Light and matter co-confined multi-photon lithography.

Mask-free multi-photon lithography enables the fabrication of arbitrary nanostructures low cost and more accessible than conventional lithography. A major challenge for multi-photon lithography is to achieve ultra-high precision and desirable lateral resolution due to the inevitable optical diffraction barrier and proximity effect. Here, we show a strategy, light and matter co-confined multi-photon lithography, to overcome the issues via combining photo-inhibition and chemical quenchers. We deeply explore the quenching mechanism and photoinhibition mechanism for light and matter co-confined multiphoton lithography. Besides, mathematical modeling helps us better understand that the synergy of quencher and photo-inhibition can gain a narrowest distribution of free radicals. By using light and matter co-confined multiphoton lithography, we gain a 30 nm critical dimension and 100 nm lateral resolution, which further decrease the gap with conventional lithography.

Construction of poly (ionic liquid)-derived gold/silver alloy@nitrogen-doped carbon shell and its application for ratiometric electrochemical detection of nitric oxide.

A nitrogen-doped carbon shell loaded with a gold and silver alloy (Au/Ag@NCS) was constructed for highly sensitive electrochemical detection of NO. The Au/Ag@NCS material was prepared by use of SiO2 particles as a template to polymerize imidazolium-based ionic liquids loaded with gold and silver salts, and subsequent carbonization treatment and template removal. The hollow structure of the carbon material acted as a carrier for electrochemical sensing, offering high specific surface area, large pore capacity, robust electron conductivity, and excellent mechanical stability. The inclusion of gold in the composite enhanced its catalytic and sensing capabilities, while silver oxidation was employed as a reference signal for accurate detection. By utilization of the Au/Ag@NCS-modified electrode, a wide detection range from 0.5 nM to 1.05 µM with a low detection limit of 0.32 nM was achieved for NO detection. The electrochemical sensor also exhibited high selectivity and excellent stability. The fabricated sensor was further utilized to explore the release of NO from breast cancer cells, revealing that the electrochemical platform could be regarded as an important method to study the daily tests of NO in clinical application.

Progress in approved drugs from natural product resources.

Natural products (NPs) have consistently played a pivotal role in pharmaceutical research, exerting profound impacts on the treatment of human diseases. A significant proportion of approved molecular entity drugs are either directly derived from NPs or indirectly through modifications of NPs. This review presents an overview of NP drugs recently approved in China, the United States, and other countries, spanning various disease categories, including cancers, cardiovascular and cerebrovascular diseases, central nervous system disorders, and infectious diseases. The article provides a succinct introduction to the origin, activity, development process, approval details, and mechanism of action of these NP drugs.

Stereoselective Synthesis of ß, γ-Fused Bicyclic γ-Ureasultams via an Intramolecular Mannich and aza-Michael Addition Cascade.

A novel approach has been developed for the synthesis of bicyclic ß, γ-fused bicyclic γ-ureasultams containing two consecutive chiral centers through an intramolecular Mannich and aza-Michael addition cascade of alkenyl sulfamides. The straightforward practical procedure and readily available starting materials enable the synthesis of variously substituted ureasultams. In addition, bicyclic γ-ureasultams is a class of potential biotin analogues.

Deep learning on tertiary lymphoid structures in hematoxylin-eosin predicts cancer prognosis and immunotherapy response.

Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models' discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis.

Ultrasound-Assisted CRISPRi-Exosome for Epigenetic Modification of α-Synuclein Gene in a Mouse Model of Parkinson's Disease.

Currently, there is a lack of effective treatment for Parkinson's disease (PD). In PD patients, aberrant methylation of SNCA (α-synuclein gene) has been reported and may be a potential therapeutic target. In this study, we established an epigenetic regulation platform based on an exosomal CRISPR intervention system. With the assist of focused ultrasound (FUS) opening the blood-brain barrier, engineered exosomes carrying RVG (rabies viral glycoprotein) targeting peptide, sgRNA (single guide RNA), and dCas9-DNMT3A (named RVG-CRISPRi-Exo) were efficiently delivered into the brain lesions and induced specific methylation of SNCA. In vivo, FUS combined with RVG-CRISPRi-Exo significantly improved motor performance, balance coordination, and neurosensitivity in PD mice, greatly down-regulated the elevation of α-synuclein (α-syn) caused by modeling, rescued cell apoptosis, and alleviated the progression of PD in mice. [18F]-FP-DTBZ imaging suggested that the synaptic function of the nigrostriatal pathway could be restored, which was conducive to the control of motor behavior in PD mice. Pyrosequencing results showed that RVG-CRISPRi-Exo could methylate CpG at specific sites of SNCA, and this fine-tuned editing achieved good therapeutic effects in PD model mice. In vitro, RVG-CRISPRi-Exo down-regulated SNCA transcripts and α-syn expression and relieved neuronal cell damage. Collectively, our findings provide a proof-of-principle for the development of targeted brain nanodelivery based on engineered exosomes and provide insights into epigenetic regulation of brain diseases.

Insight into the Storage Mechanism of Sandwich-Like Molybdenum Disulphide/Carbon Nanofibers Composite in Aluminum-Ion Batteries.

Aluminum-ion batteries (AIBs) have become a research hotspot in the field of energy storage due to their high energy density, safety, environmental friendliness, and low cost. However, the actual capacity of AIBs is much lower than the theoretical specific capacity, and their cycling stability is poor. The exploration of energy storage mechanisms may help in the design of stable electrode materials, thereby contributing to improving performance. In this work, molybdenum disulfide (MoS2) was selected as the host material for AIBs, and carbon nanofibers (CNFs) were used as the substrate to prepare a molybdenum disulfide/carbon nanofibers (MoS2/CNFs) electrode, exhibiting a residual reversible capacity of 53 mAh g-1 at 100 mA g-1 after 260 cycles. The energy storage mechanism was understood through a combination of electrochemical characterization and first-principles calculations. The purpose of this study is to investigate the diffusion behavior of ions in different channels in the host material and its potential energy storage mechanism. The computational analysis and experimental results indicate that the electrochemical behavior of the battery is determined by the ion transport mechanism between MoS2 layers. The insertion of ions leads to lattice distortion in the host material, significantly impacting its initial stability. CNFs, serving as a support material, not only reduce the agglomeration of MoS2 grown on its surface, but also effectively alleviate the volume expansion caused by the host material during charging and discharging cycles.

Enhanced Fe(ii)/Fe(iii) cycle by boron enabled efficient Cr(vi) removal with microscale zero-valent iron.

Recently, researchers have been paying much attention to zero-valent iron (ZVI) in the field of pollution remediation. However, the depressed electron transport from the iron reservoir to the iron oxide shell limited the wide application of ZVI. This study was aimed at promoting the performance of microscale ZVI (mZVI) for hexavalent chromium (Cr(vi)) removal by accelerating iron cycle with the addition of boron powder. It was found that the addition of boron powder enhanced the Cr(vi) removal rate by 2.1 times, and the proportion of Cr(iii) generation after Cr(vi) removal process also increased, suggesting that boron could promote the reduction pathway of Cr(vi) to Cr(iii). By further comparing the Cr(vi) removal percentage of Fe(iii) with or without the boron powder, we found that boron powder could promote the percentage removal of Cr(vi) with Fe(iii) from 10.1% to 33.6%. Moreover, the presence of boron powder could decrease the potential gap values (ΔEp) between Fe(iii) reduction and Fe(ii) oxidation from 0.668 V to 0.556 V, further indicating that the added boron powder could act as an electron sacrificial agent to promote the reduction process of Fe(iii) to Fe(ii), and thus enhancing the reduction of Cr(vi) with Fe(ii). This study shed light on the promoted mechanism of Cr(vi) removal with boron powder and provided an environmentally friendly and efficient approach to enhance the reactivity of the mZVI powder, which would benefit the wide application of mZVI technology in the environmental remediation field.

Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Uniform Nanoscale Ion-Selective Membrane Prepared by Precision Control of Solution Spreading and Evaporation.

Ion-selective membrane has broad application in various fields, while the present solution-processed techniques can only prepare uniform membrane with microscale thickness. Herein, a high-quality polymer membrane with nanoscale thickness and uniformity is precisely prepared by controlling solution spreading and solvent evaporation stability/rate. With the arrayed capillaries, the stable spreading of polymer solution with volume of microliter induces the formation of solution film with micrometers thickness. Moreover, the fast increase of solution dynamic viscosity during solvent evaporation inhibits nonuniform Marangoni flow and capillary flow in solution film. Consequently, the uniform Nafion-Li membranes with ∼200 nm thickness are prepared, while their Li+ conductivity is 2 orders of magnitude higher than that of commercially Nafion-117 membrane. Taking lithium-sulfur battery as a model device, the cells (capacities of 8-10 mAh cm-2) can stably operate for 150 cycles at a S loading of 12 mg cm-2 and an electrolyte/sulfur ratio of ∼7.

Regioselective Olefination and Arylation of Arene-Tethered Diols Using the Easily Foldable Directing Groups.

Arene-tethered diols constitute a valuable class of structural motifs of drug and bioactive natural product molecules. In this study, a regioselective protocol for olefination and arylation of arene-tethered 1,2-diols and 1,3-diols has been developed using easily foldable acetal structures for attaching pyridine and nitrile directing groups. The method overcomes the steric hindrance effect of the short-chain diols and affords products in high yield and regioselectivity. This efficient cascaded catalysis has been successfully utilized in the syntheses of natural products such as peucedanol, decursinol, and marmesin.

Ratiometric electrochemical determination of hydroxyl radical based on graphite paper modified with metal-organic frameworks and impregnated with salicylic acid.

Hydroxyl radical (•OH) detection is pivotal in medicine, biochemistry and environmental chemistry. Yet, electrochemical method-specific detection is challenging because of hydroxyl radicals' high reactivity and short half-life. In this study, we aimed to modify the electrode surface with a specific recognition probe for •OH. To achieve this, we conducted a one-step hydrothermal process to fabricate a CoZnMOF bimetallic organic framework directly onto conductive graphite paper (Gp). Subsequently, we introduced salicylic acid (SA) and methylene blue (MB), which easily penetrated the pores of CoZnMOF. By selectively capturing •OH by SA and leveraging the electrochemical signal generated by the reaction product, we successfully developed an electrochemical sensor Gp/CoZnMOF/SA + MB. The prepared sensor exhibited a good linear relationship with •OH concentrations ranging from 1.25 to 1200 nM, with a detection limit of 0.2 nM. Additionally, the sensor demonstrated excellent reproducibility and accuracy due to the incorporation of an internal reference. It exhibited remarkable selectivity for •OH detection, unaffected by other electrochemically active substances. The establishment of this sensor provides a way to construct MOF-modified sensors for the selective detection of other reactive oxygen species (ROS), offering a valuable experimental basis for ROS-related disease research and environmental safety investigations.

Extracellular Vehicles from Commensal Skin Malassezia restricta Inhibit Staphylococcus aureus Proliferation and Biofilm Formation.

The colonizing microbiota on the body surface play a crucial role in barrier function. Staphylococcus aureus (S. aureus) is a significant contributor to skin infection, and the utilization of colonization resistance of skin commensal microorganisms to counteract the invasion of pathogens is a viable approach. However, most studies on colonization resistance have focused on skin bacteria, with limited research on the resistance of skin fungal communities to pathogenic bacteria. Extracellular vehicles (EVs) play an important role in the colonization of microbial niches and the interaction between distinct strains. This paper explores the impact of Malassezia restricta (M. restricta), the fungus that dominates the normal healthy skin microbiota, on the proliferation of S. aureus by examining the distribution disparities between the two microorganisms. Based on the extraction of EVs, the bacterial growth curve, and biofilm formation, it was determined that the EVs of M. restricta effectively suppressed the growth and biofilm formation of S. aureus. The presence of diverse metabolites was identified as the primary factor responsible for the growth inhibition of S. aureus, specifically in relation to glycerol phospholipid metabolism, ABC transport, and arginine synthesis. These findings offer valuable experimental evidence for understanding microbial symbiosis and interactions within healthy skin.

Microbiomes in pancreatic cancer can be an accomplice or a weapon.

Recently, several investigations have linked the microbiome to pancreatic cancer progression. It is critical to reveal the role of different microbiomes in the occurrence, development, and treatment of pancreatic cancer. The current review summarizes the various microbiota types in pancreatic cancer while updating and supplementing the mechanisms of the representative gut, pancreatic, and oral microbiota, and their metabolites during its pathogenesis and therapeutic intervention. Several novel strategies have been introduced based on the tumor-associated microbiome to optimize the early diagnosis and prognosis of pancreatic cancer. The pros and cons involving different microbiomes in treating pancreatic cancer are discussed. The microbiome-related clinical trials for pancreatic cancer theranostics are outlined. This convergence of cutting-edge knowledge will provide feasible ideas for developing innovative therapies against pancreatic cancer.

Facile electrochemiluminescence sensing platform based on Gd2O3:Eu3+ nanocrystals for organophosphorus pesticides detection in vegetable samples.

In this work, europium ion-doped gadolinium trioxide nanocrystals (Gd2O3:Eu3+ NCs) were successfully synthesized and applied to construct an electrochemiluminescence (ECL) sensor. Compared with pure Gd2O3, the doping of Eu3+ ions caused enhanced ECL intensity and more stable signals. Based on the excellent ECL performance of Gd2O3:Eu3+ NCs, we constructed a new ECL sensing platform for the detection of organophosphorus pesticides (OPs). The ECL sensor showed a good linear relationship in the concentration range of 1 nM to 1 pM, with a limit of detection of 0.12 pM (S/N = 3) for dichlorvos (DDVP). In addition, the constructed ECL sensor was applied for the detection of DDVP in vegetable samples, and good recoveries were obtained. The results indicated that the ECL sensor exhibited fantastic performance properties and had good application prospects in OPs detection.

Poly(3-hexylthiophene)/perovskite Heterointerface by Spinodal Decomposition Enabling Efficient and Stable Perovskite Solar Cells.

The best research-cell efficiency of perovskite solar cells (PSCs) is comparable with that of mature silicon solar cells (SSCs); However, the industrial development of PSCs lags far behind SSCs. PSC is a multiphase and multicomponent system, whose consequent interfacial energy loss and carrier loss seriously affect the performance and stability of devices. Here, by using spinodal decomposition, a spontaneous solid phase segregation process, in situ introduces a poly(3-hexylthiophene)/perovskite (P3HT/PVK) heterointerface with interpenetrating structure in PSCs. The P3HT/PVK heterointerface tunes the energy alignment, thereby reducing the energy loss at the interface; The P3HT/PVK interpenetrating structure bridges a transport channel, thus decreasing the carrier loss at the interface. The simultaneous mitigation of energy and carrier losses by P3HT/PVK heterointerface enables n-i-p geometry device a power conversion efficiency of 24.53% (certified 23.94%) and excellent stability. These findings demonstrate an ingenious strategy to optimize the performance of PSCs by heterointerface via Spinodal decomposition.

Fully bio-based epoxy resins from lignin and epoxidized soybean oil: Rigid-flexible, tunable properties and high lignin content.

The application of epoxidized soybean oil (ESO) in thermosetting polymers is impeded by its unsatisfactory thermomechanical properties. Here, in order to address the limitation, technical lignin was modified by tung oil anhydride and then used as the hardener to compensate for the inherent flexibility defects of ESO thermosets (TLs). As the lignin content increased, a notable improvement in the activation energy of TLs was observed, attributed to the restraining effect of lignin's rigid structure on segmental relaxation. Concurrently, the tensile strength of TLs increased from 2.8 MPa to 34.0 MPa, concomitant with a decrease in elongation at break from 32.9 % to 8.0 %. Comparative analysis with TL-0 (devoid of lignin) demonstrated substantial enhancements in glass transition temperature, shape fixation ratio, and shape recovery ratio for TL-50 (comprising 50 wt% of lignin), elevating from 16.9 °C, 89.1 %, and 89.5 % to 118.6 °C, 94.0 %, and 99.3 %, respectively. These results unequivocally highlight the favorable dynamic mechanical and shape memory properties conferred upon TLs by lignin addition. While the introduction of lignin adversely affected thermal stability, a notable improvement in char yield (800 °C) was observed. Collectively, these findings underscore the potential of technical lignin as a promising bio-based curing agent for ESO.

A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Effectiveness and prognosis of covered stents with different diameters in transjugular intrahepatic portosystemic shunt: a meta-analysis.

PURPOSE: This meta-analysis was designed to evaluate the clinical outcomes of transjugular intrahepatic portosystemic shunt (TIPS) conducted utilizing stents of different diameters, thus providing recommendations for more logical selections of covered stents for patients with portal hypertension, in particular for the Asian population. MATERIALS AND METHODS: Web of Science, PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure and Wan Fang were searched for randomized controlled trials and cohort studies from inception until February 2023. The meta-analysis was carried out using Revman 5.4 Software. Heterogeneity between researches was assessed by the χ2 test and I2 index. The outcomes evaluated were the incidence of post-TIPS hepatic encephalopathy (HE), variceal rebleeding, shunt dysfunction, 1-year overall survival and decrease in portal pressure gradient (PPG). RESULTS: Eight appropriate clinical trials with 1246 patients were selected (638 and 608 patients in the experimental and control groups, respectively). In regards to preoperative PPG reduction, there was no discernible difference between the two groups [mean difference = 1.15, 95% confidence interval (CI) = -0.29-2.58, P = 0.12]. The rate of post-TIPS HE was significantly higher in patients in the 8 mm stent group than in the 6-7 mm stent group [odds ratio (OR) = 0.54, 95% CI = 0.42-0.70, P < 0.00001, I2 = 46%]. There were no significant differences in the rates of variceal rebleeding (OR = 1.05, 95% CI = 0.67-1.65, P = 0.84, I2 = 0%), shunt dysfunction (OR = 0.88, 95% CI = 0.53-1.47, P = 0.64, I2 = 0%) and 1-year overall survival (OR = 0.86, 95% CI = 0.50-1.50, P = 0.61, I2 = 0%). CONCLUSION: Asian populations with portal hypertension may benefit more from TIPS with 6-7 mm covered stents because they can reduce the risk of postoperative HE while offering similar efficacy when compared to 8 mm covered stents.

Plantago asiatica L. polysaccharides: Physiochemical properties, structural characteristics, biological activity and application prospects: A review.

Plantago asiatica L. (PAL), a traditional herb, has been used in East Asia for thousands of years. In recent years, polysaccharides extracted from PAL have garnered increased attention due to their outstanding pharmacological and biological properties. Previous research has established that PAL-derived polysaccharides exhibit antioxidant, anti-inflammatory, antidiabetic, antitumor, antimicrobial, immune-regulatory, intestinal health-promoting, antiviral, and other effects. Nevertheless, a comprehensive summary of the research related to Plantago asiatica L. polysaccharides (PALP) has not been reported to date. In this paper, we review the methods for isolation and purification, physiochemical properties, structural features, and biological activities of PALP. To provide a foundation for research and application in the fields of medicine and food, this review also outlines the future development prospects of plantain polysaccharides.