MiR-106a-5p targets PFKFB3 and improves sepsis through regulating macrophage pyroptosis and inflammatory response.

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is a critical regulator of glycolysis and plays a key role in modulating the inflammatory response, thereby contributing to the development of inflammatory diseases such as sepsis. Despite its importance, the development of strategies to target PFKFB3 in the context of sepsis remains challenging. In this study, we employed a miRNA-based approach to decrease PFKFB3 expression. Through multiple meta-analyses, we observed a downregulation of miR-106a-5p expression and an upregulation of PFKFB3 expression in clinical sepsis samples. These changes were also confirmed in blood monocytes from patients with early sepsis and from a mouse model of lipopolysaccharide (LPS)-induced sepsis. Overexpression of miR-106a-5p significantly decreased the LPS-induced increase in glycolytic capacity, inflammatory response, and pyroptosis in macrophages. Mechanistically, we identified PFKFB3 as a direct target protein of miR-106a-5p and demonstrated its essential role in LPS-induced pyroptosis and inflammatory response in macrophages. Furthermore, treatment with agomir-miR-106a-5p conferred a protective effect in an LPS mouse model of sepsis, but this effect was attenuated in myeloid-specific Pfkfb3 KO mice. These findings indicate that miR-106a-5p inhibits macrophage pyroptosis and inflammatory response in sepsis by regulating PFKFB3-mediated glucose metabolism, representing a potential therapeutic option for the treatment of sepsis.

Characterization of a small molecule inhibitor of the NLRP3 inflammasome and its potential use for acute lung injury.

Accumulating data support the key roles of the NLRP3 inflammasome, an essential component of the innate immune system, in human pathophysiology. As an emerging drug target and a potential biomarker for human diseases, small molecule inhibitors of the NLRP3 inflammasome have been actively pursued. Our recent studies identified a small molecule, MS-II-124, as a potent NLRP3 inhibitor and potential imaging probe. In this report, MS-II-124 was further characterized by an unbiased and comprehensive analysis through Eurofins BioMAP Diversity PLUS panel that contains 12 human primary cell-based systems. The analysis revealed promising activities of MS-II-124 on inflammation and immune functions, further supporting the roles of the NLRP3 inflammasome in these model systems. Further studies of MS-II-124 in mouse model of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and NLRP3 knockout mice demonstrated its target engagement, efficacy to suppress inflammatory cytokines and infiltration of immune cells in the lung tissues. In summary, the results support the therapeutic potential of MS-II-124 as a NLRP3 inhibitor and warrant future studies of this compound and its analogs to develop therapeutics for ALI/ARDS.

Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

PM10-bound trace elements in pan-European urban atmosphere.

Although many studies have discussed the impact of Europe's air quality, very limited research focused on the detailed phenomenology of ambient trace elements (TEs) in PM10 in urban atmosphere. This study compiled long-term (2013-2022) measurements of speciation of ambient urban PM10 from 55 sites of 7 countries (Switzerland, Spain, France, Greece, Italy, Portugal, UK), aiming to elucidate the phenomenology of 20 TEs in PM10 in urban Europe. The monitoring sites comprised urban background (UB, n = 26), traffic (TR, n = 10), industrial (IN, n = 5), suburban background (SUB, n = 7), and rural background (RB, n = 7) types. The sampling campaigns were conducted using standardized protocols to ensure data comparability. In each country, PM10 samples were collected over a fixed period using high-volume air samplers. The analysis encompassed the spatio-temporal distribution of TEs, and relationships between TEs at each site. Results indicated an annual average for the sum of 20 TEs of 90 ± 65 ng/m3, with TR and IN sites exhibiting the highest concentrations (130 ± 66 and 131 ± 80 ng/m3, respectively). Seasonal variability in TEs concentrations, influenced by emission sources and meteorology, revealed significant differences (p < 0.05) across all monitoring sites. Estimation of TE concentrations highlighted distinct ratios between non-carcinogenic and carcinogenic metals, with Zn (40 ± 49 ng/m3), Ti (21 ± 29 ng/m3), and Cu (23 ± 35 ng/m3) dominating non-carcinogenic TEs, while Cr (5 ± 7 ng/m3), and Ni (2 ± 6 ng/m3) were prominent among carcinogenic ones. Correlations between TEs across diverse locations and seasons varied, in agreement with differences in emission sources and meteorological conditions. This study provides valuable insights into TEs in pan-European urban atmosphere, contributing to a comprehensive dataset for future environmental protection policies.

Research on Convex Fiber Grating Tactile Sliding Sensor Based on Mechanical Fingers.

In order to solve the problem of flexible sliding tactile composite sensing in the actual grasp of intelligent robot fingers, this paper proposes a research on a convex fiber grating tactile sliding sensor based on mechanical fingers. Based on the sensing principle of fiber Bragg grating, 3D printing technology was used to encapsulate the FBG sensor array with elastic 50 A resin, a double-layer "hemispherical cuboid" distributed sensing unit was designed, and the FBG slippery tactile sensor was actually pasted on the surface of the mechanical finger for static and dynamic experiments. The experimental results show that the slippery tactile sensor designed in this paper has a good linear relationship with temperature and strain. The temperature sensitivities of the polymer-packaged FBGs are KT1 = 13.04 pm/°C and KT2 = 12.91 pm/°C, and they have a pressure sensitivity of 40.4 pm/N and 31.2 pm/N, respectively. The FBG sliding tactile sensor not only realizes the identification of the sliding signal generation point and the end point but also completes the classification and identification of sandpaper, cardboard, and polypropylene plastic, and it has a high degree of fit with the robot finger, which has certain application value for the intelligent robot sliding tactile signal perception.

Research on FBG Tactile Sensing Shape Recognition Based on Convolutional Neural Network.

Shape recognition plays a significant role in the field of robot perception. In view of the low efficiency and few types of shape recognition of the fiber tactile sensor applied to flexible skin, a convolutional-neural-network-based FBG tactile sensing array shape recognition method was proposed. Firstly, a sensing array was fabricated using flexible resin and 3D printing technology. Secondly, a shape recognition system based on the tactile sensing array was constructed to collect shape data. Finally, shape classification recognition was performed using convolutional neural network, random forest, support vector machine, and k-nearest neighbor. The results indicate that the tactile sensing array exhibits good sensitivity and perception capability. The shape recognition accuracy of convolutional neural network is 96.58%, which is 6.11%, 9.44%, and 12.01% higher than that of random forest, k-nearest neighbor, and support vector machine. Its F1 is 96.95%, which is 6.3%, 8.73%, and 11.94% higher than random forest, k-nearest neighbor, and support vector machine. The research of FBG shape sensing array based on convolutional neural network provides an experimental basis for shape perception of flexible tactile sensing.

Clinical outcome and survival rate of condylar constrained knee prosthesis in revision total knee arthroplasty: an average nine point six year follow-up.

PURPOSE: Condylar constrained knee prostheses (CCK) are increasingly used in revision total knee arthroplasty (rTKA), but the clinical effectiveness and long-term survival remain a debate. The purpose of this study is to report the long-term clinical and radiographic outcome, implant survival rate, and surgical safety of revision total knee arthroplasty with condylar constrained knee prosthesis. METHODS: A retrospective cohort study was performed on patients undergoing rTKA with CCK. The cases who received rTKA with CCK from January 2005 to January 2022 were selected. The duration of operation, the estimated perioperative blood loss, and the intraoperative blood transfusion rate were recorded to evaluate surgical safety. The pain visual analog scale (VAS), range of motion (ROM), the Hospital for Special Surgery (HSS) score, the Knee Society Score (KSS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the Oxford knee score (OKS) was recorded to assess clinical outcome. Standard anteroposterior, lateral, skyline and long-standing AP radiographs of the lower limbs were conducted to assess radiographic outcome. Implant survival was analyzed by Kaplan-Meier survival estimates. RESULTS: Fifty-five cases were followed up for an average of 9.6 years (1-18 years), including 16 males and 38 females, with an average age of 66 and an average BMI of 26.9 kg/m2. The  main reasons for revision were periprosthetic infection (32 knees, 58.2%) and aseptic loosening (13 knees, 23.6%). The duration of operation was 149 ± 56.2 min. The perioperative blood loss was 973.6 ± 421.6 ml. At the last follow-up, VAS (8.0 ± 1.1 to 1.3 ± 1.4), ROM (82.7° ± 26.1° to 108.4° ± 11.8°), HSS (45.0 ± 10.4 to 85.3 ± 8.6), KSKS (38.4 ± 12.1 to 88.5 ± 12.0), KSFS (19.6 ± 12.9 to 68.8 ± 15.1), WOMAC (67.9 ± 12.5 to 14.4 ± 9.5), and OKS (9.9 ± 4.2 to 41.6 ± 7.7) were significantly improved (P < 0.001). A total of five complications were observed, all of which were periprosthetic infection. Non-progressive radiolucent lines were observed in 26 knees (47.3%). The 10-year survival rate for no operation was 96.0%. The ten year survival rate for no revision was 98.0%. CONCLUSION: The use of CCK prosthesis for rTKA can achieve good long-term efficacy and prosthesis survival.

Strain-modulated Ru-O Covalency in Ru-Sn Oxide Enabling Efficient and Stable Water Oxidation in Acidic Solution.

RuO2 is one of the benchmark electrocatalysts used as the anode material in proton exchange membrane water electrolyser. However, its long-term stability is compromised due to the participation of lattice oxygen and metal dissolution during oxygen evolution reaction (OER). In this work, weakened covalency of Ru-O bond was tailored by introducing tensile strain to RuO6 octahedrons in a binary Ru-Sn oxide matrix, prohibiting the participation of lattice oxygen and the dissolution of Ru, thereby significantly improving the long-term stability. Moreover, the tensile strain also optimized the adsorption energy of intermediates and boosted the OER activity. Remarkably, the RuSnOx electrocatalyst exhibited excellent OER activity in 0.1 M HClO4 and required merely 184 mV overpotential at a current density of 10 mA cm-2 . Moreover, it delivered a current density of 10 mA cm-2 for at least 150 h with negligible potential increase. This work exemplifies an effective strategy for engineering Ru-based catalysts with extraordinary performance toward water splitting.

Learning dynamic graph representations through timespan view contrasts.

The rich information underlying graphs has inspired further investigation of unsupervised graph representation. Existing studies mainly depend on node features and topological properties within static graphs to create self-supervised signals, neglecting the temporal components carried by real-world graph data, such as timestamps of edges. To overcome this limitation, this paper explores how to model temporal evolution on dynamic graphs elegantly. Specifically, we introduce a new inductive bias, namely temporal translation invariance, which illustrates the tendency of the identical node to keep similar labels across different timespans. Based on this assumption, we develop a dynamic graph representation framework CLDG that encourages the node to maintain locally consistent temporal translation invariance through contrastive learning on different timespans. Except for standard CLDG which only considers explicit topological links, our further proposed CLDG＋＋additionally employs graph diffusion to uncover global contextual correlations between nodes, and designs a multi-scale contrastive learning objective composed of local-local, local-global, and global-global contrasts to enhance representation capabilities. Interestingly, by measuring the consistency between different timespans to shape anomaly indicators, CLDG and CLDG＋＋are seamlessly integrated with the task of spotting anomalies on dynamic graphs, which has broad applications in many high-impact domains, such as finance, cybersecurity, and healthcare. Experiments demonstrate that CLDG and CLDG＋＋both exhibit desirable performance in downstream tasks including node classification and dynamic graph anomaly detection. Moreover, CLDG significantly reduces time and space complexity by implicitly exploiting temporal cues instead of complicated sequence models. The code and data are available at https://github.com/yimingxu24/CLDG.

CD44 and its implication in neoplastic diseases.

CD44, a nonkinase single span transmembrane glycoprotein, is a major cell surface receptor for many other extracellular matrix components as well as classic markers of cancer stem cells and immune cells. Through alternative splicing of CD44 gene, CD44 is divided into two isoforms, the standard isoform of CD44 (CD44s) and the variant isoform of CD44 (CD44v). Different isoforms of CD44 participate in regulating various signaling pathways, modulating cancer proliferation, invasion, metastasis, and drug resistance, with its aberrant expression and dysregulation contributing to tumor initiation and progression. However, CD44s and CD44v play overlapping or contradictory roles in tumor initiation and progression, which is not fully understood. Herein, we discuss the present understanding of the functional and structural roles of CD44 in the pathogenic mechanism of multiple cancers. The regulation functions of CD44 in cancers-associated signaling pathways is summarized. Moreover, we provide an overview of the anticancer therapeutic strategies that targeting CD44 and preclinical and clinical trials evaluating the pharmacokinetics, efficacy, and drug-related toxicity about CD44-targeted therapies. This review provides up-to-date information about the roles of CD44 in neoplastic diseases, which may open new perspectives in the field of cancer treatment through targeting CD44.

Single-cell RNA sequencing data analysis utilizing multi-type graph neural networks.

Single-cell RNA sequencing (scRNA-seq) is the sequencing technology of a single cell whose expression reflects the overall characteristics of the individual cell, facilitating the research of problems at the cellular level. However, the problems of scRNA-seq such as dimensionality reduction processing of massive data, technical noise in data, and visualization of single-cell type clustering cause great difficulties for analyzing and processing scRNA-seq data. In this paper, we propose a new single-cell data analysis model using denoising autoencoder and multi-type graph neural networks (scDMG), which learns cell-cell topology information and latent representation of scRNA-seq data. scDMG introduces the zero-inflated negative binomial (ZINB) model into a denoising autoencoder (DAE) to perform dimensionality reduction and denoising on the raw data. scDMG integrates multiple-type graph neural networks as the encoder to further train the preprocessed data, which better deals with various types of scRNA-seq datasets, resolves dropout events in scRNA-seq data, and enables preliminary classification of scRNA-seq data. By employing TSNE and PCA algorithms for the trained data and invoking Louvain algorithm, scDMG has better dimensionality reduction and clustering optimization. Compared with other mainstream scRNA-seq clustering algorithms, scDMG outperforms other state-of-the-art methods in various clustering performance metrics and shows better scalability, shorter runtime, and great clustering results.

Impact of intraosseous regional administration of tranexamic acid in total knee arthroplasty on perioperative blood loss: a protocol for a randomised controlled trial.

INTRODUCTION: Total knee arthroplasty (TKA) is a common surgical intervention to treat joint diseases. However, TKA is associated with significant blood loss. Tranexamic acid (TXA) has been used to reduce perioperative bleeding and postoperative blood transfusion. This study aims to explore the effectiveness and safety of intraosseous regional administration (IORA) of TXA in TKA and compare differences in perioperative blood loss between IORA of TXA, intravenous infusion of TXA, and combined IORA and intravenous infusion of TXA. METHODS AND ANALYSIS: This randomised controlled trial will enrol 105 patients with osteoarthritis who meet the inclusion criteria for unilateral TKA. Patients were randomly divided into three groups using the random number table method. Group A received 1.0 g of TXA via IORA, group B received 1.0 g of TXA via intravenous infusion 15 min prior to the tourniquet release, and group C received both IORA of 1.0 g of TXA and intravenous infusion of 1.0 g of TXA. The primary outcome measure is perioperative total blood loss. Secondary outcomes include bleeding events, venous thromboembolism events, inflammation reactions, other complications and knee function assessments. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Peking Union Medical College Hospital and registered in the Chinese Clinical Trial Registry. Informed consent will be obtained from all the patients before enrolment. The trial will be conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The results of this study will be disseminated through peer-reviewed publications, conference presentations and social media platforms. The findings will provide valuable insights into the use of IORA of TXA in TKA and may lead to the development of new strategies for perioperative blood management in joint replacement surgery. TRIAL REGISTRATION NUMBER: The Ethics Committee of Peking Union Medical College Hospital (approval number: K2371); Chinese Clinical Trial Registry (trial registration number: ChiCTR2200066293).

Correlation Between Diaphragmatic Excursion and Exercise Tolerance Improvement Following Pulmonary Rehabilitation in Patients with Chronic Obstructive Pulmonary Disease-Obstructive Sleep Apnea Overlap Syndrome.

Purpose: We assess the predictive value of diaphragm excursion (DE) in enhancing exercise tolerance following pulmonary rehabilitation (PR) among patients with COPD-OSA overlap syndrome. Material and Methods: This prospective cohort study enrolled 63 patients diagnosed with COPD-OSA overlap syndrome who actively participated in a PR program from January 2021 to May 2023. Among these, 58 patients successfully completed the 20-week PR program, with exercise tolerance assessed through the measurement of six-minute walk distance (6MWD), and DE evaluated by ultrasonography. The responder to PR in terms of exercise ability was defined as a patient who showed an increase of >30m in 6MWD. The cutoff value for predicting PR response based on DE was determined using receiver operating characteristic (ROC) curves. Results: Following the PR program, significant improvements were observed in mMRC, 6MWD, DE during deep breathing, and diaphragm thickness fraction (DTF). Of the participants, 33 patients (57%) were classified as responders, while 25 patients (43%) were considered non-responders. Baseline values of FEV1% predicted, 6MWD, DE during deep breathing, DTF, and PaO2 exhibited a significant elevation in responders as compared to non-responders. The changes of 6MWD were positively associated with the baseline values of DTF and DE during deep breathing, FEV1% predicted and PaO2, while negatively correlated with baseline value of mMRC. The predictive performance in terms of the area under the ROC curve for determining responder's DTF was found to be 0.769, accompanied by a sensitivity of 85% and specificity of 68%, using a cutoff value at 17.26%. Moreover, it was observed that DE during deep breathing could predict the area under the ROC curve for responders to be 0.753, with a sensitivity of 91% and specificity of 56% at a cutoff value of 3.61cm. Conclusion: Diaphragm excursion serves as a valuable predictor for determining the enhancement of exercise tolerance following PR in patients with COPD-OSA overlap syndrome. Trial Registration: ChiCTR1800020257, www.chictr.org.cn/index.aspx.

Toward a Sustainable Approach for Durably Hydrophilic and UV Protective PET Fabric through Surface Activation and Immobilization Integrating Epigallocatechin Gallate and Citric Acid.

Enhancing the hydrophilicity and UV protective property of poly(ethylene terephthalate) (PET) fabric are two significant ways to upgrade its quality and enlarge the applicable area. Biobased finishes are greatly welcomed for the fabrication of sustainable textiles; however, their application on PET fabric is still challenging compared with the case of natural fabric. This study presents a strategy that immobilizes epigallocatechin gallate (EGCG) onto PET fabric using citric acid (CA) for durably hydrophilic and UV-proof properties with negligible color change. A controllable surface-activating method integrating alkaline and deep eutectic solvent (DES) is customized for the PET fabric to promote the reactions among PET, CA, and EGCG. The hydrophilic, antistatic, and UV protective properties of functionalized PET fabric were explored. Results show that the hydrophilicity of the PET fabric after direct EGCG treatment increases but drops sharply after first-round washing due to weak interactions. The combined alkaline/DES pretreatment increases the number of hydrophilic groups and the roughness of PET fibers. After EGCG modification, the moisture regain (MR) of PET fabric increases from 0.41 to 0.64%. The contact angle and electrostatic charge half-life (T1/2) decreases from >120 to 23°, and from >60 to 0.13 s, respectively. The MR and T1/2 are well retained after a 10-cycle washing. In addition, the UV protective factor of the PET fabric increases from 18 to 36. A very slight yellowing phenomenon occurs on the PET fabric after the treatment. In all, this research attempts to integrate a biobased finishing agent and an eco-friendly cross-linker on synthetic fiber for durable functions, which is transferrable to the sustainable fabrication of other polymeric materials such as fibers or films.

Kinship analysis and pedigree reconstruction by RAD sequencing in cattle.

Kinship and pedigree, used for estimating inbreeding, heritability, selection, and gene flow, are useful for breeding and animal conservation. However, as the size of crossbred populations increases, inaccurate generation and parentage assignment in livestock farms increase. Restriction-site-associated DNA sequencing is a cost-effective platform for single nucleotide polymorphism (SNP) discovery and genotyping. Here, we performed a kinship analysis and pedigree reconstruction for Angus and Xiangxi yellow cattle. A total of 975 cattle, including 923 offspring with 24 known sires and 28 known dams, were sampled and subjected to SNP discovery and genotyping. The identified SNP panel included 7,305 SNPs capturing the maximum difference between paternal and maternal genome information, allowing us to distinguish F1 from F2 generations with 90% accuracy. In conclusion, we provided a low-cost and efficient SNP panel for kinship analyses and the improvement of local genetic resources, which are valuable for breed improvement, local resource utilization, and conservation.

Surgical treatment for pelvic haemophilic pseudotumour: a retrospective analysis of 21 cases.

Background: Due to the rarity of pelvic haemophilic pseudotumour (PHPT) and demanding surgical technique for PHPT excision, no study reports the mid-term follow-up outcomes of surgical treatment of PHPT in a relatively large cohort. PHPT with varying degrees of bony pelvic involvement and infection status necessitates different operative procedures, yet there is currently no classification system for PHPT based on surgical practice. Methods: The study was conducted between June 25, 2004 and July 18, 2023, in Peking Union Medical College Hospital and Nanfang Hospital in China. We performed a retrospective analysis involving 21 patients with 24 PHPTs with a mean follow-up period of 7.1 years. The demographic information, PHPT characteristics, surgical data, and perioperative complications were analysed. Findings: 21 consecutive male patients with 24 PHPTs (21 primary PHPTs and three recurrent PHPTs) that underwent surgical treatment were involved in the study. A classification system including four subtypes was introduced as (I) PHPT confined to soft tissue; (II) PHPT involving bony pelvic without pelvic discontinuity; (III) PHPT causing pelvic discontinuity; (IV) Infectious PHPT. Of the 24 PHPTs, 11 (45.8%) were identified as Type I, five (20.8%) as Type II, three (12.5%) as Type III, and five (20.8%) as Type IV. At the time of surgery, the patients had a mean age of 37.0 ± 9.5 years (Range, 24-52 years). The mean maximum diameter of PHPTs upon surgery was 17.0 ± 7.7 cm (Range, 4.3-40.0 cm). The mean surgical duration was 192 ± 77 min (Range, 60-330 min) and the median intraoperative blood loss was 400 mL (IQR, 225-950 mL, Range, 100-3000 mL). One patient (4.8%) underwent intraoperative cardiopulmonary arrest and expired the following week. Four PHPTs (16.7%) presented postoperative wound infections and poor wound healing. During the follow-up period, five PHPTs (20.8%) experienced pseudotumour recurrence. Interpretation: Our findings suggest that surgical treatment for PHPTs is feasible and relatively safe. Symptomatic and progressive PHPTs should undergo surgical intervention as early as possible to minimise the surgical risks. Intraoperative use of abundant gelatin sponges in PHPT excision draws attention to severe embolism complications. Funding: There are no sources of funding for this manuscript.

PAHs removal by soil washing with thiacalix[4]arene tetrasulfonate.

Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods-chemical, thermal, and bioremediation-along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies.

Design and Discovery of Novel NLRP3 Inhibitors and PET Imaging Radiotracers Based on a 1,2,3-Triazole-Bearing Scaffold.

The NOD-like receptor (NLR) family pyrin-domain-containing 3 (NLRP3) inflammasome, an essential component of the innate immune system, has been emerging as a viable drug target and a potential biomarker for human diseases. In our efforts to develop novel small molecule NLRP3 inhibitors, a 1-(5-chloro-2-methoxybenzyl)-4-phenyl-1H-1,2,3-triazole scaffold was designed via a rational approach based on our previous leads. Structure-activity relationship studies and biophysical studies identified a new lead compound 8 as a potent (IC50: 0.55 ± 0.16 µM), selective, and direct NLRP3 inhibitor. Positron emission tomography (PET) imaging studies of [11C]8 demonstrated its rapid and high brain uptake as well as fast washout in mice and rhesus macaque. Notably, plasma kinetic analysis of this radiotracer from the PET/magnetic resonance imaging studies in rhesus macaque suggested radiometabolic stability. Collectively, our data not only encourage further studies of this lead compound but also warrant further optimization to generate additional novel NLRP3 inhibitors and suitable central nervous system PET radioligands with translational promise.

Design and simulation of a compact polarization beam splitter based on dual-core photonic crystal fiber with elliptical gold layer.

For the polarization multiplexing requirements in all-optical networks, this work presents a compact all-fiber polarization beam splitter (PBS) based on dual-core photonic crystal fiber (PCF) and an elliptical gold layer. Numerical analysis using the finite element method (FEM) demonstrates that the mode modulation effect of the central gold layer effectively reduces the dimensions of the proposed PBS. By determining reasonable structural parameters of the proposed PCF, the coupling length ratio (CLR) between X- and Y-polarized super-modes can approach 2, achieving a minimal device length of 0.122 mm. The PBS exhibits a maximum extinction ratio (ER) of - 65 dB at 1.55 µm, with an operating bandwidth spanning 100 nm (1.5-1.6 µm) and a stable insertion loss (IL) of ~ 1.5 dB at 1.55 µm. Furthermore, the manufacture feasibility and performance verification scheme are also investigated. It is widely anticipated that the designed PBS will play a crucial role in the ongoing development process of miniaturization and integration of photonic devices.

SLCO4A1, as a novel prognostic biomarker of non­small cell lung cancer, promotes cell proliferation and migration.

Solute carrier organic anion transporter family member 4A1 (SLCO4A1) is a membrane transporter protein. The role of this molecule in non­small cell lung cancer (NSCLC) remains unclear. Bulk sequencing was carried out using early­stage NSCLC tissues with lymph node metastasis to identify SLCO4A1 that influences NSCLC cell proliferation, metastasis and prognosis. The in vitro functional assays carried out included the following: Cell Counting Kit­8, plate colony formation, Transwell and wound healing assays. The molecular techniques used included reverse transcription­quantitative PCR, western blotting and immunohistochemistry. The present study revealed the role of SLCO4A in NSCLC. SLCO4A1 was found to be expressed at high levels in NSCLC tissues and cells, and promotes cell proliferation, migration and invasion. Kaplan­Meier survival analysis indicated that patients with NSCLC and high expression of SLCO4A1 had a poor prognosis. SLCO4A was revealed to regulate the expression of the proliferation­related proteins Ki­67 and PCNA, and that of the extracellular matrix proteins vimentin and E­cadherin. Mechanistically, SLCO4A1 may affect the MAPK signaling pathway to promote NSCLC cell proliferation, migration and invasion. In addition, bioinformatics analysis demonstrated a strong association between SLCO4A1 and tumor infiltrating immune cells, highlighting its critical role in immune therapies such as immune checkpoint inhibitor treatment of patients with NSCLC.