Effect of anti-thyroid antibodies on recurrent miscarriage: A meta-analysis.

SETTING: Previous studies addressed the association between anti-thyroid antibodies and recurrent miscarriage (RM), however, the role of anti-thyroid antibodies in RM patients is debatable. OBJECTIVES: Therefore, we conducted this meta-analysis and the aim of this current study was to assess whether anti-thyroid peroxidase (anti-TPO) and/or anti-thyroglobulin (anti-TG) antibody positivity was associated with RM. DESIGN: A meta-analysis was conducted. PARTICIPANTS: Recurrent miscarriage patients. METHODS: STATA 12.0 software were applied to compute odds ratios (ORs)/relative risks (RRs) and 95% CIs regarding association between anti-TPO and anti-TG antibodies and the prevalence of RM. RESULTS: N = 28 studies (8875 participants) explored effect of anti-thyroid antibodies on RM. Analysis of the 28 studies revealed significant association between anti-TPO, anti-TG antibodies and the prevalence of RM with a random effects model (OR/RR = 2.02; 95% CI: 1.63-2.51, p < 0.001; I2 = 44.3%, p value for Q test = 0.004). Analysis of the 20 studies revealed significant association between anti-TPO antibodies and the prevalence of RM with a random effects model (OR/RR = 1.59; 95% CI: 1.25-2.03, p < 0.001; I2 = 43.1%, p value for Q test = 0.022). Analysis of the 14 studies revealed significant association between anti-TG antibodies and the prevalence of RM with a random effects model (OR/RR = 2.25; 95% CI: 1.56-3.23, p < 0.001; I2 = 49.2%, p value for Q test = 0.019). CONCLUSIONS: Based on the currently available analysis, our findings suggest that women with anti-TPO and/or anti-TG antibodies have a higher risk of RM than that in negative antibody women. Further investigation is needed to better clarify the exact role of the anti-thyroid antibodies in RM and whether treatment is of benefit. LIMITATIONS: First, differences from various detection methods and reagents used in different studies may affect the diagnostic interpretation of anti-thyroid antibodies, which might influence the accuracy of this meta-analysis. Second, positive anti-thyroid antibodies seem likely to be part of a more general disorder of maternal immune system, due to restrictions of funding and condition, a complete autoantibody screening investigation is hardly to conduct in all participants, and this could be a possible limitation of all included studies. Third, there is no mention of thyroxine therapy on RM, making the meta-analysis even more limited.

The landscape of different molecular modules in an immune microenvironment during tuberculosis infection.

Tuberculosis is a chronic inflammatory disease caused by Mycobacterium tuberculosis. When tuberculosis invades the human body, innate immunity is the first line of defense. However, how the innate immune microenvironment responds remains unclear. In this research, we studied the function of each type of cell and explained the principle of an immune microenvironment. Based on the differences in the innate immune microenvironment, we modularized the analysis of the response of five immune cells and two structural cells. The results showed that in the innate immune stress response, the genes CXCL3, PTGS2 and TNFAIP6 regulated by the nuclear factor kappa B(NK-KB) pathway played a crucial role in fighting against tuberculosis. Based on the active pathway algorithm, each immune cell showed metabolic heterogeneity. Besides, after tuberculosis infection, structural cells showed a chemotactic immunity effect based on the co-expression immunoregulatory module.

Quercetin acts via the G3BP1/YWHAZ axis to inhibit glycolysis and proliferation in oral squamous cell carcinoma.

There is increasing evidence that the GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) plays important roles in the formation of various tumors. However, the biological functions and mechanism of G3BP1 in promoting the progression of oral squamous cell carcinoma remain largely unknown. The impacts of quercetin on glycolysis and proliferation of the CAL27 oral squamous cell carcinoma line were investigated, and the mediating role of the G3BP1/YWHAZ pathway was explored. CAL27 cells stably over- or underexpressing G3BP1 were treated with quercetin, and then cell proliferation was assayed together with the expression of proteins involved in glucose uptake, glycolysis, and lactate production, as well as the activity of hexokinase, pyruvate kinase, and lactate dehydrogenase. CAL27 cells expressed G3BP1 and YWHAZ at significantly higher levels than normal oral squamous cells. CAL27 cells showed the highest expression of both proteins among the three carcinoma lines (TSCCA, SCC15, 42 CAL27). Overexpressing G3BP1 in CAL27 cells markedly induced glucose uptake, glycolysis, cell proliferation, and YWHAZ expression. Knocking down G3BP1 or YWHAZ exerted the opposite effects, which were similar to the effects of inhibiting glycolysis. Quercetin repressed glucose uptake, glycolysis, cell proliferation, and G3BP1/YWHAZ signaling in a dose-dependent way, and these effects were antagonized by G3BP1 overexpression. Quercetin can inhibit glycolysis and cell proliferation of oral squamous cell carcinoma, apparently by inhibiting the G3BP1/YWHAZ axis.

Photo-thermal Cooperative Carbonylation of Ethanol with CO2 on Cu2 O-SrTiCuO3-x.

Carbonylation of ethanol with CO2 as carbonyl source into value-added esters is of considerable significance and interest, while remains of great challenge due to the harsh conditions for activation of inert CO2 in that the harsh conditions result in undesired activation of α-C-H and even cleavage of C-C bond in ethanol to deteriorate the specific activation of O-H bond. Herein, we propose a photo-thermal cooperative strategy for carbonylation of ethanol with CO2 , in which CO2 is activated to reactive CO via photo-catalysis with the assistance of *H from thermally-catalyzed dissociation of alcoholic O-H bond. To achieve this proposal, an interfacial site and oxygen vacancy both abundant SrTiCuO3-x supported Cu2 O (Cu2 O-SrTiCuO3-x ) has been designed. A production of up to 320 µmol g-1 h-1 for ethyl formate with a selectivity of 85.6 % to targeted alcoholic O-H activation has been afforded in photo-thermal assisted gas-solid process under 3.29 W cm-1 of UV/Vis light irradiation (144 °C) and 0.2 MPa CO2 . In the photo-driven activation of CO2 and following carbonylation, CO2 activation energy decreases to 12.6 kJ mol-1 , and the cleavage of alcoholic α-C-H bond has been suppressed.

Increased serum adenosine deaminase activity in patients with adult-onset Still's disease.

BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology, lacking specific diagnosis and disease activity evaluation indicators. This study will analyze the activity and clinical significance of Adenosine deaminase (ADA) in AOSD patients. METHODS: Totally 53 AOSD patients, 60 patients with other autoimmune diseases including systemic lupus erythematosus (SLE), sjogren syndrome (SS) and rheumatoid arthritis (RA), as well as 60 healthy subjects were included in this study. AOSD activity was determined by Pouchot score. We analyzed the correlation between ADA activity and clinical parameters. In addition, the correlation between ADA activity and disease activity score was also analyzed. RESULTS: This study showed that the activity of ADA in AOSD patients was significantly higher than that of healthy controls, SLE, SS and RA patient groups (p < 0.0001). The ADA activity of AOSD patients decreased significantly after systemic treatment (p < 0.0001). Correlation analysis showed that ADA activity was positively correlated with ALT(r = 0.54, p < 0.0001), AST (r = 0.82, p < 0.0001) and serum ferritin (r = 0.67, p < 0.001). ADA activity was negatively correlated with white blood cell (r = - 0.42, p = 0.002) and platelet counts (r = - 0.44, p = 0.001). We also found a significant positive correlation between the activity of ADA and Pouchot score in AOSD patients (r = 0.51, p = 0.001). Receiver operating characteristic (ROC) curve analysis showed that ADA activity had a sensitivity of 93.3%, and a specificity of 83% for the diagnosis of AOSD, with an area under the curve of 0.93. CONCLUSION: This study showed that serum ADA activity can be used as a potential biomarker for AOSD diagnosis and disease activity assessment.

Atomic Pt-Catalyzed Heterogeneous Anti-Markovnikov C-N Formation: Pt10 Activating N-H for Pt1δ+-Activated C═C Attack.

C-N formation is of great significance to synthetic chemistry, as N-containing products are widely used in chemistry, medicine, and biology. Addition of an amine to an unsaturated carbon-carbon bond is a simple yet effective route to produce new C-N bonds. But how to effectively conduct an anti-Markovnikov addition with high selectivity has been a great challenge. Here, we proposed a strategy for highly regioselective C-N addition via hydroamination by using supported Pt. It has been identified that atomic-scale Pt is the active site for C-N addition with Pt12+ for Markovnikov C-N formation and atomic Pt (Pt1δ+ and Pt10) contributing to anti-Markovnikov C-N formation. A selectivity of up to 92% to the anti-Markovnikov product has been achieved with atomic Pt in the addition of styrene and pyrrolidine. A cooperating catalysis for the anti-Markovnikov C-N formation between Pt1δ+ and Pt10 has been revealed. The reaction mechanism has been studied by EPR spectra and in situ FT-IR spectra of adsorption/desorption of styrene and/or pyrrolidine. It has been demonstrated that Pt10 activates amine to be electrophilic, while Pt1δ+ activates C═C by π-bonding to make ß-C nucleophilic. The attack of nucleophilic ß-C to electrophilic amine affords the anti-Markovnikov addition. This strategy proves highly effective to a variety of substrates in anti-Markovnikov C-N formation, including aromatic/aliphatic amines reacting with aromatic olefins, aromatic/aliphatic olefins with aromatic amines, and linear aliphatic olefins with secondary aliphatic amines. It is believed that the results provide evidence for the function of varied chemical states in monatomic catalysis.

Low-dose lymphocyte immunotherapy rebalances the peripheral blood Th1/Th2/Treg paradigm in patients with unexplained recurrent miscarriage.

BACKGROUND: The published results regarding lymphocytes immunotherapy for unexplained recurrent miscarriage (uRM) patients are conflicting due to different screening criteria and therapeutic protocols. The objective of the present study is to evaluate the effectiveness of immunotherapy using low-dose lymphocytes in patients with uRM and Th1/Th2/Treg paradigm disorders. METHODS: Sixty-four uRM patients who received low-dose lymphocytes immunotherapy served as the immunotherapy group, while the other 35 women who did not receive the treatment served as the control group. The proportions of peripheral blood Th1 cells, Th2 cells and Treg cells; and the concentration of TGF-ß1 in serum were detected by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively, before and after the immunotherapy. RESULTS: The proportion of Th1 cells was significantly decreased while the proportions of Th2 cells and Treg cells were significantly increased in immunotherapy group patients after treatment. In addition, the concentration of TGF-ß1 in serum was significantly higher after immunotherapy than before. Forty-three uRM patients achieved pregnancy after receiving immunotherapy and 5 patients underwent miscarriages in the immunotherapy group (11.6%, 5/43), while 8 of the 23 pregnant patients experienced a miscarriage in the control group (34.8%, 8/23; p < 0.05). CONCLUSIONS: Low-dose lymphocyte immunotherapy is beneficial for restoring balance in the Th1/Th2/Treg paradigm and improving pregnancy outcome in uRM patients. TRIAL REGISTRATION: NCT03081325 . ClinicalTrials.gov . Retrospectively registered July 2015.

Potential Vaccine Targets against Rabbit Coccidiosis by Immunoproteomic Analysis.

The aim of this study was to identify antigens for a vaccine or drug target to control rabbit coccidiosis. A combination of 2-dimensional electrophoresis, immunoblotting, and mass spectrometric analysis were used to identify novel antigens from the sporozoites of Eimeria stiedae. Protein spots were recognized by the sera of New Zealand rabbits infected artificially with E. stiedae. The proteins were characterized by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) analysis in combination with bioinformatics. Approximately 868 protein spots were detected by silver-staining, and a total of 41 immunoreactive protein spots were recognized by anti-E. stiedae sera. Finally, 23 protein spots were successfully identified. The proteins such as heat shock protein 70 and aspartyl protease may have potential as immunodiagnostic or vaccine antigens. The immunoreactive proteins were found to possess a wide range of biological functions. This study is the first to report the proteins recognized by sera of infected rabbits with E. stiedae, which might be helpful in identifying potential targets for vaccine development to control rabbit coccidiosis.

Carbon nanofibers: synthesis and applications.

As a novel functional material, carbon nanofiber has many interesting applications in the chemical industry, material science, and energy storage fields. Chemical vapor dispersion and carbonization polymer nanofibers are the two important routes to synthesize carbon nanofibers. In this mini-review, the synthesis mechanisms of carbon nanofibers are illustrated and some novel applications of carbon nanofiber were also summarized.

Photocatalytic degradation of sulfonamides in suspensions of coral-like graphene carbon nitride with nitrogen vacancies.

Sulfonamides (SNs) belong to a category of broad-spectrum antibiotics, which have attracted growing concerns owing to the adverse effects on ecosystem. In this paper, coral-like graphitic carbon nitrides with nitrogen vacancies were prepared by polymerization of melamine in the presence of NH4Cl, and the effect of NH4Cl amount on the structure and photocatalytic performance of g-C3N4 in degradation of sulfonamide antibiotics such as sulfamethoxazole (SMX), sulfadiazine (SDZ) and sulfathiazole (STZ) was systematically studied. It was found that the addition of NH4Cl results in the formation of coral-like g-C3N4 with nitrogen vacancies, and optimal photocatalyst (PCN-1 sample) prepared with a melamine to NH4Cl mass ratio of 1:1 showed the highest photocatalytic activity towards SNs degradation due to the quick electron-hole migration, efficient separation capacity and excellent photoelectric properties. The electron paramagnetic resonance (EPR) technique was used to determine the reactive oxygen species (ROSs) that are responsible for the degradation of SNs, and the detailed degradation pathway of STZ was proposed according to the identification of the intermediates by liguid chromatography-high resolution mass spectrometry (LC-HRMS).

Establishment and evaluation of Voting algorithm-based internal quality control (ViQC), a patient-based real-time quality control.

BACKGROUND: Patient-Based Real-Time Quality Control (PBRTQC) has emerged as a supplementary programme to traditional internal quality control (iQC) mechanisms. Despite its growing popularity, practical applications in clinical settings reveal several challenges. The primary objective of this research is to introduce and develop an Artificial Intelligence (AI)-based method, named Voting algorithm based iQC (ViQC), designed to enhance the precision and reliability of existing PBRTQC systems. METHODS: In this study, we conducted a retrospective analysis of 111,925 inpatient serum glucose test results from Nanjing Drum Tower Hospital, Nanjing, China, to provide an unbiased data set. The Voting iQC (ViQC) algorithm, established by the principles of the Voting algorithm, was then developed. Its analytical performance was evaluated through the calculation of random errors (RE). Subsequently, its clinical efficacy was assessed by comparison with five statistical algorithms: Moving Average (MA), Exponentially Weighted Moving Average (EWMA), Moving Median (movMed, MM), Moving Quartile (MQ), and Moving Standard Deviation (MovSD). RESULTS: The ViQC model incorporates a variety of machine learning models, including logistic regression, Bayesian methods, K-Nearest Neighbor, decision trees, random forests, and gradient boosting decision trees, to establish a robust predictive framework. This model consistently maintains a false positive rate below 0.002 across all six evaluated error factors, showcasing exceptional precision. Notably, its performance further excels with an error factor of 3.0, where the false positive rate drops below 0.001, and achieves an accuracy rate as high as 0.965 at an error factor of 2.0. The classification effectiveness of ViQC model is evaluated by an area under the curve (AUC) exceeding 0.97 for all error factors. In comparison to five conventional PBRTQC statistical methods, ViQC significantly enhances error detection efficiency, maximum reducing the trimmed average number of patient samples required for detecting errors from 724 to 168, thereby affirming its superior error detection capability. CONCLUSION: The new established PBRTQC using artificial intelligence yielded satisfactory performance compared to the traditional PBBTQC in real world setting.

Ligustilide enhances pregnancy outcomes via improvement of endometrial receptivity and promotion of endometrial angiogenesis in rats.

Ligustilide (LIG) is the main active ingredient of Angelica sinensis (Oliv.) Diels, which could promote focal angiogenesis to exert neuroprotection. However, there was no report that verified the exact effects of LIG on endometrial angiogenesis and the pregnancy outcomes. To explore the effects of LIG on low endometrial receptivity (LER) and angiogenesis, pregnancy rats were assigned into Control (saline treatment), LER (hydroxyurea-adrenaline treatment), LIG 20 mg/kg and LIG 40 mg/kg groups. Hematoxylin and eosin (H&E) staining was performed to evaluate endometrial morphology. Quantitative real-time PCR, immunofluorescence staining, western blot and immunohistochemistry staining were employed to assess the expression of endometrial receptivity factors and angiogenesis-related gene/protein, respectively. RNA sequencing was used to analyze the effects of LIG on LER caused by Kidney deficiency and blood stasis. We found that endometrial thickness and the implanted embryo number were substantially reduced in the hydroxyurea-adrenaline-treated pregnancy rats. At the same time, the gene and protein expressions of ERα, LIF, VEGFA and CD31 in the endometrium were markedly reduced, while the expressions of MUC1, E-cadherin were increased in the LER group. Administration of LIG raised the endometrial thickness and implanted embryos, as well as reversed the expressions of these factors. Collectively, our findings revealed that LIG could facilitate embryo implantation via recovery of the endometrium receptivity and promotion of endometrial angiogenesis.

Modelling the self-assembly of elastomeric proteins provides insights into the evolution of their domain architectures.

Elastomeric proteins have evolved independently multiple times through evolution. Produced as monomers, they self-assemble into polymeric structures that impart properties of stretch and recoil. They are composed of an alternating domain architecture of elastomeric domains interspersed with cross-linking elements. While the former provide the elasticity as well as help drive the assembly process, the latter serve to stabilise the polymer. Changes in the number and arrangement of the elastomeric and cross-linking regions have been shown to significantly impact their assembly and mechanical properties. However, to date, such studies are relatively limited. Here we present a theoretical study that examines the impact of domain architecture on polymer assembly and integrity. At the core of this study is a novel simulation environment that uses a model of diffusion limited aggregation to simulate the self-assembly of rod-like particles with alternating domain architectures. Applying the model to different domain architectures, we generate a variety of aggregates which are subsequently analysed by graph-theoretic metrics to predict their structural integrity. Our results show that the relative length and number of elastomeric and cross-linking domains can significantly impact the morphology and structural integrity of the resultant polymeric structure. For example, the most highly connected polymers were those constructed from asymmetric rods consisting of relatively large cross-linking elements interspersed with smaller elastomeric domains. In addition to providing insights into the evolution of elastomeric proteins, simulations such as those presented here may prove valuable for the tuneable design of new molecules that may be exploited as useful biomaterials.

A Low Dose of Ouabain Alters the Metabolic Profile of Adult Rats Experiencing Intrauterine Growth Restriction in a Sex-Specific Manner.

Intrauterine growth restriction (IUGR) increases the risk of type 2 diabetes mellitus (T2DM) and metabolic diseases. The pancreas of fetuses with IUGR is usually characterized by pancreatic dysplasia and reduced levels of insulin secretion caused by the diminished replication of ß-cells. Previous studies showed that a low dose of ouabain could reduce the apoptosis of embryonic nephric cells during IUGR and partially restore the number of nephrons at birth. The rescued kidneys functioned well and decreased the prevalence of hypertension. Thus, we hypothesized that ouabain could rescue pancreatic development during IUGR and reduce the morbidity of T2DM and metabolic diseases. Maternal malnutrition was used to induce the IUGR model, and then a low dose of ouabain was administered to rats with IUGR during pregnancy. Throughout the experiment, we monitored the pattern of weight increase and evaluated the metabolic parameters in the offspring in different stages. Male, but not female, offspring in the IUGR group presented catch-up growth. Ouabain could benefit the impaired glucose tolerance of male offspring; however, this desirable effect was eliminated by aging. The insulin sensitivity was significantly impaired in male offspring with IUGR, but it was improved by ouabain, even during old age. However, in the female offspring, low birth weight appeared to be a beneficial factor even in old age; administering ouabain exacerbated these favorable effects. Our data suggested that IUGR influenced glucose metabolism in a sex-specific manner and ouabain treatment during pregnancy exerted strongly contrasting effects in male and female rats.

The risk and outcome of malignant brain edema in post-mechanical thrombectomy: acute ischemic stroke by anterior circulation occlusion.

BACKGROUND AND PURPOSE: Malignant brain edema (MBE) occurring after mechanical thrombectomy (MT) in acute ischemic stroke (AIS) could lead to severe disability and mortality. We aimed to investigate the incidence, predictors, and clinical outcomes of MBE in patients with AIS after MT. METHODS: The clinical and imaging data of 155 patients with AIS of anterior circulation after MT were studied. Standard non-contrast CT was used to evaluate baseline imaging characteristics at admission. Clinical outcomes were measured using the 90-day modified Rankin Scale (mRS) score. Based on the follow-up CT scans performed within 72 h after MT, the patients were classified into MBE and non-MBE group. MBE was defined as a midline shift of ≥ 5 mm with signs of local brain swelling. Univariate and multivariate regression analyses were used to analyze the relationship between MBE and clinical outcomes and identify the predictors that correlate with MBE. RESULTS: MBE was observed in 19.4% of the patients who underwent MT and was associated with a lower rate of favorable 90-day clinical outcomes. Significant differences were observed in both MBE and non-MBE groups: baseline Alberta Stroke Program Early CT (ASPECT) score, hyperdense middle cerebral artery sign (HMCAS), baseline signs of early infarct, angiographic favorable collaterals, number of retrieval attempts, and revascularization rate. Multivariate analysis indicated that low baseline ASPECT score, absent HMCAS, angiographic poor collaterals, more retrieval attempt count, and poor revascularization independently influenced the occurrence of MBE in AIS patients with anterior circulation after MT. CONCLUSION: MBE was associated with a lower rate of favorable 90-day clinical outcomes. Low baseline ASPECT score, absent HMCAS, angiographic poor collaterals, more retrieval attempt count and poor revascularization were independently associated with MBE after MT.

FAM3C in circulating tumor-derived extracellular vesicles promotes non-small cell lung cancer growth in secondary sites.

Rationale: Metastasis is a complex process with a molecular underpinning that remains unclear. We hypothesize that cargo proteins conducted by extracellular vesicles (EVs) released from tumors may confer growth and metastasis potential on recipient cells. Here, we report that a cytokine-like secreted protein, FAM3C, contributes to late-stage lung tumor progression. Methods: EV protein profiling was conducted with an unbiased proteomic mass spectrometry analysis on non-small cell lung cancer (NSCLC) and normal lung fibroblast cell lines. Expression of FAM3C was confirmed in a panel of NSCLC cell lines, and correlated to the invasive and metastatic potentials. Functional phenotype of endogenous FAM3C and tumor-derived EVs (TDEs) were further investigated using various biological approaches in RNA and protein levels. Metastasis potential of TDEs secreted by FAM3C-overexpressing carcinoma cells was validated in mouse models. Results: Transcriptomic meta-analysis of pan-cancer datasets confirmed the overexpression of FAM3C - a gene encoding for interleukin-like EMT inducer (ILEI) - in NSCLC tumors, with strong association with poor patient prognosis and cancer metastasis. Aberrant expression of FAM3C in lung carcinoma cells enhances cellular transformation and promotes distant lung tumor colonization. In addition, higher FAM3C concentrations were detected in EVs extracted from plasma samples of NSCLC patients compared to those of healthy subjects. More importantly, we defined a hitherto-unknown mode of microenvironmental crosstalk involving FAM3C in EVs, whereby the delivery and uptake of FAM3C via TDEs enhances oncogenic signaling - in recipient cells that phenocopies the cell-endogenous overexpression of FAM3C. The oncogenicity transduced by FAM3C is executed via a novel interaction with the Ras-related protein RalA, triggering the downstream activation of the Src/Stat3 signaling cascade. Conclusions: Our study describes a novel mechanism for FAM3C-driven carcinogenesis and shed light on EV FAM3C as a driver for metastatic lung tumors that could be exploited for cancer therapeutics.

PhyloPro: a web-based tool for the generation and visualization of phylogenetic profiles across Eukarya.

SUMMARY: With increasing numbers of eukaryotic genome sequences, phylogenetic profiles of eukaryotic genes are becoming increasingly informative. Here, we introduce a new web-tool Phylopro (http://compsysbio.org/phylopro/), which uses the 120 available eukaryotic genome sequences to visualize the evolutionary trajectories of user-defined subsets of model organism genes. Applied to pathways or complexes, PhyloPro allows the user to rapidly identify core conserved elements of biological processes together with those that may represent lineage-specific innovations. PhyloPro thus provides a valuable resource for the evolutionary and comparative studies of biological systems.

Cytochrome P450 3A5 polymorphism affects the metabolism of sorafenib and its toxicity for hepatocellular carcinoma cells in vitro.

OBJECTIVE: Cytochrome P450 3A5 (CYP3A5) is a highly polymorphic gene and the encoded protein variants differ in catalytic activity, leading to inter-individual variation in metabolic ability. The aim of the current study was to investigate the effects of seven allelic variants on the ability of CYP3A5 to metabolize sorafenib in vitro and further explore the impacts of CYP3A5 polymorphism on the proliferation and apoptosis of hepatocellular carcinoma cell line (HepG2) induced by sorafenib. METHODS: Wild-type and variant CYP3A5 enzymes were expressed in Spodoptera frugiperda insect cells using a baculovirus dual-expression system, and protein expression was checked by western blot. The enzymes were incubated with sorafenib at 37°C for 30 min, and formation of the major metabolite sorafenib N-oxide was assayed using ultra-performance liquid chromatography and tandem mass spectrometry. Intrinsic clearance values (Vmax/Km) were calculated for each enzyme. Additionally, recombinant HepG2 cells transfecting with CYP3A5 variants were used to investigate the effects of sorafenib on the proliferation of HepG2 cells. RESULTS: Intrinsic clearance of the six variants CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 was 26.41-71.04% of the wild-type (CYP3A5*1) value. In contrast, the clearance value of the variant CYP3A5*6 was significantly higher (174.74%). Additionally, the decreased ATP levels and cell viability and the increased cell apoptosis in HepG2 cells transfected with CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 were observed, whereas, the increased ATP levels and cell viability and the reduced cell apoptosis in HepG2 cells transfected with CYP3A5*6 were also investigated when compared to CYP3A5*1. CONCLUSION: Our results suggest that CYP3A5 polymorphism influences sorafenib metabolism and pharmacotherapeutic effect in hepatic carcinomas. These data may help explain differential response to drug therapy for hepatocellular carcinoma, and they support the need for individualized treatment.

Ultra-trace and quantitative SERS detection of polycyclic aromatic hydrocarbons based on Au nanoscale convex polyhedrons with embedded probe molecules.

Surface-enhanced Raman scattering (SERS) has great potential for the detection of marine pollutants, but it is still restricted in ultra-trace and quantitative analysis. Here, a strategy for the detection of polycyclic aromatic hydrocarbons (PAHs) was proposed based on Au nanoscale convex polyhedrons (Au NCPs) coated with high-energy facets and embedded with 4-ATP as a probe molecule. Au NCPs acted as SERS substrates and led to limits of detection (LODs) for six common PAHs that reached 0.01 nM. Using internal calibration, the relative standard deviations (RSD) of the spectral stability and reproducibility were as low as 3.36% and 5.11%, respectively. The maximum mean relative errors (AREs) of the predicted and true values were 6.28%. The results indicate that the resulting Au NCPs improved the ultra-trace and quantitative detection of SERS, thus suggesting that the Au NCPs have practical application value in SERS.

Mesoscale Mechanism of P-dopant Defects and Interface Synergy for Phenols Degradation.

The semiconductor based photocatalysis has become a hot spot of current research, and the key challenges are the construction of strong functional heterojunction photocatalysts, and insights on the working mechanism involved. In this work, we constructed a NiFe- LDHs/P-TCN heterojunction with P-dopant defects and interface synergy and elucidated its mesoscale mechanism among different constituent interfaces. The interface photoelectron transfer was detected by PAS, EPR and other methods, and the enhancing mechanism of the defect sites for interface electron transfer and photocatalytic activity was proposed. The interfacial electrons, photoelectric properties and photocatalytic activity are found to be positively correlated. The result is conducive for a better understanding on working mechanism of heterogeneous photocatalysts, which opened a broader research space for the rational design and construction of functional interfaces.