The association of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage in patients with chronic hepatitis B.

The utility of measurement of serum immunoglobulin and complement in chronic hepatitis B (CHB) patients remains controversial. This study aimed to investigate the association of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage in CHB patients. A total of 687 patients with CHB who underwent liver biopsy were enrolled. Serum immunoglobulin and complement were measured before liver biopsy, and liver pathological results were recorded. Associations of serum immunoglobulin and complement levels and liver fibrosis and inflammation stage were analysed. C3, C4, IgG and IgG1 had statistically significant differences among different fibrosis and different inflammation groups. Both C3 and C4 negatively correlated with fibrosis and inflammation stage, but IgG and IgG1 showed opposite results. C3, C4, IgG and IgG1 had statistical significance to predict ≥S2, ≥S3 and S4, and also had statistical significance to predict ≥G2, ≥G3 and G4. The area under curve (AUC) of the combination of C3, C4 and IgG (C3 + C4 + IgG) for predicting ≥S2, ≥S3 and S4 was 0.640 (95% CI: 0.603, 0.676), 0.674 (95% CI: 0.638, 0.709) and 0.744 (95% CI: 0.710, 0.776), respectively. The AUC of C3 + C4 + IgG for predicting ≥G2, ≥G3 and G4 was 0.723 (95% CI: 0.688, 0.756), 0.674 (95% CI: 0.638, 0.709) and 0.771 (95% CI: 0.738, 0.802), respectively. C3, C4, IgG and IgG1 are correlated with liver fibrosis and inflammation stage in CHB patients. C3, C4, IgG and IgG1 have diagnostic value for liver fibrosis and inflammation. C3 + C4 + IgG may improve diagnostic accuracy.

Effectiveness of SARS-CoV-2-inactivated vaccine and the correlation to neutralizing antibodies: A test-negative case-control study.

Severe acute respiratory syndrome coronavirus 2 breakthrough infection in highly vaccinated populations raises study on the effectiveness for inactivated vaccine, including effectiveness of the vaccine dose, the continuance of effectiveness, the effectiveness against severe/critical coronavirus disease 2019 and against secondary attacks. A population of 10 870 close contacts were investigated in a Delta variant's epidemic. The effectiveness of vaccination was estimated in a test-negative case-control study. In addition, serum was used to detect neutralizing antibodies, to explore their correlation to effectiveness. The vaccine effectiveness (VE) values were estimated for populations aged 12 years or older. The overall adjusted VE was 56.2% and a two-dose vaccine was more effective than a one-dose vaccine (56.7% vs. 43.8%). In addition, the population that got the second dose vaccine within 2 months showed higher VE than the population vaccinated for longer than 2 months (61.5% vs. 52.3%). Among the population who vaccinated 2 doses or within 2 months, a higher level of neutralizing antibodies was observed. For infected cases, vaccinated populations showed lower rates of transmission (2.63% vs. 4.36%). Further, those vaccinated cases, who were not found causing transmission, had a higher level of antibodies. The study provided a full view of the effectiveness of inactivated vaccines in a real-world setting. The time-related VE against infection and lower transmission of breakthrough vaccinated cases were observed, which may indicate that a necessity of a booster vaccine to maintain the effectiveness and high level of neutralizing antibody.

A Cross-Sectional Study of Clostridium Difficile Infection in Inpatients with Antibiotic Associated Diarrhea.

BACKGROUND: Clostridium difficile (C. difficile) is a Gram-positive, anaerobic, spore-forming bacillus that can cause pseudomembranous colitis and other C. difficile-associated diseases, resulting in significant morbidity and mortality. The incidence and clinical features vary by geography. METHODS: In this cross-sectional study, we examined the incidence and clinical features of C. difficile infection (CDI) within a 2,900-bed academic medical center in a southern area of China from January 1, 2017, to December 31, 2020. All adult inpatients (aged ≥ 18 years) who submitted loose stool samples for C. difficile testing over this period were considered for the study. RESULTS: This cross-sectional study showed that the average incidence of CDI was 2.07 cases/100,000 hospital patient-days. The mean age of these inpatients was 71.21 ± 2.83 years (range 30 - 93 years), and 83.61% (51/61) were treated in medical units. We found that 85.25% (52/61) of inpatients with CDI were aged > 60 years. Multivariate logistic regression analysis revealed that age > 60 years, and admission to the geriatric treatment unit or neurosurgery treatment unit were indeed independent risk factors for CDI in inpatients. CONCLUSIONS: The incidence of CDI in the southern area of China was low. Age > 60 years, and treatment in geriatric or neurosurgery units were independent risk factors for CDI inpatients.

Co-Reactant-Mediated Low-Potential Anodic Electrochemiluminescence Platform and Its Immunosensing Application.

Screening high-performance anodic electrochemiluminescence (ECL) systems with low triggering potential is a promising way to broaden their applications. In addition to electrochemiluminophore, co-reactant also plays an important role in the ECL process, since the oxidation of co-reactants is one of the most important steps in the anodic ECL process. Herein, a novel co-reactant-mediated high-performance low-potential Au nanocluster (AuNC)-based ECL system has been successfully developed. Benefiting from the isopropyl substitution and hydroxyl addition to the triethylamine (TEA), the BSA-AuNC/2-(diisopropylamino)ethanol (DIPEA-OH) ECL system achieved higher energy efficiency at a lower potential of 0.75 V. In addition, compared with the BSA-AuNC/TEA system, the ECL intensity and quantum yield (ΦECL) with DIPEA-OH as a co-reactant increased 22.34-fold and 13-fold (as high as 68.17%), respectively. Based on the low potential, high ΦECL of the AuNC/DIPEA-OH ECL system, a sandwich-type immunosensor has been constructed for a highly selective SARS-CoV-2 N protein assay. In the absence of any complex signal amplification strategies, the ECL immunosensor for the SARS-CoV-2 N protein detection showed a linear range of 0.001-100 ng/mL and a detection limit of 0.35 pg/mL. Moreover, the ECL platform had good reproducibility and stability and exhibited acceptable detection performance in the detection of actual serum samples. This work established a framework for in-depth design and study of anode ECL co-reactants for AuNCs and other luminophores, and expanded the potential application of ECL sensors in the clinical diagnosis of COVID-19.

Antenna effect of pyridoxal phosphate on the fluorescence of mitoxantrone-silicon nanoparticles and its application in alkaline phosphatase assay.

As a kind of sensing and imaging fluorescent probe with the merit of low toxicity, good stability, and environment-friendly, silicon nanoparticles (SiNPs) are currently attracting extensive research. In this work, we obtained mitoxantrone-SiNPs (MXT-SiNPs) with green emission by one-pot synthesis under mild temperature condition. The antenna based on pyridoxal phosphate (PLP) was designed for light-harvesting to enhance the luminescence of MXT-SiNPs and to establish a novel sensing strategy for alkaline phosphatase (ALP). PLP transfers the absorbed photon energy to MXT-SiNPs by forming Schiff base. When PLP is dephosphorized by ALP, the released free hydroxyl group reacts with aldehyde group to form internal hemiacetal, which leads to the failure of Schiff base formation. Based on the relationship between antenna formation ability and PLP hydrolysis degree, the activity of ALP can be measured. A good linear relationship was obtained from 0.2 to 3.0 U/L, with a limit of detection of 0.06 U/L. Furthermore, the sensing platform was successfully used to detect ALP in human serum with recovery of 97.6-106.2%. The rational design of antenna elements for fluorescent nanomaterials can not only provide a new pathway to manipulate the luminescence, but also provide a new direction for fluorescence sensing strategy.

Electrochemiluminescence Immunoassay Platform with Immunoglobulin G-Encapsulated Gold Nanoclusters as a "Two-In-One" Probe.

Biomolecule-functionalized Au nanoclusters (AuNCs) have drawn great interest in the electrochemiluminescence (ECL) field due to their unique optical/electrical properties, biocompatibility, and versatile bioapplication potentials. Herein, we proposed a two-in-one ECL probe of immunoglobulin G-encapsulated AuNCs (IgG-AuNCs) for the development of a high-performance ECL immunoassay (ECLIA) platform. The IgG-AuNCs were not only used as an ECL probe due to their excellent anodic ECL performance with triethylamine (TEA) as a coreactant but also used as the biorecognition element because of their well-retained bioactivity of the IgG. As a proof of concept, a new type of competitive immunosensing platform has been applied to detect IgG representing several merits of facile preparation, rapid detection, sample saving, and good analytical performance. The sensing platform exhibited a linear range of 0.5-50,000 ng/mL with a limit of detection of 0.06 ng/mL for IgG detection with high selectivity. In addition, this convenient ECLIA platform also performed well in real serum sample detection. Notably, our work not only proved the "two-in-one" immuno-AuNC probe-based ECLIA strategy but also developed a rational framework for study of ECL bioassay platforms based on multifunctional AuNCs and other related nanomaterials.

Stimuli-Responsive Microfluidic Interface Enables Highly Efficient Capture and Release of Circulating Fetal Cells for Non-Invasive Prenatal Testing.

Circulating fetal nucleated cells (CFCs) carrying whole genomic coding of the fetus in maternal blood have been pursued as ideal biomarkers for noninvasive prenatal testing (NIPT). However, a significant limitation is the need to enrich sufficient cells in quantity and purity for fetal genetic disorder diagnosis. This study for the first time demonstrates a stimuli-responsive ligand enabling interface on array patterned microfluidic chip (NIPT-Chip) for high efficient isolation and release of CFCs in untreated whole blood. Deterministic lateral displacement (DLD)-array was patterned in the chip to increase collision frequency between CFCs and surface-anchored antibody to achieve high efficient cell capture. More importantly, the stimuli-responsive interface enables gentle release of captured CFCs through a thiol exchange reaction for downstream gene analysis of NIPT. With the advantages of simple processing, efficient isolation, and gentle release, NIPT-Chip offers great potential for clinical translation of circulating fetal cell-based NIPT.

Ascorbate Oxidase Mimetic Activity of Copper(II) Oxide Nanoparticles.

Although oxidase mimetic nanozymes have been widely investigated, specific biological molecules have rarely been explored as substrates, particularly in the case of ascorbate oxidase (AAO) mimetic nanozymes. Herein, we demonstrate for the first time that copper(II) oxide nanoparticles (CuO NPs) catalyze the oxidation of ascorbic acid (AA) by dissolved O2 (as a green oxidant) to form dehydroascorbic acid (DHAA), thus functioning as a new kind of AAO mimic. Under neutral conditions, the Michaelis-Menten constant of CuO NPs (0.1302 mm) is similar to that of AAO (0.0840 mm). Furthermore, the robustness of CuO NPs is greater than that of AAO, thus making them suitable for applications under various conditions. As a demonstration, a fluorescence AA sensor based on the AAO mimetic activity of CuO NPs was developed. To obtain a fluorescent product, o-phenylenediamine (OPDA) was used to react with the DHAA produced by the oxidation of AA catalyzed by CuO NPs. The developed sensor was cost-effective and easy to fabricate and exhibited high selectivity/sensitivity with a wide linear range (1.25×10-6 to 1.125×10-4 m) and a low detection limit (3.2×10-8 m). The results are expected to aid in expanding the applicability of oxidase mimetic nanozymes in a variety of fields such as biology, medicine, and detection science.

Highly sensitive colorimetric sensor for detection of iodine ions using carboxylated chitosan-coated palladium nanozyme.

Although a massive research has been devoted on the exploration of noble metal-based nanozyme, less progress has been made in the investigation of palladium (Pd) nanozyme and the interaction between ions and Pd nanozyme. In this study, a new type of Pd nanozyme was prepared by a facile one-pot approach by using carboxylated chitosan as the stabilizer. Owing to the synergistic effect of carboxylated chitosan stabilized Pd nanoparticles (CC-PdNPs) can effectively catalyze the H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine sulfate (TMB) accompanied by a blue color change (oxidized TMB), indicating the peroxidase-like activity of CC-PdNPs. Furthermore, the Michaelis-Menten constants and catalytic stability of CC-PdNPs render them suitable for environmental analysis and bio-detection. Here, we found that while introducing the iodine ions (I-) into the reaction medium, the peroxidase-like activity of CC-PdNPs has been rapidly and effectively inhibited through the formation of Pd-I bond; thus, the active sites of PdNPs can be blocked by I-. Based on this specific inhibition by I-, a facile colorimetric assay has been performed for the detection of I- with an extremely low limit of detection (0.19 nM). Furthermore, the practicality of the proposed sensor also has been demonstrated in tap water, and the satisfactory recoveries were obtained. Our study not only demonstrated a novel Pd-based nanozyme but also provided guidance for I- sensing for environmental analysis, food inspection, and bio-detection. Graphical abstract.

New photothermal immunoassay of human chorionic gonadotropin using Prussian blue nanoparticle-based photothermal conversion.

A new near-infrared-based photothermal immunosensing strategy was developed for the sensitive and feasible detection of human chorionic gonadotropin (HCG) by use of a Prussian blue nanoparticle-based photothermal conversion system. Prussian blue nanospheres synthesized by the one-pot method were used for the labeling of anti-HCG detection antibody. A sandwich-type immunoreaction was initially conducted on a monoclonal anti-HCG antibody-coated microplate with a nanoparticle-labeled signal antibody. Accompanying formation of the sandwiched immunocomplex, Prussian blue nanospheres caused photothermal conversion under 980-nm laser irradiation, thereby resulting in an increase of the temperature of the detection system measured by a portable digital thermometer. The properties and factors influencing the analytical performance of the photothermal immunoassay were studied in detail. Under the optimal conditions, the Prussian blue nanoparticle-based photothermal immunoassay exhibited good temperature responses relative to target HCG concentrations within the dynamic range of 0.01-100 ng mL-1 at a low detection limit of 5.8 pg mL-1. This system also displayed good anti-interference behavior with regard to other cancer biomarkers, good reproducibility, and relatively long storage stability. The method accuracy was evaluated for analysis of human serum specimens, giving results that matched well with those obtained with a commercial HCG enzyme-linked immunosorbent assay kit. Importantly, this protocol is promising for advanced development of photothermal immunoassays. Graphical abstract.

The association of five preoperative serum tumor markers and pathological features in patients with breast cancer.

BACKGROUND: The utility of frequently used serum tumor markers in breast cancer remains controversial. The study aimed to investigate the role of preoperative carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), and ferritin (FER) in the management of breast cancer and their relationships with pathological features. METHODS: A total of 804 patients with breast mass who underwent breast surgery and 305 healthy volunteers were enrolled. Preoperative serum levels of CEA, CA125, CA153, CA724, and FER were measured. And the pathological features of all the patients were recorded. The association of preoperative serum tumor markers and pathological features was analyzed. RESULTS: Among the 804 patients, 355 were identified as malignant cases and 449 as benign cases. CEA, CA153, and FER of patients with breast cancer were higher than those of healthy volunteer group and patients with benign breast diseases. The area under curve (AUC) of CEA, CA153, and FER for distinguishing patients with breast cancer and subjects with non-breast cancer was 0.688 (95% CI: 0.656-0.721), 0.609 (95% CI: 0.574-0.645), and 0.623 (95% CI: 0.586-0.660), respectively. CA153 correlated with tumor size, node status, and TNM stage, whereas CA125 with node status. No statistic differences of the five markers were observed among the four molecular subtypes. CONCLUSION: Preoperative levels of CEA, CA153, and FER exhibit low diagnostic accuracy for breast cancer (stage I-III). CA153 correlates with tumor burden, suggesting its prognostic value. The five serum markers do not correlate with molecular subtypes.

Alkaline peroxidase activity of cupric oxide nanoparticles and its modulation by ammonia.

We herein report the intrinsic alkaline peroxidase-like activity exhibited by CuO nanoparticles when 3-(4-hydroxyphenyl)propionic acid was employed as a substrate. Based on this observation, a fluorometric assay method with a low detection limit of 0.81 µM was established for H2O2 determination under alkaline conditions. Notably, ammonia was found to inhibit the alkaline peroxidase-like activity of the CuO nanoparticles. Thus, a sensing platform for the determination of urea and urease was successfully constructed, with the limits of detection for urea and urease being 27 µM and 2.6 U L-1, respectively. This platform was then applied for the detection of urea in human urine and urease in soil, which yielded satisfactory results. These results suggest that it is possible to extend the catalytic potential of peroxidase and its mimetics from acidic and neutral conditions to include activity in alkaline media as well. Furthermore, this strategy is a novel method for the analysis of urea and urease. The assay developed in this work is facile, inexpensive, convenient, and highly selective and sensitive. Therefore, it is expected that this system can serve as a template for the development of similar enzyme nano-mimics.

Metformin modifies plasma microbial-derived extracellular vesicles in polycystic ovary syndrome with insulin resistance.

INTRODUCTION: This study investigated changes in plasma microbial-derived extracellular vesicles (EVs) in patients with polycystic ovary syndrome and insulin resistance (PCOS-IR) before and after metformin treatment, and aimed to identify bacterial taxa within EVs that were biologically and statistically significant for diagnosis and treatment. METHODS: The case-control study was conducted at Xiamen Chang Gung Hospital, Hua Qiao University. Plasma samples were collected from five PCOS-IR patients of childbearing age before and after 3 months of metformin treatment, and the samples were sequenced. The diversity and taxonomic composition of different microbial communities were analyzed through full-length 16 S glycosomal RNA gene sequencing. RESULTS: After metformin treatment, fasting plasma glucose levels and IR degree of PCOS-IR patients were significantly improved. The 16 S analysis of plasma EVs from metformin-treated patients showed higher microbial diversity. There were significant differences in EVs derived from some environmental bacteria before and after metformin treatment. Notably, Streptococcus salivarius was more abundant in the metformin-treated group, suggesting it may be a potential probiotic. DISCUSSION: The study demonstrated changes in the microbial composition of plasma EVs before and after metformin treatment. The findings may offer new insights into the pathogenesis of PCOS-IR and provide new avenues for research.

Background-Free SERS Nanosensor for Endogenous Hydrogen Sulfide Detection Based on Prussian Blue-Coated Gold Nanobipyramids.

Surface-enhanced Raman scattering (SERS) has great potential in biological analysis due to its specificity, sensitivity, and non-invasive nature. However, effectively extracting Raman information and avoiding spectral overlapping from biological background interference remain major challenges. In this study, we developed a background-free SERS nanosensor consisting of gold nanobipyramids (Au NBPs) core-Prussian blue (PB) shell (Au NBPs@PB), for endogenous H2S detection. The PB shell degraded quickly upon contact with endogenous H2S, generating a unique Raman signal response in the Raman silent region (1800-2800 cm-1). By taking advantage of the high SERS-activity of Au NBPs and H2S-triggered spectral changes of PB, these SERS nanosensors effectively minimize potential biological interferences. The nanosensor exhibits a detection range of 2.0 µM to 250 µM and a limit of detection (LOD) of 0.34 µM, with good reproducibility and minimal interference. We successfully applied this background-free SERS platform to monitor endogenous H2S concentrations in human serum samples with satisfied results.

Assessing the risk of prenatal depressive symptoms in Chinese women: an integrated evaluation of serum metabolome, multivitamin supplement intake, and clinical blood indicators.

Background: Prenatal depressive symptoms (PDS) is a serious public health problem. This study aimed to develop an integrated panel and nomogram to assess at-risk populations by examining the association of PDS with the serum metabolome, multivitamin supplement intake, and clinical blood indicators. Methods: This study comprised 221 pregnant women, categorized into PDS and non-PDS groups based on the Edinburgh postnatal depression scale. The participants were divided into training and test sets according to their enrollment time. We conducted logistic regression analysis to identify risk factors, and employed liquid chromatography/high resolution mass spectrometry-based serum metabolome analysis to identify metabolic biomarkers. Multiple factor analysis was used to combine risk factors, clinical blood indicators and key metabolites, and then a nomogram was developed to estimate the probability of PDS. Results: We identified 36 important differential serum metabolites as PDS biomarkers, mainly involved in amino acid metabolism and lipid metabolism. Multivitamin intake works as a protective factor for PDS. The nomogram model, including multivitamin intake, HDL-C and three key metabolites (histidine, estrone and valylasparagine), exhibited an AUC of 0.855 in the training set and 0.774 in the test set, and the calibration curves showed good agreement, indicating that the model had good stability. Conclusion: Our approach integrates multiple models to identify metabolic biomarkers for PDS, ensuring their robustness. Furthermore, the inclusion of dietary factors and clinical blood indicators allows for a comprehensive characterization of each participant. The analysis culminated in an intuitive nomogram based on multimodal data, displaying potential performance in initial PDS risk assessment.

Highly specific and sensitive sandwich-type electrochemiluminescence biosensor for HPV16 DNA detection based on the base-stacking effect and bovine serum albumin carrier platform.

The detection of specific DNA sequences and the identification of single nucleotide polymorphisms are important for disease diagnosis. Herein, by combining the high specificity of the base-stacking effect with the high reproducibility of bovine serum albumin (BSA) modified electrodes and the high loading performance of DNA nanoclews (DNA NCs), a novel sandwich-type electrochemiluminescence (ECL) biosensor is reported for the highly specific detection of HPV16 (chosen as the model target). The capture probes are loaded by BSA carrier platforms modified on the gold electrode surface to improve reproducibility. DNA NCs loaded with a large amount of Ru(phen)32+ worked as signal probes. The template probe is composed of the complementary strand of the target and two free nucleic acid anchors at the head and tail. In the presence of the target DNA, the template probes can form stacked base pairs with target, generating high base-stacking energy. This results in the shorter free anchors of template probes being able to bind to the capture and signal probes. This eventually forms a sandwich structure that allows Ru(phen)32+ to be near the electrode surface, producing an ECL signal. There is a linear relationship between the signal and the target concentration range from 10 fM to 100 pM, with a detection limit of 5.03 fM (S/N=3). Moreover, the base-stacking effect has single base recognition ability for base pairs, effectively avoiding false positive signals. The results of this strategy for clinical samples are consistent with classical methods.

Evaluation of a two-test strategy for HIV screening in a low-prevalence setting and the indications for optimizing clinical management.

Objectives: To evaluate a two-test strategy for HIV screening in the low-prevalence population and to assess the feasibility of utilizing the optimal signal-to-cutoff (S/CO) threshold on the chemiluminescence immunoassay(CMIA) and an additional rapid test on the gold immune-chromatography assay (GICA) for screening positive patients and optimization of clinical management. Methods: We conducted a retrospective study of samples analyzed by the fourth-generation Architect HIV Ag/Ab combo assay (CMIA) in a large medical center between June 2017 and August 2020. Reactive samples underwent a second screening test using the rapid test GICA, followed by Western blot (WB) as the confirmatory test. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal S/CO. We calculated sensitivity, specificity, and predictive value based on our population. The performance of the single-test strategy (CMIA) was compared with that of the two-test strategy (CMIA and GICA). Logistic regression was used to analyze the factors of clinical characteristics leading to false positive results. Results: A total of 220558 samples were screened by CMIA, and 429 patients met the inclusion criteria. Of these, CMIA produced 199 false-positive results with a median S/CO of 1.93(IQR1.45-3.68) and 230 positive results with a median S/CO of 455.1 (IQR169.3-709.7). The optimal S/CO of the single-test strategy was 8.82, which achieved a sensitivity of 100% and a positive predictive value (PPV) of 90.9%. The two-test strategy (CMIA and GICA) provided a sensitivity of 100% and a PPV of 98.7%, which best correlated with the confirmatory test WB. The combination of S/CO 8.82 on the CMIA assay and additional test results of GICA can be defined as four types used to interpret HIV serostatus. The false positive rate (FPR) was high in the female, the age≤18 group, the pre-operative patients, and the patients from the clinical departments of Pediatrics, Gynecology and Obstetrics, and Oncology, etc. Conclusions: The false positive rate is high in the low-prevalence setting by using CMIA. The two-test strategy (CMIA and GICA) is recommended for HIV screening in hospitals. Hopefully, the clinicians will be able to interpret HIV serostatus and facilitate clinical decision-making while waiting for the confirmatory results.

Evaluating the value of anti-SARS-CoV-2 antibody detection and neutralizing responses with euvirus: A population of 10776 close contacts in the epidemic of Fujian.

BACKGROUND: Nucleic acid detection represents limitations due to its false-negative rate and technical complexity in the COVID-19 pandemic. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests are widely spread all over the world presently. However, there is no report on the effectiveness of anti-SARS-CoV-2 antibody testing methods in China. METHODS: We gathered 10776 serum samples from close contacts of the SARS-CoV-2 infections in Fujian of China and used 2 chemiluminescence immunoassays (Wantai Bio., Yahuilong Bio.) and 2 lateral flow immunoassays (Lizhu Bio. and Dongfang Bio.) to perform the anti-SARS-CoV-2 antibody tests in China. RESULTS: The 4 antibody tests have great diagnostic value for infected or uninfected, especially in the neutralizing antibodies tests, the AUC can reach 0.939 (Wantai Bio.) and 0.916 (Yahuilong Bio.). Furthermore, we used pseudoviruses and euvirus neutralization assay to validate the effectiveness of these antibody test, the results of pseudoviruses neutralization assay or euvirus neutralization assay shows a considerable correlation with the 4 antibody detection respectively, particularly in euvirus neutralization assay, neutralizing antibodies detected by Wantai Bio. or Yahuilong Bio., the correlation can get the level of 0.93 or 0.82. CONCLUSIONS: The findings of this study demonstrate that the detections of antibodies have profound value in the diagnosis of COVID-19.

Highly reproducible and sensitive electrochemical biosensor for Chlamydia trachomatis detection based on duplex-specific nuclease-assisted target-responsive DNA hydrogels and bovine serum albumin carrier platform.

16S ribosomal-RNA (16S rRNA) is often used as an ultrasensitive marker for Chlamydia trachomatis (CT) detection because of its species specificity and high copy number in CT. Robust methods for 16S rRNA detection must be developed to realize the early diagnosis of CT infections. In this work, a highly reproducible and sensitive electrochemical biosensor based on duplex-specific nuclease (DSN)-assisted target-responsive DNA hydrogels and bovine serum albumin (BSA) carrier platform for CT detection was developed. Target rRNA can trigger the DNA hydrogel response, which causes it to be repeatedly cleaved by DSN, ultimately leading to the release of a large amount of horseradish peroxidase-labelled streptavidin (SA-HRP) embedded in the hydrogel beforehand. The released SA-HRP was stably captured by the capture probes that were orderly loaded at the gold electrode with the help of a BSA layer. Then, SA-HRP catalyzed the redox reaction of 3,3',5,5'-tetramethylbenzidine and H2O2, producing a current signal that can be detected. The current signal was proportional to the concentration of CT 16S rRNA from 10 fM to 25 pM with a detection limit of 5.8 fM (S/N = 3). The signal conversion function of the DNA hydrogel avoids the instability of nonhomogeneous nucleic acid hybridization on the gold electrode surface, and combined with optimization by BSA for capture probe modification, this electrochemical biosensor is highly reproducible with a relative standard deviation of 4.3% for the detection of 10 samples of the same concentration. The proposed strategy provides a highly reproducible and sensitive detection method for the extensive screening of CT.

METTL3 preferentially enhances non-m6A translation of epigenetic factors and promotes tumourigenesis.

METTL3 encodes the predominant catalytic enzyme to promote m6A methylation in nucleus. Recently, accumulating evidence has shown the expression of METTL3 in cytoplasm, but its function is not fully understood. Here we demonstrated an m6A-independent mechanism for METTL3 to promote tumour progression. In gastric cancer, METTL3 could not only facilitate cancer progression via m6A modification, but also bind to numerous non-m6A-modified mRNAs, suggesting an unexpected role of METTL3. Mechanistically, cytoplasm-anchored METTL3 interacted with PABPC1 to stabilize its association with cap-binding complex eIF4F, which preferentially promoted the translation of epigenetic factors without m6A modification. Clinical investigation showed that cytoplasmic distributed METTL3 was highly correlated with gastric cancer progression, and this finding could be expanded to prostate cancer. Therefore, the cytoplasmic METTL3 enhances the translation of epigenetic mRNAs, thus serving as an oncogenic driver in cancer progression, and METTL3 subcellular distribution can assist diagnosis and predict prognosis for patients with cancer.