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1.
Mol Cancer ; 23(1): 89, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702722

ABSTRACT

Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture and intracellular content release. Originally investigated as a targeted therapy for cancer cells carrying oncogenic RAS mutations, ferroptosis induction now exhibits potential to complement chemotherapy, immunotherapy, and radiotherapy in various cancer types. However, it can lead to side effects, including immune cell death, bone marrow impairment, liver and kidney damage, cachexia (severe weight loss and muscle wasting), and secondary tumorigenesis. In this review, we discuss the advantages and offer an overview of the diverse range of documented side effects. Furthermore, we examine the underlying mechanisms and explore potential strategies for side effect mitigation.


Subject(s)
Ferroptosis , Neoplasms , Humans , Neoplasms/therapy , Neoplasms/etiology , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/genetics , Ferroptosis/genetics , Ferroptosis/drug effects , Animals , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology
2.
Adv Clin Exp Med ; 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38269477

ABSTRACT

BACKGROUND: Prostate cancer (PC) prevention is effectively achieved through its inhibition. Oridonin (ORD), an active diterpenoid isolated from Rabdosia rubescens, has been shown to have an inhibitory effect on PC cells, although its impact on PC is unknown. OBJECTIVES: The present work investigated the actions and probable mechanisms of ORD on cellular proliferation, apoptosis, PC, and the wingless-type MMTV integration site family member 2 (Wnt)/ß-catenin signaling pathway using the androgen-independent PC-3 cell line. MATERIAL AND METHODS: In this study, cell viability was analyzed with MTT assay method, apoptotic morphology determined using DAPI dye method, while protein (CD1333, OCT-4, Nanog, SOX-2 & Aldh1A1) and mRNA expressions were analyzed with western blotting and real time polymerase chain reaction (PCR). RESULTS: We demonstrated a concentration-dependent ORD inhibition of PC-3 cell proliferation and inhibition of induction apoptosis. Furthermore, ORD decreased PC-3 Wnt-2, phosphorylated glycogen synthase kinase-3 (p-GSK3), and ß-catenin protein levels and downregulated cyclin-D1 and c-myc messenger ribonucleic acid (mRNA). CONCLUSIONS: Oridonin inhibited proliferation and induced apoptosis in PC-3 cells, with the findings suggesting that it acted via the Wnt/ß-catenin pathway to exert its effects. This study demonstrates that ORD may impact PC.

3.
Angew Chem Int Ed Engl ; 63(5): e202308597, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38081137

ABSTRACT

The co-assembly naphthalimide/perylene diimide (NDINH/PDINH) supramolecular photocatalysts were successfully synthesized via a rapid solution dispersion method. A giant internal electric field (IEF) in co-assembly structure was built by the larger local dipole. NDINH coated on PDINH could reduce the reflected electric field over PDINH to improve its responsive activity to ultraviolet light. Resultantly, an efficient full-spectrum photocatalytic overall water splitting activity with H2 and O2 evolution rate of 317.2 and 154.8 µmol g-1 h-1 for NDINH/PDINH together with optimized O2 evolution rate with 2.61 mmol g-1 h-1 using AgNO3 as a sacrificial reagent were achieved. Meanwhile, its solar-to-hydrogen efficiency was enhanced to 0.13 %. The enhanced photocatalytic activity was primarily attributed to the IEF between NDINH and PDINH, significantly accelerating transfer and separation of photogenerated carriers. Additionally, a direct Z-Scheme pathway of carriers contributed to a high redox potential. The strategy provided a new perspective for the design of supramolecular photocatalysts.

4.
Cell Death Discov ; 9(1): 384, 2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37863956

ABSTRACT

The mechanism of nuclear size determination and alteration during normal lineage development and cancer pathologies which is not fully understood. As recently reported, chromatin modification can change nuclear morphology. Therefore, we screened a range of pharmacological chemical compounds that impact the activity of chromatin-modifying enzymes, in order to get a clue of the specific types of chromatin-modifying enzymes that remarkably effect nuclear size and shape. We found that interrupted activity of chromatin-modifying enzymes is associated with nuclear shape abnormalities. Furthermore, the activity of chromatin-modifying enzymes perturbs cell fate determination in cellular maintenance and lineage commitment. Our results indicated that chromatin-modifying enzyme regulates cell fate decision during lineage differentiation and is associate with nuclear size alteration.

5.
Cell Commun Signal ; 21(1): 274, 2023 10 05.
Article in English | MEDLINE | ID: mdl-37798762

ABSTRACT

BACKGROUND: Our previous study found that bone marrow-derived mesenchymal stem cells (BMSCs) promote Helicobacter pylori (H pylori)-associated gastric cancer (GC) progression by secreting thrombospondin-2 (THBS2). Extracellular vesicles (EVs) are important carriers for intercellular communication, and EVs secreted by BMSCs have been shown to be closely related to tumor development. The aim of this study was to investigate whether BMSC-derived microvesicles (MVs, a main type of EV) play a role in H. pylori-associated GC by transferring THBS2. METHODS: BMSCs and THBS2-deficient BMSCs were treated with or without the supernatant of H. pylori for 12 h at a multiplicity of infection of 50, and their EVs were collected. Then, the effects of BMSC-derived MVs and THBS2-deficient BMSC-derived MVs on the GC cell line MGC-803 were assessed by in vitro proliferation, migration, and invasion assays. In addition, a subcutaneous xenograft tumor model, a nude mouse intraperitoneal metastasis model, and a tail vein injection metastasis model were constructed to evaluate the effects of BMSC-derived MVs and THBS2-deficient BMSC-derived MVs on GC development and metastasis in vivo. RESULTS: BMSC-derived MVs could be readily internalized by MGC-803 cells. BMSC-derived MVs after H. pylori treatment significantly promoted their proliferation, migration and invasion in vitro (all P < 0.05) and promoted tumor development and metastasis in a subcutaneous xenograft tumor model, a nude mouse intraperitoneal metastasis model, and a tail vein injection metastasis model in vivo (all P < 0.05). The protein expression of THBS2 was significantly upregulated after H. pylori treatment in BMSC-derived MVs (P < 0.05). Depletion of the THBS2 gene reduces the tumor-promoting ability of BMSC-MVs in an H. pylori infection microenvironment both in vitro and in vivo. CONCLUSION: Overall, these findings indicate that MVs derived from BMSCs can promote H. pylori-associated GC development and metastasis by delivering the THBS2 protein. Video Abstract.


Subject(s)
Extracellular Vesicles , Helicobacter pylori , Mesenchymal Stem Cells , MicroRNAs , Stomach Neoplasms , Mice , Animals , Humans , Stomach Neoplasms/metabolism , Helicobacter pylori/genetics , Bone Marrow , Mice, Nude , Thrombospondins/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/genetics , Tumor Microenvironment
6.
ACS Appl Mater Interfaces ; 15(37): 44433-44443, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37682724

ABSTRACT

We explored the electrical activity and extremes inside individual suspended zinc oxide (ZnO) nanowires (NWs) (diameter: 50-550 nm, length: 5-50 µm) subjected to high forward bias-induced Joule heating using two-terminal current-voltage measurements. NWs were isolated using a reproducible nanometrology technique, employing a nanomanipulator inside a scanning electron microscope. Schottky behavior is observed between installed tips and ZnO NW. The suspended ZnO NWs exhibited an average electrical resistivity ρ (approximately 2.3 × 10-2 Ω cm) and a high electron density n (exceeding 1.89 × 1018 cm-3), comparable to that of InP NWs, GaN NWs, and InAs NWs (1018∼1019 cm-3), suggesting the potential to drive advancements in high-performance NW devices. A maximum breakdown current density (JBD) of ∼0.14 MA/cm2 and a maximum breakdown power density (PBD) of 6.93 mW/µm3 were obtained, both of which are higher than substrate-bound ZnO NWs and consistent with previously reported results obtained from probed ZnO NWs grown vertically on the substrate. Moreover, we discovered that NWs experienced thermal breakdown due to Joule heating and exploited this breakdown mechanism to further investigate the temperature distribution along the ZnO NWs, as well as its dependence on the electrical properties and thermal conductance of contact electrodes. Thermal conductance was determined to be ∼0.4 nW K-1 and ∼1.66 pW K-1 at the tungsten(W)-ZnO NW and platinum(Pt)-ZnO NW contacts, respectively. In addition, we measured the elastic modulus (130-171 GPa), which closely approximated bulk values. We also estimated the nanoindentation hardness to be between 5 and 10 GPa. This work provides valuable insights into the electrical activity and extreme mechanisms, thus providing a better understanding of the potentials and limitations associated with utilizing suspended NWs in 3D nanodevices.

8.
Commun Biol ; 6(1): 712, 2023 07 11.
Article in English | MEDLINE | ID: mdl-37433832

ABSTRACT

Proper organization of intracellular assemblies is fundamental for efficient promotion of biochemical processes and optimal assembly functionality. Although advances in imaging technologies have shed light on how the centrosome is organized, how its constituent proteins are coherently architected to elicit downstream events remains poorly understood. Using multidisciplinary approaches, we showed that two long coiled-coil proteins, Cep63 and Cep152, form a heterotetrameric building block that undergoes a stepwise formation into higher molecular weight complexes, ultimately generating a cylindrical architecture around a centriole. Mutants defective in Cep63•Cep152 heterotetramer formation displayed crippled pericentriolar Cep152 organization, polo-like kinase 4 (Plk4) relocalization to the procentriole assembly site, and Plk4-mediated centriole duplication. Given that the organization of pericentriolar materials (PCM) is evolutionarily conserved, this work could serve as a model for investigating the structure and function of PCM in other species, while offering a new direction in probing the organizational defects of PCM-related human diseases.


Subject(s)
Centrioles , Centrosome , Protein Serine-Threonine Kinases , Humans , Cell Cycle , Molecular Weight , Protein Domains , Protein Serine-Threonine Kinases/metabolism
9.
Am J Transl Res ; 15(6): 4228-4236, 2023.
Article in English | MEDLINE | ID: mdl-37434838

ABSTRACT

OBJECTIVE: To explore the relationship between glucose metabolism and acute radiation enteritis from chemoradiotherapy for rectal cancer. METHODS: In this retrospective study, the clinical data of 75 rectal cancer patients who received concurrent chemoradiotherapy in Binzhou Second People's Hospital from February 2019 to February 2022 were collected and analyzed. According to the Radiation Therapy Oncology Group (RTOG)/European Organization for Research on Treatment of Cancer (EORTC) radiation response grading criteria, the patients were classified into four groups with different glucose metabolism statuses: NGR (normal glucose regulation) group, IFG (impaired fasting glucose) group, IGT (impaired glucose tolerance) group, and DM (diabetes mellitus) group. Two-factor logistic regression was used to analyze whether IFG, IGT, or DM were risk factors for acute radiation enteritis. RESULTS: (1) The fasting plasma glucose (FPG, F=20.550, P < 0.001), 2-hour post-meal blood glucose (2hPG, F=14.920, P < 0.001), triglycerides (TG, F=3.355, P=0.024), high-density lipoprotein cholesterol (HDL-C) (F=4.109, P=0.010), low-density lipoprotein cholesterol (LDL-C, F=4.545, P=0.006), and systolic blood pressure (SBP, F=5.398, P=0.002) differed greatly among the NGR group, IFG group, IGT group, and DM group, all P < 0.05. (2) The incidence of acute radiation enteritis was 34.67% in the 75 patients, and in DM patients it was higher than in the NGR, IFG, or IGT patients (χ2=14.702, P=0.002). (3) There were significant differences in BMI (F=3.594, P=0.044) and DBP (F=3.954, P=0.033) among the asymptomatic group, mild group, and severe group (P < 0.05). (4) Body mass index (BMI) was positively correlated with acute radiation enteritis in IFG, IGT, and DM patients (OR=1.361, P=0.020). (5) DM was positively correlated with acute radiation enteritis (OR=6.167, P=0.039). CONCLUSIONS: DM was significantly correlated with acute radiation enteritis induced by concurrent chemoradiotherapy for rectal cancer, while IFG and IGT were not.

10.
J Hazard Mater ; 454: 131441, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37116326

ABSTRACT

A novel photocatalyst, Bi2WO6/NiO/Ag, with hierarchical flower-like Z-scheme heterojunction, which exhibited excellent stability and photocatalytic activity over a wide light spectrum, was firstly synthesized and used in the remediation of real oil sands process water (OSPW) and achieved complete removal of aromatics, classical naphthenic acids (NAs), and heteroatomic NAs after 6 h of photocatalytic treatment. The acute toxicity of OSPW was completely eliminated after only 2 h of treatment. h+ and ∙OH were found to be the major oxidative species in the photocatalytic system. The enhanced photocatalytic efficiency is the result of the unique Z-scheme electron transfer among electron mediators Ag, NiO, and Bi2WO6, which was supported by the in-situ irradiated XPS. The study benefits the design of engineered passive treatment approach for OSPW remediation through solar light-driven catalyst.

11.
Mol Cell ; 82(24): 4627-4646.e14, 2022 12 15.
Article in English | MEDLINE | ID: mdl-36417913

ABSTRACT

Cell lineage specification is accomplished by a concerted action of chromatin remodeling and tissue-specific transcription factors. However, the mechanisms that induce and maintain appropriate lineage-specific gene expression remain elusive. Here, we used an unbiased proteomics approach to characterize chromatin regulators that mediate the induction of neuronal cell fate. We found that Tip60 acetyltransferase is essential to establish neuronal cell identity partly via acetylation of the histone variant H2A.Z. Despite its tight correlation with gene expression and active chromatin, loss of H2A.Z acetylation had little effect on chromatin accessibility or transcription. Instead, loss of Tip60 and acetyl-H2A.Z interfered with H3K4me3 deposition and activation of a unique subset of silent, lineage-restricted genes characterized by a bivalent chromatin configuration at their promoters. Altogether, our results illuminate the mechanisms underlying bivalent chromatin activation and reveal that H2A.Z acetylation regulates neuronal fate specification by establishing epigenetic competence for bivalent gene activation and cell lineage transition.


Subject(s)
Chromatin , Histones , Histones/genetics , Histones/metabolism , Acetylation , Transcriptional Activation , Chromatin/genetics , Protein Processing, Post-Translational , Nucleosomes
12.
Water Environ Res ; 94(8): e10773, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35946784

ABSTRACT

Multi-isotope method was used to analyze the migration and transformation characteristics of nitrogen in groundwater in the center of a typical confined water basin, and a simplified isotope mixing model was established to quantify the contribution of potential nitrate sources in the center of the basin. Based on the water quality monitoring results, the contour map of nitrate concentration in groundwater in the center of the basin was drawn. The results showed that the nitrate concentration in groundwater in the center of the basin increased gradually from upstream to downstream. The high value area of nitrate concentration in phreatic water is mainly affected by agricultural activities and infiltration of sewage discharge from upstream urban areas. The high value area of nitrate concentration in confined water is mainly due to the water level depression funnel caused by large exploitation of confined water. The quantitative results of N-O isotope mixing model for potential nitrate sources show that the main recharge sources of groundwater in the center of the basin are atmospheric precipitation, agricultural irrigation water, and the lateral inflow of upstream groundwater. Agricultural irrigation water has the highest contribution rate of 67.01%. The main recharge sources of confined aquifer in the center of the basin are phreatic water leakage and lateral inflow of upstream confined water. The contribution rate of upstream confined water is between 45.55% and 56.35%, which is basically maintained at about 50%. Compared with the calculation results of D-O isotope mixing model, the accuracy of the established N-O isotope mixing model meets the basic requirements. The results of this study can provide technical reference and theoretical support for the identification and quantitative research of potential nitrate sources in groundwater under the same type of hydrogeological conditions. PRACTITIONER POINTS: Multiple isotope fingerprint comparison to identify nitrate source contribution ratio. Migration and transformation of nitrogen in the center of a typical confined water basin Simplified the traditional isotope mixing model to quickly quantify the source of contamination.


Subject(s)
Groundwater , Water Pollutants, Chemical , China , Environmental Monitoring/methods , Nitrates , Nitrogen , Nitrogen Isotopes/analysis , Water Pollutants, Chemical/analysis
13.
Mol Autism ; 13(1): 19, 2022 05 10.
Article in English | MEDLINE | ID: mdl-35538503

ABSTRACT

BACKGROUND: The zinc finger domain containing transcription factor Myt1l is tightly associated with neuronal identity and is the only transcription factor known that is both neuron-specific and expressed in all neuronal subtypes. We identified Myt1l as a powerful reprogramming factor that, in combination with the proneural bHLH factor Ascl1, could induce neuronal fate in fibroblasts. Molecularly, we found it to repress many non-neuronal gene programs, explaining its supportive role to induce and safeguard neuronal identity in combination with proneural bHLH transcriptional activators. Moreover, human genetics studies found MYT1L mutations to cause intellectual disability and autism spectrum disorder often coupled with obesity. METHODS: Here, we generated and characterized Myt1l-deficient mice. A comprehensive, longitudinal behavioral phenotyping approach was applied. RESULTS: Myt1l was necessary for survival beyond 24 h but not for overall histological brain organization. Myt1l heterozygous mice became increasingly overweight and exhibited multifaceted behavioral alterations. In mouse pups, Myt1l haploinsufficiency caused mild alterations in early socio-affective communication through ultrasonic vocalizations. In adulthood, Myt1l heterozygous mice displayed hyperactivity due to impaired habituation learning. Motor performance was reduced in Myt1l heterozygous mice despite intact motor learning, possibly due to muscular hypotonia. While anxiety-related behavior was reduced, acoustic startle reactivity was enhanced, in line with higher sensitivity to loud sound. Finally, Myt1l haploinsufficiency had a negative impact on contextual fear memory retrieval, while cued fear memory retrieval appeared to be intact. LIMITATIONS: In future studies, additional phenotypes might be identified and a detailed characterization of direct reciprocal social interaction behavior might help to reveal effects of Myt1l haploinsufficiency on social behavior in juvenile and adult mice. CONCLUSIONS: Behavioral alterations in Myt1l haploinsufficient mice recapitulate several clinical phenotypes observed in humans carrying heterozygous MYT1L mutations and thus serve as an informative model of the human MYT1L syndrome.


Subject(s)
Autism Spectrum Disorder , Behavior, Animal , Nerve Tissue Proteins , Obesity , Transcription Factors , Animals , Autism Spectrum Disorder/genetics , Behavior, Animal/physiology , Haploinsufficiency , Mice , Nerve Tissue Proteins/genetics , Transcription Factors/genetics
14.
J Microbiol ; 60(6): 627-639, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35437622

ABSTRACT

Virulence factor gamma-glutamyltransferase (GGT) of H. pylori consumes glutamine (Gln) in the stomach to decrease the tricarboxylic acid metabolite alpha-ketoglutarate (α-kg) and alter the downstream regulation of α-kg as well as cellular biological characteristics. Our previous research indicated that under H. pylori infection, mesenchymal stem cells (MSCs) migrated to the stomach and participated in gastric cancer (GC) development either by differentiating into epithelial cells or promoting angiogenesis. However, how MSCs themselves participate in H. pylori-indicated GC remains unclear. Therefore, a GGT knockout H. pylori strain (Hp-KS-1) was constructed, and downstream histone H3K9 and H3K27 methylation and the PI3K/AKT signaling pathway of α-kg were detected using Western blotting. The biological characteristics of MSCs were also examined. An additive α-kg supplement was also added to H. pylori-treated MSCs to investigate alterations in these aspects. Compared to the control and Hp-KS-1 groups, H. pylori-treated MSCs reduced Gln and α-kg, increased H3K9me3 and H3K27me3, activated the PI3K-AKT signaling pathway, and promoted the proliferation, migration, self-renewal, and pluripotency of MSCs. The addition of α-kg rescued the H. pylori-induced alterations. Injection of MSCs to nude mice resulted in the largest tumors in the H. pylori group and significantly reduced tumor sizes in the Hp-KS-1 and α-kg groups. In summary, GGT of H. pylori affected MSCs by interfering with the metabolite α-kg to increase trimethylation of histone H3K9 and H3K27, activating the PI3K/AKT signaling pathway, and promoting proliferation, migration, self-renewal, and pluripotency in tumorigenesis, elucidating the mechanisms of MSCs in GC development.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Mesenchymal Stem Cells , Stomach Neoplasms , Animals , Cell Proliferation/physiology , Helicobacter Infections/pathology , Histones/metabolism , Methylation , Mice , Mice, Nude , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Stomach Neoplasms/metabolism , gamma-Glutamyltransferase/genetics , gamma-Glutamyltransferase/metabolism
15.
Oncol Lett ; 23(4): 108, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35242236

ABSTRACT

Multiple myeloma is the second most commonly diagnosed hematologic malignancy. As an incurable disease, the molecular mechanisms underlying its many aspects remain unclear. Intracellular calcium ion is an essential signaling molecule that modulates malignant cell behavior, and abnormal regulation of cellular calcium homeostasis may promote cancer cell survival and induce drug resistance. Transient receptor potential (TRP) cation channels are a superfamily of non-selective Ca2+-permeable channels that regulate intracellular calcium signaling and are involved in the regulation of various characteristics of cancer cells. Emerging evidence shows a close connection between TRP channels and multiple myeloma. This review summarizes the roles of TRP channels in multiple myeloma progression, metastasis, bone destruction, and drug resistance. TRPV1 and TRPV2 orchestrate the progression of multiple myeloma, while TRPM7 promotes myeloma cell dissemination and spreading. TRPV2 and TRPV4, that activate osteoclasts, contribute to the development of osteolytic bone disease caused by multiple myeloma. Both TRPV1 inhibition and TRPV2 activation synergize with bortezomib in the chemotherapy of multiple myeloma, and TRPC1 can determine the responsiveness of multiple myeloma to MTI-101, a cyclic beta-hairpin peptide. Antagonizing TRPA1 can alleviate bortezomib-induced painful peripheral neuropathy. Future studies in this field may identify certain TRP channels as markers or therapeutic targets for predicting the prognosis, preventing progression, and improving drug responsiveness in patients with multiple myeloma.

16.
Chemosphere ; 286(Pt 1): 131543, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34303045

ABSTRACT

Heavy metal ions in chelated forms have aroused great concerns because of their high solubility, poor biodegradation and extreme stability. In this research, an efficient strategy, interior microelectrolysis-Fenton-recycle ferrite (IM-Fenton-RF), was developed to treat simulated electroplating wastewater containing chelated copper at room temperature. The decomplexation of chelated copper was carried out by both interior microelectrolysis and Fenton reactions. IM process can not only partly degrade the complexes of chelated copper via the microelectrolysis reaction but also it produces Fe2+ ions for the Fenton reaction. After decomplexation, the IM-Fenton effluent directly flowed into the RF reactor for copper ions removal. Under optimum reaction conditions (reflux ratio = 0.37, Fe2+ concentration = 9.20 g/L at pH 10.18), 99.9% copper was removed by the IM-Fenton-RF system. The produced IM-Fenton-RF sludge is based on ferrite precipitate and has several advantages over metal hydroxides sludge. Ferrite sludge is stable owing to the stability of ferrite's crystal structure, while the toxicity characteristic leaching procedure (TCLP) test meets relevant standards. The sedimentation rate and volume of ferrite sludge were 3.86 times faster and 11.0 times lower than those of metal hydroxides sludge. Furthermore, the yielding sludge of ferrite can be recovered and utilized for the synthesis of Fe-C metallic species, the main compound of IM packing for interior microelectrolysis reaction. All these results show that a combination of IM-Fenton and RF is an effective approach to treat wastewater containing chelated copper, showing great potential for industrial applications.


Subject(s)
Metals, Heavy , Wastewater , Electroplating , Ferric Compounds
17.
Cell Prolif ; 54(10): e13114, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34435402

ABSTRACT

OBJECTIVES: Bone marrow-derived cells (BMDCs), especially mesenchymal stem cells (MSCs), may be involved in the development of Helicobacter pylori-associated gastric cancer (GC) in mice, but the specific mechanism remains unclear, and evidence from human studies is lacking. MATERIALS AND METHODS: To verify the role of BM-MSCs in H pylori-associated GC, green fluorescent protein (GFP)-labelled BM-MSCs were transplanted into the subserosal layers of the stomach in a mouse model of chronic H pylori infection. Three months post-transplantation, the mice were sacrificed, and the gastric tissues were subjected to histopathological and immunofluorescence analyses. In addition, we performed fluorescence in situ hybridization (FISH) and immunofluorescence analyses of gastric tissue from a female patient with H pylori infection and a history of acute myeloid leukaemia who received a BM transplant from a male donor. RESULTS: In mice with chronic H pylori infection, GFP-labelled BM-MSCs migrated from the serous layer to the mucosal layer and promoted GC progression. The BM-MSCs differentiated into pan-cytokeratin-positive epithelial cells and α-smooth muscle actin-positive cancer-associated fibroblasts (CAFs) by secreting the protein thrombospondin-2. FISH analysis of gastric tissue from the female patient revealed Y-chromosome-positive cells. Immunofluorescence analyses further confirmed that Y-chromosome-positive cells showed positive BM-MSCs marker. These results suggested that allogeneic BMDCs, including BM-MSCs, can migrate to the stomach under chronic H pylori infection. CONCLUSIONS: Taken together, these findings imply that BM-MSCs participate in the development of chronic H pylori-associated GC by differentiating into both gastric epithelial cells and CAFs.


Subject(s)
Bone Marrow Cells/metabolism , Bone Marrow/metabolism , Gastric Mucosa/metabolism , Helicobacter Infections/metabolism , Mesenchymal Stem Cells/metabolism , Stomach Neoplasms/metabolism , Thrombospondins/metabolism , Animals , Bone Marrow/microbiology , Cell Differentiation/physiology , Cell Proliferation/physiology , Epithelial Cells/metabolism , Epithelial Cells/microbiology , Female , Gastric Mucosa/microbiology , Helicobacter Infections/microbiology , Helicobacter pylori/pathogenicity , Humans , Male , Mice , Mice, Inbred BALB C , Stomach Neoplasms/microbiology
18.
Sci Prog ; 104(3): 368504211026761, 2021.
Article in English | MEDLINE | ID: mdl-34463600

ABSTRACT

Identification of the vulnerabilities in the structural stiffness is one of the most crucial issues in improving this property of machine tools. In this paper, the Flexibility Matrix Diagonal element method, based on hammer testing, is proposed as an effective approach to identifying the stiffness weakness of cantilever structures. To verify the proposed method, the element stiffness weakening is used to simulate the weak parts regarding stiffness. Several scenarios, with single and multiple weakness points, including various noise levels, are studied, using finite element simulations. Next, a novel method, to measure the accuracy of the algorithm and quantify the weakness level, under noise conditions, is proposed. The advantage of this method, compared to the ones based on Flexibility Difference Method, is the higher identification accuracy under noise interference. Finally, the cantilever beam with elastic support is experimentally studied. The natural frequencies and modal shapes are obtained, according to the singular value decomposition method, to establish the flexibility matrix. In addition, using only the lowest three modes, a series of numerical examples and experiments are provided, to illustrate the validity and the considerable practical engineering value of the method.

19.
Sci Prog ; 104(2): 368504211016969, 2021.
Article in English | MEDLINE | ID: mdl-34034575

ABSTRACT

Determining the weak parts of a structure is one of the key issues in the field of machine tool stiffness improvement. However, studies show that overcoming the static deformation with acquisition difficulty is a complex problem in practical structures. This study considers the machine tool cantilever structure, as a cantilever beam and bar structure, where the objective is to propose a weakness index, to identify the weak part, using system reconstruction to extract the measured static deformation data and the fitting data. Stiffness reduction is used to simulate weak parts, while the effectiveness of the method is evaluated, in the case of various weakness values and of different noise levels, using the finite element simulation approach. The validity of the proposed method is illustrated through comparison of the theoretical results to the experimental ones, using the cantilever structure of a test machine tool. The research content provides some means of improving the machining accuracy of machine tools.

20.
Genes (Basel) ; 12(3)2021 03 14.
Article in English | MEDLINE | ID: mdl-33799396

ABSTRACT

F-box genes play an important role in the growth and development of plants, but there are few studies on its role in a plant's response to abiotic stresses. In order to further study the functions of F-box genes in tomato (Solanum lycopersicum, Sl), a total of 139 F-box genes were identified in the whole genome of tomato using bioinformatics methods, and the basic information, transcript structure, conserved motif, cis-elements, chromosomal location, gene evolution, phylogenetic relationship, expression patterns and the expression under cold stress, drought stress, jasmonic acid (JA) treatment and salicylic acid (SA) treatment were analyzed. The results showed that SlFBX genes were distributed on 12 chromosomes of tomato and were prone to TD (tandem duplication) at the ends of chromosomes. WGD (whole genome duplication), TD, PD (proximal duplication) and TRD (transposed duplication) modes seem play an important role in the expansion and evolution of tomato SlFBX genes. The most recent divergence occurred 1.3042 million years ago, between SlFBX89 and SlFBX103. The cis-elements in SlFBX genes' promoter regions were mainly responded to phytohormone and abiotic stress. Expression analysis based on transcriptome data and qRT-PCR (Real-time quantitative PCR) analysis of SlFBX genes showed that most SlFBX genes were differentially expressed under abiotic stress. SlFBX24 was significantly up-regulated at 12 h under cold stress. This study reported the SlFBX gene family of tomato for the first time, providing a theoretical basis for the detailed study of SlFBX genes in the future, especially the function of SlFBX genes under abiotic stress.


Subject(s)
Evolution, Molecular , Gene Expression Regulation, Plant , Multigene Family , Phylogeny , Plant Proteins , Solanum lycopersicum , Chromosomes, Plant/genetics , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Plant Proteins/biosynthesis , Plant Proteins/genetics , Stress, Physiological
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