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Background: Anaplastic thyroid carcinoma (ATC) is a rare but the most aggressive type of thyroid carcinoma. Nevertheless, limited advances were made to reduce mortality and improve survival over the last decades. Therefore, identifying novel diagnostic biomarkers and therapeutic targets for ATC patients is still needed., Materials and Methods: RNA sequencing data and corresponding clinical features were available from GEO and TCGA databases. We integrated WGCNA and PPI network analysis to identify hub genes associated with ATC development, and RT-qPCR was employed for data verification. Univariate and LASSO Cox regression analyses were used to generate prognostic signatures., Results: Based on PPI and WGCNA, 6 hub genes were identified, namely KIF2C, PBK, TOP2A, CDK1, KIF20A, and ASPM, which play vital roles in ATC development. Subsequently, RT-qPCR experiments showed that most of these genes were significantly upregulated in CAL-62 cells compared to Nthy-ori 3-1 cells. Moreover, a prognostic signature featuring GPSM2, FGF5, ASXL3, CYP4B1, CLMP, and DUXAP9 was generated, which was also verified by RT-qPCR results and proved as an independent predictor of poorer prognosis of ATC. Additionally, a nomogram incorporating the risk score and clinicopathological parameters was further constructed for accurate prediction of 1-, 3- and 5-year survival probabilities of ATC., Conclusions: Our study identified 6 key genes critical to ATC development and constructed a prognostic signature. These findings provide reliable biomarkers and a relatively comprehensive tumorigenesis profile of ATC, which may inform future strategies for clinical diagnosis and pharmaceutical design., Competing Interests: Declarations Ethics approval and consent to participate Our study is based on open-source data, thus no ethical issues or other conflicts of interest exist. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Breast cancer (BC) is the most common malignant tumor in women, and the majority of BC-related deaths are due to tumor metastasis. There is emerging evidence for the role of long noncoding RNAs (lncRNAs) in tumor progression. Nevertheless, lncRNAs that drive metastasis in patients with BC and the underlying mechanisms of lncRNAs are still largely elusive. In this study, we showed that LINC00882 was highly expressed in metastatic BC tissues, and a receiver operating characteristic (ROC) curve was able to distinguish well between BC cases with lymph node metastasis (LNM) and those without LNM. Functionally, LINC00882 promoted BC invasion and metastasis in vitro and in vivo. Mechanistically, at the transcriptional level, CEBP-β could bind directly to the LINC00882 promoter region and activate its transcription. Moreover, at the posttranscriptional level, m 6 A modification of LINC00882 mediated by methyltransferase-like 14 (METTL14) promoted its expression via an IGF2BP2-dependent pathway. Furthermore, 514-615 nucleotides of LINC00882 could directly interact with poly (A) binding protein cytoplasmic 1 (PABPC1) and promote the interaction between PABPC1 and ELK3 mRNA, thereby stabilizing ELK3 mRNA and enhancing the ELK3 protein level. E-cadherin expression was suppressed via ELK3-mediated transcription inhibition, subsequently activating epithelial-mesenchymal transition to promote BC metastasis. These results highlight the role of LINC00882 in BC, and LINC00882 may be a diagnostic and therapeutic target for BC., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate Fresh BC tissues were obtained with informed patient consent and approval from the Qilu Hospital of Shandong University, and the Research Ethics Committee of Shandong University. Patients’ privacy has been fully protected. Animal experiments were conducted according to the Guidelines for Animal Health and Use (Ministry of Science and Technology, China, 2006), and were approved by the Committee for Animal Protection of Shandong University. Consent for publication Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Water activation plays a crucial role in CO 2 reduction, but improving the electrocatalytic performance through controlled water activation presents a significant challenge. Herein, we achieved electrochemical CO 2 reduction to ethene and ethanol with high selectivity by promoting water dissociation and asymmetric C-C coupling by engineering Cu surfaces with N-H-rich molecules. Direct spectroscopic evidence, coupled with density functional theory calculations, demonstrates that the N-H-rich molecules accelerate interfacial water dissociation via hydrogen-bond interactions, and the generated hydrogen species facilitate the conversion of *CO to *CHO. This enables the efficient asymmetric *CHO-*CO coupling to C 2 products with a faradaic efficiency (FE) ∼ 30% higher than that of the unmodified catalyst. Moreover, by adjustment of the relative *CHO/*CO coverage via Cu surface facet regulation, the selectivity can be entirely switched between C 2 products and CH 4 . These mechanistic insights further guided the development of a more efficient catalyst by directly modifying Cu 2 O nanocubes with the N-H-rich molecule, achieving remarkable C 2 product (mainly ethene and ethanol) FEs of 85.7% at a current density of 800 mA cm -2 and excellent stability under nearing industrial conditions. This study advances our understanding of the CO 2 reduction mechanisms and offers an effective and general strategy for enhancing electrocatalytic performance by accelerating water dissociation.

A poly(ionic liquid) probe material was prepared that is conductive, uniformly film-forming, and rich in I 2 interaction sites by structural design. Green and pollution-free electrochemical detection of gaseous I 2 was achieved based on the variation of redox peak currents, and the limit of detection was 1.44 nM. The differences in redox peak potentials were utilized for the specific detection of gaseous I 2 .

Background: An injection method called cranial ceiling elevation is used in Asian countries to reduce facial proportions. Scalp injections carry risks such as arterial embolism or compression, leading to adverse events including scalp necrosis and hair loss., Objective: No arterial studies or injection recommendations exist for the injection of specific scalp regions. We aimed to examine blood vessel types and distributions to identify relatively safe areas for scalp injections., Methods: Computed tomography scans were used to evaluate the blood vessels in the scalp of 50 cadaver heads and anatomical studies were performed. Each scalp was divided into two segments (L1/L2) and six areas (S1/S1'-S3/S3'). The total number of arteries and the probability of each named artery occurring in each section were recorded., Results: The total number of arteries in L1 was higher than that in L2 (L1, 78.76 ± 31.07; L2, 75.28 ± 28.68). The most frequently distributed artery in both L1 and L2 was the parietal branch of the superficial temporal artery. No significant difference was observed between the total number of arteries and the number of each named artery in the S1/S1'-S3/S3' segments. Except for S2' and S3', the number of named arteries in L1 was higher than that in L2., Conclusions: Large-volume scalp injections are not recommended. For injections within 30° above the ear, it is advisable to inject at L2. For other regions, it is also recommended to inject at L2. The periosteal layer should be selected for injection., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society. 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.)

To evaluate the levels of YKL40, IL-6(interleukin-6), IL-8(interleukin-8), IL-10(interleukin-10), TNF-α (tumor necrosis factor-α) in OSAS (obstructive sleep apnea syndrome)children and explore the mechanism of YKL40 promoting inflammatory factors overexpression in tonsils. qPCR and ELISA were used to identify the expression of YKL40, IL-6, IL-8, IL-10, and TNF-α in the tonsils of OSAS children. Primary tonsil lymphocytes (PTLCs) were cultured and recombinant human YKL40(rhYKL40)was used to stimulate PTLCs in different concentrations and at different time points. The activation of NF-κB in PTLCs was screened by western blotting. Relative mRNA of YKL40, IL-6, IL-8, TNF-α was over expressed in OSAS-derived tonsil tissue and the levels of YKL40, IL-6, IL-8, and TNF-α was increased in OSAS-derived protein supernatant of tonsil tissue.The relative mRNA expression of IL-6, IL-8 and TNF-α increased under the treatment of YKL40 (100 ng/mmol for 24 h). The phosphorylation of p65 in NF-κB pathway was stimulated in the process. The levels of YKL40, IL-6, IL-8, and TNF-α increases in OSAS children, and YKL40 promotes the overexpression of IL-6, IL-8 and TNF-α in PTLCs via NF-κB pathway. The result implements that inflammation may play an important role in the pathogenesis of OSAS in children., (© 2024. The Author(s).)

Purpose: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV)., Methods: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients., Results: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not., Conclusion: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Courtship interactions are remarkably diverse in form and complexity among species. How neural circuits evolve to encode new behaviors that are functionally integrated into these dynamic social interactions is unknown. Here we report a recently originated female sexual behavior in the island endemic Drosophila species D. santomea, where females signal receptivity to male courtship songs by spreading their wings, which in turn promotes prolonged songs in courting males. Copulation success depends on this female signal and correlates with males' ability to adjust his singing in such a social feedback loop. Functional comparison of sexual circuitry across species suggests that a pair of descending neurons, which integrates male song stimuli and female internal state to control a conserved female abdominal behavior, drives wing spreading in D. santomea. This co-option occurred through the refinement of a pre-existing, plastic circuit that can be optogenetically activated in an outgroup species. Combined, our results show that the ancestral potential of a socially-tuned key circuit node to engage the wing motor circuit facilitates the expression of a new female behavior in appropriate sensory and motivational contexts. More broadly, our work provides insights into the evolution of social behaviors, particularly female behaviors, and the underlying neural mechanisms., (© 2024. The Author(s).)

Background: According to current statistics, renal cancer accounts for 3% of all cancers worldwide. Renal cell carcinoma (RCC) is the most common solid lesion in the kidney and accounts for approximately 90% of all renal malignancies. Increasing evidence has shown an association between immune infiltration in RCC and clinical outcomes. To discover possible targets for the immune system, we investigated the link between tumor-infiltrating immune cells (TIICs) and the prognosis of RCC., Aim: To investigate the effects of 22 TIICs on the prognosis of RCC patients and identify potential therapeutic targets for RCC immunotherapy., Methods: The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions. Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC. A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes. Furthermore, multivariate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC. A value of P < 0.05 was regarded as statistically significant., Results: Compared to normal tissues, RCC tissues exhibited a distinct infiltration of immune cells. An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC. High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve ( P = 1 E-05 ). The immunological risk score model was demonstrated to be a dependable predictor of survival risk (area under the curve = 0.747) via the receiver operating characteristic curve. According to multivariate Cox regression analysis, the immune risk score model independently predicted RCC patients' prognosis (hazard ratio = 1.550, 95%CI: 1.342-1.791; P < 0.001). Finally, we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC., Conclusion: TIICs play various roles in RCC prognosis. The immunological risk score is an independent predictor of poor survival in kidney cancer cases., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Gut microbial bile salt hydrolases (gmBSHs), an important class of bacteria-produced cysteine hydrolases, play a crucial role in bile acid metabolism. Modulating the total gmBSH activity is a feasible way for ameliorating some metabolic diseases including colorectal cancer, type 2 diabetes, and obesity. This study reported the discovery and characterization of a botanical compound as a covalent pan -inhibitor of gmBSHs. Following the screening of more than 100 botanical compounds, tanshinones were found with strong time-dependent anti- Ef BSH effects. After that, a total of 17 naturally occurring tanshinones were collected, and their anti- Ef BSH potentials were tested. Among all tested tanshinones, tetrahydro tanshinone I (THTI) exhibited the most potent inhibitory effects against five gmBSHs ( Ef BSH, Ls BSH, Bt BSH, Cp BSH, and Bl BSH), showing the IC 50 values ranging from 0.28 ± 0.05 μM to 1.62 ± 0.07 μM. Further investigations showed that THTI could covalently modify the conserved catalytic cysteine (Cys2) of all tested gmBSHs, while this agent could strongly inhibit the total gmBSHs activity in live microorganisms and murine gut luminal content. Collectively, THTI is identified as a naturally occurring covalent pan -inhibitor of gmBSHs, which offers a promising lead compound to develop more efficacious gmBSHs inhibitors for the management of bile acid metabolism and related metabolic disorders.

Purpose: To analyze the risk of dental implant failure for patients with a history of antidepressant use through a systematic review and meta-analysis., Materials and Methods: An electronic search was performed up to June 2023 in three databases including PubMed/MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials; data on the comparison of implant failure rate for patients with and without the use of antidepressants were included. Meta-analyses for the risk ratio of implant failure rate at patient level and implant level were performed., Results: Overall, 11 clinical studies were selected for inclusion in this review. The meta-analyses showed a risk ratio of 2.44 (95% CI &#61; 1.75 to 3.39; P < .0001) and 2.44 (95% CI &#61; 1.73 to 3.46; P < .0001) for the implant failure at patient level and implant level, respectively. The comparisons presented a low heterogeneity for the patient-level analysis and a moderate heterogeneity for the implant-level analysis among the pooled studies. Subgroup analyses also revealed that patients who received only selective serotonin reuptake inhibitors (SSRIs) or SSRIs with other types of antidepressants had a higher risk of implant failure than those who were not on any antidepressants., Conclusions: The current review demonstrates that the use of antidepressants such as SSRIs may increase the risk of dental implant failure at both patient level and implant level. Although limited evidence suggests that a certain type of SSRI (sertraline) may have more influence on implant failure than other SSRIs, future studies are needed to confirm this finding.

Understanding how sleep affects the glymphatic system and human brain networks is crucial for elucidating the neurophysiological mechanism underpinning aging-related memory declines. We analyzed a multimodal dataset collected through magnetic resonance imaging (MRI) and polysomnographic recording from 72 older adults. A proxy of the glymphatic functioning was obtained from the Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index. Structural and functional brain networks were constructed based on MRI data, and coupling between the two networks (SC-FC coupling) was also calculated. Correlation analyses revealed that DTI-ALPS was negatively correlated with sleep quality measures [e.g., Pittsburgh Sleep Quality Index (PSQI) and apnea-hypopnea index]. Regarding human brain networks, DTI-ALPS was associated with the strength of both functional connectivity (FC) and structural connectivity (SC) involving regions such as the middle temporal gyrus and parahippocampal gyrus, as well as with the SC-FC coupling of rich-club connections. Furthermore, we found that DTI-ALPS positively mediated the association between sleep quality and rich-club SC-FC coupling. The rich-club SC-FC coupling further mediated the association between DTI-ALPS and memory function in good sleepers but not in poor sleepers. The results suggest a disrupted glymphatic-brain relationship in poor sleepers, which underlies memory decline. Our findings add important evidence that sleep quality affects cognitive health through the underlying neural relationships and the interplay between the glymphatic system and multimodal brain networks., (© 2024. The Author(s).)

Ecosystem service value （ESV） is an important indicator related to regional ecological well-being, and understanding its evolution can provide references for regional ecological civilization construction and sustainable development. The Taihang Mountains, an important ecological security barrier in North China, were taken as an example. Based on land use data from 2000 to 2020, this study revealed the changes in land use and ecosystem service value in the Taihang Mountains and conducted multi-scenario simulations of ESV in 2035. Additionally, the land use transfer matrix, improved equivalent factor method, and mixed-cell cellular automata model were used. The results showed that： ① From 2000 to 2020, the main land use types in the Taihang Mountains were cropland, forest land, and grassland. The area of cropland and grassland significantly decreased, whereas the area of forest land and construction land remained stable. The scale of land use transfer was 2.06×10 4 km 2 , with a high intensity of transfer from cropland and grassland to other areas, mainly guided by ecological construction. ② The ecosystem service functions in the Taihang Mountains were mainly dominated by regulation services, and the overall ESV showed a stable upward trend, increasing by 1.51×10 10 RMB from 2000 to 2020. The spatial distribution of ESV was uneven, and the polarization phenomenon was evident, with high-value areas concentrated in the high-altitude areas in the northern and central-southern parts and low-value areas mostly located in the flat foothills and central plateaus on both sides. They were greatly influenced by human activities. ③ By 2035, compared with that in 2020, the ESV in the Taihang Mountains was projected to increase by 5.37 billion RMB in the natural growth scenario, 4.34 billion RMB in the urban development scenario, and 7.64 billion RMB in the ecological tourism scenario, mainly due to the conversion from cropland and grassland to forest land. The natural growth scenario showed a high intensity of spatial transformation of ESV, the urban development scenario experienced severe ESV loss in cropland, and the ecological tourism scenario showed a significant increase in ESV, which was an effective path for promoting green development in the Taihang Mountains. The research results can provide scientific references for the healthy management and sustainable development of the ecosystem in the Taihang Mountains.

The recent interest in developing low-cost, biocompatible, and lightweight bioelectronic devices has focused on organic electrochemical transistors (OECTs), which have the potential to fulfill these requirements. In this study, three types of poly(3-hexylthiophene) (P3HT)-based block copolymers (BCPs) incorporating different insulating blocks (poly( n butyl acrylate) (PBA), polystyrene, and poly(ethylene oxide) (PEO)) were synthesized for application in OECTs. The morphological, crystallographic, and electrochemical properties of these BCPs are systematically investigated. Accordingly, P3HT- b -PBA demonstrates superior performance in the KCl-based aqueous electrolyte, with a higher product of mobility and capacitance (μ C *) at 170 F s -1 cm -1 V -1 than that of the P3HT homopolymer at 58 F s -1 cm -1 V -1 . P3HT- b -PBA exhibits better stability over 50 ON/OFF switching cycles than do other BCPs and P3HT homopolymers. With regard to the performance in the KPF 6 -based aqueous electrolyte, P3HT- b -PBA outperforms with a higher μ C * of 9.2 F s -1 cm -1 V -1 than that of 8.6 F s -1 cm -1 V -1 observed from P3HT. Notably, both polymers exhibited almost no decay in device performance over 110 ON/OFF switching cycles. The strongly different performance of polymers in these two electrolytes is due to the side chain's hydrophobicity and interdigitated lamellar structures, thereby retarding the doping kinetics of the highly hydrated Cl - ions compared with the slightly hydrated PF 6 - ions. Concerning the improved performance of P3HT- b -PBA, this is attributed to its soft and hydrophobic backbone. Our morphological and crystallographic analyses reveal that P3HT- b -PBA experiences minimal structural disorder when swelled by the electrolyte, maintaining its original structure better than the P3HT homopolymer and the hydrophilic BCP of P3HT- b -PEO. The hydrophobic nature of P3HT- b -PBA contributes to the stability of its backbone structure, ensuring enhanced capacitance during the operation of the OECT operation. These findings provide reassurance about the stability and performance of P3HT- b -PBA in the field of OECT applications. In summary, this study represents the first exploration of P3HT-based BCPs for OECT applications and investigates their structure-performance relationships in mixed ionic-electronic conductors.

Background: The aim of this retrospective study was to investigate the risk of tooth loss for teeth adjacent and nonadjacent to dental implants., Methods: A total of 787 patients with an average follow-up of 57.1 months were examined to define the tooth loss, cumulative survival rate, and odds ratio (OR) for teeth adjacent versus nonadjacent to implants. A multivariate logistic regression was employed to assess the association between dental history and various recorded etiologies of tooth loss among teeth adjacent to implants., Results: The incidence of tooth loss for teeth adjacent to implants was 8.1% at the tooth level and 15.1% at the patient level, while 0.7% and 9.5% at the tooth and patientlevel for teeth nonadjacent to implants. The 10-year cumulative survival rate for teeth adjacent to implants was 89.2%, and the primary etiology of tooth loss was root fracture (45.2%). The risk of tooth loss among teeth adjacent versus nonadjacent to implants was significantly higher (OR 13.15). Among teeth adjacent to implants, root canal-treated teeth had a significantly higher risk of tooth loss due to root fracture (OR 7.72), a history of existing restoration significantly increased the risk of tooth loss due to caries (OR 3.05), and a history of periodontitis significantly increased the risk of tooth loss due to periodontitis (OR 38.24)., Conclusion: The present study demonstrated that after patients received dental implant treatment, teeth adjacent to implants showed a 13.2-fold higher risk of tooth loss compared to teeth nonadjacent to implants, with the primary etiology being root fracture., (© 2024 American Academy of Periodontology.)

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe dermatological conditions, predominantly affecting women with mortality rates of 4.8-48%. Antibiotics are common triggers. They cause painful mucous membrane erosions in various body parts. Treatment involves steroids, creams, and therapy. Pregnant women with SJS-related vaginal stenosis face challenges of delivery route., Case Report: A 34-year-old primigravida woman presented at term with vaginal stenosis consequent to a 10-year-history of Stevens-Johnson syndrome triggered by cephalosporin. On pediatric Pederson speculum examination, vaginal stenosis, adhesion, scarred cervix, telangiectasis of the vaginal mucosa, and moderate bleeding after examination were noted. The risks of severe genital tract laceration and excessive bleeding from vaginal birth was discussed with the couple. Shared clinical decision making was reached to undergo a cesarean delivery., Conclusion: SJS and TEN can result in severe genital complications in women, sometimes requiring cesarean sections due to genital scarring., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Background: Periodontal disease constitutes a widely prevalent category of non-communicable diseases and ranks among the top 10 causes of disability worldwide. Little however is known about diagnostic errors in dentistry. In this work, by retrospectively deploying an electronic health record (EHR)-based trigger tool, followed by gold standard manual review, we provide epidemiological estimates on the rate of diagnostic misclassification in dentistry through a periodontal use case., Methods: An EHR-based trigger tool (a retrospective record review instrument that uses a list of triggers (or clues), i.e., data elements within the health record, to alert reviewers to the potential presence of a wrong diagnosis) was developed, tested and run against the EHR at the two participating sites to flag all cases having a potential misdiagnosis. All cases flagged as potentially misdiagnosed underwent extensive manual reviews by two calibrated domain experts. A subset of the non-flagged cases was also manually reviewed., Results: A total of 2,262 patient charts met the study's inclusion criteria. Of these, the algorithm flagged 1,124 cases as potentially misclassified and 1,138 cases as potentially correctly diagnosed. When the algorithm identified a case as potentially misclassified, compared to the diagnosis assigned by the gold standard, the kappa statistic was 0.01. However, for cases the algorithm marked as potentially correctly diagnosed, the review against the gold standard showed a kappa statistic of 0.9, indicating near perfect agreement. The observed proportion of diagnostic misclassification was 32 %. There was no significant difference by clinic or provider characteristics., Conclusion: Our work revealed that about a third of periodontal cases are misclassified. Diagnostic errors have been reported to happen more frequently than other types of errors, and to be more preventable. Benchmarking diagnostic quality is a first step. Subsequent research endeavor will delve into comprehending the factors that contribute to diagnostic errors in dentistry and instituting measures to prevent them., Clinical Significance: This study sheds light on the significance of diagnostic excellence in the delivery of dental care, and highlights the potential role of technology in aiding diagnostic decision-making at the point of care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all-cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non-H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan-Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all-cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696-0.882 for 30-day; HR = 0.860, 95% CI: 0.778-0.950 for 90-day; and HR = 0.883, 95% CI: 0.811-0.961 for 1-year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m 2 , coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients., (© 2024, The American College of Clinical Pharmacology.)

Gut microbial Loop-1 β-glucuronidases (gmGUS) played an important role in irinotecan-induced gastrointestinal toxicity by regulating the level of its active metabolite SN38 through enterohepatic recirculation. gmGUS inhibition has emerged as a promising approach to relieve its dose-limiting intestinal toxicity and improve its medication efficacy. This study aims to investigate the inhibitory effects and mechanisms of Platycladi cacumen and its main constituent hinokiflavone against four different types of Loop-1 gmGUS (EeGUS, SaGUS, CpGUS and EcGUS). Our results showed that the ethanol extract of Platycladi cacumen displayed strong broad-spectrum inhibition against four gmGUS, and hinokiflavone could potently inhibit EeGUS, SaGUS, CpGUS and EcGUS with IC 50 values of 0.09 ± 0.01 μM, 0.44 ± 0.01 μM, 0.20 ± 0.01 μM and 0.69 ± 0.10 μM, respectively. Inhibition kinetic analyses demonstrated that hinokiflavone acted as a strong competitive inhibitor of EeGUS with K i value of 0.13 μM, while it displayed non-competitive inhibition against SaGUS, CpGUS and EcGUS, with the K i values of 0.43 μM, 0.33 μM and 0.76 μM, respectively. Docking simulations revealed that hinokiflavone could tightly bind with Tyr-485 and Glu-516 in catalytic sites of EeGUS, as well it created strong interactions with amino acids in loop structures of SaGUS (Asn-362), CpGUS (Phe-363, Met-364, Ala-365 and Arg-375) and EcGUS (Leu-361) to interfere the substrate entry into the catalytic pocket. Collectively, these results confirmed that hinokiflavone from Platycladi cacumen is a potent naturally occurring inhibitor of gmGUS with broad efficiency, suggesting hinokiflavone will be helpful for alleviating intestinal toxicity in irinotecan 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.)

Metabolic responses to cellular stress are pivotal in cell ferroptosis, with mitophagy serving as a crucial mechanism in both metabolic processes and ferroptosis. This study aims to elucidate the effects of high glucose on cardiomyocytes (CMs) and cardiac fibroblasts (CFs) regarding ferroptosis and to uncover the underlying mechanisms involved. We examined alterations in glycolysis, mitochondrial oxidative phosphorylation (OXPHOS), and mitophagy, which are essential for metabolic adaptations and ferroptosis. High glucose exposure induced ferroptosis specifically in CMs, while CFs exhibited resistance to ferroptosis, increased glycolytic activity, and no change in OXPHOS. Moreover, high glucose treatment enhanced mitophagy and upregulated mitochondrial ferritin (FTMT). Notably, the combination of FTMT and the autophagy-related protein nuclear receptor coactivator 4 (NCOA4) increased under high glucose conditions. Silencing FTMT significantly impeded mitophagy and eliminated ferroptosis resistance in CFs cultured under high glucose conditions. The transcription factor forkhead box A1 (FOXA1) was upregulated in CFs upon high glucose exposure, playing a crucial role in the increased expression of FTMT. Within the 5'-flanking sequence of the FTMT mRNA, approximately -500 nt from the transcription initiation site, three putative FOXA1 binding sites were identified. High glucose augmented the binding affinity between FOXA1 and these sequences, thereby promoting FTMT transcription. In summary, high glucose upregulated FOXA1 expression and stimulated FTMT promoter activity in CFs, thereby promoting FTMT-dependent mitophagy and conferring ferroptosis resistance in CFs., 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.)

Introduction: This study aimed to compare the clinical efficacy of sexual stimulation with that of placebo in the treatment of distal ureteral stones., Methods: We searched PubMed, Web of Science, Cochrane Library, and Google Scholar from January 1, 2000 to December 31, 2022 for studies comparing the efficacy of sexual stimulus with that of placebo for the treatment of distal ureteral stones. RevMan 5.3 software was used to pool the data. The study protocol was registered on PROSPERO (Registration Number: CRD42023432408)., Results: A total of six randomized controlled trials comprising 535 cases of distal ureteral stones were included in this study. Among these, 273 cases were associated with sexual intercourse or masturbation 3-4 times a week, while 262 cases only received symptomatic treatment. The pooled results showed that the 2-week [risk ratios (RR) = 1.77, 95 % confidence interval (CI): 1.34, 2.33] and 4-week [RR = 1.48, 95 % CI: 1.29, 1.69] ureteral stone expulsion rates of the sexually stimulated group were significantly higher than those of the placebo group (p s  < 0.01). Additionally, sexual stimulation was associated with a shorter ureteral stone expulsion time [weighted mean differences (WMD) = -3.74, 95 % CI: -6.27, -1.22, p < 0.01] and a decreased prevalence of renal colic attacks [WMD = -0.61, 95 % CI: -1.01, -0.22, p < 0.01] compared with those of the placebo group., Conclusion: Appropriate sexual stimulation can enhance the spontaneous expulsion of distal ureteral stones in patients presenting with tolerable pain., 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., (© 2024 The Authors.)

Objective: To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion (OLIF), and put forward preventive measures., Methods: From October 2015 to December 2019, 23 patients who underwent reoperation after OLIF in four spine surgery centers were retrospectively analyzed. There were 9 males and 14 females with an average age of (61.89±8.80) years old ranging from 44 to 81 years old. The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases, discogenic low back pain in 1 case, degenerative lumbar spondylolisthesis in 6 cases, lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases. Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation. There were 17 cases of single fusion segment, 2 of 2 fusion segments, 4 of 3 fusion segments. All the cases underwent reoperation within 3 months after the initial surgery. The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy, cage adjustment and neurolysis in 2 cases, arthroplasty and neurolysis under endoscope in 1 case, posterior laminectomy and neurolysis in 1 case, pedicle screw adjustment in 1 case, exploration and decompression under percutaneous endoscopic in 1 case, interbody fusion cage and pedicle screw revision in 1 case. Visual analogue scale (VAS) and Oswestry disability index (ODI) index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up. During the follow-up process, the phenomenon of fusion cage settlement or re-displacement, as well as the condition of intervertebral fusion, were observed. The changes in intervertebral space height before the first operation, after the first operation, before the second operation, 3 to 5 days after the second operation, 6 months after the second operation, and at the latest follow-up were measured and compared., Results: There was no skin necrosis and infection. All patients were followed up from 12 to 48 months with an average of (28.1±7.3) months. Nerve root injury symptoms were relieved within 3 to 6 months. No cage transverse shifting and no dislodgement, loosening or breakage of the instrumentation was observed in any patient during the follow-up period. Though the intervertebral disc height was obviously increased at the first postoperative, there was a rapid loss in the early stage, and still partially lost after reoperation. The VAS for back pain recovered from (6.20±1.69) points preoperatively to (1.60±0.71) points postoperatively( P <0.05). The ODI recovered from (40.60±7.01)% preoperatively to (9.14±2.66)% postoperatively( P <0.05)., Conclusion: There is a risk of reoperation due to failure after OLIF surgery. The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone, intraoperative endplate injury, significant subsidence of the fusion cage after surgery, postoperative fusion cage displacement, nerve damage, etc. As long as it is discovered in a timely manner and handled properly, further surgery after OLIF surgery can achieve better clinical results, but prevention still needs to be strengthened.

Background: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period., Methods: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values., Results: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality., Conclusions: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively., (© 2024. The Author(s).)

Objectives: To investigate the causes of space-occupying tumor bed cysts formed early after glioma resection by measuring the osmotic pressure gradient between cystic fluid, serum, and cerebrospinal fluid (CSF) and propose a new method of bedside ultrasound-assisted puncture and drainage (UAP&D) under local anesthesia for treatment., Methods: Bedside UAP&D under local anesthesia was performed through a burr hole on the skull flap.Following a successful puncture, cystic fluid was collected, while blood and CSF were obtained through vein and lumbar puncture, respectively. The osmotic pressure of all fluids collected was measured. The appearance, biochemical composition, and results of microbial culture of cystic fluid and CSF were analyzed. Within 24 h after UAP&D, a CT examination and Glasgow coma scale (GCS) were assessed., Results: The osmotic pressure of cystic fluid was higher than that of serum and CSF. White blood cell count and protein concentration were higher in the cystic fluid compared to the CSF. Conversely, the concentration of chloride ions and glucose were lower. CT scan confirmed the correct placement of the cysts' drainage tube and that the cysts' volume decreased significantly with continued drainage. Accompanied by a reduction in the volume of cysts, there were significant improvements in GCS score within 24 h after UAP&D. All drainage tubes were removed within 2-5 days, and no puncture tract hemorrhage or infection was observed., Conclusion: The osmotic pressure gradient between cystic fluid, serum, and CSF caused the formation of early post-operative space-occupying tumor bed cysts for glioma. UAP&D aligns with the concept that micro-invasive neurosurgery is an effective treatment method for such cysts., 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.)

Purpose: In recent decades, the occurrence of heart failure with preserved ejection fraction (HFpEF) has outweighed that of heart failure with reduced ejection fraction by degrees, but few drugs have been demonstrated to improve long-term clinical outcomes in patients with HFpEF. Levosimendan, a calcium-sensitizing cardiotonic agent, improves decompensated heart failure clinically. However, the anti-HFpEF activities of levosimendan and underlying molecular mechanisms are unclear., Methods: In this study, a double-hit HFpEF C57BL/6N mouse model was established, and levosimendan (3 mg/kg/week) was administered to HFpEF mice aged 13 to 17 weeks. Different biological experimental techniques were used to verify the protective effects of levosimendan against HFpEF., Results: After four weeks of drug treatment, left ventricular diastolic dysfunction, cardiac hypertrophy, pulmonary congestion, and exercise exhaustion were significantly alleviated. Junction proteins in the endothelial barrier and between cardiomyocytes were also improved by levosimendan. Among the gap junction channel proteins, connexin 43, which was especially highly expressed in cardiomyocytes, mediated mitochondrial protection. Furthermore, levosimendan reversed mitochondrial malfunction in HFpEF mice, as evidenced by increased mitofilin and decreased ROS, superoxide anion, NOX4, and cytochrome C levels. Interestingly, after levosimendan administration, myocardial tissue from HFpEF mice showed restricted ferroptosis, indicated by an increased GSH/GSSG ratio; upregulated GPX4, xCT, and FSP-1 expression; and reduced intracellular ferrous ion, MDA, and 4-HNE levels., Conclusion: Regular long-term levosimendan administration can benefit cardiac function in a mouse model of HFpEF with metabolic syndromes (namely, obesity and hypertension) by activating connexin 43-mediated mitochondrial protection and sequential ferroptosis inhibition in cardiomyocytes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Human pancreatic lipase (hPL) is a vital digestive enzyme responsible for breaking down dietary fats in humans, inhibiting hPL is a feasible strategy for preventing and treating obesity. This study aims to investigate the structure-activity relationships (SARs) of flavonoids as hPL inhibitors, and to find potent hPL inhibitors from natural and synthetic flavonoids. In this work, the anti-hPL effects of forty-nine structurally diverse naturally occurring flavonoids were assessed and the SARs were summarized. The results demonstrated that the pyrogallol group on the A ring was a key moiety for hPL inhibition. Subsequently, a series of baicalein derivatives were synthesized, while 4'-amino baicalein (ABA) and 4'-pyrrolidine baicalein (PBA) were identified as novel potent hPL inhibitors (IC 50  < 1 μM). Further investigations showed that scutellarein, ABA and PBA potently inhibited hPL in a non-competitive manner (K i  < 1 μM). Among all tested flavonoids, PBA showed the most potent anti-hPL effect in vitro, while this agent also exhibited favorable safety profiles, unique tissue distribution (high exposure level to intestinal system but low exposure levels to deep organs) and impressive in vivo effects for lowering blood triglyceride levels in mice. Collectively, this work uncovers the SARs of flavonoids against hPL, while a newly synthetic flavonoid (PBA) emerges as a potent hPL inhibitor with favorable safety profiles and impressive anti-hPL effects in vivo., 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: Research studies on Asian women's preferences for breast augmentation and the factors that influence decision-making are scarce or unrepresentative., Methods: This study was conducted from September 2016 to September 2017, a period of one year. We developed a questionnaire for Chinese female with breast augmentation intentions based on the Breast-Q questionnaire, the world's most popular breast augmentation assessment tool, and conducted questionnaire surveys in 35 hospitals located in 19 provinces in mainland China among female who came to hospitals to inquire about breast augmentation surgery., Results: A total of 2066 questionnaires were collected from female interested in breast augmentation. The age range at the time of response was 19-53 years (mean 31.2 ± 6.8 years). More than half of the respondents (58.1%) were married, and 70.4% of them had children. The respondents rated their dressed image significantly higher than their nude image. Their partners also rated their breast image poorly, with 43% rating it fair and 30.4% negatively. Internal reasons, such as improving self-confidence and creating a better body image, were the main motivators for breast augmentation. More than half of the respondents had only limited understanding of breast augmentation surgery or had heard of it but did not fully understand it (33.2% and 27.5%, respectively), and 69.4% had considered breast augmentation for less than three years. A total of 49.2% of the respondents learned about breast augmentation surgery through the Internet. A total of 43.8% of the respondents did not receive support from family members or partners. Surgical safety (20.4%), surgical effect (17.1%), and surgeon's skill (16.6%) were given the highest priority. The surgeon's professionalism, popularity, and academic background were also high on people's list of considerations., Conclusions: The results of our breast augmentation survey provide data on many Chinese women considering breast augmentation. This will help plastic surgeons better understand the characteristics, preferences, and concerns of Chinese women undergoing breast augmentation and will be used to guide patient-doctor communication and help Chinese women make the most informed decisions., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Exoristobia philippinensis (Hymenoptera: Encyrtidae) is a worldwide parasitic wasp. This work presents the mitochondrial genome (mitogenome) of E. philippinensis for the first time. The complete mitochondrial genome of E. philippinensis was sequenced and annotated, which was 15,751 bp in length, and encoded 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). All 13 PCGs were initiated by the ATN (ATG, ATT, and ATA) codon, terminated with the stop codon TAA except for ND1 which ends with TAG. Phylogenetic analysis showed that E. philippinensis has a sister relationship with the genus Lamennaisia ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Dry-cured ham is important source of bioactive peptides. In this study, the antioxidant activities of peptides and components from low and fully salted dry-cured hams were compared by peptidomics. And novel antioxidant peptides were identified and characterized. The results showed that the peptides (<3 KDa) extracted from low-salt dry-cured ham had higher antioxidant activity. Therefore, the antioxidant peptides in low-salt dry-cured ham were further characterized and the mechanism of their antioxidant activity was investigated. From the five candidate peptides selected, we found DWPDARGIWHND (DD12) to be highly stable, non-sensitizing, and non-toxic with the highest free radical scavenging activity. Molecular docking predicted that DD12 interacted with Keap1 through hydrogen-bond formation and hydrophobic interactions, suggesting that DD12 had good cellular antioxidant activity. DD12 peptide can bind to DPPH• and ABTS•+, resulting in strong free radical scavenging activity. Our findings support the development and application of natural antioxidant peptides in dry-cured ham., 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.)

Anagyrus , a genus of Encyrtidae (Hymenoptera, Chalcidoidea), represents a successful group of parasitoid insects that attack various mealybug pests of agricultural and forestry plants. Until now, only 20 complete mitochondrial genomes have been sequenced, including those in this study. To enrich the diversity of mitochondrial genomes in Encyrtidae and to gain insights into their phylogenetic relationships, the mitochondrial genomes of two species of Anagyrus were sequenced, and the mitochondrial genomes of these species were compared and analyzed. Encyrtid mitochondrial genomes exhibit similarities in nucleotide composition, gene organization, and control region patterns. Comparative analysis of protein-coding genes revealed varying molecular evolutionary rates among different genes, with six genes ( ATP8 , ND2 , ND4L , ND6 , ND4 and ND5 ) showing higher rates than others. A phylogenetic analysis based on mitochondrial genome sequences supports the monophyly of Encyrtidae; however, the two subfamilies, Encyrtinae and Tetracneminae, are non-monophyletic. This study provides valuable insights into the phylogenetic relationships within the Encyrtidae and underscores the utility of mitochondrial genomes in the systematics of this family., Competing Interests: The authors have declared that no competing interests exist., (Cheng-Hui Zhang, Hai-Yang Wang, Yan Wang, Zhi-Hao Chi, Yue-Shuo Liu, Guo-Hao Zu.)

Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factor is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation. The expression levels of FoxO3 in BMSCs during aging were detected in vivo and in vitro. To explore the role of FoxO3 in osteogenic and adipogenic differentiation, primary BMSCs were isolated from young and aged mice. FoxO3 expression was modulated by adenoviral vector transfection. The role of FoxO3 in bone-fat balance was evaluated by alizarin red S staining, oil red O staining, quantitative reverse transcription-polymerase chain reaction, Western blot, and histological analysis. Age-related bone loss and fat deposit are associated with downregulation of FoxO3. Overexpression of FoxO3 alleviated age-related bone loss and marrow fat accumulation in aged mice. Mechanistically, FoxO3 reduced adipogenesis and enhanced osteogenesis of BMSCs via downregulation of PPAR-γ and Notch signaling, respectively. In conclusion, FoxO3 is an essential factor controlling the fate of BMSCs and is a potential target for the prevention of age-related osteoporosis.

In the context of using aircraft as a pivotal tool for detecting radioactive hotspots, the acquisition of radioactivity data was conducted through a CeBr 3 scintillation crystal detector mounted on a helicopter. However, challenges arose, including managing extensive data volumes, computationally demanding tasks, and susceptibility to local optima issues. To address these challenges and leverage the benefits of the Sparrow Search Algorithm (SSA) in global optimization and convergence speed, an improved SSA was devised. This improved version integrated SSA principles with the intricacies of searching for radioactive hotspots. The algorithm employed a matrix segmentation method to process data matrices derived from measured data, aiming to enhance efficiency and accuracy. An empirical analysis was conducted, performing 100 iterations on an experimental matrix to scrutinize the impact of matrix segmentation. Computation times and results were compared across different segmentation levels, confirming the favorable algorithmic outcomes of the method. The practical viability and convergence stability of the algorithm were further assessed using genuine measured data, with segmented matrices generated for evaluation. Remarkably, a comparison between computational outcomes and manually identified data reaffirmed the algorithm's reliability in effectively detecting radioactive hotspots., 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: Aristolochic acids (AAs) are naturally occurring nitro phenanthrene carboxylic acids primarily found in plants of the Aristolochiaceae family. Aristolochic acid D (AAD) is a major constituent in the roots and rhizomes of the Chinese herb Xixin (the roots and rhizomes of Asarum heterotropoides F. Schmidt), which is a key material for preparing a suite of marketed Chinese medicines. Structurally, AAD is nearly identical to the nephrotoxic aristolochic acid I (AAI), with an additional phenolic group at the C-6 site. Although the nephrotoxicity and metabolic pathways of AAI have been well-investigated, the metabolic pathway(s) of AAD in humans and the influence of AAD metabolism on its nephrotoxicity has not been investigated yet., Aim of the Study: To identify the major metabolites of AAD in human tissues and to characterize AAD O-glucuronidation kinetics in different enzyme sources, as well as to explore the influence of AAD O-glucuronidation on its nephrotoxicity., Materials and Methods: The O-glucuronide of AAD was biosynthesized and its chemical structure was fully characterized by both 1 H-NMR and 13 C-NMR. Reaction phenotyping assays, chemical inhibition assays, and enzyme kinetics analyses were conducted to assess the crucial enzymes involved in AAD O-glucuronidation in humans. Docking simulations were performed to mimic the catalytic conformations of AAD in human UDP-glucuronosyltransferases (UGTs), while the predicted binding energies and distances between the deprotonated C-6 phenolic group of AAD and the glucuronyl moiety of UDPGA in each tested human UGT isoenzyme were measured. The mitochondrial membrane potentials (MMP) and reactive oxygen species (ROS) levels in HK-2 cells treated with either AAI, or AAD, or AAD O-glucuronide were tested, to elucidate the impact of O-glucuronidation on the nephrotoxicity of AAD., Results: AAD could be rapidly metabolized in human liver and intestinal microsomes (HLM and HIM, respectively) to form a mono-glucuronide, which was purified and fully characterized as AAD-6-O-β-D-glucuronide (AADG) by NMR. UGT1A1 was the predominant enzyme responsible for AAD-6-O-glucuronidation, while UGT1A9 contributed to a lesser extent. AAD-6-O-glucuronidation in HLM, HIM, UGT1A1 and UGT1A9 followed Michaelis-Menten kinetics, with the K m values of 4.27 μM, 9.05 μM, 3.87 μM, and 7.00 μM, respectively. Docking simulations suggested that AAD was accessible to the catalytic cavity of UGT1A1 or UGT1A9 and formed catalytic conformations. Further investigations showed that both AAI and AAD could trigger the elevated intracellular ROS levels and induce mitochondrial dysfunction and in HK-2 cells, but AADG was hardly to trigger ROS accumulation and mitochondrial dysfunction., Conclusion: Collectively, UGT1A-catalyzed AAD 6-O-glucuronidation represents a crucial detoxification pathway of this naturally occurring AAI analogs in humans, which is very different from that of AAI., 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.)

Neurologic Rosai-Dorfman disease (RDD) is a rare type of non-Langerhans cell histiocytosis that affects the central nervous system. Most neurologic RDDs grow like meningiomas, have clear boundaries, and can be completely resected. However, a few RDDs are invasive and aggressive, and no effective treatment options are available because the molecular mechanisms involved remain unknown. Here, we report a case of deadly and glucocorticoid-resistant neurologic RDD and explore its possible pathogenic mechanisms via single-cell RNA sequencing. First, we identified two distinct but evolutionarily related histiocyte subpopulations (the C1Q+ and SPP1+ histiocytes) that accumulated in the biopsy sample. The expression of genes in the KRAS signaling pathway was upregulated, indicating gain-of-function of KRAS mutations. The C1Q+ and SPP1+ histiocytes were highly differentiated and arrested in the G1 phase, excluding the idea that RDD is a lympho-histio-proliferative disorder. Second, although C1Q+ histiocytes were the primary RDD cell type, SPP1+ histiocytes highly expressed several severe inflammation-related and invasive factors, such as WNT5A, IL-6, and MMP12, suggesting that SPP1+ histiocytes plays a central role in driving the progression of this disease. Third, oligodendrocytes were found to be the prominent cell type that initiates RDD via MIF and may resist glucocorticoid treatment via the MDK and PTN signaling pathways. In summary, in this case, we report a rare presentation of neurologic RDD and provided new insight into the pathogenic mechanisms of progressive neurologic RDD. This study will also offer evidence for developing precision therapies targeting this complex disease., (© 2024. The Author(s).)

Obesity is associated with alterations in lipid metabolism and gut microbiota dysbiosis. This study investigated the effects of puerarin, a bioactive isoflavone, on lipid metabolism disorders and gut microbiota in high-fat diet (HFD)-induced obese mice. Supplementation with puerarin reduced plasma alanine aminotransferase, liver triglyceride, liver free fatty acid (FFA), and improved gut microbiota dysbiosis in obese mice. Puerarin's beneficial metabolic effects were attenuated when farnesoid X receptor (FXR) was antagonized, suggesting FXR-mediated mechanisms. In hepatocytes, puerarin ameliorated high FFA-induced sterol regulatory element-binding protein (SREBP) 1 signaling, inflammation, and mitochondrial dysfunction in an FXR-dependent manner. In obese mice, puerarin reduced liver damage, regulated hepatic lipogenesis, decreased inflammation, improved mitochondrial function, and modulated mitophagy and ubiquitin-proteasome pathways, but was less effective in FXR knockout mice. Puerarin upregulated hepatic expression of FXR, bile salt export pump (BSEP), and downregulated cytochrome P450 7A1 (CYP7A1) and sodium taurocholate transporter (NTCP), indicating modulation of bile acid synthesis and transport. Puerarin also restored gut microbial diversity, the Firmicutes / Bacteroidetes ratio, and the abundance of Clostridium celatum and Akkermansia muciniphila . This study demonstrates that puerarin effectively ameliorates metabolic disturbances and gut microbiota dysbiosis in obese mice, predominantly through FXR-dependent pathways. These findings underscore puerarin's potential as a therapeutic agent for managing obesity and enhancing gut health, highlighting its dual role in improving metabolic functions and modulating microbial communities.

Food allergy (FA) poses a growing global food safety concern, yet no effective cure exists in clinics. Previously, we discovered a potent antifood allergy compound, butyrolactone I (BTL-I, 1 ), from the deep sea. Unfortunately, it has a very low exposure and poor pharmacokinetic (PK) profile in rats. Therefore, a series of structural optimizations toward the metabolic pathways of BTL-I were conducted to provide 18 derives ( 2 - 19 ). Among them, BTL-MK ( 19 ) showed superior antiallergic activity and favorable pharmacokinetics compared to BTL-I, being twice as potent with a clearance (CL) rate of only 0.5% that of BTL-I. By oral administration, C max and area under the concentration-time curve (AUC 0-∞ ) were 565 and 204 times higher than those of BTL-I, respectively. These findings suggest that butyrolactone methyl ketone (BTL-BK) could serve as a drug candidate for the treatment of FAs and offer valuable insights into optimizing the druggability of lead compounds.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2 , in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results., 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., (© 2024 The Authors.)

Gut microbial β-glucuronidases (gmβ-GUS) played crucial roles in regulating a variety of endogenous substances and xenobiotics on the circulating level, thus had been recognized as key modulators of drug toxicity and human diseases. Inhibition or inactivation of gmβ-GUS enzymes has become a promising therapeutic strategy to alleviate drug-induced intestinal toxicity. Herein, the Rhodiola crenulata extract (RCE) was found with potent and broad-spectrum inhibition on multiple gmβ-GUS enzymes. Subsequently, the anti-gmβ-GUS activities of the major constituents in RCE were tested and the results showed that 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (PGG) acted as a strong and broad-spectrum inhibitor on multiple gmβ-GUS (including EcGUS, CpGUS, SaGUS, and EeGUS). Inhibition kinetic assays demonstrated that PGG effectively inhibited four gmβ-GUS in a non-competitive manner, with the K i values ranging from 0.12 μM to 1.29 μM. Docking simulations showed that PGG could tightly bound to the non-catalytic sites of various gmβ-GUS, mainly via hydrogen bonding and aromatic interactions. It was also found that PGG could strongly inhibit the total gmβ-GUS activity in mice feces, with the IC 50 value of 1.24 μM. Collectively, our findings revealed that RCE and its constituent PGG could strongly inhibit multiple gmβ-GUS enzymes, suggesting that RCE and PGG could be used for alleviating gmβ-GUS associated enterotoxicity., 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.)

Aim: To develop and validate an automated electronic health record (EHR)-based algorithm to suggest a periodontal diagnosis based on the 2017 World Workshop on the Classification of Periodontal Diseases and Conditions., Materials and Methods: Using material published from the 2017 World Workshop, a tool was iteratively developed to suggest a periodontal diagnosis based on clinical data within the EHR. Pertinent clinical data included clinical attachment level (CAL), gingival margin to cemento-enamel junction distance, probing depth, furcation involvement (if present) and mobility. Chart reviews were conducted to confirm the algorithm's ability to accurately extract clinical data from the EHR, and then to test its ability to suggest an accurate diagnosis. Subsequently, refinements were made to address limitations of the data and specific clinical situations. Each refinement was evaluated through chart reviews by expert periodontists at the study sites., Results: Three-hundred and twenty-three charts were manually reviewed, and a periodontal diagnosis (healthy, gingivitis or periodontitis including stage and grade) was made by expert periodontists for each case. After developing the initial version of the algorithm using the unmodified 2017 World Workshop criteria, accuracy was 71.8% for stage alone and 64.7% for stage and grade. Subsequently, 16 modifications to the algorithm were proposed and 14 were accepted. This refined version of the algorithm had 79.6% accuracy for stage alone and 68.8% for stage and grade together., Conclusions: Our findings suggest that a rule-based algorithm for suggesting a periodontal diagnosis using EHR data can be implemented with moderate accuracy in support of chairside clinical diagnostic decision making, especially for inexperienced clinicians. Grey-zone cases still exist, where clinical judgement will be required. Future applications of similar algorithms with improved performance will depend upon the quality (completeness/accuracy) of EHR data., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The commercialization of lithium-sulfur (Li-S) batteries has been hindered by the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs). Herein, we reported a viologen-based ionic conjugated mesoporous polymer (TpV-Cl), which acts as the cathode host for modifying Li-S batteries. The viologen component serves as a reversible electron conveyer, leading to a comprehensive enhancement in the adsorption of polysulfides and improved conversion rate of polysulfides during the electrochemical process. As a result, the S@TpV-PS cathode exhibits outstanding cycling performance, achieving 300 cycles at 2.0 C (1 C = 1675 mA g - 1 ) with low decay rate of 0.032% per cycle. Even at a high sulfur loading of 4.0 mg cm - 2 , S@TpV-PS shows excellent cycling stability with a Coulombic efficiency of up to 98%. These results highlight the significant potential of S@TpV-PS in developing high-performance Li-S batteries., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

A light beam can be spatially structured in the complex amplitude to possess orbital angular momentum (OAM), which introduces an extra degree of freedom alongside the intrinsic spin angular momentum (SAM) associated with circular polarization. Furthermore, superimposing two such twisted light (TL) beams with distinct SAM and OAM produces a vector vortex beam (VVB) in nonseparable states where not only complex amplitude but also polarization is spatially structured and entangled with each other. In addition to the nonseparability, the SAM and OAM in a VVB are intrinsically coupled by the optical spin-orbit interaction and constitute the profound spin-orbit physics in photonics. In this work, we present a comprehensive theoretical investigation, implemented on the first-principles base, of the intriguing light-matter interaction between VVBs and WSe 2 monolayers (WSe 2 -MLs), one of the best-known and promising two-dimensional (2D) materials in optoelectronics dictated by excitons, encompassing bright exciton (BX) as well as various dark excitons (DXs). One of the key findings of our study is that a substantial enhancement of the photoexcitation of gray excitons (GXs), a type of spin-forbidden DX, in a WSe 2 -ML can be achieved through the utilization of a 3D-structured TL with the optical spin-orbit interaction. Moreover, we show that a spin-orbit-coupled VVB surprisingly allows for the imprinting of the carried optical information onto GXs in 2D materials, which is robust against the decoherence mechanisms in the materials. This suggests a promising method for deciphering the transferred angular momentum from structured light to excitons.

The palladium-catalyzed sequential cross-coupling/annulation of ortho -vinyl bromobenzenes with aryl bromides generating phenanthrenes was characterized by density functional theory (DFT). The Pd(II)-Pd(IV) pathway (Path V) is shown to be less probable than the bimetallic pathway (Path I), the latter proceeding via the following six steps: oxidative addition, vinyl-C(sp 2 )-H activation, Pd(II)-Pd(II) transmetalation, C-C coupling, aryl-C(sp 2 )-H activation, and reductive elimination. The aryl-C(sp 2 )-H activation process acts as the rate-determining step (RDS) of the entire chemical transformation, with an activation free energy barrier of ca. 27.4-28.8 kcal·mol -1 , in good agreement with the corresponding experimental data (phenanthrenes' yields of ca. 65-90% at 130 °C after 5 h of reaction). The K 2 CO 3 additive effectively reduces the activation free energy barrier of the RDS through direct participation in the reaction while preferentially modulating the charge distributions and increasing the stability of corresponding intermediates and complexes along the reaction path. Furthermore, bonding and electronic structure analyses of the key structures indicate that the chemo- and regioselectivities of the reaction are strongly influenced by both electronic effects and steric hindrance.

Along with the development of nuclear power, concerns about radioactive emissions and the potential for nuclear leakage have been widely raised, particularly of harmful iodine isotopes. However, as a significant component of nuclear air waste, the enrichment and detection of air-dispersed gaseous iodine remain a challenge. In this work, it is focused on developing an attraction-immobilization-detection strategy-based fluorescence method for the on-site detection of volatile iodine, by employing a photoluminescent ionic polyimine network-polyvinylpyrrolidone (IPIN-PVP) composite membrane. This strategy synergizes ion-induced dipole interactions from IPIN and complexation effects from PVP, allowing effective iodine enrichment and immobilization. As a result, the optimized IPIN-PVP membrane exhibits rapid response times of 5 s and a low detection limit of 4.087 × 10 -8  m for gaseous iodine. It also introduces a portable handheld detection device that utilizes the composite membrane, offering a practical solution for real-time on-site detection of volatile iodine. This innovation enhances nuclear safety measures and disaster management by providing rapid and reliable iodine detection capabilities., (© 2024 Wiley‐VCH GmbH.)

Hazardous biological pathogens in the air pose a significant public environmental health concern as infected individuals emit virus-laden aerosols (VLAs) during routine respiratory activities. Mask-wearing is a key preventive measure, but conventional filtration methods face challenges, particularly in high humidity conditions, where electrostatic charge decline increases the risk of infection. This study introduces a bio-based air filter comprising glycine ionic liquids (GILs) and malleable polymer composite (GILP) with high polarity and functional group density, which are wrapped around a melamine-formaldehyde (MF) resin skeleton, forming a conductive, porous GIL functionized ionic network air filter (GILP@MF). When subjected to low voltage, the GILP@MF composite efficiently captures VLAs including nanoscale virus particles through the enhanced electrostatic attraction, especially in facing high humidity bioaerosols exhaled by human body. The filtration/collection efficiency and quality factor can reach 98.3% and 0.264 Pa -1 at 0.1 m s -1 , respectively. This innovative filter provides effective VLA protection and offers potential for non-invasive respiratory virus sampling, advancing medical diagnosis efforts., 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: Ampelopsideae J. Wen & Z.L. Nie is a small-sized tribe of Vitaceae Juss., including ca. 47 species from four genera showing a disjunct distribution worldwide across all the continents except Antarctica. There are numerous species from the tribe that are commonly used as medicinal plants with immune-modulating, antimicrobial, and anti-hypertensive properties. The tribe is usually recognized into three clades, i.e., Ampelopsis Michx., Nekemias Raf., and the Southern Hemisphere clade. However, the relationships of the three clades differ greatly between the nuclear and the plastid topologies. There has been limited exploration of the chloroplast phylogenetic relationships within Ampelopsideae, and studies on the chloroplast genome structure of this tribe are only available for a few individuals. In this study, we aimed to investigate the evolutionary characteristics of plastid genomes of the tribe, including their genome structure and evolutionary insights., Results: We sequenced, assembled, and annotated plastid genomes of 36 species from the tribe and related taxa in the family. Three main clades were recognized within Ampelopsideae, corresponding to Ampelopsis, Nekemias, and the Southern Hemisphere lineage, respectively, and all with 100% bootstrap supports. The genome sequences and content of the tribe are highly conserved. However, comparative analyses suggested that the plastomes of Nekemias demonstrate a contraction in the large single copy region and an expansion in the inverted repeat region, and possess a high number of forward and palindromic repeat sequences distinct from both Ampelopsis and the Southern Hemisphere taxa., Conclusions: Our results highlighted plastome variations in genome length, expansion or contraction of the inverted repeat region, codon usage bias, and repeat sequences, are corresponding to the three lineages of the tribe, which probably faced with different environmental selection pressures and evolutionary history. This study provides valuable insights into understanding the evolutionary patterns of plastid genomes within the Ampelopsideae of Vitaceae., (© 2024. The Author(s).)

Entomopathogenic nematodes (EPNs) use the chemical cues emitted by insects and insect-damaged plants to locate their hosts. Steinernema carpocapsae, a species of EPN, is an established biocontrol agent used against insect pests. Despite its promising potential, the molecular mechanisms underlying its ability to detect plant volatiles remain poorly understood. In this study, we investigated the response of S. carpocapsae infective juveniles (IJs) to 8 different plant volatiles. Among these, carvone was found to be the most attractive volatile compound. To understand the molecular basis of the response of IJs to carvone, we used RNA-Seq technology to identify gene expression changes in response to carvone treatment. Transcriptome analysis revealed 721 differentially expressed genes (DEGs) between carvone-treated and control groups, with 403 genes being significantly upregulated and 318 genes downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the responsive DEGs to carvone attraction were mainly involved in locomotion, localization, behavior, response to stimulus, and olfactory transduction. We also identified four upregulated genes of chemoreceptor and response to stimulus that were involved in the response of IJs to carvone attraction. Our results provide insights into the potential transcriptional mechanisms underlying the response of S. carpocapsae to carvone, which can be utilized to develop environmentally friendly strategies for attracting EPNs., 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.)

Electrical stimulation (ES) is proposed as a therapeutic solution for managing chronic wounds. However, its widespread clinical adoption is limited by the requirement of additional extracorporeal devices to power ES-based wound dressings. In this study, a novel sandwich-structured photovoltaic microcurrent hydrogel dressing (PMH dressing) is designed for treating diabetic wounds. This innovative dressing comprises flexible organic photovoltaic (OPV) cells, a flexible micro-electro-mechanical systems (MEMS) electrode, and a multifunctional hydrogel serving as an electrode-tissue interface. The PMH dressing is engineered to administer ES, mimicking the physiological injury current occurring naturally in wounds when exposed to light; thus, facilitating wound healing. In vitro experiments are performed to validate the PMH dressing's exceptional biocompatibility and robust antibacterial properties. In vivo experiments and proteomic analysis reveal that the proposed PMH dressing significantly accelerates the healing of infected diabetic wounds by enhancing extracellular matrix regeneration, eliminating bacteria, regulating inflammatory responses, and modulating vascular functions. Therefore, the PMH dressing is a potent, versatile, and effective solution for diabetic wound care, paving the way for advancements in wireless ES wound dressings., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10 μM significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)-1β, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD., 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 Masson SAS.. All rights reserved.)