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Abstract RNA methylation modification influences various processes in the human body and has gained increasing attention from scholars. Predicting genes associated with RNA methylation pathways can significantly aid biologists in studying RNA methylation processes. Several prediction methods have been investigated, but their performance is still limited by the scarcity of positive samples. To address the challenge of data imbalance in RNA methylation-associated gene prediction tasks, this study employed a generative adversarial network to learn the feature distribution of the original dataset. The quality of synthetic samples was controlled using the Classifier Two-Sample Test (CTST). These synthetic samples were then added to the data blocks to mitigate class distribution imbalance. Experimental results demonstrated that integrating the synthetic samples generated by our proposed model with the original data enhances the prediction performance of various classifiers, outperforming other oversampling methods. Moreover, gene ontology (GO) enrichment analyses further demonstrate the effectiveness of the predicted genes associated with RNA methylation pathways. The model generating gene samples with PyTorch is available at https://github.com/heyheyheyheyhey1/WGAN-GP_RNA_methylation

Abstract Ovarian cancer (OC) is one of the most prevalent and lethal malignancies affecting the female reproductive system, due to its tendency for metastasis and recurrence. This study identified the overexpression of LINC01320 (or long intergenic nonprotein coding RNA 1320) in tissues of ovarian cancer through the analysis of patient samples and online datasets. In vitro and in vivo experiments demonstrate that silencing of LINC01320 expression led to inhibition of proliferation and metastasis of OC cells. RNA pull-down followed by liquid chromatography tandem mass spectrometry (RNA pull-down-LC-MS/MS) revealed that LINC01320 interacted with purine-rich element binding protein B (PURB), a transcriptional repressor. Furthermore, the RNA-seq analysis identified damage-specific DNA binding protein 2 (DDB2) as a major common target of LINC01320 and PURB. Mechanistically, LINC01320 could recruit PURB to the promoter region of DDB2 to repress DDB2 transcription; thus, promoting the expression of NEDD4L and impeding the TGF-β/SMAD signaling pathway, and ultimately facilitating the progression of OC. Finally, rescue experiments confirmed the involvement of the DDB2/NEDD4L/TGF-β axis in LINC01320-mediated OC progression. In conclusion, this study unveils for the first time the pivotal function of the LINC01320/PURB/DDB2/NEDD4L/TGF-β axis and explores its prospective clinical implications in OC.

Abstract Background Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. Methods This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. Results A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW. Conclusion This pilot trial preliminarily confirmed that nebulized inhalation of PAW can alleviate pneumonia in moderate COVID-19 patients with antiviral treatment failure, with no adverse reactions observed. This still needs to be verified by large-scale studies. Trial registration Chinese Clinical Trial Registry; No.: ChiCTR2300078706 (retrospectively registered, 12/15/2023); URL: www.chictr.org.cn .

Geometric deep learning has demonstrated a great potential in non-Euclidean data analysis. The incorporation of geometric insights into learning architecture is vital to its success. Here we propose a curvature-enhanced graph convolutional network (CGCN) for biomolecular interaction prediction. Our CGCN employs Ollivier-Ricci curvature (ORC) to characterize network local geometric properties and enhance the learning capability of GCNs. More specifically, ORCs are evaluated based on the local topology from node neighborhoods, and further incorporated into the weight function for the feature aggregation in message-passing procedure. Our CGCN model is extensively validated on fourteen real-world bimolecular interaction networks and analyzed in details using a series of well-designed simulated data. It has been found that our CGCN can achieve the state-of-the-art results. It outperforms all existing models, as far as we know, in thirteen out of the fourteen real-world datasets and ranks as the second in the rest one. The results from the simulated data show that our CGCN model is superior to the traditional GCN models regardless of the positive-to-negative-curvature ratios, network densities, and network sizes (when larger than 500).

Abstract Adding corrosion inhibitors is considered to be a cost-effective way to inhibit metal corrosion. In this study, we report the synthesis of a bi-mannich base corrosion inhibitor (BMT) with an impressive inhibition efficiency on carbon steel in H2S and HCl co-existing solution. At the BMT concentration of 9 ppm, the inhibition efficiency (η) of 96.9%, 97.6% and 98.0% were determined by weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy, respectively. The adsorption of BMT on the carbon steel surface follows the Langmuir adsorption isotherm, and the calculated free energy indicates that the adsorption is a spontaneous process. This research also delves into understanding the adsorption behavior and corrosion inhibition mechanism of BMT on carbon steel surfaces through quantum chemistry calculations. The results of this study provide guidance for the application of BMT as a corrosion inhibitor in sour and acid environments.

Abstract Borgs are huge extrachromosomal elements (ECE) of anaerobic methane-consuming “Candidatus Methanoperedens” archaea. Here, we used nanopore sequencing to validate published complete genomes curated from short reads and to reconstruct new genomes. 13 complete and four near-complete linear genomes share 40 genes that define a largely syntenous genome backbone. We use these conserved genes to identify new Borgs from peatland soil and to delineate Borg phylogeny, revealing two major clades. Remarkably, Borg genes encoding nanowire-like electron-transferring cytochromes and cell surface proteins are more highly expressed than those of host Methanoperedens, indicating that Borgs augment the Methanoperedens activity in situ. We reconstructed the first complete 4.00 Mbp genome for a Methanoperedens that is inferred to be a Borg host and predicted its methylation motifs, which differ from pervasive TC and CC methylation motifs of the Borgs. Thus, methylation may enable Methanoperedens to distinguish their genomes from those of Borgs. Very high Borg to Methanoperedens ratios and structural predictions suggest that Borgs may be capable of encapsulation. The findings clearly define Borgs as a distinct class of ECE with shared genomic signatures, establish their diversification from a common ancestor with genetic inheritance, and raise the possibility of periodic existence outside of host cells.

Abstract Background The axillary lymph-node metastatic burden is closely associated with treatment decisions and prognosis in breast cancer patients. This study aimed to explore the value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT)–based radiomics in combination with ultrasound and clinical pathological features for predicting axillary lymph-node metastatic burden in breast cancer. Methods A retrospective analysis was conducted and involved 124 patients with pathologically confirmed early-stage breast cancer who had undergone 18F-FDG PET/CT examination. The ultrasound, PET/CT, and clinical pathological features of all patients were analysed, and radiomic features from PET images were extracted to establish a multi-parameter predictive model. Results The ultrasound lymph-node positivity rate and PET lymph-node positivity rate in the high nodal burden group were significantly higher than those in the low nodal burden group (χ 2 = 19.867, p

Testicular aging manifests as impaired spermatogenesis and morphological alterations in Drosophila. Nonetheless, the comprehensive molecular regulatory framework remains largely undisclosed. This investigation illustrates the impact of copper overload on testicular aging and underscores the interplay between copper overload and lncRNA. Copper overload triggers Cuproptosis through the mitochondrial TCA cycle, facilitating intracellular interactions with Ferroptosis, thereby governing testicular aging. Dysfunction of lncRNA:CR43306 also contributes to testicular aging in Drosophila, emphasizing the significance of lncRNA:CR43306 as a novel aging-associated lncRNA. Moreover, copper overload exacerbates spermatid differentiation defects mediated by lncRNA:CR43306 deficiency through oxidative stress, copper, and iron transport. Therapeutically, Ferrostatin-1 and Resveratrol emerge as potential remedies for addressing testicular aging. This study offers perspectives on the regulatory mechanisms involving copper overload and lncRNA:CR43306 deficiency in the context of testicular aging.

IntroductionEnhancing the efficacy of online food safety supervision requires thoughtful selection and efficient application of regulatory measures.MethodsThis study examined the current state of online food safety supervision in the important food producing city in central China of Zhengzhou. The effectiveness of supervision frequency and penalty on food safety governance of online catering was examined through model construction based on the optimal law enforcement theory. The efficacy of monitoring was evaluated using real supervision and punishment data from the online catering sector in a Chinese new first-tier city.Results and discussionResults showed that although high-frequency and high-penalty supervision are two common methods of online food safety governance, the deterrent effect of high-frequency supervision on online food businesses is more significant for improving the supervision efficiency of the online catering market. Simultaneously, bolstering the education of caterers and food operators as well as raising their degree of training are also efficient ways to raise the efficacy of government oversight. The application of law enforcement economics is broadened in this study, which also has implication for the advancement of credit rating and classification supervision in the area of food safety for online catering.

Tripartite motif-containing protein 59 (TRIM59) is a biomarker for multiple tumors with crucial roles. However, the specific role of TRIM59 in germ cells remains largely unknown. Here, we investigated the effects and underlying regulatory mechanisms of TRIM59 on germ cells using the mouse spermatogonial cell line GC-1. Our results demonstrated that TRIM59 promoted proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, TRIM59 maintained GC-1 cell behaviors through ubiquitination of AXIN1 to activate β-catenin signaling. Furthermore, activation of β-catenin signaling reversed the effects mediated by Trim59 knockdown in GC-1 cells. Collectively, our study revealed a major role and regulatory mechanism of TRIM59 in GC-1 cells, which sheds new light on the molecular pathogenesis of defects in spermatogenesis and may provide therapeutic targets for treatment of male infertility.

RING finger 187 (RNF187), a ubiquitin-ligating (E3) enzyme, plays a crucial role in the proliferation of cancer cells. However, it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells. To investigate the potential involvement of RNF187 in germ cell development, we conducted interference and overexpression assays using GC-2 cells, a mouse spermatocyte-derived cell line. Our findings reveal that the interaction between RNF187 and histone H3 increases the viability, proliferation, and migratory capacity of GC-2 cells. Moreover, we provide evidence demonstrating that RNF187 interacts with H3 and mediates the ubiquitination of H3 at lysine 57 (K57) or lysine 80 (K80), directly or indirectly resulting in increased cellular transcription. This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediating histone H3 ubiquitination, thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of gene transcription. These discoveries provide a new theoretical foundation for further comprehensive investigations into the function of RNF187 in the reproductive system.

Mountains are important suppliers of freshwater to downstream areas, affecting large populations in particular in High Mountain Asia (HMA). Yet, the propagation of water from HMA headwaters to downstream areas is not fully understood, as interactions in the mountain water cycle between the cryo-, hydro- and biosphere remain elusive. We review the definition of blue and green water fluxes as liquid water that contributes to runoff at the outlet of the selected domain (blue) and water lost to the atmosphere through vapor fluxes, that is evaporation from water, ground, and interception plus transpiration (green) and propose to add the term white water to account for the (often neglected) evaporation and sublimation from snow and ice. We provide an assessment of models that can simulate the cryo-hydro-biosphere continuum and the interactions between spheres in high mountain catchments, going beyond disciplinary separations. Land surface models are uniquely able to account for such complexity, since they solve the coupled fluxes of water, energy, and carbon between the land surface and atmosphere. Due to the mechanistic nature of such models, specific variables can be compared systematically to independent remote sensing observations – providing vital insights into model accuracy and enabling the understanding of the complex watersheds of HMA. We discuss recent developments in spaceborne earth observation products that have the potential to support catchment modeling in high mountain regions. We then present a pilot study application of the mechanistic land surface model Tethys & Chloris to a glacierized watershed in the Nepalese Himalayas and discuss the use of high-resolution earth observation data to constrain the meteorological forcing uncertainty and validate model results. We use these insights to highlight the remaining challenges and future opportunities that remote sensing data presents for land surface modeling in HMA.

Abstract This study aimed to analyze the characteristics of the non-specific uptake (NSU) of 18F-labeled fibroblast activation protein inhibitor (18F-FAPI) of the pancreas and investigate the related factors. Totally, 78 patients who underwent both 18F-fluorodeoxyglucose (FDG) and 18F-FAPI PET/CT examinations were divided into normal (n = 53) and NSU (n = 25) groups. The differences in general information, medical history, laboratory indexes and uptake were compared. Receiver operating characteristic (ROC) curves were used to analyze the optimal cut-off values. The correlations between 18F-FAPI-SUVmax and blood cell analysis, liver function indexes, tumor markers, and inflammatory indices were analyzed. The logistic regression model was used to estimate the independent factors. Both 18F-FAPI (4.48 ± 0.98 vs. 2.01 ± 0.53, t = 11.718, P

Abstract Extracellular electron transfer (EET) via microbial nanowires drives globally-important environmental processes and biotechnological applications for bioenergy, bioremediation, and bioelectronics. Due to highly-redundant and complex EET pathways, it is unclear how microbes wire electrons rapidly (>106 s−1) from the inner-membrane through outer-surface nanowires directly to an external environment despite a crowded periplasm and slow (

In recent years, polymyxin has been used as a last-resort therapy for carbapenem-resistant bacterial infections. The emergence of heteroresistance (HR) to polymyxin hampers the efficacy of polymyxin treatment by amplifying resistant subpopulation. However, the mechanisms behind polymyxin HR remain unclear. Small noncoding RNAs (sRNAs) play an important role in regulating drug resistance. The purpose of this study was to investigate the effects and mechanisms of sRNA on polymyxin B (PB)-HR in carbapenem-resistant Klebsiella pneumoniae. In this study, a novel sRNA PhaS was identified by transcriptome sequencing. PhaS expression was elevated in the PB heteroresistant subpopulation. Overexpression and deletion of PhaS were constructed in three carbapenem-resistant K. pneumoniae strains. Population analysis profiling, growth curve, and time-killing curve analysis showed that PhaS enhanced PB-HR. In addition, we verified that PhaS directly targeted phoP through the green fluorescent protein reporter system. PhaS promoted the expression of phoP, thereby encouraging the expression of downstream genes pmrD and arnT. This upregulation of arnT promoted the 4-amino-4-deoxyL-arabinosaccharide (L-Ara4N) modification of lipid A in PhaS overexpressing strains, thus enhancing PB-HR. Further, within the promoter region of PhaS, specific PhoP recognition sites were identified. ONPG assays and RT-qPCR analysis confirmed that PhaS expression was positively modulated by PhoP and thus up-regulated by PB stimulation. To sum up, a novel sRNA enhancing PB-HR was identified and a positive feedback regulatory pathway of sRNA-PhoP/Q was demonstrated in the study. This helps to provide a more comprehensive and clear understanding of the underlying mechanisms behind polymyxin HR in carbapenem-resistant K. pneumoniae.

Background: Surveillance systems revealed that the prevalence of vancomycin-resistant Enterococcus faecium (VREfm) has increased. We aim to investigate the epidemiological and genomic characteristics of VREfm in China. Methods: We collected 20,747 non-redundant E. faecium isolates from inpatients across 19 hospitals in six provinces between January 2018 and June 2023. VREfm was confirmed by antimicrobial susceptibility testing. The prevalence was analyzed using changepoint package in R. Genomic characteristics were explored by whole-genome sequencing. Results: 5.59% (1159/20,747) of E. faecium isolates were resistant to vancomycin. The prevalence of VREfm increased in Guangdong province from 5% before 2021 to 20−50% in 2023 (p

Plasmid-mediated conjugation is a common mechanism for most bacteria to transfer antibiotic resistance genes (ARGs). The conjugative transfer of ARGs is emerging as a major threat to human beings. Although several transfer-related factors are known to regulate this process, small RNAs (sRNAs)-based regulatory roles remain to be clarified. Here, the Hfq-binding sRNA GadY in donor strain Escherichia coli (E. coli) SM10λπ was identified as a new regulator for bacterial conjugation. Two conjugation models established in our previous studies were used, which SM10λπ carrying a chromosomally integrated IncP-1α plasmid RP4 and a mobilizable plasmid pUCP24T served as donor cells, and P. aeruginosa PAO1 or E. coli EC600 as the recipients. GadY was found to promote SM10λπ-PAO1 conjugation by base-pairing with its target mRNA SdiA, an orphan LuxR-type receptor that responds to exogenous N-acylated homoserine lactones (AHLs). However, SM10λπ-EC600 conjugation was not affected due to EC600 lacking AHLs synthase. It indicates that the effects of GadY on conjugation depended on AHLs-SdiA signalling. Further study found GadY bound SdiA to negatively regulate the global RP4 repressors KorA and KorB. When under ciprofloxacin or levofloxacin treatment, GadY expression in donor strain was enhanced, and it positively regulated quinolone-induced SM10λπ-PAO1 conjugation. Thus, our study provides a novel role for sRNA GadY in regulating plasmid-mediated conjugation, which helps us better understand bacterial conjugation to counter antibiotic resistance.

Abstract Background This retrospective study aims to evaluate the diagnostic value of volume measurement of central pulmonary arteries using computer tomography pulmonary angiography (CTPA) for predicting pulmonary hypertension (PH). Methods A total of 59 patients in our hospital from November 2013 to April 2021 who underwent both right cardiac catheterization (RHC) and CTPA examination were included. Systolic pulmonary artery pressure (SPAP), mean PAP (mPAP), and diastolic PAP (DPAP) were acquired from RHC testing. Patients were divided into the non-PH group (18 cases) and the PH group (41 cases). The diameters of the main pulmonary artery (DMPA), right pulmonary artery (DRPA), and left pulmonary artery (DLPA) were measured manually. A 3D model software was used for the segmentation of central pulmonary arteries. The cross-sectional areas (AMPA, ARPA, ALPA) and the volumes (VMPA, VRPA, VLPA) were calculated. Measurements of the pulmonary arteries derived from CTPA images were compared between the two groups, and correlated with the parameters of RHC testing. ROC curves and decision curve analysis (DCA) were used to evaluate the benefit of the three-dimensional CTPA parameters for predicting PH. A multiple linear regression model with a forward-step approach was adopted to integrate all statistically significant CTPA parameters for PH prediction. Results All parameters (DMPA, DRPA, DLPA, AMPA, ARPA, ALPA, VMPA, VRPA, and VLPA) of CTPA images exhibited significantly elevated in the PH group in contrast to the non-PH group (P

ABSTRACTPseudomonas aeruginosa is an opportunistic pathogen that causes acute and chronic infections in immunocompromised individuals. Small regulatory RNAs (sRNAs) regulate multiple bacterial adaptations to environmental changes, especially virulence. Our previous study showed that sRNA PrrH negatively regulates the expression of a number of virulence factors, such as pyocyanin, rhamnolipid, biofilm, and elastase in the P. aeruginosa strain PAO1. However, previous studies have shown that the prrH-deficient mutant attenuates virulence in an acute murine lung infection model. All ΔprrH-infected mice survived the entire 28-day course of the experiment, whereas all mice inoculated with the wild-type or the complemented mutant succumbed to lung infection within 4 days of injection, but the specific mechanism is unclear. Herein, we explored how PrrH mediates severe lung injury by regulating the expression of virulence factors. In vivo mouse and in vitro cellular assays demonstrated that PrrH enhanced the pathogenicity of PAO1, causing severe lung injury. Mechanistically, PrrH binds to the coding sequence region of the mRNA of exsA, which encodes the type III secretion system master regulatory protein. We further demonstrated that PrrH mediates a severe inflammatory response and exacerbates the apoptosis of A549 cells. Overall, our results revealed that PrrH positively regulates ExsA, enhances the pathogenicity of P. aeruginosa, and causes severe lung injury.IMPORTANCEPseudomonas aeruginosa is a Gram-negative bacterium and the leading cause of nosocomial pneumonia. The pathogenicity of P. aeruginosa is due to the secretion of many virulence factors. Small regulatory RNAs (sRNAs) regulate various bacterial adaptations, especially virulence. Therefore, understanding the mechanism by which sRNAs regulate virulence is necessary for understanding the pathogenicity of P. aeruginosa and the treatment of the related disease. In this study, we demonstrated that PrrH enhances the pathogenicity of P. aeruginosa by binding to the coding sequence regions of the ExsA, the master regulatory protein of type III secretion system, causing severe lung injury and exacerbating the inflammatory response and apoptosis. These findings revealed that PrrH is a crucial molecule that positively regulates ExsA. Type III-positive strains are often associated with a high mortality rate in P. aeruginosa infections in clinical practice. Therefore, this discovery may provide a new target for treating P. aeruginosa infections, especially type III-positive strains.

Abstract Purpose The accurate assessment of axillary lymph node metastasis (LNM) in early-stage breast cancer (BC) is of great importance. This study aimed to construct an integrated model based on clinicopathology, ultrasound, PET/CT, and PET radiomics for predicting axillary LNM in early stage of BC. Materials and methods 124 BC patients who underwent 18 F-fluorodeoxyglucose (18 F-FDG) PET/CT and whose diagnosis were confirmed by surgical pathology were retrospectively analyzed and included in this study. Ultrasound, PET and clinicopathological features of all patients were analyzed, and PET radiomics features were extracted to establish an ultrasound model (clinicopathology and ultrasound; model 1), a PET model (clinicopathology, ultrasound, and PET; model 2), and a comprehensive model (clinicopathology, ultrasound, PET, and radiomics; model 3), and the diagnostic efficacy of each model was evaluated and compared. Results The T stage, US_BIRADS, US_LNM, and PET_LNM in the positive axillary LNM group was significantly higher than that of in the negative LNM group (P = 0.013, P = 0.049, P

Abstract As a common malignant tumor among women, ovarian cancer poses a serious threat to their health. This study demonstrates that long non-coding RNA NRSN2-AS1 is over-expressed in ovarian cancer tissues using patient sample and tissue microarrays. In addition, NRSN2-AS1 is shown to promote ovarian cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NRSN2-AS1 stabilizes protein tyrosine kinase 2 (PTK2) to activate the β-catenin pathway via repressing MG-53-mediated ubiquitinated degradation of PTK2, thereby facilitating ovarian cancer progression. Rescue experiments verify the function of the NRSN2-AS1/PTK2/β-catenin axis and the effects of MG53 on this axis in ovarian cancer cells. In conclusion, this study demonstrates the key role of the NRSN2-AS1/PTK2/β-catenin axis for the first time and explores its potential clinical applications in ovarian cancer.

Although federated learning is gaining prevalence in smart sensor networks, substantial risks to data privacy and security persist. An improper application of federated learning techniques can lead to critical privacy breaches. Practical and effective privacy-enhanced federated learning (PEPFL) is a widely used federated learning framework characterized by low communication overhead and efficient encryption and decryption processes. Initially, our analysis scrutinized security vulnerabilities within the PEPFL framework and identified an effective attack strategy. This strategy enables the server to derive private keys from content uploaded by participants, achieving a 100% success rate in extracting participants’ private information. Moreover, when the number of participants does not exceed 300, the attack time does not surpass 3.72 s. Secondly, this paper proposes a federated learning model that integrates homomorphic encryption and secret sharing. By using secret sharing among participants instead of secure multi-party computation, the amount of effective information available to servers is reduced, thereby effectively preventing servers from inferring participants’ private gradients. Finally, the scheme was validated through experiments, and it was found to significantly reduce the inherent collusion risks unique to the federated learning scenario. Moreover, even if some participants are unavailable, the reconstructable nature of secret sharing ensures that the decryption process can continue uninterrupted, allowing the remaining users to proceed with further training. Importantly, our proposed scheme exerts a negligible impact on the accuracy of model training.

Thousands of genes are expressed in the testis of mice. However, the details about their roles during spermatogenesis have not been well-clarified for most genes. The purpose of this study was to examine the effect of Slc26a1 deficiency on mouse spermatogenesis and male fertility. Slc26a1-knockout (KO) mice were generated using CRISPR/Cas9 technology on C57BL/6J background. We found no obvious differences between Slc26a1-KO and Slc26a1-WT mice in fertility tests, testicular weight, sperm concentrations, or morphology. Histological analysis found that Slc26a1-KO mouse testes had normal germ cell types and mature sperm. These findings indicated that Slc26a1 was dispensable for male fertility in mice. Our results may save time and resources by allowing other researchers to focus on genes that are more meaningful for fertility studies. We also found that mRNAs of two Slc26a family members (Slc26a5 and Slc26a11) were expressed on higher mean levels in Slc26a1-KO total mouse testes, compared to Slc26a1-WT mice. This effect was not found in mouse GC-1 and GC-2 germ cell lines with the Slc26a1 gene transiently knocked down. This result may indicate that a gene compensation phenomenon was present in the testes of Slc26a1-KO mice.

Summary: Molecular representation learning plays an important role in molecular property prediction. Existing molecular property prediction models rely on the de facto standard of covalent-bond-based molecular graphs for representing molecular topology at the atomic level and totally ignore the non-covalent interactions within the molecule. In this study, we propose a molecular geometric deep learning model to predict the properties of molecules that aims to comprehensively consider the information of covalent and non-covalent interactions of molecules. The essential idea is to incorporate a more general molecular representation into geometric deep learning (GDL) models. We systematically test molecular GDL (Mol-GDL) on fourteen commonly used benchmark datasets. The results show that Mol-GDL can achieve a better performance than state-of-the-art (SOTA) methods. Extensive tests have demonstrated the important role of non-covalent interactions in molecular property prediction and the effectiveness of Mol-GDL models. Motivation: Geometric deep learning (GDL) has demonstrated huge power and enormous potential in molecular data analysis. However, a great challenge still remains for highly efficient molecular representations. Currently, covalent-bond-based molecular graphs are the de facto standard for representing molecular topology at the atomic level. Here, we demonstrate that molecular graphs constructed only from non-covalent bonds can achieve similar or even better results than covalent-bond-based models in molecular property prediction. This demonstrates the great potential of novel molecular representations beyond the de facto standard of covalent-bond-based molecular graphs. Based on the finding, we propose molecular geometric deep learning (Mol-GDL). In our Mol-GDL, molecular topology is modeled as a series of molecular graphs, each focusing on a different scale of atomic interactions. In this way, both covalent interactions and non-covalent interactions are incorporated into the molecular representation on an equal footing.

Summary: Combinatorial drug therapy is a promising approach for treating complex diseases by combining drugs with synergistic effects. However, predicting effective drug combinations is challenging due to the complexity of biological systems and the limited understanding of pathophysiological mechanisms and drug targets. In this paper, we proposed a computational framework called VGAETF (Variational Graph Autoencoder Tensor Decomposition), which leveraged multi-relational graph to model complex relationships between entities in biological systems and predicted disease-related synergistic drug combinations in an end-to-end manner. In the computational experiments, VGAETF achieved high performances (AUROC [the area under receiver operating characteristic] = 0.9767, AUPR [the area under precision-recall] = 0.9660), outperforming other compared methods. Moreover, case studies further demonstrated the effectiveness of VGAETF in identifying potential disease-related synergistic drug combinations.

ABSTRACT Pseudomonas aeruginosa (P. aeruginosa) is one of the leading causes of chronic infections, including reinfection, relapse, and persistent infection, especially in cystic fibrosis patients. Relapse P. aeruginosa infections are more harmful because of repeated hospitalization and undertreatment of antimicrobials. However, relapse P. aeruginosa infection in China remains largely unknown. Herein, we performed a 3-year retrospective study from 2019 to 2022 in a tertiary hospital, which included 442 P. aeruginosa isolates from 196 patients. Relapse infection was identified by screening clinical records and whole-genome sequencing (WGS). We found that 31.6% (62/196) of patients had relapsed infections. The relapse incidence of carbapenem-resistant P. aeruginosa infection (51.4%) is significantly higher than that of carbapenem-susceptible P. aeruginosa infection (20.2%, P < 0.0001). These isolates were assigned to 50 distinct sequence types and sporadically distributed in phylogeny, indicating that relapsed infections were not caused by certain lineages. Fast adaptation and evolution of P. aeruginosa isolates were reflected by dynamic changes of antimicrobial resistance, gene loss and acquisition, and single-nucleotide polymorphisms during relapse episodes. Remarkably, a convergent non-synonymous mutation that occurs in a pyochelin-associated virulence gene fptA (T1056C, M252T) could be a considerable target for the diagnosis and treatment of relapse P. aeruginosa infection. These findings suggest that integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapsed infections. Continued surveillance of the genomic dynamics of relapse P. aeruginosa infection will generate further knowledge for optimizing treatment and prevention in the future. IMPORTANCE Pseudomonas aeruginosa is a predominant pathogen that causes various chronic infections. Relapse infections promote the adaptation and evolution of antimicrobial resistance and virulence of P. aeruginosa, which obscure evolutionary trends and complicate infection management. We observed a high incidence of relapse P. aeruginosa infection in this study. Whole-genome sequencing (WGS) revealed that relapse infections were not caused by certain lineages of P. aeruginosa isolates. Genomic dynamics of relapse P. aeruginosa among early and later stages reflected a plasticity scattered through the entire genome and fast adaptation and genomic evolution in different ways. Remarkably, a convergent evolution was found in a significant virulence gene fptA, which could be a considerable target for diagnosis and treatment. Taken together, our findings highlight the importance of longitudinal surveillance of relapse P. aeruginosa infection in China since cystic fibrosis is rare in Chinese. Integrated utilization of WGS and medical records provides opportunities for improved diagnostics of relapse infections.

Both heavy metals and antibiotics exert selection pressure on bacterial resistance, and as they are commonly co-contaminated in the environment, they may play a larger role in bacterial resistance. This study examined how breeding cycles affect antibiotic resistance genes (ARGs) in chicken manure and the surrounding topsoils at 20, 50, 100, 200, and 300 m from twelve typical laying hen farms in the Ningxia Hui Autonomous Region of northwest China. Six antibiotics, seven heavy metals, ten mobile genetic elements (MGEs), and microbial community affected the ARGs profile in chicken dung and soil samples. Tetracycline antibiotic residues were prevalent in chicken manure, as were relatively high content of aureomycin during each culture period. Zinc (Zn) content was highest among the seven heavy metals in chicken feces. Chicken dung also enriched aminoglycosides, MLSB, and tetracycline ARGs, notably during brooding and high production. The farm had a minimal influence on antibiotics in the surrounding soil, but its effect on ARGs and MGEs closer to the farm (50 m) was stronger, and several ARGs and MGEs increased with distance. Manure microbial composition differed dramatically throughout breeding cycles and sampling distances. ARGs were more strongly related with antibiotics and heavy metals in manure than soil, whereas MGEs were the reverse. Antibiotics, heavy metals, MGEs, and bacteria in manure accounted 12.28%, 22.25%, 0.74%, and 0.19% of ARGs composition variance, respectively, according to RDA and VPA. Bacteria (2.89%) and MGEs (2.82%) only affected soil ARGs composition. These findings showed that heavy metals and antibiotics are the main factors affecting faecal ARGs and bacteria and MGEs soil ARGs. This paper includes antibiotic resistance data for large-scale laying hen husbandry in northwest China and a theoretical framework for decreasing antibiotic resistance.

A sharp increase in multidrug-resistant tuberculosis (MDR-TB) threatens human health. Spontaneous mutation in essential gene confers an ability of Mycobacterium tuberculosis resistance to anti-TB drugs. However, conventional laboratory strategies for identification and prediction of the mutations in this slowly growing species remain challenging. Here, by combining XCas9 nickase and the error-prone DNA polymerase A from M. tuberculosis, we constructed a CRISPR-guided DNA polymerase system, CAMPER, for effective site-directed mutagenesis of drug-target genes in mycobacteria. CAMPER was able to generate mutagenesis of all nucleotides at user-defined loci, and its bidirectional mutagenesis at nick sites allowed editing windows with lengths up to 80 nucleotides. Mutagenesis of drug-targeted genes in Mycobacterium smegmatis and M. tuberculosis with this system significantly increased the fraction of the antibiotic-resistant bacterial population to a level approximately 60- to 120-fold higher than that in unedited cells. Moreover, this strategy could facilitate the discovery of the mutation conferring antibiotic resistance and enable a rapid verification of the growth phenotype-mutation genotype association. Our data demonstrate that CAMPER facilitates targeted mutagenesis of genomic loci and thus may be useful for broad functions such as resistance prediction and development of novel TB therapies.

Despite enormous potential of solar-driven biocatalysis, most living systems lack photoactive proteins and require toxic and expensive synthetic materials limiting the performance. Here, a class of natural photoconductors is demonstrated through sub-picosecond heme-to-heme electron transfer in bacteria-produced protein nanowires.

Biochar (BC) and ferrihydrite (Fh) were used together in activation of H2O2 for removal of sulfamethazine (SMZ), a refractory antibiotic pollutant. The results show a complementary effect between biochar and ferrihydrite on activation of H2O2, namely biochar accelerated Fe(Ⅲ)/Fe(Ⅱ) cycle through electron donation/transfer, while ferrihydrite enhanced the yield of •OH through a sustainable release of dissolved Fe. Thus several times more •OH was produced in the co-activated system (BC + Fh/H2O2) than either in the ferrihydrite-catalyzed Fenton-like system (Fh/H2O2) or in the biochar-activated system (BC/H2O2). Consequently, a more efficient oxidation of SMZ was observed in BC + Fh/H2O2, in which the reaction rate constant (kobs) is 30.7 times in Fh/H2O2 and 6.08 times in BC/H2O2, respectively. This research provides a simple and sustainable strategy for enhancing the efficiency of Fenton-like oxidation of pollutants.

IntroductionPatients undergoing cranial ionizing radiation therapy for brain malignancies are at increased risk of long-term neurocognitive decline, which is poorly understood and currently untreatable. Although the molecular pathogenesis has been intensively researched in many organisms, whether and how ionizing radiation alters functional neurotransmission remains unknown. This is the first study addressing physiological changes in neurotransmission after ionizing radiation exposure.MethodsTo elucidate the cellular mechanisms of radiation damage, using calcium imaging, we analyzed the effects of ionizing radiation on the neurotransmitter-evoked responses of prothoracicotropic hormone (PTTH)-releasing neurons in Drosophila larvae, which play essential roles in normal larval development.ResultsThe neurotransmitters dopamine and tyramine decreased intracellular calcium levels of PTTH neurons in a dose-dependent manner. In gamma irradiated third-instar larvae, a dose of 25 Gy increased the sensitivity of PTTH neurons to dopamine and tyramine, and delayed development, possibly in response to abnormal functional neurotransmission. This irradiation level did not affect the viability and arborization of PTTH neurons and successful survival to adulthood. Exposure to a 40-Gy dose of gamma irradiation decreased the neurotransmitter sensitivity, physiological viability and axo-dendritic length of PTTH neurons. These serious damages led to substantial developmental delays and a precipitous reduction in the percentage of larvae that survived to adulthood. Our results demonstrate that gamma irradiation alters neurotransmitter-evoked responses, indicating synapses are vulnerable targets of ionizing radiation.DiscussionThe current study provides new insights into ionizing radiation-induced disruption of physiological neurotransmitter signaling, which should be considered in preventive therapeutic interventions to reduce risks of neurological deficits after photon therapy.

RationaleTo explore the clinical role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in differentiating malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung cancer.MethodsOver a 8-year period, we retrospectively reviewed PET/CT data of lung cancer patients with pleural effusion, with 237 participants enrolled for analysis. The nature of pleural effusion was confirmed using pleural cytology or biopsy. MPE versus BPE comparison and multiple regression analysis were performed. Receiver operating characteristic (ROC) curve analysis was used for evaluating the diagnostic performance.ResultsOf the 237 participants, 170 had MPEs and 67 had BPEs. Compared with BPEs, MPEs had higher pleural SUVmax and thicker pleura and were more common among non-small cell lung cancers, peripheral tumors, and women (p < 0.05). BPEs had larger and higher 18F-FDG uptake thoracic lymph nodes and more complications of pneumonia (p < 0.05) than MPEs. Multiple regression analysis was used to identify the pleural SUVmax (odds ratio, OR = 38.8), sex (OR = 0.033), and mediastinal lymphoid node size (OR = 0.86) as independent risk factors for MPEs. The sensitivity, specificity, and area under the ROC curve (AUC) in the combined ROC curve analysis by using the three factors were 95.3%, 95.5%, and 0.989, respectively.Conclusion18F-FDG PET/CT integrated imaging is an effective non-invasive method for differential diagnosis of MPE in patients with lung cancer. Pleural SUVmax combined with thoracic lymph nodes and sex has high diagnostic value.

During spermatogenesis, mitochondria extend along the whole length of spermatid tail and offer a structural platform for microtubule reorganization and synchronized spermatid individualization, that eventually helps to generate mature sperm in Drosophila. However, the regulatory mechanism of spermatid mitochondria during elongation remains largely unknown. Herein, we demonstrated that NADH dehydrogenase (ubiquinone) 42 kDa subunit (ND-42) was essential for male fertility and spermatid elongation in Drosophila. Moreover, ND-42 depletion led to mitochondrial disorders in Drosophila testes. Based on single-cell RNA-sequencing (scRNA-seq), we identified 15 distinct cell clusters, including several unanticipated transitional subpopulations or differentiative stages for testicular germ cell complexity in Drosophila testes. Enrichments of the transcriptional regulatory network in the late-stage cell populations revealed key roles of ND-42 in mitochondria and its related biological processes during spermatid elongation. Notably, we demonstrated that ND-42 depletion led to maintenance defects of the major mitochondrial derivative and the minor mitochondrial derivative by affecting mitochondrial membrane potential and mitochondrial-encoded genes. Our study proposes a novel regulatory mechanism of ND-42 for spermatid mitochondrial derivative maintenance, contributing to a better understanding of spermatid elongation.

The lack of discernible vehicle contour features in low-light conditions poses a formidable challenge for nighttime vehicle detection under hardware cost constraints. Addressing this issue, an enhanced histogram of oriented gradients (HOGs) approach is introduced to extract relevant vehicle features. Initially, vehicle lights are extracted using a combination of background illumination removal and a saliency model. Subsequently, these lights are integrated with a template-based approach to delineate regions containing potential vehicles. In the next step, the fusion of superpixel and HOG (S-HOG) features within these regions is performed, and the support vector machine (SVM) is employed for classification. A non-maximum suppression (NMS) method is applied to eliminate overlapping areas, incorporating the fusion of vertical histograms of symmetrical features of oriented gradients (V-HOGs). Finally, the Kalman filter is utilized for tracking candidate vehicles over time. Experimental results demonstrate a significant improvement in the accuracy of vehicle recognition in nighttime scenarios with the proposed method.

Abstract Background Stem cell niche maintains stem cell population identity and is essential for the homeostasis of self-renewal and differentiation in Drosophila testes. However, the mechanisms of CySC lineage signals-mediated soma–germline communications in response to external stimuli are unclear. Methods Pre-initiation complex functions were evaluated by UAS-Gal4-mediated cell effects. RNA sequencing was conducted in NC and eIF5 siRNA-treated cells. Genetic interaction analysis was used to indicate the relationships between eIF5 and eIF1A/eIF2γ in Drosophila testes. Results Here, we demonstrated that in CySCs, translation initiation factor eIF5 mediates cyst cell differentiation and the non-autonomously affected germ cell differentiation process. CySCs lacking eIF5 displayed unbalanced cell proliferation and apoptosis, forming testicular germ cell tumors (TGCTs) during spermatogenesis. eIF5 transcriptional regulation network analysis identified multiple metabolic processes and several key factors that might be involved in germ cell differentiation and TGCT formation. Importantly, knockdown of eIF1A and eIF2γ, key components of pre-initiation complex, mimicked the phenotype of knocking down eIF5 in the stem cell niche of Drosophila testes. Genetic interaction analysis indicated that eIF5 was sufficient to rescue the phenotype of tumorlike structures induced by down-regulating eIF1A or eIF2γ in CySCs. Conclusions These findings demonstrated that CySC lineage eIF5, together with eIF1A or eIF2γ, mediates soma–germline communications for the stem cell niche homeostasis in Drosophila testes, providing new insights for the prevention of TGCTs.

Despite the rapidly growing interest in nanoparticle-mediated controllable male contraception and recovery of male fertility, novel applications of nanoparticles in these processes are limited by a knowledge gap regarding their transport and distribution in the testes. Here, we investigated the fate of gold nanoparticles in the mouse testes using two injection methods, namely, interstitial testicular injection (IT-AuNPs, AuNPs exposure in the interstitial compartment of the testes) and rete testis injection (RT-AuNPs, AuNPs exposure in the adluminal compartment of the seminiferous tubules). In this study, we used 100 nm spherical AuNPs and microinjected with 5 μL AuNPs (30 mg/mL) for the experiments. For IT-AuNP injection, we found that AuNPs could not penetrate through the Sertoli cell-mediated blood–testis barrier (BTB) of the seminiferous tubules, and no male reproductive toxicity was observed. For RT-AuNP injection, AuNPs could be retrogradely transported from the adluminal compartment to the interstitial compartment of the testes via Sertoli cell-mediated endocytosis/exocytosis, resulting in damage and the release of inflammatory cytokines in the mouse testis. Our results highlight a retrograde nanoparticle transport function of Sertoli cells, thereby providing a mechanistic overview of the development and use of nanobiotechnology in male reproduction. Synopsis: This study provides new insights into male reproductive immunotoxicity for AuNPs exposure and elucidates a mechanism via Sertoli cell-mediated endocytosis/exocytosis.

Abstract Background Osteosarcoma (OS) is the most common malignant tumor of bone, and the clinical efficacy of current treatments and associated survival rates need to be further improved by employing novel therapeutic strategies. Although various studies have shown that BMI1 protein is universally upregulated in OS cells and tissues, its specific role and underlying mechanism have not yet been fully explored. Methods Expression of BMI1 protein in OS cells was detected by western blot. The effect of BMI1 on proliferation and migration of OS cells (143B and U-2OS cell lines) was investigated in vitro using CCK-8, colony formation and transwell assays, and in vivo using subcutaneous tumorigenesis and lung metastasis assays in xenograft nude mice. Expression of epithelial–mesenchymal transition (EMT)-associated proteins was detected by immunofluorescence imaging. Bioinformatic analysis was performed using ENCODE databases to predict downstream targets of BMI1. SIK1 mRNA expression in osteosarcoma cells was detected by quantitative real-time reverse transcription PCR (qPCR). Chromatin immunoprecipitation-qPCR (ChIP-qPCR) was used to investigate expression of BMI1-associated, RING1B-associated, H2AK119ub-associated and H3K4me3-associated DNA at the putative binding region of BMI1 on the SIK1 promoter in OS cells. Results Using both in vitro and in vivo experimental approaches, we found that BMI1 promotes OS cell proliferation and metastasis. The tumor suppressor SIK1 was identified as the direct target gene of BMI1 in OS cells. In vitro experiments demonstrated that SIK1 could inhibit proliferation and migration of OS cells. Inhibition of SIK1 largely rescued the altered phenotypes of BMI1-deficient OS cells. Mechanistically, we demonstrated that BMI1 directly binds to the promoter region of SIK1 in a complex with RING1B to promote monoubiquitination of histone H2A at lysine 119 (H2AK119ub) and inhibit H3K4 trimethylation (H3K4me3), resulting in inhibition of SIK1 transcription. We therefore suggest that BMI1 promotes OS cell proliferation and metastasis by inhibiting SIK1. Conclusions Our results reveal a novel molecular mechanism of OS development promoted by BMI1 and provides a new potential target for OS treatment.

Background: Synucleinopathies, which are major pathological features of Parkinson’s disease (PD), are characterized by misfolded aggregates of α-synuclein in the peripheral and central nervous system. Icariin (ICA) is the main active component of Epimedium flavonoids. Our previous study found that ICA decreases α-synuclein expression in APPV717I transgenic mice. Methods: The aim of the present study was to examine the potential applications and mechanisms of ICA in PD using A53T α-synuclein transgenic (A53T Tg) mice. After 3 months of intragastric ICA administration, rotarod and pole tests were used to assess behavioral changes in A53T Tg mice at 8 and 13 months of age. SH-SY5Y cells over-expressing wild-type α-synuclein were used to further examine the pharmacological effect and underlying mechanism of ICA. Western blotting and immunocytochemistry were used to detect the expression levels of α-synuclein and its related proteins. Results: ICA significantly improved the impaired motor function and coordination in A53T Tg mice. It also decreased the expression, Ser129 phosphorylation, and aggregation of α-synuclein in SH-SY5Y cells transfected with α-synuclein and the striatum of A53T Tg mice. Moreover, ICA increased the expression of parkin, which is associated with the ubiquitin-proteasome system (UPS), and decreased the level of polo-like kinase 2 (PLK2), an enzyme that phosphorylates α-synuclein. Conclusions: ICA alleviated motor impairments in A53T mice, an effect which may be associated with the decreased phosphorylation and aggregation of α-synuclein through PLK2 and parkin regulation.

The properties of prepared foamed lightweight soils (FLSs) using prefabricated foam requires high foam stability. This paper investigates the geometrical characteristics of different foam densities, different types of foaming agents in the air, and the presence of slurry. Then, it studies their effects on the pore structure and mechanical properties of FLS. Results show that with the increase in foam density the bleeding rate of foam in the air for 1 h increases and the foam with a foam density of 50 kg/m3 is the most stable in the air. The stability of foam in slurry is not directly related to the property of foam in the air. The FLS prepared with the same foaming agent had the best performance with the FLS designed with a foam density of 50 kg/m3, which had the smallest average pore size and the most minor pore size distribution, and had the highest compressive strength. Among the three different foaming agents, Type-S was the best, and the slurry had the lowest rate of increase in wet density after the defoaming test, indicating that the foam had the best stability in the cement slurry. The FLS prepared with the density of 50 kg/m3 using the Type-S foaming agent and mixed with the slurry of cement, fly ash:slag:water = 105:105:140:227.5, was hardened to a mean pore size of 299 μm, and the 7 days, 28 days, and 56 days compressive strengths were 0.92 MPa, 2.04 MPa, and 2.48 MPa, respectively, which had the smallest average pore size and the highest compressive strength among the FLSs prepared using the three foaming agents.

Abstract We study the mechanism of topological mass-generation for 3d Chern-Simons (CS) gauge theories, where the CS term can retain the gauge symmetry and make gauge boson topologically massive. Without CS term the 3d massless gauge boson has a single physical transverse polarization state, while adding the CS term converts it into a massive physical polarization state and conserves the total physical degrees of freedom. We formulate the mechanism of topological mass-generation at S-matrix level. For this, we propose and prove a Topological Equivalence Theorem (TET) which connects the N-point scattering amplitude of the gauge boson’s physical polarization states ( A P a $$ {A}_{\mathrm{P}}^a $$ ) to that of the transverse polarization states ( A T a $$ {A}_{\mathrm{T}}^a $$ ) under high energy expansion. We present a general 3d power counting method on the leading energy dependence of the scattering amplitudes in both topologically massive Yang-Mills (TMYM) and topologically massive gravity (TMG) theories. With these, we uncover a general energy cancellation mechanism for N -gauge boson scattering amplitudes which predicts the cancellation E 4 → E 4−N at tree level. Then, we compute the 4-gauge boson amplitudes of A P a $$ {A}_{\mathrm{P}}^a $$ -states and A T a $$ {A}_{\mathrm{T}}^a $$ -states, with which we explicitly demonstrate the TET and establish such energy cancellations for N = 4. We further extend the double-copy approach to reconstruct the massive 4-graviton amplitude of TMG from the massive 4-gauge boson amplitude of TMYM. With these, we uncover striking large energy cancellations in the 4-graviton amplitude: E 12 → E 1, and establish its correspondence to the leading energy cancellation E 4 → E 0 in the 4-gauge boson amplitude of TMYM.

We study the mechanism of topological mass generation for 3-dimensional Chern–Simons gauge theories and propose a brand-new topological equivalence theorem to connect scattering amplitudes of the physical gauge boson states to that of the transverse states under high-energy expansion. We prove a general energy cancelation mechanism for N-point physical gauge boson amplitudes, which predicts large cancelations of E4 − L → E(4 − L) − N at any L-loop level (L ⩾ 0). We extend the double-copy approach to construct massive graviton amplitudes and to study their structures. We newly uncovered a series of strikingly large energy cancelations E12 → E1 of the tree-level 4-graviton scattering amplitude under high-energy expansion and establish a new correspondence between the 2 energy cancelations in the topologically massive Yang–Mills gauge theory and the topologically massive gravity theory. We further study the scattering amplitudes of Chern–Simons gauge bosons and gravitons in the nonrelativistic limit.

Although the scale of China’s online food industry grew rapidly in recent years, the risky operational practices of business were not adequately prohibited. Based on the repeated illegal behaviors of online food enterprises, this study constructs the intertemporal utility model of online food enterprises from the perspective of behavioral economics. It was discovered that the presence of cognitive biases with a short-term focus in online food businesses would result in dangerous food sales behavior. The myopic unsafe online food quantity deviation of businesses would decrease as the cognitive deviation coefficient and penalty factor of online food businesses increase. Due to the existence of myopic cognitive bias, it is difficult for online food businesses to perceive the difference between the discount factor in the short term and the long term during the decision-making process. Therefore, they will not choose to sell a significant quantity of dangerous food. However, during the sales behavior phase, food-settled enterprises would opt to offer more dangerous food due to myopic cognitive bias. According to the different behaviors of online food enterprises in different periods, this study provides some corresponding supervision strategies for government regulators in the near and far future. Even though government departments could act quickly to investigate and deal with food safety incidents that are less harmful, the long-term solutions to ensure continued online food safety and optimize the online business environment are to build comprehensive system of online food safety regulation, improve information disclosure of online food enterprises, and enhance the government online governance structures.

ObjectiveThe aim of this study was to evaluate the performance of Fluoride-18 (18F)-PSMA-1007-PET/CT radiomics for the tumor malignancy and clinical risk stratification in primary prostate cancer (PCa).Materials and MethodsA total of 161 pathological proven PCa patients in a single center were retrospectively analyzed. Prostate-specific antigen (PSA), Gleason Score (GS) and PET/CT indexes (SUVmin, SUVmax, and SUVmean) were compared according to risk stratification. Radiomics features were extracted from PCa 18F-PSMA-1007-PET/CT imaging. The radiomics score integrating all selected parameters and clinicopathologic characteristics was used to construct a binary logistic regression and nomogram classifier. Predictors contained in the individualized prediction nomogram included radiomics score, PSA level and metastasis status.ResultsThe radiomics signature, which consisted of 30 selected features, was significantly associated with PSA level and Gleason score (P < 0.001 for both primary and validation cohorts). Predictors contained in the individualized prediction nomogram included radiomics score, PSA level and metastasis status. The model showed good discrimination with an area under the ROC curve of 0.719 for the GS. Combined clinical-radiomic score nomogram had a similar benefit to utilizing the PET/CT radiomic features alone for GS discrimination.ConclusionThe 18F-PSMA-1007-PET/CT radiomics signature can be used to facilitate preoperative individualized prediction of GS; incorporating the radiomics signature, PSA level, and metastasis status had similar benefits to those of utilizing the PET/CT radiomics features alone.

Foamed lightweight soil (FLS) is a lightweight cementitious material containing a large number of tiny closed pores and has been widely used as a filler in places such as railways, roads and airports. However, there has been little research into the resistance of FLS to sulphate attack in practical engineering applications. The performance of FLS against different sulphate erosion concentrations was studied to elucidate the engineering characteristics of using large volumes of FLS as fill material for the road base in the construction of intelligent networked vehicle test sites. The results showed that the compressive strength of FLS prepared using 30% Portland cement (C), 30% granulated blast furnace slag (GBFS), 40% fly ash (FA) and a small amount of a concrete antiseptic agent (CA) as cementitious materials reached 0.8 and 1.9 MPa at 7 and 28 d, respectively, when the wet density was about 600 kg/m3, which met the design requirements. The FLS prepared via the above-mentioned cementitious system had a low carbon emission, with a CO2 emission reduction rate of up to 70%. It also had excellent sulphate attack resistance: the corrosion resistance coefficient of the cementitious material system reached 0.97, which was considerably better than that of C (0.83). For an erosion medium environment with SO42− concentrations of less than 1000 mg/L (moderate), 40% GBFS or FA can be used to prepare FLS. When the concentration of SO42− is less than 4000 mg/L (severe), 30% C, 30% GBFS and 40% FA can be used as cementitious materials, preferably in combination with an appropriate amount of CA, to prepare FLS.

ObjectiveDistant metastasis (DM) is an important prognostic factor in differentiated thyroid cancer (DTC) and determines the course of treatment. This study aimed to establish a predictive nomogram model that could individually estimate the risk of DM and analyze the prognosis of female DTC patients (FDTCs).Materials and methodsA total of 26,998 FDTCs were retrospectively searched from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2018 and randomly divided into validation and training cohorts. Univariate and multivariate analyses were performed to screen for prognostic factors and construct a prediction nomogram. The performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), concordance index (C-index), and a calibration curve. The overall survival (OS) and cancer-specific survival (CSS) were evaluated by Kaplan–Meier (K-M) analysis.ResultsA total of 263 (0.97%) FDTCs were reported to have DM. K-M analysis showed the association of multiple-organ metastases and brain involvement with lower survival rates (P < 0.001) in patients. Tumor size, age at diagnosis, thyroidectomy, N1 stage, T3–4 stage, and pathological type were independent predictive factors of DM in FDTCs (all P < 0.001). Similarly, age at diagnosis, Black, DM, T3–4 stage, thyroidectomy, and lung metastasis were determined as independent prognostic factors for FDTCs (all P < 0.001). Several predictive nomograms were established based on the above factors. The C-index, AUC, and calibration curves demonstrated a good performance of these nomogram models.ConclusionOur study was successful in establishing and validating nomograms that could predict DM, as well as CSS and OS in individual patients with FDTC based on a large study cohort. These nomograms could enable surgeons to perform individualized survival evaluation and risk stratification for FDTCs.

Abstract Spermatogonia transit-amplifying (TA) divisions are crucial for the differentiation of germline stem cell daughters. However, the underlying mechanism is largely unknown. In the present study, we demonstrated that CG6015 was essential for spermatogonia TA-divisions and elongated spermatozoon development in Drosophila melanogaster. Spermatogonia deficient in CG6015 inhibited germline differentiation leading to the accumulation of undifferentiated cell populations. Transcriptome profiling using RNA sequencing indicated that CG6015 was involved in spermatogenesis, spermatid differentiation, and metabolic processes. Gene Set Enrichment Analysis (GSEA) revealed the relationship between CG6015 and the epidermal growth factor receptor (EGFR) signaling pathway. Unexpectedly, we discovered that phosphorylated extracellular regulated kinase (dpERK) signals were activated in germline stem cell (GSC)-like cells after reduction of CG6015 in spermatogonia. Moreover, Downstream of raf1 (Dsor1), a key downstream target of EGFR, mimicked the phenotype of CG6015, and germline dpERK signals were activated in spermatogonia of Dsor1 RNAi testes. Together, these findings revealed a potential regulatory mechanism of CG6015 via EGFR signaling during spermatogonia TA-divisions in Drosophila testes.

Abstract Stem cell niche is regulated by intrinsic and extrinsic factors. In the Drosophila testis, cyst stem cells (CySCs) support the differentiation of germline stem cells (GSCs). However, the underlying mechanisms remain unclear. In this study, we found that somatic CG6015 is required for CySC maintenance and GSC differentiation in a Drosophila model. Knockdown of CG6015 in CySCs caused aberrant activation of dpERK in undifferentiated germ cells in the Drosophila testis, and disruption of key downstream targets of EGFR signaling (Dsor1 and rl) in CySCs results in a phenotype resembling that of CG6015 knockdown. CG6015, Dsor1, and rl are essential for the survival of Drosophila cell line Schneider 2 (S2) cells. Our data showed that somatic CG6015 regulates CySC maintenance and GSC differentiation via EGFR signaling, and inhibits aberrant activation of germline dpERK signals. These findings indicate regulatory mechanisms of stem cell niche homeostasis in the Drosophila testis.

A coupling mechanism between flicker noise and hot carrier degradation (HCD) is revealed in this work. Predicting the flicker noise properties of fresh and aged devices is becoming essential for circuit designs, requiring an understanding of the fundamental noise behaviors. While certain models for fresh devices have been proposed, those for aged devices have not been reported yet because of the lack of a clear mechanism. The flicker noise of aged FinFETs is characterized based on the measure-stress-measure (MSM) method and analyzed from the device physics. It is found that both the mean and deviations of the noise power spectral density increase compared with the fresh counterparts. A coupling mechanism is proposed to explain the trap time constants, leading to the trap characterizations in their energy profiles. The amplitude and number of contributing traps are also changing and are dependent on the mode of HCD and determined by the position of the induced traps. A microscopic picture is developed from the perspective of trap coupling, reproducing well the measured noise of advanced nanoscale FinFETs. The finding is important for accurate flicker noise calculations and aging-aware circuit designs.

This study simulated the production process of low-carbon foamed lightweight soil (LCFLS) prepared using prefabricated foam technology in real engineering conditions. The preparation and properties of LCFLS with a wet density of 600 kg/m3 were systematically investigated. The effects of different mix designs of large dosing granulated blast furnace slag and fly ash on the properties of LCFLS were investigated. The workability, rheological properties, and mechanical properties of LCFLS were studied. XRD, TG–DTG, and SEM were used to analyze the hydration mechanism of LCFLS. The results showed that fly ash could improve the flowability of LCFLS, while excessive fly ash could lead to foam and slurry delamination. Granulated blast furnace slag improved the mechanical properties of LCFLS, while excess granulated blast furnace slag caused the foam to break and merge, affecting the soil’s homogeneity. The higher the dynamic yield stress of the freshly mixed slurry, the better the homogeneity, and the smaller and more evenly distributed pore sizes formed after hardening. The main hydration products of LCFLS were C-S-H gel and CH, with small amounts of the carbonation products CaCO3, Hc, and Mc. The LCFLS prepared with 30% cement, 30% fly ash, and 40% granulated blast furnace slag had a flowability of 170–180 mm, with slight differences between wet and quasi-dry densities. The rheological properties of the slurry following the Bingham model showed a dynamic yield stress of 9.41 Pa, an average pore size after hardening of around 300 μm, and compressive strengths at 7 d and 28 d reaching 0.92 MPa and 2.04 MPa, respectively.

In response to the spread of colistin resistance gene mcr-1, China banned the use of colistin in livestock fodders. We used a time-series analysis of inpatient colonization data from 2011–2019 to accurately reveal the associated fluctuations of mcr-1 that occurred in inpatients in response to the ban.