The tumor microenvironment is highly complex, and immune escape is currently considered an important hallmark of cancer, largely contributing to tumor progression and metastasis. Named for their ...capability of killing target cells autonomously, natural killer (NK) cells serve as the main effector cells toward cancer in innate immunity and are highly heterogeneous in the microenvironment. Most current treatment options harnessing the tumor microenvironment focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. The limited success achieved by T cell immunotherapy highlights the importance of developing new-generation immunotherapeutics, for example utilizing previously ignored NK cells. Although tumors also evolve to resist NK cell-induced cytotoxicity, cytokine supplement, blockade of suppressive molecules and genetic engineering of NK cells may overcome such resistance with great promise in both solid and hematological malignancies. In this review, we summarized the fundamental characteristics and recent advances of NK cells within tumor immunometabolic microenvironment, and discussed potential application and limitations of emerging NK cell-based therapeutic strategies in the era of presicion medicine.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Metasurfaces can be used to precisely control polarization state of the scattered light. Here, we present a metasurface-based terahertz device. On the one hand, it serves as a high performance linear ...polarization converter in transmission of over 80% power with weak reflection. It is capable of rotating linear polarization orientation angle with respect to
-axis continuously from -90° to +90° at 0.84 THz. On the other hand, it serves as a circular polarizer. It can transform a linear polarized wave into a circular polarized wave at 2.49 THz. The transmitted and reflected field are both circular polarized with 50% power. The proposed device with dual functionalities can be applied to modulate the polarization state of the signal in THz wireless communication.
Metabolic reprogramming is a hallmark of cancer. However, systematic characterizations of metabolites in triple-negative breast cancer (TNBC) are still lacking. Our study profiled the polar ...metabolome and lipidome in 330 TNBC samples and 149 paired normal breast tissues to construct a large metabolomic atlas of TNBC. Combining with previously established transcriptomic and genomic data of the same cohort, we conducted a comprehensive analysis linking TNBC metabolome to genomics. Our study classified TNBCs into three distinct metabolomic subgroups: C1, characterized by the enrichment of ceramides and fatty acids; C2, featured with the upregulation of metabolites related to oxidation reaction and glycosyl transfer; and C3, having the lowest level of metabolic dysregulation. Based on this newly developed metabolomic dataset, we refined previous TNBC transcriptomic subtypes and identified some crucial subtype-specific metabolites as potential therapeutic targets. The transcriptomic luminal androgen receptor (LAR) subtype overlapped with metabolomic C1 subtype. Experiments on patient-derived organoid and xenograft models indicate that targeting sphingosine-1-phosphate (S1P), an intermediate of the ceramide pathway, is a promising therapy for LAR tumors. Moreover, the transcriptomic basal-like immune-suppressed (BLIS) subtype contained two prognostic metabolomic subgroups (C2 and C3), which could be distinguished through machine-learning methods. We show that N-acetyl-aspartyl-glutamate is a crucial tumor-promoting metabolite and potential therapeutic target for high-risk BLIS tumors. Together, our study reveals the clinical significance of TNBC metabolomics, which can not only optimize the transcriptomic subtyping system, but also suggest novel therapeutic targets. This metabolomic dataset can serve as a useful public resource to promote precision treatment of TNBC.
Tumors are not only aggregates of malignant cells but also well-organized complex ecosystems. The immunological components within tumors, termed the tumor immune microenvironment (TIME), have long ...been shown to be strongly related to tumor development, recurrence and metastasis. However, conventional studies that underestimate the potential value of the spatial architecture of the TIME are unable to completely elucidate its complexity. As innovative high-flux and high-dimensional technologies emerge, researchers can more feasibly and accurately detect and depict the spatial architecture of the TIME. These findings have improved our understanding of the complexity and role of the TIME in tumor biology. In this review, we first epitomized some representative emerging technologies in the study of the spatial architecture of the TIME and categorized the description methods used to characterize these structures. Then, we determined the functions of the spatial architecture of the TIME in tumor biology and the effects of the gradient of extracellular nonspecific chemicals (ENSCs) on the TIME. We also discussed the potential clinical value of our understanding of the spatial architectures of the TIME, as well as current limitations and future prospects in this novel field. This review will bring spatial architectures of the TIME, an emerging dimension of tumor ecosystem research, to the attention of more researchers and promote its application in tumor research and clinical practice.
Objectives
We aimed to compare the therapeutic outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) as first-line therapies in patients with small single perivascular hepatocellular ...carcinoma (HCC).
Methods
A total of 144 eligible patients with small (≤ 3 cm) single perivascular (proximity to hepatic and portal veins) HCC who underwent RFA (
N
= 70) or MWA (
N
= 74) as first-line treatment were included. The overall survival (OS), disease-free survival (DFS), and local tumor progression (LTP) rates between the two ablation modalities were compared. The inverse probability of treatment weighting (IPTW) method was used to reduce selection bias. Subgroup analysis was performed according to the type of hepatic vessels.
Results
After a median follow-up time of 38.2 months, there were no significant differences in OS (5-year OS: RFA 77.7% vs. MWA 74.6%;
p
= 0.600) and DFS (5-year DFS: RFA 24.7% vs. MWA 40.4%;
p
= 0.570). However, a significantly higher LTP rate was observed in the RFA group than the MWA group (5-year LTP: RFA 24.3% vs. MWA 8.4%;
p
= 0.030). IPTW-adjusted analyses revealed similar results. The treatment modality (RFA vs. MWA: HR 7.861, 95% CI 1.642–37.635,
p
= 0.010) was an independent prognostic factor for LTP. We observed a significant interaction effect of ablation modality and type of peritumoral vessel on LTP (
p
= 0.034). For patients with periportal HCC, the LTP rate was significantly higher in the RFA group than in the MWA group (
p
= 0.045). However, this difference was not observed in patients with perivenous HCC (
p
= 0.116).
Conclusions
In patients with a small single periportal HCC, MWA exhibited better tumor control than RFA.
Key Points
• Microwave ablation exhibited better local tumor control than radiofrequency ablation for small single periportal hepatocellular carcinoma.
• There was a significant interaction between the treatment effect of ablation modality and type of peritumoral vessel on local tumor progression.
• The type of peritumoral vessel is vital in choosing ablation modalities for hepatocellular carcinoma.
Abstract
Background
There are no pharmacological interventions currently available to prevent the transmission of SARS-CoV-2 or to treat COVID-19. The development of vaccines against COVID-19 is ...essential to contain the pandemic. we conducted a cross-sectional survey of Shanghai residents to understand residents’ willingness to be vaccinated with any future COVID-19 vaccines and take measures to further improve vaccination coverage.
Methods
We conducted a cross-sectional survey using self-administered anonymous questionnaires from 1 July to 8 September 2020. The main outcome was willingness of participants, and any children or older individuals living with them, to receive future COVID-19 vaccines. Logistic regression analyses were used to explore potential factors associated with vaccination willingness.
Results
A total of 1071 participants were asked about their willingness to receive future COVID-19 vaccines, for themselves and at least 747 children and 375 older individuals (≥60 years old) living with them. The highest proportion of expected willingness to vaccinate was among participants (88.6%), followed by children (85.3%) and older individuals (84.0%). The main reasons for reluctance to vaccinate among 119 participants were doubts regarding vaccine safety (60.0%) and efficacy (28.8%). Participants with a self-reported history of influenza vaccination were more likely to accept COVID-19 vaccines for themselves adjusted odds ratio (
OR
) = 1.83; 95% confidence interval (
CI
): 1.19–2.82, their children (adjusted
OR
= 2.08; 95%
CI
: 1.30–3.33), and older individuals in their household (adjusted
OR
= 2.12; 95%
CI
: 1.14–3.99). Participants with older individuals in their families were less willing to vaccinate themselves (adjusted
OR
= 0.59; 95%
CI
: 0.40–0.87) and their children (adjusted
OR
= 0.58; 95%
CI
: 0.38–0.89).
Conclusions
Participants were more reluctant to accept COVID-19 vaccines for older individuals living with them. The presence of older individuals in the home also affected willingness of participants and their children to be vaccinated.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of ...lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC.
The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5' and 3' rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p.
We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue.
Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•This study produces Co3O4 nanoparticles (NPs) using ultrasonic wave grinding technology.•For a 100-ppb NO2 gas concentration, an Au/Co3O4-NPs/MEMS gas sensor has the greatest sensor response.•The ...Au/Co3O4-NPs/MEMS gas sensor has a higher sensitivity to NO2 than other gases (SO2, NH3, CO, tingCO2).•The average diameter of Co3O4-NPs and Au-NPs are about 6 nm and 1 nm.
This study produces Co3O4 nanoparticles (NPs) using ultrasonic wave grinding technology. The experimental results show that the average diameter of Co3O4-NPs is about 6 nm. Au nanoparticles are adsorbed onto the surface of Co3O4-NPs and integrated with a MEMS structure to form a Au/Co3O4-NPs/MEMS NO2 gas sensor. The diameter of Au nanoparticle is approximately 1 nm. For a 100-ppb NO2 gas concentration, an Au/Co3O4-NPs/MEMS gas sensor has the greatest sensor response and has a higher sensitivity to NO2 than other gases (SO2, NH3, CO, CO2) when NO2 gas is introduced at 10 ppm and at the optimal operating temperature of 136 ℃.
This study reported on a novel sandwich enzyme linked immunosorbent assay (ELISA) for the sensitive determination of Escherichia coli O157:H7 (E. coli O157:H7) by using DNA-based hybridization chain ...reaction (HCR) and biotin–streptavidin signal amplification. The anti-E. coli O157:H7 polyclonal antibody (pAb) was immobilized in the ELISA wells. The anti-E. coli O157:H7 monoclonal antibody (mAb) and initiator strand (DNA1) were labeled on gold nanoparticle (AuNP) to form a mAb–AuNP–DNA1 complex. In the presence of the target E. coli O157:H7, the sandwiched immunocomplex, which is pAb–E. coli O157:H7–mAb–AuNP–DNA1, could be formed. Two types of biotinylated hairpin were subsequently added in the ELISA well. A nicked double-stranded DNA (dsDNA) that contained abundant biotins was formed after HCR. Detection was performed after adding horseradish peroxidase–streptavidin and substrate/chromogen solution. Under optimal conditions, E. coli O157:H7 could be detected in the range of 5×102 CFU/mL to 1×107 CFU/mL; the limit of detection was 1.08×102 CFU/mL in pure culture. The LOD of the novel ELISA was 185 times lower than that of traditional ELISA. The proposed method is considerably specific and can be applied in the detection of whole milk samples inoculated with E. coli O157:H7. The coefficient of variation of in pure culture and in whole milk was 0.99–5.88% and 0.76–5.38%, respectively. This method offers a promising application in the detection of low concentrations of food-borne pathogens.
•A novel ELISA for the sensitive detection of E. coli O157:H7 using DNA-based HCR.•Biotin was formed after HCR and fixed HRP–streptavidin for higher detection signal.•The LOD of the novel method was 185-fold sensitive than that of traditional ELISA.•The method is specific and can be applied in the detection of milk samples.
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