Public Response to Federal Electronic Cigarette Regulations Analyzed Using Social Media Data Through Natural Language Processing: Topic Modeling Study.

BACKGROUND: e-Cigarette (electronic cigarette) use has been a public health issue in the United States. On June 23, 2022, the US Food and Drug Administration (FDA) issued marketing denial orders (MDOs) to Juul Labs Inc for all their products currently marketed in the United States. However, one day later, on June 24, 2022, a federal appeals court granted a temporary reprieve to Juul Labs that allowed it to keep its e-cigarettes on the market. As the conversation around Juul continues to evolve, it is crucial to gain insights into the sentiments and opinions expressed by individuals on social media. OBJECTIVE: This study aims to conduct a comprehensive analysis of tweets before and after the ban on Juul, aiming to shed light on public perceptions and sentiments surrounding this contentious topic and to better understand the life cycle of public health-related policy on social media. METHODS: Natural language processing (NLP) techniques were used, including state-of-the-art BERTopic topic modeling and sentiment analysis. A total of 6023 tweets and 22,288 replies or retweets were collected from Twitter (rebranded as X in 2023) between June 2022 and October 2022. The encoded topics were used in time-trend analysis to depict the boom-and-bust cycle. Content analyses of retweets were also performed to better understand public perceptions and sentiments about this contentious topic. RESULTS: The attention surrounding the FDA's ban on Juul lasted no longer than a week on Twitter. Not only the news (ie, tweets with a YouTube link that directs to the news site) related to the announcement itself, but the surrounding discussions (eg, potential consequences of this ban or block and concerns toward kids or youth health) diminished shortly after June 23, 2022, the date when the ban was officially announced. Although a short rebound was observed on July 4, 2022, which was contributed by the suspension on the following day, discussions dried out in 2 days. Out of the top 50 most retweeted tweets, we observed that, except for neutral (23/45, 51%) sentiment that broadcasted the announcement, posters responded more negatively (19/45, 42%) to the FDA's ban. CONCLUSIONS: We observed a short life cycle for this news announcement, with a preponderance of negative sentiment toward the FDA's ban on Juul. Policy makers could use tactics such as issuing ongoing updates and reminders about the ban, highlighting its impact on public health, and actively engaging with influential social media users who can help maintain the conversation.

Progress in antibacterial applications of nanozymes.

Bacterial infections are a growing problem, and antibiotic drugs can be widely used to fight bacterial infections. However, the overuse of antibiotics and the evolution of bacteria have led to the emergence of drug-resistant bacteria, severely reducing the effectiveness of treatment. Therefore, it is very important to develop new effective antibacterial strategies to fight multi-drug resistant bacteria. Nanozyme is a kind of enzyme-like catalytic nanomaterials with unique physical and chemical properties, high stability, structural diversity, adjustable catalytic activity, low cost, easy storage and so on. In addition, nanozymes also have excellent broad-spectrum antibacterial properties and good biocompatibility, showing broad application prospects in the field of antibacterial. In this paper, we reviewed the research progress of antibacterial application of nanozymes. At first, the antibacterial mechanism of nanozymes was summarized, and then the application of nanozymes in antibacterial was introduced. Finally, the challenges of the application of antibacterial nanozymes were discussed, and the development prospect of antibacterial nanozymes was clarified.

Atomic-Scale Mechanism of Enhanced Electron-Phonon Coupling at the Interface of MgB2 Thin Films.

In conventional Bardeen-Cooper-Schrieffer (BCS) superconductors, electron-phonon coupling is the fundamental mechanism of superconductivity. For instance, the superconductivity of magnesium diboride (MgB2) comes from the coupling between E2g modes (in-plane boron-boron bond vibrations) and self-doped charge carriers. In thin films and ceramics of BCS superconductors, interfaces with discontinuous chemical bonds may alter the local electron-phonon coupling. However, such effects remain largely unexplored. Here, we investigate the heterointerface of the MgB2 film on the SiC substrate at the atomic scale using electron microscopy and spectroscopy. We detect the presence of a thin MgO layer with a thickness of ∼1 nm between MgB2 and SiC. Atomic-level electron energy loss spectra (EELS) show MgB2-E2g mode splitting and softening near the MgB2/MgO interface, which enhances electron-phonon coupling at the interface. Our findings highlight the potential of interface engineering to enhance superconductivity via modulating local phonon states and/or electron states.

A terphenyl derivative-based colorimetric-fluorimetric probe for the detection of lysine and arginine and their bioimaging.

Lysine (Lys) and arginine (Arg) play a crucial role in the human diets, medical diagnostics, and functional biomaterial synthesis. The imbalance of intake for these two amino acids causes various diseases. Although many analytical techniques have been reported for the detection of amino acids, there are still some issues such as the need for bulky instruments, professional operators, sensitivity to be improved, and real-time detection. Here, a novel colorimetric-fluorimetric probe based on a terphenyl derivative (TPT) has been synthesized for the precise detection of Lys and Arg. In the EtOH-H2O solution of TPT, the NH2 group at the chain end of Lys/Arg undergoes a nucleophilic addition reaction with CN groups of benzothiazole groups of the probe TPT, which breaks the initial long-conjugated system of the probe molecule. As a result, blue shifts can be observed for both UV-vis absorption spectra and fluorescence spectra, accompanying with color changes of the TPT solution. The UV-vis absorption peak of TPT solution shifts from âˆ¼410 nm to âˆ¼325 nm, and the solution color changes from light-yellow to colorless. The fluorescence emission shifts from âˆ¼580 nm to âˆ¼470 nm and the bright-yellow TPT solution changes to blue under the irradiation of 365 nm UV light. For colorimetric method, the limits of detection (LoD) are 0.82 µM and 0.90 µM for Lys and Arg, respectively. For fluorimetric method, they are 2.02 nM and 1.62 nM for Lys and Arg, respectively. In addition, TPT has good selectivity and anti-interference for Lys and Arg. The synthesized probe TPT has been successfully used for the precise detection of Lys and Arg in drugs and for fluorescence imaging of living cells. This work demonstrates that terphenyl-based derivatives are promising organic probes for the detection of Lys and Arg, providing a new way for designing other amino acids probes.

Association of Wheezing Requiring Hospitalization Before 2 Years of Age With Autoimmune Diseases During Childhood: A 15-Year Follow-up Study From Birth.

PURPOSE: Wheezing in early life is most frequently caused by viral lower respiratory tract illnesses, constituting a significant disease burden in children. This study aimed to investigate the association of wheezing in early life with autoimmune diseases throughout childhood. METHODS: A population-matched retrospective cohort study was conducted in Korea between 2002 and 2017. The cohort comprised 34,959 children admitted with viral wheezing before 2 years of age and an equal number of the matched unexposed children born in 2002 and 2003. Exposed infants were defined as those hospitalized for bronchiolitis or bronchial asthma before the age of 2. Unexposed controls were matched by sex and birth year at a 1:1 ratio, using incidence density sampling. A Cox proportional hazard model controlled for multiple risk factors was employed. RESULTS: The median age at hospitalization for wheeze was 9 months (interquartile range, 5-15 months), and 63% of the exposed infants were male. Over the mean 15-year follow-up period, the incidence rate of autoimmune diseases was 74.0 and 62.2 per 10,000 person-years in the exposed and matched unexposed cohorts, respectively. The adjusted hazard ratio for any autoimmune disease in the exposed cohort was 1.15 (95% confidence interval, 1.09-1.23) in comparison with the unexposed cohort. The exposed cohort revealed an augmented risk for specific autoimmune diseases, including juvenile idiopathic arthritis, Kawasaki disease, Henoch-Schönlein purpura, psoriasis, idiopathic thrombocytopenic purpura, and immunoglobulin A nephropathy. Risks were heightened for children with multiple wheezing episodes or a persistent wheezing episode after the age of 2 years. CONCLUSIONS: This research identifies associations between early-life wheeze and the development of autoimmune diseases in childhood. Understanding these relationships can aid in recognizing the underlying pathophysiology of early-life wheeze and childhood autoimmune diseases, contributing to management strategies for these conditions.

Preoperative halo-gravity traction combined with one-stage posterior spinal fusion surgery following for severe rigid scoliosis with pulmonary dysfunction: a cohort study.

BACKGROUND: To assess the efficacy of preoperative halo-gravity traction (HGT) in treating severe spinal deformities, evaluating radiological outcomes, pulmonary function, and nutritional status. METHODS: This study retrospectively included 33 patients with severe spinal deformity who were admitted to our department from April 2018 to January 2022. All the patients underwent HGT prior to the posterior spinal fusion corrective surgery, with no patients having undergone anterior or posterior release procedures. The correction of deformity, pulmonary function tests (PFTs), and nutritional status data were collected and analyzed before and after HGT. RESULTS: A total of 33 patients (9 males, 24 females) were finally included in this study with an average age of 17.79 ± 7.96 (range 12-29) years. Among them, 20 patients were aged ≤ 16 years. The traction weight started from 1.5 kg and raised to 45.2 ± 13.2% of body weight on average progressively, with the average traction duration of 129 ± 63 days. After traction, the main curve was corrected from an average of 120.66 ± 3.89° to 94.88 ± 3.35°, and to 52.33 ± 22.36° (53%) after surgery(P < 0.05). PFTs also showed a significant increase in FVC%, FEV1%, and MEF% after traction [43.46 ± 14.76% vs. 47.33 ± 16.04%, 41.87 ± 13.68% vs. 45.19 ± 15.57%, and 40.44 ± 15.87% vs. 45.24 ± 17.91%, p < 0.05]. Total protein, albumin, and BMI were used as indicators of nutritional status. TP and albumin were significantly improved after traction, from 67.24 ± 5.43 g/L to 70.68 ± 6.98 g/L and 42.40 ± 3.44 g/L 45.72 ± 5.23 g/L, respectively(P < 0.05). No significant difference was found in deformity correction and lung function improvement between patients with traction for more or less than three months (p > 0.05). Two patients developed transient brachial plexus palsy during traction. CONCLUSIONS: Halo-gravity traction can partially correct spinal deformity, enhance pulmonary function. And HGT has been shown to facilitate an improved nutritional status in these patients. It could be used as a preoperative adjuvant treatment for severe spinal deformity. However, according to the study, a traction period longer than three months may not be necessary.

Comparing Closure Techniques for Pharyngeal Mucosa After Total Laryngectomy: Manual Suture, Linear Stapler, and Thyroid Gland Flap-A Retrospective Analysis.

Objective: This study aimed to compare the clinical effectiveness of manual suture (group A), linear stapler (group B), and thyroid gland flap (group C) for pharyngeal mucosal closure after total laryngectomy (TL) in laryngeal cancer patients. Methods: The data of laryngeal cancer patients who underwent TL between January 1, 2017, and December 1, 2021, were analyzed. Patients were categorized into group A, group B, and group C based on the closure technique. Various parameters, including general data, hospitalization days, total cost, pharyngeal closure time, pharyngeal fistula, pre- and post-surgical calcium levels, and thyroid function indexes, were compared. Results: The study included 81 patients (mean age: 64.09 ± 9.20 years), the general data of the 3 groups of patients were comparable. Tumor stage and primary tumor location varied significantly among the groups (P = .002 and P < .001, respectively). Group A was more commonly used for advanced-stage tumors with widespread invasion. Group B was primarily used for early-stage tumors localized to the larynx. Group C was preferred for cases with mucosal defects or extensive hypopharyngeal invasion. Group B presented a significantly shorter operation time and slightly lower total cost (P = .006). Pharyngeal fistula incidence was 17.28% (14/81), with comparable rates among the groups [12.35% (10/50) in group A, 12.5% (2/16) in group B, and 13.3% (2/15) in group C]. No dysphagia complications were observed during the 2-to-5-year follow-up. Blood calcium levels and thyroid function indicators showed no significant differences before and after surgery among the 3 groups (P > .05). Conclusion: Thyroid gland flap is a safe option that can be used to repair mucosal defects and close the pharyngeal cavity after TL surgery, but in the absence of mucosal defects and widespread tumor invasion, linear staplers are the most time-efficient method.

Anion Effect on the CuII-Neocuproine Mediator and Its Electrocatalysts for Dye-Sensitized Solar Cells: Polymeric Chalcogenides of PEDOT-PEDTT and [Ag2(SePh)2]n.

The synthetical methodology for the [Cu(dmp)2]2+/1+ (dmp = 2,9-dimethyl-1,10-phenanthroline; neocuproine) complexes has been systematically investigated by using various copper precursors, including CuCl2, Cu(NO3)2, and Cu(ClO4)2. After an anion exchange to trifluoromethanesulfonimide (TFSI), the tetra-coordinated CuII(dmp)2(TFSI)2-Cu(ClO4)2 (7.43%) outperformed the penta-coordinated CuII(dmp)2(TFSI)(NO3)-Cu(NO3)2 (4.30%) and CuII(dmp)2(TFSI)(Cl)-CuCl2. Polymeric chalcogenides, including a conducting copolymeric electrode of PEDOT-PEDTT [PEDOT = poly(3,4-ethylenedioxythiophene); PEDTT = poly(3,4-ethylenedithiothiophene)] and a coordination polymeric electrode of silver bezeneselenolate ([Ag2(SePh)2]n; mithrene), are introduced as the electrocatalysts for [Cu(dmp)2]2+/1+ for the first time. After optimization, dye-sensitized solar cells (DSSCs) based on carbon cloth (CC)/AgSePh-30 (10.18%) showed superior electrocatalytic ability compared to the benchmark CC/Pt (7.43%) due to numerous active sites provided by electron-donating Se atoms, high film roughness, and bottom-up 2D charge transfer routes. The DSSC based on CC/PEDTT-50 (10.38%) also outperformed CC/Pt due to numerous active sites provided by electron-donating S atoms and proper energy band structure. This work sheds light on the future design and synthesis in Cu-complex mediators and functional polymeric chalcogenides for high-performance DSSCs.

Role of physical activity and sedentary behavior in venous thromboembolism: a systematic review and dose-response meta-analysis.

Increasing studies have investigated the link between physical activity (PA) and sedentary behavior with venous thromboembolism (VTE) but the existing findings are not consistent and the independent relationship is uncertain. This meta-analysis aimed to comprehensively assess the shape of dose-response relationship between PA and sedentary behavior with VTE and further explore whether the relationship is independent after mutual adjustment. We systematically searched PubMed, Embase and Web of Science from inception to August 1, 2024. PA exposures were converted into MET-h/wk. Categorical meta-analyses and a cubic spline model were performed to evaluate the association between PA, sedentary behavior and VTE. Twenty-five articles including 31 studies were included. A curvilinear dose-response relationship between PA and VTE was observed, with steeper gradients even at lower PA levels. After adjustment for sedentary behavior, higher level of PA was independently associated with a reduced VTE risk (OR = 0.83, 95%CI:0.77-0.89). Based on population attributable fraction analyses, 2.37% (95%CI: 1.90-2.85%) of incident VTE could have been prevented if all adults had achieved half the PA minimum recommended level. A linear dose-response relationship between sedentary behavior and VTE risk was found, and there was a 2% higher risk of VTE (OR = 1.02, 95%CI: 1.00-1.03) for 1 h increment of sedentary behavior per day. After adjustment for PA, sedentary behavior was independently associated with an increased VTE risk (OR = 1.19, 95CI%:1.01-1.39). Our analyses demonstrated PA and sedentary time were indeed independently associated with the risk of VTE after mutually adjusting for sedentary time or PA, highlighting a unique perspective on their individual contributions. Further studies assessing the effects of different combinations of PA and sedentary time for assessing joint effects on VTE are needed.

Estimating Per-Class Statistics for Label Noise Learning.

Real-world data may contain a considerable amount of noisily labeled examples, which usually mislead the training algorithm and result in degraded classification performance on test data. Therefore, Label Noise Learning (LNL) was proposed, of which one popular research trend focused on estimating the critical statistics (e.g., sample mean and sample covariance), to recover the clean data distribution. However, existing methods may suffer from the unreliable sample selection process or can hardly be applied to multi-class cases. Inspired by the centroid estimation theory, we propose Per-Class Statistic Estimation (PCSE), which establishes the quantitative relationship between the clean (first-order and second-order) statistics and the corresponding noisy statistics for every class. This relationship is further utilized to induce a generative classifier for model inference. Unlike existing methods, our approach does not require sample selection from the instance level. Moreover, our PCSE can serve as a general post-processing strategy applicable to various popular networks pre-trained on the noisy dataset for boosting their classification performance. Theoretically, we prove that the estimated statistics converge to their ground-truth values as the sample size increases, even if the label transition matrix is biased. Empirically, we conducted intensive experiments on various binary and multi-class datasets, and the results demonstrate that PCSE achieves more precise statistic estimation as well as higher classification accuracy when compared with state-of-the-art methods in LNL.

MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis.

Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C-/- mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

Cu(I)-Catalyzed Highly Regioselective C-H Amidation of Quinoline N-Oxides with Dioxazolones.

A Cu(I)-catalyzed highly regioselective synthesis of 2-acetamidequinoline N-oxides using dioxazolones with quinoline N-oxides has been reported. The reaction possesses mild reaction conditions and excellent functional group compatibility. Furthermore, the addition of hydrochloric acid promotes the decomposition of copper complexes, which is beneficial for postprocessing.

PLXNA1 confers enzalutamide resistance in prostate cancer via AKT signaling pathway.

Although targeting the androgen signaling pathway by androgen receptor (AR) inhibitors, including enzalutamide, has shown therapeutic effectiveness, inevitable emergence of acquired resistance remains a critical challenge in the treatment of advanced prostate cancer (PCa). Recognizing targetable genomic aberrations that trigger endocrine treatment failure holds great promise for advancing therapeutic interventions. Here, we characterized PLXNA1, amplified in a subset of PCa patients, as a contributor to enzalutamide resistance (ENZR). Elevated PLXNA1 expression facilitated PCa proliferation under enzalutamide treatment due to AKT signaling activation. Mechanistically, PLXNA1 recruited NRP1 forming a PLXNA1-NRP1 complex, which in turn potentiated the phosphorylation of the AKT. Either inhibiting PLXNA1-NRP1 complex with an NRP1 inhibitor, EG01377, or targeting PLXNA1-mediated ENZR with AKT inhibitors, abolished the pro-resistance phenotype of PLXNA1. Taken together, combination of AKT inhibitor and AR inhibitors presents a promising therapeutic strategy for PCa, especially in advanced PCa patients exhibiting PLXNA1 overexpression.

Manganese Carbodiimide (MnNCN): A New Heterogeneous Mn Catalyst for the Selective Synthesis of Nitriles from Alcohols.

Earth-abundant manganese oxides (MnOx) were competitive candidates when screening catalysts for ammoxidation of alcohols into nitriles due to their redox property. However, over-oxidation and possible acid-catalyzed hydrolysis of nitriles into amides still limited the application of MnOx in nitrile synthesis. In this work, manganese carbodiimide (MnNCN) was first reported to be robust for the ammoxidation of alcohols into nitriles, avoiding over-oxidation and the hydrolysis. Besides the high activity and selectivity, MnNCN demonstrated wide substrate scope including the ammoxidation of primary alcohols into nitriles, the oxidative C-C bonds cleavage and ammoxidation of secondary alcohols, phenyl substituted aliphatic alcohols, and diols into nitriles. Controlled experiments and DFT calculation results revealed that the excellent catalytic performance of MnNCN originated from its high ability in the activation of O2 molecules, and favorable oxidative dehydrogenation of C=N bonds in the aldimine intermediates (RCH=NH) into nitriles, inhibiting the competitive side reaction of the oxidation of aldehydes into carboxylic acids, followed to amide byproducts. Moreover, the hydrolysis of nitriles was also inhibited over MnNCN for its weak acidity as compared with MnOx. This study provided new insights into Mn-catalyzed aerobic oxidations as a highly important complement to manganese oxides.

The expansion of MDSCs induced by exosomal PD-L1 promotes the progression of gastric cancer.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are the major factor in gastric cancer (GC) immune evasion. Nevertheless, the molecular process underlying the expansion of MDSCs induced by tumor-derived exosomes (TDEs) remains elusive. METHODS: The levels of exosomal and soluble PD-L1 in ninety GC patients were examined via enzyme-linked immunosorbent assay (ELISA) to determine their prognostic value. To investigate the correlation between exosomal PD-L1 and MDSCs, the percentage of MDSCs in the peripheral blood of 57 GC patients was assessed via flow cytometry. Through ultracentrifugation, the exosomes were separated from the GC cell supernatant and detected via Western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The function of exosomal PD-L1 in MDSCs was evaluated via immunofluorescence, Western blotting and flow cytometry in a GC cell-derived xenograft (CDX) model. RESULTS: The overall survival (OS) of GC patients in the high exosomal PD-L1 group was significantly lower than that of patients in the low exosomal PD-L1 group (P = 0.0042); however, there was no significant correlation between soluble PD-L1 and OS in GC patients (P = 0.0501). Furthermore, we found that the expression of exosomal PD-L1 was positively correlated with the proportions of polymorphonuclear MDSCs (PMN-MDSCs, r = 0.4944, P < 0.001) and monocytic MDSCs (M-MDSCs, r = 0.3663, P = 0.005) in GC patients, indicating that exosomal PD-L1 might induce immune suppression by promoting the aggregation of MDSCs. In addition, we found that exosomal PD-L1 might stimulate MDSC proliferation by triggering the IL-6/STAT3 signaling pathway in vitro. The CDX model confirmed that exosomal PD-L1 could stimulate tumor development and MDSC amplification. CONCLUSIONS: Exosomal PD-L1 has the potential to become a prognostic and diagnostic biomarker for GC patients. Mechanistically, MDSCs can be activated by exosomal PD-L1 through IL-6/STAT3 signaling and provide a new strategy against GC through the use of exosomal PD-L1 as a treatment target.

Augmented the sensitivity of photothermal-ferroptosis therapy in triple-negative breast cancer through mitochondria-targeted nanoreactor.

Ferroptosis primarily relies on reactive oxygen (ROS) production and lipid peroxide (LPO) accumulation, which opens up new opportunities for tumor therapy. However, a standalone ferroptosis process is insufficient in inhibiting tumor progression. Unlike previously reported Fe-based nanomaterials, we have engineered a novel nanoreactor named IR780/Ce@EGCG/APT, which uses metal-polyphenols network (Ce@EGCG) based on rare-earth cerium and epigallocatechin gallate (EGCG) to encapsulate IR780 and modified with the aptamer (AS1411). The intricately designed nanoreactor is specifically taken up by tumor cells, releasing Ce3+, EGCG, and IR780. On the one hand, Ce3+ triggers ROS production via a Fenton-like reaction, inducing ferroptosis in tumor cells. On the other hand, IR780 accumulates in mitochondria and disrupts mitochondrial function upon laser irradiation, leading to tumor cell apoptosis. EGCG serves as a sensitizer, simultaneously enhancing the sensitivity of tumor cells to ferroptosis and photothermal therapy. After a single dose and three times of 808 nm laser irradiation for treatment, it has been observed that the nanoreactor induces dendritic cells (DCs) maturation, facilitates cytotoxic T lymphocyte infiltration, improves immunosuppressive microenvironment, activates the systemic immune system, and generates long-term immune memory.

Interactive effects of chlorothalonil and Varroa destructor on Apis mellifera during adult stage.

The interaction between environmental factors affecting honey bees is of growing concern due to their potential synergistic effects on bee health. Our study investigated the interactive impact of Varroa destructor and chlorothalonil on workers' survival, fat body morphology, and the expression of gene associated with detoxification, immunity, and nutrition metabolism during their adult stage. We found that both chlorothalonil and V. destructor significantly decreased workers' survival rates, with a synergistic effect observed when bees were exposed to both stressors simultaneously. Morphological analysis of fat body revealed significant alterations in trophocytes, particularly a reduction in vacuoles and granules after Day 12, coinciding with the transition of the bees from nursing to other in-hive work tasks. Gene expression analysis showed significant changes in detoxification, immunity, and nutrition metabolism over time. Detoxification genes, such as CYP9Q2, CYP9Q3, and GST-D1, were downregulated in response to stressor exposure, indicating a potential impairment in detoxification processes. Immune-related genes, including defensin-1, Dorsal-1, and Kayak, exhibited an initially upregulation followed by varied expression patterns, suggesting a complex immune response to stressors. Nutrition metabolism genes, such as hex 70a, AmIlp2, VGMC, AmFABP, and AmPTL, displayed dynamic expression changes, reflecting alterations in nutrient utilization and energy metabolism in response to stressors. Overall, these findings highlight the interactive and dynamic effects of environmental stressor on honey bees, providing insights into the mechanisms underlying honey bee decline. These results emphasize the need to consider the interactions between multiple stressors in honey bee research and to develop management strategies to mitigate their adverse effects on bee populations.

Apelin-13-Loaded Macrophage Membrane-Encapsulated Nanoparticles for Targeted Ischemic Stroke Therapy via Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis.

Purpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke. Methods: MM were extracted from RAW264.7. PLGA was dissolved in dichloromethane, while Apelin-13 was dissolved in water, and CY5.5 was dissolved in dichloromethane. The precipitate was washed twice with ultrapure water and then resuspended in 10 mL to obtain an aqueous solution of PLGA nanoparticles. Subsequently, the cell membrane was evenly dispersed homogeneously and mixed with PLGA-COOH at a mass ratio of 1:1 for the hybrid ultrasound. DSPE-PEG-RVG29 was added and incubated for 1 h to obtain MM/ANPs. Results: In this study, we developed a functional nanoparticle delivery system (MM/ANPs) that utilizes macrophage membranes coated with DSPE-PEG-RVG29 peptide to efficiently deliver Apelin-13 to inflammatory areas using ischemic stroke therapy. MM/ANPs effectively cross the blood-brain barrier and selectively accumulate in ischemic and inflamed areas. In a mouse I/R injury model, these nanoparticles significantly improved neurological scores and reduced infarct volume. Apelin-13 is gradually released from the MM/ANPs, inhibiting NLRP3 inflammasome assembly by enhancing sirtuin 3 (SIRT3) activity, which suppresses the inflammatory response and pyroptosis. The positive regulation of SIRT3 further inhibits the NLRP3-mediated inflammation, showing the clinical potential of these nanoparticles for ischemic stroke treatment. The biocompatibility and safety of MM/ANPs were confirmed through in vitro cytotoxicity tests, blood-brain barrier permeability tests, biosafety evaluations, and blood compatibility studies. Conclusion: MM/ANPs offer a highly promising approach to achieve ischemic stroke-targeted therapy inhibiting NLRP3 inflammasome-mediated pyroptosis.

Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.

Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents.

Exploring emission spatiotemporal pattern and potential reduction capacity in China's aviation sector: Flight trajectory optimization perspective.

China's rapid expansion of civil aviation has led to an increase in pollution-related issues, causing adverse health effects on populations near airports and downwind. Accurately quantifying aviation emissions is essential for effective emission management. Here, we developed a high-resolution aviation emissions inventory for China by employing a bottom-up approach that relied on daily flight schedules. By using the Aeronautical Information Publication (AIP) to reproduce real-world flight routes rather than conventional great-circle routes, we improved the accuracy of emissions and investigated the potential for reducing these emissions. Our findings demonstrated substantial variations in domestic civil aviation emissions both spatially and temporally. Emissions peaked in most provinces during Chinese holidays, particularly the Chinese Lunar New Year and summer holidays, highlighting the importance of detailed activity data for accurate emissions calculations. Therefore, we recommend extensive utilization of real-world flight routes, particularly in areas with limited Automatic Dependent Surveillance-Broadcast (ADS-B) coverage since they provide more accurate representations of actual flight trajectories. Our study also identified regions like Shaanxi, Sichuan, Beijing, and their surroundings having considerable potential for emission reduction due to substantial deviations from great-circle routes. This approach can enhance the accuracy and spatiotemporal resolution of aviation emissions at national and global scales throughout the year, without relying on extensive, long-term real-time flight trajectories. Additionally, it provides a unique way to quantify the potential for emission reductions across provinces in civil aviation, ultimately contributing to mitigating pollution-related health impacts from aviation emissions and promoting a more sustainable aviation industry.