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1.
Nanoscale ; 16(28): 13687-13693, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38967228

ABSTRACT

Van der Waals heterostructures based on transition metal dichalcogenides (TMDs) have emerged as excellent candidates for next-generation optoelectronics and valleytronics, due to their fascinating physical properties. The understanding and active control of the relaxation dynamics of heterostructures play a crucial role in device design and optimization. Here, we investigate the back-gate modulation of exciton dynamics in a WS2/WSe2 heterostructure by combining time-resolved photoluminescence (TRPL) and transient absorption spectroscopy (TAS) at cryogenic temperatures. We find that the non-radiative relaxation lifetimes of photocarriers in heterostructures can be electrically controlled for samples with different twist-angles, whereas such lifetime tuning is not present in standalone monolayers. We attribute such an observation to doping-controlled competition between interlayer and intralayer recombination pathways in high-quality WS2/WSe2 samples. The simultaneous measurement of TRPL and TAS lifetimes within the same sample provides additional insight into the influence of coexisting excitons and background carriers on the photo-response, and points to the potential of tailoring light-matter interactions in TMD heterostructures.

2.
World J Gastrointest Oncol ; 16(6): 2504-2519, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38994160

ABSTRACT

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

3.
Theor Appl Genet ; 137(8): 190, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39043952

ABSTRACT

KEY MESSAGE: Extensive and comprehensive phenotypic data from a maize RIL population under both low- and normal-Pi treatments were used to conduct QTL mapping. Additionally, we integrated parental resequencing data from the RIL population, GWAS results, and transcriptome data to identify candidate genes associated with low-Pi stress in maize. Phosphorus (Pi) is one of the essential nutrients that greatly affect the maize yield. However, the genes underlying the QTL controlling maize low-Pi response remain largely unknown. In this study, a total of 38 traits at both seedling and maturity stages were evaluated under low- and normal-Pi conditions using a RIL population constructed from X178 (tolerant) and 9782 (sensitive), and most traits varied significantly between low- and normal-Pi treatments. Twenty-nine QTLs specific to low-Pi conditions were identified after excluding those with common intervals under both low- and normal-Pi conditions. Furthermore, 45 additional QTLs were identified based on the index value ((Trait_under_LowPi-Trait_under_NormalPi)/Trait_under_NormalPi) of each trait. These 74 QTLs collectively were classified as Pi-dependent QTLs. Additionally, 39 Pi-dependent QTLs were clustered in nine HotspotQTLs. The Pi-dependent QTL interval contained 19,613 unique genes, 6,999 of which exhibited sequence differences with non-synonymous mutation sites between X178 and 9782. Combined with in silico GWAS results, 277 consistent candidate genes were identified, with 124 genes located within the HotspotQTL intervals. The transcriptome analysis revealed that 21 genes, including the Pi transporter ZmPT7 and the strigolactones pathway-related gene ZmPDR1, exhibited consistent low-Pi stress response patterns across various maize inbred lines or tissues. It is noteworthy that ZmPDR1 in maize roots can be sharply up-regulated by low-Pi stress, suggesting its potential importance as a candidate gene for responding to low-Pi stress through the strigolactones pathway.


Subject(s)
Chromosome Mapping , Phosphorus , Quantitative Trait Loci , Zea mays , Zea mays/genetics , Zea mays/growth & development , Chromosome Mapping/methods , Phosphorus/metabolism , Phenotype , High-Throughput Nucleotide Sequencing , Genes, Plant , Genome, Plant , Gene Expression Regulation, Plant , Computer Simulation
4.
Free Radic Biol Med ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39048340

ABSTRACT

Increasing evidence underscores the pivotal role of ferroptosis in Parkinson's Disease (PD) pathogenesis. Acteoside (ACT) has been reported to possess neuroprotective properties. However, the effects of ACT on ferroptosis and its molecular mechanisms remain unknown. This study aimed to explore whether ACT can regulate ferroptosis in dopaminergic (DA) neurons within both in vitro and in vivo PD models and to elucidate the underlying regulatory mechanisms. PD models were established and treated with various concentrations of ACT. Cell viability assays, Western blot, lipid peroxidation assessments, immunohistochemistry, and transmission electron microscopy were employed to confirm ACT's inhibition of ferroptosis and its protective effect on DA neurons across PD models. Immunofluorescence staining, MitoSOX staining, and confocal laser scanning microscopy further validated ACT's regulation regulatory effects on ferroptosis via the Nrf2-mitophagy pathway. Four animal behavioral tests were used to assess behavioral improvements in PD animals. ACT inhibited ferroptosis in PD models in vitro, as evidenced by increased cell viability, the upregulation of GPX4 and SLC7A11, reduced lipid peroxides, and attenuation of mitochondrial morphological alterations typical of ferroptosis. By activating the Nrf2-mitophagy axis, ACT enhanced mitochondrial integrity and reduced lipid peroxidation, mitigating ferroptosis. These in vitro results were consistent with in vivo findings, where ACT treatment significantly preserved DA neurons, curbed ferroptosis in these cells, and alleviated cognitive and behavioral deficits. This study is the first demonstration of ACT's capability to inhibit neuronal ferroptosis and protect DA neurons, thus alleviating behavioral and cognitive impairments in both in vitro and in vivo PD models. Furthermore, The suppression of ferroptosis by ACT is achieved through the activation of the Nrf2-mitophagy signaling pathway. Our results show that ACT is beneficial for both treating and preventing PD. They also offer novel therapeutic options for treating PD and molecular targets for regulating ferroptosis.

5.
Orthop Surg ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982570

ABSTRACT

BACKGROUND: Osteoporosis is a common metabolic disorder that significantly impacts quality of life in the elderly population. Macrophages play a crucial role in the development of osteoporosis by regulating bone metabolism through cytokine secretion. However, there is a lack of scholarly literature in the field of bibliometrics on this topic. OBJECTIVE: This study provides a detailed analysis of the research focus and knowledge structure of macrophage studies in osteoporosis using bibliometrics. METHODS: The scientific literature on macrophage research in the context of osteoporosis, retrieved from the Web of Science Core Collection (WoSCC) database spanning from January 1999 to December 2023, has been incorporated for bibliometric examination. The data is methodically analyzed and visually represented using analytical and visualization tools including VOSviewer, CiteSpace, Scimago Graphica, the Bibliometrix R package, and Pajek. RESULTS AND CONCLUSIONS: In the last quarter-century, there has been a consistent rise in the quantity of scholarly publications focusing on the relationship between macrophages and osteoporosis, resulting in a total of 1499 research documents. These studies have originated from 45 different countries, with China, South Korea, and the United States being the most prominent contributors, and the United States having the highest frequency of citations. Noteworthy research institutions involved in this field include Shanghai Jiao Tong University, Wonkwang University, Huazhong University of Science and Technology, and Seoul National University. The Journal of Bone and Mineral Research is widely regarded as the premier and most frequently referenced publication in the field. These publications involve the collaboration of 8744 authors, with Lee Myeung Su contributing the most articles, and Takayanagi being the most co-cited author. Key emerging research focal points are encapsulated in keywords such as "mTOR," "BMSCs," "bone regeneration," and "exosome." The relationships between exosome from macrophage sources and those from BMSCs, along with the regulatory role of the mTOR signaling pathway on macrophages, represent crucial directions for future development in this field. This study represents the inaugural comprehensive bibliometric analysis detailing trends and advancements in macrophage research within the osteoporosis domain. It delineates recent frontiers and hotspots, providing valuable insights for researchers in this particular area of study.

6.
Theor Appl Genet ; 137(7): 158, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38864891

ABSTRACT

Examining the connection between P and starch-related signals can help elucidate the balance between nutrients and yield. This study utilized 307 diverse maize inbred lines to conduct multi-year and multi-plot trials, aiming to explore the relationship among P content, starch content, and 100-kernel weight (HKW) of mature grains. A significant negative correlation was found between P content and both starch content and HKW, while starch content showed a positive correlation with HKW. The starch granules in grains with high-P and low-starch content (HPLS) were significantly smaller compared to grains with low-P high-starch content (LPHS). Additionally, mian04185-4 (HPLS) exhibited irregular and loosely packed starch granules. A significant decrease in ZmPHOs genes expression was detected in the HPLS line ZNC442 as compared to the LPHS line SCML0849, while no expression difference was observed in AGPase encoding genes between these two lines. The down-regulated genes in ZNC442 grains were enriched in nucleotide sugar and fatty acid anabolic pathways, while up-regulated genes were enriched in the ABC transporters pathway. An accelerated breakdown of fat as the P content increased was also observed. This implied that HPLS was resulted from elevated lipid decomposition and inadequate carbon sources. The GWAS analysis identified 514 significantly associated genes, out of which 248 were differentially expressed. Zm00001d052392 was found to be significantly associated with P content/HKW, exhibiting high expression in SCML0849 but almost no expression in ZNC442. Overall, these findings suggested new approaches for achieving a P-yield balance through the manipulation of lipid metabolic pathways in grains.


Subject(s)
Phosphorus , Starch , Transcriptome , Zea mays , Zea mays/genetics , Zea mays/metabolism , Starch/metabolism , Phosphorus/metabolism , Edible Grain/genetics , Edible Grain/metabolism , Gene Expression Regulation, Plant , Genome-Wide Association Study , Quantitative Trait Loci , Phenotype
7.
Inorg Chem ; 63(26): 11919-11923, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38870223

ABSTRACT

A yolk-shell Au NPs@carbon porous nanoreactor with an active gold (Au) core and a porous carbon shell has been fabricated and demonstrates excellent high activity and cyclic stability as a heterogeneous catalyst for the three-component coupling reaction of aldehyde, amine, and alkyne. Remarkably, the unique yolk-shell nanostructure can protect gold nanoparticles (Au NPs) from aggregation, allow for efficient mass transport, and benefit substrate enrichment, giving rise to enhanced activity, stability, and recyclability.

8.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38860831

ABSTRACT

Measurement device independent quantum key distribution (MDI QKD) has attracted growing attention for its immunity to attacks at the measurement unit, but its unique structure limits the secret key rate. Utilizing the wavelength division multiplexing (WDM) technique and reducing error rates are effective strategies for enhancing the secret key rate. Reducing error rates often requires active feedback control of wavelengths using precise external references. However, for a multiwavelength laser, employing multiple references to stabilize each wavelength output places stringent demands on these references and significantly increases system complexity. Here, we demonstrate a stable, wavelength-tunable multiwavelength laser with an output wavelength ranging from 1270 to 1610 nm. Through precise temperature control and stable drive current, we passively lock the laser wavelength, achieving remarkable wavelength stability. This significantly reduce the error rate, leading to an almost doubling of the secret key rate compared to previous experiments. Furthermore, the exceptional wavelength stability offered by our multiwavelength laser, combined with the WDM technique, has further boosted the secret key rate of MDI QKD. With a wide wavelength tuning range of 5.1 nm, our multiwavelength laser facilitates flexible operation across multiple dense wavelength division multiplexing channels. Coupled with high wavelength stability and multiple wavelength outputs simultaneously, this laser offers a promising solution for a high-rate MDI QKD system.

10.
Orthop Surg ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38923347

ABSTRACT

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co-cited journal. These publications come from 14,801 authors, with Liu Zong-Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong-Yan having published the most papers. Ronald S. Weinstein was co-cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.

11.
Nanoscale ; 16(22): 10637-10644, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38738309

ABSTRACT

The poor hydrostability of most reported metal-organic frameworks (MOFs) has become a daunting challenge in their practical applications. Recently, MOFs combined with multifunctional polymers can act as a functional platform and exhibit unique catalytic performance; they can not only inherit the outstanding properties of the two components but also offer unique synergistic effects. Herein, an original porous polymer-confined strategy has been developed to prepare a superhydrophobic MOF composite to significantly enhance its moisture or water resistance. The selective nucleation and growth of MOF nanocrystals confined in the pore of PDVB-vim are closely related to the structure-directing and coordination-modulating properties of PDVB-vim. The resultant MOF/PDVB-vim composite not only produces superior superhydrophobicity without significantly disturbing the original features but also exhibits a novel catalytic activity in the Friedel-Crafts alkylation reaction of indoles with trans-ß-nitrostyrene because of the accessible sites and synergistic effects.

12.
Nano Lett ; 24(21): 6286-6295, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38747346

ABSTRACT

Moiré superlattices have become a fertile playground for topological Chern insulators, where the displacement field can tune the quantum geometry and Chern number of the topological band. However, in experiments, displacement field engineering of spontaneous symmetry-breaking Chern bands has not been demonstrated. Here in a rhombohedral trilayer graphene moiré superlattice, we use a thermodynamic probe and transport measurement to monitor the Chern number evolution as a function of the displacement field. At a quarter filling of the moiré band, a novel Chern number of three is unveiled to compete with the well-established number of two upon turning on the electric field and survives when the displacement field is sufficiently strong. The transition can be reconciled by a nematic instability on the Fermi surface due to the pseudomagnetic vector field potentials associated with moiré strain patterns. Our work opens more opportunities to active control of Chern numbers in van der Waals moiré systems.

13.
Arch Virol ; 169(5): 114, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700535

ABSTRACT

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.


Subject(s)
Epstein-Barr Virus Infections , Herpesvirus 4, Human , Stomach Neoplasms , Humans , Stomach Neoplasms/virology , Stomach Neoplasms/pathology , Male , Female , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/mortality , Middle Aged , Herpesvirus 4, Human/genetics , Prognosis , Retrospective Studies , Aged , Adult , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/genetics , Ki-67 Antigen/metabolism , RNA, Viral/genetics , Gastrectomy
14.
Nature ; 630(8016): 346-352, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38811731

ABSTRACT

Vertical three-dimensional integration of two-dimensional (2D) semiconductors holds great promise, as it offers the possibility to scale up logic layers in the z axis1-3. Indeed, vertical complementary field-effect transistors (CFETs) built with such mixed-dimensional heterostructures4,5, as well as hetero-2D layers with different carrier types6-8, have been demonstrated recently. However, so far, the lack of a controllable doping scheme (especially p-doped WSe2 (refs. 9-17) and MoS2 (refs. 11,18-28)) in 2D semiconductors, preferably in a stable and non-destructive manner, has greatly impeded the bottom-up scaling of complementary logic circuitries. Here we show that, by bringing transition metal dichalcogenides, such as MoS2, atop a van der Waals (vdW) antiferromagnetic insulator chromium oxychloride (CrOCl), the carrier polarity in MoS2 can be readily reconfigured from n- to p-type via strong vdW interfacial coupling. The consequential band alignment yields transistors with room-temperature hole mobilities up to approximately 425 cm2 V-1 s-1, on/off ratios reaching 106 and air-stable performance for over one year. Based on this approach, vertically constructed complementary logic, including inverters with 6 vdW layers, NANDs with 14 vdW layers and SRAMs with 14 vdW layers, are further demonstrated. Our findings of polarity-engineered p- and n-type 2D semiconductor channels with and without vdW intercalation are robust and universal to various materials and thus may throw light on future three-dimensional vertically integrated circuits based on 2D logic gates.

15.
Chemosphere ; 361: 142388, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38777202

ABSTRACT

Mycotoxins and pesticides frequently coexist in agricultural commodities on a global scale. The potential transgenerational consequences induced by these substances pose a significant threat to human health. However, there is a lack of data concerning the effects of co-contamination by these chemicals in the F1 generation following parental exposure. This investigation delved into the mixture effects of T-2 toxin (T-2) and epoxiconazole (EPO) on the offspring of zebrafish (Danio rerio). The findings revealed that exposure across generations to a combination of T-2 and EPO resulted in toxicity in the larvae of the F1 generation. This was demonstrated by a significant increase in the levels or activities of malondialdehyde (MDA), thyroxine (T4), Caspase3, and cas9, along with a decrease in the levels of cyp19a, ERα, and ERß. These outcomes suggested that cross-generational exposure to T-2 and EPO in D. rerio disrupted oxidative balance, induced cell apoptosis, and affected the endocrine system. Moreover, these effects were magnified when the F1 generation was continuously exposed to these compounds. Notably, these adverse effects could persist in subsequent generations without additional exposure. This study underscored the potential dangers associated with the simultaneous presence of T-2 and EPO on the development of fish offspring and the resulting environmental hazards to aquatic ecosystems. These findings emphasized the significant health risks posed by cross-generational exposure and highlighted the need for additional legislative measures to address these concerns.


Subject(s)
T-2 Toxin , Triazoles , Zebrafish , Animals , T-2 Toxin/toxicity , Triazoles/toxicity , Water Pollutants, Chemical/toxicity , Larva/drug effects , Female , Apoptosis/drug effects , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Epoxy Compounds
16.
Inorg Chem ; 63(17): 7705-7713, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38620065

ABSTRACT

Herein, three In(III)-based metal-organic frameworks (In-MOFs) with different degrees of interpenetration (DOI), namely In-MOF-1, In-MOF-2, and In-MOF-3, constructed by In3+ and Y-shaped ligands 4,4',4″-s-triazine-2,4,6-triyltribenzoate (H3TATB), are successfully synthesized through the ionothermal/solvothermal method. Subsequently, three novel In-MOFs, including noninterpenetration polycatenation, 2-fold interpenetrated, and 4-fold interpenetrated structure, are employed as the platform for systematically investigating the separation efficiency of CO2/N2, CO2/CH4, and CO2/CH4/N2 mixture gas system. Among them, In-MOF-2 shows the highest CO2 uptake capacities at 298 K and simultaneously possesses the low adsorption enthalpy of CO2 (26.4 kJ/mol at low coverage), a feature desirable for low-energy-cost adsorbent regeneration. The CO2/N2 (v: v = 15/85) selectivity of In-MOF-2 reaches 37.6 (at 298 K and 1 bar), also revealing outstanding selective separation ability from flue gases and purifying natural gas, affording a unique robust separation material as it has moderate DOI and pore size. In-MOF-2 shows exceptional stability and feasibility to achieve reproducibility. Aperture adjustment makes In-MOF-2 a versatile platform for selectively capturing CO2 from flue gases or purifying natural gas.

17.
Bioorg Chem ; 147: 107367, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38626492

ABSTRACT

Lung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. Euphorbia kansui yielded 13-oxyingenol-dodecanoate (13OD), an ingenane-type diterpenoid, which had a strong cytotoxic effect on NSCLC cells. The underlying mechanism and potential target, however, remained unknown. The study found that 13OD effectively inhibited the cell proliferation and colony formation of NSCLC cells (A549 and H460 cells), with less toxicity in normal human lung epithelial BEAS-2B cells. Moreover, 13OD can cause mitochondrial dysfunction, and apoptosis in NSCLC cells. Mechanistically, the transcriptomics results showed that differential genes were mainly enriched in the mTOR and AMPK signaling pathways, which are closely related to cellular autophagy, the related indicators were subsequently validated. Additionally, bafilomycin A1 (Baf A1), an autophagy inhibitor, reversed the mitochondrial damage caused by 13OD. Furthermore, the Omics and Text-based Target Enrichment and Ranking (OTTER) method predicted ULK1 as a potential target of 13OD against NSCLC cells. This hypothesis was further confirmed using molecular docking, the cellular thermal shift assay (CETSA), and Western blot analysis. Remarkably, ULK1 siRNA inhibited 13OD's toxic activity in NSCLC cells. In line with these findings, 13OD was potent and non-toxic in the tumor xenograft model. Our findings suggested a possible mechanism for 13OD's role as a tumor suppressor and laid the groundwork for identifying targets for ingenane-type diterpenoids.


Subject(s)
Autophagy-Related Protein-1 Homolog , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Proliferation/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Structure-Activity Relationship , Autophagy-Related Protein-1 Homolog/metabolism , Autophagy-Related Protein-1 Homolog/antagonists & inhibitors , Molecular Structure , Diterpenes/pharmacology , Diterpenes/chemistry , Apoptosis/drug effects , Animals , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis
18.
Opt Express ; 32(7): 11629-11642, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38571005

ABSTRACT

The perturbation of atmosphere turbulence is a significant challenge in orbital angular momentum shift keying-based free space optical communication (OAM-SK-FSO). In this study, we propose an adaptive optical demodulation system based on deep learning techniques. A conditional convolutional GAN (ccGAN) network is applied to recover the distorted intensity pattern and assign it to its specified class. Compared to existing methods based on convolutional neural networks (CNNs), our network demonstrates powerful capability in recovering the distorted light beam, resulting in a higher recognition accuracy rate under the same conditions. The average recognition accuracy rates are 0.9928, 0.9795 and 0.9490 when the atmospheric refractive index structure constant $C_n^2$ is set at 3 × 10-13, 4.45 × 10-13, 6 × 10-13m-2/3, respectively. The ccGAN network provides a promising potential tool for free space optical communication.

19.
World J Gastrointest Oncol ; 16(2): 273-286, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38425407

ABSTRACT

Advanced hepatocellular carcinoma (HCC) is a severe malignancy that poses a serious threat to human health. Owing to challenges in early diagnosis, most patients lose the opportunity for radical treatment when diagnosed. Nonetheless, recent advancements in cancer immunotherapy provide new directions for the treatment of HCC. For instance, monoclonal antibodies against immune checkpoint inhibitors (ICIs) such as programmed cell death protein 1/death ligand-1 inhibitors and cytotoxic t-lymphocyte associated antigen-4 significantly improved the prognosis of patients with HCC. However, tumor cells can evade the immune system through various mechanisms. With the rapid development of genetic engineering and molecular biology, various new immunotherapies have been used to treat HCC, including ICIs, chimeric antigen receptor T cells, engineered cytokines, and certain cancer vaccines. This review summarizes the current status, research progress, and future directions of different immunotherapy strategies in the treatment of HCC.

20.
ACS Nano ; 18(11): 7989-8001, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38438318

ABSTRACT

A substantial ferroelectric polarization is the key for designing high-performance ferroelectric nonvolatile memories. As a promising candidate system, the BaTiO3/La0.67Sr0.33MnO3 (BTO/LSMO) ferroelectric/ferromagnetic heterostructure has attracted a lot of attention thanks to the merits of high Curie temperature, large spin polarization, and low ferroelectric coercivity. Nevertheless, the BTO/LSMO heterostructure suffers from a moderate FE polarization, primarily due to the quick film-thickness-driven strain relaxation. In response to this challenge, we propose an approach for enhancing the FE properties of BTO films by using a Sr3Al2O6 (SAO) buffering layer to mitigate the interfacial strain relaxation. The continuously tunable strain allows us to illustrate the linear dependence of polarization on epitaxial strain with a large strain-sensitive coefficient of ∼27 µC/cm2 per percent strain. This results in a giant polarization of ∼80 µC/cm2 on the BTO/LSMO interface. Leveraging this large polarization, we achieved a giant tunneling electroresistance (TER) of ∼105 in SAO-buffered Pt/BTO/LSMO ferroelectric tunnel junctions (FTJs). Our research uncovers the fundamental interplay between strain, polarization magnitude, and device performance, such as on/off ratio, thereby advancing the potential of FTJs for next-generation information storage applications.

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