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Abstract An origin discrimination model for rice from five production regions in Heilongjiang Province was constructed based on the combination of confocal microscopy Raman spectroscopy and chemometrics. A total of 150 field rice samples were collected from the Fangzheng, Chahayang, Jiansanjiang, Xiangshui, and Wuchang production areas. The optimal sample processing conditions, instrument parameter settings, and spectrum acquisition techniques were identified by investigating the influencing factor. The Raman spectra of milled rice within the range of 100–3200 cm−1 were selected as the raw data, and the optimal preprocessing method combination consisting of normalization, Savitzky–Golay smoothing, and multivariate scatter correction was identified. Subsequently, the competitive adaptive reweighted sampling and discrete binary particle swarm optimization algorithms were employed to optimize the feature wavelength selection, resulting in the screening of 226 and 1899 feature wavelength variables, respectively. Using the full Raman spectrum data and feature wavelength data as inputs, partial least squares discriminant analysis, support vector machine and extreme learning machine origin discrimination models were constructed. The results indicated that the BPSO-GA-SVM model exhibited the best predictive ability, achieving a testing set accuracy of 86.67%.

BackgroundEmergence delirium(ED) is a common postoperative complication in children undergoing tonsillectomy and adenoidectomy under general anesthesia. There is no high-quality evidence on the relationship between esketamine and ED. The systematic review and meta-analysis was performed to investigate the effect of perioperative esketamine use on ED in children undergoing tonsillectomy and adenoidectomy.MethodWe searched Embase, The Cochrane Library, PubMed, MEDLINE, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, VIP, and SinoMed from inception to 1 September, 2024. Two evaluators identified randomized controlled trials comparing perioperative use of esketamine with placebo or other drugs in children undergoing tonsillectomy and adenoidectomy. Incidence of ED was the primary outcome of the study. Data synthesis was performed by using Review Manager 5.4 software.ResultsTwenty-three relevant studies involving a total of 1,996 children were identified. Perioperative use of esketamine reduced the incidence of ED in children undergoing tonsillectomy and adenoidectomy (RR = 0.33, 95% CI: [0.25, 0.44], p

The primary node molecules in the cell signaling network in cancer tissues are maladjusted and mutated in comparison to normal tissues, which promotes the occurrence and progression of cancer. Pancreatic cancer (PC) is a highly fatal cancer with increasing incidence and low five-year survival rates. Currently, there are several therapies that target cell signaling networks in PC. However, PC is a “cold tumor” with a unique immunosuppressive tumor microenvironment (poor effector T cell infiltration, low antigen specificity), and targeting a single gene or pathway is basically ineffective in clinical practice. Targeted matrix therapy, targeted metabolic therapy, targeted mutant gene therapy, immunosuppressive therapy, cancer vaccines, and other emerging therapies have shown great therapeutic potential, but results have been disappointing. Therefore, we summarize the identified and potential drug-resistant cell signaling networks aimed at overcoming barriers to existing PC therapies.

Abstract Missing labels in multi-label datasets are a common problem, especially for minority classes, which are more likely to occur. This limitation hinders the performance of classifiers in identifying and extracting information from minority classes. Oversampling is an effective method for addressing imbalanced multi-label problems by generating synthetic instances to create a class-balanced dataset. However, the existing oversampling algorithms mainly focus on the location of the generated data, and there is a lack of design on how to complete the labels of the synthetic data. To address this issue, we propose MLAWSMOTE, a synthetic data generation algorithm based on matrix factorization weights. We introduce a weak supervised learning method in the oversampling method, optimize the weights of features and labels by using label correlation, and iteratively learn the ideal label weights. The mapping relationship between features and labels is learned from the dataset and the label correlation matrix. The oversampling ratio is defined based on the discrepancy between observed labels and the ideal label of synthetic instances. It mitigates the impact of missing minority labels on the model’s predictions. The labeling of synthetic instances is performed based on label prediction, and the potential labeling distribution is complemented. Experimental results on multiple multi-label datasets under different label missing ratios demonstrate the effectiveness of the proposed method in terms of ACC, Hamming loss, MacroF1 and MicroF1. In the validation of the four classifiers, MacroF1 decreased by 24.78%, 17.81%, 3.8% and 19.56%, respectively, with the increase of label loss rate. After applying MLAWSMOTE only decreased by 15.79%, 13.63%, 3.78% and 15.21%.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor deficits due to the depletion of nigrostriatal dopamine. Stem cell differentiation therapy emerges as a promising treatment option for sustained symptom relief. In this study, we successfully developed a one-step differentiation system using the YFBP cocktail (Y27632, Forskolin, SB431542, and SP600125) to effectively convert human umbilical cord mesenchymal stem cells (hUCMSCs) into dopaminergic neurons without genetic modification. This approach addresses the challenge of rapidly and safely generating functional neurons on a large scale. After a 7-day induction period, over 80 % of the cells were double-positive for TUBB3 and NEUN. Transcriptome analysis revealed the dual roles of the cocktail in inducing fate erasure in mesenchymal stem cells and activating the neuronal program. Notably, these chemically induced cells (CiNs) did not express HLA class II genes, preserving their immune-privileged status. Further study indicated that YFBP significantly downregulated p53 signaling and accelerated the differentiation process when Pifithrin-α, a p53 signaling inhibitor, was applied. Additionally, Wnt/β-catenin signaling was transiently activated within one day, but the prolonged activation hindered the neuronal differentiation of hUCMSCs. Upon transplantation into the striatum of mice, CiNs survived well and tested positive for dopaminergic neuron markers. They exhibited typical action potentials and sodium and potassium ion channel activity, demonstrating neuronal electrophysiological activity. Furthermore, CiNs treatment significantly increased the number of tyrosine hydroxylase-positive cells and the concentration of dopamine in the striatum, effectively ameliorating movement disorders in PD mice. Overall, our study provides a secure and reliable framework for cell replacement therapy for Parkinson's disease.

Abstract Background Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co‐differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. Methods Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real‐time polymerase chain reaction, Cell Counting Kit‐8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. Results PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA‐432‐5p (miR‐432‐5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR‐433‐3p in PMECs, and upregulate zinc finger AN1‐type containing 5 (ZFAND5) expression by targeting miR‐3613‐5p in PCs. Conclusions Our results suggest that circPMS1 promotes cell proliferation through the miR‐432‐5p/DEPDC1 or miR‐432‐5p/POL2D axis in PASMCs, through the miR‐433‐3p/MXI1 axis in PMECs, and through the miR‐3613‐5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.

Abstract Imbalanced class distributions are common in real-world scenarios, including datasets with multiple labels. One widely acknowledged approach to addressing imbalanced distributions is through oversampling, a technique that both balances the class distribution and improves the effectiveness of classification models. However, when generating synthetic data for multi-label datasets, complexities arise due to the presence of multiple-label sets, which require careful placement and labeling. We propose MLCSMOTE-FRST, an algorithm for synthetic data generation based on label-specific clustering and fuzzy rough set theory. Generation ratios and dependency samples are provided by clusters specific to each label, with a focus on the overall label distribution and the distribution within each cluster. The labels are supported by intra-cluster positive samples, determined using fuzzy rough set theory, which helps to capture the consensus label set. Experimental results on multi-label datasets using four classifiers demonstrate the effectiveness of the proposed method in terms of macro-F1 and micro-F1 scores.

Abstract Background Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) has been implicated in numerous inflammatory and cancerous conditions. However, its precise molecular mechanisms in endometriosis (EMs) remains unclear. The aim of this study is to examine the influence of IGF2BP3 on the occurrence and progression of EMs and to elucidate its underlying molecular mechanism. Methods Efects of IGF2BP3 on endometriosis were confrmed in vitro and in vivo. Based on bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assays and Fluorescent in situ hybridization (FISH) were used to show the association between IGF2BP3 and UCA1. Single-cell spatial transcriptomics analysis shows the expression distribution of glutaminase 1 (GLS1) mRNA in EMs. Study the effect on glutamine metabolism after ectopic endometriotic stromal cells (eESCs) were transfected with Sh-IGF2BP3 and Sh-UCA1 lentivirus. Results Immunohistochemical staining have revealed that IGF2BP3 was upregulated in ectopic endometriotic lesions (EC) compared to normal endometrial tissues (EN). The proliferation and migration ability of eESCs were greatly reduced by downregulating IGF2BP3. Additionally, IGF2BP3 has been observed to interact with urothelial carcinoma associated 1 (UCA1), leading to increased stability of GLS1 mRNA and subsequently enhancing glutamine metabolism. Results also demonstrated that IGF2BP3 directly interacts with the 3’ UTR region of GLS1 mRNA, influencing its expression and stability. Furthermore, UCA1 was able to bind with c-MYC protein, stabilizing c-MYC mRNA and consequently enhancing GLS1 expression through transcriptional promotion. Conclusion These discoveries underscored the critical involvement of IGF2BP3 in the elevation and stability of GLS1 mRNA in the context of glutamine metabolism by interacting with UCA1 in EMs. The implications of our study extended to the identification of possible therapeutic targets for individuals with EMs.

Bioaerosols are a subset of important airborne particulates that present a substantial human health hazard due to their allergenicity and infectivity. Chemical reactions in atmospheric processes can significantly influence the health hazard presented by bioaerosols; however, few studies have summarized such alterations to bioaerosols and the mechanisms involved. In this paper, we systematically review the chemical modifications of bioaerosols and the impact on their health effects, mainly focusing on the exacerbation of allergic diseases such as asthma, rhinitis, and bronchitis. Oxidation, nitration, and oligomerization induced by hydroxyl radicals, ozone, and nitrogen dioxide are the major chemical modifications affecting bioaerosols, all of which can aggravate allergenicity mainly through immunoglobulin E pathways. Such processes can even interact with climate change including the greenhouse effect, suggesting the importance of bioaerosols in the future implementation of carbon neutralization strategies. In summary, the chemical modification of bioaerosols and the subsequent impact on health hazards indicate that the combined management of both chemical and biological components is required to mitigate the health hazards of particulate air pollution.

Abstract Background Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. Methods We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. Results (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. Conclusion FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH.

A steady dysfunctional state caused by chronic antigen stimulation in the tumor microenvironment (TME) is known as CD8+ T cell exhaustion. Exhausted-like CD8+ T cells (CD8+ Tex) displayed decreased effector and proliferative capabilities, elevated co-inhibitory receptor generation, decreased cytotoxicity, and changes in metabolism and transcription. TME induces T cell exhaustion through long-term antigen stimulation, upregulation of immune checkpoints, recruitment of immunosuppressive cells, and secretion of immunosuppressive cytokines. CD8+ Tex may be both the reflection of cancer progression and the reason for poor cancer control. The successful outcome of the current cancer immunotherapies, which include immune checkpoint blockade and adoptive cell treatment, depends on CD8+ Tex. In this review, we are interested in the intercellular signaling network of immune cells interacting with CD8+ Tex. These findings provide a unique and detailed perspective, which is helpful in changing this completely unpopular state of hypofunction and intensifying the effect of immunotherapy.

Abstract Background Our previous study found that mouse embryonic neural stem cell (NSC)–derived exosomes (EXOs) regulated NSC differentiation via the miR‐9/Hes1 axis. However, the effects of EXOs on brain microvascular endothelial cell (BMEC) dysfunction via the miR‐9/Hes1 axis remain unknown. Therefore, the current study aimed to determine the effects of EXOs on BMEC proliferation, migration, and death via the miR‐9/Hes1 axis. Methods Immunofluorescence, quantitative real‐time polymerase chain reaction, cell counting kit‐8 assay, wound healing assay, calcein‐acetoxymethyl/propidium iodide staining, and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs. Results EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. The overexpression of miR‐9 promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. Moreover, miR‐9 downregulation inhibited BMEC proliferation and migration and also promoted cell death. Hes1 silencing ameliorated the effect of amtagomiR‐9 on BMEC proliferation and migration and cell death. Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia‐induced mice. Meanwhile, EXO treatment improved cerebrovascular alterations. Conclusion NSC‐derived EXOs can promote BMEC proliferation and migration and reduce cell death via the miR‐9/Hes1 axis under hypoxic conditions. Therefore, EXO therapeutic strategies could be considered for hypoxia‐induced vascular injury.

To reduce power waste and improve the operational safety of renewable energy grids, this study proposes an auxiliary decision-making method for power dispatching based on flexible super-capacitors and proximal policy optimization algorithms. The results demonstrated that the impedance of Mn&Ni-based composite electrodes was small, about $118~\Omega $ , and when the current density was 1A/g, the constant current charging and discharging time could reach 128 seconds, with a specific capacitance of 39F/g. In addition, when the power density of the capacitor was 8500W/kg, the energy density could reach up to 125Wh/kg. As for the auxiliary decision-making model for power dispatching, the reward value of the proximal policy optimization algorithm began to converge after approximately 50,000 iterations, at which point its reward value was approximately 257. The reward value of the one-step scheduling strategy gradually stabilized at around 1.0 after the number of scheduling steps reached 560,000. When the energy output rate of renewable energy units was high, the consumption rate of renewable energy was 90.1%. The above results indicate that the power scheduling method combining flexible super-capacitors and proximal policy optimization algorithms can effectively achieve the storage of electricity and improve the consumption rate of renewable energy.

Schistosomiasis, caused by Schistosoma japonicum, continues to pose a major public health threat in East Asia, with an estimated 71 million people at risk of infection. Domestic animals, especially buffaloes and goats, serve as important reservoir hosts, facilitating the transmission of the parasite to humans. While praziquantel (PZQ) is the first-line treatment for schistosomiasis due to its broad-spectrum efficacy against adult schistosomes, its prophylactic potential is less explored. This study aimed to evaluate the efficacy of PZQ in preventing S. japonicum infection in buffaloes and goats via assessing worm burden, worm size, hematological changes, and immune modulation. In the present study, buffaloes and goats were pretreated with PZQ at various doses (7–25 mg/kg body weight), followed by infection with S. japonicum cercariae. The results showed significant reductions in total worm burden and female worm burden, with one oral administration at 13 mg/kg for buffaloes and one injection at 25 mg/kg for goats offering the most robust protection. Worm length was also significantly reduced in both buffaloes and goats, indicating that PZQ not only prevented infection in this study but also inhibited worm growth. Furthermore, PZQ pretreatment modulated immune responses, as evidenced by increased levels of nitric oxide (NO) and interleukin-2 (IL-2) in buffaloes and Lym% in goats. These findings suggest that PZQ has significant prophylactic potential in livestock, offering a practical solution for reducing schistosome transmission from animals to humans in endemic regions. Additionally, this study indicates that PZQ pretreatment does not contribute to resistance development, as newly established infections are effectively cleared during the initial treatment window.

Abstract Schistosomiasis is a neglected tropical disease that affects humans and animals in tropical and subtropical regions worldwide. Schistosome eggs are responsible for the pathogenesis and transmission of schistosomiasis, thus reducing egg production is vital for prevention and control of schistosomiasis. However, the mechanisms underlying schistosome reproduction remain unclear. Annexin proteins (ANXs) are involved in the physiological and pathological functions of schistosomes, but the specific regulatory mechanisms and roles of ANX A13 in the development of Schistosoma japonicum and host–parasite interactions remain poorly understood. Therefore, in this study, the expression profiles of SjANX A13 at different life cycle stages of S. japonicum were assessed using quantitative PCR. In addition, the expression profiles of the homolog in S. mansoni were analyzed in reference to public datasets. The results of RNA interference showed that knockdown of SjANX A13 significantly affected the development and egg production of female worms in vivo. The results of an immune protection assay showed that recombinant SjANX A13 increased production of immunoglobulin G-specific antibodies. Finally, co-culture of S. japonicum exosomes with LX-2 cells using a transwell system demonstrated that SjANX A13 is involved in host–parasite interactions via exosomes. Collectively, these results will help to clarify the roles of SjANX A13 in the development of S. japonicum and host–parasite interactions as a potential vaccine candidate.

Abstract Background Trans- inferior alveolar nerve (IAN) implantation technique was wildly used while the potential appropriate angle range in which the residual alveolar bone can bear the stress without absorption are currently unclear. This study aimed to evaluate the stress distribution pattern of the interface between bone and implant by finite element analysis (FEA) to determine the appropriate range of the implant tilt angle. Methods Cone beam computed tomography (CBCT) images of 120 patients with missing mandibular second molars and vertical bone height

Abstract Endometriosis is a gynecological inflammatory disease that is linked with immune cells, specifically macrophages. IL-33 secreted from macrophages is known to accelerate the progression of endometriosis. The periodic and repeated bleeding that occurs in women with endometriosis leads to excess iron in the microenvironment that is conducive to ferroptosis, a process related to intracellular ROS production, lipid peroxidation and mitochondrial damage. It is suggested that eESCs may specifically be able to inhibit ferroptosis. However, it is currently unclear whether IL-33 directly regulates ferroptosis to influence the disease course in endometriosis. In this study, eESCs co-cultured with macrophages or stimulated with IL-33/ST2 were observed to have increased cell viability and migration. Additionally, IL-33/ST2 decreased intracellular iron levels and lipid peroxidation in eESCs exposed to erastin treatment. Furthermore, IL-33/ST2 treatment resulted in a notable upregulation in SLC7A11 expression in eESCs due to the downregulation of negative transcription factor ATF3, thereby suppressing ferroptosis. The P38/JNK pathway activated by IL-33/ST2 was also found to inhibit the transcription factor ATF3. Therefore, we concluded that IL-33/ST2 inhibits the ATF3-mediated reduction in SLC7A11 transcript levels via the P38/JNK pathway. The findings reveal that macrophage-derived IL-33 upregulates SLC7A11 in eESCs through the p38/JNK/ATF3 pathway, ultimately resulting in protection against ferroptosis in eESCs. Moreover, we conducted an experiment using endometriosis model mice that showed that a combination of IL-33-Ab and erastin treatment alleviated the disease, showing the promise of combining immunotherapy and ferroptosis therapy.

Abstract Background Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non‐invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD–PH). Methods This study included 535 patients with COPD–PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD–PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan–Meier curves were used for a survival analysis. The nomograms were developed as online network software. Results Tricuspid regurgitation velocity, right ventricular diameter, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), the red blood cell count, New York Heart Association functional class and sex were non‐invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT‐proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD–PH and were used to create a predictive nomogram of overall survival rates. Conclusions The proposed nomograms based on a large sample size of patients with COPD–PH could be used as non‐invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD–PH. Additionally, the online network has the potential to provide artificial intelligence‐assisted diagnosis and treatment. Highlights A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non‐invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD–PH.

Abstract Well‐defined nanostructures are crucial for precisely understanding nano‐bio interactions. However, nanoparticles (NPs) fabricated through conventional synthesis approaches often lack poor controllability and reproducibility. Herein, a synthetic biology‐based strategy is introduced to fabricate uniformly reproducible protein‐based NPs, achieving precise control over heterogeneous components of the NPs. Specifically, a ferritin assembly toolbox system is developed that enables intracellular assembly of ferritin subunits/variants in Escherichia coli. Using this strategy, a proof‐of‐concept study is provided to explore the interplay between ligand density of NPs and their tumor targets/penetration. Various ferritin hybrid nanocages (FHn) containing human ferritin heavy chains (FH) and light chains are accurately assembled, leveraging their intrinsic binding with tumor cells and prolonged circulation time in blood, respectively. Further studies reveal that tumor cell uptake is FH density‐dependent through active binding with transferrin receptor 1, whereas in vivo tumor accumulation and tissue penetration are found to be correlated to heterogeneous assembly of FHn and vascular permeability of tumors. Densities of 3.7 FH/100 nm2 on the nanoparticle surface exhibit the highest degree of tumor accumulation and penetration, particularly in tumors with high permeability compared to those with low permeability. This study underscores the significance of nanoparticle heterogeneity in determining particle fate in biological systems.

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

Schistosomiasis is a fatal zoonotic parasitic disease that also threatens human health. The main pathological features of schistosomiasis are granulomatous inflammation and subsequent liver fibrosis, which is a complex, chronic, and progressive disease. Extracellular vesicles (EVs) derived from schistosome eggs are broadly involved in host-parasite communication and act as important contributors to schistosome-induced liver fibrosis. However, it remains unclear whether substances secreted by the EVs of Schistosoma japonicum, a long-term parasitic "partner" in the hepatic portal vein of the host, also participate in liver fibrosis. Here, we report that EVs derived from S. japonicum worms attenuated liver fibrosis by delivering sja-let-7 into hepatic stellate cells (HSCs). Mechanistically, activation of HSCs was reduced by targeting collagen type I alpha 2 chain (Col1α2) and downregulation of the TGF-β/Smad signaling pathway both in vivo and in vitro. Overall, these results contribute to further understanding of the molecular mechanisms underlying host-parasite interactions and identified the sja-let-7/Col1α2/TGF-β/Smad axis as a potential target for treatment of schistosomiasis-related liver fibrosis.

Abstract Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.

Background Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. Methods and Results Deep RNA sequencing and quantitative real‐time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P

Overcoming the immunosuppressive tumor microenvironment and identifying widely used immunosuppressants with minimal side effects are two major challenges currently hampering cancer immunotherapy. Regulatory T cells (Tregs) are present in almost all cancer tissues and play an important role in preserving autoimmune tolerance and tissue homeostasis. The tumor inflammatory microenvironment causes the reprogramming of Tregs, resulting in the conversion of Tregs to immunosuppressive phenotypes. This process ultimately facilitates tumor immune escape or tumor progression. However, current systemic Treg depletion therapies may lead to severe autoimmune toxicity. Therefore, it is crucial to understand the mechanism of Treg reprogramming and develop immunotherapies that selectively target Tregs within tumors. This article provides a comprehensive review of the potential mechanisms involved in Treg cell reprogramming and explores the application of Treg cell immunotherapy. The interference with reprogramming pathways has shown promise in reducing the number of tumor-associated Tregs or impairing their function during immunotherapy, thereby improving anti-tumor immune responses. Furthermore, a deeper understanding of the mechanisms that drive Treg cell reprogramming could reveal new molecular targets for future treatments.

Abstract Background Chronic obstructive pulmonary disease (COPD) is one of the world’s leading causes of death and a major chronic respiratory disease. Aerobic exercise, the cornerstone of pulmonary rehabilitation, improves prognosis of COPD patients; however, few studies have comprehensively examined the changes in RNA transcript levels and the crosstalk between various transcripts in this context. This study identified the expression of RNA transcripts in COPD patients who engaged in aerobic exercise training for 12 weeks, and further constructions of the possible RNAs networks were made. Methods Peripheral blood samples for all four COPD patients who benefited from 12 weeks of PR were collected pre- and post-aerobic exercises and evaluated for the expression of mRNA, miRNA, lncRNA, and circRNA with high-throughput RNA sequencing followed by GEO date validation. In addition, enrichment analyses were conducted on different expressed mRNAs. LncRNA-mRNA and circRNA-mRNA coexpression networks, as well as lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA competing expression networks (ceRNAs) in COPD were constructed. Results We identified and analyzed the differentially expressed mRNAs and noncoding RNAs in the peripheral blood of COPD patients’ post-exercise. Eighty-six mRNAs, 570 lncRNAs, 8 miRNAs, and 2087 circRNAs were differentially expressed. Direct function enrichment analysis and Gene Set Variation Analysis showed that differentially expressed RNAs(DE-RNAs) correlated with several critical biological processes such as chemotaxis, DNA replication, anti-infection humoral response, oxidative phosphorylation, and immunometabolism, which might affect the progression of COPD. Some DE-RNAs were validated by Geo databases and RT-PCR, and the results were highly correlated with RNA sequencing. We constructed ceRNA networks of DE-RNAs in COPD. Conclusions The systematic understanding of the impact of aerobic exercise on COPD was achieved using transcriptomic profiling. This research offers a number of potential candidates for clarifying the regulatory mechanisms that exercise has on COPD, which could ultimately help in understanding the pathophysiology of COPD.

Abstract Aims Myocardial infarction (MI) is one of the serious diseases with great mortality over the world. Myocardial mitochondrial oxidative stress has been implicated as a key player in MI. The histidine triad nucleotide‐binding protein 2 (HINT2) is a nucleotide hydrolase and transferase located in mitochondria. HINT2 has multiple functions such as regulating mitochondrial lipid metabolism and respiration and glucose homeostasis. Although HINT2 has been shown to protect against MI, the underlying mechanisms were not fully elucidated. In this study, the effects of HINT2 on oxidative stress during MI were explored. Methods and results MI mouse models in both wild‐type and HINT2‐deficient mice were established. The expression of HINT2 in HINT2‐deficient mice was determined by quantitative real‐time PCR and western blot. The levels of oxidative stress were measured, including the levels of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione (GSH). The myocardial functions, as indicated by left ventricular end‐diastolic diameter (LVEDD), left ventricular end‐systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fractional shortening (LVFS), were monitored. Both mRNA and protein expressions of HINT2 in the myocardial tissues were significantly down‐regulated in MI mice starting at 6 h post‐MI. MI induced oxidative stress 6 h post‐MI in myocardial tissues of wild‐type mice, as suggested by the enhanced MDA and NO levels and decreased SOD and GSH levels. The expression of HINT2 was negatively correlated to the MDA and NO levels and positively correlated to the SOD and GSH levels. HINT2‐deficient MI mice had significantly elevated levels of MDA and NO and significantly decreased levels of SOD and GSH when compared with wild‐type MI mice. HINT2‐deficient MI mice had higher LVEDD and LVESD and lower LVEF and LVFS compared with wild‐type MI mice, indicating that HINT2 deficiency exacerbated myocardial dysfunction. Conclusions HINT2 deficiency causes deteriorative oxidative stress in MI mice, leading to exacerbated myocardial dysfunction.

Lossless image compression is an important research field in image compression. Recently, learning-based lossless image compression methods achieved impressive performance compared with traditional lossless methods, such as WebP, JPEG2000, and FLIF. The aim of the lossless image compression algorithms is to use shorter codelength to represent images. To encode an image with fewer bytes, eliminating the redundancies among the pixels in the image is highly important. Hence, in this paper, we explore the idea of combining an autoregressive model for the raw images based on the end-to-end lossless architecture proposed to enhance the performance. Furthermore, inspired by the successful achievements of Channel-conditioning models, we propose a Multivariant Mixture distribution Channel-conditioning model (MMCC) in our network architecture to boost performance. The experimental results show that our approach outperforms most classical lossless compression methods and existing learning-based lossless methods.

Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, accounting for the second most common cause of gastrointestinal tumors. As one of the intestinal barriers, gut bacteria form biofilm, participate in intestinal work, and form the living environment of intestinal cells. Metagenomic next-generation sequencing (mNGS) of the gut bacteria in a large number of CRC patients has been established, enabling specific microbial signatures to be associated with colorectal adenomato-carcinoma. Gut bacteria are involved in both benign precursor lesions (polyps), in situ growth and metastasis of CRC. Therefore, the term tumorigenic bacteria was proposed in 2018, such as Escherichia coli, Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, etc. Meanwhile, bacteria toxins (such as cytolethal distending toxin (CDT), Colibactin (Clb), B. fragilis toxin) affect the tumor microenvironment and promote cancer occurrence and tumor immune escape. It is important to note that there are differences in the bacteria of different types of CRC. In this paper, the role of tumorigenic bacteria in the polyp-cancer transformation and the effects of their secreted toxins on the tumor microenvironment will be discussed, thereby further exploring new ideas for the prevention and treatment of CRC.

MicroRNAs (miRNAs) are versatile regulators of pulmonary arterial remodeling in idiopathic pulmonary arterial hypertension (IPAH). We herein aimed to characterize miRNAs in peripheral blood mononuclear cell (PBMC) and plasma exosomes, and investigate specific miRNA expression in pulmonary artery cells and lung tissues in IPAH. A co-dysregulated miRNA was identified from the miRNA expression profiles of PBMC and plasma exosomes in IPAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the potential function of differentially expressed miRNAs. Real-time quantitative reverse transcription polymerase chain reaction was used to validate the expression of specific miRNAs in hypoxia-induced pulmonary microvascular endothelial cells (PMECs), pulmonary artery smooth muscle cells (PASMCs), pericyte cells (PCs), and lung tissues of patients with IPAH and rats. Finally, the miRNA-mRNA mechanisms of miR-122-5p were predicted. MiR-122-5p was the only co-upregulated miRNA in PBMC and plasma exosomes in patients with IPAH. Functional analysis of differentially expressed miRNAs revealed associations with the GO terms “transcription, DNA-templated,” “cytoplasm,” and “metal ion binding” in both PBMC and plasma exosomes, KEGG pathway MAPK signaling in PBMC, and KEGG-pathway human papillomavirus infection in plasma exosomes. Hypoxic PMECs and PCs, lung tissue of patients with IPAH, and rats showed increased expression of miR-122-5p, but hypoxic PASMCs showed decreased expression. And miR-122-5p mimics and inhibitor affected cell proliferation. Finally, miR-122-5p was found to potentially target DLAT (in lung tissue) and RIMS1 (in PMECs) in IPAH. According to the dual-luciferase assay, miR-122-5p bound to DLAT or RIMS1. In studies, DLAT imbalance was associated with cell proliferation and migration, RIMS1 is differentially expressed in cancer and correlated with cancer prognosis. Our findings suggest that the miR-122-5p is involved in various biological functions in the adjacent vascular wall cells in IPAH.

Endowing a robust pressure-sensitive adhesive (PSA) with sensable properties is of great significance for in-situ stress detection and information encryption in the fields of electronics, energy storage, flexible sensing, etc. However, it remains great challenge due to the difficulty in balancing interfacial wetting and cohesive strength. Herein, a microphase-separated strategy is proposed to construct an ionogel with a lower modulus of 1.96MPa, a strength of 728kPa as well as a remarkable toughness of 2258.9kJ/m3, which can be used as a sturdy PSA bonded to various substrates (metals, polar plastics, non-polar plastics) under gentle pressure. The comparable modulus and cohesive strength give it an excellent adhesion strength of 1340kPa, which far exceeds most of reported high-performance PSAs. Furthermore, due to the orientation of a large number of ionic groups, the adhesion strength increases by 31.3% once a voltage of 20V is applied. Finally, the sensitive force-resistance response of such PSA that can be used for encrypted messaging was demonstrated.

Numerous viruses manipulate host factors for viral production. We demonstrated that human enterovirus A71 (EVA71), a primary causative agent for hand, foot, and mouth disease (HFMD), increased the level of the DNA damage response (DDR) marker γ-H2AX. DDR is primarily mediated by the ataxia telangiectasia mutated (ATM), ATM and Rad3-related (ATR), or DNA-dependent protein kinase (DNA-PK) pathways. Upregulation of γ-H2AX by EVA71 was dependent on the ATR but not the ATM or DNA-PK pathway. As a nuclear factor, there is no previous evidence of cytoplasmic distribution of γ-H2AX. However, the present findings demonstrated that EVA71 encouraged the localization of γ-H2AX to the cytoplasm. Of note, γ-H2AX formed a complex with structural protein VP3, non-structural protein 3D, and the viral genome. Treatment with an inhibitor or CRISPR/Cas9 technology to decrease or silence the expression of γ-H2AX decreased viral genome replication in host cells; this effect was accompanied by decreased viral protein expression and virions. In animal experiments, caffeine was used to inhibit DDR; the results revealed that caffeine protected neonatal mice from death after infection with EVA71, laying the foundation for new therapeutic applications of caffeine. More importantly, in children with HFMD, γ-H2AX was upregulated in peripheral blood lymphocytes. The consistent in vitro and in vivo data on γ-H2AX from this study suggested that caffeine or other inhibitors of DDR might be novel therapeutic agents for HFMD.

Abstract Background Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH). Methods Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP. Results Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats. Conclusion Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH.

Article highlights This paper uses the image binary segmentation method to separate the gray images of µ-CT scans of glutenite cores, and the pore space and skeleton of different rocks are characterized. And 3D gray images of 3D digital cores are constructed by PerGeos. The pore network model is used to analyze the reservoir pore structure, and the characteristic parameters of pore structure (such as pore radius, throat radius, pore-throat ratio, shape factor and coordination number of rock) are extracted, and the porosity and permeability are calculated to quantitatively evaluate the pore structure. The experiment data reveal that the main pore space of low permeability glutenite reservoir in the study area is micro-pore, with low pore coordination number, small pore-throat ratio, small pore radius and poor pore connectivity. These characteristics contribute to the low permeability reservoir, which has no obvious law of porosity and permeability, and its permeability is mainly affected by pore structure.

Abstract Background While optimizing spirometry is a challenge for lung function labs, long-term variability if any between IOS (impulse oscillometry) parameters and spirometry is not clearly known in stable COPD (chronic obstructive pulmonary disease) and chronic asthma. The forced oscillation technique is increasingly employed in routine lung function testing. Our aim in this study was to determine the variability in oscillometric parameters between clinic visits over weeks or months in two patient groups during a period of clinical stability. Moreover, the research assessed relationships between IOS parameters long-term variability and COPD severity. Methods We used data from 73 patients with stable COPD and 119 patients with stable asthma at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Patients were included if they had three or more clinic visits where spirometry and IOS were performed during a clinically stable period. Data recorded from the first three visits were used. The standard deviation (SDbv), the coefficient of variation (COV), intraclass correlation coefficient (ICC) and the coefficient of repeatability (COR) were calculated, Wilcoxon Mann–Whitney test was used for data that did not conform to normality of distributions, Kruskal Wallis test was used to compare with multiple groups, post hoc comparison was analyzed by Bonferroni, Spearman correlation coefficients for non-parametric data, the multiple regression analyses to determine the relationship between long-term variability and airflow obstruction. Results (1) The repeatability of IOS resistance parameters with ICC values > 0.8 was high in COPD and asthma. ICC values of IOS resistance parameters were higher than IOS reactance parameters; (2) the repeatability of spirometry parameters with ICC values 0.05) and R5-R20 (P > 0.05). Conclusion IOS resistance parameters have good long-term repeatability in asthma and COPD. Additionally, repeatability of spirometry parameters is lower than IOS resistance parameters in different GOLD stages.

Abstract Background Shaoyao Decoction (SYD) is a canonical herbal medicine prescription formulated by Liu Wan-Su in AD 1186. SYD has been widely used to treat inflammatory bowel disease by clearing heat and damp, removing stasis toxin in the intestine; however, the precise mechanisms and therapeutic material basis remain largely unclear. In the present study, we measured the effects of SYD on colitis symptom, epithelial barrier function, epithelial ferroptosis, colonic protein and mRNA expression of glutathione peroxidase 4 (GPX4) in colitis model, and determined whether SYD restored barrier loss in colitis by modulation of GPX4-regulated ferroptosis pathway. Methods Colitis was established by infusion with 1 mL 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in ethanol (40% v/v) in rats at a 125 mg/kg dose. Ferroptosis in epithelial cells was determined by flow cytometer. GPX4 promoter-firefly luciferase fusion construct was transfected to Caco-2 cell to determine GPX4 transcription. MS analysis was used to identified ingredients in SYD. Results Different doses of SYD significantly alleviated colitis, decreased ferroptosis in epithelial cells, knockout of GPX4 significantly reversed SYD-induced alleviation effects on colitis, restoration of epithelial barrier function, and epithelial ferroptosis. Wogonoside, wogonin, palmatine, paeoniflorin and liquiritin were identified as active ingredients of SYD-exerted alleviation effects of colitis based on GPX4 agonistic transcription. Conclusion SYD alleviated chemically induced colitis by activation of GPX4, inhibition of ferroptosis in epithelial cells and further restoration of barrier function. Wogonoside, wogonin, palmatine, paeoniflorin and liquiritin were identified as the key therapeutic material basis of SYD-exerted anti-colitis effects. The findings provide a scientific basis for the therapeutic effect of SYD on colitis.

The cellular prion protein (PrPc) is a cell surface glycoprotein that is highly expressed in a variety of cancer tissues in addition to the nervous system, and its elevated expression is correlated to poor prognosis in many cancer patients. Our team previously found that patients with colorectal cancer (CRC) with high-level PrPc expression had significantly poorer survival than those with no or low-level PrPc expression. Mouse antibodies for PrPc inhibited tumor initiation and liver metastasis of PrPc-positive human CRC cells in mouse model experiments. PrPc is a candidate target for CRC therapy. In this study, we newly cloned a mouse anti-PrPc antibody (Clone 6) and humanized it, then affinity-matured this antibody using a CHO cell display with a peptide antigen and full-length PrPc, respectively. We obtained two humanized antibody clones with affinities toward a full-length PrPc of about 10- and 100-fold of that of the original antibody. The two humanized antibodies bound to the PrPc displayed significantly better on the cell surface than Clone 6. Used for Western blotting and immunohistochemistry, the humanized antibody with the highest affinity is superior to the two most frequently used commercial antibodies (8H4 and 3F4). The two new antibodies have the potential to be developed as useful reagents for PrPc detection and even therapeutic antibodies targeting PrPc-positive cancers.

Abstract Background Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH. Methods Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E2) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA. Results Many circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E2 strongly regulated it. E2 decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E2 reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E2 and miR‐21‐5p antagonist. Conclusions miR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E2 on MCT‐PH through ERβ.

Abstract Background and objective End-tidal PCO2 (PetCO2) patterns during exercise testing as well as ventilatory equivalents for CO2 have been reported for different pulmonary vascular diseases but seldomly for the significant differences in exercise response depending on the etiology of pulmonary hypertension. We aimed to compare PetCO2 change pattern in IPAH and CTEPH with varying severity during incremental cardiopulmonary exercise testing (CPET). Methods 164 IPAH patients and 135 CTEPH patients referred to Shanghai Pulmonary Hospital between 2012 and 2019 were retrospectively recruited into the study. All patients performed CPET and also underwent right-heart catheterization (RHC). Forty-four healthy subjects also performed CPET and were included as controls. Results PetCO2 was significantly lower in IPAH and CTEPH patients as compared to normal subjects. Moreover, the PetCO2 did not rise, in fact fell from rest to anaerobic threshold (AT), then further decreased until peak in both IPAH and CTEPH. PetCO2 value at rest, unloaded, AT and peak were proportionately reduced as the World Health Organization functional class (WHO-Fc) increased in both IPAH and CTEPH patients. The PETCO2 in IPAH patients had significant differences during all phases of exercise between WHO-Fc I-II and III-IV subgroup. CTEPH also demonstrated significant difference except for PetCO2 at peak. PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P

Abstract Ferroptosis is a regulated iron-dependent cell death characterized by the accumulation of lipid peroxidation. A myriad of facets linking amino acid, lipid, redox, and iron metabolisms were found to drive or to suppress the execution of ferroptosis. However, how the cells decipher the diverse pro-ferroptotic stress to activate ferroptosis remains elusive. Here, we report that protein O-GlcNAcylation, the primary nutrient sensor of glucose flux, orchestrates both ferritinophagy and mitophagy for ferroptosis. Following the treatment of ferroptosis stimuli such as RSL3, a commonly used ferroptosis inducer, there exists a biphasic change of protein O-GlcNAcylation to modulate ferroptosis. Pharmacological or genetic inhibition of O-GlcNAcylation promoted ferritinophagy, resulting in the accumulation of labile iron towards mitochondria. Inhibition of O-GlcNAcylation resulted in mitochondria fragmentation and enhanced mitophagy, providing an additional source of labile iron and rendering the cell more sensitive to ferroptosis. Mechanistically, we found that de-O-GlcNAcylation of the ferritin heavy chain at S179 promoted its interaction with NCOA4, the ferritinophagy receptor, thereby accumulating labile iron for ferroptosis. Our findings reveal a previously uncharacterized link of dynamic O-GlcNAcylation with iron metabolism and decision-making for ferroptosis, thus offering potential therapeutic intervention for fighting disease.

Most heterogeneous change detection methods based on transfer learning may not yield satisfactory results due to the lack of comprehensive utilization of the global and local characteristics of the image. In this article, we propose an unsupervised heterogeneous change detection method based on iterative joint global–local translation (IJGLT). The two heterogeneous images are first segmented into superpixels with the same boundary. Unlike the transfer learning methods for classification tasks that directly reduce the distance of the distribution of all data, we construct a translation function to decrease the difference between unchanged superpixels while increasing the difference of changed superpixels. During the translation process, the overall distribution is constrained using pseudo change labels, and the local manifold preserving is utilized to maintain the spatial structure and local adjacency relationship of superpixels. By comparing the translated superpixels of the heterogeneous images, the change map is obtained and then refined with pseudo change labels taking an iterative approach until convergence. Using the public and self-made optical-SAR heterogeneous datasets with different resolutions, the experimental results demonstrate that IJGLT is superior to several typical comparison methods with a maximum overall accuracy of 0.98 and a kappa coefficient of 0.9.

BackgroundHypertension is a major public health concern that strongly influences the quality of life of people worldwide. Keshan disease (KD) is an endemic cardiomyopathy related to low selenium, threatening residents in rural areas of 16 provinces in China. Furthermore, the prevalence of hypertension in the KD-endemic areas has been increasing annually. However, hypertension research associated with KD has only focused on endemic regions, and no studies have compared hypertension prevalence between endemic and non-endemic areas. Therefore, this study investigated the prevalence of hypertension to provide a basis for preventing and controlling hypertension in the KD-endemic areas, even in rural areas.MethodsWe extracted blood pressure information from cardiomyopathy investigation data from a cross-sectional study of the KD-endemic and non-endemic areas. The hypertension prevalence between the two groups was compared using the Chi-square test or Fisher s exact test. Additionally, Pearson’s correlation coefficient was employed to evaluate the relationship between the per capita gross domestic product (GDP) and hypertension prevalence.ResultsThere was a statistically significant increase of hypertension prevalence in the KD-endemic areas (22.79%, 95% confidence interval [CI]: 22.30–23.27%) over the non-endemic areas (21.55%, 95% CI: 21.09–22.02%). In the KD-endemic areas, more men had hypertension than women (23.90% vs. 21.65%, P < 0.001). Furthermore, the hypertension prevalence was higher in the north than in the south in the KD-endemic areas (27.52% vs. 18.76%, P < 0.001), non-endemic areas (24.86% vs. 18.66%, P < 0.001), and overall (26.17% vs. 18.68%, P < 0.001). Finally, the prevalence of hypertension positively correlated with per capita GDP at province level.ConclusionsThe increasing hypertension prevalence is a public health problem in the KD-endemic areas. Healthy diets, such as high consumption of vegetables and seafoods, and foods that are rich in selenium, might help prevent and control hypertension in the KD-endemic areas and other rural areas in China.

Liver fibrosis (LF) is a chronic progressive disease with no definitive treatment. The aim of this study was to assess helminth-derived molecules as potential therapeutic targets to prevent or reverse LF. A mouse model of carbon tetrachloride (CCL4)-induced LF was established and sja-let-7 was overexpressed by treatment with a miRNA agomir once per week. After four weeks, serum biochemistry, hepatic hydroxyproline content measurements, liver histology, mRNA expression profiling of fibrotic markers, the dual-luciferase reporter assay, and fluorescence in situ hybridization (FISH) were performed. Administration of the sja-let-7 agomir markedly ameliorated hepatosplenomegaly and reduced the liver hydroxyproline content. Liver histological analysis showed significant reductions in collagen deposition in the sja-let-7 agomir-treated mice. Additionally, the mRNA levels of both pro-fibrotic markers and pro-inflammatory cytokines were diminished after treatment. Furthermore, the dual-luciferase reporter assay and FISH identified the α2 chain of collagen type 1 (Col1α2) as the direct target of sja-let-7. Accordingly, the progression of LF was attenuated by targeting Col1α2 and the TGF-β/Smad signaling pathway.

Abstract Steel–concrete (SC) composite widely used in military defensive project is due to its impressive mechanical properties, long-lived service, and low cost. However, the growing use of hypervelocity kinetic weapons in the present war puts forward higher requirements for the anti-explosion and penetration performance of military protection engineering. Here, inspired by the special ‘brick-and-mortar’ (BM) structural feature of natural nacre, we successfully construct a nacre-inspired steel–concrete (NISC) engineering composite with 2510 kg/m3, possessing nacre-like lamellar architecture via a bottom-up assembling technique. The NISC engineering composite exhibits nacreous BM structural similarity, high compressive strength of 68.5 MPa, compress modulus of 42.0 GPa, Mohs hardness of 5.5, Young’s modulus of 41.5 GPa, and shear modulus of 18.4 GPa, higher than pure concrete. More interestingly, the hypervelocity impact tests reveal the penetration capability of our NISC target material is obviously stronger than that of pure concrete, enhanced up to about 46.8% at the striking velocity of 1 km/s and approximately 30.9% at the striking velocity of 2 km/s, respectively, by examining the damages of targets, the trajectories, penetration depths, and residual projectiles. This mechanically integrated enhancement can be attributed to the nacre-like BM structural architecture derived from assembling the special steel-bar array frame-reinforced concrete platelets. This study highlights a key role of nacre-like structure design in promoting the enhanced hypervelocity impact resistance of steel–concrete composites.

Abstract Background N-acetyltransferase 13 (NAT13) is a probable catalytic component of the ARD1A-NARG1 complex possessing alpha (N-terminal) acetyltransferase activity. Results In this study, a full-length complementary DNA (cDNA) encoding Schistosoma japonicum NAT13 (SjNAT13) was isolated from schistosome cDNAs. The 621 bp open reading frame of SjNAT13 encodes a polypeptide of 206 amino acids. Real-time PCR analysis revealed SjNAT13 expression in all tested developmental stages. Transcript levels were highest in cercariae and 21-day-old worms, and higher in male adult worms than female adult worms. The rSjNAT13 protein induced high levels of anti-rSjNAT13 IgG antibodies. In two independent immunoprotection trials, rSjNAT13 induced 24.23% and 24.47% reductions in the numbers of eggs in liver. RNA interference (RNAi) results showed that small interfering RNA (siRNA) Sj-514 significantly reduced SjNAT13 transcript levels in worms and decreased egg production in vitro. Conclusions Thus, rSjNAT13 might play an important role in the development and reproduction of schistosomes.

Abstract Background Cardiopulmonary exercise testing (CPET) and pulmonary function testing (PFT) are noninvasive methods to evaluate the respiratory and circulatory systems. This research aims to evaluate and monitor chronic thromboembolic pulmonary hypertension (CTEPH) noninvasively and effectively by these two methods. Moreover, the research assesses the predictive value of CPET and PFT parameters for severe CTEPH. Methods We used data from 86 patients with CTEPH (55 for test set, and 31 for validation set) at the Shanghai Pulmonary Hospital Affiliated to Tongji University. The clinical, PFT and CPET data of CTEPH patients of different severity classified according to pulmonary artery pressure (PAP) (mm Hg) were collected and compared. Logistic regression analysis was performed to appraise the predictive value of each PFT and CPET parameter for severe CTEPH. The performance of CPET parameters for predicting severe CTEPH was determined by receiver operating characteristic (ROC) curves and calibration curves. Results Data showed that minute ventilation at anaerobic threshold (VE @ AT) (L/min) and oxygen uptake at peak (VO2 @ peak) (mL/kg/min) were independent predictors for severe CTEPH classified according to PAP (mm Hg). Additionally, the efficacy of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) in identifying severe CTEPH was found to be moderate with the area under ROC curve (AUC) of 0.769 and 0.740, respectively. Furthermore, the combination of VE @ AT (L/min) and VO2 @ peak (mL/kg/min) had a moderate utility value in identifying severe CTEPH with the AUC of 0.843. Conclusion Our research suggests that CPET and PFT can noninvasively and effectively evaluate, monitor and predict the severity of CTEPH.

This work analyzes the Tungsten Inert Gas (TIG)welded joint of AZ31 magnesium alloy and the pitting corrosion stress field at different depths under tensile load via the ANSYS finite element method. The strengths of the stress and strain fields inside the corrosion pit were substantially higher than the average strength level of the matrix. Therefore, under the influence of the applied load, the corrosion pit will fail first. Based on the study of pitting corrosion, a model was developed to explain how pitting corrosion cracks propagate in magnesium alloy welded joints. Finally, the variation of residual strength was revealed to study the corrosion dynamic mechanism of the joints.

ABSTRACT: Pigeon paramyxovirus type 1 (PPMV-1), a variant of Newcastle disease virus (NDV), causes severe Newcastle disease (ND) in pigeons. However, there is no PPMV-1 vaccine available worldwide. In this study, a strain of PPMV-1 was isolated from outbreaks in a vaccinated racing pigeon (Columbia livia) loft in China, namely, PPMV-1/pigeon/Gansu/China/02/2020 (GS02). Experimental infection with GS02 showed mortality rates of 100% and 87.50% in 4- and 12-week-old pigeons, respectively, suggesting that GS02 is virulent and more sensitive to young pigeons. The whole genome of GS02 determined the fusion (F) protein possessing virulence cleavage site 112RRQKRF117. Phylogenetic analysis indicated that GS02 was a subgenotype VI.2.1.1.2.2 (VIk) of Class II NDV and more closely related to the JS/06/20/Pi (MW271791) strain, but it was far from the genetic distance from the commercial vaccine chicken-origin La Sota strain. Using inactivated GS02 as a vaccine candidate and inactivated vaccine La Sota to immunize the pigeons, both of them provided complete protection against GS02 challenge. The GS02 vaccine candidate induced higher antibody titers than the La Sota vaccine, and cross-reactivity testing showed antigenically slight differences between GS02 and La Sota. These results indicated that the GS02 candidate could be a potential pigeon-derived vaccine for the prevention and control of PPMV-1 in pigeons.