Electrochemical-Fluorescent Bimodal Biosensor Based on Dual CRISPR-Cas12a Multiple Cascade Amplification for ctDNA Detection.

Circulating tumor DNA (ctDNA) is a critical biomarker for early tumor detection. However, accurately quantifying low-abundance ctDNA in human serum remains a significant challenge. To address this challenge, we introduce a bimodal biosensor tailored for detecting the epidermal growth factor receptor (EGFR) mutation L858R in specific nonsmall cell lung cancer (NSCLC) patients. This biosensor utilizes dual CRISPR-Cas12a systems to quantify the target via fluorescence and electrochemical signals. In our system, the EGFR L858R exhibits resistance to digestion by the restriction enzyme MscI, which activates the first CRISPR-Cas12a protein and inhibits the binding of magnetic beads with fluorescein (FAM)-labeled hybridization chain reaction (HCR) products, thereby reducing the fluorescence signal. This activation also inhibits the cleavage activity of the second CRISPR-Cas12a protein, allowing the electrode to sustain a higher electrochemical signal from nanomaterials. The wild-type EGFR (wt EGFR) produces the opposite effect. Consequently, the concentration of EGFR L858R can be accurately quantified and verified using both fluorescence and electrochemical signals. The biosensor offers a dynamic detection ranging from 10 fM to 1 µM, with a detection limit of 372 aM. It demonstrates excellent specificity, reproducibility, stability, and recovery rates. Moreover, the sensor's enhanced analytical sensitivity highlights its critical role in biosensing applications and early disease diagnosis.

Dual electrochemical signal "signal-on-off" sensor based on CHA-Td-HCR and CRISPR-Cas12a for MUC1 detection.

Mucin 1 (MUC1) is frequently overexpressed in various cancers and is essential for early cancer detection. Current methods to detect MUC1 are expensive, time-consuming, and require skilled personnel. Therefore, developing a simple, sensitive, highly selective MUC1 detection sensor is necessary. In this study, we proposed a novel "signal-on-off" strategy that, in the presence of MUC1, synergistically integrates catalytic hairpin assembly (CHA) with DNA tetrahedron (Td)-based nonlinear hybridization chain reaction (HCR) to enhance the immobilization of electrochemically active methylene blue (MB) on magnetic nanoparticles (MNP), marking the MB signal "on". Concurrently, the activation of CRISPR-Cas12a by isothermal amplification products triggers the cleavage of single-stranded DNA (ssDNA) at the electrode surface, resulting in a reduction of MgAl-LDH@Fc-AuFe-MIL-101 (containing ferrocene, Fc) on the electrode, presenting the "signal-off" state. Both MB and MgAl-LDH@Fc-AuFe-MIL-101 electrochemical signals were measured and analyzed. Assay parameters were optimized, and sensitivity, stability, and linear range were assessed. Across a concentration spectrum of MUC1 spanning from 10 fg/mL to 100 ng/mL, the MB and MgAl-LDH@Fc-AuFe-MIL-101 signals were calibrated with each other, demonstrating a "signal-on-off" dual electrochemical signaling pattern. This allows for the precise and quantitative detection of MUC1 in clinical samples, offering significant potential for medical diagnosis.

An electrochemical ratiometric immunosensor for the detection of NMP22 based on ZIF-8@MWCNTs@Chit@Fc@AuNPs and AuPt-MB.

Nuclear matrix protein 22 (NMP22) is one of the most important tumor markers of bladder cancer and is significantly elevated in the urine of bladder cancer patients. Therefore, in this work, a highly sensitive ratiometric electrochemical immunosensor was constructed to detect NMP22 based on ZIF-8@MWCNTs@Chit@Fc@AuNPs composites. ZIF-8 had a large surface area and good adsorption ability. Multi-Walled Carbon Nanotubes (MWCNTs) can optimize the electrical conductivity of ZIF-8, so that the electrode surface of ferrocene (Fc) obtains a stable and strong electrochemical signal. In addition, AuPt-MB provided another strong detection signal methylene blue (MB) while immobilizing the secondary antibody (Ab2) through Au-N and Pt-N bonds. A ratiometric electrochemical sensor was formed based on ZIF-8@MWCNTs@Chit@Fc@AuNPs and AuPt-MB, which showed a great linear connection between IMB/IFc and the logarithmic concentration of NMP22 with a detection limit of 3.33 fg mL-1 (S/N = 3) under optimized specifications in the concentration interval of 0.01 pg mL-1 to 1000 ng mL-1. In addition, the ratiometric immunosensor showed good selectivity and stability.

Survivin as a potential biomarker in the diagnosis of bladder cancer: A systematic review and meta-analysis.

Early detection, diagnosis, and treatment take on critical significance in preventing and treating bladder cancer. As indicated by numerous studies, survivin can serve as a biomarker of bladder cancer, whereas the results of a wide variety of studies have been controversial. This paper is to assess the accuracy of survivin in the diagnosis of bladder cancer by a meta-analysis. The studies regarding the diagnosis of bladder cancer using survivin were systematically retrieved from the CNKI, WanFang, CBM, VIP, Web of science, cochrane library and pubmed were extracted, and the literature quality was assessed. Meta-analysis was conducted using STATA 16.0 MP. 2,082 relevant studies were searched, and 40 studies were finally covered for meta-analysis. The pooled specificity and pooled sensitivity of survivin mRNA was 0.95 (95%CI: 0.91, 0.97) and 0.94 (95%CI: 0.88, 0.97). The pooled specificity and pooled sensitivity of survivin protein reached 0.95 (95%CI: 0.90, 0.97) and 0.87 (95%CI: 0.78, 0.92). The pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the curve, and diagnostic odds ratio for survivin mRNA reached 17.7 (95%CI: 10.3, 30.6), 0.07 (95%CI: 0.04, 0.12), 0.98 (95%CI: 0.97, 0.99) and 266 (95%CI: 114, 621), respectively. For survivin protein was 16.4 (95%CI: 7.9, 33.9), 0.14 (95%CI: 0.08, 0.24), 0.97 (95%CI: 0.95, 0.98) and 117 (95%CI: 38, 357), respectively. Survivin takes on great significance in diagnosing bladder cancer. However, due to some limitations in the number and quality of covered studies, this conclusion should be validated through additional higher quality clinical studies.

Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension.

BACKGROUND AND OBJECTIVES: Malignant hypertension (MHT) characterized by acute hypertension with retinopathy or multiorgan damage, is a severe form of hypertensive emergency and associated with target organ involvement and poor kidney outcome. However, the underlying mechanisms are unclear. METHODS: Eighty-four patients with acute severe hypertension from the Nephrology Department and Emergency Department in a single center during January 2016 and December 2017 were prospectively enrolled and divided into MHT ( n  = 48) and non-MHT ( n  = 36) subgroups according to target organ evaluation. Forty healthy controls were recruited. Serum soluble Fms-like tyrosine kinase-1 (sFlt-1) levels and plasma ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity were examined at baseline and 12-month follow-up. Renal endpoints were defined as a significant decrease in the estimated glomerular filtration rate (eGFR) of more than 40% or the occurrence of end-stage renal disease. RESULTS: Serum sFlt-1 levels were persistently elevated in MHT. Baseline serum sFLT-1 levels were correlated with plasma ADAMTS13 activity and markers of target organ damage. Plasma ADAMTS13 activity was reduced in both MHT and non-MHT patients and recovered to the normal range at 12-month follow-up. During an average follow-up time of 53 ±â€Š13 months, the restoration of reduced ADAMTS13 activity was correlated with the improvement of kidney function and independently reduced the risk of renal endpoints. CONCLUSIONS: Abnormal angiogenesis and endothelial damage are involved in the pathophysiology of hypertensive emergency. Evaluation of ADAMTS13 and sFlt-1 may help in the diagnosis and assessment of MHT. Recovery of ADAMTS13 predicts better renal outcome in patients with hypertensive emergencies.

C3aR Antagonist Alleviates C3a Induced Tubular Profibrotic Phenotype Transition via Restoring PPARα/CPT-1α Mediated Mitochondrial Fatty Acid Oxidation in Renin-Dependent Hypertension.

BACKGROUND: Renin-dependent hypertension with tubulointerstitial injury remains a problem with high prevalence in the clinic. However, whether and how renin participates in tubulointerstitial injury remains incompletely understood. New evidence suggests that renin cleaves C3 into C3a and C3b. In the present study, we aimed to explore the role of renin-mediated C3a/C3a receptor (C3aR) signaling in renin-dependent hypertension-induced kidney injury and illustrate the detailed mechanisms. METHODS: C3a concentration changes in serum from healthy volunteers incubated with recombinant renin were detected by ELISA. C3aR expression in human tubular epithelial cells was evaluated in renal biopsy sections from malignant arteriolonephrosclerosis and benign arteriolonephrosclerosis patients. C3aR changes in human kidney 2 (HK2) cells were detected after the cells were treated with human serum, renin and aliskiren. The C3a analogue and C3aR antagonist SB290157 were used to stimulate HK2 cells to explore the downstream signaling of C3a/C3aR activation. For in vivo studies, two-kidney, one-clipped (2K1C) hypertensive rat model was established to simulate renin-dependent hypertension conditions. C3a and C3aR expression was detected in the clipped kidneys. SB290157 was injected intraperitoneally to block C3a/C3aR signaling in 2K1C rats. RESULTS: The results showed that renin cleaved C3 into C3a and activated C3a/C3aR signaling in tubular epithelial cells (TECs) from both humans and rats. In vitro results demonstrated that C3a/C3aR activation impaired peroxisome proliferator-activated receptor alpha (PPARα)/carnitine palmitoyltransterase-1alpha (CPT-1α)-mediated mitochondrial fatty acid oxidation (Mito FAO) in HK2 cells and induced HK2 cell transition to a profibrotic phenotype, which was inhibited by treatment with the C3aR antagonist SB290157. In vivo results showed that renin mRNA levels, C3a concentrations, C3aR levels and tubulointerstitial fibrosis increased concurrently in the clipped kidney cortex of 2K1C rats. Treatment with the C3aR antagonist SB290157 significantly mitigated the effect of renin induction of C3aR expression and alleviated renin-dependent hypertension-induced tubulointerstitial fibrosis by improving PPARα/CPT-1α-mediated Mito FAO in TECs, as well as inhibiting tubular profibrotic phenotype transition. CONCLUSIONS: Our results prove that renin activates C3a/C3aR signaling to promote renal tubulointerstitial fibrosis by impairing PPARα/CPT-1α-mediated tubular Mito FAO. SB290157 confers a potential therapeutic approach for renin-dependent hypertension-induced kidney injury.

Association between visceral fat area and serum uric acid in Chinese adults: A cross-sectional study.

BACKGROUND AND AIMS: Hyperuricemia has become a vital public health problem affecting the health of residents. The visceral fat area (VFA) is closely related to many chronic diseases. However, the association between VFA and hyperuricemia within the Chinese adult population remains nebulous. The aim of the research is to assess the relationship between VFA and serum uric acid levels. METHODS AND RESULTS: From June 2020 to June 2021, a total of 340 Chinese adults (240 in the control group and 100 in the hyperuricemia group) were recruited from the physical examination center of Hongqi Hospital Affiliated to Mudanjiang Medical University. General demographic characteristics were collected by questionnaire. VFA was measured by a body composition analyzer, and serum biochemical indices were detected by clinical laboratory. VFA in the hyperuricemia group was higher than in the control group (P＜0.05). Further, VFA demonstrated a positive correlation with serum uric acid level (rs = 0.370, P＜0.001). To further explore this relationship, we divided the VFA into quartiles (＜P25, P25-P50, P50-P75, ≥P75). Upon comparison with the ＜P25 group, we found the VFA in the P25-P50, P50-P75, and ≥P75 groups to be associated with a substantially escalated risk of hyperuricemia, even after adjusting for age, gender, body weight, fasting plasma glucose, calcium, alanine transaminase, urea, alkaline phosphatase, and γ-glutamyltransferase. The OR and 95% CI were 2.547 (1.023, 6.341), 3.788 (1.409, 10.187) and 3.723 (1.308, 10.595), respectively (P＜0.05). CONCLUSION: VFA has a positive correlation with serum uric acid levels and may serve as a crucial predictive marker for hyperuricemia.

Determination of purines in prepackaged food using optimum acid hydrolysis followed by high performance liquid chromatography.

A high performance liquid chromatography was established to determine purine content of prepackaged food. Chromatographic separation was performed on Agilent5 TC-C18 column. Ammonium formate (10 mmol/L, pH = 3.385) and methanol (99:1) were used as mobile phase. Purine concentration and peak area showed good linear relationships in the range from 1 to 40 mg/L (guanine, hypoxanthine, adenine) and xanthine exhibited a good linear relationship ranged from 0.1 to 4.0 mg/L. Recoveries of four purines ranged from 93.03% to 107.42%. Purine content in prepackaged food was following: animal derived prepackaged food: 16.13-90.18 mg/100 g; beans and bean products: 66.36-157.11 mg/100 g; fruits and fruit products: 5.64-21.79 mg/100 g; instant rice and flour products: 5.68-30.83 mg/100 g; fungi, algae, fungi and algae products: 32.57-70.59 mg/100 g. This proposed method had good precision and accuracy with a wide linear range for detection of purine. Animal derived prepackaged food was purine-rich food, purine content of plant derived prepackaged food varied greatly.

Noncoding RNAs as a potential biomarker for the prognosis of bladder cancer: a systematic review and meta-analysis.

OBJECTIVE: The relationship between noncoding RNAs and the prognosis of bladder cancer (BC) is still controversial. The purpose of this study is to evaluate the relationship between noncoding RNAs and prognosis by meta-analysis. METHODS: Comprehensive retrieval of PubMed, Embase, the Cochrane Library, the Web of Science, CNKI, and WanFang databases is related to the correlation between noncoding RNAs and the prognosis of BC. Data were extracted, and the literature quality was evaluated. STATA16.0 served for the meta-analysis. RESULTS: 1. CircRNAs: High circ-ZFR expression led to poor overall survival (OS) of BC. 2. LncRNAs: Low lnc-GAS5 expression predicted poor OS of BC, high lnc-TUG1 expression predicted poor OS of BC. 3. MiRNAs: High miR-21 expression predicted poor OS of BC, high miR-222 expression led to poor OS of BC, high miR-155 expression predicted poor progression-free survival (PFS) of BC, high miR-143 expression caused poor PFS of BC, low miR-214 expression could result in poor recurrence-free survival (RFS) of BC. CONCLUSIONS: High circ-ZFR, lnc-TUG1, miR-222, and miR-21 expressions were correlated with poor OS of BC; high miR-155 and miR-143 expression predicted poor PFS of BC; low lnc-GAS5 expression predicted poor OS of BC; low miR-214 expression predicted poor RFS of BC.

The Impact of Government-Led Farmland Construction on Market-Oriented Farmland Transfer-Evidence from Shandong, China.

This study explored the impact of government-led high-standard farmland construction (HSFC) on market-oriented farmland transfer using a unified analysis framework of HSFC and farmland transfers. We used a binary probit model based on 660 questionnaires from five counties in Shandong Province, China to empirically analyze this impact. The results show that HSFC can significantly promote farmland lease-in while inhibiting lease-out. We found that farmland fragmentation plays a significant role in moderating this impact, which is illustrated by the fact that improved farmland fragmentation does not promote HSFC in the context of farmland lease-in. Furthermore, it can effectively alleviate the inhibitory effect of HSFC on farmland lease-out. The impact of HSFC on farmland transfer has significant labor transfer heterogeneity. For households with a low degree of labor transfer, HSFC can significantly promote farmland lease-in and inhibit lease-out, while for households with a high degree of labor transfer, the above effect is not significant.

Lead absorption capacity in different parts of plants and its influencing factors: a systematic review and meta-analysis.

People pose a serious risk by plants contaminated with lead in soil. However, the strength of lead enrichment capacity in root, stem, and leaf of the plant is still controversial. Therefore, a meta-analysis was conducted to investigate the ability of lead enrichment of root, stem, and leaf and the main influencing factors for lead absorption. The results of this study indicated that all parts of plant can significantly accumulate lead. Concentrations of lead followed an order of root > stem > leaf. Alkaline soil was conducive to the absorption of lead. When the lead concentration in the soil was higher than 20 mg/kg, the lead absorption in root was more. Lead is absorbed most in trees and least in Gramineae. It is argued that this study is beneficial to select plants suitable for absorption of lead from polluted soil. This study also can help to clarify the influencing factors for lead enrichment in different parts of the plant.

Repetitive transcranial magnetic stimulation combined with cognitive behavioral therapy treatment in alcohol-dependent patients: A randomized, double-blind sham-controlled multicenter clinical trial.

Background: Alcohol dependence (AD) is a complex addictive disorder with a high relapse rate. Previous studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioral therapy (CBT) may be effective for AD, and we aim to explore more effective treatment options to reduce relapse rates for AD. Materials and methods: A total of 263 AD patients were recruited. They were divided into six groups according to the location and the type of rTMS: left dorsolateral prefrontal cortex (DLPFC), right DLPFC, sham stimulation, and whether they received CBT treatment: with a fixed schedule (C1) and without a fixed plan (C0). There were included in sham rTMS + C0 group (n = 50), sham rTMS + C1 group (n = 37), right rTMS + C0 group (n = 45), right rTMS + C1 group (n = 42), left rTMS + C0 group (n = 49), left rTMS + C1 group (n = 40). We used obsessive compulsive drinking scale (OCDS), visual analogue scale (VAS), alcohol dependence scale (ADS), montreal cognitive assessment (MoCA), generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 items (PHQ-9), and Pittsburgh sleep quality index (PSQI) to assess alcohol cravings, alcohol dependence, cognition, anxiety, depression, and sleep quality. They were followed up and evaluated for relapse. Results: The sham rTMS + C0 group relapse rate was significantly higher than the right rTMS + C1 group (P = 0.006), the left rTMS + C0 group (P = 0.031), the left rTMS + C1 group (P = 0.043). The right rTMS + C0 group showed significantly higher relapse rate compared to the right rTMS + C1 group (P = 0.046). There was no significant difference in relapse rates between other groups. The repeated-measures ANOVA showed an interaction effect between group and time was significant in the rate of patient health questionnaire-9 items (PHQ-9) scale reduction (P = 0.020). Logistic analysis indicated that smoking and alcohol consumption were independent determinants of relapse (P < 0.05). At 24 weeks of follow-up, Kaplan-Meier survival analysis reveal that there is statistically significant relapse rate between six groups (P = 0.025), left rTMS + C1 group has the best treatment effect for alcohol dependent patients. Cox regression analysis confirmed that current smoking, total cholesterol, and total bilirubin (TBIL) level were risk factors of relapse (P < 0.05). Conclusion: This study is the first to suggest that the combination of rTMS and CBT may be a potentially effective treatment for reducing relapse.

Sandwich-type immunosensor based on COF-LZU1 as the substrate platform and graphene framework supported nanosilver as probe for CA125 detection.

CA125 is a tumor marker which mainly exists in ovarian, the detection for it with high sensitivity is conducive to improve the effectiveness of tumor prevention and control at early state. Multi-layer graphene oxide derivatives from graphene, and has poor conductivity and high stacked properties that limit its further application. Multi-layer reduced graphene oxide frame (MrGOF) was composed of single-layer graphene sheet and exhibited 3D structure with good dispersion, better conductivity and electrochemical properties after multi-layer graphene oxide underwent alkaline peeling and thermally reduction, the modified graphene are easy to load and combine functional groups and metal nanoparticles. Covalent organic frameworks (COFs) presents a stable frame and through covalent bond connection and has porous properties to adsorb biomolecules, which allows the immobilization of antibody molecules by the porosity and improve the sensitivity of the detection in sensing field. Through the adsorption of COFs for antibody and the probe labeled with functional graphene, we constructed a sandwich type immunosensor with the new material COF-LZU1 as the platform to anchor the CA125 first-antibody and MrGOF combined with amino group and loaded with silver nanoparticles (AgNPs) as the probe to detect tumor marker CA125. The linear range of detection was from 0.001 U/mL to 40 U/mL, with the detection limit was calculated to be 0.00023 U/mL (S/N =3). The prepared immunosensor showed a good application ability for real human serum, which can be attributed to the adsorption of COF-LZU1 for the CA125 first-antibody, and ability to deliver electrons and signal amplification of AgNPs anchored on the sheet structure of MrGOF.

Electrochemical Detection of Nuciferine in the Lotus Leaf Based on Efficient Catalysis by Zirconium-MOFs.

BACKGROUND: Nuciferine is an amorphine alkaloid in lotus leaf that has anti-inflammatory, lipid-lowering and hypoglycemic effects, so the quantitation of detected nuciferine is important. OBJECTIVE: An electrochemical method was developed for nuciferine detection based on efficient catalysis by Zr-MOFs (Metal-organic frameworks). METHODS: In this work, the ratiometric electrochemical method was developed for nuciferine detection based on efficient catalysis by Zr-MOFs. UiO66 is a Zr-MOFs nanomaterial and can absorb methylene blue (MB) by electrostatic action to form UiO66-MB nanocomposite. The UiO66-MB nanocomposite can be used as an enhancer to catalyze nuciferine decomposition and a carrier to provide a two-dimensional environment for the reaction of nuciferine. Moreover, good catalytic properties of UiO66 were first time used for the detection of nuciferine. RESULTS: This method has a linear detection range from 0.1 to approximately 20 µg/mL, and a low detection limit of 0.03 µg/mL (S/N=3). The recovery was from 98.1 to 102% and the RSD was from 0.45 to 3.65%, indicating that the proposed method can be applied for the analysis of real samples. CONCLUSION: The proposed electrochemical method can be used to detect nuciferine in lotus leaves. HIGHLIGHTS: The ratiometric electrochemical method was used for the detection of nuciferine. The MB can be used as an internal standard for anti-interference. And, UiO66 is used to catalyze the decomposition of nuciferine. Great catalytic properties of UiO66 were first time used for the detection of nuciferine.

Dual function metal-organic frameworks based ratiometric electrochemical sensor for detection of doxorubicin.

Cancer is one of the main diseases threatening human health in the world. Doxorubicin (DOX) is a common anti-cancer drug that can be used for chemotherapy to extend a cancer patient's life. It is our common wish that treatment process of cancer is efficient and secure. Therefore, it is of great significance to develop sensitive, rapid and accurate techniques for anti-cancer drug doxorubicin (DOX) detection. Herein, in our work, a ratiometric electrochemical sensor for DOX detection was designed, which based on MB@MWCNTs/UiO-66-NH2 composites. The porous materials UiO-66-NH2 magically shoulder double function in our ratiometric electrochemical strategy, which can reduce the interior error caused by the various complex materials. Specifically, on the one hand, it can be used to catalyze DOX, which can provide a great current signal to be detected, on the other hand, its special property of absorbing molecules was utilized to load materials as internal reference. Consequently, we chose methylene blue (MB) as the substance that can generate an internal reference signal, because it is a specific and stable electroactive substance. Then, we added MWCNTs as a part of the material modified on the ratiometric electrochemical platform to enhance the signal of the target due to its feature of good electrical conductivity. Under the optimized conditions, the ratiometric electrochemical sensor displayed a wide linear detection with the range from 0.1 µM to 75 µM and the limit of detection (LOD) of 0.051 µM. The applicability of this method in the analysis of actual human saliva samples has been confirmed by the results of selectivity, stability, and reproducibility tests, which was prospective in clinical application.

Physiological Responses of Ribosomal Protein S12 K43 Mutants of Corynebacterium glutamicum.

Bacterial resistance to streptomycin is often acquired as a consequence of mutations in rpsL, the gene encoding ribosomal protein S12. Corynebacterium glutamicum is a non-pathogenic Gram-positive soil bacterium that has been widely used in industry. In a previous study, we screened several streptomycin-resistant rpsL K43 mutants of C. glutamicum, and surprisingly found that two of them also confer chloramphenicol and/or kanamycin resistance. In order to understand whether or not a single mutation of rpsLK43 could confer resistance to multiple antibiotics, in this study we attempted to construct saturation mutagenesis of rpsL K43 by rational genetic manipulation. Despite many efforts had been made, only nine mutants were successfully constructed. They were indeed resistant to streptomycin, but not to other antibiotics. This suggested that other mutations should be acquired, contributing to multiple antibiotics in the screened strains. The growth and enhanced green fluorescent protein (eGFP) expression of these nine mutants were then investigated. The results showed that they grew differently in CGXII minimal medium, but not in BHI medium. When cultured in the absence of streptomycin, the expression of eGFP was positively proportional to the growth, approximately, while in the presence of streptomycin, the expression of eGFP was proportional to the ability of streptomycin resistance.

A label-free electrochemical immunosensor for CA125 detection based on CMK-3(Au/Fc@MgAl-LDH)n multilayer nanocomposites modification.

A label-free electrochemical immunosensor was constructed for cancer antigen 125 (CA125) detection based on multiple-enlargement means of layer-by-layer (LBL) assembly of ordered mesoporous carbon (CMK-3), gold nanoparticles (Au NPs) and MgAl layered double hydroxides containing ferrocenecarboxylic acid (Fc@MgAl-LDH). A CMK-3(Au/Fc@MgAl-LDH)n multilaminate nanocomposites was designed using technology of LBL self-assembly among negatively charged Au NPs, positively charged CMK-3 and Fc@MgAl-LDH nanosheets. The CMK-3(Au/Fc@MgAl-LDH)n multilaminate nanocomposites was used as carriers to increase the immobilization of antibody and the number of loading Fc, conductors to strengthen conductivity and enhancers to amplify signal of Fc step-by-step. Besides, this special and excellent way of LBL assembly can immensely amplify the signal of immunosensor and more immobilize the biomolecules, and label-free method is a more simple the measuring way and the procedure. The immunosensor displayed a wider linear range of 0.01 U ml-1-1000 U ml-1 and a lower detection limit of 0.004 U ml-1. Therefore, the sensor can stablely and accurately be applied for CA125 detection in clinical cancer diagnosis.

ZLN005 protects against ischemia-reperfusion-induced kidney injury by mitigating oxidative stress through the restoration of mitochondrial fatty acid oxidation.

To date, the treatment of acute kidney injury (AKI) remains a difficult problem for clinicians. In the present study, we assessed whether ZLN005, a novel peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) agonist, can protect against ischemic AKI in vivo and in vitro. Notably, ZLN005 treatment significantly alleviated Ischemia-reperfusion (I/R)-induced tubular injury and reversed the decrease in hypoxia-reoxygenation-induced cell viability by restoring PGC-1α expression in a dose-dependent manner. This beneficial effect of ZLN005 was associated with the preservation of mitochondrial fatty acid oxidation (MitoFAO) and the alleviation of oxidative stress. Cotreatment with etomoxir, a specific inhibitor of carnitine palmitoyltransferase-1α (CPT-1α) activity, or CPT-1α siRNA abrogated ZLN005-induced antistress responses by mitigating reactive oxygen species production and decreasing apoptosis under ischemia-hypoxia conditions by suppressing MitoFAO. Further studies revealed that activation of endoplasmic reticulum (ER) stress may be involved in the effect of CPT-1α inhibition observed in vivo and in vitro. Collectively, our results suggest that ZLN005 confers a protective effect on I/R-induced kidney injury by mitigating ER stress through the restoration of MitoFAO by targeting PGC-1α.

COVID-19 pandemic effect on trading and returns: Evidence from the Chinese stock market.

Using a daily foreign and institution flows data, this paper studies how institutional and foreign investors respond to the COVID-19 pandemic events in China. The results indicate that during the COVID-19 crisis foreign investors play a market stabilization role showing significant negative feedback trading, whereas institution investors do not stabilize the market. And compared to the pre-COVID-19 period, foreign investors even exhibit stronger negative feedback trading. Further analyses confirm that foreign investors' negative feedback is mainly driven by their response to negative returns. Moreover, both institutional and foreign investors' trading show stronger forecastability of future returns during the pandemic period. And the negative returns after foreigners' selling and positive returns after institutional buying are much stronger during the crisis period.

Oxidative removal of antibiotic resistant E. coli by sulfidated zero-valent iron: Homogeneous vs heterogeneous activation.

As an emerging contaminant in water, antibiotic resistant bacteria are threatening the public health gravely. In this study, sulfidated ZVI was used to activate persulfate, for antibiotic resistant E. coli and antibiotic resistant genes removal. Impressively, 7 log of antibiotic resistant E. coli was inactivated within 30 min, in sulfidated ZVI activated persulfate system (S/Fe = 0.05). Electron paramagnetic resonance and free radical quenching experiments suggested that sulfidation treatment did not change the specie of radicals. SO4•-and HO• were the main reactive oxygen species for the removal of antibiotic resistant E. coli and genes. Investigation on the activation mechanism of persulfate indicated that persulfate decomposition was mainly attributed to heterogeneous activation. More importantly, in-situ characterization (ATR-FTIR) indicated that the main charge transfer complex was formed on the surface of sulfidated ZVI, which would predominantly mediate the generation of SO4•- and HO•. Finally, the proposed system was evaluated in modeling water and secondary effluent. Results revealed that only 2.86 log and 0.84 log of antibiotic resistant E. coli were inactivated in the presence of NOM (10 mg/L) and HCO3- (84 mg/L), respectively. Besides, sulfidated ZVI activated persulfate system could be pH-dependent in actual wastewater treatment.