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1.
Aging (Albany NY) ; 162024 Jul 26.
Article in English | MEDLINE | ID: mdl-39068670

ABSTRACT

BACKGROUND: The expression patterns and prognostic value of Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family genes in breast cancer remain to be elucidated. METHODS: The expression levels, prognostic value, and biological function of PLODs were determined using Oncomine, cBioPortal, GEPIA, Timer, UALCAN, PrognoScan, GeneMANIA, Metascape, and breast cancer tissue microarrays. RESULTS: The expressions of PLOD1 and PLOD3 were upregulated in breast cancer tissues, indicating worse clinical stages. High expression levels of PLOD family genes were associated with worse disease-free survival and distant metastasis-free survival, while high expression levels of PLOD1 and PLOD3 were related to worse overall survival in all breast cancer patients. The levels of PLOD family genes were all significantly higher in the age ≤51 y group, HR-negative patients, and triple negative breast cancer (TNBC) patients. They are associated with tumor-infiltrating immune cells (TIICs), including CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells. According to co-expression gene analysis and functional enrichment, they are associated with protein hydroxylation, collagen biosynthesis and modifying enzymes, collagen metabolism, RNA splicing, extracellular matrix organization, VEGFA-VEGFR2 signaling pathway, and skeletal system development. Immunohistochemistry showed that the expressions of all PLOD family genes were significantly elevated in breast cancer tissues. PLOD1 expression was positively correlated with ER, TNBC status, and tumor grade. PLOD2 expression was positively connected with Ki-67 status. PLOD3 expression was positively related with age and tumor grade. CONCLUSIONS: PLOD family genes are novel potential prognostic biomarkers for breast cancer, and targeting PLOD inhibitors might be an effective strategy for breast cancer therapy.

2.
J Colloid Interface Sci ; 676: 927-936, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39068837

ABSTRACT

Large-scale durable aqueous zinc ion batteries for stationary storage are realized by spray-coating conductive PEDOT(Poly(3,4-ethylenedioxythiophene)) wrapping MnO2/carbon microspheres hybrid cathode in this work. The porous carbon microspheres with multiple layers deriving from sucrose provide suitable accommodation for MnO2 active materials, exposing more redox active sites and enhancing the contact surface between electrolyte and active materials. As a result, MnO2/microspheres are adhered to the current collector by a conductive PEDOT coating without any binder. The ternary design retards the structural degradation during cycling and shortens the electron and ion transport path, rendering the full batteries high capacity and long cycle stability. The resulting batteries perform the capacity of 277, 227, 110, 85 and 50 mAh/g at 0.2, 0.5, 1, 2 and 5 A/g, respectively. After 3000 cycles the initial capacity retains 86%, and 80% after 5000 cycles. GITT indicates PEDOT wrapping MnO2/microspheres cathode enables better ion intercalating kinetics than conventional MnO2. The work could represent a novel and significant step forward in the studies on the large-scale application of zinc ion batteries.

3.
Plant Physiol Biochem ; 214: 108969, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39068877

ABSTRACT

Quercus aliena, a native Chinese tree species, is significant in industry and landscaping. However, it is traditionally propagated by seeds with many limitations, such as pest infestations, seed yield and quality. Thus, this study firstly introduces a somatic embryogenesis (SE) system for Q. aliena, enhancing its cultivation prospects. Thereinto, the development stage of zygotic embryo had a significant effect on SE, only immature embryos in 10-11 weeks after full bloom (WAF), rich in endogenous abscisic acid (ABA), could induce SE. Exogenous application ABA had positive roles in the early development process of both primary and secondary SE, while its antagonist had opposite roles. Transcriptome analysis showed that transcription regulation occupied the major position. Mfuzz cluster and WGCNA co-expression analysis showed that 24 candidate genes were involved in the SE process. The expression of the 24 genes were also affected by exogenous ABA signals, among which QaLEC2, QaCALS11 and QaSSRP1 occupied the important roles. Additionally, the callose content were also affected by exogenous ABA signals, which had significantly positive correlations with the expression of QaLEC2 and QaCALS11. This study not only established an efficient reproduction system for Q. aliena, but also revealed the difference in embryogenic ability of zygotic embryos from the aspects of transcriptome and endogenous hormone content, and lay a foundation for clarifying the molecular mechanism of SE, and provided a reference for exploring the vital roles of ABA in SE.

4.
Cell Mol Neurobiol ; 44(1): 57, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060759

ABSTRACT

Optogenetics, a revolutionary technique integrating optical and genetic methodologies, offers unparalleled precision in spatial targeting and temporal resolution for cellular control. This approach enables the selective manipulation of specific neuronal populations, inducing subtle electrical changes that significantly impact complex neural circuitry. As optogenetics precisely targets and modulates neuronal activity, it holds the potential for significant breakthroughs in understanding and potentially altering the course of neurodegenerative diseases, characterized by selective neuronal loss leading to functional deficits within the nervous system. The integration of optogenetics into neurodegenerative disease research has significantly advanced in the field, offering new insights and paving the way for innovative treatment strategies. Its application in clinical settings, although still in the nascent stages, suggests a promising future for addressing some of the most challenging aspects of neurodegenerative disorders. In this review, we provide a comprehensive overview of these research undertakings.


Subject(s)
Neurodegenerative Diseases , Optogenetics , Optogenetics/methods , Humans , Neurodegenerative Diseases/therapy , Neurodegenerative Diseases/genetics , Animals , Neurons/metabolism
5.
BMC Oral Health ; 24(1): 848, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060994

ABSTRACT

BACKGROUND: Worldwide, dental caries is a bacterial biofilm-mediated condition with a high morbidity in children and adolescents. Flavonoids are a class of active natural products with antibacterial and anti-inflammatory effect. In vivo and in vitro studies have shown that they can promote tooth mineralization and reduce inflammation. However, the association of flavonoids intake and dental caries in children and adolescents remain unclear. AIM: This study was to evaluated the association of flavonoid and its subclass intake and dental caries in children and adolescents. METHODS: Data of participants aged 2-17 years were extracted from the National Health and Nutrition Examination Survey (NHANES) database (2017-2018). Dental caries was measured via the decayed or filled surfaces in primary teeth or permanent teeth (dfs/DFS) index. The weighted univariable and multivariable logistic regression models were utilized to explore the association of flavonoids intake with dental caries in children and adolescents, with odds ratios (ORs) with 95% confidence intervals (CIs). Subgroups analyses based on age, and overweight/obesity were further assessed the association. Subgroup analysis were further performed to explore whether the association between subclasses of anthocyanidins and catechins with dental caries was robust stratified by age and individual with overweight/obesity. RESULTS: Among totally 1,818 children and adolescents, 786 (43.2%) had dental caries. High intake of anthocyanidins (OR=0.69, 95%CI: 0.52-0.92) and catechins (OR=0.64, 95%CI: 0.44-0.92) were associated with lower odds of dental caries. Similar results were discovered in individuals aged ≥6 years (anthocyanidins, OR=0.62, 95%CI: 0.43-0.90; catechins, OR=0.62, 95%CI: 0.40-0.96), and without overweight/obesity (anthocyanidins, OR=0.58, 95%CI: 0.37-0.90; catechins, OR=0.51, 95%CI: 0.31-0.84). Further investigation found that high intake of cyanidin, petunidin, malvidin, peonidin, (+)-Catechin, (-)-Epigallocatechin, and (-)-epicatechin were associated with lower odds of dental caries in children and adolescents. CONCLUSION: High intake of anthocyanidins and catechins were associated with lower odds of dental caries in children and adolescents and are a promising intervention to be further explored in children and adolescents.


Subject(s)
Dental Caries , Flavonoids , Nutrition Surveys , Humans , Adolescent , Child , Dental Caries/prevention & control , Dental Caries/epidemiology , Cross-Sectional Studies , Male , Female , Child, Preschool , United States/epidemiology , Databases, Factual
6.
Animals (Basel) ; 14(14)2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39061522

ABSTRACT

For mammary carcinomas in pet rabbits, prognostic biomarkers are poorly defined, and treatment is limited to surgical excision. Additional treatment options are needed for rabbit patients for which surgery is not a suitable option. In human breast cancer, the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) represents a prognostic biomarker and possible therapeutic target. This retrospective immunohistochemical study examined IDO1 in 96 pet rabbit mammary carcinomas with known mitotic count, hormone receptor status, and percentage of stromal tumor infiltrating lymphocytes (TILs). Tumors were obtained from 96 pet rabbits with an average of 5.5 years. All rabbits with reported sex (n = 88) were female or female-spayed. Of the carcinomas, 94% expressed IDO1, and 86% had sparse TILs consistent with cold tumors. Statistically significant correlations existed between a higher percentage of IDO1-positive tumor cells, lower mitotic counts, and increased estrogen receptor expression. The threshold for significance was IDO1 staining in >10% of tumor cells. These results lead to the assumption that IDO1 expression contributes to tumorigenesis and may represent a prognostic biomarker and possible therapeutic target also in pet rabbit mammary carcinomas. They also support the value of rabbits for breast cancer research.

7.
Animals (Basel) ; 14(14)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39061534

ABSTRACT

To survive in low-oxygen environments, yaks effectively avoid hypoxia-induced pulmonary arterial hypertension through vascular remodeling. The TGF-ß/BMP signaling pathway plays a key role in maintaining the homeostasis of pulmonary artery smooth muscle cells (PASMCs). However, little is known about the molecular regulatory mechanisms by which the TGF-ß/BMP signaling pathway contributes to the proliferation of yak PASMCs. In this study, yak PASMCs were cultured in vitro, and a hypoxia model was constructed to investigate the effect of TGFß/BMP signaling on yak PASMC proliferation. Hypoxia treatment increased the proliferation of yak PASMCs significantly. As the duration of hypoxia increased, the expression levels of TGF-ß1 and the phosphorylation levels of Smad2/3 were upregulated significantly. The BMP signaling pathway was transiently activated by hypoxia, with increases in BMPR2 expression and Smad1/5 phosphorylation, and these changes were gradually reversed with prolonged hypoxia exposure. In addition, exogenous TGF-ß1 activated the TGF-ß signaling pathway, increased the phosphorylation levels of the downstream proteins Smad2 and Smad3, and increased the proliferation and migration rates of yak PASMCs significantly. Finally, treatment with noggin (an inhibitor of BMP signaling) significantly reduced BMPR2 protein expression levels and Smad1/5 phosphorylation levels and increased yak PASMC proliferation and migration rates. In summary, these results revealed that under hypoxic conditions, the dynamic regulation of the TGF-ß/BMP signaling pathway promotes the proliferation of yak PASMCs.

8.
Dev Biol ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39067502

ABSTRACT

Germ cells mutant for bam or bgcn are locked in a germline stem cell (GSC)-like state, leading to tumor-like overgrowth in Drosophila ovaries. Our previous studies have demonstrated that germline overgrowth in bam mutants can be suppressed by defects in the miRNA pathway but enhanced by a null mutation in hippo. However, the genetic epistasis between the miRNA and Hippo pathways still remains unknown. Here, we determined that the miRNA pathway acts downstream of the Hippo pathway in regulating this process. Germ cells mutant for bam or bgcn and defective in both pathways divide very slowly, phenocopying those defective only in the miRNA pathway. In addition, we found that Yki, a key oncoprotein in the Hippo pathway, promotes the growth of both wild-type germ cells and bam mutant GSC-like cells. Like wild-type GSCs, bam mutant GSC-like cells predominantly stay in the G2 phase. Remarkably, many of those defective in the miRNA pathway are arrested before entering this phase. Furthermore, our studies identified bantam as a critical miRNA promoting germline overgrowth in bam or bgcn mutants. Taken together, these findings establish a genetic circuitry controlling Drosophila female germline overgrowth.

9.
FASEB J ; 38(14): e23830, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39072875

ABSTRACT

Hepatocyte nuclear factor 4 alpha (HNF4α) and the pregnane X receptor (PXR) are involved in hepatocyte regeneration. It is not clear whether HNF4α is involved in hepatocyte regeneration through the regulation of PXR. This study aims to explore the regulatory relationship between HNF4a and PXR, and whether it affects hepatocyte regeneration. A mouse PXR gene reporter and an HNF4α overexpression plasmid were constructed and transfected into mouse hepatoma cells (Hepa1-6). Overexpression of HNF4α, detection of the PXR gene reporter fluorescence value, PXR gene, and protein expression analysis were conducted to explore the regulatory relationship between HNF4α and PXR. Apoptosis and cell cycle data were measured to verify whether HNF4α is involved in hepatocyte regeneration through PXR. The luciferase gene reporter assay results indicated when HNF4α was overexpressed, the fluorescence value of the PXR gene reporter was higher than that in the control at 24 h. With increasing HNF4α expression, the PXR gene and protein expression increased, indicating that HNF4α binds to the PXR promoter and upregulates PXR expression. Apoptosis and cell cycle analysis results demonstrated that when the expression of HNF4α increased, the expression of PXR increased, the apoptosis rate decreased, and the proliferation rate increased. Meanwhile, when the upward trend of PXR gene expression was inhibited by ketoconazole, the proliferation rate decreased. By inhibiting HNF4α and creating a partial hepatectomy (PHx), we demonstrated that HNF4α can upregulate PXR to promote liver regeneration in vivo. Therefore, HNF4α is shown to improve hepatocyte regeneration by upregulating PXR, which provides a reference for future research on the combined application of drugs for the treatment of liver injury.


Subject(s)
Apoptosis , Hepatocyte Nuclear Factor 4 , Hepatocytes , Pregnane X Receptor , Up-Regulation , Hepatocyte Nuclear Factor 4/metabolism , Hepatocyte Nuclear Factor 4/genetics , Animals , Hepatocytes/metabolism , Pregnane X Receptor/metabolism , Pregnane X Receptor/genetics , Mice , Liver Regeneration/genetics , Cell Line, Tumor , Receptors, Steroid/metabolism , Receptors, Steroid/genetics , Promoter Regions, Genetic
10.
Clin Respir J ; 18(7): e13792, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39072902

ABSTRACT

OBJECTIVE: To evaluate the predictive value of echo features of radial probe endobronchial ultrasound (RP-EBUS) in the differential diagnosis of malignant and benign 1esions. METHODS: The clinical data of 336 patients with peripheral pulmonary lesions (PPLs) undergoing RP-EBUS were analyzed in order to evaluate the predictive value of the three EBUS echo features including continuous margin, absence of a linear-discrete air bronchogram, and heterogeneous in pulmonary lesions. The sensitivity and specificity for each echoic feature or in combination in diagnosing malignancy or benignity were determined. RESULTS: 336 cases of PPLs including 216 cases of malignant lesions and 120 cases of benign lesions. The sensitivity and specificity of the continuous margin to the diagnosis of malignant lesions were 86.11% and 17.50%. The sensitivity and specificity of the absence of a linear-discrete air bronchogram to the diagnosis of malignant lesions were 66.67% and 57.50%, and the positive predictive value was 73.85%. The sensitivity and specificity of heterogeneity to the diagnosis of malignant lesions were 65.28% and 72.50%, and the positive predictive value was 81.03%. The combination of heterogeneous and absence of a linear-discrete air bronchogram could improve the diagnostic specificity to 87.50%, and the positive predictive value to 80.77%. CONCLUSION: The two EBUS echo features of heterogeneous and absence of a linear-discrete air bronchogram have predictive value for PPLs, especially in the presence of two features the pulmonary lesions should be highly suspected malignant tumors.


Subject(s)
Bronchoscopy , Endosonography , Lung Neoplasms , Sensitivity and Specificity , Humans , Male , Female , Middle Aged , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Aged , Endosonography/methods , Diagnosis, Differential , Bronchoscopy/methods , Adult , Retrospective Studies , Predictive Value of Tests , Lung/diagnostic imaging , Lung/pathology , Aged, 80 and over
11.
Foods ; 13(14)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39063347

ABSTRACT

To enhance the selenium (Se) intake of the general public, the present study implemented biofortification techniques in alfalfa sprouts. Alfalfa sprouts possess unique nutritional value and provide an optimal Se-enriched supplemental Se source. The impact of sodium selenite (Na2SeO3) on alfalfa shoot germination, shoot length, and biomass was assessed experimentally, and changes in the antioxidant capacity of sprouts treated with optimal Se concentrations were investigated. In addition, the transcriptome of alfalfa sprouts treated with the optimal Na2SeO3 concentration was sequenced. Gene co-expression networks, constructed through differential gene analysis and weighted gene co-expression network analysis, were used to identify the core genes responsible for Se enrichment in alfalfa sprouts. The findings of the present study offer novel insights into the effects of Se treatment on the nutrient composition of alfalfa sprouts, in addition to introducing novel methods and references that could facilitate production of Se-enriched alfalfa sprouts and associated products.

12.
Entropy (Basel) ; 26(7)2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39056952

ABSTRACT

While collecting training data, even with the manual verification of experts from crowdsourcing platforms, eliminating incorrect annotations (noisy labels) completely is difficult and expensive. In dealing with datasets that contain noisy labels, over-parameterized deep neural networks (DNNs) tend to overfit, leading to poor generalization and classification performance. As a result, noisy label learning (NLL) has received significant attention in recent years. Existing research shows that although DNNs eventually fit all training data, they first prioritize fitting clean samples, then gradually overfit to noisy samples. Mainstream methods utilize this characteristic to divide training data but face two issues: class imbalance in the segmented data subsets and the optimization conflict between unsupervised contrastive representation learning and supervised learning. To address these issues, we propose a Balanced Partitioning and Training framework with Pseudo-Label Relaxed contrastive loss called BPT-PLR, which includes two crucial processes: a balanced partitioning process with a two-dimensional Gaussian mixture model (BP-GMM) and a semi-supervised oversampling training process with a pseudo-label relaxed contrastive loss (SSO-PLR). The former utilizes both semantic feature information and model prediction results to identify noisy labels, introducing a balancing strategy to maintain class balance in the divided subsets as much as possible. The latter adopts the latest pseudo-label relaxed contrastive loss to replace unsupervised contrastive loss, reducing optimization conflicts between semi-supervised and unsupervised contrastive losses to improve performance. We validate the effectiveness of BPT-PLR on four benchmark datasets in the NLL field: CIFAR-10/100, Animal-10N, and Clothing1M. Extensive experiments comparing with state-of-the-art methods demonstrate that BPT-PLR can achieve optimal or near-optimal performance.

13.
Forensic Sci Int Genet ; 73: 103094, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39059037

ABSTRACT

The use of genetic data for timber species and population assignment is a powerful tool for combating the illegal timber trade, but the challenges of extracting DNA from timber have prevented the routine use of genetics as a supply chain management tool. To overcome these challenges, we explored the feasibility of focused ultrasound extraction (FUSE) for rapid DNA release from timber. Using high-pressure ultrasound pulses, FUSE generates a cavitation bubble cloud that disintegrates samples into acellular debris, resulting in the mechanical release of DNA. In this work, FUSE was applied to white oak (Quercus alba) timber shavings to test the feasibility of using FUSE for timber DNA extraction for the first time. Results showed that FUSE processing disintegrated the tissue samples and released significant quantities of DNA. After five minutes of tissue processing DNA quantities of 0.21 ± 0.02 ng/mg, 0.99 ± 0.32 ng/mg, and 0.14 ± 0.01 ng/mg, were released from medium, coarse, and combination shaving groups, respectively. Amplification and sequencing of regions within the matK and rbcL chloroplast genes confirmed that the quality of DNA prepared with FUSE was suitable for PCR and short-read sequencing applications. Overall, these results show that FUSE can serve as a DNA sample preparation method capable of releasing high-quality DNA from timber in a fraction of the time required by conventional extraction methods. Based on the improved efficiency of DNA release with FUSE, ongoing work aims to develop this technology into portable systems that can be used to rapidly prepare timber samples for genetic species identification.

14.
Toxicon ; 247: 107857, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-38996976

ABSTRACT

Fluoride is a double-edged sword. It was widely used for early caries prevention while excessive intake caused a toxicology effect, affected enamel development, and resulted in dental fluorosis. The study aimed to evaluate the protective effect and mechanism of Epigallocatechin-3-gallate (EGCG) on the apoptosis induced by fluoride in ameloblast-like cells. We observed that NaF triggered apoptotic alterations in cell morphology, excessive NaF arrested cell cycle at the G1, and induced apoptosis by up-regulating Bax and down-regulating Bcl-2. NaF activated the insulin-like growth factor receptor (IGFR), and phosphatidylinositol-3-hydroxylase (p-PI3K), while dose-dependently down-regulating the expression of Forkhead box O1 (FoxO1). EGCG supplements reversed the changes in LS8 morphology, the cell cycle, and apoptosis induced by fluoride. These results indicated that EGCG possesses a protective effect against fluoride toxicity. Furthermore, EGCG suppressed the activation of p-PI3K and the down-regulation of FoxO1 caused by fluoride. Collectively, our findings suggested that EGCG attenuated fluoride-induced apoptosis by inhibiting the PI3K/FoxO1 signaling pathway. EGCG may serve as a new alternative method for dental fluorosis prevention, control, and treatment.


Subject(s)
Ameloblasts , Apoptosis , Catechin , Fluorides , Phosphatidylinositol 3-Kinases , Signal Transduction , Catechin/analogs & derivatives , Catechin/pharmacology , Apoptosis/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Animals , Fluorides/toxicity , Fluorides/pharmacology , Ameloblasts/drug effects , Ameloblasts/metabolism , Signal Transduction/drug effects , Forkhead Box Protein O1/metabolism , Cell Line , Mice , Sodium Fluoride/toxicity , Fluorosis, Dental
15.
J Chromatogr A ; 1730: 465168, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39018739

ABSTRACT

In recent years, some insects have become foods due to their high nutritional value. In order to solve the problem of the lack of quality control methods for insect foods, this study proposes a comprehensive control model using silkworm chrysalis (SC) as an example. Firstly, five-wavelength mean fusion fingerprints (FWMFF) and UV quantum fingerprints of 21 batches of SC were established. And the 21 batches of SC were classified into different grades from different perspectives by using the comprehensive linear quantified fingerprint method (CLQFM) as a quality evaluation method for qualitative and quantitative analysis. Secondly, this paper fully considered the issue of the reliability of fingerprint evaluation, which guaranteed the accuracy of the evaluation results. On this basis, the antioxidant capacity of the samples was used in vitro 1,1-Diphenyl-2-picrylhydrazylradical (DPPH) scavenging assay using IC50. The relationship between fingerprints and antioxidant activity was also discussed. Finally, the content of endogenous neurotransmitter (ACh) in SC determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in the range of 0.25-2.11µg/g. Overall, the present study proposes a comprehensive quality control strategy for functional foods based on the quality assessment of SC.


Subject(s)
Acetylcholine , Antioxidants , Bombyx , Quality Control , Tandem Mass Spectrometry , Animals , Antioxidants/analysis , Antioxidants/chemistry , Bombyx/chemistry , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Acetylcholine/analysis , Acetylcholine/chemistry , Reproducibility of Results
16.
Int J Cancer ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958227

ABSTRACT

In patients with non-small cell lung cancer (NSCLC), oncogenic variants present in <5% of cases are considered rare, the predominant of which include human epidermal growth factor receptor 2 (HER2) mutations, mesenchymal-epithelial transition (MET) alterations, c-ros oncogene 1 (ROS1) rearrangements, rearrangement during transfection (RET) fusions, v-raf mouse sarcoma virus oncogene homolog B1 (BRAF) mutations, and neurotrophic troponin receptor kinase (NTRK) fusions. Brain metastases (BMs) occur in approximately 10%-50% of patients with NSCLC harboring rare genetic variants. The recent advent of small-molecule tyrosine kinase inhibitors and macromolecular antibody-drug conjugates (ADCs) has conferred marked survival benefits to patients with NSCLC harboring rare driver alterations. Despite effective brain lesion control for most targeted agents and promising reports of intracranial remission associated with novel ADCs, BM continues to be a major therapeutic challenge. This review discusses the recent advances in the treatment of NSCLC with rare genetic variants and BM, with a particular focus on intracranial efficacy, and explores future perspectives on how best to treat these patients.

17.
Opt Lett ; 49(13): 3636-3639, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950228

ABSTRACT

We report a 20-W-level acetylene-filled nested hollow-core anti-resonant fiber (nested HC-ARF) amplified spontaneous emission (ASE) source at 3.1 µm. A 1535 nm hundred-watt wavelength tunable single-frequency fiber laser with a high signal-to-noise ratio and narrow linewidth is built for pumping acetylene molecules. Simultaneously, a homemade 120 µm core diameter eight-tube nested HC-ARF is used as a gas chamber to obtain high pump laser coupling efficiency. The mid-infrared (mid-IR) ASE source output power of 21.8 W is achieved at 3.1 µm through the low-pressure acetylene gas-filled nested HC-ARF, and the slope efficiency is 25.1%. In addition, the ASE source features an excellent beam quality of Mx 2 = 1.16 and My 2 = 1.13. To the best of our knowledge, for the first time, it is a record output power for such mid-infrared ASE sources while maintaining excellent beam quality. This work provides a new way to achieve high-power mid-infrared emission.

18.
Sci Rep ; 14(1): 15139, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956423

ABSTRACT

Mineral element accumulation in plants is influenced by soil conditions and varietal factors. We investigated the dynamic accumulation of 12 elements in straw at the flowering stage and in grains at the mature stage in eight rice varieties with different genetic backgrounds (Japonica, Indica, and admixture) and flowering times (early, middle, and late) grown in soil with various pH levels. In straw, Cd, As, Mn, Zn, Ca, Mg, and Cu accumulation was influenced by both soil pH and varietal factors, whereas P, Mo, and K accumulation was influenced by pH, and Fe and Ni accumulation was affected by varietal factors. In grains, Cd, As, Mn, Cu, Ni, Mo, Ca, and Mg accumulation was influenced by both pH and varietal factors, whereas Zn, Fe, and P accumulation was affected by varietal factors, and K accumulation was not altered. Only As, Mn, Ca and Mg showed similar trends in the straw and grains, whereas the pH responses of Zn, P, K, and Ni differed between them. pH and flowering time had synergistic effects on Cd, Zn, and Mn in straw and on Cd, Ni, Mo, and Mn in grains. Soil pH is a major factor influencing mineral uptake in rice straw and grains, and genetic factors, flowering stage factors, and their interaction with soil pH contribute in a combined manner.


Subject(s)
Minerals , Oryza , Soil , Oryza/genetics , Oryza/metabolism , Soil/chemistry , Hydrogen-Ion Concentration , Minerals/metabolism , Minerals/analysis , Genetic Background , Edible Grain/metabolism , Edible Grain/genetics
19.
Heliyon ; 10(12): e32619, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38952379

ABSTRACT

Purpose: It is difficult to differentiate between primary central nervous system lymphoma and primary glioblastoma due to their similar MRI findings. This study aimed to assess whether pharmacokinetic parameters derived from dynamic contrast-enhanced MRI could provide valuable insights for differentiation. Methods: Seventeen cases of primary central nervous system lymphoma and twenty-one cases of glioblastoma as confirmed by pathology, were retrospectively analyzed. Pharmacokinetic parameters, including Ktrans, Kep, Ve, and the initial area under the Gd concentration curve, were measured from the enhancing tumor parenchyma, peritumoral parenchyma, and contralateral normal parenchyma. Statistical comparisons were made using Mann-Whitney U tests for Ve and Matrix Metallopeptidase-2, while independent samples t-tests were used to compare pharmacokinetic parameters in the mentioned regions and pathological indicators of enhancing tumor parenchyma, such as vascular endothelial growth factor and microvessel density. The pharmacokinetic parameters with statistical differences were evaluated using receiver-operating characteristics analysis. Except for the Wilcoxon rank sum test for Ve, the pharmacokinetic parameters were compared within the enhancing tumor parenchyma, peritumoral parenchyma, and contralateral normal parenchyma of the primary central nervous system lymphomas and glioblastomas using variance analysis and the least-significant difference method. Results: Statistical differences were observed in Ktrans and Kep within the enhancing tumor parenchyma and in Kep within the peritumoral parenchyma between these two tumor types. Differences were also found in Matrix Metallopeptidase-2, vascular endothelial growth factor, and microvessel density within the enhancing tumor parenchyma of these tumors. When compared with the contralateral normal parenchyma, pharmacokinetic parameters within the peritumoral parenchyma and enhancing tumor parenchyma exhibited variations in glioblastoma and primary central nervous system lymphoma, respectively. Moreover, the receiver-operating characteristics analysis showed that the diagnostic efficiency of Kep in the peritumoral parenchyma was notably higher. Conclusion: Pharmacokinetic parameters derived from dynamic contrast-enhanced MRI can differentiate primary central nervous system lymphoma and glioblastoma, especially Kep in the peritumoral parenchyma.

20.
Angew Chem Int Ed Engl ; : e202410710, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949854

ABSTRACT

Metallo-supramolecular cages have garnered tremendous attention for their diverse yet molecular-level precision structures. However, physical properties of these supramolecular ensembles, which are of potential significance in molecular electronics, remain largely unexplored. We herein constructed a series of octahedral metallo-cages and cage-fullerene complexes with notably enhanced structural stability. As such, we could systematically evaluate the electrical conductivity of these ensembles at both single-molecule level and aggregated bulk state (as well-defined films). Our findings reveal that counteranions and fullerene guests play a pivotal role in determining the electrical conductivity of aggregated state, while such effects are less significant for single-molecule conductance. Both counteranions and fullerenes effectively tune the electronic structures and packing density of metallo-supramolecular assemblies, and facilitate efficient charge transfer between the cage hosts and fullerenes, resulting in a notable one order of magnitude increase in electrical conductivity of the aggregated state.

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