Discovery of the first selective, small-molecule GFRα2/3 inhibitors through DNA-encoded library technology.

Studies have shown that disrupting the formation of the ligand-RET-GFRα complex could be an effective way of treating pain and itch. Compared to traditional high-throughput screens, DNA encoded libraries (DELs) have distinguished themselves as a powerful technology for hit identification in recent years. The present work demonstrates the use of DEL technology identifying compound 16 as the first GFRa2/GFRa3 small molecule inhibitor (0.1/0.2 µM respectively) selective over RET. This molecule represents an opportunity to advance the development of small-molecule inhibitors targeting the GFRα-RET interface for the treatment of pain and itch.

Elevated temperature as a dominant driver to aggravate cadmium toxicity: Investigations through toxicokinetics and omics.

Despite the great interest in the consequences of global change stressors on marine organisms, their interactive effects on cadmium (Cd) bioaccumulation/biotoxicity are very poorly explored, particularly in combination with the toxicokinetic model and molecular mechanism. According to the projections for 2100, this study investigated the impact of elevated pCO2 and increased temperature (isolated or joint) on Cd uptake dynamics and transcriptomic response in the marine copepod Tigriopus japonicus. Toxicokinetic results showed significantly higher Cd uptake in copepods under increased temperature and its combination with elevated pCO2 relative to the ambient condition, linking to enhanced Cd bioaccumulation. Transcriptome analysis revealed that, under increased temperature and its combination with elevated pCO2, up-regulated expression of Cd uptake-related genes but down-regulation of Cd exclusion-related genes might cause increased cellular Cd level, which not only activated detoxification and stress response but also induced oxidative stress and concomitant apoptosis, demonstrating aggravated Cd biotoxicity. However, these were less pronouncedly affected by elevated pCO2 exposure. Therefore, temperature seems to be a primary factor in increasing Cd accumulation and its toxicity in the future ocean. Our findings suggest that we should refocus the interactive effects between climate change stressors and Cd pollution, especially considering temperature as a dominant driver.

5 mC modification of steroid hormone biosynthesis-related genes orchestrates feminization of channel catfish induced by high-temperature.

To elucidate the mechanism behind channel catfish feminization induced by high temperature, gonad samples were collected from XY pseudo-females and wild-type females and subjected to high-throughput sequencing for Whole-Genome-Bisulfite-Seq (WGBS) and transcriptome sequencing (RNA-Seq). The analysis revealed 50 differentially methylated genes between wild-type females and XY pseudo-females, identified through the analysis of KEGG pathways and GO enrichment in the promoter of the genome and differentially methylated regions (DMRs). Among these genes, multiple differential methylation sites observed within the srd5a2 gene. Repeatability tests confirmed 7 differential methylation sites in the srd5a2 gene in XY pseudo-females compared to normal males, with 1 specific differential methylation site (16608174) distinguishing XY pseudo-females from normal females. Interestingly, the expression of these genes in the transcriptome showed no difference between wild-type females and XY pseudo-females. Our study concluded that methylation of the srd5a2 gene sequence leads to decreased expression, which inhibits testosterone synthesis while promoting the synthesis of 17ß-estradiol from testosterone. This underscores the significance of the srd5a2 gene in the sexual differentiation of channel catfish, as indicated by the ipu00140 KEGG pathway analysis.

Exaggerated placental site in a cesarean scar: Misdiagnosed as gestational trophoblastic neoplasia: A case report.

The present study reports a rare case of an exaggerated placental site (EPS) in a caesarean scar that was misdiagnosed as gestational trophoblastic neoplasia (GTN) by imaging, resulting in unnecessary surgical treatment. A 38-year-old woman underwent hysteroscopic resection of a cesarean scar pregnancy (CSP). The patient's serum ß-human chorionic gonadotropin (ß-hCG) level was elevated (76,196 mIU/ml) at the 24-day postoperative follow-up visit. On postoperative day 51, the patient experienced vaginal bleeding for three days and ß-hCG levels were 2,799 mIU/ml. Ultrasonography and MRI revealed a heterogeneous mass and hypervascularity. The patient was diagnosed with a GTN in a cesarean scar and treated with methotrexate (MTX). ß-hCG levels decreased after 3 MTX doses, but the mass did not change in size and was still hypervascular on imaging. Total hysterectomy was performed due to the serious side effects of chemotherapy and the lack of desire to preserve fertility. The histological findings supported the diagnosis of an EPS reaction. The present case is unique because of the rare intrauterine mass and possibility of retained trophoblastic changes causing EPS. EPS differs from GTN both clinically and pathologically and should be considered a possible diagnosis in any woman who has irregular bleeding following CSP resection.

Assessing the particulate matter emission reduction characteristics of small turbofan engine fueled with 100 % HEFA sustainable aviation fuel.

With the continuous increase in global air transportation, the impact of ultrafine particulate matter (PM) emissions from aviation on human health and environmental pollution is becoming increasingly severe. In addition to carbon reduction throughout the lifecycle, Sustainable Aviation Fuels (SAF) also represent a significant pathway for reducing PM emissions. However, due to issues such as airworthiness safety and adaptability, existing research has mostly focused on the emission performance of SAF when blended with traditional fuels at <50 %, leaving the emission characteristics of higher blending ratios to be explored. In this study, using measurement methods recommended by the International Civil Aviation Organization (ICAO), the PM emission reduction characteristics of small turbofan engines fueled with 100 % Hydroprocessed Esters and Fatty Acids (HEFA)-SAF were experimentally evaluated and compared with traditional fuels RP-3 and Diesel, while avoiding the interference of lubricant blending combustion. The results showed that the peak number concentration of particle size distribution (PSD), PM total number, as well as the number and mass concentration of non-volatile particulate matter (nvPM) decreased initially and then increased with rising thrust conditions. HEFA-SAF exhibits PSD with smaller diameters, and the Geometric Mean Diameter (GMD) ranges from 7.7 nm to 20.3 nm under all conditions. Both volatile particulates (vPM) and nvPM from HEFA-SAF are significantly reduced, with nvPM number emission index (EIn) being 92 % and 71 % lower than Diesel and RP-3, respectively. The nvPM mass emission index (EIm) also shows reductions of 96 % and 89 % compared to Diesel and RP-3. Microscopic characterization also indicated that using HEFA-SAF emitted fewer and smaller PMs. This study establishes a foundation for evaluating the effectiveness of 100 % SAF in reducing PM emissions within the aviation sector, and contributes to the airworthiness regulations development related to the use of SAF in a variety of application environments, alongside enhancing environmental protection measures.

Energy-Efficient and Highly Reliable Geographic Routing Based on Link Detection and Node Collaborative Scheduling in WSN.

Energy efficiency and data reliability are important indicators to measure network performance in wireless sensor networks. In existing research schemes of routing protocols, the impact of node coverage on the network is often ignored, and the possibility that multiple sensor nodes may sense the same spatial point is not taken into account, which results in a waste of network resources, especially in large-scale networks. Apart from that, the blindness of geographic routing in data transmission has been troubling researchers, which means that the nodes are unable to determine the validity of data transmission. In order to solve the above problems, this paper innovatively combines the routing protocol with the coverage control technique and proposes the node collaborative scheduling algorithm, which fully considers the correlation characteristics between sensor nodes to reduce the number of active working nodes and the number of packets generated, to further reduce energy consumption and network delay and improve packet delivery rate. In order to solve the problem of unreliability of geographic routing, a highly reliable link detection and repair scheme is proposed to check the communication link status and repair the invalid link, which can greatly improve the packet delivery rate and throughput of the network, and has good robustness. A large number of experiments demonstrate the effectiveness and superiority of our proposed scheme and algorithm.

Assessing environmental and human health risks: Insight from the enantioselective metabolism and degradation of fenpropidin.

Fenpropidin (FPD), a widely employed chiral fungicide, is frequently detected in diverse environments. In an in vitro rat liver microsomes cultivation (RLMs), the metabolism exhibited the order of R-FPD > S-FPD, with respective half-lives of 10.42 ± 0.11 and 12.06 ± 0.15 min, aligning with kinetic analysis results. CYP3A2 has been demonstrated to be the most significant oxidative enzyme through CYP450 enzyme inhibition experiments. Molecular dynamics simulations unveiled the enantioselective metabolic mechanism, demonstrating that R-FPD forms hydrogen bonds with the CYP3A2 protein, resulting in a higher binding affinity (-6.58 kcal mol-1) than S-FPD. Seven new metabolites were identified by Liquid chromatography time-of-flight high-resolution mass spectrometry, which were mainly generated through oxidation, reduction, hydroxylation, and N-dealkylation reactions. The toxicity of the major metabolites predicted by the TEST procedure was found to be stronger than the predicted toxicity of FPD. Moreover, the enantioselective fate of FPD was studied by examining its degradation in three soils with varying physical and chemical properties under aerobic, anaerobic, and sterile conditions. Enantioselective degradation of FPD occurred in soils without enantiomeric transformation, displaying a preference for R-FPD degradation. R-FPD is a low-risk stereoisomer both in the environment and in mammals. The research presented a systematic and comprehensive method for analyzing the metabolic and degradation system of FPD enantiomers. This approach aids in understanding the behavior of FPD in the environment and provides valuable insights into their potential risks to human health.

Ocean acidification alleviated nickel toxicity to a marine copepod under multigenerational scenarios but at a cost with a loss of transcriptome plasticity during recovery.

Marine ecosystem has been experiencing multiple stressors caused by anthropogenic activities, including ocean acidification (OA) and nickel (Ni) pollution. Here, we examined the individual/combined effects of OA (pCO2 1000 µatm) and Ni (6 µg/L) exposure on a marine copepod Tigriopus japonicus for six generations (F1-F6), followed by one-generation recovery (F7) in clean seawater. Ni accumulation and several important phenotypic traits were measured in each generation. To explore within-generation response and transgenerational plasticity, we analyzed the transcriptome profile for the copepods of F6 and F7. The results showed that Ni exposure compromised the development, reproduction and survival of copepods during F1-F6, but its toxicity effects were alleviated by OA. Thus, under OA and Ni combined exposure, due to their antagonistic interaction, the disruption of Ca2+ homeostasis, and the inhibition of calcium signaling pathway and oxytocin signaling pathway were not found. However, as a cost of acclimatization/adaption potential to long-term OA and Ni combined exposure, there was a loss of transcriptome plasticity during recovery, which limited the resilience of copepods to previously begin environments. Overall, our work fosters a comprehensive understanding of within- and transgenerational effects of climatic stressor and metal pollution on marine biota.

Combined exposure to hypoxia and nanoplastics leads to negative synergistic oxidative stress-mediated effects in the water flea Daphnia magna.

In this study, we investigated the combined effects of hypoxia and NPs on the water flea Daphnia magna, a keystone species in freshwater environments. To measure and understand the oxidative stress responses, we used acute toxicity tests, fluorescence microscopy, enzymatic assays, Western blot analyses, and Ingenuity Pathway Analysis. Our findings demonstrate that hypoxia and NPs exhibit a negative synergy that increases oxidative stress, as indicated by heightened levels of reactive oxygen species and antioxidant enzyme activity. These effects lead to more severe reproductive and growth impairments in D. magna compared to a single-stressor exposure. In this work, molecular investigations revealed complex pathway activations involving HIF-1α, NF-κB, and mitogen-activated protein kinase, illustrating the intricate molecular dynamics that can occur in combined stress conditions. The results underscore the amplified physiological impacts of combined environmental stressors and highlight the need for integrated strategies in the management of aquatic ecosystems.

Multistress Interplay: Time and Duration of Ocean Acidification Modulate the Toxicity of Mercury and Other Metals.

The current understanding of multistress interplay assumes stresses occur in perfect synchrony, but this assumption is rarely met in the natural marine ecosystem. To understand the interplay between nonperfectly overlapped stresses in the ocean, we manipulated a multigenerational experiment (F0-F3) to explore how different temporal scenarios of ocean acidification will affect mercury toxicity in a marine copepod Pseudodiaptomus annandalei. We found that the scenario of past acidification aggravated mercury toxicity but current and persistent acidification mitigated its toxicity. We specifically performed a proteomics analysis for the copepods of F3. The results indicated that current and persistent acidification initiated the energy compensation for development and mercury efflux, whereas past acidification lacked the barrier of H+ and had dysfunction in the detoxification and efflux system, providing a mechanistic understanding of mercury toxicity under different acidification scenarios. Furthermore, we conducted a meta-analysis on marine animals, demonstrating that different acidification scenarios could alter the toxicity of several other metals, despite evidence from nonsynchronous scenarios remaining limited. Our study thus demonstrates that time and duration of ocean acidification modulate mercury toxicity in marine copepods and suggests that future studies should move beyond the oversimplified scenario of perfect synchrony in understanding multistress interaction.

High-performance pyrite nano-catalyst driven photothermal/chemodynamic synergistic therapy for Osteosarcoma.

Osteosarcoma (OS) is an aggressive bone tumor with strong invasiveness, rapid metastasis, and dreadful mortality. Chemotherapy is a commonly used approach for OS treatment but is limited by the development of drug resistance and long-term adverse effects. To date, OS still lacks the curative treatment. Herein, we fabricated pyrite-based nanoparticles (FeS2@CP NPs) as synergetic therapeutic platform by integrating photothermal therapy (PTT) and chemo-dynamic therapy (CDT) into one system. The synthetic FeS2@CP NPs showed superior Fenton reaction catalytic activity. FeS2@CP NPs-based CDT efficaciously eradicated the tumor cells by initiating dual-effect of killing of apoptosis and ferroptosis. Furthermore, the generated heat from FeS2@CP under near-infrared region II (NIR-II) laser irradiation could not only inhibit tumor's growth, but also promote tumor cell apoptosis and ferroptosis by accelerating •OH production and GSH depletion. Finally, the photothermal/NIR II-enhanced CDT synergistic therapy showed excellent osteosarcoma treatment effects both in vitro and in vivo with negligible side effects. Overall, this work provided a high-performance and multifunctional Fenton catalyst for osteosarcoma synergistic therapy, which provided a pathway for the clinical application of PTT augmented CDT.

A Rapid and Sensitive Gold Nanoparticle-Based Lateral Flow Immunoassay for Chlorantraniliprole in Agricultural and Environmental Samples.

Chlorantraniliprole (CAP) is a new type of diamide insecticide that is mainly used to control lepidopteran pests. However, it has been proven to be hazardous to nontarget organisms, and the effects of its residues need to be monitored. In this study, five hybridoma cell lines were developed that produced anti-CAP monoclonal antibodies (mAbs), of which the mAb originating from the cell line 5C5B9 showed the highest sensitivity and was used to develop a gold nanoparticle-based lateral flow immunoassay (AuNP-LFIA) for CAP. The visible limit of detection of the AuNP-LFIA was 1.25 ng/mL, and the detection results were obtained in less than 10 min. The AuNP-LFIA showed no cross-reactivity for CAP analogs, except for tetraniliprole (50%) and cyclaniliprole (5%). In the detection of spiked and blind samples, the accuracy and reliability of the AuNP-LFIA were confirmed by a comparison with spiked concentrations and verified by ultra-performance liquid chromatography-tandem mass spectrometry. Thus, this study provides the core reagents for establishing CAP immunoassays and a AuNP-LFIA for the detection of residual CAP.

Enantioselective Toxicity and Potential Endocrine-Disruptive Effects of the Insecticides Flufiprole and Ethiprole on Danio rerio.

Phenylpyrazole insecticides are widely used as chiral pesticides. However, the enantioselective toxicity and potential endocrine-disrupting effects of these insecticides on aquatic organisms remain unclear. Herein, the enantioselective toxicity and potential endocrine-disrupting effects of flufiprole and ethiprole were investigated by using zebrafish embryos/larvae as a model. The acute toxicity of R-flufiprole and R-ethiprole toward zebrafish embryos and larvae was 1.8-3.1-fold higher than that of the S-configuration. Additionally, R-flufiprole and R-ethiprole had a greater effect on the expression of genes related to the hypothalamus-pituitary-gonad axis in zebrafish compared with the S-configuration. Nevertheless, both S-flufiprole and S-ethiprole exhibited a greater interference effect on the expression of genes related to the hypothalamus-pituitary-thyroid axis and a greater teratogenic effect on zebrafish than the R-configuration. Thus, this study demonstrates that both flufiprole and ethiprole exhibit enantioselective acute toxicity and developmental toxicity toward zebrafish. Furthermore, those pesticides potentially possess enantioselective endocrine-disrupting effects.

Mechanisms of adsorption and functionalization of biochar for pesticides: A review.

Agricultural production relies heavily on pesticides. However, factors like inefficient application, pesticide resistance, and environmental conditions reduce their effective utilization in agriculture. Subsequently, pesticides transfer into the soil, adversely affecting its physicochemical properties, microbial populations, and enzyme activities. Different pesticides interacting can lead to combined toxicity, posing risks to non-target organisms, biodiversity, and organism-environment interactions. Pesticide exposure may cause both acute and chronic effects on human health. Biochar, with its high specific surface area and porosity, offers numerous adsorption sites. Its stability, eco-friendliness, and superior adsorption capabilities render it an excellent choice. As a versatile material, biochar finds use in agriculture, environmental management, industry, energy, and medicine. Added to soil, biochar helps absorb or degrade pesticides in contaminated areas, enhancing soil microbial activity. Current research primarily focuses on biochar produced via direct pyrolysis for pesticide adsorption. Studies on functionalized biochar for this purpose are relatively scarce. This review examines biochar's pesticide absorption properties, its characteristics, formation mechanisms, environmental impact, and delves into adsorption mechanisms, functionalization methods, and their prospects and limitations.

Single and combined effects of increased temperature and methylmercury on different stages of the marine rotifer Brachionus plicatilis.

Rapid, anthropogenic activity-induced global warming is a severe problem that not only raises water temperatures but also shifts aquatic environments by increasing the bioavailability of heavy metals (HMs), with potentially complicated effects on aquatic organisms, including small aquatic invertebrates. For this paper, we investigated the combined effects of temperature (23 and 28 °C) and methylmercury (MeHg) by measuring physiological changes, bioaccumulation, oxidative stress, antioxidants, and the mitogen-activated protein kinase signaling pathway in the marine rotifer Brachionus plicatilis. High temperature and MeHg adversely affected the survival rate, lifespan, and population of rotifers, and bioaccumulation, oxidative stress, and biochemical reactions depended on the developmental stage, with neonates showing higher susceptibility than adults. These findings demonstrate that increased temperature enhances potentially toxic effects from MeHg, and susceptibility differs with the developmental stage. This study provides a comprehensive understanding of the combined effects of elevated temperature and MeHg on rotifers. ENVIRONMENTAL IMPLICATION: Methylmercury (MeHg) is a widespread and harmful heavy metal that can induce lethal effects on aquatic organisms in even trace amounts. The toxicity of metals can vary depending on various environmental conditions. In particular, rising temperatures are considered a major factor affecting bioavailability and toxicity by changing the sensitivity of organisms. However, there are few studies on the combinational effects of high temperatures and MeHg on aquatic animals, especially invertebrates. Our research would contribute to understanding the actual responses of aquatic organisms to complex aquatic environments.

Multifunctional photocatalyst of graphitic carbon embedded with Fe2O3/Fe3O4 nanocrystals derived from lichen for efficient photodegradation of tetracycline and methyl blue.

We propose a feasible and economical method of constructing biomass-based multifunctional photocatalysts with excellent adsorption performance and high photodegradation abilities toward tetracycline (TC) and methyl blue (MB) under visible light. A series of novel hybrids of porous graphitic carbon embedded with Fe2O3/Fe3O4 nanocrystals (denoted as Fe2O3/Fe3O4@C) were derived from lichen doped with different dosages of Fe3+ by calcination at 700°C under a N2 atmosphere. The Fe2O3/Fe3O4@C hybrids exhibited nanoflake-like shapes, mesoporous structures, and efficient visible light harvesting, thus indicating enhanced adsorption ability and photoactivity toward pollutants. The formed Fe2O3/Fe3O4 heterojunction improved the separation efficiency and inhibited the recombination of photogenerated carriers, whereas the carbon network improved the transfer of photogenerated electrons. Under optimised conditions, the Fe2O3/Fe3O4@C-1 hybrid demonstrated enhanced photodegradation efficiencies of 96.4% for TC and 100% for MB under visible light. In addition, electron spin resonance and trapping measurements were performed to identify active species and determine the photocatalytic mechanism toward pollutants. •O2- and •OH were the active species involved, playing critical roles in the TC and MB photodegradation processes. In addition, a bacterium test revealed that the products of TC degradation by Fe2O3/Fe3O4@C-1 showed low biological toxicity. This work provides a promising preparation strategy or biomass-based photocatalysts for application in environmental pollutant treatment.

Multigenerational effects of elevated temperature on host-microbiota interactions in the marine water flea Diaphanosoma celebensis exposed to micro- and nanoplastics.

Rising ocean temperatures are driving unprecedented changes in global marine ecosystems. Meanwhile, there is growing concern about microplastic and nanoplastic (MNP) contamination, which can endanger marine organisms. Increasing ocean warming (OW) and plastic pollution inevitably cause marine organisms to interact with MNPs, but relevant studies remain sparse. Here, we investigated the interplay between ocean warming and MNP in the marine water flea Diaphanosoma celebensis. We found that combined exposure to MNPs and OW induced reproductive failure in the F2 generation. In particular, the combined effects of OW and MNPs on the F2 generation were associated with key genes related to reproduction and stress response. Moreover, populations of predatory bacteria were significantly larger under OW and MNP conditions during F2 generations, suggesting a potential link between altered microbiota and host fitness. These results were supported by a host transcriptome and microbiota interaction analysis. This research sheds light on the complex interplay between environmental stressors, their multigenerational effects on marine organisms, and the function of the microbiome.

A Meta-analysis Reveals Global Change Stressors Potentially Aggravate Mercury Toxicity in Marine Biota.

Growing evidence demonstrates that global change can modulate mercury (Hg) toxicity in marine organisms; however, the consensus on such effect is lacking. Here, we conducted a meta-analysis to evaluate the effects of global change stressors on Hg biotoxicity according to the IPCC projections (RCP 8.5) for 2100, including ocean acidification (-0.4 units), warming (+4 °C), and their combination (acidification-warming). The results indicated an overall aggravating effect (ln RRΔ = -0.219) of global change on Hg toxicity in marine organisms, while the effect varied with different stressors; namely, acidification potentially alleviates Hg biotoxicity (ln RRΔ = 0.117) while warming and acidification-warming have an aggravating effect (ln RRΔ = -0.328 and -0.097, respectively). Moreover, warming increases Hg toxicity in different trophic levels, i.e., primary producers (ln RRΔ = -0.198) < herbivores (ln RRΔ = -0.320) < carnivores (ln RRΔ = -0.379), implying increasing trends of Hg biomagnification through the food web. Notably, ocean hypoxia appears to boost Hg biotoxicity, although it was not considered in our meta-analysis because of the small sample size. Given the persistent global change and combined effects of these stressors in marine environments, multigeneration and multistressor research is urgently needed to fully disclose the impacts of global change on Hg pollution and its risk.

Transcriptional profiles reveal histologic origin and prognosis across 33 The Cancer Genome Atlas tumor types.

Background: In recent years, with the development of transcriptome sequencing, the molecular characteristics of tumors are gradually revealed. Because of the complexity of tumor transcriptome, there is a need to look for the molecular signatures which can be used to evaluate the tissue origin and cell stemness of tumors in order to promote the diagnosis and treatment of tumors. Methods: Tumor tissue-specific gene sets (TTSGs) consisting of 200 genes were selected using RNA expression data of 9,875 patients from 33 tumor types. t-distributed Stochastic Neighbor Embedding (t-SNE) was used for dimensionality reduction and visualization of TTSGs in each tumor type. To evaluate oncogenic dedifferentiation and loss of cell stemness, Euclidean distance from each sample to a human embryo single-cell RNA-seq dataset (GSE36552) of TTSGs was calculated as TTSGs index indicating dissimilarity of tumors and embryo. TTSGs index was evaluated for prognosis in each tumor type. Two published signature indexes, the mRNA signature index (mRNAsi) and CIBERSORT, were compared to assess the correlation between the TTSGs index with cell stemness and immune microenvironment. Finally, the difference of prognosis, immune microenvironment and radiotherapy outcomes were compared between patients with high and low TTSGs index. Results: In this study, all 33 tumor types in The Cancer Genome Atlas (TCGA) were embedded into isolated clusters by t-SNE and confirmed by k-nearest neighbors (kNN) algorithm. Clusters of squamous-cell carcinoma were adjacent to each other revealing similar histologic origin. Basal-like breast cancer was separated from luminal and HER-2-amplified subtypes and closed to squamous-cell carcinoma. TTSGs index was related to overall survival outcomes in cancers derived from liver, thyroid, brain, cervical and kidney. There was a positive correlation between mRNAsi and TTSGs index in pan-kidney and pan-neuronal cancers. Furthermore, cell fractions of M2 macrophages and total leukocytes increased in the group with higher TTSGs index. Patients with higher TTSGs index had longer overall survival time and less radiation therapy resistance compared to patients with lower TTSGs index. Conclusions: The signature of TTSGs is related to tumor expression features that distinguish tumors of different histologic origin using t-SNE. The signature also relates to prognosis of certain kinds of tumors.

Stroke as initial manifestation of non-small cell lung cancer with Trousseau syndrome.

OBJECTIVE: Stroke is a rare but fatal complication of advanced cancer with Trousseau syndrome, especially as initial symptoms. Here, we report the clinical characteristics, treatment, and prognosis of patients with non-small cell lung cancer (NSCLC) who initially presenting with acute multiple cerebral infarction. METHODS: The clinical characteristics, imaging, treatment, and oncological outcomes of 10 patients diagnosed with Trousseau syndrome and NSCLC between 2015 and 2021 at Guangdong Sanjiu Brain Hospital were retrospectively collected and analyzed. The clinical course of two typical cases were presented. RESULTS: All 10 patients with pathologically confirmed lung adenocarcinoma initially presented with neurological symptoms, including hemiplegic paralysis (7 patients, 70%), dizziness (5 patients, 50%), and unclear speech (3 patients, 30%). The median age was 63.5 years. Eight and two cases were stage III and IV, respectively, at the initial diagnosis. Five patients underwent driver gene testing, revealing three patients with EGFR-sensitive mutations, one patient with ALK fusion, and one patient with wild-type EGFR. All 10 patients received antiplatelet therapy, and six patients subsequently received anti-cancer treatment. The median overall survival of the patients was 8.5 months (95% confidence interval) and 1-year survival rate was 57.1%. Patients who received antitumor treatment, especially those harboring driver gene mutations and received tyrosine kinase inhibitors, had better neurological symptom recovery and superior oncological prognosis (median overall survival, not reached versus 7.4 months, p = 0.038). CONCLUSION: Trousseau syndrome, presenting as multiple cerebral infarctions, is a rare complication of lung adenocarcinoma. Both antiplatelet and antitumor treatment are recommended to achieve better neurological recovery and oncological prognosis in these patients.