Efficacy and immunogenicity of AS04-HPV-16/18 vaccine in females with existing cervical HR-HPV infection at first vaccination: A pooled analysis of four large clinical trials worldwide.

Females with existing high-risk HPV (HR-HPV) infections remain at risk of subsequent multiple or recurrent infections, on which benefit from HPV vaccines was under-reported. We pooled individual-level data from four large-scale, RCTs of AS04-HPV-16/18 vaccine to evaluate efficacy and immunogenicity in females DNA-positive to any HR-HPV types at first vaccination. Females receiving the AS04-HPV-16/18 vaccine in the original RCTs constituted the vaccine group in the present study, while those unvaccinated served as the control group. Vaccine efficacy (VE) against new infections and associated cervical intraepithelial neoplasia (CIN) 2+ in females DNA-negative to the considered HR-HPV type but positive to any other HR-HPV types, VE against reinfections in females DNA-positive to the considered HR-HPV type but cleared naturally during later follow-up, and levels of anti-HPV-16/18 IgG were assessed. Our final analyses included 5137 females (vaccine group = 2532, control group = 2605). The median follow-up time was 47.88 months (IQR: 45.72-50.04). For the prevention of precancerous lesions related to the non-infected HR-HPV types at baseline, VE against HPV-16/18 related CIN 2+ was 82.70% (95% CI: 63.70-93.00%). For the prevention of reinfections related to the infected HR-HPV types following natural clearance, VE against HPV-16/18 12MPI was non-significant (p > .05), albeit robust immunity persisted for at least 48 months. Females with existing HR-HPV infections at first vaccination still benefit from vaccination in preventing precancers related to the non-infected types at baseline. VE against reinfections related to the infected types following natural clearance remains to be further investigated.

Subtle Structural Differences Affect the Inhibitory Potency of RGD-Containing Cyclic Peptide Inhibitors Targeting SPSB Proteins.

The SPRY domain-containing SOCS box proteins SPSB1, SPSB2, and SPSB4 utilize their SPRY/B30.2 domain to interact with a short region in the N-terminus of inducible nitric oxide synthase (iNOS), and recruit an E3 ubiquitin ligase complex to polyubiquitinate iNOS, resulting in the proteasomal degradation of iNOS. Inhibitors that can disrupt the endogenous SPSB-iNOS interactions could be used to augment cellular NO production, and may have antimicrobial and anticancer activities. We previously reported the rational design of a cyclic peptide inhibitor, cR8, cyclo(RGDINNNV), which bound to SPSB2 with moderate affinity. We, therefore, sought to develop SPSB inhibitors with higher affinity. Here, we show that cyclic peptides cR7, cyclo(RGDINNN), and cR9, cyclo(RGDINNNVE), have ~6.5-fold and ~2-fold, respectively, higher SPSB2-bindng affinities than cR8. We determined high-resolution crystal structures of the SPSB2-cR7 and SPSB2-cR9 complexes, which enabled a good understanding of the structure-activity relationships for these cyclic peptide inhibitors. Moreover, we show that these cyclic peptides displace full-length iNOS from SPSB2, SPSB1, and SPSB4, and that their inhibitory potencies correlate well with their SPSB2-binding affinities. The strongest inhibition was observed for cR7 against all three iNOS-binding SPSB proteins.

Multifunctional TiN-MXene-Co@CNTs Networks as Sulfur/Lithium Host for High-Areal-Capacity Lithium-Sulfur Batteries.

The inevitable shuttling and slow redox kinetics of lithium polysulfides (LiPSs) as well as the uncontrolled growth of Li dendrites have strongly limited the practical applications of lithium-sulfur batteries (LSBs). To address these issues, we have innovatively constructed the carbon nanotubes (CNTs) encapsulated Co nanoparticles in situ grown on TiN-MXene nanosheets, denoted as TiN-MXene-Co@CNTs, which could serve simultaneously as both sulfur/Li host to kill "three birds with one stone" to (1) efficiently capture soluble LiPSs and expedite their redox conversion, (2) accelerate nucleation/decomposition of solid Li2S, and (3) induce homogeneous Li deposition. Benefiting from the synergistic effects, the TiN-MXene-Co@CNTs/S cathode with a sulfur loading of 2.5 mg cm-2 could show a high reversible specific capacity of 1129.1 mAh g-1 after 100 cycles at 0.1 C, and ultralong cycle life over 1000 cycles at 1.0 C. More importantly, it even achieves a high areal capacity of 6.3 mAh cm-2 after 50 cycles under a sulfur loading as high as 8.9 mg cm-2 and a low E/S ratio of 5.0 µL mg-1. Besides, TiN-MXene-Co@CNTs as Li host could deliver a stable Li plating/striping behavior over 1000 h.

Cost-effectiveness of the screen-and-treat strategies using HPV test linked to thermal ablation for cervical cancer prevention in China: a modeling study.

BACKGROUND: Self-sampling HPV test and thermal ablation are effective tools to increase screening coverage and treatment compliance for accelerating cervical cancer elimination. We assessed the cost-effectiveness of their combined strategies to inform accessible, affordable, and acceptable cervical cancer prevention strategies. METHODS: We developed a hybrid model to evaluate costs, health outcomes, and incremental cost-effectiveness ratios (ICER) of six screen-and-treat strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (HPV genotyping, colposcopy or none) and thermal ablation, from a societal perspective. A designated initial cohort of 100,000 females born in 2015 was considered. Strategies with an ICER less than the Chinese gross domestic product (GDP) per capita ($10,350) were considered highly cost-effective. RESULTS: Compared with current strategies in China (physician-HPV with genotype or cytology triage), all screen-and-treat strategies are cost-effective and self-HPV without triage is optimal with the most incremental quality-adjusted life-years (QALYs) gained (220 to 440) in rural and urban China. Each screen-and-treat strategy based on self-collected samples is cost-saving compared with current strategies (-$818,430 to -$3540) whereas more costs are incurred using physician-collected samples compared with current physician-HPV with genotype triage (+$20,840 to +$182,840). For screen-and-treat strategies without triage, more costs (+$9404 to +$380,217) would be invested in the screening and treatment of precancerous lesions rather than the cancer treatment compared with the current screening strategies. Notably, however, more than 81.6% of HPV-positive women would be overtreated. If triaged with HPV 7 types or HPV16/18 genotypes, 79.1% or 67.2% (respectively) of HPV-positive women would be overtreated with fewer cancer cases avoided (19 cases or 69 cases). CONCLUSIONS: Screen-and-treat strategy using self-sampling HPV test linked to thermal ablation could be the most cost-effective for cervical cancer prevention in China. Additional triage with quality-assured performance could reduce overtreatment and remains highly cost-effective compared with current strategies.

A real-world analysis of trametinib in combination with hydroxychloroquine or CDK4/6 inhibitor as third- or later-line therapy in metastatic pancreatic adenocarcinoma.

BACKGROUND: There are no standard third-line treatment options for metastatic pancreatic ductal adenocarcinoma (mPDAC). Trametinib in combination with hydroxychloroquine (HCQ) or CDK4/6 inhibitors for pancreatic adenocarcinoma showed promising efficacy in preclinical studies. However, the regimens have not been well examined in patients with mPDAC. METHODS: Patients with mPDAC who received the combination of trametinib and HCQ or CDK4/6 inhibitors as third- or later-line therapy were reviewed. The efficacy and prognosis were further analyzed. RESULTS: A total of 13 mPDAC patients were enrolled, of whom 8 and 5 patients were treated with trametinib plus HCQ or a CDK4/6 inhibitor (palbociclib or abemaciclib), respectively. All enrolled patients had either KRAS G12D or G12V mutations and had received a median of 3 prior lines of therapy (range, 2-6). The median trametinib treatment duration was 1.4 months. Of the 10 patients with measurable disease, only 1 patient achieved stable disease, and the remaining patients had progressive disease. Moreover, in patients treated with trametinib plus HCQ and a CDK4/6 inhibitor, the median progression-free survival was 2.0 and 2.8 months, respectively, and the median overall survival was 4.2 and 4.7 months, respectively. Moreover, 5 (50%) patients experienced grade 3-4 adverse events in 10 patients with available safety data. CONCLUSIONS: The combination of trametinib and HCQ or CDK4/6 inhibitors may not be an effective later-line treatment for mPDAC, and the current preliminary findings need to be confirmed by other studies with larger sample sizes.

Estimation of economic burden throughout course of cervical squamous intraepithelial lesion and cervical cancer in China: A nationwide multicenter cross-sectional study.

Objective: Cervical squamous intraepithelial lesion (SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment. Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses ("diagnosis", "initial treatment", "chemoradiotherapy", "follow-up" and "recurrence/progression/metastasis") to estimate the total costs. The median and interquartile range (IQR) of total costs (including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated. Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL (LSIL) (n=549), high-grade SIL (HSIL) (n=803), cervical cancer stage IA (n=226), IB (n=610), IIA (n=487), IIB (n=282), III (n=452) and IV (n=62). In urban areas, the estimated total costs of LSIL and HSIL were [Formula: see text]1,637.7 (IQR: [Formula: see text]956.4-[Formula: see text]2,669.2) and [Formula: see text]2,467.1 (IQR: [Formula: see text]1,579.1-[Formula: see text]3,762.3), while in rural areas the costs were [Formula: see text]459.0 (IQR: [Formula: see text]167.7-[Formula: see text]1,330.3) and [Formula: see text]1,230.5 (IQR: [Formula: see text]560.6-[Formula: see text]2,104.5), respectively. For patients with cervical cancer stage IA, IB, IIA, IIB, and III-IV, the total costs were [Formula: see text]15,034.9 (IQR: [Formula: see text]11,083.4-[Formula: see text]21,632.4), [Formula: see text]19,438.6 (IQR: [Formula: see text]14,060.0-[Formula: see text]26,505.9), [Formula: see text]22,968.8 (IQR: [Formula: see text]16,068.8-[Formula: see text]34,615.9), [Formula: see text]26,936.0 (IQR: [Formula: see text]18,176.6-[Formula: see text]41,386.0) and [Formula: see text]27,332.6 (IQR: [Formula: see text]17,538.7-[Formula: see text]44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage. Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas.

A Comprehensive Prognostic Analysis of POLD1 in Hepatocellular Carcinoma.

BACKGROUND: DNA polymerase delta 1 catalytic subunit (POLD1) plays a key role in DNA replication and damage repair. A defective DNA proofreading function caused by POLD1 mutation contributes to carcinogenesis, while POLD1 overexpression predicts poor prognosis in cancers. However, the effect of POLD1 in hepatocellular carcinoma (HCC) is not well-understood. METHODS: Expression patterns of POLD1 were evaluated in TCGA and the HPA databases. Kaplan-Meier curves and Cox regression were used to examine the prognostic value of POLD1. The prognostic and predictive value of POLD1 was further validated by another independent cohort from ICGC database. The influences of DNA copy number variation, methylation and miRNA on POLD1 mRNA expression were examined. The correlation between infiltrating immune cells and POLD1 expression was analyzed. GO and KEGG enrichment analyses were performed to detect biological pathways associated with POLD1 expression in HCC. RESULTS: POLD1 was overexpressed in HCC (n = 369) compared with adjacent normal liver (n = 50). POLD1 upregulation was significantly correlated with positive serum AFP and advanced TNM stage. Kaplan-Meier and multivariate analyses suggested that POLD1 overexpression predicts poor prognosis in HCC. DNA copy gain, low POLD1 methylation, and miR­139-3p downregulation were associated with POLD1 overexpression. Besides, POLD1 expression was associated with the infiltration levels of dendritic cell, macrophage, B cell, and CD4 + T cell in HCC. Functional enrichment analysis suggested "DNA replication", "mismatch repair" and "cell cycle" pathways might be involved in the effect of POLD1 on HCC pathogenesis. Additionally, POLD1 mRNA expression was significantly associated with tumor mutation burden, microsatellite instability, and prognosis in various tumors. CONCLUSIONS: POLD1 may be a potential prognostic marker and promising therapeutic target in HCC.

In situ monitoring of the plasmon catalytic reaction of p-nitroaniline at a gas-liquid-solid three phase interface.

Localized surface plasmon resonance (LSPR) is caused by the irradiation of light on a metal surface. Here we present a surface plasmon catalytic reaction at the gas-liquid-solid three phase interface. Electrochemical deposition was used to prepare Ag nanostructure/Cu mesh surface-enhanced Raman scattering (SERS) substrates. Surface wettability was adjusted by changing the processing time of the surfactant. Then a three-phase interface platform was constructed with good SERS performance and active surface plasmon catalytic capacity by droplet detection. At the gas-liquid-solid three phase interface, different oxygen supplies for the catalytic reaction were offered on surfaces with different wettability values. Thus, in this study, surface plasmon catalytic reaction of p-nitroaniline (PNA) was successfully in situ monitored and the reaction mechanism was explored. Otherwise, density functional theory (DFT) was used to calculate the Raman spectra and energy levels of the reactants and reaction products. Moreover, this work provides a new platform for monitoring the surface plasmon reaction at the gas-liquid-solid three-phase interface and contributes to the development of the study in the surface plasmon catalytic reaction field.

Prenatal inflammation exposure-programmed hypertension exhibits multi-generational inheritance via disrupting DNA methylome.

The multi-generation heredity trait of hypertension in human has been reported, but the molecular mechanisms underlying multi-generational inheritance of hypertension remain obscure. Recent evidence shows that prenatal inflammatory exposure (PIE) results in increased incidence of cardiovascular diseases, including hypertension. In this study we investigated whether and how PIE contributed to multi-generational inheritance of hypertension in rats. PIE was induced in pregnant rats by intraperitoneal injection of LPS or Poly (I:C) either once on gestational day 10.5 (transient stimulation, T) or three times on gestational day 8.5, 10.5, and 12.5 (persistent stimulation, P). Male offspring was chosen to study the paternal inheritance. We showed that PIE, irrespectively induced by LPS or Poly (I:C) stimulation during pregnancy, resulted in multi-generational inheritance of significantly increased blood pressure in rat descendants, and that prenatal LPS exposure led to vascular remodeling and vasoconstrictor dysfunction in both thoracic aorta and superior mesenteric artery of adult F2 offspring. Furthermore, we revealed that PIE resulted in global alteration of DNA methylome in thoracic aorta of F2 offspring. Specifically, PIE led to the DNA hypomethylation of G beta gamma (Gßγ) signaling genes in both the F1 sperm and the F2 thoracic aorta, and activation of PI3K/Akt signaling was implicated in the pathologic changes and dysregulated vascular tone of aortic tissue in F2 LPS-P offspring. Our data demonstrate that PIE reprogrammed DNA methylome of cells from the germline/mature gametes contributes to the development of hypertension in F2 PIE offspring. This study broadens the current knowledge regarding the multi-generation effect of the cumulative early life environmental factors on the development of hypertension.

Zinc-metal-organic frameworks with tunable UV diffuse-reflectance as sunscreens.

BACKGROUND: UV exposure continues to induce many health issues, though commercial sunscreens are available. Novel UV filters with high safety and efficacy are urgently needed. Metal-organic frameworks (MOFs) could be a suitable platform for UV filter development, due to their tunable optical, electrical, and photoelectric properties by precise controlled synthesis. RESULTS: Herein, four zinc-based MOFs with various bandgap energies were chose to investigate their optical behaviors and evaluate their possibility as sunscreens. Zeolitic imidazolate framework-8 (ZIF-8) was found to possess the highest and widest UV reflectance, thereby protecting against sunburn and DNA damage on mouse skin and even achieving a comparable or higher anti-UV efficacy relative to the commercially available UV filters, TiO2 or ZnO, on pig skin, a model that correlates well with human skin. Also, ZIF-8 exerted appealing characteristics for topical skin use with low radical production, low skin penetration, low toxicity, high transparency, and high stability. CONCLUSION: These results confirmed ZIF-8 could potentially be a safe and effective sunscreen surrogate for human, and MOFs could be a novel source to develop more effective and safe UV filters.

Revisiting the effect of f-functions in predicting the right reaction mechanism for hypervalent iodine reagents.

To understand the effect of f-functions in predicting the right reaction mechanism for hypervalent iodine reagents, we adopt the Ahlrichs basis set family def2-SVP and def2-TZVP to revisit the potential energy surfaces of IBX-mediated oxidation and Togni I's isomerisation. Our results further prove that f-functions (in either Pople, Dunning, or Ahlrichs basis set series) are indispensable to predict the correct rate-determining step of hypervalent iodine reagents. The f-functions have a significant impact on the predicted reaction barriers for processes involving the IX (X = O, OH, CF3 , etc.) bond cleavage and formation, for example, in the reductive elimination step or the hypervalent twist step. We furthermore explore two hypervalent twist modes that account for the different influences of f-functions for IBX and Togni I. Our findings may be helpful for theoretical chemists to appropriately study the reaction mechanism of hypervalent iodine reagents.

Structural basis for the regulation of inducible nitric oxide synthase by the SPRY domain-containing SOCS box protein SPSB2, an E3 ubiquitin ligase.

Relatively high concentration of nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in response to a variety of stimuli is a source of reactive nitrogen species, an important weapon of host innate immune defense. The SPRY domain-containing SOCS box protein 2 (SPSB2) is an E3 ubiquitin ligase that regulates the lifetime of iNOS. SPSB2 interacts with the N-terminal region of iNOS via a binding site on the SPRY domain of SPSB2, and recruits an E3 ubiquitin ligase complex to polyubiquitinate iNOS, leading to its proteasomal degradation. Although critical residues for the SPSB2-iNOS interaction have been identified, structural basis for the interaction remains to be explicitly determined. In this study, we have determined a crystal structure of the N-terminal region of iNOS in complex with the SPRY domain of SPSB2 at 1.24 Å resolution. We have resolved the roles of some flanking residues, whose contribution to the SPSB2-iNOS interaction was structurally unclear previously. Furthermore, we have evaluated the effects of SPSB2 inhibitors on NO production using transient transfection and cell-penetrating peptide approaches, and found that such inhibitors can elevate NO production in RAW264.7 macrophages. These results thus provide a useful basis for the development of potent SPSB2 inhibitors as well as recruiting ligands for proteolysis targeting chimera (PROTAC) design.

A highly sensitive acetylcholinesterase electrochemical biosensor based on Au-Tb alloy nanospheres for determining organophosphate pesticides.

Accurately detect the residues of organophosphate pesticides (OPs) in food and environment is critical to our daily lives. In this study, we developed a novel acetylcholinesterase (AChE) biosensor based on Au-Tb alloy nanospheres (NSs) for rapid and sensitive detection of OPs for the first time. Au-Tb alloy NSs that with good conductivity and biocompatibility were produced with a mild hydrothermal. Under optimal conditions, the AChE biosensor was obtained by a simple assembly process, with a big linear range (10-13-10-7M) and the limit of detection was 2.51 × 10-14M for the determination of methyl parathion. Moreover, the determination of methyl parathion with the prepared biosensor presented a high sensitivity, outstanding repeatability and superior stability compared with other reported biosensors. Through the determination of tap water and Yanming lake samples, it was proved that the modified biosensor with satisfactory recoveries (96.76%-108.6%), and are realizable in the determination of OPs in real samples.

Predicting the right mechanism for hypervalent iodine reagents by applying two types of hypervalent twist models: apical twist and equatorial twist.

Since hypervalent twist followed by reductive elimination is a general reaction pattern for hypervalent iodine reagents, mechanistic studies about the hypervalent twist step could provide significant guidance for experiments. Previous studies have shown that there are two types of hypervalent twist models, i.e. apical twist and equatorial twist. We applied both hypervalent twist models to explain the isomerization mechanism of two important electrophilic trifluoromethylating reagents, Togni I and Togni II. Up to now, there are less detailed studies about the different hypervalent twist modes between both reagents. Here, we successfully identified Togni II's isomerization pathway via equatorial twist, and suggested that different hypervalent twist models should be considered to predict the right mechanisms of reactions with hypervalent iodine reagents participating. This study will also be helpful to design new Togni type reagents with higher intrinsic reactivity and stability by avoiding the formation of acyclic by-products.

Effects of calcium dobesilate (CaD) interference on serum creatinine measurements: a national External Quality Assessment (EQA)-based educational survey of drug-laboratory test interactions.

Objectives: Drug-laboratory test interactions (DLTIs) are one of the major sources of laboratory errors. Calcium dobesilate (CaD) interference on serum creatinine testing is a widespread problem that has long been ignored in China. A national EQA-based survey was launched to investigate the current status of CaD interference on creatinine routine methods used in China and enhance the education of CaD interference in clinical laboratories. Methods: A descriptive survey was developed to characterize the status quo of Chinese laboratory professionals' cognition to CaD interference. Four of survey samples which were spiked with/without interference additive were shipped to 175 participant laboratories. The target reference values from a reference measurement procedure were compared against the results from participating laboratories to evaluate the CaD interference on serum creatinine measurements using enzymatic method or Jaffé method. Results: The lack of knowledge of DLTIs and the barriers to collect information from pharmacological and laboratory data systems had become the main problems on implementing DLTIs education in China. A significant negative influence of CaD on enzymatic method was observed regardless of measurement platforms. Jaffé method was generally free from interaction with CaD but showed poor precision and accuracy at low creatinine concentrations. Conclusions: More efforts should be made to enhance the education of DLTIs in clinical laboratories in China.

Flexible SERS substrate based on Ag nanodendrite-coated carbon fiber cloth: simultaneous detection for multiple pesticides in liquid droplet.

We report a method for preparing flexible substrates based on 3D Ag nanodendrites (Ag NDs)/carbon fiber cloth substrate with superhydrophobic surface. Ag NDs were deposited on carbon fiber cloth by electrochemical deposition, and the superhydrophobicity of the surface was achieved by low surface energy modification. The cylinder shape of the carbon fiber provides a three-dimensional structure for Ag NDs, increasing the "hot spot" effect, and is the excellent choice as SERS substrate. At the same time, micro/nanostructures provided by fibers and nanodendrites can easily obtain ultra-wet surfaces. The analyte solution can be directly detected in a droplet onto the superhydrophobic surface without pretreatment, which greatly shortens the detection time. The lowest concentration of crystal violet (CV) that can be detected is 10-10 M, demonstrating good SERS sensitivity of the prepared substrate. It was successfully applied in simultaneous detection of at least three molecules. Thiram and malachite green (MG) can be detected simultaneously in real lake water. Moreover, the conductivity, physical flexibility, and stability of the flexible carbon fiber cloth gives this substrate potential in other fields such as electrochemistry. Graphical abstract Flexible SERS substrate based on Ag nanodendrite-coated carbon fiber cloth: simultaneous detection for multiple pesticides in liquid droplet.

Naphthoquinone Derivatives with Anti-Inflammatory Activity from Mangrove-Derived Endophytic Fungus Talaromyces sp. SK-S009.

Twelve 1, 4-naphthoquinone derivatives, including two new (1 and 2) and 10 known (3-12), were obtained from endophytic fungus Talaromyces sp. SK-S009 isolated from the fruit of Kandelia obovata. All structures were identified through extensive analysis of the nuclear magnetic resonance (NMR), mass spectrometry (MS) and circular dichroism (CD), as well as by comparison with literature data. These compounds significantly inhibited the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in the murine macrophage cell line (RAW 264.7 cells). The half maximal inhibitory concentration (IC50) values, except for compound 2, were lower than that of indomethacin (26.3 µM). Compound 9 inhibited the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in RAW 264.7 macrophages. Additionally, compound 9 reduced the mRNA levels of pro-inflammatory factors interleukin (IL)1ß, IL-6, and tumor necrosis factor (TNF)-α. The results of this study demonstrated that these 1, 4-naphthoquinone derivatives can inhibit LPS-induced inflammation.

One-Step Preparation Method of Flexible Metafilms on the Water-Oil Interface: Self-Assembly Surface Plasmon Structures for Surface-Enhanced Raman Scattering Detection.

The present study demonstrated a one-step method for the first time to fabricate self-assembled gold nanoparticle (AuNP) metafilms at the water-toluene interface by adding polystyrene-polyisoprene-polystyrene as the support layer. The thiolated polyethylene glycol and ethanol were used to tune the surface charge density on the AuNPs, constructing a balanced situation at the water-toluene interface. The flexible (AuNP) metafilm can be easily obtained after evaporation of the toluene phase and further used as a surface-enhanced Raman scattering (SERS) substrate for trace thiram detection. The SERS sensitivity was tested using standard Raman probes such as crystal violet and malachite green, both with the detect concentration reaching 1 × 10-11 M. Moreover, the excellent reproducibility and elastic properties make the metafilm promising in practical detection. Hence, the trace thiram detection on an orange pericarp was inspected with the detection limit of 0.5 ppm (1 × 10-6 M) as well as a favorable linearity relation with a correlation coefficient of 0.979, exactly matching the realistic application requirements.

Comparison of three different chemiluminescence assays and a rapid liquid chromatography tandem mass spectrometry method for measuring serum aldosterone.

Background This study aimed to quantify and compare serum aldosterone (sALD) levels through three different chemiluminescence immunoassays (CLIAs) and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Methods Serum samples from 221 patients with suspected primary aldosteronism (PA) were retrospectively included in this study conducted at the Peking Union Medical College Hospital from June to August in 2017. sALD levels were determined using the LC-MS/MS method and three different CLIA systems, viz., DiaSorin® XL, iSYS and Auto Lumo A2000. Pooled fresh serum samples were used for recalibration. Passing-Bablok regression analysis, correlation matrix, and Bland-Altman plots were used to evaluate the concurrence among ALD levels determined using the three CLIAs. Results Within-laboratory precision of the four assays ranged from 2.1% to 9.4%, except the coefficient variation (CV) of one of the CLIAs, which exceeded 20.0% for samples with low sALD levels. sALD levels determined using LC-MS/MS were significantly lower than those determined using the other three CLIAs (p < 0.0001). Spearman's correlation coefficient of the four assays ranged from 0.745 to 0.950 (p < 0.0001). The Bland-Altman plot showed that the average bias (%) for the three CLIAs and LC-MS/MS ranged from -69.3 to -49.2. After recalibration, this correlation did not improve among the assays. However, the bias and bias percentage at the medical decision level improved between LC-MS/MS and DiaSorin® XL/iSYS. Conclusions Significant inconsistencies between the results of CLIAs and LC-MS/MS indicate that different sALD measures cannot be used interchangeably.

Measuring lipoprotein-associated phospholipase A2 activity in China: Protocol comparison and recalibration.

BACKGROUND: Lp-PLA2 is a novel inflammation marker in cardiovascular disease. While several manufactures have registered Lp-PLA2 activity reagents, few studies have investigated the consistency among these assays. In this study, we compared and recalibrated Lp-PLA2 activity assays. METHODS: Serum samples from 110 patients and 140 healthy individuals were collected for method comparison and reference interval validation, respectively. Fresh human serum pools (847 and 442 U/L) were used for recalibration. Lp-PLA2 activity was analyzed using all five assays with a Beckman AU 5800 analyzer. Passing-Bablok regression equations and Bland-Altman plots were used to estimate the relationship and bias among the results. A 2.5% confidence interval (CI) and 97.5% CI were used to establish a laboratory reference interval. RESULTS: Assay imprecision varied from 0.8%-2.9%, while the overall coincidence rates ranged from 75.5%-98.2%. Passing-Bablok regression shows excellent linear correlation between Evermed and Diasys (R2  = 0.999), while that between Diazyme and Evermed was poor (R2  = 0.846). The R2 and correlation coefficient r among assays were 0.846-0.999 and 0.8947-0.9993, respectively. The mean bias percentages ranged from -71.5%-1.6% and -2.0%-11.6% before and after recalibration. As Diazyme and Diasys were not comparable, the Diazyme assay was not recalibrated. The reference intervals determined for Diasys, Evermed, Hengxiao, and Zybio were 184-605, 208-704, 81-328, and 273-696 U/L, respectively. CONCLUSIONS: Our results indicate that recalibration increased assay agreement and also highlight the need for each laboratory to establish its own reference interval for Lp-PLA2 activity.