Search

Yuwei Jiang,1,2,* Wenjun Dang,3,* Lirong Sui,1 Tianci Gao,1 Xiangying Kong,1 Jin Guo,1 Shuang Liu,1 Hong Nie,3 Zhimei Jiang1,2 1College of Rehabilitation Medicine, Jiamusi University, Jiamusi City, Hei longJiang Province, People’s Republic of China; 2Pediatric Cerebral Palsy Prevention and Treatment Center of Heilongjiang Province, Jiamusi City, Hei longJiang Province, People’s Republic of China; 3College of Jiamusi, HeiLongJiang University of Chinese Medicine, Jiamusi City, Hei longJiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhimei Jiang; Shuang Liu, Email 15704601990@163.com; 307692456@qq.comAbstract: We conducted an umbrella evaluation to quantitatively synthesize previous systematic reviews and meta-analyses, thereby collating evidence on the association between vitamin D and core symptoms in people with autism in anticipation of informing clinical vitamin D supplementation. Based on the pre-established protocol, we ended up with 9 studies. Based on rigorous analysis, we found that vitamin D deficiency early in life is a risk factor for the development of ASD and that vitamin D supplementation improves the core symptoms of ASD. Our study concludes that vitamin D supplementation is beneficial for individuals with autism, that vitamin D deficiency early in embryonic life increases the risk of ASD, and that our study supports the idea that prevention begins with vitamin D supplementation early in life. At the same time, we must recognize that our current conclusions support the benefits of vitamin D supplementation for children with ASD, but we are unable to determine the causal relationship, ie, how vitamin D works in ASD, and we need more basic research to explore the mechanisms involved.Keywords: autism spectrum disorders, vitamin D, core symptoms, 25(OH)D, umbrella review

Objective·To explore the expression of sorting nexin 1 (SNX1) in colorectal cancer (CRC) and its impact on the proliferation and migration of CRC cells.Methods·Transcriptomic data and clinical pathological information of CRC were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases for enrichment analysis with Gene Set Enrichment Analysis (GSEA) software. The expression of SNX1 in CRC tissues and cells was detected by quantitative real-time polymerase chain reaction (qPCR), Western blotting, and immunohistochemistry staining (IHC). Small interfering RNA (siRNA) was used to knock down the expression of SNX1 to observe its effect on tumor cell proliferation and migration. Correlation analysis was conducted to explore the potential molecular mechanisms underlying SNX1-mediated CRC cell migration, and mRNA level validation was performed in SNX1 knockdown cell lines.Results·Analysis of CRC patients data in TCGA and tissue microarrays revealed that SNX1 expression was downregulated in CRC tissues and correlated with tumor diameter and distant metastasis. Knockdown of SNX1 enhanced tumor cell proliferation and migration. The expression of SNX1 was negatively correlated with metastasis associated in colon cancer 1 (MACC1), mesenchymal to epithelial transition factor (MET), and Notch; knockdown of SNX1 led to upregulation of these genes. Silencing SNX1 resulted in the downregulation of the epithelial marker cadherin 1 (CDH1) and the upregulation of vimentin (VIM) and Snail family transcriptional repressor 1 (SNAI1).Conclusion·SNX1 expression was significantly downregulated in CRC tissues and correlated with patient prognosis. Low expression of SNX1 enhanced the proliferation and migration of CRC cells and was associated with the MACC1-MET pathway and EMT. SNX1 may serve as a potential biomarker for poor prognosis and a novel therapeutic target in CRC.

For large-scale low earth orbit (LEO) satellite networks, two new inter-satellite link (ISL) connection strategies named Grid-V and Grid+ were proposed, which improved the traditional Grid connection strategy. The proposed strategies made full use of the ISL connected to adjacent and cross-adjacent orbits. The Grid-V connection strategy abandoned the intra-orbit links of the Grid connection strategy and used ISL of the adjacent and cross-adjacent orbits to form the network topology. The Grid+ connection strategy, while retaining the Grid connection strategy, allowed satellites to establish cross-satellite connections with satellites in the same orbit or the cross-adjacent orbits. For the large-scale LEO satellite network with a Walker-Delta constellation configuration, a shortest distance inter-satellite routing algorithm was designed based on the proposed ISL connection strategies, and system-level simulations were conducted from the perspectives of geometric topology and packet respectively to evaluate the performance of each connection strategy. Simulation results show that, from the perspective of geometric topology, the proposed strategies can effectively reduce the average number of routing hops and path switches. At the packet level, the proposed strategies exhibit better performance in terms of round-trip time and jitter, path occupation ratio, average throughput and so on.

The water vapor content is a crucial factor in assessing cloud water resources, and the content and distribution of cloud liquid water are important reference indicators for determining the quantity and location of catalysts in weather modification operations. Based on inversion results of G-band water vapor radiometer, ground-based microwave radiometer and cloud radar, combined with FY-4A measurements, meteorological observations, radar products and reanalysis data, distribution characteristics of water vapor and liquid water in the warm zone of a stratiform cloud is studied in North China on 15 May 2021, in order to provide some reference for the study of macro-micro structure and precipitation mechanism of the warm zone of precipitable stratiform clouds and weather modification operations.The horizontal distribution of the warm zone is not uniform, and there is also clear horizontal inhomogeneity in the distribution of water vapor and liquid water. The integrated water vapor content and liquid water path, detected by G-band water vapor radiometer, fluctuate during the level flight of aircraft, with maximum values of 4.00 cm and 1.87 mm, respectively. As the cloud top height and cloud thickness decrease in the warm zone, the integrated water vapor content and liquid water path also decrease to 0.89 cm and 0.13 mm. The liquid water path detected by G-band water vapor radiometer is primarily derived from low-level clouds in the warm zone and is also influenced by high-level supercooled water clouds or mixed clouds. With the onset of precipitation, the ground-based microwave radiometer detected a surge in integrated water vapor content and liquid water path, reaching peaks of 8.62 cm and 3.85 mm, respectively. The thickness of liquid water content accumulation zone, as well as its maximum value and height in the vertical direction, initially increase and then decrease with precipitation. The temporal and spatial evolution of liquid water is highly significant for understanding the occurrence and development of precipitation, as well as for identifying the timing and location of precipitation enhancement in warm zones. The liquid water content retrieved by the cloud radar also exhibits a jump phenomenon. When the reflectivity factor of the cloud radar is high and the falling velocity and velocity dispersion of particles are high below 1 km, the liquid water content is abundant, leading to significant rainfall on the ground. Particle collision is the primary mechanism of precipitation in the warm zone.

ObjectivesQuantitatively assess the severity and predict the mortality of interstitial lung disease (ILD) associated with Rheumatoid arthritis (RA) was a challenge for clinicians. This study aimed to construct a radiomics nomogram based on chest computed tomography (CT) imaging by using the ILD-GAP (gender, age, and pulmonary physiology) index system for clinical management.MethodsChest CT images of patients with RA-ILD were retrospectively analyzed and staged using the ILD-GAP index system. The balanced dataset was then divided into training and testing cohorts at a 7:3 ratio. A clinical factor model was created using demographic and serum analysis data, and a radiomics signature was developed from radiomics features extracted from the CT images. Combined with the radiomics signature and independent clinical factors, a nomogram model was established based on the Rad-score and clinical factors. The model capabilities were measured by operating characteristic curves, calibration curves and decision curves analyses.ResultsA total of 177 patients were divided into two groups (Group I, n = 107; Group II, n = 63). Krebs von den Lungen-6, and nineteen radiomics features were used to build the nomogram, which showed favorable calibration and discrimination in the training cohort [AUC, 0.948 (95% CI: 0.910–0.986)] and the testing validation cohort [AUC, 0.923 (95% CI: 0.853–0.993)]. Decision curve analysis demonstrated that the nomogram performed well in terms of clinical usefulness.ConclusionThe CT-based radiomics nomogram model achieved favorable efficacy in predicting low-risk RA-ILD patients.

This paper precisely explores the structure and characteristics of college students’ healthy human capital and its influencing factors. It aims to enhance students’ positive and healthy mindset and promote optimism in life and learning. A solid analytical framework is constructed by sorting out the ordered multicategorical logistic regression model and parameter estimation methods and the application steps of the propensity score matching model. College students from ten colleges and universities in Hunan Province were selected as research subjects, and a questionnaire was designed to assess their healthy human capital. The specific factors affecting college students’ healthy human capital accumulation were analyzed in depth through the probability density analysis of propensity score matching, standard support hypothesis testing, and the parallel line test and regression results of the ordered multicategorical regression model. The findings show that the curves of the experimental and control groups after propensity score matching almost overlap in the [0.2,0.4] interval, indicating the method’s validity. A more important finding is that the number of college students with poor self-assessed physical health is 8.063 times higher than that of college students with self-assessed mental health as good, which emphasizes the significant impact of mental health on healthy human capital. Therefore, to effectively improve the health human capital of college students, students, families and universities must form a linkage mechanism and work together to cultivate college students’ health awareness.

Ethnopharmacological Relevance: 2,3,5,4'-tetrahydroxy-stilbene-2-O-β-D-glucoside (TSG) is the principal bioactive compound contained in Polygonum multiflorum Thunb. (PMT), which is traditionally recorded to possess tonic and anti-aging efficacy., Aim of the Study: To identify the TSG-provided promotion on liver regeneration (LR) following partial hepatectomy (PHx) in mice and to explicate its involved mechanism., Materials and Methods: The promotion of TSG on LR was evaluated by hematoxylin and eosin (H&E), 5-bromodeoxyuridinc (BrdU) and Ki-67 staining, and measuring the level of proliferating cell nuclear antigen (PCNA) and Cyclin D1 in mice with PHx at different time points. Gene Expression Omnibus (GEO, GSE15239) database and the label-free quantitative proteomics from liver of mice at 24 h after PHx were integrated to identify potential involved critical proteins, which were verified by Western-blot, Real-time polymerase chain reaction (RT-PCR), molecular docking and luciferase activity assay. Primary hepatocytes isolated from mice were used to investigate the TSG-provided promotion on proliferation in vitro., Results: TSG (20 mg/kg) promoted LR in mice after PHx. Results from RNA expression data from clinical samples and proteomic analysis from liver tissues indicated that peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid metabolism pathway were crucially associated with the TSG-provided promotion on LR. TSG enhanced the nuclear translocation of PPARα and the mRNA expression of a series of PPARα-regulated downstream genes. In addition, TSG lowered hepatic triglyceride (TG) and non-esterified fatty acid (NEFA) amounts and increased hepatic adenosine triphosphate (ATP) level in mice after PHx. TSG up-regulated the transcriptional activity of PPARα in vitro. Next results displayed that TSG promoted cell proliferation as well as ATP level in mice primary hepatocytes, which were abolished when PPARα was suppressed. Meanwhile, the cell viability was also elevated in mice primary hepatocytes treated with ATP., Conclusion: Activating PPARα-mediated fatty acid β-oxidation (FAO) pathway led to the production of ATP, which contributed to the TSG-provided promotion on LR after PHx in mice., 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: Coronary artery lesions are the most severe complications of Kawasaki disease. Despite recent advances, evidence of the association between risk factors and coronary artery lesion is lacking. In this study, we demonstrated the potential clinical indicators that could assist to evaluate the prevalence of coronary artery lesion among paediatric patients with Kawasaki disease., Methods: We retrospectively enrolled 260 paediatric patients with Kawasaki disease. Patients with coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries were included in this study. Medical records of each patient were collected. Logistic regression analysis was performed to explore risk factors and the occurrence of coronary artery lesion in patients with Kawasaki disease., Results: Respectively, 64 (24.6%), 39 (15%), and 56 patients (21.5%) of the participants had coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries. Univariate analysis revealed that age, gender, duration of fever, time of initial use of intravenous immunoglobulin, erythrocyte sedimentation rate, white blood cell counts, time of platelet increase, the maximum value of platelet, albumin, and immunoglobulin G level was associated with coronary artery lesion. In multivariable logistic analysis, those younger and mainly males were associated with all three outcomes of coronary artery lesion, lower serum albumin levels, and later initial use of intravenous immunoglobulin were linked to a higher risk of coronary dilation and coronary aneurysm., Conclusions: The potential risk factors that could be used to estimate the occurrence of coronary artery lesion in Kawasaki disease patients are young age, male, lower serum albumin lever, and later initial use of intravenous immunoglobulin. However, long-term follow-up and multi-centre studies are required to verify our findings in the future.

An increasing number of traditional Chinese medicine(TCM) have been confirmed to possess analgesic bioactivity. 701 Dieda Zhentong patch(701-DZP) which includes 14 kinds of TCMs exhibited excellent efficacy in alleviating back or leg pain after a soft-tissue injury. In this study, UPLC/MS was used to construct the fingerprint of 701-DZP and excavate the potential bioactive ingredients of it. 21 compounds were detected and identified in the fingerprint including 12 compounds that pass through the skin and 6 compounds observed in the plasma. Then, the role of 701-DZP in neuropathic pain(NPP) was assessed by network pharmacology and CCI rats. 701-DZP inhibited pain sensitization(MWT and TWL) and the release of inflammation mediators(IL-1β and IL-6) in CCI rats which were in keeping with the core targets of the PPI network. The results of IHC and Western blot showed that the expression of the P2X3 receptor in the DRG and SC of CCI rats was significantly reduced after the treatment with 701-DZP. Moreover, the 701-DZP down-regulated the level of phosphorylation of ERK1/2 MAPK instead of P38 MAPK in the DRG of CCI rats. In conclusion, this study has clarified 6 potential analgesic active compounds of 701-DZP and explored the analgesic properties, which may inhibit the expression of the P2X3 receptor to reduce the release of inflammatory mediators based on the ERK1/2 MAPK pathway to alleviate the NPP., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The gap connexins of astrocytes play a crucial role in facilitating neuronal coordination and maintaining the homeostasis of the central nervous system. Cx30/Cx43 are the main proteins constituting these gap junctions, and the glutamate transporter EAAT1 associates with nerve injury. However, the role and mechanism underlying the changes of astrocytic connexins and EAAT1 during cerebral ischemia-reperfusion injury remain unclear. In this study, we investigated the expressions of Cx30, Cx43, and EAAT1 in OGD/R-treated astrocytes and in a MCAO/R animal model using gap junction inhibitors and siRNAs targeting Cx43 and Cx30. The differences of cell viability, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), reactive oxygen species (ROS) and glutamate in cells and tissues were detected. Our results indicate that OGD/R exposure leads to the decline of astrocyte activity, which, in turn, adversely affects neuronal health. Ischemia-reperfusion induced increasing Cx43 and EAAT1 expression and decreasing Cx30 expression in astrocytes and animal brain tissue. Moreover, ischemia-reperfusion resulted in heightened MDA and ROS levels and reduced CAT and SOD activities in both astrocytes and the surrounding brain tissue. The release of glutamate from astrocytes and its concentration in animal brain tissue significantly increased following ischemia-reperfusion. Inhibition Cx43 expression through Gap26 or siRNA effectively mitigated the increase in EAAT1 and glutamate levels, as well as the oxidative stress changes induced by ischemia-reperfusion. Therefore, Brain astrocytes may mediate the effects of cerebral ischemia-reperfusion injury by influencing glutamate transporters and glutamate dynamics in response to oxidative stress through Cx30/Cx43., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Shell color is an important economic trait and one of the target traits in breeding and production. Non-coding RNA (ncRNA) refers to RNA molecules transcribed from the genome and do not encoding proteins, which can regulate the expression of target genes after transcription and participate in the regulation of many important traits, such as the formation of shell color and body color. In this study, we detected the porphyrins in the shells of three Manila clams with different shell colors, explored the expression pattern and function of Uroporphyrinogen III synthetase (UROS) in the shell color pigmentation of Ruditapes philippinarum, and found that it might be involved in the synthesis of porphyrins and potentially in the synthesis of melanin. The results showed that the expression levels of heme synthesis-related genes such as UROS, Uroporphyrinogen decarboxylase (UROD), Ferrochelatase (FECH), Hephaestin (HEPH), and pigment synthesis-related genes (Peroxidasin PXDN) in the positive group were significantly reduced compared with the control group after injection of UROS dsRNA, indicating that UROS plays a crucial role in the porphyrin synthesis pathway. Additionally, transmission electron microscopy and melanin extraction experiments also proved that it might participate in the synthesis of melanin. We further explored and verified the relationship between TCONS_00025035-miR-101-UROS and identified the changes in the expression level of UROS through RNA interference and injection of miR-101 antagomir, respectively. Our results imply that miR-101 antagonists affect the expression of UROS. Furthermore, dual-luciferase reporter gene experiments confirmed the relationship between TCON_00025035, miR-101, and UROS. The regulatory relationship between TCONS_00025035 and miR-101 is negative, and the regulatory relationship between miR-101 and UROS is also negative. In summary, we verified the function of UROS through RNA interference, qPCR, in situ hybridization, and melanin content detection. We speculated that there was a negative relationship between miR-101 and UROS, and there was also a negative relationship between TCONS_00025035 and miR-101. TCONS_00025035 might regulate UROS through the regulation of miR-101, and UROS might also regulate other pigmentation-related genes and affect the formation of pigments, thereby influencing porphyrin and melanin formation in Manila clam., 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.)

Pathological retinal neovascularization (RNV) is a prevalent characteristic of various ocular diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and retinal vein occlusion (RVO). While the importance of N6-methyladenosine (m6A) modification in diverse disease contexts is well-established, its functional role in pathological RNV remains unclear. Herein, we investigated the involvement of m6A modification and its core methyltransferase, METTL14, in a model of oxygen-induced retinopathy (OIR) to elucidate their contribution to retinal angiogenesis. In this study, we observed heightened levels of m6A modification and elevated expression of METTL14 in the OIR model, suggesting their potential implication in pathological RNV. Employing targeted knockdown of METTL14, we revealed that its depletion activated autophagy flux in human retinal vascular endothelial cells (HRVECs), consequently inhibiting the angiogenic capacity of endothelial cells. Mechanistically, we demonstrated that METTL14 exerts its regulatory influence on autophagy flux by modulating the stability of ATG7, a pivotal protein involved in autophagy. Specifically, METTL14 knockdown led to increased ATG7 expression at both mRNA and protein levels, accompanied by reduced m6A methylation of ATG7 mRNA and enhanced mRNA stability. Moreover, silencing of ATG7 counteracted the effects of METTL14 knockdown on endothelial cell functions, emphasizing ATG7 as a downstream target of METTL14-mediated autophagy in HRVECs. After all, our findings provide valuable insights into the pathogenesis of retinal pathological angiogenesis and potential therapeutic targets for the treatment of ocular neovascular diseases., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Cavidine (CAV) is the main bioactive ingredient of Corydalis ternata f. yanhusuo (Y.H.Chou & Chun C.Hsu) Y.C.Zhu, which is a traditional Chinese herbal containing a variety of uses such as analgesic, anticancer, and anti-inflammatory properties., Aim of the Study: The goal is to screen Corydalis yanhusuo for anti-central sensitization active components and investigate and clarify the pharmacological mechanism and therapeutic efficacy of the active ingredient CAV in the treatment of chronic pain., Material and Methods: First, cell membrane immobilized chromatography was used to screen the bioactive ingredients in Corydalis yanhusuo. Spare nerve injury (SNI) model and complete Freund's adjuvant (CFA) mice model were constructed to identify the analgesic effect of CAV. RNA-seq and bioinformatics analyses were used to explore the potential targets of CAV in CFA mice and SNI mice. HE staining was used to observe the infiltration of inflammatory cells in the dorsal root ganglion (DRG) and spinal cord(SC) of CFA mice and SNI mice. WB and qPCR were used to detect the level of inflammatory factors TNF-α, IL-1β, and IL-6 in DRG and SC of mice. SNI and CFA mice were used to study the effect and mechanism of CAV on microglial activation., Results: 9 potential active ingredients were screened out from Corydalis yanhusuo that can regulate P2X3 receptors. CAV showed good analgesic effects, increased the mechanical pain and thermal pain thresholds of CFA mice and SNI mice, inhibited the expression of DRG and SC inflammatory factors, downregulated IBA-1, and inhibited microglial activation. Further in vivo and in vitro experiments showed that CAV significantly inhibited the expression of P2X3 receptors and the activation of its downstream MAPK pathway in DRG neurons and SC., Conclusion: This study is the first to indicate that CAV exerts an analgesic effect by inhibiting microglia activation via the P2X3 signaling pathway axis, providing the clinical utility of CAV in chronic pain therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The high-altitude, low-oxygen environment of the Qinghai-Tibet Plateau poses significant challenges for the introduction of superior livestock breeds. However, local plateau species have adapted to thrive and reproduce under these harsh conditions. Understanding the molecular mechanisms behind plateau animals' adaptation to low-oxygen environments is essential for breeding livestock suited to high-altitude regions. Tibetan pigs, which have undergone long-term natural selection and artificial breeding, have developed the ability to survive and reproduce in hypoxic environments. In this study, we conducted whole-genome resequencing of 30 Tibetan pigs from high-altitude regions and 30 Diannan small-ear pigs from low-altitude areas, to identify candidate genes that support Tibetan pigs' adaptation to hypoxic conditions through selection signal analysis. Additionally, we performed transcriptome sequencing on five tissues (heart, liver, spleen, lung, and bone marrow) from both Tibetan pigs and Diannan small-ear pigs to identify genes with significant differential expression between the two breeds. We then integrated the genomic and transcriptomic data by examining the expression of candidate genes identified in selection signal analysis across different tissues. The selection signal analysis identified 10 genes- HES 4, ANGPT 1, HIF3 A, SPHK 2, PCK 2, RCN 3, HIGD2 A, DNM 2, IRF 9, and SRF -that were under positive selection in the Tibetan pig population and are associated with hypoxia adaptation. When combined with transcriptome data, we found that five of these genes- HIF3 A, RCN 3, HIGD2 A, PCK 2, and IRF 9-exhibited differential expression. Through an integrated approach of selection signal and transcriptome analysis, we identified five key functional genes that contribute to the adaptation of Tibetan pigs to hypoxic environments. These findings offer new insights into the adaptability of plateau animals., 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 Ni, Tang, Zhu, Li, Zhang, Nie, Ye, Wang, Zhu, Kong and Gou.)

Aim: As non-operative management of rectal cancer proliferates, re-staging and surveillance methods are critical in selecting appropriate patients for organ preservation versus proctectomy. In previous work, the authors have shown that transrectal acoustic resolution photoacoustic microscopy (ARPAM) co-registered with ultrasound can differentiate residual cancer from complete tumoural response to neoadjuvant therapy. We hypothesize that these findings are due to changes in microvascular density (MVD)., Methods: Patients with rectal adenocarcinoma who underwent neoadjuvant therapy, transrectal photoacoustic imaging and resection were included. We first compared immunohistochemical staining with erythroblast transformation-specific-related gene (ERG) immunostain to standard CD31 to confirm adequate identification of endothelium. Tissue sections from identical blocks were stained with CD31 and ERG, and then a correlation was calculated between manually labelled CD31-stained vessels and ERG nuclei density. Second, representative tissue blocks from responders, partial responders and non-responders were stained with ERG. ERG nuclei density was quantified as a proxy for MVD., Results: CD31 MVD and ERG nuclei density were strongly correlated (R 2  = 0.87; P < 0.01). In the tumour bed of patients after neoadjuvant therapy, MVD of complete responders (599 nuclei/mm 2 ; 95% CI 434-764) is significantly higher (P < 0.01) than that of partial responders (185 nuclei/mm 2 ; 95% CI 64-306) and non-responders (117 nuclei/mm 2 ; 95% CI 42-192). No significant difference was found between the partial responders and non-responders (P = 0.60)., Conclusion: Microvascular density appears highest in cases of complete tumour response to neoadjuvant therapy, similar to normal rectal tissue. The histological microvascular patterns seen in treated tissue may explain the imaging patterns seen in photoacoustic microscopy., (© 2024 Association of Coloproctology of Great Britain and Ireland. Published by John Wiley & Sons Ltd.)

Background: Malnutrition is a complication of chronic kidney disease (CKD). Whether malnutrition, assessed via the geriatric nutritional risk index (GNRI), is associated with the incidence and risk of CKD in older individuals remains unclear., Methods: Data from the National Health and Nutrition Examination Survey and the UK Biobank database were used. Older participants over 60 years old with available data for GNRI assessment and CKD diagnosis were enrolled. Logistic regression models and Cox regression models were used to assess associations between the geriatric nutritional risk index and the risk of and mortality associated with CKD., Results: This study enrolled 13,162 participants from the NHANES and 66,326 participants from the UK Biobank. We identified 6,135 and 16,662 CKD patients in the NHANES and UK Biobank, respectively, with the majority being male (74% in the NHANES and 52% in the UK Biobank). The average age of CKD patients was 72.3 (SD 7.2) years in the NHANES and 64.9 (SD 2.9) years in the UK Biobank. The median follow-up times of older CKD patients were 81 months and 162 months in the NHANES and UK Biobank, respectively. According to the cross-sectional analysis, individuals with a lower GNRI had an increased likelihood of having CKD, with odds ratios of 1.38 (95% CI: 1.05-1.80, P = 0.020) in the NHANES and 2.35 (95% CI: 1.89-2.92, P < 0.001) in the UK Biobank. According to our analysis of the risk of incident CKD in the UK Biobank, a lower GNRI was associated with a greater incidence of CKD (HR: 1.11, 95% CI: 1.04-1.18; P = 0.002). According to the analysis of the risk of mortality, a lower GNRI was associated with an increased risk of death among older CKD patients (NHANES: HR: 1.69, 95% CI: 1.13-2.53, P = 0.011; UK Biobank: HR: 2.28, 95% CI: 1.94-2.69, P < 0.001)., Conclusion: Malnutrition assessed by the GNRI was significantly and independently associated with the incidence of CKD. Moreover, CKD patients with malnutrition also have a high risk of mortality., (© 2024. The Author(s).)

Mounting evidence in animal experiments proves that early life stage exposure to organophosphate flame retardants (OPFRs) affects the locomotor behavior and changes the transcriptions of central nervous system genes. Unfortunately, their effect on human motor neuron (MN) development, which is necessary for body locomotion and survival, has not yet characterized. Here, we utilized a spinal cord MN differentiation model from human embryonic stem cells (ESCs) and adopted this model to test the effects of two typical OPFRs tris (2-butoxyethyl) phosphate (TBEP) and tris (2-chloroethyl) phosphate (TCEP), on MN development and the possible mechanisms underlying. Our findings revealed TBEP exerted a much more inhibitory effect on MN survival, while TCEP exhibited a stronger stimulatory effect on ESCs differentiation into MN, and thus TBEP exhibited a stronger inhibition on MN development than TCEP. RNA sequencing analysis identified TBEP and TCEP inhibited MN survival mainly by disrupting extracellular matrix (ECM)-receptor interaction. Focusing on the pathway guided MN differentiation, we found both TBEP and TCEP activated BMP signaling, whereas TCEP simultaneously downregulated Wnt signaling. Collectively, this is the first study demonstrated TBEP and TCEP disrupted human MN development by affecting their survival and differentiation, thereby raising concern about their potential harm in causing MN disorders., 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.)

Liver fibrosis is a key process in the progression of chronic liver disease to cirrhosis. Currently, early diagnosis and precise staging of liver fibrosis remain great challenges. Extracellular matrix (ECM) molecules expressed specifically during liver fibrosis are ideal targets for bioimaging and detection of liver fibrosis. Here, we report that fluorescent probes based on a nucleic acid aptamer (ZY-1) targeting cellular fibronectin (cFN), a critical ECM molecule significantly accumulating during liver fibrosis, are promising bioimaging agents for the staging of liver fibrosis. In the work, the outstanding binding affinity of ZY-1 to cFN was validated through an in vitro model of human-derived hepatic stellate cells (HSCs). Subsequently, we constructed different ZY-1-based fluorescent probes and explored the real-time imaging performance of these fluorescent probes in CCl 4 -induced mouse models of different liver fibrosis stages. The ZY-1-based fluorescent probes, for the first time, effectively identified and distinguished early-stage liver fibrosis (stage 3 of Ishak 6) from advanced liver fibrosis (stage 5 of Ishak 6). The proof-of-concept study provides compelling evidences that ZY-1-based probes are a promising tool for the early diagnosis and staging of liver fibrosis and paves the way for further development of clinical-related diagnosis strategies for fibrotic diseases of the liver and other organs. STATEMENT OF SIGNIFICANCE: Currently, early diagnosis and accurate staging of liver fibrosis continue to present significant challenges. This study demonstrates that fluorescent probes based on the nucleic acid aptamer ZY-1, which targets cellular fibronectin (cFN)-a crucial extracellular matrix (ECM) molecule that significantly accumulates during liver fibrosis-are promising bioimaging agents for staging liver fibrosis. The ZY-1-based fluorescent probes effectively identified and differentiated early-stage liver fibrosis from advanced liver fibrosis. This proof-of-concept study not only provides compelling evidence that ZY-1-based probes show promise for the early diagnosis and staging of liver fibrosis but also paves the way for further investigations into the use of ZY-1 in detecting other diseases associated with cFN., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Although solid polymer electrolytes have been developed for several decades, poly(ethylene oxide) (PEO) or polymers with ethoxy (EO) segments are still one of the most promising candidates for advanced batteries. The low ionic conductivity and lithium-ion transference number as well as the deterioration of mechanical properties after coupling with lithium salts restrict its further adoption. Herein, a serial of PEO-based composite electrolytes optimized by waterborne polyurethane are prepared via blend method. With the assistance of H 2 O, ionic type waterborne polyurethane assembles into flexible micelles, in which hydrophobic segments as the core and hydrophilic groups as the shell. Utilizing this feature of waterborne polyurethane, PEO and Li salt (LiTFSI) aqueous solution is slowly added to the organic solution of waterborne polyurethane to compound in situ, and polymer composite electrolytes are fabricated. The multilevel (hydrogen bonds with different binding energy) and multiscale (deformation of flexible micelles) dynamic interaction endows the composite electrolyte with attractive mechanical properties. The assembled Li|Li symmetric battery with the molar ratio of EO to Li salts of 8:1 exhibits excellent cycling stability up to 800 h at 0.1 mA cm -2 , and the assembled Li|LiFePO 4  battery can be stably cycled at 1C for >400 cycles., (© 2024 Wiley‐VCH GmbH.)

Background: The purpose of this research was to evaluate the efficacy of Narcotrend (NT) monitoring on cognitive dysfunction in patients undergoing anesthesia blockade for gastrointestinal tumors and its effect on cerebral oxygen metabolism and inflammatory response., Methods: Patients preparing to undergo resection of gastrointestinal tumor resection were included and randomly divided into a control group (depth of anesthesia assessed by physician experience) and a research group (depth of anesthesia monitored by NT). HR and MAP were monitored at the preoperatively (T 0 ), 12 h postoperative (T 1 ), 24 h postoperative (T 2 ), and 48 h postoperative (T 3 ) stages. MMSE score was recorded to assess changes in cognitive function. Intracerebral oxygenation indicators (CjvO 2 , CERO 2, and rSO 2 ) were assessed by a blood gas analyzer. ELISA assay was conducted to explore the serum inflammatory indexes (CRP, IL-1β, and TNF-α) and neurological function indicators (NSE and MBP)., Results: MAP was higher in the research group than in the control group at T 1 and T 2 (P < 0.05). MMSE scores at T1, T2, and T3 stages were higher in the research group than in the control (P < 0.05). The incidence of POCD was also lower in the research group compared with the control (P < 0.05). CjvO 2 , CERO 2, and rSO 2 were significantly higher (P < 0.05) and were positively correlated with the MMSE scores. Postoperative serum inflammatory indexes were significantly elevated in both groups, but more significantly in the control group (P < 0.05). Both neurological function indicators were usually reduced after surgery, but the reduction was more significant in the research group (P < 0.05)., Conclusion: NT monitoring of anesthetic depth has a less physical impact on patients with gastrointestinal tumor anesthetic block, reduces the degree of postoperative POCD, and has significant clinical value., (© 2024. The Author(s).)

As health equity becomes a prioritized goal in global health policy, extensive research has revealed that socio-economic and geographical factors jointly exacerbate barriers to medical service access for both internal and international migrant populations, further accelerating existing health disparities. This study explores healthcare service utilization disparities among internal migrants in China, a population profoundly affected by the country's economic reforms and urbanization since the late 1970s. These transformations have led to significant migratory movements and subsequent healthcare challenges for these populations. Leveraging data from the 2017 China Migrant Dynamic Survey, comprising 169,989 samples across 28 provinces, we introduce a novel metric-the "No Treatment ratio" (NT-ratio). This ratio quantifies the proportion of migrants who, after falling ill, choose not to seek treatment relative to the total migrant population in a given province or region, serving as a critical measure of health risk. Building upon Anderson's Behavioral Model of Health Services Use, we adapted the model to better reflect the unique circumstances of migrant populations. The study employs spatial autocorrelation, hotspot analysis, and geodetector techniques to dissect the multifaceted factors influencing healthcare disparities. Our Findings reveal that the NT-ratio is significantly higher in eastern and northeastern China. Key factors influencing the NT-ratio include age, left-behind experiences, health education, and per capita medical resources. In response to these disparities, we recommend optimizing the distribution of medical resource, strengthening tiered diagnosis and treatment systems, and integrating health, education, and social security resources. These measures aim to improve healthcare utilization among migrant populations and reduce health inequities, aligning with global health objectives., 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 Li, Yamada, Gao, Yang and Nie.)

The BTB gene superfamily is widely distributed among higher eukaryotes and plays a significant role in numerous biological processes. However, there is limited knowledge about the structure and function of BTB genes in the critically endangered species Alligator sinensis , which is endemic to China. A total of 170 BTB genes were identified from the A. sinensis genome, classified into 13 families, and unevenly distributed across 16 chromosomes. Analysis of gene duplication events yielded eight pairs of tandem duplication genes and six pairs of segmental duplication genes. Phylogenetics shows that the AsBTB genes are evolutionarily conserved. The cis-regulatory elements in the AsBTB family promoter region reveal their involvement in multiple biological processes. Protein interaction network analysis indicates that the protein interactions of the AsBTB genes are centered around CLU-3, mainly participating in the regulation of biological processes through the ubiquitination pathway. The expression profile and protein interaction network analysis of AsBTB genes during sex differentiation and early gonadal development indicate that AsBTB genes are widely expressed in this process and involves numerous genes and pathways for regulation. This study provides a basis for further investigation of the role of the BTB gene in sex differentiation and gonadal development in A. sinensis .

Long non-coding RNAs (lncRNAs) play an important role in various biological processes in plants. However, there have been few reports on the evolutionary signatures of lncRNAs in closely related cotton species. The lncRNA transcription patterns in two tetraploid cotton species and their putative diploid ancestors were compared in this paper. By performing deep RNA sequencing, we identified 280 429 lncRNAs from 21 tissues in four cotton species. lncRNA transcription evolves more rapidly than mRNAs, and exhibits more severe turnover phenomenon in diploid species compared to that in tetraploid species. Evolutionarily conserved lncRNAs exhibit higher expression levels, and lower tissue specificity compared with species-specific lncRNAs. Remarkably, tissue expression of homologous lncRNAs in Gossypium hirsutum and G. barbadense exhibited similar patterns, suggesting that these lncRNAs may be functionally conserved and selectively maintained during domestication. An orthologous lncRNA, lncR4682, was identified and validated in fibers of G. hirsutum and G. barbadense with the highest conservatism and expression abundance. Through virus-induced gene silencing in upland cotton, we found that lncR4682 and its target genes GHPAS2 and GHKCS19 positively regulated fiber elongation. In summary, the present study provides a systematic analysis of lncRNAs in four closely related cotton species, extending the understanding of transcriptional conservation of lncRNAs across cotton species. In addition, LncR4682-PAS2-KCS19 contributes to cotton fiber elongation by participating in the biosynthesis of very long-chain fatty acids., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Stingers, evolved from ovipositors, are an important defense organ for the Apidae , Vespidae , and Formicidae species. However, the molecular mechanism of stinger development remains unclear. Here, we show that the earliest time point for the appearance of stingers in Apis mellifera is at the 1-day-old worker pupal stage based on morphological observations and anatomy from the pre-pupal to adult stages. To discover the genes related to stinger development, we first comprehensively compared the stinger transcriptome at different stages and screened 1282, 186, and 166 highly expressed genes in the stingers of 1- and 5-day-old worker pupae and newly emerged worker bees (NEBs), respectively, then identified 25 DEGs involved in the early stage of stinger development. We found that Dll was a key candidate gene in the early development of A. mellifera stingers by combining analyses of the protein-protein interaction network and spatiotemporal expression patterns. An RNAi experiment showed that about 20% of individuals exhibited tip bending in the piercing parts of their stingers in the Dll -dsRNA-treated group, with the morphology presenting as side-side or front-back tip bending. This indicates that Dll plays a vital role in the early development of A. mellifera stingers. Together, our study provides insight into the molecular mechanism of Hymenoptera stinger development and an inspiration for the molecular breeding of gentle honeybee species with stinger abnormalities.

Objective: To probe the involvement of long noncoding RNA zinc finger antisense 1 (ZFAS1)/microRNA (miR)-186-5p axis in inhibiting oxidative stress in myocardial ischemia-reperfusion injury (MIRI) by targeting B-cell translocation gene 2 (BTG2)., Methods: The MIRI mice model was established by ligating the left anterior descending branch of the left coronary artery in C57BL/6 mice. The in vitro MIRI model was constructed by hypoxia and reoxygenation of HL-1 cardiomyocytes. Cardiomyocyte apoptosis and the extent of myocardial injury in mice were detected. The apoptosis rates, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in HL-1 cells were assessed. The relationship among ZFAS1, miR-186-5p, and BTG2 was verified., Results: High ZFAS1 and BTG2 levels and low miR-186-5p levels were demonstrated in I/R-injured myocardial tissues and in H/R-treated cardiomyocytes. Interference with ZFAS1 or elevation of miR-186-5p inhibited apoptosis and oxidative stress in H/R model cardiomyocytes and I/R-injured myocardial tissues. Overexpressing BTG2 impaired the ameliorative effects of miR-186-5p on MIRI. ZFAS1 negatively regulated miR-186-5p expression by acting as a molecular sponge. miR-186-5p targeted to regulate BTG2 negatively., Conclusion: Interfering with ZFAS1 can upregulate miR-186-5p and thus inhibit BTG2 expression, thereby ameliorating MIRI.

Peat is typically used as a carrier for microbial inoculants; however, due to its non-renewable nature alternatives need to be identified as reliable and renewable carriers for mineral-solubilizing inoculants. In pot experiments, solid microbial inoculants were comprised of peat (P), biochar (BC), and spent mushroom substrates (SMS) using Medicago sativa L. as experimental materials, and the purpose of this study is to assess the effect of solid microbial inoculants on soil multifunctionality and plant growth. The results revealed that the SMS microbial inoculant had the greatest positive impact on plant biomass and significantly stimulated soil multifunctionality which is typically managed or assessed based on various soil functions or processes that are crucial for sustaining productivity, in contrast to the peat microbial inoculant, particularly at a supply level of 100 g/pot. There was no significant correlation between soil multifunctionality and bacterial/fungal microbial diversity. However, according to the co-occurrence network of bacteria and fungi, soil multifunctionality was intimately correlated with the biodiversity of the main ecological clusters (modules) of bacteria and fungi, rather than to the entire soil microbial community structure. The keystone species of module hubs and connectors play critical roles in maintaining the stability of ecological clusters of microbial co-occurrence networks and linkages between ecological clusters. Soil pH is a major predictor of changes in plant biomass, and leads to changes therein by affecting the major ecological clusters of bacterial and fungal co-occurrence networks. These results suggested that SMS may serve as a good alternative to peat as a carrier of mineral-solubilizing microorganisms to maintain soil multifunctionality and promote plant growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Sophocarpine is a bioactive compound extracted from the dried root of Sophorae Flavesentis Aiton, a plant that has been used for thousands of years for various conditions including skin itch and pain. Its antipruritic and analgesic effects are suggested in publications, while the molecular mechanisms underneath interacting with TRP channels are not understood., Aim of the Study: We investigated the anti-inflammatory, antipruritic, and analgesic effects of sophocarpine in a murine inflammatory itch and pain model to elucidate the underlying mechanisms., Materials and Methods: We evaluated sophocarpine's anti-pruritic and analgesic effects by monitoring mice's scratching and wiping behaviors, and the anti-inflammatory effect by measuring psoriasis area and severity index (PASI) score. The mRNA and protein expression of TRPA1/TRPV1 was analyzed by real-time quantitative polymerase chain reaction and western blotting. We further investigated the relationship between sophocarpine and TRPA1/TRPV1 in mice administered allyl-isothiocyanate (AITC) or capsaicin and by molecular docking., Results: We found that sophocarpine decreased scratching bouts, wipes, and the PASI score, reduced the TNF-α and IL-1β in the skin and TRPA1 and TRPV1 in the trigeminal ganglion. Pretreatment of sophocarpine decreased AITC-induced scratching bouts and wipes and capsaicin-induced wipes. We also found potential competitive bindings between sophocarpine and AITC/capsaicin to TRPA1/TRPV1., Conclusions: Sophocarpine is a potential competitive inhibitor of TRPA1 and TRPV1 channels eliciting strong anti-inflammatory, anti-pruritic, and analgesic effects, suggesting its significant therapeutic potential in treating diseases with inflammatory itch and pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Aloperine (ALO), an alkaloid isolated from Sophora alopecuroides L., possesses multiple pharmacological activities and holds a promise potential for the treatment of various clinical conditions, including skin hypersensitivity, cancer, and inflammatory disorders. The purpose of this study was to investigate the role of ALO in acetaminophen (N-acetyl-para-aminophenol (APAP))-induced acute liver injury and its underlying mechanisms., Materials and Methods: An animal model of acute liver injury was induced by intraperitoneal injection of APAP (150 mg/kg). Prior to APAP injection, ALO (40 mg/kg) was administered daily for 7 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were then measured using an automated chemical analyzer. Histopathological changes were evaluated using hematoxylin and eosin staining. Oxidative stress levels were measured by detecting superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). Pro-inflammatory cytokines were detected in serum and liver tissues using ELISA and quantitative real-time polymerase chain reaction (q-PCR). The expression of members of the HMGB1/TLR4/NF- κ B signaling pathway and NLRP3 inflammasome were determined by Western blot and/or q-PCR. In addition, the expression and location of NLRP3, cleaved caspase-1, high-mobility group box 1 (HMGB1), and phosphorylated p65 (p-p65) were detected by immunofluorescence., Results: Pretreatment with ALO significantly protected mice from APAP-induced acute liver injury, with decreased MDA content, and significantly increased GSH and SOD activities. Furthermore, ALO pretreatment reduced the release of pro-inflammatory cytokines (IL-1 β and TNF- α ) and decreased the expression of caspase-1, cleaved caspase-1, and NLRP3. In addition, ALO pretreatment also inhibited the activation of the HMGB1/TLR4/NF- κ B signaling pathway., Conclusion: Taken together, ALO can ameliorate APAP-induced acute liver injury by inhibiting oxidative stress, inflammation by inhibiting the HMGB1/TLR4/NF- κ B, and NLRP3/inflammasome pathway., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Hui Chen et al.)

Introduction: Placental trophoblast dysfunction has been proved to be closely related to the pathogenesis of preeclampsia. Coronaryxin-like actin-binding protein 1C (CORO1C) plays an important role in cell proliferation, apoptosis, invasion, and signal transduction, but its involvement in trophoblast dysfunction and preeclampsia remains uncertain., Methods: The expression of CORO1C in placental tissues of preeclampsia (PE) pregnant women and pregnant mice PE model were detected by real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB) and immunohistochemical (IHC) staining. Next, the proliferation, invasion, migration and apoptosis were performed to explore the functions of CORO1C in HTR8/SVneo cell. Furthermore, the expression of CORO1C were detected in lncMALAT1 knockdown and overexpression HTR-8/SVneo cell. And then we investigated the possible regulatory mechanism of lncMALAT1 on CORO1C through bioinformatics analysis, FISH assays, RIP assays, RNA pull down and dual luciferase reporter assays. Finally, we further validated that lncMALAT1 regulate the function of placental trophoblast cells through CORO1C., Results: The expression of CORO1C was significantly decreased in the placenta of PE patients and mice model, and positively associated with neonatal birth weight. And we found that CORO1C inhibited trophoblast proliferation, migration and invasion. Furthermore, reduced expression of lncMALAT1 impaired CORO1C level, thereby resulting in trophoblast dysfunction. Mechanistically, the dysregulation of lncMALAT1 promoted the expression of miR-133a-3p, strongly enhancing its binding to the 3'UTR region of CORO1C mRNA for degradation., Discussion: This study demonstrated that the dysregulation of CORO1C via lncMALAT1/miR-133a-3p axis impairs trophoblast function and contributes to preeclampsia pathogenesis, providing novel insights in PE therapy through modulating CORO1C level., 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 Ltd.. All rights reserved.)

Background: Uric acid (UA) serves as a crucial endogenous antioxidant in the body, offering protection against oxidative stress, whichmaycontributetoepilepsypathogenesis. The association between serum UA levels and epilepsy remains uncertain. This study aimed to examine the potential connections between serum UA levels and epilepsy in US adults., Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018, a cross-sectional analysis was conducted. Weighted logistic regression analyses were employed to assess the potential link between serum UA levels and the risk of epilepsy. Additionally, sensitivity analyses were conducted to evaluate the reliability of the results., Results: We included 15,373 participants, of whom 136 (0.79 %) had epilepsy. Following adjustment for multiple variables, participants with serum UA levels <4.1 mg/dl had an odds ratio of 2.24 (95 % CI: 1.12-4.47, P = 0.023) for epilepsy compared to those with serum UA levels of 5.8-6.5 mg/dl. The results of the sensitivity analyses corroborated the initial findings., Conclusions: Our study revealed a significant association between lower serum UA levels and heightened risks of epilepsy, suggesting that low UA levels may serve as an independent risk factor for epilepsy. A marginal increase in UA levels within the normal range may act as a protective factor against epilepsy., 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.)

Differences in electrical properties of media are the basis for determining the type and extent of contamination using geophysical methods. However, differences in heavy metals and organic matter complicate the electrical properties of compound-contaminated media, and existing geophysical methods cannot independently identify compound contamination. Therefore, this study proposes a geophysical detection system that combines electrical resistance tomography (ERT) and induced polarization methods and establishes a solid theory as the basis for the system application through laboratory experiments, model analysis, and site applications. The study reveals that as the organics volume proportion increases, the resistivity and normalized chargeability of contaminated media increased slowly, followed by a rapid increase, and finally reached a stable state. The specific type of compound significantly influences the electrical properties, while the resistivity of different kinds of compound-contaminated media reaches the same maximum value as the organics volume proportion increases. The medium type determines the contaminated media's lower resistivity limit and upper normalized chargeability limit. Additionally, the interplay between heavy metal type, content, and medium complicates the electrical properties of the media, with the compound type exerting a significant impact on resistivity. Archie's law and random forest modeling reveal that the inflection point for resistivity change occurs at 40 % and 80 % organics volume proportions, while the inflection point for normalized chargeability change occurs at 30 % and 70 % organics volume proportions in compound-contaminated media. These inflection points depend on the types of compounds, compositions, proportions, and media, and their importance for the electrical properties of the media changes with the increasing organics volume proportion. Based on the changing patterns of resistivity and normalized chargeability in heavy metal-organic compound contaminated media, the modified geophysical detection system can effectively identify the pollution type and intensity, which provides accurate pollution information to develop effective treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Adult severe caries (ASC) brings severe oral dysfunction and treatment difficulties to patients, and yet no clear pathogenic mechanism for it has been found. This study is focused on the composition of dental plaque microbiome profiles in order to identify disease-relevant species and to investigate into their interactions with the S. mutans . Samples of dental plaque were collected for metagenomic analysis. The acidification, aciduricity, oxidative stress tolerance, and gtf (glucosyltransferase) gene expression of S. mutans cocultured with V. parvula which was identified as ASC-related dominant bacterium. The biofilm formation and extracellular exopolysaccharide (EPS) synthesis of dual-strain were analyzed with scanning electron microscopy (SEM), crystal violet (CV) staining, live/dead bacterial staining, and confocal laser scanning microscopy (CLSM). Furthermore, rodent model experiments were performed to validate the in vivo cariogenicity of the dual-species biofilm. The most significantly abundant taxon found associated with ASC was V. parvula . In vitro experiments found that V. parvula can effectively promote S. mutans mature biofilm formation with enhanced acid resistance, hydrogen peroxide detoxicity, and biofilm virulence. Rodent model experiments revealed that V. parvula was incapable of causing disease on its own, but it significantly heightened the biofilm virulence of S. mutans when being co-infected and augmented the progression, quantity, and severity of dental caries. Our findings demonstrated that V. parvula may act as a synergistic pathobiont to modulate the metabolic activity, spatial structure, and pathogenicity of biofilms of S. mutans in the context of ASC.IMPORTANCEAdult severe caries (ASC), as a special type of acute caries, is rarely reported and its worthiness of further study is still in dispute. Yet studies on the etiology of severe caries in adults have not found a clear pathogenic mechanism for it. Knowledge of the oral microbiota is important for the treatment of dental caries. We discovered that the interaction between V. parvula and S. mutans augments the severity of dental caries in vivo , suggesting V. parvula may act as a synergistic pathobiont exacerbating biofilm virulence of S. mutans in ASC. Our findings may improve the understanding of ASC pathogenesis and are likely to provide a basis for planning appropriate therapeutic strategies.

Colorectal cancer (CRC) stands as the second most common cause of cancer-related mortality globally and p53, a widely recognized tumor suppressor, contributes to the development of CRC. Ubiquitin-specific protease 36 (USP36), belonging to the deubiquitinating enzyme family, is involved in tumor progression across multiple cancers. However, the underlying molecular mechanism in which USP36 regulates p53 signaling pathway in CRC is unclear. Here, our study revealed that USP36 was increased in CRC tissues and associated with unfavorable prognosis. Functionally, elevated USP36 could promote proliferation, migration, and invasion of CRC cells in vitro and in vivo. Mechanistically, USP36 could interact with and stabilize RBM28 via deubiquitination at K162 residue. Further, upregulated RBM28 could bind with p53 to suppress its transcriptional activity and therefore inactivate p53 signaling pathway. Collectively, our investigation identified the novel USP36/RBM28/p53 axis and its involvement in promoting cell proliferation and metastasis in CRC, which presents a promising therapeutic strategy for CRC treatment., (© 2024. The Author(s).)

Skin inflammation and immune regulation have been suggested to be associated with allergic contact dermatitis (ACD) progression, but whether the system's immune regulation is a cause or a potential mechanism is still unknown. This study aims to assess the upstream and downstream of systemic immune factors on ACD within a bidirectional Mendelian-randomization design. A bidirectional two-sample MR analysis was employed to implement the results from genome-wide association studies for 52 system immune factors and ACD. Genetic associations with systemic immune factors and ACD were obtained from the IEU Open GWAS project database. The inverse-variance weighted (IVW) method was adopted as the primary MR analysis, MR-Egger, weighted median, MR-pleiotropy residual sum, and outlier (MR-PRESSO) was also used as the sensitivity analyses. Only Tumor necrosis factor ligand superfamily member 11 (TNFS11) from among 52 systemic immune factors was associated with a protective effect of ACD. However, ACD was associated with a decrease in Interleukin-9 (IL9) and an increase in C-X-C motif chemokine 1 (GROα), Tumor necrosis factor ligand superfamily member 10 (TRAIL), C4, and complement factor B of the assessed systemic immune factors. This study identified TNFS11 as the upstream regulator and IL9, GROα, TRAIL, C4, and complement factor B as the downstream regulator of ACD, providing opportunities for new therapeutic exploitation of ACD. Nonetheless, these associations of systemic immune factors need to be verified in vivo.

Background: The association of hypertension and blood pressure control with fecundability among women is not yet elucidated. The purpose of this study was to evaluate the hypothesis that maternal preconception hypertension would be associated with reduced fecundability and that blood pressure control could reduce excess risk., Methods: Using the National Free Preconception Checkup Projects in Guangdong Province, China, 1422 couples whose female partners had been diagnosed with hypertension and 997 703 reference couples whose female partners were without hypertension were included in this prospective cohort study. Fecundability was measured by time to pregnancy (TTP) and infertility (TTP >12 months)., Results: Compared with women without hypertension, those with controlled hypertension (time ratio, 1.47 [95% CI, 1.24-1.73]) or uncontrolled hypertension (time ratio, 1.59 [95% CI, 1.34-1.90]) were associated with prolonged TTP and increased risk of infertility (relative risk, 1.19 [95% CI, 1.09-1.31]; relative risk, 1.24 [95% CI, 1.14-1.34]). However, using instrumental variable analyses, there was no significant association between blood pressure control and TTP (time ratio, 0.68 [95% CI, 0.34-1.36]; P =0.270) or infertility (relative risk, 0.97 [95% CI, 0.70-1.34]; P =0.849) among women with hypertension. These results were consistent in the propensity score matching and inverse probability of treatment weighting analyses., Conclusions: Maternal hypertension, with or without controlled blood pressure, was independently associated with prolonged TTP and an increased risk of infertility. These findings may provide insights for the implementation of preconception hypertension screening and the design of future trials.

Aspergillus oryzae is an ideal cell factory for protein expression with powerful protein processing and secretion capabilities. The current study aimed to explore the homologous expression of A. oryzae lipase AOL (GenBank: KP975533) by constructing an auxotrophic A. oryzae △pyrG△nptB and subsequently characterizing the immobilization and catalytic properties of recombinant lipase. Initially, the pyrG gene knocked out in wild-type A. oryzae by homologous recombination, followed by the creation of a uridine/uracil auxotroph transformation. Through this system, the protease gene nptB was precisely knocked out, leading to a substantial decrease in extracellular (39.04%) and intracellular (90.07%) protease activity. The A. oryzae △nptB△pyrG strain was used as host for homologous expression of lipase AOL. After transformation of linearized lipase-expression cassette, the engineered A. oryzae AOL-8 was screened out with the lipase gene copy number of 14, exhibiting extracellular and intracellular lipase activities of 1.75 U/mL and 46.4 U/g, respectively. Subsequently, the production and immobilization of the recombinant lipase, via physical adsorption on macroporous resin XRZ04B, were achieved through submerged fermentation of the AOL-8 strain. The results of esterification catalytic properties of immobilized recombinant lipase indicated that the lipase exhibited optimal catalytic activity with lauric acid and methanol as substrates, a reaction temperature of 35 °C, and n-hexane as the preferred solvent medium; its highest conversion rate can reach at 72.3%., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cathode prelithium agent is regarded as the most applicable approach to compensate the initial capacity loss in lithium ion batteries (LIBs). Li2NiO2 (LNO) has attracted numerous attention due to its superior environmental stability and reliable synthesis approach. To promote the commercial application of LNO, the understanding of the degradation mechanism induced by air-exposure and finding reliable strategies to improve the air stability are necessary. Herein, by preserving the LNO in different environments (relative humidity of 70% and 40%), the surface chemistry evolution of LNO is subtly investigated, which shows Li2CO3 and LiOH cover the surface of the LNO, which decline the Li+ diffusion kinetics as well as the charge capacity. What's more, the slurry turns gel when the LNO exposed to the environment of 70% relative humidity for 2 days and 40% relative humidity for 5 days. Facile approaches, including washing the deteriorative LNO with ethanol, reacting the alkali components with H3BO3, and coating the LNO with Al2O3 are conducted to recover the disabled LNO, which retains 84.2% of initial capacity. In addition, a coating approach is proposed for the fresh LNO to effectively improve the air stability. This work provides guideline to the commercial application of the LNO., (© 2024 Wiley‐VCH GmbH.)

Heterogeneous Fenton process is a promising water treatment technology for sterilization and degradation of organic pollutants, due to the strong oxidation of hydroxyl radicals (OH˙) generated. However, the low H 2 O 2 activation efficiency and the instability of catalyst leading to low OH˙ production restricted development of this technology. Herein, we synthesized a novel porous activated carbon-loaded nano silver oxide (nAg 2 O/AC) catalyst to enhance the activation of H 2 O 2 for removing bacteria ( E. coli ) and micropollutants (Tetracycline, TC) from water. In the nAg 2 O/AC Fenton system, reductive hydroxyl groups on AC accelerated Ag(i)/Ag cycle through mediated electron transfer, which markedly increased H 2 O 2 activation efficiency to 73.7% (About 2.9 times that of traditional Fenton). Hence, nAg 2 O/AC Fenton achieved up to 6.0 log and 100% removal efficiency for E. coli and TC, respectively. The OH˙ as the major oxidizing species in nAg 2 O/AC Fenton system was detected and verified by radical scavenging tests and electron spin resonance (ESR) measurement. After 4 and 5 cycles of experiments, the removal of E. coli and TC still reached 5.2 log and 96%, respectively, confirming good stability of nAg 2 O/AC for considerable application prospects. This study concluded that nAg 2 O/AC is a promising H 2 O 2 catalyst for simultaneous removal of bacteria and micropollutants in aqueous environment., Competing Interests: 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., (This journal is © The Royal Society of Chemistry.)

Manila clam (Ruditapes philippenarum) is an important shellfish aquaculture product. The large-scale breeding of clams is often affected by V. anguillarum and causes large-scale death. However, the pathogenesis, immune response and metabolic pathway of V. anguillarum are still unclear. In this study, we found that the bacterial load in the hepatopancreas of R. philippinarum peaked at 48 h after V. anguillarum infection, and then gradually decreased, while the activity of lysozyme reached the peak at 12 h. Tissue section observation reveals that the infected hepatopancreas cells lost normal structure or necrosis. Additionally, six small RNA libraries were constructed using hepatopancreas of clams. A total of 15 differentially expressed (DE) microRNA (miRNA) were identified at 48 h after V. anguillarum infection, including 8 upregulated and 7 downregulated miRNAs. GO and KEGG enrichment results indicated the prediction of 48 known miRNAs and 127 new miRNAs, with functional annotation suggests that endocytosis pathway and bacterial recognition proteins may play key roles in immune response. The sequencing results were basically consistent with the qRT-PCR validation, indicating the accuracy of the data. This study provides a new idea to explore the immune regulation mechanism of shellfish after V. anguillarum infection, which brings important reference significance for modern immunological research., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study investigates the compatibility of excipients with the model system SDI-X and their role in the induced crystallization of the amorphous compound-X in tablet formulations. We aimed to establish a straightforward and practical screening approach for evaluating excipient-induced crystallization of SDI in tablet matrices. Three methodologies-binary powder mixture, binary compact, and bilayer tablets-were employed to qualitatively and quantitatively evaluate the recrystallization of SDI-X with various excipients under accelerated storage conditions. The results demonstrated that binary compacts, providing direct physical contact between SDI-X and excipients, are superior in reflecting realistic drug-excipient contact within pharmaceutical tablets, enabling a more accurate assessment of excipient-induced crystallization for SDI-X. In contrast, the broadly used conventional binary blends can significantly underestimate this risk due to insufficient proximity. In addition, the bilayer tablets further confirmed that crystallization initiates at the contact surface between SDI-X and the excipients. The study highlighted that not only hygroscopicity but also the type of excipient and its physical contact with SDI-X significantly influence the recrystallization extent and rate of SDI-X. Interestingly, less hygroscopic diluents such as mannitol and lactose induced much higher levels of crystallization of SDIs, contrary to expectations based on moisture content alone. This suggests that the excipient type and contact surface are more critical in inducing recrystallization than just the level of moisture. The findings emphasize the need for careful excipient selection, study design, and sample preparation to enable appropriate assessments of SDI-excipient compatibility., 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Following the introduction of metabolic dysfunction-associated steatotic liver disease (MASLD) as a replacement term for nonalcoholic fatty liver disease, the relationship between MASLD and cannabis use has yet to be established. With the global rise in cannabis consumption, understanding its impact on MASLD is critical for clinical guidance. Our study investigated the association between cannabis use, MASLD, and clinically significant fibrosis (CSF) among U.S. adults. Methods: Data were collected from the National Health and Nutrition Examination Survey for the period 2017 to 2018 to conduct a cross-sectional analysis. The diagnosis of hepatic steatosis and CSF was based on median values of the controlled attenuation parameter and liver stiffness measurement, with thresholds of 285 dB/m and 8.6 kPa, respectively. Information on cannabis use was obtained through self-report questionnaires. Multinomial logistic regression models and subgroup analyses were used to investigate the association between cannabis use and MASLD with CSF. Results: Our study assessed data from 2,756 U.S. adults (51.1% female; 32.2% white; mean age 39.41 ± 11.83 years), who had complete information on liver stiffness measurements through transient elastography alongside reported cannabis use. Results indicated that cannabis use overall was not associated with liver stiffness in patients with MASLD. However, among females, cannabis use was associated with MASLD accompanied by CSF, with an adjusted odds ratio (OR) of 0.47 (95% confidence interval [CI]: 0.24-0.91). Heavy cannabis use (9 to 30 times per month) was associated with MASLD accompanied by CSF among female participants, with an adjusted OR of 0.12 (95% CI: 0.02-0.88). Conclusion: In our study, cannabis use did not show a significant association with liver stiffness in patients diagnosed with MASLD. However, heavy cannabis consumption in women was associated with MASLD accompanied by CSF. These findings suggest that the effects of cannabis on liver health may differ based on gender and frequency of cannabis use, emphasizing the need for further research in this area.

The estimation of postmortem interval (PMI) has long been a focal point in the field of forensic science. Following the death of an organism, microorganisms exhibit a clock-like proliferation pattern during the course of cadaver decomposition, forming the foundation for utilizing microbiology in PMI estimation. The establishment of PMI estimation models based on datasets from different seasons is of great practical significance. In this experiment, we conducted microbiota sequencing and analysis on gravesoil and mouse intestinal contents collected during both the winter and summer seasons and constructed a PMI estimation model using the Random Forest algorithm. The results showed that the MAE of the gut microbiota model in summer was 0.47 ± 0.26 d, R2 = 0.991, and the MAE of the gravesoil model in winter was 1.04 ± 0.22 d, R2 = 0.998. We propose that, in practical applications, it is advantageous to selectively build PMI estimation models based on seasonal variations. Additionally, through a combination of morphological observations, gravesoil microbiota sequencing results, and soil physicochemical data, we identified the time of cadaveric rupture for mouse cadavers, occurring at around days 24-27 in winter and days 6-9 in summer. This study not only confirms previous research findings but also introduces novel insights, contributing to the foundational knowledge necessary to advance the utilization of microbiota for PMI estimation., Competing Interests: The authors declare there are no competing interests., (©2024 Zhao et al.)

Highly vertically thermally conductive silicon rubber (SiR) composites are widely used as thermal interface materials (TIMs) for chip cooling. Herein, inspired by water transport and transpiration of Moso bamboo-forests extensively existing in south China, and guided by filler self-assembly simulation, bamboo-forest-like heat conduction networks, with bamboo-stems-like vertically aligned polydopamine-coated carbon fibers (VA-PCFs), and bamboo-leaves-like horizontally layered Al 2 O 3 (HL-Al 2 O 3 ), are rationally designed and constructed. VA-PCF/HL-Al 2 O 3 /SiR composites demonstrated enhanced heat conduction properties, and their through-plane thermal conductivity and thermal diffusivity reached 6.47 W (mK) -1 and 3.98 mm 2  s -1 at 12 vol% PCF and 4 vol% Al 2 O 3 loadings, which are 32% and 38% higher than those of VA-PCF (12 vol%) /SiR composites, respectively. The heat conduction enhancement mechanisms of VA-PCF/HL-Al 2 O 3 networks on their SiR composites are revealed by multiscale simulation: HL-Al 2 O 3 bridges the separate VA-PCF heat flow channels, and transfers more heat to the matrix, thereby increasing the vertical heat flux in composites. Along with high volume resistivity, low compression modulus, and coefficient of thermal expansion, VA-PCF/HL-Al 2 O 3 /SiR composites demonstrate great application potential as TIMs, which is proven using multiphysics simulation. This work not only makes a meaningful attempt at simulation-driven biomimetic material structure design but also provides inspiration for the preparation of TIMs., (© 2024 Wiley‐VCH GmbH.)

Parkinson's disease (PD) is a prevalent neurodegenerative disorder for which novel treatment approaches are continuously sought. This study investigates the role of high-mobility group A1 (HMGA1) in modulating inflammatory responses and oxidative stress injury in PD. We utilized the murine dopaminergic neuronal cell line MN9D, treating cells with 1-methyl-4-phenylpyridinium ion (MPP + ) to mimic PD conditions. The expression levels of HMGA1 and insulin receptor substrate 2 (IRS2) were measured using quantitative polymerase chain reaction and Western blot assay. Cell damage was assessed with cell counting kit-8 and lactate dehydrogenase assays. Inflammatory response and oxidative stress were evaluated by quantifying interleukin (IL)-1β, IL-6, tumor necrosis factor-α, reactive oxygen species, superoxide dismutase, and malondialdehyde (MDA) levels using enzyme-linked immunosorbent assay and commercial kits. The binding interaction between HMGA1 and IRS2 was analyzed using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. Our findings revealed that MPP + treatment increased the expression of HMGA1 and IRS2. Downregulation of HMGA1 enhanced cell viability, reduced inflammation, and mitigated oxidative stress in MPP + -induced cells. Further investigation demonstrated that HMGA1 bounded to the IRS2 promoter, enhancing IRS2 expression. Overexpression of IRS2 counteracted the protective effects of HMGA1 downregulation. In conclusion, HMGA1 exacerbates MPP + -induced cell damage by activating IRS2 transcription, which in turn heightens inflammation and oxidative stress. These findings suggest that targeting HMGA1 could be a potential therapeutic strategy for PD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To reduce the mercury content in flue gas from coal-fired power plants and to obtain high-performance, low-cost mercury adsorbents, a novel composite material was prepared by structural design through the in situ growth method. Functionalization treatments such as the modification of functional groups and multilayer loading of polymetallic were conducted. These materials include the MOF material UiO-66 and modified biochar doped with Fe/Ce polymetallic, both of which contain unsaturated metal centrals and oxygen-containing functional groups. On the basis of obtaining the effects of adsorption temperature and composite ratio on the Hg 0 removal characteristics, coupling and synergistic mechanisms between the various types of active centers included were investigated by using a variety of characterization and analysis tools. The active adsorption sites and oxidation sites were identified during this process, and the constitutive relationship between the physicochemical properties and the performance of Hg 0 removal was established. The temperature-programmed desorption technique, Grand Canonical Monte Carlo simulation, and adsorption kinetic model were employed to reveal the mechanism of Hg 0 removal. The results showed that the UiO-66-Br@MBC composite adsorbent possessed an excellent Hg 0 removal performance at adsorption temperatures ranging from 50 to 250 °C, and targeted construction of adsorption and oxidation sites while maintaining thermal stability. The Hg 0 removal by the composites is the result of both adsorption and oxidation. The micropores and small pore mesopores in the samples provide physical adsorption sites. The modified biochar acts as a carrier to facilitate the full exposure of the central metal zirconium ions, the formation of more active sites, and the process of electron transfer. The doping modification of the Br element can enhance the overall redox ability of the sample, and the introduced Fe and Ce polymetallic ions can work in concert to promote the oxidation process of Hg 0 . The excellent regulation of the ratio between adsorption and oxidation sites on the surface of the composite material finally led to a significant boost in the samples' capacity to remove Hg 0 .

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease characterized by disability and deformity. To better understand ONFH at molecular level and to explore the possibility of early diagnosis, instead of diagnosis based on macroscopic spatial characteristics, a matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) method was developed for ONFH disease for the first time. The most challenging step for ONFH MSI is to deal with human bone tissues which are much harder than the other biological samples studied by the reported MSI studies. In this work, the MSI sectioning method of hard bone tissues was established using tender acids and a series of test criteria. Small-molecule metabolites, such as lipids and amino acids, were detected in bone sections, realizing the in situ detection of spatial distribution of biometabolites. By comparing the distribution of metabolites from different regions of normal femoral head, ONFH bone tissue (ONBT), and adjacent ONFH bone tissue (ANBT), the whole process of femoral head from normal stage to necrosis was monitored and visualized at molecular level. Moreover, this developed MSI method was used for metabolomics study of ONFH. 72 differential metabolites were identified, suggesting that disturbances in energy metabolism and lipid metabolism affected the normal life activities of osteoblasts and osteoclasts. This study provides new perspectives for future pathological studies of ONFH., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp 2 -hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP) + /S100 calcium binding protein B (S100β) + enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP + EGCs into GFAP + /S100β + EGCs while promoting the differentiation of GFAP + /S100β + EGCs back into GFAP + EGCs. Furthermore, DHA induced apoptosis in GFAP + /S100β + EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Following catheter ablation, vascular access management involves potential complications and prolonged recovery. Recently, suture-mediated closure (SMC) devices were approved for venous access procedures. The objective of this study is to evaluate the safety of a commercially available SMC for multiple access site venous closure by duplex ultrasound (DUS) in asymptomatic subjects with non-visible complications., Methods: Thirty-six subjects (63 ± 10.7 years old, 12 female) were enrolled. Following catheter ablation for atrial fibrillation, all subjects had SMC of every venous access site. Subjects underwent DUS of femoral veins and arteries. DUS was performed at discharge, and again at 30 days. Subjects were evaluated for clinically apparent vascular complications., Results: Mean procedure duration was 138.6 min, and the time to hemostasis was 3.1 min/access site and 9.5 min/subject. Median time to ambulation was 193.5 min, and median time to discharge was 5.95 h, with discharge as early as 2.4 h. A median of 2 sheaths/vein and a median of 2 SMC devices/vein were used. There were no major complications and a 16.7% (6/36) minor complication rate at discharge. All complications resolved at 30 days. The complication rate was not higher in patients with 2 SMC per access site as compared to the patients who just received 1 SMC per access site., Conclusions: This study demonstrates the safety of multi-access closure using SMC, following catheter ablation procedures, for closure of sites that use sheath sizes from ≤ 8F to ≥ 15F and for those that use 2 or more SMCs per access site., (© 2024. The Author(s).)