Deciphering the molecular classification of pediatric sepsis: integrating WGCNA and machine learning-based classification with immune signatures for the development of an advanced diagnostic model.

Introduction: Pediatric sepsis (PS) is a life-threatening infection associated with high mortality rates, necessitating a deeper understanding of its underlying pathological mechanisms. Recently discovered programmed cell death induced by copper has been implicated in various medical conditions, but its potential involvement in PS remains largely unexplored. Methods: We first analyzed the expression patterns of cuproptosis-related genes (CRGs) and assessed the immune landscape of PS using the GSE66099 dataset. Subsequently, PS samples were isolated from the same dataset, and consensus clustering was performed based on differentially expressed CRGs. We applied weighted gene co-expression network analysis to identify hub genes associated with PS and cuproptosis. Results: We observed aberrant expression of 27 CRGs and a specific immune landscape in PS samples. Our findings revealed that patients in the GSE66099 dataset could be categorized into two cuproptosis clusters, each characterized by unique immune landscapes and varying functional classifications or enriched pathways. Among the machine learning approaches, Extreme Gradient Boosting demonstrated optimal performance as a diagnostic model for PS. Discussion: Our study provides valuable insights into the molecular mechanisms underlying PS, highlighting the involvement of cuproptosis-related genes and immune cell infiltration.

Uncovering the Achilles heel of genetic heterogeneity: machine learning-based classification and immunological properties of necroptosis clusters in Alzheimer's disease.

Background: Alzheimer's disease (AD) is an age-associated neurodegenerative disease, and the currently available diagnostic modalities and therapeutic agents are unsatisfactory due to its high clinical heterogeneity. Necroptosis is a common type of programmed cell death that has been shown to be activated in AD. Methods: In this study, we first investigated the expression profiles of necroptosis-related genes (NRGs) and the immune landscape of AD based on GSE33000 dataset. Next, the AD samples in the GSE33000 dataset were extracted and subjected to consensus clustering based upon the differentially expressed NRGs. Key genes associated with necroptosis clusters were identified using Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm, and then intersected with the key gene related to AD. Finally, we developed a diagnostic model for AD by comparing four different machine learning approaches. The discrimination performance and clinical relevance of the diagnostic model were assessed using various evaluation metrics, including the nomogram, calibration plot, decision curve analysis (DCA), and independent validation datasets. Results: Aberrant expression patterns of NRGs and specific immune landscape were identified in the AD samples. Consensus clustering revealed that patients in the GSE33000 dataset could be classified into two necroptosis clusters, each with distinct immune landscapes and enriched pathways. The Extreme Gradient Boosting (XGB) was found to be the most optimal diagnostic model for the AD based on the predictive ability and reliability of the models constructed by four machine learning approaches. The five most important variables, including ACAA2, BHLHB4, CACNA2D3, NRN1, and TAC1, were used to construct a five-gene diagnostic model. The constructed nomogram, calibration plot, DCA, and external independent validation datasets exhibited outstanding diagnostic performance for AD and were closely related with the pathologic hallmarks of AD. Conclusion: This work presents a novel diagnostic model that may serve as a framework to study disease heterogeneity and provide a plausible mechanism underlying neuronal loss in AD.

Searching Behavior in the Tropical Fire Ant Solenopsis geminata (Hymenoptera: Formicidae).

Social insects have evolved different search strategies to find target objects in unknown environments. In the present study, the searching behavior of the tropical fire ant Solenopsis geminata was investigated in a circular arena. The average time, search path, speed, and search patterns of worker ants in a circular arena were determined. The results showed that fire ant workers followed six major search patterns. The variation in the searching patterns of workers may explain the different levels of exploration. Most workers (56.8%) tended to search in small loops and progressively increase the search area size. These workers mostly turned in one direction, either clockwise or counterclockwise. More workers turned in a consistent pattern than in an inconsistent pattern. Moving speed was also higher in workers that maintained their turning directions than in those that changed directions. We thus propose that following search patterns consisting of loops of increasing size may be an effective strategy. The tropical fire ant S. geminata is a globally invasive species that was introduced to Taiwan 40 years ago and has continued to threaten residents. Based on behavioral studies of S. geminata, we may gain a better understanding of their exploratory behavior in the ecosystem in Taiwan.

Analysis of Recent Interception Records Reveals Frequent Transport of Arboreal Ants and Potential Predictors for Ant Invasion in Taiwan.

We uncovered taxonomic diversity, country of origin and commodity type of intercepted ants at Taiwanese borders based on an 8 year database of 439 interception records. We found intercepted ants arrived predominantly via timber, a pattern likely reflecting the high domestic demand for foreign timber in Taiwan. The most frequently intercepted species were either arboreal or wood-dwelling ants, raising a concern of these ants constituting a next wave of ant invasion in Taiwan. Further analyses indicate that the taxonomic composition of intercepted ants does not match that of established non-native ant species, suggesting that interception data alone fails to provide adequate power to predict the establishment success of ants. Yet, interception frequency and selected life-history traits (i.e., flexible colony founding mode and general nesting habits) were shown to jointly serve as a practical predictor of the establishment risk of non-native ants. Consistent with other border interception databases, secondary introduction (i.e., species arriving from their introduced ranges instead of their native ranges) also represents a major pathway for transport of invasive ants into Taiwan, suggesting its role in shaping the global invasion of ants. Our findings offer baseline information for constructing a prediction framework for future ant invasions and assist in the decision-making process of quarantine authorities in Taiwan.

Carriers and cutters: size-dependent caste polyethism in the tropical fire ant (Solenopsis geminata).

Body size is an important life-history trait in eusocial insects which plays a key role in colony fitness. The division of labour, represented by caste polyethism, correlates with divergent morphological traits. Size polymorphism has been noted in the tropical fire ant, Solenopsis geminata; however, little is known regarding the differences in the size distributions of workers performing foraging tasks. In the present study, task partitioning was observed in the foraging activities of S. geminata. Two subgroups among foraging workers of S. geminata were discovered using the Gaussian mixture model: a large worker group (head width ≥ 0.924 mm) and a small worker group (head width < 0.924 mm). The foraging worker population comprised two distinct groups - 25.64% were large workers and 74.36% were small workers. Larger workers delivered heavier seeds faster than smaller workers, but this difference became less apparent when lighter seeds were being carried. When large prey such as crickets was encountered during foraging, S. geminata partitioned their tasks into cutting and transportation. The large workers were observed to cut cricket prey into fragments with their longer mandibles, and the small workers then transported these fragments back to the nest. These results present evidence of task partitioning among tropical fire ants, with different tasks being performed by ants of different castes.

Human papillomavirus up-regulates MMP-2 and MMP-9 expression and activity by inducing interleukin-8 in lung adenocarcinomas.

Human papillomavirus (HPV) infection is associated with non-smoking female lung cancer. Our previous report demonstrated that HPV 16 promotes lung tumor cell progression by up-regulating interleukin-17 (IL-17). IL-17 and its downstream signaling mediator, interleukin-8 (IL-8), have been implicated to modulate a variety of pro-angiogenic factors and play important roles in tumor angiogenesis and metastasis. Accordingly, we hypothesized that HPV infection may potentiate tumorigenic and metastatic characteristics of the infected cells through IL-8. The goal of the present study was to determine whether HPV infection in lung adenocarcinoma cells can promote the expression of IL-8 and metalloproteinases (MMPs) to make the transformed cells equipped with angiogenic and metastatic characteristics. The expression of IL-8 and MMPs in HPV 16 E6-transfected H1299 cells was analyzed to examine the hypothesis. HPV 16 E6 up-regulates pro-angiogenic MMP-2 and MMP-9 through inducing IL-8 expression in lung cancer cells. The results indicate that, in addition to cell proliferation-related machinery, HPV infection promotes the expression and activities of angiogenic and metastatic molecules in lung adenocarcinoma cells. The cytokines induced by HPV infection may work together to confer the malignant and tumorigenic potentials on the infected cells by promoting machineries of growth, angiogenic and metastatic characteristics.

The insecticidal activities of fire ant (Hymenoptera: Formicidae) venoms against Plutella xylostella (Lepidoptera: Plutellidae) larvae.

Although fire ants frequently have negative impacts on agricultural systems and public health, they have additional beneficial insecticidal effects. To evaluate the potential effect of fire ant venoms on agricultural pests, the compositions of the venoms and their insecticidal activities against Plutella xylostella (L.) larvae were evaluated under laboratory conditions. The alkaloids found in Solenopsis geminata (F.) venom are primarily saturated C11, which occur in both cis and trans forms, whereas the venom of S. invicta Buren contains six principal alkaloids (from trans C1, to C17). Moreover, the proportions of unsaturated alkaloids in the venom of polygynous S. invicta were significantly higher than the corresponding proportions in the monogynous S. invicta, as shown by our previous studies. Fire ant venoms were topically applied to the dorsal thoracic region of fourth-instar larvae of P. xylostella. The results of the experiment showed that the larval symptoms induced by fire ant venom include contractile, flaccid paralysis, black coloration and death. P. xylostella larvae were most susceptible to S. geminata venom. The order of the susceptibilities of the larvae to the venoms was as follows: S. geminata > S. invicta (monogyne form) > S. invicta (polygyne form), as measured by the corresponding LT50 values at 24 h.

Up-regulation of interleukin-17 expression by human papillomavirus type 16 E6 in nonsmall cell lung cancer.

BACKGROUND: Human papillomavirus (HPV) 16/18 infection is associated with nonsmoking lung cancer. In this study, the authors investigated a putative correlation between interleukin (IL)-17 expression and HPV infection in clinical nonsmall cell lung cancer (NSCLC) tissues and examined the effects of HPV infection on a human NSCLC cell line. METHODS: IL-17 expression was investigated in 79 NSCLC tumor tissues by immunohistochemistry. Growth rate, IL-17 mRNA, and secreting protein levels were also examined in HPV 16/18 E6-transfected H1299 human NSCLC cells. RESULTS: Immunohistochemical data showed that 48.1% of lung tumors had IL-17 staining, which was significantly associated with patients' sex (P = .03), HPV infection (P = .002), and tumor stage (P = .03). Significant correlations of IL-17 with IL-6 (P < .001) and IL-17 with Mcl-1 (P < .001) expression were also observed. Cell growth rate was increased, and IL-17/Mcl-1 expression levels were elevated in HPV 16 E6-transfected H1299 cells. The transfected E6 oncoproteins can significantly up-regulate expression levels of IL-17 and antiapoptotic protein Mcl-1. CONCLUSIONS: The study suggests that HPV infection-induced IL-17 levels can stimulate Mcl-1 expression through the PI3K pathway and promote lung tumor cell progression through a p53- and IL-6-independent pathway.