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Abstract Background Previous studies have reported that anemia was associated with depression, but the association between changes in depressive symptoms and the risk of anemia was unclear. This study aimed to explore whether changes in depressive symptoms were associated with anemia among the middle-aged and elderly adults. Methods A total of 6112 patients aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) were included in this analysis. Elevated Depression Symptoms (EDS) was defined as the Center for Epidemiological Studies Depression Scale-10 score ≥ 10. Depression status was defined as no depressive symptom [no EDS at Wave 1 (2011–2012) and Wave 2 (2013–2014)], decreasing depressive symptoms (EDS at Wave 1, no EDS at Wave 2), increasing depressive symptoms (no EDS at Wave 1, EDS at Wave 2), persistent depressive symptoms (EDS at Wave 1 and Wave 2). Multivariable logistic regression analyses were conducted to estimate the relationships between depressive symptoms and the changes and risk of anemia. Results During the follow-up of Wave 1 and Wave 3 (2015–2016), 906 participants (14.82%) developed anemia, the multivariable-adjusted odds ratio for the depressive symptom compared with the no depressive symptom was 1.24 (95% CI, 1.12–1.58) for anemia. From Wave 2 to Wave 3, there were 828 participants (14.62%) diagnosed with anemia. Compared to participants with no depressive symptom, those with persistent depressive symptoms during Wave 1 and Wave 2 had the significantly elevated risk of anemia (odds ratio 1.44, 95% CI 1.21–1.84). Conclusions The present study demonstrated that baseline depressive symptoms and changes in depressive symptoms were associated with increased risks of anemia.

Background: Mozart’s Sonata for Two Pianos in D Major (K448) is a classic double piano work. This study investigated its effect on children with epilepsy (EP) and analyzed the changes in electroencephalography (EEG) among children on the basis of acoustic quality. Methods: The clinical data of 150 children with EP in the Affiliated Hospital (Group) of Putian University from March 2020 to March 2023 were retrospectively analyzed. They were divided into group A (n = 73, antiepileptic drug therapy) and group B (n = 77, antiepileptic drug therapy + Mozart K448) in accordance with the treatment methods. The seizure frequency, frequency of epileptic discharges (EDs), and Quality of Life in Childhood Epilepsy Questionnaire-16 in both groups were compared before and after treatment. The changes in EEG before, during, and after music appreciation were observed. The effects of the acoustic characteristics (rhythm, root mean square value, roughness, and spectral flux) of Mozart K448 on EDs in children were explored. Results: After treatment, group A had a higher seizure frequency (P < 0.001), a higher frequency of EDs (P < 0.05), and significantly lower scores of cognition and emotion than group B (P < 0.001), without significant difference in the scores of social function and physical function (P > 0.05). The frequency of EDs before music appreciation was significantly higher than that during music appreciation (P < 0.01). Spearman correlation analysis showed that the rhythm, spectral flux, and roughness in Mozart K488 were related to the decrease in EDs among children with EP (P < 0.001). Conclusion: This study confirmed the application effect of Mozart K448 in children with EP. Mozart K448 can decrease the seizure frequency, reduce the ED occurrence, and improve the quality of life. The acoustic characteristics of K448 may be the reason for improving EP in children.

Abstract Membrane reactors are known for their efficiency and superior operability compared to traditional batch processes, but their limited diversity poses challenges in meeting various reaction requirements. Herein, we leverage the molecular tunability of covalent organic frameworks (COFs) to broaden their applicability in membrane reactors. Our COF membrane demonstrates an exceptional ability to achieve complete conversion in just 0.63 s at room temperature—a benchmark in efficiency for Knoevenagel condensation. This performance significantly surpasses that of the corresponding homogeneous catalyst and COF powder by factors of 176 and 375 in turnover frequency, respectively. The enhanced concentration of reactants and the rapid removal of generated water within the membrane greatly accelerate the reaction, reducing the apparent activation energy. Consequently, this membrane reactor enables reactions that are unattainable using both COF powders and homogeneous catalysts. Considering the versatility, our findings highlight the substantial promise of COF-based membrane reactors in organic transformations.

Abstract Parkinson’s disease (PD) exhibits heterogeneity in terms of symptoms and prognosis, likely due to diverse neuroanatomical alterations. This study employs a contrastive deep learning approach to analyze Magnetic Resonance Imaging (MRI) data from 932 PD patients and 366 controls, aiming to disentangle PD-specific neuroanatomical alterations. The results reveal that these neuroanatomical alterations in PD are correlated with individual differences in dopamine transporter binding deficit, neurodegeneration biomarkers, and clinical severity and progression. The correlation with clinical severity is verified in an external cohort. Notably, certain proteins in the cerebrospinal fluid are strongly associated with PD-specific features, particularly those involved in the immune function. The most notable neuroanatomical alterations are observed in both subcortical and temporal regions. Our findings provide deeper insights into the patterns of brain atrophy in PD and potential underlying molecular mechanisms, paving the way for earlier patient stratification and the development of treatments to slow down neurodegeneration.

Abstract Background The research aims to explore the characteristics of intestinal flora, nutritional status and immune function in patients with different types of obese colon cancer. Methods A retrospective analysis is conducted on 64 cases of obese colon cancer diagnosed from June 2018 to January 2020. According to the histological staging of the cancer, they are classified into adenocarcinoma, adenosquamous carcinoma and undifferentiated carcinoma, with corresponding cases of 24, 22 and 18, respectively. The intestinal flora (Bifidobacterium, Lactobacillus, Enterococcus faecalis, Escherichia coli, and yeast), nutritional status (Hb, Alb, PA, TFN, and PNI), immune function (IgG, IgM, IgA, CD4 +, CD8 +, and CD4 +/CD8 +) are analyzed in the different groups of patients. Survival curves are evaluated by Kaplan-Meier method and log-rank test for tumour death, local recurrence, and distant metastasis. Results There were no statistically significant differences in intestinal flora (Bifidobacterium, Lactobacillus, Enterococcus faecalis, Escherichia coli, and yeast), nutritional status (Hb, Alb, PA, TFN, and PNI) and immune function (IgG, IgM, IgA, CD4 +, CD8 +, and CD4 +/CD8 +) between different groups. There was a significant correlation between intestinal flora, nutritional status and immune function for all three. The survival curves of tumour death, local recurrence and distant metastasis in different groups of obese colon cancer patients were statistically significant. The tumor mortality rate, local recurrence, and distant metastasis rate in adenocarcinoma were 78.65%, 54.25% and 48.26% respectively. Conclusion There are differences in intestinal flora, nutritional status and immune function among different types of obese colon cancer patients, but adenocarcinoma has the least benefit in intestinal flora, poor nutritional status, and weakest immune function.

Abstract Doxorubicin’s antitumor effectiveness may be constrained with ineffective tumor penetration, systemic adverse effects, as well as drug resistance. The co-loading of immune checkpoint inhibitors and doxorubicin into liposomes can produce synergistic benefits and address problems, including quick drug clearance, toxicity, and low drug penetration efficiency. In our previous study, we modified a nanobody targeting CTLA-4 onto liposomes (LPS-Nb36) to be an extremely potent CTLA-4 signal blocker which improve the CD8+ T-cell activity against tumors under physiological conditions. In this study, we designed a drug delivery system (LPS-RGD-Nb36-DOX) based on LPS-Nb36 that realized the doxorubicin and anti-CTLA-4 Nb co-loaded and RGD modification, and was applied to antitumor therapy. We tested whether LPS-RGD-Nb36-DOX could targets the tumor by in vivo animal photography, and more importantly, promote cytotoxic T cells proliferation, pro-inflammatory cytokine production, and cytotoxicity. Our findings demonstrated that the combination of activated CD8+ T cells with doxorubicin/anti-CTLA-4 Nb co-loaded liposomes can effectively eradicate tumor cells both in vivo and in vitro. This combination therapy is anticipated to have synergistic antitumor effects. More importantly, it has the potential to reduce the dose of chemotherapeutic drugs and improve safety.

Neurodegenerative diseases (NDDs) are prevalent in the elderly. The pathogenesis of NDDs is complex, and currently, there is no cure available. With the increase in aging population, over 20 million people are affected by common NDDs alone (Alzheimer’s disease and Parkinson’s disease). Therefore, NDDs have profound negative impacts on patients, their families, and society, making them a major global health concern. Rho-associated kinases (ROCKs) belong to the serine/threonine protein kinases family, which modulate diverse cellular processes (e.g., apoptosis). ROCKs may elevate the risk of various NDDs (including Huntington’s disease, Parkinson’s disease, and Alzheimer’s disease) by disrupting synaptic plasticity and promoting inflammatory responses. Therefore, ROCK inhibitors have been regarded as ideal therapies for NDDs in recent years. Fasudil, one of the classic ROCK inhibitor, is a potential drug for treating NDDs, as it repairs nerve damage and promotes axonal regeneration. Thus, the current review summarizes the relationship between ROCKs and NDDs and the mechanism by which fasudil inhibits ROCKs to provide new ideas for the treatment of NDDs.

Background Lymphocyte antigen 9 (LY9) participates in the development of several tumors and diseases but has not been reported yet in lung adenocarcinoma (LUAD). Methods First, we analyzed the expression and prognostic value of LY9 in pan-cancer, including LUAD. Additionally, we conducted a correlation analysis of LY9 expression in LUAD with immune cell infiltration using the TIMER database and the CIBERSORT algorithm, and with immune checkpoints using the GEPIA database. Also, we constructed a potential ceRNA network for LY9. Furthermore, we explored LY9-related pathways by Gene Set Enrichment Analysis (GSEA). Finally, validation of differential expression at the mRNA level was obtained from the GEO database. We collected LUAD tissues for Quantitative Real-time PCR (qRT-PCR) to verify the expression of LY9, CD8, and CD4 and calculated the correlation between them. We also conducted immunohistochemistry (IHC) to verify the protein expression of LY9. Results Results showed that LY9 was highly expressed in various tumors, including LUAD. Besides, patients with high LY9 expression presented longer overall survival (OS) and more multiple lymphocyte infiltrations. The expression of LY9 in LUAD strongly and positively correlates with multiple immune cell infiltration and immune checkpoints. The functional enrichment analysis indicated that LY9 was involved in multiple immune-related pathways and non-small cell lung cancer. Moreover, a ceRNA regulatory network of LINC00943-hsa-miR-141-3p-LY9 might be involved. Finally, GSE68465 dataset confirmed differential expression of LY9 mRNA levels in LUAD and the qRT-PCR results verified LY9 had a strong and positive correlation with CD4 and CD8 T cells. Unfortunately, IHC did not detect the expression of LY9 protein level in tumor tissues and WB experiments validated the protein expression of LY9 in the OCI-AML-2 cell line. Conclusions Therefore, we hypothesized that LY9 could serve as a potential, novel prognostic biomarker for LUAD and could predict immunotherapy efficacy at the mRNA level.

This review summarizes the clinical efficacy and experimental research of traditional Chinese medicine (TCM) moxibustion in the intervention of ovarian injury. Clinical and experimental research results have shown that as a nonpharmacological treatment method, Chinese medical moxibustion therapy is of great significance in the treatment of ovarian injuries such as diminished ovarian reserve, polycystic ovarian syndrome, premature ovarian failure, and premature ovarian insufficiency. Moxibustion, heat-sensitive moxibustion, and electroacupuncture have significant effects in improving ovarian function, overall treatment efficacy, pregnancy rate, ovulation rate, and sex hormone levels and have higher safety. Their therapeutic mechanisms have also been demonstrated. In conclusion, TCM moxibustion therapy has a significant effect in the treatment of ovarian injury, providing a new option for the treatment of the ovarian injury.

Abstract Background Enterocytozoon bieneusi is a zoonotic pathogen widely distributed in animals and humans. It can cause diarrhea and even death in immunocompromised hosts. Approximately 800 internal transcribed spacer (ITS) genotypes have been identified in E. bieneusi. Farmed foxes and raccoon dogs are closely associated to humans and might be the reservoir of E. bieneusi which is known to have zoonotic potential. However, there are only a few studies about E. bieneusi genotype identification and epidemiological survey in foxes and raccoon dogs in Henan and Hebei province. Thus, the present study investigated the infection rates and genotypes of E. bieneusi in farmed foxes and raccoon dogs in the Henan and Hebei provinces. Result A total of 704 and 884 fecal specimens were collected from foxes and raccoon dogs, respectively. Nested PCR was conducted based on ITS of ribosomal RNA (rRNA), and then multilocus sequence typing (MLST) was conducted to analyze the genotypes. The result showed that infection rates of E. bieneusi in foxes and raccoon dogs were 18.32% and 5.54%, respectively. Ten E. bieneusi genotypes with zoonotic potential (NCF2, NCF3, D, EbpC, CHN-DC1, SCF2, CHN-F1, Type IV, BEB4, and BEB6) were identified in foxes and raccoon dogs. Totally 178 ITS-positive DNA specimens were identified from foxes and raccoon dogs and these specimens were then subjected to MLST analysis. In the MLST analysis, 12, 2, 7 and 8 genotypes were identified in at the mini-/ micro-satellite loci MS1, MS3, MS4 and MS7, respectively. A total of 14 multilocus genotypes were generated using ClustalX 2.1 software. Overall, the present study evaluated the infection of E. bieneusi in foxes and raccoon dogs in the Henan and Hebei province, and investigated the zoonotic potential of the E. bieneusi in foxes and raccoon dogs. Conclusions These findings expand the geographic distribution information of E. bieneusi’ host in China and was helpful in preventing against the infection of E. bieneusi with zoonotic potential in foxes and raccoon dogs.

Abstract Purpose PAQR7 plays a key role in cell apoptosis as a progesterone membrane receptor. The physiological mechanism of PAQR7 in ovarian function and its anti-apoptotic action in mammals remain poorly understood. Methods We first added 0.2 µM aminoglutethimide (AG), an inhibitor of endogenous progesterone (P4) secretion, and transfected siPAQR7 co-incubated with P4 in human KGN cells to identify granulosa cell apoptosis, respectively. Additionally, we used Paqr7 knockout (PAQR7 KO) mice to assess the role of PAQR7 in the ovary. Results The PAQR7 deficiency significantly increased apoptosis of KGN cells, and this significant difference disappeared following P4 supplementation. The Paqr7 −/− female mice showed a prolonged estrous cycle, reduced follicular growth, increased the number of atresia follicles, and decreased the concentrations of E2 and AMH. The litters, litter sizes, and spontaneous ovulation in the Paqr7−/− mice were significantly decreased compared with the Paqr7+/+ mice. In addition, we also found low expression of PAQR7 in GCs from human follicular fluids of patients diagnosed with decreased ovarian reserve (DOR) and ovaries of mice with a DOR-like phenotype, respectively. Conclusions The present study has identified that PAQR7 is involved in mouse ovarian function and fertilization potential. One possible mechanism is mediating the anti-apoptotic effect of P4 on GC apoptosis via the BCL-2/BAX/CASPASE-3 signaling pathway. The mechanism underlying the effect of PAQR7 on ovarian development and aging remains to be identified.

Abstract Background Fibrinogen plays pivotal roles in multiple biological processes. Genetic mutation of the fibrinogen coding genes can result in congenital fibrinogen disorders (CFDs). We identified a novel heterozygous missense mutation, FGG c.1168G > T (NCBI NM_000509.6), and conducted expression studies and functional analyses to explore the influence on fibrinogen synthesis, secretion, and polymerization. Methods Coagulation tests were performed on the patients to detect the fibrinogen concentration. Whole-exome sequencing (WES) and Sanger sequencing were employed to detect the novel mutation. Recombinant fibrinogen-producing Chinese hamster ovary (CHO) cell lines were built to examine the recombinant fibrinogen synthesis and secretion by western blotting and enzyme-linked immunosorbent assay (ELISA). The functional analysis of fibrinogen was performed by thrombin-catalyzed fibrin polymerization assay. In silico molecular analyses were carried out to elucidate the potential molecular mechanisms. Results The clinical manifestations, medical history, and laboratory tests indicated the diagnosis of hypodysfibrinogenemia with bleeding phenotype in two patients. The WES and Sanger sequencing revealed that they shared the same heterozygous missense mutation, FGG c.1168G > T. In the expression studies and functional analysis, the missense mutation impaired the recombinant fibrinogen's synthesis, secretion, and polymerization. Furthermore, the in silico analyses indicated novel mutation led to the hydrogen bond substitution. Conclusion The study highlighted that the novel heterozygous missense mutation, FGG c.1168G > T, would change the protein secondary structure, impair the “A: a” interaction, and consequently deteriorate the fibrinogen synthesis, secretion, and polymerization.

Abstract We previously reported that circIGF1R is significantly downregulated in non-small cell lung cancer (NSCLC) cells and tissues. It inhibits cancer cell invasion and migration, although the underlying molecular mechanisms remain elusive. The invasion and migration of NSCLC cells was analyzed by routine in vivo and in vitro functional assays. Fluorescent in situ hybridization, luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation (RIP) assay were performed to explore the molecular mechanisms. Mechanism of action of paclitaxel-induced RBFOX3-mediated inhibition of NSCLC invasion and migration was investigated through in vitro and in vivo experiments.Our study reveals that circIGF1R acts as a Competing Endogenous RNA (ceRNA) for miR-1270, thereby regulating Van-Gogh-like 2 (VANGL2) expression and subsequently inhibiting NSCLC cell invasion and migration via the Wnt pathway. We also found that RNA binding protein fox-1 homolog 3 (RBFOX3) enhances circIGF1R biogenesis by binding to IGF1R pre-mRNA, which in turn suppresses migration and invasion in NSCLC cells. Additionally, the chemotherapeutic drug paclitaxel was shown to impede NSCLC invasion and migration by inducing RBFOX3-mediated circIGF1R biogenesis.RBFOX3 inhibits the invasion and migration of NSCLC cells through the circIGF1R/ miR-1270/VANGL2 axis, circIGF1R has the potential to serve as a biomarker and therapeutic target for NSCLC.

In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined presence has raised widespread concern regarding potential risks to organisms. However, the combined toxicity and mechanisms of NPs and TCS remain unclear. In this study, we investigated the toxic effects of polystyrene NPs and TCS and their mechanisms on KGN cells, a human ovarian granulosa cell line. We exposed KGN cells to NPs (150 μg/mL) and TCS (15 μM) alone or together for 24 hours. Co-exposure significantly reduced cell viability. Compared with exposure to NPs or TCS alone, co-exposure increased reactive oxygen species (ROS) production. Interestingly, co-exposure to NPs and TCS produced synergistic effects. We examined the activity of superoxide dismutase (SOD) and catalase (CAT), two antioxidant enzymes; it was significantly decreased after co-exposure. We also noted an increase in the lipid oxidation product malondialdehyde (MDA) after co-exposure. Furthermore, co-exposure to NPs and TCS had a more detrimental effect on mitochondrial function than the individual treatments. Co-exposure activated the NRF2–KEAP1–HO-1 antioxidant stress pathway. Surprisingly, the expression of SESTRIN2, an antioxidant protein, was inhibited by co-exposure treatments. Co-exposure to NPs and TCS significantly increased the autophagy-related proteins LC3B-II and LC3B-Ⅰ and decreased P62. Moreover, co-exposure enhanced CASPASE-3 expression and inhibited the BCL-2/BAX ratio. In summary, our study revealed the synergistic toxic effects of NPs and TCS in vitro exposure. Our findings provide insight into the toxic mechanisms associated with co-exposure to NPs and TCS to KGN cells by inducing oxidative stress, activations of the NRF2-KEAP1-HO-1 pathway, autophagy, and apoptosis.

Abstract Access to sustainable energy is paramount in today’s world, with a significant emphasis on solar and water-based energy sources. Herein, we develop photo-responsive ionic dye-sensitized covalent organic framework membranes. These innovative membranes are designed to significantly enhance selective ion transport by exploiting the intricate interplay between photons, electrons, and ions. The nanofluidic devices engineered in our study showcase exceptional cation conductivity. Additionally, they can adeptly convert light into electrical signals due to photoexcitation-triggered ion movement. Combining the effects of salinity gradients with photo-induced ion movement, the efficiency of these devices is notably amplified. Specifically, under a salinity differential of 0.5/0.01 M NaCl and light exposure, the device reaches a peak power density of 129 W m−2, outperforming the current market standard by approximately 26-fold. Beyond introducing the idea of photoelectric activity in ionic membranes, our research highlights a potential pathway to cater to the escalating global energy needs.

Abstract Both endotherms and ectotherms may raise their body temperature to limit pathogen infection. Endotherms do this by increasing their basal metabolism; this is called ‘fever’. Ectotherms do this by migrating to warmer places; this is called ‘behavioral fever’. White spot syndrome virus (WSSV) is the most lethal pathogen of cultured shrimp. This study examined the existence of behavioral fever in WSSV-infected Penaeus vannamei shrimp. Shrimp weighing 15 ± 0.5 g were inoculated intramuscularly with WSSV and kept in a four-compartment system (4-CS) with all the chambers at 27 °C or with a thermal gradient (27–29–31–33 °C). During the first 4 days post-inoculation, 94% of the WSSV-inoculated shrimp died in the 4-CS with a fixed temperature (27 °C), while only 28% died in the 4-CS with a temperature gradient. The inoculated animals clearly demonstrated a movement towards the warmer compartments, whereas this was not the case with the mock- and non-inoculated animals. With primary lymphoid organ cell cultures, it was demonstrated that the increase of temperature from 27–29 °C to 31–33 °C inhibits virus replication. It is concluded that behavioral fever is used by shrimp to elevate their temperature when infected with WSSV. Behavioral fever prevents WSSV infection and mortality.

This paper proposes an advanced deep learning model that integrates the Diffusion-Transformer structure and parallel attention mechanism for the tasks of growth estimation and disease detection in jujube forests. Existing methods in forestry monitoring often fall short in meeting the practical needs of large-scale and highly complex forest areas due to limitations in data processing capabilities and feature extraction precision. In response to this challenge, this paper designs and conducts a series of benchmark tests and ablation experiments to systematically evaluate and verify the performance of the proposed model across key performance metrics such as precision, recall, accuracy, and F1-score. Experimental results demonstrate that compared to traditional machine learning models like Support Vector Machines and Random Forests, as well as common deep learning models such as AlexNet and ResNet, the model proposed in this paper achieves a precision of 95%, a recall of 92%, an accuracy of 93%, and an F1-score of 94% in the task of disease detection in jujube forests, showing similarly superior performance in growth estimation tasks as well. Furthermore, ablation experiments with different attention mechanisms and loss functions further validate the effectiveness of parallel attention and parallel loss function in enhancing the overall performance of the model. These research findings not only provide a new technical path for forestry disease monitoring and health assessment but also contribute rich theoretical and experimental foundations for related fields.

Abstract Background Ovarian aging is a process of decline in its reserve leading to ovary dysfunction and even reduced health quality in offspring. However, aging-related molecular pathways in the ovary remain obscure. Lysine succinylation (Ksuc), a newly post-translational modification (PTM), has been found to be broadly conserved in both eukaryotic and prokaryotic cells, and associated with multiple pathophysiological processes. There are no relevant reports revealing a link between the molecular mechanisms of ovarian aging and Ksuc. Methods The level of Ksuc in ovaries of aged and premature ovarian insufficiency (POI) mice were detected by immunoblotting and immunohistochemical. To further explore the role of Ksuc in ovarian aging, using in vitro mouse ovary tissue culture and an in vivo mouse model with changed Ksuc level. Results Increased Ksuc in ovaries of aged and POI mice and distribution of Ksuc in various types of mice ovarian cells and the high level of Ksuc in granulosa cells (GCs) were revealed. Histological assessments and hormone levels analyses showed that the high Ksuc level down-regulated the ovarian index and the anti-Müllerian hormone (AMH) and estrogen levels, and increased follicular atresia. Moreover, in the high Ksuc groups, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) intensities and the expression of Cleaved-caspase-3 increased and the expression of B-cell lymphoma-2 (Bcl-2) decreased together with positively-expressed P21, an aging-related marker. These results suggest that ovarian aging is likely associated with alteration in Ksuc. Conclusion The present study has identified Ksuc in mouse ovary and found that high Ksuc level most likely contributes to ovarian aging which is expected further investigation to provide new information for delaying physiological ovarian aging and treating pathological ovarian aging.

Abstract This study proposes a multi‐scale transformation method based on morphological reconstruction and membership filtering, termed as MMFuse, to fuse infrared and visible images. This method employs a fuzzy c‐means clustering algorithm for multi‐scale decomposition by introducing morphological reconstruction operations and modifying member partitions to ensure noise resistance and image detail preservation. In addition, the MMFuse utilises the image attributes of layers as their fusion weights at each scale for adaptive feature fusion, which reduces the difficulty of manual adjustment of fusion weights. Moreover, on the basis of histogram enhancement, a visible image enhancement method is proposed, which can help exploit additional texture details in low‐light visible images and transfer these details to the fused image. The experiments performed on public datasets indicates that the MMFuse can generate sharp and clean fused images with high robustness and good fusion results for the images corrupted by different noises. Moreover, the results of this method appear as high‐quality visible images with clear highlighted infrared targets.

In this study, an innovative approach based on multimodal data and the transformer model was proposed to address challenges in agricultural disease detection and question-answering systems. This method effectively integrates image, text, and sensor data, utilizing deep learning technologies to profoundly analyze and process complex agriculture-related issues. The study achieved technical breakthroughs and provides new perspectives and tools for the development of intelligent agriculture. In the task of agricultural disease detection, the proposed method demonstrated outstanding performance, achieving a precision, recall, and accuracy of 0.95, 0.92, and 0.94, respectively, significantly outperforming the other conventional deep learning models. These results indicate the method’s effectiveness in identifying and accurately classifying various agricultural diseases, particularly excelling in handling subtle features and complex data. In the task of generating descriptive text from agricultural images, the method also exhibited impressive performance, with a precision, recall, and accuracy of 0.92, 0.88, and 0.91, respectively. This demonstrates that the method can not only deeply understand the content of agricultural images but also generate accurate and rich descriptive texts. The object detection experiment further validated the effectiveness of our approach, where the method achieved a precision, recall, and accuracy of 0.96, 0.91, and 0.94. This achievement highlights the method’s capability for accurately locating and identifying agricultural targets, especially in complex environments. Overall, the approach in this study not only demonstrated exceptional performance in multiple tasks such as agricultural disease detection, image captioning, and object detection but also showcased the immense potential of multimodal data and deep learning technologies in the application of intelligent agriculture.

This study introduces a novel high-accuracy fruit fly detection model based on the Transformer structure, specifically aimed at addressing the unique challenges in fruit fly detection such as identification of small targets and accurate localization against complex backgrounds. By integrating a step attention mechanism and a cross-loss function, this model significantly enhances the recognition and localization of fruit flies within complex backgrounds, particularly improving the model’s effectiveness in handling small-sized targets and its adaptability under varying environmental conditions. Experimental results demonstrate that the model achieves a precision of 0.96, a recall rate of 0.95, an accuracy of 0.95, and an F1-score of 0.95 on the fruit fly detection task, significantly outperforming leading object detection models such as YOLOv8 and DETR. Specifically, this research delves into and optimizes for challenges faced in fruit fly detection, such as recognition issues under significant light variation, small target size, and complex backgrounds. Through ablation experiments comparing different data augmentation techniques and model configurations, the critical contributions of the step attention mechanism and cross-loss function to enhancing model performance under these complex conditions are further validated. These achievements not only highlight the innovativeness and effectiveness of the proposed method, but also provide robust technical support for solving practical fruit fly detection problems in real-world applications, paving new paths for future research in object detection technology.

Premature ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by the abnormal alteration of hormone levels such as FSH and E2. POI causes infertility, severe daily life disturbances, and long-term health risks. However, the underlying mechanism remains largely unknown. In this study, we found that POI is associated with the cellular senescence of ovarian granulosa cells, and TRIM28 mediates oxidative stress (OS)-induced cellular senescence in granulosa cells. Mechanistically, OS causes a decrease in TRIM28 protein levels in KGN cells. Subsequently, it triggers an increase in the levels of autophagy marker proteins ATG5 and LC3B-II, and the downregulation of P62. Abnormal autophagy induces an increase in the levels of cellular senescence markers γ-H2A.X, P16, and P21, provoking cellular senescence in vitro. The overexpression of ovarian TRIM28 through a microinjection of lentivirus attenuated autophagy, cellular senescence, and follicular atresia in the ovaries of POI mice and improved mouse fertility in vivo. Our study highlights the triggers for POI, where the reduction of TRIM28, which is regulated by reactive oxygen species, causes follicular atresia and POI via triggering autophagy and inducing granulosa cell senescence. Shedding light on TRIM28 may represent a potential intervention strategy for POI.

With the development and maturity of autonomous driving technology, parcel terminal distribution has taken the lead as an application scenario for unmanned delivery vehicles that autonomously perform the task of delivering packages between distribution centres and customers. The traditional terminal delivery model faces challenges such as high costs, low efficiency and time conflicts between delivery and customer convenience. Considering the multiple demands of parcels terminal delivery, this paper proposes a space-time route planning model coordinated with task assignment for autonomous delivery vehicle fleet with the objective of minimizing the total transportation distance and designs a route planning with task assignment algorithm. Firstly, a method of period division and the concept of reliable service time are put forward and a task integration approach is introduced. Then, the task assignment model based on task network and the shortest space-time route planning model are built. According to the characteristics of the model, a route planning with task assignment algorithm by improving the Tabu Search algorithm is designed to gain the best delivery space-time routes of autonomous delivery vehicle fleet. Simulation results show that the approach system of space-time route planning designed in this paper can effectively accomplish task assignment and route planning simultaneously.

This paper examines the effects and mechanism paths of monetary policy on firms' "short-term debt for long-term investment (SDFLI)" behavior using panel data of Chinese A-share listed firms from 2007-2019. The findings indicate that loose monetary policy suppresses corporate SDFLI behavior by lengthening corporate credit maturity structure through the credit maturity structure channel. In addition, heterogeneity analysis shows that loose monetary policy significantly inhibits the SDFLI behavior of state-owned enterprises(SOEs), non-high-tech firms, and firms in regions with high bank competition levels through the credit term structure channel, and the monetary policy credit term structure channel fails for non-state-owned enterprises(non-SOEs), high-tech firms, and firms in regions with low bank competition levels. The results of the heterogeneity analysis validate the plausibility that monetary policy affects firms' SDFLI behavior through the credit term structure channel.

Owing to the rapid development of big data technology, use of machine learning methods to identify soil pollution of potentially contaminated sites (PCS) at regional scales and in different industries has become a research hot spot. However, due to the difficulty in obtaining key indexes of site pollution sources and pathways, current methods have problems such as low accuracy of model predictions and insufficient scientific basis. In this study, we collected the environmental data of 199 PCS in 6 typical industries involving heavy metal and organic pollution. Then, 21 indexes based on basic information, potential for pollution from product and raw material, pollution control level, and migration capacity of soil pollutants were used to established the soil pollution identification index system. We fused the original indexes into the new feature subset with 11 indexes through the method of consolidation calculation. The new feature subset was then used to train machine learning models of random forest (RF), support vector machine (SVM), and multilayer perceptron (MLP), and tested to determine whether it improved the accuracy and precision of soil pollination identification models. The results of correlation analysis showed that the four new indexes created by feature fusion have the correlation with soil pollution is similar to the original indexes. The accuracies and precisions of three machine learning models trained on the new feature subset were 67.4%− 72.9% and 72.0%− 74.7%, which were 2.1%− 2.5% and 0.3%− 5.7% higher than these of the models trained on original indexes, respectively. When the PCS were divided into typical heavy metal and organic pollution sites according to the enterprise industries, the accuracy of the model trained on the two datasets for identifying soil heavy metal and organic pollution were significantly improve to approximately 80%. Owing to the imbalance in positive and negative samples in the prediction of soil organic pollution, the precisions of soil organic pollution identification models were 58%− 72.5%, which were significantly lower than their accuracies. According to the factors analysis based on the model interpretability of SHAP, most of the indexes of basic information, potential for pollution from product and raw material, and pollution control level had different degrees of impact on soil pollution. However, the indexes of migration capacity of soil pollutants had the least effect in the classification task of soil pollution identification of PCS. Among the indexes, traces of soil pollution, industrial utilization years/start-up time, pollution control risk scores and enterprise scale having the greatest effects on soil pollution with the mean SHAP values of 0.17–0.36, which reflected their contribution rate on soil pollution and could help to optimize the current index scoring of the technical regulation for identifying site soil pollution. This study provides a new technical method to identify soil pollution based on big data and machine learning methods, in addition to providing a reference and scientific basis for environmental management and soil pollution control of PCS.

Nanoplastics (NPs) have recently emerged in the context of global plastic pollution. They may be more toxic than macroplastics litter and microplastic fragments due to its abundances, tiny sizes, and cellular accessibility. The female reproductive toxicity of NPs has been widely documented for aquatic animals, but their effects and underlying mechanisms remain poorly understood in mammals. This study aimed to explore the effects of NPs on female reproduction using human ovarian granulosa cells (GCs) and female mice. The accumulation of polystyrene NPs (PS-NPs) in human granulosa-like tumor cells (KGN cells) and the ovaries of female Balb/c mice were evaluated by exposure to fluorescent PS-NPs. Proliferation and apoptosis, reactive oxygen species (ROS), and Hippo signaling pathway-related factors were analyzed in KGN cells. In addition, fertility rate, litter size, ovarian weight and microstructure, follicle development, serum level of anti-Mullerian hormone, and apoptosis in ovaries were examined in female mice. Here, the PS-NPs can penetrate the KGN cells and accumulate in the ovaries. In vitro, 100 μg/ml PS-NPs inhibited proliferation, induced apoptosis, accumulated ROS, activated three key regulators of the Hippo signaling pathway (MST1, LATS1, and YAP1), and downregulated the mRNA levels of CTGF and Cyr61 in KGN cells. Furthermore, salidroside, an antioxidative compound extracted from Rhodiola rosea, alleviated the damage of PS-NPs to KGN and inhibited the activation of the Hippo signal pathway. In vivo, exposure to 1 mg/day PS-NPs resulted in decreased fertility, abnormal ovarian function, and increased ovarian apoptosis in female mice. Overall, our data suggest that PS-NPs cause granulosa cell apoptosis and affect ovarian functions, leading to reduced fertility in female mice, by inducing oxidative stress and dysregulating the Hippo pathway.

Objectives: Even though guidelines are available to guide dysphagia identification and management practice, there is still a gap between evidence and practice, which requires improvement. The purpose of this study was to determine the effect of using tailored, multifaceted strategies to improve evidence-based post-stroke dysphagia identification and management practice in a community hospital. Methods: Guided by the Knowledge to Action framework, the tailored, multifaceted strategies were developed and implemented for 5 months in a community hospital using a before-and-after study design. These strategies consisted of training intervention, policy intervention, and audit and feedback intervention. Nurses’ level of knowledge and adherence, were collected in March 2019 and again in January 2020. Patients’ quality of life and satisfaction were evaluated during the pre-intervention period (between February 2019 and April 2019) and the post-intervention period (between November 2019 and January 2020). Results: A total of 55 patients with post-stroke dysphagia (28 in the pre-intervention period and 27 in the post-intervention period) and 17 registered nurses were recruited. Following implementation, there were statistically significant improvements in patients’ outcomes (quality of life and satisfaction) and nurses’ outcomes (level of knowledge and adherence). Conclusions: This study assists in closing the research-practice gap by using tailored, multifaceted strategies to increase the use of evidence-based nursing care for dysphagia identification and management practices.

The total flavonoids form Passiflora edulis peel were extracted by compound enzyme assisted ultrasonic method. Taking the yield of flavonoids as the index, the effects of the amount of compound enzyme, enzymatic hydrolysis time, liquid-solid ratio and ultrasonic time on the extraction of total flavonoids from Passiflora edulis peel were analyzed by single factor tests. The main influencing factors and optimal combination of flavonoids extraction were further analyzed by response surface test (Box-Behnken), and the scavenging rate and reducing power of DPPH free radical and hydroxyl free radical were detected in vitro. The results showed that the optimum extraction conditions for ultrasonic extraction of total flavonoids from Passiflora edulis peel assisted by composite enzyme were as follows: The ratio of cellulase to pectinase was 2:1, the dosage of composite enzyme was 4.8%, the enzymolysis time was 1 h, the ethanol concentration was 60%, the liquid-material radio was 30:1 mL/g, and the ultrasonic time was 41 min. Under the optimized conditions, the total flavonoids yield was (2.20%±0.05%), which was similar to the predicted yield 2.24% (

Plastic particle pollution poses an emerging threat to ecological and human health. Laboratory animal studies have illustrated that nano-sized plastics can accumulate in the testis and cause testosterone deficiency and spermatogenic impairment. In this study, TM3 mouse Leydig cells were in vitro exposed to polystyrene nanoparticles (PS-NPs, size 20 nm) at dosages of 50, 100 and 150 μg/mL to investigate their cytotoxicity. Our results demonstrated that PS-NPs can be internalized into TM3 Leydig cells and led to a concentration-dependent decline in cell viability. Furthermore, PS-NPs stimulation amplified ROS generation and initiated cellular oxidative stress and apoptosis. Moreover, PS-NPs treatment affected the mitochondrial DNA copy number and collapsed the mitochondrial membrane potential, accompanied by a disrupted energy metabolism. The cells exposed to PS-NPs also displayed a down-regulated expression of steroidogenesis-related genes StAR, P450scc and 17β-HSD, along with a decrease in testosterone secretion. In addition, treatment with PS-NPs destructed plasma membrane integrity, as presented by increase in lactate dehydrogenase release and depolarization of cell membrane potential. In summary, these data indicated that exposure to PS-NPs in vitro produced cytotoxic effect on Leydig cells by inducing oxidative injury, mitochondrial impairment, apoptosis, and cytomembrane destruction. Our results provide new insights into male reproductive toxicity caused by NPs.

IntroductionVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals.MethodsA total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis.ResultsAt 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron.DiscussionThis study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges.Clinical trial registrationhttps://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

Studying the temporal and spatial relationship between water body nutrients and landscape elements in the agricultural watershed will be helpful in revealing the process of non-point source pollution (NPSP). In order to quantitatively analyze the effects of landscape elements on nitrogen and phosphorus at multiple scales, the Qi River basin located at the tail of the Three Gorges Reservoir was selected as the study area, and various methods such as t-test, one-way analysis of variance, pearson correlation and redundancy analysis were used. The results showed that the nitrogen (N) and phosphorus (P) parameters in the dry season were higher than those in the rainy season, and the spatial differences of N and P in the watershed were significant (with the 95 % level). This may be due to the difference in surface runoff, which led to higher nitrogen and phosphorus concentrations in dry season than in rainy season. Built land percetage (BLP), the largest patch index and the paddy land percentage had the largest coefficients of variation (greater than 40 %). The 100 m buffer zone had the lowest correlation with the catchment, and the 300–1000 m buffer zone had the strongest correlation. The correlation coefficient in the rainy season was greater than that in the dry season. The interpretation rate of all selected indicators in the rainy season exceeded 51.87 % (significant with the 95 % confidence level), while the dry season on the same scale increased by 7.12 %-14.28 % (significant with the 95 % confidence level). Topography and land use/cover had obvious effects on N and P parameters in water bodies. N and P were typically positively correlated with paddy land percentage, dry land percentage and built land percentage, patch density and Shannon diversity index, but they had a negative correlation with the largest patch index. The optimal spatial scale of N and P management in the rainy season was within the buffer range of 100 m–500 m, while the optimal management scale in the dry season was the 500 m buffer and catchment. The amount of N and P entering the river could be reduced to varying degrees by setting up hedges and increasing the route into the river. The results of this study will be helpful for the prevention and control of NPSP in the subtropical basin.

1,3,6,8-Tetrabromocarbazole (1368-BCZ) is identified as an emerging contaminant that exerts angiogenic effects. Multiple studies indicated there was a positive correlation between angiogenesis and nuclear factor kappa B (NF-κB) activation. While the role of NF-κB in inflammation and apoptosis has been well known, the potential biological effects of 1368-BCZ on NF-κB signaling and related mechanism remain unclear. We, therefore, explored the possible effects of 1368-BCZ on the NF-κB pathway at the gene and protein levels and confirmed that NF-κB activation by 1368-BCZ exposure caused an augmented phosphorylated protein level, induction of NF-κB response element (κBRE)-driven luciferase activity and upregulation of transcriptional level of downstream responsive genes. Although 1368-BCZ did not produce detectable changes in hepatic fibrosis in vivo, it obviously altered the apoptosis in human hepatocellular carcinoma (HepG2) cells. Furthermore, the induction of apoptosis was confirmed by the increased cleaved caspase-3 level. These data revealed the activating effects of 1368-BCZ on NF-κB and its involvement in the underlying mechanisms, providing additional information for toxicology studies of emerging contaminants and introducing a mechanism-based toxicological evaluation of emerging pollutants.

Salmonela enterica serovar Typhimurium (S. Typhimurium) is a food-borne pathogen that can form biofilms to increase its resistance to the external environment. Through the detection of biofilm of several S. Typhimurium strains in this study, strain CDC3 with strong biofilm forming capacity and strain CVCC3384 with weak biofilm forming capacity were identified. The genes expressed in planktonic and biofilm cells of two S. Typhimurium strains were analysed by transcriptome sequencing. Results showed that the genes related to the signal transduction pathway were upregulated and genes related to motility were downregulated in strain CDC3. By comparing biofilms and planktonic cells of the two strains, we found that CDC3 regulates biofilm formation mainly through the two-component system kdpABC, while strain CVCC3384 does so mainly through motility and quorum sensing. This study revealed regulation mechanism of biofilms formation between different biofilm forming capacity strains, and provided a theoretical basis for subsequent research.

Background: Since lobaplatin (LBP) has been approved to treat metastatic breast cancer in China, this study aimed to evaluate the safety and efficacy of LBP-based chemotherapy in clinical practice. Methods: This trial was a prospective, open-label, multicenter phase IV clinical trial that enrolled patients with unresectable locally advanced or recurrent/metastatic breast cancer from 34 sites between July 2013 and March 2017. Patients were treated with LBP monotherapy or in combination for four to six cycles. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: A total of 1179 patients were analyzed; 59 (5.0%) were treated with LBP alone, 134 (11.4%) with LBP plus paclitaxel, 263 (22.3%) with LBP plus docetaxel, 237 (20.1%) with LBP plus gemcitabine, 403 (34.2%) with LBP plus vinorelbine, and 83 (7.0%) with other LBP-based regimens. The overall incidence of adverse events (AEs) was 95.2%, and 57.9% of patients had grade >3 AEs. The most common grade >3 AEs were neutropenia (43.9%), leukopenia (39.4%), anemia (17.8%), and thrombopenia (17.7%). LBP monotherapy showed the lowest incidence of grade >3 AEs (39.0%), followed by LBP plus docetaxel (52.9%), LBP plus paclitaxel (59.0%), LBP plus vinorelbine (62.5%), and LBP plus gemcitabine (62.9%). The ORR and DCR were 36.8 and 77.0%, respectively. The median PFS was 5.5 months (95% confidence interval: 5.2–5.9). Conclusion: LBP-based chemotherapy shows favorable efficacy in patients with advanced breast cancer, with manageable safety profile. Trial registration: This trial was registered with ChiCTR.org.cn, ChiCTR-ONC-13003471.

Plastic mulch films (PMFs) are widely used to improve crop quality and quantity. Although they provide a range of benefits, they degrade into widespread microplastics (MPs), which can cause an unavoidable risk of environmental problems. The residue of PMFs is a significant source of MPs in soils, which can then spread into various ecosystems and be easily absorbed by organisms due to their small size, and subsequently transported through food chain. Notably, MPs have been found in the human placenta, stool and blood, raising an urgent reminder of the potential dangers of MPs to human health. This review summarizes recent studies concerning the effects of MPs on the reproductive system in soil invertebrates, aquatic animals and rodents of both sexes and the mechanisms by which MPs affect the animal reproductive system. The studies on females demonstrated that MPs decrease oocyte quantity and quality, and induce ovary fibrosis, pyroptosis and apoptosis of granulosa cells. In addition, disrupted integrity of the blood-testis barrier, damaged spermatogenesis and compromised sperm quality have been shown in most studies on male animals. The studies on the mechanisms of these effects have provided evidence that MPs act on the animal reproductive system through reactive oxygen species-related mechanisms by initiating the Wnt/β-Catenin and NLRP3/Caspase-1 pathways in females, and the Nrf2/HO-1/NF-κB, p38 MAPK and MAPK/Nrf2 pathways in males. Taken together, these studies reveal the reproductive toxicity of MPs from PMF on animals and serve as a reminder to properly dispose of PMF waste.

Background: Chlorinated flame retardant Dechlorane 602 (Dec 602) has been detected in daily food, indicating that it may pose a risk to intestinal health. The intestinal microenvironment plays an important role in intestinal health. Intestinal microbiota and metabolites are two important factors for maintaining the microenvironment. However, little is known about the effects of Dec 602 on intestinal microbiota and metabolites. Objectives: We aimed to probe the effects of Dec 602 on the intestine by revealing the changes that Dec 602 caused to the intestinal microbiota and metabolites. Methods: Adult female C57BL/6 mice were exposed to Dec 602 (low/high doses: 1.0/10.0 μg/kg body weight per day) orally for 7 consecutive days, and sacrificed after 7 days of recovery. The composition of colonic microbiota was measured by 16S rRNA gene sequencing, and the colonic metabolites were determined by LC-ESI-MS/MS. Finally, the effects of Dec 602 on the colon were validated by histopathological analysis. Results: The intestinal microbiota composition was altered toward a pro-inflammatory status after exposure to Dec 602. Dec 602 exposure also up-regulated oxidative metabolites (glutathione disulfide, taurine and retinoic acid) and pro-inflammatory metabolites (prostaglandin E2). On the other hand, antioxidative metabolites (s-adenosylmethionine and 11-cis-retinol) and anti-inflammatory metabolites (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) were down-regulated after exposure to Dec 602. Infiltration of lymphocytes in the colonic lamina propria was observed in the mice treated with Dec 602 for 7 days, and it was not recovered after another 7 days without further treatment. Conclusion: Dec 602 interfered with the colonic microbiota and metabolome, and exhibited inflammatory features. Histopathological studies confirmed that Dec 602 exposure did induce colonic inflammation.

As a common zoonotic intestinal parasite, Giardia duodenalis could infect humans and various mammals worldwide, including pet dogs, leading to giardiasis. This study detected the infection of G. duodenalis in asymptomatic pet dogs in Zhengzhou, and evaluated the possibility of zoonosis and the relationship between gut microbiota and fecal characteristics. We randomly collected 448 fresh fecal samples from Zhengzhou, and G. duodenalis was screened based on the beta-giardin (bg), glutamate dehydrogenase (gdh), and triose phosphate isomerase (tpi) genes. The difference of gut microbiota between five G. duodenalis-positive and five G. duodenalis-negative samples was investigated by 16S rRNA gene sequencing. The overall prevalence of G. duodenalis was 7.1% (32/448) based on bg, gdh, and tpi locus, two G. duodenalis assemblages (C = 13, D = 14) and five (15.6%) mixed infection (C + D) were identified. Moreover, compared with the G. duodenalis-negative group, the diversity of gut microbiota increased in G. duodenalis-positive group. The decrease of Lactobacillus spp. and considerable increase of Prevotella spp. were associated with the fecal characteristics. These results show that the transmission of zoonotic giardiasis between humans and pet dogs is rare in Zhengzhou, central China, and support the use of Lactobacillus spp. as a potential probiotic agent to improve intestinal health in dogs, or even humans, by treating G. duodenalis. Therefore, the public health significance of G. duodenalis to humans, companion animals, and the environment should be further evaluated from One Health perspective.

Abstract Revolutionary CART therapy still faces the challenge of severe cytokine release syndrome (CRS). While IL6 and IL1 have been demonstrated as essential contributors, GM-CSF is one of the most abundant inflammatory cytokines secreted by CART and has also been suggested in contributing to CRS. To minimize GM-CSF production from CART to reduce its associated toxicity, we conducted a pilot study (ChiCTR2000032124) of CRISPR-edited GM-CSF knockout (KO) in CART secreting anti-IL6 scFv and IL1RA, with additional TCR KO for tracing edited CART. The initial results of three patients (1 Non-Hodgkin lymphoma (NHL) and 2 multiple myelomas (MMs)) are summarized as: 3/3 complete response, 2/3 none CRS, 1/3 grade 2 CRS, and 0/3 neurotoxicity. The analysis revealed low levels of GM-CSF, IL6 and IL1B at the time of interferon-gamma (IFNG) peaks, and elevated IL1RA. We also observed significant expansion of CD3– CART during treatment and no aberrant expansion of CD3– CART in the follow-up. Re-expansion of CD3– CART was observed in two patients while recurring CD19+ cells were eradicated in the patient with NHL. In summary, our study supported the safety and durable potency of CRISPR-edited CART in patients, providing a novel platform for developing autologous or allogeneic CART to minimize GM-CSF-associated toxicity in addition to autonomous IL6/IL1 blockade.

Abstract Background To establish the normal reference range of fetal thorax by two-dimensional (2D) and three-dimensional (3D) ultrasound VOCAL technique and evaluate the application in diagnosing fetal thoracic malformations. Methods A prospective cross-sectional study was undertaken involving 1077 women who have a normal singleton pregnancy at 13–40 weeks gestational age (GA). 2D ultrasound and 3D ultrasound VOCAL technique were utilized to assess fetal thoracic transverse diameter, thoracic anteroposterior diameter, thoracic circumference, thoracic area, lung volume, thoracic volume and lung-to-thoracic volume ratio. The nomograms of 2D and 3D fetal thoracic measurements were created to GA. 50 cases were randomly selected to calculate intra- and inter-observer reliability and agreement. In addition, the case groups including congenital skeletal dysplasia (SD) (15), congenital diaphragmatic hernia (CDH) (30), pulmonary sequestration (PS) (25) and congenital cystic adenomatoid malformation (CCAM) (36) were assessed by the nomograms and followed up subsequently. Results Both 2D and 3D fetal thoracic parameters increased with GA using a quadratic regression equation. The intra- and inter-observer reliability and agreement of each thoracic parameter were excellent. 2D fetal thoracic parameters could initially evaluate the fetal thoracic development and diagnose the skeletal thoracic deformity, and lung volume, thoracic volume and lung-to-thorax volume ratio were practical to diagnose and differentiate CDH, PS and CCAM. Conclusion We have established the normal fetal thoracic reference range at 13–40 weeks, which has a high value in diagnosing congenital thoracic malformations.

Abstract In situ consolidation is the most common treatment to conserve cultural relics, but materials for preserving fragile organic cultural relics in humid archaeological excavation sites are scarce. To solve the problem, a moisture-curable polyurethane (MCPU) prepolymer was synthesized by reacting isophorone diisocyanate with polyethylene glycol 600. The standard acetone–dibutylamine method, Fourier transform infrared spectroscopy, gel chromatography and thermogravimetric analysis were utilized to determine the change in isocyanate groups before and after the reaction, the prepolymer molecular weight, the thermal decomposition kinetic parameters and the MCPU film lifetime. The results showed that the number-average molecular weight of the prepolymer was 749, and the weight average molecular weight was 1684. Isophorone groups in the prepolymer react with moisture in the air to form colorless, transparent, flexible films. The thermal decomposition of the MCPU films was a first-order reaction, and the decomposition process consisted of two stages. The Dakin equation was used to obtain the thermal aging equation lg t = 4600.82/T − 8.07, meaning that at 15 °C, the sample has an approximately 150-year lifetime. A new conservation material was developed, and its thermal decomposition kinetics were studied, which are significant for the conservation of fragile organic cultural relics in humid environments.

Abstract In this study, in order to analyze the materials and techniques used for the production of the inscribed plaques, multi-analytical scientific approach, including optical microscopy (OM), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM–EDS), X-ray diffraction (XRD), micro-attenuated total reflection Fourier transform infrared spectroscopy (μ-ATR-FTIR), and micro-Raman spectroscopy (μ-Raman), were used to explore the materials and techniques utilized to create the “Chun Rong Xuan Mao” birthday inscribed plaque of the Qing Dynasty. The results showed that the plaque was made of cypress wood and decorative parts consisting of the surface lacquer layers, plaster lacquer layers and primer lacquer layers. Chinese lacquer was the principal material used in the surface lacquer layers; gypsum and Chinese lacquer were the materials used in the plaster lacquer layers; and the primer lacquer layers was composed of Chinese lacquer, calcite, and mixed pigments by cinnabar and minium. The surface lacquer layers of the inscribed plaque were lacquered black. Gypsum lacquer plaster has been commonly used in the ground layer of lacquerware in modern history. This study confirmed the existence of technology to make lacquerware using gypsum lacquer plaster in the Bashu area during the late Qing Dynasty. Moreover, this study not only provides new findings regarding the traditional production of inscribed plaques and offers technical support for the protection and restoration of such plaques but also has great significance to exploring the history of ancient techniques of lacquering and decorating lacquerware.

Abstract Background Chilling stress is the major factor limiting plant productivity and quality in most regions of the world. In the present study, we aimed to evaluate the effects of putrescine (Put) and polyamine inhibitor d-arginine (d-arg) on the chilling tolerance of anthurium (Anthurium andraeanum). Results Anthurium seedlings were pretreated with five different concentrations of Put solution or d-arg solution. Subsequently, the seedlings were subjected to chilling stress at 6 °C for 3 days, followed by a recovery at 25 °C for 1 day. Relative permeability of the plasma membrane, as well as physiological and morphologic parameters was assessed during the experiments. Additionally, transcriptome sequencing and patterns of differential gene expression related to chilling response were analyzed by qRT-PCR in 1.0 mM Put-treated and untreated anthurium seedlings. Results indicated that the supplementation of exogenous Put decreased the extent of membrane lipid peroxidation and the accumulation of malondialdehyde (MDA), promoted the antioxidant activities and proline content and maintained the morphologic performances compared with the control group. This finding indicated that the application of exogenous Put could effectively decrease the injury and maintain the quality of anthurium under chilling conditions. In contrast, the treatment of d-arg exhibited the opposite effects, which confirmed the effects of Put. Conclusions This research provided a possible approach to enhance the chilling tolerance of anthurium and reduce the energy consumption used in anthurium production.

Abstract Review helpfulness prediction aims to prioritize online reviews by quality. Existing methods largely combine review texts and star ratings for helpfulness prediction. However, star ratings are used in a way that has either little representation capacity or limited interaction with review texts. As a result, rating information has yet to be fully exploited during the combination. This paper aims to overcome the two drawbacks. A deep interactive architecture is proposed to learn the text–rating interaction (TRI) for helpfulness modeling. TRI enlarges the representation capacity of star ratings while enhancing the influence of rating information on review texts. TRI is evaluated on six real-world domains of the Amazon 5-Core dataset. Extensive experiments demonstrate that TRI can better predict review helpfulness and beat the state of the art. Ablation studies and qualitative analysis are provided to further understand model behaviors and the learned parameters.

Background Circular RNA (circRNA) is a novel molecular marker and target candidate that is closely associated with tumor invasion and migration. The mechanism of action of hsa_circ_0005035 (circ‐IGF1R) in non‐small cell lung cancer remains unclear. In this study, we aimed to study the mechanism of action of circ‐IGF1R in lung cancer. Methods We screened circ‐IGF1R, one of the most notable differential expressions, from the Gene Expression Omnibus database, GSE104854, for further research. The expression level of circ‐IGF1R was examined using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) in five different lung cancer cell lines and 50 pairs of lung cancer and adjacent tissues. Wound‐healing and Transwell assays were used for verifying the biological function of circ‐IGF1R. The effect of overexpressing circ‐IGF1R on the transcriptome of whole lung cancer cells was explored in lung cancer cell lines using RNA‐seq. Results The expression level of circ‐IGF1R was notably lower in lung cancer tissues and lung cancer cell lines than in the adjacent normal tissues and cells (P

On the last day of 2019, 44 pneumonia cases with unknown etiology were reported to the World Health Organization (WHO) Country Office of China. This was the first cluster of what would be defined later as coronavirus disease (COVID-19). A self-administered questionnaire with multiple-choice items was created in Microsoft Forms (Microsoft Corp. Redmond, WA. 2020). A 5-point Likert scale with ten items, where "1" refers to "Totally disagree" and "5" refers to "Totally agree," was developed to evaluate the anxiety induced by the COVID-19 outbreak highlighting the suggested sources of stress and anxious emotions, e.g., "When I or any family member go outside home during this COVID-19 outbreak I feel anxious". A 5-point Likert scale with 14 items, where "1" refers to "Not at all like me" and "5" refers to "Just like me," was developed to evaluate people's protective behaviors against coronavirus infection from 3 dimensions: Routine Protective Behaviors (RPB), Post-exposure Protective Behaviors (PPB), and Post-exposure Risky Behaviors (PRB). Items in RPB are aimed to measure individuals' protective behaviors in daily life when facing the epidemic. A multiple-choice scale of 12 items was developed to assess public awareness of COVID-19 as an emerging infectious disease. The primary objective of this work was to develop psychometrically sound scales to assess COVID-19 induced anxiety (CIAS), protective behaviors towards COVID-19 (PBCS), and COVID-19 related knowledge. The results indicated that COVID-19 induced the 6-item version of the CIAS can adequately measure anxiety level. Infectious disease outbreaks represent specific health-related crises that may impact people's emotions in different patterns according to their emerging nature. Therefore, the CIAS was designed to cover the potential anxiety sources for the general population during the COVID-19 outbreak.

Objective Cancer metastasis remains the primary cause of cancer-related death worldwide. In a previous study, we found that levels of BTB/POZ domain-containing protein KCTD12 are lower in metastatic melanoma cells than in parental melanoma cells. The purpose of this study was to identify the roles of KCTD12 in cancer metastasis.Methods The Cancer Genome Atlas (TCGA) datasets were used to evaluate the relationship between KCTD12 and skin cutaneous melanoma (SKCM) prognosis. The effects of endogenous KCTD12 on biological behaviors were examined using the MTT assay. The impacts of KCTD12 on melanoma stemness were explored using spheroid formation assay. KCTD12 knockout A375 cells were generated to confirm the inhibitory effect of KCTD12 on CD271, and a mouse metastatic model was used to determine the impact of KCTD12 on melanoma metastasis in vivo.Results KCTD12 levels were lower in lung metastatic cells than in paired parental melanoma cells, and low KCTD12 expression indicated a poor prognosis in SKCM. Cancer metastasis-related capacities were higher in lung metastatic cells than in parental melanoma cells. Moreover, KCTD12 knockdown enhanced tumor growth and metastasis both in vitro and in vivo. Mechanistically, the interaction between KCTD12 and CD271 might be responsible for the stemness transformation after KCTD12 knockdown.Conclusions This study identifies for the first time the role of the interaction between KCTD12 and CD271 in inducing melanoma cell stemness transformation. Moreover, KCTD12 repression enhances melanoma cell growth, adhesion, migration and invasion.

Melatonin (MLT), an evolutionarily conserved pleiotropic molecule, is implicated in numerous physiological processes in plants and animals. However, the effects of MLT on microbes have seldom been reported. In this study, we examined the influence of exogenous MLT on the growth and hypocrellin biosynthesis of bambusicolous fungus Shiraia sp. S9. Hypocrellin A (HA) is a photoactivated and photoinduced perylenequinone (PQ) toxin in Shiraia. Exogenous MLT at 100.00 μM not only decreased fungal conidiation and spore germination but inhibited HA contents significantly in fungal cultures under a light/dark (24 h:24 h) shift. MLT treatment was associated with higher activity of antioxidant enzymes (superoxide dismutase, catalase and peroxidase) and a marked decline in reactive oxygen species (ROS) production in the mycelia. Moreover, MLT induced endogenous nitric oxide (NO) production during the culture. The NO donor sodium nitroprusside (SNP) potentiated MLT-induced inhibition of O2− production, but NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) enhanced O2− production, whereas MLT-induced NO level was increased by the ROS scavenger vitamin C (Vc). The changes in NO and H2O2 were proved to be involved in the MLT-induced downregulation of the expressions of HA biosynthetic genes, leading to the suppression of HA production. This study provides new insight into the regulatory roles of MLT on fungal secondary metabolism activities and a basis for understanding self-resistance in phototoxin-producing fungi.

Optical signals of pH probes mainly driven from the formation or rupture of covalent bonds, whereas the changes in covalent bonds usually require higher chemical driving forces, resulting in limited sensitivity and reversibility of the probes. The exploration of high-performance pH probes has been a subject of intense investigation. Herein, a new pH probe has been developed, with optical property investigation suggesting the probe has excellent signal-to-noise ratio, and fluorescence intensity shows exponential growth, combined with a visible color change, as pH increased from 5.1 to 6.0; Moreover, the probe has outstanding stability and reversibility, with more than 90% of the initial signal intensity remaining after 30 cycles. In order to better understand the special fluorescence behavior of the reported probe, the non-halogenated isomer is introduced for comparison, combined with the results of structural analysis, quantitative calculation and optical experiments, and the possible mechanism of the special supramolecular aggregation-caused quenching effect induced by the halogen atom is discussed.

The development of efficient and metal-free heterogeneous catalysts for the chemical fixation of CO2 into value-added products is still a challenge. Herein, we reported two kinds of polar group (−COOH, −OH)-functionalized porous ionic polymers (PIPs) that were constructed from the corresponding phosphonium salt monomers (v-PBC and v-PBH) using a solvothermal radical polymerization method. The resulting PIPs (POP-PBC and POP-PBH) can be used as efficient bifunctional heterogeneous catalysts in the cycloaddition reaction of CO2 with epoxides under relatively low temperature, ambient pressure, and metal-free conditions without any additives. It was found that the catalytic activities of the POP-PBC and POP-PBH were comparable with the homogeneous catalysts of Me-PBC and PBH and were higher than that of the POP-PPh3-COOH that was synthesized through a post-modification method, indicating the importance of the high concentration catalytic active sites in the heterogeneous catalysts. Reaction under low CO2 concentration conditions showed that the activity of the POP-PBC (with a conversion of 53.8% and a selectivity of 99.0%) was higher than that of the POP-PBH (with a conversion of 32.3% and a selectivity of 99.0%), verifying the promoting effect of the polar group (−COOH group) in the porous framework. The POP-PBC can also be recycled at least five times without a significant loss of catalytic activity, indicating the high stability and robustness of the PIPs-based heterogeneous catalysts.

Mycosporine-like amino acids (MAAs) are widespread in various microbes and protect them against harsh environments. Here, four different Aphanizomenon species were isolated from severely eutrophic waterbodies, Lake Dianchi and the Guanqiao fishpond. Morphological characters and molecular phylogenetic analysis verified that the CHAB5919, 5921, and 5926 strains belonged to the Aphanizomenon flos-aquae clade while Guanqiao01 belonged to the Aphanizomenon gracile clade. Full wavelength scanning proved that there was obvious maximal absorption at 334 nm through purified methanol extraction, and these substances were further analyzed by HPLC and UPLC-MS-MS. The results showed that two kinds of MAAs were discovered in the cultured Aphanizomenon strains. One molecular weight was 333.28 and the other was 347.25, and the daughter fragment patterns were in accordance with the previously articles reported shinorine and porphyra-334 ion characters. The concentration of the MAAs was calibrated from semi-prepared MAAs standards from dry cells of Microcystis aeruginosa PCC7806 algal powder, and the purity of shinorine and porphyra-334 were 90.2% and 85.4%, respectively. The average concentrations of shinorine and porphyra-334 were 0.307–0.385 µg/mg and 0.111–0.136 µg/mg in Aphanizomenon flos-aquae species, respectively. And there was only one kind of MAAs (shinorine) in Aphanizomenon gracile species.,with a content of 0.003–0.049 µg/mg dry weight among all Aphanizomenon gracile strains. The shinorine concentration in Aphanizomenon flos-aquae was higher than that in Aphanizomenon gracile strains. The total MAAs production can be ranked as Aphanizomenon flos-aquae > Aphanizomenon gracile.