A correlation study of adhesion G protein-coupled receptors as potential therapeutic targets for breast cancer.

BACKGROUND: Adhesion G protein-coupled receptors (aGPCRs), a distinctive subset of the G protein-coupled receptor (GPCR) superfamily, play crucial roles in various physiological and pathological processes, with implications in tumor development. Despite the global prevalence of breast cancer (BRCA), specific aGPCRs as potential drug targets or biomarkers remain underexplored. METHODS: UALCAN, GEPIA, Kaplan-Meier Plotter, MethSurv, cBiopportal, String, GeneMANIA, DAVID, Timer, Metascape, and qPCR were applied in this work. RESULTS: Our analysis revealed significantly increased transcriptional levels of ADGRB2, ADGRC1, ADGRC2, ADGRC3, ADGRE1, ADGRF2, ADGRF4, and ADGRL1 in BRCA primary tumors. Further analysis indicated a significant correlation between the expressions of certain aGPCRs and the pathological stage of BRCA. High expression of ADGRA1, ADGRF2, ADGRF4, ADGRG1, ADGRG2, ADGRG4, ADGRG6, and ADGRG7 was significantly correlated with poor overall survival (OS) in BRCA patients. Additionally, high expression of ADGRF2 and ADGRF4 indicated inferior recurrence-free survival (RFS) in BRCA patients. The RT-qPCR experiments also confirmed that the mRNA levels of ADGRF2 and ADGRF4 were higher in BRCA cells and tissues. Functional analysis highlighted the diverse roles of aGPCRs, encompassing GPCR signaling and metabolic energy reserves. Moreover, aGPCRs may exert influence or actively participate in the development of BRCA through their impact on immune status. CONCLUSION: aGPCRs, particularly ADGRF2 and ADGRF4, hold promise as immunotherapeutic targets and prognostic biomarkers in BRCA.

Recent progress in analytical strategies of arsenic-binding proteomes in living systems.

Arsenic (As) is one of the most concerning elements due to its high exposure risks to organisms and ecosystems. The interaction between arsenicals and proteins plays a pivotal role in inducing their biological effects on living systems, e.g., arsenicosis. In this review article, the recent advances in analytical techniques and methods of As-binding proteomes were well summarized and discussed, including chromatographic separation and purification, biotin-streptavidin pull-down probes, in situ imaging using novel fluorescent probes, and protein identification. These analytical technologies could provide a growing body of knowledge regarding the composition, level, and distribution of As-binding proteomes in both cells and biological samples, even at the organellar level. The perspectives on analysis of As-binding proteomes are also proposed, e.g., isolation and identification of minor proteins, in vivo targeted protein degradation (TPD) technologies, and spatial As-binding proteomics. The application and development of sensitive, accurate, and high-throughput methodologies of As-binding proteomics would enable us to address the key molecular mechanisms underlying the adverse health effects of arsenicals.

Intelligent Microsystem for Sound Event Recognition in Edge Computing Using End-to-End Mesh Networking.

Wireless acoustic sensor networks (WASNs) and intelligent microsystems are crucial components of the Internet of Things (IoT) ecosystem. In various IoT applications, small, lightweight, and low-power microsystems are essential to enable autonomous edge computing and networked cooperative work. This study presents an innovative intelligent microsystem with wireless networking capabilities, sound sensing, and sound event recognition. The microsystem is designed with optimized sensing, energy supply, processing, and transceiver modules to achieve small size and low power consumption. Additionally, a low-computational sound event recognition algorithm based on a Convolutional Neural Network has been designed and integrated into the microsystem. Multiple microsystems are connected using low-power Bluetooth Mesh wireless networking technology to form a meshed WASN, which is easily accessible, flexible to expand, and straightforward to manage with smartphones. The microsystem is 7.36 cm3 in size and weighs 8 g without housing. The microsystem can accurately recognize sound events in both trained and untrained data tests, achieving an average accuracy of over 92.50% for alarm sounds above 70 dB and water flow sounds above 55 dB. The microsystems can communicate wirelessly with a direct range of 5 m. It can be applied in the field of home IoT and border security.

Investigation of Self-Powered IoT Sensor Nodes for Harvesting Hybrid Indoor Ambient Light and Heat Energy.

Sensor nodes are critical components of the Internet of Things (IoT). Traditional IoT sensor nodes are typically powered by disposable batteries, making it difficult to meet the requirements for long lifetime, miniaturization, and zero maintenance. Hybrid energy systems that integrate energy harvesting, storage, and management are expected to provide a new power source for IoT sensor nodes. This research describes an integrated cube-shaped photovoltaic (PV) and thermal hybrid energy-harvesting system that can be utilized to power IoT sensor nodes with active RFID tags. The indoor light energy was harvested using 5-sided PV cells, which could generate 3 times more energy than most current studies using single-sided PV cells. In addition, two vertically stacked thermoelectrical generators (TEG) with a heat sink were utilized to harvest thermal energy. Compared to one TEG, the harvested power was improved by more than 219.48%. In addition, an energy management module with a semi-active configuration was designed to manage the energy stored by the Li-ion battery and supercapacitor (SC). Finally, the system was integrated into a 44 mm × 44 mm × 40 mm cube. The experimental results showed that the system was able to generate a power output of 192.48 µW using indoor ambient light and the heat from a computer adapter. Furthermore, the system was capable of providing stable and continuous power for an IoT sensor node used for monitoring indoor temperature over a prolonged period.

Toxic effects of polystyrene nanoplastics and polybrominated diphenyl ethers to zebrafish (Danio rerio).

Nanoplastics (NPs) are good carriers of persistent organic pollutants (POPs) such as polybrominated diphenyl ethers (PBDEs), and can alter their bioavailability and toxic impacts to aquatic organisms. This study highlights the single and combined toxic effects of polystyrene nanoplastics (PS-NPs) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, one of the dominant congeners of PBDEs) on zebrafish embryos after an exposure duration of up to 120 hpf. Results showed that PS-NPs and BDE-47 co-exposure exacerbated the morphological deformities in terms of pericardial edema, yolk sac edema and curved tail in zebrafish larvae. Compared to BDE-47 single exposure, the combined exposure caused lower survival rates, shorter body lengths, and accelerated spontaneous movements. Further, PS-NPs were quickly aggregated on the surface of the embryonic chorions covered almost the entire membrane at 12 and 48 hpf, and concentration dependent accumulation was also found in the brain, mouth, trunk, gills, heart, liver and gastrointestinal tract at the larval stages. During the recovery period (7 days), PS-NPs were released from all the organs, with the highest elimination from the gastrointestinal tract. Histopathological examination revealed that co-exposure caused greater damage to retinal structures, muscle fibers and cartilage tissues. Responses of hypothalamic-pituitary-thyroid axis (CRH, TSHß, NIS, TTR, Dio2, TG, TRα and TRß) and reproduction (Esr2 and Vtg1) related genes were also investigated, and results showed that the co-exposure induced more significant upregulated expressions of TSHß, TG, Doi 2, and TRß, compared to BDE-47 single exposure. In conclusion, co-exposure to NPs and BDE-47 exacerbated developmental and thyroid toxicity in zebrafish, generally elucidating the toxicological effects mediated by complex chemical interactions between NPs with POPs in the freshwater environment.

Identification of ribosomal protein L24 (RPL24) from the oriental river prawn, Macrobrachium nipponense, and its roles in ovarian development.

Ribosomal proteins exhibit various extraribosomal functions in addition to their roles in protein synthesis. In this study, complementary DNA (cDNA) of ribosomal protein L24 in Macrobrachium nipponense (MnRPL24) was isolated, and its role in ovarian development was investigated using quantitative real-time PCR (qPCR), immunohistochemistry (IHC), RNA interference (RNAi) and histological observations. The complete cDNA of MnRPL24 is 564 base pairs (bps) and contains a 486 bp open reading frame (ORF) encoding 162 amino acids (aas). The highest expression level of MnRPL24 among eight tissues was found in the ovary, specifically in the stage I ovary. The MnRPL24 protein existed in the cytoplasm and nucleus of developing oocytes, and also existed in the cytoplasm of follicle cells in developing ovaries. After MnRPL24 knockdown by RNAi, the expression levels of vitellogenin (Vg), vitellogenin receptor (Vgr), cyclin-dependent kinase 2 (Cdc2) and M-phase cyclin (Cyclin B) genes and the gonadsomatic index (GSI) did not show the typical trend of gradually elevation with ovarian development and finally decrease in the later stage of ovarian cycle. Moreover, the oviposition rate (OR) was downregulated, and oocyte development was delayed after MnRPL24 knockdown. After eyestalk ablation, the MnRPL24 expression level was considerably elevated in the initial stages and decreased in the late stage of the ovarian development cycle. This investigation illustrates a possible regulatory role of MnRPL24 in the ovarian development of M. nipponense, and MnRPL24 may act as a stimulator of early ovarian development.

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Chronic stress is a serial of non-specific neuroendocrine reactions in the body when stimulated by stressors for a long time, which has been shown to have a significant effect on tumor development. Chronic stress can activate the hypothalamus-pituitary-adrenal axis and the sense-adrenal myelin system, promote catecholamine and adrenal corticosteroid secretion, regulate the downstream pathways at all levels, and modulate the secretion of immune cells and immune factors, inhibit protective immune response, and induce inflammation, thus promoting tumor cell proliferation and metastasis. Some drugs and psychotherapy can alleviate the patient's stress state, block the nerve signal transmission at all levels of access, regulate the immune system, or can become an effective means to intervene in chronic stress in tumor patients for clinical treatment to provide reference for intervention ideas. However, due to lack of relevant clinical trials, the clinical intervention effect of various drugs and psychotherapy is uncertain and needs more studies to verify the effect.

Occurrence of antibiotics and their associations with antibiotic resistance genes and bacterial communities in Guangdong coastal areas.

The concentration of 8 antibiotics and 21 antibiotic resistance genes were investigated in the coastal areas of Guangdong, China. Total concentrations of antibiotics ranged from 0.43 ng/L to 1040.31 ng/L. The concentrations of tetracyclines were much higher than that of sulfonamides in most sampling sites. The abundance of target antibiotic resistance genes ranged from 1.82 × 105 to 5.9 × 109 copies/mL and tetM accounted for the highest percentages of detected antibiotic resistance genes in most sampling sites. Furthermore, the dominant phyla in water samples were Proteobacteria, Bacteroidetes and Actinobacteria. The relationship between antibiotics, antibiotic resistance genes, and bacterial communities was also investigated. As a result, the abundance of sul1 was positively correlated with the concentration of sulfadiazine, sulfamethoxazole and sulfonamide p-methyl oxypyrimidine. Besides, sulfonamide p-methyl oxypyrimidine, sulfadiazine and p-aminobenzenesulfonamide were significantly correlated with the bacterial communities. These findings suggested that the residues of antibiotics in coastal areas of Guangdong affect the distribution of antibiotic resistance genes and alter the microbial communities.

Improving Hydrophilicity and Inducing Bone-Like Apatite Formation on PPBES by Polydopamine Coating for Biomedical Application.

Copoly(phthalazinone biphenyl ether sulfone) (PPBES) as a commercially available polyarylether is a promising orthopaedic implant material because its mechanical properties are similar to bone. However, the bioinert surface of polyarylether causes some clinical problems after implantation, which limits its application as an implant material. In this study, the surface of PPBES was modified by a biomineralization method of polydopamine-assisted hydroxyapatite formation (pHAF) to enhance its cytocompatibility. Polydopamine (PDA) coating, inspired by the adhesion mechanism of mussels, can readily endow PPBES with high hydrophilicity and the ability to integrate via the bone-like apatite coating. PPBES and PDA-coated PPBES were evaluated by scanning electronic microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. The water contact angles were reduced significantly after coating with PDA. PDA was successfully synthesized on PPBES and more PDA was obtained by increasing the temperature. Bone-like apatite on PPBES (apatite-coated PPBES) was confirmed by SEM and transmission electron microscopy (TEM). The cytotoxicity of pristine PPBES and apatite-coated PPBES were characterized by culturing of NIH-3T3 cells. Bone-like apatite synthesized by pHAF could further enhance cytocompatibility in vitro. This study provides a promising alternative for biofunctionalized PPBES with improved cytocompatibility for bone implant application.

Divergent Phenotypes of Human Regulatory T Cells Expressing the Receptors TIGIT and CD226.

Regulatory T cells (Tregs) play a central role in counteracting inflammation and autoimmunity. A more complete understanding of cellular heterogeneity and the potential for lineage plasticity in human Treg subsets may identify markers of disease pathogenesis and facilitate the development of optimized cellular therapeutics. To better elucidate human Treg subsets, we conducted direct transcriptional profiling of CD4(+)FOXP3(+)Helios(+) thymic-derived Tregs and CD4(+)FOXP3(+)Helios(-) T cells, followed by comparison with CD4(+)FOXP3(-)Helios(-) T conventional cells. These analyses revealed that the coinhibitory receptor T cell Ig and ITIM domain (TIGIT) was highly expressed on thymic-derived Tregs. TIGIT and the costimulatory factor CD226 bind the common ligand CD155. Thus, we analyzed the cellular distribution and suppressive activity of isolated subsets of CD4(+)CD25(+)CD127(lo/-) T cells expressing CD226 and/or TIGIT. We observed TIGIT is highly expressed and upregulated on Tregs after activation and in vitro expansion, and is associated with lineage stability and suppressive capacity. Conversely, the CD226(+)TIGIT(-) population was associated with reduced Treg purity and suppressive capacity after expansion, along with a marked increase in IL-10 and effector cytokine production. These studies provide additional markers to delineate functionally distinct Treg subsets that may help direct cellular therapies and provide important phenotypic markers for assessing the role of Tregs in health and disease.

Identification of tubular injury microRNA biomarkers in urine: comparison of next-generation sequencing and qPCR-based profiling platforms.

BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate protein levels post-transcriptionally. miRNAs play important regulatory roles in many cellular processes and have been implicated in several diseases. Recent studies have reported significant levels of miRNAs in a variety of body fluids, raising the possibility that miRNAs could serve as useful biomarkers. Next-generation sequencing (NGS) is increasingly employed in biomedical investigations. Although concordance between this platform and qRT-PCR based assays has been reported in high quality specimens, information is lacking on comparisons in biofluids especially urine. Here we describe the changes in miRNA expression patterns in a rodent model of renal tubular injury (gentamicin). Our aim is to compare RNA sequencing and qPCR based miRNA profiling in urine specimen from control and rats with confirmed tubular injury. RESULTS: Our preliminary examination of the concordance between miRNA-seq and qRT-PCR in urine specimen suggests minimal agreement between platforms probably due to the differences in sensitivity. Our results suggest that although miRNA-seq has superior specificity, it may not detect low abundant miRNAs in urine samples. Specifically, miRNA-seq did not detect some sequences which were identified by qRT-PCR. On the other hand, the qRT-PCR analysis was not able to detect the miRNA isoforms, which made up the majority of miRNA changes detected by NGS. CONCLUSIONS: To our knowledge, this is the first time that miRNA profiling platforms including NGS have been compared in urine specimen. miRNAs identified by both platforms, let-7d, miR-203, and miR-320, may potentially serve as promising novel urinary biomarkers for drug induced renal tubular epithelial injury.

Molecular and functional characterization of ribosome protein S24 in ovarian development of Macrobrachium nipponense.

Ribosomal proteins (RPs) have mang extraribosomal functions including regulation of ovarian development in some organisms. In order to solve the problem of rapid ovarian maturation in Macrobrachium nipponense aquaculture, this study identified a RPS24 (MnRPS24) gene from M. nipponense, which encodes a protein of ßßαßαααα folding structure type. MnRPS24 exhibited the greatest expressions in the female adult stage among the six growth stages, in the ovary among the nine tissues, and in the stage I ovary among the six ovarian development stages. The MnRPS24 protein located in the cytoplasm of oogonia, previtellogenic and early-vitellogenic oocytes, and the follicular cells surrounding the oocytes. The expression of the vitellogenin (MnVg), vitellogenin receptor (MnVgr), cell cycle protein B (MnCyclin B) and cell division cyclin 2 (MnCdc2) genes were increased by recombinant MnRPS24 protein incubation. Conversely, the expression of the Wee1 kinase (MnWee1) gene was decreased. MnRPS24 gene silencing downregulated the expression for MnVg, MnVgr, MnCyclin B and MnCdc2 and upregulated the expression for MnWee1. Furthermore, MnRPS24 gene silencing delayed the vitellogenesis of oocytes, halting the progression of ovarian development. The findings of this research demonstrate that MnRPS24 could potentially function as a stimulator in promoting the development of ovaries in M. nipponense.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Adjuvant intra-arterial thrombolysis during mechanical thrombectomy is an effective means of improving outcomes for patients with large vessel occlusion stroke: A systematic review and meta-analysis.

OBJECTIVE: It is unknown whether adjunctive intra-arterial thrombolysis (IAT) during mechanical thrombectomy (MT) improves outcomes in patients with large vessel occlusion (LVO) stroke. This systematic review and meta-analysis aimed to compare the safety and efficacy of MT with and without IAT for the treatment of LVO stroke. METHODS: A systematic literature search of PubMed, Embase, and the Cochrane Library was conducted to identify studies that compared rates of 3-month functional independence (modified Rankin Scale score 0-2), successful revascularization, symptomatic intracranial hemorrhage, and 3-month mortality for MT+IAT and MT alone. Meta-analyses were performed using random effects models, and effect sizes were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was assessed with Cochran's Q test and I2 statistic. RESULTS: Twelve studies met eligibility criteria, comprising one randomized controlled trial and 11 observational cohort studies involving 2584 patients. Compared to MT alone, MT+IAT had a 43% higher odds of 3-month functional independence (OR 1.43, 95% CI 1.11-1.83; I2 =21%) and a 23% decrease in odds for 3-month mortality (OR 0.77, 95% CI 0.60-0.99; I2 =0%). There were no differences in successful revascularization (OR 1.39, 95% CI 0.89-2.17; I2 =57%) or symptomatic intracranial hemorrhage (OR 0.87, 95% CI 0.56-1.35; I2 =6%) between the two groups. CONCLUSIONS: The present study has demonstrated that, compared with MT alone, the use of adjunct IAT during MT in patients with LVO stroke resulted in better functional outcomes and lower mortality.

PDA-BPs integrated mussel-inspired multifunctional hydrogel coating on PPENK implants for anti-tumor therapy, antibacterial infection and bone regeneration.

Currently, many cancer patients with bone defects are still threatened by tumor recurrence, postoperative bacterial infection, and massive bone loss. Many methods have been studied to endow bone implants with biocompatibility, but it is difficult to find an implant material that can simultaneously solve the problems of anticancer, antibacterial and bone promotion. Here, a multifunctional gelatin methacrylate/dopamine methacrylate adhesive hydrogel coating containing 2D black phosphorus (BP) nanoparticle protected by polydopamine (pBP) is prepared by photocrosslinking to modify the surface of poly (aryl ether nitrile ketone) containing phthalazinone (PPENK) implant. The multifunctional hydrogel coating works in conjunction with pBP, which can deliver drug through photothermal mediation and kill bacteria through photodynamic therapy at the initial phase followed by promotion of osteointegration. In this design, photothermal effect of pBP control the release of doxorubicin hydrochloride loaded via electrostatic attraction. Meanwhile, pBP can generate reactive oxygen species (ROS) to eliminate bacterial infection under 808 nm laser. In the slow degradation process, pBP not only effectively consumes excess ROS and avoid apoptosis induced by ROS in normal cells, but also degrade into PO43- to promote osteogenesis. In summary, nanocomposite hydrogel coatings provide a promising strategy for treatment of cancer patients with bone defects.

Stabilization of Apatite Coatings on PPENK Surfaces by Mechanical Interlocking to Promote Bioactivity and Osseointegration In Vivo.

Apatite coatings with high stability can effectively improve the surface bioactivity and osteogenic activity of implant materials. In clinical practice, the ability of apatite coatings to bond with the substrate is critical to the effect of implants. Here, we propose a strategy to construct a three-dimensional (3D) nanoporous structure on the surface of a poly(phthalazinone ether nitrile ketone) (PPENK) substrate and introduce a polydopamine (PDA) coating with grafted phosphonate groups to enhance the overall deposition of a bone-like apatite coating in the 3D nanoporous structure during mineralization. This method leads to a mechanical interlocking between the apatite coating and the substrate, which increases the stability of the apatite coating. The apatite coating confers a better bioactive surface to PPENK and also promotes osteogenic differentiation and adhesion of MC3T3-E1 osteoblasts in vitro. The samples are then implanted into rat femurs to characterize in vivo osseointegration. Micro-CT data and histological staining of tissue sections reveal that PPENK with a stable apatite coating induces less fibrous capsule formation and no inflammatory response and promotes osteogenic differentiation and bone-bonding strength. This enhances the long-term use of PPENK implant materials and shows great potential for clinical application as orthopedic implants.

LiNbO3 dynamic memristors for reservoir computing.

Information in conventional digital computing platforms is encoded in the steady states of transistors and processed in a quasi-static way. Memristors are a class of emerging devices that naturally embody dynamics through their internal electrophyiscal processes, enabling nonconventional computing paradigms with enhanced capability and energy efficiency, such as reservoir computing. Here, we report on a dynamic memristor based on LiNbO3. The device has nonlinear I-V characteristics and exhibits short-term memory, suitable for application in reservoir computing. By time multiplexing, a single device can serve as a reservoir with rich dynamics which used to require a large number of interconnected nodes. The collective states of five memristors after the application of trains of pulses to the respective memristors are unique for each combination of pulse patterns, which is suitable for sequence data classification, as demonstrated in a 5 × 4 digit image recognition task. This work broadens the spectrum of memristive materials for neuromorphic computing.

Constructing interactive networks of functional genes and metabolites to uncover the cellular events related to colorectal cancer cell migration induced by arsenite.

Tumor cell migration induced by arsenite (iAsIII) is closely associated with cancer progression. However, transcriptomic and metabolic traits of migrative human cells exposed to iAsIII remain to be well characterized. Here, the combination of transcriptomics and metabolomics approaches were employed to construct interactive networks of functional genes and metabolites in human colorectal cancer (DLD-1) cells exposed to iAsIII. The number of DLD-1 cells passing through the Transwell membrane was at least 6 times greater in the iAsIII-treated groups than in controls. Following iAsIII treatment, the expression of ZEB1 and SLUG protein was significantly upregulated while the expression of CRB2 was downregulated (p < 0.05), indicating the onset of epithelial to mesenchymal transition (EMT). Meanwhile, integrin- and collagen-mediated biological adhesion were enhanced by SLUG under iAsIII treatment. The expression of matrix metallopeptidase (MMP) genes was fostered by iAsIII, which have the functions to degrade extracellular matrix. Glutamine metabolism could be considerably interfered by iAsIII, and in turn glutamine supplementation could effectively enhance DLD-1 cell movement. Overall, our results suggested that DLD-1 cell migration could be promoted by iAsIII via a series of cellular events, including EMT activation, altered cell adhesion, MMP-dependent matrix degradation, accompanying with a metabolic focus on glutamine.

Altered generation pattern of reactive oxygen species triggering DNA and plasma membrane damages to human liver cells treated with arsenite.

Human exposure to arsenic via drinking water is one of globally concerned health issues. Oxidative stress is regarded as the denominator of arsenic-inducing toxicities. Therefore, to identify intracellular sources of reactive oxygen species (ROS) could be essential for addressing the detrimental effects of arsenite (iAsIII). In this study, the contributions of different pathways to ROS formation in iAsIII-treated human normal liver (L-02) cells were quantitatively assessed, and then concomitant oxidative impairs were evaluated using metabolomics and lipidomics approaches. Following iAsIII treatment, NADPH oxidase (NOX) activity and expression levels of p47phox and p67phox were upregulated, and NOX-derived ROS contributed to almost 60.0 % of the total ROS. Moreover, iAsIII also induced mitochondrial superoxide anion and impaired mitochondrial respiratory function of L-02 cells with a decreasing ATP production. The inhibition of NOX activity significantly rescued mitochondrial membrane potential in iAsIII-treated L-02 cells. Purine and glycerophospholipids metabolisms in L-02 cells were disrupted by iAsIII, which might be used to represent DNA and plasma membrane damages, respectively. Our study supported that NOX could be the primary pathway of ROS overproduction and revealed the potential mechanisms of iAsIII toxicity related to oxidative stress.

Quantitative Investigation of Water Sensitivity and Water Locking Damages on a Low-Permeability Reservoir Using the Core Flooding Experiment and NMR Test.

Production of oil and gas energy is often greatly hindered by reservoir formation damage, particularly the occurrences of water sensitivity and water locking damages on a low-permeability reservoir. For the purpose of this paper, a formation damage assessment methodology combining core flooding experiment and NMR (nuclear magnetic resonance) T 2 relaxation tests is performed and applied to quantitatively determine water sensitivity/water locking damage on sandstone oil formation. XRD tests are used to analyze the mineral composition of cores. Core flooding experiments are designed to simulate the two damages and determine the permeability reduction. NMR tests are introduced to compare water saturation before and after flooding through rock cores, calculate the porosity damage and changes of the pore size, and analyze the mechanism of water sensitivity and water locking damages. Also, SEM experiments are used to determine the pore morphology before and after damage. Low-permeability sandstone rock cores cored from the Jilantai reservoir are assessed through this whole set of experiments. The results demonstrate that the permeability and porosity of core samples strongly decrease with the occurrence of water sensitivity/water locking damage, reflecting that the Jilantai reservoir has strong water sensitivity and is prone to be damaged by water locking. Compared with the previous formation damage assessment ideas, much attention is given to the microchanges of cores after damage, and using fluorinated oil instead of kerosene can help observe the distribution of water in rock core samples after each flooding by the NMR T 2 spectra.