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IntroductionCognitive impairment in patients with end-stage renal disease (ESRD) is associated with brain structural damage. However, no prior studies have investigated the relationship between brain texture features and the cognitive function in ESRD patients. This study aimed to investigate changes in brain texture features in ESRD patients and their relationships with cognitive function using voxel-based 3D brain texture analysis (TA), and further predict individual cognitive-related brain damage in ESRD patients.MethodsForty-seven ESRD patients and 45 control subjects underwent whole-brain high-resolution 3D T1-weighted imaging scans and neuropsychological assessments. The voxel-based 3D brain TA was performed to examine inter-group differences in brain texture features. Additionally, within the ESRD group, the relationships of altered texture features with neuropsychological function and clinical indicators were analyzed. Finally, receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of brain texture features for cognitive-related brain damage in ESRD patients.ResultsCompared to the control group, the ESRD group exhibited altered texture features in several brain regions, including the insula, temporal lobe, striatum, cerebellum, and fusiform gyrus (p

BackgroundMost patients with multiple hepatocellular carcinoma (MHCC) are at advanced stage once diagnosed, so that clinical treatment and decision-making are quite tricky. The AJCC-TNM system cannot accurately determine prognosis, our study aimed to identify prognostic factors for MHCC and to develop a prognostic model to quantify the risk and survival probability of patients.MethodsEligible patients with HCC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and then prognostic models were built using Cox regression, machine learning (ML), and deep learning (DL) algorithms. The model’s performance was evaluated using C-index, receiver operating characteristic curve, Brier score and decision curve analysis, respectively, and the best model was interpreted using SHapley additive explanations (SHAP) interpretability technique.ResultsA total of eight variables were included in the follow-up study, our analysis identified that the gradient boosted machine (GBM) model was the best prognostic model for advanced MHCC. In particular, the GBM model in the training cohort had a C-index of 0.73, a Brier score of 0.124, with area under the curve (AUC) values above 0.78 at the first, third, and fifth year. Importantly, the model also performed well in test cohort. The Kaplan–Meier (K-M) survival analysis demonstrated that the newly developed risk stratification system could well differentiate the prognosis of patients.ConclusionOf the ML models, GBM model could predict the prognosis of advanced MHCC patients most accurately.

BackgroundDepression is a common mental illness with a high prevalence in overweight or obese individuals. Recent studies suggest that the Metabolic Score for Visceral Fat (METS-VF) is a novel metric for assessing visceral fat levels, potentially linking metabolic disturbances to depression. This study explores the association between METS-VF and depression severity in overweight or obese U.S. adults.MethodsData were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 dataset, including 9,415 overweight or obese participants. Depression severity was measured using the Patient Health Questionnaire-9 (PHQ-9). To assess the association between METS-VF and depression, the study methodology included multivariate logistic regression, subgroup analyses, generalized additive model (GAM), and smoothed curve fitting. This study also calculated BMI for the Non-Hispanic Asian population from 2011-2018 and incorporated this data as part of a sensitivity analysis.ResultsElevated levels of METS-VF in overweight or obese participants were significantly associated with increased PHQ-9 scores and an increased likelihood of depression. Notably, this association remained significant after adjustment for multiple covariates. Smoothed curve-fitting plots showed no nonlinear association between METS-VF and PHQ-9 scores. Subgroup analyses confirmed the robustness of these results across populations, particularly among people under the age of fifty. The sensitivity analyses confirmed the robustness of the results in this study.ConclusionMETS-VF levels were positively associated with depression severity and the likelihood of depression in overweight or obese individuals, with the association being particularly pronounced in people under 50 years of age.

The ultrasound-assisted extraction technique was used for extracting polysaccharides of Tricholoma matsutake (PTM) in this work. The effects of different parameters, i.e., solid-to-liquid ratio, ultrasonic power, extraction time, and extraction temperature on the PTM yield were optimized using a rotatable, orthogonal central composite design. In the derived optimal conditions, the PTM yield was 16.97 ± 0.06%, which corresponded well with the regression model predicted value of 16.85%. The extracted PTM was purified, and the structural characteristics and antioxidant activities were investigated. The PTM was found to be composed mainly of fructose, mannose, glucose, and galactose with a molar molecular ratio of 1:2.25:9.35:5, and an average molecular weight of 90,100 Da. High antioxidant effects of PTM were seen in the tests of DPPH, hydroxyl, and ABTS radical scavenging, along with a moderate superoxide radical scavenging rate.

IntroductionResidential load forecasting is a challenging task due to the random fluctuations caused by complex correlations and individual differences. The existing short-term load forecasting models usually introduce external influencing factors such as climate and date. However, these additional information not only bring computational burden to the model, but also have uncertainty. To address these issues, we propose a novel multi-level feature fusion model based on graph attention temporal convolutional network (MLFGCN) for short-term residential load forecasting.MethodsThe proposed MLFGCN model fully considers the potential long-term dependencies in a single load series and the correlations between multiple load series, and does not require any additional information to be added. Temporal convolutional network (TCN) with gating mechanism is introduced to learn potential long-term dependencies in the original load series. In addition, we design two graph attentive convolutional modules to capture potential multi-level dependencies in load data. Finally, the outputs of each module are fused through an information fusion layer to obtain the highly accurate forecasting results.ResultsWe conduct validation experiments on two real-world datasets. The results show that the proposed MLFGCN model achieves 0.25, 7.58% and 0.50 for MAE, MAPE and RMSE, respectively. These values are significantly better than those of baseline models.DiscussionThe MLFGCN algorithm proposed in this paper can significantly improve the accuracy of short-term residential load forecasting. This is achieved through high-quality feature reconstruction, comprehensive information graph construction and spatiotemporal features capture.

IntroductionAtopic dermatitis (AD) is a common, chronic, recurrent inflammatory skin disease. To date, no meta-analysis have been conducted on the prevalence and risk factors of AD in children aged 1–7 years in Mainland China.MethodsWe conducted a meta-analysis of the prevalence and risk factors of AD among children aged 1–7 years in China. Chinese and English publications were searched in Chinese and English databases on AD epidemiology published between 1999 and 2023. Two researchers independently screened the literature, extracted the data, and evaluated their quality. A meta-analysis was performed using a random-effects model (I2 > 50%) with 95% confidence intervals (CIs) for the forest plots. Data were processed using the RevMan 5.3.ResultsNineteen studies (data from 127,660 samples) met the inclusion criteria. The pooled prevalence of AD in Chinese children aged 1–7 years was 8%. Over the last decade, the prevalence of AD has increased. The prevalence of AD among children in southern China was higher than that in northern China and was the highest at the provincial level in Zhejiang, Shanxi, and Anhui. The prevalence of AD was dependent on the family history of allergy, passive smoking, households with pets, plush toys, and residential area.DiscussionThe prevalence of AD in children (age 1–7 years) in China has increased. Further studies are needed to monitor the prevalence of AD in Chinese children. Therefore, early prevention and screening should be performed for children with a family history of AD, and their living environment should be improved to reduce allergen stimulation, thus reducing the development of AD.

Environmental heterogeneity partly drives microbial succession in arthropods, while the microbial assembly mechanisms during environmental changes remain largely unknown. Here, we explored the temporal dynamics and assembly mechanisms within both bacterial and fungal communities in Liriomyza huidobrensis (Blanchard) during the transition from field to laboratory conditions. We observed a decrease in bacterial diversity and complexity of bacterial-fungal co-occurrence networks in leaf miners transitioning from wild to captive environments. Both neutral and null models revealed that stochastic processes, particularly drift (contributing over 70%), play a crucial role in governing bacterial and fungal community assembly. The relative contribution of ecological processes such as dispersal, drift, and selection varied among leaf miners transitioning from wild to captive states. Furthermore, we propose a hypothetical scenario for the assembly and succession of microbial communities in the leaf miner during the short- and long-term transition from the wild to captivity. Our findings suggest that environmental heterogeneity determines the ecological processes governing bacterial and fungal community assembly in leaf miners, offering new insights into microbiome and mycobiome assembly mechanisms in invasive pests amidst environmental change.

Herpes zoster (HZ), also known as shingles, remains a significant global health issue and most commonly seen in elderly individuals with an early exposure history to varicella-zoster virus (VZV). Currently, the licensed vaccine Shingrix, which comprises a recombinant VZV glycoprotein E (gE) formulated with a potent adjuvant AS01B, is the most effective shingles vaccine on the market. However, undesired reactogenicity and increasing global demand causing vaccine shortage, prompting the development of novel shingles vaccines. Here, we developed novel vaccine candidates utilising multiple nanoparticle (NP) platforms to display the recombinant gE antigen, formulated in an MF59-biosimilar adjuvant. In naïve mice, all tested NP vaccines induced higher humoral and cellular immune responses than Shingrix, among which, the gEM candidate induced the highest cellular response. In live attenuated VZV (VZV LAV)-primed mouse and rhesus macaque models, the gEM candidate elicited superior cell-mediated immunity (CMI) over Shingrix. Collectively, we demonstrated that NP technology remains a suitable tool for developing shingles vaccine, and the reported gEM construct is a highly promising candidate in the next-generation shingles vaccine development.

BackgroundCognitive impairment in the elderly may lead to potential increased sensitivity to anesthetic agents targeting receptors associated with cognition. This study aimed to explore the effect of cognitive status on propofol consumption during surgery in elderly patients.MethodsSixty elderly patients scheduled for laparoscopic radical prostatectomy were allocated to either a cognitively normal [CogN, Montreal Cognitive Assessment (MoCA) score ≥26] or cognitively impaired (CogI, MoCA

BackgroundMonocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to identify key monocyte-related genes and elucidate their mechanisms in PRAD.MethodUtilizing the TCGA-PRAD dataset, immune cell infiltration levels were assessed using CIBERSORT, and their correlation with patient prognosis was analyzed. The WGCNA method pinpointed 14 crucial monocyte-related genes. A diagnostic model focused on monocytes was developed using a combination of machine learning algorithms, while a prognostic model was created using the LASSO algorithm, both of which were validated. Random forest and gradient boosting machine singled out CCNA2 as the most significant gene related to prognosis in monocytes, with its function further investigated through gene enrichment analysis. Mendelian randomization analysis of the association of HLA-DR high-expressing monocytes with PRAD. Molecular docking was employed to assess the binding affinity of CCNA2 with targeted drugs for PRAD, and experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD.ResultBased on the identification of 14 monocyte-related genes by WGCNA, we developed a diagnostic model for PRAD using a combination of multiple machine learning algorithms. Additionally, we constructed a prognostic model using the LASSO algorithm, both of which demonstrated excellent predictive capabilities. Analysis with random forest and gradient boosting machine algorithms further supported the potential prognostic value of CCNA2 in PRAD. Gene enrichment analysis revealed the association of CCNA2 with the regulation of cell cycle and cellular senescence in PRAD. Mendelian randomization analysis confirmed that monocytes expressing high levels of HLA-DR may promote PRAD. Molecular docking results suggested a strong affinity of CCNA2 for drugs targeting PRAD. Furthermore, immunohistochemistry experiments validated the upregulation of CCNA2 expression in PRAD and its correlation with patient prognosis.ConclusionOur findings offer new insights into monocyte heterogeneity and its role in PRAD. Furthermore, CCNA2 holds potential as a novel targeted drug for PRAD.

A Ground Coupled Heat Pump (GCHP) is a highly energy efficient heating, ventilation, and air conditioning (HVAC) system that utilises the ground as the heat source when heating and as the heat sink when cooling. This paper investigates GCHP systems with horizontal Ground Heat Exchangers (GHEs) in the rural industry, exemplifying the technology for poultry (chicken) sheds in Australia. This investigation aims to provide an Artificial Neural Network (ANN) model that can be used for GCHP design at various locations with different climates. To this extent, a Transient System Simulation Tool (TRNSYS) model for a typical horizontal GHE applied in a rural farm was first verified. Using this model, over 700,000 hourly performance data items were obtained, covering over 80 different yearly loading patterns under three different climate conditions. The simulated performance data was then used to train the ANN. As a result, the trained ANN can predict the performance of GCHP systems with identical (multiple) GHEs even under climatic conditions (and locations) that have not been specifically trained for. Unlike other works, the newly introduced ANN model is accurate even with limited types of input data, with high accuracy (less than 5% error in most cases tested). This ANN model is 100 times computationally faster than TRNSYS simulations and 10,000 times faster than finite element models.

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3′,5′-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension.Systematic Review Registration:http://www.chinadrugtrials.org.cn, identifier CTR20210064.

IntroductionMetaraminol is a sympathomimetic amine vasopressor that can be administrated through a peripheral venous access. However, limited evidence restricts its application in critically ill patients. This study aimed to investigate the safety and efficacy of peripheral metaraminol infusion in patients with neurological conditions.MethodsPatients who received peripheral metaraminol infusion between May 2019 and April 2022 were recruited. Data on baseline characteristics, clinical parameters, and infusion-related complications were retrospectively collected and analyzed.Results273 patients who received metaraminol were enrolled. Of these, 35 (12.8%) patients required central venous catheter insertion due to inability in achieving hemodynamic stability following peripheral metaraminol monotherapy. In 29,574.2 hours of vasopressor infusion, metaraminol infusion resulted achievement of the target blood pressure 73.4% of the time. Meanwhile, adverse events occurred in 5 patients and resolved after local tissue treatment.DiscussionMetaraminol could provide hemodynamic support and avoid complications associated with a central venous catheter and delay in vasopressor administration. Through careful and close monitoring, peripheral metaraminol infusion is safe and feasible for patients with neurological conditions. Future large-scale, prospective, multicenter studies are needed to evaluate the safety and efficacy of metaraminol infusion through a peripheral intravenous catheter.

BackgroundPositive lifestyle adjustments have become effective methods in treating gastroesophageal reflux disease (GERD). Utilizing short video platforms to encourage GERD patients for effective self-disease management is a convenient and cost-effective approach. However, the quality of GERD-related videos on short video platforms is yet to be determined, and these videos may contain misinformation that patients cannot recognize. This study aims to assess the information quality of GERD-related short videos on TikTok and Bilibili in China.MethodsSearch and filter the top 100 GERD-related videos on TikTok and Bilibili based on comprehensive rankings. Two independent gastroenterologists conducted a comprehensive evaluation of the video quality using the Global Quality Score and the modified DISCERN tool. Simultaneously, the content of the videos was analyzed across six aspects: definition, symptoms, risk factors, diagnosis, treatment, and outcomes.ResultsA total of 164 GERD-related videos were collected in this study, and videos from non-gastrointestinal health professionals constitute the majority (56.71%), with only 28.66% originating from gastroenterology health professionals. The overall quality and reliability of the videos were relatively low, with DISCERN and GQS scores of 2 (IQR: 2–3) and 3 (IQR: 2–3), respectively. Relatively speaking, videos from gastrointestinal health professionals exhibit the highest reliability and quality, with DISCERN scores of 3 (IQR: 3–4) and GQS scores of 3 (IQR: 3–4), respectively.ConclusionOverall, the information content and quality of GERD-related videos still need improvement. In the future, health professionals are required to provide high-quality videos to facilitate effective self-disease management for GERD patients.

Hepatocellular Carcinoma (HCC) patients often develop resistance to tyrosine kinase inhibitors (TKIs) like sorafenib (SR) and lenvatinib (RR). We established HCC cell lines resistant to these drugs and analyzed the correlation between protein and metabolite profiles using bioinformatics. Our analysis revealed overexpression of MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1, and downregulation of IFITM3, CA4, AGR2, and SLC51B in drug-resistant cells. Differential signals are mainly enriched in steroid hormone biosynthesis, cell adhesion, and immune synapses, with metabolic pathways including cytochrome P450 drug metabolism, amino acid metabolism, and glycolysis. Proteomics and metabolomics analysis showed co-enrichment signals in drug metabolism, amino acids, glucose metabolism, ferroptosis, and other biological processes. Knocking down MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1 significantly reduced drug resistance, indicating their potential as therapeutic response biomarkers. This study characterizes protein and metabolic profiles of drug-resistant HCC cells, exploring metabolite-protein relationships to enhance understanding of drug resistance mechanisms and clinical treatment.

BackgroundAngiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in the development and advancement of cancer. Although blocking angiogenesis has shown success in treating different types of solid tumors, its relevance in prostate adenocarcinoma (PRAD) has not been thoroughly investigated.MethodThis study utilized the WGCNA method to identify angiogenesis-related genes and assessed their diagnostic and prognostic value in patients with PRAD through cluster analysis. A diagnostic model was constructed using multiple machine learning techniques, while a prognostic model was developed employing the LASSO algorithm, underscoring the relevance of angiogenesis-related genes in PRAD. Further analysis identified MAP7D3 as the most significant prognostic gene among angiogenesis-related genes using multivariate Cox regression analysis and various machine learning algorithms. The study also investigated the correlation between MAP7D3 and immune infiltration as well as drug sensitivity in PRAD. Molecular docking analysis was conducted to assess the binding affinity of MAP7D3 to angiogenic drugs. Immunohistochemistry analysis of 60 PRAD tissue samples confirmed the expression and prognostic value of MAP7D3.ResultOverall, the study identified 10 key angiogenesis-related genes through WGCNA and demonstrated their potential prognostic and immune-related implications in PRAD patients. MAP7D3 is found to be closely associated with the prognosis of PRAD and its response to immunotherapy. Through molecular docking studies, it was revealed that MAP7D3 exhibits a high binding affinity to angiogenic drugs. Furthermore, experimental data confirmed the upregulation of MAP7D3 in PRAD, correlating with a poorer prognosis.ConclusionOur study confirmed the important role of angiogenesis-related genes in PRAD and identified a new angiogenesis-related target MAP7D3.

BackgroundThe relationship between early perihematomal edema (PHE) and hematoma expansion (HE) is unclear. We investigated this relationship in patients with acute spontaneous intracerebral hemorrhage (ICH), using radiomics.MethodsIn this multicenter retrospective study, we analyzed 490 patients with spontaneous ICH who underwent non-contrast computed tomography within 6 h of symptom onset, with follow-up imaging at 24 h. We performed HE and PHE image segmentation, and feature extraction and selection to identify HE-associated optimal radiomics features. We calculated radiomics scores of hematoma (Radscores_HEA) and PHE (Radscores_PHE) and constructed a combined model (Radscore_HEA_PHE). Relationships of the PHE radiomics features or Radscores_PHE with clinical variables, hematoma imaging signs, Radscores_HEA, and HE were assessed by univariate, correlation, and multivariate analyses. We compared predictive performances in the training (n = 296) and validation (n = 194) cohorts.ResultsShape_VoxelVolume and Shape_MinorAxisLength of PHE were identified as optimal radiomics features associated with HE. Radscore_PHE (odds ratio = 1.039, p = 0.032) was an independent HE risk factor after adjusting for the ICH onset time, Glasgow Coma Scale score, baseline hematoma volume, hematoma shape, hematoma density, midline shift, and Radscore_HEA. The areas under the receiver operating characteristic curve of Radscore_PHE in the training and validation cohorts were 0.808 and 0.739, respectively. After incorporating Radscore_PHE, the integrated discrimination improvements of Radscore_HEA_PHE in the training and validation cohorts were 0.009 (p = 0.086) and −0.011 (p

BackgroundThe transcription factor, SOX13 is part of the SOX family. SOX proteins are crucial in the progression of many cancers, and some correlate with carcinogenesis. Nonetheless, the biological and clinical implications of SOX13 in human breast cancer (BC) remain rarely known.MethodsWe evaluated the survival and expression data of SOX13 in BC patients via the UNLCAL, GEPIA, TIMER, and Kaplan-Meier plotter databases. Immunohistochemistry (IHC) was used to verify clinical specimens. The gene alteration rates of SOX13 were acquired on the online web cBioportal. With the aid of the TCGA data, the association between SOX13 mRNA expression and copy number alterations (CNA) and methylation was determined. LinkedOmics was used to identify the genes that co-expressed with SOX13 and the regulators. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuCellAI and TIMER2.0 databases. SOX13 correlated drug resistance analysis was performed using the GDSC2 database.ResultsHigher SOX13 expression was discovered in BC tissues in comparison to normal tissues. Moreover, increased gene mutation and amplification of SOX13 were found in BC. Patients with increased SOX13 expression levels showed worse overall survival (OS). Cox analysis showed that SOX13 independently served as a prognostic indicator for poor survival in BC. Further, the expression of SOX13 was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells. In terms of drug sensitivity analysis, we found higher expression level of SOX13 predicts a high IC50 value for most of 198 drugs which predicts drug resistance.ConclusionThe present findings demonstrated that high expression of SOX13 negatively relates to prognosis and SOX13 plays an important role in cancer immunity. Therefore, SOX13 may potentially be adopted as a biomarker for predicting BC prognosis and infiltration of immune cells.

Phenological traits, such as leaf and flowering dates, are proven to be phylogenetically conserved. The relationship between phylogenetic conservation, plant phenology, and climatic factors remains unknown. Here, we assessed phenological features among flowering plants as evidence for phylogenetic conservatism, the tendency for closely related species to share similar ecological and biological attributes. We use spring phenological traits data from 1968-2018 of 65 trees and 49 shrubs in Xi’an (temperate climate) and Guiyang (subtropical climate) to understand plant phenological traits’ relationship with phylogeny. Molecular datasets are employed in evolutionary models to test the phylogenetic conservatism in spring phenological characteristics in response to climate-sensitive phenological features. Significant phylogenetic conservation was found in the Xi’an plant’s phenological traits, while there was a non-significant conservation in the Guiyang plant species. Phylogenetic generalized least squares (PGLS) models correlate with phenological features significantly in Xi’an while non-significantly in Guiyang. Based on the findings of molecular dating, it was suggested that the Guiyang species split off from their relatives around 46.0 mya during the middle Eocene of the Tertiary Cenozoic Era, while Xi’an species showed a long evolutionary history and diverged from their relatives around 95 mya during the late Cretaceous Mesozoic Era. First leaf dates (FLD) indicative of spring phenology, show that Xi’an adjourned the case later than Guiyang. Unlike FLD, first flower dates (FFD) yield different results as Guiyang flowers appear later than Xi’an’s. Our research revealed that various factors, including phylogeny, growth form, and functional features, influenced the diversity of flowering phenology within species in conjunction with local climate circumstances. These results are conducive to understanding evolutionary conservation mechanisms in plant phenology concerning evolutionary processes in different geographical and climate zones.

ObjectivePrevious research has shown numerous health benefits of yoga, a multicomponent physical and mental activity. The three important aspects of both traditional and modern yoga are breath work, postures, and meditation. However, the neural mechanisms associated with these three aspects of yoga remain largely unknown. The present study investigated the neural underpinnings associated with each of these three yoga components in long- and short-term yoga practitioners to clarify the neural advantages of yoga experience, aiming to provide a more comprehensive understanding of yoga’s health-promoting effects.MethodsParticipants were 40 Chinese women, 20 with a long-term yoga practice and 20 with a short-term yoga practice. Functional near-infrared spectroscopy was conducted while participants performed abdominal breathing, mental imagery of yoga postures, and mindfulness meditation. The oxygenated hemoglobin concentrations activated in the brain during these three tasks were used to assess the neural responses to the different aspects of yoga practice. The self-reported mastery of each yoga posture was used to assess the advantages of practicing yoga postures.ResultsBlood oxygen levels in the dorsolateral prefrontal cortex during breath work were significantly higher in long-term yoga practitioners than in short-term yoga practitioners. In the mental imagery of yoga postures task, self-reported data showed that long-term yoga practitioners had better mastery than short-term practitioners. Long-term yoga practitioners demonstrated lower activation in the ventrolateral prefrontal cortex, with lower blood oxygen levels associated with performing this task, than short-term yoga practitioners. In the mindfulness meditation task, blood oxygen levels in the orbitofrontal cortex and the ventrolateral prefrontal cortex were significantly higher in long-term yoga practitioners than in short-term yoga practitioners.ConclusionThe three core yoga components, namely, yogic breathing, postures, and meditation, showed differences and similarities in the activation levels of the prefrontal cortex. Long-term practice of each component led to the neural benefits of efficient activation in the prefrontal cortex, especially in the dorsolateral prefrontal cortex, orbitofrontal cortex, and ventrolateral prefrontal cortex.

Obesity is associated with chronic inflammation in the central nervous system (CNS), and neuroinflammation has been shown to have detrimental effects on mood and cognition. The growth hormone secretagogue receptor (GHSR), the biologically relevant receptor of the orexigenic hormone ghrelin, is primarily expressed in the brain. Our previous study showed that neuronal GHSR deletion prevents high-fat diet-induced obesity (DIO). Here, we investigated the effect of neuronal GHSR deletion on emotional and cognitive functions in DIO. The neuron-specific GHSR-deficient mice exhibited reduced depression and improved spatial memory compared to littermate controls under DIO. We further examined the cortex and hippocampus, the major regions regulating cognitive and emotional behaviors, and found that the neuronal deletion of GHSR reduced DIO-induced neuroinflammation by suppressing proinflammatory chemokines/cytokines and decreasing microglial activation. Furthermore, our data showed that neuronal GHSR deletion suppresses neuroinflammation by downregulating AMPK-autophagy signaling in neurons. In conclusion, our data reveal that neuronal GHSR inhibition protects against DIO-induced depressive-like behavior and spatial cognitive dysfunction, at least in part, through AMPK-autophagy signaling-mediated neuroinflammation.

PurposeCerebral vasospasm (CVS) is a common complication that occurs after neurosurgical clipping of intracranial aneurysms in patients with aSAH. This complication can lead to clinical deterioration and a poor prognosis. The aim of this study is to explore the risk factors for CVS in aSAH patients who have undergone neurosurgical clipping, develop a nomogram for CVS, and evaluate its performance.MethodsPatients with aSAH who underwent neurosurgical clipping in the Department of Neurosurgery from January 2018 to January 2023 were selected as the subjects of this research. The clinical data of these patients were retrospectively analyzed. Logistic multivariate regression analysis was employed to identify the independent risk factors of CVS. A clinical prediction model in the form of a nomogram for CVS was developed using the R programming language and subsequently evaluated for its performance and quality.ResultsA total of 156 patients with aSAH were included in the analysis, comprising 109 patients in the training set and 47 patients in the validation set. In the training cohort, 27 patients (24.77%) developed CVS after neurosurgical clipping, while in the validation cohort, 15 patients (31.91%) experienced CVS. Multivariate regression analysis revealed that age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade were independent risk factors for CVS. The nomogram exhibited excellent discriminative performance in both the training set (AUC = 0.885) and the validation set (AUC = 0.906).ConclusionCVS was a prevalent complication following neurosurgical clipping in patients with aSAH, with a highly intricate pathogenesis and pathophysiological course. Early prediction of CVS represented a significant challenge in clinical practice. In this study, age, Hcy, WBC, glucose/potassium ratio, aneurysm location, and modified Fisher grade emerged as independent risk factors for CVS. The resulting nomogram demonstrated substantial predictive value.

BackgroundThe escalating resistance of Klebsiella pneumoniae, a prevalent pathogen in healthcare settings, especially its carbapenem-resistant K. pneumoniae (CRKP), to a wide array of antibiotics, notably β-lactams, constitutes a formidable challenge for healthcare and global public health management.MethodsThis research compared the resistance phenotypes and genomic profiles of CRKP and Non-CRKP isolates in a Beijing hospital, focusing on high-risk blaKPC-2 gene-bearing CRKP clones and the structure of mobile genetic elements facilitating their spread across hospital departments. Forty K. pneumoniae isolates were collected from various departments of the hospital and subjected to antimicrobial susceptibility testing and whole-genome sequencing to analyze their resistance phenotypes and genomic features.ResultsThe study revealed that among the 31 CRKP isolates, ST11 is the most common sequence type, with K47 and OL101 being the dominant capsule types, primarily observed in the respiratory department. In terms of antimicrobial susceptibility: 87.5% of the isolates exhibited multidrug resistance (MDR), with a high resistance rate of 30% against tigecycline. All CRKP isolates demonstrated resistance to multiple drug classes (≥5 CLSI classes). Non-CRKP isolates also showed high resistance rates to minocycline and doxycycline (77.8%). the ST11-KL47-OL101 type emerged as the predominant clone among the CRKP isolates carrying the blaKPC-2 gene. This dominance appears to be mediated by the pKpnR03_2 plasmid, which harbors not only blaKPC-2 and rmtb but also gene clusters pertinent to iron transport and arsenic resistance. These isolates, clustering in the C3 clade of the phylogenetic tree, exhibited minor genetic variations and close evolutionary relationships, suggesting a plasmid-driven spread across various hospital departments.ConclusionIn summary, our study highlights the extensive spread of antibiotic-resistant K. pneumoniae across various departments in our hospital, with a particular emphasis on the dominant clonal proliferation of the ST11-KL47-OL101 CRKP strain. This finding underscores the significant role of plasmid-mediated gene transfer in the evolution and dissemination of resistant strains within hospital environments. The study emphasizes the necessity for ongoing surveillance of antibiotic resistance and genomic analysis in hospital settings to effectively monitor and manage these challenges.

BackgroundAdolescence is a crucial period for the development of depression, and previous studies have suggested that the Behavioral Activation System (BAS) plays a significant role. However, little is known about the underlying mechanisms. This study aimed to explore the mediating role of anhedonia in the relationship between BAS and depressive symptoms among Chinese adolescents.MethodA total of 1,023 high-school students aged 15–18 years participated in the study, with 916 continuing their participation three months later. All participants completed the Behavioral Inhibition System/Activation System (BIS/BAS) scale, Dimensional Anhedonia Rating Scale (DARS), Children’s Depression Inventory (CDI), and the State-Trait Anxiety Inventory (STAI-S/T). Pathway model analysis was performed to examine the concurrent and prospective mediating effects of anhedonia and the potential moderating effect of sex.ResultAnhedonia in the domains of social activities, hobbies and sensory experiences significantly mediated the cross-sectional relationship between BAS and depressive level three months later. Furthermore, the beta-value of the mediating effect of social activities was significantly higher than that of the other domains of hedonic capacity cross-sectionally and longitudinally. However, sex showed no significant moderating effect.ConclusionOur findings underscore the importance of hedonic capacity, especially within the social domain, in the development of depressive symptoms. These findings contribute to the early diagnosis and prevention of depressive disorders.

PurposeTo explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping.MethodsA total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc.ResultsVAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05).ConclusionsIn this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.

Inhibitor of apoptosis proteins (IAPs) are crucial components of apoptosis that perform vital roles in the regulation of caspase activity in organisms. In this study, two IAPs genes were identified from Cotesia chilonis, the dominant parasitic wasp of Chilo suppressalis. CcIAP1 gene is a typical IAP and contains two BIR domains and a RING domain, whereas CcIAP gene is an atypical IAP1 only containing two BIR domains. Phylogenetic analysis indicated that CcIAP1 and CcIAP were grouped with other Hymenopteran IAPs and IAP1 in C. suppressalis. Real-time quantitative PCR revealed that CcIAP1 and CcIAP genes were both highly induced at −6°C and 30°C, and expression was highest at the third instar stage. The expression of CcIAP1 and CcIAP genes were significantly induced during parasitism of C. suppressalis, and the 7-d time point resulted in the highest expression levels for both genes, in which was an advanced stage of larval development of C. chilonis. RNAi experiments showed that CcIAP1 gene was the key IAP in the regulation of apoptosis of C. chilonis and its host. In conclusion, CcIAP1 and CcIAP correlate with the development of C. chilonis and their responses to temperature stress.

IntroductionAstaxanthin (AST) is a type of carotenoid with strong antioxidant effects. However, the development and use of AST are limited by its water insolubility and low bioavailability. This study aims to investigate whether AST@PLGA can inhibit UC and reveal its possible mechanism.MethodsWe tested the particle size, polydispersity index, and zeta potential of AST@PLGA. Then, the in vitro release and antioxidant capacity of AST@PLGA were tested. Finally, the mouse model of colitis was established and SOD, MDA, TNF-α, IL-1β, IL-6 and P38 as well as ERK were detected from mice.ResultsParticle size, polydispersity index and zeta potential of AST @PLGA were 66.78 ± 0.64 nm, 0.247 and -9.8 ± 0.53 mV, respectively, and were stable within 14 days. Then, it was observed that the AST@PLGA nanoparticles not only maintained the effect of AST but also had a sustained release effect. Experiments in mice showed that AST@PLGA effectively reduced MDA, TNF-α, IL-1β and IL-6 levels and increased SOD levels. AST@PLGA also downregulated the protein expression of P38 and ERK. The results showed the positive protective effect of AST@PLGA in inhibiting acute colitis.DiscussionAST@PLGA nanoparticles have good stability and alleviating effect in colitis, which could be functional foods in the future.

Endometrial cancer (EC) is one of the most common gynecological cancers, and its risk factors include obesity and metabolic, genetic, and other factors. Recently, the circadian rhythm has also been shown to be associated with EC, as the severity of EC was found to be related to night work and rhythm disorders. Therefore, circadian rhythm disorders (CRDs) may be one of the metabolic diseases underlying EC. Changes in the circadian rhythm are regulated by clock genes (CGs), which in turn are regulated by non-coding RNAs (ncRNAs). More importantly, the mechanism of EC caused by ncRNA-mediated CRDs is gradually being unraveled. Here, we review existing studies and reports and explore the relationship between EC, CRDs, and ncRNAs.

Background: The application of exercise therapy (ET) in chronic obstructive pulmonary disease (COPD) is generating increasing clinical efficacy and social-economic value. In this study, research trends, evolutionary processes and hot topics in this field are detailed, as well as predictions of future development directions.Methods: Search for literature in the field of COPD and ET and analyze data to generate knowledge graphs using VOSiewer and CiteSpace software. The time frame for the search was from 2011 to January 2021. Then we extracted full-text key information (such as title, journal category, publication date, author, country and institution, abstract, and keyword) and obtained the co-citation analysis. Use hierarchal clustering analysis software developed by VOSviewer to map common citations, and use Citespace software to plot trend networks.Results: The United States topped the list with 27.91% of the number of articles posted, followed by the UK at 25.44%. Imperial College London was the highest number of article publications in institutions, followed by Maastricht University and the University of Toronto. The Royal Brompton Harefield NHS Foundation Trust was one of many research institutions and currently holds the highest average citations per item (ACI) value, followed by Imperial College London and the University of Leuven. Judging from the number of publications related to ET and COPD, it is mainly published in cell biology, respiratory pulmonary diseases, and rehabilitation experiments study medicine. The European Respiration Journal is the most widely published in this field, followed by the International Journal of Chronic Obstructive Pulmonary Disease and Respiratory Medicine.Conclusion: COPD combined with ET is widely used in clinical practice and is on the rise. A distinctive feature of the field is multidisciplinary integration. Rehabilitation research for COPD involves multidisciplinary collaboration, tissue engineering, and molecular biology mechanism studies to help patients remodel healthy breathing. Multidisciplinary rehabilitation measures provide a solid foundation for advancing clinical efficacy in the field of COPD.

Mitochondrion and ferroptosis are related to tumorigenesis and tumor progression of hepatocellular carcinoma (HCC). Therefore, this study focused on exploring the participation of lncRNAs in mitochondrial dysfunction and ferroptosis using public datasets from The Cancer Genome Atlas (TCGA) database. We identified the mitochondrion- and ferroptosis-related lncRNAs by Pearson’s analysis and lasso-Cox regression. Moreover, real-time quantitative reverse transcription PCR (RT-qPCR) was utilized to further confirm the abnormal expression of these lncRNAs. Based on eight lncRNAs, the MF-related lncRNA prognostic signature (LPS) with outstanding stratification ability and prognostic prediction capability was constructed. In addition, functional enrichment analysis and immune cell infiltration analysis were performed to explore the possible functions of lncRNAs and their impact on the tumor microenvironment. The pathways related to G2M checkpoint and MYC were activated, and the infiltration ratio of regulatory T cells and M0 and M2 macrophages was higher in the high-risk group. In conclusion, these lncRNAs may affect mitochondria functions, ferroptosis, and immune cell infiltration in HCC through specific pathways, which may provide valuable insight into the progression and therapies of HCC.

In order to study the deterioration characteristics of the tunnel surrounding rock under the scouring of flowing groundwater, we ratioed similar acidic solutions based on groundwater composition. The microstructure of granite samples cored on site, deformation features, and evolution characteristics of mechanical parameters under saturations with different flow rates and various pH values were analyzed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), nuclear magnetic resonance (NMR), and X-ray diffraction (XRD). The results indicate the following: 1) compared with the static water condition, the higher flow rate produces greater relative changes in granite’s microstructure, porosity, mass, and pH of the immersed solution. Moreover, the rate of change is relatively fast in the early stage and gradually slows down until it reaches a stable state. 2) Compared with the natural dry condition, the solution with a lower pH value causes the structural framework of the specimen to loosen, the mass loss degree to increase, and the porosity dispersion to intensify. 3) The dynamic water is more sensitive than the static water to the elastic vertical wave velocity of granite. Compared with the dry sample, the elastic longitudinal wave velocity of the sample in acidic solution with pH = 2 and flow rates of 0, 150, and 300 mm·s−1 for 49 days decreased by 8.7, 10.9, and 13.5%, respectively, which accelerates the instability and failure of the granite surroundings.

BackgroundDetection of mild cognitive impairment (MCI) is essential to screen high risk of Alzheimer’s disease (AD). However, subtle changes during MCI make it challenging to classify in machine learning. The previous pathological analysis pointed out that the hippocampus is the critical hub for the white matter (WM) network of MCI. Damage to the white matter pathways around the hippocampus is the main cause of memory decline in MCI. Therefore, it is vital to biologically extract features from the WM network driven by hippocampus-related regions to improve classification performance.MethodsOur study proposes a method for feature extraction of the whole-brain WM network. First, 42 MCI and 54 normal control (NC) subjects were recruited using diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI), and T1-weighted (T1w) imaging. Second, mean diffusivity (MD) and fractional anisotropy (FA) were calculated from DTI, and the whole-brain WM networks were obtained. Third, regions of interest (ROIs) with significant functional connectivity to the hippocampus were selected for feature extraction, and the hippocampus (HIP)-related WM networks were obtained. Furthermore, the rank sum test with Bonferroni correction was used to retain significantly different connectivity between MCI and NC, and significant HIP-related WM networks were obtained. Finally, the classification performances of these three WM networks were compared to select the optimal feature and classifier.Results(1) For the features, the whole-brain WM network, HIP-related WM network, and significant HIP-related WM network are significantly improved in turn. Also, the accuracy of MD networks as features is better than FA. (2) For the classification algorithm, the support vector machine (SVM) classifier with radial basis function, taking the significant HIP-related WM network in MD as a feature, has the optimal classification performance (accuracy = 89.4%, AUC = 0.954). (3) For the pathologic mechanism, the hippocampus and thalamus are crucial hubs of the WM network for MCI.ConclusionFeature extraction from the WM network driven by hippocampus-related regions provides an effective method for the early diagnosis of AD.

BackgroundIntensive care unit-acquired weakness (ICU-AW) is common in critical illness patients and is well described. Extracorporeal membrane oxygenation (ECMO) is used as a life-saving method and patients with ECMO support often suffer more risk factors of ICU-AW. However, information on the frequency and clinical characteristics of ICU-AW in patients with ECMO support is lacking. Our study aims to clarify the frequency and characteristics of ICU-AW in ECMO patients.MethodsWe conducted a retrospective study, ICU-AW was diagnosed when patients were discharged with a Medical Research Council (MRC) sum score

ObjectiveTo explore the application of quantitative magnetic resonance imaging in the diagnosis of autism in children.MethodsSixty autistic children aged 2–3 years and 60 age- and sex-matched healthy children participated in the study. All the children were scanned using head MRI conventional sequences, 3D-T1, diffusion kurtosis imaging (DKI), enhanced T2*- weighted magnetic resonance angiography (ESWAN) and 3D-pseudo continuous Arterial Spin-Labeled (3D-pcASL) sequences. The quantitative susceptibility mapping (QSM), cerebral blood flow (CBF), and brain microstructure of each brain area were compared between the groups, and correlations were analyzed.ResultsThe iron content and cerebral blood flow in the frontal lobe, temporal lobe, hippocampus, caudate nucleus, substantia nigra, and red nucleus of the study group were lower than those in the corresponding brain areas of the control group (P < 0.05). The mean kurtosis (MK), radial kurtosis (RK), and axial kurtosis (AK) values of the frontal lobe, temporal lobe, putamen, hippocampus, caudate nucleus, substantia nigra, and red nucleus in the study group were lower than those of the corresponding brain areas in the control group (P < 0.05). The mean diffusivity (MD) and fractional anisotropy of kurtosis (FAK) values of the frontal lobe, temporal lobe and hippocampus in the control group were lower than those in the corresponding brain areas in the study group (P < 0.05). The values of CBF, QSM, and DKI in frontal lobe, temporal lobe and hippocampus could distinguish ASD children (AUC > 0.5, P < 0.05), among which multimodal technology (QSM, CBF, DKI) had the highest AUC (0.917) and DKI had the lowest AUC (0.642).ConclusionQuantitative magnetic resonance imaging (including QSM, 3D-pcASL, and DKI) can detect abnormalities in the iron content, cerebral blood flow and brain microstructure in young autistic children, multimodal technology (QSM, CBF, DKI) could be considered as the first choice of imaging diagnostic technology.Clinical Trial Registration[http://www.chictr.org.cn/searchprojen.aspx], identifier [ChiCTR2000029699].

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized with a gradual loss of midbrain substantia nigra (SN) dopamine (DA) neurons. An excessive evidence demonstrated that microglia-mediated inflammation might be involved in the pathogenesis of PD. Thus, inhibition of neuroinflammation might possess a promising potential for PD treatment. Icariin (ICA), a single active component extracted from the Herba Epimedii, presents amounts of pharmacological properties, such as anti-inflammation, anti-oxidant, and anti-aging. Recent studies show ICA produced neuroprotection against brain dysfunction. However, the mechanisms underlying ICA-exerted neuroprotection are fully illuminated. In the present study, two different neurotoxins of 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS)-induced rat midbrain DA neuronal damage were applied to investigate the neuroprotective effects of ICA. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the mechanisms underlying ICA-mediated DA neuroprotection. In vitro data showed that ICA protected DA neurons from LPS/6-OHDA-induced DA neuronal damage and inhibited microglia activation and pro-inflammatory factors production via the suppression of nuclear factor-κB (NF-κB) pathway activation. In animal results, ICA significantly reduced microglia activation and significantly attenuated LPS/6-OHDA-induced DA neuronal loss and subsequent animal behavior changes. Together, ICA could protect DA neurons against LPS- and 6-OHDAinduced neurotoxicity both in vivo and in vitro. These actions might be closely associated with the inhibition of microglia-mediated neuroinflammation. [ABSTRACT FROM AUTHOR]

The frequency of earthquakes on active faults is usually revealed by palaeoseismic trenching and geological dating. Nonetheless, field trenching and sampling are sometimes limited by difficulties in logistics, therefore impeding palaeoseismological studies. As surface rupture earthquakes create fault scarps that evolve with time, they may also provide important information about the timing of earthquakes. In this study, we provide a new approach to determine earthquake history based on the morphology of fault scarps. We select the Muztagh Ata and Tahman normal faults in the Chinese Pamir as a test area, on which fault scarps are well preserved but the earthquake history has not been quantified yet. We first simulate fault scarp degradation using a nonlinear transport model to obtain the empirical relationship between scarp width and its evolution time. We then measure 68 fault scarps from high-resolution topographic data derived from WorldView-2 stereo imagery. The measured fault scarps are clustered in four groups, each group possibly representing one earthquake event. Combining the time-width relationship and scarp width measurements, we infer that four earthquakes occurred at 0.1±0.4 kyrs before the present (BP), 2.1±0.5 kyrs BP, 2.9±0.4 kyrs BP and 4.9±0.5 kyrs BP, respectively. The first event is likely to be the most recent earthquake occurred on the faults, i.e., the 1895 Tashkurgan earthquake ( ∼0.13 kyrs BP). Based on the estimated earthquake recurrence intervals and vertical offsets, we obtain a vertical slip rate of 2.2±0.3 mm/yr on the Muztagh Ata and Tahman faults, conforming to previous geological rate estimates.

Background: The information is relatively scarce regarding the occurrence of drug-induced acute kidney injury (AKI) when anti-coronavirus disease 2019 (COVID-19) drugs are prescribed for patients with diabetes mellitus (DM).Objective: The objective of this study was to evaluate a pharmacovigilance signal for AKI upon the use of common drugs prescribed for COVID-19 treatment, especially in patients with DM.Methods: The FDA Adverse Event Reporting System (FAERS) database were used, and data from the first quarter of 2020 to the third quarter of 2021 were retrieved. A disproportionality analysis was performed to determine whether AKI was more frequently reported with anti-COVID-19 drugs compared to that with other drugs in different populations. Further, reporting odds ratios (RORs) and their 95% confidence intervals (CIs) were used to calculate disproportionality. Results: We identified 33,488 COVID-19 patients and 2397 COVID-19 patients with DM. AKI was the most frequent adverse drug reaction (ADR) reported in this patient population. The primary suspected drugs related to AKI in more than half of the reports (75.60%, 127/168) were four common anti-COVID-19 drugs (remdesivir, tocilizumab, hydroxychloroquine, and lopinavir/ritonavir). Compared with other drugs in the same time window, remdesivir and lopinavir/ritonavir were associated with an increased risk of AKI in all COVID-19 patients (ROR: 3.97, 95% CI: 3.51–4.50; ROR: 4.02, 95% CI: 3.11–5.19, respectively). In COVID-19 patients with DM, remdesivir was significantly associated with AKI (ROR: 5.65, 95% CI: 4.06–7.87); meanwhile, there was a new AKI signal associated with tocilizumab (ROR: 2.37, 95% CI: 1.19–4.72). After sensitivity analyses in COVID-19 patients with DM, consistent results for remdesivir were observed; however, the AKI signals for tocilizumab were unstable.Conclusion: Our study confirmed the association of AKI with the usage of common anti-COVID-19 drugs (especially remdesivir and tocilizumab) in DM patients. These safety signals suggested more individualized treatments for COVID-19 patients with comorbidities. Cross-disciplinary collaborative is needed to improve current strategy of clinical treatment and develop new approaches to management.

The timing of flowering is a key determinant for plant reproductive. It has been demonstrated that microRNAs (miRNAs) play an important role in transition from the vegetative to reproductive stage in cotton; however, knowledge remains limited about the regulatory role of miRNAs involved in flowering time regulation in cotton. To elucidate the molecular basis of miRNAs in response to flowering time in cotton, we performed high-throughput small RNA sequencing at the fifth true leaf stage. We identified 56 and 43 miRNAs that were significantly up- and downregulated in two elite early flowering cultivars (EFC) compared with two late flowering cultivars (LFC), respectively. The miRNA targets by RNA sequencing analysis showed that GhSPL4 in SBP transcription factor family targeted by GhmiR156 was significantly upregulated in EFCs. Co-expression regulatory network analysis (WGCNA) revealed that GhSOC1, GhAP1, GhFD, GhCOL3, and GhAGL16 act as node genes in the auxin- and gibberellin-mediated flowering time regulatory networks in cotton. Therefore, elucidation of miRNA-mediated flowering time regulatory network will contribute to our understanding of molecular mechanisms underlying flowering time in cotton.

The paper studies the uniaxial compression mechanical properties of pillars under the deep and high-humidity environment. We make the pillars cored from the −750 m mine room of Wengfu Phosphate Mine into the standard dolomite samples and test with a humidity control device developed by ourselves. Combining with uniaxial compression tests and microstructure inspections, we study the mechanical deterioration rule and damage mechanism of the dry samples and the wet ones that have been placed in a high-humidity condition (90% RH) for 30, 60 and 90 d, respectively. The results show that: 1) When the sample is placed in the humidity device, its original layered or sheet crystal morphology will change into sponge-like or flocculent morphology. As the placement time increases, the structure of the sample becomes looser and the boundaries between layers become blurred. The numbers of micro-cracks and micro-pores increase. 2) In the initial stage of water molecule intrusion (0–30 d), the strength and mass damages of the rock sample are less, and the damage rate is low. As high-humidity action time increases (30–90 d), the damage rates of both strength and mass gradually grow. 3) The failure modes of dolomites include shear failure and tensile/shear mixed failure, which are controlled by the storage time under high-humidity condition. As time goes by, more macroscopic cracks appear and the failure mode of the rock changes from shear to tensile. 4) Based on the X-ray diffraction and scanning electron microscopy analysis on mineral components, together with the principle of chemical kinetics, we discuss the chemical reaction process between dolomite and gaseous water molecules, and summarize the chemical damage mechanism of rocks during the water-rock interaction. The research has a certain guiding significance for the durability and stability prediction of pillars under deep high-humidity conditions.

Exposure to a catastrophic event or intense stimulation can trigger fear memories, and the threatening memories persist even over a lifetime. Exposure therapy is based on extinction learning and is widely used to treat fear-related disorders, but its effect on remote fear memory is modest. Berberine, an isoquinoline alkaloid derived from Coptis chinensis or Berberis spp., has been recently reported to exert a diversity of pharmacological effects on the central nervous system, such as facilitating extinction of drug memory. Here, we explored the effect of berberine on extinction of fear memory using a classical contextual fear conditioning (CFC) paradigm, which is Pavlovian conditioning, can rapidly create fear memories related to contexts. Twenty-four hours or 30 days after CFC training, mice were subjected to context extinction (10 days) to extinguish their behaviors and treated with 12.5 or 25 mg/kg berberine intragastrically 1 or 6 h after each extinction session, followed by reinstatement and spontaneous recovery tests. The results showed that intragastric administration of 25 mg/kg berberine 1 h after extinction significantly promoted the extinction of recent and remote fear memories and prevented reinstatement and spontaneous recovery of extinguished fear in mice. These findings indicate that berberine combined with extinction training could serve as a promising novel avenue for the treatment of fear-related disorders.

Renal ischemia-reperfusion injury (IRI) is an inevitable process in kidney transplantation, leading to acute kidney injury, delayed graft function (DGF), and even graft loss. Ferroptosis is an iron-dependent regulated cell death in various diseases including IRI. We aimed to identify subtypes of renal IRI and construct a robust DGF predictive signature based on ferroptosis-related genes (FRGs). A consensus clustering analysis was applied to identify ferroptosis-associated subtypes of 203 renal IRI samples in the GSE43974 dataset. The FRG-associated DGF predictive signature was constructed using the Least Absolute Shrinkage and Selection Operator (LASSO), and its robustness was further verified in the validation set GSE37838. The present study revealed two ferroptosis-related patient clusters (pBECN1 and pNF2 cluster) in renal IRI samples based on distinct expression patterns of BECN1 and NF2 gene clusters. Cluster pBECN1 was metabolically active and closely correlated with less DGF, while pNF2 was regarded as the metabolic exhausted subtype with higher incidence of DGF. Additionally, a six-gene (ATF3, SLC2A3, CXCL2, DDIT3, and ZFP36) ferroptosis-associated signature was constructed to predict occurrence of DGF in renal IRI patients and exhibited robust efficacy in both the training and validation sets. High-risk patients tended to have more infiltration of dendritic cells, macrophages, and T cells, and they had significantly enriched chemokine-related pathway, WNT/β-catenin signaling pathway, and allograft rejection. Patients with low risks of DGF were associated with ferroptosis-related pathways such as glutathione and fatty acid metabolism pathways. In conclusion, patient stratification with distinct metabolic activities based on ferroptosis may help distinguish patients who may respond to metabolic therapeutics. Moreover, the DGF predictive signature based on FRGs may guide advanced strategies toward prevention of DGF in the early stage.

LAG-3 is one of the common tumor immune checkpoints. LAG-3 can inhibit the activation and proliferation of T cells, and can also suppress immunity by regulating other immune-related cell functions. FGL1 was recently discovered to be the main ligand of immune checkpoint LAG-3 and play a critical role in the inhibition of T cells. However, the FGL1 expression in circulating tumor cells (CTCs) and its clinical significance in hepatocellular carcinoma (HCC) remain unclear. Therefore, this bioinformatics analysis was performed to assess the expression of FGL1 in various tumors and its association with immune infiltration. After that, CTCs from 109 HCC patients were detected and the immunofluorescence staining was performed (CD45, EpCAM, CK8/18/19, Vimentin, Twist, DAPI and FGL1). Then, we investigated FGL1 expression and EMT of CTCs and analyzed its relationship with patient survival and clinical relevance. Bioinformatic results showed that FGL1 expression was abnormal in various tumor and it was correlated with the infiltration level of several immune cells. FGL1 expression was detected in CTCs of 40 patients (36.7%). The proportion of advanced TNM stage (P

Neurophysiological effect of human exposure to radiofrequency signals has attracted considerable attention, which was claimed to have an association with a series of clinical symptoms. A few investigations have been conducted on alteration of brain functions, yet no known research focused on intrinsic connectivity networks, an attribute that may relate to some behavioral functions. To investigate the exposure effect on functional connectivity between intrinsic connectivity networks, we conducted experiments with seventeen participants experiencing localized head exposure to real and sham time-division long-term evolution signal for 30 min. The resting-state functional magnetic resonance imaging data were collected before and after exposure, respectively. Group-level independent component analysis was used to decompose networks of interest. Three states were clustered, which can reflect different cognitive conditions. Dynamic connectivity as well as conventional connectivity between networks per state were computed and followed by paired sample t-tests. Results showed that there was no statistical difference in static or dynamic functional network connectivity in both real and sham exposure conditions, and pointed out that the impact of short-term electromagnetic exposure was undetected at the ICNs level. The specific brain parcellations and metrics used in the study may lead to different results on brain modulation.

Ratooning is the cultivation practice of two harvests in one cropping season by producing a second crop from the original stubble, which could provide higher resource use efficiency and economic benefit compared with direct sown crops. Nitrogen (N) fertilizer and planting density (D) play a vital role in sorghum (Sorghum bicolor L.) production; however, limited information is available on the effects on yield and quality of the sorghum-ratoon system. To address this question, field experiments were conducted with three N treatments (120 kg N ha–1, N1; 180 kg N ha–1, N2; and 255 kg N ha–1, N3) and three D treatments (82,500 plant ha–1, D1; 105,000 plant ha–1, D2; and 127,500 plant ha–1, D3). The yield of the main crop was significantly higher than that of the ratoon crop. Increasing N could increase the yield and yield attributes of both main and ratoon crops, and the effect on the ratoon crop was greater than the main crop. With increasing D, the grain yield of both main and ratoon crops increased, though 1,000-grain weight and grain weight per ear decreased. The sorghum grain of the ratoon crop contained higher starch, protein, and tannin contents but lower fat content, indicating a better quality for liquor production. The quality traits were significantly affected by N and D, but the differences between treatments were smaller than that between the main and ratoon crop. Our results indicated that increasing the yield of ratoon crops could obtain a high yield and quality of the sorghum-ratoon system. It was recommended that 120 kg N ha–1 with 127,500 plant ha–1 for the main crop and a small amount of N be top-dressed in three new buds left on stubble in each hill for the ratoon crop.

The asparaginase and isoaspartyl peptidase 1 (ASRGL1) is an L-asparaginase and beta-aspartyl peptidase enzyme that may be involved in the formation of L-aspartate, a neurotransmitter that can operate as an excitatory neurotransmitter in some brain regions. Although variants in ASRGL1 have been reported in retinitis pigmentosa (RP) patients, the in vivo functions and mechanisms of ASRGL in RP remains unknown due to the lack of suitable disease models. To explore the role of ASRGL in RP, we generated an Asrgl1 knockout mouse model (Asrgl1 KO) using the CRISPR/Cas9 technique. Asrgl1 ablation in mice led to an attenuated electroretinogram (ERG) response around 8 months. The thickness of the outer nuclei layer (ONL) started to decrease around 9 months in Asrgl1 KO mice and gradually intensified at 12 and 15 months. Immunostaining revealed thinner inner segment (IS) and thinner outer segment (OS) as well as the progressive degeneration of rod and cone cells in Asrgl1 KO mice. One hundred forty-nine transcriptional differentially expressed genes (DEGs) were found by RNA-seq in Asrgl1 KO retina. These DEGs were linked to a number of biological processes that were considerably enriched, including gastrointestinal disease and organismal injury and abnormalities. By analysis of canonical pathways, glucocorticoid receptor signaling was the most significant canonical pathway altered in Asrgl1 KO retina. Several molecules, including NFE2L2, IL-4, Foxp3, and Fos, were in the central nodes of the interaction network in Asrgl1 KO retina. In summary, our study provided a knockout mouse model for a better understanding of the molecular mechanism for ASRGL1-related RP.

Due to the unique geographical characteristics of cold alpine and high-altitude regions, glaciers, permafrost, ground ice, rock glaciers, and other periglacial geomorphology have developed with fragile habitats, and these areas are often the birthplaces of many river basins and natural hazards. With global warming and the extensive cryogenesis and physical weathering, the thermal state of permafrost and the mass balance of glaciers have been changed, and thus it can be deduced that the surface deformation is of great concern. To obtain ground subsidence or uplift over a large area to understand local surface changes, the small baseline subset interferometric synthetic aperture radar (SBAS-InSAR) technique was applied to process 89-scene of Sentinel-1A images ranging from December 25, 2017 to January 2, 2021 to obtain surface deformation for these 3 years for the eastern Tianshan Mountains, China. The surface deformation characteristics of the area were analyzed to provide a basic dataset for environmental protection policies and mitigation or reduction of natural hazards in this region, and to verify the applicability of SBAS-InSAR technology in alpine and high-altitude areas. The results show that the SBAS-InSAR technique processing with sentinel-1A dataset cannot be effectively used to acquire ground deformation in areas covered by trees, scrub/shrub, glaciers, snow, and ground ice, where the decohered phenomenon is serious. In other regions, SBAS-InSAR can effectively measure surface subsidence or uplift. Surface deformation is significant throughout the study area, with rates ranging from −70.7 to 50.8 mm/a and with an average rate of 1.1 mm/a. There are obvious regions of uplift in the northwest, northeast, and central sections of the study area, with uplift greater than 155.73 mm in 3 years, and three obvious regions of subsidence in the northeast and west sections of the study area, with subsidence of at least −125.20 mm in 3 years. The remaining areas of deformation are scattered, with smaller amounts of settlement and uplift and with an isolated and sporadic distribution. Areas with elevations of 3,150 to 4,275 m.a.s.l., slopes of 15°–50°, and southwest, west, and northwest aspects are geologic disaster-prone regions and should receive more attention and more field monitoring. The results of this study have important implications for local environmental protection and hazard prevention.

Programmed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1 mRNA is abundant in many tissues. To address this puzzle, we investigated the function of PD-L1 in mammary gland development. Interestingly, we found that PD-L1 is enriched in protein C receptor (Procr)-expressing mammary stem cells (MaSCs), and PD-L1-expressing mammary basal cells (PD-L1+ basal cells) exhibit robust mammary regeneration capacity in transplantation assay. The lineage tracing experiment showed that PD-L1+ cells can differentiate into all lineages of mammary epithelium cells, suggesting that PD-L1+ basal cells have the activities of MaSCs. Furthermore, PD-L1 deficiency significantly impairs mammary development and reduces mammary regeneration capacity of mammary basal cells, suggesting that PD-L1 is not only enriched in MaSCs but also improves activities of MaSCs. In summary, these results demonstrated that PD-L1 is enriched in MaSCs and promotes mammary gland development and regeneration. Mechanistically, our data indicated that PD-L1 expression is induced by continuous activation of Wnt/ß-catenin signaling. In conclusion, these results demonstrated that PD-L1 is a marker of MaSCs, and PD-L1 is essential for mammary development. Our study provides novel insight into the physiological functions of PD-L1 in tissue development.