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Aim: This study explored the role of the Hedgehog pathway in epithelial cells during cervical cancer [CC] progression, providing new insights for improving current CC treatment., Background: Abnormal activation of the Hedgehog signaling pathway is associated with the malignant transformation of CC epithelial cells. Single-cell atlas of CC and the role of Hedgehog pathway in epithelial cells during CC progression remain to be explored., Objective: To comprehensively analyze the mechanism of Hedgehog pathway activation in CC epithelial cells and its impact on tumor progression by applying single-cell RNA sequencing [scRNA-seq] analysis., Methods: The scRNA-seq data were acquired from the Gene Expression Omnibus [GEO] database and then processed with the Seurat package. FindNeighbors and Find- Clusters functions were applied to cluster the cells. The CellMarker database was used for subgroup annotation. Differentially expressed genes [DEGs] in each cell subgroup were filtered by FindAllMarkers function. Biological function analysis for the gene set of interest was performed using Clusterprofiler package. AUCell function was employed to calculate the score of the Hedgehog pathway. The differentiation trajectory in epithelial cell subtypes was generated by performing Pseudotime analysis. Finally, protein-protein network [PPI] was used to investigate the interactions between the Hedgehog pathway and other pathways enriched in the gene set of interest., Results: A total of 9 major cell subpopulations were classified and the proportion of epithelial cells was the highest in CC samples. Further analysis revealed that the Hedgehog pathway was abnormally activated in STYK1+ and TP73+ epithelial cell subtypes. Pseudo-time trajectory analysis showed that the differentiation trajectory of STYK1+ epithelial cells gradually transformed into defense-to-virus cells or into proliferation cells, while TP73+ epithelial cells eventually differentiated into two branches of response to estrogen and virus-induced proliferation. PPI analysis showed that the Hedgehog pathway was involved in the proliferation and viral process of epithelial cells in CC., Conclusion: The current study comprehensively analyzed the features of CC samples and differentiation trajectories of epithelial cell subtypes, as well as the role of the Hedgehog pathway in epithelial cells during CC progression. More importantly, effective target genes were discovered for the molecular diagnosis and precise treatment of CC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

To reveal the connections between the 2024 moment magnitude ( M w ) 7.5 Noto earthquake in Japan and the seismicity swarms that preceded it, we investigated its rupture process through near-source waveform analysis and source imaging techniques, combining seismic and geodetic datasets. We found notable complexity in the initial rupture stages. A strong fault asperity, which remained unbroken in preceding seismic swarms, slowed down the rupture. Then, a second rupture initiated at the opposite edge of the asperity, and the asperity succumbed to double-pincer rupture fronts. The failure of this high-stress drop asperity drove the earthquake into a large-scale event. Our observations help unravel the crucial role of fault asperities in controlling swarm migration and rupture propagation and underscore the need for detailed seismological and interdisciplinary studies to assess seismic risk in swarm-prone regions.

Monotherapy, especially the use of antibodies targeting vascular endothelial growth factor (VEGF), has shown limitations in treating choroidal neovascularization (CNV) since reactive oxygen species (ROS) also exacerbate CNV formation. Herein, we developed a combination therapy based on a DNA origami platform targeting multiple components of ocular neovascularization. Our study demonstrated that ocular neovascularization was markedly suppressed by intravitreal injection of a rectangular DNA origami sheet modified with VEGF aptamers (Ap) conjugated to an anti-VEGF antibody (aV) via matrix metalloproteinase (MMP)-cleavable peptide linkers in a mouse model of CNV. Typically, the DNA origami-based therapeutic platform selectively accumulates in neovascularization lesions owing to the dual-targeting ability of the aV and Ap, followed by the cleavage of the peptide linker by MMPs to release the antibody. Together, the released antibody and Ap inhibited VEGF activity. Moreover, the residual bare DNA origami could effectively scavenge ROS, reducing oxidative stress at CNV sites and thus maximizing the synergistic effects of inhibiting neovascularization.

The ED has been increasingly recognized as a key setting for suicide prevention. Zero Suicide (ZS) is an aspirational goal to eliminate suicide for all patients within a health care system through utilization of best practices. However, there has been limited exploration of ZS implementation within the ED. As ED nurses play an important role in suicide prevention through their close contact with patients at risk for suicide, ZS implementation would benefit from tailored strategies for ED nurse leadership. We describe the ZS framework and provides strategies for nurse leaders to adapt each ZS component in the adult ED., Competing Interests: Declaration of competing interest The views expressed in this manuscript are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, the National Institutes of Health, or the United States Government. The funding sources were not involved in the development, writing, or submission of this manuscript. The authors have no conflicts of interest to declare., (Published by Elsevier Inc.)

At present, no consensus has been reached on the generation mechanism of anisotropy in materials fabricated by laser powder bed fusion (LPBF), and most attention has been focused on crystallographic texture. In this paper, an analysis and test were carried out on the hardness, defect distribution, residual stress distribution, and microstructure of WE43 magnesium alloy fabricated by LPBF. The results indicate that LPBF WE43 exhibits obvious anisotropy-the hardness HV of X-Z surface (129.9 HV on average) and that of Y-Z surface (130.7 HV on average) are about 33.5% higher than that of X-Y surface (97.6 HV on average), and the endurable load is smaller in the stacking direction Z compared to the X and Y directions. The factors contributing more to the anisotropy are listed as follows in sequence. Firstly, the defect area of the X-Y projection surface is about 13.2% larger than that of the other two surfaces, so this surface shows greatly reduced mechanical properties due to the exponential relationship between the material strength and the number of defects. Secondly, for laser scanning in each layer/time, the residual stress accumulation in the Z direction is higher than that in the X and Y directions, which may directly reduce the mechanical properties of the material. Finally, more fine grains are distributed in X-Z and Y-Z surfaces when comparing them with those in an X-Y surface, and this fine-grain strengthening mechanism also contributes to the anisotropy. After T5 aging heat treatment (250 °C/16 h), a stronger crystallographic texture is formed in the <0001> direction, with the orientation density index increasing from 10.92 to 21.38, and the anisotropy disappearing. This is mainly caused by the enhancement effect of the texture in the <0001> direction on the mechanical properties in the Z direction cancelling out the weakening effect of the defects in the X-Y surface in the Z direction.

Background: The association between sleep patterns and young students' mental health, which is crucial for their development, remains understudied in rural China. Therefore, the relationship between sleep patterns and mental health among primary and junior high school students in rural China was examined., Method: A total of 1592 primary and junior high school students from rural areas of Gansu Province were surveyed, and the Depression Anxiety and Stress Scale (DASS) was utilized to assess mental health, alongside self-reported data on their daily sleep patterns., Results: Significant sleep inadequacies were identified: 28% of students received less than 8 h of sleep on weekdays, and 19% went to bed later than recommended. On weekends, 38% of students had delayed bedtimes, though only 7.2% received less than 8 h of sleep. Notably, a "U-shaped" relationship was uncovered between sleep duration and mental health for students on weekends, with optimal mental health correlated with receiving 10-11 h of sleep, while both shorter and longer sleep durations on weekends worsened outcomes. This pattern is absent on weekdays. Additionally, adequate sleep and an earlier bedtime was linked to a 6-8% decrease in mental health risks., Conclusions: These findings provide valuable insights for policymakers seeking to enhance student mental well-being in rural settings, emphasizing the importance of implementing measures that promote balanced sleep habits among young students.

Precision spectroscopy of hyperfine splitting (HFS) is a crucial tool for investigating the structure of nuclei and testing quantum electrodynamics. However, accurate theoretical predictions are hindered by two-photon exchange (TPE) effects. We propose a novel formalism that accounts for nuclear excitations and recoil in TPE, providing a model-independent description of TPE effects on HFS in light ordinary and muonic atoms. Combining our formalism with pionless effective field theory at next-to-next-to-leading order, the predicted TPE effects on HFS are 41.7(4.4) kHz and 0.117(13) meV for the 1S state in deuterium and the 2S state in muonic deuterium. These results align within 1σ and 1.3σ from recent measurements and highlight the importance of nuclear structure effects on HFS and indicate the value of more precise measurements in future experiments.

Constrained many-objective optimization problems (CMaOPs) have gradually emerged in various areas and are significant for this field. These problems often involve intricate Pareto frontiers (PFs) that are both refined and uneven, thereby making their resolution difficult and challenging. Traditional algorithms tend to over prioritize convergence, leading to premature convergence of the decision variables, which greatly reduces the possibility of finding the constrained Pareto frontiers (CPFs). This results in poor overall performance. To tackle this challenge, our solution involves a novel dual-population constrained many-objective evolutionary algorithm based on reference point and angle easing strategy (dCMaOEA-RAE). It relies on a relaxed selection strategy utilizing reference points and angles to facilitate cooperation between dual populations by retaining solutions that may currently perform poorly but contribute positively to the overall optimization process. We are able to guide the population to move to the optimal feasible solution region in a timely manner in order to obtain a series of superior solutions can be obtained. Our proposed algorithm's competitiveness across all three evaluation indicators was demonstrated through experimental results conducted on 77 test problems. Comparisons with ten other cutting-edge algorithms further validated its efficacy., Competing Interests: The authors declare there are no competing interests., (©2024 Ji et al.)

Background: The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020. In response to the COVID-19 pandemic, the trial was stopped in March 2020. In person delivery of the SPHERe intervention to a vulnerable population was not possible during the COVID-19 pandemic. We describe here how trial procedures and intervention delivery were adapted in response to the COVID-19 pandemic., Methods: Restrictions imposed by the COVID-19 pandemic on the clinically vulnerable PH population meant that trial delivery was changed from a centre-based rehabilitation programme to remotely delivered group online sessions. This led to minor alterations to the eligibility criteria. These changes followed a consultation process with stakeholders and people with PH and were approved by the funder and independent trial committees., Conclusions: We describe the modified SPHERe trial protocol in response to restrictions imposed by the COVID-19 pandemic. SPHERe is the first randomised controlled trial to assess the clinical and cost-effectiveness of an online group rehabilitation programme for people with PH compared to usual care., Trial Registration: ISRCTN no. 10608766. Prospectively registered on 18th March 2019, updated 16th August 2023., (© 2024. The Author(s).)

To explore the size, morphology, and distribution patterns of internal pore defects in WE43 magnesium alloy formed by laser powder bed fusion (LPBF), as well as their impact on its mechanical properties, computer tomography (CT), metallographic microscopy, and scanning electron microscopy were used to observe the material's microstructure and the morphology of tensile test fractures. The study revealed that a large number of randomly distributed non-circular pore defects exist internally in the LPBF-formed WE43 magnesium alloy, with a defect volume fraction of 0.16%. Approximately 80% of the defects had equivalent diameters concentrated in the range of 10∼40 μm, and 56.2% of the defects had sphericity values between 0.65∼0.7 μm, with the maximum defect equivalent diameter being 122 μm. There were a few spherical pores around 20 μm in diameter in the specimens, and unfused powder particles were found in pore defects near the edges of the parts. Under the test conditions, the fusion pool structure of LPBF-formed WE43 magnesium alloy resembled a semi-elliptical shape with a height of around 66 μm, capable of fusion three layers of powder material in a single pass. Columnar grains formed at the edge of individual fusion pools, while the central area exhibited equiaxed grains. The "scale-like pattern" formed by overlapping fusion pool structures resulted in the microstructure of LPBF-formed WE43 magnesium alloy mainly consisting of fine equiaxed grains with a size of 2.5 μm and columnar grains distributed in a band-like manner.

This paper address the performance optimization of the battery heat sink module by analyzing the lattice structure of the battery heat sink module through in-depth modeling and simulation, and combining the laser powder bed fusion (LPBF)-forming technology with mechanical and corrosion resistance experiments for a comprehensive study. It is found that the introduction of the lattice skeleton significantly improves the thermal conductivity of the phase change material (PCM), realizing the efficient distribution and fast transfer of heat in the system. At the same time, the lattice skeleton makes the heat distribution in the heat exchanger more uniform, improves the utilization rate of the PCM, and helps to maintain the stability of the cell temperature. In addition, the melting of PCM in the lattice heat exchanger is more uniform, thus maximizing its latent heat capacity. In summary, by optimizing the lattice structure and introducing the lattice skeleton, this study successfully improves the performance of the battery heat dissipation system, which provides a strong guarantee for the high efficiency and stable operation of the battery, and provides new ideas and references for the development of the battery heat dissipation technology.

Wound infection poses a significant challenge to the natural healing process. It can impede various stages of wound healing, thereby hindering tissue regeneration and increasing the risk of systemic complications. Wound dressings emerged as a crucial option in the management of infections. Herein, we investigate fabrics coated with copper-based nanoparticles for potential wound dressing application. We synthesized copper and copper-nickel (Cu-Ni) core-shell nanoparticles via a polyol synthesis and investigated their particle growth dynamics and chemical stability. The nickel coating stabilized the nanoparticles against oxidation and dissolution, while dampening the localized surface plasmon resonance of copper. When coated on the fabrics, we found that Cu-Ni NPs were slightly less effective as an antibacterial agent than Cu NPs, however the cytotoxicity of Cu-Ni NPs was significantly reduced compared to pure Cu. Additionally, we show that the discoloration of nanoparticle-coated fabrics depended on pH, thus enabling the visualization of pH levels of simulated wound fluids which can provide information on the inflammatory state of the wound. Our work contributes to the understanding of copper-based nanoparticles and their potential applications in healthcare., Competing Interests: The authors declare no financial or non-financial conflicts of interest that could influence the objectivity or integrity of the presented research., (This journal is © The Royal Society of Chemistry.)

Background: Psoriasis refers to a highly prevalent and immunologically mediated dermatosis with considerable deterioration in life quality. Wogonin, a sort of flavonoid, has been mentioned to elicit protective activities in skin diseases. However, whether Wogonin is implicated in the treatment of psoriasis and its specific mechanisms are not fully understood., Aim: The present work attempted to elaborate the role of Wogonin during the process of psoriasis and to concentrate on the associated action mechanism., Methods: Cell counting kit-8 (CCK-8) method was initially applied to assay the viability of human keratinocyte HaCaT cells treated by varying concentrations of Wogonin. To mimic psoriasis in vitro, HaCaT cells were exposed to M5 cytokines. CCK-8 and 5-Ethynyl-2'-deoxyuridine  assays were adopted for the measurement of cell proliferation. Inflammatory levels were examined with enzyme-linked immunosorbent assay. Immunofluorescence staining tested nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) and Caspase-1 expressions. Western blot examined the protein expressions of proliferation-, inflammation-, pyroptosis-associated factors, and NLRP3., Results: Wogonin treatment antagonized the proliferation, inflammatory response, and NLRP3/caspase-1/Gasdermin-D (GSDMD)-mediated pyroptosis in M5-challenged HaCaT cells. Besides, NLRP3 elevation partially abrogated the effects of Wogonin on M5-induced proliferation, inflammatory response, and NLRP3/caspase-1/GSDMD-mediated pyroptosis in HaCaT cells., Conclusion: In a word, Wogonin might exert anti-proliferation, anti-inflammatory and anti-pyroptosis activities in M5-induced cell model of psoriasis and the blockade of NLRP3/Caspase-1/GSDMD pathway might be recognized as a potential mechanism underlying the protective mechanism of Wogonin in psoriasis, suggesting Wogonin as a prospective anti-psoriasis drug., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Right ventricular (RV) fibrosis is an important pathological change that occurs during the development of right heart failure (RHF) induced by pulmonary hypertension (PH). Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown to play a major role in left heart failure, but it is unclear whether it has a positive effect on RHF. This study aimed to clarify the effect of DAPA on PH-induced RHF and investigate the underlying mechanisms., Methods: We conducted experiments on two rat models with PH-induced RHF and cardiac fibroblasts (CFs) exposed to pathological mechanical stretch or transforming growth factor-beta (TGF-β) to investigate the effect of DAPA., Results: In vivo, DAPA could improve pulmonary hemodynamics and RV function. It also attenuated right heart hypertrophy and RV fibrosis. In vitro, DAPA reduced collagen expression by increasing the production of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). Additionally, DAPA was found to reduce reactive oxygen species (ROS) levels in CFs and the right heart in rats. Similar to DAPA, the ROS scavenger N-acetylcysteine (NAC) exerted antifibrotic effects on CFs. Therefore, we further investigated the mechanism by which DAPA promoted collagen degradation by reducing ROS levels., Conclusions: In summary, we concluded that DAPA ameliorated PH-induced structural and functional changes in the right heart by increasing collagen degradation. Our study provides new ideas for the possibility of using DAPA to treat RHF., 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: Few studies have examined county-level hotspots of veteran suicide and associated place-based contributors, limiting development of targeted community-level prevention strategies. The objectives of this national spatial analysis of all veteran suicides were to identify areas of the United States with higher-than-expected veteran suicide rates and determine county-level social and economic characteristics associated with areas of higher risk., Methods: Using Bayesian hierarchical modeling, county-level standardized mortality ratios for veteran suicide deaths were estimated for time periods 2011-2018, 2011-2014, and 2015-2018. Adjusted relative risk, accounting for community characteristics, for each county was then estimated and associations between community characteristics and veteran suicide risk were examined. Analyses were conducted in 2023-2024., Results: Risk of veteran suicide is predominantly concentrated in the Mountain West and West. Significant predictors of risk across all time periods were per capita number of firearm retailers (2011-2018 relative risk [RR]=1.065 [95% credible interval [CI] 1.030-1.102]), the proportion of residents who moved in the past year (2011-2018 RR=1.060 [95% CI 1.039-1.081]), the proportion of residents who live alone (2011-2018 RR=1.067 [95% CI 1.046-1.089]), the proportion of residents in rental housing (2011-2018 RR=1.041 [95% CI 1.018-1.065]), and the proportion of married residents (2011-2018 RR=0.915 [95% CI 0.890-0.941])., Conclusions: This study contributes to a comprehensive public health approach to veteran suicide prevention by identifying where resources are needed most, and which place-based intervention targets have the largest potential for impact. Findings suggest that public health efforts to address suicide among veterans should address community-level firearm access and identify ways to alleviate deleterious effects of social fragmentation., (Published by Elsevier Inc.)

Herein, we report a DNA origami plasmonic nanoantenna for the programmable surface-enhanced Raman scattering (SERS) detection of cytokine release syndrome (CRS)-associated cytokines (e.g., tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)) in cancer immunotherapy. Typically, the nanoantenna was made of self-assembled DNA origami nanotubes (diameter: ∼19 nm; length: ∼90 nm) attached to a silver nanoparticle-modified silicon wafer (AgNP/Si). Each DNA origami nanotube contains one miniature gold nanorod (AuNR) inside (e.g., length: ∼35 nm; width: ∼7 nm). Intriguingly, TNF-α and IFN-γ logically regulate the opening of the nanotubes and the dissociation of the AuNRs from the origami structure upon binding to their corresponding aptamers. On this basis, we constructed a complete set of Boolean logic gates that read cytokine molecules as inputs and return changes in Raman signals as outputs. Significantly, we demonstrated that the presented system enables the quantification of TNF-α and IFN-γ in the serum of tumor-bearing mice receiving different types of immunotherapies (e.g., PD1/PD-L1 complex inhibitors and STING agonists). The sensing results are consistent with those of the ELISA. This strategy fills a gap in the use of DNA origami for the detection of multiple cytokines in real systems.

Background: Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress)., Objective: To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans., Design: Survey-based non-randomized cohort study with matched comparators., Participants: A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses., Main Measures: Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data., Key Results: Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (M Infected  = 3.16, 95%CI: 2.5, 3.8; M Uninfected  = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression., Conclusion: SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment., (© 2024. The Authors.)

Mosquito-borne viruses (MBVs) are a large class of viruses transmitted mainly through mosquito bites, including dengue virus, Zika virus, Japanese encephalitis virus, West Nile virus, and chikungunya virus, which pose a major threat to the health of people around the world. With global warming and extended human activities, the incidence of many MBVs has increased significantly. Mosquito saliva contains a variety of bioactive protein components. These not only enable blood feeding but also play a crucial role in regulating local infection at the bite site and the remote dissemination of MBVs as well as in remodeling the innate and adaptive immune responses of host vertebrates. Here, we review the physiological functions of mosquito salivary proteins (MSPs) in detail, the influence and the underlying mechanism of MSPs on the transmission of MBVs, and the current progress and issues that urgently need to be addressed in the research and development of MSP-based MBV transmission blocking vaccines., (© 2023 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.)

Objective: This purpose of this study is to investigate the effectiveness and safety of utilizing the arterial spin-labeling (ASL) combined with diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) combined with DWI double mismatch in the endovascular treatment of patients diagnosed with wake-up stroke (WUS)., Methods: In this single-center trial, patients diagnosed with WUS underwent thrombectomy if acute ischemic lesions were observed on DWI indicating large precerebral circulation occlusion. Patients with no significant parenchymal hypersignal on FLAIR and ASL imaging showing a hypoperfusion tissue to infarct core volume ratio of at least 1.2 were included. The participants were divided into groups receiving endovascular thrombectomy plus medical therapy or medical therapy alone, based on their subjective preference. Functional outcomes were assessed using the ordinal score on the modified Rankin scale (mRs) at 90 days, along with the rate of functional independence., Results: In this study, a total of 77 patients were included, comprising 38 patients in the endovascular therapy group and 39 patients in the medical therapy group. The endovascular therapy group exhibited more favorable changes in the distribution of functional prognosis measured by mRs at 90 days, compared to the medical therapy group (adjusted common odds ratio, 3.25; 95% CI, 1.03 to 10.26; P < 0.01). Additionally, the endovascular therapy group had a higher proportion of patients achieving functional independence (odds ratio, 4.0; 95% CI, 1.36 to 11.81; P < 0.01). Importantly, there were no significant differences observed in the incidence of intracranial hemorrhage or mortality rates between the two groups., Conclusion: Guided by the ASL-DWI and FLAIR-DWI double mismatch, endovascular thrombectomy combined with standard medical treatment appears to yield superior functional outcomes in patients with WUS and large vessel occlusion compared to standard medical treatment alone., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pain is a private experience observable through various verbal and non-verbal behavioural manifestations, each of which may relate to different pain-related functions. Despite the importance of understanding the cerebral mechanisms underlying those manifestations, there is currently limited knowledge on the neural correlates of the facial expression of pain. In this functional magnetic resonance imaging (fMRI) study, noxious heat stimulation was applied in healthy volunteers and we tested if previously published brain signatures of pain were sensitive to pain expression. We then applied a multivariate pattern analysis to the fMRI data to predict the facial expression of pain. Results revealed the inability of previously developed pain neurosignatures to predict the facial expression of pain. We thus propose a Facial Expression of Pain Signature (FEPS) conveying distinctive information about the brain response to nociceptive stimulations with minimal or no overlap with other pain-relevant brain signatures associated with nociception, pain ratings, thermal pain aversiveness, or pain valuation. The FEPS may provide a distinctive functional characterization of the distributed cerebral response to nociceptive pain associated with the socio-communicative role of non-verbal pain expression. This underscores the complexity of pain phenomenology by reinforcing the view that neurosignatures conceived as biomarkers must be interpreted in relation to the specific pain manifestation(s) predicted and their underlying function(s). Future studies should explore other pain-relevant manifestations and assess the specificity of the FEPS against simulated pain expressions and other types of aversive or emotional states.

MicroRNAs (miRNA) are endogenously produced small, non-coded, single-stranded RNAs. Due to their involvement in various cellular processes and cross-communication with extracellular components, miRNAs are often coined the "grand managers" of the cell. miRNAs are frequently involved in upregulation as well as downregulation of specific gene expression and thus, are often found to play a vital role in the pathogenesis of multiple diseases. Central nervous system (CNS) diseases prove fatal due to the intricate nature of both their development and the methods used for treatment. A considerable amount of ongoing research aims to delineate the complex relationships between miRNAs and different diseases, including each of the neurological disorders discussed in the present review. Ongoing research suggests that specific miRNAs can play either a pathologic or restorative and/or protective role in various CNS diseases. Understanding how these miRNAs are involved in various regulatory processes of CNS such as neuroinflammation, neurovasculature, immune response, blood-brain barrier (BBB) integrity and angiogenesis is of empirical importance for developing effective therapies. Here in this review, we summarized the current state of knowledge of miRNAs and their roles in CNS diseases along with a focus on their association with neuroinflammation, innate immunity, neurovascular function and BBB., 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.

The heat shock protein 70 family contains the stress proteins ubiquitous in plants. These proteins are involved in the responses to different abiotic stress conditions and have highly conserved gene sequences. However, little is known about the molecular mechanisms of Fritillaria cirrhosa in response to high-temperature stress. Here, 26 HSP70s, FcHSP70-1 to FcHSP70-26, were identified from the transcriptome data of root, bulb, stem, leaf, and fruit samples of F. cirrhosa. The proteins encoded by FcHSP70s had the lengths ranging from 560 aa to 944 aa, with the molecular weight of 61.64-100.01 kDa and the theoretical isoelectric point between 5.00 and 6.59. The secondary structural elements of HSP70s were mainly random coils and α-helixes. Subcellular localization prediction revealed that FcHSP70s were distributed in mitochondria, chloroplasts, nuclei, endoplasmic reticulum, and cytoplasm. The phylogenetic tree showed that 7 members of the HSP70 family belonged to the Dnak subfamily and 19 members belonged to the HSP110/SSE subfamily. In addition, the qRT-PCR results showed that the expression of FcHSP70-5, FcHSP70-8, FcHSP70-17, FcHSP70-18, and FcHSP70-23 in F. cirrhosa was significantly up-regulated at 35 ℃, which indicated that these genes might play a role in the response to high temperature stress. In addition, compared with other tissues, stems and leaves were sensitive to high temperature stress, with the expression of 18 genes up-regulated by 18.18 and 8.03 folds on average, respectively. These findings provide valuable information about the molecular mechanism of HSP70s of F. cirrhosa in response to high temperature stress.

Background: Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer., Methods: Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs)., Results: Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18-1.27) in men, and 1.26 (1.22-1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10-2.51) for men and 1.94 (1.78-2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = -1.01 in men, p<0.001; Beta = -0.98 in women, p<0.001)., Conclusions: Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle., Funding: This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ)., Competing Interests: LB, ZM, XF, CJ, TW, CY, JD, HM, ZH, HS, LW, MZ, GJ No competing interests declared, (© 2024, Bian, Ma et al.)

Objective: The aim of the work described here was to explore a potential method for improving the diagnostic detection of hepatocellular carcinoma (HCC) based on the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) Version 2017., Methods: We retrospectively evaluated 585 liver nodules in 427 patients at risk for HCC from December 2020 to March 2023. The nodules were categorized as LR-1 to LR-M based on CEUS LI-RADS Version 2017 and were randomly subclassified into a developmental cohort (DC) and a validation cohort (VC) at 3:1. In the DC, the cutoff value of the time difference (∆T) for differentiating HCC from other malignancies by LR-M was calculated and used to reclassify nodules in the VC. The diagnostic effect on HCC detection before and after reclassification was further assessed., Results: According to the current CEUS LI-RADS, 140 of 426 (32.9%) confirmed HCC nodules were misclassified as LR-M. In the DC (439 nodules), the receiver operating characteristic (ROC) curve revealed that the cutoff value of ∆T (wash-out onset time minus contrast arrival time) recommended for HCC diagnosis was greater than 21 s. In the VC (146 nodules), 34 HCCs were correctly categorized as LR-5 according to the cutoff value, and after reclassification, LR-5 had higher accuracy (67.1% vs. 89.0%, p < 0.001) and sensitivity (56.0% vs. 87.2%, p < 0.001) for HCC diagnosis with high specificity (100% vs. 94.6%, p = 0.500)., Conclusion: Using the time difference method could identify HCC nodules misdiagnosed as LR-M and improve the diagnostic performance of current CEUS LI-RADS., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Tuberculosis (TB) remains endemic in Singapore. Singapore's clinical practice guidelines for the management of tuberculosis were first published in 2016. Since then, there have been major new advances in the clinical management of TB, ranging from diagnostics to new drugs and treatment regimens. The National TB Programme convened a multidisciplinary panel to update guidelines for the clinical management of drug-susceptible TB infection and disease in Singapore, contextualising current evidence for local practice., Method: Following the ADAPTE framework, the panel systematically reviewed, scored and synthesised English-language national and international TB clinical guidelines published from 2016, adapting recommendations for a prioritised list of clinical decisions. For questions related to more recent advances, an additional primary literature review was conducted via a targeted search approach. A 2-round modified Delphi process was implemented to achieve consensus for each recommendation, with a final round of edits after consultation with external stakeholders., Results: Recommendations for 25 clinical questions spanning screening, diagnosis, selection of drug regimen, monitoring and follow-up of TB infection and disease were formulated. The availability of results from recent clinical trials led to the inclusion of shorter treatment regimens for TB infection and disease, as well as consensus positions on the role of newer technologies, such as computer-aided detection-artificial intelligence products for radiological screening of TB disease, next-generation sequencing for drug-susceptibility testing, and video observation of treatment., Conclusion: The panel updated recommendations on the management of drug-susceptible TB infection and disease in Singapore.

We propose an ultra-compact mode filtering wavelength demultiplexer design with a footprint of 3µ m ×3µ m . Our device can route input T E 1 mode signals at 1310 nm and 1550 nm to different output ports while simultaneously blocking fundamental transverse electric ( T E 0 ) mode input. Our device is designed based on the topology optimization algorithm, which results in an ultra-compact footprint combining wavelength routing and mode filtering functions for the first time, to the best of our knowledge. Our final optimized devices demonstrated insertion losses of 1.26 dB and 1.47 dB for the C- and O-band output ports, respectively, with inter-port crosstalk as low as -21.25 d B and -30.99 d B . The extinction ratios between T E 1 mode and T E 0 mode are 24.02 dB and 30.12 dB at the 1310 nm and 1550 nm output ports. The combination of small footprint, broad transmission bandwidth, T E 1 to T E 0 mode selectively filtering, and C- and O-band T E 1 mode demultiplexing functions make this a uniquely versatile device that can play an important role in future high density mode-wavelength multiplexing systems.

The proportion of lung cancer in never smokers is rising, especially among Asian women, but there is no effective early detection tool. Here, we developed a polygenic risk score (PRS), which may help to identify the population with higher risk of lung cancer in never-smoking women. We first performed a large GWAS meta-analysis (8595 cases and 8275 controls) to systematically identify the susceptibility loci for lung cancer in never-smoking Asian women and then generated a PRS using GWAS datasets. Furthermore, we evaluated the utility and effectiveness of PRS in an independent Chinese prospective cohort comprising 55 266 individuals. The GWAS meta-analysis identified eight known loci and a novel locus (5q11.2) at the genome-wide statistical significance level of P < 5 × 10 -8 . Based on the summary statistics of GWAS, we derived a polygenic risk score including 21 variants (PRS-21) for lung cancer in never-smoking women. Furthermore, PRS-21 had a hazard ratio (HR) per SD of 1.29 (95% CI = 1.18-1.41) in the prospective cohort. Compared with participants who had a low genetic risk, those with an intermediate (HR = 1.32, 95% CI: 1.00-1.72) and high (HR = 2.09, 95% CI: 1.56-2.80) genetic risk had a significantly higher risk of incident lung cancer. The addition of PRS-21 to the conventional risk model yielded a modest significant improvement in AUC (0.697 to 0.711) and net reclassification improvement (24.2%). The GWAS-derived PRS-21 significantly improves the risk stratification and prediction accuracy for incident lung cancer in never-smoking Asian women, demonstrating the potential for identification of high-risk individuals and early screening., (© 2023 UICC.)

Background: Negative mental health-related effects of SARS-COV-2 infection are increasingly evident. However, the impact on suicide-related outcomes is poorly understood, especially among populations at elevated risk., Objective: To determine risk of suicide attempts and other self-directed violence (SDV) after SARS-COV-2 infection in a high-risk population., Design: We employed an observational design supported by comprehensive electronic health records from the Veterans Health Administration (VHA) to examine the association of SARS-COV-2 infection with suicide attempts and other SDV within one year of infection. Veterans with SARS-COV-2 infections were matched 1:5 with non-infected comparators each month. Three periods after index were evaluated: days 1-30, days 31-365, and days 1-365., Participants: VHA patients infected with SARS-COV-2 between March 1, 2020 and March 31, 2021 and matched non-infected Veteran comparators., Main Measures: Suicide attempt and other SDV events for the COVID-19 and non-infected comparator groups were analyzed using incidence rates per 100,000 person years and hazard ratios from Cox regressions modeling time from matched index date to first event. Subgroups were also examined., Key Results: 198,938 veterans with SARS-COV-2 (COVID-19 group) and 992,036 comparators were included. Unadjusted one-year incidence per 100,000 for suicide attempt and other SDV was higher among the COVID-19 group: 355 vs 250 and 327 vs 235, respectively. The COVID-19 group had higher risk than comparators for suicide attempts: days 1-30 hazard ratio (HR) = 2.54 (CI:2.05, 3.15), days 31-365 HR = 1.30 (CI:1.19, 1.43) and days 1-365 HR = 1.41 (CI:1.30, 1.54), and for other SDV: days 1-30 HR = 1.94 (CI:1.51, 2.49), days 31-365 HR = 1.32 (CI:1.20, 1.45) and days 1-365 HR = 1.38 (CI:1.26, 1.51)., Conclusions: COVID-19 patients had higher risks of both suicide attempts and other forms of SDV compared to uninfected comparators, which persisted for at least one year after infection. Results support suicide risk screening of those infected with SARS-COV-2 to identify opportunities to prevent self-harm., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection., (© 2024 Wiley Periodicals LLC.)

Background: Implementation strategies can be a vital leveraging point for enhancing the implementation and dissemination of evidence-based suicide prevention interventions and programming. However, much remains unknown about which implementation strategies are commonly used and effective for supporting suicide prevention efforts., Methods: In light of the limited available literature, a scoping review was conducted to evaluate implementation strategies present in current suicide prevention studies. We identified studies that were published between 2013 and 2022 that focused on suicide prevention and incorporated at least one implementation strategy. Studies were coded by two independent coders who showed strong inter-rater reliability. Data were synthesized using descriptive statistics and a narrative synthesis of findings., Results: Overall, we found that studies most commonly utilized strategies related to iterative evaluation, training, and education. The majority of studies did not include direct measurement of suicide behavior outcomes, and there were few studies that directly tested implementation strategy effectiveness., Conclusion: Implementation science strategies remain an important component for improving suicide prevention and intervention implementation. Future research should consider the incorporation of more type 3 hybrid designs as well as increased systematic documentation of implementation strategies., Trial Registration:  < de-identified > ., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Previous studies mainly focused on risk factors in patients with mild cognitive impairment (MCI) or dementia. The aim of the study was to provide basis for preventing MCI in cognitive normal populations., Methods: The data came from a longitudinal retrospective study involving individuals with brain magnetic resonance imaging scans, clinical visits, and cognitive assessment with interval of more than 3 years. Multiple machine-learning technologies, including random forest, support vector machine, logistic regression, eXtreme Gradient Boosting, and naïve Bayes, were used to establish a prediction model of a future risk of MCI through a combination of clinical and image variables., Results: Among these machine learning models; eXtreme Gradient Boosting (XGB) was the best classification model. The classification accuracy of clinical variables was 65.90%, of image variables was 79.54%, of a combination of clinical and image variables was 94.32%. The best result of the combination was an accuracy of 94.32%, a precision of 96.21%, and a recall of 93.08%. XGB with a combination of clinical and image variables had a potential prospect for the risk prediction of MCI. From clinical perspective, the degree of white matter hyperintensity (WMH), especially in the frontal lobe, and the control of systolic blood pressure (SBP) were the most important risk factor for the development of MCI., Conclusion: The best MCI classification results came from the XGB model with a combination of both clinical and imaging variables. The degree of WMH in the frontal lobe and SBP control were the most important variables in predicting MCI., 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 Zhu, Liu, Ji, Liu and Huang.)

Background: C2H2-zinc finger transcription factors comprise one of the largest and most diverse gene superfamilies and are involved in the transcriptional regulation of flowering. Although a large number of C2H2 zinc-finger proteins (C2H2-ZFPs) have been well characterized in a number of model plant species, little is known about their expression and function in Coptis teeta . C. teeta displays two floral phenotypes (herkogamy phenotypes). It has been proposed that the C2H2-zinc finger transcription factor family may play a crucial role in the formation of floral development and herkogamy observed in C. teeta . As such, we performed a genome-wide analysis of the C2H2-ZFP gene family in C. teeta . Results: The complexity and diversity of C. teeta C2H2 zinc finger proteins were established by evaluation of their physicochemical properties, phylogenetic relationships, exon-intron structure, and conserved motifs. Chromosome localization showed that 95 members of the C2H2 zinc-finger genes were unevenly distributed across the nine chromosomes of C. teeta , and that these genes were replicated in tandem and segmentally and had undergone purifying selection. Analysis of cis-acting regulatory elements revealed a possible involvement of C2H2 zinc-finger proteins in the regulation of phytohormones. Transcriptome data was then used to compare the expression levels of these genes during the growth and development of the two floral phenotypes (F-type and M-type). These data demonstrate that in groups A and B, the expression levels of 23 genes were higher in F-type flowers, while 15 genes showed higher expressions in M-type flowers. qRT-PCR analysis further revealed that the relative expression was highly consistent with the transcriptome data. Conclusion: These data provide a solid basis for further in-depth studies of the C2H2 zinc finger transcription factor gene family in this species and provide preliminary information on which to base further research into the role of the C2H2 ZFPs gene family in floral development in C. teeta ., Competing Interests: Author Q-QH was employed by Zhongshan Zhongzhi Pharmaceutical Group 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 Duan, Zhao, Yu, Xiang, Xiao, Cui, Hu, Baldwin, Lu and Liang.)

The influence of frying times (0, 2, 4, 6, 8, and 10 min) on the continuous changes in the water distribution and the concentrations of key volatile compounds in chicken breast during the frying process were studied. The fried chicken samples could be distinguished by PCA of E-nose and PLS-DA of GC-MS. A total of 40 volatile compounds were identified by GC-MS, and 28 compounds were verified to be the key compounds after further screening by OAVs. The T 22 was increased first and then decreased, while the M 22 and M 23 in fried chicken were considerably decreased and increased with increasing frying time, respectively. The content of the water and the total peak area of LF-NMR in fried chicken samples during the frying process significantly decreased, and the water was transferred from high to low degrees of freedom. In addition, water content, T 21 , T 22 , M 22 and L* value were positively correlated with most alcohols and aldehydes, and were negatively correlated with pyrazines, while a*, b*, M 23 and all amino acids were positively correlated with pyrazines and were negatively correlated with most alcohols and aldehydes. The results may guide the production processes of fried chicken and help produce high-quality chicken products., 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 Ltd. All rights reserved.)

Objectives: This study was conducted to develop nomograms for predicting repeat intrahepatic recurrence (rIHR) and overall survival (OS), after radiofrequency ablation (RFA), treatment in patients with recurrent colorectal liver metastases (CLMs) after hepatectomy based on clinicopathologic features., Methods: A total of 160 consecutive patients with recurrent CLMs after hepatectomy who were treated with ultrasound-guided percutaneous RFA from 2012 to 2022 were retrospectively included. Patients were randomly divided into a training cohort and a validation cohort, with a ratio of 8:2. Potential prognostic factors associated with rIHR and OS, after RFA, were identified by using the competing-risks and Cox proportional hazard models, respectively, and were used to construct the nomogram. The nomogram was evaluated by Harrell's C-index and a calibration curve., Results: The 1-, 2-, and 3-year rIHR rates after RFA were 58.8%, 70.2%, and 74.2%, respectively. The 1-, 3- and 5-year OS rates were 96.3%, 60.4%, and 38.5%, respectively. In the multivariate analysis, mutant RAS , interval from hepatectomy to intrahepatic recurrence ≤ 12 months, CEA level >5 ng/ml, and ablation margin <5 mm were the independent predictive factors for rIHR. Mutant RAS , largest CLM at hepatectomy >3 cm, CEA level >5 ng/ml, and extrahepatic disease were independent predictors of poor OS. Two nomograms for rIHR and OS were constructed using the respective significant variables. In both cohorts, the nomogram demonstrated good discrimination and calibration., Conclusions: The established nomograms can predict individual risk of rIHR and OS after RFA for recurrent CLMs and contribute to improving individualized management.

Building a positive therapeutic relationship is a challenging, yet critical, first step in conducting youth psychotherapy. A number of studies in the youth treatment literature have indicated that a positive therapeutic alliance is related to increased treatment attendance, participation, and outcome. Some research has examined therapist behaviours for engaging therapy clients; however, developmental differences in alliance formation have had limited exploration. The current study surveyed clinicians about their use of specific engagement strategies and the developmental stage of their youth clients. It was hypothesised that participants would differentially rate the importance of different aspects of therapeutic engagement based upon a youth client's developmental stage and that these would correspond with differences in specific engagement strategies. A total of 64 clinicians with experience treating youth completed the study. The participants completed a questionnaire administered online that asked them to rate the importance of developmental differences to forming a therapeutic relationship and provide example client behaviours from their clinical experience for each developmental stage. Results showed clinicians felt the relative importance of collaboration, advocacy, and trustworthiness increased with age. These differences were also evidenced in the specific strategies clinicians endorsed in relation to each engagement factor across developmental stages. This program of research will eventually aid in the development of new guidelines for engaging clients in youth psychotherapy. In addition, the results may be used to enhance psychotherapy training for those working with children and adolescents., (© 2024 John Wiley & Sons Ltd.)

Background: Stem cell-released exosomes (EXs) have shown beneficial effects on regenerative diseases. Our previous study has revealed that EXs of endothelial progenitor cells (EPC-EXs) can elicit favorable effects on endothelial function. EXs may vary greatly in size, composition, and cargo uptake rate depending on the origins and stimulus; notably, EXs are promising vehicles for delivering microRNAs (miRs). Since miR-210 is known to protect cerebral endothelial cell mitochondria by reducing oxidative stress, here we study the effects of miR-210-loaded EPC-EXs (miR210-EPC-EXs) on ischemic brain damage in acute ischemic stroke (IS)., Methods: The miR210-EPC-EXs were generated from EPCs transfected with miR-210 mimic. Middle cerebral artery occlusion (MCAO) surgery was performed to induce acute IS in C57BL/6 mice. EPC-EXs or miR210-EPC-EXs were administrated via tail vein injection 2 hrs after IS. To explore the potential mechanisms, inhibitors of the vascular endothelial growth factor receptor 2 (VEGFR2)/PI3 kinase (PI3K) or tyrosine receptor kinase B (TrkB)/PI3k pathways were used. The brain tissue was collected after treatments for infarct size, cell apoptosis, oxidative stress, and protein expression (VEGFR2, TrkB) analyses on day two. The neurological deficit score (NDS) was evaluated before collecting the samples., Results: 1) As compared to EPC-EXs, miR210-EPC-EXs profoundly reduced the infarct volume and improved the NDS on day two post-IS. 2) Fewer apoptosis cells were detected in the peri-infarct brain of mice treated with miR210-EPC-EXs than in EPC-EXs-treated mice. Meanwhile, the oxidative stress was profoundly reduced by miR210-EPC-EXs. 3) The ratios of p-PI3k/PI3k, p- VEGFR2/VEGFR2, and p-TrkB/TrkB in the ipsilateral brain were raised by miR210-EPC-EXs treatment. These effects could be significantly blocked or partially inhibited by PI3k, VEGFR2, or TrkB pathway inhibitors., Conclusion: These findings suggest that miR210-EPC-EXs protect the brain from acute ischemia- induced cell apoptosis and oxidative stress partially through the VEGFR2/PI3k and TrkB/PI3k signal pathways., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: The PARAMEDIC-3 trial evaluates the clinical and cost-effectiveness of an intraosseous first strategy, compared with an intravenous first strategy, for drug administration in adults who have sustained an out-of-hospital cardiac arrest., Methods: PARAMEDIC-3 is a pragmatic, allocation concealed, open-label, multi-centre, superiority randomised controlled trial. It will recruit 15,000 patients across English and Welsh ambulance services. Adults who have sustained an out-of-hospital cardiac arrest are individually randomised to an intraosseous access first strategy or intravenous access first strategy in a 1:1 ratio through an opaque, sealed envelope system. The randomised allocation determines the route used for the first two attempts at vascular access. Participants are initially enrolled under a deferred consent model.The primary clinical-effectiveness outcome is survival at 30-days. Secondary outcomes include return of spontaneous circulation, neurological functional outcome, and health-related quality of life. Participants are followed-up to six-months following cardiac arrest. The primary health economic outcome is incremental cost per quality-adjusted life year gained., Conclusion: The PARAMEDIC-3 trial will provide key information on the clinical and cost-effectiveness of drug route in out-of-hospital cardiac arrest.Trial registration: ISRCTN14223494, registered 16/08/2021, prospectively registered., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GDP is co-chair of the International Liaison Committee on Resuscitation (ILCOR). CD and JPN are emeritus members of the ILCOR Advanced Life Support task force. KC and HP are current members of the ILCOR Advanced Life Support task force. GDP is editor-in-chief and JPN is founding editor of Resuscitation Plus. KC is associate editor of Resuscitation Plus and guest editor for the research methodology special edition., (© 2023 The Authors.)

Inosine monophosphate (IMP) plays a significant role in meat taste, yet the molecular mechanisms controlling IMP deposition in muscle tissues still require elucidation. The present study systematically and comprehensively explores the molecular network governing IMP deposition in different regions of Jingyuan chicken muscle. Two muscle groups, the breast and leg, were examined as test materials. Using nontargeted metabolomic sequencing, we screened and identified 20 metabolites that regulate IMP-specific deposition. We maintained regular author and institution formatting, used clear, objective, and value-neutral language, and avoided biased or emotional language. We followed a consistent footnote style and formatting features and used precise word choice with technical terms where appropriate. Out of these, 5 were identified as significant contributors to the regulation of IMP deposition. We explained technical term abbreviations when first used and ensured a logical flow of information with causal connections between statements. The results indicate that PGM1, a key enzyme involved in synthesis, is higher in the breast muscle compared to the leg muscle, which may provide an explanation for the increased deposition of IMP in the breast muscle. We aimed for a clear structure with logical progression, avoided filler words, and ensured grammatical correctness. The activity of key enzymes (PKM2, AK1, AMPD1) involved in this process was higher in the breast muscle than in the leg muscle. In the case of IMP degradation metabolism, the activity of its participating enzyme (PurH) was lower in the breast muscle than in the leg muscle. These findings suggest that the increased deposition of IMP in Jingyuan chickens' breast muscle may result from elevated metabolism and reduced catabolism of key metabolites. In summary, a metaomic strategy was utilized to assess the molecular network regulation mechanism of IMP-specific deposition in various segments of Jingyuan chicken. These findings provide insight into genetic improvement and molecular breeding of meat quality traits for top-notch broilers., (Copyright © 2023. Published by Elsevier Inc.)

Maize kernels are complex biological systems composed of three genetic sources, namely maternal tissues, progeny embryos, and progeny endosperms. The lack of gene expression profiles with spatial information has limited the understanding of the specific functions of each cell population, and hindered the exploration of superior genes in kernels. In our study, we conduct microscopic sectioning and spatial transcriptomics analysis during the grain filling stage of maize kernels. This enables us to visualize the expression patterns of all genes through electronical RNA in situ hybridization, and identify 11 cell populations and 332 molecular marker genes. Furthermore, we systematically elucidate the spatial storage mechanisms of the three major substances in maize kernels: starch, protein, and oil. These findings provide valuable insights into the functional genes that control agronomic traits in maize kernels., (© 2023. The Author(s).)

Medical record high-risk flags for suicide indicate patients are receiving enhanced care and alert treating providers to patients' high-risk status. Risk of suicide mortality remains high after flag inactivation, suggesting a need to improve inactivation determinations. This study describes variation in flag inactivation documentation, examines whether documentation varies by patient or facility characteristics, and explores the association between inactivation documentation type and subsequent suicide attempts. In a national sample of veterans with a documented suicide attempt who received a high-risk flag for suicide ( n = 224), medical record review was used to categorize provider documentation of the rationale and procedures for high-risk flag inactivation. Mixed-effects logistic regression models were used to examine patient and facility characteristics associated with flag inactivation documentation type and to examine the association between documentation type and subsequent suicide attempts. Flag inactivation documentation fell into one of two categories: documentation stating the patient no longer met criteria for the high-risk flag (minimal documentation; n = 98, 43.8%); and documentation that included a review of one or more criteria for high-risk flag inactivation ( more than minimal documentation; n = 126, 56.3%). Flag inactivation documentation was not associated with patient or facility characteristics. Veterans with minimal documentation (vs. more than minimal) were more likely to have a suicide attempt after flag inactivation (adjusted odds ratio, AOR = 2.20; 95% CI [1.01, 4.78]; p = .046). Findings suggest a need to better understand flag inactivation procedures in place and to develop a set of standardized procedures to reduce risk of premature high-risk flag inactivation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Household air pollution (HAP) is associated with the development of lung cancer, yet few studies investigated the exposure patterns and joint associations with tobacco smoking. In our study, we included 224 189 urban participants from China Kadoorie Biobank (CKB), 3288 of which diagnosed with lung cancer during the follow-up. Exposure to four HAP sources (solid fuels for cooking/heating/stove and environmental tobacco smoke exposure) was assessed at baseline. Distinct HAP patterns and their associations with lung cancer were examined through latent class analysis (LCA) and multivariable Cox regression. A total of 76.1% of the participants reported regular cooking and 52.2% reported winter heating, of which 9% and 24.7% used solid fuels, respectively. Solid fuel heating increased lung cancer risk (Hazards ratio [HR]: 1.25, 95% confidence interval [CI]: 1.08-1.46). LCA identified three HAP patterns; the "clean fuel cooking and solid fuel heating" pattern significantly increased lung cancer risk (HR: 1.25, 95% CI: 1.10-1.41), compared to low HAP pattern. An additive interaction was observed between heavy smoking and "clean fuel cooking and solid fuel heating" (relative excess risk [RERI]: 1.32, 95% CI: 0.29-2.47, attributable proportion [AP]: 0.23, 95% CI: 0.06-0.36). Cases resulting from solid fuel account for ~4% of total cases (population attribute fraction [PAF] overall : 4.31%, 95% CI: 2.16%-6.47%, PAF ever smokers : 4.38%, 95% CI: 1.54%-7.23%). Our results suggest that in urban China, solid fuel heating increased the risk of lung cancer, particularly among heavy smokers. The whole population could benefit from cleaner indoor air quality by reducing using solid fuels, especially smokers., (© 2023 UICC.)

To investigate the influence of pelvic incidence (PI) on the kyphosis curve patterns and clinical outcomes in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis and to construct a classification of AS according to the PI value for surgical decision-making. 107 AS patients underwent single-level lumbar pedicle subtraction osteotomy (PSO) and finished a minimal of 2-year follow-up. All patients were divided into three groups: low PI (PI ≤ 40°), moderate PI (40° < PI ≤ 60°), and high PI (PI > 60°). Standing lateral radiographs were taken to evaluate the location of kyphotic apex, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (SVA), spino-sacral angle (SSA), global kyphosis (GK), PI, sacral slope (SS), and pelvic tilt (PT). Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were used to evaluate quality of life. Before surgery, a significant difference was shown in the average LL and the mean GK in high PI group was the largest among the three groups. Correction of SVA, GK and LL in high PI group was the smallest among the three group. No significant difference in clinical outcomes was found among the three groups before surgery and at the final follow-up. Regarding the preoperative sagittal profile, the kyphosis curve pattern of moderate PI group is similar to that of low PI group. For AS patients in these two groups, harmonious sagittal alignment can be restored by a single-level PSO. However, the sagittal imbalance is insufficiently realigned by a single-level PSO in a patient with high PI., 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. Published by Elsevier Ltd.)

Endosperm filling in maize (Zea mays), which involves nutrient uptake and biosynthesis of storage reserves, largely determines grain yield and quality. However, much remains unclear about the synchronization of these processes. Here, we comprehensively investigated the functions of duplicate NAM, ATAF1/2, and CUC2 (NAC)-type transcription factors, namely, ZmNAC128 and ZmNAC130, in endosperm filling. The gene-edited double mutant zmnac128 zmnac130 exhibits a poorly filled kernel phenotype such that the kernels have an inner cavity. RNA sequencing and protein abundance analysis revealed that the expression of many genes involved in the biosynthesis of zein and starch is reduced in the filling endosperm of zmnac128 zmnac130. Further, DNA affinity purification and sequencing combined with chromatin-immunoprecipitation quantitative PCR and promoter transactivation assays demonstrated that ZmNAC128 and ZmNAC130 are direct regulators of 3 (16-, 27-, and 50-kD) γ-zein genes and 6 important starch metabolism genes (Brittle2 [Bt2], pullulanase-type starch debranching enzyme [Zpu1], granule-bound starch synthase 1 [GBSS1], starch synthase 1 [SS1], starch synthase IIa [SSIIa], and sucrose synthase 1 [Sus1]). ZmNAC128 and ZmNAC130 recognize an additional cis-element in the Opaque2 (O2) promoter to regulate its expression. The triple mutant zmnac128 zmnac130 o2 exhibits extremely poor endosperm filling, which results in more than 70% of kernel weight loss. ZmNAC128 and ZmNAC130 regulate the expression of the transporter genes sugars that will eventually be exported transporter 4c (ZmSWEET4c), sucrose and glucose carrier 1 (ZmSUGCAR1), and yellow stripe-like2 (ZmYSL2) and in turn facilitate nutrient uptake, while O2 plays a supporting role. In conclusion, ZmNAC128 and ZmNAC130 cooperate with O2 to facilitate endosperm filling, which involves nutrient uptake in the basal endosperm transfer layer (BETL) and the synthesis of zeins and starch in the starchy endosperm (SE)., Competing Interests: Conflict of interest statement. The authors declare to have no conflicts of interest., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Supplemented Erzhi Wan (SEZW) is a Traditional Chinese Medicine commonly used in the treatment of androgenetic alopecia (AGA). This study aims to verify the effectiveness of SEZW for the treatment of AGA in mice and explore the potential molecular mechanisms underlying its function using network pharmacology and molecular docking., Methods: Forty mice were divided into five groups: Control, AGA-model, AGA-Positive, SEZW Low Dose, and SEZW High Dose. Hair regrowth in mice was evaluated by scoring hair on days 0, 14, and 28 post-treatment and weighing mouse hair on day 28 post-treatment. The targets of the active compounds of SEZW were obtained using the Traditional Chinese Medicine Database. AGA-related targets were downloaded from five databases. Then, the overlapping genes were identified. A protein-protein interaction network was constructed using the STRING database. Hub targets were determined through analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Finally, molecular docking of active compounds and hub targets was performed., Results: Hair regrowth in mice in the SEZW treatment groups was significantly enhanced relative to that in the AGA-model mice. A total of 59 potential drug-disease targets were identified. Based on the GO/KEGG analysis results, oxidative stress and gland development were identified as potential mechanisms of action of SEZW in AGA treatment. The PI3K-Akt and AGE-RAGE signaling pathways and seven hub targets were identified as the potential underlying mechanism of SEZW function. Molecular docking results showed that the most active SEZW compounds bind stably to several of the candidate disease targets., Conclusion: SEZW is effective in the treatment of AGA in a mouse model. Combined with network pharmacological analysis, the potential mechanisms, signaling pathways, and hub targets of SEZW in the treatment of AGA were identified, providing new ideas for further studies., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Ji et al.)

A sulfur-containing metal-organic framework, donated as UiO-66-NSMe, was prepared by the post-synthetic modification (PSM) of UiO-66-NH 2 with 2-(Methylthio)benzaldehyde, and the successful synthesis of PSM was confirmed by X-ray photoelectron spectroscopy (XPS), FT-IR and 1 H NMR studies. According to the characteristics of mercury thiophilic, UiO-66-NSMe could be used as a luminescent sensor for Hg 2+ detection with a high selectivity and sensitivity ( K sv = 2.5 × 10 4 M -1 ; LOD = 20 nM), which could be attributed to the coordination between sulfur sites and Hg 2+ based on XPS results. In practical applications, UiO-66-NSMe yielded satisfactory recovery rates (ranging from 96.1% to 99.5%) when it was employed for detecting Hg 2+ in spiked environmental samples. Furthermore, UiO-66-NSMe was successfully employed to detect mercury (II) residues with the in situ rapid nondestructive imaging in simulated fresh agricultural products. Thus, this PSM strategy could provide good guidance for environmental protection methodologies in the future.

Background: Fractures are rare events and can occur because of a fall. Fracture counts are distinct from other count data in that these data are positively skewed, inflated by excess zero counts, and events can recur over time. Analytical methods used to assess fracture data and account for these characteristics are limited in the literature., Methods: Commonly used models for count data include Poisson regression, negative binomial regression, hurdle regression, and zero-inflated regression models. In this paper, we compare four alternative statistical models to fit fracture counts using data from a large UK based clinical trial evaluating the clinical and cost-effectiveness of alternative falls prevention interventions in older people (Prevention of Falls Injury Trial; PreFIT)., Results: The values of Akaike information criterion and Bayesian information criterion, the goodness-of-fit statistics, were the lowest for negative binomial model. The likelihood ratio test of no dispersion in the data showed strong evidence of dispersion (chi-square = 225.68, p-value < 0.001). This indicates that the negative binomial model fits the data better compared to the Poisson regression model. We also compared the standard negative binomial regression and mixed effects negative binomial models. The LR test showed no gain in fitting the data using mixed effects negative binomial model (chi-square = 1.67, p-value = 0.098) compared to standard negative binomial model., Conclusions: The negative binomial regression model was the most appropriate and optimal fit model for fracture count analyses., Trial Registration: The PreFIT trial was registered as ISRCTN71002650., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: The optimum route for drug administration in cardiac arrest is unclear. Recent data suggest that use of the intraosseous route may be increasing. This study aimed to explore changes over time in use of the intraosseous and intravenous drug routes in out-of-hospital cardiac arrest in England., Methods: We extracted data from the UK Out-of-Hospital Cardiac Arrest Outcomes registry. We included adult out-of-hospital cardiac arrest patients between 2015-2020 who were treated by an English Emergency Medical Service that submitted vascular access route data to the registry. The primary outcome was any use of the intraosseous route during cardiac arrest. We used logistic regression models to describe the association between time (calendar month) and intraosseous use., Results: We identified 75,343 adults in cardiac arrest treated by seven Emergency Medical Service systems between January 2015 and December 2020. The median age was 72 years, 64% were male and 23% presented in a shockable rhythm. Over the study period, the percentage of patients receiving intraosseous access increased from 22.8% in 2015 to 42.5% in 2020. For each study-month, the odds of receiving any intraosseous access increased by 1.019 (95% confidence interval 1.019 to 1.020, p < 0.001). This observed effect was consistent across sensitivity analyses. We observed a corresponding decrease in use of intravenous access., Conclusion: In England, the use of intraosseous access in out-of-hospital cardiac arrest has progressively increased over time. There is an urgent need for randomised controlled trials to evaluate the clinical effectiveness of the different vascular access routes in cardiac arrest., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CDD, RF, CJ, JPN, GDP and KC are co-investigators of the PARAMEDIC-3 trial (a randomised controlled trial of the IV versus IO route for vascular access in out-of-hospital cardiac arrest). JPN is Editor in Chief and GDP is an editor of Resuscitation. CDD and KC are editorial board members of Resuscitation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Affective states are typically accompanied by facial expressions, but these behavioral manifestations are highly variable. Even highly arousing and negative valent experiences, such as pain, show great instability in facial affect encoding. The present study investigated which neural mechanisms are associated with variations in facial affect encoding by focusing on facial encoding of sustained pain experiences. Facial expressions, pain ratings, and brain activity (BOLD-fMRI) during tonic heat pain were recorded in 27 healthy participants. We analyzed facial expressions by using the Facial Action Coding System (FACS) and examined brain activations during epochs of painful stimulation that were accompanied by facial expressions of pain. Epochs of facial expressions of pain were coupled with activity increase in motor areas (M1, premotor and SMA) as well as in areas involved in nociceptive processing, including primary and secondary somatosensory cortex, posterior and anterior insula, and the anterior part of the mid-cingulate cortex. In contrast, prefrontal structures (ventrolateral and medial prefrontal) were less activated during incidences of facial expressions, consistent with a role in down-regulating facial displays. These results indicate that incidences of facial encoding of pain reflect activity within nociceptive pathways interacting or possibly competing with prefrontal inhibitory systems that gate the level of expressiveness., (© 2023. The Author(s).)