A bimetallic peroxidase-mimicking nanozyme with antifouling property for construction of sensor array to identify phosphoproteins and diagnose cancers.

Protein phosphorylation is a significant post-translational modification that plays a decisive role in the occurrence and development of diseases. However, the rapid and accurate identification of phosphoproteins remains challenging. Herein, a high-throughput sensor array has been constructed based on a magnetic bimetallic nanozyme (Fe3O4@ZNP@UiO-66) for the identification and discrimination of phosphoproteins. Attributing to the formation of Fe-Zr bimetallic dual active centers, the as-prepared Fe3O4@ZNP@UiO-66 exhibits enhanced peroxidase-mimicking catalytic activity, which promotes the electron transfer from Zr center to Fe(II)/Fe(III). The catalytic activity of Fe3O4@ZNP@UiO-66 can be selectively inhibited by phosphoproteins due to the strong interaction between phosphate groups and Zr centers, as well as the ultra-robust antifouling capability of zwitterionic dopamine nanoparticle (ZNP). Considering the diverse binding affinities between various proteins with the nanozyme, the catalytic activity of Fe3O4@ZNP@UiO-66 can be changed to various degree, leading to the different absorption responses at 420 nm in the hydrogen peroxide (H2O2) - 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) system. By simply extracting different absorbance intensities at various time points, a sensor array based on reaction kinetics for the discrimination of phosphoproteins from other proteins is constructed through linear discriminant analysis (LDA). Besides, the quantitative determination of phosphoproteins and identification of protein mixtures have been realized. Further, based on the differential level of phosphoproteins in cells, the differentiation of cancer cells from normal cells can also be implemented by utilizing the proposed sensor array, showing great potential in disease diagnosis.

Maximum intensity projection based on high frame rate contrast-enhanced ultrasound for the differentiation of breast tumors.

Objective: We explored the role of maximum intensity projection (MIP) based on high frame rate contrast-enhanced ultrasound (H-CEUS) for the differentiation of breast tumors. Methods: MIP imaging was performed in patients with breast tumors who underwent H-CEUS examinations. The microvasculature morphology of breast tumors was assessed. The receiver operating characteristic curve was plotted to evaluate the diagnostic performance of MIP. Results: Forty-three breast tumors were finally analyzed, consisting of 19 benign and 24 malignant tumors. For the ≤30-s and >30-s phases, dot-, line-, or branch-like patterns were significantly more common in benign tumors. A tree-like pattern was only present in the benign tumors. A crab claw-like pattern was significantly more common in the malignant tumors. Among the tumors with crab claw-like patterns, three cases of malignant tumors had multiple parallel small spiculated vessels. There were significant differences in the microvasculature morphology for the ≤30-s and >30-s phases between the benign and malignant tumors (all p < 0.001). The area under the curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the ≤30-s phase were all higher than those of the >30-s phase for the classification of breast tumors. Conclusion: MIP based on H-CEUS can be used for the differentiation of breast tumors, and the ≤30-s phase had a better diagnostic value. Multiple parallel small spiculated vessels were a new finding, which could provide new insight for the subsequent study of breast tumors.

Isolation of starch and protein degrading strain Bacillus subtilis FYZ1-3 from tobacco waste and genomic analysis of its tolerance to nicotine and inhibition of fungal growth.

Aerobic fermentation is an effective technique for the large-scale processing of tobacco waste. However, the specificity of the structure and composition of tobacco-derived organic matter and the toxic alkaloids in the material make it currently difficult to directly use microbial agents. In this study, a functional strain FYZ1-3 was isolated and screened from thermophilic phase samples of tobacco waste composting. This strain could withstand temperatures as high as 80°C and grow normally at 0.6% nicotine content. Furthermore, it had a strong decomposition capacity of tobacco-derived starch and protein, with amylase activity of 122.3 U/mL and protease activity and 52.3 U/mL, respectively. To further understand the mechanism of the metabolic transformation of the target, whole genome sequencing was used and the secondary metabolite gene cluster was predicted. The inhibitory effect of the strain on common tobacco fungi was verified using the plate confrontation and agar column methods. The results showed that the strain FYZ1-3 was Bacillus subtilis, with a genome size of 4.17 Mb and GC content of 43.68%; 4,338 coding genes were predicted. The genome was annotated and analyzed using multiple databases to determine its ability to efficiently degrade starch proteins at the molecular level. Moreover, 14 functional genes related to nicotine metabolism were identified, primarily located on the distinct genomic island of FYZ1-3, giving a speculation for its nicotine tolerance capability on the molecular mechanism. By mining the secondary metabolite gene cluster prediction, we found potential synthetic bacteriocin, antimicrobial peptide, and other gene clusters on its chromosome, which may have certain antibacterial properties. Further experiments confirmed that the FYZ1-3 strain was a potent growth inhibitor of Penicillium chrysogenum, Aspergillus sydowii, A. fumigatus, and Talaromyces funiculosus. The creation and industrial use of the functional strains obtained in this study provide a theoretical basis for its industrial use, where it would be of great significance to improve the utilization rate of tobacco waste.

Crosstalk between autophagy inhibitor and salidroside-induced apoptosis: A novel strategy for autophagy-based treatment of hepatocellular cancer.

Autophagy regulates many cell function related to cancer, including cell proliferation, invasion and apoptosis. Therefore, we investigated the potential value of crosstalk between autophagy and apoptosis. The present study demonstrated that seven autophagy related genes were screened from the biological network of salidroside (Sal) acting on liver cancer. The GO analysis showed that these genes were mainly involved in apoptosis and autophagy. The KEGG analysis showed that these genes regulated the process of liver cancer through Th17 cell differentiation, PI3K-Akt signaling pathway and other pathways. Moreover, seven genes were positively correlated with tumor purity, number of B cells, number of CD4+ T cells, number of CD8+ T cells, number of macrophages, number of dendritic cells and number of neutrophils. The overall survival time of liver cancer patients in the high expression group of BIRC5, HSP90AB1 and MTOR was lower than that in the low expression group (P < 0.05), while the overall survival time of the liver cancer patients in the high expression group of DLC1 and FOXO1 was higher than that in the low expression group (P < 0.05). In the pan-cancer analysis, we also found that BIRC5, HSP90AB1, MTOR, and ITGA6 were highly expressed in various cancers, while DLC1, FOXO1, and FOS were low expressed in various cancers. In the molecule docking analysis, we found that FOS, HSP90AB1, and MTOR had the best binding ability. Notably, in the vitro validation experiments, Sal was confirmed to induce autophagy and apoptosis, inhibite invasion and metastasis of liver cancer cells through the PI3K/Akt/mTOR signaling pathway. Meanwhile, inhibition of autophagy by chloroquine diphosphate (CQ) promoted Sal-induced mitochondrial apoptosis via corresponding cell and animal experiments. We speculated that Sal-induced autophagy might be a protective mechanism, inhibition of autophagy could further promote the progression of liver cancer. It may provide important insight into the molecular mechanism of crosstalk between autophagy and apoptosis, and provide a new theoretical basis of Sal combined with autophagy inhibitors as a adjuvant chemotherapeutic strategy for human liver cancer.

Understanding the Microstructure Evolution of 8Cr4Mo4V Steel under High-Dose-Rate Ion Implantation.

In this study, the effect of microstructure under various dose rates of plasma immersion ion implantation on 8Cr4Mo4V steel has been investigated for crystallite size, lattice strain and dislocation density. The phase composition and structure parameters including crystallite size, dislocation density and lattice strain have been investigated by X-ray diffraction (XRD) measurements and determined from Scherrer's equation and three different Williamson-Hall (W-H) methods. The obtained results reveal that a refined crystallite size, enlarged microstrain and increased dislocation density can be obtained for the 8Cr4Mo4V steel treated by different dose rates of ion implantation. Compared to the crystallite size (15.95 nm), microstrain (5.69 × 10-3) and dislocation density (8.48 × 1015) of the dose rate of 2.60 × 1017 ions/cm2·h, the finest grain size, the largest microstrain and the highest dislocation density of implanted samples can be achieved when the dose rate rises to 5.18 × 1017 ions/cm2·h, the effect of refining is 26.13%, and the increment of microstrain and dislocation density are 26.3% and 45.6%, respectively. Moreover, the Williamson-Hall plots are fitted linearly by taking ßcosθ along the y-axis and 4sinθ or 4sinθ/Yhkl or 4sinθ(2/Yhkl)1/2 along the x-axis. In all of the W-H graphs, it can be observed that some of the implanted samples present a negative and a positive slope; a negative and a positive slope in the plot indicate the presence of compressive and tensile strain in the material.

Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling.

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1-/- mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP Myosin Cre+ mice) experienced smaller infarct sizes. Measurements of cardiac adenosine levels demonstrated that postischemic elevations of adenosine persisted during reperfusion after targeting ENTs. Finally, studies in mice with global or myeloid-specific deletion of the Adora2b adenosine receptor (Adora2bloxP/loxP LysM Cre+ mice) implied that Adora2b signaling on myeloid-inflammatory cells in cardioprotection provided by ENT inhibition. These studies reveal a previously unrecognized role for myocyte-specific ENT1 in cardioprotection by enhancing myeloid-dependent Adora2b signaling during reperfusion. Extension of these findings implicates adenosine transporter inhibitors in cardioprotection against ischemia and reperfusion injury.

Correlation of miR-125b with Treg/Th17 Cell Imbalance in Condyloma Acuminatum and Its Regulation on Autophagy of Keratinocytes.

Condyloma acuminatum (CA), a sexually transmitted disease caused by human papillomavirus (HPV) infection, the present research aims to analyze the mechanism of microRNA-125b (miR-125b) in condyloma acuminatum (CA) and its correlation with Treg/Th17 cell imbalance, the objective is to provide new research ideas for the prevention and treatment of CA in the future. The study population comprised 57 CA patients admitted between April 2020 and June 2022 (observation group, OG) and 64 concurrent healthy controls (control group, CG). The peripheral blood miR-125b and Treg/Th17 cells in all participants were detected to identify the correlation of miR-125b with CA severity and Treg/Th17 cells, and the diagnostic value of miR-125b for CA was analyzed. Then keratinocytes (KCs) from skin lesions of CA patients were isolated. Besides, autophagic proteins LC3-II and Beclin-1 in KCs were measured by Western blotting and immunofluorescence staining. miR-125b expression and Th17 cell percentage were lower in OG than in CG, and reduced gradually with the increase of CA severity, while the Treg cell percentage was higher versus CG and increased as CA worsened (P<0.05). miR-125b exhibited a positive association with Th17 cell percentage and an inverse correlation with Treg cell percentage (P<0.05). ROC analysis identified the excellent diagnostic effect of miR-125b on CA (P<0.05). In vitro, increasing miR-125b decreased the ability of KCs to proliferate, enhanced the apoptosis rate, and elevated LC3-II and Beclin-1 expression (P<0.05). In Conclusion, miR-125b, under-expressed in CA, is closely related to Th17/Treg cell imbalance, the mechanism is related to inhibiting the autophagy of KCs and promoting their abnormal proliferation.

Mechanical Behaviour Evaluation of Full Iron Tailings Concrete Columns under Large Eccentric Short-Term Loading.

In this study, full iron tailings concrete (FITC) was created using iron tailings from a tailings pond in Qian'an, China. Iron tailings account for 86.8% of the total mass of solid raw materials in the FITC. To enable large-scale use of FITC, a comprehensive investigation of the structural behaviour of full-iron tailing-reinforced concrete (FITRC) specimens is warranted. Therefore, eight rectangular reinforced concrete (RC) columns with conventional reinforced concrete (CRC) as a control were tested to investigate the effects of section dimensions, initial eccentricities, and concrete strengths, on the structural behaviour of FITRC columns under large eccentric short-term loading. The experimental and analytical results indicated that the sectional strain of the FITRC columns satisfied the plane-section assumption under short-term loading, and the lateral deflection curve agreed well with the half-sinusoidal curve. In addition, the FITRC columns exhibited a slightly lower cracking load and lower ultimate load capacity than the CRC columns, and the crack widths were larger than those of the CRC columns. The reduction in the load capacity observed in the FITRC was within the permissible range stated in the design code, thereby satisfying the code requirements. The deformation coefficients of the FITRC and CRC columns were identical, and the cracking and ultimate loads calculated according to the current code and theories were in good agreement with the measured results.

The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.

Despite increasing availability and more successful interventional approaches to restore coronary reperfusion, myocardial ischemia-reperfusion injury is a substantial cause of morbidity and mortality worldwide. During myocardial ischemia, the myocardium becomes profoundly hypoxic, thus causing stabilization of hypoxia-inducible transcription factors (HIF). Stabilization of HIF leads to a transcriptional program that promotes adaptation to hypoxia and cellular survival. Transcriptional consequences of HIF stabilization include increases in extracellular production and signaling effects of adenosine. Extracellular adenosine functions as a signaling molecule via the activation of adenosine receptors. Several studies implicated adenosine signaling in cardioprotection, particularly through the activation of the Adora2a and Adora2b receptors. Adenosine receptor activation can lead to metabolic adaptation to enhance ischemia tolerance or dampen myocardial reperfusion injury via signaling events on immune cells. Many studies highlight that clinical strategies to target the hypoxia-adenosine link could be considered for clinical trials. This could be achieved by using pharmacologic HIF activators or by directly enhancing extracellular adenosine production or signaling as a therapy for patients with acute myocardial infarction, or undergoing cardiac surgery.

Preparation, characteristic and anti-inflammatory effect of selenium nanoparticle-enriched probiotic strain Enterococcus durans A8-1.

BACKGROUND: Elemental selenium, a new type of selenium supplement, can be biosynthesized via microorganisms. This study is to characterize a patent probiotic bacteria Enterococcus durans A8-1, capable of reducing selenite (Se6+ or Se4+) to elemental selenium (Se0) with the formation of Se nanoparticles (SeNPs). METHODS: The selenium nanoparticles synthesized from A8-1 were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and X-ray photoelectron energy (XPS). The Caco2 cells were used to investigate the effects of Se-enriched A8-1 on the viability, membrane integrity, and the regulation of cellular inflammation through MTT and ELISA assays. The selenium-enriched metabolic function of A8-1 was analyzed by transcriptome sequencing. RESULTS: E. durans A8-1 has the ability to synthesize intracellular SeNPs that are incubated with 60 mg/L sodium selenite for 18 h at 37 °C with 7 % inoculum under aerobic conditions. The selenium-enriched transformation rate increased to 43.46 %. After selenium enrichment, there were no significant morphological changes in E. durans A8-1 cells. The cells also exhibited no cytotoxicity when incubated with Caco-2 cells, and increased cellular proliferation. Furthermore, Se-enriched A8-1 cells antagonize the adhesion of S. typhimurium ATCC14028 onto the surface of Caco-2 cells protecting cell membrane integrity and was assessed by measuring LDH and AKP activities (P <0.001, P <0.001). Moreover, Se-enriched A8-1 could protect Caco-2 cells from inflammation induced by lipopolysaccharide and help the cells alleviate the inflammation through the reduced expression of cytokine IL-8 (P = 0.0012, P <0.001) and TNF-α (P <0.001, P <0.001). Based on transcriptome sequencing in Se-enriched E. durans A8-1 cells, there were 485 up-regulated genes and 322 down-regulated genes (Padj < 0.05). There were 19 predicted up-regulated genes that are highly related to the potential selenium metabolism pathway, which focuses on the transportation of Na2SeO3 by membrane proteins, and gradually reduces Na2SeO3 to elemental selenium aggregates that are deposited onto the membrane surface via the intracellular redox response. CONCLUSION: E. durans A8-1 could convert extracellular selenite into intracellular biological SeNPs via redox pathway with strong selenium-rich metabolism, and its biological SeNPs have anti-inflammatory properties, which have the potential for the development of composite selenium nanomaterials and can be further studied for the function of SeNPs with potential applications.

Decoding the transcriptome of denervated muscle at single-nucleus resolution.

BACKGROUND: Skeletal muscle exhibits remarkable plasticity under both physiological and pathological conditions. One major manifestation of this plasticity is muscle atrophy that is an adaptive response to catabolic stimuli. Because the heterogeneous transcriptome responses to catabolism in different types of muscle cells are not fully characterized, we applied single-nucleus RNA sequencing (snRNA-seq) to unveil muscle atrophy related transcriptional changes at single nucleus resolution. METHODS: Using a sciatic denervation mouse model of muscle atrophy, snRNA-seq was performed to generate single-nucleus transcriptional profiles of the gastrocnemius muscle from normal and denervated mice. Various bioinformatics analyses, including unsupervised clustering, functional enrichment analysis, trajectory analysis, regulon inference, metabolic signature characterization and cell-cell communication prediction, were applied to illustrate the transcriptome changes of the individual cell types. RESULTS: A total of 29 539 muscle nuclei (normal vs. denervation: 15 739 vs. 13 800) were classified into 13 nuclear types according to the known cell markers. Among these, the type IIb myonuclei were further divided into two subgroups, which we designated as type IIb1 and type IIb2 myonuclei. In response to denervation, the proportion of type IIb2 myonuclei increased sharply (78.12% vs. 38.45%, P < 0.05). Concomitantly, trajectory analysis revealed that denervated type IIb2 myonuclei clearly deviated away from the normal type IIb2 myonuclei, indicating that this subgroup underwent robust transcriptional reprogramming upon denervation. Signature genes in denervated type IIb2 myonuclei included Runx1, Gadd45a, Igfn1, Robo2, Dlg2, and Sh3d19 (P < 0.001). The gene regulatory network analysis captured a group of atrophy-related regulons (Foxo3, Runx1, Elk4, and Bhlhe40) whose activities were enhanced (P < 0.01), especially in the type IIb2 myonuclei. The metabolic landscape in the myonuclei showed that most of the metabolic pathways were down-regulated by denervation (P < 0.001), while some of the metabolic signalling, such as glutathione metabolism, was specifically activated in the denervated type IIb2 myonulei. We also investigated the transcriptomic alterations in the type I myofibres, muscle stem cells, fibro-adipogenic progenitors, macrophages, endothelial cells and pericytes and characterized their signature responses to denervation. By predicting the cell-cell interactions, we observed that the communications between myofibres and muscle resident cells were diminished by denervation. CONCLUSIONS: Our results define the myonuclear transition, metabolic remodelling, and gene regulation networks reprogramming associated with denervation-induced muscle atrophy and illustrate the molecular basis of the heterogeneity and plasticity of muscle cells in response to catabolism. These results provide a useful resource for exploring the molecular mechanism of muscle atrophy.

Mesophilic condition is more conducive to methane production yield and tylosin removal on tylosin fermentation dreg anaerobic digestion.

Anaerobic digestion (AD) of antibiotic fermentation dreg is effective because of its satisfactory methanogenic performance and antibiotic removal rate. Thermophilic AD, an important branch, has not been studied. This study explored the effects of mesophilic and thermophilic AD on tylosin fermentation dreg (TFD) alone-digestion and co-digestion with food waste. The methane production (245-420 mL/g-VS) of mesophilic AD was 20.7%-28.6% higher than thermophilic AD, but the maximum methane production rate (RM), lag period (λ), and hydrolysis rate constant (kh) of thermophilic AD were 1.81, 0.236 and 3.16 times higher than those of mesophilic AD, respectively. However, the residual tylosin in mesophilic AD was always higher than that in thermophilic AD. The addition of food waste increased the methane production rate and yield under both temperature conditions. Therefore, due to the higher rate and yield of methane production, mesophilic AD, especially co-digestion, is more suitable for the treatment of TFD.

Effect of co-digestion of tylosin fermentation dreg and food waste on anaerobic digestion performance.

In this study, the effects of adding different food waste proportions (volatile solids ratio of 3:7, 5:5, 7:3) to tylosin fermentation dreg on anaerobic digestion were investigated. The results showed that the co-digestion group (294-399 mL·g-VS-1) increased methane production by 14.8%-55.5% compared with tylosin fermentation dreg alone-digestion (256 mL·g-VS-1). The correlation analysis showed that pH, total volatile fatty acids and acetic acid were the most important factors affecting cumulative methane production. Tylosin in the solid and liquid phases decreased significantly after anaerobic digestion, indicating that tylosin could be effectively removed by co-digestion, and the total removal rate was 68.2%-83.7%. Therefore, due to the satisfactory methane yield and the tolerable tylosin removal rate, it is feasible to make the co-digestion of tylosin fermentation dreg and food waste.

Discovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration.

Isocitrate dehydrogenase 1 (IDH1), which catalyzes the conversion of isocitrate to α-ketoglutarate, is one of key enzymes in the tricarboxylic acid cycle (TCA). Hotspot mutation at Arg132 in IDH1 that alters the function of IDH1 by further converting the α-ketoglutarate(α-KG) to 2-hydroxyglutarate (2-HG) have been identified in a variety of cancers. Because the IDH1 mutations occur in a significant portion of gliomas and glioblastomas, it is important that IDH1 inhibitors have to be brain penetrant to treat IDH1-mutant brain tumors. Here we report the efforts to design and synthesize a novel serial of mutant IDH1 inhibitors with improved activity and the blood-brain barrier (BBB) penetration. We show that compound 5 exhibits good brain exposure and potent 2-HG inhibition in a HT1080-derived mouse xenograft model, which makes it a potential preclinical candidate to treat IDH1-mutant brain tumors.

Pathogenicity and complete genome sequence of a fowl adenovirus serotype 8b isolate from China.

In this study, we determined and analyzed the complete nucleotide sequence of the genome of a fowl adenovirus isolate SD1356 in China and examined its pathogenicity in specific pathogen-free chick embryos and newly hatched chicks. The full genome of SD1356 was 44,454 nucleotides in length with 58.1% G + C content. Sequence alignment and phylogenetic analysis revealed that strain SD1356 was clustered together belonging to serotype 8b of fowl adenoviruses E species (FAdV-8b). No regions homologous to early regions E1, E3, and E4 of mastadenoviruses were recognized, and being very similar to the typical organization of FAdV-E genomes. All infected embryos died 4-6 d post-inoculation with visible lesions, such as hyperemic, stunting, and clubbed down, etc. Additionally, adenovirus was found in tissues or cloacal swabs of all infected birds and most of the contact uninfected controls, despite lack of clinical signs and pathological changes. Together, our study describes the genomic characteristics of an FAdV-8b strain isolated in China. The reported FAdV-8b strain SD1356 is fetal to chick embryos and possesses horizontal transmission capacity in chickens.

Effect of genistein on apoptosis of lung adenocarcinoma A549 cells and expression of apoptosis factors.

PURPOSE: To investigate the effect of genistein (GEN) on the apoptosis of lung adenocarcinoma cells and the expression of Bcl-2 and Bax, so as to screen effective antitumor drugs for the clinical treatment of lung adenocarcinoma. METHODS: Lung adenocarcinoma A549 cells were cultured in vitro and treated with different concentrations of GEN. The untreated cells were set as control group. MTT assay and Annexin V/PI double staining were used to analyze cell proliferation and apoptosis after GEN treatment. RT-qPCR and Western blot were used to detect the expression of Bcl-2 and Bax at mRNA and protein levels, respectively. RESULTS: Cell p roliferation a ssay s howed t hat GEN c ould inhibit the proliferation of lung adenocarcinoma cell line A549 in vitro in a dose-dependent manner. Cell apoptosis assay showed that, compared with the control group, the apoptotic rate of A549 cells was significantly increased after GEN treatment. RT-qPCR and Western blot showed that the expression levels of anti-apoptotic factor Bcl-2 in A549 cells were significantly decreased at both mRNA and protein levels at 48 hrs after treatment with GEN, but the levels of pro-apoptotic Bax were significantly increased at both mRNA and protein levels. CONCLUSION: GEN can inhibit the proliferation of A549 lung adenocarcinoma cells in vitro and induce their apoptosis. The antitumor activity of GEN is achieved by downregulating Bcl-2 and upregulating Bax. Therefore, GEN can be applied to the clinical treatment of lung adenocarcinoma.

Effects of neoadjuvant chemotherapy on minimum alveolar concentration values of sevoflurane and desflurane in patients with hepatocellular carcinoma complicated with jaundice.

The effects of neoadjuvant chemotherapy on the minimum alveolar concentration (MAC) values of sevoflurane and desflurane in patients with hepatocellular carcinoma (HCC) complicated with jaundice were investigated. Eighty patients with HCC complicated with jaundice were selected. Forty patients underwent the neoadjuvant chemotherapy and were grouped into the desflurane group (Group D) and the sevoflurane group (Group S). Patients in all chemotherapy groups received 2 cycles of chemotherapy prior to surgery and underwent surgical treatment 3 weeks after chemotherapy. The remaining 40 patients in the control group were divided into the desflurane group (Group C1) and the sevoflurane group (Group C2). Changes in MAP, HR and BIS at different time points before and after anesthesia induction and skin incision were compared among the groups. Results showed that there were no significant differences in MAP, HR and BIS before anesthesia induction (T0) (P>0.05); at each time point from T1 to T6, MAP, HR and BIS of Group D were significantly lower than those of Group C1 (P>0.05). Furthermore, MAP, HR and BIS of Group S were significantly lower than those of Group C2 (P>0.05). The MACMean of sevoflurane and desflurane were compared among all patient groups using the mean method. MACMean values of Group D were significantly lower than those of Group C1 (P<0.05). Notably, MACDixon values of sevoflurane and desflurane were compared among all patient groups using the Dixon method and the differences were statistically significant (P<0.05). Logistic regression analyses were conducted, respectively, which revealed that the MAC of sevoflurane and desflurane were associated with whether patients received the neoadjuvant chemotherapy. MACLog of sevoflurane and desflurane were decreased in patients receiving the neoadjuvant chemotherapy. The results suggested that neoadjuvant chemotherapy can reduce MAC values of sevoflurane and desflurane in HCC patients complicated with jaundice and may improve these patients' sensitivity to sevoflurane and desflurane.

Carrier-Free Microspheres of an Anti-Cancer Drug Synthesized via a Sodium Catalyst for Controlled-Release Drug Delivery.

There are several challenges involved in the development of effective anti-cancer drugs, including accurate drug delivery without toxic side effects. Possible systemic toxicity and the rapid biodegradation of drug carriers are potential risks in the use of carriers for drug-delivery formulations. Therefore, the carrier-free drug delivery of an anti-cancer drug is desirable. Herein, 4-amino-2-benzyl-6-methylpyrimidine (ABMP) was synthesized via a new method using a sodium catalyst, and proved to be effective in inducing breast cancer cell (MDA-MB-231) apoptosis. Moreover, the transparent amorphous state solid of ABMP was demonstrated to have a slow-release property in phosphate buffer solution (PBS). Microspheres of ABMP were prepared with diameters in the range of 5-15 µm. The slow-release property of the ABMP microspheres indicated their potential use for controlled-release drug delivery. We believe that microspheres of ABMP have potential as a new kind of carrier-free anti-cancer drug delivery system.

Methylphenidate ameliorates hypoxia-induced mitochondrial damage in human neuroblastoma SH-SY5Y cells through inhibition of oxidative stress.

AIMS: Methylphenidate (MPH) is a dopamine-reuptake inhibitor approved for the treatment of attention-deficit/hyperactivity disorder (ADHD). Nonetheless, the cellular and molecular mechanisms of MPH are still unknown. We attempt to determine whether MPH protect neuron cells against oxidative stress by using human neuroblastoma SH-SY5Y cells. MAIN METHODS: The SH-SY5Y cells were cultured in normoxic and hypoxic conditions in the presence of different doses of MPH. Then, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and adenosine triphosphate (ATP) production were quantitatively measured by using flow cytometry or spectrophotometry. The mitochondrial ultrastructure of the cells was observed by electron microscope, and the function of mitochondrial was evaluated by measuring mitochondrial membrane potential (MMP) using flow cytometry. The levels of SOD and heme oxygenase-1 (HO-1) proteins were detected by Western blot. KEY FINDINGS: We found that low doses of MPH treatment (50-500 ng/mL) led to decreased ROS and MDA production (P<0.05), increased GSH and SOD as well as ATP concentration (P<0.05) in hypoxic SH-SY5Y cells. Additionally, low doses of MPH significantly inhibited mitochondrial swelling and decreased the percentage of JC-1 monomer positive cells. However, we did not observe the same effects of MPH in normoxia. SIGNIFICANCE: Our results show that low doses of MPH play protective roles in maintaining mitochondrial homeostasis in response to hypoxia-induced oxidative stress. Our findings may provide novel insight into the mechanisms of MPH in the treatment of ADHD, and shed light on the disease mechanisms of ADHD.

16S rRNA genes Illumina sequencing revealed differential cecal microbiome in specific pathogen free chickens infected with different subgroup of avian leukosis viruses.

Intestinal flora play important roles in the pathogenisis of many pathogens. This study examined the cecal microbiome of chickens infected with avian leukosis virus (ALV) using 16S rRNA genes Illumina sequencing. One-day-old specific pathogen free chicks were inoculated in the abdomen with subgroup J or K of ALV. At 21-day-old, chickens positive for ALV viremia were selected and their cecal contents were extracted and examined for the composition of gut microflora by illumina sequencing of the V3+V4 region of the 16S rRNA genes. The results showed that there is a clear association with loss of important bacterial populations in concert with an enrichment of potentially pathogenic populations and ALV infections, despite of the virus subgroups. In addition, ALV-K infected chickens revealed a preference for opportunistic pathogens in Firmicutes such as Staphylococcus and Weissella and some genus from Bacillales. Whereas, ALV-J infected chickens were characterized by a larger number of notable pathogens like Escherichia-Shigella from Proteobacteria, and other condition pathogens including Enterococcus and members of Erysipelotrichaceae from Firmicutes, and members of Helicobacteraceae from Bacteroidetes. Collectively, our results suggest that relative abundance data from the cecal microbiome differentiates healthy chickens from those infected with ALVs. Most importantly, there was a significant difference in the gut microbiome of chickens infected with ALV-K compared to those with ALV-J infected ones. This strongly suggests that ALV infection may be associated with the microbiome and there may be multiple underlying mechanisms by which the microbiome is involved in the pathogenisis of different subgroup of ALV infections.