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Stress granules (SGs) are membrane-less organelles that cell forms via liquid-liquid phase separation (LLPS) under stress conditions such as oxidative stress, ER stress, heat shock and hypoxia. SG assembly is a stress-responsive mechanism by regulating gene expression and cellular signaling pathways. Cancer cells face various stress conditions in tumor microenvironment during tumorigenesis, while SGs contribute to hallmarks of cancer including proliferation, invasion, migration, avoiding apoptosis, metabolism reprogramming and immune evasion. Here, we review the connection between SGs and cancer development, the limitation of SGs on current cancer therapy and promising cancer therapeutic strategies targeting SGs in the future. [ABSTRACT FROM AUTHOR]

Epstein‐Barr virus (EBV) is a tumorigenic virus that can cause various human malignancies such as nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature micro (mi)RNAs, mostly exhibiting oncogenic properties and promoting cancer progression. However, we have previously found that one EBV‐encoded miRNA, namely EBV‐miR‐BART6‐3p, acts as a tumor suppressor by inhibiting metastasis and invasion. Here, we report that EBV‐miR‐BART6‐3p inhibits the proliferation of EBV‐associated cancers, NPC, and GC, by targeting and downregulating a long non‐coding RNA (lncRNA), LOC553103. Through proteomics analysis, we determined that stathmin (STMN1) is affected by EBV‐miR‐BART6‐3p and LOC553103. Further, via RNA immunoprecipitation and luciferase reporter assay, we confirmed that LOC553103 directly binds and stabilizes the 3′UTR region of STMN1 mRNA. These results indicate that the EBV‐miR‐BART6‐3p/LOC553103/STMN1 axis regulates the expression of cell cycle‐associated proteins, which then inhibit EBV‐associated tumor cell proliferation. These findings provide potential targets or strategies for novel EBV‐related cancer treatments, as well as contributes new insights into the understanding of EBV infection‐related carcinogenesis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: LGR4 expression in serous ovarian cancer paraffin-embedded tissues and fresh tissues were investigated, and its expression associated with clinicopathological parameters and prognosis in serous ovarian cancer was explored. METHODS: From Dec, 2009 to Jan, 2020, 122 paraffin-embedded serous ovarian cancer patients and 41 paired paratumor tissues who were both diagnosed and operated at the memorial hospital of Sun Yat-sen University and Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were selected in this research, respectively, and all of these tissues were performed by immunohistochemistry (IHC) with a polyclonal antibody for LGR4. Meanwhile, from Aug, 2013 to Mar, 2019, 15 cases of serous ovarian cancer fresh tissues and 15 cases of paratumor fresh tissues who were operated at Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were performed with Quantitative Real-time PCR to detect the mRNA expression of LGR4, respectively. RESULTS: LGR4 expression was much higher both in paraffin-embedded and fresh cancer tissues than that in paratumor tissues, respectively, and its expression was associated with recurrence free survival and overall survival in serous ovarian cancer patients. Moreover, in a multivariate model LGR4 was an indeed independent predictor of poor survival in serous ovarian cancer patients. CONCLUSION: LGR4 is upregulated in serous ovarian cancer, and LGR4 is an indeed useful independent prognostic predictor in serous ovarian cancer, and it may provide important clinical value of serous ovarian cancer. [ABSTRACT FROM AUTHOR]

Understanding the trend characteristics of design rainstorm and spatial heterogeneity of extreme precipitation is of great importance to reduce disasters induced by rare extreme precipitation. Using a high-resolution (0.5° × 0.5°) daily gridded data set of precipitation across mainland China from 1961 to 2013, this study investigated the historical changing trend and spatial heterogeneity of design rainstorm using the 30-year moving window method (30YM). Differences in the quantification of the design rainstorm were compared for the use of the 30YM and the 30-year-based increasing window method (30YBI). The results show that a significant increasing intensity but no spatially uniform trend of design rainstorm can be observed across mainland China based on the 30YM analysis. The south, east, and northeast China mainly showed an increasing trend, but the southwest and north China presented a decreasing trend. The spatial heterogeneity of the design rainstorm was greatly enhanced if the nonstationarity assumption was adopted on the national scale. The heterogeneity showed an increasing trend mainly in southeast, north, northeast, and northwest China, and a decreasing trend in southwest and west China, indicating significant regional variation in spatial heterogeneity. For most areas of mainland China, especially for southeastern, northeastern, and western China, use of the most recent precipitation sub-series to quantify the design rainstorm may weaken the potential nonstationarity and guarantee the safety of infrastructure in these areas where design rainfall increases. [ABSTRACT FROM AUTHOR]

• A general two-dimension lattice system, " k -within- r × s -out-of- m × n " model, with non-homogeneous components is proposed. • A lower bound of system reliability calculating method is developed by employing finite Markov chain imbedding approach. • The system, in which the components are positioned in the cylinder shape, can be translated into the two-dimension lattice model to obtain the system reliability. The lattice system in which the components are regularly distributed in a two dimensional area are studied due to the fact that it can be used to describe the system model in various applications, e.g., safety monitoring system, phased array radar, design of array antenna or liquid crystal display. In the previous research, the common shared assumption is that the lattice system is composed with homogeneous components. However, when we conduct a reliability evaluation of the system, this hypothesis is easy to be violated, because maintenance action may take upon to replace the aging components with new ones, which leads the residual life of the components are different from each other. In this paper we employ finite Markov chain imbedding approach and use the " k -within- r × s -out-of- m × n " model to obtain a lower bound calculating method for reliability of the lattice system with non-homogeneous components. By changing parameters or adding conditions, we propose some transformed models from the original one. Some numerical examples are applied to illustrate how to compute the reliability of these models and address some property of the lattice system. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate TCF4 expression in epithelial ovarian cancer, and to explore its correlation with clinicopathological parameters and clinical prognosis of epithelial ovarian cancer. METHODS: From 2009 to 2017, 188 cases of paraffin-embedded epithelial ovarian cancer tissues and 41 paratumor ovarian tissues which had been confirmed at the memorial hospital of Sun Yat-sen University were collected in this study, and the expression of TCF4 was performed by immunohistochemistry using a polyclonal antibody specific for TCF4. RESULTS: The expression of TCF4 protein was associated with disease progression free survival and overall survival in epithelial ovarian cancer patients; and TCF4 overexpression was associated with age, FIGO stage, lymph node metastasis, intraperitoneal metastasis, intestinal metastasis, vital status, intraperitoneal recurrence, and serum CA153. Moreover, in a multivariate Cox regression analysis TCF4 overexpression was an indeed independent prognostic factor in epithelial ovarian cancer. CONCLUSIONS: TCF4 may play an oncogenic role in epithelial ovarian cancer, and TCF4 is a useful independent prognostic biomarker of epithelial ovarian cancer, and it may provide a candidate target therapy treatment in future. [ABSTRACT FROM AUTHOR]

Carbendazim (CBZ), a systemic, broad-spectrum benzimidazole fungicide, is widely used to control fungal diseases and has been regarded as an endocrine disruptor that causes mammalian toxicity in different target organs. Here, we discovered that chronic administrations of CBZ at 0.2, 1, and 5 mg/kg body weight for 14 weeks not only changed the composition of gut microbiota but also induced significant increases in body, liver, and epididymal fat weight in mice. At the biochemical level, the serum triglyceride (TG) and glucose levels also increased after CBZ exposure. Moreover, the level of serum lipoprotein lipase (LPL), which plays an important role in fatty acid release from TG, was decreased significantly. For gut microbiota, 16S rRNA gene sequencing and real-time qPCR revealed that CBZ exposure significantly perturbed the mice gut microbiome, and gas chromatography found that the production of short-chain fatty acids were altered. Moreover, CBZ exposure increased the absorption of exogenous TG in the mice intestine and inhibited the TG consumption, eventually leading the serum triglyceride to maintain higher levels. The increase of lipid absorption in the intestine direct caused hyperlipidemia and the multi-tissue inflammatory response. In response to the rise of lipid in blood, the body maintains the balance of lipid metabolism in mice by reducing lipid synthesis in the liver and increasing lipid storage in the fat. Chronic CBZ exposure induced the gut microbiota dysbiosis and disturbed lipid metabolism, which promoted the intestinal absorption of excess triglyceride and caused multiple tissue inflammatory responses in mice. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a common tumor in southern China with marked ethnic and geographic distributions and concomitant Epstein–Barr virus (EBV) infection. However, the molecular basis of NPC remains largely unknown, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. Whole-genome sequencing of a collection of 12 EBV-positive paired NPC tumor/peripheral blood samples from Hunan Province was performed, and the FBXO11 gene was subjected to further functional analyses. We identified 69 missense mutations in signaling pathways typically altered in cancer, including NF-κB and Wnt/Hedgehog/Notch. Additionally, 122 variations were identified in non-coding regions. Among these, a subset of genes was confirmed as dysregulated in NPC by mining the NPC cDNA microarray database. The randomly selected gene, FBXO11, could promote the malignant progression of NPC in vitro. Full-length EBV genomes from 8 of the 12 patients with NPC were also successfully assembled, and latent EBV infection is a primary cause of NPC. The various subtypes of EBV detected exhibited clear correlations with its geographical distribution. This study has explored novel biological markers and tumorigenic pathways with substantial potential to enhance therapeutic strategies for NPC. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the potential anticancer effect and mechanisms of salvianolic acid B on osteosarcoma. Salvianolic acid B suppressed osteosarcoma cell proliferation and induced apoptosis in the osteosarcoma MG63 cell line, and activated the expressions of cleaved caspase-3, phosphorylated-tumor protein (p)38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated-p53 (p-p53) proteins in the MG63 cells. Additionally, Salvianolic acid B also increased the level of reactive oxygen species (ROS) generation in the MG63 cells. The silencing of p38 expression inhibited the anticancer effect of salvianolic acid B on the levels of cell proliferation, p-p53 protein expression and ROS generation level in the MG63 cells. All these data supported the hypothesis that the anticancer effect of salvianolic acid B includes the suppression of cell proliferation and induces apoptosis in MG63 cells, and that p38 is important in the anticancer effect of salvianolic acid B on osteosarcoma cells due to the direct regulation of ROS generation. These data suggest that salvianolic acid B is important in the proliferation of osteosarcoma cells due to the direct regulation of p38-mediated ROS signaling. [ABSTRACT FROM AUTHOR]

ABSTRACT Owing to their essential influence on human society and natural environment exerted by inducing disasters, such as floods and droughts, further studies on precipitation extremes in China are needed. This study presents the regional frequency and spatial-temporal patterns of precipitation extremes in China based on a high-resolution (0.5° × 0.5°) daily precipitation dataset from 1961 to 2013. With fuzzy c-means, L-moments methods and other scientific statistical tests, a regional frequency analysis ( RFA) is conducted, aiming to further understand the regional and spatial distribution of precipitation extremes across China. The results show that: (1) the whole Mainland China can be divided into 50 homogeneous regions on the basis of the characteristics of mean annual precipitation and location indices. (2) For most of the regions, Generalized Extreme Value ( GEV), Generalized Normal ( GNO) and Pearson type III ( PE3) distributions of precipitation extremes fit well, according to the results of goodness-of-fit ( GOF) test. (3) For RX1DAY, GEV has the best-fit distribution in the east, northeast and southwest of China, whereas GNO distribution mostly fits the northern and parts of southwest and southeast; in addition, regions which fit PE3 and Generalized Logistic ( GLO) distribute dispersedly across the country. (4) For RX5DAY, GEV mainly fits in the middle, southwestern and southern; GNO and PE3 apply best to the northeastern and northern, respectively. (5) Return periods of 20, 50 and 100 years for their best-fit distributions decrease gradually from southeastern China to northwestern China. Compared with the results of GEV distribution fitted to each grid, RFA may provide more accurate estimates of rainfall quantiles. Definitely, the study results will not only benefit further understanding of the unique and complex features of extreme precipitation in the whole Mainland China but also contribute to the nation-scale flood prevention, control and management in the backdrop of the changing climate. [ABSTRACT FROM AUTHOR]

Biosorbents, such as algae and yeast, have been applied in heavy metal adsorption due to their low cost and efficacy. However, they cannot be recycled and reused after direct application, which may cause a secondary pollution. In this study, we used bio-electrospraying technique to immobilize Saccharomyces cerevisiae (a byproduct from food fermentation) onto the surface of poly(ε-caprolactone)/chitosan/rectorite ternary composites based nanofibrous mats. This technique not only combined the advantages of both S. cerevisiae (cheap) and nanofibers (large surface area) in heavy metal removal, but also made biosorbents easy to recollect and reuse. Layer-by-layer structured nanofibrous mats were also fabricated by alternating electrospinning and bio-electrospraying for a couple of times and loaded more S. cerevisiae for enhancing heavy metal biosorption. The morphology of S. cerevisiae loaded nanofibrous mats with different numbers of layers was observed. Biosorption assay was performed on PbNO 3 solution under different pH values, contact time, initial concentrations of Pb 2+ and biosorbents weights, at last the elemental composition was measured before and after biosorption. The results showed that S. cerevisiae loaded nanofibrous mats had a biosorption capacity of Pb 2+ up to 238 mg/g. Desorption assay indicated that these mats were reusable and maintained high biosorption capacity after three biosorption-desorption cycles. [ABSTRACT FROM AUTHOR]

The fungicide imazalil (IMZ) is used extensively in vegetable and fruit plantations and as a post-harvest treatment to avoid rot. Here, we revealed that ingestion of 25, 50 and 100 mg IMZ kg −1 body weight for 28 d induced gut microbiota dysbiosis and colonic inflammation in mice. The relative abundance of Bacteroidetes , Firmicutes and Actinobacteria in the cecal contents decreased significantly after exposure to 100 mg kg −1 IMZ for 28 d. In feces, the relative abundance in Bacteroidetes , Firmicutes and Actinobacteria decreased significantly after being exposed to 100 mg kg −1 IMZ for 1, 14 and 7 d, respectively. High throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene revealed a significant reduction in the richness and diversity of microbiota in cecal contents and feces of IMZ-treated mice. Operational taxonomic units (OTUs) analysis identified 49.3% of OTUs changed in cecal contents, while 55.6% of OTUs changed in the feces after IMZ exposure. Overall, at the phylum level, the relative abundance of Firmicutes , Proteobacteria and Actinobacteria increased and that of Bacteroidetes decreased in IMZ-treated groups. At the genus level, the abundance of Lactobacillus and Bifidobacterium decreased while those of Deltaproteobacteria and Desulfovibrio increased in response to IMZ exposure. In addition, it was observed that IMZ exposure could induce colonic inflammation characterized by infiltration of inflammatory cells, elevated levels of lipocalin-2 (lcn-2) in the feces, and increased mRNA levels of Tnf-α , IL-1β , IL-22 and IFN-γ in the colon. Our findings strongly suggest that ingestion of IMZ has some risks to human health. [ABSTRACT FROM AUTHOR]

Human SPLUNC1 can suppress nasopharyngeal carcinoma ( NPC) tumor formation; however, the correlation between SPLUNC1expression and NPC patient prognosis has not been reported. In the present study, we used a large-scale sample of 1015 tissue cores to detect SPLUNC1 expression and its association with patient prognosis. SPLUNC1 expression was reduced in NPC samples compared to nontumor nasopharyngeal epithelium tissues. Positive expression of SPLUNC1 in NPC predicted a better prognosis (disease-free survival, P = 0.034; overall survival, P = 0.048). Cox's proportional hazards model revealed that SPLUNC1 could be a significant prognostic factor affecting disease-free survival ( P = 0.027). A c DNA micro-array analyzed by significant analysis of micro-array (SAM) and ingenuity pathway analysis (IPA) revealed that an indirect interaction existed between SPLUNC1 and retinoic acid (RA) in the cancer regulatory network. To further investigate the molecular mechanisms involved, we utilized several bioinformatics tools and identified 12 retinoid X receptors heterodimer binding sites in the promoter region of the SPLUNC1 gene. The transcriptional activity of the SPLUNC1 promoter was up-regulated significantly by all-trans-retinoic acid ( ATRA). SPLUNC1 and retinoic acid receptor expression were induced significantly by ATRA, and removal of ATRA led to a progressive loss of SPLUNC1 and retinoic acid receptor expression. ATRA inhibited proliferation and induced the differentiation of NPC cells. Interestingly, over-expression of SPLUNC1 sensitized NPC cells to ATRA, whereas knockdown of SPLUNC1 in HNE1 cells increased cell viability. Under SPLUNC1 knockdown conditions, differentiation was reversed by ATRA treatment. We concluded that SPLUNC1 could potentially predict prognosis for NPC patients and play an important role in ATRA-induced growth inhibition and differentiation in NPC cells. [ABSTRACT FROM AUTHOR]

Cyclodextrins are among the most popular host compounds in supramolecular chemistry. In this paper we describe a versatile approach to the multivalent functionalization of cyclodextrins by using photochemical thiol-alkene addition reactions ('thiol-ene click chemistry'). Starting from cyclodextrins allylated at the 2-OH, 3-OH and/or 6-OH positions, a range of thiols could be introduced in good to excellent yields. By using alkanethiols substituted with hydroxy, carboxylic acid, ester, protected amine, and tetraethyleneglycol groups, a broad variety of functionalized cyclodextrins was obtained. By using fluorinated alkanethiols, highly fluorinated cyclodextrins (up to 56 wt.-% of fluorine) were obtained in excellent yield. [ABSTRACT FROM AUTHOR]

Rechargeable molecular-cluster batteries (MCBs) based on the manganese cluster complex [Mn12O12(CH3CH2C(CH3)2COO)16(H2O)4] ([Mn12]) that exhibited a capacity of approximately 200 A h kg−1 in the battery voltage range of 4.0 to 2.0 V were developed. In these batteries, the capacity of approximately 100 A h kg−1 in the range of 4.0-3.0 V is caused by a chemical reduction from [Mn12]0 to [Mn12]8−, whereas the other half in the range of 3.0-2.0 V cannot be explained by a redox change of the Mn ions. We performed the cyclic voltammetry (CV) and 7Li solid-state NMR measurements on the Mn12-MCBs to investigate the origin of the capacity below 3.0 V. Pseudo-rectangular-shaped CV curves in the range of 3.0-2.0 V demonstrate the presence of an electrical double-layer (EDL) capacitance in Mn12-MCBs, which corresponds to approximately 100 A h kg−1. 7Li NMR studies suggest that Li ions form an EDL with electrons in carbon black electrodes in the capacitance voltage range. The capacitance effects are not formed by the single-carbon electrodes alone, but appear only in the mixture of Mn12 and the carbon black electrodes. This type of coexistence of capacitance effects and redox reaction in one electrochemical cell is quite unusual and can serve as a new working principle for high-performance energy-storage devices. [ABSTRACT FROM AUTHOR]

Microarray analysis was used to bring a comprehensive insight into underlying molecular mechanisms and obtain a whole assessment of aberrant gene expression in nasopharyngeal carcinoma (NPC). Combined with microdissection, gene expression profiles in 23 NPCs and 10 nontumor nasopharyngeal epithelial tissue samples were analyzed. Gene expression patterns suggested the dysregulation of the GTP/GDP-bound Ras cycle and an abnormal hyperactivity of cell cycle in NPC. Alterations in the WNT pathway suggest that this pathway may be activated in NPC. A 6-feature weighted-voting model was chosen because it represented the main characteristics of NPCs and predicted NPCs most accurately from the nontumor tissues (33 of 34 correct calls; 97.1% accuracy, Fisher’s exact test, P value = 8.389 × 10−8). The data generated in this study represent a comprehensive list of genes aberrantly regulated in NPC. The 6-feature weighted-voting model may provide an extensive list of potential molecular markers for early diagnosis. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment. KCNK1 is a potassium channel differentially expressed in many tumors, but the mechanisms underlying its function in breast cancer remain unclear. This study shows that KCNK1 is overexpressed in breast cancer promoting proliferation, invasion and metastasis by increasing glycolysis and activating Lactate Dehydrogenase A. [ABSTRACT FROM AUTHOR]

A century ago, the Warburg effect was first proposed, revealing that cancer cells predominantly rely on glycolysis during the process of tumorigenesis, even in the presence of abundant oxygen, shifting the main pathway of energy metabolism from the tricarboxylic acid cycle to aerobic glycolysis. Recent studies have unveiled the dynamic transfer of mitochondria within the tumor microenvironment, not only between tumor cells but also between tumor cells and stromal cells, immune cells, and others. In this review, we explore the pathways and mechanisms of mitochondrial transfer within the tumor microenvironment, as well as how these transfer activities promote tumor aggressiveness, chemotherapy resistance, and immune evasion. Further, we discuss the research progress and potential clinical significance targeting these phenomena. We also highlight the therapeutic potential of targeting intercellular mitochondrial transfer as a future anti-cancer strategy and enhancing cell-mediated immunotherapy. [ABSTRACT FROM AUTHOR]

Immune evasion contributes to cancer growth and progression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) and programmed cell death ligands (PD-Ls) are considered to be the major immune checkpoint molecules. The interaction of PD-1 and PD-L1 negatively regulates adaptive immune response mainly by inhibiting the activity of effector T cells while enhancing the function of immunosuppressive regulatory T cells (Tregs), largely contributing to the maintenance of immune homeostasis that prevents dysregulated immunity and harmful immune responses. However, cancer cells exploit the PD-1/PD-L1 axis to cause immune escape in cancer development and progression. Blockade of PD-1/PD-L1 by neutralizing antibodies restores T cells activity and enhances anti-tumor immunity, achieving remarkable success in cancer therapy. Therefore, the regulatory mechanisms of PD-1/PD-L1 in cancers have attracted an increasing attention. This article aims to provide a comprehensive review of the roles of the PD-1/PD-L1 signaling in human autoimmune diseases and cancers. We summarize all aspects of regulatory mechanisms underlying the expression and activity of PD-1 and PD-L1 in cancers, including genetic, epigenetic, post-transcriptional and post-translational regulatory mechanisms. In addition, we further summarize the progress in clinical research on the antitumor effects of targeting PD-1/PD-L1 antibodies alone and in combination with other therapeutic approaches, providing new strategies for finding new tumor markers and developing combined therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear. Methods: RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein. Results: We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5′-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma. Conclusions: These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Cancer vaccines, designed to activate the body's own immune system to fight against tumors, are a current trend in cancer treatment and receiving increasing attention. Cancer vaccines mainly include oncolytic virus vaccine, cell vaccine, peptide vaccine and nucleic acid vaccine. Over the course of decades of research, oncolytic virus vaccine T-VEC, cellular vaccine sipuleucel-T, various peptide vaccines, and DNA vaccine against HPV positive cervical cancer have brought encouraging results for cancer therapy, but are losing momentum in development due to their respective shortcomings. In contrast, the advantages of mRNA vaccines such as high safety, ease of production, and unmatched efficacy are on full display. In addition, advances in technology such as pseudouridine modification have cracked down the bottleneck for developing mRNA vaccines including instability, innate immunogenicity, and low efficiency of in vivo delivery. Several cancer mRNA vaccines have achieved promising results in clinical trials, and their usage in conjunction with other immune checkpoint inhibitors (ICIs) has further boosted the efficiency of anti-tumor immune response. We expect a rapid development of mRNA vaccines for cancer immunotherapy in the near future. This review provides a brief overview of the current status of mRNA vaccines, highlights the action mechanism of cancer mRNA vaccines, their recent advances in clinical trials, and prospects for their clinical applications. [ABSTRACT FROM AUTHOR]

In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF is a well‐established precancerous lesion, and a portion of OSF cases eventually progress to oral squamous cell carcinoma (OSCC). However, the specific molecular mechanisms underlying the malignant transformation of OSCC from OSF are poorly understood. In this study, the leading‐edge techniques of Spatial Transcriptomics (ST) and Spatial Metabolomics (SM) are integrated to obtain spatial location information of cancer cells, fibroblasts, and immune cells, as well as the transcriptomic and metabolomic landscapes in OSF‐derived OSCC tissues. This work reveals for the first time that some OSF‐derived OSCC cells undergo partial epithelial–mesenchymal transition (pEMT) within the in situ carcinoma (ISC) region, eventually acquiring fibroblast‐like phenotypes and participating in collagen deposition. Complex interactions among epithelial cells, fibroblasts, and immune cells in the tumor microenvironment are demonstrated. Most importantly, significant metabolic reprogramming in OSF‐derived OSCC, including abnormal polyamine metabolism, potentially playing a pivotal role in promoting tumorigenesis and immune evasion is discovered. The ST and SM data in this study shed new light on deciphering the mechanisms of OSF‐derived OSCC. The work also offers invaluable clues for the prevention and treatment of OSCC. [ABSTRACT FROM AUTHOR]

The given text discusses a road segmentation method called MSAN that uses multi-modal scale-aware attentions to segment roads in real-time for autonomous driving. The method combines RGB and depth information to improve prediction results and outperforms single modality models. The MSAN architecture consists of two attention modules, one for feature fusion across modalities and scales and another for scale-aware fusion. The experiments show that MSAN achieves high performance and efficiency on multiple datasets. However, the method relies heavily on labeled data, which limits its adaptability to different scenarios. Future research aims to reduce data dependency through few-shot learning strategies. [Extracted from the article]

Ferroptosis, a new type of non-apoptotic cell death which depends on the iron pathway, plays an important role in cancer therapy. There are various ways to induce ferroptosis, among which radiotherapy is one method, but a single radiotherapy method may also have difficulties in patients' drug resistance and radiation resistance, which will affect the therapeutic effect. In this study, we constructed Fenton reaction anti-cancer iron-carrying nano-carbon-dot liposomes (Fe-CDs-PEG) with CDs as the core, which can enhance sensitivity to radiotherapy by inducing ferroptosis in lung cancer cells. Extracellular Fe-CDs-PEG can catalyze H2O2 to produce hydroxyl radicals (˙OH) and consume glutathione (GSH). After Fe-CDs-PEG enters lung cancer cells, it can lead to the occurrence of excess iron, iron metabolism disorder, GSH consumption, and accumulation of reactive oxygen species (ROS), leading to the accumulation of lipid peroxides on the cell membrane, activating the ferroptosis pathway, to achieve sensitization to radiotherapy. This CD-based tool would provide a new idea for an efficient therapy for lung cancer. [ABSTRACT FROM AUTHOR]

Single cell RNA sequencing (scRNA‐seq) provides a great convenience for studying tumor occurrence and development for its ability to study gene expression at the individual cell level. However, patient‐derived tumor tissues are composed of multiple types of cells including tumor cells and adjacent non‐malignant cells such as stromal cells and immune cells. The spatial locations of various cells in situ tissues plays a pivotal role in the occurrence and development of tumors, which cannot be elucidated by scRNA‐seq alone. Spatially resolved transcriptomics (SRT) technology emerges timely to explore the unrecognized relationship between the spatial background of a particular cell and its functions, and is increasingly used in cancer research. This review provides a systematic overview of the SRT technologies that are developed, in particular the more widely used cutting‐edge SRT technologies based on next‐generation sequencing (NGS). In addition, the main achievements by SRT technologies in precisely unveiling the underappreciated spatial locations on gene expression and cell function with unprecedented high‐resolution in cancer research are emphasized, with the aim of developing more effective clinical therapeutics oriented to a deeper understanding of the interaction between tumor cells and surrounding non‐malignant cells. [ABSTRACT FROM AUTHOR]

Currently, more than 170 modifications have been identified on RNA. Among these RNA modifications, various methylations account for two-thirds of total cases and exist on almost all RNAs. Roles of RNA modifications in cancer are garnering increasing interest. The research on m6A RNA methylation in cancer is in full swing at present. However, there are still many other popular RNA modifications involved in the regulation of gene expression post-transcriptionally besides m6A RNA methylation. In this review, we focus on several important RNA modifications including m1A, m5C, m7G, 2′-O-Me, Ψ and A-to-I editing in cancer, which will provide a new perspective on tumourigenesis by peeking into the complex regulatory network of epigenetic RNA modifications, transcript processing, and protein translation. [ABSTRACT FROM AUTHOR]

The poor prognosis of serous ovarian cancer (SOC) is due to its high invasive capacity and cisplatin resistance of SOC cells, whereas the molecular mechanisms remain poorly understood. In the present study, the expression and function of non‐muscle myosin heavy chain IIB (MYH10) in SOC are identified by immunohistochemistry, in vitro, and in vivo studies, respectively. The mechanism of MYH10 is demonstrated by co‐immunoprecipitation, GST pull‐down, confocal laser assays, and so on. The results show that the knockdown of MYH10 suppressed SOC cell proliferation, migration, invasion, metastasis, and cisplatin resistance both in vivo and in vitro. Further studies confirm that the MYH10 protein functional domain combines with non‐muscle myosin heavy chain IIA (MYH9) to recruit the deubiquitinating enzyme Ubiquitin‐specific proteases 45 and deubiquitinates snail to inhibit snail degradation, eventually promoting tumorigenesis, progression, and cisplatin resistance in SOC. In clinical samples, MYH10 expression is significantly elevated in SOC samples compared to the paratumor samples. And the expression of MYH10 is positively correlated with MYH9 expression. MYH10+/MYH9+ co‐expression is an independent prognostic factor for predicting SOC patient survival. These findings uncover a key role of the MYH10‐MYH9‐snail axis in SOC carcinogenesis, progression, and cisplatin resistance, and provide potential novel therapeutic targets for SOC intervention. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs, which are covalently closed loop structures formed by precursor mRNAs (pre-mRNAs) through back-splicing. CircRNAs are abnormally expressed in many tumors, and play critical roles in a variety of tumors as oncogenes or tumor suppressor genes by sponging miRNAs, regulating alternative splicing and transcription, cis-regulating host genes, interacting with RNA binding proteins (RBPs) or encoding polypeptides. Among them, the regulation of circRNAs on their corresponding host genes is a critical way for circRNAs to exit their functions. Accumulating evidence suggests that circRNAs are able to regulate the expression of host genes at the transcriptional level, post-transcriptional level, translational level, post-translational level, or by encoding polypeptides. Therefore, this paper mainly summarized the roles and association of circRNAs and their corresponding host genes in tumorigenesis and tumor progression, generalized the circRNAs that function synergistically or antagonistically with their host genes, and elaborated the mechanisms of mutual regulation between circRNAs and their host genes. More importantly, this review provides specific references for revealing the potential application of circRNAs combined with their host genes in tumor diagnosis, treatment and prognosis. [ABSTRACT FROM AUTHOR]

Semiconductiong polymer nanoparticles (Pdots) have a wide range of applications in biomedical fields including biomolecular probes, tumor imaging, and therapy. However, there are few systematic studies on the biological effects and biocompatibility of Pdots in vitro and in vivo. The physicochemical properties of Pdots, such as surface modification, are very important in biomedical applications. Focusing on the central issue of the biological effects of Pdots, we systematically investigated the biological effects and biocompatibility of Pdots with different surface modifications and revealed the interactions between Pdots and organisms at the cellular and animal levels. The surfaces of Pdots were modified with different functional groups, including thiol, carboxyl, and amino groups, named Pdots@SH, Pdots@COOH, and Pdots@NH2, respectively. Extracellular studies showed that the modification of sulfhydryl, carboxyl, and amino groups had no significant effect on the physicochemical properties of Pdots, except that the amino modification affected the stability of Pdots to a certain extent. At the cellular level, Pdots@NH2 reduced cellular uptake capacity and increased cytotoxicity due to their instability in solution. At the in vivo level, the body circulation and metabolic clearance of Pdots@SH and Pdots@COOH were superior to those of Pdots@NH2. The four kinds of Pdots had no obvious effect on the blood indexes of mice and histopathological lesions in the main tissues and organs. This study provides important data for the biological effects and safety assessment of Pdots with different surface modifications, which pave the way for their potential biomedical applications. [ABSTRACT FROM AUTHOR]

Transfer RNAs (tRNAs) are a class of non-coding RNAs responsible for amino acid translocation during protein synthesis and are ubiquitously found in organisms. With certain modifications and under specific conditions, tRNAs can be sheared and fragmented into small non-coding RNAs, also known as tRNA-derived small RNAs (tDRs). With the development of high-throughput sequencing technologies and bioinformatic strategies, more and more tDRs have been identified and their functions in organisms have been characterized. tRNA and it derived tDRs, have been shown to be essential not only for transcription and translation, but also for regulating cell proliferation, apoptosis, metastasis, and immunity. Aberrant expression of tDRs is associated with a wide range of human diseases, especially with tumorigenesis and tumor progression. The tumor microenvironment (TME) is a complex ecosystem consisting of various cellular and cell-free components that are mutually compatible with the tumor. It has been shown that tDRs regulate the TME by regulating cancer stem cells, immunity, energy metabolism, epithelial mesenchymal transition, and extracellular matrix remodeling, playing a pro-tumor or tumor suppressor role. In this review, the biogenesis, classification, and function of tDRs, as well as their effects on the TME and the clinical application prospects will be summarized and discussed based on up to date available knowledge. [ABSTRACT FROM AUTHOR]

Near-data processing (NDP) architecture is promised to break the bottleneck of data movement in many scenarios (e.g., databases and recommendation systems), which limits the efficiency of data processing. Different from traditional SSD, NDP-based SSD not only needs to handle normal I/Os (e.g., read and write), but also needs to handle NDP requests that contain data processing operations. NDP and normal I/O requests share some function units of NDP-based SSD, such as flash chips and embedded processors. However, existing works ignore the resource competition between normal I/Os and NDP requests, which drastically degrades the performance. In this article, we propose a novel scheduling technique called Horae, which can efficiently schedule hybrid NDP-normal I/O requests in NDP-based SSD to improve performance. Horae exploits the critical paths on critical resources to maximize the parallelism of multiple stages of requests. The experimental results on typical workloads show that Horae can significantly improve the performance of hybrid NDP-normal I/O requests over the state-of-the-art scheduling algorithms of NDP-based SSDs. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) act as gene expression regulators and are involved in cancer progression. However, their functions have not been sufficiently investigated in nasopharyngeal carcinoma (NPC). Methods: The expression profiles of circRNAs in NPC cells within different metastatic potential were reanalyzed. Quantitative reverse transcription PCR and in situ hybridization were used to detect the expression level of circPVT1 in NPC cells and tissue samples. The association of expression level of circPVT1 with clinical properties of NPC patients was evaluated. Then, the effects of circPVT1 expression on NPC metastasis were investigated by in vitro and in vivo functional experiments. RNA immunoprecipitation, pull-down assay and western blotting were performed to confirm the interaction between circPVT1 and β-TrCP in NPC cells. Co-immunoprecipitation and western blotting were performed to confirm the interaction between β-TrCP and c-Myc in NPC cells. Results: We find that circPVT1, a circular RNA, is significantly upregulated in NPC cells and tissue specimens. In vitro and in vivo experiments showed that circPVT1 promotes the invasion and metastasis of NPC cells. Mechanistically, circPVT1 inhibits proteasomal degradation of c-Myc by binding to β-TrCP, an E3 ubiquiting ligase. Stablization of c-Myc by circPVT1 alters the cytoskeleton remodeling and cell adhesion in NPC, which ultimately promotes the invasion and metastasis of NPC cells. Furthermore, c-Myc transcriptionally upregulates the expression of SRSF1, an RNA splicing factor, and recruits SRSF1 to enhance the biosynthesis of circPVT1 through coupling transcription with splicing, which forms a positive feedback for circPVT1 production. Conclusions: Our results revealed the important role of circPVT1 in the progression of NPC through the β-TrCP/c-Myc/SRSF1 positive feedback loop, and circPVT1 may serve as a prognostic biomarker or therapeutic target in patients with NPC. [ABSTRACT FROM AUTHOR]

Inorganic–organic hybrid materials based on amorphous mesoporous silica containing organized nitroxide radicals within its mesopores have been prepared using the micellar self-assembly of TEOS solutions containing the nitroxide functionalized amphiphile (4-(N,N-dimethyl-N-hexadecylammonium)-2,2,6,6-tetramethyl-piperidin-N-oxyl-iodide) (CAT-16). This template has been used both in its pure form and in various mixtures with cetyl trimethylammonium bromide (CTAB). The samples have been characterized by chemical analysis, N 2 sorption studies, magnetic susceptibility measurements, and various spectroscopic methods. While electron paramagnetic resonance (EPR) spectra indicate that the strength of the intermolecular spin–spin interactions can be controlled via the CAT-16/CTAB ratio, nuclear magnetic resonance (NMR) data suggest that these interactions are too weak to facilitate cooperative magnetism. [ABSTRACT FROM AUTHOR]

• Extreme rainfall is more intense and frequent in urban than rural areas at the hourly than daily scale. • Urban areas provide a more favorable environment for the hourly rather than daily extreme rainfall. • Enhanced-CC behavior and urban–rural thermodynamic contrast are responsible for scale difference. • Similarities are found between climate warming and urban in intensifying hourly extreme rainfall. Despite the substantial progress in understanding the response of extreme precipitation to climate warming across different time scales, the response of these events to urbanization remains uncertain. Here, we evaluate changes in hourly and daily extreme precipitation during 1981–2020 in the urbanized Pearl River Delta, China, using observations and numerical simulations. The results of observations show that hourly rather than daily extreme precipitation in urban areas is more intense and frequent than in rural ones. Hourly extreme intensity increases ∼134 % faster than the daily one, and the urban downwind increase is most evident in hourly extreme precipitation frequency. The numerical simulations also show that the presence of urban areas increases hourly extreme intensity by ∼26 %, but increases daily extreme intensity by only ∼13 % when averaged over urban areas. The increases of precipitation intensities are local, and the increases across the whole region are much smaller than those over urban areas. Both observations and simulations indicate that urbanization exacerbates extreme precipitation and redistributes its spatial pattern, which is more pronounced at the hourly scale, potentially leading to a higher probability of hazardous urban flash floods. Our analysis of meteorological conditions elucidates that urban areas tend to create a drier and warmer surface environment and a more unstable atmosphere compared with surrounding rural areas. Moist air from surrounding rural areas is brought in to compensate for moisture anomalies and low pressure over the cities. This provides the air above urban areas with moisture, generating stronger updrafts, thus intensifying extreme precipitation over the cities. Urban areas provide a more favorable environment for the enhancement of hourly rather than daily extreme precipitation, and their differential responses to urbanization are mainly due to the mechanisms associated with enhanced-Clausius-Clapeyron behavior and the greater enhanced urban–rural thermal and moisture contrast in hourly extreme precipitation. Similarities can be found between the mechanisms of climate warming-induced and urban-induced intensification of localized hourly extreme precipitation Our results highlight the importance of understanding scale difference brought by urban environment, and thus provide a scale-based understanding of urban precipitation modification. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) is a key process in which precursor RNAs produce different mature RNAs, and the disorder of AS is a key factor in promoting cancer development. Compared with coding RNA, studies on the functions of long non-coding RNAs (lncRNAs) are far from enough. In fact, lncRNA is an important participant and regulator in the process of AS. On the one hand, lncRNAs regulate cancer progression as AS products of precursor messenger RNA (mRNA), but on the other hand, precursor lncRNA generates cancer-related abnormal splicing variants through AS. In addition, lncRNAs directly or indirectly regulate the AS events of downstream target genes, thus affecting the occurrence and development of cancer. Here, we reviewed how lncRNAs regulate AS and influence oncogenesis in different ways. [ABSTRACT FROM AUTHOR]

Recent studies have revealed that long non-coding RNAs participate in all steps of cancer initiation and progression by regulating protein-coding genes at the epigenetic, transcriptional, and post-transcriptional levels. Long non-coding RNAs are in turn regulated by other genes, forming a complex regulatory network. The regulation networks between the p53 tumor suppressor and these RNAs in nasopharyngeal carcinoma remains unclear. The aims of this study were to investigate the regulatory roles of the TP53 gene in regulating long non-coding RNA expression profiles and to study the function of a TP53-regulated long non-coding RNA (LOC401317) in the nasopharyngeal carcinoma cell line HNE2. Long non-coding RNA expression profiling indicated that 133 long non-coding RNAs were upregulated in the human NPC cell line HNE2 cells following TP53 overexpression, while 1057 were downregulated. Among these aberrantly expressed long non-coding RNAs, LOC401317 was the most significantly upregulated one. Further studies indicated that LOC401317 is directly regulated by p53 and that ectopic expression of LOC401317 inhibits HNE2 cell proliferation in vitro and in vivo by inducing cell cycle arrest and apoptosis. LOC401317 inhibited cell cycle progression by increasing p21 expression and decreasing cyclin D1 and cyclin E1 expression and promoted apoptosis through the induction of poly(ADP-ribose) polymerase and caspase-3 cleavage. Collectively, these results suggest that LOC401317 is directly regulated by p53 and exerts antitumor effects in HNE2 nasopharyngeal carcinoma cells. [ABSTRACT FROM AUTHOR]

In this research, we successfully developed a green, economical and effective one–step hydrothermal method for the synthesis of fluorescent nitrogen–doped carbon dots (N–CDs) by utilizing fresh tea leaves and urea as the carbon and nitrogen sources, respectively. The obtained N–CDs were characterized by TEM, XPS and FT–IR. We found that the N–CDs were near–spherical with an average size of about 2.32 nm, and contained abundant oxygen and nitrogen functional groups. The N–CDs exhibited bright blue fluorescence under ultraviolet illumination, with the maximum emission at 455 nm. Meanwhile, the as–prepared N–CDs could be selectively quenched by Fe3+ ions. The quenching of N–CDs is linearly correlated with the concentration of Fe3+ in the range of 0.1–400 μM with a low detection limit of 0.079 μM. Significantly, the N–CDs present excellent biocompatibility and high photostability. The results also depict that multicolor fluorescence is displayed under a fluorescence microscope and successfully applied for the detection of intracellular Fe3+. To sum up, the fluorescent N–CDs are expected to be a sensitive detection probe for Fe3+ in biological systems. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs play an important role in tumor genesis and progression, but they have not been sufficiently studied in patients with nasopharyngeal carcinoma (NPC). Methods: The circular RNA, circCAMSAP1, was screened in NPC cells by RNA sequencing analysis. The expression of circCAMSAP1 in NPC tissues was examined by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization. Wound-healing, transwell, MTT and flow cytometry assays, and nude mouse tumor models were used to explore the effect of circCAMSAP1 on proliferation and metastasis of NPC in vitro or in vivo. The downstream proteins regulated by circCAMSAP1 were screened using mass spectrometry. The interaction between circCAMSAP1 and the SERPINH1 mRNA was identified using the circular RNA immunoprecipitation method and the luciferase reporter assay. The interaction between SERPINH1 and transcription factor c-Myc was verified through Co-immunoprecipitation (Co-IP) and immunofluorescence. The effect of c-Myc on the generation of circCAMSAP1 was examined through RT-qPCR and chromatin immunoprecipitation. Finally, the splicing factors that promote the production of circCAMSAP1 were explored by RT-qPCR and RNA immunoprecipitation (RIP). Results: We found that circCAMSAP1 was highly expressed in NPC tissues and promoted NPC proliferation and metastasis. Additionally, circCAMSAP1 promoted SERPINH1 expression through improved SERPINH1 mRNA stability by binding to the 3′-untranslated region (3'UTR) of SERPINH1. Highly expressed SERPINH1 reduced the ubiquitination-degradation rate of c-Myc, causing increased tumorigenesis. Meanwhile, c-Myc, cooperating with splicing factor 10 (SRSF10), could also promote CAMSAP1 pre-mRNA transcription and back-splicing, forming a positive feedback of circCAMSAP1 production, resulting in the proliferation and metastasis of NPC. Conclusions: Our findings revealed that circCAMSAP1 promotes NPC proliferation and metastasis by binding to the 3'UTR of SERPINH1, suggesting that the positive feedback of circCAMSAP1-SERPINH1-c-Myc may serve as a prognostic biomarker or therapeutic target in patients with NPC. [ABSTRACT FROM AUTHOR]

Abstract: An avalanche photodiodes (APDs)-based heterodyne technique for FM/cw laser rangefinder (FM/cw LRF) is described. Based on a modified APDs model, the properties of heterodyne are theoretically analyzed and experimentally demonstrated under different illumination intensities and multiplications, both the amplitude and the signal to noise ratio (SNR) of the difference frequency signal are inversely proportional to the unmultiplied current at a high multiplication and are proportional to the square of multiplication at a low multiplication. [Copyright &y& Elsevier]

Background: Natural killer (NK) cells have gained considerable attention and hold great potential for their application in tumor immunotherapy. This is mainly due to their MHC-unrestricted and pan-specific recognition capabilities, as well as their ability to rapidly respond to and eliminate target cells. To artificially generate therapeutic NK cells, various materials can be utilized, such as peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK cell lines. Exploiting the therapeutic potential of NK cells to treat tumors through in vivo and in vitro therapeutic modalities has yielded positive therapeutic results.This review provides a comprehensive description of NK cell therapeutic approaches for tumors and discusses the current problems associated with these therapeutic approaches and the prospects of NK cell therapy for tumors.Conclusion: Natural killer (NK) cells have gained considerable attention and hold great potential for their application in tumor immunotherapy. This is mainly due to their MHC-unrestricted and pan-specific recognition capabilities, as well as their ability to rapidly respond to and eliminate target cells. To artificially generate therapeutic NK cells, various materials can be utilized, such as peripheral blood mononuclear cells (PBMCs), umbilical cord blood (UCB), induced pluripotent stem cells (iPSCs), and NK cell lines. Exploiting the therapeutic potential of NK cells to treat tumors through in vivo and in vitro therapeutic modalities has yielded positive therapeutic results.This review provides a comprehensive description of NK cell therapeutic approaches for tumors and discusses the current problems associated with these therapeutic approaches and the prospects of NK cell therapy for tumors. [ABSTRACT FROM AUTHOR]

The cyclic signal amplification technology has been widely applied for the ultrasensitive detection of many important biomolecules, such as nucleic acids, proteins, enzymes, adenosine triphosphate (ATP), metal ions, exosome, etc. Due to their low content in the complex biological samples, traditional detection methods are insufficient to satisfy the requirements for monitoring those biomolecules. Therefore, effective and sensitive biosensors based on cyclic signal amplification technology are of great significance for the quick and simple diagnosis and treatment of diseases. Fluorescent biosensor based on cyclic signal amplification technology has become a research hotspot due to its simple operation, low cost, short time, high sensitivity and high specificity. This paper introduces several cyclic amplification methods, such as rolling circle amplification (RCA), strand displacement reactions (SDR) and enzyme-assisted amplification (EAA), and summarizes the research progress of using this technology in the detection of different biomolecules in recent years, in order to provide help for the research of more efficient and sensitive detection methods. [ABSTRACT FROM AUTHOR]

Cancer/testis antigens (CTAs) are a group of tumor antigens expressed in numerous cancer tissues, as well as in the testis and placental tissues. There are over 200 CTAs supported by serology and expression data. The expression patterns of CTAs reflect the similarities between the processes of gametogenesis and tumorigenesis. It is notable that CTAs are highly expressed in three types of cancers (lung cancer, bladder cancer, and skin cancer), all of which have a metal etiology. Here, we review the expression, regulation, and function of CTAs and their translational prospects as cancer biomarkers and treatment targets. Many CTAs are highly immunogenic, tissue-specific, and frequently expressed in cancer tissues but not under physiological conditions, rendering them promising candidates for cancer detection. Some CTAs are associated with clinical outcomes, so they may serve as prognostic biomarkers. A small number of CTAs are membrane-bound, making them ideal targets for chimeric antigen receptor (CAR) T cells. Mounting evidence suggests that CTAs induce humoral or cellular immune responses, providing cancer immunotherapeutic opportunities for T-cell receptors (TCRs), CAR T cell, antibody-based therapy and peptide- or mRNA-based vaccines. Indeed, CTAs are the dominating non-mutated targets in mRNA cancer vaccine development. Clinical trials on CTA TCR and vaccines have shown effectiveness, safety, and tolerance, but these successes are limited to a small number of patients. In-depth studies on CTA expression and function are needed to improve CTA-based immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a condition of high blood pressure that is usually concurrent with proteinuria in pregnancy. PE complicates the management of both maternal and fetal health and contributes to most adverse pregnancy outcomes, but the mechanism underlying the development of PE remains unclear. In this study, we performed a case-control study to compare the gut microbiota of PE (n = 26), abnormal placental growth (APG, n = 25) and healthy pregnant women (n = 28) and analyzed the potential pathogenic role of gut microbiota in PE progression. Results: The clinical pathophysiological state did not affect the bacterial diversity, while the compositions of the gut microbiota were significantly altered in both the PE and APG groups compared with healthy pregnant women. At the phylum level, TM7 was significantly increased in women with APG. Heterogeneity was observed at the genus level, especially in genera with positive LDA scores, suggesting the stage-dependent effect of gut microbiota on the development of PE. The beneficial bacterium Lactobacillus was markedly depleted in the PE and APG groups but was only correlated with blood pressure (BP) and proteinuria levels in the PE group. Two different bacterial taxa belonged to Lactobacillus showed different correlations (OTU255 and OTU784 were significantly related to PE and APG, respectively). Conclusions: Our results indicated that shifts in the gut microbiota might occur from the early stages of the development of PE, which is of possible etiological and therapeutic importance. [ABSTRACT FROM AUTHOR]

Abstract: Recently, the UBAPl gene, a putative nasopharyngeal carcinoma (NPC) related gene, which is located at human chromosome 9p21-22 where loss of heterozygosity frequently occurs in NPC, was cloned. The present study aimed to explore the purification approach to UBAP1 protein and its expression pattern in NPC with tissue microarray. The full length coding sequence of UBAP1 was subcloned into a prokaryotic expression vector, pGEX-4T-2, and expressed in Escherichia coli as a GST-fusion protein. With modification of the purification method, GST–UBAP1 fusion protein achieved a high level of purity. The New Zealand rabbit was immunized with the purified fusion protein to prepare polyclonal antiserum following standard protocols. With this antiserum, high-throughput analysis of UBAP1 protein expression using immunohistochemistry was performed on self-made tissue microarrays consisting of 316 nasopharyngeal specimens from 148 NPC and 168 non-cancerous nasopharyngeal epithelia with different morphological features. Consequently, we found that there was a significant decrease in the percentage of positive expression in all NPC on protein levels for UBAP1 (23%), compared to that of the non-NPC (89%) (P <0.01). The result suggests that UBAP1 might be a potential effective diagnosis candidate for NPC and decreased expression of UBAP1 protein is a possible point of dysfunction along the pathogenesis pathway for NPC that may contribute to malignant transformation. [Copyright &y& Elsevier]

Background: Pyroptosis is a lytic cell death form executed by gasdermins family proteins. Induction of tumor pyroptosis promotes anti-tumor immunity and is a potential cancer treatment strategy. Triptolide (TPL) is a natural product isolated from the traditional Chinese herb which possesses potent anti-tumor activity in human cancers. However, its role in pyroptosis remains to be elucidated. Methods: Cell survival was measured by colony formation assay. Cell apoptosis was determined by Annexin V assay. Pyroptosis was evaluated by morphological features and release of interleukin 1β and lactate dehydrogenase A (LDHA). Immunofluorescence staining was employed to measure subcellular localization of proteins. Tumorigenicity was assessed by a xenograft tumor model. Expression levels of mRNAs or proteins were determined by qPCR or western blot assay, respectively. Results: Triptolide eliminates head and neck cancer cells through inducing gasdermin E (GSDME) mediated pyroptosis. Silencing GSDME attenuates the cytotoxicity of TPL against cancer cells. TPL treatment suppresses expression of c-myc and mitochondrial hexokinase II (HK-II) in cancer cells, leading to activation of the BAD/BAX-caspase 3 cascade and cleavage of GSDME by active caspase 3. Silencing HK-II sensitizes cancer cells to TPL induced pyroptosis, whereas enforced expression of HK-II prevents TPL induced pyroptosis. Mechanistically, HK-II prevents mitochondrial translocation of BAD, BAX proteins and activation of caspase 3, thus attenuating cleavage of GSDME and pyroptosis upon TPL treatment. Furthermore, TPL treatment suppresses NRF2/SLC7A11 (also known as xCT) axis and induces reactive oxygen species (ROS) accumulation, regardless of the status of GSDME. Combination of TPL with erastin, an inhibitor of SLC7A11, exerts robust synergistic effect in suppression of tumor survival in vitro and in a nude mice model. Conclusions: This study not only provides a new paradigm of TPL in cancer therapy, but also highlights a crucial role of mitochondrial HK-II in linking glucose metabolism with pyroptosis. [ABSTRACT FROM AUTHOR]

Background: Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer. Main body: Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies. Conclusion: In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy. [ABSTRACT FROM AUTHOR]

Background: Pyroptosis is a lytic cell death form executed by gasdermins family proteins. Induction of tumor pyroptosis promotes anti-tumor immunity and is a potential cancer treatment strategy. Triptolide (TPL) is a natural product isolated from the traditional Chinese herb which possesses potent anti-tumor activity in human cancers. However, its role in pyroptosis remains to be elucidated. Methods: Cell survival was measured by colony formation assay. Cell apoptosis was determined by Annexin V assay. Pyroptosis was evaluated by morphological features and release of interleukin 1β and lactate dehydrogenase A (LDHA). Immunofluorescence staining was employed to measure subcellular localization of proteins. Tumorigenicity was assessed by a xenograft tumor model. Expression levels of mRNAs or proteins were determined by qPCR or western blot assay, respectively. Results: Triptolide eliminates head and neck cancer cells through inducing gasdermin E (GSDME) mediated pyroptosis. Silencing GSDME attenuates the cytotoxicity of TPL against cancer cells. TPL treatment suppresses expression of c-myc and mitochondrial hexokinase II (HK-II) in cancer cells, leading to activation of the BAD/BAX-caspase 3 cascade and cleavage of GSDME by active caspase 3. Silencing HK-II sensitizes cancer cells to TPL induced pyroptosis, whereas enforced expression of HK-II prevents TPL induced pyroptosis. Mechanistically, HK-II prevents mitochondrial translocation of BAD, BAX proteins and activation of caspase 3, thus attenuating cleavage of GSDME and pyroptosis upon TPL treatment. Furthermore, TPL treatment suppresses NRF2/SLC7A11 (also known as xCT) axis and induces reactive oxygen species (ROS) accumulation, regardless of the status of GSDME. Combination of TPL with erastin, an inhibitor of SLC7A11, exerts robust synergistic effect in suppression of tumor survival in vitro and in a nude mice model. Conclusions: This study not only provides a new paradigm of TPL in cancer therapy, but also highlights a crucial role of mitochondrial HK-II in linking glucose metabolism with pyroptosis. [ABSTRACT FROM AUTHOR]

Background: Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer. Main body: Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies. Conclusion: In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy. [ABSTRACT FROM AUTHOR]