Identification of phase-I and phase-II metabolites and the metabolic pathway of the novel synthetic cannabinoid 5F-EDMB-PICA in vitro.

5F-EDMB-PICA is a newly emerged synthetic cannabinoid which has been characterized in relevant literature in recent years. Although phase-I metabolites of 5F-EDMB-PICA have been partly reported, the phase-II metabolism of this synthetic cannabinoid has not been studied yet. In this study, we established a phase-I and phase-II metabolism model in vitro by using pooled human liver microsomes, NADPH regeneration system, and UGT incubation system, with 1 mg/ml 5F-EDMB-PICA added and incubated at 37 °C for 60 min. The metabolites were analyzed by Q Exactive™ Hybrid Quadrupole-Orbitrap™ Mass Spectrometer, via which we discovered and identified 14 phase-I metabolites and 4 phase-II metabolites of 5F-EDMB-PICA, involving pathways such as ester hydrolysis, dehydrogenation, hydrolytic defluorination, hydroxylation, dihydroxylation, glucuronidation, and combinations of the pathways mentioned above. We recommend considering the monohydroxylation metabolites (M9, M10) with higher content and intact ester and 5-fluoropentyl structures as potential biomarkers of 5F-EDMB-PICA.

Cepharanthine Triggers Ferroptosis Through Inhibition of NRF2 For Robust ER Stress Against Lung Cancer.

BACKGROUND: Severe endoplasmic reticulum (ER) stress elicits apoptosis to suppress lung cancer. Our previous research identified that Cepharanthine (CEP), a kind of phytomedicine, possessed powerful anti-cancer efficacy, for which the underlying mechanism was still uncovered. Herein, we investigated how CEP induced ER stress and worked against lung cancer. METHODS: The differential expression genes (DEGs) and enrichment were detected by RNA-sequence. The affinity of CEP and NRF2 was analyzed by cellular thermal shift assay (CETSA) and molecular docking. The function assay of lung cancer cells was measured by western blots, flow cytometry, immunofluorescence staining, and ferroptosis inhibitors. RESULTS: CEP treatment enriched DEGs in ferroptosis and ER stress. Further analysis demonstrated the target was NRF2. In vitro and in vivo experiments showed that CEP induced obvious ferroptosis, as characterized by the elevated iron ions, ROS, COX-2 expression, down-regulation of GPX4, and atrophic mitochondria. Moreover, enhanced Grp78, CHOP, p-eIF2A expression, ß-amyloid mass, and disappearing parallel stacked structures of ER were observed in CEP group, suggesting ER stress was aroused. CEP exhibited excellent anti-lung cancer efficacy, as evidenced by the increased apoptosis, reduced proliferation, diminished cell stemness, and prominent inhibition of tumor grafts in animal models. Furthermore, the addition of ferroptosis inhibitors weakened CEP-induced ER stress and apoptosis. CONCLUSION: In summary, our findings proved CEP drives ferroptosis through inhibition of NRF2 for induction of robust ER stress, thereby leading to apoptosis and attenuated stemness of lung cancer cells. The current work presents a novel mechanism for the anti-tumor efficacy of the natural compound CEP.

Ecotoxicity of hexavalent chromium [Cr (VI)] in soil presents predominate threats to agricultural production with the increase of soil Cr contamination.

The relative severity between chromium (Cr)-mediated ecotoxicity and its bioaccumulation has rarely been compared and evaluated. This study employed pot incubation experiments to simulate the soil environment with increased Cr pollution and study their effects on the growth of crops, including pepper, lettuce, wheat, and rice. Results showed that increasing total Cr presented ascendant ecotoxicity in upland soils when pH > 7.5, and significantly reduced the yield of pepper, lettuce and wheat grain by 0.3-100 %, whereas, this effect was weakened even reversed as the pH decreased. Surprisingly, a series of soils with Cr concentration of 22.7-623.5 mg kg-1 did not cause Cr accumulation in four crops over the Chinese permissible limit. The toxicity of Cr was highly associated with extractable Cr, where Cr (VI) made the greater contributions than Cr (III). Conclusively, the ecotoxicity of Cr poses a greater environmental issue as compared to the bioaccumulation of Cr in crops in upland soils, while extractable Cr (VI) makes the predominant contributions to the ecotoxicity of Cr as the total Cr increased. Our study proposes a synchronous consideration involving total Cr and Cr (VI) as the theoretical basis to establish a more reliable soil quality standard for safe production in China.

Polymer Fiber Rigid Network with High Glass Transition Temperature Reinforces Stability of Organic Photovoltaics.

Organic photovoltaics (OPVs) need to overcome limitations such as insufficient thermal stability to be commercialized. The reported approaches to improve stability either rely on the development of new materials or on tailoring the donor/acceptor morphology, however, exhibiting limited applicability. Therefore, it is timely to develop an easy method to enhance thermal stability without having to develop new donor/acceptor materials or donor-acceptor compatibilizers, or by introducing another third component. Herein, a unique approach is presented, based on constructing a polymer fiber rigid network with a high glass transition temperature (Tg) to impede the movement of acceptor and donor molecules, to immobilize the active layer morphology, and thereby to improve thermal stability. A high-Tg one-dimensional aramid nanofiber (ANF) is utilized for network construction. Inverted OPVs with ANF network yield superior thermal stability compared to the ANF-free counterpart. The ANF network-incorporated active layer demonstrates significantly more stable morphology than the ANF-free counterpart, thereby leaving fundamental processes such as charge separation, transport, and collection, determining the device efficiency, largely unaltered. This strategy is also successfully applied to other photovoltaic systems. The strategy of incorporating a polymer fiber rigid network with high Tg offers a distinct perspective addressing the challenge of thermal instability with simplicity and universality.

Regulation of fat crystals in water-in-oil emulsions by high-intensity ultrasound: Crystal size and tracing of droplet distribution.

In this paper, two emulsion systems with high and low solid fat contents were prepared from 20 % water phase and 80 % oil phase by adjusting the palm oil/palm stearin/soybean oil ratio. Different ultrasonic power and time were used for the pretreatment of emulsion with different solid fat content, and the application characteristics of ultrasonic in W/O emulsions were explored and evaluated. Directly using high-intensity ultrasound to prepare fatty emulsions would weaken the hardness and storage modulus G' of the samples. Although ultrasound reduced the size of fat crystals in emulsions, the interaction between water droplets and fat crystals needs to be considered. After ultrasonic treatment, water droplets were difficult to immobilize on the crystal surface and thus acted as an active filler to stabilize the emulsion together with the fat crystal network. In high solid fat emulsion systems, an increase in ultrasound power (from 100 W to 200 W) could more affect the crystallization behavior of fats than an increase in ultrasound duration (from 30 s to 60 s), and the distribution of crystals and droplets was more uniform. In the low solid fat emulsion system, the texture of the sample after ultrasonic treatment was softer, and the surface was more delicate and smoother. However, the higher ultrasonic intensity (200 W) was not conducive to the preparation of the spread. Although the ultrasound with excessive intensity promoted the formation of small crystals, it would also lead to the aggregation of small crystals. These small crystals cannot form a uniform crystal network, which increases the fluidity of emulsions.

Detection of calcitonin gene-related peptide based on increased antigen-driven interaction with antibody variable regions.

Introduction: Calcitonin gene-related peptide (CGRP) is involved in trigeminal neuralgia and migraine, and measuring the CGRP concentration in the serum is crucial for the early prediction of these conditions. Current methods for CGRP detection are primarily radioimmunoassay, which needs radioactive substances and enzyme-linked immunosorbent assays (ELISAs) which need long detection time and some have a narrow detection range. Methods: The genes of anti-CGRP antibody variable regions were cloned into pDong1 vector to obtain pDong1/Fab-CGRP, with which phage-Fab was prepared, and the concentration of CGRP was detected by competitive ELISA. The pDong1/Fab-CGRP was modified to obtain pDong1/OS-CGRP, with which the co-expression solution containing phage-displayed heavy chain variable fragments (phage-VH) and light chain was obtained. CGRP was detected by OS-ELISA based on phage-VH, antibody light chain, and anti-light chain antibody. The VL gene was cloned into the pMAL vector to obtain pMAL-VL (CGRP), with which maltose binding protein fused with VL (MBP-VL) was prepared. CGRP was detected by OS-ELISA employing MBP-VL and phage-VH. Results: OS-ELISAs that measure the CGRP concentration by quantifying the interaction between variable regions were investigated. OS-ELISA using phage-VH and secreted light chains in the same culture system exhibited a limit of detection (LOD) of 0.05 nM, offering higher sensitivity than competitive assay with an LOD of 0.75 nM, whereas using phage-VH and separately prepared MBP-VL exhibited an LOD of 0.15 nM and a broader detection range of 0.15-500 nM than competitive ELISA, whose detection range was 0.75-10 nM. Discussion: The combination of the two OS assays achieved high sensitivity and a broad detection range for CGRP, which may have significance in clinical applications.

Comparative proteomics reveals that fatty acid metabolism is involved in myocardial adaptation to chronic hypoxic injury.

Congenital heart disease (CHD) is the most serious form of heart disease, and chronic hypoxia is the basic physiological process underlying CHD. Some patients with CHD do not undergo surgery, and thus, they remain susceptible to chronic hypoxia, suggesting that some protective mechanism might exist in CHD patients. However, the mechanism underlying myocardial adaptation to chronic hypoxia remains unclear. Proteomics was used to identify the differentially expressed proteins in cardiomyocytes cultured under hypoxia for different durations. Western blotting assays were used to verify protein expression. A Real-Time Cell Analyzer (RTCA) was used to analyze cell growth. In this study, 3881 proteins were identified by proteomics. Subsequent bioinformatics analysis revealed that proteins were enriched in regulating oxidoreductase activity. Functional similarity cluster analyses showed that chronic hypoxia resulted in proteins enrichment in the mitochondrial metabolic pathway. Further KEGG analyses found that the proteins involved in fatty acid metabolism, the TCA cycle and oxidative phosphorylation were markedly upregulated. Moreover, knockdown of CPT1A or ECI1, which is critical for fatty acid degradation, suppressed the growth of cardiomyocytes under chronic hypoxia. The results of our study revealed that chronic hypoxia activates fatty acid metabolism to maintain the growth of cardiomyocytes.

Nanomaterials-based advanced systems for photothermal / photodynamic therapy of oral cancer.

The traditional clinical approaches for oral cancer consist of surgery, chemotherapy, radiotherapy, immunotherapy, and so on. However, these treatments often induce side effects and exhibit limited efficacy. Photothermal therapy (PTT) emerges as a promising adjuvant treatment, utilizing photothermal agents (PTAs) to convert light energy into heat for tumor ablation. Another innovative approach, photodynamic therapy (PDT), leverages photosensitizers (PSs) and specific wavelength laser irradiation to generate reactive oxygen species (ROS), offering an effective and non-toxic alternative. The relevant combination therapies have been reported in the field of oral cancer. Simultaneously, the advancement of nanomaterials has propelled the clinical application of PTT and PDT. Therefore, a comprehensive understanding of PTT and PDT is required for better application in oral cancer treatment. Here, we review the use of PTT and PDT in oral cancer, including noble metal materials (e.g., Au nanoparticles), carbon materials (e.g., graphene oxide), organic dye molecules (e.g., indocyanine green), organic molecule-based agents (e.g., porphyrin-analog phthalocyanine) and other inorganic materials (e.g., MXenes), exemplify the advantages and disadvantages of common PTAs and PSs, and summarize the combination therapies of PTT with PDT, PTT/PDT with chemotherapy, PTT with radiotherapy, PTT/PDT with immunotherapy, and PTT/PDT with gene therapy in the treatment of oral cancer. The challenges related to the PTT/PDT combination therapy and potential solutions are also discussed.

Dictyophora indusiata polysaccharide mediates priming of the NLRP3 inflammasome activation via TLR4/ NF-κB signaling pathway to exert immunostimulatory effects.

Dictyophora indusiata, commonly known as bamboo fungus, is a type of edible mushroom that is highly popular worldwide for its rich flavor and nutritional value. It is also recognized for its pharmaceutical efficacy, with medicinal benefits attributed to its consumption. One of the most important components of Dictyophora indusiata is polysaccharide, which has been acknowledged as a promising regulator of biological response due to its immunostimulatory and anti-inflammatory properties. However, the specific roles of polysaccharide in modulating the NOD-like receptor protein 3 (NLRP3) inflammasome activation within macrophages remain relatively under-researched. To investigate this further, the mechanism by which Dictyophora indusiata polysaccharide (DIP) exerts its immunostimulatory activity in RAW 264.7 macrophages was analyzed. Results indicated that DIP has the potential to facilitate the priming of NLRP3 inflammasome activation by enhancing TLR4 expression, phosphorylation of IκB-α, and nuclear translocation of NF-κB p65 subunit. It was noted that DIP was unable to mediate the second step of NLRP3 inflammasome activation. The findings of this study provide compelling evidence that DIP has immunomodulatory effects by modulating the NLRP3 inflammasome in RAW264.7 macrophages.

Study on synergistic mechanism of molybdenum disulfide/sodium carboxymethyl cellulose composite nanofiber mats for photothermal/photodynamic antibacterial treatment.

Innovative antibacterial therapies using nanomaterials, such as photothermal (PTT) and photodynamic (PDT) treatments, have been developed for treating wound infections. However, creating secure wound dressings with these therapies faces challenges. The primary focus of this study is to prepare an antibacterial nanofiber dressing that effectively incorporates stable loads of functional nanoparticles and demonstrates an efficient synergistic effect between PTT and PDT. Herein, a composite nanofiber mat was fabricated, integrating spherical molybdenum disulfide (MoS2) nanoparticles. MoS2 was deposited onto polylactic acid (PLA) nanofiber mats using vacuum filtration, which was further stabilized by sodium carboxymethyl cellulose (CMC) adhesion and glutaraldehyde (GA) cross-linking. The composite nanofibers demonstrated synergistic antibacterial effects under NIR light irradiation, and the underlying mechanism was explored. They induce bacterial membrane permeability, protein leakage, and intracellular reactive oxygen species (ROS) elevation, ultimately leading to >95 % antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), which is higher than that of single thermotherapy (almost no antibacterial activity) or ROS therapy (about 80 %). In addition, the composite nanofiber mats exhibited promotion effects on infected wound healing in vivo. This study demonstrates the great prospects of composite nanofiber dressings in clinical treatment of bacterial-infected wounds.

Complete remission of advanced pancreatic cancer induced by claudin18.2-targeted CAR-T cell therapy: a case report.

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy. Therefore, novel effective therapeutic strategies are urgently needed. Here, we report a case of complete remission of advanced PC induced by claudin18.2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18.2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18.2-targeted CAR-T cell infusion at a dose of 1.2 × 106 cells/kg on November 21, 2022. During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18.2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months. Unfortunately, the patient experienced claudin18.2-negative relapse in July, 2023. Despite antigen-negative relapse after claudin18.2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18.2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC.

A heterogeneous cobalt cubane polymer co-catalyst for cooperative water oxidation.

We achieve a successful transition of Co4O4 molecules from a homogeneous to a heterogeneous system by modifying the functional groups at their termini. The resulting cocatalyst, denoted as Co4O4-poly, not only preserved the catalytic sites of Co4O4 molecules but also exhibited outstanding performance in catalyzing water oxidation.

Metal Sulfide S-Scheme Homojunction for Photocatalytic Selective Phenylcarbinol Oxidation.

Metal sulfide-based homojunction photocatalysts are extensively explored with improved photocatalytic performance. However, the construction of metal sulfide-based S-scheme homojunction remains a challenge. Herein, the fabrication of 2D CdIn2S4 nanosheets coated 3D CdIn2S4 octahedra (referred to as 2D/3D n-CIS/o-CIS) S-scheme homojunction photocatalyst is reported by simply adjustment of polyvinyl pyrrolidone amount during the solvothermal synthesis. The formation of S-scheme homojunction within n-CIS/o-CIS is systematically investigated via a series of characterizations, which can generate an internal electric field to facilitate the separation and migration of photogenerated electron-hole pairs. The 2D/3D n-CIS/o-CIS composite exhibits significantly improved photocatalytic activity and stability in the selective oxidation of phenylcarbinol (PhCH2OH) to benzaldehyde (PhCHO) when compared to pure n-CIS and o-CIS samples under visible light irradiation. It is hoped that this work can contribute novel insights into the development of metal sulfides S-scheme homojunction photocatalysts for solar energy conversion.

Correlation of ventricle epicardial fat volume and triglyceride-glucose index in patients with chronic heart failure.

To explore the association of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance (CMR) and the insulin resistance indicator of triglyceride-glucose (TyG) index in patients with chronic HF (CHF), this retrospective cohort study included adult CHF patients with confirmed diagnosis of heart failure from January 2018 to December 2020. All patients underwent 3.0T CMR, and EFV were measured under short-axis cine. Spearman correlation, multivariate linear regression, and restricted cubic spline (RCS) regression were used to analyze their association. There were 516 patients with CHF, of whom 69.8% were male. Median EFV was 57.14mL and mean TyG index was 8.48. Spearman correlation analysis showed that TyG index was significantly correlated with the EFV in CHF patients (r = 0.247, P < 0.001). Further analysis showed that TyG index levels were significantly associated with EFV as both continuous variables (Unstandardized ß = 6.556, P < 0.001) and across the increasing quartiles (ß = 7.50, 95% CI [1.41, 13.59], P < 0.05). RCS demonstrated there were a positive trend and linear association between EFV and TyG index in CHF patients (P for nonliearity = 0.941). In patients with CHF, the TyG index was positively and linearly associated with the EFV, which supports the metabolic roles of epicardial adipose tissue regarding insulin resistance.

Enhanced L-serine production by Corynebacterium glutamicum based on novel insights into L-serine exporters.

The L-serine exporters ThrE and SerE play important roles in L-serine production by Corynebacterium glutamicum. Deletion of both thrE and serE decreased L-serine titer by 60%, suggesting the existence of other L-serine exporters. A comparative transcriptomics identified NCgl0254 and NCgl0255 as novel L-serine exporters. Further analysis of the contributions of ThrE, SerE, NCgl0254, and NCgl0255 found that SerE was the major L-serine exporter in C. glutamicum and these four L-serine exporters were responsible for 79.7% of L-serine export. Deletion of one L-serine exporter upregulated the transcription levels of the other three, which might be coursed by increased intracellular concentrations of L-serine. Overexpression of NCgl0254 and NCgl0255 increased L-serine titer by 20.8% in C. glutamicum A36, while overexpression of the four L-serine exporters increased L-serine production by 31.9% (41.1 g·L-1 ) in C. glutamicum A36. The identification of novel L-serine exporters in C. glutamicum will help to improve industrial production of L-serine.

A Facile Design for Water-Oxidation Molecular Catalysts Precise Assembling on Photoanodes.

Regulating the interfacial charge transfer behavior between cocatalysts and semiconductors remains a critical challenge for attaining efficient photoelectrochemical water oxidation reactions. Herein, using bismuth vanadate (BiVO4 ) photoanode as a model, it introduces an Au binding bridge as holes transfer channels onto the surfaces of BiVO4 , and the cyano-functionalized cobalt cubane (Co4 O4 ) molecules are preferentially immobilized on the Au bridge due to the strong adsorption of cyano groups with Au nanoparticles. This orchestrated arrangement facilitates the seamless transfer of photogenerated holes from BiVO4 to Co4 O4 molecules, forming an orderly charge transfer pathway connecting the light-absorbing layer to reactive sites. An exciting photocurrent density of 5.06 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (3.4 times that of BiVO4 ) is obtained by the Co4 O4 @Au(A)/BiVO4 photoanode, where the surface charge recombination is almost completely suppressed accompanied by a surface charge transfer efficiency over 95%. This work represents a promising strategy for accelerating interfacial charge transfer and achieving efficient photoelectrochemical water oxidation reaction.

Curcumin and analogues in mitigating liver injury and disease consequences: From molecular mechanisms to clinical perspectives.

BACKGROUND: Liver injury is a prevalent global health concern, impacting a substantial number of individuals and leading to elevated mortality rates and socioeconomic burdens. Traditional primary treatment options encounter resource constraints and high costs, prompting exploration of alternative adjunct therapies, such as phytotherapy. Curcumin demonstrates significant therapeutic potential across various medical conditions, particularly emerging as a promising candidate for liver injury treatment. PURPOSE: This study aims to provide current evidence maps of curcumin and its analogs in the context of liver injury, covering aspects of biosafety, toxicology, and clinical trials. Importantly, it seeks to summarize the intricate mechanisms modulated by curcumin. METHODS: We conducted a comprehensive search of MEDLINE, Web of Science, and Embase up to July 2023. Titles and abstracts were reviewed to identify studies that met our eligibility criteria. The screening process involved three authors independently assessing the potential of curcumin mitigating liver injury and its disease consequences by reviewing titles, abstracts, and full texts. RESULTS: Curcumin and its analogs have demonstrated low toxicity in vitro and in vivo. However, the limited bioavailability has hindered their advanced use in liver injury. This limitation can potentially be addressed by nano-curcumin and emerging drug delivery systems. Curcumin plays a role in alleviating liver injury by modulating the antioxidant system, as well as cellular and molecular pathways. The specific mechanisms involve multiple pathways, such as NF-κB, p38/MAPK, and JAK2/STAT3, and the pro-apoptosis Bcl-2/Bax/caspase-3 axis in damaged cells. Additionally, curcumin targets nutritional metabolism, regulating the substance in liver cells and tissues. The microenvironment associated with liver injury, like extracellular matrix and immune cells and factors, is also regulated by curcumin. Initial evaluation of curcumin and its analogs through 12 clinical trials demonstrates their potential application in liver injury. CONCLUSION: Curcumin emerges as a promising phytomedicine for liver injury owing to its effectiveness in hepatoprotection and low toxicity profile. Nevertheless, in-depth investigations are warranted to unravel the complex mechanisms through which curcumin influences liver tissues and overall physiological milieu. Moreover, extensive clinical trials are essential to determine optimal curcumin dosage forms, maximizing its benefits and achieving favorable clinical outcomes.

Fluorescence quenching-based immunological probe for ticagrelor monitoring.

Introduction: Ticagrelor is extensively utilized for the treatment of acute coronary syndromes (ACS), but its platelet aggregation inhibitory effects can potentially result in tissue bleeding, posing a serious risk to patients' lives. Methods: In this study, we developed highly sensitive full length anti-ticagrelor Quenchbodies (Q-bodies) for fast monitoring of ticagrelor both in solution and serum for the first time. Ticagrelor coupled with N- hydroxysuccinimide (Ticagrelor-NHS) ester was also designed and synthesized for interaction and biological activity detection. Results: Both ATTO-labeled MEDI2452 (2452A) Q-body and TAMRA-labeled IgG 152 (152T) Q-body demonstrated efficient detection of ticagrelor and its active metabolite (TAM). The 2452A Q-body exhibited a broader detection range, while the 152T Q-body displayed a lower limit of detection (LOD). Under physiological conditions (Ticagrelor:TAM, 3:1), the concentration of ticagrelor was further measured, yielding LOD values of 4.65 pg/mL and 2.75 pg/mL for the two Q-bodies, with half-maximal effect concentrations of 8.15 ng/mL and 3.0 ng/mL, respectively. Discussion: Compared with traditional liquid chromatography-mass spectrometry (LC-MS) methods, anti-ticagrelor Q-bodies have higher sensitivity and detection speed. It enabled the completion of analysis within 3 min, facilitating rapid preoperative detection of blood drug concentration in ACS to determine the feasibility of surgery and mitigate the risk of intraoperative and postoperative hemorrhage. The swift detection of ticagrelor holds promise for enhancing individualized drug administration, preventing adverse reactions, and providing preoperative guidance.

Enhanced light extraction efficiency of GaN-based green micro-LED modulating by a thickness-tunable SiO2 passivation structure.

Green micro-light emitting diodes (micro-LEDs) is one of the three primary color light sources as full-color display, which serves as a key research object in the field of micro-LED display. As the micro-LED size decreases, the surface-area-to-volume ratio of the device increases, leading to more serious damage on the sidewall by inductively coupled plasma (ICP) etching. The passivation process of SiO2 provides an effective method to reduce sidewall damage caused by ICP etching. In this work, green rectangular micro-LEDs with passivation layer thickness of 0∼600 nm was designed using the finite-difference time-domain (FDTD) simulation. In order to verify the simulation results, the micro-LED array was fabricated by parallel laser micro-lens array (MLA) lithography in high speed and large area. The effect of the SiO2 passivation layer thickness on the performance of the green micro-LED was analyzed, which shows that the passivation layer thickness-light extraction efficiency curve fluctuates periodically. For the sample with 90 nm thickness of SiO2 passivation layer, there exists a small leakage current and higher operating current density, and the maximum external quantum efficiency (EQE) is 2.8 times higher than micro-LED without SiO2 passivation layer.

Immunoinformatics Prediction and Protective Efficacy of Vaccine Candidate PiuA-PlyD4 Against Streptococcus Pneumoniae.

Purpose: This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments. Methods: In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored. Results: PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81±2.32) ×105. The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process. Conclusion: The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae.