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Accurate and rapid detection of nicosulfuron herbicide residues in field-grown maize is essential for implementing chemical remediation and optimizing spraying strategies. However, current detection methods are costly and time-consuming. This study analyzed residue levels in six maize varieties-both resistant and sensitive types-under two herbicide concentrations, categorizing residues into low, medium, and high levels. We developed the HerbiResNet model to predict and classify herbicide residues in maize leaves using spectral data. The model achieved a coefficient of determination (R²) of 0.88 for residue prediction and an accuracy of 0.87 for residue level classification on the test set, significantly outperforming traditional regression models (SVR, PLSR) and classical neural networks (MLP, AlexNet). Additionally, we explored combining spectral technology with deep learning, revealing strong correlations between specific spectral bands (around 550 nm, 680 nm, 750 nm, and 1000 nm) and herbicide residues as well as physiological changes in maize. This provides a solid theoretical foundation for the broader application of spectral technology in agriculture. Overall, the HerbiResNet model demonstrates substantial potential for precision agriculture and sustainable agricultural practices., 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.)

To explore the role of AVAPS combined with TCM monitoring in the weaning of patients with AECOPD. In this study, 100 patients with AECOPD were included, who were divided into the AVAPS group and the S/T group after weaning. The respiration-related parameters were compared between the two groups at the time of weaning and after 1 h and 12 h of noninvasive ventilation. The correlations between PtcCO 2 and PaCO 2 and the differences in each parameter were compared. The predictive value of PtcCO 2 variability after 1 h and 12 h of noninvasive respiratory support for the 48-h reintubation rate were analysed. Logistic regression analysis was performed to explore the risk factors affecting the 48-h reintubation rate of AECOPD patients. After 1 h and 12 h of treatment with different ventilation modes, the variations in the respiration-related parameters in the AVAPS group were all significantly greater than those in the S/T group (P < 0.05). In the AVAPS group, the incidence of 48-hour reintubation was lower, the time to reintubation was longer, and length of hospital and ICU stays were shorter (P < 0.05). The ROC curve revealed that PtcCO 2 variability - 2 , the ROX index - 2 and their combination had predictive value for the 48-h reintubation rate of AECOPD patients. The logistic regression revealed that after 12 h of noninvasive support, a PtcCO 2 variability ≥ - 5.8% with a ROX index ≤ 9.6 was independent risk factors affecting the 48 h reintubation rate in weaning patients with AECOPD (OR = 2.815; P < 0.05). For patients with AECOPD, the AVAPS ventilation mode combined with PtcCO 2 monitoring can significantly improve respiratory physiological parameters and reduce the 48 h reintubation rate. After 12 h of noninvasive support, a PtcCO 2 variability ≥ - 5.8% with a ROX index ≤ 9.6 is considered as a independent risk factor for reintubation 48 h after weaning., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The procedures used for this study conform to the standards of medical ethics. All the subjects signed an informed consent form before the collection of TCM and Arterial blood gases., (© 2025. The Author(s).)

The expansion of GGC repeats within NOTCH2NLC leads to translation of the uN2CpolyG protein, the primary pathogenic factor in neuronal intranuclear inclusion disease (NIID). The aim of this study was to explore the deposition of uN2CpolyG as an amyloid in the vessel wall, leading to uN2CpolyG cerebral amyloid angiopathy-related cerebral microbleeds (CMBs). A total of 97 patients with genetically confirmed NIID were enrolled in this study. We analysed the presence of CMBs using susceptibility-weighted imaging sequences and compared general clinical information, cerebrovascular risk factors, stroke history, antiplatelet medication use and MRI features between NIID patients with and without CMBs. We also performed haematoxylin and eosin, Perl's, Congo red and Thioflavin S staining, ubiquitin, p62 and uN2CpolyG immunostaining on brain tissue obtained from four NIID patients. A total of 354 CMBs were detected among 41 patients with NIID, with nearly half located in the deep brain, one-third in the lobes and ∼20% in the infratentorial area. No significant differences in cerebrovascular disease risk factors or history of antiplatelet drug use were observed between patients with and without CMBs. However, patients with CMBs had suffered a higher incidence of previous ischaemic and haemorrhagic stroke events. This group also had a higher incidence of recent subcortical infarcts and a higher proportion of white matter lesions in the external capsule and temporal pole. Conversely, patients without CMBs showed higher detection of high signals at the corticomedullary junction on diffusion-weighted imaging and more pronounced brain atrophy. Haematoxylin and eosin staining showed blood vessel leakage and haemosiderin-laden macrophage clusters, and Prussian blue staining revealed iron deposition in brain tissue. CMBs occurred more frequently in small vessels lacking intranuclear inclusions, and extensive degeneration of endothelial cells and smooth muscle fibres was observed mainly in vessels lacking inclusions. Congo red-positive amyloid deposition was observed in the cerebral vessels of NIID patients, with disordered filamentous fibres appearing under an electron microscope. Additionally, the co-localization of Thioflavin S-labelled amyloid and uN2CpolyG protein in the cerebral vascular walls of NIID patients further suggested that uN2CpolyG is the main pathogenic protein in this form of amyloid angiopathy. In conclusion, we reviewed patients with GGC repeat expansion of NOTCH2NLC from a new perspective, providing initial clinical, neuroimaging and pathological evidence suggesting that uN2CpolyG might contribute to a distinct type of cerebral amyloid angiopathy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Advancements in diagnostic and therapeutic approaches have led to a remarkable reduction in the morbidity and mortality rates associated with a variety of diseases. In the context of acute ischemic heart disease, significant milestones have been achieved, beginning with the establishment of cardiac ICUs. These were pivotal in providing specialized care for patients with severe heart conditions. Subsequent to this development, methods to restore blood flow in areas compromised by arterial blockages were introduced. Initially, systemic thrombolysis was the primary method used, but it has since been largely supplanted by primary percutaneous coronary intervention (PCI), also known as primary coronary angioplasty, which is now the preferred treatment due to its effectiveness and safety. The incidence of out-of-hospital cardiac arrest (OHCA) where resuscitation attempts have been made, whether successful or not, is significant and presents a considerable challenge. Unfortunately, the mortality rate among these patients remains distressingly high, and efforts to reduce it are fraught with difficulty. It is crucial to acknowledge that survival from an OHCA does not automatically equate to a favorable clinical outcome, as serious neurological impairments are common sequelae of such events. In addition to mortality rates, the term "survival with favorable neurologic outcome" has emerged as another critical measure of the success of resuscitation efforts. This parameter underscores the importance of not only saving lives but also preserving the quality of life for survivors. The ability to restore both life and cognitive function is a testament to the comprehensiveness of care provided to OHCA patients., 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 molecular basis for the liquid-liquid phase separation (LLPS) behavior of various biomolecular components in the cell is the formation of multivalent and low-affinity interactions. When the content of these components exceeds a certain critical concentration, the molecules will spontaneously coalesce to form a new liquid phase; i.e., LLPS occurs. Intrinsically disordered proteins (IDPs) are usually rich in amino acids with charged side-chains, and thus, LLPS-involving interactions between their side-chains are of great interest. However, the molecular details of the coalescence of such charged IDPs in a salt solution are still lacking. Here, we focus on two types of peptide-chains with oppositely charged amino acids in extreme arrangements and investigate their aggregation patterns in various ionic environments. The results show that the interaction patterns between peptide-chains with nonuniform charge arrangement sequences are more sensitive to the surrounding cationic environment, and Na + ions are more likely to cause aggregation of ASP residues compared to Mg 2+ ions. As the ionic concentration increases, the electrostatic interactions between oppositely charged residues are gradually converted into a negative-negative amino acid interaction network bridged by Na + ions, while the positive charge-rich regions are more strongly inclined to be exposed to the solvent environment and gain greater freedom of movement. Simultaneously, this effect will reach saturation with a further increase of salt concentration. The present study enriches insights into the electrostatic dominant factors in phase separation phenomena at the atomic level, which will hopefully inspire the design and application of targeted LLPS in the future.

Rationale: Mesenchymal stem cells (MSCs) possess potent immunomodulatory capability, but occasionally, clinical application of MSCs is hindered by compromised cell functionality and insufficient therapeutic efficacy. Methods: Here, well-established mouse models of dextran sulfate sodium (DSS)-induced colitis and streptozotocin (STZ)-induced type 1 diabetes (T1D) were used to evaluate therapeutic immunomodulatory effects of human umbilical cord-derived MSCs. MSCs were examined at the fifth (P5) and the fifteenth (P15) passages, and three-dimensional (3D) culture was conducted by Matrigel incorporation. A series of biochemical, histopathological and cellular assays were performed to investigate the MSC function and therapeutic performance, and immunoregulation was evaluated by in vitro co-culture with T cells and in vivo analyses of T-cell infiltration into target tissues. RNA sequencing (RNA-seq) analysis followed by immunofluorescence staining, gene expression analyses and chemical regulation were used to investigate the molecular targets. Results: MSCs lose therapeutic immunomodulatory effects after extensive expansion to P15 when cell senescence occurs. Intriguingly, 3D preconditioning of MSCs in Matrigel promotes diminished immunoregulatory capability despite extensive passages, which benefits function of P15-MSCs to modulate T-cell subsets in co-culture, suppress infiltration of pro-inflammatory T cells in the colon and pancreas tissues after infusion, ameliorate systemic inflammation, and alleviate colitis and T1D in mice. Mechanistically, 3D culture provokes transcriptomic reprogramming of MSCs toward a Yes-associated protein 1 (YAP1)-marked, Hippo signaling pathway-upregulated state with promoted release of the anti-inflammatory cytokine, transforming growth factor-beta1 (TGF-β1). Moreover, chemical regulation of YAP1 by clinically relevant drugs, verteporfin (VP) and prostaglandin E2 (PGE2), affects TGF-β1 expression and the immunomodulatory capability of MSCs during dimensional culture. Conclusions: Taken together, these findings unravel YAP1-based dimensional and chemical coordination of expanded MSC immunoregulation, which will shed light on precisely controlled translational application., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Hepatocellular carcinoma (HCC) is a primary malignant neoplasm exhibiting a high mortality rate. Taxifolin is a naturally occurring flavonoid compound that exhibits a range of pharmacological properties. The effects of taxifolin on HCC remain largely unexplored. Therefore, the aim of this study was to examine the potential roles of taxifolin in the development and progression of HCC. In this study, CCK-8 assay was utilized to examine the impact of taxifolin on the cell viability. The copper ions level and the activity of mitochondrial respiratory chain were determined by the correspondent kits. The biological properties of HCC cells were evaluated using colony formation, transwell, flow cytometry, and TUNEL assays, respectively. Transcriptome sequencing was carried out either with or without taxifolin treatment. The expression of cuproptosis-related proteins was determined by Western blot. We observed significant decrease of cell viability, Glutathione (GSH), and mitochondrial respiratory chain under the treatment of taxifolin, while an increase of copper ions level. Taxifolin was observed to suppress HCC progression both in vitro and in vivo. The intersection analysis was performed between upregulated genes and cuproptosis-related genes to obtain one intersection gene-SLC31A1. The knockdown of SLC31A1 reversed the tumor-suppressive effects induced by taxifolin. Taxifolin inhibited HCC progression through inducing cuproptosis in an SLC31A1-mediated manner., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: This study was approved by the Ethics Committee of Chengdu Public Health Clinical Center (Approval No: YJ-K2024-13-01, Chengdu, China; time of ethics approval: 2024-01-13)., (© 2025. The Author(s) under exclusive licence to Japan Human Cell Society.)

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease in neonates. Fucosyltransferase 2 (Fut2) regulates intestinal epithelial cell fucosylation. In this study, we aimed to investigate butyrate-mediated upregulation of Fut2 expression and the underlying mechanisms., Methods: In vivo and in vitro models were established. SP600125 was used to inhibit the MEK4-JNK pathway, and anisomycin was used to activate the MEK4-JNK pathway. Fut2, occludin, and ZO-1 expressions were assessed. Furthermore, intestinal permeability was analyzed by FITC-Dextran. The expression of proteins in the MEK-4-JNK pathway was examined by western blotting., Results: In vivo, the addition of exogenous butyrate notably upregulated Fut2, occludin, and ZO-1 expressions and reduced intestinal permeability in mice with NEC. Butyrate may increase the phosphorylation of MEK4, JNK, and c-jun, which are key components of the MEK4-JNK pathway. Additionally, SP600125 inhibited their phosphorylation, which was reversed by anisomycin treatment. In vitro, butyrate substantially increased occludin and ZO-1 expressions. Butyrate considerably increased Fut2 expression and markedly upregulated p-MEK4, p-JNK, and p-c-jun expressions. SP600125 administration decreased their expressions, while anisomycin administration increased their expressions., Conclusion: Butyrate upregulated Fut2 expression via activation of the MEK4-JNK pathway, improved intestinal barrier integrity, and protected neonatal mice from NEC., Impact: We found that exogenous butyrate could improve intestinal barrier integrity and protect against NEC in neonatal mice. Our data showed that exogenous butyrate supplementation upregulated Fut2 expression by activating the MEK4-JNK pathway. Our study provides novel insights into the pathogenesis of NEC, thereby laying an experimental foundation for future clinical research on the use of butyrate in NEC treatment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Spinal cord injury (SCI) is a disabling disease associated with microglial activation. Tripartite motif containing 32 (TRIM32) is an E3 ubiquitin ligase that plays a role in SCI. This study aimed to explore the role of TRIM32 in SCI and its potential mechanisms. We established an SCI mouse model to assess the function of TRIM32 using quantitative real-time polymerase chain reaction (qPCR), and hematoxylin and eosin staining. Additionally, a lipopolysaccharides (LPS)-induced cell injury model was generated to explore the impact of TRIM32 on pyroptosis using qPCR, propidium iodide staining, and western blotting. The ubiquitylation of NEK7 was analyzed using western blotting, co-immunoprecipitation, and immunofluorescence staining. The results showed that TRIM32 expression was increased in SCI mice and LPS-induced BV-2 cells. Overexpression of TRIM32 ameliorated SCI in mice and suppressed pyroptosis in LPS-treated BV-2 cells. Additionally, the E3 ligase TRIM32 promoted the ubiquitylation of NEK7 at the K64 site, leading to the downregulation of NEK7 levels. Inhibiting NEK7 ubiquitylation reversed the suppression of pyroptosis by TRIM32. In conclusion, TRIM32 inhibits microglia pyroptosis by facilitating the ubiquitylation of NEK7 at the K64 site, thereby alleviating the progression of SCI. The findings suggest that TRIM32 has the potential to be a therapeutic target of SCI., Competing Interests: Declarations. Ethics Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Shuyang Hospital of Traditional Chinese Medicine. Consent to Participate: Not applicable. Consent to Publish: Not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To investigate the effects of music intervention on the vital signs, weight gain, feeding, hospital stays, and cost of premature infants., Methods: 100 premature infants were randomized into two groups: the experimental group (given music for 30 min at a time, once every day until discharge) and the control group (without music). To compare the vital signs (RR, HR, SPO 2 ) before, during, and after the music intervention, as well as the weight gain and feeding, follow up to 3 months after discharge., Results: Although respiratory rate (RR) showed a decreasing trend at certain time points during and after music exposure, these changes did not reach statistical significance after adjusting for multiple comparisons. The experimental group had a shorter time to regain birth weight (6.07 ± 2.47 days) compared to the control group (8.93 ± 4.31 days) and a shorter time of intravenous nutrition (8.6 ± 3.87 days vs. 11.66 ± 5.85 days). The experimental group also exhibited a lower fasting rate, a faster-sucking speed, a lower hospital stay (10.36 ± 4.36 days vs. 12.46 ± 5.73 days), lower cost, higher NBNA scores, and a lower re-hospitalization rate within 3 months after the first discharge., Conclusions: Early music intervention may contribute to the growth and development of preterm infants, improve feeding, reduce hospitalization duration and costs, and improve short-term prognosis, though effects on respiratory rate require further study with a larger sample size.

Understanding the characteristics of graphite-water interfaces is of scientific significance and practical importance. Ordered stripe structures have been observed at this interface, with their origins debated between condensed gas molecules and airborne hydrocarbons. Atomic force microscopy (AFM) studies have revealed variations in the morphology, formation and growth of these ordered structures. Here, we investigate the graphite-water interface under different environmental conditions using PeakForce Quantitative Nanomechanical (PF-QNM) AFM. Our findings reveal that stripe structures with 4 nm width and 0.5 nm periodicity, form and grow under wet laboratory conditions but not in pure inert gas or cleanroom environments. These stripes appear more readily when the graphite surface is immersed in water, with growth associated with gas nanodomains on the surface. This suggests that atmospheric contaminants migrate to the water-graphite interface, potentially facilitated by gas states. These findings underscore the impact of environmental conditions on graphitic materials, providing new insights into the mechanisms underlying stripe formation and growth., (© 2024 The Author(s). ChemPhysChem published by Wiley-VCH GmbH.)

The rGO/CMC/β-CD (RCβ) hydrogel was synthesized from reduced graphene oxide (rGO), β-cyclodextrin (β-CD) and sodium carboxymethyl cellulose (CMC) by radical polymerization. A novel hydrogel adsorbent was created by growing the metal-organic framework (Cu-BTC) in-situ on RCβ hydrogel, which has excellent adsorption capacities for cationic dyes in wastewater. The adsorption parameters such as the amount of adsorbent, pH of solution and adsorption time were optimized through batch adsorption experiments. Under the optimal conditions of pH 6.0, adsorbent dosage of 0.01 g and experimental temperature of 25 °C, Langmuir isothermal model was used to fit the maximum adsorption capacities of methylene blue (MB), crystal violet (CV) and malachite green (MG), which were 892.66, 842.75 and 633.77 mg g -1 , respectively. The fitting results of adsorption kinetics revealed that the pseudo-second-order model can describe the adsorption process better. Based on proposed studies, the dye molecules were adsorbed onto RCβ@Cu-BTC hydrogel mainly through electrostatic interaction, hydrogen bonding and π-π interactions. After five cycles, the adsorption efficiency of the RCβ@Cu-BTC hydrogel for MB, CV and MG can still reach 80 %, 77 % and 72 %, which shows that the adsorbent has good adsorption performance. Various adsorption experiments show that RCβ@Cu-BTC hydrogel has great potential in treating dye wastewater., 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.)

Background: Influenza virus-induced pneumonia (IVP) is an infectious pulmonary disease characterized by exacerbated pulmonary inflammation caused by invasion of the influenza virus. IVP continues to threaten public health due to its high morbidity and mortality rates. Geniposide is one of the major bioactive constituents of G. jasminoides, which exerts antiviral and anti-inflammatory effects on influenza A virus (IAV) infection., Purpose: To investigate therapeutic effects and comprehensive mechanisms of geniposide on IAV infection and subsequent pneumonia., Methods: ICR mice were infected intranasally with H1N1 (A/FM/1/47) to detect the anti-IAV activity of geniposide. Proteomics combined with function-integrated analysis were conducted to gain insight into the comprehensive mechanisms of geniposide. Subsequently, western blot was used to detect the phosphorylation of signal transducer and activator of transcription 1 (STAT1), signal transducer and activator of transcription 2 (STAT2), Interferon regulatory factor 9 (IRF9) and Janus kinase 1 (JAK1) in Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in lung tissue. Finally, RT-qPCR was used to detect the levels of interleukin 6 (IL-6), interleukin 17 (IL-17), interferon-γ (IFN-γ) and the STAT1 inhibitor (fludarabine) was used to verify the targeting between STAT1 and geniposide in RAW cells., Results: Geniposide could significantly reduce the lung index, diminish lung pathology, decrease the virus loads and the inflammatory cytokines expression induced by IAV infection. A total of 411 differentially expressed proteins were identified among control, model, and geniposide-treated group in proteomic analysis. According to function-integrated analysis, 15 KEGG pathways were enriched and divided into 9 groups (modules), including influenza A, NOD-like receptor signaling, RIG-I-like receptor signaling, and so on. Among these modules, the most intensely interacting module pair was the NOD-like receptor signaling and influenza A, in which STAT1 and STAT2 acted as hubs with critical bridgeness role in the target network of geniposide. This indicated that geniposide may mitigate inflammation and alleviate IVP by JAK/STAT signaling pathways. Moreover, validation experiments confirmed that geniposide can significantly inhibit STAT1 and STAT2 phosphorylation as well as down-regulated expression of IL-6, IFN-γ and IL-17 in lung. Furthermore, when RAW cells were treated with the STAT1 inhibitor (fludarabine), the inhibitory effect of geniposide on IFN-γ and IL-6 was attenuated significantly., Conclusions: Geniposide can attenuate IAV-induced pneumonia by regulating inflammatory cytokines production through the JAK/STAT pathway., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated in vitro and in vivo. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC., Competing Interests: Declaration of competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Accumulating evidence indicates that maternal exposure to carbon black nanoparticles (CBNPs) during gestation can induce multiple system abnormalities in offspring, whereas its potential mechanism in respiratory disease is still largely unknown. In order to explore the effect of maternal exposure to CBNPs on offspring's lung and latent pathogenesis, we respectively established in vivo model of pregnant rats exposed to CBNPs and ex vivo model of lung epithelial cells treated with pups' serum of pregnant rats exposed to CBNPs. After maternal exposure to CBNPs, epithelial-mesenchymal transition (EMT) and fibrosis levels increased as a result of DDRGK1-mediated reticulophagy upregulated in offspring's lung. DDRGK1 as FAM134B's cargo bound with FAM134B to mediate reticulophagy. Transcription factor "SP1" positively regulated DDRGK1 gene expression by binding to its promoter. Furthermore, the upregulation of NSUN2 elevated m 5 C methylation of SP1 mRNA and the protein level of SP1 subsequently increased through Ybx1 recognizing and stabilizing m 5 C-methylated SP1 mRNA, followed by the increased levels of reticulophagy and fibrosis in lung epithelial cells treated with offspring's serum of matrix exposed to CBNPs during gestation. In conclusion, NSUN2/Ybx1/m 5 C-SP1 axis promoted DDRGK1-mediated reticulophagy, which played an important role in EMT-induced fibrosis in offspring's lung tissue after maternal exposure to CBNPs during gestation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The clinical manifestations of cow's milk protein allergy (CMPA) in neonates are non-specific and involve multiple organ systems. CMPA may also adversely affect physical growth and central nervous system development in neonates, lead to functional disorders, and increase anxiety and stress among family members. Due to the lack of specific clinical manifestations and diagnostic methods, the diagnosis and management of CMPA in neonates continue to pose significant clinical challenges. To facilitate standardized diagnosis and treatment of CMPA in neonates, the Neonatology Group of the Pediatric Branch of the Chinese Medical Association and the Editorial Committee of the Chinese Journal of Pediatrics have jointly developed the "Expert Consensus on Diagnosis and Management of Neonatal Cow's Milk Protein Allergy (2023)". This article presents and interprets the key points of the consensus regarding dietary and nutritional management of CMPA in neonates.

Background : Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. Methods : In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. Results : We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. Conclusions : oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role.

The incorporation of aromatic difluoromethyl motifs has proven to be a fruitful strategy for enhancing the therapeutic profiles of modern pharmaceutical candidates. While the defluorofunctionalization of trifluoromethylarenes offers a promising pathway toward diverse aromatic difluoromethyl compounds, current methods are predominantly limited to two-component reactions. Multicomponent cascade reactions (MCRs) involving a transient aromatic difluoromethyl radical are still uncommon and highly sought after, owing to their capacity to rapidly generate challenging molecular structures. In this study, we present a photocatalytic manifold that combines commercially available trifluoromethylarenes, feedstock dienes, and various nucleophiles to achieve a modular defluorinative MCR. This method features mild reaction conditions and a broad substrate scope with excellent functional group compatibility. Furthermore, this protocol enables a previously unreported process of defluorinative editing for the resulting MCR aromatic difluoromethyl adducts. Preliminary mechanistic studies support the proposed photoexcited palladium catalytic cycle., Competing Interests: The authors declare the following competing financial interest(s): X. Zhang, Z. Li and K. Wei are inventors on a Chinese patent application (Application No. CN202410093803X)., (© 2024 The Authors. Published by American Chemical Society.)

Background: Spinal cord injury (SCI) elicits excess neuroinflammation and resident microglial pyroptosis, leading further terrible neurological collapse and locomotor dysfunction. However, the current clinical therapy is useless and a feasible treatment is urgent to be explored. Cynarin is a natural component in artichoke playing anti-inflammatory and anti-aging roles in hepatoprotection and cardioprotection, but it is unclear that the pharmacologic action and underlying mechanism of Cynarin in neuropathy., Methods: Using the SCI mouse model and the BV2 cell line, we here investigated whether Cynarin reduces neuroinflammation and pyroptosis to promote neurological recovery after SCI., Results: Our results showed that treatment with Cynarin reduces the level of neuroinflammation and microglial pyroptosis. Moreover, the mice treated with Cynarin exhibited lower level of reactive oxygen species (ROS) and cell death, less damage of neurohistology and better locomotor improvement of hindlimbs than the untreated mice and the nuclear factor erythroid 2-related factor 2 (Nrf2)-inhibited mice. Mechanically, Cynarin inhibited the assembly of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome by Nrf2-dependent expression to attenuate microglial pyroptosis and neuroinflammation., Conclusions: To sum up, the current study suggested that administration of Cynarin is a promising compound for anti-neuroinflammation and anti-pyroptosis after SCI. It may be an efficient Nrf2 activator and a NLRP3 inhibitor for microglia in neuropathies., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Determining the optimal timing of surgical intervention for Neonatal necrotizing enterocolitis (NEC) poses significant challenges. This study develops a predictive model using the long short-term memory network (LSTM) with a focal loss (FL) to identify infants at risk of developing Bell IIB + NEC early and issue timely surgical warnings., Methods: Data from 791 neonates diagnosed with NEC are gathered from the Neonatal Intensive Care Unit (NICU), encompassing 35 selected features. Infants are categorized into those requiring surgical intervention (n = 257) and those managed medically (n = 534) based on the Mod-Bell criteria. A fivefold cross-validation approach is employed for training and testing. The LSTM algorithm is utilized to capture and utilize temporal relationships in the dataset, with FL employed as a loss function to address class imbalance. Model performance metrics include precision, recall, F1 score, and average precision (AP)., Results: The model tested on a real dataset demonstrated high performance. Predicting surgical risk 1 day in advance achieved precision (0.913 ± 0.034), recall (0.841 ± 0.053), F1 score (0.874 ± 0.029), and AP (0.917 ± 0.025). The 2-days-in-advance predictions yielded (0.905 ± 0.036), recall (0.815 ± 0.057), F1 score (0.857 ± 0.035), and AP (0.905 ± 0.029)., Conclusion: The LSTM model with FL exhibits high precision and recall in forecasting the need for surgical intervention 1 or 2 days ahead. This predictive capability holds promise for enhancing infants' outcomes by facilitating timely clinical decisions., (© 2024. The Author(s).)

DNA-RNA hybrid duplexes play essential roles during the reverse transcription of RNA viruses and DNA replication. The opening and conformation changes of individual base pairs are critical to their biological functions. However, the microscopic mechanisms governing base pair closing and opening at the atomic level remain poorly understood. In this study, we investigated the thermodynamic and kinetic parameters of the dA-rU base pair in a DNA-RNA hybrid duplex using 4 μs all-atom molecular dynamics (MD) simulations at different temperatures. Our results showed that the thermodynamic parameters of the dA-rU base pair aligned with the predictions of the nearest-neighbor model and were close to those of the AU base pair in RNA. The temperature dependence of the average lifetimes of both the open and the closed states, as well as the transition path times, were obtained. The free-energy barrier for a single base pair opening and closing arises from an increase in enthalpy due to the disruption of the base-stacking interactions and hydrogen bonding, along with an entropy loss attributed to the accompanying restrictions, such as torsional angle constraints and solvent viscosity.

Background: Fine particulate matter (PM 2.5 ) is noxious to female reproductive development and facilitates the occurrence of subsequent diseases. Early menopause is initiative factor of female aging. But due to the lack of historical exposure of PM 2.5 , we could not gain insight into the linkage between ambient PM 2.5 exposure and early menopause., Methods: We conducted a community-based retrospective cross-sectional study and pooled 1173 postmenopausal women. The machine learning algorithm of LightGBM was processed to derive the historical concentrations of PM 2.5 based on aerography of 1956-2022. The quantile g-computation and binary logistic regression were employed to estimate the mixed and single associations between PM 2.5 and early menopause., Results: The visibility topped the most important feature for derivations of historical PM 2.5 concentrations. The R 2 of 10-fold cross-validation and predictive capability during processing were all above 0.8. The prevalence of early menopause was 7.3 %. Each 10 µg/m 3 PM 2.5 increased the prevalence of early menopause during prior 2 years exposure (OR: 1.49, 95 %CI: 1.03-2.16) and spring and autumn (OR: 1.28, 95 %CI: 1.07-1.54). After adjusting the reverse effects of temperature, the prior 2 years exposure of PM 2.5 remained positively associated with early menopause in the fourth quantile vs the first quantile (OR: 3.36, 95 %CI: 1.53-7.36) in the spring and autumn. The higher BMI (OR: 1.40, 95 %CI: 1.14-1.72), waistline (OR: 1.42, 95 %CI: 1.09-1.85) and unfavourable dietary habits of less meat (OR: 1.72, 95 %CI: 1.11-2.68), more fried food (OR: 2.39, 95 %CI: 1.15-4.99) elevated the prevalence of early menopause., Conclusions: The accurate environmental exposure assessment of historical PM 2.5 vigorously promoted the researches on the relationship between PM 2.5 and early menopause. It sounds the alarm on female infertility menace associated with particulate matter especially during the turbulent 2 years before menopause., 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 Authors. Published by Elsevier Inc. All rights reserved.)

While autoantibodies in bullous pemphigoid (BP) are known to activate the innate immune response, their direct effect on keratinocytes, and the contribution of BP-IgG autoantibody-dependent keratinocyte responses to BP pathology is largely unknown. Herein, we performed multiplex immunoassays and bulk RNA-seq on primary keratinocytes treated with IgG from BP patients or controls. We identified a pro-inflammatory and proteolytic response with release of several cytokines (IL-6, IL-24, TGF-β1), chemokines (CXCL16, CTACK, MIP-3β, RANTES), C1s, DPP4, and MMP-9. We further validated this response using spatial transcriptomics and scRNA-seq of diseased and control skin. Blistering itself appeared to be major driver of this inflammatory response, with attached BP skin and spongiotic dermatitis revealing highly similar transcriptomes. Based on elevated levels of MyD88 and MyD88-dependent cytokines, we studied the impact of MyD88 deficiency in keratinocytes and demonstrated that MyD88 regulates BP-IgG-induced expression of IL-8, IL-24, and MMP-9. Induction of experimental BP in mice with Krt14 -specific Myd88 knockout revealed significantly decreased disease severity with decreased serum levels of IL-1β, IL-4, and IL-9 indicating the contributory role of keratinocyte-derived skin inflammation towards systemic response. Our work demonstrates the key contributions of keratinocyte and MyD88 dependent signaling in response to autoantibodies in BP., Key Messages: -IgG antibodies from bullous pemphigoid (BP) patients induce significant upregulation of several inflammatory markers in keratinocytes including cytokines (IL-6, IL-24, TGF-β1), chemokines (CXCL16, CTACK, MIP-3β, RANTES), C1s, DPP4, and MMP9. Several of these markers, including IL-8, IL-24, and MMP9 are regulated by MyD88.-Spatial transcriptomics reveals that BP patient blistered skin demonstrated similar transcriptomic profiles to BP-IgG-treated keratinocytes. With attached skin demonstrating a comparable transcriptome to that seen in spongiotic dermatitis.-In a mouse BP model, keratinocyte-specific MyD88 deficiency results in decreased disease severity with a subsequent decrease in serum IL-1β, IL-4, and IL-9 levels., Capsule Summary: IgG from patients with bullous pemphigoid (BP) induces a pro-inflammatory response in keratinocytes, indicating their direct role in driving the inflammatory response in BP.

Granular microporous hydrogels are emerging as effective biomaterial scaffolds for tissue engineering due to their improved characteristics compared to traditional nanoporous hydrogels, which better promote cell viability, cell migration, cellular/tissue infiltration, and tissue regeneration. Recent advances have resulted in the development of granular hydrogels made of non-spherical microgels, which compared to those made of spherical microgels have higher macroporosity, more stable mechanical properties, and better ability to guide the alignment and differentiation of cells in anisotropic tissue. The development of these hydrogels as an emerging research area is attracting increasing interest in regenerative medicine. This review first summarizes the fabrication techniques available for non-spherical microgels with different aspect-ratios. Then, it introduces the development of granular microporous hydrogels made of non-spherical microgels, their physicochemical characteristics, and their applications in tissue regeneration. The limitations and future outlook of research on microporous granular hydrogels are also critically discussed., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Metal exposure has been reported to be associated with metabolic syndrome (MetS), however, the evidence remains inconclusive, particularly in elderly individuals. From May to July 2016, serum levels of 16 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) in 852 elderly individuals (≥65 years) residing in Wuhan, China. Biological detection and disease recognition were based on individual surveys conducted during health check-ups. Spearman's rank correlation analysis was performed to identify the correlation among serum metals. The data were Ln-transformed to fit a normal distribution for further analyses. Linear and logistic regression were applied to explore the associations between metals and diseases. Restricted cubic spline (RCS) analysis was utilized to examine dose-response relationships. The Weighted Quantile Sum (WQS) score was applied to determine the empirical weights of each heavy metal in the context of their combined effect on metabolic diseases. The prevalence of MetS, hypertension, diabetes, and hyperlipidemia were 46.36 %, 68.90 %, 24.65 %, and 21.60 %, respectively. Serum metal mixture was positively associated with the prevalence of MetS (OR = 1.92, 95 % CI: 1.30-2.82), hypertension (OR = 1.50, 95 % CI: 1.01-2.23), and diabetes (OR = 2.18, 95 % CI: 1.48-3.22). In single metal models, we found that serum zinc levels were associated with an increased risk of MetS, while rubidium had a protective effect against MetS. Interestingly, different metals had distinct effects on specific diseases in this study: lithium and barium were more likely to influence blood pressure, while selenium had a more significant effect on blood glucose. Lipids were more susceptible to the effects of zinc, selenium, and strontium. Platelet count (PLT) and lymphocyte count (LYM) mediated the association between selenium exposure and hyperlipidemia, while neutrophil count (NEU) mediated the relationship between serum rubidium exposure and MetS. Our findings offer valuable etiological insights into the relationship between serum heavy metals and the prevalence of MetS, suggesting that peripheral blood cells may play a mediating role in this association., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhang rong reports financial support was provided by National Natural Science Foundation of China. Pang yaxian reports financial support was provided by National Natural Science Foundation of China. 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. 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 Authors. Published by Elsevier Inc. All rights reserved.)

Disruption of the blood-brain barrier (BBB) is an important pathological hallmark of ischemic stroke. Blood-brain barrier disruption (BBBD) is a consequence of ischemia and may also exacerbate damage to brain parenchyma. Therefore, maintaining BBB integrity is critical for the central nervous system (CNS) homeostasis. This review offers a concise overview of BBB structure and function, along with the mechanisms underlying its impairment following a stroke. In addition, we review the recent imaging techniques employed to study blood-brain barrier permeability (BBBP) in the context of ischemic brain injury with the goal of providing imaging guidance for stroke diagnosis and treatment from the perspective of the BBBD. This knowledge is vital for developing strategies to safeguard the BBB during cerebral ischemia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The asymmetric cycloaddition between N -2,2,2-trifluoroethylisatin ketimines and unsymmetrical dicarbonyl-activated alkenes catalyzed by a bifunctional squaramide has been discovered. The present study demonstrates an efficient approach for the regio-, diastereo-, and enantioselective synthesis of densely functionalized 5'-trifluoromethylated 3,2'-pyrrolidinyl spirooxindoles featuring three different types of carbonyl groups.

Indoor environments serve as reservoirs for a variety of emerging pollutants (EPs), such as phthalates (PAE), with intricate interactions occurring between these compounds and indoor oxidants alongside dust particles. However, the precise mechanisms governing these interactions and their resulting environmental implications remain unclear. By theoretical simulations, this work uncovers multi-functional compounds and high oxygen molecules as important products arising from the interaction between DEP/DEHP and O 3 , which are closely linked to SOA formation. Further analysis reveals a strong affinity of DEP/DEHP for mineral dust surfaces, with an adsorption energy of 22.11/30.91 kcal mol -1 , consistent with a higher concentration of DEHP on the dust surface. Importantly, mineral particles are found to inhibit every step of the reaction process, albeit resulting in lower product toxicity compared to the parent compounds. Thus, timely removal of dust in an indoor environment may reduce the accumulation and residue of PAEs indoors, and further reduce the combined exposure risk produced by PAEs-dust. This study aims to enhance our understanding of the interaction between PAEs and SOA formation, and to develop a fundamental reaction model at the air-solid surface, thereby shedding light on the microscopic behaviors and pollution mechanisms of phthalates on indoor dust surfaces., 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.)

Structure, stability, electronic structure, spectroscopy and chemical bonding properties of a fluorine atom doped gas-phase small to medium-sized magnesium clusters, FMg n (n = 2-20), systematically investigated by CALYPSO software together with density functional theory (DFT). Structural calculations showed that FMg n has a structural diversity which is rarely reported in other magnesium-based clusters before. F atoms were always located in the outer layer of the Mg n host clusters and only two or three Mg atoms surround it. FMg 18 was revealed to be supposed to have robust relative stability. Charge transfer and density of states were calculated for analyzing the electronic structure characteristics. Theoretical calculations of IR, Raman and UV-Vis spectra were computed to provide data guidelines for future experimental observations. Finally, the F-Mg and Mg-Mg chemical bonds of the FMg n clusters were analyzed, including the critical bonding points (BCPs) of Laplacian of electron density (Δρ), electron localization function (ELF) and interaction region indicator (IRI). The kind and strength of chemical bonds reveal the mechanism by which the F atom was rapidly stabilized by Mg n (n = 2-20) host clusters., (© 2024. The Author(s).)

Problem: Chest radiography is a crucial tool for diagnosing thoracic disorders, but interpretation errors and a lack of qualified practitioners can cause delays in treatment. Aim: This study aimed to develop a reliable multi-classification artificial intelligence (AI) tool to improve the accuracy and efficiency of chest radiograph diagnosis. Methods: We developed a convolutional neural network (CNN) capable of distinguishing among 26 thoracic diagnoses. The model was trained and externally validated using 795,055 chest radiographs from 13 datasets across 4 countries. Results: The CNN model achieved an average area under the curve (AUC) of 0.961 across all 26 diagnoses in the testing set. COVID-19 detection achieved perfect accuracy (AUC 1.000, [95% confidence interval {CI}, 1.000 to 1.000]), while effusion or pleural effusion detection showed the lowest accuracy (AUC 0.8453, [95% CI, 0.8417 to 0.8489]). In external validation, the model demonstrated strong reproducibility and generalizability within the local dataset, achieving an AUC of 0.9634 for lung opacity detection (95% CI, 0.9423 to 0.9702). The CNN outperformed both radiologists and nonradiological physicians, particularly in trans-device image recognition. Even for diseases not specifically trained on, such as aortic dissection, the AI model showed considerable scalability and enhanced diagnostic accuracy for physicians of varying experience levels (all P < 0.05). Additionally, our model exhibited no gender bias ( P > 0.05). Conclusion: The developed AI algorithm, now available as professional web-based software, substantively improves chest radiograph interpretation. This research advances medical imaging and offers substantial diagnostic support in clinical settings., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Zeye Liu et al.)

Volatile organic compounds (VOCs) as environmental pollutants were associated with respiratory diseases. Pulmonary fibrosis (PF) was characterized by an increase of extracellular matrix, leading to deterioration of lung function. The adverse effects on lung and the potential mechanism underlying VOCs induced PF had not been elucidated clearly. In this study, the indoor VOCs exposure mouse model along with an ex vivo biosensor assay was established. Based on scRNA-seq analysis, the adverse effects on lung and potential molecular mechanism were studied. Herein, the results showed that VOCs exposure from indoor decoration contributed to decreased lung function and facilitated pulmonary fibrosis in mice. Then, the whole lung cell atlas after VOCs exposure and the heterogeneity of fibroblasts were revealed. We explored the molecular interactions among various pulmonary cells, suggesting that endothelial cells contributed to fibroblasts activation in response to VOCs exposure. Mechanistically, pulmonary microvascular endothelial cells (MPVECs) secreted Gas6 after VOCs-induced PANoptosis phenotype, bound to the Axl in fibroblasts, and then activated fibroblasts. Moreover, Atf3 as the key gene negatively regulated PANoptosis phenotype to ameliorate fibrosis induced by VOCs exposure. These novel findings provided a new perspective about MPVECs could serve as the initiating factor of PF induced by VOCs exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of this study was to examine the effects of NH 3 variations across different positions within a cage-reared duck house on the egg production performance and fecal microbiome in Muscovy ducks. Totals of 3,168 female Muscovy ducks (180 ± 2 d) were randomly assigned to 1,056 cages. From d 293 to 300, the egg production rate and levels of NH 3 , H 2 S, CO 2 , temperature, humidity, light intensity, and dust particles were recorded. Two spatial distribution-based experimental classification methods were applied, one grouping ducks into Front, Middle, and End categories, and the other into First, Second, and Third layers. On d 300, serum and feces samples were collected for further analysis. The result showed that both the egg production rate and serum PROG level in the Front were higher than End (P < 0.05). However, no significant differences were found among the First, Second, and Third groups. Among the environmental factors, ammonia (NH 3 ) is a major harmful gas in cage-reared duck houses, with observed concentrations showing a gradient from lower levels in the Front group to higher levels in the Middle group (P < 0.05), and even higher levels in the End group (P < 0.05). Gene sequencing of the 16S rRNA gene revealed a higher relative abundance of Firmicutes in both the Front and Middle groups compared to the End group (P < 0.05). Specifically, within the Firmicutes phylum, the relative abundance of Lactobacillus and Romboutsia was notably higher in the Front group compared to both the Middle and End groups (P < 0.05). What's more, the abundance of Lactobacillus had a negative correlation with NH 3 concentration and positive correlation with egg production rate. In conclusion, NH 3 concentrations showed variations across different areas of the cage-reared duck house, with higher levels detected at the rear. The elevated NH 3 level was identified as the main factor negatively impacting egg production in Muscovy ducks and contributing to a decline in the abundance of Firmicutes, specifically Lactobacillus., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We explored the effects of two formulas, extensively hydrolyzed formula (EHF) and amino acid-based formula (AAF), on the gut microbiota and short-chain fatty acids (SCFAs) in infants with food protein-induced enterocolitis syndrome (FPIES)., Methods: Fecal samples of thirty infants with bloody diarrhea receiving EHF or AAF feeding were collected at enrollment, diagnosis of FPIES, and four weeks after diagnosis. The gut microbiota and SCFAs were analyzed using 16 S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively., Results: Microbial diversity of FPIES infants was significantly different from that of the controls. FPIES infants had a significantly lower abundance of Bifidobacterium and a higher level of hexanoic acid compared with controls. In EHF-fed FPIES infants, microbial richness was significantly decreased over time; while the microbial diversity and richness in AAF-fed FPIES infants exhibited no differences at the three time points. By four weeks after diagnosis, EHF-fed FPIES infants contained a decreased abundance of Acinetobacter, whereas AAF-fed FPIES infants contained an increased abundance of Escherichia-Shigella. EHF-fed infants experienced significantly decreased levels of butyric acid and hexanoic acid at four weeks after diagnosis., Conclusions: Infants with FPIES had intestinal dysbiosis and different formulas differentially affected gut microbiota and SCFAs in FPIES infants., Impact: We firstly report the impacts of two different nutritional milk formulas on the gut microbial composition and SCFAs levels in infants with FPIES. We show that infants with FPIES have obvious intestinal dysbiosis and different formulas differentially affect gut microbiota and SCFAs in FPIES infants. Understanding the effects of different types of formulas on gut microbial colonization and composition, as well as the related metabolites in infants with FPIES could help provide valuable insights for making choices about feeding practices., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Possessing excellent electronic properties and high chemical stability, semiconducting n-type two-dimensional (2D) tin dioxide (SnO 2 ) nanosheets have been featured in sensing and electrocatalysis applications recently. Derived from non-layered crystal structures, 2D SnO 2 has abundant unsaturated dangling bonds existing at the surface, providing interfacial activity. How the surface chemistry alters the electronic properties of 2D SnO 2 nanomaterials remains unexplored. In this study, we synthesised ultra-thin 2D SnO 2 nanosheets using a liquid metal (LM) touch printing technique and investigated experimentally and theoretically how the interactions of organic solvents composed of alkyl and hydroxyl groups with the surface of LM-derived 2D SnO 2 modulate the electronic properties. It was found that alkane solvents can physically absorb onto the SnO 2 surface with no impact on the material conductivity. Alcohol-based solvents on the other hand interact with the SnO 2 surface via chemical absorptions primarily, in which oxygen atoms of hydroxyl groups in the alcohols form bonds with the surface atoms of SnO 2 . The binding stability is determined by the length and configuration of the hydrocarbon chain in alcohols. As representative long-chain alcohols, 1-octanol and 1-pentanol attach onto the SnO 2 surface strongly, lowering the binding energy of Sn 4+ and reducing the electron transfer ability of SnO 2 nanosheets. Consequently, the electronic properties, i.e. conductivity and electronic mobility of SnO 2 nanosheet-based electronic devices are decreased significantly.

This study addresses the issue of construction stagnation affecting the adhesion and tensile properties of hydraulic asphalt concrete with acid aggregate. It investigates the impact of rest periods on the tensile characteristics of such materials under standard construction conditions. The influence of varying rest durations and asphalt temperatures on the tensile behavior of the concrete is assessed through indoor experiments. The bonding between asphalt and aggregate is examined, along with the tensile property variations of the concrete. The study found that the standstill time significantly affects the adhesion of asphalt, with the adhesion decreasing progressively with increased temperature and rest time, irrespective of the addition of anti-stripping agents. However, the inclusion of these agents can mitigate the reduction in adhesion. Furthermore, the study identified that rest duration has a more substantial impact on adhesion than temperature. The splitting tests demonstrate that the tensile properties of asphalt concrete are considerably affected by the resting time. Over a period of 0, 10, 20, and 30 days of rest, an increase in splitting strength and a decrease in splitting displacement were observed. The findings offer valuable insights for predicting the tensile performance of asphalt concrete in practical engineering applications after a period of rest.

Air pollution has been recognized as a contributing factor to sleep disorders (SD), which have been correlated with an elevated susceptibility to a variety of human diseases. Nevertheless, research has not definitively established a connection between SD and interior decorative volatile organic compounds (ID-VOCs), a significant indoor air pollutant. In this study, we employed a mouse model exposed to ID-VOCs to explore the impacts of ID-VOCs exposure on sleep patterns and the potential underlying mechanism. Of the 23 key compositions of ID-VOCs identified, aromatic hydrocarbons were found to be the most prevalent. Exposure to ID-VOCs in mice resulted in SD, characterized by prolonged wake fullness and decreased sleep during the light period. ID-VOCs exposure triggered neuroinflammatory responses in the suprachiasmatic nucleus (SCN), with microglia activation leading to the overproduction of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and complement component 1q (C1q), ultimately inducing A1 astrocytes. Consequently, the upregulation of branched chain amino acid transaminase 2 (BCAT2) in A1 astrocytes resulted in elevated extracellular glutamate and disruption of the wake-sleep transition mechanism, which might be the toxicological mechanism of SD caused by ID-VOCs., 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.)

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles published in or before June 2023 using PubMed, Google Scholar, and Web of Science. The searched keywords in scientific databases were ferroptosis, cancer, tumor, traditional Chinese medicine, botanical drugs, and phytomedicine. Only research related to ferroptosis, the metabolites from TCM, and cancer was considered. In this review, we introduce an overview of the current knowledge regarding the ferroptosis mechanisms and review the research advances on the metabolites of TCM inhibiting cancer by targeting ferroptosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Zhuang, Zhao, Gu, Zhang, Bi, Wang, Bao, Li, Zhang and Zhu.)

The dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics., (© 2024. The Author(s).)

Purpose: Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature., Case Presentation: A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg)., Conclusion: Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We report a case of fibrous dysplasia (FD) with aneurysmal bone cyst (ABC)-like change in a child with orbital involvement, review the related cases, and discuss clinical features, therapy, and prognosis of this disease., Case Presentation: A 10-year-old girl had right proptosis (degree of exophthalmos: OD 16 mm, OS 13 mm) and limited vision (visual acuity: OD 1.0, OS 0.8) without trauma. Preoperative CT showed a 5.0*4.3 cm right-sided crania-orbital communicating tumor. MRI indicated a well-defined multicystic mass with scattered fluid levels and soap bubble-like alterations. The child underwent total tumor resection and orbital parietal titanium mesh reconstruction. At 20 months of follow-up, the child has recovered from ocular problems, and the tumor has not recurred., Conclusion: FD combined with ABC rarely occurs in orbit and generally begins with ocular symptoms. The etiology is uncertain. Early diagnosis and surgery are essential. Complete resection is suggested whenever possible because residual lesions may recur., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Owing to the widespread use and improper emissions of carbon black nanoparticles (CBNPs), the adverse effects of CBNPs on human health have attracted much attention. In toxicological research, carbon black is frequently utilized as a negative control because of its low toxicity and poor solubility. However, recent studies have indicated that inhalation exposure to CBNPs could be a risk factor for severe and prolonged pulmonary inflammation and fibrosis. At present, the pathogenesis of pulmonary fibrosis induced by CBNPs is still not fully elucidated, but it is known that with small particle size and large surface area, CBNPs are more easily ingested by cells, leading to organelle damage and abnormal interactions between organelles. Damaged organelle and abnormal organelles interactions lead to cell structure and function disorders, which is one of the important factors in the development and occurrence of various diseases, including pulmonary fibrosis. This review offers a comprehensive analysis of organelle structure, function, and interaction mechanisms, while also summarizing the research advancements in organelles and organelle interactions in CBNPs-induced pulmonary fibrosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hydraulic asphalt concrete is known for its excellent seepage control performance and strong deformation resistance. This engineering material has widespread applications in the seepage control structures of hydraulic buildings. Recent projects have investigated the use of acidic aggregates to improve economic efficiency. However, they have also highlighted the weaker adhesion between acidic aggregates and asphalt, which necessitates stringent construction process control. This study investigates the impact of resting conditions on the tensile properties of acidic aggregate hydraulic asphalt concrete. The results of the tensile testing indicate that the storage time significantly affects the performance of asphalt concrete. The tensile strength of the specimens without anti-stripping agents decreased from 1.711 MPa to 0.914 MPa after resting periods of 0, 10, 20, and 30 days. The specimens treated with anti-stripping agents also showed a decrease in tensile strength over time, similar to the trend observed in the previous specimens. Digital specimen simulations indicated a decrease in cohesion between the asphalt and the aggregate from 5.375 MPa to 2.664 MPa after 30 days, representing a reduction of 50.44%. To counteract the effect of the storage time on the bonding between acidic aggregates and asphalt, this study recommends reducing the grading index and maximum size of aggregates, decreasing the coarse aggregate content, and selecting smooth aggregate shapes.

Objective: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer., Methods: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed., Results: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3., Conclusions: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies., (© 2024. The Author(s).)

Purpose: Numerous methods have been proposed to characterise tubercle lateralisation. However, their normal values and related changes remain unclear. Accordingly, it was aimed to determine the potential sex and age effects and determined the optimal individualised method of diagnosing lateralisation of the tibial tubercle in patients with recurrent patellar dislocation (RPD)., Methods: Measurements included the tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance and tibial tubercle lateralisation (TTL); and the proximal tibial width (PTW), trochlear width (TW) and trochlear dysplasia index (TDI), for adjustment. A two-way analysis of variance was used to determine the effect of age, sex and their interaction within the normal group. When the age effect was statistically significant, a nonlinear regression was created. Areas under the receiver-operating characteristic curve (AUCs) were calculated to assess diagnostic accuracy., Results: A total of 277 normal participants (mean [SD] age, 13.5 [2.6] years; 125 [45.1%] female) and 227 patients with RPD (mean [SD] age, 13.5 [2.6] years; 161 [58.1%] female) were analysed. It was found that in the normal group, in patients aged 7-10, TT-PCL distance (p = 0.006), TTL (p = 0.007) and TT-PCL/PTW (p < 0.001) were significantly larger in females than in males. A significant sex effect was also detected on TT-TG/TW (p = 0.014). TT-TG distance, TT-PCL distance, TTL and TT-PCL/PTW (in male patients) approached an established normal adult value of 12.3 mm, 20.9 mm, 0.64 and 0.28, respectively, with increasing age (p < 0.001). The AUC was greater for TT-TG/TDI and TT-TG/TW (p ≤ 0.01) and TT-TG/TDI outperformed TT-TG/TW in patients aged 15-18 (p = 0.004)., Conclusions: Tubercle lateralisation increased with age and was affected by sex, with the exception of TT-TG distance and TT-TG/TDI. TT-TG/TDI is the optimal method of diagnosing a lateralized tibial tubercle in patients with RPD. These findings assist with the evaluation of tubercle lateralisation in that they provide a proper protocol for paediatric and adolescent populations with RPD; and thus, will help determine whether medial tubercle transfer should be included among the tailored surgical procedures considered for the treatment of patients with RPD., Level of Evidence: Level III., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Long-term exposure to inhalable silica particles may lead to severe systemic pulmonary disease, such as silicosis. Exosomes have been demonstrated to dominate the pathogenesis of silicosis, but the underlying mechanisms remain unclear. Therefore, this study aimed to explore the roles of exosomes by transmitting miR-107, which has been linked to the toxic pulmonary effects of silica particles. We found that miR-107, miR-122-5p, miR-125a-5p, miR-126-5p, and miR-335-5p were elevated in exosomes extracted from the serum of patients with silicosis. Notably, an increase in miR-107 in serum exosomes and lung tissue was observed in the experimental silicosis mouse model, while the inhibition of miR-107 reduced pulmonary fibrosis. Moreover, exosomes helped the migration of miR-107 from macrophages to lung fibroblasts, triggering the transdifferentiation of cell phenotypes. Further experiments demonstrated that miR-107 targets CDK6 and suppresses the expression of retinoblastoma protein phosphorylation and E2F1, resulting in cell-cycle arrest. Overall, micron-grade silica particles induced lung fibrosis through exosomal miR-107 negatively regulating the cell cycle signaling pathway. These findings may open a new avenue for understanding how silicosis is regulated by exosome-mediated cell-to-cell communication and suggest the prospect of exosomes as therapeutic targets., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Neuronal intranuclear inclusion disease (NIID) is an underdiagnosed neurodegenerative disorder caused by pathogenic GGC expansions in NOTCH2NLC . However, an increasing number of reports of NOTCH2NLC GGC expansions in patients with Alzheimer disease, essential tremor, Parkinson disease, amyotrophic lateral sclerosis, and oculopharyngodistal myopathy have led to the proposal of a new concept known as NOTCH2NLC -related GGC repeat expansion disorders (NREDs). The majority of studies have mainly focused on screening for NOTCH2NLC GGC repeat variation in populations previously diagnosed with the associated disease, subsequently presenting it as a novel causative gene for the condition. These studies appear to be clinically relevant but do have their limitations because they may incorrectly regard the lack of MRI abnormalities as an exclusion criterion for NIID or overlook concomitant clinical presentations not typically observed in the associated diseases. Besides, in many instances within these reports, patients lack pathologic evidence or undergo long-term follow-up to conclusively rule out NIID. In this review, we will systematically review the research on NOTCH2NLC 5' untranslated region GGC repeat expansions and their association with related neurologic disorders, explaining the limitations of the relevant reports. Furthermore, we will integrate subsequent studies to further demonstrate that these patients actually experienced distinct clinical phenotypes of NIID., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)