be sensitive to temperature. Finally, atmospheric implications of the role of temperature on the heterogeneous reaction of NO2 with mineral aerosol are discussed.


Subject(s)
Aluminum Oxide/chemistry , Nitrates/chemical synthesis , Nitrites/chemical synthesis , Nitrogen Dioxide/chemistry , Temperature , Nitrates/chemistry , Nitrites/chemistry
18.
J Phys Chem A ; 117(19): 3972-9, 2013 May 16.
Article in English | MEDLINE | ID: mdl-23600701

ABSTRACT

Heterogeneous reactions on mineral aerosols remain an important subject in atmospheric chemistry because of their role in altering the properties of particles and the budget of trace gases. Yet, the role of coadsorption of trace gases onto mineral aerosols and potential synergistic effects are largely uncertain, especially synergistic effects between inorganic and organic gas-phase pollutants. In this study, synergistic effects between HCOOH and SO2 were investigated for the first time using in situ diffuse-reflectance infrared Fourier transform spectroscopy (DRIFTS). It was found that the heterogeneous reaction of HCOOH is hindered significantly by coexisting SO2. The total amount of formate decreased, whereas the total amount of sulfate was not affected during coadsorption on the surface of α-Fe2O3. Futhermore, part of the formate on the surface was catalytically decomposed to CO2 by α-Fe2O3 with the help of SO2. These results suggest a possible mechanism for the observed correlations between sulfate and carboxylate in the atmosphere.


Subject(s)
Air Pollutants/chemistry , Ferric Compounds/chemistry , Formates/chemistry , Sulfates/chemistry , Sulfur Dioxide/chemistry , Adsorption , Aerosols , Atmosphere/chemistry , Catalysis , Kinetics , Spectroscopy, Fourier Transform Infrared
19.
BMC Musculoskelet Disord ; 14: 307, 2013 Oct 27.
Article in English | MEDLINE | ID: mdl-24161032

ABSTRACT

BACKGROUND: Individual studies have reported different results regarding the association of HLA alleles with RA in Chinese populations. This study was performed to systematically summarize results on the association of HLA-DRB1 with rheumatoid arthritis (RA) in China. METHODS: We examined the case-control studies concerned about the relationship between HLA-DRB1 and RA and differences of clinical and laboratory parameters between the HLA-DR4 (DR4)+ and DR4- in RA patients in Chinese populations. Odds ratios (ORs) and weighted mean difference (WMD) with corresponding 95% confidence intervals (CI) was used to describe the relationship. RESULTS: 22 studies with 1690 cases and 1793 controls were included. Chinese populations with RA had significantly higher frequencies of HLA-DRB1*04, *0401, *0404, *0405 and *0410 than controls (ORDRB1*04 =4.19, 95% CI =3.44-5.11, p<0.00001; ORDRB1*0401 =2.53, 95% CI =1.54-4.16, p=0.0003; ORDRB1*0404 =2.28, 95% CI =1.28-4.06, p=0.005; ORDRB1*0405=3.71, 95% CI =2.52-5.45, p<0.00001; ORDRB1*0410 =2.99, 95% CI =1.25-7.14, p=0.01 respectively). As to laboratory parameters, Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid factor (RF), Anti-cyclic citrullinated peptide antibodies (Anti-CCP ) in patients with DR4+ were higher than patients with DR4- (WMD=0.26, 95% CI =0.15-0.37, p<0.00001; WMD = 0.26, 95% CI =0.12-0.41, p=0.0005; WMD = 0.44, 95% CI =0.23-0.65, p<0.00001; WMD = 0.58, 95% CI =0.24-0.91, p=0.0007 respectively). As to clinical features, there was no difference in duration of morning stiffness, number of swollen joints, number of joint tenderness, X-ray phases and joint function between the DR4+ and DR4- in RA patients. CONCLUSIONS: It was found that HLA-DRB1*04, *0401, *0404, *0405 and *0410 are risk factors for RA in Chinese populations. ESR, CRP, RF, Anti-CCP are different between the DR4+ and DR4- in RA patients in Chinese populations, while there's no difference for indexes of clinical features.


Subject(s)
Arthritis, Rheumatoid/genetics , HLA-DRB1 Chains/genetics , Alleles , Asian People , Case-Control Studies , China , Genetic Predisposition to Disease , Humans
20.
J Environ Sci (China) ; 25(5): 933-43, 2013 May 01.
Article in English | MEDLINE | ID: mdl-24218823

ABSTRACT

A novel nanoadsorbent for the removal of heavy metal ions is reported. Cotton was first hydrolyzed to obtain cellulose nanocrystals (CNCs). CNCs were then chemically modified with succinic anhydride to obtain SCNCs. The sodic nanoadsorbent (NaSCNCs) was further prepared by treatment of SCNCs with saturated NaHCO3 aqueous solution. Batch experiments were carried out with SCNCs and NaSCNCs for the removal of Pb2+ and Cd2+. The effects of contact time, pH, initial adsorption concentration, coexisting ions and the regeneration performance were investigated. Kinetic studies showed that the adsorption equilibrium time of Pb2+ and Cd2+ was reached within 150 min on SCNCs and 5 min on NaSCNCs. The adsorption capacities of Pb2+ and Cd2+ on SCNCs and NaSCNCs increased with increasing pH. The adsorption isotherm was well fitted by the Langmuir model. The maximum adsorption capacities of SCNCs and NaSCNCs for Pb2+ and Cd2+ were 367.6 mg/g, 259.7 mg/g and 465.1 mg/g, 344.8 mg/g, respectively. SCNCs and NaSCNCs showed high selectivity and interference resistance from coexisting ions for the adsorption of Pb2+. NaSCNCs could be efficiently regenerated with a mild saturated NaCl solution with no loss of capacity after two recycles. The adsorption mechanisms of SCNCs and NaSCNCs were discussed.


Subject(s)
Cadmium/chemistry , Carboxylic Acids/chemistry , Cellulose/chemistry , Lead/chemistry , Nanoparticles/chemistry , Water Pollutants, Chemical/chemistry , Adsorption , Hydrogen-Ion Concentration , Recycling , Solutions
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