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The dental follicle (DF) plays an indispensable role in tooth eruption by regulating bone remodeling through their influence on osteoblast and osteoclast activity. The process of tooth eruption involves a series of intricate regulatory mechanisms and signaling pathways. Disruption of the parathyroid hormone‑related protein (PTHrP) in the PTHrP‑PTHrP receptor signaling pathway inhibits osteoclast differentiation by DF cells (DFCs), thus resulting in obstructed tooth eruption. Furthermore, parathyroid hormone receptor‑1 mutations are linked to primary tooth eruption failure. Additionally, the Wnt/β‑catenin, TGF‑β, bone morphogenetic protein and Hedgehog signaling pathways have crucial roles in DFC involvement in tooth eruption. DFC signal loss or alteration inhibits osteoclast differentiation, affects osteoblast and cementoblast differentiation, and suppresses DFC proliferation, thus resulting in failed tooth eruptions. Abnormal tooth eruption is also associated with a range of systemic syndromes and genetic diseases, predominantly resulting from pathogenic gene mutations. Among these conditions, the following disorders arise due to genetic mutations that disrupt DFCs and impede proper tooth eruption: Cleidocranial dysplasia associated with Runt‑related gene 2 gene mutations; osteosclerosis caused by CLCN7 gene mutations; mucopolysaccharidosis type VI resulting from arylsulfatase B gene mutations; enamel renal syndrome due to FAM20A gene mutations; and dentin dysplasia caused by mutations in the VPS4B gene. In addition, regional odontodysplasia and multiple calcific hyperplastic DFs are involved in tooth eruption failure; however, they are not related to gene mutations. The specific mechanism for this effect requires further investigation. To the best of our knowledge, previous reviews have not comprehensively summarized the syndromes associated with DF abnormalities manifesting as abnormal tooth eruption. Therefore, the present review aims to consolidate the current knowledge on DFC signaling pathways implicated in abnormal tooth eruption, and their association with disorders of tooth eruption in genetic diseases and syndromes, thereby providing a valuable reference for future related research.

Background: Traumatic brain injury (TBI) is a common neurosurgical disease in emergency rooms with poor prognosis, imposing severe burdens on patients and their families. Evidence indicates that piracetam and compound porcine cerebroside and ganglioside injection (CPCGI) can improve cognitive levels in TBI patients to enhance functional prognosis, but there is still a research gap regarding the efficacy of CPCGI. This study aims to determine the effectiveness and safety of CPCGI in improving cognitive and functional outcomes in TBI patients., Methods: This study is a multicenter, randomized, parallel-group, double-blind trial aiming to recruit 900 adult patients with mild to moderate TBI. After providing informed consent, 600 patients will be randomly assigned to the CPCGI group (20 ml/d, for 14 days), and 300 patients will be randomized to the piracetam group as a control (20 ml/d, for 14 days), followed up for 3 months after treatment. The primary outcome is the change in the Montreal Cognitive Assessment (MoCA) score from baseline after 3 months. The main secondary outcome measures include Mini-Mental State Examination (MMSE) scores, Glasgow Outcome Scale-Extended (GOS-E), and the Barthel Index at 1 and 3 months., Discussion: This multi-center clinical trial aims to provide high-quality evidence on the efficacy and safety of CPCGI in improving cognitive and functional outcomes in mild to moderate TBI patients., Trial Registration: ChiCTR2000040466, date of registration: November 28, 2020., 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.)

In this paper, we present a novel three-dimensional spatial path planning algorithm based on the Vector Field Histogram* (VFH*) approach, specifically tailored for underwater robotics applications. Our method leverages the strengths of VFH* in obstacle avoidance while enhancing its capability to handle complex three-dimensional environments. Through extensive simulations, we demonstrate the superior performance of our algorithm compared to traditional methods, such as RS-RRT algorithm. Our results show significant improvements in terms of computational efficiency and path optimality, making it a viable solution for real-time path planning in dynamic underwater environments.

The Pacific white shrimp Litopenaeus vannamei is a representative species of decapod crustacean and an economically important marine aquaculture species worldwide. However, research on the genes involved in muscle growth and development in shrimp is still lacking. MyoD is recognized as a crucial regulator of myogenesis and plays an essential role in muscle growth and differentiation in various animals. Nonetheless, little information is available concerning the function of this gene among crustaceans. In this study, we identified a sequence of the MyoD gene (LvMyoD) with a conserved bHLH domain in the L. vannamei genome. Phylogenetic analysis revealed that both the overall protein sequence and specific functional sites of LvMyoD are highly conserved with those of other crustacean species and that they are evolutionarily closely related to vertebrate MyoD and Myf5. LvMyoD expression is initially high during early muscle development in shrimp and gradually decreases after 40 days post-larval development. In adults, the muscle-specific expression of LvMyoD was confirmed through RT-qPCR analysis. Knockdown of LvMyoD inhibited the growth of the shrimp in body length and weight. Histological observation and transcriptome sequencing of muscle samples after RNA interference (RNAi) revealed nuclear agglutination and looseness in muscle fibers. Additionally, we observed significant effects on the expression of genes involved in heat shock proteins, myosins, actins, protein synthesis, and glucose metabolism. These findings suggest that LvMyoD plays a critical role in regulating muscle protein synthesis and muscle cell differentiation. Overall, this study highlights the involvement of LvMyoD in myogenesis and muscle growth, suggesting that it is a potentially important regulatory target for shrimp breeding 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.)

The family Diogenidae Ortmann, 1892 is a diverse and abundance group of hermit crabs, but their systematics and phylogenetic relationships are highly complex and unresolved. Herein, we gathered nucleotide sequence data from two mitochondrial (16S rRNA and COI) and two nuclear (NaK and PEPCK) genes for a total of 2,308 bp in length across 38 species from six extant diogenid genera. Molecular data were combined with 41 morphological characters to estimate the largest phylogeny of diogenid hermit crabs to date with the aim of testing the proposed taxonomic scheme of Diogenidae and addressing intergeneric relationships within this family. Despite conflicts between mitochondrial and nuclear DNA trees, the combined-data tree reflects the contributions of each dataset, and improves tree resolution and support for internal nodes. Contrary to traditional classification, our total evidence revealed a paraphyletic Diogenidae based on internally nested representatives of Coenobitidae Dana, 1851. Within Diogenidae, the studied diogenid hermit crabs were split between two clades with high support, which contradicts recent morphological classification scheme for Diogenidae sensu lato based on fossil records. The genus Diogenes Dana, 1851 was found nested inside Paguristes Dana, 1851, which formed a clade being separated from the remainder, pointing towards paraphyly in Paguristes . In another clade, Dardanus Paulson, 1875 occupied a basal position relative to the other diogenids, while Calcinus Dana, 1851 and Clibanarius Dana, 1852 showed sister relationships and formed a cluster with Ciliopagurus Forest, 1995. Among the morphological characters examined, carapace shield and telson were identified as phylogenetically significant for grouping diogenid genera, while phylogenetic insignificance of gill number was evidenced by its mosaic pattern in diogenid phylogeny. The present study sheds light on the controversial generic phylogeny of Diogenidae and highlights the necessity for thorough taxonomic revisions of this family as well as some genera ( e.g ., Paguristes ) to reconcile current classifications with phylogenetic relationships., Competing Interests: The authors declare that they have no competing interests., (© 2024 Cheng et al.)

The implementation of nanocomposite materials as electrode layers represents a potential turning point for next-generation of solid oxide cells in order to reduce the use of critical raw materials. However, the substitution of bulk electrode materials by thin films is still under debate especially due to the uncertainty about their performance and stability under operando conditions, which restricts their use in real applications. In this work, we propose a multiphase nanocomposite characterized by a highly disordered microstructure and high cationic intermixing as a result from thin-film self-assembly of a perovskite-based mixed ionic-electronic conductor (lanthanum strontium cobaltite) and a fluorite-based pure ionic conductor (samarium-doped ceria) as an oxygen electrode for reversible solid oxide cells. Electrochemical characterization shows remarkable oxygen reduction reaction (fuel cell mode) and oxygen evolution activity (electrolysis mode) in comparison with state-of-the-art bulk electrodes, combined with outstanding long-term stability at operational temperatures of 700 °C. The disordered nanostructure was implemented as a standalone oxygen electrode on commercial anode-supported cells, resulting in high electrical output in fuel cell and electrolysis mode for active layer thicknesses of only 200 nm (>95% decrease in critical raw materials with respect to conventional cathodes). The cell was operated for over 300 h in fuel cell mode displaying excellent stability. Our findings unlock the hidden potential of advanced thin-film technologies for obtaining high-performance disordered electrodes based on nanocomposite self-assembly combining long durability and minimized use of critical raw materials.

The language network of the human brain has core components in the inferior frontal cortex and superior/middle temporal cortex, with left-hemisphere dominance in most people. Functional specialization and interconnectivity of these neocortical regions is likely to be reflected in their molecular and cellular profiles. Excitatory connections between cortical regions arise and innervate according to layer-specific patterns. Here, we generated a gene expression dataset from human postmortem cortical tissue samples from core language network regions, using spatial transcriptomics to discriminate gene expression across cortical layers. Integration of these data with existing single-cell expression data identified 56 genes that showed differences in laminar expression profiles between the frontal and temporal language cortex together with upregulation in layer II/III and/or layer V/VI excitatory neurons. Based on data from large-scale genome-wide screening in the population, DNA variants within these 56 genes showed set-level associations with interindividual variation in structural connectivity between the left-hemisphere frontal and temporal language cortex, and with the brain-related disorders dyslexia and schizophrenia which often involve affected language. These findings identify region-specific patterns of laminar gene expression as a feature of the brain's language network., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: The data and information contained within electronic health records (EHR) provide a rich, diverse, longitudinal view of real-world patient histories, offering valuable opportunities to study antecedent risk factors for cognitive decline. However, the extent to which such records' data have been utilized to elucidate the risk factors of cognitive decline remains unclear., Methods: A scoping review was conducted following the PRISMA guideline, examining articles published between January 2010 and April 2023, from PubMed, Web of Science, and CINAHL. Inclusion criteria focused on studies using EHR to investigate risk factors for cognitive decline. Each article was screened by at least two reviewers. Data elements were manually extracted based on a predefined schema. The studied risk factors were classified into categories, and a research gap was identified., Results: From 1,593 articles identified, 80 were selected. The majority (87.5%) were retrospective cohort studies, with 66.3% using datasets of over 10,000 patients, predominantly from the US or UK. Analysis showed that 48.8% of studies addressed medical conditions, 31.3% focused on medical interventions, and 17.5% on lifestyle, socioeconomic status, and environmental factors. Most studies on medical conditions were linked to an increased risk of cognitive decline, whereas medical interventions addressing these conditions often reduced the risk., Conclusions: EHR data significantly enhanced our understanding of medical conditions, interventions, lifestyle, socioeconomic status, and environmental factors related to the risk of cognitive decline., Competing Interests: Competing interests: Authors have nothing to disclose. Additional Declarations: No competing interests reported. Declaration of Generative AI and AI-assisted technologies in the writing process During the preparation of this work the authors used GPT-4 in order to improve the readability and language. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Traumatic brain injury (TBI) persists as a substantial clinical dilemma, largely because of the absence of effective treatments. This challenge is exacerbated by the hindered clearance of intracranial metabolic byproducts and the continual accrual of deleterious proteins. The glymphatic system (GS) and meningeal lymphatic vessels (MLVs), key elements of the intracranial lymphatic network, play critical roles in the clearance of harmful substances. Cannabidiol (CBD) has shown promise in reducing metabolite overload and bolstering cognitive performance in various neurodegenerative diseases. The precise mechanisms attributing to its beneficial effects in TBI scenarios, however, are yet to be distinctly understood. Utilizing a fluid percussion injury paradigm, our research adopted a multifaceted approach, encompassing behavioral testing, immunofluorescence and immunohistochemical analyses, laser speckle imaging, western blot techniques, and bilateral cervical efferent lymphatic ligation. This methodology aimed to discern the influence of CBD on both neurological outcomes and intracranial lymphatic clearance in a murine TBI model. We observed that CBD administration notably ameliorated motor, memory, and cognitive functions, concurrently with a significant reduction in the concentration of phosphorylated tau protein and amyloid-β. In addition, CBD expedited the turnover and elimination of intracranial tracers, increased cerebral blood flow, and enhanced the efficacy of fluorescent tracer migration from MLVs to deep cervical lymph nodes (dCLNs). Remarkably, CBD treatment also induced a reversion in aquaporin-4 (AQP-4) polarization and curtailed neuroinflammatory indices. A pivotal discovery was that the surgical interruption of efferent lymphatic conduits in the neck nullified CBD's positive contributions to intracranial waste disposal and cognitive improvement, yet the anti-neuroinflammatory actions remained unaffected. These insights suggest that CBD may enhance intracranial metabolite clearance, potentially via the regulation of the intracranial lymphatic system, thereby offering neurofunctional prognostic improvement in TBI models. Our findings underscore the potential therapeutic applicability of CBD in TBI interventions, necessitating further comprehensive investigations and clinical validations to substantiate these initial conclusions.

Traumatic brain injury (TBI) is the primary cause of child mortality and disability worldwide. It can result in severe complications that significantly impact children's quality of life, including post-traumatic epilepsy (PTE). An increasing number of studies suggest that TBI-induced oxidative stress and neuroinflammatory sequelae (especially, inflammation in the hippocampus region) may lead to the development of PTE. Due to the blood-brain barrier (BBB), typical systemic pharmacological therapy for TBI cannot deliver berberine (BBR) to the targeted location in the early stages of the injury, although BBR has strong anti-inflammatory properties. To break through this limitation, a microenvironment-responsive gelatin methacrylate (GM) hydrogel to deliver poly(propylene sulfide) 60 (PPS 60 ) and BBR (GM/PB) is developed for regulating neuroinflammatory reactions and removing reactive oxygen species (ROS) in the brain trauma microenvironment through PPS 60 . In situ injection of the GM/PB hydrogel efficiently bypasses the BBB and is administered directly to the surface of brain tissue. In post-traumatic brain injury models, GM/PB has the potential to mitigate oxidative stress and neuroinflammatory responses, facilitate functional recovery, and lessen seizing. These findings can lead to a new treatment for brain injuries, which minimizes complications and improves the quality of life., (© 2024 Wiley‐VCH GmbH.)

The complement component 5a/complement component 5 receptor 1 (C5a/C5aR1) pathway plays a crucial role in the onset and development of inflammation, but relevant studies in fish are lacking. In this study, we successfully characterized the relationship between half-smooth tongue sole (Cynoglossus semilaevis) C5aR1 (CsC5aR1) and bacterial inflammation. First, we showed that the overexpression of CsC5aR1 significantly increased bacterial pathological damage in the liver and intestine, whereas inhibition attenuated the damage. The in vitro experiments suggested that CsC5aR1 was able to positively regulate the phagocytic activity and respiratory burst of tongue sole macrophages. In terms of both transcriptional and translational levels, overexpression/inhibition of CsC5aR1 was followed by a highly consistent up-regulation/decrease of its downstream canonical inflammatory factor interleukin-6 (CsIL-6). Furthermore, we stimulated macrophages by lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and found a broad-spectrum response to bacterial infections by the C5a/C5aR1 complement pathway together with the downstream inflammatory factor CsIL-6. Subsequently, we directly elucidated that CsIL-6 is an indicator of C5a/C5aR1-mediated inflammation at different infection concentrations, different infectious bacteria (Vibrio anguillarum and Mycobacterium marinum), and different detection levels. These results might provide a new inflammation bio-marker for early warning of bacteria-induced hyperinflammation leading to fish mortality and a promising target for the treatment of bacterial inflammation in teleost., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Objective. To evaluate the inter- and intra-rater reliability for the identification of bad channels among neurologists, EEG Technologists, and naïve research personnel, and to compare their performance with the automated bad channel detection (ABCD) algorithm for detecting bad channels. Approach. Six Neurologists, ten EEG Technologists, and six naïve research personnel (22 raters in total) were asked to rate 1440 real intracranial EEG channels as good or bad. Intra- and interrater kappa statistics were calculated for each group. We then compared each group to the ABCD algorithm which uses spectral and temporal domain features to classify channels as good or bad. Main results. Analysis of channel ratings from our participants revealed variable intra-rater reliability within each group, with no significant differences across groups. Inter-rater reliability was moderate among neurologists and EEG Technologists but minimal among naïve participants. Neurologists demonstrated a slightly higher consistency in ratings than EEG Technologists. Both groups occasionally misclassified flat channels as good, and participants generally focused on low-frequency content for their assessments. The ABCD algorithm, in contrast, relied more on high-frequency content. A logistic regression model showed a linear relationship between the algorithm's ratings and user responses for predominantly good channels, but less so for channels rated as bad. Sensitivity and specificity analyses further highlighted differences in rating patterns among the groups, with neurologists showing higher sensitivity and naïve personnel higher specificity. Significance. Our study reveals the bias in human assessments of intracranial electroencephalography (iEEG) data quality and the tendency of even experienced professionals to overlook certain bad channels, highlighting the need for standardized, unbiased methods. The ABCD algorithm, outperforming human raters, suggests the potential of automated solutions for more reliable iEEG interpretation and seizure characterization, offering a reliable approach free from human biases., (Creative Commons Attribution license.)

Background: Current treatment modalities for spontaneous esophageal perforation remain controversial because of their rarity., Objective: To describe our institution's experience in managing patients with spontaneous esophageal rupture and conduct a meta-analysis of existing studies to determine the best evidence-based treatment options., Methods: We enrolled patients with spontaneous esophageal rupture who underwent their first treatment at our institution. We also identified studies through a systematic search of the MEDLINE, EMBASE, and Cochrane Library databases before April 1, 2024, for inclusion in the meta-analysis., Results: This case series included data from 17 patients with delayed diagnosis who were treated with esophageal stents, with an immediate mortality rate of 5.9%. In addition to the cases from our institution, we obtained 944 patients from 46 studies in the final analysis. The combined immediate mortality rate was 11% (95% confidence interval [CI]: 0.08-0.15). The combined re-intervention rate was 11% (95% CI: 0.05-0.19). The combined immediate mortality was 6% (95% CI: 0.04-0.09) after primary closure, 14% (95% CI: 0.02-0.32) after T-tube drain repair, 2% (95% CI: 0.00-0.15) after esophagectomy, 8% (95% CI: 0.03-0.15) after stent placement, and 22% (95% CI: 0.03-0.47) after conservative treatment. The subgroup analysis based on the timing of the intervention showed that the immediate mortality rate in patients initiating treatment within 24 h of rupture was 3% (95% CI: 0.01-0.08), whereas that in patients initiating treatment > 24 h later was 12% (95% CI: 0.08-0.18)., Conclusion: Outcomes are best after esophagectomy, and primary closure or esophageal stenting is a good option compared with other treatment modalities. Prognosis is related to the timing of intervention, and accurate diagnosis and treatment within 24 h significantly reduces the risk of death in patients. Patients with delayed diagnosis may have a better prognosis with stent placement., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Green manuring is a conservation agricultural practice that improves soil quality and crop yield. However, increasing the active nitrogen (N) and carbon (C) pools during green manure (GM) amendment may accelerate soil N transformation and stimulate N loss. Previous studies have reported the effects of cover crop incorporation on N 2 O emission; however, the driving mechanisms and other N losses remain unclear. Therefore, we conducted a comprehensive meta-analysis of 109 published articles (517 paired observations) to clarify the effects of GM amendment on soil reactive N (Nr) losses (N 2 O emissions, NH 3 volatilization, and N leaching and runoff), N pools, and N cycling functional gene abundance. The results showed that green manuring increased soil microbial biomass N (MBN) and NO 3 - -N concentrations and stimulated N 2 O emission but significantly lowered N leaching and yield-scaled NH 3 volatilization. Practices of green manuring made a dominant contribution to the variation in N 2 O emissions and NH 3 volatilization after GM application. Furthermore, applying legume-based GM, using N derived from GM (GMN) as an additional input, and short-term GM amendment each stimulated N 2 O emissions. In contrast, adopting non-legume GM, using GMN to partially substitute mineral N, and applying GM to the soil surface or paddy field mitigated NH 3 loss during GM amendment. Additionally, the variation in NH 3 volatilization was positively related to soil pH and N application rate (NAR) but had a negative relationship with mean annual precipitation (MAP). This study highlighted the marked effects of green manuring on soil N retention and loss. Agricultural operations that adopt GM amendment should select suitable GM species and optimize mineral N inputs to minimize N loss., 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.)

Senecaviurs A (SVA) infection, an emerging infectious disease in pig populations, is characterized by vesicular lesions predominantly affecting the mouth, snout, and hooves of infected pigs, similar to the symptoms of Foot and Mouth Disease Virus (FMDV). This disease first spread into China in 2015, causing great panic in the pig breeding industry. To determine the prevalence of SVA in pig herds in China from 2018 to 2021, a total of 4,901 pig tissue samples were collected from 18 provinces, autonomous regions and municipalities (P.A.M.s) for epidemiological investigation, virus isolation and genetic analysis. In 2021, the individual positive rates (IPRs) from the perspective of spatial distribution in East China, South China, Central China, North China, Southwest China, Northwest China, and Northeast China were 0, 0, 1.69, 0.94, 11.70, 3.31 and 2.21%, respectively. The herd positive rates (HPRs) were 0, 0, 9.52, 9.09, 50.00, 7.69 and 23.08%. From the perspective of temporal distribution, the IPR showed an overall downwards trend from 2018 to 2021, with only a slight increase in 2020. Moreover, the HPR decreased from 36.63 to 10.07%. From the perspective of population distribution in 2021, the IPR (2.62%) and HPR (12.00%) in apparently healthy pig herds (slaughterhouses) were greater than those in non-healthy pig herds (2.10 and 5.13%, respectively), consistent with the results in 2019. To characterize the prevalent strains, 10 SVA strains isolated from positive samples in 2019 were clustered in Clades I and VII; SVA-FJ039-2019, SVA-HuN032-2019, SVA-GX011-2019, SVA-FJ036-2019, SVA-GXF011-2019 and SVA-GXF053-2019 were clustered in Clade I; and SVA-FJ018-2019, SVA-SD069-2019, SVA-SD072-2019, and SVA-SD074-2019 were clustered in Clade VII. In conclusion, until 2021, the prevalence of SVA in pig herds in China was still relatively high, the contaminated area was still large, and there were a number of hidden infections. In the future, the epidemic status of SVA in pig herds in China must be closely monitored and the prevention and control measures must be adjusted in a timely manner., Competing Interests: LT was employed by New Hope Liuhe Co., Ltd. The remaining 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, Gao, Tao, Cui, Zhang, Zheng, Wei, Gu, Sha and Ni.)

Purpose: To develop and validate a prediction model based on imaging data for the prognosis of mild chronic subdural hematoma undergoing atorvastatin treatment., Methods: We developed the prediction model utilizing data from patients diagnosed with CSDH between February 2019 and November 2021. Demographic characteristics, medical history, and hematoma characteristics in non-contrast computed tomography (NCCT) were extracted upon admission to the hospital. To reduce data dimensionality, a backward stepwise regression model was implemented to build a prognostic prediction model. We calculated the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model by a tenfold cross-validation procedure., Results: Maximum thickness, volume, mean density, morphology, and kurtosis of the hematoma were identified as the most significant predictors of good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The prediction model exhibited good discrimination, with an area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.74-0.90) and good calibration (p = 0.613). The validation analysis showed the AUC of the final prognostic prediction model is 0.80 (95% CI 0.71-0.86) and it has good prediction performance., Conclusion: The imaging data-based prediction model has demonstrated great prediction accuracy for good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The study results emphasize the importance of imaging data evaluation in the management of CSDH patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included., Methods: Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran's Q test and leave-one-out method, respectively., Results: T2DM is associated with a reduced risk of esophageal (OR: 0.77, 95% CI: 0.71 to 0.83, P< 0.001), gastric (OR: 0.87, 95% CI: 0.84 to 0.90, P< 0.001) and colorectal cancer (OR: 0.88, 95% CI: 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR: 0.92, 95% CI: 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR: 1.92, 95% CI: 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI: 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI: 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI: 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI: 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI: 0.65 to 0.99, P=0.044)., Conclusion: T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels., 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 An, Zhang, Sha, Xu and Liu.)

Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam-like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of l-oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated., Methods: The study adopts a multicenter, randomized, double-blind, parallel-group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: l-oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow-up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments., Discussion: There is no robust evidence to suggest that l-oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question., Trial Registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565., 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., (© 2024 The Author(s). Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Despite accumulating evidence linking defective lysosome function with autoimmune diseases, how the catabolic machinery is regulated to maintain immune homeostasis remains unknown. Late endosomal/lysosomal adaptor, MAPK and mTOR activator 5 (Lamtor5) is a subunit of the Ragulator mediating mechanistic target of rapamycin complex 1 (mTORC1) activation in response to amino acids, but its action mode and physiological role are still unclear. Here it is demonstrated that Lamtor5 level is markedly decreased in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE). In parallel, the mice with myeloid Lamtor5 ablation developed SLE-like manifestation. Impaired lysosomal function and aberrant activation of mTORC1 are evidenced in Lamtor5 deficient macrophages and PBMCs of SLE patients, accompanied by blunted autolysosomal pathway and undesirable inflammatory responses. Mechanistically, it is shown that Lamtor5 is physically associated with ATP6V1A, an essential subunit of vacuolar H + -ATPase (v-ATPase), and promoted the V0/V1 holoenzyme assembly to facilitate lysosome acidification. The binding of Lamtor5 to v-ATPase affected the lysosomal tethering of Rag GTPase and weakened its interaction with mTORC1 for activation. Overall, Lamtor5 is identified as a critical factor for immune homeostasis by intergrading v-ATPase activity, lysosome function, and mTOR pathway. The findings provide a potential therapeutic target for SLE and/or other autoimmune diseases., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Epistasis, the phenomenon where the effect of one gene (or variant) is masked or modified by one or more other genes, can significantly contribute to the observed phenotypic variance of complex traits. To date, it has been generally assumed that genetic interactions can be detected using a Cartesian, or multiplicative, interaction model commonly utilized in standard regression approaches. However, a recent study investigating epistasis in obesity-related traits in rats and mice has identified potential limitations of the Cartesian model, revealing that it only detects some of the genetic interactions occurring in these systems. By applying an alternative approach, the exclusive-or (XOR) model, the researchers detected a greater number of epistatic interactions and identified more biologically relevant ontological terms associated with the interacting loci. This suggests that the XOR model may provide a more comprehensive understanding of epistasis in these species and phenotypes. To further explore these findings and determine if different interaction models also make up distinct epistatic networks, we leverage network science to provide a more comprehensive view into the genetic interactions underlying BMI in this system., Results: Our comparative analysis of networks derived from Cartesian and XOR interaction models in rats ( Rattus norvegicus ) uncovers distinct topological characteristics for each model-derived network. Notably, we discover that networks based on the XOR model exhibit an enhanced sensitivity to epistatic interactions. This sensitivity enables the identification of network communities, revealing novel trait-related biological functions through enrichment analysis. Furthermore, we identify triangle network motifs in the XOR epistatic network, suggestive of higher-order epistasis, based on the topology of lower-order epistasis., Conclusions: These findings highlight the XOR model's ability to uncover meaningful biological associations as well as higher-order epistasis from lower-order epistatic networks. Additionally, our results demonstrate that network approaches not only enhance epistasis detection capabilities but also provide more nuanced understandings of genetic architectures underlying complex traits. The identification of community structures and motifs within these distinct networks, especially in XOR, points to the potential for network science to aid in the discovery of novel genetic pathways and regulatory networks. Such insights are important for advancing our understanding of phenotype-genotype relationships., Competing Interests: Competing interests The authors declare no competing interests.

With the rapid development of industries, agriculture, and urbanization (including transportation and population growth), there has been a significant alteration in the emission and atmospheric deposition of heavy metal pollutants. This has consequently given rise to a range of ecological and environmental health issues. In this study, we conducted a comprehensive two-year investigation on the temporal and spatial distribution characteristics of heavy metals in atmospheric deposition across China based on the Nationwide Nitrogen Deposition Monitoring Network (NNDMN). The atmospheric bulk deposition of Lead (Pb), Arsenic (As), Nickel (Ni), Selenium (Se), Chromium (Cr) and Cadmium (Cd) were 6.32 ± 1.59, 4.49 ± 0.57, 1.31 ± 0.21, 1.05 ± 0.16, 0.60 ± 0.06 and 0.21 ± 0.03 mg m -2  yr -1 , respectively, with a large variation among the different regions of China. The order for atmospheric deposition flux was Southwest China > Southeast China > North China > Northeast China > Qinghai-Tibet Plateau and rural area > urban area > background area. The concentrations of heavy metals in bulk deposition exhibit seasonal variation with higher levels observed during winter compared to summer and spring, which are closely associated with anthropogenic activities. The Positive Matrix Factorization (PMF) results indicated that combustion, industrial emissions and traffic are the primary contributors to atmospheric deposition of heavy metals. The single factor pollution index (P i ) of heavy metals is consistently below 1, and the composite pollution index (N i ) is 0.16 across China, indicating that atmospheric heavy metal deposition is at a pollution-free level. The comprehensive potential ecological risk index of heavy metals is 11.8, with Cd exhibiting the highest single factor potential ecological risk index at 7.09, suggesting that more attention should be paid to Cd deposition in China. The present study reveals the spatial-temporal distribution pattern of atmospheric heavy metals deposition in China, identifying regional source characteristics and providing a theoretical foundation and strategies for reducing emissions of atmospheric pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In addition to presenting significant diagnostic and treatment challenges, lung adenocarcinoma (LUAD) is the most common form of lung cancer. Using scRNA-Seq and bulk RNA-Seq data, we identify three genes referred to as HMR, FAM83A, and KRT6A these genes are related to necroptotic anoikis-related gene expression. Initial validation, conducted on the GSE50081 dataset, demonstrated the model's ability to categorize LUAD patients into high-risk and low-risk groups with significant survival differences. This model was further applied to predict responses to PD-1/PD-L1 blockade therapies, utilizing the IMvigor210 and GSE78220 cohorts, and showed strong correlation with patient outcomes, highlighting its potential in personalized immunotherapy. Further, LUAD cell lines were analyzed using quantitative PCR (qPCR) and Western blot analysis to confirm their expression levels, further corroborating the model's relevance in LUAD pathophysiology. The mutation landscape of these genes was also explored, revealing their broad implication in various cancer types through a pan-cancer analysis. The study also delved into molecular subclustering, revealing distinct expression profiles and associations with different survival outcomes, emphasizing the model's utility in precision oncology. Moreover, the diversity of immune cell infiltration, analyzed in relation to the necroptotic anoikis signature, suggested significant implications for immune evasion mechanisms in LUAD. While the findings present a promising stride towards personalized LUAD treatment, especially in immunotherapy, limitations such as the retrospective nature of the datasets and the need for larger sample sizes are acknowledged. Prospective clinical trials and further experimental research are essential to validate these findings and enhance the clinical applicability of our prognostic model., (© 2024. The Author(s).)

Anlotinib and osimertinib are a class of tyrosine kinase inhibitors for the treatment of malignant tumor. The combination of anlotinib and osimertinib is currently used for treating non-small cell lung cancer (NSCLC) patients. This study aimed to develop a simple and rapid isotope-labeled UHPLC-MS/MS method for the simultaneous determination of anlotinib and osimertinib in human plasma. The analytes were extracted by protein precipitation with acetonitrile and were then separated on a Shim-pack GIST C18 column. The detection was performed on Shimadzu 8050 triple quadruple mass spectrometer in the positive electrospray ionization mode with multiple reaction monitoring. The precursor-to-product ion transitions were m/z 408.10→ 339.75, 500.25→ 72.20 and 413.50 → 344.50 for anlotinib, osimertinib and D5-anlotinib, respectively. Validation is based on US Food and Drug Administration guidelines. The linearity ranges were 0.5-100 ng/mL for anlotinib and were 1-500 ng/mL for osimertinib with the correlation coefficients (r  2) ≥ 0.99. Accuracy and precision, matrix effect, extraction recovery and stability of anlotinib and osimertinib were acceptable after validation. The UHPLC-MS/MS method was successfully validated and was applied to monitor the concentration of anlotinib and osimertinib in NSCLC patients., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Exosomes constitute an emerging biomarker for cancer diagnosis because they carry multiple proteins that reflect the origins of the parent cell. The highly sensitive detection of exosomes is a crucial prerequisite for the diagnosis of cancer. In this study, we report an exosome detection system based on quantum weak value amplification (WVA). The WVA detection system consists of a reflection detection light path and a Zr-ionized biochip. Zr-ionized biochips effectively capture exosomes through the specific interaction between zirconium dioxide and the phosphate groups on the lipid bilayer of exosomes. Aptamer-modified gold nanoparticles (Au NPs) are then used to specifically recognize proteins on exosomes to enhance the detection signal. The sensitivity and resolution of the detection system are 2944.07 nm/RIU and 1.22 × 10 -5 RIU, respectively. The concentration of exosomes can be directly quantified by the WVA system, ranging from 10 5 -10 7 particles/mL with the detection limit of 3 × 10 4 particles/mL. The use of Au NPs-EpCAM for the specific enhancement of breast cancer MDA-MB-231 exosomes is demonstrated. The results indicate that the WVA detection system can be a promising candidate for the detection of exosomes as tumor markers.

Background: Colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Liver metastasis (LM) is the main cause of death in patients with CRC. Therefore, identification of patients with the greatest risk of liver metastasis is critical for early treatment and reduces the mortality of patients with colorectal cancer liver metastases., Methods: Initially, we characterized cell composition through single-cell transcriptome analysis. Subsequently, we employed copy number variation (CNV) and pseudotime analysis to delineate the cellular origins of LM and identify LM-related epithelial cells (LMECs). The LM-index was constructed using machine learning algorithms to forecast the relative abundance of LMECs, reflecting the risk of LM. Furthermore, we analyzed drug sensitivity and drug targeted gene expression in LMECs and patients with a high risk of LM. Finally, functional experiments were conducted to determine the biological roles of metastasis-related gene in vitro., Results: Single-cell RNA sequencing analysis revealed different immune landscapes between primary CRC and LM tumor. LM originated from chromosomal variants with copy number loss of chr1 and chr6p and copy number gain of chr7 and chr20q. We identified the LMECs cluster and found LM-associated pathways such as Wnt/beta-catenin signaling and KRAS signaling. Subsequently, we identified ten metastasis-associated genes, including SOX4, and established the LM-index, which correlates with poorer prognosis, higher stage, and advanced age. Furthermore, we screened two drugs as potential candidates for treating LM, including Linsitinib&#95;1510, Lapatinib&#95;1558. Immunohistochemistry results demonstrated significantly elevated SOX4 expression in tumor samples compared to normal samples. Finally, in vitro experiments verified that silencing SOX4 significantly inhibited tumor cell migration and invasion., Conclusion: This study reveals the possible cellular origin and driving factors of LM in CRC at the single cell level, and provides a reference for early detection of CRC patients with a high risk of LM., Competing Interests: The authors affirm that there are no potential conflicts of interest that could be perceived in terms of business or financial relationships in the conduct of this study., (© 2024 Sha et al.)

Cells are the essential building blocks of living organisms, responsible for carrying out various biochemical reactions and performing specific functions. In eukaryotic cells, numerous membrane organelles have evolved to facilitate these processes by providing specific spatial locations. In recent years, it has also been discovered that membraneless organelles play a crucial role in the subcellular organization of bacteria, which are single-celled prokaryotic microorganisms characterized by their simple structure and small size. These membraneless organelles in bacteria have been found to undergo Liquid-Liquid phase separation (LLPS), a molecular mechanism that allows for their assembly. Through extensive research, the occurrence of LLPS and its role in the spatial organization of bacteria have been better understood. Various biomacromolecules have been identified to exhibit LLPS properties in different bacterial species. LLPS which is introduced into synthetic biology applies to bacteria has important implications, and three recent research reports have shed light on its potential applications in this field. Overall, this review investigates the molecular mechanisms of LLPS occurrence and its significance in bacteria while also considering the future prospects of implementing LLPS in synthetic biology., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

This paper presents the data collection method and introduces the dataset about consumers' consider-then-choose behaviors in the household vacuum cleaner market. First, we designed a questionnaire that collected participants' consideration and choice data, social network data, demographic information, and preferences for product features. In addition, we obtained data on vacuum cleaner product features through web scraping from online shopping websites. After data cleaning and processing, the resulting dataset enables investigation into customer preferences in two stages, namely the consideration and choice stages and the impact of social influence on the two-stage decision-making process. This dataset is unique as it is the first of its kind to collect both customers' revealed preferences in a two-stage decision-making process and their ego social networks. This enables the modeling of customer preferences while accounting for social influence. The published survey questionnaire can be used as a template to collect data on other products in support of customer preferences modeling and the design for market systems., (© 2024 The Authors.)

Diversified cropping systems, such as intercropping, have shown multifunctionality in agronomic productivity promotion, pest control, and soil health improvement. However, the intense interaction between crop species stimulates soil carbon and nitrogen turnover, and intercropping systems cause inexplicit effects on soil greenhouse gas emissions (GHG). Therefore, a comprehensive meta-analysis using 52 published articles (531 paired observations) was conducted to elucidate the effects of intercropping on soil N 2 O, CO 2 , and CH 4 emissions under different environmental conditions and field practices to identify the primary driving factors, such as climate, soil and field practices. The results showed that intercropping treatment had a non-significant impact on the three GHG emissions on average. However, using a cereal-legume intercropping regime, adopting moderate N application rate or intercropping in alkaline soils could significantly mitigate soil N 2 O emission. Additionally, intercropping in soils with high soil organic carbon reduce soil CH 4 emission. On the contrary, increasing intercropping duration, or adopted in soils with moderate soil total N tended to stimulate CO 2 emission. The mixed-effect model selection indicated that initial soil pH, MAP, MAT, tillage regime, and intercropping duration and type were significant moderators in regulating soil GHG emissions. Our findings explicitly elucidated soil GHG responses to intercropping practice. Further studies are warranted on the evaluation of long-term intercropping effects to improve the comprehensive understanding of C and N balance and global warming potential under intercropping., 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.)

Investigating spatial pattern of adaptive variation and its underlying processes can inform the adaptive potential distributed within species ranges, which is increasingly important in the context of a changing climate. A correct interpretation of adaptive variation pattern requires that population history and the ensuing population genetic structure are taken into account. Here we carried out such a study by integrating population genomic analyses, demographic model testing and species distribution modeling to investigate patterns and causes of adaptive differentiation in a widespread mantis shrimp, Oratosquilla oratoria, along a replicated, broad-scale temperature gradient in the northwestern Pacific (NWP). Our results supported a strong hierarchical ecogeographic structure dominated by habitat-linked divergence among O. oratoria populations accompanied with introgressive hybridization. A combined F ST outlier and environmental correlation analyses revealed remarkable temperature-associated clines in allele frequency across paired North-South populations on Chinese and Japanese coasts, and identified a suite of loci associated with temperature adaptation. Further demographic model testing revealed the observed clinal variation derived partly from Pleistocene divergence followed by recent secondary contact. More importantly, the likelihood of hybridization is predicted to increase as climate change progresses, which would break barriers to gene flow and enable the spread of adaptive genetic variation. These results support that not only is temperature-driven adaptive differentiation occurs in O. oratoria but that such pattern is likely attributed to ancient adaptive variation, sustained by contemporary ocean conditions and a semi-permeable barrier to gene flow maintained by selection. They moreover provide genomic insights into the distribution of adaptive potential across O. oratoria' s species range. This work can serve as a case study to characterize adaptive diversity of marine species in the NWP by integrating environmental and genetic data at temporal and spatial scales in a population genomic framework, which would improve management and conservation actions under climate change., 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.)

A new species of the subfamily Stegocephalinae, Stegocephaluscarolus sp. nov. , is described from a seamount in the Caroline Plate. Two related species, S.cascadiensis (Moore, 1992) and S.longicornis (Gurjanova, 1962), were previously reported in the North Pacific. Important morphological characters which differentiate S.carolus sp. nov. from S.cascadiensis are found in antenna 1, the mouthparts, pereopod 7 and the length of rami of uropods 2 and 3. The new species differs from S.longicornis by characters of antenna 1, the mouthparts and the shape of epimeral plate 3. Additionally, the morphological differences between the new species and the remaining seven species of Stegocephalus are also presented., Competing Interests: The authors have declared that no competing interests exist., (Yanrong Wang, Zhongli Sha, Xianqiu Ren.)

Traumatic Brain Injury (TBI) is a prevalent form of neurological damage that may induce varying degrees of cognitive dysfunction in patients, consequently impacting their quality of life and social functioning. This article provides a mini review of the epidemiology in Chinese TBI patients and etiology of cognitive impairment. It analyzes the risk factors of cognitive impairment, discusses current management strategies for cognitive dysfunction in Chinese TBI patients, and summarizes the strengths and limitations of primary testing tools for TBI-related cognitive functions. Furthermore, the article offers a prospective analysis of future challenges and opportunities. Its objective is to contribute as a reference for the prevention and management of cognitive dysfunction in Chinese TBI patients., 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 Liu, Yu, Liu, Zhao, Yuan, Sha, Liu, Qian, Nie and Jiang.)

Aim: We aim to identify the specific CD4 + T-cell subtype influenced by brain-to-CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI)., Method: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4 + T-cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining., Results: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4 + T cells, specifically CD11b-positive CD4 + T cells, within the affected region. The population of CD4 + CD11b + T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. Administration of CD4 + CD11b + T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy., Conclusion: The infiltration of CD4 + CD11b + T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain-to-CLN signaling., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background and Objectives: The focus on evidence-based neurosurgery has led to a considerable amount of neurosurgical evidence based on randomized controlled trials (RCTs) being published. Nevertheless, there has been no systematic appraisal of China's contribution to RCTs. Information about the changes in characteristics of Chinese neurosurgical RCTs before and during the COVID-19 pandemic is limited. This study aims to perform a detailed examination and comprehensive analysis of the characteristics of Chinese neurosurgical RCTs and to examine the differences before and during the COVID-19 pandemic., Methods: We conducted a comprehensive database search including PubMed, Web of Science, Embase, and Cochrane Library up to March 2023, with a criterion of inclusion based on an impact factor above 0. We subsequently examined the design and quality parameters of the included RCTs and assessed the differences before and during the COVID-19 pandemic (based on follow-up ending before or after January 2020). Moreover, we investigated potential factors that may affect the quality and developmental trends of neurosurgical RCTs in China., Results: The main focus of the 91 neurosurgical RCTs was vascular disease (47.3%) and trauma (18.7%). Over half of the trials used Consolidated Standards of Reporting Trial diagrams (69.2%), and the majority compared nonsurgical treatments (63.7%). Larger trials tended to have better quality scores, but those with significant efficacy were less likely to have power calculations. Over time, there was an increase in the use of Consolidated Standards of Reporting Trial diagrams and well-specified outcomes. The COVID-19 pandemic may have hindered the completion of neurosurgical RCTs in China, but it has had little impact on the design and quality so far., Conclusion: Chinese neurosurgeons have made significant progress in advancing neurosurgical RCTs despite challenges. However, shortcomings in sample size and power calculation need attention. Improving the rigor, rationality, and completeness of neurosurgical RCT design is crucial., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague-Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects., Competing Interests: The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be interpreted as potential conflicts of interest., (Copyright © 2024 Yang Liu et al.)

This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone., (© 2024. The Author(s).)

Objective: It is a common clinical phenomenon that blood infiltrates into the injured tendon caused by sports injuries, accidental injuries, and surgery. However, the role of blood infiltration into the injured tendon has not been investigated., Methods: A blood-induced rat model was established and the impact of blood infiltration on inflammation and HO of the injured tendon was assessed. Cell adhesion, viability, apoptosis, and gene expression were measured to evaluate the effect of blood treatment on tendon stem/progenitor cells (TSPCs). Then RNA-seq was used to assess transcriptomic changes in tendons in a blood infiltration environment. At last, the small molecule drug PI3K inhibitor LY294002 was used for in vivo and in vitro HO treatment., Results: Blood caused acute inflammation in the short term and more severe HO in the long term. Then we found that blood treatment increased cell apoptosis and decreased cell adhesion and tenonic gene expression of TSPCs. Furthermore, blood treatment promoted osteochondrogenic differentiation of TSPCs. Next, we used RNA-seq to find that the PI3K/AKT signaling pathway was activated in blood-treated tendon tissues. By inhibiting PI3K with a small molecule drug LY294002, the expression of osteochondrogenic genes was markedly downregulated while the expression of tenonic genes was significantly upregulated. At last, we also found that LY294002 treatment significantly reduced the tendon HO in the rat blood-induced model., Conclusion: Our findings indicate that the upregulated PI3K/AKT signaling pathway is implicated in the aggravation of tendon HO. Therefore, inhibitors targeting the PI3K/AKT pathway would be a promising approach to treat blood-induced tendon HO., Competing Interests: The authors declare no competing financial interests., (© 2023 The Authors.)

Listeria monocytogenes (Lm), a foodborne bacterium, can infect people and has a high fatality rate in immunocompromised individuals. Listeriolysin O (LLO), the primary virulence factor of Lm, is critical in regulating the pathogenicity of Lm. This review concludes that LLO may either directly or indirectly activate a number of host cell viral pathophysiology processes, such as apoptosis, pyroptosis, autophagy, necrosis and necroptosis. We describe the invasion of host cells by Lm and the subsequent removal of Lm by CD8 T cells and CD4 T cells upon receipt of the LLO epitopes from major histocompatibility complex class I (MHC-I) and major histocompatibility complex class II (MHC-II). The development of several LLO-based vaccines that make use of the pore-forming capabilities of LLO and the immune response of the host cells is then described. Finally, we conclude by outlining the several natural substances that have been shown to alter the three-dimensional conformation of LLO by binding to particular amino acid residues of LLO, which reduces LLO pathogenicity and may be a possible pharmacological treatment for Lm., Competing Interests: Declaration of Competing Interest 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Inverted perovskite solar cells (PSCs) are a promising technology for commercialization due to their reliable operation and scalable fabrication. However, in inverted PSCs, depositing a high-quality perovskite layer comparable to those realized in normal structures still presents some challenges. Defects at grain boundaries and interfaces between the active layer and carrier extraction layer seriously hinder the power conversion efficiency (PCE) and stability of these cells. In this work, it is shown that synergistic bulk doping and surface treatment of triple-cation mixed-halide perovskites with phenylpropylammonium bromine (PPABr) can improve the efficiency and stability of inverted PSCs. The PPABr ligand is effective in eliminating halide vacancy defects and uncoordinated Pb 2+ ions at both grain boundaries and interfaces. In addition, a 2D Ruddlesden-Popper (2D-RP) perovskite capping layer is formed on the surface of 3D perovskite by using PPABr post-treatment. This 2D-RP perovskite capping layer possesses a concentrated phase distribution ≈n = 2. This capping layer not only reduces interfacial non-radiative recombination loss and improves carrier extraction ability but also promotes stability and efficiency. As a result, the inverted PSCs achieve a champion PCE of over 23%, with an open-circuit voltage as high as 1.15 V and a fill factor of over 83%., (© 2023 Wiley-VCH GmbH.)

Nitrogen (N) fertilization profoundly improves crop agronomic yield but triggers reactive N (Nr) loss into the environment. Nitrous (N 2 O) and ammonia (NH 3 ) emissions are the main Nr species that affect climate change and eco-environmental health. Biochar is considered a promising soil amendment, and its efficacy on individual Nr gas emission reduction has been widely reported. However, the interactions and trade-offs between these two Nr species after biochar addition have not been comprehensively analysed. The influencing factors, such as biochar characteristics, environmental conditions, and management measures, remain uncertain. Therefore, 35 publications (145 paired observations) were selected for a meta-analysis to explore the simultaneous mitigation potential of biochar on N 2 O and NH 3 emissions after its application on arable soil. The results showed that biochar application significantly reduced N 2 O emission by 7.09% while having no significant effect on NH 3 volatilisation. Using biochar with a low pH, moderate BET, or pyrolyzed under moderate temperatures could jointly mitigate N 2 O and NH 3 emissions. Additionally, applying biochar to soils with moderate soil organic carbon, high soil total nitrogen, or low cation exchange capacity showed similar responses. The machine-learning model suggested that biochar pH is a dominating moderator of its efficacy in mitigating N 2 O and NH 3 emissions simultaneously. The findings of this study have major implications for biochar application management and aid the further realisation of the multifunctionality of biochar application in agriculture, which could boost agronomic production while lowering environmental costs., 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 © 2023 Elsevier Inc. All rights reserved.)

How many species of life are there on Earth? This is a question that we want to know but cannot yet answer. Some scholars speculate that the number of species may reach 2.2 billion when considering cryptic diversity and that each morphology-based insect species may contain an average of 3.1 cryptic species. With nearly two million described species, such high estimates of cryptic diversity would suggest that cryptic species are widespread. The development of molecular species delimitation has led to the discovery of a large number of cryptic species, and cryptic biodiversity has gradually entered our field of vision and attracted more attention. This paper introduces the concept of cryptic species, how they evolve, and methods by which they may be discovered and confirmed, and provides theoretical and methodological guidance for the study of hidden species. A workflow of how to confirm cryptic species is provided. In addition, the importance and reliability of multi-evidence-based integrated taxonomy are reaffirmed as a way to better standardize decision-making processes. Special focus on cryptic diversity and increased funding for taxonomy is needed to ensure that cryptic species in hyperdiverse groups are discoverable and described. An increased focus on cryptic species in the future will naturally arise as more difficult groups are studied, and thereby, we may finally better understand the rules governing the evolution and maintenance of cryptic biodiversity., (© 2024 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Background: We aimed to identify plasma biomarkers of atrial fibrillation (AF) progression and recurrence after catheter ablation., Methods: Using AF gene profiling data from GEO database, a weighted gene co-expression network analysis (WGCNA) was conducted to determine the most significant module and hub genes associated with AF. Subsequently, 318 consecutively admitted patients who had undergone radiofrequency catheter ablation were enrolled in this study., Results: WGCNA results revealed that paired immunoglobulin-like type 2 receptor alpha (PILRA) was the only black module gene highly correlated with clinical traits. Plasma soluble PILRα (sPILRα) levels were elevated in patients with AF and significantly elevated in patients with persistent versus paroxysmal AF (4.64 ± 2.74 vs. 3.04 ± 1.56 ng/mL, p < 0.001). Elevated sPILRα level was an independent risk factor for AF progression even after adjusting for traditional factors (adjusted odds ratio: 3.06, 95 % confidence interval [CI]: 1.88-5.27, p < 0.001) and AF recurrence after catheter ablation in patients with persistent AF (adjusted hazards ratio: 4.41, 95 % CI: 1.22-15.92, p = 0.023)., Conclusions: WGCNA screening of GEO microarray gene profiling data showed PILRA expression levels to be correlated with AF progression and recurrence after catheter ablation in patients with persistent AF., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Tuberostemonine has several biological activity, the aim of study examined the impact of tuberostemonine on the proliferation of TGF-β1 induced cell model, and its ability to alleviate pulmonary fibrosis stimulated by bleomycin in mice., Methods: In vitro , we assessed the effect of tuberostemonine (350, 550 and 750 µM) on the proliferation of cells stimulated by TGF-β1 (10 μg/L), as well as on parameters such as α-SMA vitality, human fibronectin, collagen, and hydroxyproline levels in cells. In vivo , we analyzed inflammation, hydroxyproline, collagen activity and metabolomics in the lungs of mice. Additionally, a comprehensive investigation into the TGF-β/smad signaling pathway was undertaken, targeting lung tissue as well as HFL cells., Results: Within the confines of an in vitro setup, the tuberostemonine manifested a discerned IC50 of 1.9 mM. Furthermore, a significant reduction of over fifty percent was ascertained in the secretion levels of hydroxyproline, fibronectin, collagen type I, collagen type III and α-SMA. In vivo , tuberostemonine obviously improved the respiratory function percentage over 50% of animal model and decreased the hydroxyproline, lung inflammation and collagen deposition. A prominent decline in TGF-β/smad pathway functioning was identified within both the internal and external cellular contexts., Conclusions: Tuberostemonine is considered as a modulator to alleviate fibrosis and may become a new renovation for pulmonary fibrosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

MicroRNAs play crucial roles in various biological processes, including but not limited to differentiation, development, disease, and immunity. However, their immunoregulatory roles in half-smooth tongue sole are lacking. Our previous studies indicated that miR-722 could target C5aR1 to modulate the complement pathway to alleviate inflammatory response and even affect the mortality after the bacterial infection with Vibrio anguillarum. Driven by the purpose of revealing the underlying mechanisms, in this study, we investigated the effects of miR-722 on the gene expression and alternative splicing (AS) in the liver of half-smooth tongue sole after Vibrio anguillarum infection, with the approach of miR-722 overexpression/silencing and subsequent RNA-seq. Among the different comparisons, the I group (miR-722 inhibitor and V. anguillarum) versus blank control (PBS) exhibited the highest number of differentially expressed genes (DEGs), suggesting that the immune response was overactivated after inhibiting the miR-722. In addition, enrichment analyses were performed to reveal the functions of DEGs and differential AS (DAS) genes, reflecting the enrichment of RNA splicing and immune-related pathways including NF-κB and T cell receptor signaling pathway. Comparing the M group (miR-722 mimic and V. anguillarum) with the negative control (random sequence and V. anguillarum), two immune-related genes, cd48 and mapk8, were differentially expressed, of which mapk8 was also differentially spliced, indicating their importance in the immune response. Furthermore, representative gene analysis was performed, suggesting their corresponding functional changes due to AS. To verify the RNA-seq data, quantitative real-time PCR was employed with twenty pairs of primers for DEGs and DAS events. Overall, our results demonstrated that miR-722 could mediate the transcriptome-wide changes of gene expression and AS in half-smooth tongue sole, and provided insights into the regulatory role of miR-722 in immune responses, laying the foundation for further functional analyses and practical applications in aquaculture., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Incorporating health equity considerations into guideline development often requires information beyond that gathered through traditional evidence synthesis methodology. This article outlines an operationalization plan for the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-equity criterion to gather and assess evidence from primary studies within systematic reviews, enhancing guideline recommendations to promote equity. We demonstrate its use in a clinical guideline on medical cannabis for chronic pain., Study Design and Setting: We reviewed GRADE guidance and resources recommended by team members regarding the use of evidence for equity considerations, drafted an operationalization plan, and iteratively refined it through team discussion and feedback and piloted it on a medicinal cannabis guideline., Results: We propose a seven-step approach: 1) identify disadvantaged populations, 2) examine available data for specific populations, 3) evaluate population baseline risk for primary outcomes, 4) assess representation of these populations in primary studies, 5) appraise analyses, 6) note barriers to implementation of effective interventions for these populations, and 7) suggest supportive strategies to facilitate implementation of effective interventions., Conclusion: Our approach assists guideline developers in recognizing equity considerations, particularly in resource-constrained settings. Its application across various guideline topics can verify its feasibility and necessary adjustments., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale : Meningeal lymphatic vessels (MLVs) are essential for the clearance of subdural hematoma (SDH). However, SDH impairs their drainage function, and the pathogenesis remains unclear. Herein, we aimed to understand the pathological mechanisms of MLV dysfunction following SDH and to test whether atorvastatin, an effective drug for SDH clearance, improves meningeal lymphatic drainage (MLD). Methods : We induced SDH models in rats by injecting autologous blood into the subdural space and evaluated MLD using Gadopentetate D, Evans blue, and CFSE-labeled erythrocytes. Whole-mount immunofluorescence and transmission electron microscopy were utilized to detect the morphology of MLVs. Phosphoproteomics, western blot, flow cytometry, and in vitro experiments were performed to investigate the molecular mechanisms underlying dysfunctional MLVs. Results : The basal MLVs were detected to have abundant valves and play an important role in draining subdural substances. Following SDH, these basal MLVs exhibited disrupted endothelial junctions and dilated lumen, leading to impaired MLD. Subsequent proteomics analysis of the meninges detected numerous dephosphorylated proteins, primarily enriched in the adherens junction, including significant dephosphorylation of ERK1/2 within the meningeal lymphatic endothelial cells (LECs). Subdural injection of the ERK1/2 kinase inhibitor PD98059 resulted in dilated basal MLVs and impaired MLD, resembling the dysfunctional MLVs observed in SDH. Moreover, inhibiting ERK1/2 signaling severely disrupted intercellular junctions between cultured LECs. Finally, atorvastatin was revealed to protect the structure of basal MLVs and accelerate MLD following SDH. However, these beneficial effects of atorvastatin were abolished when combined with PD98059. Conclusion : Our findings demonstrate that SDH induces ERK1/2 dephosphorylation in meningeal LECs, leading to disrupted basal MLVs and impaired MLD. Additionally, we reveal a beneficial effect of atorvastatin in improving MLD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: To identify prognostic factors in patients with primary chronic subdural hematoma (CSDH) undergoing wait-and-watch management., Methods: A case-control study was conducted in a single center from February 2019 to November 2021 to identify independent influencing factors of wait-and-watch management in mild CSDH patients using wait-and-watch as monotherapy. A total of 39 patients who responded to wait-and-watch management (cases) and 24 nonresponders (controls) matched for age, sex, height, weight, MGS-GCS (Markwalder grading scale and Glasgow Coma Scale), and bilateral hematoma were included. Demographics, blood cell counts, serum biochemical levels, imaging data, and relevant clinical features at baseline were collected., Results: Univariate analysis revealed significant differences between cases and controls in hematoma volume, ability to urinate, maximal thickness of the hematoma, and hypodensity of the hematoma. Hypodense hematoma and hematoma volume were independently associated with the outcome in multivariate analysis. Combining these independently influencing factors revealed an area under the receiver operator characteristic curve of 0.741 (95% CI 0.609-0.874, sensitivity = 0.783, specificity = 0.667)., Conclusions: The results of this study may aid in identifying patients with mild primary CSDH who could benefit from conservative management. While wait-and-watch management may be an option in some cases, clinicians need to suggest medical interventions, such as pharmacotherapy, when appropriate., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Aim: We aimed to assess the effects of cerebral glucagon-like peptide-1 receptor (GLP-1R) activation on the glymphatic system and whether this effect was therapeutic for traumatic brain injury (TBI)., Methods: Immunofluorescence was employed to evaluate glymphatic system function. The blood-brain barrier (BBB) permeability, microvascular basement membrane, and tight junction expression were assessed using Evans blue extravasation, immunofluorescence, and western blot. Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis was evaluated using Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and western blot. Cognitive function was assessed using behavioral tests., Results: Cerebral GLP-1R activation restored glymphatic transport following TBI, alleviating BBB disruption and neuronal apoptosis, thereby improving cognitive function following TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor TGN-020 abolished the protective effect of the GLP-1R agonist against cognitive impairment., Conclusion: Cerebral GLP-1R activation can effectively ameliorate neuropathological changes and cognitive impairment following TBI; the underlying mechanism could involve the repair of the glymphatic system damaged by TBI., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

MicroRNAs (miRNAs) are small non-coding RNAs involved in various biological processes, including immunity. Previously, we investigated the miRNAs of half-smooth tongue sole (Cynoglossus semilaevis) and found that miR-722 (designated Cse-miR-722) was significantly differentially expressed after infection with Vibrio anguillarum, reflecting its importance in immune response. Our preliminary bioinformatic analysis suggested that Cse-miR-722 could target C5aR1 (designated CsC5aR1), which was known to play crucial roles in complement activation and inflammatory response, as a receptor of C5a. However, the underlying mechanisms of their interactions and specific functions in inflammatory and immune response are still enigmas. In this study, we successfully cloned the precursor sequence of Cse-miR-722 (94 bp) and the full length of CsC5aR1 (1541 bp, protein molecular weight 39 kDa). The target gene of Cse-miR-722 was verified as CsC5aR1 by a dual luciferase reporter assay, and Cse-miR-722 was confirmed to regulate CsC5aR1 at the protein level using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The expression of CsC5aR1 and Cse-miR-722 in liver cells and four immune tissues of half-smooth tongue sole changed significantly after LPS stimulation and infection with V. anguillarum. To explore the functional role of Cse-miR-722 in half-smooth tongue sole, we performed both in vitro and in vivo experiments. Cse-miR-722 was observed to affect phagocytosis and respiratory burst activity of macrophages by regulating CsC5aR1 in half-smooth tongue sole. Furthermore, we found that Cse-miR-722 regulated the expression of CsC5aR1, CsC5a, and the inflammatory factors CsIL1-β, CsIL6, CsIL8, and CsTNF-α both in vitro and in vivo. In addition, Cse-miR-722 reduced mortality and pathological damage. This study clarified the regulatory mechanism of Cse-miR-722 on CsC5aR1 and provided insight into the regulatory roles of Cse-miR-722 in immune responses, laying a theoretical foundation for the feasibility of using miR-722 to prevent and control bacterial diseases in teleost., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2023. Published by Elsevier B.V.)