Nondestructive Demolding of Structure-Designable High-Aspect-Ratio Nanoimprint Template.

Demolding is a crucial step in nanoimprint lithography (NIL) for successfully transferring template structures onto resist materials. The process, however, is often hindered by the adhesion and friction between the template and resist, leading to inevitable defects on the replicas and posing challenges in replicating templates with high-aspect-ratio (HAR) structures. Here, we introduce a novel approach using the dissolvable template method to achieve the nondestructive demolding of structure-designable HAR nanoimprint templates. The templates were fabricated by the 3D lithography technology, employing a positive photoresist that can be easily dissolved in alkaline solutions after exposure to ultraviolet (UV) radiation. By implementing this method, we successfully transferred dense arrays of pillars with a minimal diameter of 1.2 µm and a significant aspect ratio of 18, as well as a microlens array diffuser with randomly distributed structural parameters. The dissolvable template method paves the way for stress-free demolding, broadening NIL's application range.

Discovery of SIRT1-Activating Hydrogen Sulfide Donating Derivatives for Efficient Resistant of Myocardial Ischemic Injury.

Activating SIRT1 or promoting SIRT1 expression are both protective against myocardial ischemia. Combining these approaches would be an effective strategy for treating ischemic heart disease. Herein, we identified lead compounds with SIRT1 activation activity through screening the natural product library, and five series of H2S donating derivatives were designed and synthesized. Among them, compound 17 exerted an effective cardioprotective effect in vitro and in vivo. The addition of H2S scavenger attenuated the protective activity, emphasizing the critical involvement of H2S in the myocardial ischemia process. Interestingly, 17 exhibited stronger direct SIRT1 activative ability and induced higher SIRT1 expression capability compared to the lead. Furthermore, 17 attenuates oxidative stress-induced cardiomyocytes apoptosis by activating the SIRT1-PGC1α signaling pathway. Our study validated the promising potential of activating SIRT1 and promoting SIRT1 expression through H2S to improve cardiomyocytes function, providing novel insights into the protective mechanisms during the progression of ischemic heart disease.

Boronic acid-functionalized magnetic covalent organic frameworks based solid-phase extraction coupled with hydrophilic interaction chromatography-tandem mass spectrometry for the determination of trace gentamicin residues in milk.

Boric acid-functionalized magnetic covalent organic frameworks (Fe3O4-TpBD-B) with large surface area and high porosity were prepared and applied for magnetic solid-phase extraction adsorbent of gentamicin from milk before UPLC-MS/MS detection. By utilizing a new HILIC chromatographic column with zwitterionic sulfoalkyl betaine stationary phase based on ethyl bridged hybrid particles (BEH), isomers of gentamicin (C1, C1a, and C2+C2a components). The developed methods demonstrated good linearity (R2 > 0.99), acceptable accuracy and good precision (<10 %), and low limit of quantitation (1.59 ng mL⁻1 for C1, 1.52 ng mL⁻1 for C1a and 2.72 ng mL⁻1 for C2+C2a). In addition, this method has been effectively applied to the analysis of real milk samples.

D-π-A type fluorescent dyes: Effect of π-bridge units on optical and G4 DNA binding properties.

Fluorescent solvatochromic dyes that are sensitive to the nature of local microenvironmental, have been explored as probes in applications ranging from the imaging biomolecules to understanding of basic biomolecule functions. To expand the scope of fluorescent solvatochromic dyes for G-quadruplex (G4) DNA structures, and to illustrate the relationship between structure and properties, three newly designed D-π-A type fluorescent dyes were synthesized by introducing diarylimidazole to carbazole skeleton linked to benzene, furan or thiophene π-conjugated bridge and connected with pyridinium acceptor, respectively. Their structural characteristics, optical properties, and G4 DNA binding properties were discussed in detail. In general, the incorporation of furan and thiophene as π-conjugated bridges leads the better conjugation and molecular coplanarity with more efficient intramolecular charge transfer (ICT) effect compared with benzene bridge. The fluorescence intensities induced upon interaction were found that TP-6 with thiophene π-conjugated bridge had the strongest response toward G4 DNAs. In addition, the application of this dye as a fluorescent agent for living cell imaging was also demonstrated.

Identification and bioactivity evaluation of twelve previously undescribed depsidone derivatives from Garcinia oligantha.

Phytochemical studies on the leaves and twigs of Garcinia oligantha Merr. led to the isolation of twelve previously undescribed depsidone derivatives (oliganthdepsidones A-L, 1-12). Their structures were elucidated by extensive spectroscopic analysis including 1H and 13C NMR, HSQC, HMBC and NOESY along with HRESIMS. The structures of oliganthdepsidones G and J were finally determined using DFT-NMR chemical shift calculations and DP4+ methods. Cytotoxicity test in four human cancer cell lines indicated that oliganthdepsidone F had relatively strong cytotoxic effect against A375 (melanoma), A549 (lung cancer), HepG2 (liver cancer), and MCF-7 (breast cancer) cell lines with IC50 of 18.71, 15.44, 10.92, and 15.90 µM, respectively. The dose- and time-dependent antiproliferative effects of oliganthdepsidone F on these cell lines were also observed by CCK-8 test. As determined by fluorescent microscopy and flow cytometry in these cell lines, oliganthdepsidone F could promote cell apoptosis, leading to the inhibition of cell proliferation. The results of wound healing assay and transwell assay showed that oliganthdepsidone F could inhibit the migration and invasion of A549 and MCF-7 cell lines in a concentration-dependent manner.

Microscopic and Transcriptomic Analyses to Elucidate Antifungal Mechanisms of Bacillus velezensis TCS001 Lipopeptides against Botrytis cinerea.

Botrytis cinerea is an important fungal pathogen that causes gray mold disease in plants. Previously, Bacillus velezensis TCS001 live culture presented broad-spectrum antifungal activity against various plant pathogenic fungi and oomycetes, particularly B. cinerea. Here, the bioactivity of lipopeptides produced by TCS001 against B. cinerea was investigated. The IC50 values of the crude lipopeptide extract (CLE) from TCS001 to suppress mycelial growth and conidial germination were 14.20 and 49.39 mg/L, respectively. SEM and TEM imaging revealed that CLE caused morphological deformities and ultrastructural changes in the mycelium. Transcriptomic analyses combined with ΔBcpsd mutant construction demonstrated that the CLE could confer antifungal activity via suppressing Bcpsd expression in the pathogen. In addition, the CLE activated the plant immune system by increasing the content of defense-related enzymes and the expression of marker genes in immunity signaling pathways in cucumber plants. Therefore, TCS001 CLE could be potentially developed into biopesticides for the biocontrol of gray mold disease.

Carnosic Acid: A Novel Selective Inhibitor of ERAP1 by Direct Binding and Its Modulation of Antigen Processing and Presentation.

ERAP1 is an emerging target for a large subclass of severe autoimmune diseases known as "MHC-I-opathy", together with tumor immunity. Nevertheless, effective inhibitors targeting ERAP1 remain a challenge. In this study, a novel food-derived natural product ERAP1-targeting inhibitor, carnosic acid, was identified, and to our knowledge, it is one of the best active compounds among the highly selective inhibitors targeting the orthosteric site of ERAP1. The results reveal that carnosic acid could bind strongly, like a key to the ERAP1 active site in the biased S1' pocket, which is different from the binding mode of the existing orthosteric site inhibitors. HLA-B27-mediated cell modeling validated that carnosic acid has the activity to reverse the AS-associated cellular phenotype brought on by ERAP1 through inhibition. Our findings provide insights into the design of potent inhibitors against the ERAP1 orthosteric site and the discovery of a key direct target of carnosic acid.

Iron-based materials functionalized with carbon and phosphorus recovered from sludge enhanced the formation of stable minerals to passivate lead and chromium in wastewater and soil.

The bioaccumulation and toxicity of heavy metals are serious threats to human activities and ecological health. The exploitation of environmentally friendly passivated materials is major importance for the remediation of heavy metal contaminated soil. This research developed a new type of environmental functional material with a core-shell structure, which is an iron-based material functionalized with phosphorus and carbon from sludge for heavy metal pollution remediation. The results indicated that the C/P@Fe exhibits excellent heavy metal removal ability, and the maximum removal rates of the two heavy metals in simulated wastewater could reach 100% under optimum reaction conditions. It also effectively converts the labile Cr/Pb into the stable fraction after 28 days of incubation, which increased the maximum residual fraction percentage of Cr and Pb by 32.43% and 160% in soil. Further analysis found that the carbon layer wrapped around the iron base could improve the electron transport efficiency of reducing iron, phosphorus and ferrum could react with heavy metal ions to form stable minerals, such as FeCr2O4, FeO·Cr2O3, Pb5(PO4)3OH, PbCO3, 2PbCO3·Pb(OH)2 and PbS, after reacting with C/P@Fe. The study demonstrated that the Iron-based materials functionalized with carbon and phosphorus from sludge provided a more efficient way to remove heavy metals.

[Research progress in raw and processed Raphani Semen and prediction of quality markers].

Raphani Semen, with both edible and medicinal values, is a typical Chinese herbal medicine with different effects before and after processing. The raw helps ascending and the cooked helps descending. This paper comprehensively summarizes the differences in chemical constituents and pharmacological effects between raw and processed Raphani Semen that are reported in recent years. Based on the principle of quality markers(Q-markers) of traditional Chinese medicines, the chemical constituent sources, chemical constituent detection techniques, and correlation between bidirectional regulatory efficacy and chemical constituents are compared between raw and processed Raphani Semen. The results suggest that sulforaphene and glucoraphanin could be used as candidate Q-markers of raw and processed Raphani Semen, respectively. This review is expected to provide a reference for further research on the processing, new drug development, and improvement of safety and effectiveness of Raphani Semen in clinical application.

Hypoglycemic TCM formulas (Huangqi-Gegen drug pair) have the potential as an Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurological disorder. There is a considerable unmet medical need among those suffering from it. HYPOTHESIS AND PURPOSE: Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications. STUDY DESIGN AND METHODS: Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (Aß)1-42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of Aß in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic Aß-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD. RESULTS: Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandin-endoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the "four qi and five flavors" system of TCM theory, the main pharmacological qualities were "cold" and "sweet." Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi-Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced Aß deposition in the brain of the CL2006 strain of C. elegans. CONCLUSIONS: Huangqi-Gegen is a promising treatment of AD, and its mechanism may be induced by suppressing the protein production of AChE and PTGS2, reducing 5-HT intake, and then decreasing Aß deposition.

Sustainable Sea of Internet of Things: Wind Energy Harvesting System for Unmanned Surface Vehicles.

Harvesting wind energy from the environment and integrating it with the internet of things and artificial intelligence to enable intelligent ocean environment monitoring are effective approach. There are some challenges that limit the performance of wind energy harvesters, such as the larger start-up torque and the narrow operational wind speed range. To address these issues, this paper proposes a wind energy harvesting system with a self-regulation strategy based on piezoelectric and electromagnetic effects to achieve state monitoring for unmanned surface vehicles (USVs). The proposed energy harvesting system comprises eight rotation units with centrifugal adaptation and four piezoelectric units with a magnetic coupling mechanism, which can further reduce the start-up torque and expand the wind speed range. The dynamic model of the energy harvester with the centrifugal effect is explored, and the corresponding structural parameters are analyzed. The simulation and experimental results show that it can obtain a maximum average power of 23.25 mW at a wind speed of 8 m/s. Furthermore, three different magnet configurations are investigated, and the optimal configuration can effectively decrease the resistance torque by 91.25% compared with the traditional mode. A prototype is manufactured, and the test result shows that it can charge a 2200 µF supercapacitor to 6.2 V within 120 s, which indicates that it has a great potential to achieve the self-powered low-power sensors. Finally, a deep learning algorithm is applied to detect the stability of the operation, and the average accuracy reached 95.33%, which validates the feasibility of the state monitoring of USVs.

Controlling the Selectivity of Electrocatalytic NO Reduction through pH and Potential Regulation on Single-Atom Catalysts.

Electrocatalytic nitrogen oxide reduction (NOxRR) emerges as an effective way to bring the disrupted nitrogen cycle back into balance. However, efficient and selective NOxRR is still challenging partly due to the complex reaction mechanism, which is influenced by experimental conditions such as pH and electrode potential. Here, we have studied the enzyme-inspired iron single-atom catalysts (Fe-N4-C) and identified that the selectivity roots in the first step of the nitric oxide reduction. Combining the constrained molecular dynamics (MD) simulations with the quasi-equilibrium approximation, the effects of electrode potential and pH on the reaction free energy were considered explicitly and predicted quantitatively. Systematic heat maps for selectivity between single-N and N-N-coupled products in a wide pH-potential space are further developed, which have reproduced the experimental observations of NOxRR. The approach presented in this study allows for a realistic simulation of the electrocatalytic interfaces and a quantitative evaluation of interfacial effects. Our results in this study provide valuable and straightforward guidance for selective NOx reduction toward desired products by precisely designing the experimental conditions.

Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

Micromirror Array with Adjustable Reflection Characteristics Based on Different Microstructures and Its Application.

The conventional reflective optical surface with adjustable reflection characteristics requires a complex external power source. The complicated structure and preparation process of the power system leads to the limited modulation of the reflective properties and difficulty of use in large-scale applications. Inspired by the biological compound eye, different microstructures are utilized to modulate the optical performance. Convex aspheric micromirror arrays (MMAs) can increase the luminance gain while expanding the field of view, with a luminance gain wide angle > 90° and a field-of-view wide angle close to 180°, which has the reflective characteristics of a large gain wide angle and a large field-of-view wide angle. Concave aspheric micromirror arrays can increase the luminance gain by a relatively large amount of up to 2.66, which has the reflective characteristics of high gain. Industrial-level production and practical applications in the projection display segment were carried out. The results confirmed that convex MMAs are able to realize luminance gain over a wide spectrum and a wide range of angles, and concave MMAs are able to substantially enhance luminance gain, which may provide new opportunities in developing advanced reflective optical surfaces.

Successful surgical treatment of impending paradoxical embolism with pulmonary embolism and myocardial infarction.

BACKGROUND: Paradoxical embolism is a rare cause of acute arterial occlusion. This phenomenon arises when embolic material travels from the venous system crosses an abnormal shunt such as patent foramen ovale, atrial septal defects, ventricular septal defects, or pulmonary arteriovenous malformations, into the arterial system. Impending paradoxical embolism refers to the presence of an entrapped thrombus in the patent foramen ovale. CASE PRESENTATION: We report a case of a 68-year-old female patient who presented with an impending paradoxical embolism, alongside both concomitant pulmonary embolism and myocardial infarction with ST-segment elevation. Swiftly addressed through emergency cardiac surgery and systemic anticoagulation, the patient's condition was effectively treated. CONCLUSIONS: While the ideal treatment strategy for impending paradoxical embolism remains a topic of debate due to limited and inconclusive evidence, emergent open surgery should be contemplated in patients as it signifies a critical clinical emergency.

A rapidly time-varying equatorial jet in Jupiter's deep interior.

Planetary magnetic fields provide a window into the otherwise largely inaccessible dynamics of a planet's deep interior. In particular, interaction between fluid flow in electrically conducting interior regions and the magnetic field there gives rise to observable secular variation (time dependency) of the externally observed magnetic field. Secular variation of Jupiter's field has recently been revealed1-3 and been shown to arise, in part, from an axisymmetric, equatorial jet2. Whether this jet is time dependent has not previously been addressed, yet it is of critical importance for understanding the dynamics of the planet's interior. If steady, it would probably be a manifestation of deep dynamo convective flow (and jets are anticipated as part of that flow4-9) but if time dependent on a timescale much shorter than the convective turnover timescale of several hundred years, it would probably have a different origin. Here we show that the jet has a wavelike fluctuation with a period of roughly 4 years, strongly suggestive of the presence of a torsional oscillation10 (a cylindrically symmetric oscillating flow about the rotation axis) or a localized Alfvén wave in Jupiter's metallic hydrogen interior. This opens a pathway towards revealing otherwise hidden aspects of the magnetic field within the metallic hydrogen region and hence constraining the dynamo that generates Jupiter's magnetic field.

3D Printed Conductive Hydrogel Patch Incorporated with MSC@GO for Efficient Myocardial Infarction Repair.

Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo. In addition, MI also triggers apoptosis and damage of cardiomyocytes (CMs), hindering the normal repair of the infarcted heart. GO flakes exhibit a protective effect against the apoptosis of implanted MSCs. In the mouse model of MI, MSC@GO hydrogel patch implantation supported cardiac repair by reducing cell apoptosis, promoting gap connexin protein Cx43 expression, and then boosting cardiac function. Together, this study demonstrated that the conductive hydrogel patch has versatile conductivity and mechanical support function and could therefore be a promising candidate for heart repair.

An integrated methodology for quality assessment of therapeutic antibodies with potential long circulation half-life in harvested cell culture fluid using FcRn immobilized hydrophilic magnetic graphene.

Designing modified therapeutic antibodies with enhanced FcRn-binding affinity holds promise in the extension of circulation half-lives and potential refinement of pharmacokinetics. During the development of these new-generation therapeutic antibodies, FcRn binding affinity of IgGs is emphasized and monitored as a critical quality attribute (CQA), alongside other critical assessments including titer and aggregation level. However, the traditional workflow for assessing the overall quality of expressed IgGs in harvested cell culture fluid (HCCF) is blamed to be cumbersome and time-consuming. This study presents an integrated methodology for the rapid quality assessment of IgGs in HCCF by selectively extracting IgGs with favorable high FcRn affinity for subsequent analysis using size exclusion chromatography (SEC). The approach utilizes innovative adsorbents known as FcRn immobilized hydrophilic magnetic graphene (MG@PDA@PAMAM-FcRn) in a magnetic solid-phase extraction (MSPE) process. To simulate the in vivo binding dynamics, MSPE binding and dissociation was performed at pH 6.0 and 7.4, respectively. The composite have demonstrated enhanced extraction efficiency and impurity removal ability in comparison to commercially available magnetic beads. The SEC monomer peak area value provides the output of this method, the ranking of which enabled the facile identification of superior HCCF samples with high overall quality of IgG. Optimization of MSPE parameters was performed, and the method was validated for specificity, precision, sensitivity, and accuracy. The proposed method exhibited an analytical time of 0.6 h, which is 7-22 times shortened in comparison to the conventional workflow.

Cerebral Embolism and MINOCA Secondary to Left Atrial Myxoma after Occlusion of Atrial Septal Defect by Amplatzer Occluder: A Case Report.

Primary heart tumors are rare, with atrial myxomas being the most common type. Atrial myxomas can lead to embolisms, heart obstruction, and systemic symptoms. Herein, we report a case of 72-year-old woman who presented with a left atrial myxoma at the atrial septal defect occluder, a new acute cerebral infarction, and MINOCA (myocardial infarction with no obstructive coronary atherosclerosis). Left atrial myxoma is a common primary cardiac tumor; however, left atrial myxomas arising after percutaneous atrial septal defect occlusion are rare. Additionally, the patient presented with a new case of multiple systemic emboli. The patient underwent surgical resection of a left atrial myxoma, occluder, and left atrium, and atrial septal repair, and was discharged with good recovery for outpatient follow-up. The possibility of a cardiac tumor, especially an atrial myxoma, which can lead to a series of complications, should be considered at the closure site after percutaneous atrial septal closure. Therefore, active surgical treatment and long-term follow-up are warranted in such cases.