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Abstract Lung cancer leads in causing cancer-related mortality worldwide, continually posing a significant threat to human health. Current imaging diagnostic techniques, while offering non-invasive detection, suffer from issues such as insufficient sensitivity and the risks associated with radiation exposure. Pathological diagnosis, the gold standard for confirmation, also faces challenges like invasiveness and high costs. In treatment, surgery, radiotherapy, and chemotherapy are the main modalities, each encountering challenges related to precision, environmental adaptability, and side effects. Nanotechnology’s advancement provides new solutions for the diagnosis and treatment of lung cancer, promising to enhance diagnostic accuracy and reduce side effects during treatment. This article introduces the main types of nanomaterials used in the field of lung cancer, offering a comprehensive overview of current research on the application of nanotechnology in early screening, diagnosis, treatment, and monitoring of lung cancer, and summarizing ongoing clinical research findings.

Abstract Observational studies have suggested links between standing height, BMI, body fat percentage, and inguinal hernia risk, but with inconsistent results. We conducted Mendelian randomization (MR) method to investigate their causal relationships. Independent SNPs associated with standing height, BMI, and body fat percentage were extracted from GWAS data as instrumental variables (IVs). Two-sample MR initially explored causal relationships between these factors and inguinal hernia risk. Multivariable Mendelian randomization (MVMR) assessed the direct causal effects of exposures on inguinal hernia. Positive findings from the MVMR analysis were independently validated. The inverse-variance weighted Methods (IVW), weighted median(WM), and MR-Egger were used for the MR estimates. Sensitivity analyses were used to examine the stability and reliability of the results. Two-sample MR analysis revealed a suggestive causal association between height and inguinal hernia (OR = 1.091, 95% CI = 1.003–1.186, P = 0.042). BMI (OR = 0.846, 95% CI = 0.774–0.924, P

Wholly defined ex vivo expansion conditions for biliary tree stem cell (BTSC) organoids were established, consisting of a defined proliferative medium (DPM) used in combination with soft hyaluronan hydrogels. The DPM consisted of commercially available Kubota's Medium (KM), to which a set of small molecules, particular paracrine signals, and heparan sulfate (HS) were added. The small molecules used were DNA methyltransferase inhibitor (RG108), TGF- β Type I receptor inhibitor (A83-01), adenylate cyclase activator (Forskolin), and L-type Ca2+ channel agonist (Bay K8644). A key paracrine signal proved to be R-spondin 1 (RSPO1), a secreted protein that activates Wnts. Soluble hyaluronans, 0.05 % sodium hyaluronate, were used with DPM to expand monolayer cultures. Expansion of organoids was achieved by using DPM in combination with embedding organoids in Matrigel that was replaced with a defined thiol-hyaluronan triggered with PEGDA to form a hydrogel with a rheology [G*] of less than 100 Pa. The combination is called the BTSC-Expansion-Glycogel-System (BEX-gel system) for expanding BTSCs as a monolayer or as organoids. The BTSC organoids were expanded more than 3000-fold ex vivo in the BEX-gel system within 70 days while maintaining phenotypic traits indicative of stem/progenitors. Stem-cell-patch grafting of expanded BTSC organoids was performed on the livers of Fah-/- mice with tyrosinemia and resulted in the rescue of the mice and restoration of their normal liver functions. The BEX-gel system for BTSC organoid expansion provides a strategy to generate sufficient numbers of organoids for the therapeutic treatments of liver diseases.

Abstract MAX phases, a unique class of layered ternary compounds, along with their two-dimensional derivatives, MXenes, have drawn considerable attention in many fields. Notably, their one-dimensional (1D) counterpart exhibits more distinct properties and enhanced assemblability for broader applications. We propose a conformal synthetic route for 1D-MAX phases fabrication by integrating additional atoms into nanofibers template within a molten salt environment, enabling in-situ crystalline transformation. Several 1D-MAX phases are successfully synthesized on a large scale. Demonstrating its potential, a copper-based layer-by-layer composites containing 1% by volume of 1D-Ti2AlC reinforced phase achieves an impressive 98 IACS% conductivity and a friction coefficient of 0.08, while maintaining mechanical properties comparable to other Cu-MAX phase composites, making it suitable for advanced industrial areas. This strategy may promise opportunities for the fabrication of various 1D-MAX phases.

Abstract Background Postpartum depression (PPD) is widely recognized as the most prevalent mental health crisis following childbirth and has been linked to sleep disturbances. However, the potential causal relationships between various sleep traits and PPD remain unclear. This study employs a bidirectional two-sample Mendelian randomization (MR) approach to investigate these associations. Methods The inverse-variance-weighted method was used to evaluate the causally linked sleep traits on postpartum depression. The weighted median, weighted mode, and MR-Egger were used to estimate the robustness of the inverse-variance-weighted method. The leave-one-out method estimated the sensitivity of the result. Cochran’s Q method was used for the heterogeneous test. The MR-Egger intercept and MR-PRESSO methods detected the horizontal pleiotropy. Results We examined the genetic causal relationships between nine sleep traits and postpartum depression. Sleep apnea syndrome (OR: 1.122; 95%CI: 1.063–1.185; p = 0.000), sleeplessness/insomnia (OR: 1.465; 95%CI: 1.104–1.943; p = 0.008), and frequency of tiredness/lethargy in last 2 weeks (OR: 1.725; 95%CI: 1.345–2.213; p = 0.000) genetically predicted the increased risk of postpartum depression. The reverse Mendelian randomization analysis showed PPD caused sleeplessness/insomnia (β: 0.006; 95%CI: 0.001–0.010; p = 0.016) and frequency of tiredness/lethargy in last 2 weeks (β: 0.007; 95%CI: 0.002–0.011; p = 0.004). The remaining six sleep traits showed no significant association with PPD. There was no heterogeneity or horizontal pleiotropy. Conclusions Genetic evidence reveals causal relationships between specific sleep traits and PPD, including sleep apnea syndrome, sleeplessness/insomnia, and tiredness. Whether certain sleep health indicators suggest a risk of postpartum depression or sleep issues that are caused by PPD, both may offer insights into the prevention and treatment of PPD.

Abstract The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The primary advantage of using the “dose and LET” physical system is its relative simplicity, especially for presenting and recording results. Inclusion of additional information such as the energy spectrum of charged particles renders this approach adequate to describe the biological effects of large dose levels from homogeneous sources. The primary disadvantage of this system is that it does not provide a unique description of the stochastic nature of radiation interactions. We and others have used dose-averaged LET (LET d ) as a correlative physical quantity to the relative biological effectiveness (RBE) of proton beams. This approach is based on established experimental findings that proton RBE increases with LET d . However, this approach might not be applicable to intensity-modulated proton therapy or other applications in which the proton energy spectrum is highly heterogeneous. In the current study, we irradiated cancer cells with scanning proton beams with identical LET d (3.4 keV/µm) but arising from two different proton energy/LET spectra (a narrow spectrum in group 1 and a widespread heterogeneous spectrum in group 2). Clonogenic survival after irradiation revealed significant differences in RBE at any cell surviving fraction: e.g., at a surviving fraction of 0.1, the RBE was 0.97 ± 0.03 in group 1 and 1.16 ± 0.04 in group 2 (p≤0.01), validating our hypothesis that LET d alone may not adequately indicate proton RBE. Further analysis showed that microdosimetric spectrum (the probability density function of the stochastic physical quantity lineal energy y) was helpful for interpreting observed differences in biological effects. However, more accurate use of microdosimetric spectrum to quantify RBE requires a cell line–specific mechanistic model.

Abstract Background To assess the capability of multimodal apparent diffusion (MAD) weighted magnetic resonance imaging (MRI) to distinguish between malignant and benign breast lesions, and to predict Ki-67 expression level in breast cancer. Methods This retrospective study was conducted with 93 patients who had postoperative pathology-confirmed breast cancer or benign breast lesions. MAD images were acquired using a 3.0 T MRI scanner with 16 b values. The MAD parameters, as flow (fF, DF), unimpeded (fluid) (fUI), hindered (fH, DH, and αH), and restricted (fR, DR), were calculated. The differences of the parameters were compared by Mann–Whitney U test between the benign/malignant lesions and high/low Ki-67 expression level. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC). Results The fR in the malignant lesions was significantly higher than in the benign lesions (P = 0.001), whereas the fUI and DH were found to be significantly lower (P = 0.007 and P

Abstract A large amount of arsenic-containing wastewater discharged by the non-ferrous metal industry will cause serious environmental problems if it is not properly treated. Pyrolysis char of waste tire is a kind of solid waste. Since the surface properties of tire derived char (TC) are affected by tar/ash adhesion during pyrolysis, it is necessary to modify TC to treat wastewater containing As(V) effectively as an adsorbent. At present, most studies on the modification of TC are prepared into activated carbon by high temperature activation in N2 atmosphere. In this study, TC was modified at room temperature and air atmosphere, and Fe(OH)3-TCNaOH adsorbent with particle size of 61–75 μm was obtained under the premise of the removal rate of As(V) and the settling performance of the adsorbent. When the initial concentration of As(V) was 5 mg/L, the removal rate of As(V) by Fe(OH)3-TCNaOH with a particle size of 61–75 μm could reach 90% within 30 min under a wide pH range (3–9). The adsorption of As(V) by Fe(OH)3-TCNaOH was most affected by the coexistence of PO4 3-, which resulted in the removal rate of As(V) decreased by about 20%. The adsorption mechanism shows that the significant increase in the number of 3–5 nm mesoporous pores of Fe(OH)3-TCNaOH and the formation of H bonds are beneficial to the adsorption of Fe(OH)3-TCNaOH to As(V), and improve the stability of Fe-As complex.

Abstract Genetic biocontrol technologies present promising and eco-friendly strategies for the management of pest and insect-transmitted diseases. Although considerable advancements achieve in gene drive applications targeting mosquitoes, endeavors to combat agricultural pests have been somewhat restricted. Here, we identify that the testis-specific serine/threonine kinases (TSSKs) family is uniquely expressed in the testes of Cydia pomonella, a prominent global invasive species. We further generated male moths with disrupted the expression of TSSKs and those with TSSKs disrupted using RNA interference and CRISPR/Cas9 genetic editing techniques, resulting in significant disruptions in spermiogenesis, decreased sperm motility, and hindered development of eggs. Further explorations into the underlying post-transcriptional regulatory mechanisms reveales the involvement of lnc117962 as a competing endogenous RNA (ceRNA) for miR-3960, thereby regulating TSSKs. Notably, orchard trials demonstrates that the release of male strains can effectively suppress population growth. Our findings indicate that targeting TSSKs could serve as a feasible avenue for managing C. pomonella populations, offering significant insights and potential strategies for controlling invasive pests through genetic sterile insect technique (gSIT) technology.

Abstract Accumulating evidence has shown that some hallucinogens, such as LSD, have fast and persistent effects on anxiety and depression. According to a proposed mechanism, LSD activates the TrkB and HTR2A signaling pathways, which enhance the density of neuronal dendritic spines and synaptic function, and thus promote brain function. Moreover, TrkB signaling is also known to be crucial for neural stem cell (NSC)-mediated neuroregeneration to repair dysfunctional neurons. However, the impact of LSD on neural stem cells remains to be elucidated. In this study, we observed that LSD and BDNF activated the TrkB pathway in human NSCs similarly to neurons. However, unlike BDNF, LSD did not promote NSC proliferation. These results suggest that LSD may activate an alternative mechanism to counteract the effects of BDNF-TrkB signaling on NSCs. Our findings shed light on the previously unrecognized cell type-specificity of LSD. This could be crucial for deepening our understanding of the mechanisms underlying the effects of LSD.

Abstract With the development of industry and agriculture, eutrophication caused by increasing amounts of phosphorus in the environment has attracted people's attention. On the other hand, copper tailings (CT) is a kind of solid waste with large quantity, large area, and easy to cause groundwater and soil pollution. CT is also a potential resource because of its large specific surface area. CT is intended to be used as an adsorbent for removal phosphate in water, but trace heavy metals and a small amount of phosphate in CT may bring negative effects. Calcium hydroxide (Ca(OH)2) was used to modify CT (CCT), hoping to fix the heavy metals and phosphate in CT at the same time. It was found that the removal capacity of CCT was significantly higher than that of CT. The process of phosphate removal by CCT involves electrostatic sorption and surface precipitation, and there is a synergistic effect between CT and Ca(OH)2. The phosphate removal rate of CCT-0.4 increased with the increase of pH value under alkaline conditions. The XRD patterns of phosphate sorption by CCT mean that Ca3(PO4)2, Ca5(PO4)3(OH) and AlPO4 exist in CCT after phosphate removal, indicating that surface precipitation occurs during the removal process. In summary, the removal mechanism of phosphate by CCT is mainly electrostatic attraction and surface precipitation.

Abstract It is a consensus in the international manned space field that factors such as microgravity during the space flight can cause anxiety, depression and other important brain function abnormalities in astronauts. However, the neural mechanism at the molecular level is still unclear. Due to the limitations of research conditions, studies of biological changes in the primate brain have been comparatively few. We took advantage of -6° head-down bed rest (HDBR), one of the most implemented space analogues on the ground, to investigate the effects of simulated weightlessness on non-human primate brain metabolites. The Rhesus Macaque monkeys in the experiment were divided into three groups: the control group, the 42-day simulated weightlessness group with HDBR, and the recovery group, which had 28 days of free activity in the home cage after the HDBR. Liquid chromatography-mass spectrometry (LC-MS) was used to perform metabolomics analysis on specific brain areas of the monkeys under three experimental conditions. Our results show that simulated weightlessness can cause neurotransmitter imbalances, the amino acid and energy metabolism disorders, and hormone disturbances. But these metabolomics changes are reversible after recovery. Our study suggests that long-term brain damage in space flight might be reversible at the metabolic level. This lays a technical foundation for ensuring brain health and enhancing the brain function in future space studies.

The effects of Aronia melanocarpa (AM) dietary supplementation on production performance, meat and egg quality, yolk volatile substances and antioxidant capacity of laying hens. A total of 480 Roman brown laying hens aged 25 wks were randomly divided into control, LAM, MAM and HAM groups and fed 0%, 1%, 4% and 7% AM, respectively. The results showed that AM dietary supplementation significantly increased the eggshell strength, significantly reduced 24 h dripping loss of breast and thigh muscles, and increased pH and 48 h dripping loss of breast and thigh muscles. Cooking loss was significantly lower only in the HAM group for breast muscle. The MAM group was able to significantly increase albumen height and Haugh units. Esters gradually decreased with the increase in AM content, and the addition of AM led to a decrease in alcoholic compounds but increased the contents of alkenes, alkanes, ketones, and acids. The dietary AM supplementation significantly reduces the MDA content of serum, liver, ovary, chest muscle, thigh muscle and yolk and increases the activities of GSH-Px, T-SOD and T-AOC. In summary, dietary AM supplementation could improve antioxidant capacity and expression of related genes, thereby improving meat and egg quality.

Abstract The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e–h+) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (1O2) via e–h+ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (•OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors. Graphical abstract

Abstract Background The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear. Methods The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers. Results The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value 1.2 or

Abstract The aftermath of a natural disaster leaves victims trapped in rubble which is challenging to detect by smart drones due to the victims in low visibility under the adverse disaster environments and victims in various sizes. To overcome the above challenges, a transformer fusion-based scale-aware attention network (TFSANet) is proposed to overcome adverse environmental impacts in disaster areas by robustly integrating the latent interactions between RGB and thermal images and to address the problem of various-sized victim detection. Firstly, a transformer fusion model is developed to incorporate a two-stream backbone network to effectively fuse the complementary characteristics between RGB and thermal images. This aims to solve the problem that the victims cannot be seen clearly due to the adverse disaster area, such as smog and heavy rain. In addition, a scale-aware attention mechanism is designed to be embedded into the head network to adaptively adjust the size of receptive fields aiming to capture victims with different scales. Extensive experiments on two challenging datasets indicate that our TFSANet achieves superior results. The proposed method achieves 86.56% average precision (AP) on the National Institute of Informatics—Chiba University (NII-CU) multispectral aerial person detection dataset, outperforming the state-of-the-art approach by 4.38%. On the drone-captured RGBT person detection (RGBTDronePerson) dataset, the proposed method significantly improves the AP of the state-of-the-art approach by 4.33%.

Abstract Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.

Abstract Thyroid surgery often results in ischemia–reperfusion injury (IRI) to the parathyroid glands, yet the mechanisms underlying this and how to ameliorate IRI remain incompletely explored. Our study identifies a polyphenolic herbal extract—gallic acid (GA)—with antioxidative properties against IRI. Through flow cytometry and CCK8 assays, we investigate the protective effects of GA pretreatment on a parathyroid IRI model and decode its potential mechanisms via RNA-seq and bioinformatics analysis. Results reveal increased apoptosis, pronounced G1 phase arrest, and significantly reduced cell proliferation in the hypoxia/reoxygenation group compared to the hypoxia group, which GA pretreatment mitigates. RNA-seq and bioinformatics analysis indicate GA’s modulation of various signaling pathways, including IL-17, AMPK, MAPK, transient receptor potential channels, cAMP, and Rap1. In summary, GA pretreatment demonstrates potential in protecting parathyroid cells from IRI by influencing various genes and signaling pathways. These findings offer a promising therapeutic strategy for hypoparathyroidism treatment.

IntroductionAccurate and rapid diagnosis is crucial for the effective treatment of parasitosis. Traditional etiological methods, especially microscopic examination, are time-consuming, labor-intensive, and prone to false or missed detections. In response to these challenges, this study explores the use of artificial intelligence (AI) for the detection and classification of human parasite eggs through the YOLOv4 deep learning object detection algorithm.MethodsEggs from species such as Ascaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), Enterobius vermicularis (E. vermicularis), Ancylostoma duodenale (A. duodenale), Schistosoma japonicum (S. japonicum), Paragonimus westermani (P. westermani), Fasciolopsis buski (F. buski), Clonorchis sinensis (C. sinensis), and Taenia spp. (T. spp.) were collected and prepared as both single species and mixed egg smears. These samples were photographed under a light microscope and analyzed using the YOLO (You Only Look Once) v4 model.ResultsThe model demonstrated high recognition accuracy, achieving 100% for Clonorchis sinensis and Schistosoma japonicum, with slightly lower accuracies for other species such as E. vermicularis (89.31%), F. buski (88.00%), and T. trichiura (84.85%). For mixed helminth eggs, the recognition accuracy rates arrived at Group 1 (98.10, 95.61%), Group 2 (94.86, 93.28 and 91.43%), and Group 3 (93.34 and 75.00%), indicating the platform’s robustness but also highlighting areas for improvement in complex diagnostic scenarios.DiscussionThe results show that this AI-assisted platform significantly reduces reliance on professional expertise while maintaining real-time efficiency and high accuracy, offering a powerful tool for the diagnosis and treatment of parasitosis. With further optimization, such as expanding training datasets and refining recognition algorithms, this AI system could become a key resource in both clinical and public health efforts to combat parasitic infections.

BackgroundCurrently developed molecular markers can predict the effectiveness of cancer immunotherapy and screen beneficiaries to some extent, but they are not stable enough. Therefore, there is an urgent need for discovering novel biomarkers. At the same time, sex factor plays a vital role in the response to immunotherapy, so it is particularly important to identify sex-related molecular indicators.MethodsWe integrated a pan-cancer cohort consisting of 2348 cancer patients who received immune checkpoint inhibitors and targeted sequencing. Using somatic mutation profiles, we identified mutational signatures, molecular subtypes, and frequently mutated genes, and analyzed their relationships with immunotherapeutic outcomes. We also explored sex disparities of determined biomarkers in response to treatments.ResultsWe found that male patients exhibited better immunotherapy outcomes and higher tumor mutational burden. A total of seven mutational signatures were identified, among which signatures 1 and 3 were associated with worse immunotherapy outcomes, while signatures 2 and 6 correlated with better outcomes. Gender-based analysis revealed that mutational signature 1 continued to show a worse immunotherapy outcome in female patients, whereas signature 6 demonstrated a better outcome in male patients. Based on mutational activities, we identified four potential molecular subtypes with gender differences and relevance to treatment outcomes. PI3K-AKT, RAS signaling pathways, and 68 significantly mutated genes were identified to be associated with immunotherapy outcomes, with nine genes (i.e., ATM, ATRX, DOT1L, EP300, EPHB1, NOTCH1, PBRM1, RBM10, and SETD2) exhibiting gender differences. Finally, we discovered co-mutated gene pairs and TP53 p.R282W mutations related to treatment outcomes, highlighting their gender-specific differences.ConclusionThis study identified several molecular biomarkers related to cancer immunotherapy outcomes in terms of mutational signatures, molecular subtypes, and mutated genes, and explored their gender-relatedness in order to provide clues and basis for clinical treatment efficacy evaluation and patient selection.

ObjectiveDeveloping and validating a clinical prediction nomogram of 28-day mortality in critically ill patients with acute gastrointestinal injury (AGI).MethodsFirstly, the construction of a clinical prediction model was developed using data obtained from a prospective observational study from May 2023 to April 2024. Then, data from a prospective multicenter observational study conducted in the intensive care units of 12 teaching hospitals in 2014 were utilized to independently and externally validate the clinical prediction model developed in the first part. We first screened the covariates of the development cohort by univariate cox regression, and then carried out cox regression analysis on the development cohort by backward stepwise regression to determine the optimal fitting model. Subsequently, a nomogram was derived from this model.ResultsA total of 1102 and 379 patients, 28-day mortality occurred in 20.3% and 15.8% of patients respectively, were included in the development and validation cohort, respectively. We developed a nomogram in critically ill patients with AGI and the AGI grade, APACHE II score, Mechanical ventilation (MV), Feeding intolerance (FI) and daily calorie intake (DCI) in 72 h, were independent predictors of 28-day mortality, with the OR of the AGI grade was 1.910 (95% CI, 1.588–2.298; P < 0.001), the OR of APACHE II score was 1.099 (95% CI, 1.069–1.130; P < 0.001), the OR of MV was 1.880 (95% CI, 1.215–2.911; P = 0.005), the OR of FI was 3.453 (95% CI, 2.414–4.939; P < 0.001) and the DCI > 0.7 or < 0.5 of calorie target is associated with increased 28-day mortality, with OR of 1.566 (95% CI, 1.024–2.395; P = 0.039) and 1.769 (95% CI, 1.170–2.674; P = 0.007), respectively. Independent external validation of the prediction model was performed. This model has good discrimination and calibration. The DCA and CIC also validated the good clinical utility of the nomogram.ConclusionThe prediction of 28-day mortality can be conveniently facilitated by the nomogram that integrates AGI grade, APACHE II score, MV, FI and DCI in 72 h in critically ill patients with AGI.

This study examined the effect of magneto-induced electric field (MIEF) treatment under varying pH conditions on the physicochemical, structural, and rheological properties of citrus pectin (CP). The results indicate that as the pH increased (to 4.0, 7.0, and 10.0), the molecular weight, degree of esterification, and galacturonic acid content of CP decreased. At pH values of 4.0 and 7.0, MIEF treatment caused fractures in the side chains of CP, while at pH 10.0, the main chain broke. MIEF treatment under these conditions enhanced the steady-state fluid behavior and dynamic viscoelastic properties of CP by promoting increased entanglements of neutral sugar side chains. Overall, the combined effect of pH and MIEF led to the breakdown of the main or side chains of CP, reducing its molecular weight and thereby influencing its rheological properties. In effect, this study provides a green modification technique for CP and its application to functional foods.

Background Kabuki syndrome (KS) is a rare developmental disorder characterised by multiple congenital anomalies and intellectual disability. UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome), which encodes a histone demethylase, is one of the two major pathogenic risk genes for KS. Although intellectual disability is a key phenotype of KS, the role of UTX in cognitive function remains unclear. Currently, no targeted therapies are available for KS.Aims This study aimed to investigate how UTX regulates cognition, to explore the mechanisms underlying UTX dysfunction and to identify potential molecular targets for treatment.Methods We generated UTX conditional knockout mice and found that UTX deletion downregulated calmodulin transcription by disrupting H3K27me3 (trimethylated histone H3 at lysine 27) demethylation.Results UTX-knockout mice showed decreased phosphorylation of calcium / calmodulin-dependent protein kinase II, impaired long-term potentiation and deficit in remote contextual fear memory. These effects were reversed by an Food and Drug Administration-approved drug desipramine.Conclusions Our results reveal an epigenetic mechanism underlying the important role of UTX in synaptic plasticity and cognitive function, and suggest that desipramine could be a potential treatment for KS.

Asia, the world's highest emitting region with surging electricity demand, must transition to clean energy sources for sustainable development. Despite significant progress in solar power deployment, its penetration in the electricity mix remains relatively low. This study employs process tracing to compare solar power development in China and Thailand from 2000 to 2023, representing state-driven and society-centered governance approaches. By analyzing data from secondary sources and conducting online stakeholder interviews, we assess the role of energy governance in fostering resilience during the low-carbon transition. We find state-driven governance exhibits resilience in addressing immediate crises, while society-centered governance drives societal transformation towards a low-carbon future. While state-centric governance suits large-scale centralized renewables, society-centered governance is crucial for distributed renewable projects. Path-dependent governance determines how the energy sector takes in niche innovation, and the reinforced governance structure constrains energy resilience given the interaction within and of the sector with other societal actors. The findings provide insights to inform evidence-based policies and interventions for renewable deployment.

Abstract Background The adolescent depression associated with childhood trauma has been confirmed, but the underlying mechanisms remain unclear. This study aims to explore the chain-mediated role of borderline personality traits and self-control in the relationship between childhood trauma and adolescent depression. Methods A cross-sectional study was conducted on 2,664 students from a senior high school through online questionnaires from October to December 2022 in Henan, China. Childhood Trauma Questionnaire-Short Form, Borderline Personality Dimension of Personality Diagnostic Questionnaire-4, Self-Control Scale, and Children’s Depression Inventory were used to measure childhood trauma, borderline personality traits, and self-control. Results The prevalence of depression in adolescents was 21.17%, while the prevalence of borderline personality was 12.00%. childhood trauma (r = 0.50, p

Abstract This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

Abstract Zygotic genome activation (ZGA) is a universal process in early embryogenesis of metazoan, when the quiescent zygotic nucleus initiates global transcription. However, the mechanisms related to massive genome activation and allele-specific expression (ASE) remain not well understood. Here, we develop hybrids from two deeply diverged (120 Mya) ascidian species to symmetrically document the dynamics of ZGA. We identify two coordinated ZGA waves represent early developmental and housekeeping gene reactivation, respectively. Single-cell RNA sequencing reveals that the major expression wave exhibits spatial heterogeneity and significantly correlates with cell fate. Moreover, allele-specific expression occurs in a species- rather than parent-related manner, demonstrating the divergence of cis-regulatory elements between the two species. These findings provide insights into ZGA in chordates.

Abstract As of today, blockchain technology is virtually absent from rail transit applications, however, it has promising potential. For cloud‐based systems or conventional systems, there is too much information at the centre, resulting in a high level of data processing. However, if the data processing capability can be provided at the edge station or at the edge equipment, it greatly reduces the operation and maintenance pressure, at the same time, if the edge device takes the form of a blockchain, it is possible to increase the safety protection capability. It is important to reduce operating and maintenance risks for metro equipment systems by installing fault diagnosis and health management capabilities. This paper presents a blockchain‐based platform for subway applications. The assistance includes design, construction, operation, and maintenance assistance, energy saving assistance, manpower reduction assistance, fire protection linkage assistance at transfer stations, federal learning analysis and artificial intelligence analysis, as well as specific implementation plans for implementing vent valve equipment as examples.

The abundance and activity of estrogen receptor alpha (ERα) are tightly regulated by ubiquitin-specific peptidase 22 (USP22) during the progression of breast cancer (BCa). However, the post-transcriptional modifications on the USP22-ERα axis remain elusive. N6-methyladenosine (m6A) is critical to modulate RNA status in eukaryotic cells. Here, we find that METTL14 positively regulates the mRNA expression of USP22 and ERα. Mechanistically, METTL14 potently binds to the USP22 and ERα mRNA, and thereby enhancing their stability through m6A modification. YTHDC1 and YTHDF1 function as readers for m6A-modified USP22 and ERα, respectively. Additionally, METTL14 promotes the growth and migration of ERα+ BCa via the USP22-ERα-Cyclin D1 axis. Enforced expression of USP22/ERα significantly reverses the METTL14 depletion-induced growth and migration inhibition in BCa. Moreover, our analysis of clinical samples shows that the expression of METTL14, USP22, and ERα is upregulated and correlated in BCa tissues. Overall, our findings reveal the key role of the METTL14-USP22-ERα axis in BCa progression, which further provides a druggable target to treat BCa.

Malaria remains a major public health concern. The rapid spread of resistance to antimalarial drugs is a major challenge for malaria eradication. Timely and accurate molecular monitoring based on practical detection methods is a critical step toward malaria control and elimination. In this study, two rapid detection techniques, allele-specific PCR (AS‒PCR) and recombinase-aided amplification (RAA) combined with CRISPR/Cas12a, were established, optimized and assessed to detect single nucleotide polymorphisms in the Plasmodium falciparum exonuclease (Pfexo) gene related to suspected piperaquine resistance. Moreover, phosphorothioate and artificial mismatches were introduced into the allele-specific primers for AS‒PCR, and crRNA-mismatched bases were introduced into the RAA‒CRISPR/Cas12a assay because crRNAs designed according to conventional rules fail to discriminate genotypes. As a result, the detection limits of the AS‒PCR and RAA‒CRISPR/Cas12a assays were 104 copies/μL and 103 copies/μL, respectively. The detection threshold for dried blood spots was 100‒150 parasites/μL, with no cross-reactivity against other genotypes. The average cost of AS‒PCR is approximately $1 per test and takes 2–3 h, whereas that of the RAA‒CRISPR/Cas12a system is approximately $7 per test and takes 1 h or less. Therefore, we provide more options for testing single nucleotide polymorphisms in the Pfexo gene, considering economic conditions and the availability of instruments, equipment, and reagents, which can contribute to the molecular monitoring of antimalarial resistance.

Leptin is a peptide hormone primarily produced by adipose tissue, which plays a crucial role in regulating energy balance by controlling appetite and energy expenditure. To better understand the intricate physiological functions of leptin in hepatocytes in tongue sole (Cynoglossus semilaevis), this study presents an integrated transcriptomic and metabolomic analysis of tongue sole hepatocytes following stimulation with lepA and lepB. Comparative analysis identified 2971 and 2900 upregulated differentially expressed genes (DEGs) and 1895 and 1821 downregulated DEGs in response to lepA and lepB stimulation, respectively. Notably, 5706 genes were commonly regulated by both stimulations, suggesting overlapping functional roles of these two leptin proteins. GO and KEGG enrichment analysis indicated significant enrichment in immune response (JAK-STAT signaling pathway, NF-κB signaling pathway, etc.) and lipid metabolism pathways, such as fatty acid synthesis, with similar findings for lepB. Metabolomic analysis demonstrated clear separation between treatment and control groups, with 34 medium- to long-chain fatty acids and numerous differentially expressed metabolites (DEMs) identified. KEGG analysis of the metabolome paralleled the transcriptomic findings, with shared pathways in lipid metabolism and immune function. Finally, joint analysis highlighted co-enrichment in linoleic acid metabolism and leishmaniasis pathways. Detailed mechanistic insights revealed the activation of JAK-STAT and NF-κB signaling pathways, modulation of arachidonic acid metabolism, and the influence on the MAPK signaling pathway. Additionally, lepA uniquely co-enriched in the fatty acid synthesis pathway, with specific gene regulation affecting the synthesis of various fatty acids. The study concluded that lepA and lepB exerted significant regulatory effects on lipid metabolism and immune responses in tongue sole hepatocytes through complex molecular networks. To our current knowledge, this represents the first direct evidence of leptin's role in immune function within teleost fish and offers valuable insights into the molecular mechanisms of lipid metabolism underlying the actions of lepA and lepB.

Background Subclinical insomnia (sINSO) represents an early stage of insomnia but lacks effective biomarkers for its recognition. The electroencephalogram(EEG) microstates, reflecting brain network dynamics, may provide potential biomarkers by comparing resting-state EEG parameters between sINSO patients and healthy controls.Methods Resting-state EEG data from 20 sINSO subjects and 20 healthy controls, under both open and closed eye conditions, were analyzed using microstate clustering (labeled A, B, C, and D) and machine learning to evaluate their discriminative power.Results The microstate global explained variance of the eyes-closed data was better than that of the eyes-open data. In the sINSO group under closed-eye conditions, the tendencies and transition probabilities for microstate changes are as follows: A to D at 7.7%, B to D at 10.7%, C to A at 7.3%, and D to B at 10.8%. Under open-eye conditions, they are: A to C at 9.1%, B to C at 8.4%, C to D at 9.4%, and D to C at 8.9%. Machine learning classification showed higher accuracy in closed-eye conditions, reaching 77.6%.Conclusion Resting-state EEG microstates exhibit significant differences between sINSO and healthy individuals. These microstates are promising biomarkers for distinguishing sINSO, with closed-eye data providing the most reliable discrimination.

Abstract Although the postdispersal functions of diaspore (fruit and its appendages) have been reported, little is known about their protective/defensive functions. In this context, diaspores with appendages (persistent inner tepals and/or fruit wings) that experienced predispersal herbivory by insects in natural populations of Rheum nanum were investigated, and the seed abortion percentage, seed and embryo masses, and germination of seeds from diaspores with different categories of insect herbivory were measured and compared. Predispersal insect herbivory of R. nanum diaspores was prevalent in the four investigated populations, but the percentage of diaspores with appendages (persistent inner tepals and and/or fruit wings) damaged by insects was significantly higher than that of diaspores with the pericarp damaged by insects. Seeds from diaspores with gnawed appendages experienced significantly less damage than those with gnawed pericarps. Importantly, we conclude that fruit appendages of R. nanum help to mechanically protect developing seeds from predispersal insect herbivory.

The majority of previous studies have asserted that the high quality of local institutions can improve the productivity effects of trade policies; yet, only a few studies have acknowledged the heterogeneous impact of these institutions. Using data from Chinese manufacturing plants, we examine the moderating effects of regional-level regulations on the effectiveness of national services trade policy. The key findings are threefold: First, as the initial degree of service liberalization advances, the productivity effect of trade liberalization diminishes. Second, opening access to foreign enterprises can substitute for pro-competitive regulatory reform. Regardless of whether the regulatory institutions related to administrative processes, law enforcement, and commercial service have improved, services trade liberalization can have significant productivity effects. Third, in contrast, when regulations to protect for local incumbents impose prohibitive costs for new entrants, the impact of services trade liberalization is highly contingent on local regulatory improvement. The confirmation that trade liberalization can potentially serve as an alternative measure for local regulation reform in Chinese context distinguishes this study from others.

The dysfunction of pancreatic β-cells plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite numerous studies demonstrating the anti-inflammatory and antioxidant properties of puerarin, the protective effects of puerarin on β-cells remain poorly understood. Hence, this study aimed to explore the effects of puerarin on β-cell dysfunction in a hyperglycemic environment via the PINK/Parkin-mediated mitochondrial autophagy pathway. The alterations in cell viability of MIN6 cells exposed to glucose concentrations of 5 mM, 10 mM, 20 mM, and 30 mM for 24 h, 48 h, and 72 h, respectively, were assessed using the CCK-8 assay to optimize the modeling conditions. Subsequently, cellular insulin secretion was measured using enzyme-linked immunosorbent assay (ELISA), apoptosis rate by flow cytometry, mitochondrial membrane potential alteration by JC-1, cellular ROS production by the DCFH-DA fluorescent probe, and fusion of cellular autophagosomes and lysosomes through adenoviral infection analysis. Furthermore, gene and protein expression levels of the PINK/Parkin-mediated mitochondrial autophagy pathway and mitochondrial apoptosis pathway were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. Results indicated a significant decrease in MIN6 cell viability following 48 h of exposure to 30 mM glucose concentration. Puerarin intervention markedly attenuated ROS production, restored mitochondrial membrane potential, induced PINK/Parkin-mediated mitochondrial autophagy, suppressed activation of the mitochondrial apoptotic pathway, mitigated apoptosis, and enhanced insulin secretion in a high glucose (HG) environment. The findings of this investigation contribute to a deeper understanding of the precise mechanism underlying the protective effects of puerarin on β-cells and offer a theoretical foundation for advancing puerarin-based therapeutics aimed at ameliorating T2DM.

Abstract In this report, a new series of mono‐, di‐, tri‐, and tetra‐cationic pyridinium and vinyl pyridinium‐modified [2.2]paracyclophanes as useful molecular tectons for supramolecular systems are described. Regioselective functionalization at specific positions, followed by resolution step and successive transformations through Pd‐catalyzed Suzuki‐Miyaura and Mizoroki‐Heck cross‐coupling chemistry furnish a series of modular PCP scaffolds. In our proof‐of‐concept study, on N‐methylation, the PCPs bearing (cationic) pyridyl functionalities were demonstrated as useful molecular receptors in host‐guest supramolecular assays. The PCPs on grafting with light‐responsive azobenzene (−N=N−) functional core as side‐groups impart photosensitivity that can be remotely transformed on irradiation, offering photo‐controlled smart molecular functions. Furthermore, the symmetrical PCPs bearing bi‐, and tetra‐pyridyl functionalities at the peripheries have enormous potential to serve as ditopic and tetratopic 3D molecular tectons for engineering non‐covalent supramolecular assemblies with new structural and functional attributes.

Bisphenol A (BPA) is a widely used plasticizer known to cause various disorders. Despite a global reduction in the use of BPA-containing products, prenatal exposure to low-dose BPA, even those below established safety limits, has been linked to neurological and behavioral deficits in childhood. The precise mechanisms underlying these effects remain unclear. In the present study, we observed a significant increase in the number of cortical neurons in offspring born to dams exposed to low-dose BPA during pregnancy. We also found that this prenatal exposure to low-dose BPA led to increased proliferation but reduced migration of cortical neurons. Transcriptomic analysis via RNA sequencing revealed an aberrant activation of the cAMP-PKA-CREB pathway in offspring exposed to BPA. The use of H89, a selective PKA inhibitor, effectively rescued the deficits in both proliferation and migration of cortical neurons. Furthermore, offspring from dams exposed to low-dose BPA exhibited manic-like behaviors, including hyperactivity, anti-depressant-like responses, and reduced anxiety. While H89 normalized hyperactivity, it didn't affect the other behavioral changes. These results suggest that the overactivation of PKA plays a causative role in BPA-induced changes in neuronal development. Our data also indicate that manic-like behaviors induced by prenatal low-dose BPA exposure may be influenced by both altered neuronal development and abnormal PKA signaling in adulthood.

Meaning in life, which has two possible sources: self-acceptance and social support, is essential to the mental health and development of college students. The current study aims to further clarify the symptom-level relations between meaning in life, self-acceptance, and social support, finding possible ways to improve meaning in the life of college students. Thousand three hundred and forty-eight Chinese college students completed the online questionnaire, including Self-acceptance Questionnaire, Social Support Rating Scale, and Meaning in Life Questionnaire and the data from 1,263 participants was used. Cross-sectional network analysis was used to examine the relation between self-acceptance and social support. We also explored the relation between dimensions of self-acceptance and social support and meaning in life using the flow network. The results show symptom “SlA” (self-acceptance) is the bridge symptom linking self-acceptance and social support. In the flow diagrams, “SlA” is directly and positively associated with the presence of meaning. Objective Support shares the strongest positive association with the search for meaning. The symptom “SIA” may be an important targeting symptom when trying to improve the meaning in life of college students. Additionally, social support is essential for college students to develop meaning in life.

Abstract As a novel form of regulated cell death (RCD), disulfidptosis offering a significant opportunity in better understanding of tumor pathogenesis and therapeutic strategies. Long non-coding RNAs (lncRNAs) regulate the biology functions of tumor cells by engaging with a range of targets. However, the prognostic value of disulfidptosis-related lncRNAs (DRlncRNAs) in lung adenocarcinoma (LUAD) remains unclear. Therefore, our study aimed at establishing a prognostic model for LUAD patients based on DRlncRNAs. RNA-seq data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Subsequently, a prognostic model based on DRlncRNAs was constructed using LASSO and COX regression analysis. Patients were stratified into high- and low-risk groups based on their risk scores. Differences between the high-risk and low-risk groups were investigated in terms of overall survival (OS), functional enrichment, tumor immune microenvironment (TIME), somatic mutations, and drug sensitivity. Finally, the role of lncRNA GSEC in LUAD was validated through in vitro experiments. Using the prognostic model consists of 5 DRlncRNAs (AL365181.2, GSEC, AC093673.1, AC012615.1, AL606834.1), the low-risk group exhibited a markedly superior survival in comparison to the high-risk group. The significant differences were observed among patients from different risk groups in OS, immune cell infiltration, immune checkpoint expression, immunotherapy response, and mutation landscape. Experimental results from cellular studies demonstrate the knockdown of lncRNA GSEC leading to a significant reduction in the proliferation and migration abilities of LUAD cells. Our prognostic model, constructed using 5 DRlncRNAs, exhibited the capacity to independently predict the survival of LUAD patients, providing the potentially significant assistance in prognosis prediction, and treatment effects optimization. Moreover, our study established a foundation for further research on disulfidptosis in LUAD and proposed new perspectives for the treatment of LUAD.

Abstract Introduction Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by bone abnormalities, vascular calcification, and some other complications. Although there are diagnostic criteria for CKD-MBD, in situations when conducting target feature examining are unavailable, there is a need to investigate and discover alternative biochemical criteria that are easy to obtain. Moreover, studying the correlations between the newly discovered biomarkers and the existing ones may provide insights into the underlying molecular mechanisms of CKD-MBD. Methods We collected a cohort of 116 individuals, consisting of three subtypes of CKD-MBD: calcium abnormality, phosphorus abnormality, and PTH abnormality. To identify the best biomarker panel for discrimination, we conducted six machine learning prediction methods and employed a sequential forward feature selection approach for each subtype. Additionally, we collected a separate prospective cohort of 114 samples to validate the discriminative power of the trained prediction models. Results Using machine learning under cross validation setting, the feature selection method selected a concise biomarker panel for each CKD-MBD subtype as well as for the general one. Using the consensus of these features, best area under ROC curve reached up to 0.95 for the training dataset and 0.74 for the perspective dataset, respectively. Discussion/Conclusion For the first time, we utilized machine learning methods to analyze biochemical criteria associated with CKD-MBD. Our aim was to identify alternative biomarkers that could serve not only as early detection indicators for CKD-MBD, but also as potential candidates for studying the underlying molecular mechanisms of the condition.

Abstract The advance of genetic function indicators has enabled the observation of neuronal activities at single-cell resolutions. A major challenge for the applications on mammalian brains is the limited optical access depth. Currently, the method of choice to access deep brain structures is to insert miniature optical components. Among these validated miniature optics, the gradient-index (GRIN) lens has been widely employed for its compactness and simplicity. However, due to strong fourth-order astigmatism, GRIN lenses suffer from a small imaging field of view, which severely limits the measurement throughput and success rate. To overcome these challenges, we developed geometric transformation adaptive optics (GTAO), which enables adaptable achromatic large-volume correction through GRIN lenses. We demonstrate its major advances through in vivo structural and functional imaging of mouse brains. The results suggest that GTAO can serve as a versatile solution to enable large-volume recording of deep brain structures and activities through GRIN lenses.

Abstract Background The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring. Methods A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–phthalates exposure interactions. Results There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28–2.37; dominant: aOR = 1.86, 95% CI:1.25–2.78; recessive: aOR = 2.50, 95% CI: 1.26–4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54–121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed. Conclusions The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

Abstract Objective To explore the timing of general anesthesia for pediatric patients who have recovered from novel coronavirus infection and summarize anesthesia-related complications. Methods We summarized the perioperative management of children under 14 years of age who underwent general anesthesia in our hospital according to national epidemic prevention and control requirements. We compared the incidence of postoperative pulmonary complications within 2 weeks (Group A), 3–4 weeks (Group B), and 5–6 weeks (Group C) after COVID-19 recovery. Results There were differences among the three groups in terms of decreased blood oxygen saturation (

Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system, particularly aberrant hippocampal neurogenesis. In this study, we applied in vivo fluorescent tracing using NestinCreERT2::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells (NSCs) and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus. We found abnormal orientation of tamoxifen-induced tdTomato+ (tdTom+) NSCs in adult mice 2 months after treatment with EtOH (5.0 g/kg, i.p.) for 7 consecutive days. EtOH markedly inhibited tdTom+ NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood. EtOH (100 mM) also significantly inhibited the proliferation to 39.2% and differentiation of primary NSCs in vitro. Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus, which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycin-enhancer of zeste homolog 2 pathway. In vivo tracing revealed that EtOH induced abnormal orientation of tdTom+ NSCs and spatial misposition defects of newborn neurons, thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.

Abstract Background Cancer‐associated fibroblasts (CAFs) play a vital role in facilitating tumor progression through extensive reciprocal interplay with cancer cells. Tumor‐derived extracellular vesicles (EVs) are the critical mediators involved in the crosstalk between cancer cells and stromal cells, contributing to the metastasis of cancers. Yet, the biological mechanisms of tumor‐derived EVs in triggering CAFs phenotype to stimulate the lymph node (LN) metastasis of bladder cancer (BCa) are largely unknown. Here, we aimed to explore the effects and molecular mechanisms of tumor‐derived EV‐mediated CAFs phenotype in regulating BCa LN metastasis. Methods The high‐throughput sequencing was utilized to identify the crucial long non‐coding RNA (lncRNA) associated with CAF enrichment in BCa. The functional role of the transition of fibroblasts to CAFs induced by LINC00665‐mediated EVs was investigated through the in vitro and in vivo assays. Chromatin isolation by RNA purification assays, fluorescence resonance energy transfer assays, cytokine profiling and patient‐derived xenograft (PDX) model were performed to explore the underlying mechanism of LINC00665 in the LN metastasis of BCa. Results We found that CAFs are widely enriched in the tumor microenvironment of BCa, which correlated with BCa lymphangiogenesis and LN metastasis. We then identified a CAF‐associated long non‐coding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. Clinically, LINC00665 was associated with LN metastasis and poor prognosis in patients with BCa. Mechanistically, LINC00665 transcriptionally upregulated RAB27B expression and induced H3K4me3 modification on the promoter of RAB27B through the recruitment of hnRNPL. Moreover, RAB27B‐induced EVs secretion endowed fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 overexpression to form a RAB27B‐HGF‐c‐Myc positive feedback loop, enhancing the lymphangiogenesis and LN metastasis of BCa. Importantly, we demonstrated that blocking EV‐transmitted LINC00665 or HGF broke this loop and impaired BCa lymphangiogenesis in a PDX model. Conclusion Our study uncovers a precise mechanism that LINC00665 sustains BCa LN metastasis by inducing a RAB27B‐HGF‐c‐Myc positive feedback loop between BCa cells and fibroblasts, suggesting that LINC00665 could be a promising therapeutic target for patients with LN metastatic BCa.

Aqueous zinc ion batteries (AZIBs) demonstrate tremendous competitiveness and application prospects because of their abundant resources, low cost, high safety, and environmental friendliness. Although the advanced electrochemical energy storage systems based on zinc ion batteries have been greatly developed, many severe problems associated with Zn anode impede its practical application, such as the dendrite formation, hydrogen evolution, corrosion and passivation phenomenon. To address these drawbacks, electrolytes, separators, zinc alloys, interfacial modification and structural design of Zn anode have been employed at present by scientists. Among them, the structural design for zinc anode is relatively mature, which is generally believed to enhance the electroactive surface area of zinc anode, reduce local current density, and promote the uniform distribution of zinc ions on the surface of anode. In order to explore new research directions, it is crucial to systematically summarize the structural design of anode materials. Herein, this review focuses on the challenges in Zn anode, modification strategies and the three-dimensional (3D) structure design of substrate materials for Zn anode including carbon substrate materials, metal substrate materials and other substrate materials. Finally, future directions and perspectives about the Zn anode are presented for developing high-performance AZIBs.

The advancement of solid-state hydrogen storage materials is critical for the realization of a sustainable hydrogen economy. This comprehensive review elucidates the state-of-the-art characterization techniques employed in solid-state hydrogen storage research, emphasizing their principles, advantages, limitations, and synergistic applications. We critically analyze conventional methods such as the Sieverts technique, gravimetric analysis, and secondary ion mass spectrometry (SIMS), alongside composite and structure approaches including Raman spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). This review highlights the crucial role of in situ and operando characterization in unraveling the complex mechanisms of hydrogen sorption and desorption. We address the challenges associated with characterizing metal-based solid-state hydrogen storage materials discussing innovative strategies to overcome these obstacles. Furthermore, we explore the integration of advanced computational modeling and data-driven approaches with experimental techniques to enhance our understanding of hydrogen–material interactions at the atomic and molecular levels. This paper also provides a critical assessment of the practical considerations in characterization, including equipment accessibility, sample preparation protocols, and cost-effectiveness. By synthesizing recent advancements and identifying key research directions, this review aims to guide future efforts in the development and optimization of high-performance solid-state hydrogen storage materials, ultimately contributing to the broader goal of sustainable energy systems.

Rare-earth-metal-based materials have emerged as frontrunners in the quest for high-performance hydrogen storage solutions, offering a paradigm shift in clean energy technologies. This comprehensive review delves into the cutting-edge advancements, challenges, and future prospects of these materials, providing a roadmap for their development and implementation. By elucidating the fundamental principles, synthesis methods, characterization techniques, and performance enhancement strategies, we unveil the immense potential of rare-earth metals in revolutionizing hydrogen storage. The unique electronic structure and hydrogen affinity of these elements enable diverse storage mechanisms, including chemisorption, physisorption, and hydride formation. Through rational design, nanostructuring, surface modification, and catalytic doping, the hydrogen storage capacity, kinetics, and thermodynamics of rare-earth-metal-based materials can be significantly enhanced. However, challenges such as cost, scalability, and long-term stability need to be addressed for their widespread adoption. This review not only presents a critical analysis of the state-of-the-art but also highlights the opportunities for multidisciplinary research and innovation. By harnessing the synergies between materials science, nanotechnology, and computational modeling, rare-earth-metal-based hydrogen storage materials are poised to accelerate the transition towards a sustainable hydrogen economy, ushering in a new era of clean energy solutions.

Exosome-like nanovesicles (ELNs) derived from plants are nanoscale vesicles isolated from edible plant sources. Lycium ruthenicum Murray (LRM) has garnered growing attention for its dietary value and therapeutic benefits. In this study, a PEG6000-based method was developed to isolate LRM-ELNs. Response surface methodology (RSM) was used to optimize the extraction conditions to obtain the optimal extraction efficiency. When PEG6000 concentration was at 11.93%, relative centrifugal force was 9720 g, and incubation time was 21.12 h, the maximum LRM-ELN yield was 4.24 g/kg. This optimization process yielded LRM-ELNs with a particle size of 114.1 nm and a surface charge of −6.36 mV. Additionally, LRM-ELNs mitigated Aβ-induced apoptosis in HT22 cells by enhancing mitochondrial membrane potential (MMP), lowering the Bax/Bcl-2 ratio, and reducing Cleaved Caspase-3 expression. Furthermore, LRM-ELNs alleviated Aβ-induced oxidative stress in HT22 cells by promoting the nuclear translocation of Nrf2 and upregulating the expression of HO-1 and NQO1. These findings indicate that LRM-ELNs exert protective effects against Aβ-induced damage in HT22 cells and may be considered as a potential dietary supplement for Alzheimer’s disease prevention.