BMI-based metabolic syndrome severity score and arterial stiffness in a cohort Chinese study.

BACKGROUND AND AIMS: To investigate the relationship between metabolic syndrome severity z score(MetS-Z) and arterial stiffness(AS). METHODS AND RESULTS: A total of 7621 participants who took three physical examination and brachial-ankle pulse wave velocity(ba-pwv) test from 2006 were enrolled. Cumulative MetS-Z(cMetS-Z) was calculated by using blood pressure, triglycerides, HDL cholesterol, blood glucose and BMI. AS was assessed by ba-pwv. Cox regression model was used to evaluate the risk of AS. All participants were divided into four groups according to cMetS-Z(Q1-Q4). The average age of the participants was 43.06 ± 8.91 years old. During a median follow-up of 6.27 years, 1831cases of AS were identified. The incident rate of AS increased gradually from group Q1 to Q4. Compared with the lowest cMetS-Z(group Q1), the adjusted hazard ratio (HR) and 95% confidence interval (CI) of group Q2-Q4 for AS were 1.27 (1.09-1.47),1.28(1.10-1.48) and 1.45 (1.24-1.69) respectively. The cubic spline model indicated cMetS-Z had a liner relationship with AS and the cut-off value was lower than zero. Sub-group analysis suggested cMetS-Z was related to AS especially among participants who were younger and without obesity or hypertension or diabetes. CONCLUSION: Higher cMetS-Z was associated with an increased risk of AS in this cohort community study, and this relationship seemed to be stronger among normal healthy subjects. REGISTRATION NUMBER: ChiCTR-TNC-11001489. CLINICAL TRIAL: January 1st 2006, ChiCTR-TNC-11001489 and 2011.

Whether weekend warriors (WWs) achieve equivalent benefits in lipid accumulation products (LAP) reduction as other leisure-time physical activity patterns? -Results from a population-based analysis of NHANES 2007-2018.

BACKGROUND: Obesity is characterized by excessive fat accumulation in the body. Physical activity (PA) is an effective intervention to combat obesity, but the effectiveness of different PA patterns on controlling obesity is unclear. Lipid accumulation product (LAP), derived from waist circumference and triglycerides, is a novel indicator for obesity evaluation. However, the association between PA patterns (i.e., weekend warriors and regularly active) and LAP remains unexplored. This study aims to elucidate the relationship between PA patterns and LAP in US adult population. METHODS: Adult individuals with complete data on LAP, PA patterns, and other covariates from the National Health and Nutrition Examination Survey (NHANES) database (2007-2018) were included in this study. Multivariate linear regression models were utilized to explore the association between PA patterns and LAP. Subgroup analyses, interaction tests, restricted cubic spline (RCS) regression analyses, and threshold and saturation effect analyses were also performed to investigate the stability and nonlinearity of PA-LAP association, respectively. RESULTS: A total of 11,212 participants were included in this study. After adjusting for all potential covariates, being regularly active (RA) (ß=-8.85, P < 0.05) obtained significantly higher LAP reduction as opposed to being weekend warriors (WWs) (ß=-4.70, P = 0.3841). Furthermore, subgroup analyses and interaction tests indicated that the PA-LAP association was more pronounced in individuals with higher education levels (P interaction = 0.0084) and diabetes (P interaction = 0.0062). Additionally, a significant, non-linear, and negative correlation between weekly total PA and LAP in non-inactive individuals was identified by RCS analysis (P for overall < 0.001, P for nonlinearity = 0.009). A threshold of 440 min in weekly total PA was found to arouse favorable LAP reduction. CONCLUSIONS: Being regularly active obtained better LAP reduction as opposed to being WWs. For non-inactive adults, engaging in more than 440 min of PA per week helps to reduce LAP effectively.

The receptor-like kinases BAM1 and BAM2 are required for root xylem patterning.

Xylem patterning in the root is established through the creation of opposing gradients of miRNAs and their targets, transcripts of the HD-ZIP III family of transcriptions factors, enabled by the cell-to-cell spread of the former. The miRNAs regulating xylem patterning, miR165/6, move through plasmodesmata, but how their trafficking is regulated remains elusive. Here, we describe that simultaneous mutation of the plasma membrane- and plasmodesmata-localized receptor-like kinases (RLKs) BARELY ANY MERISTEM (BAM) 1 and 2 or expression of the geminivirus-encoded BAM1/2-interactor C4 results in higher accumulation and broader distribution of the HD-ZIP III transcripts despite normal total accumulation of miR165/6, and ultimately causes defects in xylem patterning, which depend on the function of the aforementioned miRNA targets. Taken together, our results show that BAM1 and BAM2 are redundantly required for proper xylem patterning in the Arabidopsis root, by ensuring the proper distribution and accumulation of miR165/6-targeted transcripts.

Ecological restoration for eutrophication mitigation in urban interconnected water bodies: Evaluation, variability and strategy.

Many urban water bodies grapple with low flow flux and weak hydrodynamics. To address these issues, projects have been implemented to form integrated urban water bodies via interconnecting artificial lake or ponds with rivers, but causing pollution accumulation downstream and eutrophication. Despite it is crucial to assess eutrophication, research on this topic in urban interconnected water bodies is limited, particularly regarding variability and feasible strategies for remediation. This study focused on the Loucun river in Shenzhen, comprising an pond, river and artificial lake, evaluating water quality changes pre-(post-)ecological remediation and establishing a new method for evaluating the water quality index (WQI). The underwater forest project, involving basement improvement, vegetation restoration, and aquatic augmentation, in the artificial lake significantly reduced total nitrogen (by 43.58%), total phosphorus (by 79.17%) and algae density (by 36.90%) compared to pre-remediation, effectively controlling algal bloom. Rainfall, acting as a variable factor, exacerbated downstream nutrient accumulation, increasing total phosphorus by 4.56 times and ammonia nitrogen by 1.30 times compared to the dry season, and leading to algal blooms in the non-restoration pond. The improved WQI method effectively assesses water quality status. The interconnected water body exhibits obvious nutrient accumulation in downstream regions. A combined strategy that reducing nutrient and augmenting flux was verified to alleviate accumulation of nutrients downstream. This study provides valuable insights into pollution management strategies for interconnected pond-river-lake water bodies, offering significant reference for nutrient mitigation in such urban water bodies.

Comparison of the relative efficacy of ß-lactam/ß-lactamase inhibitors and carbapenems in the treatment of complicated urinary tract infections caused by ceftriaxone-non-susceptible Enterobacterales: a multicentre retrospective observational cohort study.

BACKGROUND: Treating complicated urinary tract infections (cUTIs) caused by ESBL-producing Enterobacterales represents a significant clinical challenge. The present study was thus developed to explore the relative efficacy of ß-lactam/ß-lactamase inhibitors (BLBLIs) and carbapenems for the treatment of hospitalized patients suffering from cUTIs caused by BLBLI-susceptible ceftriaxone-non-susceptible Enterobacterales. METHODS: Data from 557 patients from four Chinese teaching hospitals diagnosed with cUTIs caused by ceftriaxone-non-susceptible Enterobacterales from January 2017 to May 2022 were retrospectively assessed. RESULT: The 30 day rate of treatment failure, defined by unresolved symptoms or mortality, was 10.4% (58/557). Independent predictors of 30 day treatment failure included immunocompromised status, bacteraemia, septic shock, lack of infection source control and appropriate empirical treatment. When data were controlled for potential confounding variables, BLBLI treatment exhibited a comparable risk of 14 day (OR 1.61, 95% CI 0.86-3.00, P = 0.133) and 30 day treatment failure (OR 1.45, 95% CI 0.66-3.15, P = 0.354) relative to carbapenem treatment for the overall cohort of patients. In contrast, BLBLI treatment in immunocompromised patients was associated with an elevated risk of both 14 day (OR 3.18, 95% CI 1.43-7.10, P = 0.005) and 30 day treatment failure (OR 3.06, 95% CI 1.07-8.80, P = 0.038) relative to carbapenem treatment. CONCLUSIONS: These results suggested that carbapenem treatment may be superior to BLBLI treatment for immunocompromised patients suffering from cUTIs caused by ceftriaxone-non-susceptible Enterobacterales species. However, these results will need to be validated in appropriately constructed randomized controlled trials to ensure appropriate patient treatment.

The R2R3-MYB transcription factor FaMYB63 participates in regulation of eugenol production in strawberry.

The biosynthetic pathway of volatile phenylpropanoids, including 4-allyl-2-methoxyphenol (eugenol), has been investigated in petunia (Petunia hybrida). However, the regulatory network for eugenol accumulation in strawberry (Fragaria × ananassa Duch.) fruit remains unclear. Here, an R2R3-type MYB transcription factor (TF; FaMYB63) was isolated from strawberry by yeast one-hybrid (Y1H) screening using the promoter of the FaEGS1 (eugenol synthase 1 [EGS 1]) gene, which encodes the enzyme responsible for the last step in eugenol biosynthesis. FaMYB63 is phylogenetically distinct from other R2R3-MYB TFs, including FaEOBІІ (EMISSION OF BENZENOID II [EOBII]), which also participates in regulating eugenol biosynthesis in strawberry receptacles. Reverse transcription quantitative PCR (RT-qPCR) assays showed that the expression of FaMYB63 was tissue-specific and consistent with eugenol content through strawberry fruit development, was repressed by abscisic acid, and was activated by auxins (indole-3-acetic acid). Overexpression and RNA interference-mediated silencing of FaMYB63 resulted in marked changes in the transcript levels of the biosynthetic genes FaEGS1, FaEGS2, and FaCAD1 (cinnamyl alcohol dehydrogenase 1 [CAD1]) and, thereby, the accumulation of eugenol. Electrophoretic mobility shift, Y1H, GUS activity, and dual-luciferase activity assays demonstrated that the transcript levels of FaEOBІІ and FaMYB10 were regulated by FaMYB63, but not the other way around. Together, these results demonstrate that FaMYB63 directly activates FaEGS1, FaEGS2, FaCAD1, FaEOBІІ, and FaMYB10 to induce eugenol biosynthesis during strawberry fruit development. These findings deepen the understanding of the regulatory network that influences eugenol metabolism in an edible fruit crop.

Covalent Binding Mechanism of Furmonertinib and Osimertinib With Human Serum Albumin.

As third-generation tyrosine kinase inhibitors, furmonertinib and osimertinib exhibit better efficacy than first- and second-generation tyrosine kinase inhibitors in patients with advanced non-small cell lung cancer. However, radioactive pharmacokinetics studies showed that parent-related components remain in human plasma for at least 21 days after oral administration. Similar pharmacokinetic profiles were found in pyrotinib and neratinib, which have been identified to covalently bind with human serum albumin at Lys-190, leading to low extraction recovery in protein precipitation. However, the binding mechanism of furmonertinib and osimertinib in human plasma has not been confirmed. Comprehensive techniques were used to investigate the mechanism of this binding, including ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry and online/offline radioactivity profiling. SDS-PAGE and further autoradiography were also used to detect drug-protein adducts. We found that most furmonertinib exists in the human plasma following ex vivo incubation in the form of protein-drug adducts. Only lysine-furmonertinb adducts were found in pronase digests. A standard reference of lysine-furmonertinib was synthesized and confirmed by NMR. Through peptide mapping analysis, we confirmed that furmonertinib almost exclusively binds with human serum albumin (HSA) in plasma following ex vivo incubation, via Michael addition at Lys-195 and Lys-199, instead of Lys-190. Two peptides found to bond with furmonertinib were ASSAKQR and LKCASLQK. Osimertinib was also found to bond with Lys-195 and Lys-199 of HSA via peptide mapping analysis. SIGNIFICANCE STATEMENT: Here we report that furmonertinib and osimertinib can covalently bind with human serum albumin at the site of Lys-195 and Lys-199 instead of Lys-190, potentially leading to the long duration of drug-protein adducts in the human body.

Anisotropic Nonlocal Damping in Ferromagnet/α-GeTe Bilayers Enabled by Splitting Energy Bands.

The understanding and manipulation of anisotropic Gilbert damping is crucial for both fundamental research and versatile engineering and optimization. Although several works on anisotropic damping have been reported, no direct relationship between the band structure and anisotropic damping was established. Here, we observed an anisotropic damping in Fe/GeTe manipulated by the symmetric band structures of GeTe via angle-resolved photoemission spectroscopy. Moreover, the anisotropic damping can be modified by the symmetry of band structures. Our Letter provides insightful understandings of the anisotropic Gilbert damping in ferromagnets interfaced with Rashba semiconductors and suggests the possibility of manipulating the Gilbert damping by band engineering.

Apolipoprotein A-1 protected hepatic ischaemia-reperfusion injury through suppressing macrophage pyroptosis via TLR4-NF-κB pathway.

BACKGROUND AND AIMS: Apolipoprotein A-1 (ApoA-1), the major apolipoprotein of high-density lipoprotein, plays anti-atherogenic role in cardiovascular diseases and exerts anti-inflammation effect in various inflammatory and infectious diseases. However, the role and mechanism of ApoA-1 in hepatic ischaemia-reperfusion (I/R) injury is unknown. METHODS: In this study, we measured ApoA-1 expression in human liver grafts after transplantation. Mice partial hepatic I/R injury model was made in ApoA-1 knockout mice, ApoA-1 mimetic peptide D-4F treatment mice and corresponding control mice to examine the effect of ApoA-1 on liver damage, inflammation response and cell death. Primary hepatocytes and macrophages were isolated for in vitro study. RESULTS: The results showed that ApoA-1 expression was down-regulated in human liver grafts after transplantation and mice livers subjected to hepatic I/R injury. ApoA-1 deficiency aggravated liver damage and inflammation response induced by hepatic I/R injury. Interestingly, we found that ApoA-1 deficiency increased pyroptosis instead of apoptosis during acute phase of hepatic I/R injury, which mainly occurred in macrophages rather than hepatocytes. The inhibition of pyroptosis compensated for the adverse impact of ApoA-1 deficiency. Furthermore, the up-regulated pyroptosis process was testified to be mediated by ApoA-1 through TLR4-NF-κB pathway and TLR4 inhibition significantly improved hepatic I/R injury. In addition, we confirmed that D-4F ameliorated hepatic I/R injury. CONCLUSIONS: Our study has identified the protective role of ApoA-1 in hepatic I/R injury through inhibiting pyroptosis in macrophages via TLR4-NF-κB pathway. The effect of ApoA-1 may provide a novel therapeutic approach for hepatic I/R injury.

A clinical indicator-based prognostic model predicting treatment outcomes of pulmonary tuberculosis: a prospective cohort study.

OBJECTIVES: Identifying prognostic factors helps optimize the treatment regimen and promote favorable outcomes. We conducted a prospective cohort study on patients with pulmonary tuberculosis to construct a clinical indicator-based model and estimate its performance. METHODS: We performed a two-stage study by recruiting 346 pulmonary tuberculosis patients diagnosed between 2016 and 2018 in Dafeng city as the training cohort and 132 patients diagnosed between 2018 and 2019 in Nanjing city as the external validation population. We generated a risk score based on blood and biochemistry examination indicators by the least absolute shrinkage and selection operator (LASSO) Cox regression. Univariate and multivariate Cox regression models were used to assess the risk score, and the strength of association was expressed as the hazard ratio (HR) and 95% confidence interval (CI). We plotted the receiver operating characteristic (ROC) curve and calculated the area under the curve (AUC). Internal validation was conducted by 10-fold cross-validation. RESULTS: Ten significant indicators (PLT, PCV, LYMPH, MONO%, NEUT, NEUT%, TBTL, ALT, UA, and Cys-C) were selected to generate the risk score. Clinical indicator-based score (HR: 10.018, 95% CI: 4.904-20.468, P < 0.001), symptom-based score (HR: 1.356, 95% CI: 1.079-1.704, P = 0.009), pulmonary cavity (HR: 0.242, 95% CI: 0.087-0.674, P = 0.007), treatment history (HR: 2.810, 95% CI: 1.137-6.948, P = 0.025), and tobacco smoking (HR: 2.499, 95% CI: 1.097-5.691, P = 0.029) were significantly related to the treatment outcomes. The AUC was 0.766 (95% CI: 0.649-0.863) in the training cohort and 0.796 (95% CI: 0.630-0.928) in the validation dataset. CONCLUSION: In addition to the traditional predictive factors, the clinical indicator-based risk score determined in this study has a good prediction effect on the prognosis of tuberculosis.

MicroRNA-588 regulates the invasive, migratory and vasculogenic mimicry-forming abilities of hypoxic glioma cells by targeting ROBO1.

BACKGROUND: The microenvironment of hypoxia is an important factor contributing to the development of glioblastoma (GBM). MicroRNA-588 and its potential target Roundabout-directed receptor 1 (ROBO1) have been reported to promote tumor invasion and proliferation in diseases such as gastric, pancreatic and hepatocellular carcinoma, while their function in GBM and response to hypoxic states remain elusive. METHODS: A microarray was leveraged to identify differentially expressed microRNAs in U251 glioma cells cultured under normoxic and hypoxic conditions. The expression of miR-588 was assessed using quantitative real-time PCR (qRT‒PCR). Gain- and loss-of-function studies were used to evaluate the role of miR-588 under hypoxic and normoxic conditions. Cell invasion, migration, proliferation, and vasculogenic mimicry (VM) formation experiments were performed. The relationship between miR-588 and ROBO1 was confirmed using western blot and luciferase reporter assays. Intracranial xenograft tumor mouse models were used to study the function of miR-588 in vivo. RESULTS: The expression of miR-588 was significantly upregulated in hypoxic glioma cells relative to normoxic glioma cells. miR-588 inhibited the invasive, migratory and VM-forming abilities of glioma cells in vitro and in vivo. Mechanistically, roundabout guidance receptor 1 (ROBO1) is a direct, functionally relevant target of miR-588 in glioma. ROBO1 knockdown suppressed the expression of matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9), thereby inhibiting the invasive, migratory and VM-forming abilities of glioma. CONCLUSIONS: MiR-588 regulated the behaviors of hypoxic glioma cells by targeting ROBO1. miR-588 can be used as a prognostic marker for glioma and has potential implications in glioma gene therapy.

Design and synthesis of novel anti-multidrug-resistant staphylococcus aureus derivatives of glycyrrhetinic acid by blocking arginine biosynthesis, metabolic and H2S biogenesis.

With the soaring number of multidrug-resistant bacteria, it is imperative to develop novel efficient antibacterial agents and discovery new antibacterial pathways. Herein, we designed and synthesized a series of structurally novel glycyrrhetinic acid (GA) derivatives against multidrug-resistant Staphylococcus aureus (MRSA). The in vitro antibacterial activity of these compounds was evaluated using the microbroth dilution method, agar plate coating experiments and real-time growth curves, respectively. Most of the target derivatives showed moderate antibacterial activity against Staphylococcus aureus (S. aureus) and MRSA (MIC = 3.125-25 µM), but inactivity against Escherichia coli (E. Coli) and Pseudomonas aeruginosa (P. aeruginosa) (MIC > 200 µM). Among them, compound 11 had the strongest antibacterial activity against MRSA, with an MIC value of 3.125 µM, which was 32 times and 64 times than the first-line antibiotics penicillin and norfloxacin, respectively. Additionally, transcriptomic (RNA-seq) and quantitative polymerase chain reaction (qPCR) analysis revealed that the antibacterial mechanism of compound 11 was through blocking the arginine biosynthesis and metabolic and the H2S biogenesis. Importantly, compound 11 was confirmed to have good biocompatibility through the in vitro hemolysis tests, cytotoxicity assays and the in vivo quail chicken chorioallantoic membrane (qCAM) experiments. Current study provided new potential antibacterial candidates from glycyrrhetinic acid derivatives for clinical treatment of MRSA infections.

Mesenchymal stem cells, as glioma exosomal immunosuppressive signal multipliers, enhance MDSCs immunosuppressive activity through the miR-21/SP1/DNMT1 positive feedback loop.

BACKGROUND: The immunosuppressive microenvironment in glioma induces immunotherapy resistance and is associated with poor prognosis. Glioma-associated mesenchymal stem cells (GA-MSCs) play an important role in the formation of the immunosuppressive microenvironment, but the mechanism is still not clear. RESULTS: We found that GA-MSCs promoted the expression of CD73, an ectonucleotidase that drives immunosuppressive microenvironment maintenance by generating adenosine, on myeloid-derived suppressor cells (MDSCs) through immunosuppressive exosomal miR-21 signaling. This process was similar to the immunosuppressive signaling mediated by glioma exosomal miR-21 but more intense. Further study showed that the miR-21/SP1/DNMT1 positive feedback loop in MSCs triggered by glioma exosomal CD44 upregulated MSC exosomal miR-21 expression, amplifying the glioma exosomal immunosuppressive signal. Modified dendritic cell-derived exosomes (Dex) carrying miR-21 inhibitors could target GA-MSCs and reduce CD73 expression on MDSCs, synergizing with anti-PD-1 monoclonal antibody (mAb). CONCLUSIONS: Overall, this work reveals the critical role of MSCs in the glioma microenvironment as signal multipliers to enhance immunosuppressive signaling of glioma exosomes, and disrupting the positive feedback loop in MSCs with modified Dex could improve PD-1 blockade therapy.

Resilience level and its association with maladaptive coping behaviours in the COVID-19 pandemic: a global survey of the general populations.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has induced a significant global concern on mental health. However few studies have measured the ability of individuals to "withstand setbacks, adapt positively, and bounce back from adversity" on a global scale. We aimed to examine the level of resilience, its determinants, and its association with maladaptive coping behaviours during the pandemic. METHODS: The Association of Pacific Rim Universities (APRU) conducted a global survey involving 26 countries by online, self-administered questionnaire (October 2020-December 2021). It was piloted-tested and validated by an expert panel of epidemiologists and primary care professionals. We collected data on socio-demographics, socioeconomic status, clinical information, lifestyle habits, and resilience levels measured by the Brief Resilience Scale (BRS) among adults aged ≥ 18 years. We examined factors associated with low resilience level, and evaluated whether low resilience was correlated with engagement of maladaptive coping behaviours. RESULTS: From 1,762 surveys, the prevalence of low resilience level (BRS score 1.00-2.99) was 36.4% (America/Europe) and 24.1% (Asia Pacific). Young age (18-29 years; adjusted odds ratio [aOR] = 0.31-0.58 in older age groups), female gender (aOR = 1.72, 95% C.I. = 1.34-2.20), poorer financial situation in the past 6 months (aOR = 2.32, 95% C.I. = 1.62-3.34), the presence of one (aOR = 1.56, 95% C.I. = 1.19-2.04) and more than two (aOR = 2.32, 95% C.I. = 1.59-3.39) medical conditions were associated with low resilience level. Individuals with low resilience were significantly more likely to consume substantially more alcohol than usual (aOR = 3.84, 95% C.I. = 1.62-9.08), take considerably more drugs (aOR = 12.1, 95% C.I. = 2.72-54.3), buy supplements believed to be good for treating COVID-19 (aOR = 3.34, 95% C.I. = 1.56-7.16), exercise less than before the pandemic (aOR = 1.76, 95% C.I. = 1.09-2.85), consume more unhealthy food than before the pandemic (aOR = 2.84, 95% C.I. = 1.72-4.67), self-isolate to stay away from others to avoid infection (aOR = 1.83, 95% C.I. = 1.09-3.08), have an excessive urge to disinfect hands for avoidance of disease (aOR = 3.08, 95% C.I. = 1.90-4.99) and transmission (aOR = 2.54, 95% C.I. = 1.57-4.10). CONCLUSIONS: We found an association between low resilience and maladaptive coping behaviours in the COVID-19 pandemic. The risk factors identified for low resilience in this study were also conditions known to be related to globalization-related economic and social inequalities. Our findings could inform design of population-based, resilience-enhancing intervention programmes.

Early Pregnancy Fetal Facial Ultrasound Standard Plane-Assisted Recognition Algorithm.

OBJECTIVES: Ultrasound screening during early pregnancy is vital in preventing congenital disabilities. For example, nuchal translucency (NT) thickening is associated with fetal chromosomal abnormalities, particularly trisomy 21 and fetal heart malformations. Obtaining accurate ultrasound standard planes of a fetal face during early pregnancy is the key to subsequent biometry and disease diagnosis. Therefore, we propose a lightweight target detection network for early pregnancy fetal facial ultrasound standard plane recognition and quality assessment. METHODS: First, a clinical control protocol was developed by ultrasound experts. Second, we constructed a YOLOv4 target detection algorithm based on the backbone network as GhostNet and added attention mechanisms CBAM and CA to the backbone and neck structure. Finally, key anatomical structures in the image were automatically scored according to a clinical control protocol to determine whether they were standard planes. RESULTS: We reviewed other detection techniques and found that the proposed method performed well. The average recognition accuracy for six structures was 94.16%, the detection speed was 51 FPS, and the model size was 43.2 MB, and a reduction of 83% compared with the original YOLOv4 model was obtained. The precision for the standard median sagittal plane was 97.20%, and the accuracy for the standard retro-nasal triangle view was 99.07%. CONCLUSIONS: The proposed method can better identify standard or non-standard planes from ultrasound image data, providing a theoretical basis for automatic acquisition of standard planes in the prenatal diagnosis of early pregnancy fetuses.

Does music intervention relieve depression or anxiety in people living with dementia? A systematic review and meta-analysis.

BACKGROUND: This study aimed to summarize the available evidence on music intervention alleviating depression or anxiety in dementia. METHODS: A comprehensive literature search was performed to analyze the effects of music intervention on depression or anxiety. Subgroups were created to explore the effect of intervention period, duration, and frequency on efficacy. The effect size was reported as a mean standardized difference (SMD) with 95% confidence interval (CI). RESULTS: The analysis included 19 articles involving 614 samples. Thirteen studies for relieving depression revealed that, with an increase in intervention period, the efficacy decreased and then increased, whereas with an increase of intervention duration, the effect became better. A weekly intervention is ideal. Seven studies verifying the impact on anxiety relief revealed that the effect of intervention within 12 wk is significant; with an increase of intervention duration, the effect became better. A weekly intervention is ideal. Collaborative analysis showed that long low-frequency interventions are more efficient than short high-frequency interventions. CONCLUSIONS: Music intervention can relieve depression or anxiety in people living with dementia. Weekly short interventions of more than 45 min are effective for emotional regulation. Future research should concentrate on severe dementia and follow-up impact.

A Machine Learning Model Based on GRU and LSTM to Predict the Environmental Parameters in a Layer House, Taking CO2 Concentration as an Example.

In a layer house, the CO2 (carbon dioxide) concentration above the upper limit can cause the oxygen concentration to be below the lower limit suitable for poultry. This leads to chronic CO2 poisoning in layers, which manifests as listlessness, reduced appetite, weak constitution, decreased production performance, and weakened resistance to disease. Regulating ventilation may ensure a suitable CO2 concentration in layer houses. Predicting the changes in CO2 concentration and regulating the CO2 concentration in advance are key to ensuring healthy large-scale breeding of layers. In recent years, machine learning and deep learning methods have been increasingly applied to this field. A CO2 prediction model for layer house is proposed based on a GRU (gated recurrent unit) and LSTM (long short-term memory). The temperature, humidity, and CO2 were determined as inputs to the model by the correlation coefficient. The datasets of the experimental layer house were continuously measured during June-July 2023, using a self-developed environmental monitor, and the monitored data were used as samples for model inputs. There were 22,000 time series data in the datasets. In this study, multivariate time series data were standardized via data pre-processing to improve model training. GRU and LSTM models were constructed. The models were trained using a training set. Then, these trained models were used to provide predictions on a test set. The prediction errors were calculated using the true values of the test set and the predicted values provided by the models. To test the performance of the model and accuracy of the predictions, predictions were made for different numbers of datasets. The results demonstrated that the combined prediction model had good generalization, stability, and convergence with high prediction accuracy. Due to the structure of the model, the stability of the LSTM model was higher than that of the GRU model, and its prediction accuracy and speed were lower than those of the GRU model. When the datasets of the GRU model were 15,000 to 17,000, The MAE of the GRU was 70.8077 to 126.7029 ppm, and the prediction time of the GRU is 16 to 24 ms. When the LSTM model's datasets were 15,000-20,000, the MAE of LSTM was 78.8596 to 136.0896 ppm, and the prediction time of the GRU was 17 to 26 ms.

EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3.

BACKGROUND: Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), a newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in the pathophysiological processes and TME remodelling of various tumours. METHODS: CircRNA sequencing analysis was performed to explore circRNA expression profiles in normal and glioma tissues. The biological function of a novel circRNA, namely, circNEIL3, in glioma development was confirmed both in vitro and in vivo. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation (RIP), luciferase reporter, and co-immunoprecipitation assays were conducted. RESULTS: We identified circNEIL3, which could be cyclized by EWS RNA-binding protein 1(EWSR1), to be upregulated in glioma tissues and to correlate positively with glioma malignant progression. Functionally, we confirmed that circNEIL3 promotes tumorigenesis and carcinogenic progression of glioma in vitro and in vivo. Mechanistically, circNEIL3 stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3) protein, a known oncogenic protein, by preventing HECTD4-mediated ubiquitination. Moreover, circNEIL3 overexpression glioma cells drives macrophage infiltration into the tumour microenvironment (TME). Finally, circNEIL3 is packaged into exosomes by hnRNPA2B1 and transmitted to infiltrated tumour associated macrophages (TAMs), enabling them to acquire immunosuppressive properties by stabilizing IGF2BP3 and in turn promoting glioma progression. CONCLUSIONS: This work reveals that circNEIL3 plays a nonnegligible multifaceted role in promoting gliomagenesis, malignant progression and macrophage tumour-promoting phenotypes polarization, highlighting that circNEIL3 is a potential prognostic biomarker and therapeutic target in glioma.

miR-3184-3p enriched in cerebrospinal fluid exosomes contributes to progression of glioma and promotes M2-like macrophage polarization.

Liquid biopsy is a novel strategy for tumour diagnosis. The contents of cerebrospinal fluid (CSF) exosomes could reflect glioma status, hence sampling exosomes from CSF is a means of liquid biopsy for glioma. However, few studies have focused on the function of microRNAs in CSF exosomes. In this study, we found that miR-3184-3p was enriched in CSF exosomes in glioma patients and was downregulated after tumour resection. We found that miR-3184 facilitates glioma progression in two ways. On the one hand, miR-3184 directly promotes proliferation, migration, and invasion while inhibiting apoptosis in glioma. On the other hand, miR-3184 in glioma-derived exosomes polarizes macrophages to an M2-like phenotype, which further aggravates tumour progression. Overall, the current findings uncovered a new mechanism and highlighted the significant role of miR-3184 in glioma progression. Furthermore, exosomal miR-3184 could be a considerable factor with potential applications in glioma diagnosis and treatment in the future.

Elevated levels of body mass index and waist circumference, but not high variability, are associated with an increased risk of atrial fibrillation.

BACKGROUND: Although obesity has been associated with risk of atrial fibrillation (AF), the associations of variability of obesity measures with AF risk are uncertain, and longitudinal studies among Chinese population are still lacking. We aimed to evaluate the impacts of obesity and variability of body mass index (BMI) and waist circumference (WC) on the risk of atrial fibrillation (AF) in a large Chinese cohort study. METHODS: A total of 44,135 participants of the Kailuan Study who were free of cancer and cardiovascular disease and underwent three consecutive surveys from 2006 to 2010 were followed for incident AF until 2020. Average BMI and WC over time and variability were calculated. Cox proportional hazards regression models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of obesity and variability in BMI and WC with AF risk. RESULTS: During a mean follow-up of 9.68 years, there were 410 cases of incident AF. In multivariable-adjusted models, compared with normal BMI/WC, individuals with general obesity and abdominal obesity had increased risk of AF, with corresponding HRs of 1.73 (95% CI: 1.31-2.30) and 1.38 (95% CI: 1.11-1.60), respectively. The short-term elevation in AF risk persisted for the obese even after adjustment for updated biologic intermediaries and weight. Variability in BMI and WC were not associated with the risk of AF. The restricted cubic spline models indicated significant linear relationships between levels of WC and BMI and risk of AF. CONCLUSIONS: Elevated levels of BMI and WC were associated with an increased risk of AF, whereas variability in BMI and WC were not. Therefore, achieving optimal levels of BMI and WC could be valuable in AF prevention.