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The β-catenin-dependent canonical Wnt signaling is pivotal in organ development, tissue homeostasis, and cancer. Here, we identified an upstream enhancer of Ctnnb1 - the coding gene for β-catenin, named ieCtnnb1 ( i ntestinal e nhancer of Ctnnb1 ), which is crucial for intestinal homeostasis. ieCtnnb1 is predominantly active in the base of small intestinal crypts and throughout the epithelia of large intestine. Knockout of ieCtnnb1 led to a reduction in Ctnnb1 transcription, compromising the canonical Wnt signaling in intestinal crypts. Single-cell sequencing revealed that ieCtnnb1 knockout altered epithelial compositions and potentially compromised functions of small intestinal crypts. While deletion of ieCtnnb1 hampered epithelial turnovers in physiologic conditions, it prevented occurrence and progression of Wnt/β-catenin-driven colorectal cancers. Human ieCTNNB1 drove reporter gene expression in a pattern highly similar to mouse ieCtnnb1. ieCTNNB1 contains a single-nucleotide polymorphism associated with CTNNB1 expression levels in human gastrointestinal epithelia. The enhancer activity of ieCTNNB1 in colorectal cancer tissues was stronger than that in adjacent normal tissues. HNF4α and phosphorylated CREB1 were identified as key trans-factors binding to ieCTNNB1 and regulating CTNNB1 transcription. Together, these findings unveil an enhancer-dependent mechanism controlling the dosage of Wnt signaling and homeostasis in intestinal epithelia., Competing Interests: XH, CZ, JT, JW, XM, GZ, MW, MY, YL, YZ No competing interests declared, (© 2024, Hua et al.)

Organometal halide perovskite single crystals (SCs) are the most promising candidates for the next generation of radiation detection materials. However, surface defects severely affect their detection performance and limit further applications. Here, we identified the surface defect types of FAPbBr 3 SCs and employed phenethylammonium iodide (PEAI) solution to treat the crystal surface and to investigate their effects on ion migration, photoelectric performance, and X-ray detection performance. Our experimental results demonstrated that the surface defects, such as the metallic Pb and Br vacancies, can be effectively passivated by both the PEAI and the two-dimensional (2D) PEA 2 PbI 4 layers. The PEAI layer can elongate the carrier lifetime, lower the trap density, and suppress ion migration in FAPbBr 3 SCs. The 2D PEA 2 PbI 4 layer can form a dense and full surface coverage, suppress ion migration, and lower the dark current of the SCs. The X-ray sensitivity of the PEAI-passivated FAPbBr 3 SC detectors is 227.93 μCGy air -1 cm -2 , which is an order of magnitude higher than that of the pristine FAPbBr 3 SC detectors. This work demonstrates that surface treatment plays a critical role in the crystal quality and the X-ray detection performance of SCs.

Inflammation can affect the progression of cancer at tumor sites, such as in osteosarcoma, by intensifying metastasis and complicating outcomes. The current diagnostic methods lack the specificity and sensitivity required for early and accurate detection, particularly in differentiating between inflammation-induced changes and tumor activities. To address this, a novel "hedgehog ball"-shaped nanoprobe, Fe 3 O 4 @Au-pep-CQDs, was developed and designed to enhance the detection of caspase-1, a key marker of inflammation. This magnetic nanoprobe facilitates simultaneous fluorescence (FL) and electrochemiluminescence (ECL) detection. Magnetic separation minimizes the quenching of nanoparticles in solution and eliminates the need for frequent electrode replacement in ECL tests, thereby simplifying diagnostic procedures. The experimental results showed that in the detection of caspase-1, the nanoprobe had a detection limit of 0.029 U/mL (FL) and 0.033 U/mL (ECL) and had a dynamic range of 0.05 to 1.0 U/mL. Additionally, the nanoprobe achieved high recovery rates of 94.36 to 102.44% (FL) and 94.36-100.12% (ECL) in spiked biological samples. Furthermore, the nanoprobe's capabilities were extended to in vivo bioimaging to provide direct, intuitive visualization of biological processes. These novel nanoprobes were able to significantly enhance the accurate detection of inflammation at tumor sites, thereby optimizing both diagnostic and therapeutic strategies.

Background: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques., Methods: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up., Results: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] μm versus 87.2 [95% CI, 69.9 to 104.5] μm; difference, 34.2 [95% CI, 9.7 to 58.6] μm; P =0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P =0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P =0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P =0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P =0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P =0.047)., Conclusions: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857., Competing Interests: None.

This study developed and validated a deep learning-based diagnostic model with uncertainty estimation to aid radiologists in the preoperative differentiation of pathological subtypes of renal cell carcinoma (RCC) based on computed tomography (CT) images. Data from 668 consecutive patients with pathologically confirmed RCC were retrospectively collected from Center 1, and the model was trained using fivefold cross-validation to classify RCC subtypes into clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). An external validation with 78 patients from Center 2 was conducted to evaluate the performance of the model. In the fivefold cross-validation, the area under the receiver operating characteristic curve (AUC) for the classification of ccRCC, pRCC, and chRCC was 0.868 (95% CI, 0.826-0.923), 0.846 (95% CI, 0.812-0.886), and 0.839 (95% CI, 0.802-0.88), respectively. In the external validation set, the AUCs were 0.856 (95% CI, 0.838-0.882), 0.787 (95% CI, 0.757-0.818), and 0.793 (95% CI, 0.758-0.831) for ccRCC, pRCC, and chRCC, respectively. The model demonstrated robust performance in predicting the pathological subtypes of RCC, while the incorporated uncertainty emphasized the importance of understanding model confidence. The proposed approach, integrated with uncertainty estimation, offers clinicians a dual advantage: accurate RCC subtype predictions complemented by diagnostic confidence metrics, thereby promoting informed decision-making for patients with RCC., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Simplified anaerobic digestion (SAD) of substrates facilitates microbial methanogenic pathways. In this study, a methane-producing microbial consortium from cow dung was enriched to determine the metabolism and metabolic pathway in the SAD of methanol. The results showed that methanol as a sole substrate produced 167 mL of methane at 10 days significantly higher than 58 mL, 17.6 mL, and 4 mL generated when methanol was combined with sodium formate, sodium formate alone, or sodium acetate. The relative abundance of Methanobacterium, Candidatus_Methanomethylophilus, Methanomassiliicoccus, and Methanosarcina was increased by 5.96 %, 3.77 %, 2.85 %, and 0.14 % in the methanol substrate of AD, respectively. Macrogenome sequencing indicates that methanol wasconverted into Methyl-CoM in the presence of Methanosarcina, which combines with Coenzyme B to produce methane. This study revealed that methanol is converted into methane by a simple pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chalcophosphates are an important type of infrared nonlinear optical (NLO) candidates in view of their rich anionic motifs. Here, two copper chalcophosphates Cu 3 PSe 4 (CPSe) and Cs 2 CuP 3 S 9 (CCPS) were synthesized and studied as IR NLO materials. They both feature three-dimensional polyanionic frameworks constructed by similar T2-supertetrahedra, and the structure of CCPS can be derived from CPSe via introducing Cs and substituting Se with S. This structural evolution results in phase-matchable NLO behavior, enlarged optical band gap, and enhanced laser-induced damage threshold for CCPS. These results are elucidated by structure analysis and theoretical calculations, and the increased structural anisotropy contributes to the phase matchable behavior of CCPS. This work presents a case on how to adjust NLO properties via certain structure considerations, which may be extended to more systems for obtaining high-performance NLO materials.

Exposure to Pb 2+ in the environment, especially in water, poses a significant threat to human health and urgently necessitates the development of highly sensitive Pb 2+ detection methods. In this study, we have integrated the high sensitivity of electrochemical techniques with allosteric transcription factors (aTFs) to develop an innovative electrochemical biosensing platform. This biosensors leverage the specific binding and dissociation of DNA to the aTFs (PbrR) on electrode surfaces to detect Pb 2+ . Under the optimal conditions, the platform has a broad linear detection range from 1 pM to 10 nM and an exceptionally low detection threshold of 1 pM, coupled with excellent selectivity for Pb 2+ . Notably, the biosensor demonstrates regenerative capabilities, enabling up to five effective Pb 2+ measurements. After one week of storage at 4 °C, effective lead ion detection was still possible, demonstrating the biosensor's excellent stability, this can effectively save the cost of detection. The biosensor also achieves a recovery rate of 93.3% to 106.6% in real water samples. The biosensor shows its potential as a robust tool for the ultrasensitive detection of Pb 2+ in environmental monitoring. Moreover, this research provides new insights into the future applications of aTFs in electrochemical sensing.

Alkaline phosphatase (ALP) is abnormally expressed in some cancers and promotes the growth, metastasis, and invasion of cancer cells. The detection of ALP is of great significance for both pathological study and clinical detection. In this work, a europium (Eu)-based fluorescence detection sensor was prepared in a mild reaction condition. LaF 3 :Eu nanoparticles was mixed with ethylene imine polymer (PEI) and Ag + ions. PEI was used as stabilizer and reducing agent, and Ag + ions were reduced as molecular-like silver clusters (ML-Ag NCs). The fluorescence of LaF 3 :Eu nanoparticles was enhanced by ML-Ag NCs through energy transfer. When ascorbic acid 2-phosphate (AAP) was hydrolyzed to ascorbic acid (AA) in the presence of ALP, AA reduced Ag + ions to silver nanoparticles (Ag NPs) and quenched the fluorescence of LaF 3 :Eu/PEI/Ag. The activity of ALP was detected by measuring the fluorescence intensity of Eu 3+ at 618 nm. In the concentration range from 2.0 to 16.0 U/L, the fluorescence intensity ratio ((F 0 -F)/F 0 ) had a linear relationship with the logarithm of ALP concentration. The limit of detection (LOD) was 1.3 U/L. Moreover, the ALP activity was detected successfully in cancer cells by this method. The sensing platform has application potential in the detection of ALP activity in biological systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microplastic (MP) accumulation has recently become a pressing global environmental challenge. As a major producer and consumer of plastic products, China's MP pollution has garnered significant attention from researchers. However, accurate and comprehensive investigations of national-level MP pollution are still lacking. In this study, we systematically collated a national MP pollution dataset consisting of 7766 water, soil, and sediment sampling sites from 544 publicly published studies, revealing the spatiotemporal distribution and potential risks of MP pollution in China. The results indicate that MP distribution is influenced by various regional factors, including economic development level, population distribution, and geographical environment, exhibiting considerable range and complexity. MP concentrations are generally higher in economically prosperous areas, but the degree of pollution varies significantly across different environmental media. Given the uncertainty and lack of standardized data in traditional microplastic risk assessment methods, this article highlights the urgency of developing a comprehensive big data and artificial intelligence (AI)-based regulatory framework. This work provides a substantial amount of accurate MP pollution data and offers a fresh perspective on leveraging AI for microplastic pollution regulation., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Hip fractures present a significant healthcare challenge, especially within aging populations, where they are often caused by falls. These fractures lead to substantial morbidity and mortality, emphasizing the need for timely surgical intervention. Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors. The study cohort included 547 patients, with 94 experiencing hip fracture. To assess the risk of hip fracture, clinical variables and clinical variables combined with hip DXA imaging features were evaluated as predictors, followed by a novel staged approach. Hip DXA imaging features included those extracted by convolutional neural networks (CNNs), shape measurements, and texture features. Two ensemble machine learning models were evaluated: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and imaging features) using the logistic regression as the base classifier and bootstrapping for ensemble learning. The staged approach was developed using uncertainty quantification from Ensemble 1 which was used to decide if hip DXA imaging features were necessary to improve prediction for each subject. Ensemble 2 exhibited the highest performance, achieving an Area Under the Curve (AUC) of 0.95, an accuracy of 0.92, a sensitivity of 0.81, and a specificity of 0.94. The staged model also performed well, with an AUC of 0.85, an accuracy of 0.86, a sensitivity of 0.56, and a specificity of 0.92, outperforming Ensemble 1, which had an AUC of 0.55, an accuracy of 0.73, a sensitivity of 0.20, and a specificity of 0.83. Furthermore, the staged model suggested that 54.49 % of patients did not require DXA scanning, effectively balancing accuracy and specificity, while offering a robust solution when DXA data acquisition is not feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of advanced modeling strategies. Our staged approach offers a cost-effective holistic view of patient health. It can identify individuals at risk of hip fracture with a high accuracy while reducing unnecessary DXA scans. This approach has great promise to guide the need for interventions to prevent hip fracture while reducing diagnostic cost and exposure to radiation., Competing Interests: All authors declare that there are no conflicts of interest., (© 2024 The Authors. Published by Elsevier Inc.)

Background and Objectives: Geographical variation existed in the incidences of Guillain-Barré syndrome (GBS), but no national population-based study has evaluated the incidences of GBS in China. This study aimed to estimate the incidence of GBS in urban China and evaluate the worldwide variation in the incidence of GBS., Methods: Firstly, we did a population-based study to calculate the incidence of GBS in urban China based on the National Urban Medical Insurance database from 2013 to 2017. To identify GBS cases, natural language processing was used first for handling the lengthy and unstructured diagnostic information and then checked by prestigious neurologists. Secondly, a systematic review and meta-analysis were performed to analyze the incidence of GBS worldwide. Up to July 4, 2022, Medline, Embase, and Web of Science were retrieved to identify the population-based studies regarding the incidence of GBS. The basic information and the statistics regarding incidence were extracted. Quality assessment considered sample representativeness, condition assessment, and statistical methods., Results: A total of 1.44 billion person-years in insurance data was covered, with 3,534 GBS cases identified. The annual incidences of GBS in urban China between 2013 and 2017 ranged from 0.41 (95% CI: 0.27 to 0.58) to 0.58 (95% CI: 0.38 to 0.82) per 100,000 person-years. The incidence was the highest in Northwest China and the lowest in Northeast China. The meta-analysis included 122 articles. The quality assessment showed that the quality scores of 43.3% of studies were ≥ 0.75 (the total score is 1). The global incidence of GBS was 1.12 (95% CI: 0.98 to 1.27) per 100,000 person-years. The incidences in West Europe, South Asia, and North Europe were higher, while the incidences in Australia and New Zealand, Southeast Asia, and North Africa were lower. The incidence of enteric infections was positively associated with the incidence of GBS (coefficient=0.0000185, P=0.007). The incidence in Europe, Australia, and America rose significantly from 1960 to 2020 (coefficient=0.01, t=2.52, P=0.015)., Discussion: There is a clear regional variation of the GBS incidence at both national and global levels. Careful control of enteric infections should be conducted to reduce the disease burden., Competing Interests: Author GL was employed by Peking University Health Information Technology Co., Ltd., and author JXW was employed by Shanghai Songsheng Business Consulting Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Zhao, Bao, Liu, Liang, Wei, Liu, Wang, Zhan, Wang and Fan.)

This study investigated the diagnostic potential of targeted next-generation sequencing (tNGS) for pulmonary infections. The positivity rate of tNGS was significantly higher than that of traditional microbial culture (92.6 % vs 25.2 %, χ2 = 378.272, P < 0.001). The proportion of two or more species of pathogens detected using tNGS exceeded that detected using microbial culture (χ2 = 337.283, P < 0.001). There were inconsistencies between the results of the tNGS antibiotic resistance gene and the drug susceptibility test resistance phenotype. The tNGS technique demonstrates rapid and effective capabilities in identifying bacteria, fungi, viruses, and specific pathogens, with a detection sensitivity that surpasses that of conventional culture methodologies. Microbial drug resistance genotypes detected by tNGS cannot accurately predict drug resistance phenotypes and require further improvement or integration with traditional microbial culture to establish a foundation for effective clinical treatment., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose. The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Urban composite non-point source (UCNPS) has an increasing degree of influence on the urban receiving waters. However, there remains a dearth of precise techniques to characterize and evaluate the contribution of UCNPS. Therefore, this study developed a source analytical methodology system based fluorescence excitation-emission matrices spectroscopy (EEMs) and Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS).Specifically, it utilized parallel factor analysis (PARAFAC), two-dimensional correlation spectroscopy (2D-COS), end-member mixing analysis (EMMA), and non-metric multidimensional scaling (NMDS) to analysis UCNPS pollution characteristics and quantify its contributions to river DOM. The results of its application in typical hilly and plain urban within the Yangtze River Basin, China revealed that road and roof runoff exhibited high aromaticity and humic-like content, and the characteristics of pipe sediment was similar with domestic sewage. The component of Rivers had sequences of changes under rainfall perturbations. But terrestrial humic-like represented the initial input in all cases, and it can provide some indication of UCNPS input. The results of EMMA showed that the contribution of road runoff, roof runoff, pipeline sediment and domestic sewage to river DOM was 9.0 %-36.0 %, 2.6 %-19.1 %, 2.3 %-28.8 % and 5.9 %-25.9 %, respectively, and the specific contribution was mainly affected by rainfall level, regional terrain and drainage system. The methodology system of this study can provide technical support for the traceability and precise control of UCNPS pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Optical flow ratio (OFR) is a novel computational fractional flow reserve derived from optical coherence tomography (OCT). However, the impact of combining post-stenting morphology (OCT) and physiology (OFR) remains largely unknown., Method: OCT and OFR were analyzed at the independent core laboratory. Target lesion failure (TLF) was defined as the composite of cardiac death, target lesion myocardial infarction and target lesion revascularization. Suboptimal stent deployment was identified with at least one TLF-related OCT or OFR characteristics., Results: A total of 448 ACS patients (459 vessels) were assessed. Stent expansion<80%, MSA<4.5 mm 2 and stent edge lipid-rich plaque and OFR<0.90 were independent predictors of TLR (all p value<0.001). Patients with OCT-suboptimal [adjusted hazard ratio (HR): 7.88, 95% CI: 2.73-22.72, p<0.001] or OFR-suboptimal (adjusted HR: 5.78, 95% CI: 2.54-13.14, p<0.001) stent deployment showed significantly higher risk of TLF compared to those with optimal stent deployment with a significant interaction (p interaction <0.001). OCT and OFR both-suboptimal stent deployment was confirmed as an independent predictor of TLF (adjusted HR: 9.39, 95% CI: 4.25-20.76, p<0.001)., Conclusion: Combined OCT and OFR conferred an optimal reclassification of stent deployment, which may aid in decision-making regarding a tailored PCI strategy for optimal stent deployment., (Copyright © 2024. Published by Elsevier Inc.)

Preoperative diagnosis of periprosthetic joint infection (PJI) is critical to guide treatment options and improve patient outcomes. In this letter, we discuss results from our experiences with a novel nomogram diagnosis model based on serum and synovial fluid indicators for the preoperative diagnosis of PJI. The results showed that the novel nomogram diagnosis model can distinguish PJI from aseptic loosening before the operation. And it is also a useful candidate for the selection of the timing of current secondary revision., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Protein aggregates are emerging therapeutic targets in rare monogenic causes of cardiomyopathy and amyloid heart disease, but their role in more prevalent heart failure syndromes remains mechanistically unexamined. We observed mis-localization of desmin and sarcomeric proteins to aggregates in human myocardium with ischemic cardiomyopathy and in mouse hearts with post-myocardial infarction ventricular remodeling, mimicking findings of autosomal-dominant cardiomyopathy induced by R120G mutation in the cognate chaperone protein, CRYAB. In both syndromes, we demonstrate increased partitioning of CRYAB phosphorylated on serine-59 to NP40-insoluble aggregate-rich biochemical fraction. While CRYAB undergoes phase separation to form condensates, the phospho-mimetic mutation of serine-59 to aspartate (S59D) in CRYAB mimics R120G-CRYAB mutants with reduced condensate fluidity, formation of protein aggregates and increased cell death. Conversely, changing serine to alanine (phosphorylation-deficient mutation) at position 59 (S59A) restored condensate fluidity, and reduced both R120G-CRYAB aggregates and cell death. In mice, S59D CRYAB knock-in was sufficient to induce desmin mis-localization and myocardial protein aggregates, while S59A CRYAB knock-in rescued left ventricular systolic dysfunction post-myocardial infarction and preserved desmin localization with reduced myocardial protein aggregates. 25-Hydroxycholesterol attenuated CRYAB serine-59 phosphorylation and rescued post-myocardial infarction adverse remodeling. Thus, targeting CRYAB phosphorylation-induced condensatopathy is an attractive strategy to counter ischemic cardiomyopathy.

Parkinson's disease (PD) poses a formidable challenge in neurology, marked by progressive neuronal loss in the substantia nigra. Despite extensive investigations, understanding PD's pathophysiology remains elusive, with no effective therapeutic intervention identified to alter its course. Oxyphylla A (OPA), a natural compound extracted from Alpinia oxyphylla, exhibits promise in experimental models of various neurodegenerative disorders (ND), notably through novel mechanisms like α-synuclein degradation. The purpose of this investigation was to explore the neuroprotective potential of OPA on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PD models, with a focus on mitochondrial functions. Additionally, potential OPA targets for neuroprotection were explored. PC12 cells and C57BL/6 mice were lesioned with 6-OHDA as PD models. Impaired mitochondrial membrane potential (Δψm) was assessed using JC-1 staining. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were also detected to evaluate mitochondrial function and glucose metabolism in PC12 cells. Behavioral analysis and immunohistochemistry were performed to evaluate pathological lesions in the mouse brain. Moreover, bioinformatics tools predicted OPA targets. OPA restored cellular energy metabolism and mitochondrial biogenesis, preserving Δψm in 6-OHDA-induced neuronal damage. Pre-treatment mitigated loss of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and striatal dopaminergic fibers, restoring dopamine levels and ameliorating motor deficits in PD mice. Mechanistically, OPA may activate PKA/Akt/GSK-3β and CREB/PGC-1α/NRF-1/TFAM signaling cascades. Bioinformatics analysis identified potential OPA targets, including CTNNB1, ESR1, MAPK1, MAPK14, and SRC. OPA, derived from Alpinia oxyphylla, exhibited promising neuroprotective activity against PD through addressing mitochondrial dysfunction, suggesting its potential as a multi-targeted therapeutic for PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eight novel arylnaphthalide lactone lignans, designated as diphylignan A-H (1-8), and a new dibenzyltyrolactone lignan, designated as diphylignan I (9), were isolated from the roots and rhizomes of Diphylleia sinensis, along with two additional novel natural products (11 and 14) and four known metabolites (10, 12, 13, 15). The structural and stereochemical characterization of these compounds was accomplished using NMR spectroscopy and electronic circular dichroism (ECD) analysis. The cytotoxic activities of all isolated compounds were assessed against A-549 and SMMC-7721 cell lines. Notably, compound 2 demonstrated the most significant cytotoxicity, with IC 50 values of 10.27 and 11.58 µmol·L -1 against A-549 and SMMC-7721 cell lines, respectively, exhibiting greater potency than the positive control, cisplatin., (Copyright © 2024 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Isoxazoline insecticides have shown broad-spectrum insecticidal activity against a variety of insect pests. However, the high toxicity of isoxazoline compounds towards honeybees restricts their application in crop protection. To mitigate this issue, a series of isoxazoline derivatives containing 2-phenyloxazoline were designed and synthesized. Bioassays revealed that several compounds exhibited promising insecticidal activities against Plutella xylostella, with G28 showing particularly excellent insecticidal activity, reflected by an LC 50 value of 0.675 mg/L, which is comparable to that of fluxametamide (LC 50  = 0.593 mg/L). Furthermore, G28 also exhibited effective insecticidal activity against Solenopsis invicta. Importantly, bee toxicity experiments indicated that G28 had significantly lower acute oral toxicity (LD 50  = 2.866 μg/adult) compared to fluxametamide (LD 50  = 1.083 μg/adult) and fluralaner (LD 50  = 0.022 μg/adult), positioning it as a promising candidate with reduced toxicity to bees. Theoretical simulation further elucidated the reasons for the selective differences in the ability of isoxazoline to achieve higher insecticidal activity while maintaining lower bee toxicity. This research suggests that isoxazoline compounds containing 2-phenyloxazoline group hold potential as new insecticide candidates and offers insights into the development of novel isoxazoline insecticides with both high efficacy and environmental safety., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Drug resistance of malignant tumor leads to disease progression be the bottleneck in clinical treatment. Antiangiogenic therapy, which aims to "starve" the tumor by inhibiting angiogenesis, is one of the key strategies in clinical oncology treatments. Recently, dozens of investigational antibody drugs and biosimilars targeting angiogenesis have obtained regulatory approval for the treatment of various malignancies. Moreover, a new generation of bispecific antibodies based on the principle of antiangiogenesis are being advanced for clinical trial to overcome antiangiogenic resistance in tumor treatment or enhance the efficacy of monotherapy. Tumors often develop resistance to antiangiogenesis therapy, presenting as refractory and sometimes even resistant to new therapies, for which there are currently no effective management strategies. Thus, a detailed understanding of the mechanisms mediating resistance to antiangiogenesis antibodies is crucial for improving drug effectiveness and achieving a durable response to antiangiogenic therapy. In this review, we provide a novel perspective on the tumor microenvironment, including antibody structure, tumor stroma, and changes within tumor cells, to analyze the multifactorial reasons underlying resistance to antiangiogenesis antibodies. The review also enumerates biomarkers that indicate resistance and potential strategies for monitoring resistance. Furthermore, based on recent clinical and preclinical studies, we summarize potential strategies and translational clinical trials aimed at overcoming resistance to antiangiogenesis antibodies. This review provides a valuable reference for researchers and clinical practitioners involved in the development of new drugs or therapeutic strategies to overcome antiangiogenesis antibodies resistance., (© 2024 The Author(s). Drug Development Research published by Wiley Periodicals LLC.)

Objective: Clinical practice guidelines (CPGs) for Integrated Traditional Chinese and Western Medicine (TCM and WM) are important medical documents used to assist medical decision-making and are of great significance for standardizing clinical pathways. However, due to the constraints of text format, it is difficult for Integrated TCM and WM CPGs to play a real role in medical practice. In addition, how to standardize the structure and semantic relationships between Integrated TCM and WM CPG knowledge, and realize the construction of computable, sharable and reliable CPGs, remains an urgent issue to be addressed. Therefore, we are proposing an ontology of CPGs for Integrated TCM and WM., Methods: We first initialized domain concepts and relationships to ensure the accuracy of the ontology knowledge structure. We then screened CPGs that meet the standards for Integrated TCM and WM, analyzed and classified the contents, and extracted the common structures. Based on the seven-step ontology construction method combined with inference-complement, referring to the representation methods and hierarchical relationships of terms and concepts in MeSH, ICD-10, SNOMED-CT, and other ontologies and terminology sets, we formed the concept structure and semantic relationship tables for the ontology. We also achieved the matching and mapping between the ontology and reference ontologies and term sets. Next, we defined the aspects and constraints of properties, selected multiple Integrated TCM and WM CPGs as instances to populate, and used ontology reasoning tools and formulated defined inference rules to reason and extend the ontology. Finally, we evaluated the performance of the ontology., Results: The content of the Integrated TCM and WM CPGs is divided into nine parts: basic information, background, development method, clinical question, recommendation, evidence, conclusion, result, and reason for recommendations. The Integrated TCM and WM CPG ontology has 152 classes and defines 90 object properties and 114 data properties, with a maximum classification depth of 4 layers. The terms of disease, drug and examination item names in the ontology have been standardized., Conclusions: This study proposes an Integrated TCM and WM CPG ontology. The ontology adopts a modular design, which has both sharing and scaling ability, and can express rich guideline knowledge. It provides important support for the semantic processing and computational application of guideline documents., (© 2024 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Objectives: Subsegmentectomy has been adopted for non-small cell lung cancer (NSCLC) for decades. This study aimed to compare the features between subsegmentectomy, segmentectomy and wedge resection for NSCLC., Materials and Methods: NSCLC patients who underwent subsegmentectomy, segmentectomy, or wedge resection between 2014 and 2019 were retrospectively screened. Demographic, radiomic, and perioperative characteristics between patients were compared. Further, log-rank test, univariate and multivariate Cox regression were used for prognostic evaluation., Results: There were 276, 670, and 494 patients undergoing subsegmentectomy, segmentectomy, and wedge resection, respectively. Patients with segmentectomy and subsegmentectomy had larger tumor sizes and greater distances to the pleura than those with wedge resection. Subsegmentectomy and segmentectomy were more likely to achieve adequate surgical margins than wedge resection (82.0 % vs. 79.5 % vs. 64.7 %, P < 0.001), which was especially true for nodules away from the pleura (80.2 % vs. 81.4 % vs. 55.8 %, P < 0.001). In addition, anatomic resection allowed for more lymph node dissection and required less preoperative localization than wedge reception. Subsegmentectomy preserved about two subsegments than segmentectomy (P < 0.001). The incidence of prolonged air leakage after subsegmentectomy (3.3 %) and wedge (1.8 %) was similar (P = 0.308). Notably, 66.8 % of patients who underwent segmentectomy or subsegmentectomy were considered unsuitable for wedge. During the follow-up (55.1 months), no tumor recurrence or death occurred in patients undergoing subsegmentectomy. No significant recurrence-free survival (P = 0.140) or overall survival (P = 0.370) difference existed between these groups., Conclusions: Subsegmentectomy could achieve more adequate surgical margins than wedge resection and showed superiority for deep nodules. Compared to segmentectomy, subsegmentectomy could preserve more lung parenchyma., Competing Interests: Declaration of Competing interest We wish to confirm that there are no conflicts of interest associated with this publication. We confirm that the manuscript has been read and approved by all named authors, and the order of authors listed in the manuscript has been approved by all of us., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Traumatic brain injury (TBI), especially neuroinflammation after TBI persists for a long time and causes significant neurodegenerative pathologies and neuropsychiatric problems., Purpose: In this study, the neuroprotective effect of AnGong NiuHuang (AGNH) on TBI was investigated and the mechanism was revealed by integrating multiple omics., Methods: The rats with TBI were administrated with AGNH for 5 consecutive days and the effect was evaluated by using modified neurologic severity score (mNSS), brain edema, H&E staining, Nissl staining and TUNEL staining. The mechanism was revealed by using RNA sequencing (RNA-seq) and metabolomic analysis. The inflammatory factors, apoptosis-related proteins and identified vital targets were validated by enzyme-linked immunosorbent assay, western blotting and immunofluorescence staining., Results: Administration of AGNH decreased mNSS, brain edema, brain structure damage, but increased Nissl body density in the rats with TBI. Additionally, AGNH reduced IL-1β, IL-17A, TNF-α, MMP9, MCP-1, IL-6, Bax and TUNEL staining,but elevated Bcl2 level. Integrating transcriptomic analysis and metabolomic analysis identified vital targets and critical metabolic pathways. Importantly, AGNH treatment reduced the expression of TLR4, MYD88, NLRP3, BTK, IL-18 and Caspase 1 as well as glycerophospholipid metabolism-related protein AGPAT2 and PLA2G2D, and decreased the nuclear translocation of NF-κB p65 in the brain of TBI rats. Additionally, AGNH increased phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylserine (PS), phosphatidylethanolamine (PE), but decreased 1-acyl-sn-glycero-3-phosphocholine (LysoPC) in the metabolic pathway of glycerophospholipid metabolism., Conclusion: Taken together, AGNH inhibited NF-κB/NLRP3 axis to suppress neuroinflammation, cell apoptosis and pyroptosis, and improved metabolic pathways of glycerophospholipid metabolism after TBI., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: The relationship between bone density and fracture has been widely studied and recognized, and the role of cortical bone in proximal femoral fractures has also been increasingly studied. However, both the determination of bone mineral density (BMD) and the determination of cortical mass are expensive and cumbersome. The purpose of this study is to investigate whether two readily available indicators, Hounsfield Units (HUs) and femoral cortical index (FCI), can be used to predict hip fracture classification and prognosis., Methods: A retrospective study was conducted on 110 patients with hip fragility fractures. Cortical index was calculated on fractured and contralateral femur FCI, with HUs calculated on the proximal femur. The correlation of the FCI and HU with diabetes, hypertension, and related indicators, such as albumin, creatinine, and urea nitrogen levels, were also analyzed in the study., Results: Both the Evans classification of intertrochanteric fractures and the Garden and Pauwels classifications of femoral neck fractures showed that as the severity of the fracture increased, the HUs and FCI decreased. Age and albumin level also had a negative correlation with HUs and FCI. There was also a significant correlation between HUs and FCI., Conclusions: The HUs and FCI, which can be easily and quickly obtained, can be used to predict the classification and prognosis of hip fractures., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Our previous study identified that nuclear factor-erythroid-2 p45-related factor 2 (NRF2) was activated in arsenite-induced tumorigenesis. However, the underlying mechanisms of NRF2 mediating apoptosis in arsenic-induced skin carcinogenesis remain unknown. This study explored the dynamic changes in apoptosis rate and the expression of apoptosis proteins in immortalized human keratinocytes (HaCaT) malignant transformation caused by 1.0 μM NaAsO 2 at passages 0, 1, 7, 14, 21, 28, and 35. The result showed that the apoptosis rate decreased. The apoptosis-related proteins cleaved-caspase-3/caspase-3 ratio decreased in the later stages (passages 21, 28, and 35). Moreover, the expression of intrinsic ER stress pathway-related CHOP, ATF4, ATF6, and the intrinsic mitochondrial pathway-related Bax protein decreased in the later stages, while Bcl-2 and Mcl-1 increased, and NRF2 protein levels also increased. The apoptosis rate increased by silencing NRF2 expression in arsenite-transformed HaCaT (T-HaCaT) cells. Meanwhile, the expression of pro-apoptotic proteins (cleaved-caspase-3/caspase-3, CHOP, Bax) and ATF4, ATF6 increased. On the contrary, antiapoptotic protein levels (Bcl-2 and Mcl-1) decreased. The ability of colony formation and migration of T-HaCaT cells decreased. In conclusion, arsenite activated NRF2 in the later stages, decreasing apoptosis characterized by inhibiting endoplasmic reticulum stress-depended and mitochondria-depended apoptosis pathway, and further promoting NaAsO 2 -induced HaCaT cellular malignant transformation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Previous studies reported mixed findings on autistic individuals' pitch perception relative to neurotypical (NT) individuals. We investigated whether this may be partly due to individual differences in cognitive abilities by comparing their performance on various pitch perception tasks on a large sample (n = 164) of autistic and NT children and adults. Our findings revealed that: (i) autistic individuals either showed similar or worse performance than NT individuals on the pitch tasks; (ii) cognitive abilities were associated with some pitch task performance; and (iii) cognitive abilities modulated the relationship between autism diagnosis and pitch perception on some tasks. Our findings highlight the importance of taking an individual differences approach to understand the strengths and weaknesses of pitch processing in autism., (© 2023. The Author(s).)

Objective: We intended to map the single-cell profile of OLP, explore the molecular characteristics of unconventional T cells in OLP tissues., Methods: Buccal mucosa samples from OLP patients and healthy individuals were used to prepare single-cell suspension. Single-cell RNA sequencing was used to analyze the proportion of all the cells, and the molecular characteristics of unconventional T cells. Immunohistochemical staining was used to detect the expression of unconventional T cells marker genes., Results: The cell clusters from buccal mucosa were categorized into immune cells, fibroblasts, endothelial cells, and epithelial cells. Unconventional T cells with phenotype of CD247 + TRDC + NCAM1 + were identified. Immunohistochemical staining revealed higher expression of unconventional T cell marker genes in OLP tissue, predominantly in the lamina propria. In OLP, unconventional T cells are in a unique stress response state, exhibited enhanced NF-κB signaling and apoptosis inhibition, enhanced heat shock protein genes expression, weakened cytotoxic function. A large number of ligand-receptor pairs were found between unconventional T cells and other cells, particularly with fibroblasts and endothelial cells., Conclusions: This study mapped the single-cell profile of OLP, delineated the molecular characteristics of unconventional T cells in OLP, and uncovered that these unconventional T cells are in a stress response state., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Saponins are bioactive components of many medicinal plants, possessing complicated chemical structures and extensive pharmacological activities, but the production of high-value saponins remains challenging. In this study, a 6'-O-glucosyltransferase PpUGT7 (PpUGT91AH7) was functionally characterized from Paris polyphylla Smith var. yunnanensis (Franch.) Hand. -Mazz., which can transfer a glucosyl group to the C-6' position of diosgenin-3-O-rhamnosyl-(1 → 2)-glucoside (1), pennogenin-3-O-rhamnosyl-(1 → 2)-glucoside (2), and diosgenin-3-O-glucoside (5). The K M and K cat values of PpUGT7 towards the substrate 2 were 8.4 μM and 2 × 10 -3 s -1 , respectively. Through molecular docking and site-directed mutagenesis, eight residues were identified to interact with the sugar acceptor 2 and be crucial for enzyme activity. Moreover, four rare ophiopogonins and ginsenosides were obtained by combinatorial biosynthesis, including an undescribed compound ruscogenin-3-O-glucosyl-(1 → 6)-glucoside (10). Firstly, two monoglycosides 9 and 11 were generated using a known sterol 3-O-β-glucosyltransferase PpUGT80A40 with ruscogenin (7) and 20(S)-protopanaxadiol (8) as substrates, which were further glycosylated to the corresponding diglycosides 10 and 12 under the catalysis of PpUGT7. In addition, compounds 7-11 were found to show inhibitory effects on the secretion of TNF-α and IL-6 in macrophages RAW264.7. The findings provide valuable insights into the enzymatic glycosylation processes in the biosynthesis of bioactive saponins in P. polyphylla var. yunnanensis, and also serve as a reference for utilizing UDP-glycosyltransferases to construct high-value or rare saponins for development of new therapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Seven undescribed abietane diterpenoids [abietamethinols A-G (1-7)] were isolated from the twigs and leaves of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic methods including 2D NMR, and they were further confirmed by X-ray crystallographic data. Lophanic acid was considered as the precursor of 1-7 in the biosynthesis pathway hypothesis. These compounds were evaluated for their cytotoxic, anti-bacterial and anti-AIV (avian influenza virus) activities. Compound 5 showed 42.9% inhibitory activity against the cancer cell line SMMC-7721 at the concentration of 40 μM, 3 and 4 could inhibit the bacterial growth of Streptococcus sobrinus by 55.3% and 63.2% at the concentrations of 148.6 and 141.9 μM, respectively, and 4 was demonstrated with antiviral activity against AIV with the inhibitory effect of 68.4% at 25 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH., Methods: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants., Results: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma (+) /PBMC (+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one., Conclusions: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study., (© 2024 Wiley Periodicals LLC.)

Deoxynivalenol (DON) is a common mycotoxin in food that mainly pollutes grain crops and feeds, such as barley, wheat and corn. DON has caused widespread concern in the field of food and feed safety. In this study, a colorimetric immunoassay was proposed based on the aggregation of gold nanoparticles (AuNPs) due to the decomposition of Mn 2+ from gold-coated manganese dioxide (AuNP@MnO 2 ) nanosheets. In this study, 2-(dihydrogen phosphate)-l-ascorbic acid (AAP) was hydrolyzed by alkaline phosphatase (ALP) and converted to ascorbic acid (AA). Then, AuNP@MnO 2 was reduced to Mn 2+ and AuNPs aggregation occurred. Using the unique optical characteristics of AuNPs and AuNP@MnO 2 , visible color changes realized simple detection of DON with high sensitivity and portability. With increasing DON content, the color changed more obviously. To quantitatively detect DON, pictures can be taken and the blue value can be read by a smartphone. The detection limit (Ic10) of this method was 0.098 ng mL -1 , which was 326 times higher than that of traditional competitive ELISA, and the detection range was 0.177-6.073 ng mL -1 . This method exhibited high specificity with no cross-reaction in other structural analogs. The average recovery rate of DON in corn flour samples was 89.1 %-110.2 %, demonstrating the high accuracy and stability of this assay in actual sample detection. Therefore, the colorimetric immunoassay can be used for DON-related food safety monitoring., Competing Interests: Declaration of competing interest None of the authors (Xinrui Feng, Qinwei Xu, Yan Liu, Sijia Wang, Yong Cao, Chen Zhao, Shuai Peng) has any financial or personal relationship with other people or organisations that could inappropriately influence or bias the paper entitled “Smartphone-enabled colorimetric immunoassay for deoxynivalenol based on Mn(2+)-mediated aggregation of AuNPs”., (Copyright © 2024. Published by Elsevier Inc.)

Background: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies., Method: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-scale variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information., Results: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved R 2 -scores > 0.01 for 71.55 % of metabolites., Conclusion: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Published by Elsevier Ltd.)

Solid-state polymer lithium metal batteries are an important strategy for achieving high safety and high energy density. However, the issue of Li dendrites and inherent inferior interface greatly restricts practical application. Herein, this study introduces tris(2,2,2-trifluoroethyl)phosphate solvent with moderate solvation ability, which can not only complex with Li + to promote the in-situ ring-opening polymerization of 1,3-dioxolane (DOL), but also build solvated structure models to explore the effect of different solvation structures in the polymer electrolyte. Thereinto, it is dominated by the contact ion pair solvated structure with pDOL chain segments forming less lithium bonds, exhibiting faster kinetic process and constructing a robust anion-derived inorganic-rich interphase, which significantly improves the utilization rate of active Li and the high-voltage resistance of pDOL. As a result, it exhibits stable cycling at ultra-high areal capacity of 20 mAh cm -2 in half cells, and an ultra-long lifetime of over 2000 h in symmetric cells can be realized. Furthermore, matched with LiNi 0.9 Co 0.05 Mn 0.05 O 2 cathode, the capacity retention after 60 cycles is as high as 96.8% at N/P value of 3.33. Remarkably, 0.7 Ah Li||LiNi 0.9 Co 0.05 Mn 0.05 O 2 pouch cell with an energy density of 461 Wh kg -1 can be stably cycled for five cycles at 100% depth of discharge., (© 2024 Wiley‐VCH GmbH.)

Self-supervised learning (SSL) is a challenging task in sleep stage classification (SSC) that is capable of mining valuable representations from unlabeled data. However, traditional SSL methods typically focus on single-view learning and do not fully exploit the interactions among information across multiple views. In this study, we focused on a multi-domain view of the same EEG signal and developed a self-supervised multi-view representation learning framework via time series and time-frequency contrasting (MV-TTFC). In the MV-TTFC framework, we built-in a cross-domain view contrastive learning prediction task to establish connections between the temporal view and time-frequency (TF) view, thereby enhancing the information exchange between multiple views. In addition, to improve the quality of the TF view inputs, we introduced an enhanced multisynchrosqueezing transform, which can create high energy concentration TF image views to compensate for the inaccurate representations in traditional TF processing techniques. Finally, integrating temporal, TF, and fusion space contrastive learning effectively captured the latent features in EEG signals. We evaluated MV-TTFC based on two real-world SSC datasets (SleepEDF-78 and SHHS) and compared it with baseline methods in downstream tasks. Our method exhibited state-of-the-art performance, achieving accuracies of 78.64% and 81.45% with SleepEDF-78 and SHHS, respectively, and macro F1-scores of 70.39% with SleepEDF-78 and 70.47% with SHHS.

Acetylcholine regulates various cognitive functions through broad cholinergic innervation. However, specific cholinergic subpopulations, circuits and molecular mechanisms underlying recognition memory remain largely unknown. Here we show that Ngfr + cholinergic neurons in the substantia innominate (SI)/nucleus basalis of Meynert (nBM)-medial prefrontal cortex (mPFC) circuit selectively underlies recency judgements. Loss of nerve growth factor receptor (Ngfr -/- mice) reduced the excitability of cholinergic neurons in the SI/nBM-mPFC circuit but not in the medial septum (MS)-hippocampus pathway, and impaired temporal order memory but not novel object and object location recognition. Expression of Ngfr in Ngfr -/- SI/nBM restored defected temporal order memory. Fiber photometry revealed that acetylcholine release in mPFC not only predicted object encounters but also mediated recency judgments of objects, and such acetylcholine release was absent in Ngfr -/- mPFC. Chemogenetic and optogenetic inhibition of SI/nBM projection to mPFC in ChAT-Cre mice diminished mPFC acetylcholine release and deteriorated temporal order recognition. Impaired cholinergic activity led to a depolarizing shift of GABAergic inputs to mPFC pyramidal neurons, due to disturbed KCC2-mediated chloride gradients. Finally, potentiation of acetylcholine signaling upregulated KCC2 levels, restored GABAergic driving force and rescued temporal order recognition deficits in Ngfr -/- mice. Thus, NGFR-dependent SI/nBM-mPFC cholinergic circuit underlies temporal order recognition memory., (© 2024. The Author(s).)

Enantiopure Si -stereogenic organosilanes are highly valued in the fields of organic synthesis, development of advanced materials, and drug discovery. However, they are not naturally occurring, and their synthesis has been largely confined to resolution of racemic silanes or desymmetrization of symmetric silanes. In contrast, the dynamic kinetic asymmetric transformation (DYKAT) of racemic organosilanes offers a mechanistically distinct approach and would broaden the accessibility of Si -stereogenic silanes in an enantioconvergent manner. In this study, we report a Lewis base-catalyzed DYKAT of racemic chlorosilanes. The chiral isothiourea catalyst, ( S )-benzotetramisole, facilitates silyletherification with phenols, yielding ( R )-silylethers in good yields with high enantioselectivity (27 examples, up to 86% yield, up to 98:2 er ). Kinetic analysis, control experiments, and DFT calculations suggest that a two-catalyst-bound pentacoordinate silicate is responsible for the Si -configurational epimerization of the ion-paired tetracoordinated silicon intermediates.

Microstrain and the associated surface-to-bulk propagation of structural defects are known to be major roadblocks to developing high-energy and long-life batteries. However, the origin and effects of microstrain during the synthesis of battery materials remain largely unknown. Here we perform microstrain screening during real-time and realistic synthesis of sodium layered oxide cathodes. Evidence gathered from multiscale in situ synchrotron X-ray diffraction and microscopy characterization collectively reveals that the spatial distribution of transition metals within individual precursor particles strongly governs the nanoscale phase transformation, local charge heterogeneity and accumulation of microstrain during synthesis. This unexpected dominance of transition metals results in a counterintuitive outward propagation of defect nucleation and growth. These insights direct a more rational synthesis route to reduce the microstrain and crystallographic defects within the bulk lattice, leading to significantly improved structural stability. The present work on microstrain screening represents a critical step towards synthesis-by-design of defect-less battery materials., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

D-glucaric acid is a platform chemical of great importance and the consolidated bioprocessing (CBP) of lignocellulose by the microbial consortium of Trichoderma reesei C10 and Saccharomyces cerevisiae LGA-1C3S2 features prospects in biomanufacturing it. Here we compared some representative lignocelluloses in Northwest China including corn stover, wheat straw and switchgrass, and the leading pretreatments including steam explosion, subcritical water pretreatment, sodium hydroxide pretreatment, aqueous ammonia pretreatment, lime pretreatment, and diluted sulfuric acid pretreatment. It was found that sodium hydroxide pretreated switchgrass (SHPSG) was the best substrate for D-glucaric acid production, resulting in the highest D-glucaric acid titers, 11.69 ± 0.73 g/L in shake flask and 15.71 ± 0.80 g/L in 10L airlift fermenter, respectively. To the best of our knowledge, this is the highest D-glucaric acid production titer from lignocellulosic biomass. This work offers a paradigm of producing low-cost D-glucaric acid for low-carbon polyethylene 2,5-furandicarboxylate (PEF) and a reference on developing biorefinery in Northwest China., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Rs1333040 is the single-nucleotide polymorphisms (SNP) related with coronary heart disease (CHD). The aim of the present study is to examine the association between rs1333040 polymorphism genotypes and CHD and to further explore the molecular mechanism in Chinese population., Methods: A case-control study was used in this study, including 500 CHD patients and 500 control subjects. CHD patients and controls were distinguished by coronary angiography. Genotypes of rs1333040 were determined on the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell)., Results: Fisher's exact test by plink indicated a significant difference in the allele distribution between cases and controls, the allele T may be associated with a higher risk of CHD ( p  = 0.012, odds ratio (OR) = 1.258). The serum levels of low-density lipoprotein cholesterol (LDL-C) ( p  = 0.029) and Gensini score ( p  = 0.008) distributed differently in patients with various alleles. In the recessive model, the levels of high-density lipoprotein (HDL) and apolipoprotein A (ApoA) were higher in the TC + CC genotype than in the TT genotype. The TC + TT genotype was found to be risk factors against CHD in a dominant model (OR = 1.278, p  = 0.014). The TC + TT genotype along with multiple risk factors significantly positively correlated with the risk of CHD., Conclusions: The present study investigates the association between the rs1333040 polymorphism genotypes and CHD. The T allele of rs1333040 is the susceptibility site of CHD. The interaction between SNP and various risk factors plays an important role in the development of CHD.

Objective: The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS)., Methods: In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the log-rank test and univariable and multivariable Cox regressions., Results: Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (β = -0.004, p = 0.026), tumor grade (β = -0.114, p = 0.011), and IDH genotype (β = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (β = -0.005, p < 0.001), tumor grade (β = -0.144, p < 0.001), IDH genotype (β = 0.154, p < 0.001), tumor volume (β = -0.002, p = 0.001), and peritumoral edema volume (β = -0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (β = -0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (β = -0.003, p = 0.022), IDH status (β = 0.132, p = 0.001), and tumor volume (β = -0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001)., Conclusions: GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.

With increases in life expectancy, the number of patients requiring joint replacement therapy and experiencing periprosthetic osteolysis, the most common complication leading to implant failure, is growing or underestimated. In this study, we found that osteolysis progression and osteoclast differentiation in the surface of the skull bone of adult mice were accompanied by significant expansion of lymphatic vessels within bones. Using recombinant VEGF-C protein to activate VEGFR3 and promote proliferation of lymphatic vessels in bone, we counteracted excessive differentiation of osteoclasts and osteolysis caused by titanium alloy particles or inflammatory cytokines LPS/TNF-α. However, this effect was not observed in aged mice because adipogenically differentiated mesenchymal stem cells (MSCs) inhibited the response of lymphatic endothelial cells to agonist proteins. The addition of the JAK inhibitor ruxolitinib restored the response of lymphatic vessels to external stimuli in aged mice to protect against osteolysis progression. These findings suggest that inhibiting SASP secretion by adipogenically differentiated MSCs while activating lymphatic vessels in bone offers a new method to prevent periprosthetic osteolysis during joint replacement follow-up., (© 2024. The Author(s).)

Background: Oral Mucositis (OM) is a common and highly symptomatic complication of cancer therapy that affects patient function and quality of life. Jingzhi Niuhuangjiedu Tablet (JNT) is derived from the famous Chinese herbal formulas Huanglian Jiedu and Fangfeng Tongsheng decoctions, which have been widely used to treat heat toxin syndrome diseases, such as acute pharyngitis, periodontitis, oral ulcers, and oral mucositis (OM), but the underlying mechanism remains unclear., Objectives: This study validated the efficacy and explored the potential mechanisms of JNT in the treatment of OM by integrating network pharmacological analyses and experimental verification., Methods: Network pharmacology and molecular docking techniques were used to predict the active components, key targets, and potential mechanisms of action of JNT against OM. The rat OM model was established by administering 5-Fluorouracil (5-FU) and acetic acid to the rat oral mucosa. Lipopolysaccharide (LPS)-treated human gingival fibroblasts (HGFs) were used as an inflammatory cell model. The GFP-NFκB HEK293T cell line was transfected to evaluate the anti-NFκB activity of JNT., Results: A total of 236 Chinese herbal components and 201 corresponding targets were predicted for OM treatment using JNT. Bicuculine, luteolin, wogonin, and naringenin were identified as the important active compounds, while AKT1, ALB, IL6, MAPK3, and VEGFA were considered to be the major targets. Molecular docking revealed that these active compounds exhibited strong binding interactions with their targets. In vivo and in vitro experiments demonstrated that the anti-OM effect of JNT might be closely related to AKT1, NFκB, caspase-1, and NLRP3, as well as biological processes, such as inflammatory response and oxidative stress., Conclusion: Network pharmacological and experimental evidence indicates that JNT has a potential therapeutic effect on OM by regulating the Akt/NFκB/NLRP3 pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia., Methods: Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8-15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0-1 mm (central fovea), 1-3 mm (parafovea), 3-6 mm (perifovea), and 6-9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants., Results: The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0-6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P < 0.001)., Conclusions: In UMA children, CCT and blood flow may be related to myopia progression. A robust correlation between CT and CVV in the 0-6-mm macular region and reduced CT and diminished blood flow indicated an association with myopia., (© 2024. The Author(s).)

Stem-like progenitors are a critical subset of cytotoxic T cells that self-renew and give rise to expanded populations of effector cells critical for successful checkpoint blockade immunotherapy. Emerging evidence suggests that the tumor-draining lymph nodes can support the continuous generation of these stem-like cells that replenish the tumor sites and act as a critical source of expanded effector populations, underlining the importance of understanding what factors promote and maintain activated T cells in the stem-like state. Using advanced 3D multiplex immunofluorescence imaging, here we identified antigen-presentation niches in tumor-draining lymph nodes that support the expansion, maintenance, and affinity evolution of a unique population of TCF-1+PD-1+SLAMF6 hi stem-like CD8+ T cells. Our results show that contrary to the prevailing view that persistent TCR signaling drives terminal effector differentiation, prolonged antigen engagement well beyond the initial priming phase sustained the proliferation and self-renewal of these stem-like T cells in vivo . The inhibitory PD-1 pathway plays a central role in this process by mediating the fine-tuning of TCR and co-stimulatory signal input that enables selective expansion of high affinity TCR stem-like clones, enabling them to act as a renewable source of high affinity effector cells. PD-1 checkpoint blockade disrupts this fine tuning of input signaling, leading to terminal differentiation to the effector state or death of the most avid anti-tumor stem-like cells. Our results thus reveal an unexpected relationship between TCR ligand affinity recognition, a key negative feedback regulatory loop, and T cell stemness programming. Furthermore, these findings raise questions about whether anti-PD-1 checkpoint blockade during cancer immunotherapy provides a short-term anti-tumor effect that comes at the cost of diminishing efficacy due to progressive loss of these critical high affinity stem-like precursors.

To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary., (© 2024. The Author(s).)

Background: Compared with intravascular ultrasound guidance, there is limited evidence for optical coherence tomography (OCT) guidance during primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients., Aims: We investigated the role of OCT in guiding a reperfusion strategy and improving the long-term prognosis of STEMI patients., Methods: All patients who were diagnosed with STEMI and who underwent pPCI between January 2017 and December 2020 were enrolled and divided into OCT-guided versus angiography-guided cohorts. They had routine follow-up for up to 5 years or until the time of the last known contact. All-cause death and cardiovascular death were designated as the primary and secondary endpoints, respectively., Results: A total of 3,897 patients were enrolled: 2,696 (69.2%) with OCT guidance and 1,201 (30.8%) with angiographic guidance. Patients in the OCT-guided cohort were less often treated with stenting during pPCI (62.6% vs 80.2%; p<0.001). The 5-year cumulative rates of all-cause mortality and cardiovascular mortality in the OCT-guided cohort were 10.4% and 8.0%, respectively, significantly lower than in the angiography-guided cohort (19.0% and 14.1%; both log-rank p<0.001). All 4 multivariate models showed that OCT guidance could significantly reduce 5-year all-cause mortality (hazard ratio [HR] in model 4: 0.689, 95% confidence interval [CI]: 0.551-0.862) and cardiovascular mortality (HR in model 4: 0.692, 95% CI: 0.536-0.895). After propensity score matching, the benefits of OCT guidance were consistent in terms of all-cause mortality (HR: 0.707, 95% CI: 0.548-0.913) and cardiovascular mortality (HR: 0.709, 95% CI: 0.526-0.955)., Conclusions: Compared with angiography alone, OCT guidance may change reperfusion strategies and lead to better long-term survival in STEMI patients undergoing pPCI. Findings in the current observational study should be further corroborated in randomised trials.