Structure-phase transformation of bismuth oxide to BiOCl/Bi24O31Cl10 shoulder-by-shoulder heterojunctions for efficient photocatalytic removal of antibiotic.

Developing heterojunction photocatalyst with well-matched interfaces and multiple charge transfer paths is vital to boost carrier separation efficiency for photocatalytic antibiotics removal, but still remains a great challenge. In present work, a new strategy of chloride anion intercalation in Bi2O3 via one-pot hydrothermal process is proposed. The as-prepared Ta-BiOCl/Bi24O31Cl10 (TBB) heterojunctions are featured with Ta-Bi24O31Cl10 and Ta-BiOCl lined shoulder-by-shouleder via semi-coherent interfaces. In this TBB heterojunctions, the well-matched semi-coherent interfaces and shoulder-by-shoulder structures provide fast electron transfer and multiple transfer paths, respectively, leading to enhanced visible light response and improved photogenerated charge separation. Meanwhile, a type-II heterojunction for photocharge separation has been obtained, in which photogenerated electrons are drove from the CB (conduction band) of Ta-Bi24O31Cl10 to the both of bilateral empty CB of Ta-BiOCl and gathered on the CB of Ta-BiOCl, while the photogenerated holes are left on the VB (valence band) of Ta-Bi24O31Cl10, effectively hindering the recombination of photogenerated electron-hole pairs. Furthermore, the separated electrons can effectively activate dissolved oxygen for the generation of reactive oxygen species (·O2-). Such TBB heterojunctions exhibit remarkably superior photocatalytic degradation activity for tetracycline hydrochloride (TCH) solution to Bi2O3, Ta-BiOCl and Ta-Bi24O31Cl10. This work not only proposes a Ta-BiOCl/Bi24O31Cl10 shoulder-by-shoulder micro-ribbon architectures with semi-coherent interfaces and successive type-II heterojunction for highly efficient photocatalytic activity, but offers a new insight into the design of highly efficient heterojunction through phase-structure synergistic transformation strategy.

Systems pharmacology-based drug discovery from Amaryllidaceae alkaloids and investigation of mechanisms of action in treatment of Alzheimer's disease.

OBJECTIVES: Given the success of galanthamine in treating Alzheimer's disease, this study aims to establish an effective method to find drugs from Amaryllidaceae alkaloids and to clarify its mechanism in treating Alzheimer's disease. METHODS: The pharmacodynamic basis and mechanism of action between Amaryllidaceae alkaloids and Alzheimer's disease were explored by constructing a compound-target-disease network, targets protein-protein interaction, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and molecular docking verification. KEY FINDINGS: In total, a chemical library of 357 potential alkaloids was constructed. A total of 100 active alkaloid components were identified. Thirty-nine associated targets were yielded based on network construction, and the key targets were defined as HSP90AA1, ESR1, NOS3, PTGS2, and PPARG using protein-protein interaction network. Gene ontology items (490) and 68 Kyoto Encyclopedia of Genes and Genomes pathways were selected through the enrichment of target functions, including neuroactive ligand-receptor interaction, calcium signaling pathway, cAMP signaling pathway, Alzheimer disease, and serotonergic synapse that were related to Alzheimer's disease. Lastly, molecular docking demonstrated good stability in combining selected alkaloids with targets. CONCLUSIONS: This study explained the mechanisms of Amaryllidaceae alkaloids in preventing and treating Alzheimer's disease and established a novel strategy to discover new drugs from biological chemical sources.

Hybrid nanoparticle-mediated simultaneous ROS scavenging and STING activation improve the antitumor immunity of in situ vaccines.

In situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle-based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond-bridged organosilica nanoparticles, followed by coating with a Mn2+-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn2+ and SN38 comediated signaling and simultaneously scavenge preexisting H2O2 in the TME and Mn2+-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.

Deep-learning-assisted thermogalvanic hydrogel fiber sensor for self-powered in-nostril respiratory monitoring.

Direct and consistent monitoring of respiratory patterns is crucial for disease prognostication. Although the wired clinical respiratory monitoring apparatus can operate accurately, the existing defects are evident, such as the indispensability of an external power supply, low mobility, poor comfort, and limited monitoring timeframes. Here, we present a self-powered in-nostril hydrogel sensor for long-term non-irritant anti-interference respiratory monitoring, which is developed from a dual-network binary-solvent thermogalvanic polyvinyl alcohol hydrogel fiber (d = 500 µm, L=30 mm) with Fe2+/Fe3+ ions serving as a redox couple, which can generate a thermoelectrical signal in the nasal cavity based on the temperature difference between the exhaled gas and skin as well as avoid interference from the external environment. Due to strong hydrogen bonding between solvent molecules, the sensor retains over 90 % of its moisture after 14 days, exhibiting great potential in wearable respiratory surveillance. With the assistance of deep learning, the hydrogel fiber-based respiration monitoring strategy can actively recognize seven typical breathing patterns with an accuracy of 97.1 % by extracting the time sequence and dynamic parameters of the thermoelectric signals generated by respiration, providing an alert for high-risk respiratory symptoms. This work demonstrates the significant potential of thermogalvanic gels for next-generation wearable bioelectronics for early screening of respiratory diseases.

Research on Detection Method of Chaotian Pepper in Complex Field Environments Based on YOLOv8.

The intelligent detection of chili peppers is crucial for achieving automated operations. In complex field environments, challenges such as overlapping plants, branch occlusions, and uneven lighting make detection difficult. This study conducted comparative experiments to select the optimal detection model based on YOLOv8 and further enhanced it. The model was optimized by incorporating BiFPN, LSKNet, and FasterNet modules, followed by the addition of attention and lightweight modules such as EMBC, EMSCP, DAttention, MSBlock, and Faster. Adjustments to CIoU, Inner CIoU, Inner GIoU, and inner_mpdiou loss functions and scaling factors further improved overall performance. After optimization, the YOLOv8 model achieved precision, recall, and mAP scores of 79.0%, 75.3%, and 83.2%, respectively, representing increases of 1.1, 4.3, and 1.6 percentage points over the base model. Additionally, GFLOPs were reduced by 13.6%, the model size decreased to 66.7% of the base model, and the FPS reached 301.4. This resulted in accurate and rapid detection of chili peppers in complex field environments, providing data support and experimental references for the development of intelligent picking equipment.

A Noncationic Biocatalytic Nanobiohybrid Platform for Cytosolic Protein Delivery Through Controlled Perturbation of Intracellular Redox Homeostasis.

Intracellular delivery of proteins has largely been relying on cationic nanoparticles to induce efficient endosome escape, which, however, poses serious concerns on the inflammatory and cytotoxic effects. Herein, a versatile noncationic nano biohybrid platform is introduced for efficient cytosolic protein delivery by utilizing a nano-confined biocatalytic reaction. This platform is constructed by co-immobilizing glucose oxidase (GOx) and the target protein into nanoscale hydrogen-bonded organic frameworks (HOFs). The biocatalytic reaction of nano-confined GOx is leveraged to induce controlled perturbation of intracellular redox homeostasis by sustained hydrogen peroxide (H2O2) production and diminishing the flux of the pentose phosphate pathway (PPP). This in turn induces the endosome escape of nanobiohybrids. Concomitantly, GOx-mediated hypoxia leads to overexpression of azo reductase that initiated the materials' self-destruction for releasing target proteins. These biological effects collectively induce highly efficient cytosolic protein delivery. The versatility of this delivery platform is further demonstrated for various types of proteins, different protein loading approaches (in situ immobilization or post-adsorption), and in multiple cell lines. Finally, the protein delivery efficiency and biosafety are demonstrated in a tumor-bearing mouse model. This nanohybrid system opens up new avenues for intracellular protein delivery and is expected to be extensively applicable for a broad range of biomolecuels.

Portable multimodal platform with carbon nano-onions as colorimetric and fluorescent signal output for trypsin detection.

Multimodal biosensors with independent signaling pathways can self-calibrate and improve the reliability of disease biomarker detection. Herein, a colorimetric-fluorescent dual-mode paper-based biosensor with PAN/Fe(III)-CNOs (FPCs) as core components has been developed, which information is recognized by smartphone and naked eye. Using 1-(2-pyridylazo)-2-naphthol (PAN) as a mediator, Fe(III) is enriched on the surface of carbon nano-onions (CNOs), endowing FPCs with excellent mimetic enzyme activity and photothermal conversion ability, which allows it to output amplified colorimetric signals under laser irradiation. In addition, the complexation of PAN with Fe(III) broadens its absorption spectrum, which makes FPCs more suitable to be energy acceptors to quench fluorescence of polymer dots (Pdots), resulting in the changes of output fluorescent signal. Based on the above design, a portable colorimetric-fluorescent dual-mode biosensor is proposed for trypsin detection with Pdots as fluorescence sources and FPCs as fluorescence quenchers and nanoenzymes. This work provides a convenient way for constructing portable visual multimodal biosensors, which is expected to applied in various disease diagnosis.

A Magnetically Driven Biodegradable Microsphere with Mass Production Capability for Subunit Vaccine Delivery and Enhanced Immunotherapy.

Subunit vaccines have emerged as a promising strategy in immunotherapy for combating viral infections and cancer. Nevertheless, the clinical application of subunit vaccines is hindered by limitations in antigen delivery efficiency, characterized by rapid clearance and inadequate cellular uptake. Here, a novel subunit vaccine delivery system utilizing ovalbumin@magnetic nanoparticles (OVA@MNPs) encapsulated within biodegradable gelatin methacryloyl (GelMA) microspheres was proposed to enhance the efficacy of antigen delivery. OVA@MNPs-loaded GelMA microspheres, denoted as OMGMs, can be navigated through magnetic fields to deliver subunit vaccines into the lymphatic system efficiently. Moreover, the biodegradable OMGMs enabled the sustained release of subunit vaccines, concentrating OVA around lymph nodes and enhancing the efficacy of induced immune response. OMGMs were produced through a microfluidic droplet generation technique, enabling mass production. In murine models, OMGMs successfully accumulated antigens in lymph nodes abundant in antigen-presenting cells, leading to enhanced cellular and humoral immunity and pronounced antitumor effects with a single booster immunization. In conclusion, these findings highlight the promise of OMGMs as a practical subunit vaccination approach, thus addressing the limitations associated with antigen delivery efficiency and paving the way for advanced immunotherapeutic strategies.

Effect of mean heart rate on 30-day mortality in older patients with sepsis: Data from the MIMIC-IV database.

BACKGROUND: Sepsis is a critical condition with a significant risk of mortality. Advanced age is one factor in increasing mortality in intensive care. OBJECTIVES: The aim of this study is to investigate the association between mean heart rate (MHR) and 30-day mortality among older patients with sepsis in the intensive care unit (ICU). METHODS: All older patients (age 65 or older) with sepsis for first time in ICU admission in Medical Information Mart for Intensive Care-IV (MIMIC-IV) were included in this retrospective study. The effect of MHR within 24 h of ICU admission on 30-day mortality was assessed according to multivariable Cox regression models, restricted cubic splines and two-piecewise Cox regression models. RESULTS: The total number of participants was 6598 (mean heart rate, 83.8 ± 14.3 bpm). A total of 1295 (19.6%) patients died within 30 days after ICU admission. MHR within 24 h of admission was associated with 30-day mortality (J-shaped association) in older patients with sepsis in the ICU, with an inflection point at about 74 bpm and a minimal risk observed at 73 to 82 bpm of MHR. CONCLUSIONS: In this retrospective cohort study, there was a J-shaped association between MHR and 30-day mortality in older patients with sepsis admitted to the ICU and a minimal risk observed at 73 to 82 bpm of MHR. If further confirmed, this association may provide a theoretical basis for formulating the target strategy of heart rate therapy for these patients.

Alloy Reconstruction in Pyrolytic Bowknot-like Heteronuclear CoFe Clusters for Electrocatalytic Application.

The construction of doped molecular clusters is an intriguing way to perform bimetallic doping for electrocatalysts. However, efficiently harnessing the benefits of a doping strategy and alloy engineering to create a nanostructure for electrocatalytic application at the molecular level has consistently posed a challenge. Here we propose an in situ reconstruction strategy aimed at producing an alloy nanostructure through a pyrolysis process, originating from bowknot-like heterometallic clusters. The Schiff base, denoted as ligand L1 (o-vanillin ethylenediamine), was introduced as a precursor to coordinate Fe and Co metals, thereby yielding a heteronuclear metal cluster [(FeCo)(L1)2O]CH3CN. Subsequently, a comprehensive investigation of the in situ reconstruction process [(FeCo)(L1)2O](CH3CN) → [(FeCo)(L1)2O] → [M-O-M/M-O] [CH3+/CH3O+/H2C═N/C2H5+/C4H4+] → [FeCo/Fe3O4/Fe2O3/Co3O4][carbon layer] led to the formation of MOx/CoFe@NC-700 during the pyrolysis. This process reveals that the metals Fe and Co in the clusters undergo partly in situ evolution into FeCo alloys, resulting in the successful preparation of MOx/CoFe@NC (M = Fe, Co) nanomaterials that leverage the advantages of both doping strategies and alloy engineering. The synergistic interaction between alloy particles and metal oxides establishes active sites that contribute to the excellent oxygen evolution (OER) and hydrogen evolution (HER) catalytic behaviors. Notably, these materials exhibit outstanding OER and HER properties under alkaline conditions, with overpotentials of 191 and 88 mV for OER and HER, respectively, at 10 mA cm-2. Investigation of the in situ conversion of Schiff base bimetal clusters into alloy materials through pyrolysis offers a novel strategy for advancing electrocatalytic applications.

Optimal operation of energy-intensive load considering electricity carbon market.

Energy-intensive load benefits from low electricity tariff and carbon emission, since they occupy certain amounts in the total cost of the product. This paper considers energy-intensive load participation in the electricity as well as carbon trading to reduce the cost. Firstly, an electricity-carbon model is established based on the correlation value method to calculate the carbon emissions of energy-intensive load based on their electricity consumption to realize the carbon amount. Afterwards, the baseline method is used to allocate free carbon emission quotas to energy-intensive load and a reward-penalty carbon trading price mechanism considering offset is proposed. Next, the objective function to achieve maximum benefits, and to reduce output fluctuation, and to improve new energy accommodation is proposed. The case studies show that, by comparing multi-objective function optimization, the optimization target proposed in this paper can effectively reduce wind power output fluctuations and improve wind power accommodation. Through the total participation in carbon trading and electricity market income, multi-objective optimization can increase the system income while ensuring that energy-intensive load meets production requirements under the premise of reducing carbon emissions, verifying the effectiveness of the low-carbon optimal operation model proposed in this paper.

Inhaled tea polyphenol-loaded nanoparticles coated with platelet membranes largely attenuate asthmatic inflammation.

BACKGROUND: Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma. METHODS: After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting. RESULTS: Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs. CONCLUSIONS: Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.

The controllable synthesis of multi-color carbon quantum dots modified by polythiophene and their application in fluorescence detection of Au3+ and Hg2.

Herein, hydrothermal method was used to prepare a series of multi-color polythiophene modified carbon quantum dots. Under UV excitation, fluorescence their maximum emission wavelengths appear at 612 nm, 570 nm, and 540 nm respectively. The prepared CD-BTH and CD-BN can have specific detection of Au3+ and Hg2+ through fluorescence quenching effect. The detection limits for Au3+ are 3 nM and 5.4 nM respectively, and for Hg2+ are 23 nM and 90 nM respectively. CD-KN detects Au3+ specifically through fluorescence resonance, with a detection limit of 33 nM. Under the interference of other metal ions, three types of polythiophene modified quantum carbon dots exhibit excellent selectivity for the responsive ions. Meanwhile, this article also elucidates the law that as the electron withdrawing ability of the side chains of polythiophene derivatives increasing, the fluorescence emission peaks of the prepared polythiophene modified carbon dots shifts red and the fluorescence quantum yield is higher.

Safety, tolerability, and immunogenicity of an adult pneumococcal conjugate vaccine, V116 (STRIDE-3): a randomised, double-blind, active comparator controlled, international phase 3 trial.

BACKGROUND: The same pneumococcal conjugate vaccines (PCVs) have been used in adults and children in many settings. Differences in the epidemiology of pneumococcal disease between populations necessitates an adult-specific PCV. We aimed to assess the safety, tolerability, and immunogenicity of V116, an investigational 21-valent PCV designed for adults. METHODS: This randomised, double-blind, active comparator controlled, international phase 3 trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites in 11 countries or territories. Random assignment was performed using a central electronic interactive response technology system. Cohort 1 (≥50 years) was stratified by age (50-64, 65-74, 75-84, and ≥85 years) and randomised 1:1 to receive one intramuscular dose of V116, or the active comparator, PCV20. Cohort 2 (18-49 years) was randomised 2:1 to receive one intramuscular dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured before (day 1) and after vaccination (day 30). Four primary immunogenicity outcomes were assessed per-protocol. First, in cohort 1, non-inferiority of V116 to PCV20 was tested using serotype-specific OPA geometric mean titres (GMT) ratios for serotypes common to both vaccines; the lower bound of the 95% CI had to be greater than 0·5 for non-inferiority. Second, superiority of V116 to PCV20 was tested for OPA GMT ratios for the serotypes unique to V116; the lower bound of the 95% CI had to be greater than 2·0 for superiority. Third, superiority of V116 to PCV20 was evaluated by the proportions of participants with a four-fold or greater rise from day 1 to day 30 for serotypes unique to V116; the lower bound of the 95% CI of the differences in proportions (V116 - PCV20) had to be greater than 10% for superiority. Finally, in cohort 2, immunobridging was assessed for all 21 serotypes in V116 for adults aged 18-49 years to 50-64 years; the lower bound of the 95% CI for the OPA GMTs had to be greater than 0·5 for non-inferiority. The safety analysis included all randomly assigned participants who received study vaccine. The primary safety outcome was the proportion of participants with solicited injection site and solicited systemic adverse events until day 5 and vaccine-related serious adverse events up to 6 months after vaccination. This trial is registered at ClinicalTrials.gov (NCT05425732). FINDINGS: Between July 13, and Nov 22, 2022, 2754 individuals were screened and 2663 participants were randomly assigned. 2656 individuals were vaccinated (1179 in V116 cohort 1; 1177 in PCV20 cohort 1; 200 in V116 cohort 2; and 100 in PCV20 cohort 2). V116 met non-inferiority criteria compared with PCV20 for the ten serotypes common to both vaccines at day 30 in cohort 1 (p<0·0001 for each common serotype). V116 met superiority criteria compared with PCV20 in cohort 1 for ten of the 11 serotypes unique to V116 at day 30 (OPA GMT ratio: p<0·0001 for all unique serotypes except 15C, which was p=0·41; four-fold or greater rise in OPA from day 1-30: p<0·0001 for all serotypes except 15C, which was p=0·67). Immune responses in V116 participants aged 18-49 years were non-inferior compared with V116 participants aged 50-64 years for all V116 serotypes (p<0·0001 for all V116 serotypes). In cohort 1, 685 (58·2%) of participants in V116, and 778 (66·2%) of participants in PCV20 reported one or more adverse event. In cohort 2, 164 (82·0%) participants in V116 and 79 participants (79·0%) in PCV20 reported one or more adverse event. Six deaths were reported, all in cohort 1, none of which were considered vaccine-related (in V116: one due to sepsis, one due to cerebrovascular accident, one due to myocardial infarction, and one due to hepatic cirrhosis and hepatic encephalopathy; in PCV20: one due to cardiac arrest and one due to abdominal abscess). There were no vaccine-related serious adverse events. INTERPRETATION: V116 was non-inferior to PCV20 for the ten serotypes common to both vaccines and superior to PCV20 for all serotypes unique to V116, except for 15C. Immune responses successfully immunobridged between younger and older adults for all serotypes in V116. V116 was generally well tolerated with safety profile similar to PCV20. FUNDING: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

Dual-Confinement and Surface-Ionization Induced Controllable Regulate Visible-Light-Activated Colorful Afterglow of Carbon Dots for Multifunctional Applications.

Low-energy visible-light-activated carbon dots (CDs)-based afterglow materials are difficult to realize due to the inherent aromatic carbon with high-energy absorption and the lack of effective regulation. Here, a new strategy for visible-light-activated CDs is proposed by combining dual-confinement and surface-ionization, which employs NaOH for additional confinement and surface ionization of CDs in a single boric acid (BA) matrix. The comparison experiments show that: i) shifting the excitation from UV-light to vis-light is realized by enhancing the low-energy surface states n→π* transition of the CDs by surface ionization of NaOH. ii) CDs are additionally protected by a more stable Na─O ionic bond after NaOH confinement, resulting in a brighter afterglow. iii) the energy gap (ΔEST) between the lowest singlet and triplet states is gradually shortened as increasing NaOH content, facilitating intersystem crossing, prolonging the lifetime of triplet excitons and efficiency. Further, vis-light-excited colorful afterglow powders are fabricated based on Förster Resonant Energy Transfer by combining the fluorescent dye 5-carboxytetramethylrhodamine. Finally, advanced white-light-activated time-resolved anti-counterfeiting and intelligent traffic flashing signs are realized. The work may shed new light on the design of low-energy-activated afterglow materials and broaden the application scenarios in the daily lives of human society.