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In the original publication [...].
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Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m6A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage.
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Métabolisme lipidique , Souris de lignée C57BL , Protéomique , Traumatismes de la moelle épinière , Traumatismes de la moelle épinière/métabolisme , Traumatismes de la moelle épinière/anatomopathologie , Animaux , Souris , Métabolisme lipidique/physiologie , Femelle , Lipidomique , Transcriptome , Multi-omiqueRÉSUMÉ
The accurate construction of mono-, bi- and multi-layer networks has been an important challenge, especially for bi- and multi-layer networks. Monolayer, bilayer, sandwich bilayer, four-layer, and multi-layer two-dimensional pillararene-type metal-organic coordination networks have been constructed from functionalized pillar[5]arene and pillar[6]arene by utilizing the coordination interaction of cobalt and copper ions and combining with temperature control and guest induction. These two-dimensional coordination networks exhibit the excellent plasticity of pillararenes and structural variety, which are characterized by X-ray single crystal diffraction and PXRD, confirming that pillararenes units can function as excellent tunable scaffolds for structural regulation. Two-dimensional chiral double-layer structure products are also constructed from R- and S-pillar[6]arene, which are obtained by high-performance liquid chromatography. Atomic force microscopic imaging confirms the thicknesses of these networks. Moreover, these networks also exhibit high iodine adsorption capacity in aqueous environments at ambient temperature. The monolayer, bilayer, sandwich bilayer, four-layer and multi-layer structures of the pillararene-type networks represent a new facile supramolecular self-assembly strategy and platform for designing more mono-, bi- and multi-layer two-dimensional nanomaterials and chiral two-dimensional double-layer structures provide a new method for the construction of more two-dimensional chiral polymers.
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Flavivirus infection capitalizes on cellular lipid metabolism to remodel the cellular intima, creating a specialized lipid environment conducive to viral replication, assembly, and release. The Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is responsible for significant morbidity and mortality in both humans and animals. Currently, there are no effective antiviral drugs available to combat JEV infection. In this study, we embarked on a quest to identify anti-JEV compounds within a lipid compound library. Our research led to the discovery of two novel compounds, isobavachalcone (IBC) and corosolic acid (CA), which exhibit dose-dependent inhibition of JEV proliferation. Time-of-addition assays indicated that IBC and CA predominantly target the late stage of the viral replication cycle. Mechanistically, JEV nonstructural proteins 1 and 2A (NS1 and NS2A) impede 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation by obstructing the liver kinase B1 (LKB1)-AMPK interaction, resulting in decreased p-AMPK expression and a consequent upsurge in lipid synthesis. In contrast, IBC and CA may stimulate AMPK by binding to its active allosteric site, thereby inhibiting lipid synthesis essential for JEV replication and ultimately curtailing viral infection. Most importantly, in vivo experiments demonstrated that IBC and CA protected mice from JEV-induced mortality, significantly reducing viral loads in the brain and mitigating histopathological alterations. Overall, IBC and CA demonstrate significant potential as effective anti-JEV agents by precisely targeting AMPK-associated signaling pathways. These findings open new therapeutic avenues for addressing infections caused by Flaviviruses. IMPORTANCE: This study is the inaugural utilization of a lipid compound library in antiviral drug screening. Two lipid compounds, isobavachalcone (IBC) and corosolic acid (CA), emerged from the screening, exhibiting substantial inhibitory effects on the Japanese encephalitis virus (JEV) proliferation in vitro. In vivo experiments underscored their efficacy, with IBC and CA reducing viral loads in the brain and mitigating JEV-induced histopathological changes, effectively shielding mice from fatal JEV infection. Intriguingly, IBC and CA may activate 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) by binding to its active site, curtailing the synthesis of lipid substances, and thus suppressing JEV proliferation. This indicates AMPK as a potential antiviral target. Remarkably, IBC and CA demonstrated suppression of multiple viruses, including Flaviviruses (JEV and Zika virus), porcine herpesvirus (pseudorabies virus), and coronaviruses (porcine deltacoronavirus and porcine epidemic diarrhea virus), suggesting their potential as broad-spectrum antiviral agents. These findings shed new light on the potential applications of these compounds in antiviral research.
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Engineering of the interface between the perovskite and hole transport layer (HTL) has been crucial to achieving high performance. In this study, two interfacial materials, MN-CZ and CN-CZ, are designed by systematically regulating the group substitution site to study the relationship between spatial conformation and the passivation effect. The passivation groups of CN-CZ molecules exhibit a stronger "vector addition" effect, resulting in larger molecular dipoles and enhanced defect passivation and energy level regulation effects. Consequently, the CN-CZ-based perovskite solar cell (PSC) shows a high efficiency of 23.8%, which is much higher than that of the reference device. Meanwhile, the humidity and thermal stability of the unencapsulated device have been significantly improved.
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The growing variety of RNA classes, such as mRNAs, lncRNAs, and circRNAs, plays pivotal roles in both developmental processes and various pathophysiological conditions. Nonetheless, our comprehension of RNA functions in live organisms remains limited due to the absence of durable and effective strategies for directly influencing RNA levels. In this study, we combined the CRISPR-RfxCas13d system with sperm-like stem cell-mediated semi-cloning techniques, which enabled the suppressed expression of different RNA species. This approach was employed to interfere with the expression of three types of RNA molecules: Sfmbt2 mRNA, Fendrr lncRNA, and circMan1a2(2,3,4,5,6). The results confirmed the critical roles of these RNAs in embryonic development, as their loss led to observable phenotypes, including embryonic lethality, delayed embryonic development, and embryo resorption. In summary, our methodology offers a potent toolkit for silencing specific RNA targets in living organisms without introducing genetic alterations.
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Perfluoroethylcyclohexane sulfonate (PFECHS) is an emerging per- and polyfluoroalkyl substance used to replace perfluorooctane sulfonate (PFOS), mainly in aircraft hydraulic fluids. However, previous research indicates the potential neurotoxicity of this replacement chemical. In this study, marine medaka (Oryzias melastigma) was exposed to environmentally relevant concentrations of PFECHS (concentrations: 0, 0.08, 0.26, and 0.91 µg/L) from the embryonic stage for 90 days. After exposure, the brain and eyes of the medaka were collected to investigate the bioconcentration potential of PFECHS stereoisomers and their effects on the nervous systems. The determined bioconcentration factors (BCFs) of PFECHS ranged from 324 ± 97 to 435 ± 89 L/kg and from 454 ± 60 to 576 ± 86 L/kg in the brain and eyes of medaka, respectively. The BCFs of trans-PFECHS were higher than those of cis-PFECHS. PFECHS exposure significantly altered γ-aminobutyric acid (GABA) levels in the medaka brain and disrupted the GABAergic system, as revealed by proteomics, implying that PFECHS can disturb neural signal transduction like PFOS. PFECHS exposure resulted in significant alterations in multiple proteins associated with eye function in medaka. Abnormal locomotion was observed in PFECHS-exposed medaka larvae, which was rescued by adding exogenous GABA, suggesting the involvement of disrupted GABA signaling pathways in PFECHS neurotoxicity.
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Oryzias , Animaux , Oryzias/métabolisme , Polluants chimiques de l'eau/toxicitéRÉSUMÉ
The oxidation of Sn2+ can occur even after the completion of the perovskite crystallization in a low oxygen environment. Concerning this, the natural antioxidant vitamin C (VC) is introduced to the surface of Sn-Pb mixed perovskite using a postprocessing method to achieve the purpose of inhibiting Sn2+ oxidation and enhancing perovskite solar cells performance. The results indicate that the VC could effectively inhibit Sn2+ oxidation and heal the vacancy defects of the annealed perovskite film. Meanwhile, the introduction of VC significantly improves the morphology and crystalline quality of the perovskite films. After optimization, the highest power conversion efficiency of the VC-treated Sn-Pb mixed device increased to 20.44%. Moreover, the VC-treated unencapsulated device shows excellent long-term stability, retaining 75.3% of its initial efficiency after 800 h of aging in a N2 atmosphere, which is much higher than the 20.1% of the control device.
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Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.
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Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors via removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion via reverse cholesterol transport but also scavenge the overaccumulated ROS. ß-Cyclodextrin (ß-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. ß-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs in vivo circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.
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Athérosclérose , Matériaux biomimétiques , Cholestérol , Dopamine , Macrophages , Méthotrexate , Nanoparticules , Dopamine/composition chimique , Dopamine/pharmacologie , Nanoparticules/composition chimique , Athérosclérose/traitement médicamenteux , Athérosclérose/métabolisme , Athérosclérose/anatomopathologie , Souris , Animaux , Matériaux biomimétiques/composition chimique , Matériaux biomimétiques/pharmacologie , Méthotrexate/composition chimique , Méthotrexate/pharmacologie , Cholestérol/composition chimique , Macrophages/effets des médicaments et des substances chimiques , Macrophages/métabolisme , Espèces réactives de l'oxygène/métabolisme , Humains , Cyclodextrines/composition chimique , Cyclodextrines/pharmacologie , Cellules RAW 264.7 , Stress oxydatif/effets des médicaments et des substances chimiques , Vecteurs de médicaments/composition chimique , Cyclodextrines bêtaRÉSUMÉ
This study provided a systematic investigation of microplastics in Hong Kong's surface marine waters during the pandemic from 2019 to 2021. Microplastics (2.07 ± 4.00 particles/m3) exhibited significant temporal variations with higher abundance in the wet season, without a consistent trend after the mandatory mask-wearing requirement was announced. The impact of pandemic restrictions on microplastic distribution was found to be relatively minor. However, significant correlations between microplastic abundances and rainfall highlighted the substantial contribution of local emissions through surface runoff. Notably, sites in closer proximity to the Pearl River Delta exhibited higher microplastic abundances, indicating their association with emission sources. The influence of rainfall and adverse weather on marine microplastic loads demonstrated different sensitivities among various locations but can generally last for one month. These results revealed the impact of seasonal rainfall on coastal microplastics and emphasized the need for efforts to reduce microplastic discharge from land-based sources.
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Surveillance de l'environnement , Microplastiques , Pluie , Rivières , Polluants chimiques de l'eau , Hong Kong , Polluants chimiques de l'eau/analyse , Microplastiques/analyse , Rivières/composition chimique , Eau de mer/composition chimique , SaisonsRÉSUMÉ
Chronic bacterial infections, excessive inflammation, and oxidative stress significantly hinder diabetic wound healing by prolonging the inflammatory phase and complicating the healing process. In this study, phenylboronic acid functionalized dextran (PODP) was developed to encapsulate curcumin, referred to as PODP@Cur. Experimental results indicate that PODP significantly improves the water solubility of curcumin and exhibits synergistic biological activity both in vitro and in vivo. PODP@Cur is capable of accelerating drug release under the pathological microenvironment with ROS accumulation. Furthermore, phenylboronic acid (PBA) has demonstrated potential for targeted bacterial drug delivery, enhancing antibacterial efficacy and trapping free LPS/PGN from dead bacteria to reduce undesirable inflammation. In a diabetic mouse model, PODP@Cur exhibits an excellent antibacterial, anti-inflammatory and antioxidant activities to ultimately promote the efficient and safe wound healing. Due to the specific interaction between PBA and LPS, PODP@Cur could enhance antibacterial activity against bacteria, reduce toxic side effects on normal cells, and alleviate the LPS-mediated pro-inflammatory pathological microenvironment. Therefore, PODP@Cur is capable of being exploited as an efficient and safe candidate for promoting the bacteria-infected diabetic wound healing.
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Antibactériens , Acides boroniques , Curcumine , Dextrane , Diabète expérimental , Cicatrisation de plaie , Curcumine/pharmacologie , Curcumine/composition chimique , Animaux , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Dextrane/composition chimique , Souris , Acides boroniques/composition chimique , Acides boroniques/pharmacologie , Antibactériens/pharmacologie , Antibactériens/composition chimique , Diabète expérimental/traitement médicamenteux , Nanoparticules/composition chimique , Libération de médicament , Vecteurs de médicaments/composition chimique , Cellules RAW 264.7 , Mâle , Antioxydants/pharmacologie , Antioxydants/composition chimique , Infections bactériennes/traitement médicamenteuxRÉSUMÉ
The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.
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Antigène CD274 , Kinase-5 cycline-dépendante , Immunothérapie , Photothérapie dynamique , Photothérapie dynamique/méthodes , Antigène CD274/métabolisme , Antigène CD274/antagonistes et inhibiteurs , Immunothérapie/méthodes , Animaux , Kinase-5 cycline-dépendante/métabolisme , Kinase-5 cycline-dépendante/antagonistes et inhibiteurs , Humains , Lignée cellulaire tumorale , Régulation négative/effets des médicaments et des substances chimiques , Souris , Tumeurs/thérapie , Tumeurs/traitement médicamenteux , Porphyrines/composition chimique , Porphyrines/pharmacologie , Porphyrines/usage thérapeutique , Espèces réactives de l'oxygène/métabolisme , ChlorophyllidesRÉSUMÉ
Microbial degradation of fluorinated compounds raised significant attention because of their widespread distribution and potential environmental impacts. Here, we report a bacterial isolate, Rhodococcus sp. NJF-7 capable of defluorinating monofluorinated medium-chain length alkanes. This isolate consumed 2.29 ± 0.13 mmol L- 1 of 1-fluorodecane (FD) during a 52 h incubation period, resulting in a significant release of inorganic fluoride amounting to 2.16 ± 0.03 mmol L- 1. The defluorination process was strongly affected by the initial FD concentration and pH conditions, with lower pH increasing fluoride toxicity to bacterial cells and inhibiting enzymatic defluorination activity. Stoichiometric conversion of FD to fluoride was observed at neutral pH with resting cells, while defluorination was significantly lower at reduced pH (6.5). The discovery of the metabolites decanoic acid and methyl decanoate suggests that the initial attack by monooxygenases may be responsible for the biological defluorination of FD. The findings here provide new insights into microbial defluorination processes, specifically aiding in understanding the environmental fate of organic semi-fluorinated alkane chemicals.
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One of the significant topics in the field of the Internet of Things (IoT) pertains to the interaction and information sharing among people. The utilization of the Border Gateway Protocol (BGP) stack enhances the integration of web protocols and sensor networks, leading to greater accessibility. However, the BGP protocol stack introduces substantial overhead to messages transmitted at each layer, resulting in increased data overhead and energy consumption in networks by several orders of magnitude. This paper proposes a method to reduce the overhead on small and medium-sized packets. In multi-temporal networks utilizing BGP, scheduling and aggregating BGP packets at sensor nodes help achieve specific objectives. Various research methodologies and measures are employed to facilitate this, including request classification, BGP response prioritization within the network, determination of maximum acceptable delay, and overall network management. Synchronization and temporal integration of received messages at sensor nodes are performed, considering the maximum allowable delay for each message and the availability of the destination to process the accumulated messages. The evaluation results of the proposed method demonstrate a significant reduction in energy consumption and network traffic, particularly in monitoring applications within multi-stage networks. The protocol stack used is derived from the BGP standard.
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BACKGROUND: Genus Buxus plants, commonly known as "boxwood", are widely distributed in China. The stems, branches, and leaves of the plant are traditionally used for rheumatism, toothache, chest pain, abdominal gas, and other diseases. However, an overview of the genus Buxus remains to be provided. PURPOSE: To provide a scientific basis for the appropriate use and further research the recent advancements in the traditional usage, phytochemistry, and, pharmacology of Buxus. STUDY DESIGN: Chemical composition and pharmacological correlation studies through a literature review. METHODS: Between 1970 and 2023, the available data concerning Buxus was compiled from online scientific sources, such as Sci-Finder, PubMed, CNKI, Google Scholar, and the Chinese Pharmacopoeia. Plant names were verified from "The Plant List" (http://www.theplantlist.org/). RESULTS: To date, 266 structurally diverse chemicals have been extracted and identified from the genus Buxus. Alkaloids constitute one of its primary bioactive phytochemicals. A summary of the channels of action of Cyclovirobuxine D on the cytotoxicity of a variety of cancers has been provided. CONCLUSION: Numerous findings from contemporary phytochemical and pharmacological studies support the traditional use, facilitating its application. Further research is necessary to address various shortcomings, including the identification of the active ingredients and quality control of the genus Buxus.
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Buxus , Composés phytochimiques , Composés phytochimiques/pharmacologie , Composés phytochimiques/composition chimique , Composés phytochimiques/isolement et purification , Humains , Buxus/composition chimique , Antinéoplasiques d'origine végétale/pharmacologie , Antinéoplasiques d'origine végétale/composition chimique , Antinéoplasiques d'origine végétale/isolement et purification , Animaux , Structure moléculaireRÉSUMÉ
The present study explored the risk factors associated with radiotherapy in seniors diagnosed with limited-stage small cell lung cancer (LS-SCLC) to construct and validate a prognostic nomogram. The study retrospectively included 137 elderly patients with LS-SCLC who previously received radiotherapy. Univariate and multivariate COX analyses were conducted to identify independent risk factors and determine optimal cut-off values. Kaplan-Meier survival curves and nomograms were constructed to predict survival. Calibration and receiver operating characteristic (ROC) curves were used to evaluate the accuracy and consistency of the nomogram. Illness rating scale-geriatric (CIRS-G) score, treatment strategy, lymphocyte-to-monocyte ratio (LMR), white blood cell-to-monocyte ratio (WMR), and prognostic nutritional index (PNI) were discovered to be independent prognostic factors. Based on the findings of our multivariate analysis, a risk nomogram was developed to assess patient prognosis. Internal bootstrap resampling was utilized to validate the model, and while the accuracy of the AUC curve at 1 year was modest at 0.657 (95% CI 0.458-0.856), good results were achieved in predicting 3- and 5 year survival with AUCs of 0.757 (95% CI 0.670-0.843) and 0.768 (95% CI 0.643-0.893), respectively. Calibration curves for 1-, 3-, and 5 year overall survival probabilities demonstrated good cocsistency between expected and actual outcomes. Patients with concurrent chemoradiotherapy, CIRS-G score > 5 points and low PNI, WMR and LMR correlated with poor prognosis. The nomogram model developed based on these factors demonstrated good predictive performance and provides a simple, accessible, and practical tool for clinicians to guide clinical decision-making and study design.
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Tumeurs du poumon , Nomogrammes , Carcinome pulmonaire à petites cellules , Humains , Mâle , Femelle , Sujet âgé , Carcinome pulmonaire à petites cellules/radiothérapie , Carcinome pulmonaire à petites cellules/mortalité , Carcinome pulmonaire à petites cellules/anatomopathologie , Tumeurs du poumon/radiothérapie , Tumeurs du poumon/mortalité , Tumeurs du poumon/anatomopathologie , Pronostic , Études rétrospectives , Sujet âgé de 80 ans ou plus , Facteurs de risque , Courbe ROC , Stadification tumorale , Estimation de Kaplan-Meier , Évaluation de l'état nutritionnelRÉSUMÉ
In this study, a benzoselenadiazole- and pyridine-bifunctionalized hydrogen-bonded arylamide foldamer was synthesized. A co-crystallization experiment with 1,4-diiodotetrafluorobenzene showed that a new type of supramolecular double helices, which were induced by three orthogonal interactions, namely, three-center hydrogen bonding (Oâ¯Hâ¯O), Iâ¯N halogen bonding and Seâ¯N chalcogen bonding, have been constructed in the solid state. This work presents a novel instance of multiple non-covalent interactions that work together to construct supramolecular architectures.