Search

Abstract Ferroptosis is an important pathological mechanism of chronic heart failure (CHF). This study aimed to investigate the protective mechanism of Astragaloside IV (AS-IV) on CHF rats by integrating bioinformatics and ferroptosis. CHF-related targets and ferroptosis-related targets were collected. After the intersection, the common targets were obtained. The PPI network of the common targets was constructed, and topological analysis of the network was carried out. The target with the highest topological parameter values was selected as the key target. The key target p53 was obtained through bioinformatics analysis, and its molecular docking model with AS-IV was obtained, as well as molecular dynamics simulation analysis. The rat models of CHF after myocardial infarction were established by ligation of left coronary artery and treated with AS-IV for 4 weeks. AS-IV treatment significantly improved cardiac function in CHF rats, improved cardiomyocyte morphology and myocardial fibrosis, reduced mitochondrial damage, decreased myocardial MDA and Fe2+ content, increased GSH content, inhibited the expression of p53 and p-p53, and up-regulated the expression of SLC7A11 and GPX4. In conclusion, AS-IV improved cardiac function in CHF rats, presumably by regulating p53/SLC7A11/GPX4 signaling pathway and inhibiting myocardial ferroptosis.

Abstract Background Inflammation and immunity play important roles in the formation of coronary collateral circulation (CCC). The pan-immune-inflammation value (PIV) is a novel marker for evaluating systemic inflammation and immunity. The study aimed to investigate the association between the PIV and CCC formation in patients with chronic total occlusion (CTO). Methods This retrospective study enrolled 1150 patients who were diagnosed with CTO through coronary angiographic (CAG) examinations from January 2013 to December 2021 in China. The Cohen-Rentrop criteria were used to catagorize CCC formation: good CCC formation (Rentrop grade 2–3) and poor CCC formation group (Rentrop grade 0–1). Based on the tertiles of the PIV, all patients were classified into three groups as follows: P1 group, PIV ≤ 237.56; P2 group, 237.56< PIV ≤ 575.18; and P3 group, PIV > 575.18. Results A significant relationship between the PIV and the formation of CCC was observed in our study. Utilizing multivariate logistic regression and adjusting for confounding factors, the PIV emerged as an independent risk factor for poor CCC formation. Notably, the restricted cubic splines revealed a dose–response relationship between the PIV and risk of poor CCC formation. In terms of predictive accuracy, the area under the ROC curve (AUC) for PIV in anticipating poor CCC formation was 0.618 (95% CI: 0.584–0.651, P

The nabla fractional-order uncertain difference equation with Caputo-type was analyzed in this article. To begin, the existence and uniqueness theorem of solutions for nabla Caputo uncertain difference equations with almost surely bounded uncertain variables was presented. Furthermore, the uncertainty distributions of the solutions for the proposed equations were obtained by establishing a connection between the solutions of equations and their α-paths based on new comparison theorems. Finally, an application of the uncertain difference equations in a logistic population model involving Allee effect was provided and examples were performed to demonstrate the validity of the theoretical results presented.

Abstract Backgrounds Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. Methods Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020–2022 and after COVID-19 pandemic (2023). Results M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). Conclusion Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.

Abstract Background Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. Methods To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. Results Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p

Abstract The regulatory significance of ubiquitin-specific peptidase 32 (USP32) in tumor is significant, nevertheless, the biological roles and regulatory mechanisms of USP32 in non-small cell lung cancer (NSCLC) remain unclear. According to our research, USP32 was strongly expressed in NSCLC cell lines and tissues and was linked to a bad prognosis for NSCLC patients. Interference with USP32 resulted in a significant inhibition of NSCLC cell proliferation, migration potential, and EMT development; on the other hand, USP32 overexpression had the opposite effect. To further elucidate the mechanism of action of USP32 in NSCLC, we screened H1299 cells for interacting proteins and found that USP32 interacts with BAG3 (Bcl2-associated athanogene 3) and deubiquitinates and stabilizes BAG3 in a deubiquitinating activity-dependent manner. Functionally, restoration of BAG3 expression abrogated the antitumor effects of USP32 silencing. Furthermore, USP32 increased the phosphorylation level of the RAF/MEK/ERK signaling pathway in NSCLC cells by stabilizing BAG3. In summary, these findings imply that USP32 is critical to the development of NSCLC and could offer a theoretical framework for the clinical diagnosis and management of NSCLC patients in the future.

Abstract Background Dysfunction or deficiency of corneal epithelium results in vision impairment or blindness in severe cases. The rapid and effective regeneration of corneal epithelial cells relies on the limbal stem cells (LSCs). However, the molecular and functional responses of LSCs and their niche cells to injury remain elusive. Methods Single-cell RNA sequencing was performed on corneal tissues from normal mice and corneal epithelium defect models. Bioinformatics analysis was performed to confirm the distinct characteristics and cell fates of LSCs. Knockdown of Creb5 and OSM treatment experiment were performed to determine their roles of in corneal epithelial wound healing. Results Our data defined the molecular signatures of LSCs and reconstructed the pseudotime trajectory of corneal epithelial cells. Gene network analyses characterized transcriptional landmarks that potentially regulate LSC dynamics, and identified a transcription factor Creb5, that was expressed in LSCs and significantly upregulated after injury. Loss-of-function experiments revealed that silencing Creb5 delayed the corneal epithelial healing and LSC mobilization. Through cell–cell communication analysis, we identified 609 candidate regeneration-associated ligand-receptor interaction pairs between LSCs and distinct niche cells, and discovered a unique subset of Arg1 + macrophages infiltrated after injury, which were present as the source of Oncostatin M (OSM), an IL-6 family cytokine, that were demonstrated to effectively accelerate the corneal epithelial wound healing. Conclusions This research provides a valuable single-cell resource and reference for the discovery of mechanisms and potential clinical interventions aimed at ocular surface reconstruction.

Background: The lack of reference genes makes it difficult to conduct molecular biology research on the plant genus, Clematis L. Clematis lanuginosa belongs to Sect. Viticella DC of Clematis L. It is also an important ornamental cultivated variety parent of the early and late large-flowered groups. Studying the reference genes of C. lanuginosa in different tissues will provide a theoretical basis for the reference selection of early and late large-flowered groups of Clematis, which could promote research progress on molecular biology of ornamental Clematis. Results: The roots, stems, leaves, sepals, stamens, and carpels of C. lanuginosa were used as research materials, and seven candidate reference genes were used for quantitative real-time PCR analysis. Comprehensive stability analysis using geNorm, NormFinder, BestKeeper, and RefFinder software showed that suitable reference genes in C. lanuginosa root, stem, and leaf were PP2A-2 and UBC34; and in floral tissue were UBC34, PP2A-2, and ARP7. These reference genes can be used as internal reference either alone or in combination. The pairwise variation value evaluated with geNorm software showed that two internal reference genes were needed for gene expression correction in the tissues. In the floral organs, three reference genes were required for gene expression correction. Conclusions: Our results provide a foundation for future gene expression analysis of C. lanuginosa and guidance for the screening of reference genes in Clematis.How to cite: Li Q, Wang S, Lv F, et al. Selection and validation of reference genes for quantitative real-time PCR in different tissues of Clematis lanuginosa. Electron J Biotechnol 2024;70. https://doi.org/10.1016/j.ejbt.2024.04.005.

Abstract Acute myeloid leukemia (AML) is a heterogeneous hematological tumor with poor immunotherapy effect. This study was to develop a monocyte/macrophage-related prognostic risk score (MMrisk) and identify new therapeutic biomarkers for AML. We utilized differentially expressed genes (DEGs) in combination with single-cell RNA sequencing to identify monocyte/macrophage-related genes (MMGs). Eight genes were selected for the construction of a MMrisk model using univariate Cox regression analysis and LASSO regression analysis. We then validated the MMrisk on two GEO datasets. Lastly, we investigated the immunologic characteristics and advantages of immunotherapy and potential targeted drugs for MMrisk groups. Our study identified that the MMrisk is composed of eight MMGs, including HOPX, CSTB, MAP3K1, LGALS1, CFD, MXD1, CASP1 and BCL2A1. The low MMrisk group survived longer than high MMrisk group (P

Abstract C − N axially chiral compounds have recently attracted significant interest among synthetic chemistry community due to their widespread application in pharmaceuticals, advanced materials and organic synthesis. Although the emerging asymmetric Catellani reaction offers great opportunity for their modular and efficient preparation, the only operative chiral NBE strategy to date requires using half stoichiometric amount of chiral NBE and 2,6-disubstituted bromoarenes as electrophiles. We herein report an efficient assembly of C–N axially chiral scaffolds through a distinct chiral ligand strategy. The crucial chiral source, a biimidazoline (BiIM) chiral dinitrogen ligand, is used in relatively low loading and permits the use of less bulky bromoarenes. The method also features the use of feedstock plain NBE, high reactivity, good enantioselectivity, ease of operation and scale-up. Applications in the preparation of chiral optoelectronic material candidates featuring two C–N chiral axes and a chiral ligand for asymmetric C–H activation have also been demonstrated.

Abstract To investigate the application of MRI-based vertebral bone quality (VBQ) score in assessing bone mineral density (BMD) for patients with adolescent idiopathic scoliosis (AIS). We reviewed the data of AIS patients between January 2021 and October 2023 with MRI, whole-spine plain radiographs, quantitative computed tomography (QCT) and general information. VBQ score was calculated using T1-weighted MRI. Univariate analysis was applied to present the differences between variables of patients with normal BMD group (QCT Z-score > − 2.0) and low BMD group (QCT Z-score ≤ − 2.0). The correlation between VBQ score and QCT Z-score was analyzed with Pearson correlation test. A multivariate logistic regression model was used to determine the independent factors related to low BMD. Receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of VBQ score in distinguishing low BMD. A total of 136 AIS patients (mean age was 14.84 ± 2.10 years) were included, of which 41 had low BMD. The low BMD group had a significantly higher VBQ score than that in normal group (3.48 ± 0.85 vs. 2.62 ± 0.62, P

In recent years, extensive research on dynamic precipitation has led to a growing interest in exploring how deformation affects microstructure and mechanical properties. In this study, the response of microstructure and performance to cold pre-strain and the early aging stage in the Al–Zn–Mg–Cu alloy was investigated using a combination of modelling and experimental approaches. A Kampmann-Wagner based numerical framework was developed and applied to the Al–Zn–Mg–Cu alloy. The deformation or quenching induced dislocations and vacancies, their dynamics and acceleration on the diffusivities of solute atoms, and the competition between homogeneous and heterogeneous nucleation were considered in the framework. The effect of the different pre-strain levels (0%–10%) on the evolution of vacancies, dislocations, precipitation kinetics and hardening are given in detail. The results suggest that the acceleration of precipitation kinetics and hardening during the aging process following pre-strain is primarily attributed to the overall increase in diffusivity resulting from deformation-induced dislocations, rather than vacancies. The simulation framework developed in the current work effectively captures the evolution of microstructure and mechanical properties, which has significant practical implications for materials manufacturing.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases globally. Hepatic stellate cells (HSCs) are the major effector cells of liver fibrosis. HSCs contain abundant lipid droplets (LDs) in their cytoplasm during quiescence. Perilipin 5 (PLIN 5) is a LD surface‐associated protein that plays a crucial role in lipid homeostasis. However, little is known about the role of PLIN 5 in HSC activation. Methods PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection. At the same time, PLIN 5 gene knockout mice were constructed and fed with a high‐fat diet (HFD) for 20 weeks to study the role of PLIN 5 in NAFLD. The corresponding reagent kits were used to measure TG, GSH, Caspase 3 activity, ATP level, and mitochondrial DNA copy number. Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC‐MS/MS. AMPK, mitochondrial function, cell proliferation, and apoptosis‐related genes and proteins were detected by western blotting and qPCR. Results Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria, inhibition of cell proliferation, and a significant increase in cell apoptosis through AMPK activation. In addition, compared with the HFD‐fed C57BL/6J mice, PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition, decreased LD abundance and size, and reduced liver fibrosis. Conclusion These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.

Abstract The Tetraspanins (Tspan) protein family, also known as the tetraspanin family, contains 33 family members that interact with other protein molecules such as integrins, adhesion molecules, and T cell receptors by forming dimers or heterodimers. The Tspan protein family regulates cell proliferation, cell cycle, invasion, migration, apoptosis, autophagy, tissue differentiation, and immune response. More and more studies have shown that Tspan proteins are involved in tumorigenesis, epithelial-mesenchymal transition, thrombosis, tumor stem cell, and exosome signaling. Some drugs and microRNAs can inhibit Tspan proteins, thus providing new strategies for tumor therapy. An in-depth understanding of the functions and regulatory mechanisms of the Tspan protein family, which can promote or inhibit tumor development, will provide new strategies for targeted interventions in the future.

Abstract Intelligent detection of athlete behavior is beneficial for guiding sports instruction. Existing mature target detection algorithms provide significant support for this task. However, large-scale target detection algorithms often encounter more challenges in practical application scenarios. We propose SCB-YOLOv5, to detect standardized movements of gymnasts. First, the movements of aerobics athletes were captured, labeled using the labelImg software, and utilized to establish the athlete normative behavior dataset, which was then enhanced by the dataset augmentation using Mosaic9. Then, we improved the YOLOv5 by (1) incorporating the structures of ShuffleNet V2 and convolutional block attention module to reconstruct the Backbone, effectively reducing the parameter size while maintaining network feature extraction capability; (2) adding a weighted bidirectional feature pyramid network into the multiscale feature fusion, to acquire precise channel and positional information through the global receptive field of feature maps. Finally, SCB-YOLOv5 was lighter by 56.9% than YOLOv5. The detection precision is 93.7%, with a recall of 99% and mAP value of 94.23%. This represents a 3.53% improvement compared to the original algorithm. Extensive experiments have verified that our method. SCB-YOLOv5 can meet the requirements for on-site athlete action detection. Our code and models are available at https://github.com/qingDu1/SCB-YOLOv5 .

Objective: Flexible ureteroscopy (fURS) has become a widely accepted and effective technique for treating kidney stones. With the development of new laser systems, the fURS approach has evolved significantly. This literature review aims to examine the current state of knowledge on fURS treatment of kidney stones, with a particular focus on the impact of the latest laser technologies on clinical outcomes and patient safety. Methods: We conducted a search of the PubMed/PMC, Web of Science Core Collection, Scopus, Embase (Ovid), and Cochrane Databases for all randomized controlled trial articles on laser lithotripsy in September 2023 without time restriction. Results: We found a total of 22 relevant pieces of literature. Holmium laser has been used for intracavitary laser lithotripsy for nearly 30 years and has become the golden standard for the treatment of urinary stones. However, the existing holmium laser cannot completely powder the stone, and the retropulsion of the stone after the laser emission and the thermal damage to the tissue have caused many problems for clinicians. The introduction of thulium fiber laser and Moses technology brings highly efficient dusting lithotripsy effect through laser innovation, limiting pulse energy and broadening pulse frequency. Conclusion: While the holmium:yttrium-aluminum-garnet laser remains the primary choice for endoscopic laser lithotripsy, recent technological advancements hint at a potential new gold standard. Parameter range, retropulsion effect, laser fiber adaptability, and overall system performance demand comprehensive attention. The ablation efficacy of high-pulse-frequency devices relies on precise targeting, which may pose practical challenges.

Abstract Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFβ and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFβ-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin–proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFβ. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.

Abstract Background The combination of rituximab and chemotherapy is a first-line treatment for patients with B-cell non-Hodgkin lymphoma. Lenalidomide is an immunomodulatory drug that has shown promising properties and activity in a variety of hematological malignancies. This study evaluated the efficacy and safety of lenalidomide-based regimens in the treatment of B-cell non-Hodgkin lymphoma. Methods The PubMed, Science Direct, ClinicalTrials.gov, and Web of Science databases were searched for relevant studies published up to May 2022. Studies with patients diagnosed with non-Hodgkin B-cell lymphoma, who were randomly assigned to a lenalidomide treatment group or a non-lenalidomide control group were considered for inclusion in this review and meta-analysis. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of the time-to-event outcomes and risk ratios (RRs) with 95% CIs of dichotomous data were estimated. Results A total of 3593 patients from 10 studies were evaluated. The results of the pooled analysis indicated that the lenalidomide-based regimen was associated with prolonged overall survival (HR, 0.85; 95% CI 0.74–0.97; P = 0.02) and progression-free survival (HR, 0.70; 95% CI 0.57–0.88; P = 0.002). Significant differences were found in the overall response rate (RR, 1.18; 95% CI 1.04–1.33; P = 0.01) and complete response rate (RR, 1.18; 95% CI 1.00–1.39; P = 0.05) between the treatment and control groups. Conclusions Lenalidomide appears to be a promising therapeutic agent that offers the possibility of a novel combination of chemotherapy free regimen for patients with B-cell non-Hodgkin lymphoma.

BackgroundKnee osteoarthritis (KOA) is one of the most common chronic joint diseases. Physical therapy, a non-invasive approach, is extensively used in its treatment. Although bibliometrics is a reliable method to evaluate the significance and impact of research fields, systematic bibliometric analyses in this area are lacking. This study aims to perform a bibliometric analysis covering 2013 to 2022, to highlight the current state, key focuses, and trends in physical therapy for KOA.MethodsThis study utilizes the Web of Science Core Collection to gather relevant literature on physical therapy and KOA from 2013 to 2022. CiteSpace and VOSviewer software facilitated the visual analysis of the annual publications, geographic and institutional distributions, journals, authors, references, and keywords in this field.ResultsThe study analyzed 1,357 articles, showing an overall increase in publications over time from 71 countries and 2,302 institutions. The United States and Australia emerged as leaders in this field. The analysis identified 6,046 authors, with Kim L. Bennell as the most prolific and Bellamy N. receiving the most citations. BMC Musculoskeletal Disorders published the most articles, while Osteoarthritis and Cartilage received the most citations. High-impact articles were authored notably by McAlindon TE, Bannuru RR, Fernandes L, and Bennell KL. Keyword analysis highlighted a strong focus on patient self-management, exercise therapy, physical factor therapy, and remote rehabilitation.ConclusionThe bibliometric analysis confirms significant interest and ongoing research in physical therapy for KOA treatment from 2013 to 2022, indicating a growing field. Journals and authors in this area show influential and collaborative dynamics. Future research should focus on enhancing international and institutional collaboration and explore emerging trends like internet-guided treatments.

Abstract Background RNA pseudouridylation is a critical post‐transcriptional modification that influences gene expression and impacts various biological functions. Despite its significance, the role of mRNA pseudouridylation in cancer remains poorly understood. This study investigates the impact of pseudouridine synthase 7 (PUS7)‐mediated pseudouridylation of Alpha‐ketoglutarate‐dependent Dioxygenase alkB Homolog 3 (ALKBH3) mRNA in gastric cancer. Methods Immunohistochemistry and Western blotting were used to assess PUS7 protein levels in human gastric cancer tissues. The relationship between PUS7 and gastric cancer progression was examined using 3D colony formation assays and subcutaneous xenograft models. Real‐time quantitative PCR (RT‐qPCR), Western blotting, and polysome profiling assays were conducted to investigate how PUS7 regulates ALKBH3. A locus‐specific pseudouridine (Ψ) detection assay was used to identify Ψ sites on ALKBH3 mRNA. Results Our findings indicate a significant reduction of PUS7 in gastric cancer tissues compared to adjacent non‐tumour tissues. Functional analyses reveal that PUS7 inhibits gastric cancer cell proliferation and tumour growth via its catalytic activity. Additionally, PUS7 enhances the translation efficiency of ALKBH3 mRNA by modifying the U696 site with pseudouridine, thereby attenuating tumour growth. Importantly, ALKBH3 functions as a tumour suppressor in gastric cancer, with its expression closely correlated with PUS7 levels in tumour tissues. Conclusions PUS7‐dependent pseudouridylation of ALKBH3 mRNA enhances its translation, thereby suppressing gastric cancer progression. These findings highlight the potential significance of mRNA pseudouridylation in cancer biology and suggest a therapeutic target for gastric cancer. Highlights PUS7 enhances the translation efficiency of ALKBH3 through its pseudouridylation activity on ALKBH3 mRNA, thereby inhibiting gastric tumourigenesis. The expression levels of PUS7 and ALKBH3 are significantly correlated in gastric tumours, which may be potential prognostic predictors and therapeutic targets for patients with gastric cancer.

It is increasingly clear that unconscious information impairs the performance of the corresponding action when the instruction to act is delayed. However, whether this impairment occurs at the response level or at the perceptual level remains controversial. This study used fMRI and a computational model with a pre-post design to address this elusive issue. The fMRI results showed that when the unconscious information containing strong stimulus-response associations was irrelevant to subsequent stimuli, the precuneus in the parietal lobe, which is thought to be involved in sensorimotor processing, was activated. In contrast, when the unconscious information was relevant to subsequent stimuli, regardless of the strength of the stimulus-response associations, some regions in the occipital and temporal cortices, which are thought to be involved in visual perceptual processing, were activated. In addition, the percent signal change in the regions of interest associated with motor inhibition was modulated by compatibility in the irrelevant but not in the relevant stimuli conditions. Modeling of behavioral data further supported that the irrelevant and relevant stimuli conditions involved fundamentally different mechanisms. Our finding reconciles the debate about the mechanism by which unconscious information impairs action performance and has important implications for understanding of unconscious cognition.

The recycle and utilization of expired drugs is a challenge for many countries at present. The employment of expired drugs as green corrosion inhibitors is expected to address both drug recycling and corrosion prevention issues, with significant economic and environmental value. Herein, the individually and combination corrosion inhibition performance of expired amoxicillin (AMC) and penicillin V potassium tablets (PVP) for lowcarbon steel in 20% acetic acid solution containing 600 mg L-1 chloride ion are evaluated by electrochemistry and weight loss method. Both the AMC and PVP present the mixed-type corrosion inhibitors mainly affect the cathode process when used individually. The optimum inhibition efficiency is 61.22% (AMC) and 79.21% (PVP), which all appear in 5.0 × 10-3 mol L-1. The AMC and PVP are adsorbed on the steel surface by mixed physisorption and chemisorption, which are consistent with the Langmuir adsorption isotherm. The corrosion inhibition rate drops sharply when AMC and PVP are combined use with a close mole ratio. But a small amount of PVP significantly enhance the corrosion inhibition effect of AMC, the corrosion inhibition rate from 61.22 to 79.72%. The corrosion inhibition rate of AMC and PVP combination inhibitor decreased with the increase of temperature.

IntroductionGranulocytic myeloid-derived suppressor cells (G-MDSCs) show fast recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) constituting the major part of peripheral blood in the early phase. Although G-MDSCs mediate immune suppression through multiple mechanisms, they may also promote inflammation under specific conditions. MethodsG-MDSCs were isolated from 82 patients following allo-HSCT within 90 days after allo-HSCT, and their interactions with autologous CD3+ T-cells were examined. T-cell proliferation was assessed by flow cytometry following CFSE staining, while differentiation and interferon-γ secretion were characterized using chemokine receptor profiling and ELISpot assays, respectively. NK cell cytotoxicity was evaluated through co-culture with K562 cells. An aGVHD xenogeneic model in humanized mice was employed to study the in vivo effects of human leukocytes. Furthermore, transcriptional alterations in G-MDSCs were analyzed via RNA sequencing to investigate functional transitions.ResultsG-MDSCs promoted inflammation in the early-stage, by facilitating cytokine secretion and proliferation of T cells, as well as their differentiation into pro-inflammatory T helper subsets. At day 28, patients with a higher number of G-MDSCs exhibited an increased risk of developing grades II-IV aGvHD. Besides, adoptive transfer of G-MDSCs from patients at day 28 into humanized mice exacerbated aGvHD. However, at day 90, G-MDSCs led to immunosuppression, characterized by upregulated expression of indoleamine 2,3-dioxygenase gene and interleukin-10 secretion, coupled with the inhibition of T cell proliferation. Furthermore, transcriptional analysis of G-MDSCs at day 28 and day 90 revealed that 1445 genes were differentially expressed. These genes were associated with various pathways, revealing the molecular signatures of early post-transplant differentiation in G-MDSCs. In addition, genes linked to the endoplasmic reticulum stress were upregulated in patients without aGvHD. The acquisition of immunosuppressive function by G-MDSCs may depend on the activation of CXCL2 and DERL1 genes. ConclusionOur findings revealed the alteration in the immune characteristics of G-MDSCs within the first 90 days post-allo-HSCT. Moreover, the quantity of G-MDSCs at day 28 may serve as a predictive indicator for the development of aGvHD.

Abstract In next‐generation wireless communications, reconfigurable intelligent surface (RIS) has emerged as a cost‐effective technique for enhancing physical layer security (PLS) in millimeter‐wave (mmWave) communications, especially under challenging scenarios with adversarial entities and obstructions. However, the primary studies for RIS incorporation in mmWave communication systems utilized static deployments, lacking adaptability and efficiency in complex environments. To address this problem, a dynamic RIS deployment design framework is introduced for PLS enhancement in mmWave systems against jamming and eavesdropping attacks. For the design, it is aimed to maximize the secrecy rate by jointly optimizing the RIS selection with the beamforming design. The resulting optimization problem is challenging to solve due to the coupling of the RIS control factor, joint beamforming design, and non‐convex constraints. To tackle these issues, an efficient multi‐RIS‐aided PLS enhancement algorithm is proposed. It transforms the objective into a series of subproblems and employs the fractional programming technique and prox‐linear block coordinate descent updating method to solve them alternatively and obtain the optimal solution. The simulations demonstrate the advantage of the dynamic deployment, which exhibits enhanced security performance with reduced complexity compared with benchmarks. Further examinations also provide insight into optimal RIS activation configurations, achieving optimal balance for securing mmWave communications against emerging threats while maintaining system efficiency.

The Grain for Green Program and soil and water conservation engineering initiatives are crucial for controlling erosion in steep-slope agriculture. However, it is still unclear how these two management methods should be carried out in respect to the situation in mountainous areas. Therefore, taking a typical mountainous area in southwest China as an example, we simulated six scenarios in order to compare the food provisioning service (FPS) and soil conservation service of the Grain for Green Program (converting to grassland) and Construction Measures (converting to sloping terrace) under different slopes. Results showed that when farmland with a >25° slope was converted into grassland, the amount of soil erosion (M) decreased by 21.0%, while FPS decreased by only 0.7%. However, when farmland with a >25° slope was converted into sloping terrace, M decreased by 31.3% while FPS increased by 18.7%. With the increases of farmland slope ranges in the Construction Measures scenario, M gradually decreased and FPS gradually increased. Particularly when farmland >15° was converted into sloping terrace, M decreased by 63.9% and FPS increased by 52.7%. Furthermore, the trade-offs of Construction Measures are lower than that of Grain for Green on different slope ranges. Therefore, we conclude that Construction Measures are a more suitable method in mountainous areas than the Grain for Green, and we suggest that further research be conducted to consider the ecological risks of construction engineering measures.

Abstract To examine the association of adverse childhood experiences (ACEs) with anemia among older people. 24,116 participants aged 50 years or above were recruited. Multivariable linear and logistic regression was used to assess the associations of self-reported ACEs number with hemoglobin concentrations (g/dL) and presence of anemia. Older individuals with two or more ACEs, versus no ACEs, showed lower hemoglobin concentrations (β = − 0.08 g/dL, 95% confidence intervals (CI) − 0.12 to − 0.03) and higher odds of anemia (odds ratio = 1.26, 95% CI 1.01–1.59). A more pronounced association between ACEs and anemia in the lower education group was found, while the association became non-significant in those with higher education (P for ACEs-education interaction = 0.02). ACEs was associated with anemia in older people, and the association was stronger in those with lower education, highlighting the significance of early-life psychological stressors assessment and consideration of education background in geriatric care.

Abstract Objective To analyze the relationship between the polymorphism and mutation of rs7125942 and rs3736228 locus in the low-density lipoprotein receptor-related protein 5 (LRP5) genotype and bone mineral density (BMD) in postmenopausal women in Xinjiang, China, to provide a basis for prevention and treatment of the disease. Methods According to the results of dual-energy X-ray (DEXA) determination of BMD, the 136 subjects were divided into three groups: Group A: normal bone mass, Group B: osteopenia, Group C: osteoporosis. 1. Age, body, mass index (BMI), and menopause of all subjects were recorded. 2. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and clinical biochemical data were determined. 3. LRP5 locus polymorphisms were determined by time-of-flight mass spectrometry. Results 1. Compared with group A, the age, ALP, Cr, and BUN levels in group B and group C were increased, but UA levels were lower (P 0.05). 3. The ROC curves for different BMD sites such as L1, L2, L3, L4, L total, and femoral neck were 0.929, 0.955, 0.901, 0.914, 0.885, and 0.873 (P

Abstract Objective To evaluate and summarize systematic reviews of the effects and safety of awake prone positioning for COVID-19-related acute hypoxaemic respiratory failure. Methods A comprehensive search was conducted on PubMed, Embase, the Cochrane Library, Web of Science, CNKI, CSPD, CCD and CBM from their inception to March 28, 2023. Systematic reviews (SRs) of awake prone positioning (APP) for COVID-19-related acute hypoxaemic respiratory failure in adults were included. Two reviewers screened the eligible articles, and four reviewers in pairs extracted data and assessed the methodological quality/certainty of the evidence of all included SRs by AMSTAR 2 and GRADE tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a narrative description. Results A total of 11 SRs were included. The methodological quality of SRs included 1 “High”, 4 “Moderate”, 2 “Low” and 4 “Critically low” by AMSTAR 2. With the GRADE system, no high-quality evidence was found, and only 14 outcomes provided moderate-quality evidence. Data synthesis of the included SR outcomes showed that APP reduced the risk of requiring intubation (11 SRs) and improving oxygenation (3 SRs), whereas reduced significant mortality was not found in RCT-based SRs. No significant difference was observed in the incidence of adverse events between groups (8 SRs). The corrected covered area index was 27%, which shows very high overlap among studies. Conclusion The available SRs suggest that APP has benefits in terms of reducing intubation rates and improving oxygenation for COVID-19-related acute hypoxemic respiratory failure, without an increased risk of adverse events. The conclusion should be treated with caution because of the generally low quality of methodology and evidence. Trial registration The protocol for this review was registered with PROSPERO: CRD42023400986. Registered 15 April 2023.

Abstract Lentic systems (lakes and reservoirs) are emission hotpots of nitrous oxide (N2O), a potent greenhouse gas; however, this has not been well quantified yet. Here we examine how multiple environmental forcings have affected N2O emissions from global lentic systems since the pre-industrial period. Our results show that global lentic systems emitted 64.6 ± 12.1 Gg N2O-N yr−1 in the 2010s, increased by 126% since the 1850s. The significance of small lentic systems on mitigating N2O emissions is highlighted due to their substantial emission rates and response to terrestrial environmental changes. Incorporated with riverine emissions, this study indicates that N2O emissions from global inland waters in the 2010s was 319.6 ± 58.2 Gg N yr−1. This suggests a global emission factor of 0.051% for inland water N2O emissions relative to agricultural nitrogen applications and provides the country-level emission factors (ranging from 0 to 0.341%) for improving the methodology for national greenhouse gas emission inventories.

Background Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis. Methods Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk. Results During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies. Conclusion Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

Abstract With the support of the sixth‐generation mobile networks (6G) technology, the Internet‐of‐Vehicle (IoV) can realize the perception and monitoring of vehicle road information. However, due to the change of network topology and various environment, the reliable performance of the communication link is facing challenges. For the sake of improving communication quality, a cooperative vehicular network (CVN) system is established, which adopts cooperative communication and multiple input multiple output (MIMO) technology. According to the signal‐to‐noise ratio (SNR) threshold of relay vehicles, using hybrid decode‐amplify‐forward (HDAF) protocol and combining with antenna selection, the analytical expression of outage probability (OP) with Meijer‐G function is obtained. For predicting the OP accurately, the sparrow search algorithm based on back‐propagation neural network (SSA‐BPNN) is put forward. The simulation results show that the cascade order of the channels has a negative effect on the OP. Meanwhile, the prediction accuracy of SSA‐BPNN is 64.8% higher than that of BPNN, and 98.96% greater than that of general regression neural network, and the convergence rate is faster than ICS‐BPNN.

Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance the healing of bone defects through the synergistic regulation of osteogenesis and osteoclastogenesis is still a challenging task in the field of bone tissue engineering. The aim of this study was to create a dual-drug release-based core-shell nanofibers with the intent of achieving a time-controlled release to facilitate bone regeneration. We fabricated core-shell P/PCL nanofibers using coaxial electrospinning, where alendronate (ALN) was incorporated into the core layer and hydroxyapatite (HA) into shell. The surface of the nanofiber construct was further modified with mussel-derived polydopamine (PDA) to induce hydrophilicity and enhance cell interactions. Surface characterizations confirmed the successful synthesis of PDA@PHA/PCL-ALN nanofibers endowed with excellent mechanical strength (20.02 ± 0.13 MPa) and hydrophilicity (22.56°), as well as the sustained sequential release of ALN and Ca ions. In vitro experiments demonstrated that PDA-functionalized core-shell PHA/PCL-ALN scaffolds possessed excellent cytocompatibility, enhanced cell adhesion and proliferation, alkaline phosphatase activity and osteogenesis-related genes. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity and osteoclastogenesis-related gene expression. After 12-week of implantation, it was observed that PDA@PHA/PCL-ALN nanofiber scaffolds, in a rat cranial defect model, significantly promoted bone repair and regeneration. Microcomputed tomography, histological examination, and immunohistochemical analysis collectively demonstrated that the PDA-functionalized core-shell PHA/PCL-ALN scaffolds exhibited exceptional osteogenesis-inducing and osteoclastogenesis-inhibiting effects. Finally, it may be concluded from our results that the bio-inspired surface-functionalized multifunctional, biomimetic and controlled release core-shell nanofiber provides a promising strategy to facilitate bone healing.

Activated hepatic stellate cells (HSCs) have been widely recognized as a primary source of pathological myofibroblasts, leading to the accumulation of extracellular matrix and liver fibrosis. CD47, a transmembrane glycoprotein expressed on the surface of various cell types, has been implicated in non-alcoholic fatty liver disease. However, the precise role of CD47 in HSC activation and the underlying regulatory mechanisms governing CD47 expression remain poorly understood. In this study, we employed single-cell RNA sequencing analysis to investigate CD47 expression in HSCs from mice subjected to a high-fat diet. CD47 silencing in HSCs markedly inhibited the expression of fibrotic genes and promoted apoptosis. Mechanistically, we found that Yes-associated protein (YAP) collaborates with TEAD4 to augment the transcriptional activation of CD47 by binding to its promoter region. Notably, disruption of the interaction between YAP and TEAD4 caused a substantial decrease in CD47 expression in HSCs and reduced the development of high-fat diet-induced liver fibrosis. Our findings highlight CD47 as a critical transcriptional target of YAP in promoting HSC activation in response to a high-fat diet. Targeting the YAP/TEAD4/CD47 signaling axis may hold promise as a therapeutic strategy for liver fibrosis.

BackgroundPsychiatric diseases are a serious threat to human health. Studies have shown an association between ambient air pollution and psychiatric diseases, yet the results are inconsistent. ObjectiveTo explore the potential effects of air pollution exposure on psychiatric diseases using Zhengzhou City as an example. MethodsOutpatient consultation data of the Clinical Psychology Clinic at The First Affiliated Hospital of Henan University of Traditional Chinese Medicine as well as air quality data between 28 October 2013 and 28 August 2019 were collected. The exposure-lag effect between air pollutant exposure and daily outpatient visits was assessed using a distribution lag nonlinear model (DLNM), and subgroup analyses were conducted including sex (male and female), age (59 years), season (spring, summer, autumn, and winter), and types of diseases (depression and anxiety). ResultsA total of 112986 valid confirmed outpatient visit records for psychiatric diseases were collected. The largest proportions of visits in each subgroup were females, 18-59 years old, spring, and depression. The results of one-day lagged risk of total outpatient visits showed that PM2.5, PM10, SO2, and NO2 all significantly associated with an increased risk of psychiatric outpatient visits. The one-day lagged risk peaks were: PM2.5 (RR=1.0016, 95%CI: 1.0011, 1.0022), PM10 (RR=1.0012, 95%CI: 1.0001, 1.0022), SO2 (RR=1.0060, 95%CI: 1.0002, 1.0117), and NO2 (RR=1.0144, 95%CI: 1.0100, 1.0187). The cumulative lagged risk peaks were: PM2.5 (CumRR=1.0274, 95%CI: 1.0158, 1.0392), PM10 (CumRR=1.0124, 95%CI: 1.0044, 1.0205), SO2 (CumRR=1.0214, 95%CI: 1.0009, 1.0423), and NO2 (CumRR=1.0613, 95%CI: 1.0460, 1.0770). The results of subgroup analysis showed more significant impacts of air pollution exposure on females and people aged 18-59 years, and in winter. To be specific, PM2.5 (RR=1.0022, 95%CI: 1.0006, 1.0037), PM10 (RR=1.0015, 95%CI: 1.0003, 1.0027), SO2 (RR=1.0082, 95%CI: 1.0016, 1.0148), and NO2 (RR=1.0156, 95%CI: 1.0106, 1.0206) exposures associated with an increased risk of outpatient visits for psychiatric disorders in women; PM2.5 (RR=1.0018, 95%CI: 1.0011, 1.0024), PM10 (RR=1.0012, 95%CI: 1.0001, 1.0023), and NO2 (RR=1.0142, 95%CI: 1.0095, 1.0189) associated with an increased risk of visits in those 18-59 years of age; PM2.5 (RR= 1.0043, 95%CI: 1.0001, 1.0085), PM10 (RR= 1.0038, 95%CI: 1.0007, 1.0069), and NO2 (RR= 1.0215, 95%CI: 1.0117, 1.0313) in winter months significantly associated with an increased risk of psychiatric outpatient visits. In addition, the risk of depression and anxiety visits varied depending on the concentration of air pollutants and the duration of exposure. The risk of visits for depression were more affected by CO, NO2, and SO2, and the risk of visits for anxiety were more affected by PM2.5, PM10, and O3. ConclusionExposure to air pollution is associated with an increased risk of psychiatric outpatient visits. The effects vary by air pollutants as well as by sex, age, type of psychiatric illness, and season.

Abstract Background Intrahepatic cholangiocarcinoma (ICC) accounts for about 15% of primary liver cancer, and the incidence rate has been rising in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to find its signature genes and therapeutic drug. Here, we studied that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the occurrence and metastasis of intrahepatic cholangiocarcinoma through Wnt/β-catenin signal pathway. Methods IC50 of bufalin in ICC cells was determined by CCK8 and invasive and migratory abilities were verified by wound healing, cell cloning, transwell and Western blot. IF and IHC verified the expression of CAMKK2 between ICC patients and normal subjects. BLI and pull-down demonstrated the binding ability of bufalin and CAMKK2. Bioinformatics predicted whether CAMKK2 was related to the Wnt/β-catenin pathway. SKL2001, an activator of β-catenin, verified whether bufalin acted through this pathway. In vitro and in vivo experiments verified whether overexpression of CAMKK2 affects the proliferative and migratory effects of ICC. Transmission electron microscopy verified mitochondrial integrity. Associated Ca2+ levels verified the biological effects of ANXA2 on ICC. Results It was found that bufalin inhibited the proliferation and migration of ICC, and CAMKK2 was highly expressed in ICC, and its high expression was positively correlated with poor prognosis.CAMKK2 is a direct target of bufalin, and is associated with the Wnt/β-catenin signaling pathway, which was dose-dependently decreased after bufalin treatment. In vitro and in vivo experiments verified that CAMKK2 overexpression promoted ICC proliferation and migration, and bufalin reversed this effect. CAMKK2 was associated with Ca2+, and changes in Ca2+ content induced changes in the protein content of ANXA2, which was dose-dependently decreasing in cytoplasmic ANXA2 and dose-dependently increasing in mitochondrial ANXA2 after bufalin treatment. In CAMKK2 overexpressing cells, ANXA2 was knocked down, and we found that reversal of CAMKK2 overexpression-induced enhancement of ICC proliferation and migration after siANXA2. Conclusions Our results suggest that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the proliferation and migration of intrahepatic cholangiocarcinoma through Wnt/β-catenin signal pathway. Thus, bufalin, as a drug, may also be used for cancer therapy in ICC in the future.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Unhealthy dietary habit is one of major risk factors of NAFLD. However, the associations between specific types of fish and meat consumption and NAFLD remain inconclusive. We explored the associations of fish and meat consumption with NAFLD risk in middle-aged and older Chinese. Methods We collected information on 1,862 participants aged 50 years or older from Guangzhou Biobank Cohort Study in 2009 to 2010. Fish and meat consumption was assessed using a validated food-frequency questionnaire. NAFLD was diagnosed by ultrasound. Multivariable logistic regression was used to examine the associations of fish and meat consumption with the presence of NAFLD. Results The average age was 61.0 (standard deviation = 6.5) years for the participants, 50.2% were women, and 37.2% were diagnosed with NAFLD. After adjusting for age, sex, education, family income, occupation, smoking status, drinking status, physical activity and several metabolic traits, compared with 0 serving/week (one serving = 50 g), fatty fish consumption of ≥ 3 servings/week showed higher odds of NAFLD (odds ratio (OR) and 95% confidence interval (CI): 1.64 (1.12, 2.39)). The highest (≥ 11 servings/week of red meat and poultry; ≥ 3 servings/week of processed meat) versus the lowest (0–3 servings/week of red meat and poultry; 0 serving/week of processed meat) consumption of all other types of meats, including red meat, poultry and processed meat, showed no association with NAFLD (1.17 (0.75, 1.81), 1.02 (0.42, 2.50) and 0.85 (0.50, 1.45), respectively). Aquatic and sea food, and red meat had negative indirect effects on NAFLD via systolic blood pressure and/or high-density lipoprotein cholesterol. Processed meat had positive indirect effects on NAFLD via body mass index, waist circumference, fasting plasma glucose and triglycerides. Conclusion High consumption of fatty fish was associated with higher NAFLD risk. Our results, if causal, provide evidence that limiting consumption of fatty fish can be considered as part of NAFLD lifestyle prevention and treatment.

Abstract Background The aim of this study was to investigate the influence of serum iron levels in advanced gastric cancer (GC) patients treated with programmed cell death protein-1 (PD-1) inhibitors. Methods We retrospectively reviewed 149 GC patients who were treated with PD-1 inhibitors at our center. Clinicopathological characteristics, laboratory data, and clinical outcomes were analyzed. Results Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), histological subtype, and baseline serum iron levels were independent prognostic factors for overall survival (OS), while ECOG PS, multiple metastatic sites, and baseline serum iron levels were independent prognostic factors for progression-free survival (PFS). Patients with baseline low serum iron levels (LSI) had a significantly shorter median OS and PFS compared to patients with normal serum iron levels (NSI) (Median OS: 7 vs. 14 months, p = 0.001; median PFS: 3 vs. 5 months, p = 0.005). Patients with baseline LSI had a disease control rate (DCR) of 58.3% at 2 months after PD-1 inhibitor initiation (M2), compared to 81.1% in patients with NSI (p = 0.005). Patients with baseline LSI had a DCR of 43.8% at 4 months, compared to 64.2% in patients with NSI (p = 0.017). Conclusions LSI was associated with worse OS, PFS, and DCR in GC patients treated with PD-1 inhibitors and might be a quick and efficient biomarker to predict the efficacy of PD-1 inhibitors.

This paper examines the impact of firms' digital transformation on management earnings forecasts with a sample of Chinese firms. Using a deep learning model and textual analysis, we create a proxy for digital transformation based on the frequency of keywords related to digitization in firms' annual reports. Our empirical results reveal that firms that engage in more digital transformation are more likely to issue management earnings forecasts voluntarily, more often, and with greater precision. The findings are robust to alternative metrics of management earnings forecasts and digital transformation, after accounting for endogeneity, and after considering firms' future forecasts. Additional analyses on the transmission mechanisms suggest that digital transformation improves firms’ information environment, enhances internal controls, and alleviates agency problems.

Abstract In this work, we make a systematical study on the four-body $$B_{(s)} \rightarrow (\pi \pi )(\pi \pi )$$ B ( s ) → ( π π ) ( π π ) decays in the perturbative QCD (PQCD) approach, where the $$\pi \pi $$ π π invariant mass spectra are dominated by the vector resonance $$\rho (770)$$ ρ ( 770 ) and the scalar resonance $$f_0(980)$$ f 0 ( 980 ) . We improve the Gengenbauer moments for the longitudinal P-wave two-pion distribution amplitudes (DAs) by fitting the PQCD factorization formulas to measured branching ratios of three-body and four-body B decays. With the fitted Gegenbauer moments, we make predictions for the branching ratios and direct CP asymmetries of four-body $$B_{(s)} \rightarrow (\pi \pi )(\pi \pi )$$ B ( s ) → ( π π ) ( π π ) decays. As a by-product, we extract the branching ratios of two-body $$B_{(s)} \rightarrow \rho \rho $$ B ( s ) → ρ ρ from the corresponding four-body decay modes and calculate the relevant polarization fractions. We find that the $$\mathcal{B}(B^0 \rightarrow \rho ^+\rho ^-)$$ B ( B 0 → ρ + ρ - ) is consistent with the previous theoretical predictions and data. The leading-order PQCD calculations of the $$\mathcal{B}(B^+\rightarrow \rho ^+\rho ^0)$$ B ( B + → ρ + ρ 0 ) , $$\mathcal{B}(B^0\rightarrow \rho ^0\rho ^0)$$ B ( B 0 → ρ 0 ρ 0 ) and the $$f_0(B^0\rightarrow \rho ^0\rho ^0)$$ f 0 ( B 0 → ρ 0 ρ 0 ) are a bit lower than the experimental measurements, which should be further examined. It is shown that the direct CP asymmetries are large when both tree and penguin contributions are comparable to each other, but small for the tree-dominant or penguin-dominant processes. In addition to the direct CP asymmetries, the “true” and “fake” triple-product asymmetries (TPAs) originating from the interference among various helicity amplitudes in the $$B_{(s)}\rightarrow (\pi \pi )(\pi \pi )$$ B ( s ) → ( π π ) ( π π ) decays are also analyzed. The sizable averaged TPA $$\mathcal{A}_{\text {T-true}}^{1, \text {ave}}=25.26\%$$ A T-true 1 , ave = 25.26 % of the color-suppressed decay $$B^0\rightarrow \rho ^0\rho ^0 \rightarrow (\pi ^+\pi ^-)(\pi ^+\pi ^-)$$ B 0 → ρ 0 ρ 0 → ( π + π - ) ( π + π - ) is predicted for the first time, which deviates a lot from the so-called “true” TPA $$\mathcal {A}_\text {T-true}^1=7.92\%$$ A T-true 1 = 7.92 % due to the large direct CP violation. A large “fake” TPA $$\mathcal {A}_\text {T-fake}^1=24.96\%$$ A T-fake 1 = 24.96 % of the decay $$B^0\rightarrow \rho ^0\rho ^0 \rightarrow (\pi ^+\pi ^-)(\pi ^+\pi ^-)$$ B 0 → ρ 0 ρ 0 → ( π + π - ) ( π + π - ) is also found, which indicates the significance of the final-state interactions. The predictions in this work can be tested by LHCb and Belle-II experiments in the near future.

Abstract This study aimed to construct a Ginsenoside Rb1-PLGA nano drug delivery system, optimize its preparation process, characterize and evaluate the resulting Ginsenoside Rb1-PLGA Nanoparticles (GRb1@PLGA@NPs). GRb1@PLGA@NPs were prepared using the emulsion solvent evaporation method. The optimal preparation process was determined using Plackett–Burman design combined with Box-Behnken experiments. Physical characterization and in vitro release studies were conducted. LC–MS/MS technique was employed to investigate the pharmacokinetic characteristics of GRb1 and GRb1@PLGA@NPs in rat plasma. The optimal preparation process yielded GRb1@PLGA@NPs with a particle size of 120.63 nm, polydispersity index (PDI) of 0.172, zeta potential of − 22.67 mV, encapsulation efficiency of 75%, and drug loading of 11%. In vitro release demonstrated sustained drug release. Compared to GRb1, GRb1@PLGA@NPs exhibited a shortened time to peak concentration by approximately 0.72-fold. The area under the plasma concentration–time curve significantly increased to 4.58-fold of GRb1. GRb1@PLGA@NPs formulated using the optimal process exhibited uniform distribution and stable quality, its relative oral bioavailability was significantly improved compared to free GRb1.

The bacterial phase changes and the effect of dominant spoilage bacteria on quality were studied with traditional identification method and high-throughput sequence technique using Chinese traditional food soybean curd sheets as materials. Sterile soybean curd sheets were inoculated with three dominant bacteria and their combination. The total viable counts, total volatile base nitrogen (TVB-N), pH, sensory score, and texture characteristics of samples during normal temperature storage were measured periodically for spoilage potential. The scanning electron microscopy, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and Fourier transform infrared spectroscopy (FTIR) were used to determine the effect of spoilage bacteria on the protein. The results indicated the bacterial phases of soybean curd sheets changed obviously during storage, and Acinetobacter, Staphylococcus as well as Kurthia became the dominant bacteria after 2 days of storage. The selected representative spoilage bacteria were re-inoculated to the samples, one protease-producing Staphylococcus sciuri and the mixed bacteria had the strongest spoilage potential, because the TVB-N and viscosity increased greatly, while the hardness, springiness, and chewiness decreased significantly (P

ABSTRACTThe development of simple and high-throughput approaches to yield solid-state nanopores on large surface membranes may facilitate the prevalence of nanopore analysis technology and in-vitro diagnosis using portable devices. However, solid-state nanopores are typically realized by complex and high-end nanofabrication equipments. Here, we present a method to achieve nanopores on polymer membranes using silver nanoparticles (AgNPs) as templates and intense pulsed light (IPL) as a heating source. The density and size of nanopores are controllable by adjusting the spin coating rate, the concentration of nanoparticle suspension, and the size of nanoparticles (NPs). The temperature of the AgNPs can rapidly reach 1132 K under instant heating of photothermal effect through light irradiation in 2 ms, resulting in localized melting and decomposition of an underneath polycarbonate (PC) membrane to yield nanopores with sizes ranging from 10 to 270 nm. After removing the nanoparticle residues, the flexible membrane with nanopores can be integrated into a flow cell to achieve a nanopore sensor that has been used to measure the translocation behaviors of bovine serum albumin (BSA). The results have demonstrated the capability of the sensor in protein denaturation identification. This low-cost and high-throughput technique to fabricate solid-state nanopores on flexible polymeric membranes may facilitate the development of more nanopore-based flexible sensors that can be integrated with other flexible components for wearable diagnosis.

Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide. Despite significant advances in current drug therapies, issues such as poor drug targeting and severe side effects persist. In recent years, nanomedicine has been extensively applied in the research and treatment of CVDs. Among these, biomembrane-modified biomimetic nanodrug delivery systems (BNDSs) have emerged as a research focus due to their unique biocompatibility and efficient drug delivery capabilities. By modifying with biological membranes, BNDSs can effectively reduce recognition and clearance by the immune system, enhance biocompatibility and circulation time in vivo, and improve drug targeting. This review first provides an overview of the classification and pathological mechanisms of CVDs, then systematically summarizes the research progress of BNDSs in the treatment of CVDs, discussing their design principles, functional characteristics, and clinical application potential. Finally, it highlights the issues and challenges faced in the clinical translation of BNDSs.

The Lancang-Mekong River Basin (LMRB) is an important transboundary river basin containing large-scale cascade hydropower dams. There has been increasing interest in the cross-border impacts of cascade reservoirs and climate change on the water temperature of the LMRB. However, there remain limited related basin-scale quantitative studies. This study applied a deep learning method (Long short-term memory neural network, LSTM) to reconstruct the natural water temperature of the Lower Mekong River (LMR), which was compared with observation data influenced by dam operation. The aim of this study was to assess the impacts of the dams and climate change on the dynamics of water temperature in the basin. The results showed that: (1) Climate change had a relatively minor effect on the water temperature of the LMRB, with the warming effect of climate change gradually increasing from upstream to downstream. (2) The operation of the cascade reservoirs has resulted in seasonal warming and cooling of water temperature, although the average annual water temperature of the LMRB has increased by 0.27–0.59 °C. (3) The slight increase in annual average water temperature due to reservoir operation gradually weakened from upstream to downstream. (4) The increase in annual river temperature became more pronounced from 2008 to 2016 with the completion of Xiaowan, Nuozadu, and other power stations. This study characterized the responses of streamflow temperature to climate change and cascade reservoirs and can act as a reference for water resources management and hydropower development in the LMRB.

The C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-albumin ratio (NAR) serve as established markers for inflammatory diseases. However, limited studies have investigated their potential in predicting response and prognosis following infliximab (IFX) treatment. The objective of this paper was to evaluate feasibility of CAR and NAR as biomarkers to assess response to IFX induction therapy. Additionally, we attempted to determine the capacity to predict clinical remission in ulcerative colitis (UC) after 54 weeks of IFX treatment. We enrolled a total of 157 UC patients diagnosed via endoscopic mucosal biopsy at our hospital between October 2018 and June 2023. Additionally, 199 patients presenting with gastrointestinal symptoms, who underwent physical examinations, constituted the control group. Comprehensive clinical data, laboratory indicators, and endoscopic findings were systematically collected. CAR and NAR values were computed before treatment, post-induction, and subsequently at 8-week intervals. Comparisons between two groups were analyzed using the Wilcoxon rank-sum test or the independent samples t-test, and comparisons between multiple groups were analyzed using the one-way ANOVA (analysis of variance) or the Kruskal-Wallis rank sum test. We found CAR and NAR emerged as sensitive biomarkers for assessing disease activity. Notably, our findings indicated their dual predictive capability: foreseeing response post-IFX induction therapy and prognosticating the likelihood of UC patients achieving clinical remission following 54 weeks on IFX therapy.

Amomum villosum Lour. (A. villosum), known as Sharen in China, is widely used for culinary and medicinal purposes due to containing a diverse set of bioactive compounds. In this study, the optimum ethanol extraction process was optimized and the composition and biological activities (antioxidant and antitumor) of five different fractions (dichloromethane, petroleum ether, ethyl acetate, n-butanol and H2O) extracted from the ethanol extract of A. villosum were investigated. The results showed that the optimal extraction conditions were extraction temperature 80°C, extraction time 120 min, ethanol concentration 40% and solid–liquid ratio 1:25 g/mL. Moreover, 35 bioactive compounds were successfully identified by UPLC-ESI-QTOF-MS/MS from five factions for the first time, including 12 phenolic acids and derivatives, 2 organic acids, 12 flavonoids and derivatives, 2 oxylipins and 7 proanthocyanidins. Among them, ethyl acetate fraction (Fr-EtOAc) exhibited the highest content of total phenolic (374.01 mg GAE/g DW) and flavonoid (93.11 mg RE/g DW), where vanillic acid, catechin, epicatechin and protocatechuic acid were the predominant phenolic compounds that accounting for 81.65% of the quantified bioactive compounds. In addition, Fr-EtOAc demonstrated excellent total antioxidant activity (IC50 of DPPH and ABTS assays were 0.23, 0.08 mg/mL, respectively, and FRAP assay was 322.91 mg VCE/100 g DW) and antitumor activity (1,000 μg/mL, 79.04% inhibition rate). The results could provide guidance for the industrial production and application of A. villosum.

Background: People with psoriasis are at a higher risk for having central neurological problems, according to previous studies; however, it is unclear if there is a genetic link between the risk of developing psoriasis and developing central neurological disorders. In this study, the possible link between genetically predisposed psoriasis and the risk of common central nervous system disorders was comprehensively investigated. Methods: There was no overlap in the participant populations between the psoriasis and central neurological disorders genome-wide association studies, which provide the genetic resources. Inverse variance weighting, often used as Mendelian randomization (MR) analysis, is the main method. To guarantee the accuracy of our findings, a number of sensitivity studies were carried out. Results: MR analysis revealed that although psoriasis was reported to increase the risk of Parkinson's disease (OR = 4.42, 95%CI[-3.81～6.79], P = 0.58) and epilepsy (OR = 4.71, 95%CI[-2.20～5.30], P = 0.42) in this study, they did not reach statistical significance. At the same time, this study did not observe that psoriasis would increase the risk of multiple sclerosis (OR = 0.01, 95%CI [-12.61～3.83], P = 0.30) and migraine (OR = 0.99, 95%CI [0.94～1.05], P = 0.78), they also did not reach statistical significance. Under all sensitivity assessments, the results remained stable. Conclusions: Psoriasis does not appear to raise the risk of migraine, Parkinson's disease, multiple sclerosis, or epilepsy, according to our study.

Abstract Background The impact of fibroblasts on the immune system provides insight into the function of fibroblasts. In various tissue microenvironments, multiple fibroblast subtypes interact with immunocytes by secreting growth factors, cytokines, and chemokines, leading to wound healing, fibrosis, and escape of cancer immune surveillance. However, the specific mechanisms involved in the fibroblast‐immunocyte interaction network have not yet been fully elucidated. Main body and conclusion Therefore, we systematically reviewed the molecular mechanisms of fibroblast‐immunocyte interactions in fibrosis, from the history of cellular evolution and cell subtype divisions to the regulatory networks between fibroblasts and immunocytes. We also discuss how these communications function in different tissue and organ statuses, as well as potential therapies targeting the reciprocal fibroblast‐immunocyte interplay in fibrosis. A comprehensive understanding of these functional cells under pathophysiological conditions and the mechanisms by which they communicate may lead to the development of effective and specific therapies targeting fibrosis.