Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor ...microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.
Background and Aims
The study objective was to compare the effectiveness of microwave ablation (MWA) and laparoscopic liver resection (LLR) on solitary 3–5‐cm HCC over time.
Approach and Results
From ...2008 to 2019, 1289 patients from 12 hospitals were enrolled in this retrospective study. Diagnosis of all lesions were based on histopathology. Propensity score matching was used to balance all baseline variables between the two groups in 2008–2019 (n = 335 in each group) and 2014–2019 (n = 257 in each group) cohorts, respectively. For cohort 2008–2019, during a median follow‐up of 35.8 months, there were no differences in overall survival (OS) between MWA and LLR (HR: 0.88, 95% CI 0.65–1.19, p = 0.420), and MWA was inferior to LLR regarding disease‐free survival (DFS) (HR 1.36, 95% CI 1.05–1.75, p = 0.017). For cohort 2014–2019, there was comparable OS (HR 0.85, 95% CI 0.56–1.30, p = 0.460) and approached statistical significance for DFS (HR 1.33, 95% CI 0.98–1.82, p = 0.071) between MWA and LLR. Subgroup analyses showed comparable OS in 3.1–4.0‐cm HCCs (HR 0.88, 95% CI 0.53–1.47, p = 0.630) and 4.1–5.0‐cm HCCs (HR 0.77, 95% CI 0.37–1.60, p = 0.483) between two modalities. For both cohorts, MWA shared comparable major complications (both p > 0.05), shorter hospitalization, and lower cost to LLR (all p < 0.001).
Conclusions
MWA might be a first‐line alternative to LLR for solitary 3–5‐cm HCC in selected patients with technical advances, especially for patients unsuitable for LLR.
Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor ...initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive ‘sponge’ of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through ‘spongeing’ miR-34a-5p.
•XIST is up-regulated in human primary NPC tissues.•Expression of E2F3 is up-regulated in primary human NPC and negatively expressed related to miR-34a-5p.•miR-34a-5p inhibits the tumorigenic potential of NPC cells by down-regulating oncogenic E2F3 gene.•XIST's oncogenic functions are partially through reverse regulation of miRNA-34a-5p, and then activation of E2F3.
Secondary organic aerosol (SOA) formation from biogenic precursors
is affected by anthropogenic emissions, which are not well understood in
polluted areas. In this study, we accomplished a year-round ...campaign at nine
sites in polluted areas located in the Pearl River Delta (PRD) region during
2015. We measured typical biogenic SOA (BSOA) tracers from isoprene,
monoterpenes, and β-caryophyllene, as well as major gaseous and
particulate pollutants and investigated the impact of anthropogenic
pollutants on BSOA formation. The concentrations of BSOA tracers were in the
range of 45.4 to 109 ng m−3 with the majority composed of products from
monoterpenes (SOAM, 47.2±9.29 ng m−3),
isoprene (SOAI, 23.1±10.8 ng m−3), and β-caryophyllene (SOAC, 3.85±1.75 ng m−3). We found that
atmospheric oxidants, Ox (O3 plus NO2), and sulfate
correlated well with later-generation SOAM tracers, but this was not the case for
first-generation SOAM products. This suggested that high Ox and
sulfate levels could promote the formation of later-generation SOAM products,
which probably led to the relatively aged SOAM that we observed in the PRD. For
the SOAI tracers, both 2-methylglyceric acid (NO/NO2-channel
product) and the ratio of 2-methylglyceric acid to 2-methyltetrols
(HO2-channel products) exhibit NOx dependence, indicating the
significant impact of NOx on SOAI formation pathways. The
SOAC tracer was elevated in winter at all sites and was positively correlated
with levoglucosan, Ox, and sulfate. Thus, the unexpected increase in
SOAC in wintertime might be highly associated with the enhancement of
biomass burning, O3 chemistry, and the sulfate component in the PRD. The
BSOAs that were estimated using the SOA tracer approach showed the highest
concentration in fall and the lowest concentration in spring with an annual
average concentration of 1.68±0.40 µg m−3. SOAM
dominated the BSOA mass all year round. We also found that BSOA correlated
well with sulfate and Ox. This implied a significant effect from
anthropogenic pollutants on BSOA formation and highlighted that we could
reduce BSOA by controlling the anthropogenic emissions of
sulfate and Ox precursors in polluted regions.
Salicylic acid (SA) is a natural inducer of disease resistance in fruit, but its application in the food industry is limited due to low water solubility. Here, SA was encapsulated in β-cyclodextrin ...(β-CD) via the host-guest inclusion complexation method, and the efficacy of SA microcapsules (SAM) against blue mold caused by
in postharvest apple fruit was elucidated. It was observed that SAM was the most effective in inhibiting the mycelial growth of
in vitro. SAM was also superior to SA for control of blue mold under in vivo conditions. Enzyme activity analysis revealed that both SA and SAM enhanced the activities of superoxide dismutase (SOD) and phenylalanine ammonia lyase (PAL) in apple fruit, whereas SAM led to higher SOD activities than SA. Total phenolic contents in the SAM group were higher than those in the SA group at the early stage of storage. SAM also improved fruit quality by retarding firmness loss and maintaining higher total soluble solids (TSS) contents. These findings indicate that microcapsules can serve as a promising formulation to load SA for increasing
inhibition activity and improving quality attributes in apple fruit.
Accurate and generalized collaborative prediction of multi-cluster renewable energy power generation is both an inevitable trend and urgent demand as the growth of multi-region interconnected power ...grids with wind and photovoltaic (PV) power. In this paper, a novel heterogeneous spatiotemporal graph convolution network (HSTGCN) is proposed for ultra-short-term multi-modal prediction oriented to wind-PV power, which sufficiently considers spatiotemporal correlations in tens of wind farms or PV stations of each neighboring region and effectively coordinates the heterogeneities of different power generation types in different regions. This approach first designs a dynamical heterogeneous graph structure including modes, nodes, and edges to give a unified framework evolving over time for different interdependencies in the multi-cluster wind and PV sites, and then develops a hierarchical spatiotemporal learning mechanism to enhance representation power for multi-cluster prior information from temporal and spatial dimensions, integrating 2-D CNN with different sizes of filters and GCN embedded a specially designed lightweight graph convolution attention module (GCAM). Experiments including 57 operating wind farms and PV stations from 4 regions distributed over a broad spatial scale demonstrate the generalization and interpretation of HSTGCN compared with other commonly considered benchmarks.
Long noncoding RNAs (lncRNA) play essential roles in tumor progression. However, the functions of lncRNAs in the tumorigenesis and aggressiveness of neuroblastoma still remain to be determined. Here, ...we report the identification of lncRNA
as a novel driver of neuroblastoma progression by using a public microarray dataset. LncRNA
promoted the growth, invasion, and metastasis of neuroblastoma cells
and
Mechanistically,
bound to hnRNPK to facilitate its physical interaction with β-catenin, whereas hnRNPK stabilized the β-catenin by inhibiting proteasome-mediated degradation, resulting in transcriptional alteration of target genes associated with neuroblastoma progression. Both
and
were upregulated in clinical neuroblastoma tissues, and were associated with unfavorable outcome of patients. Overall, our results define an oncogenic role of
in neuroblastoma progression through hnRNPK-mediated β-catenin stabilization, with potential implications for the clinical therapeutics of neuroblastoma.
These findings reveal the oncogenic functions of a long noncoding RNA in neuroblastoma progression, offering a potential target for clinical therapeutics.
.
Emerging studies have indicated the essential functions of long noncoding RNAs (lncRNAs) during cancer progression. However, whether lncRNAs contribute to the upregulation of v-ets erythroblastosis ...virus E26 oncogene homolog 1 (Ets-1), an established oncogenic protein facilitating tumor invasion and metastasis, in gastric cancer remains elusive. Herein, we identified Ets-1 promoter-associated noncoding RNA (pancEts-1) as a novel lncRNA associated with the gastric cancer progression via mining of publicly available datasets and rapid amplification of cDNA ends. RNA pull-down, RNA immunoprecipitation, in vitro binding, and RNA electrophoretic mobility shift assays indicated the binding of pancEts-1 to non-POU domain containing octamer binding (NONO) protein. Mechanistically, pancEts-1 facilitated the physical interaction between NONO and Ets related gene (ERG), resulting in increased ERG transactivation and transcription of Ets-1 associated with gastric cancer progression. In addition, pancEts-1 facilitated the growth and aggressiveness of gastric cancer cells via interacting with NONO. In gastric cancer tissues, pancEts-1, NONO, and ERG were upregulated and significantly correlated with Ets-1 levels. High levels of pancEts-1, NONO, ERG, or Ets-1 were respectively associated with poor survival of gastric cancer patients, whereas simultaneous expression of all of them (HR = 3.012, P = 0.105) was not an independent prognostic factor for predicting clinical outcome. Overall, these results demonstrate that lncRNA pancEts-1 exhibits oncogenic properties that drive the progression of gastric cancer via regulating the NONO/ERG/Ets-1 axis.
Increasing evidence has revealed the roles of long noncoding RNAs (lncRNAs) as tumor biomarkers. Here, we introduce an immune-associated nine-lncRNA signature for predicting distant metastasis in ...locoregionally advanced nasopharyngeal carcinoma (LA-NPC). The nine lncRNAs are identified through microarray profiling, followed by RT-qPCR validation and selection using a machine learning method in the training cohort (n = 177). This nine-lncRNA signature classifies patients into high and low risk groups, which have significantly different distant metastasis-free survival. Validations in the Guangzhou internal (n = 177) and Guilin external (n = 150) cohorts yield similar results, confirming that the signature is an independent risk factor for distant metastasis and outperforms anatomy-based metrics in identifying patients with high metastatic risk. Integrative analyses show that this nine-lncRNA signature correlates with immune activity and lymphocyte infiltration, which is validated by digital pathology. Our results suggest that the immune-associated nine-lncRNA signature can serve as a promising biomarker for metastasis prediction in LA-NPC.
An efficient and practical organocatalytic asymmetric domino Michael/Mannich 3+2 cycloaddition of N‐2,2,2‐trifluoroethylisatin ketimines and arylidene azlactones by using a hydroquinine‐derived ...thiourea as the catalyst has been disclosed. Under mild conditions, a broad range of CF3‐containing 3,2’‐pyrrolidinyl spirooxindole/ dispirooxindole derivatives bearing four adjacent stereogenic centers including two vicinal spiro quaternary chiral centers were obtained in high yields (up to 99% yield) with excellent diastereoselectivities (>20:1 dr, in all case) and enantioselectivities (up to >99% ee).
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