Viability of elutriation for the extraction of microplastics from environmental soil samples.

In this study, we evaluated the suitability of elutriation, a method successfully employed in the extraction of microplastics from marine sediments, for the extraction of microplastics from freshwater and terrestrial soils. Five soils were sampled throughout Oklahoma, USA in order to capture a range of sand, silt, clay, and organic matter composition. Each soil was subjected to microplastic extraction with and without elutriation, followed by digestion in 7.5% NaOCl, and then flotation in 6 M ZnCl2. The mass of each soil was measured after elutriation to determine sample mass reduction, and multiple methods including fluorescence imaging and automated particle counting through ImageJ, Attenuated Total Reflectence-Fourier Transfor Infrared Spectroscopy (ATR-FTIR), and Pyrolysis-coupled Gas Chromatography/Mass Spectrometry (py-GC/MS) were used to determine microplastic quantity, mass, and characteristics. T-test was used to check for statistically-significant differences between methods in terms of mass or particle quantity. For all tested soils, elutriation resulted in greater sample mass reduction than non-elutriated samples, and was between 59.0-97.3% for the tested soils. Furthermore, no statistically significant (p < 0.05) differences were observed in particle quantification or polymer mass between methods, and no differences were observed for polymer or size distribution. Additionally, 33% more polymers were positively identified (R 2 = 70%) by ATR-FTIR analysis in elutriated samples compared to non-elutriated soils. The mass reduction provided by elutriation allows for the processing of larger sample volumes, leading to greater accuracy and sensitivity in detecting microplastics. As such, we recommend elutriation be performed as a pretreatment step to extract microplastics from soils.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study.

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen's criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.

Improved in vitro potency of Clofazimine derivatives against Neisseria species.

Globally, millions of infections that are resistant to antimicrobial agents are reported annually, leading to more than 700,000 fatalities. Among all, challenges arise particularly from nontuberculosis mycobacterial (NTM) and Gram-negative bacteria, as they exhibit limited treatment options in light of increasing reports of multi-drug resistant strains. Clofazimine (CFZ) is an antimycobacterial medication used to treat leprosy, and it is also known for its side effect of inducing skin pigmentation. The use of CFZ and its analogues against a broad range of Gram-negative bacteria has not been extensively investigated. In this study, we designed, synthesized and studied 11 CFZ analogues and identified examples with comparable or improved in vitro anti-bacterial activity relative to that of CFZ itself. This is the first report demonstrating in vitro activity of CFZ and its analogues against Neisseria species. The results of these studies may facilitate the development of CFZ analogues with limited side effects in humans.

Augmented Recognition of Distracted Driving State Based on Electrophysiological Analysis of Brain Network.

In this study, we propose an electrophysiological analysis-based brain network method for the augmented recognition of different types of distractions during driving. Driver distractions, such as cognitive processing and visual disruptions during driving, lead to distinct alterations in the electroencephalogram (EEG) signals and the extracted brain networks. We designed and conducted a simulated experiment comprising 4 distracted driving subtasks. Three connectivity indices, including both linear and nonlinear synchronization measures, were chosen to construct the brain network. By computing connectivity strengths and topological features, we explored the potential relationship between brain network configurations and states of driver distraction. Statistical analysis of network features indicates substantial differences between normal and distracted states, suggesting a reconfiguration of the brain network under distracted conditions. Different brain network features and their combinations are fed into varied machine learning classifiers to recognize the distracted driving states. The results indicate that XGBoost demonstrates superior adaptability, outperforming other classifiers across all selected network features. For individual networks, features constructed using synchronization likelihood (SL) achieved the highest accuracy in distinguishing between cognitive and visual distraction. The optimal feature set from 3 network combinations achieves an accuracy of 95.1% for binary classification and 88.3% for ternary classification of normal, cognitively distracted, and visually distracted driving states. The proposed method could accomplish the augmented recognition of distracted driving states and may serve as a valuable tool for further optimizing driver assistance systems with distraction control strategies, as well as a reference for future research on the brain-computer interface in autonomous driving.

Association between triglyceride-glucose related indices and mortality among individuals with non-alcoholic fatty liver disease or metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4). RESULTS: There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis.

Reliable object tracking by multimodal hybrid feature extraction and transformer-based fusion.

Visual object tracking, which is primarily based on visible light image sequences, encounters numerous challenges in complicated scenarios, such as low light conditions, high dynamic ranges, and background clutter. To address these challenges, incorporating the advantages of multiple visual modalities is a promising solution for achieving reliable object tracking. However, the existing approaches usually integrate multimodal inputs through adaptive local feature interactions, which cannot leverage the full potential of visual cues, thus resulting in insufficient feature modeling. In this study, we propose a novel multimodal hybrid tracker (MMHT) that utilizes frame-event-based data for reliable single object tracking. The MMHT model employs a hybrid backbone consisting of an artificial neural network (ANN) and a spiking neural network (SNN) to extract dominant features from different visual modalities and then uses a unified encoder to align the features across different domains. Moreover, we propose an enhanced transformer-based module to fuse multimodal features using attention mechanisms. With these methods, the MMHT model can effectively construct a multiscale and multidimensional visual feature space and achieve discriminative feature modeling. Extensive experiments demonstrate that the MMHT model exhibits competitive performance in comparison with that of other state-of-the-art methods. Overall, our results highlight the effectiveness of the MMHT model in terms of addressing the challenges faced in visual object tracking tasks.

Pillar[5]arene-Based Ion-Pair Recognition for Encapsulation of a Stilbazolium-Type Dye with Enhanced Photophysical Properties and Nonlinear Optical Activity.

Constructing organic composite materials through molecular recognition has emerged as an important theme in materials science. Here we report an ion-pair recognition system involving the use of a propoxylated pillar[5]arene (PrP5) to modulate the solid-state photophysical properties of dye trans-4'-(dimethylamino)-N-methyl-4-stilbazolium hexafluorophosphate (DMASP). Single crystal X-ray diffraction analysis reveals that the dye guest DMASP is encapsulated by PrP5 to form a 2:1 host-guest complex 2PrP5⸧DMASP in the crystalline state. The macrocyclic skeleton of PrP5 imposes restrictions on the intramolecular motions of the dye guest, leading to a significant enhancement of its fluorescence emission. Additionally, within the 2PrP5⸧DMASP complex crystal structure, DMASP molecules are found to display two possible opposite orientations in the one-dimensional channels formed by PrP5 molecules. This arrangement is believed to alter the overall solid-state packing structure of DMASP, thereby activating its nonlinear optical activity. This work not only reports a novel ion-pair molecular recognition system based on pillararenes but also provides valuable insights into the modulation of the crystalline state photophysical properties of organic dyes via cocrystal engineering.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Chromothripsis is a novel biomarker for prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms.

This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next-generation gene sequencing in a cohort of 30 patients with high-grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low-grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high-grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high-grade (G3) pNETs.

The effect of aromatherapy on patients with acute coronary syndrome: A systematic review and meta-analysis.

OBJECTIVE: To systematically investigate the efficacy of aromatherapy in patients with acute coronary syndrome (ACS). METHODS: We conducted a comprehensive search for papers published until November 2023 using the following databases: PubMed, Embase, and Cochrane Library. This study was conducted following the PRISMA and Cochrane Guidelines. The inclusion criteria were randomized controlled trials (RCTs) performed to assess the comparative effectiveness of inhalation aromatherapy versus controls in individuals diagnosed with ACS. The Jadad rating method was used to assess the quality of the included studies, and a meta-analysis was performed using the RevMan 5.4 software. Heterogeneity was quantified using the Higgins I2 (%) test. RESULTS: A total of 12 RCTs with 476 patients with ACS were included. Aromatherapy has been shown to reduce anxiety scores significantly (standard mean difference [SMD]: -1.18, 95 % confidence interval [CI]: -1.33 to -1.03; P < 0.00001) along with reduction in systolic blood pressure (MD = -8.78, 95 % CI [-13.92, -3.65], P = 0.008); diastolic blood pressure (MD = -7.76, 95 % CI [-11.39, -4.12], P < 0.001); mean artery pressure MD = -9.68, 95 % CI [-13.93.-5.44]; P < 0.0001). However, no significant effects were reported on the heart rate (MD = -6.98, 95 % CI [-15.46, 1.50], P = 0.11) and respiratory rate (MD = -0.67, 95 % CI [-2.52, 1.19], P = 0.48). A greater frequency of aromatherapy was associated greater anxiety -1.80 incidence, with 95 % CI [-2.04, -1.56]. Citrus essential oils exhibited the strongest effect (SMD = -1.97, 95 % CI [-3.34, -0.60], P = 0.005) in reducing anxiety levels. CONCLUSION: Aromatherapy appears to be an effective non-pharmacological intervention for reducing blood pressure and anxiety in individuals with ACS. This suggests that aromatherapy more than twice a day is effective in reducing anxiety levels. However, aromatherapy had no statistically significant impact on the heart or respiratory rates. Moreover, additional high-quality RCTs should be conducted to verify these results and explore the efficacy and mechanism of aromatherapy in patients with ACS.

Magnetic porous microspheres altering interfacial thermodynamics of sewage sludge to drive metabolic cooperation for efficient methanogenesis.

Controllable and recyclable magnetic porous microspheres (MPMs) have been proposed as a means for enhancing the anaerobic digestion (AD) of sludge, as they do not require continuous replenishment and can serve as carriers for anaerobes. However, the effects of MPMs on the interfacial thermodynamics of sludge and the biological responses triggered by abiotic effects in AD systems remain to be clarified. Herein, the underlying mechanisms by which MPMs alter the solid-liquid interface of sludge to drive methanogenesis were investigated. A significant increase in the contents of 13C and 2H (D) in methane molecules was observed in the presence of MPMs, suggesting that MPMs might enhance the CO2-reduction methanogenesis and participation of water in methane generation. Experimental results demonstrated that the addition of MPMs did not promote the anaerobic bioconversion of soluble organics for methanogenesis, suggesting that the enhanced methanogenesis and water participation were not achieved through promotion of the bioconversion of original liquid-state organics in sludge. Analyses of the capillary force, surface adhesion force, and interfacial proton-coupled electron transfer (PCET) of MPMs revealed that MPMs can enhance mass transfer, effective contact, and electron-proton transfer with sludge. These outcomes were confirmed by the statistical analyses of variations in the interfacial thermodynamics and PCET of sludge with and without MPMs during AD. It was thus proposed that the MPMs enhanced the PCET of sludge and PCET-driven release of protons from water by promoting the interfacial Lewis acid-base interactions of sludge, thereby resulting in the enrichment of free and attached methanogenic consortia and the high energy-conserving metabolic cooperation. This proposition was further confirmed by identifying the predominant syntrophic partners, suggesting that PCET-based efficient methanogenesis was attributable to the enrichment of genomes harbouring CO2-reducing pathway and genes encoding water-mediated proton transfer. These findings offer new insights into how substrate properties can be altered by exogenous materials to enable highly efficient methanogenesis.

Intraocular lens tilt and decentration after primary and delayed implantation in phacovitrectomy for macula-off rhegmatogenous retinal detachment repair.

PURPOSE: To evaluate the tilt and decentration of intraocular lenses (IOLs) in eyes that underwent phacovitrectomy for macula-off rhegmatogenous retinal detachment (RRD) repair. METHODS: In this retrospective cohort study, 63 patients with macula-off RRD who underwent phacovitrectomy were enrolled and divided into a primary implantation group (group A) and a delayed implantation group (group B) according to the time of IOL implantation. Routine ocular examinations, including optometry, were performed, and the IOL tilt and decentration were measured. Postoperative refractive prediction error and IOL tilt and decentration were compared between the two groups, and the relevant factors of IOL positions were analyzed. RESULTS: The mean spherical refractive prediction error (MSE) was - 0.53 ± 0.39 D in group A and - 0.09 ± 0.55 in group B. The mean absolute spherical refractive prediction error (MASE) was 0.61 ± 0.23 D in group A and 0.50 ± 0.22 D in group B. The difference in MSE (t = -3.623, P < 0.05) but not in MASE (t = 1.866, P = 0.067) between the two groups was significant. The mean IOL tilt and mean decentration were 8.54° ±3.65° and 0.55 ± 0.18 mm in group A and 10.62° ±3.29° and 0.66 ± 0.14 mm, respectively, in Group B. Differences in tilt (t = -2.373, P < 0.05) and decentration (t = -2.698, P < 0.05) between the two groups were both significant. In group B, the mean time interval between phacovitrectomy and IOL implantation (TV-I) was 25.2 ± 6.9 weeks, and the absolute values of both IOL tilt and decentration were positively correlated with TV-I. CONCLUSION: In phacovitrectomy for macula-off RRD repair, primary IOL implantation leads to a postoperative myopic shift, while delayed IOL implantation may cause greater IOL tilt and decentration.

Investigation on the Potential Functions of ZmEPF/EPFL Family Members in Response to Abiotic Stress in Maize.

Maize is an important crop used for food, feed, and fuel. Abiotic stress is an important factor affecting maize yield. The EPF/EPFL gene family encodes class-specific secretory proteins that play an important role in the response to abiotic stress in plants. In order to explore and utilize the EPF/EPFL family in maize, the family members were systematically identified, and their chromosomal localization, physicochemical properties, cis-acting element prediction in promoters, phylogenetic tree construction, and expression pattern analysis were carried out using bioinformatics techniques. A total of 18 ZmEPF/EPFL proteins were identified in maize, which are mostly alkaline and a small portion acidic. Subcellular localization results showed that ZmEPF6, ZmEPF12, and ZmEPFL2 are localized in the nucleus and cytoplasm. Analysis of cis-acting elements revealed that members of the ZmEPF/EPFL family contain regulatory elements such as light response, anoxic, low temperature, and hormone response regulatory elements. RT-qPCR results showed that these family members are indeed responding to cold stress and hormone treatments. These results of this study provide a theoretical basis for improving the abiotic stress resistance of maize in future research.

Examining the relationship between alterations in plasma cholesterol, vascular endothelin-1 levels, and the severity of sepsis in children: An observational study.

Considering the significant impact of total cholesterol (TC) and vascular endothelin-1 (ET-1) on children sepsis outcomes, this research aimed to explore the association between the levels of plasma cholesterol and vascular endothelin-1 and the severity of sepsis and evaluated its clinical implications. In this study, we examined 250 pediatric patients diagnosed with sepsis between February 2019 and April 2021, collecting data on their plasma levels of TC and ET-1. Depending on the observed outcomes, the participants were divided into 2 categories: a group with a positive prognosis (control group, n = 100) and a group with a negative prognosis (n = 50). We assessed the significance of plasma TC and ET-1 levels in forecasting the outcomes for these pediatric patients. Patients in the group with a poor prognosis experienced notably longer hospital stays and higher treatment expenses than those in the control group (P < .05). Within the first 24 hours of admission and again on days 3 and 7, the levels of ET-1 were significantly higher in the poor prognosis group, whereas plasma TC levels were notably lower in comparison to the control group (P < .05). A Spearman correlation analysis identified a significant correlation between the levels of plasma TC and ET-1 and the severity of sepsis among the children (P < .05). The diagnostic performance for the severity of sepsis in children, as measured by the area under the curve (AUC), was 0.805 for plasma TC, 0.777 for ET-1 levels, and 0.938 when both were combined. This investigation underscores a meaningful relationship between the levels of plasma TC and ET-1 in pediatric sepsis patients, suggesting these biomarkers are highly valuable in predicting patient outcomes. High levels of ET-1 and low levels of TC in these patients signify a grave condition and a poor prognosis.

Asymmetric Cu-N1O3 Sites Coupling Atop-type and Bridge-type Adsorbed *C1 for Electrocatalytic CO2-to-C2 Conversion.

2D functional porous frameworks offer a platform for studying the structure-activity relationships during electrocatalytic CO2 reduction reaction (CO2RR). Yet challenges still exist to breakthrough key limitations on site configuration (typical M-O4 or M-N4 units) and product selectivity (common CO2-to-CO conversion). Herein, a novel 2D metal-organic framework (MOF) with planar asymmetric N/O mixed coordinated Cu-N1O3 unit is constructed, labeled as BIT-119. When applied to CO2RR, BIT-119 could reach a CO2-to-C2 conversion with C2 partial current density ranging from 36.9 to 165.0 mA cm-2 in flow cell. Compared to the typical symmetric Cu-O4 units, asymmetric Cu-N1O3 units lead to the re-distribution of local electron structure, regulating the adsorption strength of several key adsorbates and the following catalytic selectivity. From experimental and theoretical analyses, Cu-N1O3 sites could simultaneously couple the atop-type (on Cu site) and bridge-type (on Cu-N site) adsorption of *C1 species to reach the CO2-to-C2 conversion. This work broadens the feasible C-C coupling mechanism on 2D functional porous frameworks.

Hippocampal PACAP signaling activation triggers a rapid antidepressant response.

BACKGROUND: The development of ketamine-like rapid antidepressants holds promise for enhancing the therapeutic efficacy of depression, but the underlying cellular and molecular mechanisms remain unclear. Implicated in depression regulation, the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is investigated here to examine its role in mediating the rapid antidepressant response. METHODS: The onset of antidepressant response was assessed through depression-related behavioral paradigms. The signaling mechanism of PACAP in the hippocampal dentate gyrus (DG) was evaluated by utilizing site-directed gene knockdown, pharmacological interventions, or optogenetic manipulations. Overall, 446 mice were used for behavioral and molecular signaling testing. Mice were divided into control or experimental groups randomly in each experiment, and the experimental manipulations included: chronic paroxetine treatments (4, 9, 14 d) or a single treatment of ketamine; social defeat or lipopolysaccharides-injection induced depression models; different doses of PACAP (0.4, 2, 4 ng/site; microinjected into the hippocampal DG); pharmacological intra-DG interventions (CALM and PACAP6-38); intra-DG viral-mediated PACAP RNAi; and opotogenetics using channelrhodopsins 2 (ChR2) or endoplasmic natronomonas halorhodopsine 3.0 (eNpHR3.0). Behavioral paradigms included novelty suppressed feeding test, tail suspension test, forced swimming test, and sucrose preference test. Western blotting, ELISA, or quantitative real-time PCR (RT-PCR) analysis were used to detect the expressions of proteins/peptides or genes in the hippocampus. RESULTS: Chronic administration of the slow-onset antidepressant paroxetine resulted in an increase in hippocampal PACAP expression, and intra-DG blockade of PACAP attenuated the onset of the antidepressant response. The levels of hippocampal PACAP expression were reduced in both two distinct depression animal models and intra-DG knockdown of PACAP induced depression-like behaviors. Conversely, a single infusion of PACAP into the DG region produced a rapid and sustained antidepressant response in both normal and chronically stressed mice. Optogenetic intra-DG excitation of PACAP-expressing neurons instantly elicited antidepressant responses, while optogenetic inhibition induced depression-like behaviors. The longer optogenetic excitation/inhibition elicited the more sustained antidepressant/depression-like responses. Intra-DG PACAP infusion immediately facilitated the signaling for rapid antidepressant response by inhibiting calcium/calmodulin-dependent protein kinase II (CaMKII)-eukaryotic elongation factor 2 (eEF2) and activating the mammalian target of rapamycin (mTOR). Pre-activation of CaMKII signaling within the DG blunted PACAP-induced rapid antidepressant response as well as eEF2-mTOR-brain-derived neurotrophic factor (BDNF) signaling. Finally, acute ketamine treatment upregulated hippocampal PACAP expression, whereas intra-DG blockade of PACAP signaling attenuated ketamine's rapid antidepressant response. CONCLUSIONS: Activation of hippocampal PACAP signaling induces a rapid antidepressant response through the regulation of CaMKII inhibition-governed eEF2-mTOR-BDNF signaling.

A Bibliometric and Visualised Analysis of Proliferative Verrucous Leucoplakia From 2003 to 2023.

BACKGROUND: Proliferative verrucous leucoplakia (PVL) is a rare but slow-growing, aggressive leucoplakia lesion associated with the highest malignant transformation rate in oral potentially malignant disorders (OPMDs). With increasing attention paid to PVL, it is urgent for us to analyse and summarise the publications globally using comprehensive bibliometric studies to help researchers propose possible future research directions and guide them to further conduct relevant studies in the domain. OBJECTIVES: The purpose of the study was to evaluate global academic productivity, impact, and collaboration of potentially malignant oral disorder PVL utilising bibliometrics based on annual number of publications, countries and regions, institution, authors, journals, citations and co-occurrences of author keywords over the last 20 years. METHODS: This study searched publications pertaining to proliferative verrucous leucoplakia in the Web of Science Core Collection, spanning from 2003 to 2023. Utilizing VOSviewer, R software, Bibliometric online analysis platform, CiteSpace software, and Microsoft Excel, we conducted a bibliometric and visualised analysis of PVL. RESULTS: The quantity of pertinent publications in this research domain displays a fluctuating but overall upward trend. In aggregate, there are 148 articles and 61 reviews, encompassing research contributions from 44 countries, 45 institutions, and involving 831 authors. Among these publications, the USA, Spain, and UK emerged as the predominant contributing nations. Predominantly, articles found their publication venue in "Pathology Research and Practice." Notably, the author with the highest number of publications and most influence is Warnakulasuriya S. The top 3 keywords include "Proliferative Verrucous Leucoplakia," "Squamous-Cell Carcinoma," "Oral Leucoplakia," and "Potentially Malignant Disorders." CONCLUSION: In this investigation, statistical analysis and network visualisation were conducted to reveal the research progress, trends, and trending topics on PVL via a thorough bibliometric analysis. We found that current publications comprise mainly case reports, there is a significant research need to explore the molecular mechanisms, specific diagnostic criteria, and effective management options for PVL. Our work should serve as a key reference and a directional guide for future research in this domain.

Intrauterine hyperglycaemia during late gestation caused mitochondrial dysfunction in skeletal muscle of male offspring through CREB/PGC1A signaling.

BACKGROUND: Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified. METHODS: Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon. RESULTS: Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their decreased transcription. Interestingly, we found that sarcopenia and mitochondrial dysfunction could even be inherited by the next generation. CONCLUSIONS: Short-term intrauterine hyperglycaemia significantly reduced lean mass in male offspring at 8 weeks, resulting in decreased exercise endurance and metabolic disorders. Disrupted organisation and function of the mitochondria in skeletal muscle were also observed among them. Foetal exposure to hyperglycaemia decreased the ratio of phosphorylated CREB and reduced the transcription of Ppargc1α, which inhibited the transcription of downstream genes involving in mitochondrial biogenesis and oxidative metabolism. Abnormal mitochondria, which might be transmitted through aberrant gametes, were also observed in the F2 generation.