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Abstract Background There is a limited evidence for humidified high-flow nasal cannula (HHFNC) use on inter-hospital transport. Despite this, its use during transport is increasing in children with respiratory distress worldwide. In 2015 HHFNC was implemented on a specialized pediatric retrieval team serving for Victoria. The aim of this study is to investigate the effect of the HHFNC implementation on the retrieval team on the paediatric intensive care unit (PICU) length of stay and respiratory support use. Methods We performed a cohort study using a comparative interrupted time-series approach controlling for patient and temporal covariates, and population-adjusted analysis. We studied 3022 children admitted to a PICU in Victoria with respiratory distress January 2010–December 2019. Patients were divided in pre-intervention era (2010–2014) and post-intervention era (2015–2019). Results 1006 children following interhospital transport and 2016 non-transport children were included. Median (IQR) age was 1.4 (0.7–4.5) years. Pneumonia (39.1%) and bronchiolitis (34.3%) were common. On retrieval, HHFNC was used in 5.0% (21/420) and 45.9% (269/586) in pre- and post-intervention era. In an unadjusted model, median (IQR) PICU length of stay was 2.2 (1.1–4.2) and 1.7 (0.9–3.2) days in the pre- and post-intervention era in transported children while the figures were 2.4 (1.3–4.9) and 2.1 (1.2–4.5) days in non-transport children. In the multivariable regression model, the intervention was associated with the reduced PICU length of stay (ratio 0.64, 95% confidential interval 0.49–0.83, p = 0.001) with the predicted reduction of PICU length of stay being − 10.6 h (95% confidential interval − 16.9 to − 4.3 h), and decreased respiratory support use (− 25.1 h, 95% confidential interval − 47.9 to − 2.3 h, p = 0.03). Sensitivity analyses including a model excluding less severe children showed similar results. In population-adjusted analyses, respiratory support use decreased from 4837 to 3477 person-hour per year in transported children over the study era, while the reduction was 594 (from 9553 to 8959) person-hour per year in non-transport children. With regard to the safety, there were no escalations of respiratory support mode during interhospital transport. Conclusions The implementation of HHFNC on interhospital transport was associated with the reduced PICU length of stay and respiratory support use among PICU admissions with respiratory distress.

Family with sequence similarity 107, member A(FAM107A) was supposed as a tumor suppressor for various types of tumors. However, no pan-cancer analysis of FAM107A is available. Therefore, we conducted a FAM107A-related pan-cancer analysis across thirty-three tumors based on TCGA database to explore the molecular characteristics of FAM107A. The FAM107A expression is reduced in most cancers, and its down-regulated expression was linked to poor overall survival and progression-free survival of tumor patients. Analysis of DNA methylation of the FAM107A gene showed a negative correlation between FAM107A expression and promoter methylation in numerous cancers. Furthermore, FAM107A expression was noted to be involved in myeloid-derived suppressor cell infiltration in multiple cancers. To explore the mechanism of FAM107A in cancers, KEGG, and GO enrichment analysis was performed and the result showed “cell adhesion” and “cAMP signaling pathway” terms as the potential impact of FAM107A on cancers. An experiment in vitro showed FAM107A knockdown promoted the proliferation, migration, and invasion of bladder cancer and renal cancer cells. Our study indicates that FAM107A may be a putative tumor suppressor in bladder cancer and other tumors.

Background: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease.Methods: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful).Results: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation.Conclusions: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.). [ABSTRACT FROM AUTHOR]

Objectives: To examine changes in out-of-hospital cardiac arrest (OHCA) characteristics and outcomes during 2003-2022, and 12-month outcomes for people who experienced OHCA during 1 January 2010 - 30 June 2022., Study Design: Retrospective observational study; analysis of Victorian Ambulance Cardiac Arrest Registry (VACAR) data., Setting, Participants: OHCA events in Victoria not witnessed by emergency medical services personnel, 1 January 2003 - 31 December 2022., Main Outcome Measures: Crude and age-standardised annual OHCA incidence rates; survival to hospital discharge., Results: Of 102 592 OHCA events included in our analysis, 67 756 were in men (66.3%). The age-standardised incidence did not change significantly across the study period (2003: 89.1 cases, 2022: 91.2 cases per 100 000 population; for trend: P = 0.50). The proportion of OHCA cases with attempted resuscitation by emergency medical services in which bystanders attempted cardio-pulmonary resuscitation increased from 40.3% in 2003/2004 to 72.2% in 2021/2022, and that of public access defibrillation from 0.9% to 16.1%. In the Utstein comparator group (witnessed OHCA events in which the initial cardiac rhythm was ventricular fibrillation or ventricular tachycardia, with attempted resuscitation by emergency medical services), the odds of survival to hospital discharge increased during 2003-2022 (adjusted odds ratio (aOR), 3.08; 95% confidence interval [CI], 2.22-4.27); however, the odds of survival was greater than in 2012 only in 2018 (aOR, 1.37; 95% CI, 1.04-1.80) and 2019 (aOR, 1.68; 95% CI, 1.28-2.21). The COVID-19 pandemic was associated with reduced odds of survival (aOR, 0.63; 95% CI, 0.54-0.74). Of 3161 people who survived OHCA and participated in 12-month follow-up, 1218 (38.5%) reported full health according to the EQ-5D., Conclusion: Utstein survival to hospital discharge increased threefold during 2003-2022, and the proportions of cases in which bystanders provided cardio-pulmonary resuscitation or public access defibrillation increased. The COVID-19 pandemic was associated with a substantial reduction in survival, and new strategies are needed to improve outcomes., (© 2024 The Author(s). Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Genome-wide association studies (GWAS) provide valuable insights into the genetic architecture of complex traits, yet interpreting their results remains challenging due to the polygenic nature of most traits. Gene set analysis offers a solution by aggregating genetic variants into biologically relevant pathways, enhancing the detection of coordinated effects across multiple genes. In this study, we present and evaluate a gene set prioritization approach utilizing Bayesian Linear Regression (BLR) models to uncover shared genetic components among different phenotypes and facilitate biological interpretation. Through extensive simulations and analyses of real traits, we demonstrate the efficacy of the BLR model in prioritizing pathways for complex traits. Simulation studies reveal insights into the model's performance under various scenarios, highlighting the impact of factors such as the number of causal genes, proportions of causal variants, heritability, and disease prevalence. Comparative analyses with MAGMA (Multi-marker Analysis of GenoMic Annotation) demonstrate BLR's superior performance, especially in highly overlapped gene sets. Application of both single-trait and multi-trait BLR models to real data, specifically GWAS summary data for type 2 diabetes (T2D) and related phenotypes, identifies significant associations with T2D-related pathways. Furthermore, comparison between single- and multi-trait BLR analyses highlights the superior performance of the multi-trait approach in identifying associated pathways, showcasing increased statistical power when analyzing multiple traits jointly. Additionally, enrichment analysis with integrated data from various public resources supports our results, confirming significant enrichment of diabetes-related genes within the top T2D pathways resulting from the multi-trait analysis. The BLR model's ability to handle diverse genomic features, perform regularization, conduct variable selection, and integrate information from multiple traits, genders, and ancestries demonstrates its utility in understanding the genetic architecture of complex traits. Our study provides insights into the potential of the BLR model to prioritize gene sets, offering a flexible framework applicable to various datasets. This model presents opportunities for advancing personalized medicine by exploring the genetic underpinnings of multifactorial traits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gholipourshahraki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although there is a high incidence of hematogenous infections in melioidosis, a tropical infectious disease, there are few systematic analyses of hematogenous melioidosis in imaging articles. A comprehensive clinical and imaging evaluation of hematogenous melioidosis be conducted in order to achieve early diagnosis of the disease., Materials and Methods: We conducted an analysis of 111 cases of melioidosis diagnosed by bacteriological culture between August 2001 and September 2022. The analysis focused on observing the main manifestations of chest imaging and clinical data, including nodules, cavities, consolidation, ground glass opacity(GGO), pleural effusion, centrilobular nodules, and temperature, leucocyte count, diabetes, etc. Our study involved univariate and multivariate analyses to identify significant diagnostic variables and risk predictive factors., Results: A total of 71.2% (79/111) of melioidosis cases were caused by hematogenous infection, and the most common organ involved was the lungs (88.5%, 100/113). The incidence of sepsis in patients with lung abnormalities was high (73%, 73/100), and the mortality rate of septic shock was 22% (22/100). Univariate analysis showed that the radiologic signs of blood culture-positive cases were more likely to have bilateral pulmonary and subpleural nodules (p = 0.003), bilateral GGO (p = 0.001), bilateral hydrothorax (p = 0.011). The multivariate analysis revealed a significant improvement in the area under the receiver operating characteristic curve (AUC) when comparing the model that included both clinical and radiologic variables to the model with clinical variables alone. The AUC increased from 0.818 to 0.932 (p = 0.012). The most important variables in the logistic regression with backward elimination were found to be nodule, GGO, and diabetes., Conclusion: The combination of CT features and clinical variables provided a valuable and timely warning for blood borne infectious melioidosis., (© 2024. The Author(s).)

A deep understanding of neuron structure and function is crucial for elucidating brain mechanisms, diagnosing and treating diseases. Optical microscopy, pivotal in neuroscience, illuminates neuronal shapes, projections, and electrical activities. To explore the projection of specific functional neurons, scientists have been developing optical-based multimodal imaging strategies to simultaneously capture dynamic in vivo signals and static ex vivo structures from the same neuron. However, the original position of neurons is highly susceptible to displacement during ex vivo imaging, presenting a significant challenge for integrating multimodal information at the single-neuron level. This study introduces a graph-model-based approach for cell image matching, facilitating precise and automated pairing of sparsely labeled neurons across different optical microscopic images. It has been shown that utilizing neuron distribution as a matching feature can mitigate modal differences, the high-order graph model can address scale inconsistency, and the nonlinear iteration can resolve discrepancies in neuron density. This strategy was applied to the connectivity study of the mouse visual cortex, performing cell matching between the two-photon calcium image and the HD-fMOST brain-wide anatomical image sets. Experimental results demonstrate 96.67% precision, 85.29% recall rate, and 90.63% F1 Score, comparable to expert technicians. This study builds a bridge between functional and structural imaging, offering crucial technical support for neuron classification and circuitry analysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anan Li reports financial support was provided by National Natural Science Foundation of China. Anan Li reports financial support was provided by Ministry of Science and Technology of the People's Republic of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Rivers are hotspots for methane (CH 4 ) emissions, and aerobic methane oxidation is a crucial process in controlling emissions. The spatio-temporal heterogeneity of river environment can greatly affect the methane oxidation process. However, currently, few studies have focused on the spatio-temporal changes in activity of methane oxidation and the associated microbiome in riverine ecosystems, which hinders a comprehensive understanding the role of this process in reducing emissions of CH 4 . Here, we investigated the variations in methane oxidation activity and community of methanotrophs in sediment of a mountain river across different reaches and seasons. The potential methane oxidation rate ranged from 24.11 to 493.03 nmol CH 4 g -1 (sediment) d -1 , which was significantly greater in sediment obtained during the winter than in that obtained during the summer. Moreover, the rate in middle reaches was significantly greater than that in upper and lower reaches in summer. The abundance of pmoA gene of methanotrophs ranged from 2.45 × 10⁶ to 2.98 × 10⁷ copies g -1 (sediment), which was also significantly greater in winter than in summer and showed significant variations among reaches. Additionally, methanotrophic diversity and community composition exhibited significant variations across both reaches and seasons, and the relative abundance of Methylococcus and Methylocystis was closely associated with methane oxidation activity. Sediment NH 4 + content, pH and temperature were potentially crucial factors affecting the activity or methanotrophic community. In conclusion, it is necessary to consider both temporal and spatial scales to improve our understanding of the significance and driving mechanisms of methane oxidation in controlling CH 4 emissions from rivers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chiral semiconducting nanomaterials offer many potential applications in photodetection, light emission, quantum information, and so on. However, it is difficult to achieve a strong circular dichroism (CD) signal in semiconducting nanocrystals (NCs) due to the complexity of chiral ligand surface engineering and multiple, uncertain mechanisms of chiroptical behavior. Here, a chiral ligand exchange strategy with cysteine on the ternary metal chalcogenide AgBiS 2 NCs is developed, and a strong, long-lasting CD signal in the near-UV region is achieved. By carefully optimizing the ligand concentration, the CD peaks are observed at 260 and 320 nm, respectively, giving insight into the different ligand binding mechanisms influencing the CD signal of AgBiS 2 NCs. Using density-functional theory, a large degree of crystal distortion by the bidentate mode of ligand chelation, and efficient ligand-NC electron transfer, synergistically resulting in the strongest CD signal (g-factor over 10 -2 ) observed in chiral ligand-exchanged semiconductor NCs to date, is demonstrated. To demonstrate the effective chiral properties of these AgBiS 2 NCs, a spin-filter device with over 86% efficiency is fabricated. This work represents a considerable leap in the field of chiral semiconductor NCs and points toward their future applications., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Background: The prevalence of myopia among adolescents is increasing precipitously in China, and the popularity of orthokeratology (OK) lenses as an effective treatment for controlling myopia progression is rising. This protocol assessed and compared the clinical dry eye parameters in children and adolescents with myopia treated with spectacles or OK lenses., Methods and Analysis: This single-masked randomized control trial will include 300 participants (aged 8-17 years) with myopia treated with OK lens (study group) or spectacles (control group). We will record the ocular surface disease index, visual analog scale score, noninvasive tear breakup time, tear meniscus height, meibomian gland score, ocular redness score, visual acuity, tear Matrix Metalloproteinase-9 concentration, tear Lymphotoxin alpha levels at baseline, and after 1-, 3-, 6-, and 12-month., Discussion: This study will be a standardized, scientific, clinical trial designed to evaluate the dry eye parameters in children and adolescents with myopia treated with OK lenses for myopia control., Ethics and Dissemination: This study has been approved by the Ethics Committee of He Eye Specialist Hospital [ethics approval number: IRB(2023)K024.01]. Before participating in the trial, written informed consent will be obtained from all patient's parents or guardians. The findings of this study will be showcased at both local and international conferences and will also be submitted for publication in reputable peer-reviewed journals., Trial Registration Number: Clinicaltrials.gov: NCT06023108 {2a, 2b}., Competing Interests: None.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. Published by Elsevier Ltd.)

Background: Daily use of low concentrations of atropine is recommended for children undergoing myopia control therapy. While the benefits of controlling myopia progression have been confirmed, the potential unwanted side effects on the ocular surface, pupil size, and quality of vision following the administration of 0.01% atropine have not been investigated., Objective: This single-arm, self-control study aimed to investigate the short-term effects of 0.01% atropine topical eye drop (He Eye Hospital Co., Ltd., Shenyang, China) on pupil size and subjective quality of vision in participants with myopia. Each 3 mL vial of eye drops contains atropine (0.01%), sodium chloride (0.9%), and benzalkonium chloride (0.005%) in an aqueous solution., Methods: Thirty-three adults (66 eyes) were recruited for the study. The mean age of the participants recruited for this study was 24.91 ± 3.36 years. This study is registered with Clinical Trials.gov (NCT06071260). Assessments were performed at baseline and 10 h, 14 h, and 18 h following the administration of 0.01% topical atropine drop (TAD). Mesopic pupil diameter (MPD), photopic pupil diameter (PPD), higher order aberration (HOA), non-invasive tear breakup time (NITBUT), tear meniscus height (TMH), tear film lipid layer (TFLL), and Redness score (RS). Subjective assessments included the quality of vision (QoV) and the ocular surface disease index (OSDI) questionnaires., Results: Following the use of 0.01% atropine, PPD significantly increased at all the time points ( p  < 0.001); MPD increased significantly at 10 h and 14 h ( p  < 0.001 and p  < 0.05, respectively). A decrease in TMH and an increase in the OSDI questionnaire scores were observed up to 10 and 14 h, respectively, after using atropine ( p  < 0.001). Glare ( p  = 0.004 at 10 h and p  = 0.003 at 14 h), blurred vision ( p  < 0.0001 at 10 h and p  = 0.035 at 14 h), and focusing difficulties ( p  < 0.0001 at 10 h and p < 0.0001 at 14 h) were significantly higher at both 10 h and 14 h after using atropine. No significant changes were observed in the HOA, NITBUT, and RS scores (all p  > 0.05) at all time points., Conclusion: Decreased TMH, dry eye symptoms, and visual symptoms will likely persist overnight but often diminish within 18 h after using 0.01% atropine eye drops., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Chen, Chen, Qin, Li, He, Yu, He, Pazo and Xu.)

The absence of effective extracellular matrix to mimic the natural tumor microenvironment remains a significant obstacle in cancer research. Matrigel, abundant in various biological matrix components, is limited in its application due to its high cost. This has prompted researchers to explore alternative matrix substitutes. Here, we have investigated the effects of the extracellular matrix derived from pig small intestinal submucosa (ECM-SIS) in xenograft tumor modeling. Our results showed that the pig-derived ECM-SIS effectively promotes the establishment of xenograft tumor models, with a tumor formation rate comparable to that of Matrigel. Furthermore, we showed that the pig-derived ECM-SIS exhibited lower immune rejection and fewer infiltrating macrophages than Matrigel. Gene sequencing analysis demonstrated only a 0.5% difference in genes between pig-derived ECM-SIS and Matrigel during the process of tumor tissue formation. These differentially expressed genes primarily participate in cellular processes, biological regulation, and metabolic processes. These findings emphasize the potential of pig-derived ECM-SIS as a cost-effective option for tumor modeling in cancer research., (Creative Commons Attribution license.)

Photoacoustic imaging (PAI) can sensitively detect regions and substances with strong optical absorption, which means that diseased tissue can be imaged with high contrast in the presence of surrounding healthy tissue through the photoacoustic effect. However, its signal intensity and resolution may be limited by background signals generated by endogenous chromophores such as melanin and hemoglobin. A feasible method for practical application of this so-called background-suppressed PAI is still lacking. In this work, a dual-wavelength differential background noise-suppressed photoacoustic tomography is developed based on organic semiconducting polymer dots (Pdots). The Pdots have a strong absorption peak at 945 nm, and then the absorption decreases sharply with the increase of wavelength, and the absorption intensity drops to only about a quarter of the original value at 1050 nm. The present system significantly suppresses the strong background noise of blood through dual-wavelength differential PAI, enabling precise monitoring of the distribution information of theranostic agents in diseased tissues. The signal-to-noise ratio of the theranostic agent distribution map is increased by about 20 dB. This work provides a platform for real-time and accurate monitoring of tumors and drugs, which helps avoid damage to healthy tissue during treatment and has clinical significance in cancer treatment., (© 2024 Wiley‐VCH GmbH.)

We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving a phasing switch error rate of 0.18% for European samples and imputation quality of r 2  = 0.75 for variants with minor allele frequencies as low as 2 × 10 -4 in white British samples. The GEL-imputed UK Biobank genome-wide association analysis identified 70% of associations found by direct exome sequencing (P < 2.18 × 10 -11 ), while extending testing of rare variants to the entire genome. Coding variants dominated the rare-variant genome-wide association results, implying less disruptive effects of rare non-coding variants., (© 2024. The Author(s).)

Introduction: The aim of this study was to examine the relationship between the morphological parameters of retinal arteriolar bifurcations and coronary artery disease (CAD)., Methods: In this cross-sectional observational study, fundus photography was conducted on 444 participants to capture retinal arteriolar bifurcations. A total of 731 fundus photographs yielded 9625 measurable bifurcations. Analyzed bifurcation parameters included the diameters of the parent vessel (d 0 ), the larger branch (d 1 ), and the smaller branch (d 2 ), as well as the angles (θ 1 ) and (θ 2 ) representing the orientation of each branch in relation to the parent vessel, respectively. Additionally, theoretical optimal angles ( θ 1 ' ) and ( θ 2 ' ), calculated from the measured parameters, provided a benchmark for ideal bifurcation geometry. The study assessed the variation in these parameters across different levels of coronary atherosclerosis severity., Results: After adjusting for anatomical characteristics including the asymmetry ratio, area ratio, and distance to the optic disc, we observed that patients with severe coronary artery stenosis had significant deviations from the theoretical optimal bifurcation angles, with a decrease in ( θ 1 ' ) and an increase in ( θ 2 ' ) compared to those with moderate stenosis., Conclusion: The findings suggest a clear alteration in retinal arteriolar bifurcation morphology among patients with severe CAD, which could potentially serve as an indicator of disease severity., Competing Interests: Declarations Conflict of Interest All named authors have declared that they did not have anything to disclose regarding conflict of interest with respect to this manuscript. Ethical Approval The study constituted a single-center, retrospective, single-blind, cross-sectional observational analysis conducted in strict accordance with the principles of the Declaration of Helsinki. The Institutional Review Board of Tiemei General Hospital, affiliated with the Liaoning Health Industry Group, approved the study (Approval No. 2021080601). All participants furnished written informed consent and agreed to the publication of all images, clinical data, and associated information contained in this manuscript. In the present study, all components with any individually identifiable information have been removed from the dataset., (© 2024. The Author(s).)

Background/purpose: Meibomian glands are sebaceous glands that release meibum onto the ocular surface; enhancing the quality and quantity of meibum secretions has been proven to improve signs and symptoms of evaporative dry eye (EDE) and meibomian gland dysfunction (MGD). This study aimed to evaluate and compare the efficacy of a heated eye mask (HEM) and eyelid massage device EyePeace (EP) in alleviating signs and symptoms of evaporative dry eye., Methods: Forty dry eye participants were recruited in a prospective, contralateral-eye trial study. After undergoing 10 min of HEM therapy, eyelid massage therapy was applied to one eye by the device. The efficiency was assessed at four time points: baseline (0 min), 5 min (5 min), 15 min (15 min), and 30 min (30 min). Non-invasive breakup time (NITBUT), redness score (RS Score), tear meniscus height (TMH), tear-film lipid layer (TFLL), endothelial cell count (ECC), meibomian gland expressibility (MGEx), meibomian gland quality (MGQ), conjunctivocorneal staining (CS), ocular surface temperature (OST), best corrected visual acuity (BCVA), intraocular pressure (IOP), central corneal thickness (CCT) flat-axis keratometry value (K1), and steep-axis keratometry value (K2), were examined., Results: Baseline clinical measurements did not have statistically significant differences between the groups (all p  > 0.05). After 30 min, a comparison was made between the HEM group and EP + HEM group, revealing significant changes only in the primary outcomes, TFLL (2.18 ± 0.45 versus 2.40 ± 0.50; p  < 0.05), and MGEx grades (0.68 ± 0.53 versus 0.98 ± 0.70; p  < 0.05). Improvements in NITBUT and TMH were sustained until 5 min and 15 min after using EP + HEM. No significant changes were observed in RS Score, MGQ, OST, CFS, BCVA, IOP, ECC, K1, K2, and CCT (all p  > 0.05) at all test time points., Conclusion: The application of a heated eye mask followed by a gentle massage using EyePeace on the eyelids can have a sustained improvement in the tear film lipid layer and meibomian gland expressivity score but not clinically significant, and does not pose any significant immediate impact on the cornea.Trial registration number: NCT06158997., 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.)

The weathering time of empty puparia could be important in predicting the minimum postmortem interval (PMImin). As corpse decomposition progresses to the skeletal stage, empty puparia often remain the sole evidence of fly activity at the scene. In this study, we used empty puparia of Sarcophaga peregrina (Diptera: Sarcophagidae) collected at ten different time points between January 2019 and February 2023 as our samples. Initially, we used the scanning electron microscope (SEM) to observe the surface of the empty puparia, but it was challenging to identify significant markers to estimate weathering time. We then utilized attenuated total internal reflectance Fourier transform infrared spectroscopy (ATR-FTIR) to detect the puparia spectrogram. Absorption peaks were observed at 1064 cm -1 , 1236 cm -1 , 1381 cm -1 , 1538 cm -1 , 1636 cm -1 , 2852 cm -1 , 2920 cm -1 . Three machine learning models were used to regress the spectral data after dimensionality reduction using principal component analysis (PCA). Among them, eXtreme Gradient Boosting regression (XGBR) showed the best performance in the wavenumber range of 1800-600 cm -1 , with a mean absolute error (MAE) of 1.20. This study highlights the value of refining these techniques for forensic applications involving entomological specimens and underscores the considerable potential of combining FTIR and machine learning in forensic practice., 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 development of simple methods for the isolation and quantification of exosomes in biological samples is important. By using the typical two-dimensional (2D) nanomaterials, graphene oxide (GO), the present work first studied the interaction of liposomes with the nanocomposites formed by adsorbing HRP on the GO surface and found the presence of liposomes led to the release of HRP from the GO surface to the solution phase triggering the luminol-H 2 O 2 chemiluminescence (CL) reaction to emit light. Benefiting from the similarity of exosomes to liposomes in both composition and morphology aspects, the GO-HRP nanocomposites with a mass ratio of 120:1 and 160:1 were employed for the quantitative detection of exosomes in 100-fold diluted serum samples. The whole detection process took about 15 min and as low as 3.2 × 10 2 particles μL -1 of exosomes could be sensitively detected. In addition to GO-HRP nanocomposites, the CL responses of other nanocomposites obtained from adsorbing HRP on other 2D nanomaterials such as layered MoS 2 for exosomes were also tested. MoS 2 -HRP exhibited similar behavior and the LODs for the detection of exosomes were 5.8 × 10 2 particles μL -1 . The proposed assays were a biomarker-independent quantitative method that achieved the quantification of exosomes in serum samples directly without an isolation process., 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.)

Traditional activators such as sodium hydroxide and sodium silicate are commonly used in the preparation of alkali-activated materials; however, their significant environmental impact, high cost, and operational risks limit their sustainable use in treating solid waste. This study explores the innovative use of carbide slag (CS) and sodium metasilicate (NS) as alternative activators in the production of sewage sludge ash-based alkali-activated materials (SSAM) with the aim of reducing the carbon footprint of the preparation process. The results demonstrate that CS effectively activates the sewage sludge ash, enhancing the compressive strength of the SSAM to 40 MPa after curing for 28 d. When used in conjunction with NS, it synergistically improves the mechanical properties. Furthermore, the microstructure and phase composition of the SSAM are characterized. Increasing the quantities of CS and NS accelerates the dissolution of the precursor materials, promoting the formation of a higher quantity of hydration products. This significantly reduces the number of voids and defects within the samples, further enhancing the densification of the microstructure. Environmental assessments reveal that CS and NS offer substantial sustainability benefits, confirming the feasibility of activating SSAM using these materials. This approach provides a less energy-intensive and more environmentally friendly alternative to conventional activation methods and presents an effective strategy for managing large volumes of sewage sludge ash and CS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The objective of this study was to assess the effectiveness of intense pulsed light (IPL) therapy in individuals diagnosed with glaucoma and dry eye disease (DED)., Methods: This randomized control study recruited 22 individuals diagnosed with glaucoma, ranging in age from 33 to 82 years. These participants were undergoing treatment with hypotensive eyedrops and had clinical indications and subjective complaints associated with dry eye. Each patient underwent three sessions of IPL therapy in one eye, while the contralateral eye served as the control eye (CT). The following parameters were assessed at three time points: baseline, week-2, and week-4. These parameters include non-invasive breakup time (NITBUT), tear meniscus height (TMH), conjunctivocorneal epithelial staining score (CS), tear film lipid layer (TFLL), meibomian gland expressibility score (MGEx), Schirmer I test, ocular bulbar redness score (OBRS), and ocular surface disease index (OSDI). Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and corneal endothelial cell count (ECC) were assessed for safety. The clinical trial was registered on 25/12/2023 at ClinicalTrials.gov website (NCT06158984)., Results: Comparing baseline and 4-week measurements revealed that the IPL group found significant improvements in NITBUT (IPL: 8.74±2.60 sec. vs CT: 5.76±1.75 sec. p <0.01), TMH (IPL: 0.23±0.05mm vs CT: 0.19±0.06mm, p =0.011), C.S. (IPL: 1.14±0.56 vs CT: 1.95±1.17, p =0.005), TFLL (IPL: 2.91±2.91 vs CT:3.36±0.58, p =0.047), MGEx score (IPL: 1.14±0.35 vs CT: 1.45±0.51, p =0.020) and OSDI scores (IPL: 31.77±15.59 vs 50.59±21.55, p =0.002) significantly improved. Conversely, other parameters showed no significant improvements ( p >0.05)., Conclusion: The progression of ocular surface disease in individuals using topical anti-glaucoma medication may worsen if the condition is not addressed. Nevertheless, IPL therapy has the potential to result in significant improvements in both objective and subjective measures of dry eye. Best-corrected visual acuity, endothelial cell count, and intraocular pressure were determined to be within the permitted limits. No adverse events were reported during the course of the study., 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 Zhang et al.)

Neuroligin-3 (Nlgn3) is an autism-associated cell-adhesion molecule that interacts with neurexins and is robustly expressed in both neurons and astrocytes. Neuronal Nlgn3 is an essential regulator of synaptic transmission but the function of astrocytic Nlgn3 is largely unknown. Given the high penetrance of Nlgn3 mutations in autism and the emerging role of astrocytes in neuropsychiatric disorders, we here asked whether astrocytic Nlgn3 might shape neural circuit properties in the cerebellum similar to neuronal Nlgn3. Imaging of tagged Nlgn3 protein produced by CRISPR/Cas9-mediated genome editing showed that Nlgn3 is enriched in the cell body but not the fine processes of cerebellar astrocytes (Bergmann glia). Astrocyte-specific knockout of Nlgn3 did not detectably alter the number of synapses, synaptic transmission, or astrocyte morphology in mouse cerebellum. However, spatial transcriptomic analyses revealed a significant shift in gene expression among multiple cerebellar cell types after the deletion of astrocytic Nlgn3. Hence, in contrast to neuronal Nlgn3, astrocytic Nlgn3 in the cerebellum is not involved in shaping synapses but may modulate gene expression in specific brain areas., (© 2024. The Author(s).)

To assess the agreement and repeatability of scotopic pupil size measurement using 2WIN-S (Adaptica, Padova, Italy) portable refractor in Chinese adults. This prospective non-randomized open-label controlled study assessed the scotopic pupil size of 100 right eyes using OPD-Scan III (Optical path difference) (Nidek Technologies, Gamagori, Japan) and 2WIN-S. OPD-Scan III and 2WIN-S measure pupil size using infrared light and detector, while 2WIN-S measures bilateral eyes simultaneously, OPD-Scan III measures unilateral eyes individually. Participants were first measured once using OPD-Scan III and two consecutive measurements were performed using 2WIN-S after 15 min of rest interval. The primary outcome was to evaluate the agreement between 2WIN-S and OPD-Scan III, and the secondary outcome was to evaluate the repeatability of 2WIN-S. Scotopic pupil size of 100 right eyes of 100 adults (28 male and 72 female) aged 18-53 years (mean 36 ± 12 years) was assessed using OPD-Scan III and 2WIN-S, respectively. The mean scotopic pupil size of OPD-Scan III and 2WIN-S was recorded to be 6.24 ± 0.88 mm and 6.27 ± 0.81 mm, respectively. For the mean scotopic pupil size of OPD-Scan III and 2WIN-S the difference was - 0.03 mm (95%CI - 0.10 to 0.04 mm), p = 0.445, the 95% limits of agreement (LOA) was - 0.71 to 0.66 mm. ICC between the two devices was 0.92 (95% CI 0.88-0.94) (ICC > 0.9 indicates excellent consistency). Coefficients of repeatability (CoR) of 2WIN-S was 0.37, which has a high repeatability. For the mean scotopic pupil size of 2WIN-S of the repeated measurements, the difference was -0.04 mm (95%CI - 0.08 to 0.01 mm), p = 0.019, the 95% limits of agreement (LOA) was - 0.41 to 0.32 mm, with a narrow LOA. However, the majority of the variations were less than ± 0.50 mm (98% of scotopic pupil size measurements were below this threshold), within the clinically acceptable range (± 0.50 mm). Our study showed excellent agreement between 2WIN-S and OPD-Scan III (ICC > 0.9) and a good repeatability of 2WIN-S (CoR = 0.37). This study suggests a novel technique for measuring pupillary responses in low light conditions, which can be considered an alternative to OPD-Scan III in clinical settings., (© 2024. The Author(s).)

Purpose: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. Methods: In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. Results: The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm 2 , and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, P  = 0.172) and CNFD (21.46 ± 8.41, P  = 0.163). Finally, at week 8, all parameters had significant improvements. Conclusion: Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).

Methane (CH 4 ) is a potent greenhouse gas, with lake ecosystems significantly contributing to its global emissions. Denitrifying anaerobic methane oxidation (DAMO) process, mediated by NC10 bacteria and ANME-2d archaea, links global carbon and nitrogen cycles. However, their potential roles in mitigating methane emissions and removing nitrogen from lake ecosystems remain unclear. This study explored the spatial variations in activities of nitrite- and nitrate-DAMO and their functional microbes in Changdanghu Lake sediments (Jiangsu Province, China). The results showed that although the average abundance of ANME-2d archaea (5.0 × 10 6 copies g -1 ) was significantly higher than that of NC10 bacteria (2.1 × 10 6 copies g -1 ), the average potential rates of nitrite-DAMO (4.59 nmol 13 CO 2 g -1 d -1 ) and nitrate-DAMO (5.01 nmol 13 CO 2 g -1 d -1 ) showed no significant difference across all sampling sites. It is estimated that nitrite- and nitrate-DAMO consumed approximately 6.46 and 7.05 mg CH 4 m -2 d -1 , respectively, which accordingly achieved 15.07-24.95 mg m -2 d -1 nitrogen removal from the studied lake sediments. Statistical analyses found that nitrite- and nitrate-DAMO activities were both significantly related to sediment nitrate contents and ANME-2d archaeal abundance. In addition, NC10 bacterial and ANME-2d archaeal community compositions showed significant correlations with sediment organic carbon content and water depth. Overall, this study underscores the dual roles of nitrite- and nitrate-DAMO processes in CH 4 mitigation and nitrogen elimination and their key environmental impact factors (sediment organic carbon and inorganic nitrogen contents, and water depth) in shallow lake, enhancing the understanding of carbon and nitrogen cycles in freshwater aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Nasopharyngeal carcinoma (NPC) is a kind of malignant head and neck tumor with high mortality. lncRNAs are valuable diagnostic biomarkers and therapeutic targets for various tumors. This study investigated the effects and mechanism of LINC00313 in nasopharyngeal carcinoma., Methods: Cell Counting Kit-8 (CCK-8) and immunohistochemistry were used for assessing cell proliferation. The levels of autophagy-related proteins, and stem cell markers were detected. Immunofluorescence assay was used for LC3 detection. Methylated RNA Immunoprecipitation (meRIP) of LINC00313 in NPC cells was assessed. The localization of LINC00313 was verified by luorescence in situ hybridization (FIHS). The interaction between LINC00313 and the downstream targets were analyzed and confirmed by immunoprecipitation (RIP). Besides, the tumorigenesis roles of LINC00313 were confirmed in tumor growth mice model., Results: LINC00313 was increased in NPC tissues and cells. LINC00313 knockdown enhanced autophagy, and decreased stemness and cell viability of NPC cells through regulating STIM1. METTL3/IGF2BP1-mediated m6A modification promoted the stabilization and up-regulation of LINC00313. LINC00313 activated AKT/mTOR pathway in NPC cells through PTBP1/STIM1 axis. Moreover, LINC00313 promoted tumor growth and metastasis in xenograft model., Conclusion: Upregulation of LINC00313 suppressed autophagy and promoted stemness of NPC cells through PTBP1/STIM1 axis., 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.)

An enhanced lateral flow assay (LFA) is presented for rapid and highly sensitive detection of acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigens with gold nanoflowers (Au NFs) as signaling markers and gold enhancement to amplify the signal intensities. First, the effect of the morphology of gold nanomaterials on the sensitivity of LFA detection was investigated. The results showed that Au NFs prepared by the seed growth method showed a 5-fold higher detection sensitivity than gold nanoparticles (Au NPs) of the same particle size, which may benefit from the higher extinction coefficient and larger specific surface area of Au NFs. Under the optimized experimental conditions, the Au NFs-based LFA exhibited a detection limit (LOD) of 25 pg mL -1 for N protein using 135 nm Au NFs as the signaling probes. The signal was further amplified by using a gold enhancement strategy, and the LOD for the detection of N protein achieved was 5 pg mL -1 . The established LFA also exhibited good repeatability and stability and showed applicability in the diagnosis of SARS-CoV-2 infection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Under fasting conditions, the pathway converting gluconeogenesis precursors into muscle glycogen becomes crucial due to reduced glycogen reserves. However, there is limited research on skeletal muscle gluconeogenesis and the impact of fasting on gluconeogenic gene expression., Methods: Sheep fetal skeletal muscle cells cultured in vitro were used to study the effects of varying lactic acid concentrations (0 to 30 mM) and 2.5 mM glucose on the expression of gluconeogenesis-related genes after 6 h of fasting. The effects on mRNA and protein expression of key genes involved in skeletal muscle gluconeogenesis were measured by quantitative real time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting at 48 h., Results: Fasting increased the expression of key gluconeogenic genes, fructose-1,6-bisphosphatase 2 ( FBP2 ), glucose-6-phosphatase 3 ( G6PC3 ), pyruvate kinase M ( PKM ), monocarboxylate transporter1 ( MCTS1 ), glucose transporter type 4 ( GLUT4 ), pyruvate carboxylase ( PC ), and lactate dehydrogenase A ( LDHA ). The mRNA levels of FBP2 , G6PC3 , and MCTS1 significantly decreased with glucose addition. Additionally, 10 mM lactic acid significantly promoted the expression of FBP2 , PC , MCTS1 , LDHA , GLUT4 , and PKM while inhibiting phosphoenolpyruvate carboxykinase ( PEPCK ) expression. At the protein level, 10 mM lactic acid significantly increased FBP2 and PKM protein expression., Conclusions: This study shows that fasting regulates key gluconeogenic gene expression in sheep skeletal muscle cells and highlights the role of lactic acid in inducing these gene expressions., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Reconstructing neuronal morphology is vital for classifying neurons and mapping brain connectivity. However, it remains a significant challenge due to its complex structure, dense distribution, and low image contrast. In particular, AI-assisted methods often yield numerous errors that require extensive manual intervention. Therefore, reconstructing hundreds of neurons is already a daunting task for general research projects. A key issue is the lack of specialized training for challenging regions due to inadequate data and training methods. This study extracted 2,800 challenging neuronal blocks and categorized them into multiple density levels. Furthermore, we enhanced images using an axial continuity-based network that improved three-dimensional voxel resolution while reducing the difficulty of neuron recognition. Comparing the pre- and post-enhancement results in automatic algorithms using fluorescence micro-optical sectioning tomography (fMOST) data, we observed a significant increase in the recall rate. Our study not only enhances the throughput of reconstruction but also provides a fundamental dataset for tangled neuron reconstruction., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

This study aimed to evaluate the validity of the Chinese translation version of OSDI-6 (C-OSDI-6) using a virtual set-up questionnaire for dry eye disease. A total of 270 participants (136 males, 50.4% and 134 females, 49.6%) with a mean age of 28.22 ± 9.01 years were assessed, diagnosed under the criteria put forth by Dry Eye Workshop completed the Chinese translated version of the OSDI-12 questionnaire (C-OSDI-12). Validity and psychometric properties were analyzed using the study data on the selected items (a new approach called virtual validation). The six items were extracted from the C-OSDI-12 as suggested by the authors of OSDI-6 and compared. The total scores of C-OSDI-12 and C-OSDI-6 were 30.27 ± 13.19 and 6.95 ± 3.53, respectively. Significant reliability was found between the total C-OSDI-6 score and the total C-OSDI-12 score (r = 0.865, p < 0.001). Infits and outfits of the C-OSDI-6 were between 1.26 and 0.78.The C-OSDI-6 proved valid and psychometrically responsive in Chinese adult dry eye participants. The findings of this virtual validation study need to be confirmed in a longitudinal validation study on real-world use., (© 2024. The Author(s).)

Background: Despite this growing interest, there remains a lack of comprehensive and systematic bibliometric analyses of ketamine research. This study aimed to summarize the progress in ketamine research through bibliometric analysis, providing insights into the development and direction of the field., Methods: Publications related to ketamine were retrieved from the Web of Science Core Collection (WoSCC) database on February 15, 2024. In conducting a comprehensive bibliometric analysis, a variety of bibliographic elements were meticulously collected to map the landscape of research within a specific field., Results: Between January 1, 2014, and December 31, 2023, a total of 10,328 articles on ketamine research were published across 1,752 academic journals by 45,891 authors from 8,914 institutions in 128 countries. The publication volume has shown a steady increase over this period. The United States of America (USA) and the People's Republic of China lead in both publication and citation counts. The National Institute of Mental Health (NIMH) and Yale University emerge as the most active institutions in this research domain. Carlos Zarate of the NIH National Institute of Mental Health was noted for the highest number of significant publications and received the most co-citations. The analysis revealed key research themes including mechanism of action, adverse events, psychiatric applications, and perioperative implications., Conclusion: This study provided comprehensive bibliometric and knowledge mapping analysis of the global ketamine research landscape, offering valuable insights into the trends, key contributors, and thematic focus areas within the field. By delineating the evolution of ketamine research, this study aims to guide future scholarly endeavors and enhance our understanding of ketamine's therapeutic potential., 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 Wang, Chang and Chen.)

Aims: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity., Methods: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated., Results: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 μg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group., Conclusion: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.

Constructed wetlands (CWs) are pivotal for wastewater treatment due to their high efficiency and numerous advantages. The impact of plant species and diversity on greenhouse gas (GHG) emissions from CWs requires a more comprehensive evaluation. Moreover, controversial perspectives persist about whether CWs function as carbon sinks or sources. In this study, horizontal subsurface flow (HSSF) CWs vegetated with Cyperus alternifolius, Typhae latifolia, Acorus calamus, and the mixture of these three species were constructed to evaluate pollutant removal efficiencies and GHG emissions, and estimate carbon budgets. Polyculture CWs can stably remove COD (86.79 %), NH 4 + -N (97.41 %), NO 3 - -N (98.55 %), and TP (98.48 %). They also mitigated global warming potential (GWP) by suppressing N 2 O emissions compared with monoculture CWs. The highest abundance of the Pseudogulbenkiania genus, crucial for denitrification, was observed in polyculture CWs, indicating that denitrification dominated in nitrogen removal. While the highest nosZ copy numbers were observed in CWs vegetated with Cyperus alternifolius, suggesting its facilitation of denitrification-related microbes. Selecting Cyperus alternifolius to increase species diversity is proposed for simultaneously maintaining the water purification capacity and reducing GHG emissions. Carbon budget estimations revealed that all four types of HSSF CWs were carbon sinks after six months of operation, with carbon accumulation capacity of 4.90 ± 1.50 (Cyperus alternifolius), 3.31 ± 2.01 (Typhae latifola), 1.78 ± 1.30 (Acorus calamus), and 2.12 ± 0.88 (polyculture) kg C/m 2 /yr. This study implies that under these operation conditions, CWs function as carbon sinks rather than sources, aligning with carbon peak and neutrality objectives and presenting significant potential for carbon reduction 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 computational method has been proven to be a promising means for pre-screening large-scale anticancer drug combinations to support precision oncology applications. Pioneering efforts have been made to develop machine learning technology for predicting drug synergy, but high computational cost for training models as well as great diversity and limited size in screening data escalate the difficulty of prediction. To address this challenge, we propose a simple machine learning framework, namely Similarity Network-based Synergy prediction (SNSynergy), for predicting synergistic effects towards new cell lines and new drug combinations by two locally weighted models CLSN and DCSN. This framework only requires a small amount of auxiliary data, like genomics information of cell lines and the molecular fingerprints or targets of drugs. Based on the assumption that similar cell lines and similar drug combinations have similar synergistic effects, CLSN and DCSN predict synergy scores through capturing individual synergy contributions of nearest cell line and drug combination neighbors, respectively. High correlations between predicted and measured synergy scores on two leading cancer cell line pharmacogenomic screening datasets (the O'Neil dataset and the NCI-ALMANAC dataset) demonstrate the effectiveness and robustness of SNSynergy. Many of the identified drug combinations are consistent with previous studies, or have been explored in clinical settings against the specific cancer type, showing that SNSynergy has the potential to supply cost-saving and effective high-throughput screening for prioritizing the most applicable cell lines and the most promising drug combinations., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study is to identify a rapid, sensitive, and non-destructive auxiliary approach for postmortem diagnosis of SCD, addressing the challenges faced in forensic practice., Methods: ATR-FTIR spectroscopy was employed to collect spectral features of blood samples from different cases, combined with pathological changes. Mixed datasets were analyzed using ANN, KNN, RF, and SVM algorithms. Evaluation metrics such as accuracy, precision, recall, F1-score and confusion matrix were used to select the optimal algorithm and construct the postmortem diagnosis model for SCD., Results: A total of 77 cases were collected, including 43 cases in the SCD group and 34 cases in the non-SCD group. A total of 693 spectrogram were obtained. Compared to other algorithms, the SVM algorithm demonstrated the highest accuracy, reaching 95.83% based on spectral biomarkers. Furthermore, by combing spectral biomarkers with age, gender, and cardiac histopathological changes, the accuracy of the SVM model could get 100%., Conclusion: Integrating artificial intelligence technology, pathology, and physical chemistry analysis of blood components can serve as an effective auxiliary method for postmortem diagnosis of SCD., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Early career members of Assembly 2 (Respiratory Intensive Care) attended the 2023 European Respiratory Society International Congress in Milan, Italy. The conference covered acute and chronic respiratory failure. Sessions of interest to our assembly members and to those interested in respiratory critical care are summarised in this article and include the latest updates in respiratory intensive care, in particular acute respiratory distress syndrome and mechanical ventilation., Competing Interests: Conflict of interest: C. Bianquis declares support for attending meetings and travel to the ERS 2023 congress from Vitalaire. Conflict of interest: T. Lacoste-Palasset declares support for attending meetings and travel to the ERS 2023 congress from Oxyvie. Conflict of interest: A.L. Vieira declares support for attending meetings and travel to the ERS 2023 congress from Vivisol. Conflict of interest: S. Leiva Agüero, C. Cantero, A. Golfe Bonmatí, J. González, X. Hu, A. Livesey, R. Guillamat Prats, G. Salai, D.L. Sykes, S. Toland, C. van Zeller, P. Viegas, S. Zaneli, C. Karagiannidis and C. Fisser have no conflict of interest to declare regarding this article., (Copyright ©The authors 2024.)

Reduced nicotinamide adenine dinucleotide (NADH) has a strong impact on physiological metabolism, and its concentration is related to metabolic and neurodegenerative diseases. A more reliable and accurate detection method for NADH quantitation is needed for early disease diagnosis and point-of-care testing. Aggregation-induced emission (AIE) materials are widely used to improve the sensitivity in analytes assays due to their anti-aggregation-caused quenching property. Here we developed TPA-BQD-Py AIE-dots transducers and evaluated its performance in NADH detection. The NADH concentration-dependent ratiometric sensing was based on electron transfer from TPA-BQD-Py AIE-dots to NADH with variable fluorescence intensity at 584 nm and 470 nm, resulting in high sensitivity (limit of detection at 110 nM), photostability, selectivity, and a rapid and reversible response. We further developed the application of TPA-BQD-Py AIE-dots transducers in in vivo NADH imaging using a smartphone and digital camera, respectively, demonstrating the potential for NADH point-of-care testing., 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.)

Oxytocin (OXT) plays important roles in autonomic control and behavioral modulation. However, it is unknown how the projection patterns of OXT neurons align with underlying physiological functions. Here, we present the reconstructed single-neuron, whole-brain projectomes of 264 OXT neurons of the mouse paraventricular hypothalamic nucleus (PVH) at submicron resolution. These neurons hierarchically clustered into two groups, with distinct morphological and transcriptional characteristics and mutually exclusive projection patterns. Cluster 1 (177 neurons) axons terminated exclusively in the median eminence (ME) and have few collaterals terminating within hypothalamic regions. By contrast, cluster 2 (87 neurons) sent wide-spread axons to multiple brain regions, but excluding ME. Dendritic arbors of OXT neurons also extended outside of the PVH, suggesting capability to sense signals and modulate target regions. These single-neuron resolution observations reveal distinct OXT subpopulations, provide comprehensive analysis of their morphology, and lay the structural foundation for better understanding the functional heterogeneity of OXT neurons., Competing Interests: Declaration of interests X.Y. is a member of the advisory board of Neuron., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The purpose of this research was to develop protocols for evaluating the bifurcation parameters of retinal arteriole and establish a reference range of normal values., Methods: In this retrospective study, we measured a total of 1314 retinal arteriolar bifurcations from 100 fundus photographs. We selected 200 from these bifurcations for testing inter-measurer and inter-method agreement. Additionally, we calculated the normal reference range for retinal arteriolar bifurcation parameters and analyzed the effects of gender, age, and anatomical features on retinal arteriolar bifurcation., Results: The measurement method proposed in this study has demonstrated nearly perfect consistency among different measurers, with interclass correlation coefficient (ICC) for all bifurcation parameters of retinal arteriole exceeding 0.95. Among healthy individuals, the retinal arteriolar caliber was narrowest in young adults and increased in children, teenagers, and the elderly; retinal arteriolar caliber was greater in females than in males; and the diameter of the inferior temporal branch exceeded that of the superior temporal branch. The angle between the two branches of retinal arteriolar bifurcation was also greater in females than in males. When using the center of the optic disc as a reference point, the angle between the two branches of the retinal arteriole at the proximal or distal ends increased. In contrast, the estimated optimum theoretical values of retinal arteriolar bifurcation were not affected by these factors., Conclusions: The method for the measurement of retinal arteriolar bifurcation in this study was highly accurate and reproducible. The diameter and branching angle of the retinal arteriolar bifurcation were more susceptible to the influence of gender, age, and anatomical features. In comparison, the estimated optimum theoretical values of retinal arteriolar bifurcation were relatively stable. Video available for this article., (© 2024. The Author(s).)

Kidney transplantation from blood type A2/A2B donors to type B recipients (A2→B) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used data from the Scientific Registry of Transplant Recipients from December 2014 until June 2022 to evaluate the association between A2→B listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2→B recipients. Among 53 409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2→B offers ("A2-eligible"). The rates of DDKT at 1-, 3-, and 5-years were 32.1%, 61.4%, and 72.1% among A2-eligible candidates and 14.1%, 29.9%, and 44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted hazard ratio (wHR) = 2.19 2.33 2.47 ; P < .001). The 7-year adjusted mortality was comparable between A2→B and B-ABOc (type B/O donors to B recipients) recipients (wHR 0.78 0.94 1.13 , P = .5). Moreover, there was no difference between A2→B vs B-ABOc DDKT recipients with regards to death-censored graft failure (wHR 0.77 1.00 1.29 , P > .9) or all-cause graft loss (wHR 0.82 0.96 1.12 , P = .6). Following its broader adoption since the implementation of the kidney allocation system, A2→B DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2→B listing for eligible type B candidates should be expanded., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

A large volume, scalable synthesis procedure of HgTe quantum dots (QDs) capped initially with short-chain conductive ligands ensures ligand exchange-free and simple device fabrication. An effective n- or p-type self-doping of HgTe QDs is achieved by varying cation-anion ratio, as well as shifting the Fermi level position by introducing single- or double-cyclic thiol ligands, that is, 2-furanmethanethiol (FMT) or 2,5-dimercapto-3,4-thiadiasole (DMTD) in the synthesis. This allows for preserving the intact surface of the HgTe QDs, thus ensuring a one order of magnitude reduced surface trap density compared with HgTe subjected to solid-state ligand exchange. The charge carrier diffusion length can be extended from 50 to 90 nm when the device active area consists of a bi-layer of cation-rich HgTe QDs capped with DMTD and FMT, respectively. As a result, the responsivity under 1340 nm illumination is boosted to 1 AW -1 at zero bias and up to 40 AW -1 under -1 V bias at room temperature. Due to high noise current density, the specific detectivity of these photodetectors reaches up to 10 10 Jones at room temperature and under an inert atmosphere. Meanwhile, high photoconductive gain ensures a rise in the external quantum efficiency of up to 1000% under reverse bias., (© 2023 Wiley‐VCH GmbH.)

Chiral halide perovskite materials promise both superior light response and the capability to distinguish circularly polarized emissions, which are especially common in the fluorescence spectra of organic chiral materials. Herein, thin-film field-effect transistors (FETs) based on chiral quasi-two-dimensional perovskites are explored, and the temperature dependence of the charge carrier transport mechanism over the broad temperature range (80-300 K) is revealed. A typical p-type charge transport behavior is observed for both left-handed ( S- C 6 H 5 (CN 2 ) 2 NH 3 ) 2 (CH 3 NH 3 ) n -1 Pb n I 3 n +1 and right-handed ( R -C 6 H 5 (CN 2 ) 2 NH 3 ) 2 (CH 3 NH 3 ) n -1 Pb n I 3 n +1 chiral perovskites, with maximum carrier mobilities of 1.7 × 10 -5 cm 2 V -1 s -1 and 2.5 × 10 -5 cm 2 V -1 s -1 at around 280 K, respectively. The shallow traps with smaller activation energy (0.03 eV) hinder the carrier transport over the lower temperature regime (80-180 K), while deep traps with 1 order of magnitude larger activation energy than the shallow traps moderate the charge carrier transport in the temperature range of 180-300 K. From the charge carrier mechanism point of view, impurity scattering is established as the dominant factor from 80 K until around 280 K, while phonon scattering becomes predominant up to room temperature. Responsivities of 0.15 A W -1 and 0.14 A W -1 for left-handed and right-handed chiral perovskite FET devices are obtained.

Estimating the age of pupa during the development time of the blow fly Chrysomya megacephala (Diptera: Calliphoridae) is of forensic significance as it assists in determining the time of colonization (TOC), which could help to determine the postmortem interval (PMI). However, establishing an objective, accurate, and efficient method for pupa age inference is still a leading matter of concern among forensic entomologists. In this study, we utilized hyperspectral imaging (HSI) technology to analyze the reflectance changes of pupa development under different temperatures (15 °C, 20 °C, 25 °C, and 30 °C). The spectrograms showed a downtrend under all temperatures. We used PCA to reduce the dimensionality of the spectral data, and then machine learning models (RF, SVR-RBF, SVR-POLY, XGBR, and Lasso) were built. RF, SVR with RBF kernel, and XGBR could show promise in accurate developmental time estimation using accumulated degree days. Among these, the XGBR model consistently exhibited the most minor errors, ranging between 3.9156 and 7.3951 (MAE). This study has identified the value of further refinement of HSI in forensic applications involving entomological specimens, and identified the considerable potential of HSI in forensic practice.

Introduction: The lipid layer of the tear film is critical to maintaining the integrity of the tear film and absence in the tear film lipid layer (TFLL) is one of the main causes of evaporative dry eye (EDE) in dry eye disease patients, resulting in excessive evaporation (so-called hyperevaporative dry eye). This study protocol will be designed to assess and compare the effects of intense pulsed light (IPL), heated eye mask (HEM), vectored thermal pulsation system (VTPS) and eyelid massage device (EMD) for improving signs and symptoms of EDE., Methods and Analysis: Patients with EDE will be randomly divided into IPL, HEM, VTPS and EMD groups and will be followed up for 6 weeks. The primary outcome measure will be non-invasive tear breakup time (NITBUT). The secondary outcome measures will include, TFLL score, meibomian gland quality and expressibility change from baseline conjunctivocorneal staining with fluorescein and lissamine, tear meniscus height, conjunctival hyperaemia (redness score) and ocular surface disease index questionnaire. Additionally, adverse events will be monitored and documented., Ethics and Dissemination: Ethics approval number: IRB(2023)K019.01. The findings will be shared regardless of the effect's direction., Trial Registration Number: NCT05923528., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Lung cancer is the leading cause of cancer mortality in the world. It greatly affects the patients' quality of life, and is thus a challenge for the daily practice in respiratory medicine. Advances in the genetic knowledge of thoracic tumours' mutational landscape, and the development of targeted therapies and immune checkpoint inhibitors, have led to a paradigm shift in the treatment of lung cancer and pleural mesothelioma. During the 2023 European Respiratory Society Congress in Milan, Italy, experts from all over the world presented their high-quality research and reviewed best clinical practices. Lung cancer screening, management of early stages of lung cancer, application of artificial intelligence and biomarkers were discussed and they will be summarised here., Competing Interests: Conflict of interest: The authors have nothing to disclose., (Copyright ©The authors 2024.)

For a long time, myeloid-derived suppressor cells (MDSCs) dilated in circulation system of colorectal cancer (CRC) patients have been puzzling clinicians. Various evidence shows that MDSCs constitute the bulk of immunosuppression in CRC, which is related to tumor growth, adhesion, invasion, metastasis, and immune escape. However, the mechanisms underlying these cells formation remain incompletely understood. In this study, we reported that CRC cell-derived LC3-dependent extracellular vesicles (LDEVs)-mediated M-MDSCs formation via TLR2-MYD88 pathway. Furthermore Hsp60 was the LDEVs surface ligand that triggered these MDSCs induction. In clinical studies, we reported that accumulation of circulating M-MDSCs as well as IL-10 and arginase1 secretion were reliant upon the levels of tumor cell-derived LDEVs in CRC patients. These findings indicated how local tumor cell-derived extracellular vesicles influence distal hematopoiesis and provided novel justification for therapeutic targeting of LDEVs in patients with CRC., Competing Interests: The authors declare no competing interests., (© 2024.)

Essential oils, intricate blends of volatile compounds obtained from a variety of sources, play a crucial role in numerous industries. To elevate product quality, deterpenation becomes an indispensable step. This study proposes an in situ isolation technique based on deep eutectic solvents (DESs) for the deterpenation of essential oil. Salient features of relevant compounds were obtained using conductor-like screening model for real solvents (COSMO-RS) and density functional theory (DFT) methods to predict deterpenation performance. Tetrabutylammonium chloride (TBAC) was chosen based on the results of theoretical analysis and experiment to extract hydroxy-terpenoids. COSMO-RS was employed to evaluate the extraction performance at different molar ratios, and then combined with experimental analysis to determine the optimal conditions. The σ-profiles of organic solvents and their interactions with terpene revealed n-hexane to be the best solvent for purifying DES. TBAC and terpenoids were obtained through the re-extraction procedure, with a recovery of 81.8-84.4%., 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.)