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Abstract Lysine-specific demethylase 1 (LSD1), a histone demethylating enzyme, plays a crucial role in cancer metastasis. Studies show LSD1 knockout promotes breast cancer lung metastasis, but it’s unknown if it alters the lung microenvironment for metastasis. In this study, we investigated the effects of exosomes from LSD1-knockdown (LSD1 KD) breast cancer cells on pre-metastatic niche formation. Injecting exosomes from LSD1 KD cells in mice resulted in a substantial increase in lung colonization by breast cancer cells, while treatment with exosomes derived from LSD1 KD cells decreased the expression of the ZO-1 and occludin, leading to increased vascular permeability. The LSD1 KD reduced the expression of circDOCK1, which augmented the levels of miR-1270 in exosomes. And miR-1270 inhibited ZO-1 expression in human endothelial cells, which enhanced their permeability. Our study uncovered a novel mechanism in which the LSD1 promotes the formation of pre-metastatic niches via the regulation of exosomal miRNA.

Abstract Background Acute lung injury (ALI) is the most lethal disease associated with sepsis, and there is a lack of effective drug treatment. As the major cells of sepsis-induced ALI, macrophages polarize toward the proinflammatory M1 phenotype and secrete multiple inflammatory cytokines to accelerate the disease process through nuclear factor kappa-B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways. Taraxerone, the main component of the Chinese medicinal Sedum, possesses numerous biological activities. However, uncertainty remains regarding the potential of taraxerone to protect against sepsis-induced ALI. This study aimed to investigate the effects and mechanisms of taraxerone against ALI. Methods An animal model for ALI was established by cecal ligation and puncture and treated with taraxerone via intraperitoneal administration. The protective effect of taraxerone on the lungs was analyzed using H&E staining, dihydroethidium staining, ELISA kits, cell counting, myeloperoxidase kit, malondialdehyde kit, glutathione kit, superoxide dismutase kit and flow cytometry. Western blotting, RT-PCR, flow cytometry, co-immunoprecipitation, and immunofluorescence were used to investigate the regulatory of taraxerone on SIRT1. Results Our study demonstrates for the first time that taraxerone can activate SIRT1 in macrophages, promoting SIRT1 activity. This activation inhibited the NF-κB signaling pathway primarily through the dephosphorylation and deacetylation of p65. Simultaneously, taraxerone disrupted the NLRP3 inflammasome signaling pathway, thereby alleviating M1 polarization of macrophages and mitigating sepsis-induced pulmonary inflammation and oxidative stress. In vivo, EX527 was used to validate the anti-inflammatory and anti-oxidative stress effects of taraxerone mediated by SIRT1. Conclusion SIRT1-mediated anti-inflammatory and anti-oxidative stress effects may be important targets for taraxerone in treating ALI.

Abstract Listeria monocytogenes (LM) possesses the ability to breach multiple barriers and elicit intricate immune responses. However, there remains a lack of explicit understanding regarding how LM evades innate immune surveillance within the body. Here, we utilized liver intravital imaging to elucidate the dynamic process of LM during infection in the liver. We discovered that LM can rapidly escape from Kupffer cells (KCs) through listeriolysin O (LLO) and proliferate within hepatocytes. Upon LM exposure to the hepatic sinusoids, neutrophils rapidly aggregate at the site of infection. Subsequently, LM can induce type I interferon (IFN-I) production primarily in the spleen, which acts systemically on neutrophils to hamper their swarming by deactivating the ERK pathway, thus evading neutrophil-mediated eradication. Furthermore, our findings suggest that virus-induced IFN-I suppresses neutrophil swarming, and COVID-19 patients exhibit impaired neutrophil aggregation function. In conclusion, our findings provide compelling evidence demonstrating that intracellular bacteria represented by LM can hijack host defense mechanisms against viral infections to evade immune surveillance. Additionally, impaired neutrophil swarming caused by IFN-I is one of the significant factors contributing to the increased susceptibility to bacterial infections following viral infections.

Introduction Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that arises from complex interactions between genetics, environment and gut microbiota. It encompasses Crohn’s disease, ulcerative colitis and IBD-unclassified. The protracted course of IBD imposes a significant burden on patients’ quality of life, economic productivity, social functioning, as well as treatment, hospitalisation and surgery. This study aims to conduct an umbrella review of meta-analyses to systematically evaluate the methodology’s quality, potential biases and validity of all epidemiological evidence focused on risk factors for IBD while providing an overview of the evidence concerning IBD risk factors.Methods and analysis We will systematically search, extract and analyse data from reported systematic reviews and meta-analyses that specifically focus on the risk factors of IBD, following the guidelines outlined in Preferred Reporting Items for Overviews of Reviews. Our search will encompass PubMed, Embase, Web of Science and the Cochrane Database of Systematic Reviews from the initial period up until April 2023 (last update), targeting systematic reviews and meta-analyses based on non-interventional studies. Inclusion criteria allow for systematic reviews and meta-analyses evaluating IBD risk factors across all countries and settings, regardless of ethnicity or sex. The identified risk factors will be categorised according to the health ecological model into innate personal traits, behavioural lifestyles, interpersonal networks, socioeconomic status and macroenvironments. To assess methodological quality for each meta-analysis included in our study, two authors will employ a measurement tool to assess the methodological quality of systematic reviews (AMSTAR)-2, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria along with evidence classification criteria.Ethics and dissemination Ethical approval is not required for this umbrella review. We will seek to submit the results for publication in a peer-reviewed journal or present it at conferences.PROSPERO registration number CRD42023417175.

Optimizing water and nitrogen (N) utilization to enhance crop yields under resource constraints is crucial. Straw and its biochar, combined with N fertilizer, are commonly used to improve soil carbon storage and crop growth. However, the effects of straw and N fertilizer management on water consumption, root and shoot characteristics, N uptake, and maize productivity remain unclear. To address this knowledge gap, a three-year (2019–2021) field experiment was conducted in Northwest China. We compared two straw incorporation methods [straw (SI) and straw-derived biochar (BI)] with straw removal (NI) at four N application rates [0 (N0), 225 (N225), 300 (N300), and 375 kg ha–1 (N375)]. Results indicated that compared with NI, both SI and BI significantly increased grain yield (GY), N uptake, and water productivity (WP) (SI < BI; P < 0.05). The maximum GYs were achieved with SIN300 and BIN225, respectively. Notably, compared with SIN300, BIN225 significantly enhanced GY by 10.8% and 5.8% and improved WP by 19.2% and 9.9% (P < 0.05). This improvement was mainly attributed to the increased water consumption after tasseling and crop transpiration (T) in evapotranspiration (ET). Furthermore, N application resulted in increased root distribution in shallow soil layers (0–0.3 m). Under BIN225, roots exhibited a longer, thinner and deeper profile, minimizing root redundancy and enhancing root efficiency in water and N absorption during the reproductive stage of maize. In contrast, SIN300 resulted in shorter, thicker, and shallower roots, leading to a reduced shoot-root ratio of 12.2% (P < 0.05). Based on the normalization and fitting curves, BI combined with reduced N (240 kg ha–1) improved WP by 24.5%, achieving 98.7% of the maximum GY for drip-irrigated maize (16.98 Mg kg–1). Overall, these findings provide a novel straw strategy for sustainable field management in arid irrigation agriculture and similar ecosystems.

Background: Predicting the severity of acute pancreatitis (AP) early poses a challenge in clinical practice. While there are well-established clinical scoring tools, their actual predictive performance remains uncertain. Various studies have explored the application of machine-learning methods for early AP prediction. However, a more comprehensive evidence-based assessment is needed to determine their predictive accuracy. Hence, this systematic review and meta-analysis aimed to evaluate the predictive accuracy of machine learning in assessing the severity of AP. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched until December 5, 2023. The risk of bias in eligible studies was assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Subgroup analyses, based on different machine learning types, were performed. Additionally, the predictive accuracy of mainstream scoring tools was summarized. Results: This systematic review ultimately included 33 original studies. The pooled c-index in both the training and validation sets was 0.87 (95 % CI: 0.84–0.89) and 0.88 (95 % CI: 0.86–0.90), respectively. The sensitivity in the training set was 0.81 (95 % CI: 0.77–0.84), and in the validation set, it was 0.79 (95 % CI: 0.71–0.85). The specificity in the training set was 0.84 (95 % CI: 0.78–0.89), and in the validation set, it was 0.90 (95 % CI: 0.86–0.93). The primary model incorporated was logistic regression; however, its predictive accuracy was found to be inferior to that of neural networks, random forests, and xgboost. The pooled c-index of the APACHE II, BISAP, and Ranson were 0.74 (95 % CI: 0.68–0.80), 0.77 (95 % CI: 0.70–0.85), and 0.74 (95 % CI: 0.68–0.79), respectively. Conclusions: Machine learning demonstrates excellent accuracy in predicting the severity of AP, providing a reference for updating or developing a straightforward clinical prediction tool.

Abstract Federated Learning (FL) suffers from the Non-IID problem in practice, which poses a challenge for efficient and accurate model training. To address this challenge, prior research has introduced clustered FL (CFL), which involves clustering clients and training them separately. Despite its potential benefits, CFL can be computationally and communicationally expensive when the data distribution is unknown beforehand. This is because CFL involves the entire neural networks of involved clients in computing the clusters during training, which can become increasingly time-consuming with large-sized models. To tackle this issue, this paper proposes an efficient CFL approach called LayerCFL that employs a Layer-wised clustering technique. In LayerCFL, clients are clustered based on a limited number of layers of neural networks that are pre-selected using statistical and experimental methods. Our experimental results demonstrate the effectiveness of LayerCFL in mitigating the impact of Non-IID data, improving the accuracy of clustering, and enhancing computational efficiency.

Abstract Background Acute lung injury (ALI) is a severe disease that can lead to acute respiratory distress syndrome (ARDS), characterized by intractable hypoxemia, poor lung compliance, and respiratory failure, severely affecting patients' quality of life. The pathogenesis of ALI has not been fully elucidated yet, and sepsis is an important cause of ALI. Among the organ injuries caused by sepsis, the lungs are the earliest damaged ones. Radix cyathulae is reported to have analgesic, anti-inflammatory, and anti-aging effects. Cyasterone is extracted from Radix cyathulae. However, it is not known whether cyasterone has protective effects for ALI. This study aims to investigate the effect of cyasterone on sepsis-related ALI and its mechanism. Methods We used the cecal ligation peferation (CLP) method to establish a mouse sepsis model, and cyasterone was given intraperitoneally on days 1–3 to observe its preventive effect on sepsis-related acute lung injury. Primary murine peritoneal macrophages were used to investigate the molecular mechanism of cyasterone in vitro. Results Cyasterone pretreatment inhibits pro-inflammatory cytokine production, NLRP3 inflammasome activation, and oxidative stress in vivo and in vitro. In addition, cyasterone attenuates sepsis-induced ALI by activating nuclear factor erythroid2-related factor (Nrf2), which may be associated with AKT(Ser473)/GSK3β(Ser9) pathway activation. Conclusions Cyasterone defends against sepsis-induced ALI by inhibiting inflammatory responses and oxidative stress, which depends heavily on the upregulation of the Nrf2 pathway through phosphorylation of AKT(Ser473)/GSK3β(Ser9). These results suggest cyasterone may be a valuable drug candidate for preventing sepsis-related ALI.

The growth status of winter wheat seedlings during the greening period is called the seedling situation. Timely and accurate determinations of the seedling situation type are important for subsequent field management measures and yield estimation. To solve the problems of low-efficiency artificial classification, subjective doping, inaccurate classification, and overfitting in transfer learning in classifying the seedling condition of winter wheat seedlings during the greening period, we propose an improved ConvNeXt winter wheat seedling status classification and identification network based on the pre-training–fine-tuning model addressing over-fitting in transfer learning. Based on ConvNeXt, a SETFL-ConvNeXt network (Squeeze and Excitation attention-tanh ConvNeXt using focal loss), a winter wheat seedling identification and grading network was designed by adding an improved SET attention module (Squeeze and Excitation attention-tanh) and replacing the Focal Loss function. The accuracy of the SETFL-ConvNeXt reached 96.68%. Compared with the classic ConvNeXt model, the accuracy of the Strong class, First class, and Third class increased by 1.188%, 2.199%, and 0.132%, respectively. With the model, we also compared the effects of different optimization strategies, five pre-training-fine-tuning models, and the degree of change in the pre-trained model. The accuracy of the fine-tuning models trained in the remaining layers increased by 0.19–6.19% using the last three frozen blocks, and the accuracy of the pre-trained model increased by 3.1–8.56% with the least degree of change method compared with the other methods. The SETFL-ConvNeXt network proposed in this study has high accuracy and can effectively address overfitting, providing theoretical and technical support for classifying winter wheat seedlings during the greening period. It also provides solutions and ideas for researchers who encounter overfitting.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the infiltration of inflammatory cells and proliferation of synovial cells. It can cause cartilage and bone damage as well as disability and is regarded as an incurable chronic disease. Available therapies cannot prevent the development of diseases due to the high toxicity of the therapeutic agents and the inefficient drug delivery. Ferroptosis, an iron-dependent manner of lipid peroxidative cell death, indicates great potential for RA therapy due to ability to damage the infiltrated inflammatory cells and proliferated fibroblast-like synoviocytes. Here, we use macrophages as vector to deliver Fe3O4 nanoparticles and sulfasalazine (SSZ) for ferroptosis and photothermal therapy of RA. The inherent property of migration towards the inflamed joints under the guidance of inflammatory factors enables macrophages to targetedly deliver the payload into the RA. Upon the irradiation of the near infrared light, the Fe3O4 nanoparticles convert the light into heat to damage the proliferated synovium. Meanwhile, the iron released from Fe3O4 nanoparticles works with SSZ to generate synergetic ferroptosis effect. The resident inflammatory cells and proliferated synovium are efficiently damaged by the ferroptosis and photothermal effect, showing pronounced therapeutic effect for RA.

Abstract Background Minimal change disease (MCD) is a major cause of nephrotic syndrome (NS) in children and a minority of adults. The higher tendency to relapse put patients at risk for prolonged exposure to steroids and other immunosuppressive agents. B cell depletion with rituximab (RTX) may be beneficial to the treatment and prevention of frequently relapsing MCD. Therefore, this study aimed to verify the therapeutic/preventive effects of low-dose RTX on the relapse in adult with MCD. Methods A total of 33 adult patients were selected for the study, including 22 patients with relapsing MCD in relapse treatment group who were treated with low-dose RTX (200 mg per week × 4 following by 200 mg every 6 months) and 11 patients in relapse prevention group with complete remission (CR) after steroid therapy were treated with RTX (200 mg ×1 every 6 months) for preventing the relapse of MCD. Results Of the 22 patients with MCD in relapse treatment group, there were 21 cases (95.45%) of remission [2 (9.09%) partial remission (PR), 19 (86.36%) CR], 1 (4.56%) no remission (NR) and 20 (90.90%) relapse-free. The Median duration of sustained remission was 16.3 months (3, 23.5 months, inter quartile range (IQR)). 11 patients in the relapse prevention group during a follow-up of 12 months (9–31 months) had no relapse. The average dose of prednisone in two groups after RTX treatment was significantly lower than before treatment. Conclusion The results of this study suggested low-dose RTX can significantly reduce relapse rate and steroid dose in adults with MCD with fewer side effects. Low-dose RTX regimens may be beneficial for the treatment of relapsing MCD in adults and may be the preferred regimen for patients at high risk for the development of adverse events from corticosteroids.

Artemisinin has an endoperoxide bridge structure, which can be cleaved by ferrous ions to generate various carbonyl radicals in an oxygen-independent manner, highlighting its potential for treating hypoxic tumors. In our study, we fabricated Tween 80 micelles loaded with Fe3O4 nanoparticles and artemisinin for cancer therapy. The synthesized Fe3O4 nanoparticles and drug-loaded micelles have particle sizes of about 5 nm and 80 nm, respectively, both exhibiting excellent dispersibility and stability. After uptake by MCF-7 cells, drug-loaded micelles release Fe2+ and ART into the cytoplasm, effectively inducing the generation of reactive oxygen species (ROS) in hypoxic conditions, thereby enhancing toxicity against cancer cells. In vitro and in vivo studies have demonstrated that ART and Fe3O4 nanoparticles are encapsulated in Tween 80 to form micelles, which effectively prevent premature release during circulation in the body. Although free ART and Fe3O4 nanoparticles can inhibit tumor growth, TW80-Fe3O4-ART micelles demonstrate a more pronounced inhibitory effect, with a tumor suppression rate of up to 85%. A novel strategy based on artemisinin and ferroptosis is thus offered, holding a favorable prospect for hypoxic cancer therapy.

Abstract Intra/extracellular ion content affects the growth and metastasis of tumor cells, as well as the efficacy of various antitumor therapies. Herein, a carbonic anhydrase inhibitor (CAI) is loaded onto pH‐responsive calcium carbonate (CaCO3) nanoparticles and then modify theses nanoparticles with liposomes to obtain biocompatible CaCO3/CAI@Lipsome (CCL) for enhance tumor radio‐immunotherapy. CCL can specially decompose in tumor microenvironment, releasing calcium ion (Ca2+) and CAI, as well as increasing the pH value of extracellular fluid. CAI restrains the flow of hydrogen ion (H+) inside and outside the tumor cells, resulting in the reversal of tumor acidic microenvironment and the increase of intracellular H+, both of which can improve the sensitivity of tumor to radiotherapy. Afterward, the increased intracellular H+ together with radiotherapy‐causes reactive oxygen species promotes calcium influx, leading to cellular calcium overload. Moreover, the CCL‐tailored content of H+ and Ca2+ strengthens radiotherapy‐induced immunogenic cell death and dendritic cell maturation, amplifying systemic anti‐tumor adaptive immunity. Meanwhile, macrophages in the CCL‐treated tumors are polarized from pro‐tumor M2 to anti‐tumor M1 under X‐ray exposure, owing to the neutralization of tumor acidic microenvironment and enhances Ca2+ content. Therefore, multi‐directional regulation of the intra/extra tumor cell pH/calcium by simple nano‐preparation would provide a powerful way to improve the efficacy of radio‐immunotherapy.

The senescence of alveolar epithelial cells (AECs) and fibroblasts plays a pivotal role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a condition lacking specific therapeutic interventions. Curculigoside (CCG), a prominent bioactive constituent of Curculigo, exhibits anti-osteoporotic and antioxidant activities. Our investigation aimed to elucidate the anti-senescence and anti-fibrotic effects of CCG in experimental pulmonary fibrosis and delineate its underlying molecular mechanisms. Our findings demonstrate that CCG attenuates bleomycin-induced pulmonary fibrosis and lung senescence in murine models, concomitantly ameliorating lung function impairment. Immunofluorescence staining for senescence marker p21, alongside SPC or α-SMA, suggested that CCG’s mitigation of lung senescence correlates closely with the deceleration of senescence in AECs and fibroblasts. In vitro, CCG mitigated H2O2-induced senescence in AECs and the natural senescence of primary mouse fibroblasts. Mechanistically, CCG can upregulate SIRT1 expression, downregulating P300 expression, enhancing Trim72 expression to facilitate P300 ubiquitination and degradation, reducing the acetylation levels of antioxidant enzymes, and upregulating their expression levels. These actions collectively inhibited endoplasmic reticulum stress (ERS) and alleviated senescence. Furthermore, the anti-senescence effects and mechanisms of CCG were validated in a D-galactose (D-gal)-induced progeroid model. This study provides novel insights into the mechanisms underlying the action of CCG in cellular senescence and chronic diseases, offering potential avenues for the development of innovative drugs or therapeutic strategies.

Currently, the treatment for sepsis-induced acute lung injury mainly involves mechanical ventilation with limited use of drugs, highlighting the urgent need for new therapeutic options. As a pivotal aspect of acute lung injury, the pathologic activation and apoptosis of endothelial cells related to oxidative stress play a crucial role in disease progression, with NOX4 and Nrf2 being important targets in regulating ROS production and clearance. Echinacoside, extracted from the traditional Chinese herbal plant Cistanche deserticola, possesses diverse biological activities. However, its role in sepsis-induced acute lung injury remains unexplored. Moreover, although some studies have demonstrated the regulation of NOX4 expression by SIRT1, the specific mechanisms are yet to be elucidated. Therefore, this study aimed to investigate the effects of echinacoside on sepsis-induced acute lung injury and oxidative stress in mice and to explore the intricate regulatory mechanism of SIRT1 on NOX4. We found that echinacoside inhibited sepsis-induced acute lung injury and oxidative stress while preserving endothelial function. In vitro experiments demonstrated that echinacoside activated SIRT1 and promoted its expression. The activated SIRT1 was competitively bound to p22 phox, inhibiting the activation of NOX4 and facilitating the ubiquitination and degradation of NOX4. Additionally, SIRT1 deacetylated Nrf2, promoting the downstream expression of antioxidant enzymes, thus enhancing the NOX4-Nrf2 axis and mitigating oxidative stress-induced endothelial cell pathologic activation and mitochondrial pathway apoptosis. The SIRT1-mediated anti-inflammatory and antioxidant effects of echinacoside were validated in vivo. Consequently, the SIRT1-regulated NOX4-Nrf2 axis may represent a crucial target for echinacoside in the treatment of sepsis-induced acute lung injury.

Objective: Screening out potential herbal medicines and herbal ingredients for the treatment of gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis.Methods: Gene expression profiles of gastric tumour tissues and normal tissue samples were obtained from the GEO database and the samples were analysed for immune cell infiltration condition and differential expressed genes of ferroptosis. Key genes were screened by protein-protein interaction (PPI) and enrichment analysis, and molecular docking was used to predict and preliminary validate potential herbal and traditional Chinese medicine components for gastric cancer based on the key genes. Finally, RT-QPCR was used to validate the prediction results.Results: Immune cell infiltration analysis revealed high levels of infiltration of activated CD4 memory T cells, monocytes, M0 macrophages in gastric tumor tissues, while plasma cells and resting mast cells had higher levels of infiltration in the paraneoplastic tissues. Differential gene expression analysis identified 1,012 upregulated genes and 880 downregulated genes, of which 84 immune related differentially expressed genes such as CTSB, PGF and PLAU and 10 ferroptosis-related differentially expressed genes such as HSF1, NOX4 and NF2 were highly expressed in gastric cancer tissues. The results of enrichment analysis showed that they mainly involve 343 biological processes such as extracellular matrix organization and extracellular structural organization; 37 cellular components such as complexes of collagen trimer and basement membrane; 35 molecular functions such as signal receptor activator activity and receptor ligand activity; 19 regulatory pathways such as cytokine-cytokine receptor interactions and retinol metabolism. Finally, two key genes, TLR4 and KRAS, were selected and 12 herbal medicines such as Radix Salviae liguliobae, Rhizoma Coptidis, Rhizoma Polygoni cuspidati and 27 herbal ingredients such as resveratrol, salvianolic acid b were predicted on the basis of key genes. Molecular docking results showed that KRAS binds tightly to coumarin and magnolol, while TLR4 can bind tightly to resveratrol, curcumin, salvianolic acid b, shikonin. Subsequently, the effect of resveratrol and magnolol was experimentally verified.Conclusion: Herbal medicines such as S. liguliobae, Rhizoma Coptidis, Rhizoma P. cuspidati and herbal ingredients such as resveratrol, curcumin, salvianolic acid b may provide research directions and alternative therapeutic approaches for immunomodulation of TME and ferroptosis of tumour cells in gastric cancer.

This study investigates the opening size effect of a novel short fiber reinforced quasi-isotropic composite laminate with unidirectionally arrayed chopped strands (UACS) under tensile load by approaches of simulations and experiments. The layup of [45/0/-45/90]s was used to fabricate novel carbon fiber laminates with various central hole diameter from 4 mm to 10 mm. Low notch sensitivity and strength reduction rate were observed in UACS open-hole laminates. It was found that when the width diameter ratio (d/w) of UACS laminate with open-hole is less than 20%, 80% of the original strength can be maintained, which can greatly reduce the design safety factor. Compared with continuous fiber laminates, high increase rate of strength reduction rate was induced by bi-angled slits with the increasing of open hole diameter. The strain distribution around the hole was affected significantly by bi-angled slits, which also inhibited the initiation and propagation of delamination effectively. The strain concentration factor of UACS laminates increases with the increasing open hole diameter. The damage progression of notched and unnotched UACS laminates were analyzed by simulation method, which are consistent well with experimental results.

BackgroundUnderstanding which group of patients with type 2 diabetes will have the most glucose lowering response to certain medications (which target different aspects of glucose metabolism) is the first step in precision medicine.AimsWe hypothesized that people with type 2 diabetes who generally have high insulin resistance, such as people of Māori/Pacific ethnicity, and those with obesity and/or hypertriglyceridemia (OHTG), would have greater glucose-lowering by pioglitazone (an insulin sensitizer) versus vildagliptin (an insulin secretagogue).MethodsA randomised, open-label, two-period crossover trial was conducted in New Zealand. Adults with type 2 diabetes, HbA1c>58mmol/mol (>7.5%), received 16 weeks of either pioglitazone (30mg) or vildagliptin (50mg) daily, then switched to the other medication over for another 16 weeks of treatment. Differences in HbA1c were tested for interaction with ethnicity or OHTG, controlling for baseline HbA1c using linear mixed models. Secondary outcomes included weight, blood pressure, side-effects and diabetes treatment satisfaction.Results346 participants were randomised (55% Māori/Pacific) between February 2019 to March 2020. HbA1c after pioglitazone was lower than after vildagliptin (mean difference -4.9mmol/mol [0.5%]; 95% CI -6.3, -3.5; p

Abstract Background The effects of COVID-19 lockdown measures on maternal and fetal health remain unclear. We examined the associations of COVID-19 lockdown with gestational length and preterm birth (PTB) in a Chinese population. Methods We obtained medical records of 595,396 singleton live infants born between 2015 and 2020 in 5 cities in Guangdong Province, South China. The exposed group (N = 101,900) included women who experienced the COVID-19 Level I lockdown (1/23–2/24/2020) during pregnancy, while the unexposed group (N = 493,496) included women who were pregnant during the same calendar months in 2015–2019. Cumulative exposure was calculated based on days exposed to different levels of emergency responses with different weighting. Generalized linear regression models were applied to estimate the associations of lockdown exposure with gestational length and risk of PTB (

BackgroundMany studies have shown that in the context of public health emergencies, the incidence rate of adolescent non-suicidal self-injury (NSSI) patients increased dramatically. This paper aims to characterize the behavioral characteristics of adolescent NSSI and analyze the influencing factors of NSSI behavior addiction characteristics.MethodsOur research was a case-control study which included 84 adolescents with NSSI (female vs. male: 59 vs. 25) and 84 healthy controls (female vs. male: 53 vs. 31). All the participants enrolled were aged 12-18 years. The differences in the scores of the following five scales were compared between the case and control groups: Egna Minnen Barndoms Uppfostran (EMBU), Perceived Social Support Scale (PSSS), Perceived Stress Scale (PSS); Bergen Social Media Addiction Scale (BSMAS) and Video Game Dependence Scale (VDG-S). The characteristics of NSSI behavior of the study group were evaluated using the Ottawa Self Inventory Chinese Revised Edition (OSIC). And a binary logistic regression model was developed to analyze the factors that influence adolescent NSSI behavioral addiction characteristics.ResultsIn the study group, the emotional warmth scores in the father’s and mother’s rearing style scores in the EMBU were significantly lower than the controls. The BSMAS and VDG-S scores were significantly higher than those in the control group. 38 cases of NSSI with addiction characteristics accounted for 45.24% in the study group. The risk factors for NSSI addiction traits were as follows: female, single-child, high level of VDG-S scores, high scores of excessive interferences in father’s rearing style, and high scores of punishments and excessive interferences in mother’s rearing style score.ConclusionFemale, only child, internet addiction, and negative parenting styles were predictors of NSSI behavioral addiction characteristics in adolescents. Targeted coping strategies should be developed to reduce the occurrence and development of self-injurious behavior, especially for female adolescents with Internet dependence in one-child families with negative parenting styles.

Graph-structured data, operating as an abstraction of data containing nodes and interactions between nodes, is pervasive in the real world. There are numerous ways dedicated to extract graph structure information explicitly or implicitly, but whether it has been adequately exploited remains an unanswered question. This work goes deeper by heuristically incorporating a geometric descriptor, the discrete Ricci curvature (DRC), in order to uncover more graph structure information. We present a curvature-based topology-aware graph transformer, termed Curvphormer. This work expands the expressiveness by using a more illuminating geometric descriptor to quantify the connections within graphs in modern models and to extract the desired structure information, such as the inherent community structure in graphs with homogeneous information. We conduct extensive experiments on a variety of scaled datasets, including PCQM4M-LSC, ZINC, and MolHIV, and obtain a remarkable performance gain on various graph-level tasks and fine-tuned tasks.

Soil aggregation plays a critical role in the maintenance of soil structure and crop productivity. Fertilization influences soil aggregation, especially by regulating soil organic carbon (SOC) and total nitrogen (TN) contents in aggregate fractions. Here, we conducted a fixed-site field experiment to quantify the effect of five N application rates: 0, 75, 150, 225, and 300 kg·N·ha−1, denoted as N0, N75, N150, N225, and N300, respectively, on soil aggregate stability, aggregate-associated SOC and TN sequestration and crop productivity. Soil aggregates were divided into >0.25 (>5, 5–2, 2–1, 1–0.5, 0.5–0.25) and 0.25 mm), decreased the proportion of micro-aggregates (5 mm macro-aggregates in N225 was significantly increased by 19.24% under dry sieving (p < 0.05). With the increase in N application rate, the bulk SOC and TN contents first increased and then decreased, and the SOC and TN of N225 were significantly increased by 17.75% and 72.33% compared with N0 (p < 0.05). More specifically, fertilization promoted the distribution and enrichment of SOC and TN in macro-aggregates and reduced the C/N of the micro-aggregates and the contribution of SOC and TN in the micro-aggregates. Compared with N0, the contribution rate of macro-aggregates to SOC and TN of N225 under wet sieving was significantly increased by 84.13 and 17.18%, respectively, while the C/N of micro-aggregates of N225 under wet and dry sieving methods was significantly decreased by 45.95 and 31.74%, respectively (p < 0.05). Moreover, fertilization improved the yield, and N225 significantly increased the total yield by 80.68% compared with N0 (p < 0.05). In conclusion, N225 was the suitable N application for improving soil aggregate stability, carbon and nitrogen sequestration, and crop productivity on the Loess Plateau, China.

Colorectal cancer (CRC) is a malignant tumor with the second highest morbidity and the third highest mortality in the world, while the therapeutic options of targeted agents remain limited. Here, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), known as the upstream of the NF-κB signaling pathway, was identified to be highly upregulated in CRC tumors and cell lines. Furthermore, the downregulation of MALT1 or inhibition of its proteolytic function by MI-2 suppressed the cell proliferation and migration of CRC cells. In vivo, suppressing the MALT1 expression or its proteasome activity effectively reduced the size of the subcutaneous tumor in nude mice. Mechanistically, miR-375 and miR-365a-3p were identified to inhibit NF-κB activation via targeting MALT1. Overall, our results highlight that a novel regulatory axis, miRNA-MALT1-NF-κB, plays a vital role in the progression of CRC and provides novel and hopeful therapeutic targets for clinical treatment.

ImportanceThe ongoing pandemic of COVID-19 is still affecting our life, but the effects of lockdown measures on gestational diabetes mellitus (GDM) in pregnant women remain unclear.AimTo investigate the association between COVID-19 lockdown and GDM.Subjects and MethodsMedical records of 140844 pregnant women during 2015-2020 were extracted from 5 hospitals in Guangdong Province, China. Pregnant women who underwent the COVID-19 Level I lockdown (1/23 - 2/24/2020) during pregnancy were defined as the exposed group (N=20472) and pregnant women who underwent the same calendar months during 2015-2019 (1/23 - 2/24) were defined as the unexposed group (N=120372). Subgroup analyses were used to explore the potential susceptible exposure window of COVID-19 lockdown on GDM. Cumulative exposure is quantitatively estimated by assigning different weights to response periods with different exposure intensities. A logistic regression model was used to estimate the association between COVID-19 lockdown exposure and GDM.ResultsThe rates of GDM in the exposed and unexposed groups were 15.2% and 12.4%, respectively. The overall analyses showed positive associations (odds ratio, OR=1.22, 95%CI: 1.17, 1.27) between lockdown exposure and GDM risk in all pregnant women. More pronounced associations were found in women who underwent the COVID-19 lockdown in their first four months of pregnancy, and the adjusted OR values ranged from 1.24 (95%CI: 1.10, 1.39) in women with 5-8 gestational weeks (GWs) to 1.35 (95%CI: 1.20, 1.52) with < 5 GWs. In addition, we found a positive exposure-response association of cumulative lockdown exposure with the risk of GDM.ConclusionsThe COVID-19 lockdown was associated with an increased risk of GDM, and the first four months of pregnancy may be the window for sensitive exposure.

In order to study the influence of the axial compression ratio and steel ratio on the shear-carrying capacity of steel-truss-reinforced beam-column joints, five shear failure interior joint specimens were designed. The effect of different coaxial pressure ratios (0.1, 0.2, and 0.3) and steel contents on the strain, ultimate bearing capacity, seismic performance, and failure pattern of cross-inclined ventral and chord bars in the joint core area was investigated. The experimental results show that the load-displacement hysteretic curves of all test specimens exhibit a bond-slip phenomenon. With the increase of the axial compression ratio, the ultimate bearing capacity of the joint core increases by 3.4% and 5.9%, respectively. While the ductility decreases by 10.3% and 13.1%, and the energy consumption capacity decreases by 3.2% and 5.8%, respectively. The shear capacity and ductility of the member with cross diagonal ventral steel angle in the joint core are increased by 12.9% and 13.4%, respectively. The shear capacity and ductility of the joint can be significantly improved by increasing the amount of steel in the core area. The expression of shear capacity suitable for this type of joint is obtained by fitting analysis, which can be used as a reference for engineering design.

Introduction There is emerging evidence for stratified glucose-lowering responses to certain oral medications for type 2 diabetes (T2D) by individual characteristics. The objective of this study was to test whether glycaemic response to representative treatments of dipeptidyl peptidase-4 inhibitors (vildagliptin) and thiazolidinediones (pioglitazone) varies according to ethnicity, gender, baseline obesity, triglyceride level or genetic variation.Methods This is a multicentre, two-period, two-treatment, open-label, randomised cross-over trial of vildagliptin and pioglitazone as second-line or third-line therapy in patients with T2D who have suboptimal glycaemic control on metformin and/or sulfonylurea therapy. It is conducted in New Zealand with a target of 300 patients (40% with Māori or Pacific ancestry) eligible if aged ≥18 and ≤80 years, with T2D for more than 1 year, on stable doses of metformin and/or sulfonylurea for at least 3 months, with HbA1c between 59 and 110 mmol/mol inclusive. Participants are assigned to complete 4 months of vildagliptin 50 mg per day or pioglitazone 30 mg per day, followed by 4 months of the other medications in randomly allocated sequences. Participant characteristics, including ethnicity, obesity, lipid profile and candidate genotypes are collected at baseline. Primary outcome variable is on treatment HbA1c. Secondary outcomes include weight change, frequency of side effects and patient preference.Ethics and dissemination Ethical approval of the trial has been obtained from the New Zealand Health and Disability Ethics Committee (18/STH/242). The trial commenced in February 2019 and recruitment is expected to be completed by March 2020. Results will be reported in articles submitted to peer-reviewed journals, as well as in presentations at national and international meetings.Trial registration number ACTRN12618001907235.

In this work, ball-like Ag nanorod aggregates have been synthesized via a simple seed-mediated method. These Ag mesostructures were characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-Vis), and X-ray diffraction (XRD). Adding a certain amount of polyvinyl pyrrolidone (PVP) can prolong its coagulation time. These Ag nanorod aggregates exhibit effective SERS effect, evaluated by Rhodamine 6G (R6G) and doxorubicin (DOX) as probe molecules. The limit of detection (LOD) for R6G and DOX are as low as 5 × 10−9 M and 5 × 10−6 M, respectively. Moreover, these Ag nanorod aggregates were found to be potential catalysts for the reduction of 4-nitrophenol (4-NP) in the presence of NaBH4.