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Background: Allergen testing has emerged as a pivotal component in prevention and treatment strategies for allergic diseases among children and the utilization of specific IgE (sIgE) through a fully automated chemiluminescent microarray immunoassay (CLMIA) has emerged as a promising trend in the simultaneous detection of multiple allergenic components of children., Methods: The accuracy and reliability of CLMIA were verified using children's serum samples that concentrated on allergens. the allergens. The clinical diagnostic practicability of CLMIA was assessed through comprehensive evaluations including measurements of the limit of detection (LOD), intra-batch, and inter-batch precision, linearity analysis, the cross-contamination rate, and the concordance rate with the Phadia system., Results: After the optimization process of CLMIA, the LODs for allergens were calculated to be below 0.01 kU/L, demonstrating the high sensitivity of CLMIA. All components exhibited good linearity within the range of 0.1-100.0 kU/L and the coefficient of determinations (R 2  > 0.99). The data of intra-batch precision (<10 %) and inter-batch data (<15 %) illustrated the high reproducibility of CLMIA. The cross-contamination rates for allergens (<0.5 %) showed the high accuracy of CLMIA without interfering. The positive concordance rate between CLMIA and the Phadia system exceeds 90 % with a good negative concordance rate (>85 %) and the Kappa coefficients (>0.8), suggesting the close alignment of CLMIA and the Phadia system and showing the satisfactory clinical potential of CLMIA in children's allergy disease., Conclusions: The application of CLMIA has been promising in allergen testing, especially for detecting multiple allergenic components in children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of skeletal muscle development through multiple mechanisms. The present study revealed that the lncRNA SOX6 AU (SRY-box transcription factor 6 antisense upstream) is reverse transcribed from upstream of the bovine sex-determining region Y (SRY)-related high-mobility-group box 6 ( SOX6 ) gene. SOX6 AU was significantly differentially expressed in muscle tissue among different developmental stages in Xianan cattle. Subsequently, knockdown and overexpression experiments discovered that SOX6 AU promoted primary skeletal muscle cells proliferation, apoptosis, and differentiation in bovine. The overexpression of SOX6 AU in bovine primary skeletal muscle cells resulted in 483 differentially expressed genes (DEGs), including 224 upregulated DEGs and 259 downregulated DEGs. GO functional annotation analysis showed that muscle development-related biological processes such as muscle structure development and muscle cell proliferation were significantly enriched. KEGG pathway analysis revealed that the PI3K/AKT and MAPK signaling pathways were important pathways for DEG enrichment. Notably, we found that SOX6 AU inhibited the mRNA and protein expression levels of the SOX6 gene. Moreover, knockdown of the SOX6 gene promoted the proliferation and apoptosis of bovine primary skeletal muscle cells. Finally, we showed that SOX6 AU promoted the proliferation and apoptosis of bovine primary skeletal muscle cells by cis-modulation of SOX6 in cattle. This work illustrates our discovery of the molecular mechanisms underlying the regulation of SOX6 AU in the development of beef.

A new synthesis of rare d-lyxose from easily available d-arabinose is disclosed. The route includes 7 steps with a total 40% yield. Inversion of configuration at C3 promoted by DAST reagent is utilized on trans-2,3-di-hydroxy pentofuranose to provide cis-2,3-di-hydroxy pentofuranose, which is hardly synthesized using normal method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest: None.

Hyperuricemic nephropathy (HN) is a common clinical complication of hyperuricemia. The pathogenesis of HN is directly related to urea metabolism in the gut microbiota. Febuxostat, a potent xanthine oxidase inhibitor, is the first-line drug used for the treatment of hyperuricemia. However, there have been few studies on the pharmacokinetics of febuxostat in HN animal models or in patients. In this study, a high-purine diet-induced HN rat model was established. The pharmacokinetics of febuxostat in HN rats was evaluated using LC-MS/MS. Astragaloside IV (AST) was used to correct the abnormal pharmacokinetics of febuxostat. Gut microbiota diversity analysis was used to evaluate the effect of AST on gut microbiota. The results showed that the delayed elimination of febuxostat caused drug accumulation after multiple administrations. Oral but not i. p. AST improved the pharmacokinetics of febuxostat in HN rats. The mechanistic study showed that AST could regulate urea metabolism in faeces and attenuate urea-ammonia liver-intestine circulation. Urease-related genera, including Eubacterium , Parabacteroides , Ruminococcus , and Clostridia , decreased after AST prevention. In addition, the decrease in pathogenic genera and increase in short-chain fatty acids (SCFA) producing genera also contribute to renal function recovery. In summary, AST improved the pharmacokinetics of febuxostat in HN rats by comprehensive regulation of the gut microbiota, including urea metabolism, anti-calcification, and short-chain fatty acid generation. These results imply that febuxostat might accumulate in HN patients, and AST could reverse the accumulation through gut microbiota regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Tang, Jiang, Pang, Xu, Yuan, Zhang, Liu and Fan.)

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Xie, Liu, Wang, Mu, Zhang, Zhao, Yuan, Guo, Wang, Xiang, Song, Jiang, Xiang and Cui.)

The Forkhead box class O proteins (FOXOs) family consists of highly conserved transcription factors, including FOXO1, FOXO3, FOXO4 and FOXO6. Each member of the FOXOs family is ubiquitously expressed and involved in regulating many biological activities such as tumor cell proliferation, apoptosis, migration and oxidative stress. The activity of FOXOs is mainly regulated by post-translational modification, and its inactivation is mainly mediated by the over-activation of its upstream modifying enzymes, which provides a possibility to use drugs to recover its activity. It is worth noting that FOXOs can not only inhibit, but also promote the occurrence and development of human tumors due to the complex effects of FOXOs. This review will summarize the structure and activity regulation of FOXOs, and discuss their tumor inhibiting effects by limiting cell proliferation and inducing apoptosis, as well as their tumor promoting effects by maintaining cell homeostasis, promoting metastasis and inducing drug resistance, so as to provide new ideas for the pathological research of related diseases and open up new ways to promote broader prevention and treatment strategies.

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality ( P< 0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P< 0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period ( P =0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR =0.62, 95% CI 0.55-0.69, P <0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P< 0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.

Globally consumed kimchi is manufactured through fermenting cruciferous vegetables containing indole glucosinolates (IG). But few reports describe the IG metabolism during the fermentation. Here, we show that indole-3-carbinol (I3C), a breakdown product of IG, is transformed during the kimchi fermentation into 3,3'-diindolylmethane (DIM) and 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1). LTr1 was found to kill the acute myeloid leukemia (AML) cells with FMS-like tyrosine kinase 3 (FLT3) receptor mutations, by inhibiting the FLT3 phosphorylation and the expression of downstream proteins (STAT5, ERK, and AKT). In the immune-depleted mice xenografted with human MV4-11 cells, LTr1 was demonstrated to reduce the tumor growth and synergize with sorafenib, an anti-AML agent in clinic. The work updates the chemical and biological knowledge about kimchi, and in particular establishes LTr1 as an FLT3 inhibitor that is effective and synergistic with sorafenib in treating AML., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Circular RNAs (circRNAs) play prominent roles in regulating the progression of cancers. This study is aimed to decipher the role of hsa&#95;circ&#95;0000730 in cervical cancer (CC).The differentially expressed circRNAs of CC were screened out from the Gene Expression Omnibus database. qRT-PCR was used to detect circ&#95;0000730 expression in CC tissues and cell lines, and the Kaplan-Meier curve was adopted to figure out the relationship between circ&#95;000730 expression and the overall survival time of CC patients. BrdU assay and Tanswell assay were utilized to examine the proliferation, migration, and invasion of CC cells. Western blot was adopted to detect PTEN protein expression. Bioinformatics analysis and dual-luciferase reporter assay were used to examine the target relationship between miR-942-5p and circ&#95;0000730 or PTEN, respectively.Circ&#95;0000730 was among the differentially expressed circRNAs in CC. Circ&#95;0000730 was significantly down-regulated in the cancer tissues of 50 CC patients and CC cell lines. Additionally, underexpression of circ&#95;0000730 was associated with the shorter survival time of CC patients. Gain- and loss-of-function assays highlighted that circ&#95;0000730 significantly inhibited the proliferation, migration, and invasion of CC cells. Mechanistically, miR-942-5p was identified as a downstream target of circ&#95;0000730, and circ&#95;0000730 could positively regulate PTEN expression via repressing miR-942-5p in CC cells.Circ&#95;0000730 inhibits the proliferation, migration, and invasion of CC cells via regulating miR-942-5p/PTEN axis. Circ&#95;0000730 probably acts as a tumor suppressor in CC, and it may be a candidate target for the treatment of CC., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Mitochondrial proteins, most of which are encoded in the nucleus and the rest of which are regulated by the mitochondrial genome, play pivotal roles in essential cellular functions. However, fluorescent probes that can be used for monitoring mitochondrial proteins have not yet been widely developed, thereby severely limiting the exploration of the functions of proteins in mitochondria. Towards this end, here we propose a near-infrared (NIR) fluorescence probe MPP to effectively illuminate the dynamic changes in mitochondrial proteins in live cells under oxidative stress, with excellent temporal and spatial resolution. Of particular importance, MPP extends the study of the pharmacology involved in apoptosis induced by anti-cancer drugs (hydroxycamptothecin (HCPT), epirubicin (Epi) and cyclophosphamide (CPA)) for the first time. Furthermore, employing a protein-activatable strategy, this probe could serve as an excellent phototherapeutic agent in photodynamic therapy (PDT). Finally, in vivo experiments suggest that this versatile probe can be used to image tumors in HeLa tumor-bearing mice for 24 h, which demonstrates that our probe could play a dual role as a robust phototherapeutic and imaging agent.

Mg-Li based alloys have been widely used in various fields. However, the widespread use of Mg-Li based alloys were restricted by their poor properties. The addition of rare earth element in Mg-Li can significantly improve the properties of alloys. In the present work, different electrochemical methods were used to investigate the electrochemical behavior of Y(iii) on the W electrode in LiCl-KCl melts and LiCl-KCl-MgCl 2 melts. In LiCl-KCl melts, typical cyclic voltammetry was used to study the electrochemical mechanism and thermodynamic parameters for the reduction of Y(iii) to metallic Y. In LiCl-KCl-MgCl 2 melts, the formation mechanism of Mg-Y intermetallic compounds was investigated, and the results showed that only one kind of Mg-Y intermetallic compound was formed under our experimental conditions. Mg-Li-Y alloys were prepared via galvanostatic electrolysis, and XRD and SEM equipped with EDS analysis were used to analyze the samples. Because of the restrictions of EDS analysis, ICP-AES was used to analyze the Li content in Mg-Li-Y alloys. The microhardness and Young's modulus of the Mg-Li-Y alloys were then evaluated., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In the present work, DNA nanopore was composed of a bundle of six DNA duplexes folded from six DNA strands and functionalized with Ramos cell aptamer and cell-penetrating peptide (CPP). Herein, we present a unique dually conjugated molecule with an aptamer and cell-penetrating peptide for targeting and recognition of Ramos cells. The aptamer sequence was specific bound to Ramos cell, at the meanwhile the nanopore assembly was taken onto the surface of cell membrane and then got into the cells with the help of CPP. Specific targeting and increased intracellular uptake of nanostructures by Ramos cells were aimed. The intracellular uptake of the structure was determined using confocal microscopy. This study is the first to describe the recognition of tumor cells with functional DNA nanopores, establishing the foundation for the tumor cell detection with low cytotoxic agents. Graphical abstract DNA nanopore was composed of a bundle of six DNA duplexes folded from six DNA strands and functionalized with Ramos cell aptamer and cell-penetrating peptide. The dually conjugated molecule was found to show both improved cellular uptake and effective Ramos cell targeting.

Based on test results and mass balance, PHA, TP metabolic regularity was revealed under different nitrate nitrogen concentrations in main anoxic stage [ c (NO 3 )] for nitrogen and phosphorus removal in single sludge system with continuous flow, then the effectiveness of using c (NO 3 ) as control parameter was proved from the perspective of the reaction mechanism. During experiment period, the influent COD, total nitrogen (TN), and total phosphorus (TP) concentrations were stabilized at (285.78±18.19), (58.13±3.79), and(7.14±0.51) mg·L -1 , respectively. The experiment was carried out under the condition that the c (NO 3 ) values were 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 and 4.0 mg·L -1 based on the feedback control structure using PLC automatic control system to control the nitrifying liquid flow with the water quality. The sludge load of COD was (0.253±0.071)kg·(kg·d) -1 , the sludge load of TP in anaerobic stage was (0.006±0.001) kg·(kg·d) -1 , the sludge load of TN in aerobic stage was (0.049±0.006) kg·(kg·d) -1 , the hydraulic retention time (HRT) in bioreactor was 9h, the sludge recycle flow was 0.5, and the mixed liquor recycle was 1.0. The results showed that effect of c (NO 3 ) value on PHA synthesis and storage rate in the ANS was conspicuous, and the percentage of PHA storage occupied 74% of COD removal when c (NO 3 ) value was 2.5 mg·L -1 .The impact of c (NO 3 ) value on PHA degraded in the main anoxic stage was great, and the percentage of PHA degradation in the main anoxic stage occupied 55% of total PHA degradation when c (NO 3 ) value was 2.5 mg·L -1 . The phosphorus released in anaerobic stage changed along with increasing c (NO 3 ), and the amount of phosphorus released obtained the maximum value 6.16 g·d -1 when c (NO 3 ) value was 2.5 mg·L -1 . In addition, under c (NO 3 ) value of 2.5 mg·L -1 , the amount of total phosphorus uptake and anoxic phosphorus uptake obtained the maximum values of 8.04 g·d -1 and 3.67 g·d -1 , respectively. Then it was confirmed that c (NO 3 ) could serve as a run controlling parameter with the best value of 2.5 mg·L -1 from the perspective of PHA and TP metabolic mechanism.

According to the 2012 statistics of the International Agency for Research on Cancer (IARC), gastric cancer is the fifth most common malignancy, and the third leading cause of cancer-related deaths worldwide. Conventional chemotherapy and radiation have shown limited efficacy for advanced gastric cancer, showing an overall survival (OS) rate of ~10 months. Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is the first approved molecularly targeted agent for HER2-overexpressing gastric cancer, which was found to prolong the OS and the progression-free survival (PFS) of patients. However, HER2 overexpression is present only in a minority of patients with gastric cancer. Hence, other targeted agents are urgently needed. Ramucirumab, a novel human IgG1 monoclonal antibody that selectively targets the extracellular domain of VEGF receptor 2 (VEGFR2), is regarded as a new standard second-line treatment for patients with advanced gastric cancer. The combination of two or more targeted agents directed against two different molecular targets may improve the survival of patients with advanced gastric cancer. Although great efforts have been made, the effect of targeted therapy for gastric cancer is limited. One key reason is that participants in clinical trials for new targeted agents were not selected by detection of the targeted molecule. Here, we review clinical trials related to molecular targets such as anti-epidermal growth factor receptor signaling including anti-HER2 and anti-EGFR1, anti-VEGF signaling, anti-mammalian target of rapamycin (mTOR), tyrosine kinase inhibitors (TKIs) and anti-MET.

Intestinal motility and barriers are often impaired due to intestinal congestion during liver transplantation. Intestinal bacteria and enterogenous endotoxins enter into the blood stream or lymphatic system and translocate to other organs, which can result in postoperative multi-organ dysfunction (MODF) and systemic inflammatory reaction syndrome (SIRS) severely affecting patient survival. However, the mechanisms underlying liver transplantation-induced intestinal injury remain unclear and effective therapies are lacking. Thus, the present study investigated whether these effects were associated with endotoxin-mediated apoptosis. Rat autologous orthotopic liver transplantation (AOLT) models were established to observe dynamic intestinal injuries at different time-points following reperfusion. Changes in the levels of endotoxins and the primary receptor, toll-like receptor 4 (TLR4), as well as its downstream signaling molecule, nuclear factor-κB (NF-κB) were all determined. Finally, immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling assays were conducted to detect caspase-3 expression and intestinal cell apoptosis, respectively. AOLT resulted in significant pathological intestinal injury, with the most serious intestine damage apparent four or eight hours following reperfusion. Furthermore, the levels of endotoxins and inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, peaked during this time period and gradually decreased to the normal level. Notably, TLR4 and downstream NF-κB expression, as well as NF-κB-mediated caspase-3 activation and intestinal cell apoptosis coincided with the intestinal pathological damage. Thus, the possible mechanism of post-liver transplantation intestinal injury was demonstrated to be associated with NF-κB activation-induced cell apoptosis.

We report a novel ratiometric and reversible fluorescent probe for Cd(2+) detection utilizing a 6-(dimethylamino)quinaldine derivative as the fluorophore and a 2-hydrazinopyridine derivative as Cd(2+) chelator. This ratiometric fluorescent probe possesses favorable photophysical properties. It shows a large (55 nm) red-shift from 515 nm to 570 nm in the emission spectrum. Moreover, this probe also exhibits an excellent linear relationship of fluorescence intensity ratio (F570/F515) (R(2)=0.989) vs. Cd(2+) concentration in the range of 0-10 µM at physiological pH, which can serve as a "quantitative detecting" probe for Cd(2+). Utilizing this sensitive and selective probe, we have successfully detected Cd(2+) in living cells.

The aim of this study was to observe the influence of gap junction (GJ) functional changes on the hepatotoxicity of TNF-α. Three different methods were employed to study functional effects of the GJ inhibition: 1) pretreatment with a GJ inhibitor; 2) inoculation of cells at high and low densities; and 3) inhibition of the expression of connexin 32 (Cx32) by small inhibitory RNA transfection. We then observed the influence of these treatments on hepatotoxicity following treatment with different concentrations of TNF-α for various duration. The hepatotoxicity of TNF-α was observed to occur in a dose- and time-dependent manner; after pretreatment inhibition, the hepatotoxicity of TNF-α was significantly reduced (P < 0.01). The hepatotoxicity of TNF-α was also found to be remarkably lower in cells that had been inoculated at low density (as measured by the amount of GJ formation among cells) than in those inoculated at density (P < 0.01). In addition, following Cx32 inhibition, the hepatotoxicity of TNF-α was significantly decreased (P < 0.01) as well. Together, these results suggest that inhibition of GJ function or of its component Cx32 significantly decreases the hepatotoxicity of TNF-α, and that the expression of Cx32 plays an important role in the hepatotoxicity of TNF-α.

A series of O3-phase NaFe(x)(Ni0.5Mn0.5)(1-x)O2 (x = 0, 0.1, 0.2, 0.3, 0.4, and 1) samples with different Fe contents was prepared and investigated as high-capacity cathodic hosts of Na-ion batteries. The partial substitution of Ni and Mn with Fe in the O3-phase lattice can greatly improve the electrochemical performance and the structural stability. A NaFe0.2Mn0.4Ni0.4O2 cathode with an optimized Fe content of x = 0.2 can deliver an initial reversible capacity of 131 mAh g(-1), a reversible capacity greater than 95% over 30 cycles, and a high rate capacity of 86 mAh g(-1) at 10 C in a voltage range of 2.0-4.0 V. The structural characterizations reveal that pristine NaMn0.5Ni0.5O2 and Fe-substituted NaFe0.2Mn0.4Ni0.4O2 lattices underwent different phase transformations from P3 to P3″ and from P3 to OP2 phases, respectively, at high voltage interval. The as-resulted OP2 phase by Fe substitution has smaller interslab distance (5.13 Å) than the P3″ phase (5.72 Å), which suppresses the co-insertion of the solvent molecules, the electrolyte anions, or both and therefore enhances the cycling stability in the high voltage charge. This finding suggests a new strategy for creating cycle-stable transition-metal oxide cathodes for high-performance Na-ion batteries.

Objective: To monitor the cisplatin-induced autophagy and investigate the function of autophagy in bladder cancer cells., Methods: The transmission electron microscope was used to detect autophagic vacuoles and the fluorescence microscope to detect GFP-LC3. The expressions of proteins, such as LC3, PARP, mTOR, P70S6K were analyzed by immunoblotting. Cell viability was analyzed by MTS assay, in which rapamycin was used to inhibit mTOR phosphorylation and enhance autophagy. LC3 expression was knocked down by RNA interference., Results: In bladder cancer cell T24, autophagic vacuoles were observed by the transmission electron microscope and GFP-LC3 aggregation was viewed by the fluorescence microscope after cisplatin treatment. The LC3-II accumulation was enhanced by cispaltin treatment. Particularly at the concentrations of 50, and 100 μmol/L for 48 h , the gray value of LC3-II/Actin(%) increased 30 and 44, respectively. Cisplatin treatment inhibited the phosphorylation of mTOR/P70S6K, which was most significant at the concentration of 100 μmol/L for 48 h. Cisplatin also induced cell viability loss, which was 12% and 45% at the concentrations of 50, and 100 μmol/L for 24 h. This effect could be enhanced by rapamycin (F=74.890,P<0.01). Furthermore, knocking down LC3 by RNA interference reduced PARP cleavage., Conclusion: Cisplatin could induce autophagy in bladder cancer cell T24, which promoted cisplatin-induced apoptosis.

Objective: To study the effect of expressed aplasia ras homolog member I (ARHI) on the malignant biological behaviors of gastric cancer including the proliferation, migration and invasion of the cell., Methods: The eukaryotic expression plasmid of ARHI was constructed and transfected into MKN-28 cell with lipofectamine 2000 as pEGFP-ARHI group, transfected with pEGFP-N1 as pEGFP-N1 group, and untreated MKN-28 as control group. The expression of ARHI was detected by Western blotting and fluorescence microscope. CCK-8 assay was used to analyze the cell proliferation, the wound-healing assay and transwell assay were performed to investigate the effects on migration and invasion., Results: Compared with the pEGFP-N1 group and control group, proliferation, invasion and migration of the pEGFP-ARHI group were depressed (P < 0.05)., Conclusion: Recombination eukaryotic expression pEGFP-ARHI could partially reverse the malignant phenotypes of gastric cancer cell MKN-28.

Panax Notoginseng Saponins (PNS) have been well known to have anti-tumor activity and enhance cytotoxicity of some cancer chemotherapy agents, but the mechanisms underlying these effects are still unknown. This study investigates the effect of PNS on cytotoxicity of cisplatin and the relationship between this effect and the modulation of gap junctions (GJ) function by PNS in a transfected cell line. The cytotoxicity of cisplatin (0.25-1 µg/mL) was increased in the presence of GJ. Inhibition of gap junction by either GJ blocker or interception of Connexin (Cx) expression decreased the cytotoxicity of cisplatin. Increasing GJ function enhanced cytotoxicity of cisplatin, only in the cells with functional GJ. PNS (50-200 µg/mL) significantly enhanced cisplatin cytotoxicity, but this effect required functional gap junctions between the cells. Exposure of the cells to PNS (50-200 µg/mL) for 4 h leads to a significant enhance in dye coupling of GJ in a dose-dependent manner. These results suggest that PNS increases the cytotoxicity of cisplatin through enhancement of GJ activity.

Background: Clinical combination of some traditional Chinese medical herbs, including berberine, with irradiation is demonstrated to improve efficacy of tumor radiotherapy, yet the mechanisms for such effect remain largely unknown. The present study investigated the effect of berberine on apoptosis induced by X-rays irradiation and the relation between this effect and gap junction intercellular communication (GJIC)., Methods: The role of gap junctions in the modulation of X-rays irradiation-induced apoptosis was explored by manipulation of connexin (Cx) expression, and gap junction function, using oleamide, a GJIC inhibitor, and berberine., Results: In transfected HeLa cells, Cx32 expression increased apoptosis induced by X-rays irradiation, while inhibition of gap junction by oleamide reduced the irradiation responses, indicating the dependence of X-rays irradiation-induced apoptosis on GJIC. Berberine, at the concentrations without cytotoxicity, enhanced apoptosis induced by irradiation only in the presence of functional gap junctions., Conclusions: These results suggest that berberine potentizes cell apoptosis induced by X-rays irradiation, probably through enhancement of gap junction activity.

2-Aminoethoxydiphenyl borate (2-APB) has recently been demonstrated to inhibit gap junction (GJ) channels, whereas the underlying mechanisms are still unknown. Using mouse TM₄ Sertoli cell which expresses connexin43 (Cx43), we explored the effects of 2-APB and its analogues on dye-coupling through junctional channels formed by Cx43 and on expression of Cx43. Exposure of the cells to 2-APB (1-50 µM) and one of its analogues diphenylboronic anhydride (DPBA) (1-30 µM) for 4 h leads to a significant decrease in dye coupling of GJ in a concentration-dependent manner. The inhibitory effects of 2-APB and DPBA are reversible since decreased GJ coupling resumes after the two compounds are washed out. The disfunction of GJ induced by 2-APB and DPBA is associated with a decrease in total amount of Cx43 protein and number of GJs on the cell membrane. 2-APB and DPBA do not alter Cx43 phosphorylation state and the level of Cx43 mRNA expression. The loss of Cx43 protein is prevented by either lysosomal or proteasomal inhibitor, suggesting that the decrease in Cx43 results from a 2-APB or DPBA-enhanced degradation of Cx43. The present results indicate that 2-APB and DPBA inhibit GJ communication through decreasing Cx43 expression in TM₄ cells.

A novel grille form complex membrane module composed of glass fiber covered with organic membrane and the dynamic membrane bioreactor (DMBR) with this complex membrane were studied. The results showed that the flux of the dynamic membrane of glass fiber tube without covering with organic membrane solution was only 4 L/(m2 x h) at a trans-membrane pressure (TMP) of 0.02 MPa. After the modification of covering with the organic membrane solution, the complex dynamic membrane flux could reach to a level of 16 L/(m2 x h) at a TMP of 0.01 MPa in operation, and after a hydraulic and chemical cleaning, the membrane flux was up to 17.1 L/(m2 x h) at a lower TMP of 0.003 MPa. When the glass fiber tube was coated with a membrane solution with a concentration of 1:4 (membrane materials/solution in volume ratio), the flux of the complex membrane worked steadily at 14.29 L/(m2 x h) more than 51 days, and according to calculation by TMP rising, the flux could maintain for almost 275 d. The average removal rates of COD and NH4+ -N were 81.96% and 83.66% respectively by the DMBR, and that were 21.01% and 3.61% only by the complex dynamic membrane. Moreover, the cost of complex membrane was approximately 40-60 yuan/m2, which was lower than the traditional organic membrane.

We purified two novel conotoxins, designated as ca11a and ca11b, from the venom of Conus caracteristicus. Based on the amino acid sequence of mature ca11a, we cloned its full-length cDNA. Based on the signal peptide of ca11a, several ca11a-like conotoxins were cloned from C. caracteristicus and C. pulicarius. These novel conotoxins have an I-superfamily cysteine pattern but with a novel signal peptide sequence, suggesting they belong to a new branch of I-superfamily, designated as I(3)-superfamily. Additionally, two O-superfamily conotoxins were also cloned based on the signal peptide of ca11a, suggesting a possible evolutionary relationship between O- and I-superfamilies.

A new conotoxin, ca16a, containing 8 cysteine residues was purified, sequenced, and cloned from a worm-hunting snail, Conus caracteristicus. This conotoxin is an extremely hydrophilic peptide comprising 34 residues, with 4 acidic and 4 basic residues. It is rich in polar Gly, Ser, and Thr residues and includes a hydroxylated Pro residue. The cysteine arrangement pattern of ca16a (-C-C-CC-C-CC-C-, designated as framework #16) is distinct from that of other known conotoxins. Furthermore, the signal peptide sequence of this conotoxin does not share any homology with those of other conotoxins. Leu residues account for almost 50% of its 20-residue signal peptide. The unique cysteine framework and signal peptide sequence of ca16a suggest that it belongs to a new conotoxin superfamily.

Objective: To investigate the prevalence of human papillomavirus (HPV) and the HPV genotype distribution in invasive squamous cell carcinoma of the uterine cervix in the Mongolian women in Inner Mongolia autonomy region., Methods: The prevalence data of HPV in our department were retrospectively reviewed. INNO-LiPA genotyping technique was used to detect HPV genotypes in the reserved carcinoma tissue specimens., Results: Totally 63 tissue specimens were collected and detected. The prevalence of HPV was 93.7%. The positive rates of HPV among different clinical staging and different pathological grading were not significantly different (P >0.05). The prevalence of HPV16 was not significantly different among different age groups (P>0.05). HPV16 (69.8%), HPV18 (4.8%), HPV31 (4.8%), HPV39 (4.8%), and HPV52 (3.2%) were the 5 dominating HPV genotypes in all cases., Conclusions: HPV infection is closely correlated with invasive squamous cell carcinoma of the uterine cervix in Mongolia women. HPV16 is the most important genotype in invasive squamous cell carcinoma of the uterine cervix, followed by HPV18, 31, and 39. HPV infection dose not affect the progression and differentiation of invasive squamous cell carcinoma of the uterine cervix.

M-superfamily conotoxins can be divided into four branches (M-1, M-2, M-3 and M-4) according to the number of amino acid residues in the third Cys loop. In general, it is widely accepted that the conotoxin signal peptides of each superfamily are strictly conserved. Recently, we cloned six cDNAs of novel M-superfamily conotoxins from Conus leopardus, Conus marmoreus and Conus quercinus, belonging to either M-1 or M-3 branch. These conotoxins, judging from the putative peptide sequences deducted from cDNAs, are rich in acidic residues and share highly conserved signal and pro-peptide region. However, they are quite different from the reported conotoxins of M-2 and M-4 branches even in their signal peptides, which in general are considered highly conserved for each superfamily of conotoxins. The signal sequences of M-1 and M-3 conotoxins composed of 24 residues start with MLKMGVVL-, while those of M-2 and M-4 conotoxins composed of 25 residues start with MMSKLGVL-. It is another example that different types of signal peptides can exist within a superfamily besides the I-conotoxin superfamily. In addition to the different disulfide connectivity of M-1 conotoxins from that of M-4 or M-2 conotoxins, the sequence alignment, preferential Cys codon usage and phylogenetic tree analysis suggest that M-1 and M-3 conotoxins have much closer relationship, being different from the conotoxins of other two branches (M-4 and M-2) of M-superfamily.

In the venoms of cone snails, alpha conotoxins are competitive antagonists of nicotinic acetylcholine receptors. Eleven novel cDNA and eight partial gene sequences (including two pseudogenes) of alpha conotoxins were identified from five species of cone snail. As expected, every cDNA encodes a precursor of prepropeptide. In all the partial genes of alpha conotoxins identified, there is a long intron inserted at a fixed position in the pro-region, dividing the encoding region into two exons. The mutation rate in exon I (encoding the signal peptide and a part of pro-region) is much lower than that in exon II (encoding the other part of pro-region, the mature peptide and 3' untranslational region). Interestingly, the sequences at the 5' and 3' end of introns are highly conserved. In addition, in the identified introns exist long dinucleotide (e.g. "GT", "CA") or trinucleotide ("CAT") repeats. In the special case of Pu 1.1, there are five almost identical repeats of a 150 bp sequence in the long intron. Taking advantage of the conserved 3' end sequence of intron, 16 alpha conotoxins, as well as a pseudogene and three kappa A conotoxins, were identified from their genomic DNAs. Based on the comparison of these cDNA and gene sequences, a hypothesis of the alpha conotoxin evolution was proposed.

A new type of fiberglass tubular self-forming dynamic membrane bioreactor (DMBR) and its application for treatment of landfill leachate on laboratory scale were studied. The results showed that the system worked with a average membrane flux 3.75 L/m2 x h) maintained by gravity filtration at a trans-membrane pressure (TMP) of 2 900 Pa for near 80 days. After the modification of membrane module, a higher membrane flux was achieved at a TMP of 1 450 Pa and the membrane flux could be maintained steadily at 6 L/(m2 x h) for a long time. At the same time, the formation and filtration performance of dynamic membrane (DM) was tested. The effluent turbidity was blow 1.0 NTU and the average removal of COD, BOD5 and NH4(+) -N in this system exceeded 71%, 96% and 98% respectively. Moreover, COD removal from the supernatant on an average of 19.34% was made only by the dynamic membrane.

The M-superfamily with the typical Cys framework (-CC-C-C-CC-) is one of the seven major superfamilies of conotoxins found in the venom of cone snails. Based on the number of residues in the last Cys loop (between C4 and C5), M-superfamily conotoxins can be provisionally categorized into four branches (M-1, M-2, M-3, M-4) [Corpuz GP, Jacobsen RB, Jimenez EC, Watkins M, Walker C, Colledge C, Garrett JE, McDougal O, Li W, Gray WR, et al. (2005) Biochemistry44, 8176-8186]. Here we report the purification of seven M-superfamily conotoxins from Conus marmoreus (five are novel and two are known as mr3a and mr3b) and one known M-1 toxin tx3a from Conus textile. In addition, six novel cDNA sequences of M-superfamily conotoxins have been identified from C. marmoreus, Conus leopardus and Conus quercinus. Most of the above novel conotoxins belong to M-1 and M-2 and only one to M-3. The disulfide analyses of two M-1 conotoxins, mr3e and tx3a, revealed that they possess a new disulfide bond arrangement (C1-C5, C2-C4, C3-C6) which is different from those of the M-4 branch (C1-C4, C2-C5, C3-C6) and M-2 branch (C1-C6, C2-C4, C3-C5). This newly characterized disulfide connectivity was confirmed by comparing the HPLC profiles of native mr3e and its two regioselectively folded isoforms. This is the first report of three different patterns of disulfide connectivity in conotoxins with the same cysteine framework.