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Many cockroach species have adapted to urban environments, and some have been serious pests of public health in the tropics and subtropics. Here, we present the 3.38-Gb genome and a consensus gene set of the American cockroach, Periplaneta americana . We report insights from both genomic and functional investigations into the underlying basis of its adaptation to urban environments and developmental plasticity. In comparison with other insects, expansions of gene families in P. americana exist for most core gene families likely associated with environmental adaptation, such as chemoreception and detoxification. Multiple pathways regulating metamorphic development are well conserved, and RNAi experiments inform on key roles of 20-hydroxyecdysone, juvenile hormone, insulin, and decapentaplegic signals in regulating plasticity. Our analyses reveal a high level of sequence identity in genes between the American cockroach and two termite species, advancing it as a valuable model to study the evolutionary relationships between cockroaches and termites. The American cockroach ( Periplaneta americana ) is an hemimetabolous insect with rapid growth, high fecundity, and remarkable tissue-regeneration capability. Here Li et al sequence its 3.38-Gb genome and perform the functional studies, yielding insights into its environmental adaptation and developmental plasticity.

Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis ( M . tb ) in this process is not fully understood. Here, we investigated the role of Rv2569c in M . tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall–associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl 2 . To investigate the function of Rv2569c in M . tb , a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M . tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M . tb , and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M . tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma which that highly aggressive and heterogeneous. Glycolysis has been implicated in the regulation of tumor microenvironment (TME) and development. In this study, we aimed to establish a glycolysis-related prognostic model for the risk stratification, prognosis prediction, and immune landscape evaluation in patients with DLBCL. Methods: Three independent datasets GSE181063, GSE10846, and GSE53786 containing gene expression profiles and clinical data were downloaded from the Gene Expression Omnibus (GEO) database. The glycolysis-related prognostic model was developed with Cox and Least Absolute Shrinkage and Selector Operation (LASSO) regression and validated. A nomogram integrating clinical factors and glycolytic risk scores was constructed. The composition of the TME was analyzed with the ESTIMATE algorithm and single-sample gene set enrichment analysis (ssGSEA). Results: A glycolytic risk model containing eight genes was developed. The area under the receiver operating characteristic (ROC) curve (AUC) for the 1-, 3-, and 5-year was 0.718, 0.695, and 0.688, respectively. Patients in the high-risk group had significantly lower immune scores, elevated tumor purity, and poorer survival compared with those in the low-risk group. The nomogram constructed based on glycolytic risk score, age, Eastern Cooperative Oncology Group performance status (ECOG-PS), use of rituximab, and cell of origin (COO) displayed better prediction performance compared with the International Prognostic Index (IPI) in DLBCL. The glycolytic risk score was negatively correlated with the infiltration level of activated CD8 T cells, activated dendritic cells, natural killer cells, and macrophages and immune checkpoint molecules including PD-L2 , CTLA4 , TIM-3 , TIGIT , and B7-H3 . Conclusion: These results suggested that the glycolytic risk model could accurately and stably predict the prognosis of patients with DLBCL and might unearth the possible explanation for the glycolysis-related poor prognosis.

Atractylodes chinensis (DC.) Koidz. (AK) is a kind of medicinal plant in the Asteraceae family, and its dried rhizomes have the functions of drying dampness, strengthening the spleen, dispelling wind and cold, and brightening the eyes. However, there remains insufficient development and utilization of other portions of the plant. To reveal the chemical characteristics and bioactivity potential of different AK parts, this study adopted UPLC-QE-MS/MS-based widely targeted metabolomics to analyze the metabolic components in ethanol extracts of AK rhizomes, fibrous roots, stems and leaves, flowers, and seeds. We then compared the antioxidant activities of these AK parts. The results showed that the highest ethanol extraction rate was from the rhizomes, while the flowers showed the strongest antioxidant activity. A total of 165 metabolites were categorized into seven major categories that included organic acids, flavonoids, and coumarins. Among these, organic acids were found with higher content in stems and leaves, fibrous roots, and seeds, while flavonoids were higher in flowers. This study explored the chemical composition and preliminary bioactivities of different AK parts based on widely targeted metabolomics. The results confirmed that the non-medicinal AK parts have high utilization values, and provided a scientific basis for the further development and utilization of this promising medicinal plant.

The coronavirus disease 2019 (COVID-19) pandemic has led to the development of numerous prognostic models for patient assessment. However, the potential utility of the predisposition, insult/infection, response, organ dysfunction (PIRO) score in evaluating COVID-19 severity and outcomes remains unexplored, presenting a gap in current research. A retrospective analysis was conducted on a cohort of 374 individuals diagnosed with COVID-19 who were admitted to the emergency department of Beijing Youan Hospital. Demographic data, treatment regimens, and seven prognostic scoring systems, including PIRO, were evaluated. To evaluate the models’ prognostic accuracy for 28-day mortality, area under the receiver operating characteristic (AUROC) analysis was employed. Comparative performance between scoring systems was quantified using the DeLong method for paired ROC curves. Of the 374 patients meeting inclusion criteria, 120 (32.1%) died within 28 day of hospitalization. Significant disparities were observed between survivors and non-survivors regarding age, laboratory parameters, and clinical scores. Analysis of patient distribution and mortality rates across different score ranges revealed a positive correlation between score magnitude and 28-day mortality. The PIRO score demonstrated superior prognostic capability, yielding an AUC of 0.898 (95% CI 0.866–0.929). The quick sequential organ failure assessment (qSOFA) score followed closely (AUC 0.882, 95% CI 0.849–0.914). Both critical illness risk score (COVID-GRAM) and national early warning score 2 (NEWS2) exhibited AUCs exceeding 0.85 (COVID-GRAM 0.854, 95% CI 0.812–0.895; NEWS2: 0.851, 95% CI 0.813–0.889). DeLong test analysis revealed statistically significant differences in AUC between PIRO and confusion, urea, respiration, systolic pressure, age ≥ 65 (CURB-65), pneumonia severity index (PSI), COVID-GRAM, rapid acute physiology score (RAPS), and NEWS2 (all p  < 0.05). Analysis revealed the PIRO scoring system as a robust predictor of 28-day mortality among COVID-19 cases presenting to the emergency setting, offering potential refinement of risk stratification and clinical management strategies.

DNA methylation at the fifth position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification for regulating gene expression, but little is known about how it regulates gene expression in insects. Here, we pursue the detailed molecular mechanism by which DNMT1-mediated 5mC maintenance regulates female reproduction in the German cockroach, Blattella germanica . Our results show that Dnmt1 knockdown decreases the level of 5mC in the ovary, upregulating numerous genes during choriogenesis, especially the transcription factor ftz-f1 . The hypomethylation at the ftz-f1 promoter region increases and prolongs ftz-f1 expression in ovarian follicle cells during choriogenesis, which consequently causes aberrantly high levels of 20-hydroxyecdysone and excessively upregulates the extracellular matrix remodeling gene Mmp1 . These changes further impair choriogenesis and disrupt fertilization by causing anoikis of the follicle cells, a shortage of chorion proteins, and malformation of the sponge-like bodies. This study significantly advances our understanding of how DNA 5mC modification regulates female reproduction in insects. The mechanism by which DNA methylation regulates female reproduction in insects is largely unknown. Here Zhao et al . demonstrate that the 5mC modification orchestrates timely choriogenesis and proper fertilization by preventing prolonged ftz-f1 expression in the German cockroach.

Human-papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC) is a distinct disease characterized by unique clinical and molecular features compared to HPV-negative OPSCC. A comprehensive bibliometric analysis of HPV-positive OPSCC research was conducted in this study to identify key trends, research hotspots, and emerging frontiers in the field. Data were retrieved from the Web of Science Core Collection database. The distributions of contributors, including countries, institutions, authors, journals, and cooperative networks related to HPV-positive OPSCC, were analyzed and visualized using VOSviewer 1.6.20, CiteSpace 6.3.R1, and the R package Bibliometrix 4.0.0. In addition, the most influential publications and high-frequency keywords were identified and analyzed to discern key topics in this field. A total of 3895 articles and reviews on HPV-positive OPSCC were identified, involving 106 countries, 620 journals, and 18949 authors. The main contributors include the USA (1908 publications), Johns Hopkins University (310 publications), the journal Head and Neck (320 publications), and Erich M. Sturgis (94 publications). The top three keywords are “survival”, “radiotherapy”, and “p16”. There has been a steadily increasing research interest in HPV-positive OPSCC over the last 23 years. Current studies focus on diagnosis, treatment strategies, prognosis, recurrence, and disease surveillance. This bibliometric analysis highlights key contributors and emerging themes, offering insights for future research directions.

ObjectivesDifferent intrathoracic perfusion therapeutic regimens are available for non-small cell lung cancer with malignant pleural effusion (MPE). Antiangiogenic agents are often used to control MPE, and the results are satisfactory. Here, we performed a network meta-analysis to reveal optimal combinations of antiangiogenic agents and chemical agents and assess their effectiveness and safety.DesignSystematic review and network meta-analysis.Data sourcesPubMed/Medline, Embase, Cochrane, Web of Science, Wanfang, VIP Database and Chinese National Knowledge Infrastructure were searched from inception to May 2023. Eligible studies were randomised controlled trials that reported on curative effect of MPE.Data extraction and synthesisThe Cochrane Collaboration tool was used to assess risk of bias. The consistency was evaluated by examining the agreement between direct and indirect effects. Network meta-analysis was performed and the ranking probabilities of being at each possible rank for each intervention were estimated. Comparison-adjusted funnel plots were obtained to assess publication bias.ResultsA total of 46 studies were included in the analysis. Among them, we included a total of seven interventions. A total of 3026 patients participated in this analysis. According to the results of the network meta-analysis, some antiangiogenic agents combined with chemotherapy regimens improved objective response rate (ORR) and disease control rate (DCR) and quality of life (QOL). The rank probabilities suggested that in terms of ORR, DCR and QOL, Endostar plus lobaplatin was the first-ranked intervention.ConclusionAdministration of antiangiogenic agents plus chemical agents significantly improved the clinical response and QOL. In addition, Endostar plus lobaplatin was the most effective combination.PROSPERO registration numberCRD42021284786.

Background Identifying thyroid nodules’ boundaries is crucial for making an accurate clinical assessment. However, manual segmentation is time-consuming. This paper utilized U-Net and its improved methods to automatically segment thyroid nodules and glands. Methods The 5822 ultrasound images used in the experiment came from two centers, 4658 images were used as the training dataset, and 1164 images were used as the independent mixed test dataset finally. Based on U-Net, deformable-pyramid split-attention residual U-Net (DSRU-Net) by introducing ResNeSt block, atrous spatial pyramid pooling, and deformable convolution v3 was proposed. This method combined context information and extracts features of interest better, and had advantages in segmenting nodules and glands of different shapes and sizes. Results DSRU-Net obtained 85.8% mean Intersection over Union, 92.5% mean dice coefficient and 94.1% nodule dice coefficient, which were increased by 1.8%, 1.3% and 1.9% compared with U-Net. Conclusions Our method is more capable of identifying and segmenting glands and nodules than the original method, as shown by the results of correlational studies.

Atherosclerosis (AS) is a chronic vascular inflammatory disease driven by lipid deposition, whose clinical management remains constrained by the limitations of existing pharmacological interventions. This review systematically elucidates the molecular mechanisms by which plant-derived compounds modulate AS through targeted regulation of the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Studies indicate that plant-derived compounds—such as terpenoids (e.g., artemisinin and tanshinone IIA) and alkaloids (e.g., berberine)—effectively attenuate the progression of AS via bidirectional modulation of the PI3K/AKT pathway. In early stages, suppression of this pathway downregulates downstream mechanistic target of rapamycin (mTOR) and nuclear factor-kappa B (NF-κB) protein expression, thereby mitigating inflammatory responses and lipid accumulation to inhibit plaque formation. Conversely, during advanced disease phases, moderate activation of the pathway upregulates key effectors, including autophagy-related protein (Beclin-1), glutathione (GSH), and glutathione peroxidase 4 (GPX4), promoting ferroptosis and autophagy in abnormal cells and thereby enhancing the stability of established plaques. It is noteworthy that the low bioavailability of plant-derived compounds and the stage-specific nature of pathway modulation remain critical challenges for clinical translation. In this review, we deepen the mechanistic understanding of plant-based interventions against AS and provide a theoretical foundation and innovative perspectives for the development of future botanically derived AS therapeutics.