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Using global data for around 180 countries and territories and 170 food/feed types primarily derived from FAOSTAT, we have systematically analyzed the changes in greenhouse gas (GHG) emission intensity (GHGi) (kg CO2eq per kg protein production) over the past six decades. We found that, with large spatial heterogeneity, emission intensity decreased by nearly two-thirds from 1961 to 2019, predominantly in the earlier years due to agronomic improvement in productivity. However, in the most recent decade, emission intensity has become stagnant, and in a few countries even showed an increase, due to the rapid increase in livestock production and land use changes. The trade of final produced protein between countries has potentially reduced the global GHGi, especially for countries that are net importers with high GHGi, such as many in Africa and South Asia. Overall, a continuous decline of emission intensity in the future relies on countries with higher emission intensity to increase agricultural productivity and minimize land use changes. Countries with lower emission intensity should reduce livestock production and increase the free trade of agricultural products and improve the trade optimality.
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Agricultura , Gases de Efeito Estufa , Agricultura/métodos , Gases de Efeito Estufa/análise , Carbono/metabolismo , Gado , Animais , Produtos AgrícolasRESUMO
Cysteine desulfhydrase (LCD) catalyzes the generation of the signaling molecule hydrogen sulfide (H2S) in plants. In this study, we found that H2S can inhibit tomato (Solanum lycopersicum) fruit ripening and SlWRKY6 undergoes differential protein persulfidation in SlLCD1-overexpressing leaves. Then, further study indicated that SlWRKY6 could be persulfidated by H2S at Cys396. By construction of slwrky6 mutants and SlWRKY6-OE lines, we found that SlWRKY6 positively regulates leaf senescence and fruit ripening by activating the transcription of ripening-related genes STAYGREEN 1 (SlSGR1) and Senescence-Associated Gene 12 (SlSAG12). In addition, SlWRKY6 interacted with kinase SlMAPK4 and was phosphorylated at Ser33. Dual luciferase transient expression assays and electrophoretic mobility shift assays indicated that SlWRKY6 persulfidation attenuated its transcriptional regulation of target genes SlSGR1 and SlSAG12, whereas SlWRKY6 phosphorylation by SlMAPK4 activated the transcription of target genes to promote fruit ripening. Moreover, we provided evidence that SlWRKY6 persulfidation attenuated its SlMAPK4-mediated phosphorylation to inhibit tomato fruit ripening. By transient expression of SlWRKY6, SlWRKY6C396A, SlWRKY6S33A and SlWRKY6S33D in slwrky6 fruits, we found that SlWRKY6 persulfidation attenuated the expression of SlSGR1 and SlSAG12 thereby delaying tomato fruit ripening, while SlWRKY6 phosphorylation increased the expression of target genes. As tomato fruits ripened, endogenous H2S production decreased, while SlMAPK4 expression increased. Therefore, our findings reveal a model in which SlWRKY6 persulfidation due to higher endogenous H2S levels in un-ripened fruit inhibits its ability to activate SlSGR1 and SlSAG12 expression, while SlWRKY6 phosphorylation by SlMAPK4 activates its transcriptional activity, thereby promoting tomato fruit ripening.
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Transcriptional reprogramming is critical for plant immunity. Several calmodulin (CaM)-binding protein 60 (CBP60) family transcription factors (TFs) in Arabidopsis (Arabidopsis thaliana), including CBP60g, Systemic Acquired Resistance Deficient 1 (SARD1), CBP60a, and CBP60b, are critical for and show distinct roles in immunity. However, there are additional CBP60 members whose function is unclear. We report here that Arabidopsis CBP60c-f, four uncharacterized CBP60 members, play redundant roles with CBP60b in the transcriptional regulation of immunity responses, whose pCBP60b-driven expression compensates the loss of CBP60b. By contrast, neither CBP60g nor SARD1 is inter-changeable with CBP60b, suggesting clade-specific functionalization. We further show that function of CBP60b clade TFs relies on DNA-binding domains (DBDs) and CaM-binding domains, suggesting that they are downstream components of calcium signaling. Importantly, we demonstrate that CBP60s encoded in earliest land plant lineage Physcomitrium patens and Selaginella moellendorffii, are functionally homologous to Arabidopsis CBP60b, suggesting that the CBP60b clade contains the prototype TFs of the CBP60 family. Furthermore, tomato and cucumber CBP60b-like genes rescue the defects of Arabidopsis cbp60b and activate the expression of tomato and cucumber SALICYLIC ACID INDUCTION DEFICIIENT2 (SID2) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) genes, suggesting that immune response pathways centered on CBP60b are also evolutionarily conserved. Together, these findings suggest CBP60b clade transcription factors are functionally conserved in evolution and positively mediate immunity.
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BACKGROUND: Triple-negative breast cancers display heterogeneity in molecular drivers and immune traits. We previously classified triple-negative breast cancers into four subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). Here, we aimed to evaluate the efficacy and safety of subtyping-based therapy in the first-line treatment of triple-negative breast cancer. METHODS: FUTURE-SUPER is an ongoing, open-label, randomised, controlled phase 2 trial being conducted at Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Eligible participants were females aged 18-70 years, with an Eastern Cooperative Oncology Group performance status of 0-1, and histologically confirmed, untreated metastatic or recurrent triple-negative breast cancer. After categorising participants into five cohorts according to molecular subtype and genomic biomarkers, participants were randomly assigned (1:1) with a block size of 4, stratified by subtype, to receive, in 28-day cycles, nab-paclitaxel (100 mg/m2, intravenously on days 1, 8, and 15) alone (control group) or with a subtyping-based regimen (subtyping-based group): pyrotinib (400 mg orally daily) for the LAR-HER2mut subtype, everolimus (10 mg orally daily) for the LAR-PI3K/AKTmut and MES-PI3K/AKTmut subtypes, camrelizumab (200 mg intravenously on days 1 and 15) and famitinib (20 mg orally daily) for the immunomodulatory subtype, and bevacizumab (10 mg/kg intravenously on days 1 and 15) for the BLIS/MES-PI3K/AKTWT subtype. The primary endpoint was investigator-assessed progression-free survival for the pooled subtyping-based group versus the control group in the intention-to-treat population (all randomly assigned participants). Safety was analysed in all patients with safety records who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT04395989). FINDINGS: Between July 28, 2020, and Oct 16, 2022, 139 female participants were enrolled and randomly assigned to the subtyping-based group (n=69) or control group (n=70). At the data cutoff (May 31, 2023), the median follow-up was 22·5 months (IQR 15·2-29·0). Median progression-free survival was significantly longer in the pooled subtyping-based group (11·3 months [95% CI 8·6-15·2]) than in the control group (5·8 months [4·0-6·7]; hazard ratio 0·44 [95% CI 0·30-0·65]; p<0·0001). The most common grade 3-4 treatment-related adverse events were neutropenia (21 [30%] of 69 in the pooled subtyping-based group vs 16 [23%] of 70 in the control group), anaemia (five [7%] vs none), and increased alanine aminotransferase (four [6%] vs one [1%]). Treatment-related serious adverse events were reported for seven (10%) of 69 patients in the subtyping-based group and none in the control group. No treatment-related deaths were reported in either group. INTERPRETATION: These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway. FUNDING: National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Shanghai Hospital Development Center, and Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , China , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Epstein-Barr virus (EBV) is detected in nearly 100% of nonkeratinizing nasopharyngeal carcinoma (NPC) and EBV-based biomarkers are used for NPC screening in endemic regions. Immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA), and recently identified anti-BNLF2b antibodies have been shown to be the most effective screening tool; however, the screening efficacy still needs to be improved. This study developed a multiplex serological assay by testing IgA and immunoglobulin G (IgG) antibodies against representative EBV antigens that are highly transcribed in NPC and/or function crucially in viral reactivation, including BALFs, BNLF2a/b, LF1, LF2, and Zta (BZLF1). Among them, BNLF2b-IgG had the best performance distinguishing NPC patients from controls (area under the curve: 0.951, 95% confidence interval [CI]: 0.913-0.990). Antibodies to lytic antigens BALF2 and VCA were significantly higher in advanced-stage than in early-stage tumors; in contrast, antibodies to latent protein EBNA1 and early lytic antigen BNLF2b were not correlated with tumor progression. Accordingly, a novel strategy combining EBNA1-IgA and BNLF2b-IgG was proposed and validated improving the integrated discrimination by 15.8% (95% CI: 9.8%-21.7%, p < .0001) compared with the two-antibody method. Furthermore, we found EBV antibody profile in patients was more complicated compared with that in healthy carriers, in which stronger correlations between antibodies against different phases of antigens were observed. Overall, our serological assay indicated that aberrant latent infection of EBV in nasopharyngeal epithelial cells was probably a key step in NPC initiation, while more lytic protein expression might be involved in NPC progression.
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Recent studies have highlighted the pivotal roles of T cell transcription factors TCF-1 and TOX in modulating the immune response in cancer, with TCF-1 maintaining CD8+ T cell stemness and TOX promoting T cell exhaustion. The prognostic significance of these factors in lung adenocarcinoma (LUAD) remains a critical area of investigation. The retrospective study included 191 patients with LUAD who underwent surgery, of whom 83% were in stages II and III. These patients were divided into exploratory (n = 135) and validation (n = 56) groups based on the time of diagnosis. Multiplex fluorescence immunohistochemistry was used to examine the infiltration levels of CD8+ T cells, TCF1+ CD8+ T cells, and TOX+ CD8+ T cells. The percentage of CD8+ T cells in tumor was markedly lower than that in stroma (p < 0.05). In tumor-draining lymph nodes (TDLNs) invaded by tumor, the proportion of stem-like TCF1+ CD8+ T cells was significantly decreased (p < 0.01). Importantly, higher infiltration levels of CD8+ T cells and TCF1+ CD8+ T cells were associated with improved disease-free survival (DFS) (p = 0.009 and p = 0.006, respectively) and overall survival (OS) (p = 0.018 and p = 0.010, respectively). This study underscores the potential of TCF1+ CD8+ T cells as prognostic biomarkers in LUAD, providing insights into the tumor immune microenvironment and guiding future therapeutic strategies.
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Adenocarcinoma de Pulmão , Linfócitos T CD8-Positivos , Fator 1-alfa Nuclear de Hepatócito , Neoplasias Pulmonares , Linfócitos do Interstício Tumoral , Humanos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Feminino , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Masculino , Pessoa de Meia-Idade , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Idoso , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Estudos Retrospectivos , Microambiente Tumoral/imunologia , Intervalo Livre de Doença , Proteínas de Grupo de Alta Mobilidade/metabolismo , TransativadoresRESUMO
Pleiotropy is frequently detected in agronomic traits of wheat (Triticum aestivum). A locus on chromosome 4B, QTn/Ptn/Sl/Sns/Al/Tgw/Gl/Gw.caas-4B, proved to show pleiotropic effects on tiller, spike, and grain traits using a recombinant inbred line (RIL) population of Qingxinmai × 041133. The allele from Qingxinmai increased tiller numbers, and the allele from line 041133 produced better performances of spike traits and grain traits. Another 52 QTL for the eight traits investigated were detected on 18 chromosomes, except for chromosomes 5D, 6D, and 7B. Several genes in the genomic interval of the locus on chromosome 4B were differentially expressed in crown and inflorescence samples between Qingxinmai and line 041133. The development of the KASP marker specific for the locus on chromosome 4B is useful for molecular marker-assisted selection in wheat breeding.
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Alelos , Cromossomos de Plantas , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Fenótipo , Pleiotropia Genética , Melhoramento VegetalRESUMO
The interfacial 2D/3D perovskite heterostructures have attracted extensive attention due to their unique ability to combine the high stability of 2D perovskites with the remarkable efficiency of 3D perovskites. However, the carrier transport mechanism within the 2D/3D perovskite heterostructures remains unclear. In this study, the carrier transport dynamics in 2D/3D perovskite heterostructures through a variety of time-resolved spectroscopic measurements is systematically investigated. Time-resolved photoluminescence results reveal nanosecond hole transfer from the 3D to 2D perovskites, with enhanced efficiency through the introduction of fluorine atoms on the phenethylammonium (PEA) cation. Transient absorption measurements unveil the ultrafast picosecond electron and energy transfer from 2D to 3D perovskites. Furthermore, it is demonstrated that the positioning of fluorination on the PEA cations effectively regulates the efficiency of charge and energy transfer within the heterostructures. These insightful findings shed light on the underlying carrier transport mechanism and underscore the critical role of cation fluorination in optimizing carrier transport within 2D/3D perovskite heterostructure-based devices.
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The directional conversion of methane to ethylene is challenging due to the dissociation of the CâH bond and the self-coupling of methyl intermediates. Herein, a novel W/WO3- x catalyst with the fork vein structure consisting of an alternating arrangement of WO3- x and W is developed. Impressively, the catalyst achieves an unprecedented C2H4 yield of 1822.73 µmol g-1 h-1, with a selectivity of 82.49%. The enhanced catalytic activity is ascribed to the multifunctional synergistic effect induced by oxygen vacancies and W sites in W/WO3- x. Oxygen vacancies provide abundant coordination of unsaturation sites, which promotes the adsorption and activation of CH4, thus reducing the dissociation energy barrier of the CâH bond. The CH2 coupling barrier on the metal W surface is significantly lower compared to WO3, so CH2 can migrate to the W site for coupling. Importantly, the W/WO3- x with high periodicity provides multiple ordered local microelectric fields, and CH2 intermediates with dipole moments undergo orientation polarization and displacement polarization driven by the electric field, thus enabling CH2 migration. This work opens a new avenue for the structural design and modulation of photocatalysts, and provides new perspectives on the migration of methylene between multiple active sites.
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Strong near-field enhancements (NFEs) of nanophotonic structures are believed to be closely related to high Purcell factors (FP). Here, we theoretically show that the correlation is partially correct; the extinction cross section (σ) response is also critical in determining FP. The divergence between NFE and FP is especially pronounced in plasmonic-dielectric hybrid systems, where the plasmonic antenna supports dipolar plasmon modes and the dielectric cavity hosts Mie-like resonances. The cavity's enhanced-field environment can boost the antenna's NFEs, but the FP is not increased concurrently due to the larger effective σ that is intrinsic to the FP calculations. Interestingly, the peak FP for the coupled system can be predicted by using the NFE and σ responses. Furthermore, the limits for FP of coupled systems are considered; they are determined by the sum of the FP of a redshifted (or modified, if applicable) antenna and an individual cavity. This contrasts starkly with the behavior of NFE which is closely associated with the multiplicative effects of the NFEs provided by the antenna and the dielectric cavity. The differing behaviors of NFE and FP in hybrid cavities have varied impacts on relevant nanophotonic applications such as fluorescence, Raman scattering and enhanced light-matter interactions.
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BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population. METHODS: A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD. RESULTS: During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD. CONCLUSIONS: Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.
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Glucose , Insuficiência Renal Crônica , Humanos , Incidência , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Triglicerídeos , Glicemia , Fatores de Risco , BiomarcadoresRESUMO
Denitrification, anaerobic ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA) are three competing processes of microbial nitrate reduction that determine the degree of ecosystem nitrogen (N) loss versus recycling. However, the global patterns and drivers of relative contributions of these N cycling processes to soil or sediment nitrate reduction remain unknown, limiting our understanding of the global N balance and management. Here, we compiled a global dataset of 1570 observations from a wide range of terrestrial and aquatic ecosystems. We found that denitrification contributed up to 66.1% of total nitrate reduction globally, being significantly greater in estuarine and coastal ecosystems. Anammox and DNRA could account for 12.7% and 21.2% of total nitrate reduction, respectively. The contribution of denitrification to nitrate reduction increased with longitude, while the contribution of anammox and DNRA decreased. The local environmental factors controlling the relative contributions of the three N cycling processes to nitrate reduction included the concentrations of soil organic carbon, ammonium, nitrate, and ferrous iron. Our results underline the dominant role of denitrification over anammox and DNRA in ecosystem nitrate transformation, which is crucial to improving the current global soil N cycle model and achieving sustainable N management.
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Compostos de Amônio , Nitratos , Nitratos/análise , Ecossistema , Desnitrificação , Carbono , Solo , Nitrogênio , OxirreduçãoRESUMO
Nitrous oxide (N2 O) is a potent greenhouse gas and causes stratospheric ozone depletion. While the emissions of N2 O from soil are widely recognized, recent research has shown that terrestrial plants may also emit N2 O from their leaves under controlled laboratory conditions. However, it is unclear whether foliar N2 O emissions are universal across varying plant taxa, what the global significance of foliar N2 O emissions is, and how the foliage produces N2 O in situ. Here we investigated the abilities of 25 common plant taxa, including trees, shrubs and herbs, to emit N2 O under in situ conditions. Using 15 N isotopic labeling, we demonstrated that the foliage-emitted N2 O was predominantly derived from nitrate. Moreover, by selectively injecting biocide in conjunction with the isolating and back-inoculating of endophytes, we demonstrated that the foliar N2 O emissions were driven by endophytic bacteria. The seasonal N2 O emission rates ranged from 3.2 to 9.2 ng N2 O-N g-1 dried foliage h-1 . Extrapolating these emission rates to global foliar biomass and plant N uptake, we estimated global foliar N2 O emission to be 1.21 and 1.01 Tg N2 O-N year-1 , respectively. These estimates account for 6%-7% of the current global annual N2 O emission of 17 Tg N2 O-N year-1 , indicating that in situ foliar N2 O emission is a universal process for terrestrial plants and contributes significantly to the global N2 O inventory. This finding highlights the importance of measuring foliar N2 O emissions in future studies to enable the accurate assigning of mechanisms and the development of effective mitigation.
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Gases de Efeito Estufa , Plantas , Solo , Atmosfera , Biomassa , Óxido Nitroso/análiseRESUMO
Background: Growing evidence suggests that concurrent ischaemic stroke (IS) exacerbates the prognosis of patients with dilated cardiomyopathy (DCM) and that this effect may be further influenced by sex. However, the exact effect of sex remains unclear. This study aimed to explore the effects of the relevant risk factors on the prognosis of patients with DCM and concurrent IS. Considering the sex differences in DCM, this study further investigated the impact of concurrent IS on the prognosis of men and women with DCM. Methods: A total of 632 patients with DCM enrolled between 2016 and 2021 were included in this study. Clinical data were obtained from medical records, and all participants were followed up in the outpatient clinic or by telephone for at least 1 year. A Cox proportional hazards model and Kaplan-Meier curves were used to evaluate the effects of concurrent IS on the prognosis of patients with DCM. Results: Patients with DCM complicated with IS (DCM-IS) had significantly lower cumulative survival rates than patients with DCM without IS (non-IS) (74.6% vs. 84.2%, χ 2 = 6.85, p = 0.009). Additionally, IS was associated with greater risks of death and heart transplantation (HTx) in men (75.8% vs. 85.1%, χ 2 = 5.02, p = 0.025), but not in women (71.0% vs. 81.5%, χ 2 = 1.91, p = 0.167). Conclusions: This large-scale multicentre prospective cohort study demonstrated a poorer prognosis in patients with concurrent DCM and IS, particularly among men. Patients with DCM should not be overlooked in IS screening, emphasis should be placed on the occurrence of IS in patients with DCM. Early and proactive secondary prevention of cerebrovascular diseases might improve the prognosis of DCM patients. More intervention studies focusing on men with DCM complicated with IS should be prioritised.
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BACKGROUND: Double expression lymphoma (DEL) is a subtype of primary central nervous system lymphoma (PCNSL) that often has a poor prognosis. Currently, there are limited noninvasive ways to detect protein expression. PURPOSE: To detect DEL in PCNSL using multiparametric MRI-based machine learning. STUDY TYPE: Retrospective. POPULATION: Forty PCNSL patients were enrolled in the study among whom 17 were DEL (9 males and 8 females, 61.29 ± 14.14 years) and 23 were non-DEL (14 males and 9 females, 55.57 ± 14.16 years) with 59 lesions (28 DEL and 31 non-DEL). FIELD STRENGTH/SEQUENCE: ADC map derived from DWI (b = 0/1000 s/mm2 ), fast spin echo T2WI, T2FLAIR, and contrast-enhanced T1 weighted imaging (T1CE) were collected at 3.0 T. ASSESSMENT: Two raters manually segmented lesions by ITK-SNAP on ADC, T2WI, T2FLAIR and T1CE. A total of 2234 radiomics features from the tumor segmentation area were extracted. The t-test was conducted to filter the features, and elastic net regression algorithm combined with recursive feature elimination was used to calculate the essential features. Finally, 12 groups with combinations of different sequences were fitted to 6 classifiers, and the optimal models were selected. STATISTICAL TESTS: Continuous variables were assessed by the t-test, while categorical variables were assessed by the non-parametric test. Interclass correlation coefficient tested variables' consistency. Sensitivity, specificity, accuracy F1-score, and area under the curve (AUC) were used to evaluate model performance. RESULTS: DEL status could be identified to varying degrees with 72 models based on radiomics, and model performance could be improved by combining different sequences and classifiers. Both SVMlinear and logistic regression (LR) combined with four sequence group had similar largest AUCmean (0.92 ± 0.09 vs. 0.92 ± 0.05), and SVMlinear was considered as the optimal model in this study since the F1-score of SVMlinear (0.88) was higher than that of LR (0.83). DATA CONCLUSION: Multiparametric MRI-based machine learning is promising in DEL detection. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY STAGE: 2.
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Linfoma , Imageamento por Ressonância Magnética Multiparamétrica , Masculino , Feminino , Humanos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Estudos Retrospectivos , Aprendizado de Máquina , Linfoma/diagnóstico por imagem , Sistema Nervoso Central , Imageamento por Ressonância Magnética/métodosRESUMO
Claudin18.2 (CLDN18.2), due to its high expression in various gastric cancer tissues, is considered an optimal target for antitumor drug molecules. In this study, we obtained the labeled compounds of [125I]I-zolbetuximab using the Iodogen method. Under the optimum labeling conditions, the molar activity of [125I]I-zolbetuximab was 1.75 × 102 GBq/µmol, and the labeling efficiency was more than 99%. The labeled compounds exhibited excellent in vitro stability in both phosphate buffer saline (PBS, pH = 7.4) and fetal bovine serum systems (FBS) (radiochemical purity >90% at 72 h). The uptake percentage of [125I]I-zolbetuximab in MKN45-CLDN18.2 cells is 24.69 ± 0.84% after 6 h. The saturation binding assay and specificity assay further demonstrated the high specificity of [125I]I-zolbetuximab for CLDN18.2. The long retention at the tumor site and rapid metabolic clearance at other organ sites of [125I]I-zolbetuximab were observed in small-animal SPECT-CT imaging. The same trend was also observed in the biodistribution study. Due to the excellent targeting ability of zolbetuximab for CLDN18.2, [125I]I-zolbetuximab exhibits strong specific binding and retention with cells and tumors highly expressing CLDN18.2. However, the balance between mAb's longer cycle time in vivo and targeting binding and retention ability should be intensively considered for using this kind of radiopharmaceutical in the diagnosis and treatment of CLDN18.2-positive gastric cancer.
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Claudinas , Animais , Humanos , Camundongos , Distribuição Tecidual , Linhagem Celular Tumoral , Claudinas/metabolismo , Radioisótopos do Iodo , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/química , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/química , Feminino , Masculino , RatosRESUMO
An unprecedented protocol has been developed for the synthesis of 3,4-heterocycle-fused coumarins from 4-aminocoumarins and aurones through iodine-catalyzed cascade reactions. Dihydropyridine-fused coumarin, pyridine-fused coumarin, and pyrrole-fused coumarin derivatives were achieved in good yields with high selectivity when CH3CN, AcOH, and DMSO were used as the solvent, respectively. This protocol provides several advantages, such as easily available starting materials, high atom economy, friendly environment, and simple procedure.
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An efficient synthetic method for constructing 2,3- and 2,4-disubstituted pyrimidio[1,2-b]indazole skeletons through I2-DMSO-mediated and substrate-controlled regioselective [4 + 2] cyclization is reported. The reaction conditions are mild, its operation is simple, and the substrate scope is wide. More than 60 pyrimidio[1,2-b]indazole derivatives have been synthesized, providing a new methodology for constructing related molecules and potentially enriching bioactive-molecule libraries.
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The electrochemical nitrogen reduction reaction (eNRR) provides a sustainable green development route for the nitrogen-neutral cycle. In this work, bimetallic CoFe-MIL-88A with two active sites (Fe, Co) were immobilized on a 2D V2CTx MXene surface by in situ growth method to achieve the purpose of the control interface. A large number of heterostructures are formed between small CoFe-MIL-88A and V2CTx, which regulate the electron transfer between the catalyst interfaces. The adsorption and activation of nitrogen on the active sites were enhanced, and the NRR reaction kinetics was accelerated. CoFe-MIL-88A is tightly arranged on V2CTx, which makes CoFe-MIL-88A/V2CTx have better hydrophobicity and can significantly inhibit the hydrogen evolution reaction. The synergistic effect of multicatalytic active sites and multi-interface structure of CoFe-MIL-88A/V2CTx MXene is propitious to nitrogen efficiently and stably to convert into ammonia under environmental conditions with superior selectivity and good catalytic activity. The NH3 yield rate is 29.47 µg h-1 mgcat-1 at -0.3 V vs RHE, and the Faradaic efficiency (FE) is 28.86% at -0.1 V vs RHE. The catalytic mechanism was verified to conform to the distal pathway. This work will provide a new way to develop an MXene-based electrocatalyst for eNRR.
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Hybrid copper(I) halides have garnered a significant amount of attention as potential substitutes in luminescence and scintillation applications. Herein, we report the discovery and crystal growth of new zero-dimensional compounds, (C2H8N)3Cu2I5 and (C2H8N)4Cu2Br6. The bromide and iodide have a triclinic structure with space group P1Ì and an orthorhombic structure with space group Pnma, respectively. (C2H8N)3Cu2I5 exhibits cyan emission peaking at 504 nm with a photoluminescence quantum yield (PLQY) of 34.79%, while (C2H8N)4Cu2Br6 shows yellowish-green emission peaking at 537 nm with a PLQY of 38.45%. The temperature-dependent photoluminescence data of both compounds were fitted to theoretical models, revealing that nonradiative intermediate states significantly affect thermal quenching and antiquenching. Electron-phonon interactions, the origin of emission line width broadening and peak shifting, were also investigated via fittings. The scintillation properties of (C2H8N)3Cu2I5 were evaluated, and an X-ray imaging device was successfully fabricated using (C2H8N)3Cu2I5. This work demonstrates the potentiality of copper halides in lighting and X-ray imaging applications.