Correlations among serum alpha-(1,6)-fucosyltransferase and early symptoms associated with Parkinson's disease: A cross-sectional retrospective study.

Alpha-(1,6)-fucosyltransferase (FUT8) has been found to play a role in modulating the central immune system and inflammatory responses. Limited studies have assessed the correlations between serum FUT8 levels and various non-motor symptoms associated with early Parkinson's disease (PD). Therefore, our research aims to investigate the associations between serum FUT8 levels and symptoms such as smell dysfunction, sleep duration, sleep problems, and MMSE scores in PD patients. FUT8 and neurofilament light chain (NfL) levels were measured using enzyme-linked immunosorbent assays (ELISA). We analyzed the correlations between serum FUT8 levels, NfL, and early symptoms of PD using Spearman's correlation, multiple linear regression, and logistic regression models. The expression of FUT8 in CSF samples from PD patients was significantly upregulated, with its protein levels in CSF being positively associated with serum levels. Furthermore, there were significant positive associations between serum FUT8 levels with NfL levels, smell dysfunction, short sleep duration, and long sleep duration. However, a significant inverse relationship was observed between FUT8 levels and MMSE scores. Additionally, we explored gender and age differences in the correlations of FUT8 levels and early symptoms in patients. This study reveals that increased FUT8 levels are positively correlated with a higher risk of early PD-associated symptoms. These findings suggest that serum FUT8 could serve as a promising biomarker for the early detection of PD.

Mg2+- or Ca2+-regulated aptamer adsorption on polydopamine-coated magnetic nanoparticles for fluorescence detection of ochratoxin A.

It has been observed that polyvalent metal ions can mediate the adsorption of DNA on polydopamine (PDA) surfaces. Exploiting this, we used two divalent metal ions (Mg2+ or Ca2+) to promote the adsorption of fluorescence-labelled ochratoxin A (OTA) aptamers on PDA-coated magnetic nanoparticles (Fe3O4@PDA). Based on the different adsorption affinities of free aptamers and OTA-bound aptamers, a facile assay method was established for OTA detection. The aptamers adsorbed on Fe3O4@PDA were removed via simple magnetic separation, and the remaining aptamers in the supernatant exhibited a positive correlation with the OTA concentration. The concentrations of Mg2+ and Ca2+ were finely tuned to attain the optimal adsorption affinity and sensitivity for OTA detection. In addition, other factors, including the Fe3O4@PDA dosage, pH, mixing order, and incubation time, were studied. Finally, under optimized conditions, a detection limit (3σ/s) of 1.26 ng/mL was achieved for OTA. Real samples of spiked red wine were analysed with this aptamer-based method. This is the first report of regulating aptamer adsorption on the PDA surface with polyvalent metal ions for OTA detection. By changing the aptamers, the method can be easily extended to other target analytes.

Length-dependent toxic effects of microplastic fibers on Chlorella pyrenoidosa.

Microplastics (MPs), a pervasive pollutant in aquatic environments, are increasingly recognized for their detrimental effects on aquatic organisms. However, the present understanding of their impact on phytoplankton, particularly freshwater microalgae, remains limited. Furthermore, previous studies have predominantly focused on MP particles, largely overlooking the most prevalent form of MPs in aquatic settings-fibers. In this study, we scrutinized the toxicological implications of microplastic fibers (MFs) spanning four distinct lengths (50 µm, 100 µm, 150 µm, and 200 µm) on the protein-nucleated algae Chlorella pyrenoidosa over a six-day period. The study unequivocally demonstrated that MFs markedly impeded C. pyrenoidosa growth, diminished photosynthetic pigment content, and induced oxidative stress, with all observed effects exhibiting a length-dependent correlation. Electron microscopy further revealed notable damage to algal cell membranes. Cell membrane shrinkage, cytoplasm outflow, and abnormalities in cell division were observed in the 150 µm and 200 µm groups. Furthermore, C. pyrenoidosa clustered around the 200 µm MF were notably denser compared to other groups. The present study demonstrated that MFs had length-dependent toxic effects on C. pyrenoidosa. These findings offer novel insights into the deleterious impact of MFs on aquatic organisms, underscoring the pivotal role of length in influencing their toxicity.

The Combined Use of Copper Sulfate and Trichlorfon Exerts Stronger Toxicity on the Liver of Zebrafish.

In aquaculture, copper sulphate and trichlorfon are commonly used as disinfectants and insecticide, sometimes in combination. However, improper use can result in biotoxicity and increased ecological risks. The liver plays a crucial role in detoxification, lipid metabolism, nutrient storage, and immune function in fish. Selecting the liver as the main target organ for research helps to gain an in-depth understanding of various aspects of fish physiology, health, and adaptability. In the present study, zebrafish were exposed to Cu (0.5 mg/L) and Tri (0.5 mg/L) alone and in combination for 21 days. The results demonstrate that both Cu and Tri caused hepatocyte structure damage in zebrafish after 21 days of exposure, with the combination showing an even greater toxicity. Additionally, the antioxidant and immune enzyme activities in zebrafish liver were significantly induced on both day 7 and day 21. A transcriptome analysis revealed that Cu and Tri, alone and in combination, impacted various physiological activities differently, including metabolism, growth, and immunity. Overall, Cu and Tri, either individually or in combination, can induce tissue damage by generating oxidative stress in the body, and the longer the exposure duration, the stronger the toxic effects. Moreover, the combined exposure to Cu and Tri exhibits enhanced toxicity. This study provides a theoretical foundation for the combined use of heavy metal disinfectants and other drugs.

Effects of Dietary Cholesterol Regulation on Spermatogenesis of Gobiocypris rarus Rare Minnow.

Cholesterol is an important component of cell membranes, and also a precursor for the synthesis of sex hormones, playing an important role in reproduction. However, few studies have focused on cholesterol and reproductive health. To investigate the toxic effects of different cholesterol levels on the spermatogenesis of rare minnows, we regulate the cholesterol content in fish by feeding them a high-cholesterol diet and cholesterol inhibitor pravastatin, and cholesterol levels, sex hormone (T and 11KT) levels, testis histology, sperm morphology and function, and the expression of genes related to sex hormone synthesis were investigated. The research findings indicate that increasing cholesterol levels significantly increases the liver weight and hepatic-somatic index, as well as the total cholesterol and free cholesterol levels in the testis, liver, and plasma of rare minnow, while inhibiting cholesterol has the opposite effect (p < 0.05). However, both increasing and decreasing cholesterol levels can suppress rare minnow testicular development, as evidenced by a decrease in testis weight, lowered gonadosomatic index, suppressed sex hormone levels, and reduced mature sperm count. Further exploration revealed that the expression of sex hormone synthesis-related genes, including star, cyp19a1a, and hsd11b2, was significantly affected (p < 0.05), which may be an important reason for the decrease in sex hormone synthesis and consequent inhibition of testicular development. At the same time, the fertilization ability of mature sperm in both treatment groups significantly decreased. Scanning electron microscopy and fluorescence polarization tests showed that reducing cholesterol levels significantly increased the rate of sperm head cell membrane damage, while both increasing and decreasing cholesterol levels led to a reduction in sperm cell membrane fluidity, which may be the main reason for the decrease in sperm fertilization ability. This study demonstrates that both increasing and decreasing the levels of cholesterol are detrimental to the fish spermatogenesis, providing fundamental information for the study of fish reproduction and also a reference for the causes of male reproductive dysfunction.

The effect of lncRNA MIR155HG-modified MSCs and exosome delivery to synergistically attenuate vein graft intimal hyperplasia.

BACKGROUND: The mesenchymal stem cells (MSCs) were used to repair tissue injury. However, the treatment effect was not satisfactory. We investigated whether lncRNA MIR155HG could promote survival and migration of MSCs under oxidative stress, which mimics in vivo environments. Furthermore, we studied the protective effect of exosomes secreted by MSCs transfected with MIR155HG on endothelial cells. This study aimed to determine whether exploiting MSCs and exosomes modified with lncRNA MIR155HG would exert synergistic therapeutic effect to attenuate vein graft intimal hyperplasia more effectively. METHODS: Lentivirus containing lncRNA MIR155HG overexpressing vector was packaged and used to infect MSCs. Then, CCK-8 assay, flow cytometry, Transwell assay, and Elisa assay were used to assess the functional changes of MSCs with overexpressed MIR155HG (OE-MSCs). Furthermore, the associated pathways were screened by Western blot. MIR155HG-MSCs-derived exosomes (OE-exo) were collected and co-cultured with human umbilicus vein endothelial cell (HUVEC). We validated the protective effect of OE-exo on HUVEC. In vivo, both MSCs and exosomes modified with MIR155HG were injected into a vein graft rat model via tail vein. We observed MSCs homing and intimal hyperplasia of vein graft using a fluorescent microscope and histological stain. RESULTS: Our study found that lncRNA MIR155HG promoted proliferation, migration, and anti-apoptosis of MSCs. NF-κB pathway took part in the regulation process induced by MIR155HG. OE-exo could enhance the activity and healing ability of HUVEC and reduce apoptosis. In vivo, OE-MSCs had a higher rate of homing to vascular endothelium. The combined treatment with OE-MSCs and OE-exo protected vascular endothelial integrity, reduced inflammatory cell proliferation, and significantly attenuated intimal hyperplasia of vein graft. CONCLUSION: LncRNA MIR155HG could promote the survival and activity of MSCs, and reduce the apoptosis of HUVECs using exosome delivery. Exploiting MSCs and exosomes modified with MIR155HG could attenuate vein graft intimal hyperplasia more effectively and maximize the surgical effect.

Development and validation of a new prediction model for calcific aortic valve stenosis.

Background: Calcific aortic valve stenosis (CAVS) is a common valvular heart disease, but there are limited reports on the construction of prediction models for CAVS. This study aimed to investigate the risk factors for CAVS and construct a predictive model for CAVS based on its common clinical features. Methods: Patients with CAVS who underwent surgical treatment in our hospital from 2016 to 2020 and those who underwent physical examination during the same period were retrospectively studied and placed in the CAVS group and normal group based on the area of aortic valve orifice less than or more than 3 cm2. A total of 548 patients were included in this study, including 106 CAVS patients and 442 normal patients. Subjects were randomly divided into training and validation sets at a 7:3 ratio. The features were dimensionally reduced using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm in the training set, and the optimal clinical features were selected. The independent predictors of patients with CAVS were determined by univariate and multivariate logistic regression, and nomogram was constructed. The calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the model in both the training set and the validation set. Results: In this study, 11 independent predictors were distinguished by multivariate logistic regression analysis: history of hypertension, history of carotid atherosclerosis, age, diastolic blood pressure, C-reactive protein, direct bilirubin, alkaline phosphatase, low-density lipoprotein (LDL), lipoprotein(a) [Lp(a)], uric acid, and cystatin C. A nomogram was constructed using the above indicators. The model was well-calibrated and showed good discrimination and accuracy [the area under the curve (AUC) =0.981] in the training set, with a sensitivity of 91.89% and a specificity of 95.48%. More importantly, the nomogram displayed a good performance in the validation set (AUC =0.955, 95% CI: 0.925-0.985), with a sensitivity of 93.75% and a specificity of 84.09%. Additionally, DCA revealed that the nomogram had high clinical practicability. Conclusions: This study successfully established a risk prediction model for CAVS based on 11 conveniently accessible clinical indicators, which might easily be used for individualized risk assessment of CAVS.

The impact of tubeless anesthesia versus intubated anesthesia on cerebral oxygen saturation and postoperative cognitive function in patients undergoing video-assisted thoracoscopic surgery: a randomized trial.

Background: In video-assisted thoracoscopic surgery (VATS), intubated anesthesia may affect cerebral oxygen balance and postoperative cognitive dysfunction (POCD). To avoid complications associated with intubated anesthesia, tubeless strategies have been proposed in recent years, but its effect on cerebral oxygen balance and POCD is still unclear. This prospective study compared the cerebral oxygen saturation and the incidence of POCD in patients undergoing VATS anesthetized with tubeless anesthesia vs. intubated anesthesia. Methods: A total of 60 patients with American Society of Anesthesiologists Standard (ASA) grade I-II who planned to undergo VATS at The First People's Hospital of Yunnan Province between May and October 2021 were selected and divided into non-intubated spontaneous ventilation group (SV group) or intubated mechanical ventilation group (MV group) by random number method. The primary outcome included the incidence of POCD and Mini-Mental State Examination (MMSE) on the 1st before operation and the 4th, 7th, 14th, and 30th day postoperatively, and cerebral oxygen saturation during surgery. Other outcomes of interest include respiratory and hemodynamic parameters, serum concentration of cognitive function related proteins [S100ß, interleukin (IL)-6, IL-1ß, and tumor necrosis factor α (TNF-α)], inflammatory cell counts, perioperative adverse events (arrhythmia, hypoxemia, asphyxia, etc.), postoperative pain scores, etc. Results: The incidence of hypercapnia in the SV group was significantly higher than in the MV group (P<0.001). Cerebral oxygen saturation at intraoperative was significantly higher than that in MV group (P<0.01). There was no significant difference in the incidence of POCD and the expression of cognitive function related proteins between the two groups (P>0.05). Leukocyte and neutrophil counts were significantly higher in the MV group after operation (P<0.05), whilst compared to the MV group, the SV group showed shorter postoperative recovery time, rest time before the first out of bed activity, chest tube duration, as well as less drainage volume of the chest tube and postoperative sore throat rarely occurred (P<0.05). Conclusions: Tubeless VATS can increase the incidence of hypercapnia and intraoperative cerebral oxygen saturation, but has no statistically significant difference in the incidence of POCD. In addition, tubeless anesthesia reduces systemic inflammatory, promotes the early postoperative mobilization, and accelerates the postoperative rehabilitation of patients. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100042381.

Deep learning algorithm reveals two prognostic subtypes in patients with gliomas.

BACKGROUND: Gliomas are highly complex and heterogeneous tumors, rendering prognosis prediction challenging. The advent of deep learning algorithms and the accessibility of multi-omic data represent a new approach for the identification of survival-sensitive subtypes. Herein, an autoencoder-based approach was used to identify two survival-sensitive subtypes using RNA sequencing (RNA-seq) and DNA methylation (DNAm) data from The Cancer Genome Atlas (TCGA) dataset. The subtypes were used as labels to build a support vector machine model with cross-validation. We validated the robustness of the model on Chinese Glioma Genome Atlas (CGGA) dataset. DNAm-driven genes were identified by integrating DNAm and gene expression profiling analyses using the R MethylMix package and carried out for further enrichment analysis. RESULTS: For TCGA dataset, the model produced a high C-index (0.92 ± 0.02), low brier score (0.16 ± 0.02), and significant log-rank p value (p < 0.0001). The model also had a decent performance for CGGA dataset (CGGA DNAm: C-index of 0.70, brier score of 0.21; CGGA RNA-seq: C-index of 0.79, brier score of 0.18). Moreover, we identified 389 DNAm-driven genes of survival-sensitive subtypes, which were significantly enriched in the glutathione metabolism pathway. CONCLUSIONS: Our study identified two survival-sensitive subtypes of glioma and provided insights into the molecular mechanisms underlying glioma development; thus, potentially providing a new target for the prognostic prediction of gliomas and supporting personalized treatment strategies.

Stressors, coping strategies and intention to leave the nursing profession: A cross-sectional nationwide study in China.

AIMS: This study aims to investigate the association between stressors, coping strategies and intention to leave the nursing profession among nurses. BACKGROUND: Job stressors and coping strategies are believed to affect turnover intention among nurses, but no large-scale study has been conducted on these associations in China yet. METHOD: A cross-sectional secondary analysis was conducted among 51,406 nurses from 1858 hospitals. Univariable and multivariable logistic regression analyses were carried out, and odds ratios were reported. RESULTS: Overall, 49.58% nurses had an intention to leave the profession. It is found that stress from health condition, family, occupational injuries, nurse-patient tension, high job demands, strict leaders and colleague relationships were significantly associated with higher intention to leave. Coping strategies such as talking to family and friends, talking to leaders, doing outdoor activities, engaging in hobbies and attending on-the-job training were significantly associated with lower intention, but social gathering, psychological counselling and suffering in silence had an opposite effect. CONCLUSIONS: Our study provides new insights into the association between stressors, coping strategies and turnover intention among nurses in China. IMPLICATIONS FOR NURSING MANAGEMENT: Evidence from this study indicates that policies promoting a safe and supportive work environment should be developed to help nurses cope with stress.

A sensitive biosensor for ochratoxin A detection based on triple-helix aptaswitch and bioorthogonal capture enabled signal amplification.

Ochratoxin A (OTA) has been classified as a possible human carcinogen and accurate monitoring of OTA is crucial for avoiding the contaminant risk. Herein, a sensitive biosensor for OTA detection was reported. This biosensor achieved a lower detection limit of 0.026 ng/mL with the linear range of 0.03-50 ng/mL, owning to the coordination of the structure-switching of the aptaswitch and bioorthogonal capture-based signal amplification of the functionalized paper. Finally it was applied in real samples precisely and a portable device was developed for the easy readout of the fluorescent signal. Notably, this approach possessed adequate simplicity with the thorough avoidance of fluorescence plate reader or complicated material modification steps for signal amplification, and it was universally applicable by replacing the aptamer sequence in the loop instead of redesigning the structure of triple-helix aptaswitch for multifarious target analytes. Taken together, we first combined the triple-helix aptaswitch and bioorthogonal capture-based signal amplification in the detection of OTA, and this novel detection method may offer a simple, cost-effective and sensitive sensing platform for agricultural products quality monitoring.

Safety and efficacy of the Amplatzer Amulet and Watchman 2.5 for left atrial appendage occlusion: A systematic review and meta-analysis.

BACKGROUND: Left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulation (OAC) to decrease the risk of stroke in patients with nonvalvular atrial fibrillation (NVAF); however, certain complications remain a concern. Amplatzer Amulet and Watchman are the two most popular used devices for preventing stroke in patients with NVAF. We assessed the safety and efficacy of LAAO using the Amplatzer Amulet and Watchman. METHODS: A meta-analysis was conducted to compare the safety and efficacy outcomes associated with the use of the Amplatzer Amulet and Watchman 2.5. The Newcastle-Ottawa Scale has been utilized to assess the quality of study. RESULTS: The meta-analysis includes seven studies involving 2926 patients (1418 patients with an amulet and 1508 with a Watchman 2.5). Generally, adverse event rates for both systems were minimal. No significant differences between the two devices were found in safety (pericardial effusion, device embolization, and cardiac tamponade) or efficacy outcomes (death, TIA, stroke, major/minor bleeding, device leak, and thromboembolic events). CONCLUSIONS: The data suggest LAAO is a safe procedure, regardless of which device was used. LAAO devices generally have low complication rates. Outcomes were comparable between the two groups with no significant differences in their safety or efficacy.

A Novel Virus Detection Strategy Enabled by TR512-Peptide-Based Bioorthogonal Capture and Enrichment of Preamplified Nucleic Acid.

High-cost viral nucleic acid detection devices (e.g., qPCR system) are limited resources for developing counties and rural areas, leading to underdiagnosis or even pandemics of viral infectious diseases. Herein, a novel virus detection strategy is reported. Such detection method is enabled by TR512-peptide-based biorthogonal capture and enrichment of commercially available Texas red fluorophore labeled nucleic acid on the functionalized paper. The GST-TR512 fusion protein electrostatically immobilized on the paper is constructed to retain the binding affinity of TR512-peptide toward Texas red fluorophore labeled nucleic acid released in the preamplification process, then the enrichment of analytes enhances fluorescence signal for rapid detection as volume of sample filters through the paper. The method is generally applicable to different nucleic acid preamplification strategies (PCR, RAA, CRISPR) and different virus types (Hepatitis B virus (HBV), African swine fever virus (ASFV), human papillomavirus (HPV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or 2019 nCoV)). Finally, a full-set virus detection device is developed in house to detect the presence of Hepatitis B virus (HBV) viral gene in patients' blood samples. Taken together, we first apply TR512-peptide in the signal enrichment and the novel detection strategy may offer an inexpensive, rapid, and portable solution for areas with limited access to a standard diagnosis laboratory.

Target-Responsive Smart Nanomaterials via a Au-S Binding Encapsulation Strategy for Electrochemical/Colorimetric Dual-Mode Paper-Based Analytical Devices.

Target-responsive nanomaterials attract growing interest in the application of drug delivery, bioimaging, and sensing due to the responsive releasing of guest molecules by the smart molecule gate. However, it remains a challenge to develop smart nanomaterials with simple assembly and low nonspecific leakage starting from encapsulation strategies, especially in the sensing field. Herein, Au nanoclusters (Au NCs) were first grown on porous carbon derived from ZIF-8 (PCZIF) to be employed as nanocarriers. By employing the Au NCs as linkers and aptamer (Apta) double-strand hybrids (target Apta and SH-complementary DNA) as capping units, we reported the novel target-responsive nanomaterials of Apta/Au NCs-PCZIF/hemin through Au-S binding encapsulation for sensing assays. The Au-S binding encapsulation strategy simplified the packaging procedure and reduced non-target responsive leakage. As a proof, ochratoxin A (OTA) as a model target participates in the double-strand hybrid competitive displacement reaction and triggered Apta conformation switches from a coil to a G-quadruplex structure accompanied by the dissociation of the gatekeeper. Simultaneously, the released hemin can initiate a self-assembly to form G-quadruplex/hemin DNAzyme. Interestingly, owing to DNAzyme providing electron transfer mediators and peroxidase-like activity, we proposed an electrochemical/colorimetric dual-mode paper-based analytical device (PAD) that provided self-verification to enhance reliability and accuracy, benefiting from independent signal conversion and transmission mechanism. As a consequence, the proposed dual-mode PAD could achieve sensitive electrochemical detection and visual prediction of OTA in the range of 1 pg/mL to 500 ng/mL and 50 pg/mL to 500 ng/mL, respectively. The electrochemical detection limit for OTA was as low as 0.347 pg/mL (S/N = 3). We believe that this work provides point-of-care testing (POCT) tools for a broad spectrum of applications.

Effects of Dietary Resveratrol, Bile Acids, Allicin, Betaine, and Inositol on Recovering the Lipid Metabolism Disorder in the Liver of Rare Minnow Gobiocypris rarus Caused by Bisphenol A.

The fatty liver is one of the main problems in aquaculture. In addition to the nutritional factors, endocrine disrupter chemicals (EDCs) are one of the causes of fatty liver in fish. Bisphenol A (BPA) is a plasticizer widely used in the production of various plastic products and exhibits certain endocrine estrogen effects. Our previous study found that BPA could increase the accumulation of triglyceride (TG) in fish liver by disturbing the expression of lipid metabolism-related genes. How to recover the lipid metabolism disorder caused by BPA and other environmental estrogens remains to be explored. In the present study, Gobiocypris rarus was used as a research model, and 0.01% resveratrol, 0.05% bile acid, 0.01% allicin, 0.1% betaine, and 0.01% inositol were added to the feed of the G. rarus that exposed to 15 µg/L BPA. At the same time, a BPA exposure group without feed additives (BPA group) and a blank group with neither BPA exposure nor feed additives (Con group) were setted. The liver morphology, hepatosomatic index (HSI), hepatic lipid deposition, TG level, and expression of lipid metabolism-related genes were analyzed after 5 weeks of feeding. The HSI in bile acid and allicin groups was significantly lower than that in Con group. The TG in resveratrol, bile acid, allicin, and inositol groups returned to Con level. Principal component analysis of TG synthesis, decomposition, and transport related genes showed that dietary bile acid and inositol supplementation had the best effect on the recovery of BPA-induced lipid metabolism disorder, followed by allicin and resveratrol. In terms of lipid metabolism-related enzyme activity, bile acid and inositol were the most effective in recovering BPA-induced lipid metabolism disorders. The addition of these additives had a restorative effect on the antioxidant capacity of G. rarus livers, but bile acids and inositol were relatively the most effective. The results of the present study demonstrated that under the present dosage, bile acids and inositol had the best improvement effect on the fatty liver of G. rarus caused by BPA. The present study will provide important reference for solving the problem of fatty liver caused by environmental estrogen in aquaculture.

The BODIPY-based chemosensor for the fluorometric determination of organochlorine pesticide dicofol.

Dicofol is an organochlorine pesticide, which is widely used in fruits, tea and other crops, and is moderately toxic to humans. Therefore, the monitoring of organochlorine pesticide-dicofol is critical for food safety. In this work, a fluorometric chemosensor based on mercaptoethanol and boron dipyrromethene (BODIPY) was first constructed to detect the dicofol. The chemosensor displayed turn-off fluorescence behavior upon dicofol with a detection limit of 200 ppb. The nucleophilicity of the glutathione and other biological thiols was studied to evaluate the reactivity of thiols with dicofol. In practical applications, an obvious color difference was observed on a paper based microfluidic device modified by phenyltriethoxysilane (PTES). We designed an integrated device for pretreatment and paper-based detection, and successfully used for the detection of dicofol in tea. The applicability was demonstrated by detection of dicofol in real tea samples with good recovery ranging from 86% to 109%. The apparatus was convenient and could be used for on-site evaluation of dicofol.

miR-18a-5p Facilitates Malignant Progression of Head and Neck Squamous Cell Carcinoma Cells via Modulating SORBS2.

This study attempted to investigate possible molecular mechanism and role of miR-18a-5p in head and neck squamous cell carcinoma (HNSCC). Differential miRNAs and their possible targets were analyzed through TCGA database. By conducting qRT-PCR, miR-18a-5p was tested to be increased and SORBS2 was assessed to be downregulated in HNSCC cells. CCK-8, Transwell, and flow cytometry assays disclosed that miR-18a-5p facilitated HNSCC cell proliferation, migration, and invasion and repressed cell apoptosis. By dual-luciferase reporter gene assay, it was verified that miR-18a-5p had binding sites into SORBS2. Rescue experiments displayed that forced expression of SORBS2 restored the impact of miR-18a-5p overexpression on HNSCC cells. Collectively, our research preliminarily identified the promotion effect of miR-18a-5p/SORBS2 axis on malignant phenotypes of HNSCC cells. Our findings may provide a preclinical reference for HNSCC treatment.

Pyrotinib in the Treatment of Women With HER2-Positive Advanced Breast Cancer: A Multicenter, Prospective, Real-World Study.

BACKGROUND: HER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes. METHODS: A total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS). RESULTS: The median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%). CONCLUSION: Pyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib.

Electrochemical/visual dual-readout aptasensor for Ochratoxin A detection integrated into a miniaturized paper-based analytical device.

Development of portable, sensitive and reliable devices for Ochratoxin A (OTA) detection is highly demanded, especially for resource-limited regions. Herein, a novel paper-based analytical device (PAD) is designed through wax printing and screen-printed technologies, which integrates sample flowing, electrode modification, cleaning and electrochemical (EC)/colorimetric signal output. To greatly enhance the detection sensitivity, we synthesized a chitosan functionalized MoS2-Au@Pt (Ch-MoS2-Au@Pt) via electrostatic self-assembly, and used it to immobilize the label aptamer (apta2) for signal regulation and amplification. Concretely, with the addition of analytes, the Ch-MoS2-Au@Pt-apta2 could be combined on the sensing interface by specific biorecognition and catalyzed reduction of H2O2, resulting in a remarkable EC response. Meanwhile, the released hydroxyl radicals (·OH) flowed to the visualization zone and promoted the oxidation of 3,3',5,5'-tetramethylbenzidine for colorimetric detection. Consequently, the dual-mode PAD achieved acceptable prediction and accurate analysis in the range of 0.1-200 ng mL-1 and 1 × 10-4-200 ng mL-1 by matching the visual and EC signal intensity, respectively. Compared with traditional single-mode sensor for OTA, the proposed dual-mode aptasensor featuring independent signal conversion and readout, not only avoided the false-positive signal associated with detection condition and operation, but also enlarged the detection ranges and improved the sensitivity. Furthermore, the consistency of EC/colorimetric assay was validated in real OTA samples. Overall, this work provided a portable, cost-effective, sensitive and visualized aptasensor platform, which could be extended to various other mycotoxins in the field of food safety.