APOA5 alleviates reactive oxygen species to promote oxaliplatin resistance in PIK3CA-mutated colorectal cancer.

Although platinum-based chemotherapy is the frontline regimen for colorectal cancer (CRC), drug resistance remains a major challenge affecting its therapeutic efficiency. However, there is limited research on the correlation between chemotherapy resistance and lipid metabolism, including PIK3CA mutant tumors. In this present study, we found that PIK3CA-E545K mutation attenuated cell apoptosis and increased the cell viability of CRC with L-OHP treatment in vitro and in vivo. Mechanistically, PIK3CA-E545K mutation promoted the nuclear accumulation of SREBP1, which promoted the transcription of Apolipoprotein A5 (APOA5). APOA5 activated the PPARγ signaling pathway to alleviate reactive oxygen species (ROS) production following L-OHP treatment, which contributed to cell survival of CRC cells. Moreover, APOA5 overexpression enhanced the stemness-related traits of CRC cells. Increased APOA5 expression was associated with PIK3CA mutation in tumor specimens and poor response to first-line chemotherapy, which was an independent detrimental factor for chemotherapy sensitivity in CRC patients. Taken together, this study indicated that PIK3CA-E545K mutation promoted L-OHP resistance by upregulating APOA5 transcription in CRC, which could be a potent target for improving L-OHP chemotherapeutic efficiency. Our study shed light to improve chemotherapy sensitivity through nutrient management in CRC.

Discriminative feature analysis of dairy products based on machine learning algorithms and Raman spectroscopy.

Discriminant analysis of similar food samples is an important aspect of achieving food quality control. The effective combination of Raman spectroscopy and machine learning algorithms has become an extremely attractive approach to develop intelligent discrimination techniques. Feature spectral analysis can help researchers gain a deeper understanding of the data patterns in food quality discrimination. Herein, this work takes the discrimination of three brands of dairy products as an example to investigate the Raman spectral feature based on the support vector machines (SVM), extreme learning machines (ELM) and convolutional neural network (CNN) algorithms. The results show that there are certain differences in the optimal spectral feature interval corresponding to different machine learning algorithms. Selecting the appropriate spectral feature interval can maintain high recognition accuracy and improve the computational efficiency of the algorithm. For example, the SVM algorithm has a recognition accuracy of 100% in the 890-980 cm-1, 1410-1500 cm-1 fusion spectral range, which takes about 200 s. The ELM algorithm also has a recognition accuracy of 100% in the 890-980 cm-1, 1410-1500 cm-1 fusion spectral range, which takes less than 0.3 s. The CNN algorithm has a recognition accuracy of 100% in the 890-980 cm-1, 1050-1180 cm-1, 1410-1500 cm-1 fusion spectral range, which takes about 80 s. In addition, by analyzing the distribution of spectral feature intervals based on Euclidean distance, the distribution of experimental samples based on feature spectra is visually displayed. Through the spectral feature analysis process of similar samples, a set of analysis strategies is provided to deeply reveal the data foundation of classification algorithms, which can provide reference for the analysis of relevant discriminative research patterns.

Freeze-thaw stability of transglutaminase-induced soy protein-maltose emulsion gel: Focusing on morphology, texture properties, and rheological characteristics.

In this study, soy protein isolate (SPI) and maltose (M) were employed as materials for the synthesis of a covalent compound denoted as SPI-M. The emulsion gel was prepared by transglutaminase (TGase) as catalyst, and its freeze-thaw stability was investigated. The occurrence of Maillard reaction was substantiated through SDS-PAGE. The analysis of spectroscopy showed that the structure of the modified protein was more stretched, changed in the direction of freeze-thaw stability. After three freeze-thaw cycles (FTC), it was observed that the water holding capacity of SPI-M, SPI/M mixture (SPI+M) and SPI emulsion gels exhibited reductions of 8.49 %, 16.85 %, and 20.26 %, respectively. Moreover, the soluble protein content also diminished by 13.92 %, 23.43 %, and 35.31 %, respectively. In comparison to unmodified SPI, SPI-M exhibited increase in gel hardness by 160 %, while elasticity, viscosity, chewability, and cohesion demonstrated reductions of 17.7 %, 23.3 %, 33.3 %, and 6.76 %, respectively. Concurrently, the SPI-M emulsion gel exhibited the most rapid gel formation kinetics. After FTCs, the gel elastic modulus (G') and viscosity modulus (G″) of SPI-M emulsion were the largest. DSC analysis underscored the more compact structure and heightened thermal stability of the SPI-M emulsion gel. SEM demonstrated that the SPI-M emulsion gel suffered the least damage following FTCs.

Fe-doping induced surface Fe2+/Fe3+ cycle and activated redox-inert TiO2 for enhanced Hg(II) electrochemical sensing: An efficient strategy to strengthen the redox activity.

Recently, Fe-based metal oxide with a variable-valence ability (i.e., the Fe2+/Fe3+ cycle) can participate in the redox of target heavy metal ions (HMIs) and enhance the electrochemical signal, which have attracted significant attention. However, it has not yet been proved whether iron-based metal oxides with variable-valence ability can activate the variable valence behavior of inert metal oxides (i.e., TiO2) and enable them to participate in the redox of target HMIs. Herein, we develop an efficient Fe-doped strategy to activate TiO2 nanoparticles for the electrochemical detection of Hg(II). TiO2 nanoparticles with the 5% Fe-doped content (FT5) possess the best detection sensitivity of 400.63 µA µM-1 cm-2 for Hg(II), which is dramatically higher than that of pure TiO2. The synergistic effects of enhanced adsorption by OVs and promoted redox activity by surface Fe2+/Fe3+ and Ti3+/Ti4+ cycle help FT5 to obtain an excellent electrochemical detection performance of Hg(II). In detail, Fe doping tune the concentration of oxygen vacancies (OVs) in TiO2 nanoparticles, which contributes to improving the adsorption ability of Hg(II). The exposed OVs on the surface of Fe-doped TiO2 nanoparticles form numerous hydroxyl groups (-OH) in water, and the hydroxyl groups can bond with Hg(II), tremendously accelerating the capture of Hg(II). Upon successfully obtaining OVs, the Ti3+ species are created in TiO2, achieving the activation of TiO2. Moreover, it is found that large amount surface Fe2+/Fe3+ and Ti3+/Ti4+ cycle on FT5 can accelerated the redox of Hg(II) and then favor to electrochemical detection performance. This study emphasizes that doping transition metal elements with variable valence states can control OVs concentration and successfully activate inert metal oxides.

[Changes in electrophysiological properties of pyramidal neuron in motor cortex during the postnatal early development of mice].

OBJECTIVE: To investigate the electrophysiological properties of pyramidal neurons in mouse motor cortex during the early postnatal development. METHODS: Thirty-six mice were randomly divided into postnatal 1-, 2-, 3-Week and 1-, 2-,3-Month groups (n=6). Membrane properties, action potentials (AP) and spontaneous excitatory postsynaptic currents (sEPSCs) of motor cortex pyramidal neurons were recorded to evaluate the changes in the intrinsic electrophysilogical characteristics by using whole cell patch clamp. Pyramidal neurons and interneurons were distinguished according to the AP firing patterns. RESULTS: Comparing with interneurons, pyramidal neurons exhibited regular spiking (RS) with smaller frequency. During the period of postnatal 1 Week-3 Months, some of the intrinsic membrane properties of motor cortex pyramidal neurons changed. Compared to the 1-Week mice, the resting membrane potential (RMP) of 2-Week decreased significantly (P＜0.01), and the membrane input resistance (Rin) of 1-Month got a hyperpolarization (P＜0.01), and they showed no significant change in the next period, while the membrane capacitance (Cm) showed no significant changes during the whole postnatal development. The AP dynamic properties changed significantly during this period. Compared to the 1-Week mice, the absolute value of the AP threshold and the AP amplitude of the 3-Week increased significantly (P＜0.01), while the spike half width of the 2-Week decreased substantially (P＜0.05), and they showed no significant change in the next period. The sEPSCs frequency and amplitude of 1- Month increased significantly compared to the 1-Week mice(P＜0.01), while during the period of next 1 Month-3 Months, the amplitude and frequency showed no significant change. CONCLUSION: These results suggest that the motor cortex pyramidal neurons have time-specific eletrophysilogical properties during the postnatal development. The electrophysiological properties can be used as a functional index to detect the degree of neurons maturity, and as a marker to distinguish the pyramidal neurons and interneurons.

An ultra-sensitive electrochemical sensor of Ni/Fe-LDH toward nitrobenzene with the assistance of surface functionalization engineering.

Hypersensitive detection of organic pollutions with high toxicity in drinking water always keeps its challenge in electroanalysis due to their low concentration and electrochemical redox inert. In this work, a novel nanomaterial modified electrode for the sensitive detection of nitrobenzene (NB) is presented, based on environmental friendly and cost-effective Ni/Fe layered double hydroxides functionalized with sodium dodecyl sulfate (Ni/Fe(SDS)-LDH). Such 2D layered composites were prepared and used to improve the sensitivity for NB detection, due to its good catalytic activity for NB reduction. Besides, the proposed electrode shows a remarkably promoted sensitivity to NB compared to Ni/Fe-LDHs modified one. It is because that the surface modifier SDS can provide more adsorption sites to significantly improve the adsorption of NB, which has been confirmed by the adsorption experiment and the characterization of Fourier transform infrared spectroscopy (FTIR). As a result, an impressive sensing behaviour is achieved at the proposed Ni/Fe(SDS)-LDHs modified electrode with a sensitivity of 15.79 µA µM-1 cm-2. This work provides a promising way to build more advanced nanomaterials to electrochemical detection of organic pollution based on energetically synergizing of adsorption by surface functionalization engineering.

A single-electron tunneling model: a theoretical analysis of a metal nanoparticle-doped epoxy resin to suppress surface charge accumulation on insulators subjected to DC voltages.

In high-voltage direct current transmission systems, charges accumulate at the gas-solid interface, distorting the local field strength, causing a reduction in the flashover voltage, and threatening the safe and reliable operation of the power system. The latest research has found that doping metal nanoparticles into an epoxy resin effectively suppresses the surface charge accumulation on insulators and improves their flashover voltage. This paper further analyzes the microscopic mechanism of this phenomenon, establishes a single-electron tunneling mode, and draws two conclusions: when there is no agglomeration of the doped nanoparticles, a higher doping concentration can be achieved, which provides a better insulative performance. The optimal metal nanoparticle radius is several to tens of nanometers. This work provides theoretical guidance for the future improvement of insulating materials through metal nanoparticle doping and has good prospects in engineering applications.

Metal nanoparticle-doped epoxy resin to suppress surface charge accumulation on insulators under DC voltage.

In high-voltage direct current (HVDC) transmission systems, electric charge accumulates on insulator surfaces, causing surface electric field distortion and flashover voltage reduction. Therefore, studying a material that can improve the insulator surface insulation strength is of great engineering value. In this work, several types of metal nanoparticles with different particle sizes and concentrations are doped into epoxy resin. The experimental phenomena enables some interesting conclusions: when no agglomeration of doped nanoparticles occurs, a higher doping concentration provides a better insulation performance. The larger the doping particle size is, the lower the insulation performance. Additionally, under the same conditions, different types of metal nanoparticles lead to slightly different results after doping. Especially after doping with low concentration (approximately 120 parts per million (ppm)) and small particle size (approximately 10 nm) nanocopper particles, the insulator surface charge accumulation was effectively suppressed, and the flashover voltage was significantly improved. Our analysis suggests that it may be related to the single-electron tunneling phenomenon. Relevant results provide a new way to improve the surface insulation strength of insulators in the future.

Functional profiles of phycospheric microorganisms during a marine dinoflagellate bloom.

Harmful algal blooms (HABs) are an ecological concern but relatively few studies have investigated the functional potential of bacterioplankton over a complete algal bloom cycle, which is critical for determining their contribution to the fate of algal blooms. To address this point, we carried out a time-series metagenomic analysis of the functional features of microbial communities at three different Gymnodinium catenatum bloom stages (pre-, peak-, and post-bloom). Different microbial composition were observed during the blooming stages. The environmental parameters and correlation networks co-contribute to microbial variability, and the former explained 38.4% of total variations of the bacterioplankton community composition. Functionally, a range of pathways involved in carbon, nitrogen, phosphorus and sulfur cycling were significantly different during the various HAB stages. Genes associated with carbohydrate-active enzymes, denitrification, and iron oxidation were enriched at the pre-bloom stage; genes involved in reductive citrate cycle for carbon fixation, carbon degradation, nitrification and phosphate transport were enhanced at the peak stage; and relative gene abundance related to sulfur oxidation, vitamin synthesis, and iron transport and storage was increased at the post-bloom stage. The ecological linkage analysis has shown that microbial functional potential especially the C/P/Fe metabolism were significantly linked to the fate of the algal blooms. Taken together, our results demonstrated that microorganisms displayed successional patterns not only at the community level, but also in the metabolic potential on HAB's progression. This work contributes to a growing understanding of microbial structural elasticity and functional plasticity and shed light on the potential mechanisms of microbial-mediated HAB trajectory.

Single shot versus continuous technique adductor canal block for analgesia following total knee arthroplasty: A PRISMA-compliant meta-analysis.

BACKGROUND: An adductor canal block (ACB) provides recognized analgesia following total knee arthroplasty (TKA). This meta-analysis compared the single-injection ACB (SACB) with the continuous-injection ACB (CACB). METHOD: Relevant studies were searched from PubMed (1996-October 2018), Embase (1980-October 2018), and Cochrane Library (CENTRAL, October 2018). Four randomized controlled trials (RCTs), which compared SACB with CACB, were included in our meta-analysis. RESULTS: Four RCTs met the inclusion criteria. Our pooled data indicated that the SACB group had similar efficacy compared with the CACB group in terms of morphine consumption (P = .19), time to first opioid request (P = .32), range of motion (P = .97), and visual analogue scale (VAS) scores at 24 hours at rest (P = .12) and movement (P = .24), without increasing the risk of complications (P = .97) and length of stay (P = .54). CONCLUSION: The SACB technique provides similar analgesia in the 24 hours following TKA compared with CACB, while the CACB method was better over 48 hours.

Long intergenic noncoding RNA 00305 sponges miR-136 to regulate the hypoxia induced apoptosis of vascular endothelial cells.

BACKGROUND: Apoptosis in vascular endothelial cells (VECs) are closely correlated to multiple endotheliocyte-related cardiovascular diseases, for example atherosclerosis. Long non-coding RNAs (lncRNAs) have been testified to play important role in regulation of VECs. The purpose of this study is to investigate the potential regulation of lncRNA long intergenic noncoding RNA 00305 (LINC00305) on hypoxia induced VECs. METHODS: Human umbilical vein endothelial cells (HUVECs) were respectively induced with normoxia or hypoxia (1%). Expression levels of lncRNA and miRNA were detected using RT-PCR. Proliferation ability was tested by CCK-8 assay. Apoptosis assay were performed using flow cytometry and TUNEL staining. Target miRNAs prediction was performed using bioinformatics analysis. RESULTS: LINC00305 expression was significantly up-regulated in hypoxia induce HUVECs. Gain- and loss-of-function experiments showed that LINC00305 enhanced expression suppressed the proliferation and enhanced the apoptosis of HUVECs, while LINC00305 lower-expression exerted the opposite effect. Bioinformatics analysis revealed that miR-136 targeted LINC00305 art 3'-UTR. Moreover, rescue experiment confirmed the reversing function of miR-136 to LINC00305 on HUVECs proliferation and apoptosis. CONCLUSION: Our study revealed the apoptosis-promoting role of LINC00305 in hypoxia-induced HUVECs via acting as miR-136 sponge, suggesting the vital function of lncRNAs on VECs apoptosis.

Biological effects of bone marrow mesenchymal stem cells on hepatitis B virus in vitro.

The aim of the present study was to explore the effects of co­culturing bone marrow­derived mesenchymal stem cells (BM-MSCs) cultured with hepatitis B virus (HBV)­infected lymphocytes in vitro. BM­MSCs and lymphocytes from Brown Norway rats were obtained from the bone marrow and spleen, respectively. Rats were divided into the following five experimental groups: Group 1, splenic lymphocytes (SLCs); group 2, HepG2.2.15 cells; group 3, BM­MSCs + HepG2.2.15 cells; group 4, SLCs + HepG2.2.15 cells; and group 5, SLCs + BM­MSCs + HepG2.2.15 cells. The viability of lymphocytes and HepG2.2.15 cells was assessed using the MTT assay at 24, 48 and 72 h, respectively. Levels of supernatant HBV DNA and intracellular HBV covalently closed circular DNA (cccDNA) were measured using quantitative polymerase chain reaction. Supernatant cytokine levels were measured by enzyme­linked immunosorbent assay (ELISA). T cell subsets were quantified by flow cytometry using fluorescence­labeled antibodies. In addition, the HBV genome sequence was analyzed by direct gene sequencing. Levels of HBV DNA and cccDNA in group 5 were lower when compared with those in group 3 or group 4, with a significant difference observed at 48 h. The secretion of interferon­Î³ was negatively correlated with the level of HBV DNA, whereas secretion of interleukin (IL)­10 and IL­22 were positively correlated with the level of HBV DNA. Flow cytometry demonstrated that the percentage of CD3+CD8+ T cells was positively correlated with the levels of HBV DNA, and the CD3+CD4+/CD3+CD8+ ratio was negatively correlated with the level of HBV DNA. Almost no mutations in the HBV DNA sequence were detected in HepG2.2.15 cells co­cultured with BM­MSCs, SLCs, or in the two types of cells combined. BM­MSCs inhibited the expression of HBV DNA and enhanced the clearance of HBV, which may have been mediated by the regulation of the Tc1/Tc2 cell balance and the mode of cytokine secretion to modulate cytokine expression.

Immunomodulatory effects of bone marrow mesenchymal stem cells overexpressing heme oxygenase-1: Protective effects on acute rejection following reduced-size liver transplantation in a rat model.

Here we explore the T-lymphocyte suppressive and immunomodulatory effects of bone marrow mesenchymal stem cells (BMMSCs) overexpressing heme oxygenase-1 (HO-1) on acute rejection following reduced-size liver transplantation (RLT) in a rat model. The proliferation activity, cell cycle progression, secretion of proinflammatory cytokines, expression of CD25 and CD71 in lymphocytes, and activity of NK cells were found to be significantly lowered, and the proportion of regulatory T cells (Tregs) was found to be increased relative to BMMSCs when Adv-HO-1/BMMSCs were co-cultured with Con A ex vivo; secretion of anti-inflammatory cytokines was significantly higher. When treated with saline, BMMSCs or Adv-HO-1/BMMSCs, post-transplantation rats receiving Adv-HO-1/BMMSCs showed better median survival time, lower rejection activity index, higher anti-inflammatory cytokine levels, lower proinflammatory cytokine levels, more peripheral Tregs, and lower natural killer cell viability. These results suggest that HO-1 enhanced and prolonged the effects of BMMSCs on acute rejection following RLT, with immunomodulatory effects in which adaptive and innate immunity, as well as paracrine signaling, may play important roles.

Mesenchymal stem cells improve the outcomes of liver recipients via regulating CD4+ T helper cytokines in rats.

BACKGROUND: Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activities in transplantation. This study aimed to determine whether BMMSCs reduce acute rejection and improve outcomes of liver transplantation in rats. METHODS: Orthotopic liver transplantation from Lewis to Brown Norway rats was performed, which was followed by the infusion of BMMSCs through the penile superficial dorsal vein. Normal saline infusion was used as a control. Animals were sacrificed at 0, 24, 72, or 168 hours after BMMSCs infusion. Liver grafts, and recipient serum and spleen tissues were obtained. Histopathology, apoptosis, serum liver enzymes, serum cytokines, and circulating regulatory T (Treg), Th1, Th2 and Th17 cells were assessed at each time point. RESULTS: BMMSCs significantly attenuated acute rejection and improved the survival rate of allogeneic liver transplantation recipients. Liver enzymes and liver apoptosis were significantly alleviated. The levels of the Th1/Th2 ratio-associated cytokines such as IL-2 and IFN-gamma were significantly reduced and IL-10 was significantly increased. The levels of the Th17/Tregs axis-associated cytokines such as IL-6, IL-17, IL-23, and TNF-alpha were significantly reduced, whereas TGF-beta concentration was significantly increased. Moreover, flow cytometry analysis showed that the infusion of BMMSCs significantly increased Th2 and Treg cells and decreased Th1 and Th17 cells. CONCLUSION: BMMSCs had immunomodulatory effects, attenuated acute rejection and improved outcomes of allogeneic liver transplantation in rats by regulating the levels of cytokines associated with Th1/Th2 and Th17/Treg ratios.

Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats.

Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activity in transplantation, and heme oxygenase-1 (HO-1) enhances their immunomodulatory effects. The aim of this study was to determine whether HO-1-transduced BMMSCs (HO-1/MSCs) improve rat liver transplantation (LTx) outcomes. Orthotopic LTx rejection models were treated with HO-1/MSCs, BMMSCs, HO-1, or normal saline, respectively. Our results showed a significant improvement in survival rates in the HO-1/BMMSCs group compared to the control groups. At all time points, liver function marker levels in the HO-1/MSCs group were significantly lower than in the other three groups; on POD 1, 7, and 14, the degree of rejection and apoptotic cells was significantly less in the HO-1/MSCs group than in the other three groups. Interleukin- (IL-) 10 and transforming growth factor-ß levels were significantly increased, while IL-2, IL-6, IL-17, IL-23, tumor necrosis factor-α, and interferon-γ levels were significantly decreased in the HO-1/MSCs group when compared to the other groups. Splenocyte Tregs were significantly increased by HO-1/MSCs compared with controls on POD 3, 5, 7, 10, 14, and 28. Summarily, we provide evidence that HO-1/MSCs improved allogeneic LTx outcomes by attenuating inflammatory responses and acute cellular rejection, as well as enhanced immunomodulatory effects compared with BMMSCs.

Overexpression of PEP-19 suppresses angiotensin II-induced cardiomyocyte hypertrophy.

The precise molecular mechanisms leading to disturbance of Ca(2+)/calmodulin-dependent intracellular signalling in cardiac hypertrophy remains unclear. As an endogenous calmodulin regulator protein, the pathophysiology role of PEP-19 during cardiac hypertrophy was investigated in the present study. We here demonstrated that PEP-19 protein levels are significantly elevated in the aortic banding model in vivo and angiotensin II-induced cardiomyocyte hypertrophy in vitro. Consistent with inhibitory actions of PEP-19 on cardiomyocyte hypertrophy, induction of CaMKII and calcineurin activation as well as hypertrophy-related genes including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was significantly inhibited by PEP-19 transfection. Moreover, PEP-19 partially ameliorates angiotensin II-induced elevation of phospho-phospholamban (Thr-17) and sarcoplasmic reticulum Ca(2+) release in cardiomyocytes. Together, our results suggest that PEP-19 attenuates angiotensin II-induced cardiomyocyte hypertrophy via suppressing the disturbance of CaMKII and calcineurin signaling.