Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes.

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

Chemical profiling of Zhi-Ke-Bao pills and its potential mechanism against cough by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and network pharmacology.

Zhi-Ke-Bao pills (ZKB), a traditional Chinese medicine preparation composed of 13 herbs, is generally used to treat cough caused by external wind cold, phlegm, etc in clinical applications, and it plays a core role in relieving cough caused by COVID-19 and influenza in China. Till now, the understanding of its chemical constituents was dramatically limited due to its chemical complexity, restricting its clinical application or development. In this work, a developed ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) method, a targeted and non-targeted strategy and network pharmacology were used to comprehensively characterize the chemical compositions in ZKB and predict its mechanism against cough. A total of 164 compounds (148 targeted compounds and 16 non-targeted ones) were identified or tentatively characterized in ZKB, including 65 flavonoids, 25 alkaloids, 19 organic acids, 41 saponins, 9 coumarins, 2 phenylpropanoids, 2 anthraquinones, and 1 other types. Among them, 37 compounds were unambiguously identified by comparison to reference standards. Meanwhile, the fragmentation behaviors of five main chemical structure types were also summarized. 309 targets and two core signaling pathways of ZKB against cough were predicted by network pharmacology, including MAPK and PI3K-Akt signaling pathways. It was the first time to characterize the chemical compounds of ZKB and reveal its potential mechanism against cough, providing the material basis for further quality control or pharmacodynamic evaluation of ZKB.

Surface-Activated Ti3C2Tx Adsorption of Acetylene Black Coupled with Polyaniline as a Signal Tag for the Detection of the ESAT-6 Antigen of Mycobacterium tuberculosis.

Early secretory antigenic target-6 (ESAT-6) is regarded as the most immunogenic protein produced by Mycobacterium tuberculosis, whose detection is of great clinical significance for tuberculosis diagnosis. However, the detection of the ESAT-6 antigen has been hampered by the expensive cost and complex experimental procedures, resulting in low sensitivity. Herein, we developed a titanium carbide (Ti3C2Tx)-based aptasensor for ESAT-6 detection utilizing a triple-signal amplification strategy. First, acetylene black (AB) was immobilized on Ti3C2Tx through a cross-linking reaction to form the Ti3C2Tx-AB-PAn nanocomposite. Meanwhile, AB served as a conductive bridge, and Ti3C2Tx can synergistically promote the electron transfer of PAn. Ti3C2Tx-AB-PAn exhibited outstanding conductivity, high electrochemical signals, and abundant sites for the loading of ESAT-6 binding aptamer II (EBA II) to form a novel signal tag. Second, N-CNTs were adsorbed on NiMn layered double hydride (NiMn LDH) nanoflowers to obtain NiMn LDH/N-CNTs, exhibiting excellent conductivity and preeminent stability to be used as electrode modification materials. Third, the biotinylated EBA (EBA I) was immobilized onto a streptavidin-coated sensing interface, forming an amplification platform for further signal enhancement. More importantly, as a result of the synergistic effect of the triple-signal amplification platform, the aptasensor exhibited a wide detection linear range from 10 fg mL-1 to 100 ng mL-1 and a detection limit of 4.07 fg mL-1 for ESAT-6. We envision that our aptasensor provides a way for the detection of ESAT-6 to assist in the diagnosis of tuberculosis.

Immune profiling of patients with extranodal natural killer/T cell lymphoma treated with daratumumab.

Natural killer/T cell lymphoma (NKTCL) is a highly aggressive, heterogeneous non-Hodgkin lymphoma resulting from malignant proliferation of cytotoxic natural killer (NK) or T cells. Previous studies demonstrated variable expression of CD38 on NKTCL tumors. Daratumumab, a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action, was hypothesized to be a novel therapeutic option for patients with relapsed or refractory (R/R) NKTCL. In the phase 2 NKT2001 study (ClinicalTrials.gov Identifier: NCT02927925) assessing the safety and efficacy of daratumumab, a suboptimal overall response rate was seen in R/R NKTCL patients. One patient, whose tumors did not express CD38, responded to treatment, suggesting that the immunomodulatory activities of daratumumab may be sufficient to confer clinical benefit. To understand the suboptimal response rate and short duration of response, we investigated the immune profile of NKTCL patients from NKT2001 in the context of daratumumab anti-tumor activity. Tumor tissue and whole blood were, respectively, analyzed for CD38 expression and patient immune landscapes, which were assessed via cytometry by time-of-flight (CyTOF), multiparameter flow cytometry (MPFC), clonal sequencing, and plasma Epstein-Barr virus (EBV)-DNA level measurements. Changes observed in the immune profiles of NKTCL patients from NKT2001, including differences in B and T cell populations between responders and nonresponders, suggest that modulation of the immune environment is crucial for daratumumab anti-tumor activities in NKTCL. In conclusion, these findings highlight that the clinical benefit of daratumumab in NKTCL may be enriched by B/T cell-related biomarkers.

Tracking of Stem Cells in Chronic Liver Diseases: Current Trends and Developments.

Stem cell therapy holds great promise for future clinical practice for treatment of advanced liver diseases. However, the fate of stem cells after transplantation, including the distribution, viability, and the cell clearance, has not been fully elucidated. Herein, recent advances regarding the imaging tools for stem cells tracking mainly in chronic liver diseases with the advantages and disadvantages of each approach have been described. Magnetic resonance imaging is a promising clinical imaging modality due to non-radioactivity, excellent penetrability, and high spatial resolution. Fluorescence imaging and radionuclide imaging demonstrate relatively increased sensitivity, with the latter excelling in real-time monitoring. Reporter genes specialize in long-term tracing. Nevertheless, the disadvantages of low sensitivity, radiation, exogenous gene risk are inevitably present in each of these means, respectively. In this review, we aim to comprehensively evaluate the current state of methods for tracking of stem cell, highlighting their strengths and weaknesses, and providing insights into their future potential. Multimodality imaging strategies may overcome the inherent limitations of single-modality imaging by combining the strengths of different imaging techniques to provide more comprehensive information in the clinical setting.

G-Quadruplex/Hemin-Mediated Polarity-Switchable and Photocurrent-Amplified System for Escherichia coli O157:H7 Detection.

The contamination of food by pathogens is a serious problem in global food safety, and current methods of detection are costly, time-consuming, and cumbersome. Therefore, it is necessary to develop rapid, portable, and sensitive assays for foodborne pathogens. In addition, assays for foodborne pathogens must be resistant to interference resulting from the complex food matrix to prevent false positives and negatives. In this study, hemin and reduced graphene oxide-MoS2 sheets (GMS) were used to design a near-infrared (NIR)-responsive photoelectrochemical (PEC) aptasensor with target-induced photocurrent polarity switching based on a hairpin aptamer (Hp) with a G-quadruplex motif. A ready-to-use analytical device was developed by immobilizing GMS on the surface of a commercial screen-printed electrode, followed by the attachment of the aptamer. In the presence of Escherichia coli O157:H7, the binding sites of Hp with the G-quadruplex motif were opened and exposed to hemin, leading to the formation of a G-quadruplex/hemin DNAzyme. Crucially, after binding to hemin, the charge transfer pathway of GMS changes, resulting in a switch of the photocurrent polarity. Further, G-quadruplex/hemin DNAzyme enhanced the cathodic photocurrent, and the proposed sensor exhibited a wide linear range ((25.0-1.0) × 107 CFU/mL), a low limit of detection (2.0 CFU/mL), and good anti-interference performance. These findings expand the applications of NIR-responsive PEC materials and provide versatile PEC methods for detecting biological analytes, especially for food safety testing.

The effects of paroxetine therapy on depressive symptom and motor function in the treatment of depression with Parkinson's disease: A meta-analysis.

BACKGROUND: Paroxetine therapy has been used for treatment of patients with depression and Parkinson's disease (dPD) in many clinical studies, but, the effects of paroxetine in dPD patients are not completely understood. The aim of this study was to systematically evaluate the effects of paroxetine therapy on depressive symptom and motor function in the treatment of dPD, in order to confer a reference for clinical practice. METHODS: Randomized controlled trials (RCTs) of paroxetine for dPD published up to October, 2022 were retrieved. Standardised mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. The outcomes of interest were as follows: the efficacy, Hamilton depression rating scale score, unified Parkinson's disease rating scale score, Hamilton anxiety rating scale score or adverse events. RESULTS: Thirty-four RCTs with 2819 participants were included. Compared with control group, the pooled effects of paroxetine therapy on depression were (22 trials; OR 3.62, 95% CI 2.63 to 4.98, P < .00001) for antidepressant response (25 trials; SMD -2.14, 95% CI -2.73 to -1.56, P < .00001) for Hamilton depression rating scale score, the pooled effects of paroxetine therapy on motor function were (10 trials; OR 4.63, 95% CI 3.15 to 6.79, P < .00001) for anti-PD efficacy (18 trials; SMD -2.02, 95% CI -2.48 to -1.55, P < .00001) for total unified Parkinson's disease rating scale score. The Hamilton anxiety rating scale score showed significant decrease in the paroxetine treatment group compared to control group (10 trials; SMD -1.93, 95% CI -2.65 to -1.22, P < .00001). In addition, paroxetine therapy reduced the number of any adverse events obviously in dPD patients (twenty trials; OR 0.42, 95% CI 0.31 to 0.57, P < .00001). CONCLUSIONS: Paroxetine therapy has clinical benefits for improvement of depressive symptom and motor function in dPD patients, moreover, it is of high drug safety. Further well-designed, multi-center RCTs needed to identify these findings.

Predicting apical hypertrophic cardiomyopathy using T-wave inversion: Three case reports.

BACKGROUND: Apical hypertrophic cardiomyopathy (AHCM) is a subtype of hypertrophic cardiomyopathy. Due to its location, the thickening of the left ventricular apex can be missed on echocardiography. Giant negative T waves (GNTs) in left-sided chest leads are the hallmark electrocardiogram (ECG) change of AHCM. CASE SUMMARY: The first patient was a 68-year-old woman complaining of recurrent chest tightness persisting for more than 3 years. The second was a 59-year-old man complaining of spasmodic chest tightness persisting for more than 2 years. The third was a 55-year-old woman complaining of recurrent chest pain persisting for 4 mo. In all three cases, GNTs were observed several years prior to apical cardiac hypertrophy after other causes of T-wave inversion were ruled out. CONCLUSION: Electrophysiological abnormalities of AHCM appear earlier than structural abnormalities, confirming the early predictive value of ECG for AHCM.

Integrated analysis of plasma proteome and cortex single-cell transcriptome reveals the novel biomarkers during cortical aging.

Background: With the increase of age, multiple physiological functions of people begin gradually degenerating. Regardless of natural aging or pathological aging, the decline in cognitive function is one of the most obvious features in the process of brain aging. Brain aging is a key factor for several neuropsychiatric disorders and for most neurodegenerative diseases characterized by onset typically occurring late in life and with worsening of symptoms over time. Therefore, the early prevention and intervention of aging progression are particularly important. Since there is no unified conclusion about the plasma diagnostic biomarkers of brain aging, this paper innovatively employed the combined multi-omics analysis to delineate the plasma markers of brain aging. Methods: In order to search for specific aging markers in plasma during cerebral cortex aging, we used multi-omics analysis to screen out differential genes/proteins by integrating two prefrontal cortex (PFC) single-nucleus transcriptome sequencing (snRNA-seq) datasets and one plasma proteome sequencing datasets. Then plasma samples were collected from 20 young people and 20 elder people to verify the selected differential genes/proteins with ELISA assay. Results: We first integrated snRNA-seq data of the post-mortem human PFC and generated profiles of 65,064 nuclei from 14 subjects across adult (44-58 years), early-aging (69-79 years), and late-aging (85-94 years) stages. Seven major cell types were classified based on established markers, including oligodendrocyte, excitatory neurons, oligodendrocyte progenitor cells, astrocytes, microglia, inhibitory neurons, and endotheliocytes. A total of 93 cell-specific genes were identified to be significantly associated with age. Afterward, plasma proteomics data from 2,925 plasma proteins across 4,263 young adults to nonagenarians (18-95 years old) were combined with the outcomes from snRNA-seq data to obtain 12 differential genes/proteins (GPC5, CA10, DGKB, ST6GALNAC5, DSCAM, IL1RAPL2, TMEM132C, VCAN, APOE, PYH1R, CNTN2, SPOCK3). Finally, we verified the 12 differential genes by ELISA and found that the expression trends of five biomarkers (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) were correlated with brain aging. Conclusion: Five differentially expressed proteins (DSCAM, CNTN2, IL1RAPL2, CA10, GPC5) can be considered as one of the screening indicators of brain aging, and provide a scientific basis for clinical diagnosis and intervention.

"Gold-plated" PCN-222(Fe) and superconductive carbon black-based sandwich-type immunosensor for detecting CYFRA21-1.

Cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) is a protein fragment dissolved in the blood after apoptosis of lung epithelial cells, which is a predictive biomarker for the diagnosis of non-small cell lung cancer (NSCLC). Detection of serum CYFRA21-1 has a significant clinical value in diagnosis, monitoring and prognosis of NSCLC. Herein, a novel electrochemical immunosensor was constructed for the sensitive detection of CYFRA21-1. First, superconductive carbon black (KB) functionalized polyethyleneimine (PEI)-gold nanoparticles (AuNPs) were covered on the surface of methylene blue (MB) and used as substrate materials to immobilize the CYFRA21-1 antibody. Then, target CYFRA21-1 was successfully detected using an electrochemical immunosensor through specific recognition of antigen and antibody. The zirconium-based metal organic framework of PCN-222(Fe) with a large pore size and three-dimensional (3D) structure can absorb abundant AuNPs through strong electrostatic interaction, which enhances the conductive properties of PCN-222(Fe) and prevents the self-aggregation of AuNPs. However, PCN-222(Fe) with peroxidase-like activity can catalyze the generation of hydroxyl free radicals (˙OH) from H2O2, which oxidized MB, leading to a decrease in the current signal. The signal response to the degradation of MB was recorded using differential pulse voltammetry (DPV). This indirect method of immunosensor offered a new strategy to address the limitations imposed by the poor conductivity of PCN-222(Fe), further enabling the amplification of the signal through the oxidative degradation of MB. Compared with traditional electrochemical immunosensors, this method has the advantages of a stable current signal and good reproducibility, providing a promising reference for the broad application of PCN-222(Fe) in electrochemical biosensors.

A sandwich-type electrochemical immunosensor for sensitive detection of HER2 based on dual signal amplification of La-MOF-PbO2 and PEI-MoS2NFs composites.

In recent decades, the incidence of breast cancer has increased year by year, posing a serious threat to human health and quality of life, and about 30% of breast cancer patients have human epidermal growth factor receptor 2 (HER2) overexpression. Therefore, HER2 has become an important biomarker and indicator for the clinical evaluation of breast cancer in diagnosis, prognosis and recurrence. In this work, polyethyleneimine functionalized MoS2 nanoflowers (PEI-MoS2NFs) with good electrical conductivity and abundant active binding sites were designed and employed as a sensing platform for immobilizing the primary antibody of HER2 (Ab1). In addition, a La-MOF-PbO2 composite with a large specific surface area and good conductivity was used to load lots of electroactive toluidine blue (TB) and the secondary antibody of HER2 (Ab2) via gold nanoparticles (AuNPs) as the linker. Thus, the constructed sandwich-type electrochemical immunosensor was applied for sensitive detection of HER2, which showed a wide linear range from 100 fg mL-1 to 10 µg mL-1 with a lower limit of detection of 15.64 fg mL-1. Therefore, the resulting immunosensor in this study would have a potential application in clinical bioanalysis.

Smartphone and paper-based device for glucose monitoring using acetylene black-hemin nanozyme as catalyst.

Glucose management is an important part of disease control for diabetes patients, thus the development of a rapid and real-time point of care testing (POCT) device for monitoring blood glucose is of great significance. In this work, a paper-based analytical device (PAD) is constructed by combining acetylene black (AB)-hemin complex modified filter paper as sensing platform with a smartphone as signal detector. Large specific surface area of AB decreases the self-associate and aggregate of hemin in aqueous solution, resulting in improved peroxidase-like activity of hemin. Compared with graphene oxide supported hemin, AB-hemin exhibits superior signal response on paper. Glucose oxidase (GOx) catalyzes the conversion of blood glucose to hydrogen peroxide, and then AB-hemin complex catalyzes the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB oxidized products (TMB+) in the presence of hydrogen peroxide, thus achieving the visual detection of blood glucose. In optimal conditions, PAD provides an applicable linear range from 0.2 mM to 30 mM and a low limit of detection (LOD) (0.06 mM). Notably, the detection accuracy of the developed paper-based sensor is in good agreement with that of the commercially available blood glucose meter (p > 0.05). Moreover, the proposed PAD presents high recoveries from 95.4% to 112% (RSD ≤ 3.2%), and therefore holds great potential for glucose monitoring and diabetes diagnosis.

An enzymatic activity regulation-based clusterzyme sensor array for high-throughput identification of heavy metal ions.

The accurate identification and sensitive quantification of heavy metal ions are of great significance, considering that pose a serious threat to environment and human health. Most array-based sensing platforms, to date, utilize nanozymes as sensing elements, but few studies have explored the application of the peroxidase-like activity of clusterzymes in identification of multiple analytes. Herein, for the first time, we developed a clusterzyme sensor array utilizing gold nanoclusters (AuNCs) as sensing elements for five heavy metal ions identification including Hg2+, Pb2+, Cu2+, Cd2+ and Co2+. The heavy metal ions can differentially regulate the peroxidase-like activity of AuNCs, and that can be converted into colorimetric signals with 3,3',5,5'-tetramethylbenzidine (TMB) as the chromogenic substrate. Subsequently, the generated composite responses can be interpreted by combining pattern recognition algorithms. The developed clusterzyme sensor array can identify five heavy metal ions at concentrations as low as 0.5 µM and their multi-component mixtures. Especially, we demonstrated the successful identification of multiple heavy metal ions in tap water and traditional Chinese medicine, with an accuracy of 100% in blind test. This study provided a simple and effective method for identification and quantification of heavy metal ions, rendering a promising technique for environmental monitoring and drug safety assurance.

[Effect of traditional Chinese medicine in attenuating chronic kidney disease and its complications by regulating gut microbiota-derived metabolite trimethylamine N-oxide: a review].

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.

Nanolobatone A, An Unprecedented Diterpenoid and Related New Casbanoids from the Hainan Soft Coral Sinularia nanolobata.

Nanolobatone A, featuring an unprecedented tricyclo[10.3.0.01,2 ]pentadecane carbon skeleton, along with four new polyoxygenated and four unusual endoperoxide-bridged casbane-type diterpenoids were isolated from the Hainan soft coral Sinularia nanolobata. The structures of the new compounds were established by extensive spectroscopic analysis, X-ray diffraction analysis, and time-dependent density functional theory/electronic circular dichroism calculations. A plausible biosynthetic pathway of new isolates was proposed. Bioassays revealed that nanolobatone A showed weak antibacterial activity against the Gram-positive bacteria Streptococcus pyogenes.

Mechanism for the restoration of degraded typical steppe by nitrogen and phosphorus co-addition.

The reduction of soil nutrient content is one of the major reasons caused grassland degradation in China. Nutrient addition is thus considered as an effective measure for the restoration of degraded grasslands. However, over-fertilization can lead to decrease in plant diversity. To clarify the appropriate amount of nutrient addition and the underlying mechanism that promotes grassland restoration, we set up a nitrogen and phosphorus co-addition experiment in a degraded typical steppe of Inner Mongolia, and examined the responses at community, functional group and species levels to nutrient addition. The results showed that nutrient addition enhanced biomass while did not reduce species richness at the community level. The biomass showed a saturation response with the increases of nutrient addition, which approached saturation under the 12.0 g N·m-2, 3.8 g P·m-2 treatment. Species richness increased significantly under the lower nutrient treatments (N <9.6 g·m-2, P < 3.0 g·m-2) compared with the control, while the two high nutrient treatments did not alter species richness. At the functional group level, biomass and abundance of perennial rhizome grasses increased significantly with the increases of nutrient addition levels. Biomass and density of annuals increased significantly under high nutrient addition levels. However, the abundance and biomass of perennial bunchgrasses and perennial forbs were rarely affected. At the species level, six target species responded differently to nutrient addition. Biomass of Leymus chinensis was significantly increased due to the increase of population density and individual biomass. Biomass of Stipa grandis, Agropyron cristatum and Cleistogenes squarrosa change little. Biomass of Potentilla acaulis and Carex korshinskyi were reduced due to the decreases in individual biomass and population density, respectively. As a measure of restoring degraded grassland, nutrient addition could significantly increase biomass and species diversity, decrease biomass of the degradation indicator species, and increase biomass of perennial rhizomes grasses.

Kill two birds with one stone: Ratiometric sensing of phosphate via a single-component probe with fluorescence-scattering dual-signal response behavior.

Ratiometric fluorescence sensors gain stronger anti-interference ability via self-calibration. Nevertheless, ratiometric analysis of phosphate (Pi) still faces problems such as complicated construction process of dual emission probes and possible interferences from outputting mono-category fluorescent signal. Herein, we propose a "kill two birds with one stone" strategy to address these challenges, by simply introducing a single-component probe, porphyrin paddlewheel framework-3 (PPF-3) nanosheets without modification, encapsulation or complex, to integrate fluorescence (FL)-second-order scattering (SOS) dual-signal for ratiometric detection of Pi. PPF-3 nanosheets are constructed by coordination of Co2+ with 5,10,15,20-tetrakis(4-carboxyl-phenyl)-porphyrin (TCPP) ligands, displaying weak FL and strong SOS, two different and independent signals. In the response system to Pi, Co2+ and TCPP serve as the recognition element and signal unit, respectively. After interacting with Pi, the high affinity for Co2+ makes Pi snatch Co2+ from the PPF-3 nanosheets, causing their structure disassembly (SOS decrease) and TCPP release (FL increase). Finally, the FL-SOS ratiometric platform is successfully employed to access Pi in real water samples. Synchronous collection of FL and SOS from the single-component probe provides a simpler and more efficient way on ratiometric sensor design as well as a new useful technique for monitoring target-induced aggregation and disaggregation behavior.

Sinulasterols D-G, four new antibacterial steroids from the South China sea soft coral Sinularia depressa.

Four new steroids, namely sinulasterols D-G (1-4), along with seven known related ones 5-11, were isolated from the Xisha soft coral Sinularia depressa. The structures of the new compounds were elucidated by a combination of extensive spectroscopic analyses, chemical conversion method, and comparison of the NMR data with those of known analogues. In in vitro bioassays, compounds 1-3 showed significant antibacterial activities against gram-positive bacteria Enterococcus faecium with minimum inhibitory concentration (MIC) values of 62.5, 125, and 125 µM, respectively, comparable with that of vancomycin (MIC: >44.2 µM).

A Novel Signal-On Electrochemiluminescence Immunosensor for the Detection of NSCLC Antigen Biomarker Based on New Co-Reaction Accelerators.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with substantial morbidity and mortality. Herein, a new signal-on electrochemiluminescence (ECL) immunosensor based on multiple amplification strategies is constructed for ultrasensitive detection of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) biomarker related to NSCLC. Polyethyleneimine (PEI) functionalized MXene is decorated with NiMn layer double hydroxide (NiMn LDH) to form MXene-PEI-NiMn LDH composite. Specially, the La-MOF@ZIF-67 bimetallic organic framework (named as LZBM) and MXene-PEI-NiMn LDH both served as coreaction accelerators to improve the ECL emission of the luminol-H2 O2 system. To be specific, Au nanoparticles (AuNPs) coated MXene-PEI-NiMn LDH is applied to immobilize primary CYFRA21-1 antibody (Ab1 ), while AuNPs decorated LZBM was used for the loading of luminol and secondary CYFRA21-1 antibody (Ab2 ) to form tracer label. Therefore, the ECL signal of the sandwich-type immunosensor is significantly enhanced due to the high loading capability for luminol and the synergistic catalytic ability for the decomposition of H2 O2 into reactive oxygen species (ROS). Under the optimal experimental conditions, the ECL immunosensor exhibited good analytical performances for CYFRA21-1 detection with a wide linear range (100 fg mL-1 -100 ng mL-1 ) and a low limit of detection (85.20 fg mL-1 ), providing a promising method for early diagnosis of NSCLC.

Concomitant Diseases and Co-contribution on Progression of Liver Stiffness in Patients with Hepatitis B Virus Infection.

BACKGROUND: The association between hepatitis B and concomitant diseases, such as fatty liver, T2DM, MetS, and Hp infection, remains unclear. AIM: The present study was to illustrate the association and explore the co-contribution on abnormal transaminase and progression of liver stiffness. METHODS: A total of 95,998 participants underwent HBsAg screening in West China Hospital from 2014 to 2017. Multivariable logistic regression was used to determine the adjusted odds ratios. RESULTS: The prevalence of HBsAg-positive rate was 8.30% of our included study population. HBsAg positive was associated with negative risk of fatty liver (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.65-0.78, p < 0.001) and MetS (OR 0.74, 95% CI 0.67-0.84, p < 0.001), and with positive risk of Hp infection (OR 1.09, 95% CI 1.02-1.17, p = 0.012) and T2DM (OR 1.18, 95% CI 1.01-1.40, p = 0.043). Besides, HBsAg-positive patients with T2DM had higher risk of elevated ALT (OR 2.09, 95% CI 1.69-2.83, p < 0.001 vs OR 1.59, 95% CI 1.51-1.68, p < 0.001), AST (OR 2.69, 95% CI 1.98-3.65, p < 0.001 vs OR 1.89, 95% CI 1.76-2.02, p < 0.001) than HBV alone. In addition to HBV, T2DM also can increase the risk of liver fibrosis (OR 3.23, 95% CI 1.35-7.71, p = 0.008) and cirrhosis (OR 4.31, 95% CI 1.41-13.20, p = 0.010). CONCLUSION: Hepatitis B patients have a lower risk of fatty liver and MetS, and a higher risk of T2DM and Hp infection. Besides, T2DM might be possibly associated with abnormal liver transaminase and fibrosis progression in HBsAg-positive patients.