Effectiveness and biocompatibility evaluation of a novel absorbable bone wax used in bone tissue.

OBJECTIVE: To determine the hemostatic effectivity and biocompatibility of a novel absorbable bone wax in comparison with a commercially available product. METHODS: 18 small fat-tail sheep were used to simulate clinical surface bleeding of sternal injury. Hemostasis effectiveness, the degree of bone healing, Mirco-CT, histopathology were evaluated over a period after the application of the material to the surgically created wound. RESULTS: The absorbable bone wax used in the study stopped bleeding immediately and did not affect bone healing. The histopathological results also showed that there were no complications associated with the new material. CONCLUSION: The results showed that the new absorbable bone wax used in this study was effective and biocompatible.

Enhancing radiotherapy response via intratumoral injection of a TLR9 agonist in autochthonous murine sarcomas.

Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to RT in transplanted tumors, but the mechanisms of this enhancement remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft-tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and 2 doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells. To characterize the immune response to CpG+RT, we performed bulk RNA-Seq, single-cell RNA-Seq, and mass cytometry. Sarcomas treated with 20 Gy and CpG demonstrated increased CD8 T cells expressing markers associated with activation and proliferation, such as Granzyme B, Ki-67, and IFN-γ. CpG+RT also upregulated antigen presentation pathways on myeloid cells. Furthermore, in sarcomas treated with CpG+RT, TCR clonality analysis suggests an increase in clonal T cell dominance. Collectively, these findings demonstrate that CpG+RT significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft-tissue sarcoma.

Metal ions-anchored bacterial outer membrane vesicles for enhanced ferroptosis induction and immune stimulation in targeted antitumor therapy.

The activation of ferroptosis presents a versatile strategy for enhancing the antitumor immune responses in cancer therapy. However, developing ferroptosis inducers that combine high biocompatibility and therapeutic efficiency remains challenging. In this study, we propose a novel approach using biological nanoparticles derived from outer membrane vesicles (OMVs) of Escherichia coli for tumor treatment, aiming to activate ferroptosis and stimulate the immune responses. Specifically, we functionalize the OMVs by anchoring them with ferrous ions via electrostatic interactions and loading them with the STING agonist-4, followed by tumor-targeting DSPE-PEG-FA decoration, henceforth referred to as OMV/SaFeFA. The anchoring of ferrous ions endows the OMVs with peroxidase-like activity, capable of inducing cellular lipid peroxidation by catalyzing H2O2 to •OH. Furthermore, OMV/SaFeFA exhibits pH-responsive release of ferrous ions and the agonist, along with tumor-targeting capabilities, enabling tumor-specific therapy while minimizing side effects. Notably, the concurrent activation of the STING pathway and ferroptosis elicits robust antitumor responses in colon tumor-bearing mouse models, leading to exceptional therapeutic efficacy and prolonged survival. Importantly, no acute toxicity was observed in mice receiving OMV/SaFeFA treatments, underscoring its potential for future tumor therapy and clinical translation.

Parking Lot Traffic Prediction Based on Fusion of Multifaceted Spatio-Temporal Features.

With the rapid growth of population and vehicles, issues such as traffic congestion are becoming increasingly apparent. Parking guidance and information (PGI) systems are becoming more critical, with one of the most important tasks being the prediction of traffic flow in parking lots. Predicting parking traffic can effectively improve parking efficiency and alleviate traffic congestion, traffic accidents, and other problems. However, due to the complex characteristics of parking spatio-temporal data, high levels of noise, and the intricate influence of external factors, there are three challenges to predicting parking traffic in a city effectively: (1) how to better model the nonlinear, asymmetric, and complex spatial relationships among parking lots; (2) how to model the temporal autocorrelation of parking flow more accurately for each parking lot, whether periodic or aperiodic; and (3) how to model the correlation between external influences, such as holiday weekends, POIs (points of interest), and weather factors. In this context, this paper proposes a parking lot traffic prediction model based on the fusion of multifaceted spatio-temporal features (MFF-STGCN). The model consists of a feature embedding module, a spatio-temporal attention mechanism module, and a spatio-temporal convolution module. The feature embedding module embeds external features such as weekend holidays, geographic POIs, and weather features into the time series, the spatio-temporal attention mechanism module captures the dynamic spatio-temporal correlation of parking traffic, and the spatio-temporal convolution module captures the spatio-temporal features by using graph convolution and gated recursion units. Finally, the outputs of adjacent time series, daily series, and weekly series are weighted and fused to obtain the final prediction results, thus predicting the parking lot traffic flow more accurately and effectively. Results on real datasets demonstrate that the proposed model enhances prediction performance.

Improving the Oxidation Resistance of Phenolic Resin Pyrolytic Carbons by In Situ Catalytic Formation of Carbon Nanofibers via Copper Nitrate.

Phenolic resin pyrolytic carbons were obtained by catalytic pyrolysis of phenolic resin at 500 °C, 600 °C, 700 °C, and 800 °C for 3 h in an argon atmosphere using copper nitrate as a catalyst precursor. The effects of copper salts on the pyrolysis process of phenolic resin as well as the structural evolution and oxidation resistance of phenolic resin pyrolytic carbons were studied. The results showed that copper oxide (CuO) generated from the thermal decomposition of copper nitrate was reduced to copper (Cu) by the gas generated from the thermal decomposition of the phenolic resin. Carbon nanofibers with tapered structures were synthesized by Cu catalysis of pyrolysis gas at 500-800 °C. The catalytic pyrolysis of phenolic resin with Cu increased the graphitization degree and reduced the pore volume of the phenolic resin pyrolytic carbons. The combined action improved the oxidation resistance of phenolic resin pyrolytic carbons.

Comparing the effect of FUAS and myomectomy on the elasticity of myometrium around targeted uterine fibroid.

BACKGROUND: Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF. METHODS: This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME. RESULTS: The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively. CONCLUSION: The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.

Heart rate variability during sleep onset in patients with insomnia with or without comorbid sleep apnea.

OBJECTIVES: Pre-sleep stress or hyperarousal is a known key etiological component in insomnia disorder. Despite this, physiological alterations during the sleep onset are not well-understood. In particular, insomnia and obstructive sleep apnea (OSA) are highly prevalent co-morbid conditions, where autonomic regulation may be altered. We aimed to characterize heart rate variability (HRV) during sleep onset as a potential measure of pre-sleep hyperarousal. METHODS: We described the profile of pre-sleep HRV measures and explore autonomic differences in participants with self-reported insomnia disorder (with no OSA, n = 69; with mild OSA, n = 70; with moderate or severe OSA, n = 66), compared to normal sleep controls (n = 123). Heart rate data during the sleep onset process were extracted for HRV analyses. RESULTS: During the sleep onset process, compared to normal sleep controls, participants with insomnia had altered HRV, indicated by higher heart rate (p = 0.004), lower SDNN (p = 0.003), reduced pNN20 (p < 0.001) and pNN50 (p = 0.010) and lower powers (p < 0.001). Participants with insomnia and moderate/severe OSA may have further deteriorated HRV outcomes compared to no/mild OSA patients with insomnia but differences were not significant. Insomnia itself was associated with significantly higher heart rate, lower pNN20, and lower high frequency power even after adjustment for age, gender, BMI and OSA severity. CONCLUSIONS: Participants with insomnia had lower vagal activity during the sleep onset period, which may be compounded by OSA, reflected in higher heart rates and lower HRV. These altered heart rate dynamics may serve as a physiological biomarker for insomnia during bedtime wakefulness, or as a potential tool to evaluate the efficacy of behavioral interventions which target bedtime stress.

Global trends in COVID-19 incidence and case fatality rates (2019-2023): a retrospective analysis.

Objectives: Analyzing and comparing COVID-19 infection and case-fatality rates across different regions can help improve our response to future pandemics. Methods: We used public data from the WHO to calculate and compare the COVID-19 infection and case-fatality rates in different continents and income levels from 2019 to 2023. Results: The Global prevalence of COVID-19 increased from 0.011 to 0.098, while case fatality rates declined from 0.024 to 0.009. Europe reported the highest cumulative infection rate (0.326), with Africa showing the lowest (0.011). Conversely, Africa experienced the highest cumulative case fatality rates (0.020), with Oceania the lowest (0.002). Infection rates in Asia showed a steady increase in contrast to other continents which observed initial rises followed by decreases. A correlation between economic status and infection rates was identified; high-income countries had the highest cumulative infection rate (0.353) and lowest case fatality rate (0.006). Low-income countries showed low cumulative infection rates (0.006) but the highest case fatality rate (0.016). Initially, high and upper-middle-income countries experienced elevated initial infection and case fatality rates, which subsequently underwent significant reductions. Conclusions: COVID-19 rates varied significantly by continent and income level. Europe and the Americas faced surges in infections and low case fatality rates. In contrast, Africa experienced low infection rates and higher case fatality rates, with lower- and middle-income nations exceeding case fatality rates in high-income countries over time.

Exploration and Practice of Introducing the Pharmaceutical Care Network Europe Classification System to Psychiatric Drugs.

This research aims to summarize and discuss issues related to psychiatric drugs by using the classification system of the Pharmaceutical Care Network Europe (PCNE) and to provide a reference for the development and direction of clinical pharmacists' work in the future. Psychiatric patients who were hospitalized in our hospital from Janurary 2023 to December 2023 were enrolled. Drug-related problems (DRPs) were evaluated using the PCNE classification system (version 9.0). The types, causes, intervention plans, acceptance of intervention plans, and statuses of DRPs were analyzed. A total of 362 patients were included, covering 405 DRP cases, with an average DRP of 1.12 for each patient. All 405 DRP cases underwent interventions, with a success rate of 83.46%. The main categories of related drugs were psychotropic drugs (70.37%), anti-infective drugs (8.89%), and cardiovascular system drugs (5.19%). The main DRPs were possible adverse drug events (21.24%), poor treatment effects (69.14%), and unnecessary medication treatment (9.63%). The main causes of DRPs were inappropriate drug selection (18.52%), inappropriate combinations of drugs (16.05%), and excessive drug dosage (13.58%). The PCNE classification system helps clinical pharmacists improve their ability to identify and solve DRPs faced by psychiatric departments, improve pharmaceutical care efficiency, and ensure rational drug use.

Machine learning prediction of pulmonary oxygen uptake from muscle oxygen in cycling.

The purpose of this study was to test whether a machine learning model can accurately predict VO2 across different exercise intensities by combining muscle oxygen (MO2) with heart rate (HR). Twenty young highly trained athletes performed the following tests: a ramp incremental exercise, three submaximal constant intensity exercises, and three severe intensity exhaustive exercises. A Machine Learning model was trained to predict VO2, with model inputs including heart rate, MO2 in the left (LM) and right legs (RM). All models demonstrated equivalent results, with the accuracy of predicting VO2 at different exercise intensities varying among different models. The LM+RM+HR model performed the best across all intensities, with low bias in predicted VO2 for all intensity exercises (0.08 ml/kg/min, 95% limits of agreement: -5.64 to 5.81), and a very strong correlation (r = 0.94, p < 0.001) with measured VO2. Furthermore, the accuracy of predicting VO2 using LM+HR or RM+HR was higher than using LM+RM, and higher than the accuracy of predicting VO2 using LM, RM, or HR alone. This study demonstrates the potential of a machine learning model combining MO2 and HR to predict VO2 with minimal bias, achieving accurate predictions of VO2 for different intensity levels of exercise.

Triborane (B3H7)-mediated regioselective substitution reactions of pyridine derivatives.

There exists an interplay between borane and a Lewis base in their adducts. However, studies on these adducts so far have mainly focused on the different reactions of B-H bonds with limited attention given to the influence of borane on the chemistry of the Lewis base, except for BF3 and BAr3. Herein, we have synthesized novel borane adducts with pyridine derivatives, Py·B3H7, in which the coordination of B3H7 efficiently achieved the intra-molecular charge transfer. The strong B-N bond in these adducts resulted in the formation of stable dearomatic intermediates of pyridine derivatives, confirmed by 1H and 11B NMR spectroscopy, from which different reactions have transpired to realize C(sp3)-H and C(sp2)-H functionalization under mild conditions. The B3H7 pyridine derivatives are stable and do not dissociate or decompose during the reaction process. The high stability of the B-N bond makes this method a good option for boron-containing drugs with potential for use in boron neutron capture therapy (BNCT).

Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors.

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.

Status and hotspot analysis of Qingfei Paidu Decoction for the prevention and treatment of COVID-19 based on bibliometric analysis.

Background: Qingfei Paidu Decoction (QFPDD) has played an important role in the prevention and treatment of COVID-19 infection in China. The present study aims to perform an econometric analysis and visualization of the literature on the treatment of COVID-19 with QFPDD in the Chinese databases and English databases. Methods: Six databases including such as Chinese databases CNKI, VIP, CBM, WANFANG as well as English databases PubMed, Web of Science were searched for publications related to the prevention and treatment of COVID-19 with QFPDD. The institutions, authors, keywords of each publication were cisualized using the software of CiteSpace. Results: A total of 187 literature on the prevention and treatment of novel coronavirus infection with QFPDD were included, of which 145 (77.5%) were in Chinese and 42 (22.5%) were in English. Those publications were written by 926 authors from 383 institutions. There were 78 theoretical studies (41.7%), 63 clinical studies (33.7%), and 46 basic studies (24.6%). The cooperative institutions with the core of "Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences" and "Shanghai University of Chinese Medicine Cross Academy of Science" have been formed, and two core teams with "Wang Yanping" and "Zhang Weidong" have been formed. The keyword analysis showed that the research mainly focuses on pathologic pathogenesis, clinical efficacy, adverse reactions, integrated Chinese and western medicine therapy, network pharmacology research. Conclusion: QFPDD has attracted worldwide attention, mechanism research and clinical research may become a future development trend. Therefore, in-depth basic research and clinical studies with large samples and multi-center cooperation should be carried out to provide high-level evidence-based evidence for the prevention and treatment of COVID-19 with QFPDD.

Distribution and effects of microplastics as carriers of heavy metals in river surface sediments.

There are few studies on microplastics (MPs) in urban river sediments compared to oceans, soils, and even rivers. In this study, the seasonal abundance of MPs, as well as their influencing factors on heavy metal adsorption in river sediments of the Ancient Canal of Zhenjiang City, China, were investigated for the first time. Through on-site sampling, microscopic observation, Raman spectroscopy, scanning electron microscopy, and high-temperature digestion, the abundance, shape, color, particle size, type, and surface characteristics of MPs in Ancient Canal sediments in different seasons, as well as the influencing factors of MPs as heavy metal carriers in different seasons, were analyzed. The results showed that the average abundance of MPs is 2049.09 ± 883.78 and 2216.36 ± 826.21 items kg-1 dry sediments in summer and winter, respectively, and different sites change significantly. In addition, particle sizes, types, colors, and shapes of MPs exhibited seasonal variations. Four MPs shapes were mainly observed: fibers, fragments, particles, and films. Among them, MPs in summer sediments are mainly fiber, and MPs in winter sediments are mainly particles. In the sediment in summer and winter, transparent MPs and small-size (<0.5 mm) MPs are the main ones, where the abundance of MPs decreased with increasing MPs size. The main MPs species are polyvinyl chloride (PVC), polystyrene (PS), polypropylene (PP), polyethylene terephthalate (PET), polycarbonate (PC), and polyethylene (PE), with PP being the predominant MPs in the sediments in different seasons. Scanning electron microscopy-energy dispersive spectrometer (SEM-EDS) revealed that the surfaces of the MPs were characterized by rough, porous, cracked, and torn, with the attachment of various heavy metal elements, and all of the heavy metal elements accumulated to different degrees on the MPs. There was a significant positive correlation (p < 0.05) between the Mn content in the MPs and the Mn content in the sediments in winter, suggesting that the Mn in the MPs in winter may be derived from the sediments. In addition, the type, shape, size, and color of MPs affect the adsorption capacity of heavy metals. Most of the adsorption of MPs on Pb showed a significant negative correlation, and the adsorption of MPs on Cr, Zn, Cu, Cd, and Mn showed a significant positive correlation. MPs can be used as carriers of heavy metals, which will further enhance the hazards of living organisms and pose a potential threat to the safety of the urban river environment.

Flaxseed polyphenols: Effects of varieties on its composition and antioxidant capacity.

This study identified phenolic compounds in five flaxseed varieties and evaluated their antioxidant activities. Results showed significant variations in phenolic acids and flavonoids among the varieties. Longya 16 had the lowest flavonoid content, Longya 13 had the lowest phenolic acid content, while Longya 10 exhibited the highest content and diversity of polyphenols, including six flavonoids (vitexin, quercitrin, quercetin, apigenin, kaempfero1, (+)-dihydroquercetin) and five phenolic acids (gallic acid, vanillic acid, ferulic acid, sinapic acid, and 4-hydroxybenzoic acid). Antioxidant activity was assessed using DPPH and ABTS radical scavenging assays, and cell-based assays under tBHP-induced oxidative stress. Flaxseed polyphenol extracts significantly reduced ROS, MDA, and GSSG levels and increased SOD and CAT activities, preserving cell vitality and morphology. These findings confirmed the significant antioxidant activity of flaxseed polyphenols, providing a theoretical basis for their application in antioxidative functional areas.

Spermatogenic cell-specific type 1 hexokinase (HK1S) is essential for capacitation-associated increase in tyrosine phosphorylation and male fertility in mice.

Hexokinase (HK) catalyzes the first irreversible rate-limiting step in glycolysis that converts glucose to glucose-6-phosphate. HK1 is ubiquitously expressed in the brain, erythrocytes, and other tissues where glycolysis serves as the major source of ATP production. Spermatogenic cell-specific type 1 hexokinase (HK1S) is expressed in sperm but its physiological role in male mice is still unknown. In this study, we generate Hk1s knockout mice using the CRISPR/Cas9 system to study the gene function in vivo. Hk1s mRNA is exclusively expressed in testes starting from postnatal day 18 and continuing to adulthood. HK1S protein is specifically localized in the outer surface of the sperm fibrous sheath (FS). Depletion of Hk1s leads to infertility in male mice and reduces sperm glycolytic pathway activity, yet they have normal motile parameters and ATP levels. In addition, by using in vitro fertilization (IVF), Hk1s deficient sperms are unable to fertilize cumulus-intact or cumulus-free oocytes, but can normally fertilize zona pellucida-free oocytes. Moreover, Hk1s deficiency impairs sperm migration into the oviduct, reduces acrosome reaction, and prevents capacitation-associated increases in tyrosine phosphorylation, which are probable causes of infertility. Taken together, our results reveal that HK1S plays a critical role in sperm function and male fertility in mice.

Oxidized LDL regulates efferocytosis through the CD36-PKM2-mtROS pathway.

Macrophage efferocytosis, the process by which phagocytes engulf and remove apoptotic cells (ACs), plays a critical role in maintaining tissue homeostasis. Efficient efferocytosis prevents secondary necrosis, mitigates chronic inflammation, and impedes atherosclerosis progression. However, the regulatory mechanisms of efferocytosis under atherogenic conditions remain poorly understood. We previously demonstrated that oxidized LDL (oxLDL), an atherogenic lipoprotein, induces mitochondrial reactive oxygen species (mtROS) in macrophages via CD36. In this study, we demonstrate that macrophage mtROS facilitate continual efferocytosis through a positive feedback mechanism. However, oxLDL disrupts continual efferocytosis by dysregulating the internalization of ACs. This disruption is mediated by an overproduction of mtROS. Mechanistically, oxLDL/CD36 signaling promotes the translocation of cytosolic PKM2 to mitochondria, facilitated by the chaperone GRP75. Mitochondrial PKM2 then binds to Complex III of the electron transport chain, inducing mtROS production. This study elucidates a novel regulatory mechanism of efferocytosis in atherosclerosis, providing potential therapeutic targets for intervention. SUMMARY: Macrophages clear apoptotic cells through a process called efferocytosis, which involves mitochondrial ROS. However, the atherogenic oxidized LDL overstimulates mitochondrial ROS via the CD36-PKM2 pathway, disrupting continual efferocytosis. This finding elucidates a novel molecular mechanism that explains defects in efferocytosis, driving atherosclerosis progression.

Interaction and coexistence characteristics of dissolved organic matter and toxic metals with per- and polyfluoroalkyl substances in landfill leachate.

Landfill leachate-containing per- and polyfluoroalkyl substances (PFAS) is both an important 'sink' and a 'source' of secondary pollution, posing serious threaten to surrounding environments. To date, the pollution characteristics of PFAS in landfill leachate, and the coexistence and interaction between PFAS and other leachate contaminants, such as dissolved organic matter (DOM) and toxic metals remains unclear. Herein, our results showed that 17 target PFAS, with concentrations ranged from 1804 to 43309 ng/L, were detected in landfill leachates. The main PFAS were short-chain and even-chain substances represented by perfluorobutanoic acid (PFBA) and perfluorobutane sulfonic acid (PFBS). Leachate derived DOM is mainly composed of protein-like and humic-like substance, among which the total contribution of protein-like substance is as high as 73.7%. Correlation analysis results showed that the distribution of PFAS was strongly correlated with the substituted functional groups (e.g., carboxyl and hydroxyl) on the aromatic ring of humic-like substance (C2 and E253/E203) and autochthonous metabolism by microbial activities (FI). Furthermore, Mn element showed a significantly strong correlation with PFAS. Both organic and inorganic substances positively correlated with toxic metals. Our findings are helpful to understand the environmental fate of PFAS, and contribute to decision-making regarding DOM, toxic metals, and PFAS management in landfill.

The architecture of silk-secreting organs during the final larval stage of silkworms revealed by single-nucleus and spatial transcriptomics.

Natural silks are renewable proteins with impressive mechanical properties and biocompatibility that are useful in various fields. However, the cellular and spatial organization of silk-secreting organs remains unclear. Here, we combined single-nucleus and spatially resolved transcriptomics to systematically map the cellular and spatial composition of the silk glands (SGs) of mulberry silkworms late in larval development. This approach allowed us to profile SG cell types and cell state dynamics and identify regulatory networks and cell-cell communication related to efficient silk protein synthesis; key markers were validated via transgenic approaches. Notably, we demonstrated the indispensable role of the ecdysone receptor (ultraspiracle) in regulating endoreplication in SG cells. Our atlas presents the results of spatiotemporal analysis of silk-secreting organ architecture late in larval development; this atlas provides a valuable reference for elucidating the mechanism of efficient silk protein synthesis and developing sustainable products made from natural silk.

Ratiometric electrochemical biosensor based on hybridization chain reaction signal amplification for sensitive microRNA-155 detection.

In this work, a sensitive ratiometric electrochemical biosensor for microRNA-155 (miRNA-155) detection is reported based on a hybridization chain reaction amplifying the electrochemical signal. The biosensor was fabricated using Au NPs as a modified material to assemble capture DNA labeled with ferrocene (Fc) molecules, and a DNA probe labeled with methylene blue (MB) was employed for the signal probe. In the presence of target miRNA-155, it can be dual hybridized with capture and signal probe, especially with signal probe to continuously produce long concatemers containing lots of MB molecules. The electrochemical signal of Fc was used for the internal signal, and the signal from MB was used as an indicator signal. As the concentration of miRNA-155 was altered, the internal reference signal of Fc remained constant, and only the indicator signal changed in a sensitive way. The change in the ratio (IMB/IFc) between the indicator signal of MB and internal reference signal of Fc can be used to monitor the concentration of miRNA-155. Under optimal conditions, the prepared ratiometric biosensor could detect miRNA-155 within a wide linear range from 100 fM to 100 nM with low detection limit of 33 fM (at S/N = 3). Moreover, the biosensor was evaluated with human serum samples, and satisfactory recoveries were obtained, indicating that the ratiometric biosensor can be applied to clinical sample analysis.