Construction of a label-free fluorescent biosensor for homogeneous detection of m6A eraser FTO in breast cancer tissues.

Fat mass and obesity-associated protein (FTO) is a crucial eraser of RNA N6- methyladenosine (m6A) modification, and abnormal FTO expression level is implicated in pathogenesis of numerous cancers. Herein, we demonstrate the construction of a label-free fluorescent biosensor for homogeneous detection of m6A eraser FTO in breast cancer tissues. When FTO is present, it specifically erases the methyl group in m6A, inducing the cleavage of demethylated DNA by endonuclease DpnII and the generation of a single-stranded DNA (ssDNA) with a 3'-hydroxyl group. Subsequently, terminal deoxynucleotidyl transferase (TdT) promotes the incorporation of dTTPs into the ssDNA to obtain a long polythymidine (T) DNA sequence. The resultant long poly (T) DNA sequence can act as a template to trigger hyperbranched strand displacement amplification (HSDA), yielding numerous DNA fragments that may be stained by SYBR Gold to produce an enhanced fluorescence signal. This biosensor processes ultrahigh sensitivity with a detection limit of 1.65 × 10-10 mg/mL (2.6 fM), and it can detect the FTO activity in a single MCF-7 cell. Moreover, this biosensor can screen the FTO inhibitors, evaluate enzyme kinetic parameters, and discriminate the FTO expression levels in the tissues of breast cancer patients and healthy persons.

A patient with acute myocardial infarction with electrocardiogram Aslanger's pattern.

BACKGROUND: Aslanger's pattern in electrocardiogram (ECG) indicates that patients may have acute inferior myocardial infarction(AMI) with concomitant critical stenoses on other coronary arteries, which needs to be evaluated the timing of revascularization as risk equivalents of ST elevation myocardial infarction(STEMI). CASE PRESENTATION: The patient was a 62-year-old male with chief complaint of intermittent exertional subxiphoid pain for 20 days from 30th June. One day after the last episode (19th July), the 18-lead electrocardiogram showed ST segment elevation of 0.05-0.1mV in lead III, ST segment depression in leads I, avL, and V2-V6, T wave inversion with positive terminal vector in lead V4-V5, and positive T wave in lead V6, which indicated Aslanger's pattern. With increased Troponin I (0.162ng/mL, 0-0.02), The patient was diagnosed as acute non-ST-segment elevation myocardial infarction (NSTEMI) and admitted to coronary ward on 20th July. The coronary angiography showed 95% stenosis in the distal left main coronary artery (LM) to the ostium of the left anterior descending artery (LAD), 90% stenosis in the proximal segment of the LAD, and 80% stenosis in the middle segment of the LAD, and TIMI blood flow was graded score 2. Three drug-eluting stents were implanted at the lesions. The patient's ECG returned close to normal one month after revascularization. CONCLUSION: We presented an acute coronary syndrome case whose ECG showed with Aslanger's pattern (i.e., isolated ST-segment elevation in lead III, associated ST-segment depression in lead V4-V6 with positive T wave/terminal vector, and greater ST-segment elevation in lead V1 than in lead V2), and was confirmed severe stenosis of the LM and the proximal segment of the LAD via coronary angiography. In clinical practice, especially in the emergency, patients with ECG presenting Aslanger's pattern should be urgently evaluated with prompt treatment, and the timing of emergency coronary angiography and revascularization should be evaluated to avoid adverse outcomes caused by delayed treatment.

Morphology and molecular phylogeny of Neolentinus in northern China.

Neolentinus is a significant genus, belonging to Gloeophyllaceae, with important economic and ecological values, which are parasites on decaying wood of broad-leaf or coniferous trees, and will cause brown rot. However, the taxonomic study is lagging behind to other groups of macrofungi, especially in China. In view of this, we conducted morphological and molecular phylogenetic studies on this genus. We have discovered new types of cheilocystidia and with extremely long lamellae in Neolentinus, and, thus proposed it as a new species-Neolentinus longifolius. At the same time, we clarified the distribution of Neolentinus cyathiformis in China and provided a detailed description. Moreover, we also described two common species, viz. Neolentinus lepideus and Neolentinus adhaerens. All the species are described based on the Chinese collections. The key to the reported species of Neolentinus from China is provided. And the phylogeny of Neolentinus from China is reconstructed based on DNA sequences of multiple loci including the internal transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene (nLSU), and the translation elongation factor 1-α gene (tef-1α). In addition, full morphological descriptions, illustrations, color photographs, taxonomic notes, and all the available sequences of Neolentinus species are provided.

Naringin ameliorates liver fibrosis in zebrafish by modulating IDO1-mediated lipid metabolism and inflammatory infiltration.

Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF.

Development of a N6-methyladenosine-directed single quantum dot-based biosensor for sensitive detection of METTL3/14 complex activity in breast cancer tissues.

The METTL3/14 complex is an important RNA N6-Methyladenosine (m6A) methyltransferase in organisms, and the abnormal METTL3/14 complex activity is associated with the pathogenesis and various cancers. Sensitive detection of METTL3/14 complex is essential to tumor pathogenesis study, cancer diagnosis, and anti-cancer drug discovery. However, traditional methods for METTL3/14 complex assay suffer from poor specificity, costly antibodies, unstable RNA substrates, and low sensitivity. Herein, we construct a single quantum dot (QD)-based förster resonance energy transfer (FRET) biosensor for sensitive detection of METTL3/14 complex activity. In the presence of METTL3/14 complex, it catalyzes the methylation of adenine in the substrate probe, leading to the formation of m6A that protects the substrate probes from MazF-mediated cleavage. The hybridization of methylated DNA substrate with biotinylated capture probe initiates polymerization reaction to obtain a biotinylated double-stranded DNA (dsDNA) with the incorporation of numerous Cy5 fluorophores. Subsequently, the Cy5-incorporated dsDNA can self-assembly onto the 605QD surface to form the 605QD-dsDNA-Cy5 nanostructure, causing FRET between 605QD donor and Cy5 acceptor. This biosensor has excellent sensitivity with a limit of detection (LOD) of 3.11 × 10-17 M, and it can measure the METTL3/14 complex activity in a single cell. Moreover, this biosensor can be used to evaluate the METTL3/14 complex kinetic parameters and screen potential inhibitors. Furthermore, it can differentiate the METTL3/14 complex expression in healthy human tissues and breast cancer patient tissues, providing a powerful tool for cancer pathogenesis study, clinical diagnosis, prognosis monitoring, and drug discovery.

Ballistic transport spectroscopy of spin-orbit-coupled bands in monolayer graphene on WSe2.

Van der Waals interactions with transition metal dichalcogenides were shown to induce strong spin-orbit coupling (SOC) in graphene, offering great promises to combine large experimental flexibility of graphene with unique tuning capabilities of the SOC. Here, we probe SOC-driven band splitting and electron dynamics in graphene on WSe2 by measuring ballistic transverse magnetic focusing. We found a clear splitting in the first focusing peak whose evolution in charge density and magnetic field is well reproduced by calculations using the SOC strength of ~ 13 meV, and no splitting in the second peak that indicates stronger Rashba SOC. Possible suppression of electron-electron scatterings was found in temperature dependence measurement. Further, we found that Shubnikov-de Haas oscillations exhibit a weaker band splitting, suggesting that it probes different electron dynamics, calling for a new theory. Our study demonstrates an interesting possibility to exploit ballistic electron motion pronounced in graphene for emerging spin-orbitronics.

A dataset of tomato fruits images for object detection in the complex lighting environment of plant factories.

Plant factories are an advanced form of facility agriculture that enable efficient plant cultivation through controllable environmental conditions, making them highly suitable for the automation and intelligent application of machinery. Tomato cultivation in plant factories has significant economic and agricultural value and can be utilized for various applications such as seedling cultivation, breeding, and genetic engineering. However, manual completion is still required for operations such as detection, counting, and classification of tomato fruits, and the application of machine detection is currently inefficient. Furthermore, research on the automation of tomato harvesting in plant factory environments is limited due to the lack of a suitable dataset. To address this issue, a tomato fruit dataset was constructed for plant factory environments, named as TomatoPlantfactoryDataset, which can be quickly applied to multiple tasks, including the detection of control systems, harvesting robots, yield estimation, and rapid classification and statistics. This dataset features a micro tomato variety and was captured under different artificial lighting conditions, including changes in tomato fruit, complex lighting environment changes, distance changes, occlusion, and blurring. By facilitating the intelligent application of plant factories and the widespread adoption of tomato planting machinery, this dataset can contribute to the detection of intelligent control systems, operation robots, and fruit maturity and yield estimation. The dataset is publicly available for free and can be utilized for research and communication purposes.

Different clinical characteristics and outcomes of hypertrophic cardiomyopathy with and without hypertension: seeking the truth.

OBJECTIVE: To determine the different clinical characteristics and outcomes of hypertrophic cardiomyopathy (HCM) patients with and without hypertension (HT). METHODS: A total of 696 HCM patients were included in this study and all HCM diagnoses were confirmed by the genetic test. Patients were analyzed separately in the septal reduction therapy (SRT) cohort and the non-SRT cohort. The primary endpoint was cardiovascular death and the secondary endpoint was all-cause death. Outcome analyses were conducted to evaluate the associations between HT and outcomes in HCM. Medications before enrollment and at discharge were collected in the post-hoc analyses. RESULTS: HCM patients without HT were younger, had a lower body mass index, were more likely to have a family history of HCM, and had a smaller left ventricular (LV) end-diastolic diameter than those with HT in both cohorts. A thicker LV wall, a higher level of N-terminal pro-B-type natriuretic peptide, and a higher extent of LV late gadolinium enhancement were additionally observed in patients without HT in the non-SRT cohort. The presence of HT did not alter the distribution pattern of late gadolinium enhancement, as well as the constituent ratio of eight disease-causing sarcomeric gene variants in both cohorts. Outcome analyses showed that in the non-SRT cohort, patients without HT had higher risks of cardiovascular death (HR = 2.537, P = 0.032) and all-cause death (HR = 3.309, P = 0.032). While such prognostic divergence was not observed in the SRT cohort. Further post-hoc analyses in the non-SRT cohort found that patients without HT received fewer non-dihydropyridine calcium channel blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers before enrollment and at discharge. CONCLUSIONS: HCM patients without HT had worse clinical conditions and higher mortality than patients with HT overall, which may result from active medical therapy in HT patients. Active SRT may have a substantial de-risking effect on patients meeting the indications.

Case report: Chronic radial artery occlusion treated with paclitaxel-coated balloon via distal transradial access.

A 38-year-old male patient was diagnosed as acute non-ST-segment elevation myocardial infarction on Apr 21st 2021 and he received percutaneous transluminal coronary angioplasty for RCA via transradial artery access. He sought for second percutaneous coronary intervention in our center for frequently exertional angina on Sep 13th 2021. Proximal right radial artery pulsation can not be touched in physical examination, indicating right radial artery occlusion (RAO). Distal transradial access was applied and RAO was confirmed via angiography. With balloon pre-dilation, the guidewire and guiding catheter crossed the occlusion and coronary intervention was successfully completed. A Reewarm 2.5 × 220 mm paclitaxel drug-coated balloon (Endovastec, China) was released at 12 atm in radial arterial lesion with 90 s. Pulsation of radial artery can be well palpated 24 h after PCI. No oral anticoagulant was added. The right radial artery remained patent after 8-month and 14-month follow-up and there was no abnormal sensation or obstacle of right hand.

Synergistic effect and mechanisms of ultrasound and AlOOH suspension on Al hydrolysis for hydrogen production.

Ultrasound can accelerate and change the reaction process and is widely used in the field of hydrogen production and storage. In this study, ultrasound (US) and AlOOH suspension (AH) are used to promote hydrogen production from Al hydrolysis. The results indicate that both US and AH greatly shorten the induction time and enhance the hydrogen production rate and yield. The promoting effect of US and AH on Al hydrolysis originates from the acoustic cavitation effect and catalytic effect, respectively. When AH is used in combination with US, Al hydrolysis has the best hydrogen production performance and the hydrogen yield can reach 96.6 % within 1.2 h, because there is a synergistic effect on Al hydrolysis between AH and US. Mechanism analyses reveal that the micro-jets and local high temperature environment arising from acoustic cavitation improve the catalytic activity of AlOOH, while the suspended AlOOH particles enhance the cavitation effect of US. This work provides a novel and feasible method to promote hydrogen production from Al hydrolysis.

Current Status of Objectification of Four Diagnostic Methods on Constitution Recognition of Chinese Medicine.

Chinese medicine (CM) has thousands of years of experience in prevention of diseases. As for CM, people's constitution is closely related to their health status, thus recognition of CM constitution is the fundamental and core content of research on constitution types. With development of technologies such as sensors, artificial intelligence and big data, objectification of the four diagnostic methods of CM has gradually matured, bringing changes in the mindset and innovations in technical means for recognition of CM constitution. This paper presents a systematic review of the latest research trends in constitution recognition based on objectification of diagnostic methods in CM.

A simple and rapid mix-and-read assay for sensitive detection of O6-methylguanine DNA methyltransferase.

We have developed a simple and rapid mix-and-read assay for the sensitive detection of O6-methylguanine DNA methyltransferase (MGMT) activity based on exonuclease III-assisted signal amplification under completely isothermal conditions (37 °C). This method is very simple and rapid (60 min) with ultrahigh sensitivity and good specificity, and it can detect MGMT activity at the single-cell level. Moreover, this method can be applied for the screening of MGMT inhibitors and the discrimination of MGMT in different cancer cells.

Construction of a dephosphorylation-mediated chemiluminescent biosensor for multiplexed detection of DNA glycosylases in cancer cells.

DNA glycosylases are engaged in the base excision repair process and play a vital role in maintaining genomic integrity. It remains a challenge for multiplexed detection of DNA glycosylases in cancer cells. Herein, we demonstrate the construction of a dephosphorylation-mediated chemiluminescent biosensor for multiplexed detection of human alkyladenine DNA glycosylase (hAAG) and uracil DNA glycosylase (UDG) in cancer cells. In this biosensor, the generation of chemiluminescence signals relies on the dephosphorylation of 3-(2'-spiroadamantyl)-4-methoxy-4-(3''-phosphoryloxyphenyl)-1,2-dioxetane (AMPPD) catalyzed by alkaline phosphatase (ALP). We design a bifunctional double-stranded DNA (dsDNA) substrate, a biotin-labelled poly-(T) probe, and two capture probes for the hAAG and UDG assay. This assay involves four steps including (1) the cleavage of the bifunctional dsDNA substrate induced by DNA glycosylases, (2) the recognition of the 3'-OH terminus of the primer by TdT and the subsequent TdT-mediated polymerization reaction, (3) the construction of the AuNPs-dsDNA-ALP nanostructures, and (4) the streptavidin-alkaline phosphatase (SA-ALP)-initiated dephosphorylation of AMPPD for the generation of an enhanced chemiluminescence signal. By taking advantage of the unique features of TdT-mediated polymerization and the intrinsic superiority of the ALP-AMPPD-based chemiluminescence system, this biosensor exhibits good specificity and high sensitivity with a detection limit of 1.53 × 10-6 U mL-1 for hAAG and 1.77 × 10-6 U mL-1 for UDG, and it can even quantify multiple DNA glycosylases at the single-cell level. Moreover, this biosensor can be applied for the measurement of kinetic parameters and the screening of DNA glycosylase inhibitors, holding great potential in DNA damage-related biomedical research and disease diagnostics.

Development of a single quantum dot-mediated FRET biosensor for amplification-free detection of ten-eleven translocation 2.

Ten-eleven translocation (TET) family proteins play key roles in multiple cellular processes by mediating the oxidation of 5-methylcytosine to directly participate in DNA demethylation, and often aberrantly expressed in various diseases. In this research, we develop a single-quantum-dot (QD)-mediated fluorescence resonance energy transfer (FRET) biosensor for amplification-free measurement of ten-eleven translocation 2 (TET2). When TET2 is present, it catalyzes the oxidation of 5-vinylcytosine in dsDNA to 5-formylmethylcytosine, and the subsequent labeling of dsDNA with Cy5 generates a biotinylated Cy5-dsDNA complex. Biotinylated Cy5-dsDNA complexes are conjugated to the streptavidin-coated 605QDs to obtain a Cy5-dsDNA-605QD nanostructures, inducing FRET from 605QD to Cy5. FRET signal can be simply measured by single-molecule counting. This biosensor enables homogeneous detection of TET2 with a limit of detection (LOD) of 0.042 ng/µL, and it can accurately measure cellular TET2 down to 1 cell. Moreover, this biosensor can be used to screen TET2 inhibitors, offering a new platform for TET2-related medical research and clinical diagnostics.

Is the Occurrence or Reversal of Nonalcoholic Fatty Liver Disease Associated with Long-Term Helicobacter pylori Infection among Chinese Adults? A Cohort Study.

BACKGROUND: Previous studies have suggested a link between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD), yet long-term follow-up studies to elucidate this association are lacking. We aimed to identify the relationship between NAFLD and H. pylori in these people. METHODS: A total of 2,934 adults between June 2013 and October 2017 were collected; among them, 675 people met the requirements. People were assessed for H. pylori infection diagnosis as detected by the carbon-13 urea breath test; they were also assessed for NAFLD diagnosis by ultrasound. RESULTS: H. pylori infection was present in 206 patients (30.5%), and 469 (69.5%) participants were classified as controls. Participants with H. pylori infection had a higher rate of incident NAFLD than those who were uninfected (37/206; 18% versus 73/469; 15.6%) (p < 0.001). Compared with the control group, the recovery rate of NAFLD in the H. pylori+ve group was low (6/206, 2.9% versus 33/469, 7.0%) (p < 0.001). Besides, the incidence of uric acid, postprandial blood glucose, TG, LDL-C, HDL-C, and fasting plasma glucose was significantly different between the two groups (p < 0.001), but no difference was found in alanine aminotransferase (ALT), liver-total protein, urea nitrogen, and cholesterol (p > 0.05). CONCLUSION: H. pylori infection was a risk factor for NAFLD and affected the occurrence or reversal of NAFLD, indicating that H. pylori infection eradication might play a role in reducing the risk of NAFLD.

Artificial Intelligence-A Good Assistant to Multi-Modality Imaging in Managing Acute Coronary Syndrome.

Acute coronary syndrome is the leading cause of cardiac death and has a significant impact on patient prognosis. Early identification and proper management are key to ensuring better outcomes and have improved significantly with the development of various cardiovascular imaging modalities. Recently, the use of artificial intelligence as a method of enhancing the capability of cardiovascular imaging has grown. AI can inform the decision-making process, as it enables existing modalities to perform more efficiently and make more accurate diagnoses. This review demonstrates recent applications of AI in cardiovascular imaging to facilitate better patient care.

Anomalous Cyclotron Motion in Graphene Superlattice Cavities.

We consider graphene superlattice miniband fermions probed by electronic interferometry in magnetotransport experiments. By decoding the observed Fabry-Pérot interference patterns together with our corresponding quantum transport simulations, we find that the Dirac quasiparticles originating from the superlattice minibands do not undergo conventional cyclotron motion but follow more subtle trajectories. In particular, dynamics at low magnetic fields is characterized by peculiar, straight trajectory segments. Our results provide new insights into superlattice miniband fermions and open up novel possibilities to use periodic potentials in electron optics experiments.

Unconventional ferroelectricity in moiré heterostructures.

The constituent particles of matter can arrange themselves in various ways, giving rise to emergent phenomena that can be surprisingly rich and often cannot be understood by studying only the individual constituents. Discovering and understanding the emergence of such phenomena in quantum materials-especially those in which multiple degrees of freedom or energy scales are delicately balanced-is of fundamental interest to condensed-matter research1,2. Here we report on the surprising observation of emergent ferroelectricity in graphene-based moiré heterostructures. Ferroelectric materials show electrically switchable electric dipoles, which are usually formed by spatial separation between the average centres of positive and negative charge within the unit cell. On this basis, it is difficult to imagine graphene-a material composed of only carbon atoms-exhibiting ferroelectricity3. However, in this work we realize switchable ferroelectricity in Bernal-stacked bilayer graphene sandwiched between two hexagonal boron nitride layers. By introducing a moiré superlattice potential (via aligning bilayer graphene with the top and/or bottom boron nitride crystals), we observe prominent and robust hysteretic behaviour of the graphene resistance with an externally applied out-of-plane displacement field. Our systematic transport measurements reveal a rich and striking response as a function of displacement field and electron filling, and beyond the framework of conventional ferroelectrics. We further directly probe the ferroelectric polarization through a non-local monolayer graphene sensor. Our results suggest an unconventional, odd-parity electronic ordering in the bilayer graphene/boron nitride moiré system. This emergent moiré ferroelectricity may enable ultrafast, programmable and atomically thin carbon-based memory devices.

Gate-Tunable Two-Dimensional Superlattices in Graphene.

We report an efficient technique to induce gate-tunable two-dimensional superlattices in graphene by the combined action of a back gate and a few-layer graphene patterned bottom gate complementary to existing methods. The patterned gates in our approach can be easily fabricated and implemented in van der Waals stacking procedures, allowing flexible use of superlattices with arbitrary geometry. In transport measurements on a superlattice with a lattice constant a = 40 nm, well-pronounced satellite Dirac points and signatures of the Hofstadter butterfly including a nonmonotonic quantum Hall response are observed. Furthermore, the experimental results are accurately reproduced in transport simulations and show good agreement with features in the calculated band structure. Overall, we present a comprehensive picture of graphene-based superlattices, featuring a broad range of miniband effects, both in experiment and in theoretical modeling. The presented technique is suitable for studying more advanced geometries which are not accessible by other methods.

Hypoglycemic agents for non-alcoholic fatty liver disease with type 2 diabetes mellitus: A protocol for systematic review and network meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries, and strongly associated with type 2 diabetes mellitus (T2DM). Several studies have shown that hypoglycemic agents are effective for NAFLD combined with T2DM. However, there is still controversy over which hypoglycemic agent is the best for NAFLD combined with T2DM patients. OBJECTIVE: To systematically evaluate the efficacy and safety of hypoglycemic agents in NAFLD combined with T2DM patients. METHODS: A comprehensive electronic search will be conducted by searching Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Clinical Trials and Chinese Biomedical Medicine. All randomized controlled trials of hypoglycemic agents interventions for NAFLD combined with T2DM will be identified. Two reviewers independently screened and evaluated each included study and extracted the outcome indexes. ADDIS 1.16.8 software will be used for the network meta-analysis and STATA 14 software will be used for drawing network evidence plots and funnel plots. CONCLUSION: This network meta-analysis will provide stronger evidence for the efficacy and safety of hypoglycemic agents in the treatment of NAFLD combined with T2DM, and provide a reference for clinical application. PROTOCOL REGISTRATION NUMBER: INPLASY202070016.