Search

Microfluidic-based nucleic acid testing (NAT) has been proven as an alternative approach for in-situ and rapid NA detection. However, these on-chip methods still require complex peripherals, which contradict the purpose of point-of-care (POC) applications. One of the major challenges is the integration of NA purification and amplification in a miniaturized setup with high mass and heat transfer efficiency. Here, we propose a hand-held in-situ nucleic acid detection device featuring a dual-functional GHz acoustofluidic resonator. The device is designed to utilize GHz acoustic streaming and acoustothermal effects to address both liquid mixing and heating issues, ensuring uniform reaction conditions and consistent thermal management in the microfluidic channel. By replacing traditional magnetic beads with polystyrene beads as matrix for solid-phase microextraction, the redundant washing and elution steps are eliminated, thereby simplifying the NA extraction process. The mixing and heating functions can be seamlessly switched by adjusting the applied power, thereby enhancing NA processing without the need for additional peripherals. The developed hand-held NAT apparatus achieved a detection limit of 10³ copies per milliliter in complex plasma samples within 35 min. Our method simplifies workflows, improves NA retention, and is suitable for processing complex biological samples, making it ideal for POC and in-field testing applications., Competing Interests: Declaration of competing interest The authors declare that there are no competing financial or non-financial interests related to the work described in this manuscript. We confirm that the work presented in this manuscript is original, and no part of it has been published or submitted for publication elsewhere. All authors have contributed to the manuscript and have approved the final version for submission., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ophiocordyceps sinensis is widely used to treat various diseases and as a health supplement. The present study comprehensively compared the metabolic differences between wild and cultivated O. sinensis through 2D 1 H- 13 C HSQC-based metabolomics, and assessed their anti-lung cancer activity on A549 cells. To characterize the global metabolic profile, sample preparation was scrutinously optimized, and both polar (1:4 methanol-water) and non-polar (1:4 methanol-chloroform) extracts of O. sinensis were investigated. A total of 47 and 10 metabolites were identified in the polar and non-polar extracts, respectively. Principal Component Analysis (PCA) revealed greater differences between the two types of O. sinensis in the polar extracts than in the non-polar extracts. Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) together with univariate tests captured 23 and 19 differential spectral features (with 22 and 11 of them assigned) between wild and cultivated O. sinensis in the polar and non-polar extracts, respectively. Meanwhile, the anti-lung cancer activities of both polar and non-polar extracts of wild and cultivated O. sinensis were assessed by MTS assay on A549 cells, and the sterols found in non-polar extracts, such as ergosterol, ergosterol peroxide, and 9,11-dehydroergosterol peroxide, and β-sitosterol, are the active ingredients with potential anti-lung cancer properties. In this study, we introduced a comprehensive strategy integrating 2D NMR-based metabolomics with in vitro assays for comparing the chemical composition and assessing the pharmacological activity of wild and cultivated O. sinensis. Our results provided a scientific basis for the potential viability of cultivated O. sinensis as an alternative to the wild counterpart., 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.)

In practical sweet cherry production, grafting onto rootstocks is a common practice to enhance environmental adaptability. Rootstocks play a crucial role in influencing scion growth and fruit quality by regulating the absorption and utilization of mineral elements. In this study, the influence of five rootstocks with or without root fertilization during the fruit color conversion period on the fruit quality of sweet cherry 'Summit' was observed. The physicochemical characteristics, external color characteristics, and total anthocyanin content of 'Summit' were significantly affected by both rootstock and fertilization, with an interaction between the two factors. The content of certain sugar components, organic acid components and phenolic acid components in 'Summit' were significantly affected by rootstocks and fertilization. 'Summit' grafted on Gisela 5 and H22 exhibited higher sugar content, while 'Summit' grafted on H11 and H17 exhibited higher organic and phenolic acid content., 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.)

Phyllanthus emblica L., a distinctive fruit, is rich in polyphenols and polysaccharide. However, there is a lack of knowledge regarding the role of these compounds as glycolipid lowering ingredients. In this study, the glycolipid lowering ingredients and their effects have been determined by gradually comparing varieties, parts, and components, splitting components, and calculating combined index via their interactions with digestion enzymes, bile acids, cholesterol micelles and probiotics. Results indicated that the glycolipid lowering ingredients were polyphenols and polysaccharide, which located in the pulp, and not influenced by the variety. Pectin with multiple structural domains, and hydrolyzable tannins, i.e. gallic acid, ellagic acid and their derivatives interacted with multiple gut action targets could regulate glycolipid digestion, absorption and metabolism. Polysaccharide and polyphenols demonstrated a synergistic effect in lowering glycolipid by interacting with gut action targets. These findings highlight the potential for further investigation and utilization of glycolipid lowering ingredients in fruits., 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.)

Conductive hydrogels have received much attention in the field of flexible wearable sensors due to their outstanding flexibility, conductivity, sensitivity and excellent compatibility. However, most conductive hydrogels mainly focus on strain sensors to detect human motion and lack other features such as temperature response. Herein, we prepared a strain and temperature dual responsive ionic conductive hydrogel (PPPNV) with an interpenetrating network structure by introducing a covalent crosslinked network of N-isopropylacrylamide (NIPAAm) and 1-vinyl-3-butylimidazolium bromide (VBIMBr) into the skeleton of the hydrogel composed of polyvinylalcohol (PVA) and polyvinylpyrrolidone (PVP). The PPPNV hydrogel exhibited excellent anti-freezing properties (-37.34 °C) and water retention with high stretchability (∼930 %) and excellent adhesion. As a wearable strain sensor, the PPPNV hydrogel has good responsiveness and stability to a wide range of deformations and exhibits high strain sensitivity (GF=2.6) as well as fast response time. It can detect large and subtle body movements with good signal stability. As wearable temperature sensors, PPPNV hydrogels can detect human physiological signals and respond to temperature changes, and the volumetric phase transition temperature (VPTT) can be easily controlled by adjusting the molar ratio of NIPAAm to VBIMBr. In addition, a bilayer temperature-sensitive hydrogel was prepared with the temperature responsive hydrogel by two-step synthesis, which shows great promising applications in temperature actuators., 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 Inc. All rights reserved.)

The photocatalytic hydrogen production performance of semiconductor materials can be improved by co-catalyst modification. In most of the studies, the size of the co-catalyst is relatively small compared to the primary catalyst. However, in this study, we employed a novel strategy by synthesizing a relatively large-sized Cu 2 MoS 4 as the co-catalyst and in situ loading smaller-sized Zn 0.5 Cd 0.5 S onto Cu 2 MoS 4 , verifying that Cu 2 MoS 4 enhances the photocatalytic hydrogen production efficiency of Zn 0.5 Cd 0.5 S. It can be observed by scanning electron microscopy (SEM) that the lateral size of 2D Cu 2 MoS 4 is at least 50 times larger than the Zn 0.5 Cd 0.5 S nanoparticle particle size. In addition, Density Functional Theory (DFT) calculations have demonstrated that the active site for hydrogen production in the composite is located in Cu 2 MoS 4 . The large-sized of Cu 2 MoS 4 not only provides more active sites but also broadens the electron transport channel, which is conducive to promoting the transfer of photogenerated electrons from Zn 0.5 Cd 0.5 S. This work enriches the study of large-sized materials as co-catalyst and provides a strategy for the construction of composite catalysts., 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 Inc. All rights reserved.)

To analyze the relationship between hot or cold, and wet or dry interacting weather, and urolithiasis-related hospitalizations. Distributed lag nonlinear model for time series design was used to build exposure-response curves for the association of daily mean temperature and relative humidity with urolithiasis-related hospitalizations. Cut-off values were determined for temperature, humidity, and dichotomous categories to define heat-cold and wet-dry meteorological conditions. Based on a total of 38,184 urolithiasis-related hospitalizations from 2018 to 2019 in Ganzhou as a large prefecture-level city in southern China, dry-heat weather during the hot season (May to September) increased the risk of urolithiasis-related hospitalizations (relative risk [RR]: 1.17, 95% confidence interval [CI]: 1.02, 1.35), with the most pronounced effects in those aged 21-40 years and male. Wet-cold weather in the cold season (December to February) increased the risk of urolithiasis-related hospitalizations in the total population (RR: 1.58, 95% CI: 1.20, 2.07). The effect was significant in the 21-60 years old age and both genders groups. Both dry-heat weather in the hot season and wet-cold weather in the cold season could trigger urolithiasis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Meiosis in mammalian oocytes is interrupted by a prolonged arrest at the germinal vesicle stage, during which oocytes have to repair DNA lesions to ensure genome integrity or otherwise undergo apoptosis. The FIRRM/FLIP-FIGNL1 complex dissociates RAD51 from the joint DNA molecules in both homologous recombination (HR) and DNA replication. However, as a type of non-meiotic, non-replicative cells, whether this RAD51-dismantling mechanism regulates genome integrity in oocytes remains elusive. Here, we show that FIRRM/FLIP is required for disassembly of RAD51-filaments and maintenance of genome integrity in oocytes. Deletion of FIRRM in oocytes leads to formation of massive nuclear RAD51 foci in oocytes of primordial follicles and activated follicles in mice. These RAD51 foci colocalize with the sites of DNA damage repair, as indicated by RPA2 and EdU, suggesting substantial DNA damage and extensive HR in oocytes. Especially in fully-grown FIRRM-deleted oocytes, RAD51 forms a net-like structure. As a consequence, FIRRM-deleted females are infertile due to aberrant homologous chromosome segregation at metaphase I and primordial follicle insufficiency at young adulthood. Hence, our study demonstrates the physiological importance of HR in maintaining genome integrity in oocytes., (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: In this study, we retrospectively examined the prognostic significance of the pathological status of esophageal squamous cell carcinoma (ESCC) patients following neoadjuvant chemoradiotherapy (NCRT) and surgery., Methods: Data of patients with cT2-4aN0-3 stage ESCC who underwent NCRT and esophagectomy during 2014-2022 were reviewed retrospectively. Survival differences were compared according to revised TN (rTN) stage (ypT0N0, ypT + N0, ypT0N+, and ypT + N+) using univariate and Cox regression analyses., Results: Of the 136 patients (59.1 ± 7.2 y) included in this study, 123 (90.4%) were males. There were 39 (28.7%) patients with ypT0N0 disease, 49 (36.0%) ypT + N0, 11 (8.1%) ypT0N+, and 37 (27.2%) ypT + N+. Additionally, 126 patients had a median follow-up period of 30 (1-90) months. The 5-year overall survival was 81.6% in ypT0N0 group, 53.1% for ypT + N0, 50.0% for ypT0N+, and 18.6% for ypT + N+ (p < 0.001) and 5-year disease-free survival was 70.1% for ypT0N0, 39.7% for ypT + N0, 33.3% for ypT0N+, and 18.4% for ypT + N+ (p < 0.001). The ypT + N0 and ypT0N + groups showed no significant differences in survival (p > 0.05). In Cox regression analysis, ypT stage and rTN stage showed an independent association with OS (p = 0.026 and 0.001, respectively). During the follow-up period, 69 (54.8%) patients developed recurrence, with ypT0N0 patients experiencing fewer local and distant recurrences compared to other groups (p < 0.001)., Conclusion: In ESCC patients, the ypT0N0 status after NCRT predicts prolonged survival, but this reduces significantly when nodal metastases or residual primary lesions are present., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board of the Tianjin Medical University Cancer Institute and Hospital. Informed consent was obtained from all the patients. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Assessing the endothelialization of occlusive devices noninvasively remains a challenge. Cardiac computed tomography angiography (CTA) can be employed to evaluate device endothelialization based on contrast uptake within the occluder., Objective: This study examined device endothelialization using cardiac CTA and investigated the pathological associations., Methods: From January 2010 to May 2022, we retrospectively analyzed 25 patients (age: 50.00 [17.00, 52.00] years; 12 Female) who underwent surgical device removal within 1 month after cardiac CTA examination (implantation period: 29.00[0.50, 108.00] months). The contrast uptake within the occluder was determined using cardiac CTA. The relationship between contrast uptake within the occluder and the endothelialization status with pathology was analyzed., Results: Contrast uptake within the occluder was identified in 76.00% of patients. Pathological examination confirmed incomplete coverage of fibrotic tissue and superposed neoendothelium on the surface of all devices exhibiting contrast uptake. This included no coverage in 47.37% of patients and partial coverage in the remaining cases. On the surface of all devices without contrast uptake, a complete range of fibrotic tissue was observed, with an incomplete range of superposed neoendothelium in 66.67% of patients. On the surface of devices with an implantation period > 6 months, 71.43% of patients had incomplete coverage of fibrotic tissue and superposed neoendothelium on the left disc, 42.86% of patients occurred the same on the right disc., Conclusions: Contrast uptake within the occluder indicated incomplete endothelialization, as confirmed by pathological validation. Late endothelialization of the device occurs frequently, and further research is required to investigate related mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sociosexual preference is critical for reproduction and survival. However, neural mechanisms encoding social decisions on sex preference remain unclear. In this study, we show that both male and female mice exhibit female preference but shift to male preference when facing survival threats; their preference is mediated by the dimorphic changes in the excitability of ventral tegmental area dopaminergic (VTA DA ) neurons. In males, VTA DA projections to the nucleus accumbens (NAc) mediate female preference, and those to the medial preoptic area mediate male preference. In females, firing-pattern (phasic-like versus tonic-like) alteration of the VTA DA -NAc projection determines sociosexual preferences. These findings define VTA DA neurons as a key node for social decision-making and reveal the sexually dimorphic DA circuit mechanisms underlying sociosexual preference.

Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive. There is a critical need for effective inhibitory optogenetic tools that are highly light-sensitive and capable of suppressing neuronal activity in deep brain tissue. In this study, we developed a highly sensitive moderately K + -selective channelrhodopsin (HcKCR1-hs) by molecular engineering of the recently discovered Hyphochytrium catenoides kalium (potassium) channelrhodopsin 1. Transcranial activation of HcKCR1-hs significantly prolongs the time to the first seizure, increases survival, and decreases seizure activity in several status epilepticus mouse models. Our approach for transcranial optogenetic inhibition of neural hyperactivity may be adapted for cell type-specific neuromodulation in both basic and preclinical settings., Competing Interests: Competing interests: K.S., X.D. C.Z. and Y.W. have filed a patent application related to this work. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Banana is sensitive to cold stress and often suffers from chilling injury with browning peel and failure to normal ripening. We have previously reported that banana chilling injury is accompanied by a reduction of miR528 accumulation, alleviating the degradation of its target gene MaPPO and raising ROS levels that cause peel browning. Here, we further revealed that the miR528-MaPPO cold-responsive module was regulated by miR156-targeted SPL transcription factors, and the miR156c-MaSPL4 module was also responsive to cold stress in banana. Transient overexpression of miR156c resulted in a more severe chilling phenotype by decreasing the expression of MaSPL4 and miR528. Conversely, the browning was alleviated in STTM-miR156c silencing and OE-MaSPL4 samples. Furthermore, DNA affinity purification sequencing and MaSPL4-overexpressing transcriptome jointly revealed that MaSPL4 may mediate the transcription of genes related to lipid metabolism and antioxidation, in addition to the miR528-MaPPO module, demonstrating MaSPL4 as a master regulator in the fruit cold response network. In summary, our results suggest that the miR156c-MaSPL4 module can mediate the chilling response in banana by regulating the miR528-MaPPO module and multiple other pathways, which provides evidence for the crosstalk between TFs and miRNAs that can be used for the molecular breeding of fruit cold tolerance., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors have read and given their approval to the final version of the manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background and Aim: The acute pulmonary infectious disease caused by influenza viruses is known as influenza virus pneumonia (IVP). In recent years, Gegen Qinlian Decoction (GQD) has been widely used to treat pulmonary inflammation; however, the underlying mechanism of action of GQD in IVP remains unclear. This study aimed to elucidate the molecular mechanism through which GQD improved IVP., Materials and Methods: The efficacy of GQD was evaluated using classical pharmacodynamic indicators in a murine model of H1N1-induced IVP. Network pharmacology predicted the material basis of GQD in improving IVP, while metabonomics and 16 s rDNA sequencing assessed its regulation on small molecule metabolites and intestinal flora. Additionally, molecular biology techniques were used to investigate the molecular mechanism underlying the improvement of IVP by GQD., Results: The study results demonstrated that GQD exhibited a significant ameliorative effect on the inflammatory response in lung tissue of IVP mice. The potential pharmacological substances of GQD for improving IVP were identified by network pharmacology combined with ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) analysis, including puerarin, baicalin, berberine, and glycyrrhizin. Further analysis of biological processes and mechanisms of action predicted that GQD could improve IVP by inhibiting activation of inflammasomes, regulating the body's immune system, and intestinal microecology. Metabolomics and microbiomics findings revealed that GQD could bi-directionally regulate lipid and amino acid metabolites by increasing the abundance of beneficial bacteria like Akkermansia and Acetobacter, thereby maintaining host metabolic balance and immune homeostasis. RT-qPCR and immunohistochemistry results indicated that GQD improved IVP by inhibiting the complement C3/NLRP3 inflammasome pathway., Conclusion: The findings of this study confirmed that GQD effectively inhibited IVP by modulating the "gut microbiota-metabolomics-immune/inflammation" axis in the host, thereby establishing a solid immunological foundation for the clinical application of GQD., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Liposomes, especially polyethylene glycol (PEG)-modified long-circulating liposomes, have been approved for market use, due to good biocompatibility, passive tumor targeting, and sustained drug release. PEG-modified long-circulating liposomes address issues such as poor stability and rapid clearance by the reticuloendothelial system. However, they still face challenges like hindering drug uptake by tumor cells and preventing tumor penetration. Inspired by the hypoxic tumor microenvironment, we constructed a hypoxia-responsive liposome (PAO-L) to enhance the intracellular uptake and photodynamic therapy (PDT) effect of chlorin e6 (Ce6). The intelligent hypoxia-cleavable PEG-AZO-OA (PAO) was prepared by coupling PEG and octadecylamine (OA) to hypoxia-sensitive azobenzene-4,4'-dicarboxylic acid (AZO) through amide reaction. The synthesized PAO was further incorporated into Ce6-loaded liposomes to enhance the circulation stability, while promote the tumor penetration and internalization by the responsive shedding of PEG from liposome surface upon reaching the hypoxic tumor tissue. PAO-L mediated PDT significantly inhibited the growth of B16F10 and 4T1 tumors, as well as lung metastasis of 4T1 breast cancer. The excellent therapeutic effect and good tolerability make PAO-L a promising candidate for enhanced PDT., Competing Interests: Declaration of competing interest The authors declared that there are no known competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethyl vanillate (EV) is an important component of flavors and fragrances and has been widely used in the food, pharmaceutical, and cosmetic industries. The highly selective preparation of EV from lignin, the most abundant monophenolic compound in nature, is a great challenge in the field of lignin depolymerization. In this study, the multi-active catalysts from alkaline ionic liquid and polyoxometalates were constructed, which were characterized by acidity, alkaline and oxidizing ability. They can efficiently cleave the CC and CO bonds of larch lignin in an ethanol/water system at 160 °C for 10 h with H 2 O 2 as an oxidizing agent. Vanillin and EV were main products with the phenolic yield of 10.14 wt% and the selectivity of EV was up to 83.63 %. The depolymerization of phenolic and non-phenolic lignin model compounds demonstrated that the cleavage of β-O-4 and C α -C β bonds contributed to the selective preparation of EV in the catalytic system. The catalyst can be recycled up to 4 times with excellent stability and recoverability. This study provides a new approach for the production of EV, which is promising in the high-valued utilization of larch waste., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xixin Duan reports financial support was provided by Jilin Provincial Department of science and technology. Kuiyuan Cao reports financial support was provided by Jilin Provincial Department of science and technology. Fang Yang reports financial support was provided by Jilin Provincial Department of science and technology. He Wan reports financial support was provided by Jilin Provincial Department of science and technology. Junyou Shi reports financial support was provided by National Natural Science Foundation of China. Zhong Sun reports financial support was provided by Jilin Province People's Government Department of Education. 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 © 2025. Published by Elsevier B.V.)

To meet the increasing demand for wearable sensor in special environment such as low temperature or underwater, a multifunctional ionic conducting hydrogel (Gel/PSAA-Al 3+ hydrogel) with anti-freezing and low swelling for human motion detection and underwater communication was prepared using gelatin (Gel), [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), acrylamide (AAm), acrylic acid (AAc), and AlCl 3 . Due to reversible hydrogen bonding, electrostatic interactions and metal coordination crosslinking between the polymer networks, the resulting Gel/PSAA-Al 3+ hydrogels present low swelling property in water and exhibit large tensile properties (~1050 %), high tensile strength (~250 kPa) and excellent fatigue resistance. In addition, the hydration capacity of SBMA and AlCl 3 endows the Gel/PSAA-Al 3+ hydrogel fantastic anti-freezing (-31.58 °C) and water retention properties. Moreover, the electrostatic interaction between SBMA and AlCl 3 due to the ion hopping mechanism endows the hydrogel with excellent ionic conductivity (6.38 mS/cm). The Gel/PSAA-Al 3+ hydrogel sensors present good biocompatibility and provide a wide operating range (0 %-1050 %), fast response time (229 ms) and recovery time (248 ms), high sensitivity (GF = 1.61) and excellent stability for detecting large and small body movements. The Gel/PSAA-Al 3+ hydrogel shows potential applications as a wearable sensor for communication at low temperature or underwater., 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 © 2025. Published by Elsevier B.V.)

The development of the human neocortex is highly dynamic, involving complex cellular trajectories controlled by gene regulation 1 . Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and the primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence. In parallel, we performed spatial transcriptomic analysis on a subset of the samples to illustrate spatial organization and intercellular communication. This atlas enables us to catalogue cell-type-specific, age-specific and area-specific gene regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification and lineage-tracing experiments, we have untangled the complex lineage relationships among progenitor subtypes during the neurogenesis-to-gliogenesis transition. We identified a tripotential intermediate progenitor subtype-tripotential intermediate progenitor cells (Tri-IPCs)-that is responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells and astrocytes. Notably, most glioblastoma cells resemble Tri-IPCs at the transcriptomic level, suggesting that cancer cells hijack developmental processes to enhance growth and heterogeneity. Furthermore, by integrating our atlas data with large-scale genome-wide association study data, we created a disease-risk map highlighting enriched risk associated with autism spectrum disorder in second-trimester intratelencephalic neurons. Our study sheds light on the molecular and cellular dynamics of the developing human neocortex., Competing Interests: Competing interests: A.R.K. is a co-founder, consultant and director of Neurona Therapeutics. J.L. is a co-founder and a member of the scientific advisory board of SensOmics, Inc. The other authors declare no competing interests., (© 2025. The Author(s).)

Introduction: The prognostic differences between neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) remain unclear., Methods: This study aims to compare the prognostic outcomes of NEC and MiNEN by analyzing the clinicopathological features of these diseases and exploring factors affecting progression after radical surgery. Additionally, we employed whole-exome sequencing to investigate the molecular mechanisms influencing the prognosis of both conditions., Results: Among the 252 patients followed, 163 underwent surgical treatment. The median time to tumor progression was 16 months (range: 9 to 56 months). Tumor pathology type (P=0.007), lymph node metastasis (P<0.0001), and distant metastasis (P<0.0001) were identified as independent factors affecting disease progression in NEC and MiNEN patients. MiNEN patients without lymph node or distant metastasis generally had a better prognosis. First-line chemotherapy regimens did not show a significant impact on disease progression (P=0.160, mPFS: 36 vs 13 vs 23 vs 15 months). However, the EP (etoposide plus cisplatin) regimen has shown good efficacy in gastric NENs (neuroendocrine neoplasms) (P=0.048, mPFS: 45 vs 12 vs 32 vs 16 months), especially in gastric MiNENs (P=0.022, mPFS: Undefined vs 11 vs 52 vs 37 months). Further investigation into the genetic mutation differences between NECs and MiNENs revealed that among previously sequenced data, rectal NECs commonly exhibited mutations in MUC16, SPTA1, ATM, PDGFB, NF1, FAT4, AR, APC, ANTXR2, and ADGRA2. In contrast, rectal MiNENs showed common mutations in NOTCH2, ZNRF3, CARD11, TP53, OBSCN, FPR1, APC, ANGPT2, ARID1A, and AR. Mutations in ANGPT2 and OBSCN were present in two rectal MiNEN cases, while NF1 and PDGFB mutations were found in two rectal NEC cases but not in MiNENs. The JAK-STAT signaling pathway appears to be specific to rectal NECs and may be involved in tumor progression., Conclusion: EP regimen remains the most effective chemotherapy option for neuroendocrine tumor patients. There were prognostic differences between NECs and MiNENs, as well as differences in genetic mutations and signaling pathways. This study provided new insights into the prognosis assessment and treatment strategies for NENs, particularly highlighting the importance of personalized treatments and the development of novel targeted therapies., (S. Karger AG, Basel.)

The catalytic properties of unary to ternary metal oxides were already well experimentally explored, and the left space seems like only high entropy metal oxides (HEOs, element types ≥5). However, the countless element compositions make the trial-and-error method of discovering HEO catalysts impossible. Herein, based on the study of the crystal phase and catalytic performance of the ACr 2 O x catalyst system, the strong correlation between the single spinel phase and good catalytic activity of CH 4 oxidation was inferred owing to the similar element importance sequences, which were acquired by the corresponding high accuracy machine learning models (cross-validation score >0.7). Furthermore, searching for negative data and choosing the proper training data resulted in high-quality regression models to search for better catalysts. Finally, the screened irregular catalyst Ni 0.04 Co 0.48 Zn 0.36 V 0.12 Cr 2 O x with outstanding sulfur and moisture resistance and long-term stability (>7000 h, T 90 = 345 °C) envisions the potential of applying the machine learning method to discover HEOs for target processes.

Cinnamon essential oil has gained widespread attention in the food industry as a safe and effective preservative. However, its low water solubility and high volatility limit its application in food, making the use of natural emulsifiers for its emulsification an increasingly popular focus of research. This study focuses on the extraction of galactomannan-rich aqueous extracts from Gleditsia sinensis seeds using a low-energy, low-pollution microwave-assisted method. The extracted aqueous extracts from Gleditsia sinensis seeds was combined with soy protein isolate to prepare a cinnamon essential oil emulsion, followed by physicochemical characterization and stabilization mechanism studies. The emulsions demonstrated excellent storage stability at 4 °C, along with robust ionic, pH, temperature, and freeze-thaw stability. Furthermore, the emulsions exhibited significant antioxidant activity and effectively inhibited the growth of Staphylococcus aureus and Listeria monocytogenes, highlighting their potential for application in food preservation. Preservation trials with orange juice confirmed that our emulsion achieved preservation comparable to that of the commercial food preservative potassium sorbate. These findings provide valuable insights for developing stable and functional natural food emulsifiers., 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 © 2025 Elsevier B.V. All rights reserved.)

Theranostic applications in atherosclerosis plaque microenvironment-triggered nanoplatforms are significantly compromised by the complex synthesis procedure, non-specific distribution, and limited therapeutic function. Therefore, development of a facile and feasible method to construct a pathology-based stimuli-responsive nanoplatform with satisfactory theranostic performance remains a demanding and highly anticipated goal. Herein, a novel class of multifunctional supra-carbon dots (CDs), denoted as MM@Ce-CDs NPs, by a simple nanoassembly and a subsequent coating with macrophage membrane (MM), is developed for the targeted reactive oxygen species-trigged theranostic and positive regulation of the pathological plaque microenvironment in AS. The harvested MM@Ce-CDs NPs exhibit activatable fluorescence properties, photoacoustic characteristics, and cascade enzyme performances, which can be effectively activated under ROS stimulation in the plaque pathological microenvironment, enabling precise control over theranostic functions, while markedly enhancing diagnostic accuracy and therapeutic efficacy for AS management. Besides, MM@Ce-CDs NPs can effectively manipulate the plaque microenvironment by reducing ROS levels and inflammation, alleviating M1 macrophage infiltration, and inhibiting foam cell formation, all together suppressing the pathological plaque development through the synergistic mechanisms. In addition, MM@Ce-CDs NPs inherit the biomimetic biological functions from MM, facilitating a highly specific target delivery to AS., (© 2025 Wiley‐VCH GmbH.)

Diblock copolyelectrolytes have significant potential in applications such as solid-state single-ion conductors, but precisely controlling their nanostructures for efficient ion transport remains a challenge. In this study, we explore the phase behavior and microphase transitions of AX BY-type diblock copolyelectrolytes under alternating electric fields using coarse-grained molecular dynamics simulations. We systematically investigate the effects of various electric field features, including unipolar and bipolar square-waves, as well as offset and non-offset sine-waves, focusing on how field strength and period influence the self-assembling morphology of the copolyelectrolytes. Under unipolar square-waves, both the lamellar and cylindrical phase regions expand, while the disordered phase regions shrink as the field strength increases. In contrast, bipolar square-waves maintain lamellar structures more robustly, with reversed stretching behavior observed in the polymer chains. As the electric field period exceeds a critical value, both waveforms converge with the results seen under constant electric fields. In addition, sine-waves induce smoother phase transitions, expanding the ordered phase regions, particularly the cylindrical phase, due to continuous field variation. We further examine the detailed structural and dynamic properties, such as mean-square displacement, polymer conformation, and chain orientation during these transitions. This work provides fundamental insights into the structural regulation of diblock copolyelectrolytes under oscillating electric fields, guiding the design of advanced polymeric electrolytes with tailored nanostructures., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Precisely assessing nectin-4 expression in tumors is important in identifying patients who may benefit from nectin-4-targeted therapies. In our previous work, we developed a bicyclic peptide-based nectin-4-targeting radiotracer 68 Ga-N188 and validated its nectin-4 detection efficacy. However, the relatively short half-life and low positron emission rate of 68 Ga limit its further application. In this study, we constructed three novel nectin-4-targeting ligands N230-232 based on a bicyclic peptide structure and labeled with radionuclide 18 F, which has a longer half-life and a higher positron emission rate, for PET imaging. Micro-PET/CT imaging-based screening showed that Al 18 F-N231 had the best imaging contrast with a tumor-to-muscle ratio of 10.97 ± 2.39. Further characterization demonstrated that ligand N231 had a high affinity to nectin-4 with a K d of 4.29 nM, and Al 18 F-N231 had a good stability and safety profile in vivo . Biodistribution studies validated the specific binding of Al 18 F-N231 to nectin-4 in vivo , with tumor uptake in the nectin-4 + SW780 tumor group being 1.45- and 3.75-fold higher than that in the nectin-4 - 5637 tumor group and blocking group, respectively. Based on the results of this work, Al 18 F-N231 has promising capability for noninvasive nectin-4 detection in vivo .

Short-wave infrared (SWIR) imaging has a wide range of applications in civil and military fields. Over the past two decades, significant efforts have been devoted to developing high-resolution, high-sensitivity, and cost-effective SWIR sensors covering the spectral range from 0.9 μm to 3 μm. These advancements stimulate new prospects across a wide array of fields including life sciences, medical diagnostics, defense, surveillance, security, free-space optics (FSO), thermography, agriculture, food inspection, and LiDAR applications. In this review, we begin by introducing monolithic SWIR image sensors and hybrid SWIR image sensors and indicate that flip-chip bump bonding technology remains the predominant integration method for hybrid SWIR image sensors owing to its outstanding performance, adaptable integration with innovative epitaxial SWIR materials, long-term stability, and long-term reliability. Subsequently, we comprehensively summarize recent advancements in epitaxial thin-film SWIR sensors, encompassing FPAs and flip-chip bump bonding technology for epitaxial InGaAs and Ge (Sn) thin-film SWIR sensors. Finally, a summary and outlook regarding the development of InGaAs and Ge (Sn) SWIR sensors are provided and discussed. The ongoing evolution of epitaxial thin-film SWIR sensors with flip-chip bump bonding technology is poised to foster new applications in both academic and industry fields.

Transforming plastics into single-atom catalysts is a promising strategy for upcycling waste plastics into value-added functional materials. Herein, a graphene-based single-atom catalyst with atomically dispersed FeN 4 Cl sites (Fe─N/Cl─C) is produced from high-density polyethylene wastes via one-pot catalytic pyrolysis. The Fe─N/Cl─C catalyst exhibited much higher turnover frequency and surface area normalized activity (K ac ) compared with the Fe─N─C catalyst without axial Cl modulation. Both experiments and density functional theory (DFT) computations demonstrated that the axial incorporation of chloride fine-tuned the coordination environment of FeN 4 sites and enhanced peroxymonosulfate (PMS) activation because of improved conductivity and modulated spin state. In situ, Raman, and infrared spectroscopic techniques revealed that PMS is activated by the Fe─N/Cl─C catalyst through an electron transfer process. The formation of a key PMS * intermediate at the Fe site effectively elevated the redox capacity of the catalyst surface to realize a fast degradation of diverse pollutants. The non-radical oxidation manner secures high selectivity toward target pollutants and high chemical utilization efficiency. A continuous operation in a column reactor also demonstrated the high efficiency and stability of the (Fe─N/Cl─C + PMS) system for practical water treatment., (© 2024 Wiley‐VCH GmbH.)

Platinum group metals (PGMs) are increasingly recycled from spent automotive catalysts due to their scarcity in nature. Many studies were developed using different leaching reagents in order to achieve greener benefits and reduce environmental pollution. This article reports for the first time direct comparison of leaching reagents on the efficiency of PGMs using microwave (MW) assisted heating. The leaching system employed HCl with/without the addition of complexing (citric acid) or oxidizing agents (HNO3, H2O2, NaClO, NaClO3). It was shown that the 11.65 M HCl could leach all elements (94% Pt, 82% Pd and 74% Rh) at 210ºC. The addition of oxidant(s) decreased the PGMs leaching efficiencies due to the formation of a protective oxide layer through surface passivation reaction. In some cases, the addition of complexing or oxidizing (H2O2) agents and a high leaching temperature (>180℃) employed in the MW leaching could enhance PGMs leachabilities, particularly for Rh (>90%). A detailed temperature study of the MW leaching demonstrated that HCl could obtain excellent recoveries (>90%) for Pt and Pd at temperatures ≥150ºC. Therefore, this research illustrates that partially replacing the HCl with citric acid is a promising approach to achieve a greener and more efficient leaching process of PGMs., (© 2025 Wiley‐VCH GmbH.)

Nanoparticles have become widely used materials in various fields, yet their mechanism of action at the cellular level after entering the human body remains unclear. Accurately observing the effect of nanosize dimensions on particle internalization and toxicity in cells is crucial, particularly under the conditions of biological activity. With the aim of helping to study the interactions between nanoparticles of varying sizes and active cell membranes, we propose a flexible biosensor system based on a field effect transistor (FET). We constructed lipid bilayers on the device in vitro to simulate the interaction between nanoparticles and lipid membranes under active conditions, with the aim of investigating the effect of differently sized nanoparticles on the cell membrane. The experimental results revealed that nanoparticles with a diameter smaller than 50 nm tend to induce mild strain and repairable damage to the membrane, whereas nanoparticles larger than 50 nm may cause more severe damage, and even transmembrane penetration, by creating unrecoverable pores. The stretching of the lipid membrane exacerbated the deformation and destruction caused by nanoparticles, even in the case of smaller particles. These above results are consistent with previous theories on the interactions between cell membranes and nanoparticles. The proposed biosensors provide a valuable tool for investigating how the nanosize dimensions of particles affect their ability to penetrate and cause destruction in dynamic cell membranes, contributing to the improvement of a more comprehensive theoretical system for understanding the interaction process between nanoparticles and cell membranes.

The rational design of advanced oxygen reduction reaction (ORR) catalysts is essential to improve the performance of energy conversion devices. However, it remains a huge challenge to construct hierarchical micro-/meso-/macroporous nanostructures, especially mesoporous transport channels in catalysts, to enhance catalytic capability. Herein, motivated by the characteristics of energetic metal-organic frameworks (EMOFs) that produce an abundance of gases during high-temperature pyrolysis, we prepared a unique tetrazine-based EMOF-derived electrocatalyst (denoted as Fe 3 C@NSC-900) consisting of highly dispersed Fe 3 C nanoparticles and N,S-codoped mesoporous carbon nanotubes. The mesopore-dominated core-shell structure endows Fe 3 C@NSC-900 with excellent catalytic activity and efficient mass transfer. Thus, optimal Fe 3 C@NSC-900 demonstrates a high half-wave potential of 0.922 V and great stability in 0.1 M KOH, outperforming commercial Pt/C and most of the reported ORR catalysts. As far as we know, this work is the first application of a tetrazine-based EMOF derivative for the electrocatalytic ORR and is expected to offer some constructive insights into potential of EMOFs for new-generation catalyst design.

Objective: This study investigates the impact of plyometric training on age-related lower limb explosive strength in male adolescents and its effectiveness in female adolescents., Methods: A thorough search was conducted across five databases from their inception until September 20, 2024. Study quality was assessed using the Cochrane Risk Assessment Tool, and data analysis was performed with Stata 15 software., Results: Plyometric training positively affected countermovement jump (CMJ) (MD = 2.90 cm, 95% CI (2.35, 3.45)), squat jump (SJ) (MD = 2.57 cm, 95% CI (1.69, 3.44)), and 20-m sprint performance (MD = - 0.09 s, 95% CI (- 0.14, - 0.05)). Subgroup analysis revealed varying improvements across age stages. In CMJ, the early adolescence (EA) group (MD = 2.57 cm, 95% CI (1.74, 3.40)), mid-adolescence (MA) group (MD = 3.04 cm, 95% CI (2.30, 3.79)), and post-adolescence (PA) group (MD = 3.89 cm, 95% CI (1.96, 5.81)) showed progressive enhancement. The MA group exhibited superior improvements in SJ (MD = 3.78 cm, 95% CI (2.19, 5.36)) and 20-m sprint (MD = - 0.11 s, 95% CI (- 0.18, - 0.05)) compared to the EA group (SJ: MD = 2.10 cm, 95% CI (1.43, 2.77); sprint: MD = - 0.06 s, 95% CI (- 0.11, - 0.01)). The PA group showed no significant improvements (SJ: MD = 1.31 cm, 95% CI (- 1.05, 3.67); sprint: MD = - 0.27 s, 95% CI (- 0.61, 0.07)). For female adolescents, plyometric training effectively improved CMJ (MD = 2.55 cm, 95% CI (1.43, 3.66)), SJ (MD = 2.33 cm, 95% CI (1.36, 3.31)), and 20-m sprint performance (MD = - 0.22 s, 95% CI (- 0.33, - 0.12))., Conclusion: Plyometric training significantly enhances lower limb explosive strength in both male and female adolescents, with age-dependent effects for male adolescents. The greatest improvement in CMJ was observed in the PA stage, followed by the MA stage, while the EA stage showed the least. The MA stage exhibited the best improvements in SJ and sprint performance., Trail Registry: The study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023406914)., Competing Interests: Declarations. Conflict of interest: All authors declare that they have no conflict of interest. Ethical approval: The study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023406914). Consent for publication: All authors agreed to the published version of the manuscript., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To investigate the efficacy and safety of transient receptor potential (TRP) channel modulators for dry eye., Methods: A thorough search for randomized clinical trials was conducted in seven databases up to February 16, 2024. Suitable studies were identified according to inclusion and exclusion criteria, extracted data were synthesized and analyzed using Review Manager 5.4, and risk of bias and quality of evidence were assessed using recommended tools., Results: Six trials with 884 patients using two kinds of TRP channel modulators (TRPV1 antagonist and TRPM8 agonist) were included. TRP channel modulators were effective in reducing subjective symptom scores (standardized mean differences [SMD], -0.41; 95 % confidence interval [CI], -0.75 to -0.07), corneal fluorescence staining (mean differences [MD], -0.19; 95 % CI, -0.37 to -0.02), impact on quality of life and daily function, and increasing the non-anesthetic Schirmer's test score (MD, 11.71; 95 % CI, 9.59 to 13.83), instant tear meniscus height (MD, 245.52; 95 % CI, 14.02 to 477.02), improvement in conjunctival hyperemia (risk ratio [RR], 2.08; 95 % CI, 1.07 to 4.06). There was no increased incidence of adverse events with TRP modulators compared to vehicle solution controls., Conclusions: TRP channel modulators have shown positive therapeutic effects in reducing the symptoms and signs of dry eye and improving the quality of life associated with the disease without raising the risk of adverse events. These modulators are expected to become a new therapy for dry eye., (Copyright © 2024 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Objective: Pharyngocutaneous Fistula (PCF) is one of the most common and challenging postoperative complications after Total Laryngectomy (TLE). This study aimed to evaluate the impact of the modified Vertical Pressure Bandage (VPB) on the occurrence of Pharyngocutaneous Fistula (PCF) after Total Laryngectomy (TLE) for Head and Neck (H&N) cancer., Methods: This retrospective study included patients with H&N cancer who underwent TLE at our hospital between January 2010 and January 2021. The patients were grouped according to whether modified VPB was used or not after surgery. The primary outcome was the occurrence of PCF. The secondary outcomes were the interval from operation to PCF, the healing time of PCF, and the length of hospital stay., Results: This study included 133 patients: 82 (aged 57.93 ± 10.18 years, 80 males) in the VPB group and 51 (aged 54.98 ± 9.22 years, 51 males) in the conventional group. Patients who received the modified VPB had a significantly lower occurrence of PCF compared with those did not (9.8% vs. 33.3%, p = 0.001). In addition, the patients in the VPB group had similar interval from the operation to the PCF (p = 0.374) and healing time of PCF (p = 0.256) but a significantly shorter length of hospital stay (p < 0.001) compared with those in conventional group. Moreover, multivariable logistic regression analysis showed that, after adjusting for age, preoperative radiotherapy, postoperative hematocrit < 35%, VPB (RR = 0.165, 95% CI 0.057‒0.474, p = 0.001) was an independent protective factor for PCF., Conclusion: The modified VPB might reduce the occurrence of PCF after TLE for H&N cancers., Level of Evidence: Level 4., Competing Interests: Declaration of competing interest The authors declare no have conflicts of interest., (Copyright © 2024 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España S.L.U. All rights reserved.)

The current researches on microplastics in different water layers of reservoirs remains limited. This study aims to investigate the microplastics in different water layers within a source water reservoir. Results revealed that the abundance of microplastics ranged from 2.07 n/L to 14.28 n/L (reservoir, water) and 3 to 7.02 n/L (river, water), while varied from 350 to 714 n/kg (dw) (reservoir, sediment) and 299 to 1360 n/kg (dw) (river, sediment). The average abundance in surface, middle, and bottom water were 6.83 n/L, 6.30 n/L, and 6.91 n/L respectively. Transparent fibrous smaller than < 0.5 mm were identified as the predominant fraction with Polypropylene and Polyethylene being the prevalent polymer types. Additionally, the pollution load index, hazard index, and pollution risk index were calculated for different layers and sediments. Results showed that surface water exhibited a moderate level of risk while the sediments posed a low level of risk. Both the middle and bottom water showed elevated levels of risk due to higher concentrations of polymers with significant toxicity indices. This study presents novel findings on the distribution of microplastics in different water layers, providing crucial data support for understanding the migration patterns of microplastics in source water reservoirs and facilitating pollution prevention efforts., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

High-entropy alloy nanoparticles (HEA-NPs) exhibit favorable properties in catalytic processes, as their multi-metallic sites ensure both high intrinsic activity and atomic efficiency. However, controlled synthesis of uniform multi-metallic ensembles at the atomic level remains challenging. This study successfully loads HEA-NPs onto a nitrogen-doped carbon carrier (HEAs) and pioneers the application in peroxymonosulfate (PMS) activation to drive Fenton-like oxidation. The HEAs-PMS system achieves ultrafast pollutant removal across a wide pH range with strong resistance to real-world water interferences. Furthermore, the nonradical HEAs-PMS system selectively transforms phenolics into high-molecular-weight products via a polymerization pathway. The unique non-mineralization regime remarkably reduces PMS consumption and achieves a high electron utilization efficiency of up to 213.4%. Further DFT calculations and experimental analysis reveal that Fe and Co in HEA-NPs act as the primary catalytic sites to complex with PMS for activation, while Ni, Cu, and Pd serve as charge mediators to facilitate electron transfer. The resulting PMS* complexes on HEAs possess a high redox potential, which drives spatially separated phenol oxidation on nitrogen-doped graphene support to form phenoxyl radicals, subsequently triggering the formation of high-molecule polymeric products via polymerization reactions. This study offers engineered HEAs catalysts for water treatment with low oxidant consumption and emissions., Competing Interests: Competing interests: The authors declare no competing interest., (© 2024. Crown.)

The hypotensive side effects caused by drugs during their use have been a vexing issue. Recent studies have found that deep learning can effectively predict the biological activity of compounds by mining patterns and rules in the data, providing a potential solution for identifying drug side effects. In this study, we established a deep learning-based predictive model, utilizing a data set comprised of compounds known to either elevate or lower blood pressure. Subsequently, the trained model was used to predict the blood pressure-lowering effects of 26,000 compounds. Based on the predicted results, we randomly selected 50 molecules for validation and compared them with literature reports. The results showed that the predictions for 30 molecules were consistent with literature reports, with known antihypertensive drugs such as reserpine, guanethidine, and mecamylamine ranking at the top. We further selected 10 of these molecules and 3 related protein targets for molecular docking, and the docking results indirectly confirmed the model's accuracy. Ultimately, we discovered and validated that salaprinol significantly inhibits ACE1 activity and lowers canine blood pressure. In summary, we have established a highly accurate activity prediction model and confirmed its accuracy in predicting potential blood pressure-lowering compounds, which is expected to help patients avoid hypotensive side effects during clinical medication and also provide significant assistance in the discovery of antihypertensive drugs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Institutional review board statement: This study was approved by the Animal Ethics Commit-tee of Guilin Medical University, and the number is GLMC202103003. The study is reported in accordance with ARRIVE guidelines ( https://arriveguidelines.org )., (© 2024. The Author(s).)

Metal nanoclusters (NCs), comprising tens to hundreds of metal atoms, are condensed matter with concrete molecular structures and discrete energy levels. Compared to metal atoms and nanoparticles, metal NCs exhibit unique physicochemical properties, especially fascinating electrocatalytic activities. This review focuses on recent progress in the precise synthesis of metal NCs and their applications in electrochemical analysis of various disease biomarkers. First, we provide a brief overview of current nanotechnology-enabled electrochemical biosensors. Subsequently, we highlight the precise synthesis of metal NCs protected by various ligands such as peptides, proteins and nucleic acids. Next, we summarize the design and construction of electrochemical biosensors that utilize metal NCs as electrode materials to detect electrochemically active and inactive disease-associated biomarkers, including small biomolecules (glucose, reactive oxygen species, cholesterol, neurotransmitters and amino acids) and biomacromolecules (proteins, enzymes, and nucleic acids). Due to unique electrocatalytic properties, high specific surface areas, and atomically modulated structures, metal NCs promote electron exchange or act as a redox medium in these electrochemical sensing platforms. Finally, we conclude with present challenges and propose future research directions, with the aim to enhance the specificity, sensitivity, and durability of customized metal NC-based electrochemical biosensors for precise disease diagnostics.

Active oxygen species (OH*/O*) derived from water electrolysis are essential for the electrooxidation of organic compounds into high-value chemicals, which can determine activity and selectivity, whereas the relationship between them remains unclear. Herein, using glycerol (GLY) electrooxidation as a model reaction, we systematically investigated the relationship between GLY oxidation activity and the formation energy of OH* (ΔG OH* ). We first identified that OH* on Au demonstrates the highest activity for GLY electrooxidation among various pure metals, based on experiments and density functional theory, and revealed that ΔG OH* on Au-based alloys is influenced by the metallic composition of OH* coordination sites. Moreover, we observed a linear correlation between the adsorption energy of GLY (E ads ) and the d-band center of Au-based alloys. Comprehensive microkinetic analysis further reveals a volcano relationship between GLY oxidation activity, the ΔG OH* and the adsorption free energy of GLY (ΔG ads ). Notably, Au 3 Pd and Au 3 Ag alloys, positioned near the peak of the volcano plot, show excellent activity, attributed to their moderate ΔG OH* and ΔG ads , striking a balance that is neither too high nor too low. This research provides theoretical insights into modulating active oxygen species from water electrolysis to enhance organic electrooxidation reactions., (© 2024 Wiley-VCH GmbH.)

Strong electron-phonon coupling can hinder exciton transport and induce undesirable non-radiative recombination, resulting in a shortened exciton diffusion distance and constrained exciton dissociation in organic solar cells (OSCs). Therefore, suppressing electron-phonon coupling is crucially important for achieveing high-performance OSCs. Here, we employ the solid additive to regulating electron-phonon coupling in OSCs. The planar configuration of SA1 confers a significant advantage in suppressing lattice vibrations in the active layers, reducing the scattering of excitons by phonons. Consequently, a slow but sustained hole transfer process is identified in the SA1-assisted film, indicating an enhancement in hole transfer efficiency. Prolonged exciton diffusion length and exciton lifetime are achieved in the blend film processed with SA1, attributed to a low non-radiative recombination rate and low energetic disorder for charge carrier transport. As a result, a high efficiency of 20 % was achieved for ternary device with a remarkable short-circuit current. This work highlights the important role of suppressing electron-phonon coupling in improving the photovoltaic performance of OSCs., (© 2024 Wiley-VCH GmbH.)

Background: Disrupted hippocampal functions and progressive neuronal loss represent significant challenges in the treatment of Alzheimer's disease (AD). How to achieve the improvement of pathological progression and effective neural regeneration to ameliorate the intracerebral dysfunctional environment and cognitive impairment is the goal of the current AD therapy. Methods: We examined the therapeutic potential of clinical-grade human derived dental pulp stem cells (hDPSCs) in cognitive function and neuropathology in AD. Specifically, we investigated the effect of neural crest-specific derived hDPSCs on endogenous neural regeneration and long-term efficacy following a single transplantation in the triple-transgenic mouse model (3xTg-AD). Results: Our research demonstrated that a single administration of clinical-grade hDPSCs yielded dramatic short-term therapeutic benefits (5 weeks) and sustained partial efficacy (6 months) with respect to improving cognitive impairment and delaying typical pathological progression in 3xTg-AD mice. Intriguingly, exogenous hDPSCs were robustly self-differentiated into newborn functional neurons in the hippocampus of 3xTg-AD mice. The foremost evidence is provided that hDPSCs promote endogenic neural regeneration by enhancing the activation of the Wnt/β-catenin pathway, which may contribute to stabilizing the hippocampal neural network to reverse memory deficits. Conclusion: These findings highlight the multifunctional potential of hDPSCs in AD treatment, which enhances cognition through alleviating neuropathology and providing neural regenerative driving force. Understanding these multiplicity effects is critical to advancing the clinical translation of stem cell-based therapies for AD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: Contrast-enhanced digital breast tomosynthesis (CEDBT) highlights breast tumors with neo-angiogenesis. A recently proposed CEDBT system with a dual-layer (DL) flat-panel detector enables simultaneous acquisition of high-energy (HE) and low-energy (LE) projection images with a single exposure, which reduces acquisition time and eliminates motion artifacts. However, x-ray scatter degrades image quality and lesion detectability. We propose a practical method for accurate and robust scatter correction (SC) for DL-CEDBT., Approach: The proposed hybrid SC method combines the advantages of a two-kernel iterative convolution method and an empirical interpolation strategy, which accounts for the reduced scatter from the peripheral breast region due to thickness roll-off and the scatter contribution from the region outside the breast. Scatter point spread functions were generated using Monte Carlo simulations with different breast glandular fractions, compressed thicknesses, and projection angles. Projection images and ground truth scatter maps of anthropomorphic digital breast phantoms were simulated to evaluate the performance of the proposed SC method and three other kernel- and interpolation-based methods. The mean absolute relative error (MARE) between scatter estimates and ground truth was used as the metric for SC accuracy., Results: DL-CEDBT shows scatter characteristics different from dual-shot, primarily due to the two energy peaks of the incident spectrum and the structure of the DL detector. Compared with the other methods investigated, the proposed hybrid SC method showed superior accuracy and robustness, with MARE of ∼ 3.1 % for all LE and HE projection images of different phantoms in both cranial-caudal and mediolateral-oblique views. After SC, cupping artifacts in the dual-energy image were removed, and the signal difference-to-noise ratio was improved by 82.0% for 8 mm iodine objects., Conclusions: A practical SC method was developed, which provided accurate and robust scatter estimates to improve image quality and lesion detectability for DL-CEDBT., (© 2024 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Background: CareHPV is a highly promising screening HPV assay that functions as a simplified and rapid point-of-care test, making it particularly well-suited for low-resource areas. It exhibits high sensitivity for detecting cervical precancerous lesions in cross-sectional study design. However, there is still limited evidence on the long-term protection of careHPV testing in the practical setting., Methods: A government-led cervical cancer screening program was implemented in Ordos City, China, specifically targeting female residents aged 35-64 years since 2016. CareHPV specimens were collected and visual inspection with acetic acid and Lugol iodine (VIA/VILI) was performed in the baseline screening. Women who were HPV-positive or VIA/VILI-suspected cancer at baseline were invited for a one-year follow-up screening. At the same time, those who were HPV-negative were scheduled for a 5-year rescreening. Women diagnosed with cervical intra-epithelial neoplasia grade 2 or worse (CIN2+) would be referred to clinical treatment as per the clinical guidelines. The current study includes participants who had valid baseline screening results and attended follow-ups with valid careHPV results conducted between January 2017 and December 2021, aiming to assess the long-term risk stratification for careHPV. Cumulative incidence rate (CIRs) and hazard ratio (HRs) for CIN2+ were calculated, using survival analysis., Results: Among the 179,306 women enrolled in the baseline screening between 2016 and 2020, 12.60 % tested positive for careHPV, with 657 cases of CIN2+ identified. The final analysis included 18,562 women in our study, of whom 58.54 % were careHPV-positive at baseline. The final analysis consisted of 17,905 women who underwent screening between 2016 and 2020 and attended follow-ups from 2017 to 2021, with valid HPV results, and 657 women who identified as CIN2+ at the baseline. The 5-year CIRs were 0.003 and 0.101 among women who tested negative and positive for baseline careHPV, respectively. The 5-year CIRs for developing CIN2+ during follow-ups were 0.009, 0.009, and 0.11 for the groups of women who transitioned from careHPV-negative to positive (831, 4.64 %), careHPV-positive to negative (6688, 37.35 %), and maintained a stable positive careHPV status (3535, 19.74 %), respectively., Conclusions: Our findings support the long-term safety and protection of careHPV testing in 5-year follow-ups of screening programs. CareHPV represents a viable option for regions with limited healthcare resources., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was supported by the Bill and Melinda Gates Foundation (INV-031449), the CAMS Innovation Fund for Medical Sciences (CIFMS 2021-I2M-1-004), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-D-003)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Using deep eutectic solvents (DES) to pretreat wheat straw (WS) and extract lignin-containing nanocellulose (LCNC). Acrylic acid/choline chloride (AA/ChCl) polymerizable deep eutectic solvents (PDES) were used as the primary polymerization network, combined with polyvinyl alcohol (PVA). Lignocellulose nanocrystals (LCNC) oxidized by sodium periodate were prepared as dialdehyde-based nanocellulose (DCNC) to serve as the crosslinking agent. Under UV light, a dual-network Polyacrylic acid-Choline chloride/Polyvinyl alcohol/dialdehyde-based nanocellulose ( (PAA-ChCl)/PVA/DCNC) ionic gel was polymerized and prepared, and make it into a sensor. The gel had the advantages of porous structure, good mechanical properties, conductive properties, fast electrical recovery and self-healing. The results revealed the relative resistance of the sensor also changed with the change of the human joint, and also responded multiple times for the continuous same cyclic action of the joint, the sensor could also distinguished different fast and slow movements. This showed the sensor could detect human movement in real time, making it promising for applications in medical devices, electronic skin and other fields, but in real time, the small movement ability of the human body's throat swallowing and bending of the fingers needs to be improved., 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.)

This study aimed to investigate the structural characterization, conformational properties, and hepatoprotectiveactivity of acidic polysaccharide (DNLPS-3) from Dendrobium nobile flower. DNLPS-3 with molecular weights of 15.65 KDa was composed of Fuc: Rha: Ara: Gal: Glc: Xyl: GalA: GlcA in a molar ratio of 0.26%: 2.38%: 4.47%: 3.55%: 0.43%: 17.84%: 69.80%: 1.26%. Structural analysis with methylation indicated that DNLPS-3 mainly contained T-Ara(f), T-Xyl(p), T-Gal(p)A, 3-Gal(p)A, 4-Gal(p)A, 3,4-Gal(p)A, 3,4-Glc(p), 2,4-Gal(p)A, 2,3,4-Gal(p), 4,6-Gal(p), 3,4,6-Gal(p). NMR results show that DNLPS-3 may be a pectin polysaccharide with →4)-α-Gal(p)A-(→main chain. In vitro experiments showed that DNLPS-3 exhibited significant hepatoprotective effects. The effect was achieved by reducing the activities of ALT and AST, suppressing the production of LDH and MDA, and enhancing the anti-oxidant activities of SOD and GSH, and the specific mechanism of its hepatoprotective effect is that DNLPS-3 up-regulates Nrf2/HO-1 pathway protein expression., Competing Interests: Declaration of competing interest This manuscript has not been published previously, in whole or in part, and is not under consideration for publication in any other journal. All authors have reviewed and approved the submission, and there are no conflicts of interest related to its publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Increased levels of p-aminobenzoic acid in aquatic environments, primarily utilized as UV filter in sunscreens, poses a serious threat to human and ecosystem health, while there is a dearth of exhaustive researches pertaining to the efficient and cost-effective elimination of p-aminobenzoic acid. Herein, a Ti/SnO 2 -Sb/CNT-α-PbO 2 /CNT-Ce-β-PbO 2 , referred to Ti/CNT/CNT-Ce-PbO 2 electrode was constructed by incorporating CNTs into the middle layer of PbO 2 electrode, and simultaneously doping CNTs and Ce in the active layer. A series of tests signify that the target electrode is successfully fabricated, which exhibits higher particle density and smaller particle size, as well as exceptional degradation performance for p-aminobenzoic acid with a degradation rate of 99.7% within 30 min coupling with peroxymonosulfate activation. The optimal degradation performance was observed at a PMS dosage of 0.07 g, Na 2 SO 4 concentration of 0.05 mol L -1 , current density of 120 mA cm -2 , and initial pH value of 6.94. Capture experiments, electron spin resonance test, liquid chromatography-mass spectrometry analysis, toxicity assessment and theoretical calculation were performed to clarify the main activate radicals, degradation pathways and intermediate toxicity. This study provides a new anode material, and conducted the first exploration of electrocatalysis integrating peroxymonosulfate activation for degradation p-aminobenzoic acid., 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.)

Exploring novel materials with intrinsic self-trapped excitons (STEs) is crucial for advancing optoelectronic technologies. In this study, 2D 3R-phase ZnIn 2 S 4 , featuring broken inversion symmetry , is introduced to investigate intrinsic STEs. This material exhibits a broadband photoluminescence (PL) emission with a full width at half maximum of 164 nm and a large Stokes shift of ≈0.6 eV, which arises from the distortion of [ZnS 4 ] 6- tetrahedral unit induced by the symmetry breaking and strong electron-phonon coupling. The photophysical properties of the STEs exhibit a high Huang-Rhys factor (15.0), rapid STEs formation time (166 fs), and extended STEs lifetime (1039 ps), as demonstrated by experimental evidence from temperature-dependent PL, Raman spectroscopy, and ultrafast absorption spectroscopy. Additionally, STE-induced photoconductive effect is elucidated, indicating that intrinsic STEs in 3R-ZnIn 2 S 4 can provide a synergistic effect that enhances absorption capacity, localization, and lifetime by capturing the self-trapped hole state. Consequently, the 2D 3R-ZnIn 2 S 4 photodetector exhibits remarkable broad-spectrum photosensitivity, including a photo-switching ratio of 11286, response times of less than 0.6 ms, responsivity of 15.2 A W -1 , detectivity of 1.02 × 10¹¹ Jones, and external quantum efficiency of 5032% under 375 nm light. These findings provide new ideas for exploring materials with intrinsic STEs to achieve novel high-performance photodetector applications., (© 2024 Wiley‐VCH GmbH.)

The early and precise diagnosis of asthma significantly impacts the long-term health outcomes of pediatric patients. The sensitivity and specificity of current biomarkers, however, are frequently limited. Our study aimed to evaluate the clinical significance of nuclear factor of activated T cells, cytoplasmic 3 (NFATc3), in pediatric bronchial asthma, focusing on its diagnostic and prognostic value for disease severity and recurrence. This observational, prospective case-control study involved 200 pediatric patients with bronchial asthma and 200 age- and sex-matched healthy controls, from January 2020 to January 2023. Follow-up varied from 1 to 3 years. We measured levels of NFATc3 and inflammatory cytokines interleukin-1β (IL-1β), IL-6, and TNF-α via enzyme-linked immunosorbent assay. NFATc3 and IL-1β levels at enrollment were markedly higher in patients with acute exacerbations and those classified as severe, compared with their less severe counterparts. Throughout the study, NFATc3, IL-1β, and IL-6 levels significantly increased in severe or acutely exacerbating cases. The diagnostic value of NFATc3 was assessed through receiver operating characteristic curve analysis, which showed its potential in diagnosing bronchial asthma and identifying severe cases. Spearman's analysis confirmed positive associations between peak NFATc3 and cytokine levels. Importantly, disease type, NFATc3 values at enrollment, as well as peak IL-6 levels were identified as independent risk factors for severe bronchial asthma. Elevated NFATc3 is linked with the severity of pediatric bronchial asthma and serves as a potential biomarker for diagnosis and severity prediction, emphasizing its role in guiding treatment strategies.

Fructose 1,6-diphosphatase 1 (FBP1) is an enzyme involved in gluconeogenesis and glycolysis inhibition. Dendritic cells (DCs) are antigen-presenting cells, and antigens presented to T cells activate the immune response. FBP1 inhibits the development of several tumors, and high FBP1 expression inhibits the proliferation, migration, and invasion of lung cancer cells. However, the mechanism through which FBP1 mediates the tumor immune microenvironment is unclear. This study mainly analyzed the role of FBP1 in regulating the function of DCs through metabolic reprogramming and immune microenvironment using in vitro and in vivo experiments. The positive association of FBP1 with DCs was found by bioinformatic analysis. The in vitro experiments revealed that the extracellular acidification rate and lactate level were lower in the FBP1 overexpression cells than in the control cells and that the lower lactate level reduced the inhibition of DC function. In addition, high FBP1 expression promoted the secretion of IL33 by activating the cGAS/STING/NF-κB/IL33 pathway, which was identified and verified via high-throughput sequencing and in vitro experiments. FBP1 activated the cGAS/STING pathway by increasing the degree of DNA damage, as revealed by the level of γH2AX and comet assay. IL33 enhanced the expression of the DC costimulatory molecules CD86 and HLA-DR as well as that of the functional factor IL-1β. The results demonstrated that FBP1 promoted the activation and maturation of DCs by inhibiting glycolysis and promoting the secretion of IL33 as well as by further activating the function of CD8 + T cells. Finally, the humanized immune system mouse models confirmed the above role of FBP1. Thus, FBP1 may serve as a new target to cure lung adenocarcinoma, and IL33 may improve the efficiency of immune therapy in lung adenocarcinoma., Competing Interests: Declaration of competing interest All authors stated that there is no conflict of interest in this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Aberrant chondrocyte metabolism significantly contributes to cartilage degeneration and osteoarthritis (OA) genesis. However, the mechanisms driving the metabolic shift in OA chondrocytes remain unclear. Interestingly, carbonic anhydrase 2 (CA2) is implicated in metabolic regulation, and its expression dramatically increases in OA chondrocytes, but its exact role and mechanism are poorly understood. This study investigates the mechanistic role of CA2 in chondrocyte metabolic homeostasis under hypoxic and inflammatory conditions., Methods: RNA-seq was performed on CA2-deficient C28/I2 cells to identify pathways affected by the loss of CA2 function. We examined CA2's impact on chondrocyte metabolism, anabolism, and catabolism using C28/I2 cells and primary chondrocytes under normoxia and hypoxia and in a model of inflammatory OA., Results: RNA-seq revealed enrichment of glycolysis, apoptosis, and TNF signaling pathways in CA2-deficient cells. Under hypoxia, CA2 expression increased 10-fold in a HIF-1α-independent manner. Knockdown of CA2 reduced extracellular lactate production, increased ADP/ATP ratio, impaired glycolysis, reduced glycolytic capacity, and lowered expression of glycolysis rate-limiting enzymes but did not disrupt pH i and ROS production. CA2 deficiency altered chondrocyte anabolic and catabolic equilibrium by affecting PI3K/AKT and RELA/p65 signaling. CA2-deficient chondrocytes displayed impeded migration, suppressed proliferation, and cell cycle arrest at the G0/G1 phase. Forced expression of CA2 stabilized chondrocyte metabolism and restored cellular functions., Conclusions: Our research uncovered a hitherto unknown mechanistic role for CA2 in regulating chondrocyte energy metabolism and inflammation, underscoring its potential as a critical mediator in OA pathogenesis. Further research using a murine model of experimental OA is warranted to capture the functional implications of CA2., Competing Interests: Declaration of competing interest All authors declare that they have no known financial conflicts of interest or personal relationships that could have influenced the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The deformability and uptake capability of cells are critical indicators of their biomechanical properties and functional behaviors, particularly in tumor heterogeneity and cancer research. Here, we introduce a microfluidic flow cytometry platform integrated with a laterally adjustable squeezing structure for the characterization of bladder tumor cells (including 5637 and EJ cell lines) and uroepithelial cells (SV-HUC-1 cell line). The deformability of these cell types under varying channel width conditions was clearly assessed using this platform. The results demonstrated that tumor cells exhibited higher deformability compared to uroepithelial cells, with the EJ cell line exhibiting the greatest difference. Furthermore, the relationship between the malignancy, deformability, and uptake capability of bladder cells was explored through co-cultivation experiments with 2 μm particles. As the malignancy increased, the cells became more deformable and exhibited stronger phagocytic capability with particles. Subsequently, the heterogeneity of tumor cells was investigated by analyzing the deformability of phagocytic and non-phagocytic subpopulations within EJ cells. The developed microfluidic platform offers a promising high-throughput method to assess the biomechanical and phagocytic characteristics of cells, providing valuable insights into tumor cell biology, and potentially improving clinical status of urinary cytology examinations for bladder cancer., 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.)

Conventional heterogeneous Fenton-like systems employing different peroxides have been developed for water/wastewater remediation. However, a large population of peroxides consumed during various Fenton-like systems with low utilization efficiency and associated secondary contamination have become the bottlenecks for their actual applications. Recent strategies for lowering the peroxide consumptions to develop economic Fenton-like systems are primarily devoted to the effective radical generation and subsequent high-efficiency radical utilization through catalysts/systems engineering, leveraging emerging nonradical oxidation pathways with higher selectivity and longer life of the reactive intermediate, as well as reactor designs for promoting the mass transfer and peroxides decomposition to improve the yield of radicals/nonradicals. However, a comparative review summarizing the mechanisms and pathways of these strategies has not yet been published. In this review, we endeavor to showcase the designated systems achieving the reduction of peroxides while ensuring high catalytic activity from the perspective of the above strategic mechanisms. An in-depth understanding of these aspects will help elucidate the key mechanisms for achieving economic peroxide consumption. Finally, the existing problems of these strategies are put forward, and new ideas and research directions for lowering peroxide consumption are proposed to promote the application of various Fenton-like systems in actual wastewater purification., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)