The existence of spontaneous magnetization in low dimensional magnetic systems has attracted intensive studies since the early 60s and research remains very active even now. Only recently, magnetic ...van der Waals (vdW) systems down to a few layers have been broadly discussed for their magnetic order ground states at finite temperature. The naturally inherited layered structure of the vdW magnetic systems possessing onsite magnetic anisotropy from band electrons can suppress the long‐range fluctuations. This provides an excellent vehicle to study the transition of magnetism to 2D limits both theoretically and experimentally. Here the current status of 2D vdW magnetic system and its potential applications are briefly summarized and discussed.
Recently, magnetic van der Waals (vdW) systems down to the single layer limit have been studied intensively. Herein, the current status of 2D vdW magnetic systems is summarized from both a theoretical and an experimental point of view. The fundamental physics of 2D magnetism are discussed, along with the future outlook and potential applications of 2D vdW magnetic systems.
Cancer metastasis leading to the dysfunction of invaded organs is the main cause of the reduced survival rates in lung cancer patients. However, the molecular mechanism for lung cancer metastasis ...remains unclear. Recently, the increased activity of inflammasome appeared to correlate with the metastatic progression and immunosuppressive ability of various cancer types. Our results showed that the mRNA levels of absence in melanoma 2 (AIM2), one of the inflammasome members, are extensively upregulated in primary tumors compared with normal tissues derived from the TCGA lung adenocarcinoma (LUAD) database. Moreover, Kaplan‐Meier analysis demonstrated that a higher mRNA level of AIM2 refers to a poor prognosis in LUAD patients. Particularly, AIM2 upregulation is closely correlated with smoking history and the absence of EGFR/KRAS/ALK mutations in LUAD. We further showed that the endogenous mRNA levels of AIM2 are causally associated with the metastatic potentials of the tested LUAD cell lines. AIM2 knockdown suppressed but overexpression promoted the migration ability and lung colony–forming ability of tested LUAD cells. In addition, we found that AIM2 upregulation is closely associated with an increased level of immune checkpoint gene set, as well as programmed cell death‐ligand 1 (PD‐L1) transcript, in TCGA LUAD samples. AIM2 knockdown predominantly repressed but overexpression enhanced PD‐L1 expression via altering the activity of PD‐L1 transcriptional regulators NF‐κB/STAT1 in LUAD cells. Our results not only provide a possible mechanism underlying the AIM2‐promoted metastatic progression and immune evasion of LUAD but also offer a new strategy for combating metastatic/immunosuppressive LUAD via targeting AIM2 activity.
The illustration of a possible mechanism for the AIM2‐fostered EMT progression and PD‐L1 expression in the metastatic/immunosuppressive lung adenocarcinoma. AIM2 increases PD‐L1 expression via activating its transcriptional regulators NF‐kB/STAT1.
Curcumin is a natural compound of Curcuma longa L. and has shown many pharmacological activities such as anti-inflammatory, anti-oxidant in both preclinical and clinical studies. Moreover, curcumin ...has hepatoprotective, neuroprotective activities and protects against myocardial infarction. Particularly, curcumin has also demonstrated favorite anticancer efficacy. But limiting factors such as its extremely low oral bioavailability hampers its application as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. This review described the main physicochemical properties of curcumin and summarized the recent studies in the design and development of oral delivery systems for curcumin to enhance the solubility and oral bioavailability, including liposomes, nanoparticles and polymeric micelles, phospholipid complexes, and microemulsions.
Radioresistance and lymph node metastasis are common phenotypes of refractory oral squamous cell carcinoma (OSCC). As a result, understanding the mechanism for radioresistance and metastatic ...progression is urgently needed for the precise management of refractory OSCC. Recently, immunotherapies, e.g. immune checkpoint inhibitors (ICIs), were employed to treat refractory OSCC; however, the lack of predictive biomarkers still limited their therapeutic effectiveness.
The Cancer Genome Atlas (TCGA)/Gene Expression Omnibus (GEO) databases and RT-PCR analysis were used to determine absent in melanoma 2 (AIM2) expression in OSCC samples. Colony-forming assay and trans-well cultivation was established for estimating AIM2 function in modulating the irradiation resistance and migration ability of OSCC cells, respectively. RT-PCR, Western blot and flow-cytometric analyses were performed to examine AIM2 effects on the expression of programmed death-ligand 1 (PD-L1) expression. Luciferase-based reporter assay and site-directed mutagenesis were employed to determine the transcriptional regulatory activity of Signal Transducer and Activator of Transcription 1 (STAT1) and NF-κB towards the AIM2-triggered PD-L1 expression.
Here, we found that AIM2 is extensively upregulated in primary tumors compared to the normal adjacent tissues and acts as a poor prognostic marker in OSCC. AIM2 knockdown mitigated, but overexpression promoted, radioresistance, migration and PD-L1 expression via modulating the activity of STAT1/NF-κB in OSCC cell variants. AIM2 upregulation significantly predicted a favorable response in patients receiving ICI treatments.
Our data unveil AIM2 as a critical factor for promoting radioresistance, metastasis and PD-L1 expression and as a potential biomarker for predicting ICI effectiveness on the refractory OSCC.
Radiotherapy is the first-line regimen for treating oral squamous cell carcinoma (OSCC) in current clinics. However, the development of therapeutic resistance impacts the anticancer efficacy of ...irradiation in a subpopulation of OSCC patients. As a result, discovering a valuable biomarker to predict radiotherapeutic effectiveness and uncovering the molecular mechanism for radioresistance are clinical issues in OSCC.
Three OSCC cohorts from The Cancer Genome Atlas (TCGA), GSE42743 dataset and Taipei Medical University Biobank were enrolled to examine the transcriptional levels and prognostic significance of neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8). Gene set enrichment analysis (GSEA) was utilized to predict the critical pathways underlying radioresistance in OSCC. The colony-forming assay was used to estimate the consequences of irradiation sensitivity after the inhibition or activation of the NEDD8-autophagy axis in OSCC cells.
NEDD8 upregulation was extensively found in primary tumors compared to normal adjacent tissues and potentially served as a predictive marker for the therapeutic effectiveness of irradiation in OSCC patients. NEDD8 knockdown enhanced radiosensitivity but NEDD8 overexpression reduced it in OSCC cell lines. The inclusion of MLN4924, a pharmaceutical inhibitor for NEDD8-activating enzyme, dose-dependently restored the cellular sensitivity to irradiation treatment in irradiation-insensitive OSCC cells. Computational simulation by GSEA software and cell-based analyses revealed that NEDD8 upregulation suppresses Akt/mTOR activity to initiate autophagy formation and ultimately confers radioresistance to OSCC cells.
These findings not only identify NEDD8 as a valuable biomarker to predict the efficacy of irradiation but also offer a novel strategy to overcome radioresistance via targeting NEDD8-mediated protein neddylation in OSCC.
Since chemotherapy is a main strategy to treat triple-negative breast cancer (TNBC) patients currently, identifying a biomarker to predict chemotherapeutic responses is urgently needed for patients ...to avoid suffering through unnecessary chemotherapeutic treatments. Here, we found that the endogenous expression of
TNFSF13
in a panel of TNBC cell lines highly correlates with paclitaxel (PTX) and doxorubicin IC
50
concentrations. Whereas knocking down
TNFSF13
enhances PTX effectiveness in PTX-insensitive MDA-MB231 cells, recombinant TNFSF13 (recTNFSF13) desensitizes PTX-sensitive HCC1806 cells to PTX treatment. Moreover, Kaplan-Meier analysis revealed that higher TNFSF13 mRNA expression significantly predicts an increased risk for cancer recurrence in estrogen receptor (ER)-negative breast cancer patients receiving an anthracycline-based treatment. Accordingly, immunohistochemistry experiments indicated that higher levels of TNFSF13 protein are detected in TNBC patients who do not respond to an anthracycline-based treatment. The in silico analysis and Western blotting demonstrated that
TNFSF13
expression inversely associates with the activity of the Akt-mTOR pathway, which acts as a negative regulator of autophagy activity. Significantly, the pharmaceutical inhibition of autophagy activity restores the therapeutic effectiveness of PTX in TNFSF13-treated HCC1806 cells. These findings suggest that TNFSF13 can serve as a predictive biomarker for TNBC patients, who can use it to decide whether to receive chemotherapy.
Key messages
TNFSF13 upregulation correlates with a poor response to chemotherapy in TNBCs.
TNFSF13 promotes autophagy initiation in chemotherapeutic resistant TNBCs.
Therapeutic targeting of autophagy initiation overcomes the TNFSF13-related chemoresistance.
TNFSF13 could be a predictive biomarker for TNBC patients receiving chemotherapy.
The frequency chirp of the directly modulated lasers (DML) has long been regarded as the performance barrier preventing the DML from being employed in high-speed optical transmissions. In contrast, ...we regard the chirp as the combination of intensity modulation (IM) and frequency modulation in this paper. By utilizing coherent detection which provides a wavelength reference by the local oscillator, FM can be converted to phase modulation via time integral. Namely, we realize a 2 dimensional complex modulation (CM) using a single DML. The channel of a complex modulation of directly modulated lasers (CM-DML) is convolutional due to the integral operation. The maximum likelihood sequence estimation can be applied for demodulation. CM-DML offers more than 10-dB system OSNR sensitivity advantages over the conventional IM-DML using coherent detection, which shrinks the sensitivity penalty to <;6 dB compared to the QPSK at 7% FEC threshold. Using CM-DML, we experimentally demonstrate the first dual polarization (DP) PAM-4 signal over >1000-km transmission of the standard single mode fiber. This reach record of the optical PAM reveals the great potentials of the CM-DML to replace the commercialized DP-QPSK products for medium reach applications.
Radiotherapy is commonly used to treat oral cancer patients in the current clinics; however, a subpopulation of patients shows poor radiosensitivity. Therefore, the aim of this study is to identify a ...biomarker or druggable target to enhance the effectiveness of radiotherapy on oral cancer patients. By performing an in silico analysis against public databases, we found that the upregulation of FOXD1, a gene encoding forkhead box d1 (Foxd1), is extensively detected in primary tumors compared to normal tissues and associated with a poor outcome in oral cancer patients receiving irradiation treatment. Moreover, our data showed that the level of FOXD1 transcript is causally relevant to the effective dosage of irradiation in a panel of oral cancer cell lines. The FOXD1 knockdown (FOXD1-KD) dramatically suppressed the colony-forming ability of oral cancer cells after irradiation treatment. Differentially expressed genes analysis showed that G3BP2, a negative regulator of p53, is predominantly repressed after FOXD1-KD and transcriptionally regulated by Foxd1, as judged by a luciferase-based promoter assay in oral cancer cells. Gene set enrichment analysis significantly predicted the inhibition of E2F-related signaling pathway but the activation of the interferons (IFNs) and p53-associated cellular functions, which were further validated by luciferase reporter assays in the FOXD1-KD oral cancer cells. Robustly, our data showed that FOXD1-KD fosters the expression of TXNIP, a downstream effector of IFN signaling and activator of p53, in oral cancer cells. These findings suggest that FOXD1 targeting might potentiate the anti-cancer effectiveness of radiotherapy and promote immune surveillance on oral cancer.
Objective
Japanese encephalitis (JE) is a critical problem of public health worldwide; however, there is limited data about the clinical features and indicators of outcome in adults with severe ...Japanese encephalitis.
Methods
The clinical manifestations and laboratory study on brain neuroimaging of patients with severe JE were statistically analyzed retrospectively. All patients were followed up for 6 months after discharge. The patients were grouped into good outcome and poor outcome according to the results of the follow-up.
Results
This retrospective study consists of 9 adults with severe JE, including 5 cases with poor outcome, defined as the modified Rankin Scale (mRS) scores of greater than or equal to 4 points, and remained ventilator dependent. Typical clinical manifestations of JE include fever (100%), altered consciousness (100%), headache (66.7%), flaccid weakness (66.7%), and status epilepticus (44.4%). Serological examination revealed that a higher percentage of neutrophils and a lower percentage of lymphocytes at admission may be associated with a poor outcome. Abnormal neuroimaging of the thalamus (85.7%), hippocampal (71.4%), midbrain (28.6%), and basal ganglia (14.3%) was found. 42.9% of patients left severe irreversible disability, and the most prominent were mental symptoms (71.4%) and memory or understanding disorder (57.1%).
Conclusion
Our data suggest that respiratory failure is one of the important causes of early death. Serologic examination, coma, and status epilepticus may indicate a poor outcome for severe JE. Additionally, the hippocampus is the second most common lesion in the adults with severe JE. A large-scale clinical trial is required to further confirm these conclusions.
Glioblastoma multiforme (GBM) is the most aggressive brain tumor and has a poor prognosis and is poorly sensitive to radiotherapy or temozolomide (TMZ) chemotherapy. Therefore, identifying new ...biomarkers to predict therapeutic responses of GBM is urgently needed. By using The Cancer Genome Atlas (TCGA) database, we found that the upregulation of histone 2A family member J (H2AFJ), but not other H2AFs, is extensively detected in the therapeutic-insensitive mesenchymal, IDH wildtype, MGMT unmethylated, or non-G-CIMP GBM and is associated with poor TMZ responsiveness independent of radiation. Similar views were also found in GBM cell lines. Whereas H2AFJ knockdown diminished TMZ resistance, H2AFJ overexpression promoted TMZ resistance in a panel of GBM cell lines. Gene set enrichment analysis (GSEA) revealed that H2AFJ upregulation accompanied by the activation of TNF-α/NF-κB and IL-6/STAT3-related pathways is highly predicted. Luciferase-based promoter activity assay further validated that the activities of NF-κB and STAT3 are causally affected by H2AFJ expression in GBM cells. Moreover, we found that therapeutic targeting HADC3 by tacedinaline or NF-κB by ML029 is likely able to overcome the TMZ resistance in GBM cells with H2AFJ upregulation. Significantly, the GBM cohorts harboring a high-level H2AFJ transcript combined with high-level expression of TNF-α/NF-κB geneset, IL-6/STAT3 geneset or HADC3 were associated with a shorter time to tumor repopulation after initial treatment with TMZ. These findings not only provide H2AFJ as a biomarker to predict TMZ therapeutic effectiveness but also suggest a new strategy to combat TMZ-insensitive GBM by targeting the interaction network constructed by TNF-α/NF-κB, IL-6/STAT3, HDAC3, and H2AFJ.
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