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Spiders are important in ecosystem and serve as predators in the biological control of pest insects in agroecosystem, where they encounter various harsh challenges including pesticides and low temperature in winter. Glyphosate-based herbicides (GBH) are widely and frequently applied to diminish weeds, exposing spiders a disturbed habitat, especially to overwintering spiders. We conducted a study combining field surveys and lab assays, to assess the effects of a GBH on the overwintering of the agrobiont wolf spider, Pardosa pseudoannulata. The GBH significantly reduced the overall overwintering spider population by about 69 %, and reduced the number of vulnerable juveniles by about 80 %. The survivors exhibited substantial fitness costs such as reproductive dysfunctions and enhanced oxidative stress responses. We then mimicked the overwinter process in lab. We housed spiders on soil patches with and without weeds to examine whether weeds contributed to the GBH's sublethal effects. Spiders overwintered independent of weeds when GBH was not applied. When GBH was applied before or during overwintering, juvenile spiders overwintered in weedy habitats exhibited reduced survival and fecundity, and increased oxidative stress compared to their counterparts in weed-free habitats. Therefore, GBH-containing weeds contributed to the persistent adverse effects of GBH on overwintering spiders. The findings revealed the cross-talk among weeds, herbicides, low temperature, and non-target organisms. The study provides novel information on the environmental risk assessment of pesticides and rational scheduling of pesticide application., 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.)

Inherently chiral calix[4]arenes represent a unique type of chiral molecules with significant applications, yet their catalytic enantioselective synthesis remains largely underexplored. We report herein the catalytic enantioselective synthesis of inherently chiral calix[4]arenes through the sequential organocatalyzed enantioselective Povarov reaction and aromatizations. The chiral phosphoric acid catalyzed three-component Povarov reaction involving amino group-substituted calix[4]arenes, aldehydes and (di)enamides desymmetrized the prochiral calix[4]arene substrates, which was followed by various aromatization methods, resulting in a diverse array of novel quinoline-containing calix[4]arenes with good yields and high enantioselectivities (up to 75 % yield, 99 % ee). The large-scale enantioselective synthesis and diverse derivatizations of the chiral calix[4]arene products highlight the value of this method. Furthermore, preliminary exploration into their photophysical and chiroptical properties demonstrate the potential applications of these novel calix[4]arene molecules., (© 2024 Wiley-VCH GmbH.)

Background: Temozolomide (TMZ) is the first-line chemotherapeutic drug for gliomas treatment. However, the clinical efficacy of TMZ in glioma patients was very limited. Therefore, it is urgently needed to discover a novel approach to increase the sensitivity of glioma cells to TMZ., Methods: Western blot, immunohistochemical staining, and qRT-PCR assays were used to explore the mechanisms underlying TMZ promoting DKK1 expression and andrographolide (AND) inhibiting DKK1 expression. HPLC was used to detect the ability of andrographolide (AND) to penetrate the blood-brain barrier. MTT assay, bioluminescence images, magnetic resonance imaging (MRI) and H&E staining were employed to measure the proliferative activity of glioma cells and the growth of intracranial tumors., Results: TMZ can promote DKK1 expression in glioma cells and brain tumors of an orthotopic model of glioma. DKK1 could promote glioma cell proliferation and tumor growth in an orthotopic model of glioma. Mechanistically, TMZ increased EGFR expression and subsequently induced the activation of its downstream MEK-ERK and PI3K-Akt pathways, thereby promoting DKK1 expression in glioma cells. Andrographolide inhibited TMZ-induced DKK1 expression through inactivating MEK-ERK and PI3K-Akt pathways. Andrographolide can cross the blood-brain barrier, the combination of TMZ and andrographolide not only improved the anti-tumor effects of TMZ but also showed a survival benefit in an orthotopic model of glioma., Conclusion: Andrographolide can enhance anti-tumor activity of TMZ against glioma by inhibiting DKK1 expression., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Diabetic retinopathy (DR) is the major ocular complication of diabetes mellitus caused by chronic hyperglycemia, which leads to incurable blindness. Currently, the effectiveness of therapeutic interventions is limited. This study aimed to investigate the function of piezo-type mechanosensitive ion channel component 1 (PIEZO1) and its potential regulatory mechanism in DR progression. The results showed that PIEZO1 expression was upregulated in the retinal tissues of streptozotocin-induced diabetic mice and high glucose (HG)-triggered Müller cells. Functionally, the knockdown of PIEZO1 improves the abnormal retinal function of diabetic mice and impedes inflammatory cytokine secretion and gliosis of Müller cells under HG conditions. Mechanistic investigations utilizing RIP-qPCR, MeRIP-qPCR, and luciferase reporter assays demonstrated that PIEZO1 was a downstream target of methyltransferase-like 3 (METTL3). These studies revealed that METTL3-mediated N6-methyladenosine (m6A) modification within the coding sequence of PIEZO1 mRNA significantly shortened its half-life. In HG-stimulated cells, there was a negative regulatory relationship between PIEZO1 and YTH domain family 2 (YTHDF2), a recognized m6A reader. The loss of YTHDF2 resulted in an extended half-life of PIEZO1 in cells with overexpression of METTL3, indicating that the effect of METTL3 on the mRNA stability of PIEZO1 was dependent on YTHDF2. Taken together, this study demonstrated the protective role of the PIEZO1 silencing in DR development, and the degradation of PIEZO1 mRNA is accelerated by METTL3/YTHDF2-mediated m6A modification., (Copyright © 2024. Published by Elsevier Inc.)

Research on islet replacement through the differentiation of functionally matured insulin-producing β-like cells for the treatment of diabetes presents a significant challenge. Neural signals in β cell differentiation significantly impact the pancreatic microenvironment in glucose metabolism, but they are not fully understood. In this study, isoproterenol, a β adrenoreceptor agonist, was introduced into pancreatic progenitor cells, derived from human pluripotent stem cells in vitro, undergoing endocrine differentiation, using 2-dimensional (2D) and 3-dimensional (3D) differentiation protocols. This resulted in increased insulin and C-peptide secretion, along with elevated expression of key pancreatic beta cell transcription factors, including PDX-1, NKX6.1, and MAFA, and improved function, demonstrated by increased responsiveness to glucose determined via a glucose-stimulated insulin secretion test. Moreover, RNA transcriptome analysis of isoproterenol-treated endocrine progenitors facilitated the identification of biological pathways and genes that contribute to mature beta cell differentiation efficiency correlated with neural signals, such as adrenoceptor beta 1, calcium/calmodulin dependent protein kinase II alpha, phospholipase C delta 4, and neurotrophic receptor tyrosine kinase 1. Among those genes, calcium/calmodulin dependent protein kinase II alpha was suggested as the most notable gene involved in the isoproterenol mechanism through inhibitor assays. This study illustrates that isoproterenol significantly enhances endocrine differentiation and underscores its effects on stem cell-derived beta cell maturation, emphasizing its therapeutic potential for the treatment of diabetes., 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 Inc.)

Background: Islet transplantation is a recommended treatment for type 1 diabetes but is limited by donor organ shortage. This study introduces an innovative approach for improving the differentiation and functionality of insulin-producing cells (IPCs) from iPSCs using 3D spheroid formation and hydrogel matrix as an alternative pancreatic islet source. The extracellular matrix (ECM) is crucial for pancreatic islet functionality, but finding the ideal matrix for β-cell differentiation has been challenging. We aimed to advance IPC differentiation and maturation through an esterified collagen hydrogel, comparing its effectiveness with conventional basement membrane extract (BME) hydrogels., Methods: iPSCs were differentiated into IPCs using a small molecule-based sequential protocol, followed by spheroid formation in concave microwells. Rheological analysis, scanning electron microscopy, and proteomic profiling were used to characterize the chemical and physical properties of each matrix. IPCs, both in single-cell form and as spheroids, were embedded in either ionized collagen or BME hydrogels, which was followed by assessments of morphological changes, pancreatic islet-related gene expression, insulin secretion, and pathway activation using comprehensive analytical techniques., Results: Esterified collagen hydrogels markedly improved the structural integrity, insulin expression, and cell-cell interactions in IPC spheroids, forming densely packed insulin-expressing clusters, in contrast to the dispersed cells observed in BME cultures. Collagen hydrogel significantly enhanced the mRNA expression of crucial endocrine markers and maturation factors, with IPC spheroids showing accelerated differentiation from day 5, suggesting a faster differentiation compared to single cells in hydrogel encapsulation. Insulin secretion in response to glucose in collagen environments, with a GSIS index of 2.46 ± 0.05, exceeded those in 2D and BME, demonstrating superior pancreatic islet functionality. Pathway analysis highlighted enhanced insulin secretion capabilities, evidenced by the upregulation of genes like Secretogranin III and Chromogranin A in collagen cultures. In vivo transplantation results showed that collagen hydrogel enhanced cluster integrity, tissue integration, and insulin secretion compared to non-embedded IPCs and BME groups., Conclusion: Esterified collagen hydrogels demonstrated superior efficacy over 2D and BME in promoting IPC differentiation and maturation, possibly through upregulation of the expression of key secretion pathway genes. Our findings suggest that using collagen hydrogels presents a promising approach to enhance insulin secretion efficiency in differentiating pancreatic β-cells, advancing cell therapy in diabetes cell therapy., (© 2024. The Author(s).)

Aging is a critical biological process, with particularly notable impacts on the kidneys. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of transferring various bioactive molecules, which exhibit beneficial therapeutic effects on kidney diseases. This study demonstrates that exosomes derived from hUC-MSCs ameliorate cellular senescence in the kidneys of naturally aging mice. These exosomes reduce the protein expression of senescence markers and senescence-associated secretory phenotypes (SASP) leading to fewer DNA damage foci and increased expression of the proliferation indicator Ki67. During the aging process, many proteins undergo phosphorylation modifications. We utilized data-independent acquisition (DIA) phosphoproteomics to study kidneys of naturally aging mice and those treated with hUC-MSC-derived exosomes. We observed elevated phosphorylation levels of the differentially phosphorylated proteins, Lamin A/C, at Ser390 and Ser392 sites, which were subsequently verified by western blotting. Overall, this study provides a new molecular characterization of hUC-MSC-derived exosomes in mitigating cellular senescence in the kidneys. SIGNIFICANCE: DIA phosphoproteomics was employed to investigate phosphorylated proteins in the kidney tissues of naturally aging mice with hUCMSC-exos treated. The results demonstrated that the DIA technique detected a higher abundance of phosphorylated proteins. We identified 24 significantly differentially phosphorylated proteins, and found that the phosphorylation of specific Lamin A/C sites is crucial for preventing cellular senescence. This study will help to better reveal the related phosphorylated proteins involved in hUCMSC-exos intervention in the kidneys of naturally aging mice, providing a foundation for future research on specific phosphorylation sites of proteins as potential therapeutic targets for renal aging-related diseases., 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 B.V.)

The emulsion gel composed of proteins and polysaccharides exhibits significant potential as a targeted delivery system for bioactives in the gastrointestinal tract. In this study, a composite emulsion was prepared by using sodium caseinate (NaCas) and gellan gum (GG), which was subsequently crosslinked with transglutaminase (TG), glucono-δ-lactone (GDL), and calcium ions (Ca 2+ ) to form emulsion gels. The physicochemical properties of the NaCas/GG emulsion gels were characterized to verify the effects of zeaxanthin dipalmitate encapsulation and protection, and a possible mechanism was discussed. The appearance and microscopy analyses revealed that the Ca 2+ -induced NaCas/GG emulsion gel exhibited superior shape retention and a denser network structure compared to GDL or TG crosslinking methods. The rheological analysis demonstrated that the Ca 2+ -crosslinked emulsion gels had higher modulus and hardness than their TG- or GDL- crosslinked counterparts. Infrared spectroscopy, molecular docking, and gelling force analysis revealed that the gelation mechanism of these emulsion gels primarily involved carbonyl-amide group crosslinking reactions, hydrogen bonding, and hydrophobic interactions. Furthermore, the Ca 2+ -crosslinked emulsion gel encapsulating zeaxanthin dipalmitate exhibited excellent thermal stability, resistance to gastrointestinal conditions, and stability. Overall, the above findings highlight that using Ca 2+ crosslinking in NaCas/GG composite emulsion yields edible composite materials with enhanced functional performance, thereby expanding the possibilities for food gel design strategies., 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.)

The high non-radiative energy loss is a bottleneck issue that impedes the improvement of organic solar cells. The formation of triplet exciton is thought to be the main source of the large non-radiative energy loss. Decreasing the rate of back charge transfer is considered as an effective approach to alleviate the relaxation of the charge-transfer state and the triplet exciton generation. Herein, we develops an efficient ternary system based on D18:N3-BO:F-BTA3 by regulating the charge-transfer state disorder and the rate of back charge transfer of the blend. With the addition of F-BTA3, a well-defined morphology with a more condensed molecular packing is obtained. Moreover, a reduced charge-transfer state disorder is demonstrated in the ternary blend, which decreases the rate of back charge transfer as well as the triplet exciton formation, and therefore hinders the non-radiative recombination pathways. Consequently, D18:N3-BO:F-BTA3-based device produces a low non-radiative energy loss of 0.183 eV and a record-high efficiency of 20.25%. This work not only points towards the significant role of the charge-transfer state disorder on the suppression of triplet exciton formation and the non-radiative energy loss, but also provides a valuable insight for enhancing the performance of OSCs., (© 2024. The Author(s).)

Spiders are an abundant group of natural enemies preying on insect pests in agroecosystem. But their potential in biological control has not been fully realized due to difficult mass production. One hindrance is the intense intraspecific aggression in spiders. Neurotransmitters such as serotonin play important roles in modulating aggression. Here, we investigated the regulatory function of serotonin (5-hydroxytryptamine [5-HT]) signaling in the intraspecific aggression in a wandering spider Pardosa pseudoannulata (Araneae, Lycosidae). The aggression was quantified with 5 escalated aggression behaviors as approach, chasing, lunging, boxing, and biting. Virgin (VG) females exhibited higher aggression levels but less 5-HT content than post-reproductive (PR) females. Systemic increase of 5-HT via 5-HT injection decreased aggression, while decrease of 5-HT via RNA interference (RNAi) of the tryptophan hydroxylase gene, increased aggression. The involvement of the four 5-HT receptors were determined via individual or combined RNAi. Co-RNAi of the three 5-HT1 genes increased overall aggression with decreased incidents of approach, chasing, lunging, and increased biting. RNAi of 5-HT1B decreased approach and increased biting, whereas RNAi of 5-HT1A or 5-HT1C did not affect aggression. RNAi of 5-HT7 decreased approach only. Therefore, different 5-HT receptor types contribute to different aspects of the inhibitory effects of 5-HT on aggression and provide several pharmacological targets for manipulating spider aggression. 5-HT injection did not affect spiders' predation on their insect prey, the brown planthopper Nilaparvata lugens. The findings reveal 1 neuronal mechanism regulating intraspecific aggression in spiders and provide an insight in developing aggression suppression strategies for spider mass rearing., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

To understand the spatial distribution of NO 2 near the surface, we utilized measured data from NO 2 monitoring stations and combined it with column concentration data from the Tropospheric Monitoring Instrument （TROPOMI）, taking the Yangtze River Delta region as the study area. We considered the impact of factors such as population, elevation, and meteorological conditions on NO 2 levels. We used automated machine learning to select five machine-learning algorithms with high simulation accuracy, namely ET, RF, XGBoost, LightGBM, and Catboost, and then integrated these five algorithms using the Stacking model to simulate the daily NO 2 concentration in the Yangtze River Delta region from March 2020 to February 2021. The results indicated that the RMAE and MAE values of the Stacking ensemble model were 7.078 and 5.270, respectively, which outperformed the single algorithms of ET, RF, XGBoost, LightGBM, and Catboost. The spatial distribution of high NO 2 concentrations in the Yangtze River Delta region, consisting of three provinces and one municipality, exhibited a U-shaped pattern with the convergence point located at the intersection of the three provinces, extending towards the southwest. Notably, urban pollution was particularly significant in the urban agglomerations centered around Shanghai, Hangzhou, Nanjing, and Hefei. There were 27 cities that exceeded the national standard daily limit. Changzhou was the city with the most serious NO 2 pollution, with the NO 2 concentration exceeding the standard for 14 d, followed by Shanghai, with 13 d. In terms of seasonal variation, the order of severity was as follows： winter, autumn, spring, and summer, with the least NO 2 pollution occurring on July 9th during the summer, and the most severe NO 2 pollution was observed on December 23rd during the winter.

Purpose: To compare the corneal epithelial remodeling in eyes with high astigmatism that had small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK)., Methods: Seventy-four patients with myopic astigmatism of greater than -2.00 diopters (D) and little binocular difference in spherical equivalent were included in this contralateral comparative study. All patients received SMILE in one eye and FS-LASIK in the other eye randomly. The corneal epithelial remodeling pattern was mapped using the latest RTVue spectral-domain optical coherence tomographer (Optovue) by region., Results: Satisfactory refractive correction was achieved in all enrolled eyes with either SMILE or FS-LASIK. The corneal epithelium gradually thickened following surgical cylinder correction, distributing mainly along the flat medium. The corneal epithelium proliferation is milder centrally but more pronounced in the mid-peripheral area after SMILE, compared with FS-LASIK. The flat-steep difference in corneal epithelial thickness (CET) is evident in the mid-peripheral and peripheral areas, which is more obvious in SMILE. Residual cylinder was positively correlated with CET in eyes that had FS-LASIK, but not SMILE. More importantly, these epithelial changes were positively correlated with the ablation depth and higher order aberrations following surgical refractive correction., Conclusions: The postoperative CET map varied between SMILE and FS-LASIK. In eyes with high astigmatism, SMILE surgery is followed by milder and more stable corneal epithelial thickening. Moreover, the corneal epithelium is sensitive to stromal ablation and corneal remodeling is crucial to the postoperative visual quality. This study rigorously distinguished the CET difference between SMILE and FS-LASIK in astigmatic eyes and shed light on subsequent research. [ J Refract Surg . 2024;40(10);e728-e741.] .

Background: Tumor development and progression is a long and complex process influenced by a combination of intrinsic (eg, gene mutation) and extrinsic (eg, environmental pollution) factors. As a detoxification organ, the liver plays an important role in human exposure and response to various environmental pollutants including nanomaterials (NMs). Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and remains a serious threat to human health. Whether NMs promote liver cancer progression remains elusive and assessing long-term exposure to subtoxic doses of nanoparticles (NPs) remains a challenge. In this study, we focused on the promotional effects of nano zinc oxide (nZnO) on the malignant progression of human HCC cells HepG2, especially aged nZnO that has undergone physicochemical transformation., Methods: In in vitro experiments, we performed colony forming efficiency, soft agar colony formation, and cell migration/invasion assays on HepG2 cells that had been exposed to a low dose of nZnO (1.5 μg/mL) for 3 or 4 months. In in vivo experiments, we subcutaneously inoculated HepG2 cells that had undergone long-term exposure to nZnO for 4 months into BALB/c athymic nude mice and observed tumor formation. ZnCl 2 was administered to determine the role of zinc ions., Results: Chronic low-dose exposure to nZnO significantly intensified the malignant progression of HCC cells, whereas aged nZnO may exacerbate the severity of malignant progression. Furthermore, through transcriptome sequencing analysis and in vitro cellular rescue experiments, we demonstrated that the mechanism of nZnO-induced malignant progression of HCC could be linked to the activation of Claudin-2 (CLDN2), one of the components of cellular tight junctions, and the dysregulation of its downstream signaling pathways., Conclusion: Long-term exposure of fresh and aged nZnO promotes hepatocellular carcinoma malignancy by up-regulating CLDN2. The implications of this work can be profound for cancer patients, as the use of various nanoproducts and unintentional exposure to environmentally transformed NMs may unknowingly hasten the progression of their cancers., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Yu et al.)

Recent advances in spatially resolved transcriptomics (SRT) have provided new opportunities for characterizing spatial structures of various tissues. Graph-based geometric deep learning have gained widespread adoption for spatial domain identification tasks. Currently, most methods define adjacency relation between cells or spots by their spatial distance in SRT data, which overlooks key biological interactions like gene expression similarities, and leads to inaccuracies in spatial domain identification. To tackle this challenge, we propose a novel method, SpaGRA (https://github.com/sunxue-yy/SpaGRA), for automatic multi-relationship construction based on graph augmentation. SpaGRA uses spatial distance as prior knowledge and dynamically adjusts edge weights with multi-head graph attention networks (GATs). This helps SpaGRA to uncover diverse node relationships and enhance message passing in geometric contrastive learning. Additionally, SpaGRA uses these multi-view relationships to construct negative samples, addressing sampling bias posed by random selection. Experimental results show that SpaGRA demonstrates superior domain identification performance on multiple datasets generated from different protocols. Using SpaGRA, we analyzed the functional regions in the mouse hypothalamus, identified key genes related to heart development in mouse embryos, and observed cancer-associated fibroblasts enveloping cancer cells in the latest Visium HD data. Overall, SpaGRA can effectively characterize spatial structures across diverse SRT datasets., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Maternal care is critically important for the survival of offspring in various animals. Spiders in the family Lycosidae are known for their hunting ability and maternal care behaviors. Predation on newly hatched spiderlings (pulli) by mother spiders decreases when they come into contact, and they carry the pulli on their dorsal surface. However, the factors inducing maternal care in lycosid spiders have not been elucidated. In this study, we investigated maternal care in Pardosa pseudoannulata (Araneae, Lycosidae) females. We proposed that the physical interaction between pulli and mother spiders induces maternal care via m-aminophenylacetylene (m-A), a novel regulator of maternal care. The presence of pulli on the dorsal abdomen of non-mother spiders suppressed pulli predation and increased the pulli-carrying rate, and the absence of pulli on the mother spiders increased pulli predation and decreased the pulli-carrying rate. The compound m-A was abundant in mother spiders, and it could be induced in non-mother spiders when they carried pulli. The topical application of m-A to non-mother spiders and m-A injection decreased pulli predation and increased the pulli-carrying rate, respectively; these findings indicate that m-A in both internal tissues and the integument is required for the induction of maternal care behavior, and the interaction between pulli and females induces the production of m-A. In-depth study of the regulatory mechanism of maternal care will enhance our understanding of spider biology and behavior., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

In tumors, the rapid proliferation of cells and the imperfect blood supply system lead to hypoxia, which can regulate the adaptation of tumor cells to the hypoxic environment through hypoxia-inducible factor-1α (HIF-1α) and promote tumor development in multiple ways. Recent studies have found that epithelial-mesenchymal transition (EMT) and ferroptosis play important roles in the progression of tumor cells. The activation of HIF-1α is considered a key factor in inducing EMT in tumor cells. When HIF-1α is activated, it can regulate EMT-related genes, causing tumor cells to gradually lose their epithelial characteristics and acquire more invasive mesenchymal traits. The occurrence of EMT allows tumor cells to better adapt to changes in the surrounding tissue, enhancing their migratory and invasive capabilities, thus promoting tumor progression. At the same time, HIF-1α also plays a crucial regulatory role in ferroptosis in tumor cells. In a hypoxic environment, HIF-1α may affect processes such as iron metabolism and oxidative stress responses, inducing ferroptosis in tumor cells. This article briefly reviews the dual role of HIF-1α in EMT and ferroptosis in tumor cells, helping to gain a deeper understanding of the regulatory pathways of HIF-1α in the development of tumor cells, providing a new perspective for understanding the pathogenesis of tumors. The regulation of HIF-1α may become an important strategy for future tumor therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Liyan Zhao reports financial support was provided by the Science and Technology Innovation and Entrepreneurship Outstanding Talent (Team) Project. If there are other authors, they 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Despite substantial breakthroughs in the treatment of hepatocellular carcinoma (HCC) in recent years, many patients are diagnosed in the middle or late stages, denying them the option for surgical excision. Therefore, it is of great importance to find effective therapeutic targets of HCC. In this study, it is found that Gap junction protein beta-2 (GJB2) is highly enriched in malignant cells based on single-cell RNA sequencing and higher expression of GJB2 indicates a worse prognosis. The localization of GJB2 in HCC cancer cells is changed compared with normal liver tissue. In cancer cells, GJB2 tends to be located in the cytoplasm and nucleus, while in normal tissues, GJB2 is mainly located on the cell membrane. GJB2 is related to glycolysis, promoting NF-κB pathway via inducing the ubiquitination degradation of IκBa, and activating HIF-1α/GLUT-1/PD-L1 pathway. In addition, GJB2 knockdown reshapes tumor immune microenvironment and Salvianolic acid B inhibits the activity of GJB2. In conclusion, GJB2 promotes HCC progression by activating glycolysis through cytoplasmic translocation and generating a suppressive tumor microenvironment. Salvianolic acid B inhibits the expression of GJB2 and enhances the sensitivity of anti-PD1 therapy, which may provide insights into the development of novel combination therapeutic strategies for HCC., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: The total volatile basic nitrogen (TVB-N) is the main indicator for evaluating the freshness of fish meal, and accurate detection and monitoring of TVB-N is of great significance for the health of animals and humans. Here, to realize fast and accurate identification of TVB-N, in this article, a self-developed electronic nose (e-nose) was used, and the mapping relationship between the gas sensor response characteristic information and TVB-N value was established to complete the freshness detection., Results: The TVB-N variation curve was decomposed into seven subsequences with different frequency scales by means of variational mode decomposition (VMD). Each subsequence was modelled using different long short-term memory (LSTM) models, and finally, the final TVB-N prediction result was obtained by adding the prediction results based on different frequency components. To improve the performance of the LSTM, the sparrow search algorithm (SSA) was used to optimize the number of hidden units, learning rate and regularization coefficient of LSTM. The prediction results indicated that the high accuracy was obtained by the VMD-LSTM model optimized by SSA in predicting TVB-N. The coefficient of determination (R 2 ), the root-mean-squared error (RMSE) and relative standard deviation (RSD) between the predicted value and the actual value of TVBN were 0.91, 0.115 and 6.39%., Conclusions: This method improves the performance of e-nose in detecting the freshness of fish meal and provides a reference for the quality detection of e-nose in other materials. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The development of flexible ITO-free devices is crucial for the industrial advancement of organic photovoltaic (OPV) technology. Here, a novel ITO-free device architecture is proposed, and ITO-free OPV devices are realized on glass substrates with performance comparable to that of ITO-based devices. It is also demonstrated that the performance of ITO-free devices on polyethylene terephthalate (PET) substrates is limited due to the higher surface roughness of PET, leading to high voltage losses, low device quantum efficiency, and high device leakage current. To address the issue of high roughness on the PET surface, a polyimide (PI) modification strategy is developed and the PI-modified PET is employed as the substrate to construct flexible ITO-free OPV devices and large-area modules with an active area of up to 16.5 cm 2 . This approach leads to decreased trap-assisted recombination losses, enhanced exciton dissociation efficiency, and a reduced density of pinholes in flexible OPV devices, resulting in improved photovoltaic performance under both strong and weak illumination conditions. The outcomes of this work are expected to advance the industrial development of flexible organic photovoltaic technology., (© 2024 Wiley‐VCH GmbH.)

l-Type amino acid transporter 1 (LAT1)-specific ligands and polyion complexes are used as brain-specific targets to deliver RNA-based drugs across the blood-brain barrier. We characterized an LAT1-targeting antisense oligonucleotide (ASO)-encapsulated nanoparticle, Phe-NPs/ASO. A 25% density of phenylalanine effectively binds to the surface of LAT1-targeting NPs in the GL261-Luc cells, and Phe-NPs/ASO shows higher binding affinity compared to that without phenylalanine by cellular binding assay. To further characterize the blood-brain barrier-targeting effect and tissue distribution following a single-dose intravenous injection in mice, we performed in vivo biodistribution studies using fluorescence imaging. The Phe-NPs/ASOs were detected in the brain tissue 1 h post-intravenous injection at an approximately 64-fold higher ratio than that of the same ASOs administered in the absence of any NP carrier. The brain tissue delivery of ASO-loaded Phe-NPs was also confirmed in a fluorescence imaging study performed in non-human primates. These results demonstrate that Phe-NPs may successfully deliver an ASO to the brain tissue across brain regions. Phe-NPs loaded with RNA-based drugs have the potential to treat diseases of the CNS, including all forms of neurodegenerative diseases., Competing Interests: The authors confirm that they are employed and are paid by BIORCHESTRA Co., Ltd. The company had no direct or indirect interests in the preparation of the research paper., (© 2024 Biorchestra.)

Allergic asthma is a major health burden on society as a chronic respiratory disease characterized by inflammation and muscle tightening around the airways in response to inhaled allergens. Daphne kiusiana Miquel is a medicinal plant that can suppress allergic airway inflammation; however, its specific molecular mechanisms of action are unclear. In this study, we aimed to elucidate the mechanisms by which D. kiusiana inhibits allergic airway inflammation. We evaluated the anti-inflammatory effects of the ethyl acetate (EA) fraction of D. kiusiana and its major compound, daphnetin, on murine T lymphocyte EL4 cells stimulated with phorbol 12-myristate 13-acetate and ionomycin in vitro and on asthmatic mice stimulated with ovalbumin in vivo. The EA fraction and daphnetin inhibited T-helper type 2 (Th2) cytokine secretion, serum immunoglobulin E production, mucus secretion, and inflammatory cell recruitment in vivo. In vitro, daphnetin suppressed intracellular Ca 2+ mobilization (a critical regulator of nuclear factor of activated T cells) and functions of the activator protein 1 transcription factor to reduce interleukin (IL)-4 and IL-13 expression. Daphnetin effectively suppressed the IL-4/-13-induced activation of Janus kinase (JAK)/signal transducer and activator of transcription 6 (STAT6) signaling in vitro and in vivo, thereby inhibiting the expression of GATA3 and PDEF, two STAT6-target genes responsible for producing Th2 cytokines and mucins. These findings indicate that daphnetin suppresses allergic airway inflammation by stabilizing intracellular Ca 2+ levels and subsequently inactivating the JAK/STAT6/GATA3/PDEF pathway, suggesting that daphnetin is a promising alternative to existing asthma treatments., Competing Interests: Declaration of competing interest None: 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Delayed enhancement cardiac computed tomography (CT) empowers the diagnosis of left atrial appendage thrombus while limited to scanning heterogeneity. We optimized the spectral CT scan and post-process protocols, incorporating delayed enhancement and spectral iodine analysis to discriminate left atrial appendage (LAA) thrombus with better morphological relationships between the left atrium, pulmonary vein, and esophagus., Methods: A total of 278 consecutive patients were retrieved from January 2019 to June 2023. All patients underwent transesophageal echocardiography (TEE) and spectral CT scan of the left atrial and pulmonary vein, with a complete period including the pulmonary venous phase and three delay phases. TEE diagnosis was used as the standard reference. For patients exhibiting LAA filling defects during the pulmonary venous phase, a delayed scan of 30 s (phase I) was performed. If the filling defects persisted, a further delayed scan of 1 min (phase II) was conducted. In cases where the filling defects persisted, an additional delayed scan of 2 min (phase III) was carried out. Iodine concentration in the filled defect area of LAA and the left atrium was measured in phase III. Moreover, 30 patients were randomly selected for water-swallowing and the other 30 for calm breathing. The image quality and esophageal dilation of the two groups were assessed by two experienced surgeons specializing in radiofrequency ablation., Results: In total, 14 patients were diagnosed with thrombi by TEE. The sensitivity, specificity, positive predictive values, negative predictive values, and AUC of phase III delayed combined with iodine quantification for thrombi diagnosis were all 100%. The water-swallowing group exhibited significantly greater esophageal filling and expansion than the calm-breathing group, contributing to a better morphology assessment with no significant difference in image quality., Conclusion: Combined with iodine quantification, delayed enhancement of spectral CT imaging presents a promising diagnostic potency for LAA thrombus. Incorporating water swallowing into the CT scan process further enables anatomical visualization of the esophagus, left atrium, and pulmonary vein, thereby providing more objective and authentic imaging evidence to assess the esophageal morphology and positional relationships., Competing Interests: The 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 Yu, Hong, Lv, Liu and Yan.)

Asteraceae is a large class of eudicots with complex capitulum, and little is known regarding the molecular regulation mechanism of flower development. APETALA1 ( AP1 ) belongs to the MADS-box gene family and plays a key role in plant floral induction and floral organ development. In this study, the bioinformatics and tissue-specific expression of AP1 homologous gene SvAP1-5 in Senecio vulgaris were analyzed. Based on VIGS technology, SvAP1-5 gene silencing plants were created, and SvAP1-5 was overexpressed in Solanum nigrum . The results of bioinformatics analysis showed that SvAP1-5 gene had typical MADS-box and K-box structure, and contains FUL motif and paleoAP1 motif at the C-terminal. SvAP1-5 belongs to the euFUL branch of AP1 gene. qRT-PCR results showed that SvAP1-5 was expressed in bracts, petals and carpels, and was highly expressed in carpels. Compared with the control group, SvAP1-5 gene silencing resulted in irregular petal dehiscence, increased stigma division, and carpel dysplasia. The fruit development of SvAP1-5 overexpressing S.nigrum plants was abnormal, and the hyperplastic tissue similar to fruit appeared. In summary, SvAP1-5 gene may be involved in the development of petals and carpels and plays an important role during the development of S.vulgaris .

Antioxidant activity of freeze-dried paprika powder and storage properties of emulsion-type pork sausages containing diverse concentrations of this powder (0%, 1%, 2%, and 3%) were analyzed. Antioxidant activities of red and yellow paprika powders were analyzed by evaluating their 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP), total phenol content (TPC), and total flavonoid content (TFC). The yellow paprika powder exhibited remarkably higher DPPH radical scavenging activity, FRAP values, and TPC than the red paprika powder (p<0.05), while TFC showed no remarkable difference between them (p>0.05). Storage properties of sausages containing the yellow paprika powder were analyzed by evaluating their water holding capacity, cooking yield, and thiobarbituric acid reactive substance (TBARS), and volatile basic nitrogen (VBN) values. The 3% yellow paprika powder group showed remarkably higher water-holding capacity and cooking yield compared to the 0% group (p<0.05). TBARS values were remarkably lower in the 2% and 3% yellow paprika powder groups than in the 0% group at all weeks (p<0.05). VBN value was remarkably lower in the 3% yellow paprika powder group than in the 0% group at all weeks (p<0.05). Overall, addition of 3% yellow paprika powder improved the storage properties of emulsion-type sausages., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Study Objective: A Bayesian network meta-analysis was performed to compare the analgesic efficacy of the following nerve block techniques: femoral nerve block (FNB), adductor canal block (ACB), infiltration between the popliteal artery and the capsule of the posterior knee (iPACK), and genicular nerve block (GNB) following total knee arthroplasty (TKA)., Design: Systematic review and network meta-analysis (NMA)., Patients and Measurements: We searched the Web of Science, PubMed, EMBASE, and Cochrane Library databases until September 20, 2022. Patients who were treated by any of the above four nerve block techniques (alone or in combination) after TKA were included. Patients who underwent minimally invasive knee surgery were excluded. The indicators included pain scores during rest and mobilization, opioid consumption after surgery, postsurgical mobilization function (ROM [range of motion], TUG [Timed-Up-and-Go] test) at 24 h and 48 h, and length of hospital stay. The risk of bias was assessed by the Cochrane risk of bias tool., Results: Forty-two studies involving 2857 patients were eligible for this study. This NMA suggested that ACB + iPACK was the most efficacious option for improving ambulation ability and shortening the length of hospital stay. Furthermore, ACB + iPACK was the best regimen for resting-pain and movement-pain relief (78% and 87%, respectively) and for reducing opioid consumption (90%) at 48 h. However, FNB + iPACK was the most efficacious option for relief of resting pain (42%) and reducing opioid consumption (68%) at 24 h; GNB was the most efficacious option for movement pain relief at 24 h (94%)., Conclusion: Considering both pain control and knee functional recovery, ACB + iPACK may be the optimal analgesic regimen for patients after TKA. At the same time, it significantly reduces pain and opioid consumption at 48 h. However, ACB + iPACK is not the recommended technique for short-term (24 h) pain control., Clinical Trial Registration: PROSPERO (CRD42022362322)., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dental anatomy education for dental technology students should be developed in alignment with digital dental laboratory practices. We hypothesized that a virtually assisted sketching-based dental anatomy teaching module could improve students' acquisition of skills essential for digital restoration design. The second-year dental technology curriculum included a novel virtual technology-assisted sketching-based module for dental anatomy education. Pre- and post-course assessments evaluated students' skill sets and knowledge bases. Computer-aided design (CAD) scores were analyzed after one year to assess how the skills students developed through this module impacted their subsequent CAD performance. Participants who undertook the dental sketching-based teaching module demonstrated significantly improved theoretical knowledge of dental anatomy, dental aesthetic perception, and spatial reasoning skills. A partial least squares structural equation model indicated that the positive effects of this module on subsequent CAD performance were indirectly mediated by dental aesthetic perception, spatial reasoning, and practice time. A virtually assisted sketching-based dental anatomy teaching module significantly improved students' acquisition of skills and knowledge and positively mediated dental technology students' CAD performance., (© 2024 American Association for Anatomy.)

The structure of molecular aggregates is crucial for charge transport and photovoltaic performance in organic solar cells (OSCs). Herein, the intermolecular interactions and aggregated structures of nonfused-ring electron acceptors (NFREAs) are precisely regulated through a halogen transposition strategy, resulting in a noteworthy transformation from a 2D-layered structure to a 3D-interconnected packing network. Based on the 3D electron transport pathway, the binary and ternary devices deliver outstanding power conversion efficiencies (PCEs) of 17.46 % and 18.24 %, respectively, marking the highest value for NFREA-based OSCs., (© 2024 Wiley-VCH GmbH.)

Distant metastases and drug resistance account for poor survival of patients with gastrointestinal (GI) malignancies such as gastric cancer, pancreatic cancer, and colorectal cancer. GI cancers most commonly metastasize to the liver, which provides a unique immunosuppressive tumour microenvironment to support the development of a premetastatic niche for tumor cell colonization and metastatic outgrowth. Metastatic tumors often exhibit greater resistance to drugs than primary tumors, posing extra challenges in treatment. The liver metastases and drug resistance of GI cancers are regulated by complex, intertwined, and tumor-dependent cellular and molecular mechanisms that influence tumor cell behavior (e.g. epithelial-to-mesenchymal transition, or EMT), tumor microenvironment (TME) (e.g. the extracellular matrix, cancer-associated fibroblasts, and tumor-infiltrating immune cells), tumor cell-TME interactions (e.g. through cytokines and exosomes), liver microenvironment (e.g. hepatic stellate cells and macrophages), and the route and mechanism of tumor cell dissemination (e.g. circulating tumor cells). This review provides an overview of recent advances in the research on cellular and molecular mechanisms that regulate liver metastases and drug resistance of GI cancers. We also discuss recent advances in the development of mechanism-based therapy for these GI cancers. Targeting these cellular and molecular mechanisms, either alone or in combination, may potentially provide novel approaches to treat metastatic GI malignancies., 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.)

In this study, we aimed to demonstrate the feasibility and safety of navigating the ureters, middle sacral artery (MSA), and superior hypogastric nerve (SHN) using indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during robot-assisted sacrocolpopexy (RSCP). Overall, 15 patients who underwent RSCP for apical vaginal prolapse were retrospectively enrolled. All patients underwent cystoscopic intraureteric instillation of 5 cc ICG (2.5 mg/mL) before RSCP and intravenous injection of 3 cc ICG during presacral dissection and mesh fixation. In all patients, the fluorescent right ureter was clearly identified in real time. The MSA was visualized on ICG-NIRF images in 80% (13/15) of patients. The mean time from ICG injection to MSA visualization was 43.7 s; the mean duration of the arterial phase was 104.3 s. Fluorescent SHN was detected in 73.3% (11/15) of patients. The time from ICG injection to SHN fluorescence was 48.4 s; the duration of fluorescence was 177.2 s. There was no transfusion, iatrogenic ureteral injury, or bowel or urinary dysfunction. Our results indicated that intraoperative ureter, MSA, and SHN mapping using ICG-NIRF images during RSCP is a valuable and safe technique to avoid iatrogenic ureteral, vascular, and neural injuries and to simplify surgical procedures. Nonetheless, further studies are required.

Background and Objective: Despite its acknowledged benefits, the selection of an optimal regional block for analgesia pediatric hernia surgery remains a subject of debate. This study endeavored to conduct a network meta-analysis and systematic review of randomized clinical trials, aiming to amalgamate insights from both direct and indirect comparisons concerning the analgesic effectiveness and safety of various regional blocks post-inguinal hernia repair in children., Method: A comprehensive literature search was performed across PubMed, EMBASE, Web of Science, and the Cochrane Library up to 12 November 2022 by two independent reviewers, employing a standardized protocol. The inclusion criteria encompassed randomized trials focusing on children undergoing inguinal hernia repair utilizing either local infiltration analgesia or regional analgesia. The primary outcomes assessed were pain scores at 2, 6, and 24 h post-operation., Results: The initial search yielded 281 records relating to 1,137 patients. The analysis of ranking probability indicated that Paravertebral Block (PVB) holds the highest likelihood (88% and 48%) of being the most effective in alleviating pain at 2 h and 6 h post-surgery. Trans vs. Abdominis Plane Block (TAPB) emerged as the superior choice for mitigating pain (83%) and decreasing morphine consumption (93%) at 24 h following the operation. Local Anesthetic Infiltration (LAI) was identified as the most effective in shortening the hospital stay, with a 90% probability., Conclusions: Regional anesthesia significantly enhances postoperative pain management in pediatric inguinal hernia repair surgery. For short-term postoperative pain relief, PVB emerges as the most effective technique. Meanwhile, TAPB provides more prolonged analgesia. Although TAPB does not exhibit a pronounced advantage in short-term analgesia, its simplicity and the absence of a need for a special position render it a viable option. However, the interpretation of these results should be approached with caution due to the presence of limited data and heterogeneity., Systematic Review Registration: PROSPERO (CRD42022376435; www.crd.york.ac.uk/prospero)., Competing Interests: The 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., (© 2024 Xue, Zhou, Yu and Yang.)

Purpose: To quantitatively evaluate the morphological parameters of meibomian glands (MGs) and lipid layer thickness (LLT) in patients with keratoconus (KC)., Methods: In this prospective, cross-sectional study, 164 eyes of 164 keratoconus patients and 64 eyes of 64 age-matched control subjects were included. An advanced automatic MG analyzer was used to quantitatively measure the morphological and functional parameters of MGs. Morphological and functional parameters of MGs, LLT, and other ocular surface parameters were compared between the control and KC groups., Results: The mean meibomian gland diameter, length, square, and gland area ratio (GA) were all significantly decreased in the KC group (all P < 0.05), while no significant difference was observed in the gland tortuosity index (TI) and gland signal index (SI) between the KC and control groups (all P > 0.05). There was no significant difference in the number of total and incomplete blinking among patients with different stages of keratoconus (all P > 0.05). The gland diameter, square, and TI were all negatively associated with KC severity (all P < 0.05), while no significant difference was observed among all stages of KC in gland length, GA, and SI (all P > 0.05). Moreover, the LLTs were positively correlated with the gland diameter, square, GA, and TI and negatively correlated with anterior corneal curvature or KC severity (all P < 0.05)., Conclusions: Atrophic morphological changes in the meibomian glands were closely correlated with the severity of keratoconus. Gland diameter may be a sensitive functional morphology metric of meibomian glands in patients with keratoconus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reversible protonic ceramic electrochemical cells (R-PCECs) offer the potential for high-efficiency power generation and green hydrogen production at intermediate temperatures. However, the commercial viability of R-PCECs is hampered by the sluggish kinetics of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) within conventional air electrodes operating at reduced temperatures. To address this challenge, this work introduces a novel approach based on the simultaneous optimization of bulk-phase metal-oxygen bonds and in-situ formation of a metal oxide nano-catalyst surface modification. This strategy is designed to expedite the ORR/OER electrocatalytic activity of air electrodes exhibiting triple (O 2- , H + , e - ) conductivity. Specifically, this engineered air electrode nanocomposite-Ba(Co 0.4 Fe 0.4 Zr 0.1 Y 0.1 ) 0.95 Ni 0.05 F 0.1 O 2.9-δ demonstrates remarkable ORR/OER catalytic activity and exceptional durability in R-PCECs. This is evidenced by significantly improved peak power density from 626 to 996 mW cm -2 and highly stable reversibility over a 100-h cycling period. This research offers a rational design strategy to achieve high-performance R-PCEC air electrodes with superior operational activity and stability for efficient and sustainable energy conversion and storage., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8 + T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients., (© 2024. The Author(s).)

The objective of the current study is to prepare amorphous solid dispersions (ASDs) containing piperine (PIP) by utilizing organic acid glycyrrhizic acid (GA) and inorganic disordered mesoporous silica 244FP (MSN/244FP) as carriers and to investigate their dissolution mechanism. The physicochemical properties of ASDs were characterized with scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) and one-dimensional proton nuclear magnetic resonance ( 1 H NMR) studies collectively proved that strong hydrogen-bonding interactions formed between PIP and the carriers in ASDs. Additionally, molecular dynamic (MD) simulation was conducted to simulate and predict the physical stability and dissolution mechanisms of the ASDs. Interestingly, it revealed a significant increase in the dissolution of amorphous PIP in ASDs in in vitro dissolution studies. Rapid dissolution of GA in pH 6.8 medium resulted in the immediate release of PIP drugs into a supersaturated state, acting as a dissolution-control mechanism. This exhibited a high degree of fitting with the pseudo-second-order dynamic model, with an R 2 value of 0.9996. Conversely, the silanol groups on the outer surface of the MSN and its porous nanostructures enabled PIP to display a unique two-step drug release curve, indicating a diffusion-controlled mechanism. This curve conformed to the Ritger-Peppas model, with an R 2 > 0.9. The results obtained provide a clear evidence of the proposed transition of dissolution mechanism within the same ASD system, induced by changes in the properties of carriers in a solution medium of varying pH levels.

Transition metal dichalcogenide TiSe 2 exhibits a superconducting dome within a low pressure range of 2-4 GPa, which peaks with the maximal transition temperature T c of ≈1.8 K. Here it is reported that applying high pressure induces a new superconducting state in TiSe 2 , which starts at ≈16 GPa with a substantially higher T c that reaches 5.6 K at ≈21.5 GPa with no sign of decline. Combining high-throughput first-principles structure search, X-ray diffraction, and Raman spectroscopy measurements up to 30 GPa, It is found that TiSe 2 undergoes a first-order structural transition from the 1T phase under ambient pressure to a new 4O phase under high pressure. Comparative ab initio calculations reveal that while the conventional phonon-mediated pairing mechanism may account for the superconductivity observed in 1T-TiSe 2 under low pressure, the electron-phonon coupling of 4O-TiSe 2 is too weak to induce a superconducting state whose transition temperature is as high as 5.6 K under high pressure. The new superconducting state found in pressurized TiSe 2 requires further study on its underlying mechanism., (© 2024 Wiley‐VCH GmbH.)

Objective: This study investigated the differences in injury profiles and safety device effectiveness among children with road traffic injuries (RTIs) involving passenger vehicles and school buses., Methods: Using data from the Emergency Department-based Injury In-depth Surveillance database, this multicentre cross-sectional study investigated the injury profiles of 14 669 children aged 12 years old and younger who experienced RTIs from 2011-2021. Demographic factors, injury distribution, severity and effect of safety device use between RITs involving passenger vehicles and school buses were compared., Results: RTIs in children most frequently occurred between 12:00 and 18:00 hours (46.9%). School bus-related RTIs peaked during school commute hours, that is, from 06:00 to 12:00 hours, and were associated with a higher prevalence of head (63.1% vs 58.9%, p<0.05) and extremity injuries (upper extremity: 8.0% vs 6.4% and lower extremity: 11.1% vs 7.6 %, p<0.05) compared with those involving passenger vehicles. However, passenger vehicle crashes showed higher proportions of neck and chest injuries, along with injuries requiring hospitalisation and intensive care. Safety devices exhibited preventive effects against head and lower extremity injuries in both vehicle types. While safety devices showed effective in reducing hospital admissions and severe injuries in passenger vehicles, their effectiveness in school buses was not observed., Conclusion: This study highlights the different epidemiology and injury profiles of RTIs among children involving passenger vehicles and school buses. Improved safety devices, particularly in school buses, are necessary to ensure the comprehensive protection of child passengers and reduce the risk of severe injuries during road traffic incidents., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sleep disturbances are widespread but usually overlooked health risk factors for coronavirus disease 2019 (COVID-19). We aimed to investigate the influence of pre-existing sleep disturbances on the susceptibility, severity, and long-term effects of COVID-19., Methods: We searched PubMed, Web of Science, and Embase for relevant articles from inception to October 27, 2023 and updated at May 8, 2024. Sleep disturbances included obstructive sleep apnea (OSA), insomnia, abnormal sleep duration, night-shift work, and any other sleep disturbances. Outcomes were COVID-19 susceptibility, hospitalization, mortality, and long COVID. The effect sizes were pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). This study is registered with PROSPERO (CRD42024503518)., Findings: A total of 48 observational studies (n = 8,664,026) were included. Pre-existing sleep disturbances increased the risk of COVID-19 susceptibility (OR = 1.12, 95% CI 1.07-1.18), hospitalization (OR = 1.25, 95% CI 1.15-1.36), mortality (OR = 1.45, 95% CI 1.19-1.78), and long COVID (OR = 1.36 95% CI 1.17-1.57). Subgroup analysis showed that younger individuals with sleep disturbances were associated with higher susceptibility and hospitalization and a lower risk of mortality than older individuals. Males with sleep disturbances were associated with higher mortality. For specific sleep disturbances, the susceptibility and hospitalization of COVID-19 were associated with OSA, abnormal sleep duration, and night-shift work; mortality of COVID-19 was linked to OSA; risk of long COVID was related to OSA, abnormal sleep duration and insomnia., Interpretation: Pre-existing sleep disturbances, especially OSA, increased the risk of COVID-19 susceptibility, hospitalization, mortality, and long COVID. Age and sex played important roles in the effect of sleep disturbances on COVID-19., Funding: The National Natural Science Foundation of China and the Key Laboratory of Respiratory Diseases of Liaoning Province., Competing Interests: None., (© 2024 The Author(s).)

Post-stroke dysphagia (PSD) is an increasingly common complication of stroke. Despite its intuitively unfavorable impact on secondary prevention medication use, limited awareness is available regarding this issue. Herein, a cross-sectional survey was conducted to determine the current use, patient-perceived needs and preferences for secondary prevention medications among PSD patients. To emphasize the unique context related to dysphagia, we recruited Chinese stroke patients with a duration of less than 5 years. These patients were initially categorized into PSD respondents with and without dysphagia. Among the 3490 eligible respondents, 42.7% reported experiencing dysphagia after stroke. Those PSD respondents were more likely to consume multiple medications and suffer from anticoagulants-associated gastrointestinal bleeding as compared to non-PSD ones (p < 0.001). More crucially, 40.2% of them had frequent difficulty in swallowing pills, 37.1% routinely crushed solid oral dosage forms (SODFs), and 23.5% coughed frequently when taking SODFs. In consequence, 87.4% responded a need for PSD-specific formulations where safe swallowing, easy swallowing, and reduced medication frequency were preferred pharmaceutical factors. These findings demonstrate an unsatisfactory situation and definite needs for PSD patients in using secondary prevention medications. Awareness should be increased to develop PSD-specific formulations for safe and effective secondary prevention., (© 2024. The Author(s).)

High performance organic solar cells (OSCs) are usually realized by using post-treatment and/or additive, which can induce the formation of metastable morphology, leading to unfavorable device stability. In terms of the industrial production, the development of high efficiency as-cast OSCs is crucially important, but it remains a great challenge to obtain appropriate active layer morphology and high power conversion efficiency (PCE). Here, efficient as-cast OSCs are constructed via introducing a new polymer acceptor PY-TPT with a high dielectric constant into the D18:L8-BO blend to form a double-fibril network morphology. Besides, the incorporation of PY-TPT enables an enhanced dielectric constant and lower exciton binding energy of active layer. Therefore, efficient exciton dissociation and charge transport are realized in D18:L8-BO:PY-TPT-based device, affording a record-high PCE of 18.60% and excellent photostability in absence of post-treatment. Moreover, green solvent-processed devices, thick-film (300 nm) devices, and module (16.60 cm 2 ) are fabricated, which show PCEs of 17.45%, 17.54%, and 13.84%, respectively. This work brings new insight into the construction of efficient as-cast devices, pushing forward the practical application of OSCs., (© 2024 Wiley‐VCH GmbH.)

Purpose: To evaluate the clinical outcomes, rotational stability, and footplate position of the toric Implantable Collamer Lens (TICL) (STAAR Surgical) in eyes with low vault and analyze factors related to rotational stability., Methods: This prospective observational study included 59 eyes of 59 patients with insufficient vault (< 250 µm). Postoperative rotation was defined as the difference between the achieved angle and the intraoperative fixation angle, and assessed with a digital anterior segment photograph after full mydriasis at 1 week and 1, 3, and 6 months postoperatively. Ultrasound biomicroscopy was used to determine the ciliary body morphology and position of the footplate. Correlation analysis was employed to identify the risk factors associated with TICL rotation at 6 months postoperatively., Results: At 6 months postoperatively, the mean central vault was 137.4 ± 61.0 µm (range: 40 to 236 µm), and the mean efficacy and safety indices were 1.04 and 1.15, respectively. The mean manifest refractive astigmatism decreased from -1.67 ± 0.82 diopters (D) preoperatively to -0.43 ± 0.33 D postoperatively, and the mean absolute rotation was 4.50 ± 3.08 degrees (range: 0 to 12.50 degrees). The angle of rotation was correlated with the preoperative spherical power ( r = -0.318, P = .014), the average value of TICL footplates position ( r = 0.284, P = .029), and postoperative astigmatism ( r = -.469, P⩽ .001)., Conclusions: TICL implantation is predictable, safe, and effective in correcting myopic astigmatism in eyes with low vault. The rotational stability was acceptable and related to the malposition of the footplate and preoperative spherical power. [ J Refract Surg . 2024;40(7):e460-e467.] .

The process of aging is characterized by structural degeneration and functional decline, as well as diminished adaptability and resistance. The aging kidney exhibits a variety of structural and functional impairments. In aging mice, thinning and graying of fur were observed, along with a significant increase in kidney indices compared to young mice. Biochemical indicators revealed elevated levels of creatinine, urea nitrogen and serum uric acid, suggesting impaired kidney function. Histological analysis unveiled glomerular enlargement and sclerosis, severe hyaline degeneration, capillary occlusion, lymphocyte infiltration, tubular and glomerular fibrosis, and increased collagen deposition. Observations under electron microscopy showed thickened basement membranes, altered foot processes, and increased mesangium and mesangial matrix. Molecular marker analysis indicated upregulation of aging-related β-galactosidase, p16-INK4A, and the DNA damage marker γH2AX in the kidneys of aged mice. In metabolomics, a total of 62 significantly different metabolites were identified, and 10 pathways were enriched. We propose that citrulline, dopamine, and indoxyl sulfate have the potential to serve as markers of kidney damage related to aging in the future. Phosphoproteomics analysis identified 6656 phosphosites across 1555 proteins, annotated to 62 pathways, and indicated increased phosphorylation at the Ser27 site of Minichromosome maintenance complex component 2 (Mcm2) and decreased at the Ser284 site of heterogeneous nuclear ribonucleoprotein K (hnRNP K), with these modifications being confirmed by western blotting. The phosphorylation changes in these molecules may contribute to aging by affecting genome stability. Eleven common pathways were detected in both omics, including arginine biosynthesis, purine metabolism and biosynthesis of unsaturated fatty acids, etc., which are closely associated with aging and renal insufficiency., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

As an empirical tool in materials science and engineering, the iconic phase diagram owes its robustness and practicality to the topological characteristics rooted in the celebrated Gibbs phase law free variables (F) = components (C) - phases (P) + 2. When crossing the phase diagram boundary, the structure transition occurs abruptly, bringing about an instantaneous change in physical properties and limited controllability on the boundaries (F = 1). Here, the sharp phase boundary is expanded to an amorphous transition region (F = 2) by partially disrupting the long-range translational symmetry, leading to a sequential crystalline-amorphous-crystalline (CAC) transition in a pressurized In 2 Te 5 single crystal. Through detailed in situ synchrotron diffraction, it is elucidated that the phase transition stems from the rotation of immobile blocks [In 2 Te 2 ] 2+ , linked by hinge-like [Te 3 ] 2- trimers. Remarkably, within the amorphous region, the amorphous phase demonstrates a notable 25% increase of the superconducting transition temperature (T c ), while the carrier concentration remains relatively constant. Furthermore, a theoretical framework is proposed revealing that the unconventional boost in amorphous superconductivity might be attributed to an intensified electron correlation, triggered by a disorder-augmented multifractal behavior. These findings underscore the potential of disorder and prompt further exploration of unforeseen phenomena on the phase boundaries., (© 2024 Wiley‐VCH GmbH.)

Climate warming and drying has led to a sharp increase in nitrogen (N) emissions from the boreal peatland soils, but the underlying microbial-mediated mechanism is still unclear. We reviewed the responses of soil N transformation and emission in alpine peatland to temperature increases and water table changes, the interaction between soil anaerobic ammonia oxidation (Anammox) and NO 3 - dissimilatory reduction processes, and soil N 2 O production pathways and their contributions. There are several knowledge gaps. First, the amount of N loss in peatlands in alpine areas is seriously underestimated because most studies focused only on soil N 2 O emissions and ignored the release of N 2 . Second, the contribution of Anammox process to N 2 emissions from peatlands is not quantified. Third, there is a lack of quantification of the relative contributions of Anammox, bacterial denitrification, and fungal co-denitrification processes to N 2 loss. Finally, the decoupling mechanism of Anammox and NO 3 - reduction processes under a warming and drying climate scenario is not clear. Considering aforementioned shortages in previous studies, we proposed the directions and contents for future research. Through building an experimental platform with field warming and water level controlling, combining stable isotope, molecular biology, and metagenomics technology, the magnitude, composition ratio and main controlling factors of N emissions (N 2 O, NO, and N 2 ) in boreal peatlands should be systematically investigated. The interaction among the main N loss processes in soils as well as the relative contributions of nitrification, anaerobic ammonia oxidation, and denitrification to N 2 O and N 2 productions should be investigated and quantified. Furthermore, the sensitive microbial groups and the coupling between soil N transformations and microbial community succession should be clarified to reveal the microbiological mechanism underlying the responses of soil N turnover process to climate warming and drying.

Achieving desirable charge-transport highway is of vital importance for high-performance organic solar cells (OSCs). Here, it is shown how molecular packing arrangements can be regulated via tuning the alkyl-chain topology, thus resulting in a 3D network stacking and highly interconnected pathway for electron transport in a simple-structured nonfused-ring electron acceptor (NFREA) with branched alkyl side-chains. As a result, a record-breaking power conversion efficiency of 17.38% (certificated 16.59%) is achieved for NFREA-based devices, thus providing an opportunity for constructing low-cost and high-efficiency OSCs., (© 2024 Wiley‐VCH GmbH.)

Photosensitizers cause oxidative damages in various biological systems under light. In this study, the method for analyzing photosensitizing activity of various dietary and medicinal sources was developed using 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (thiazolyl blue formazan; MTT-F) as a probe. Significant and quantitative decolorization of MTT-F was observed in the presence of photosensitizers used in this study under light but not under dark conditions. The decolorization of MTT-F occurred irradiation time-, light intensity-, and photosensitizer concentration-dependently. The decolorized MTT-F was reversibly reduced by living cells; the LC-MS/MS results indicated the formation of oxidized products with -1 m / z of base peak from MTT-F, suggesting that MTT-F decolorized by photosensitizers was its corresponding tetrazolium. The present results indicate that MTT-F is a reliable probe for the quantitative analysis of photosensitizing activities, and the MTT-F-based method can be an useful tool for screening and evaluating photosensitizing properties of various compounds used in many industrial purposes.

This study aimed to compare the postimplantation clinical outcomes of 2 types of posterior chamber phakic intraocular lenses (IOLs): Visian™ implantable collamer lenses (ICL; EVO+ V5; Staar Surgical, Monrovia, CA) and an implantable phakic contact lens (IPCL) (IPCL V2.0, Care Group Sight Solution, India) to correct high myopia and myopic astigmatism. This retrospective study included patients who had undergone phakic IOL implantation performed by a single surgeon between March 2021 and March 2022. Preoperative assessments included slit-lamp examination, fundus examination, spherical equivalent, uncorrected distant visual acuity (UDVA), corrected distant visual acuity (CDVA), specular microscope parameters, and optical quality analysis system parameters. Postoperative assessments after 1 year included slit-lamp examination to detect adverse effects and spherical equivalent, UDVA, CDVA, specular microscope, optical quality analysis system, and anterior-segment optical coherence tomography. Eighty eyes from 42 patients (47 eyes from 24 patients in the ICL group and 33 eyes from 18 patients in the IPCL group) were included. No statistically significant differences were observed between the 2 groups regarding preoperative parameters. At 1-year postoperatively, the mean UDVA in the ICL and IPCL groups was 0.019 ± 0.040 logMAR and 0.019 ± 0.041 logMAR, respectively. The mean CDVA was 0.001 ± 0.008 logMAR and 0.001 ± 0.007 logMAR in the ICL and IPCL groups, respectively, showing no statistically significant differences. The postoperative parameters did not differ significantly between the 2 groups. The visual acuity and refractive results of both groups were excellent, and both groups exhibited similar efficacy and safety profiles., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China., Methods: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed., Results: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis., Conclusions: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia., (© 2024. The Author(s).)

Deep cooperative multi-agent reinforcement learning has demonstrated its remarkable success over a wide spectrum of complex control tasks. However, recent advances in multi-agent learning mainly focus on value decomposition while leaving entity interactions still intertwined, which easily leads to over-fitting on noisy interactions between entities. In this work, we introduce a novel interactiOn Pattern disenTangling (OPT) method, to disentangle the entity interactions into interaction prototypes, each of which represents an underlying interaction pattern within a subgroup of the entities. OPT facilitates filtering the noisy interactions between irrelevant entities and thus significantly improves generalizability as well as interpretability. Specifically, OPT introduces a sparse disagreement mechanism to encourage sparsity and diversity among discovered interaction prototypes. Then the model selectively restructures these prototypes into a compact interaction pattern by an aggregator with learnable weights. To alleviate the training instability issue caused by partial observability, we propose to maximize the mutual information between the aggregation weights and the history behaviors of each agent. Experiments on single-task, multi-task and zero-shot benchmarks demonstrate that the proposed method yields results superior to the state-of-the-art counterparts. Our code is available at https://github.com/liushunyu/OPT.