Advanced lithography materials: From fundamentals to applications.

The semiconductor industry has long been driven by advances in a nanofabrication technology known as lithography, and the fabrication of nanostructures on chips relies on an important coating, the photoresist layer. Photoresists are typically spin-coated to form a film and have a photolysis solubility transition and etch resistance that allow for rapid fabrication of nanostructures. As a result, photoresists have attracted great interest in both fundamental research and industrial applications. Currently, the semiconductor industry has entered the era of extreme ultraviolet lithography (EUVL) and expects photoresists to be able to fabricate sub-10 nm structures. In order to realize sub-10 nm nanofabrication, the development of photoresists faces several challenges in terms of sensitivity, etch resistance, and molecular size. In this paper, three types of lithographic mechanisms are reviewed to provide strategies for designing photoresists that can enable high-resolution nanofabrication. The discussion of the current state of the art in optical lithography is presented in depth. Practical applications of photoresists and related recent advances are summarized. Finally, the current achievements and remaining issues of photoresists are discussed and future research directions are envisioned.

Customization of Manganese Oxide Cathodes via Precise Electrochemical Lithium-Ion Intercalation for Diverse Zinc-Ion Batteries.

Manganese oxide-based aqueous zinc-ion batteries (ZIBs) are attractive energy storage devices, owing to their good safety, low cost, and ecofriendly features. However, various critical issues, including poor conductivity, sluggish reaction kinetics, and unstable structure still restrict their further development. Oxygen defect engineering is an effective strategy to improve the electrochemical performance of manganese oxides, but challenging in the accurate regulation of oxygen defects. In this work, an effective and controllable defect engineering strategy-controllable electrochemical lithium-ion intercalation - is proposed to tackle this issue. The incorporation of lithium ions and oxygen defects can promote the conductivity, lattice spacing, and structural stability of Mn2O3 (MO), thus improving its capacity (232.7 mAh g-1), rate performance, and long-term cycling stability (99.0% capacity retention after 3000 cycles). Interestingly, the optimal ratio of intercalated lithium-ion varies at different temperature or mass-loading of MO, which provides the possibility to customize diverse ZIBs to meet different application conditions. In addition, the fabricated ZIBs present good flexibility, superior safety, and admirable adaptability under extreme temperatures (-20-100 °C). This work provides an inspiration on the structural customization of metal oxide nanomaterials for diverse ZIBs, and sheds light on the construction of future portable electronics.

Effects of lactic acid and ascorbic acid electrostatic spraying on the physicochemical attributes and microbial diversity of beef aged at mild temperature (10 °C).

This study aimed to clarify the effect of electrostatic spraying of lactic acid (LE) and ascorbic acid (AE) on vacuum-packaged beef aged at 10 °C. The physicochemical attributes, flavor profiles, and microbial diversities were evaluated. Beef steaks were electrostatically sprayed twice with 4% LE, 0.5% AE, or a mixture of them (LAE). Afterward, the beef was vacuum-packaged and aged. All treated beef exhibited a decrease in quality and sensory scores over time. At the end of the study period, the total viable count (TVC) and the total volatile basic nitrogen values in the control group (7.34 log CFU/g and 15.52 mg/100 g, respectively) were higher than those in the acid-treated groups. The LAE group exhibited the best color stability and the lowest TVC and Enterobacteriaceae counts after aging. High-throughput sequencing analysis revealed that acid types and electrostatic spray could change the microbiota structure. Leuconostoc was the dominant bacteria in the AE and LAE groups, while Enterococcus became the predominant bacteria in the NLE and LE groups with aging. This indicates that electrostatic spray combined with acid treatment can ensure beef quality and microbiological safety at mild temperatures.

Schizandrin A induces non-small cell lung cancer apoptosis by suppressing the epidermal growth factor receptor activation.

OBJECTIVE: The purpose of this study is to explore the biological mechanism of Schizandrin A (SchA) inducing non-small cell lung cancer (NSCLC) apoptosis. METHODS: The reverse molecular docking tool "Swiss Target Prediction" was used to predict the targets of SchA. Protein-protein interaction analysis was performed on potential targets using the String database. Functional enrichment analyses of potential targets were performed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The conformation of SchA binding to target was simulated by chemical-protein interactomics and molecular docking. The effect of SchA on the expression and phosphorylation level of EGFR was detected by Western blot. Lipofectamine 3000 and EGFR plasmids were used to overexpress EGFR. Apoptosis was tested with Annexin V-FITC and propidium iodide staining, and cell cycle was detected by propidium iodide staining. RESULTS: The "Swiss Target Prediction" database predicted 112 and 111 targets based on the 2D and 3D structures of SchA, respectively, of which kinases accounted for the most, accounting for 24%. Protein interaction network analyses showed that molecular targets such as ERBB family and SRC were at the center of the network. Functional enrichment analyses indicated that ERBB-related signaling pathways were enriched. Compound-protein interactomics and molecular docking revealed that SchA could bind to the ATP-active pocket of the EGFR tyrosine kinase domain. Laboratory results showed that SchA inhibited the phosphorylation of EGFR. Insulin could counteract the cytotoxic effect of SchA. EGFR overexpression and excess EGF or IGF-1 had limited impacts on the cytotoxicity of SchA. CONCLUSIONS: Network pharmacology analyses suggested that ERBB family members may be the targets of SchA. SchA can inhibit NSCLC at least in part by inhibiting EGFR phosphorylation, and activating the EGFR bypass can neutralize the cytotoxicity of SchA.

Mussel-inspired near-infrared light-responsive gelatin-based hydrogels for enhancing MRSA-infected wound healing.

Infected wound management is a great challenge to healthcare, especially in emergencies such as accidents or battlefields. Hydrogels as wound dressings can replace or supplement traditional wound treatment strategies, such as bandages or sutures. It is significant to develop novel hydrogel-based wound dressings with simple operation, inexpensive, easy debridement, effective antibacterial, biocompatibility, etc. Here, we designed a novel gelatin-based hydrogel wound dressing Gel-TA-Fe3+. The hydrogels used tannic-modified gelatin as the main body and Fe3+ as the crosslinking agent to achieve a controllable rapid sol-gel transition. The hydrogels exhibited tough mechanical properties, excellent antibacterial ability, biocompatibility and an acceptable temperature response to near-infrared light (NIR). Moreover, the hydrogels could promote the healing process of MRSA-infected skin wound in rats. This multifunctional hydrogel was thought to have potential for emergency treatment of bacterial infected wound.

Characteristics of Lactic Acid Bacteria as Potential Probiotic Starters and Their Effects on the Quality of Fermented Sausages.

The aim of this study was to explore the potential of commercial lactic acid bacteria (LAB) as probiotic starters in fermented sausages. We initially investigated the growth activity, acid production capability, and tolerance to fermentation conditions of Lactobacillus sakei, Lactiplantibacillus plantarum, and Pediococcus pentosaceus. All three LAB strains proved viable as starters for fermented sausages. Subsequently, we explored their potential as probiotics based on their antibacterial and antioxidant capabilities. L. plantarum exhibited stronger inhibition against Escherichia coli and Staphylococcus aureus. All three strains displayed antioxidant abilities, with cell-free supernatants showing a higher antioxidant activity compared to intact cells and cell-free extracts. Moreover, the activities of superoxide dismutase, glutathione peroxidase, and catalase were stronger in the cell-free supernatant, cell-free extract, and intact cell, respectively. Finally, we individually and collectively inoculated these three LAB strains into sausages to investigate their impact on quality during the fermentation process. External starters significantly reduced pH, thiobarbituric acid reactive substances, and sodium nitrite levels. The improvements in color and texture had positive effects, with the L. plantarum inoculation achieving higher sensory scores. Overall, all three LAB strains show promise as probiotic fermentation starters in sausage production.

Electrostatic-Interaction-Aided Microneedle Patch for Enhanced Glucose-Responsive Insulin Delivery and Three-Meal-Per-Day Blood-Glucose Regulation.

The phenylborate-ester-cross-linked hydrogel microneedle patch (MNP) was promising in the diabetic field for the glucose-responsive insulin-delivering property and simple fabrication process. However, the unfit design of the charging microneedle network limited the improvement of blood-glucose regulating performances. In this work, insulin-loaded phenylborate-ester-cross-linked MNPs, with the polyzwitterion property, were constructed based on the modified ε-polylysine and poly(vinyl alcohol). The relationship between the charging nature of the MNP network and insulin release was verified by regulating the content of postprotonated positively charged amino groups. The elaborately designed MNP possessed improved glucose-responsive insulin-delivering performance. The in vivo study revealed the satisfactory results on blood-glucose regulation by the optimized MNP under the mimic three-meal-per-day mode. Moreover, the insulin bioactivity in the MNP could be maintained for 2 weeks under 25 °C. In summary, this work developed an effective strategy to improve the glucose-responsive phenylborate-ester-cross-linked MNP and enhance its potential for clinical transformation.

Chromatin regulator SMARCAL1 modulates cellular lipid metabolism.

Biallelic mutations of the chromatin regulator SMARCAL1 cause Schimke Immunoosseous Dysplasia (SIOD), characterized by severe growth defects and premature mortality. Atherosclerosis and hyperlipidemia are common among SIOD patients, yet their onset and progression are poorly understood. Using an integrative approach involving proteomics, mouse models, and population genetics, we investigated SMARCAL1's role. We found that SmarcAL1 interacts with angiopoietin-like 3 (Angptl3), a key regulator of lipoprotein metabolism. In vitro and in vivo analyses demonstrate SmarcAL1's vital role in maintaining cellular lipid homeostasis. The observed translocation of SmarcAL1 to cytoplasmic peroxisomes suggests a potential regulatory role in lipid metabolism through gene expression. SmarcAL1 gene inactivation reduces the expression of key genes in cellular lipid catabolism. Population genetics investigations highlight significant associations between SMARCAL1 genetic variations and body mass index, along with lipid-related traits. This study underscores SMARCAL1's pivotal role in cellular lipid metabolism, likely contributing to the observed lipid phenotypes in SIOD patients.

Tough adhesion enhancing strategies for injectable hydrogel adhesives in biomedical applications.

Injectable hydrogel adhesives have gained widespread attention due to their ease of use, fast application time, and suitability for minimally invasive procedures. Several biomedical applications depend on tough adhesion between hydrogel adhesives and tissues, including wound closure and healing, hemostasis, tissue regeneration, drug delivery, and wearable electronic devices. Compared with bulk hydrogel adhesives formed ex situ, injectable hydrogel adhesives are more difficult to achieve strong adhesion strength due to a further balance of cohesion and adhesion while maintaining their flowability. In this review, the critical principles in designing tough adhesion of injectable hydrogel adhesives are summarized, including simultaneously enhancing their intrinsic interfacial toughness (Γ0inter) and mechanical dissipation (ΓDinter). Thereafter, various design strategies to enhance the Γ0inter and ΓDinter are discussed and evaluated respectively, involving multiple noncovalent/covalent interactions, topological connections, and polymer network structures. Furthermore, targeted biomedical applications of injectable hydrogel adhesives for specific tissue needs are systematically highlighted. In the end, this review outlines the challenges and trends in producing next-generation multifunctional injectable hydrogels for both practical and translational applications.

The effect of tranexamic acid on intraoperative blood loss in patients undergoing brain meningioma resections: Study protocol for a randomized controlled trial.

INTRODUCTION: Tranexamic acid (TXA) has been proven to prevent thrombolysis and reduce bleeding and blood transfusion requirements in various surgical settings. However, the optimal dose of TXA that effectively reduce intraoperative bleeding and blood product infusion in patients undergoing neurosurgical resection of meningioma with a diameter ≥ 5 cm remains unclear. METHODS: This is a single-center, randomized, double-blinded, paralleled-group controlled trial. Patients scheduled to receive elective tumor resection with meningioma diameter ≥ 5 cm will be randomly assigned the high-dose TXA group, the low-dose group, and the placebo. Patients in the high-dose TXA group will be administered with a loading dose of 20 mg/kg TXA followed by continuous infusion TXA at a rate of 5 mg/kg/h. In the low-dose group, patients will receive the same loading dose of TXA followed by a continuous infusion of normal saline. In the control group, patients will receive an identical volume of normal saline. The primary outcome is the estimated intraoperative blood loss calculated using the following formula: collected blood volume in the suction canister (mL)-the volume of flushing (mL) + the volume from the gauze tampon (mL). Secondary outcomes include calculated intraoperative blood loss, intraoperative coagulation function assessed using thromboelastogram (TEG), intraoperative cell salvage use, blood product infusion, and other safety outcomes. DISCUSSION: Preclinical studies suggest that TXA could reduce intraoperative blood loss, yet the optimal dose was controversial. This study is one of the early studies to evaluate the impact of intraoperative different doses infusion of TXA on reducing blood loss in neurological meningioma patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05230381. Registered on February 8, 2022.

Progress in the preparation and evaluation of glucose-sensitive microneedle systems and their blood glucose regulation.

Glucose-sensitive microneedle systems (GSMSs) as an intelligent strategy for treating diabetes can well solve the problems of puncture pain, hypoglycemia, skin damage, and complications caused by the subcutaneous injection of insulin. According to the various functions of each component, herein, therapeutic GSMSs are reviewed based on three parts (glucose-sensitive models, diabetes medications, and microneedle body). Moreover, the characteristics, benefits, and drawbacks of three types of typical glucose-sensitive models (phenylboronic acid based polymer, glucose oxidase, and concanavalin A) and their drug delivery models are reviewed. In particular, phenylboronic acid-based GSMSs can provide a long-acting drug dose and controlled release rate for the treatment of diabetes. Moreover, their painless, minimally invasive puncture also greatly improves patient compliance, treatment safety, and potential application prospects.

Barnacle-Inspired Wet Tissue Adhesive Hydrogels with Inherent Antibacterial Properties for Infected Wound Treatment.

Currently, antibiotics are the most common treatment for bacterial infections in clinical practice. However, with the abuse of antibiotics and the emergence of drug-resistant bacteria, the use of antibiotics has faced an unprecedented challenge. It is imminent to develop nonantibiotic antimicrobial agents. Based on the cation-π structure of barnacle cement protein, a polyphosphazene-based polymer poly[(N,N-dimethylethylenediamine)-g-(N,N,N,N-dimethylaminoethyl p-ammonium bromide (ammonium bromide)-g-(N,N,N,N-dimethylaminoethyl acetate ethylammonium bromide)] (PZBA) with potential adhesion and inherent antibacterial properties was synthesized, and a series of injectable antibacterial adhesive hydrogels (PZBA-PVA) were prepared by cross-linking with poly(vinyl alcohol) (PVA). PZBA-PVA hydrogels showed good biocompatibility, and the antibacterial rate of the best-performed hydrogel reached 99.81 ± 0.04% and 98.80 ± 2.16% against Staphylococcus aureus and Escherichia coli within 0.5 h in vitro, respectively. In the infected wound model, the healing rate of the PZBA-PVA-treated group was significantly higher than that of the Tegaderm film group due to the fact that the hydrogel suppressed inflammatory responses and modulated the infiltration of immune cells. Moreover, the wound healing mechanism of the PZBA-PVA hydrogel was further evaluated by real-time polymerase chain reaction and total RNA sequencing. The results indicated that the process of hemostasis and tissue development was prompted and the inflammatory and immune responses were suppressed to accelerate wound healing. Overall, the PZBA-PVA hydrogel is shown to have the potential for infected wound healing application.

Molecular Docking-Guided Design on Glucose-Responsive Nanoparticles for Microneedle Fabrication and "Three-Meal-per-Day" Blood-Glucose Regulation.

It was greatly significant, but difficult, to develop stimulus-responsive polymeric nanoparticles with efficient protein-loading and protein-delivering properties. Crucial obstacles were the ambiguous protein/nanoparticle-interacting mechanisms and the corresponding inefficient trial-and-error strategies, which brought large quantities of experiments in design and optimization. In this work, a molecular docking-guided universal "segment-functional group-polymer" process was proposed to simplify the previous laborious experimental step. The insulin-delivering glucose-responsive polymeric nanoparticles for diabetic treatments were taken as the examples. The molecular docking study obtained insights from the insulin/segment interactions. It was then experimentally confirmed in six functional groups for insulin-loading performances of their corresponding polymers. The optimization formulation was further proved effective in blood-glucose stabilization on the diabetic rats under the "three-meal-per-day" mode. It was believed that the molecular docking-guided designing process was promising in the protein-delivering field.

Systematic elucidation of genetic mechanisms underlying cholesterol uptake.

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we substantially improve the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function of OTX2 leads to robust reduction in serum LDL-C levels in mice and humans by increasing cellular LDL-C uptake. Altogether, we present an integrated approach that improves our understanding of the genetic regulators of LDL-C levels and provides a roadmap for further efforts to dissect complex human disease genetics.

Preparation of Ferrocene-Terminated Dendrimers for the Thermal Decomposition of Ammonium Perchlorate.

As a common oxidizer, ammonium perchlorate (AP) is an important component in composite solid propellants (CSPs). Ferrocene (Fc)-based compounds are often selected as burning rate catalysts (BRCs) to catalyze AP decomposition owing to their excellent catalytic behavior. However, one of the drawbacks of Fc-based BRCs is migration in CSPs. In this study, five Fc-terminated dendrimers are designed and synthesized to improve the anti-migration properties, and their chemical structures are confirmed systemically by the related spectra characterization techniques. Moreover, the redox performance, catalytic effect on AP decomposition, combustion performance, and mechanical properties in CSPs are also studied. The shapes of the prepared propellant samples are observed via scanning electron microscopy. The obtained Fc-based BRCs have good redox performance, a positive effect on promoting AP decomposition, excellent combustion catalytic performance, and good mechanical properties. Meanwhile, they have a higher anti-migration ability than catocene (Cat) and Fc. This study demonstrates that Fc-terminated dendrimers have great potential to be applied as anti-migration BRCs in CSPs.

Microneedles with Two-Stage Glucose-Sensitive Controlled Release for Long-Term Insulin Delivery.

Diabetes patients cannot complete effective blood glucose regulation due to their impaired pancreatic function. At present, subcutaneous insulin injection is the only treatment for patients with type 1 and severe type 2 diabetes. However, long-term subcutaneous injection will cause patients with intense physical pain and lasting psychological burden. In addition, subcutaneous injection will lead to hypoglycemia risk to a large extent because of the uncontrollable release of insulin. In this work, we developed a glucose-sensitive microneedle patch based on phenylboronic acid (PBA)-modified chitosan (CS) particles and poly(vinyl alcohol) (PVA)/poly(vinylpyrrolidone) (PVP) hydrogel for the efficient delivery of insulin. Meanwhile, through the double glucose-sensitive response process of CS-PBA particle and external hydrogel, the sudden release of insulin was well restrained, and a more persistent blood glucose control was achieved. Finally, the painless, minimally invasive, and efficient treatment effect of the glucose-sensitive microneedle patch indicated its great advantages as a new generation of injection therapy.

eccDB: a comprehensive repository for eccDNA-mediated chromatin contacts in multi-species.

SUMMARY: We developed the eccDB database to integrate available resources for extrachromosomal circular DNA (eccDNA) data. eccDB is a comprehensive repository for storing, browsing, searching, and analyzing eccDNAs from multispecies. The database provides regulatory and epigenetic information on eccDNAs, with a focus on analyzing intrachromosomal and interchromosomal interactions to predict their transcriptional regulatory functions. Moreover, eccDB identifies eccDNAs from unknown DNA sequences and analyzes the functional and evolutionary relationships of eccDNAs among different species. Overall, eccDB offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher the molecular regulatory mechanisms of eccDNAs. AVAILABILITY AND IMPLEMENTATION: eccDB is freely available at http://www.xiejjlab.bio/eccDB.

Systematic elucidation of genetic mechanisms underlying cholesterol uptake.

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank and genome-scale CRISPR-Cas9 knockout and activation screening, we have substantially improved the identification of genes whose disruption alters serum LDL-C levels. We identify 21 genes in which rare coding variants significantly alter LDL-C levels at least partially through altered LDL-C uptake. We use co-essentiality-based gene module analysis to show that dysfunction of the RAB10 vesicle transport pathway leads to hypercholesterolemia in humans and mice by impairing surface LDL receptor levels. Further, we demonstrate that loss of function of OTX2 leads to robust reduction in serum LDL-C levels in mice and humans by increasing cellular LDL-C uptake. Altogether, we present an integrated approach that improves our understanding of genetic regulators of LDL-C levels and provides a roadmap for further efforts to dissect complex human disease genetics.

Multistage ROS-Responsive and Natural Polyphenol-Driven Prodrug Hydrogels for Diabetic Wound Healing.

The high level of reactive oxygen species (ROS) and bacterial infection impede wound healing of the diabetic wound. Here, benefiting from the antioxidation effects of tannic acid (TA) and ROS-responsive phenylborate ester (PBAE), a series of ROS-responsive anti-inflammatory TA-conjugated nanoparticle hydrogels (PPBA-TA-PVA) can be obtained by conveniently mixing TA, phenylboric acid modified polyphosphazene (PPBA), and poly(vinyl alcohol) (PVA). The obtained PPBA-TA-PVA hydrogels could effectively inhibit the growth of Escherichia coli (antibacterial rate = 93.1 ± 1.1%) within 4 h and effectively scavenge both 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and •OH radicals in vitro. Besides, the cell migration rate of HDFa cells treated with PPBA-TA-PVA hydrogels (84.2 ± 4.6%) was twice the rate of normal cells (43.8 ± 8.1%) after 24 h of cocultivation. The clinical relevance was demonstrated further by assessing the PPBA-TA-PVA hydrogels in full-thickness excisional wounds in a streptozotocin (STZ)-induced diabetic rat model. The PPBA-TA-PVA hydrogels could act as effective ROS-scavenging agents to alleviate inflammation and accelerate wound closure by decreasing the proinflammatory cytokines (IL-6, IL-1ß) and increasing the gene expression of TGF-ß1, COL-1, and COL-3, which resulted in faster re-epithelialization and increased formation of granulation tissue.

Glucose-responsive nanoparticles designed via a molecular-docking-driven method for insulin delivery.

Nocturnal blood glucose regulation was one of the key challenges in diabetic treatments. However, development of the smart insulin complexes with mild and glucose-responsive delivering performances was mostly relied on experience of the senior researchers and numerous confirmation experiments. In this work, a series of bioinspired fatty-acid-modified glucose-responsive insulin-delivering polymeric nanoparticles were designed. The molecular docking technique was utilized to efficiently screen the fatty-acid-derived functional groups. The results provided the basis for polymer functionalization and simplified the optimization experiments. For the optimized formulation (C10MS), insulin-loaded C10MS successfully fulfilled the nocturnal-glycemic-controlling requirement of the diabetic rats with lower occurrence of hypoglycemia than the conventional insulin injection schemes. Such formulation also possessed good biocompatibility with the moderate elimination kinetics in vivo, which matched the demand of bio-safety in the daily treatments. Overall, this work opened up a new path for efficient design of functional polymeric materials.