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1.
J Clin Lipidol ; 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39294020

ABSTRACT

OBJECTIVES: Homozygous familial hypercholesterolemia (HoFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset cardiovascular disease. To assess the therapeutic effects of liver transplantation (LT) on HoFH patients, we observed and analyzed the outcomes of HoFH children after LT. STUDY DESIGN: This prospective cohort study included all LT candidates under 18 years old diagnosed with HoFH at Ren Ji Hospital between November 2017 and July 2021. The patients were followed until October 2023. They were treated according to the standard protocol at our center. We collected data on changes in lipid profiles, clinical manifestations, and cardiovascular complications at different time points, and recorded postoperative recipient and graft survival. RESULTS: Fourteen HoFH patients with a median age of 7 (2-12) years were included. Preoperatively, xanthomas and arcus corneas occurred in 14 and 3 patients, respectively, with 10 patients showing mild cardiovascular disease. All patients underwent LT. Recipient and graft survival rates were 100 % over a median follow-up duration of 35 (27-71) months. Median LDL-C levels dropped from 11.83 (7.99-26.14) mmol/L preoperatively to 2.3 (1.49-3.39) mmol/L postoperative at the last measurement. Thirteen patients discontinued lipid-lowering treatment after LT, while only one patient resumed statins 6 months post-operation. Xanthomas and arcus corneas significantly improved. Cardiovascular complications regressed in five patients, with no progression observed in the others. CONCLUSIONS: LT is a safe and effective treatment for severe HoFH patients beyond lipid-lowering control. Early LT improves prognosis and quality of life while minimizing the risk of cardiovascular complications.

2.
Bioresour Technol ; 413: 131527, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39326531

ABSTRACT

The thermochemical conversion technology for anaerobic digestate from food waste (ADFW) can reduce waste volume, eliminate pathogens, and recover energy through incineration, pyrolysis, gasification, and hydrothermal transformation. This paper comprehensively reviews the physicochemical features of anaerobically fermented digestate from food waste (FW), digestate treatment methods, and their advantages and disadvantages. In addition, the analysis and application of associated by-products from ADFW thermochemical conversion are also discussed. The main products include biochar, bio-oil, and biogas. Biochar can be used for soil improvement and biomedicine and bio-oil can be used forliquid fuel. Meanwhile, biogas mainly consists of CH4, CO2, and H2 and CO, which can be used in petrochemicals, metallurgy, and other fields. The catalytic pyrolysis/gasification for plastic-containing ADFW is proposed by adding iron-based industrial waste (red mud/copper) as catalysts under the CO2/CH4 atmosphere. This review helps to provide new guidelines for the ADFW utilization of desired products.

3.
Front Pediatr ; 12: 1407959, 2024.
Article in English | MEDLINE | ID: mdl-39323509

ABSTRACT

Splenic abscesses (SA), especially in children, are rare in clinical practice. The missed diagnosis rate of SA is high and the probability of rapidly diagnosing it is relatively low due to its low incidence rate and the presence of non-specific clinical symptoms and imaging manifestations. Antibiotics are the primary treatment for SA; however, ultrasound-guided percutaneous puncture suction or drainage, and splenectomy are other effective treatment strategies. In this study, we report one case of SA in a 16-year-old male patient who presented with abdominal pain, fever, and cough, and the therapeutic effect was unsatisfactory (recurrent fever). After admission, the patient was diagnosed with a solitary SA by abdominal CT with contrast and upper abdominal MRI; fever and abdominal pain were relieved and the SA gradually disappeared after antibiotic treatment.

4.
Sci China Life Sci ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39327392

ABSTRACT

As the elderly population expands, the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial. As an FDA-approved drug for chronic cholestatic liver diseases, tauroursodeoxycholic acid (TUDCA), a natural bile acid, offers additional health benefits beyond liver protection. Here, we show that TUDCA extends the lifespan and healthspan of C. elegans. Importantly, oral supplementation of TUDCA improves fitness in old mice, including clinically relevant phenotypes, exercise capacity and cognitive function. Consistently, TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics. Mechanistically, we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity. This collaboration further alleviates aging-induced endoplasmic reticulum (ER) stress and facilitates protein homeostasis, thus offering resistance to aging. In summary, our findings uncover new molecular links between an endogenous metabolite and protein homeostasis, and propose a novel anti-aging strategy that could improve both lifespan and healthspan.

5.
Nat Cancer ; 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39327501

ABSTRACT

Tumor microenvironment heterogeneity in hepatocellular carcinoma (HCC) on a spatial single-cell resolution is unclear. Here, we conducted co-detection by indexing to profile the spatial heterogeneity of 401 HCC samples with 36 biomarkers. By parsing the spatial tumor ecosystem of liver cancer, we identified spatial patterns with distinct prognosis and genomic and molecular features, and unveiled the progressive role of vimentin (VIM)high macrophages. Integration analysis with eight independent cohorts demonstrated that the spatial co-occurrence of VIMhigh macrophages and regulatory T cells promotes tumor progression and favors immunotherapy. Functional studies further demonstrated that VIMhigh macrophages enhance the immune-suppressive activity of regulatory T cells by mechanistically increasing the secretion of interleukin-1ß. Our data provide deep insights into the heterogeneity of tumor microenvironment architecture and unveil the critical role of VIMhigh macrophages during HCC progression, which holds potential for personalized cancer prevention and drug discovery and reinforces the need to resolve spatial-informed features for cancer treatment.

6.
Article in English | MEDLINE | ID: mdl-39329192

ABSTRACT

The distribution, composition, and risk assessment of 8 EDCs in the surface water of 14 national aquatic germplasm resource reserves (freshwater) were investigated during dry and wet seasons. Bisphenol A (BPA), nonylphenol (NP), and octylphenol (OP) were the main contributors of the 8 EDCs. The concentrations of phenolic pollutants in surface water during the dry season were higher than those in the wet season. However, no significant seasonal differences were found among the steroid hormones. According to the evaluation of estrogenic activity (EEQ > 1.0), E2 and EE2 were the main contributors to estrogenic activity. EDC mixtures posed a higher risk to crustaceans and fish (RQ > 1.0) and a moderate to high risk to algae (RQ > 0.1). Fish were the most sensitive aquatic organisms. In the study areas, EE2, E1, BPA, NP, and E2 had a higher risk than the other three compounds and should be controlled as a priority.

7.
Hum Exp Toxicol ; 43: 9603271241276981, 2024.
Article in English | MEDLINE | ID: mdl-39226487

ABSTRACT

Currently, the incidence of diquat (DQ) poisoning is increasing, and quickly predicting the prognosis of poisoned patients is crucial for clinical treatment. In this study, a total of 84 DQ poisoning patients were included, with 38 surviving and 46 deceased. The plasma DQ concentration of DQ poisoned patients, determined by liquid chromatography-mass spectrometry (LC-MS) were collected and analyzed with their complete blood count (CBC) indicators. Based on DQ concentration and CBC dataset, the random forest of diagnostic and prognostic models were established. The results showed that the initial DQ plasma concentration was highly correlated with patient prognosis. There was data redundancy in the CBC dataset, continuous measurement of CBC tests could improve the model's predictive accuracy. After feature selection, the predictive accuracy of the CBC dataset significantly increased to 0.81 ± 0.17, with the most important features being white blood cells and neutrophils. The constructed CBC random forest prediction model achieved a high predictive accuracy of 0.95 ± 0.06 when diagnosing DQ poisoning. In conclusion, both DQ concentration and CBC dataset can be used to predict the prognosis of DQ treatment. In the absence of DQ concentration, the random forest model using CBC data can effectively diagnose DQ poisoning and patient's prognosis.


Subject(s)
Algorithms , Diquat , Humans , Diquat/blood , Diquat/poisoning , Female , Male , Prognosis , Adult , Blood Cell Count , Middle Aged , Herbicides/poisoning , Herbicides/blood , Young Adult , Adolescent , Random Forest
8.
Front Plant Sci ; 15: 1404271, 2024.
Article in English | MEDLINE | ID: mdl-39233912

ABSTRACT

Maize lethal necrosis is attributed to the accumulation of maize chlorotic mottle virus (MCMV), an invasive virus transmitted by insect vectors. The western flower thrips (WFT) can shift host to maize, thus promoting the spread of MCMV. However, our understanding of the characteristics and interactions involved in the transmission of MCMV is still limited. This study finds that non-viruliferous WFTs showed a 57.56% higher preference for MCMV-infected maize plants compared to healthy maize plants, while viruliferous WFTs showed a 53.70% higher preference for healthy maize plants compared to MCMV-infected maize plants. We also show for the first time that both adults and larvae of WFT could successfully acquire MCMV after 1 min of acquisition access period (AAP), and after 48 h of AAP, WFT could transmit MCMV in an inoculation access period of 1 h without a latent period. Both adults and larvae of WFT can transmit MCMV for up to 2 days. Furthermore, the decreasing number of viruliferous WFTs and transmission rates as time progressed, together with the transcriptomic evidence, collectively suggest that WFTs transmit MCMV in a semi-persistent method, a mode of transmission requiring minutes to several hours for acquisition access and having a retention time of several hours to a few days. Additionally, ß-myrcene can attract WFTs significantly and is detected in Nicotiana benthamiana plants transiently expressing MCMV CP (coat protein), which is consistent with results in MCMV-infected maize plants through the metabolomic profiling and the preference analyses of WFT. Therefore, this study demonstrates the indirect interaction between MCMV and WFT by inducing maize to synthesize ß-myrcene to attract insect vectors. The exploration of specific interactions between MCMV and WFT could help to expand the mechanism studies of virus-vector-host plant interaction and put forward a new insight for the combined control of MCMV and WFT through the manipulation of plant volatiles and key insect genes.

9.
Regen Biomater ; 11: rbae107, 2024.
Article in English | MEDLINE | ID: mdl-39246578

ABSTRACT

Owing to the unpredictable size of wounds and irregular edges formed by trauma, nanofibers' highly customizable and adherent in situ deposition can contribute to intervention in the healing process. However, electrospinning is limited by the constraints of conventional polymeric materials despite its potential for anti-inflammatory and antimicrobial properties. Here, inspired by the Janus structure and biochemistry of nanometal ions, we developed an in situ sprayed electrospinning method to overcome bacterial infections and immune imbalances during wound healing. The bilayer fiber scaffold has a hydrophobic outer layer composed of polycaprolactone (PCL) and a hydrophilic inner layer composed of gelatin, poly(L-lactic acid) (PLLA), and magnesium oxide nanoparticles, constituting the PCL/PLLA-gelatin-MgO (PPGM) electrospun scaffold. This electrospun scaffold blocked the colonization and growth of bacteria and remained stable on the wound for continuous anti-inflammatory properties to promote wound healing. Furthermore, PPGM electrospinning modulated collagen deposition and the inflammatory microenvironment in the full-thickness skin model, significantly accelerating vascularization and epithelialization progression. This personalized Janus electrospun scaffold has excellent potential as a new type of wound dressing for first aid and wound healthcare.

10.
EMBO J ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39284914

ABSTRACT

ER-phagy, a selective form of autophagic degradation of endoplasmic reticulum (ER) fragments, plays an essential role in governing ER homeostasis. Dysregulation of ER-phagy is associated with the unfolded protein response (UPR), which is a major clue for evoking inflammatory diseases. However, the molecular mechanism underpinning the connection between ER-phagy and disease remains poorly defined. Here, we identified ubiquitin-associated domain-containing protein 2 (UBAC2) as a receptor for ER-phagy, while at the same time being a negative regulator of inflammatory responses. UBAC2 harbors a canonical LC3-interacting region (LIR) in its cytoplasmic domain, which binds to autophagosomal GABARAP. Upon ER-stress or autophagy activation, microtubule affinity-regulating kinase 2 (MARK2) phosphorylates UBAC2 at serine (S) 223, promoting its dimerization. Dimerized UBAC2 interacts more strongly with GABARAP, thus facilitating selective degradation of the ER. Moreover, by affecting ER-phagy, UBAC2 restrains inflammatory responses and acute ulcerative colitis (UC) in mice. Our findings indicate that ER-phagy directed by a MARK2-UBAC2 axis may provide targets for the treatment of inflammatory disease.

11.
Angew Chem Int Ed Engl ; : e202415400, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39258563

ABSTRACT

Despite the proliferation of multiple resonance (MR) materials in the blue to green spectral ranges, red MR emitters remain scarce in the literature, an area that certainly warrants attention for future applications. Here, through a clever application of classic Clar's aromatic π-sextet rule, we triumphantly constructed the first red MR emitter by substituting the conventional benzene ring core with anthracene (fewer π-sextets). Theoretical studies indicate that the quantity of π-sextets ultimately determines the optical bandgap of a molecule, rather than the number of fused benzene rings. Benefiting from the high photoluminescence quantum yield of ~94% and horizontal dipole ratio of ~90%, the corresponding narrowband red (luminescence wavelength: 608 nm) organic light-emitting diode shows a high external quantum efficiency of 27.3%, with only a slight decrease of 3.7% at an elevated luminance level of 100,000 cd/m2.

12.
Adv Sci (Weinh) ; : e2406242, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39258724

ABSTRACT

Multimodal machine learning, as a prospective advancement in artificial intelligence, endeavors to emulate the brain's multimodal learning abilities with the objective to enhance interactions with humans. However, this approach requires simultaneous processing of diverse types of data, leading to increased model complexity, longer training times, and higher energy consumption. Multimodal neuromorphic devices have the capability to preprocess spatio-temporal information from various physical signals into unified electrical signals with high information density, thereby enabling more biologically plausible multimodal learning with low complexity and high energy-efficiency. Here, this work conducts a comparison between the expression of multimodal machine learning and multimodal neuromorphic computing, followed by an overview of the key characteristics associated with multimodal neuromorphic devices. The bio-plausible operational principles and the multimodal learning abilities of emerging devices are examined, which are classified into heterogeneous and homogeneous multimodal neuromorphic devices. Subsequently, this work provides a detailed description of the multimodal learning capabilities demonstrated by neuromorphic circuits and their respective applications. Finally, this work highlights the limitations and challenges of multimodal neuromorphic computing in order to hopefully provide insight into potential future research directions.

13.
Sci Total Environ ; 952: 175874, 2024 Nov 20.
Article in English | MEDLINE | ID: mdl-39218112

ABSTRACT

The substantial generation of textile waste (TW) and red mud (RM) has resulted in significant resource wastage and environmental challenges. Co-utilization technology of solid waste is an effective approach to improve waste utilization efficiency. In this study, RM catalytic pyrolysis experiments of TW were conducted using TG-FTIR and Py-GC-MS for liquid fuel production, and TW and RM were recycled simultaneously. At the optimal experimental conditions (temperature of 600 °C and feed catalyst ratio of 2:1), the tar yield and higher heating value (HHV) of TW pyrolysis catalyzed by RM were 73.43 wt% and 32.34 kJ/g, respectively. Additionally, experiments on the pyrolysis of various TW types revealed that LDPE and PP are suitable for tar production, while cotton, nylon, and PET are more suitable as feedstock for syngas production. The RM catalytic pyrolysis mechanism of textile waste is that Fe2O3 in RM exhibits significant catalytic activity in enhancing tar and syngas yields. However, during the catalytic process, Fe2O3 undergoes reduction to Fe3O4, resulting in diminished catalytic performance of the RM. After five cycles of use, the RM essentially lost its catalytic activity due to the accumulation of char and tar. All experimental findings of this study could offer an effective guideline for TW recycle and promoting RM utilization toward the waste-to-energy circular economy.

14.
Int J Biol Macromol ; 279(Pt 2): 135234, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39218189

ABSTRACT

The mechanisms by which low light accelerates starch macromolecules degradation by auxin and gibberellin (GA) in geophytes during sprouting remain largely unknown. This study investigated these mechanisms in saffron, grown under low light (50 µmol m-2 s-1) and optimal light (200 µmol m-2 s-1) during the sprouting phase. Low light reduced starch concentration in corms by 34.0 % and increased significantly sucrose levels in corms, leaves, and leaf sheaths by 19.2 %, 9.8 %, and 134.5 %, respectively. This was associated with a 33.3 % increase in GA3 level and enhanced auxin signaling. Leaves synthesized IAA under low light, which was transported to the corms to promote GA synthesis, facilitating starch degradation through a 228.7 % increase in amylase activity. Exogenous applications of GA and IAA, as well as the use of their synthesis or transport inhibitors, confirmed the synergistic role of these phytohormones in starch metabolism. The unigenes associated with GA biosynthesis and auxin signaling were upregulated under low light, highlighting the IAA-GA module role in starch degradation. Moreover, increased respiration rate and invertase activity, crucial for ATP biosynthesis and the tricarboxylic acid cycle, were consistent with the upregulation of related unigenes, suggesting that auxin signaling accelerates starch degradation by promoting energy metabolism. Upregulated of auxin signaling (CsSAUR32) and starch metabolism (CsSnRK1) genes under low light suggests that auxin directly regulate starch degradation in saffron corms. This study elucidates that low light modulates auxin and GA interactions to accelerate starch degradation in saffron corms during sprouting, offering insights for optimizing agricultural practices under suboptimal light conditions.

15.
Nat Commun ; 15(1): 7704, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39231978

ABSTRACT

Emergent superconductivity at the LaAlO3/KTaO3 interfaces exhibits a mysterious dependence on the KTaO3 crystallographic orientations. Here by soft X-ray angle-resolved photoemission spectroscopy, we directly resolve the electronic structure of the LaAlO3/KTaO3 interfacial superconductors and the non-superconducting counterpart. We find that the mobile electrons that contribute to the interfacial superconductivity show strong k⊥ dispersion. Comparing the superconducting and non-superconducting interfaces, the quasi-three-dimensional electron gas with over 5.5 nm spatial distribution ubiquitously exists and shows similar orbital occupations. The signature of electron-phonon coupling is observed and intriguingly dependent on the interfacial orientations. Remarkably, the stronger electron-phonon coupling signature correlates with the higher superconducting transition temperature. Our observations help scrutinize the theories on the orientation-dependent superconductivity and offer a plausible and straightforward explanation. The interfacial orientation effect that can modify the electron-phonon coupling strength over several nanometers sheds light on the applications of oxide interfaces in general.

16.
Angew Chem Int Ed Engl ; : e202412459, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39261278

ABSTRACT

Inherently chiral calixarenes have garnered significant attention due to their distinctive properties, yet the development of efficient catalytic asymmetric synthesis methods remains a critical challenge. Herein, we report the asymmetric synthesis of calix[4]arenes featuring inherent or both inherent and axial chirality via a cobalt-catalyzed C-H activation/annulation strategy in high yield with excellent enantio- and diastereoselectivity (up to > 99% ee and > 20:1 dr). Electrooxidation was also suitable for this transformation to obviate the sacrificial metal oxidants, underscoring the environmentally friendly potential of this approach. A key octahedral cobaltacycle intermediate was synthesized and characterized, providing valuable insights into the mode of enantio- and diastereocontrol of this protocol. Noteworthy photoluminescence quantum yields of up to 0.94 were measured, underscoring the potential of these compounds in the domain of organic fluorescent materials.

17.
Front Endocrinol (Lausanne) ; 15: 1446714, 2024.
Article in English | MEDLINE | ID: mdl-39301321

ABSTRACT

Background: Stress hyperglycemia is now more common in intensive care unit (ICU) patients and is strongly associated with poor prognosis. Whether this association exists in critically ill patients with cardiogenic shock (CS) is unknown. This study investigated the prognostic relationship of stress hyperglycemia on critically ill patients with CS. Methods: We included 393 critically ill patients with CS from the MIMIC IV database in this study and categorized the patients into four groups based on quartiles of Stress hyperglycemia ratio (SHR). We assessed the correlation between SHR and mortality using restricted cubic spline analysis and Cox proportional hazards models. The primary outcomes observed were ICU mortality and hospitalization mortality. Results: The mean age of the entire study population was 68 years, of which 30% were male (118 cases). There was no significant difference between the four groups in terms of age, gender, BMI, and vital signs (P>0.05). There was an increasing trend in the levels of lactate (lac), white blood cell count (WBC), glutamic oxaloacetic transaminase (AST), glucose and Hemoglobin A1C (HbA1c) from group Q1 to group Q2, with the greatest change in patients in group Q4 (P<0.05) and the patients in group Q4 had the highest use of mechanical ventilation, the longest duration of mechanical ventilation, ICU stay and hospital stay. After adjusting for confounders, SHR was found to be strongly associated with patient ICU mortality, showing a U-shaped relationship. Conclusion: In critically ill patients with CS, stress hyperglycemia assessed by SHR was significantly associated with patient ICU mortality.


Subject(s)
Critical Illness , Hyperglycemia , Shock, Cardiogenic , Humans , Shock, Cardiogenic/mortality , Shock, Cardiogenic/blood , Shock, Cardiogenic/etiology , Male , Female , Critical Illness/mortality , Hyperglycemia/mortality , Hyperglycemia/blood , Hyperglycemia/complications , Aged , Prognosis , Middle Aged , Intensive Care Units/statistics & numerical data , Hospital Mortality , Blood Glucose/analysis , Blood Glucose/metabolism , Stress, Physiological
18.
ACS Appl Mater Interfaces ; 16(37): 49533-49543, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39250706

ABSTRACT

Under purely inorganic conditions, a synthesis route was devised wherein elements were introduced stepwise via coprecipitation based on differences in compound solubility. This synthesis method can change the microscopic morphology of the material without relying on a templating agent, resulting in the formation of the multilayered lamellar Ce/Eu codoped zinc oxide solid solution (ZCEOSS) with a self-assembled nested imbrication structure. The study improves the critical matter of corrosion by focusing on the electron and energy transfer mechanisms. By introduction of the bandgap modulator cerium element and fluorescence enhancer europium element into the ZnO material, the anticorrosion material has been successfully endowed with both photocathodic protection and luminescent initiative/stress dual corrosion defense functions. Due to the energy level staircase protection mechanism synergistically generated by the 4f electron shell of rare-earth elements in concert with semiconductor zinc oxide, the energy band positions were modulated to progressively guide the direction of electron flow, thereby suppressing corrosion reactions. In particular, the ZCEOSS material synthesized by doping 1% cerium and 7% europium and adding rare-earth elements at pH 7 exhibited the best corrosion inhibition performance. After immersion in simulated seawater for 96 h, Tafel polarization test results showed that compared to epoxy resin and ZnO anticorrosion systems, the ZCEOSS anticorrosion system exhibited significantly improved corrosion inhibition efficiency with enhancements of 1028.3 and 402.9%, respectively. This study provides new insights into the development of highly efficient inorganic anticorrosion materials.

19.
Plant Divers ; 46(5): 585-599, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39290880

ABSTRACT

China is a hotspot of relict plant species that were once widespread throughout the Northern Hemisphere. Recent research has demonstrated that the occurrence of long-term stable refugia in the mountainous regions of central and south-western China allowed their persistence through the late Neogene climate fluctuations. One of these relict lineages is Dipteronia, an oligotypic tree genus with a fossil record extending to the Paleocene. Here, we investigated the genetic variability, demographic dynamics and diversification patterns of the two currently recognized Dipteronia species (D ipteronia sinensis and D . dyeriana). Molecular data were obtained from 45 populations of Dipteronia by genotyping three cpDNA regions, two single copy nuclear genes and 15 simple sequence repeat loci. The genetic study was combined with niche comparison analyses on the environmental space, ecological niche modeling, and landscape connectivity analysis. We found that the two Dipteronia species have highly diverged both in genetic and ecological terms. Despite the incipient speciation processes that can be observed in D. sinensis, the occurrence of long-term stable refugia and, particularly, a dispersal corridor along Daba Shan-west Qinling, likely ensured its genetic and ecological integrity to date. Our study will not only help us to understand how populations of Dipteronia species responded to the tectonic and climatic changes of the Cenozoic, but also provide insight into how Arcto-Tertiary relict plants in East Asia survived, evolved, and diversified.

20.
Lung Cancer ; 196: 107959, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39340898

ABSTRACT

BACKGROUND: Small-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. Limited-stage (LS)-SCLC comprises only one-third of SCLC cases, resulting in limited molecularly targeted therapies and treatment options. Despite advances in thoracic and cranial irradiation leading to improved outcomes, a notable proportion of patients develop brain metastasis (BM), highlighting the importance of identifying high-risk patients for tailored screening and treatment strategies. MATERIALS AND METHODS: We analyzed baseline tumor biopsies from 180 LS-SCLC patients who received frontline definitive chemoradiotherapy (dCRT) using a 474-gene pan-cancer panel. The cumulative incidence of BM was calculated with death scored as a competing risk. Independent prognostic factors for BM risk were identified using the Fine-Gray model. RESULTS: Alterations in the cell cycle pathway, particularly RB1 mutations, were more common in patients with BM, while FLT4 mutations were more frequent in those without BM (P=0.002 and P=0.021, respectively). Significant risk factors for BM include smoking (subdistribution hazard ratio [SHR]: 1.73; 95 % confidence interval [CI]: 1.11-2.70; P=0.016), RB1 mutations (SHR: 2.19; 95 % CI: 1.27-3.81; P=0.005), and BCL3 amplification (SHR: 2.27; 95 % CI: 1.09-4.71; P=0.028). Conversely, prophylactic cranial irradiation (PCI) (SHR: 0.39; 95 % CI: 0.25-1.60; P<0.001), FLT4 mutations (SHR: 0.26; 95 % CI: 0.07-0.98; P=0.047), and NOTCH pathway alterations (SHR: 0.65; 95 % CI: 0.43-1.00; P=0.049) were associated with a lower incidence of BM in LS-SCLC. Notably, consolidation PCI therapy did not reduce the BM risk in patients with baseline RB1 mutations, with BM occurrence probabilities of 34.7 % at 20 months and 62.6 % at 40 months. CONCLUSION: Our study yields valuable insights into the genetic characteristics of LS-SCLC patients with and without BM, aiding the development of personalized treatment strategies. Identifying risk factors associated with the incidence and timing of BM, within the standard regimen of dCRT followed by PCI, may help optimize clinical decision-making for LS-SCLC.

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