Biomass-derived polymer as a flexible "zincophilic-hydrophobic" solid electrolyte interphase layer to enable practical Zn metal anodes.

Aqueous zinc ion batteries (AZIBs) face significant challenges stemming from Zn dendrite growth and water-contact attack, primarily due to the lack of a well-designed solid electrolyte interphase (SEI) to safeguard the Zn anode. Herein, we report a bio-mass derived polymer of chitin on Zn anode (Zn@chitin) as a novel and robust artificial SEI layer to boost the Zn anode rechargeability. The polymeric chitin SEI layer features both zincophilic and hydrophobic characteristics to target the suppressed dendritic Zn formation as well as the water-induced side reactions, thus harvesting a dendrite-free and corrosion-resistant Zn anode. More importantly, this polymeric interphase layer is strong and flexible accommodating the volume changes during repeated cycling. Based on these benefits, the Zn@chitin anode demonstrates prolonged cycling performance surpassing 1300 h under an ultra-large current density of 20 mA cm-2, and a long cycle life of 680 h with a record-high zinc utilization rate of 80 %. Besides, the assembled Zn@chitin/V2O5 full batteries reveal excellent capacity retention and rate performance under practical conditions, proving the reliability of our proposed strategy for industrial AZIBs. Our research offers valuable insights for constructing high-performance AZIBs, and simultaneously realizes the high-efficient use of cheap biomass from a "waste-to-wealth" concept.

Advancements in lipid-based delivery systems for functional foods: a comprehensive review of literature and patent trends.

Lipid-based delivery systems (LDS) have emerged as cornerstone techniques for bolstering the bioavailability of lipophilic bioactive compounds, addressing challenges related to solubility, stability, and absorption. This critical review examined a substantial dataset of 6,907 scientific articles and 3,021 patents from 2001-2023, elucidating the multifaceted evolution of LDS, with a particular focus on its industrial and patent-driven perspective. Notably, there were pronounced surges in functional food patent applications in 2004, 2011, and 2019. The trajectory revealed a shift from foundational nanoemulsions to more complex structures, such as double/multiple emulsions, solid lipid nanoparticles, Pickering emulsions, and bigels. The review further identified the top 10 leading institutions shaping this domain. Technologies like spray-drying, microfluidics, and phase gelation had revolutionized the landscape, resulting in refined sensory experiences, innovative reduced-fat formulations, enriched beverages, tailor-made infant nutrition, and nuanced release mechanisms for flavors. The review also spotlighted current research frontiers, notably Pickering emulsions, bigels, and multiple emulsions. These emerging technologies not only exemplified the ongoing innovation in the field but also underscored their potential in reshaping the future landscape of value-added functional foods.

Treatment of abdominal pain due to deficiency syndrome of the spleen and stomach with Bian stone plus TCM iontophoresis: A case report.

RATIONALE: Bian stone ironing and rubbing traditional Chinese medicine penetration method is based on the theory of regulating the middle and restoring balance. By using Bian stone to heat, ironing, and rubbing, pushing and rubbing in the epigastric area can regulate the spleen and stomach, restore the normal function of the middle jiao qi movement and the functions of the five organs. Bian stone hot ironing can harmonize stomach qi, nourish qi and assist yang, clear the internal organs and clear turbidity, regulate intestinal qi circulation, and promote qi stagnation. PATIENT CONCERNS: The VAS score for stomach pain is 6 points, and the SAS score is moderate anxiety, which seriously affects sleep and daily life. DIAGNOSES: epigastric pain, spleen, and stomach deficiency cold syndrome. INTERVENTIONS: Easy to digest diet, Western medicine provides famotidine acid inhibiting and protecting gastric mucosa, and mosapride promoting gastrointestinal peristalsis medication treatment; Traditional Chinese Medicine provides oral administration of Huangqi Jianzhong Tang and traditional Chinese medicine techniques such as Bianchi Ironing and Moxibustion for treatment. OUTCOMES: The patient's symptoms of stomach pain have significantly improved, with a decrease in the epigastric pain score to 0, improved anxiety, reduced fatigue, improved sleep, improved epigastric fullness, unobstructed bowel movements, and improved quality of life. The patient is very satisfied. LESSONS: The method of using Bian stone ironing and rubbing traditional Chinese medicine to treat stomach pain caused by the spleen and stomach deficiency cold can alleviate the symptoms of stomach pain in patients, and the improvement of symptoms shows a gradual increase, with significant effects. At the same time, it significantly improves patient anxiety and fatigue symptoms and can increase the sample size in future work to further clarify its clinical effects.

CCL20 and CD8A as potential diagnostic biomarkers for HBV-induced liver fibrosis in chronic hepatitis B.

Background: The main cause of the liver fibrosis (LF) remains hepatitis B virus (HBV) infection, especially in China. Histologically, liver fibrosis still occurs progressively in chronic hepatitis B (CHB) patients, even if HBV-DNA is negative or undetectable. The diagnosis of LF is beneficial to control the development of it, also it may promote the reversal of LF. Although liver biopsy is the gold standard of diagnosis in LF at present, it isa traumatic diagnosis. There are no diagnostic biomarkers as yet for the condition. It is badly in need of biomarkers clinically, which is simple to test, minimally invasive, highly specific, and sensitive. Early detection of HBV-LF development is crucial in the prevention, treatment, and prognosis prediction of HBV-LF. Cytokines are closely associated with both immune regulation and inflammation in the progression of hepatitis B virus associated-liver fibrosis (HBV-LF). In this bioinformatic study, we not only analyzed the relationship between HBV-LF and immune infiltration, but also identified key genes to uncover new therapeutic targets. Objectives: To find potential biomarkers for liver fibrosis in the development of chronic hepatic B patients. Materials and methods: We obtained two sets of data including CHB/healthy control and CHB/HBV-LF from the Integrated Gene Expression (GEO) database to select for differential expression analysis. Protein-protein interaction (PPI) network was also generated, while key genes and important gene modules involved in the occurrence and development of HBV-LF were identified. These key genes were analyzed by functional enrichment analysis, module analysis, and survival analysis. Furthermore, the relationship between these two diseases and immune infiltration was explored. Results: Among the identified genes, 150 were individually associated with CHB and healthy control in the differential gene expression (DGE) analysis. While 14 with CHB and HBV-LF. It was also analyzed in the Robust rank aggregation (RRA) analysis, 34 differential genes were further identified by Cytohubba. Among 34 differential genes, two core genes were determined: CCL20 and CD8A. CCL20 was able to predict CHB positivity (area under the receiver operating characteristic curve [AUC-ROC] = 0.883, 95% confidence interval [CI] 0.786-0.963), while HBV-LF positivity ([AUC-ROC] = 0.687, 95% confidence interval [CI] 0.592-0.779). And CD8A was able to predict CHB positivity ([AUC-ROC] = 0.960, 95% confidence interval [CI] 0.915-0.992), while HBV-LF positivity ([AUC-ROC] = 0.773, 95% confidence interval [CI] 0.680-0.856). Relationship between CCL20 gene expression and LF grades was P < 0.05, as well as CD8A. Conclusion: CCL20 and CD8A were found to be potential biomarkers and therapeutic targets for HBV-LF. It is instructive for research on the progression of LF in HBV patients, suppression of chronic inflammation, and development of molecularly targeted-therapy for HBV-LF.

Dietary Supplementation with Bupleuri Radix Reduces Oxidative Stress Occurring during Growth by Regulating Rumen Microbes and Metabolites.

Oxidative stress (OS) in ruminants is closely associated with disease; thus, improving antioxidant capacity is an important strategy for maintaining host health. Bupleuri Radix (BR) could significantly improve host health and stress levels. However, the clear antioxidant mechanism of the function of BR remains unknown. In the current study, LC-MS metabolomics combined with 16S rRNA gene sequencing was employed to explore the effects of BR on rumen microbiota and metabolites in Shanbei Fine-Wool Sheep (SFWS), and Spearman correlation analyses of rumen microbiota, metabolites, and OS were performed to investigate the mechanism of antioxidant function of BR. Our results indicated that as SFWS grows, levels of OS and antioxidant capacity increase dramatically, but providing BR to SFWS enhances antioxidant capacity while decreasing OS. Rumen microbiota and OS are strongly correlated, with total antioxidant capacity (T-AOC) showing a significant negative correlation with Succiniclasticum and a positive correlation with Ruminococcus. Importantly, the Chao1 index was significantly negatively correlated with malondialdehyde (MDA) and positively correlated with superoxide dismutase (SOD) and T-AOC. Two biomarkers connected to the antioxidant effects of BR, 5,6-DHET and LPA (a-25:0/0:0), were screened according to the results of metabolomics and Spearman analysis of rumen contents, and a significant relationship between the concentration of rumen metabolites and OS was found. Five metabolic pathways, including glycerolipid, glutathione, nucleotide, D-amino acid, and inositol phosphate metabolism, may have a role in OS. The integrated results indicate that rumen microbiota and metabolites are strongly related to OS and that BR is responsible for reducing OS and improving antioxidant capacity in post-weaned SFWS. These findings provide new strategies to reduce OS occurring during SFWS growth.

Alcohol Exposure Induces Nucleolar Stress and Apoptosis in Mouse Neural Stem Cells and Late-Term Fetal Brain.

Prenatal alcohol exposure (PAE) is a leading cause of neurodevelopmental disability through its induction of neuronal growth dysfunction through incompletely understood mechanisms. Ribosome biogenesis regulates cell cycle progression through p53 and the nucleolar cell stress response. Whether those processes are targeted by alcohol is unknown. Pregnant C57BL/6J mice received 3 g alcohol/kg daily at E8.5-E17.5. Transcriptome sequencing was performed on the E17.5 fetal cortex. Additionally, primary neural stem cells (NSCs) were isolated from the E14.5 cerebral cortex and exposed to alcohol to evaluate nucleolar stress and p53/MDM2 signaling. Alcohol suppressed KEGG pathways involving ribosome biogenesis (rRNA synthesis/processing and ribosomal proteins) and genes that are mechanistic in ribosomopathies (Polr1d, Rpl11; Rpl35; Nhp2); this was accompanied by nucleolar dissolution and p53 stabilization. In primary NSCs, alcohol reduced rRNA synthesis, caused nucleolar loss, suppressed proliferation, stabilized nuclear p53, and caused apoptosis that was prevented by dominant-negative p53 and MDM2 overexpression. Alcohol's actions were dose-dependent and rapid, and rRNA synthesis was suppressed between 30 and 60 min following alcohol exposure. The alcohol-mediated deficits in ribosomal protein expression were correlated with fetal brain weight reductions. This is the first report describing that pharmacologically relevant alcohol levels suppress ribosome biogenesis, induce nucleolar stress in neuronal populations, and involve the ribosomal/MDM2/p53 pathway to cause growth arrest and apoptosis. This represents a novel mechanism of alcohol-mediated neuronal damage.

Differential Water Conservation Capacity in Broadleaved and Mixed Forest Restoration in Latosol Soil-Eroded Region, Hainan Province, China.

The water conservation capacity of the litter and soil layers of forest ecosystems improves the function of forest ecosystems in conserving soil and water. Plantation restoration plays a key role in preventing soil erosion. In order to evaluate the water conservation capacity of plantation restoration in Latosol soil-eroded region, we analyzed the litter thickness and mass, water absorption process, water holding recovery process, and soil water holding capacity of five restoration types (Hevea brasiliensis, Acacia mangium, Eucalyptus robusta, Acacia-Eucalyptus, and Acacia-Hevea) in the Mahuangling Watershed, Hainan province. The results showed that the thickness of the litter ranged from approximately 3.42 ± 0.24 to 4.73 ± 0.81 cm, and the litter mass ranged from 5.04 ± 1.52 t·ha-1 to 13.16 ± 1.76 t·ha-1, with higher litter mass in the SL layer than in the UL layer. The litter mass of A. mangium was higher than that of H. brasiliensis, E. robusta, Acacia-Eucalyptus, and Acacia-Hevea, which was 3.16 ± 1.76 t·ha-1. A. mangium forest was significantly higher than other plantation restoration types in terms of the maximum water retention capacity (Qmax) and the effective water retention capacity (Qeff). The soil bulk weight ranged from approximately 1.52 ± 0.09 to 1.59 ± 0.08 g·cm-3, and porosity ranged from 31.77 ± 4.72 to 35.62 ± 3.02%, both of which increased with the depth of the soil layer. The water holding capacity of 0-60 cm soil varied from approximately 12.94 ± 7.91 to 45.02 ± 31.79 t·ha-1, with A. mangium having the best soil permeability and the strongest soil water holding capacity. The entropy weight method was used to conduct a comprehensive evaluation, and the results showed that the water conservation capacity of the soil layer was 1.26 times higher than that of the litter layer, in which the water conservation capacity of A. mangium was the strongest, with a comprehensive evaluation value of 0.2854, which effectively intercepted rainfall and reduced surface runoff. Hence, we suggest that the planting of A. mangium should be considered in future ecological restoration projects of the erosion area of Mahuangling in order to improve the function of conserving soil and water in a restoration forest ecosystem.

The value of audiovisual sexual stimulation with virtual reality in diagnosing erectile dysfunction.

Background: The traditional audiovisual sexual stimulation (AVSS) test may experience limitations including low erectile response rate and lack of unified diagnostic criteria. Aim: We aimed to explore the clinical value of AVSS with virtual reality (VR-AVSS) test in assessing erectile function and diagnosing erectile dysfunction (ED). Methods: Participants 18 to 60 years of age were screened for analysis in 3 clinical centers from June 2020 to March 2022. Demographic data, 5-item International Index of Erectile Function (IIEF-5), erectile hardness score (EHS), and self-reported symptom questions were collected. The ED patients and control patients were confirmed according to the IIEF-5 and EHS. All subjects watched a 60-minute erotic video by VR device during RigiScan recording. The parameters including tip average rigidity, tip effective erectile duration (duration of rigidity ≥60%, tip effective erectile duration), base average rigidity, and base effective erectile duration were evaluated. Outcomes: The main outcome of interest was the application of VR immersion technology to improve the traditional AVSS test. Results: A total of 301 ED cases and 100 eligible control patients were included for final analysis. Compared with control patients, ED cases had significantly lower IIEF-5 scores, EHS, positive response rate, and erectile rigidity and duration. The positive response rate of ED and control patients were 75.5% and 90.9%, respectively. The cutoff points of tip average rigidity, tip effective erectile duration, base average rigidity, and base effective erectile duration were 40.5% (sensitivity: 77.6%, specificity: 70.2%; P < .001), 4.75 minutes (sensitivity: 75.9%, specificity: 75.4%; P < .001), 48.5% (sensitivity: 77.6%, specificity: 75.1%; P < .001), and 7.75 minutes (sensitivity: 79.3%, specificity: 75.7%; P < .001). Clinical Implications: The technological superiority of VR will enable the VR-AVSS immersion test to be a more accurate detection than traditional AVSS modes. Strengths and Limitations: Our study applied VR immersion technology to establish the standard operation procedure for the AVSS test, which could effectively reduce the interference of adverse factors and minimize the detecting errors. However, the test data only included positive response subjects, so the true erectile status of men with a negative response to the AVSS test cannot be obtained. Conclusions: The VR-AVSS test can effectively improve the diagnostic accuracy of ED. The average rigidity and effective erectile duration were the optimal diagnostic parameters for excluding ED.

Inhibition of SARS-CoV-2 replication by a ssDNA aptamer targeting the nucleocapsid protein.

The nucleocapsid protein of SARS-CoV-2 plays significant roles in viral assembly, immune evasion, and viral stability. Due to its immunogenicity, high expression levels during COVID-19, and conservation across viral strains, it represents an attractive target for antiviral treatment. In this study, we identified and characterized a single-stranded DNA aptamer, N-Apt17, which effectively disrupts the liquid-liquid phase separation (LLPS) mediated by the N protein. To enhance the aptamer's stability, a circular bivalent form, cb-N-Apt17, was designed and evaluated. Our findings demonstrated that cb-N-Apt17 exhibited improved stability, enhanced binding affinity, and superior inhibition of N protein LLPS; thus, it has the potential inhibition ability on viral replication. These results provide valuable evidence supporting the potential of cb-N-Apt17 as a promising candidate for the development of antiviral therapies against COVID-19.IMPORTANCEVariants of SARS-CoV-2 pose a significant challenge to currently available COVID-19 vaccines and therapies due to the rapid epitope changes observed in the viral spike protein. However, the nucleocapsid (N) protein of SARS-CoV-2, a highly conserved structural protein, offers promising potential as a target for inhibiting viral replication. The N protein forms complexes with genomic RNA, interacts with other viral structural proteins during virion assembly, and plays a critical role in evading host innate immunity by impairing interferon production during viral infection. In this investigation, we discovered a single-stranded DNA aptamer, designated as N-Apt17, exhibiting remarkable affinity and specificity for the N protein. Notably, N-Apt17 disrupts the liquid-liquid phase separation (LLPS) of the N protein. To enhance the stability and molecular recognition capabilities of N-Apt17, we designed a circular bivalent DNA aptamer termed cb-N-Apt17. In both in vivo and in vitro experiments, cb-N-Apt17 exhibited increased stability, enhanced binding affinity, and superior LLPS disrupting ability. Thus, our study provides essential proof-of-principle evidence supporting the further development of cb-N-Apt17 as a therapeutic candidate for COVID-19.

Perioperative care of neonates with critical pulmonary stenosis: Case report.

RATIONALE: Summarizing the perioperative nursing experience in the successful treatment of 4 neonates with critical pulmonary stenosis (CPS). PATIENT CONCERNS: Of the 4 patients, 3 had postnatal shortness of breath and varying degrees of cyanosis, aggravated by crying and noise, and 1 had no obvious shortness of breath and cyanosis. The preoperative auscultation of the precordial region could be heard 3-4/6 systolic murmur; echocardiography was diagnosed as CPS, combined with patent ductus arteriosus, right ventricular dysplasia, and severe tricuspid regurgitation. Four children were treated with prostaglandin 5 ng/(kg-min) to maintain a certain degree of pulmonary blood flow to improve hypoxemia, effectively preventing ductus arteriosus from closure, and the infusion was discontinued 2 hours prior to the operation. Three of the children required ventilator-assisted respiration to relieve severe hypoxia and correct acidosis before surgery. DIAGNOSIS: Neonatal CPS was diagnosed. INTERVENTIONS: Four neonates with rapidly developing conditions were admitted to the hospital, a multidisciplinary in-hospital consultation was organized immediately, and a multidisciplinary collaborative team was set up, consisting of medical doctors and nurses from the medical department, the neonatal intensive care unit, cardiovascular medicine, cardiac ultrasound room, anesthesiology department, and radiology and interventional medicine department. The multidisciplinary team evaluated the treatment modality of the children and finally decided to perform percutaneous balloon pulmonary valvuloplasty. The surgical team included specialists from the Department of Cardiovascular Medicine, Department of Interventional Radiology, Cardiac Ultrasound Unit, and Department of Anesthesiology. OUTCOMES: All 4 neonates were successfully operated and discharged from the hospital. Multidisciplinary follow-up interventions were carried out 1 year after discharge, and the children were in good condition. LESSONS: The specialty nursing-led multidisciplinary collaboration model significantly improves the professional competence of nurses from various specialties, promotes the integration and development of multispecialty disciplines, and provides better quality services for children, which is the key to improving the success rate of percutaneous balloon pulmonary valvuloplasty in neonates.

MR Diffusion-Weighted Imaging in Evaluating Immediate HIFU Treatment Response of Uterine Fibroids.

BACKGROUND: Nowadays, High Intensity Focused Ultrasound (HIFU) is a common surgery option for the treatment of uterine fibroids in China, the immediate response of which is clinically evaluated using Contrast Enhanced (CE) imaging. However, the injection of gadolinium with its potential adverse effect is of concern in CE and therefore, it deserves efforts to find a better imaging method without the need for contrast agent injection for this task. OBJECTIVE: To assess the role of diffusion-weighted imaging (DWI) in evaluating the immediate therapeutic response of HIFU treatment for uterine fibroids in comparison with CE. METHODS: 68 patients with 74 uterine fibroids receiving HIFU treatment were enrolled, and immediate treatment response was assessed using post-surgical DWI images. Semi-quantitative ordinal ablation quality grading and quantitative nonperfusion volume (NPV) measurement based on DWI and CE imaging were determined by two experienced radiologists. Agreement of ablation quality grading between DWI and CE was assessed using the weighted kappa coefficient, while intraobserver, interobserver and interprotocol agreements of NPV measurements within and between DWI and CE were evaluated using the intraclass correlation (ICC) and Bland-Altman analysis. RESULTS: Grading of immediate HIFU treatment response showed a moderate agreement between DWI and CE (weighted kappa = 0.446, p < 0.001). NPV measured in 65 fibroids with DWI of Grade 3~5 showed very high ICCs for the intraobserver and interobserver agreement within DWI and CE (all ICC > 0.980, p < 0.001) and also for the interprotocol agreement between DWI and CE (ICC = 0.976, p < 0.001). CONCLUSION: DWI could provide satisfactory ablation quality grading, and reliable NPV quantification results to assess immediate therapeutic responses of HIFU treatment for uterine fibroids in most cases, which suggests that non-contrast enhanced DWI might be potentially used as a more costeffective and convenient method in a large proportion of patients for this task replacing CE imaging.

Effects of wastewater treatment plant effluent on microbial risks of pathogens and their antibiotic resistance in the receiving river.

The increase in effluent discharge from wastewater treatment plants (WWTPs) into urban rivers has raised concerns about the potential effects on pathogen risks. This study utilized metagenomic sequencing combined with flow cytometry to analyze pathogen concentrations and antibiotic resistance in a typical effluent-receiving river. Quantitative microbial risk assessment (QMRA) was employed to assess the microbial risks of pathogens. The results indicated obvious spatial-temporal differences (i.e., summer vs. winter and effluent vs. river) in microbial composition. Microcystis emerged as a crucial species contributing to these variations. Pathogen concentrations were found to be higher in the river than in the effluent, with the winter exhibiting higher concentrations compared to the summer. The effluent discharge slightly increased the pathogen concentrations in the river in summer but dramatically reduced them in winter. The combined effects of cyanobacterial bloom and high temperature were considered key factors suppressing pathogen concentrations in summer. Moreover, the prevalence of antibiotic resistance of pathogens in the river was inferior to that in the effluent, with higher levels in winter than in summer. Three high-concentration pathogens (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) were selected for QMRA. The results showed that the risks of pathogens exceeded the recommended threshold value. Escherichia coli posed the highest risks. And the fishing scenario posed significantly higher risks than the walking scenario. Importantly, the effluent discharge helped reduce the microbial risks in the receiving river in winter. The study contributes to the management and decision-making regarding microbial risks in the effluent-receiving river.

Self-Catalyzed Hydrogenated Carbon Nano-Onions Facilitates Mild Synthesis of Transparent Nano-Polycrystalline Diamond.

Transparent nano-polycrystalline diamond (t-NPD) possesses superior mechanical properties compared to single and traditional polycrystalline diamonds. However, the harsh synthetic conditions significantly limit its synthesis and applications. In this study, a synthesis routine is presented for t-NPD under low pressure and low temperature conditions, 10 GPa, 1600 °C and 15 GPa, 1350 °C similar with the synthesis condition of organic precursor. Self-catalyzed hydrogenated carbon nano-onions (HCNOs) from the combustion of naphthalene enable synthesis under nearly industrial conditions, which are like organic precursor and much lower than that of graphite and other carbon allotropes. This is made possible thanks to the significant impact of hydrogen on the thermodynamics, as it chemically facilitates phase transition. Ubiquitous nanotwinned structures are observed throughout t-NPD due to the high concentration of puckered layers and stacking faults of HCNOs, which impart a Vickers hardness about 140 GPa. This high hardness and optical transparency can be attributed to the nanocrystalline grain size, thin intergranular films, absence of secondary phase and pore-free features. The facile and industrial-scale synthesis of the HCNOs precursor, and mild synthesis conditions make t-NPD suitable for a wide range of potential applications.

Enzyme-mediated fabrication of nanocomposite hydrogel microneedles for tunable mechanical strength and controllable transdermal efficiency.

Microneedles (MNs) are increasingly used in transdermal drug delivery due to high bioavailability, simple operation, and improved patient compliance. However, further clinical applications are hindered by unsatisfactory mechanical strength and uncontrolled drug release. Herein, an enzyme-mediated approach is reported for the fabrication of nanocomposite hydrogel-based MNs with tunable mechanical strength and controllable transdermal efficiency. As a proof-of-concept, tetrakis(1-methyl-4-pyridinio)porphyrin (TMPyP) was chosen as a model drug for photodynamic therapy of melanoma. TMPyP-loaded PLGA nanoparticles (NP/TMPyP) served as an inner phase of MNs for controlled release of photosensitizers, and enzyme-mediated hyaluronic acid-tyramine (HAT) hydrogels served as an external phase for optimizing the mechanical strength of MNs. By changing the concentration of HRP and H2O2, three types of MNs were fabricated for transdermal delivery of TMPyP, which demonstrated different cross-linking densities and various mechanical strength. Among the three MNs, the HAT-Medium@NP/TMPyP-MN with a medium mechanical strength exhibited the highest values of transdermal efficiency in vitro and the longest retention time in vivo. As compared to pure TMPyP and TMPyP-loaded nanoparticles, the HAT-Medium@NP/TMPyP-MN demonstrated higher anticancer efficacy in both melanoma A375 cells and a xenografted tumor mouse model. Therefore, the enzyme-mediated nanocomposite hydrogel MNs show great promise in the transdermal delivery of therapeutic drugs with enhanced performance. STATEMENT OF SIGNIFICANCE: This study reports an enzyme-mediated approach for the fabrication of photodynamically-active microneedles (HAT@NP/TMPyP-MNs) with tunable mechanical strength and controllable transdermal efficiency. On one hand, HAT hydrogels that bear different cross-linking densities, facilitate tunable mechanical strength and optimized transdermal performances of MNs; on the other hand, NP/TMPyP and HAT network contribute to sustained release of photosensitizers. Comparing to other formulation (i.e., NP/TMPyP or TMPyP), the HAT-Medium@NP/TMPyP-MN exhibited excelling anticancer efficacy in photodynamic therapy in vitro and in vivo. We believe that the combination of enzyme-mediated polymeric cross-linking and slow-releasing nano-vehicles in a single nanocomposite platform provides a versatile approach for the fabrication of MNs with enhanced therapeutic efficacy, which holds great promise in the transdermal delivery of various therapeutic drugs in future.

Synthesis of Cu2-x Se-MoSe2 Edge-Epitaxial Heterostructure for Efficient Electrocatalytic Hydrogen Evolution.

The exposure of active edge sites of transition metal dichalcogenide (TMD) in TMD-based heterostructures is essential to enhance the catalytic activity toward electrochemical catalytic hydrogen evolution (HER). The construction of TMD-based edge-epitaxial heterostructures can maximally expose the active edge sites. However, owing to the 2D crystal structures, it remains a great challenge to vertically align layered TMDs on non-layered metal chalcogenides. Herein, the synthesis of Cu2-x Se-MoSe2 edge-epitaxial heterostructure is reported by a facile one-pot wet-chemical method. A high density of MoSe2 nanosheets grown vertically to the <111>Cu2-xSe on the surface of Cu2-x Se nanocrystals is observed. Such edge-epitaxial configuration allows the exposure of abundant active edge sites of MoSe2 and enhances the changer transfer between MoSe2 and Cu2-x Se. As a result, the obtained Cu2-x Se-MoSe2 epitaxial heterostructures show excellent HER performance as compared to that of Cu2-x Se@1T/2H-MoSe2 core@shell heterostructure with similar size. This work not only offers a novel approach for designing efficient electrochemical catalysis but also enriches the diversity of TMD-based heterostructures, holding promise for various applications in the future.

The Interaction between SARS-CoV-2 Nucleocapsid Protein and UBC9 Inhibits MAVS Ubiquitination by Enhancing Its SUMOylation.

Severe COVID-19 patients exhibit impaired IFN-I response due to decreased IFN-ß production, allowing persistent viral load and exacerbated inflammation. While the SARS-CoV-2 nucleocapsid (N) protein has been implicated in inhibiting innate immunity by interfering with IFN-ß signaling, the specific underlying mechanism still needs further investigation for a comprehensive understanding. This study reveals that the SARS-CoV-2 N protein enhances interaction between the human SUMO-conjugating enzyme UBC9 and MAVS. Increased MAVS-UBC9 interaction leads to enhanced SUMOylation of MAVS, inhibiting its ubiquitination, resulting in the inhibition of phosphorylation events involving IKKα, TBK1, and IRF3, thus disrupting IFN-ß signaling. This study highlights the role of the N protein of SARS-CoV-2 in modulating the innate immune response by affecting the MAVS SUMOylation and ubiquitination processes, leading to inhibition of the IFN-ß signaling pathway. These findings shed light on the complex mechanisms utilized by SARS-CoV-2 to manipulate the host's antiviral defenses and provide potential insights for developing targeted therapeutic strategies against severe COVID-19.

Self-Assembled Homopolymeric Spherulites from Small Molecules in Solution.

Polymeric spherulites are typically formed by melt crystallization: spherulitic growth in solution is rare and requires complex polymers and dilute solutions. Here, we report the mild and unique formation of luminescent spherulites at room temperature via the simple molecule benzene-1,4-dithiol (BDT). Specifically, BDT polymerized into oligomers (PBDT) via disulfide bonds and assembled into uniform supramolecular nanoparticles in aqueous buffer; these nanoparticles were then dissolved back into PBDT in a good solvent (i.e., dimethylformamide) and underwent chain elongation to form spherulites (rPBDT) in 10 min. The spherulite geometry was modulated by changing the PBDT concentration and reaction time. Due to the step-growth polymerization and reorganization of PBDT, these spherulites not only exhibited robust structure but also showed broad clusterization-triggered emission. The biocompatibility and efficient cellular uptake of the spherulites further underscore their value as traceable drug carriers. This system provides a new pathway for designing versatile superstructures with value for hierarchical assembly of small molecules into a complicated biological system.