The physiological and pathological roles of RNA modifications in T cells.

RNA molecules undergo dynamic chemical modifications in response to various external or cellular stimuli. Some of those modifications have been demonstrated to post-transcriptionally modulate the RNA transcription, localization, stability, translation, and degradation, ultimately tuning the fate decisions and function of mammalian cells, particularly T cells. As a crucial part of adaptive immunity, T cells play fundamental roles in defending against infections and tumor cells. Recent findings have illuminated the importance of RNA modifications in modulating T cell survival, proliferation, differentiation, and functional activities. Therefore, understanding the epi-transcriptomic control of T cell biology enables a potential avenue for manipulating T cell immunity. This review aims to elucidate the physiological and pathological roles of internal RNA modifications in T cell development, differentiation, and functionality drawn from current literature, with the goal of inspiring new insights for future investigations and providing novel prospects for T cell-based immunotherapy.

High-integrity Pueraria montana var. lobata genome and population analysis revealed the genetic diversity of Pueraria genus.

Pueraria montana var. lobata (P. lobata) is a traditional medicinal plant belonging to the Pueraria genus of Fabaceae family. Pueraria montana var. thomsonii (P. thomsonii) and Pueraria montana var. montana (P. montana) are its related species. However, evolutionary history of the Pueraria genus is still largely unknown. Here, a high-integrity, chromosome-level genome of P. lobata and an improved genome of P. thomsonii were reported. It found evidence for an ancient whole-genome triplication and a recent whole-genome duplication shared with Fabaceae in three Pueraria species. Population genomics of 121 Pueraria accessions demonstrated that P. lobata populations had substantially higher genetic diversity, and P. thomsonii was probably derived from P. lobata by domestication as a subspecies. Selection sweep analysis identified candidate genes in P. thomsonii populations associated with the synthesis of auxin and gibberellin, which potentially play a role in the expansion and starch accumulation of tubers in P. thomsonii. Overall, the findings provide new insights into the evolutionary and domestication history of the Pueraria genome and offer a valuable genomic resource for the genetic improvement of these species.

Dipeptidyl peptidase-4 inhibitors and the risk of infection: A systematic review and meta-analysis of cardiovascular outcome trials.

BACKGROUND: Since adverse events during treatment affect adherence and subsequent glycemic control, understanding the safety profile of oral anti-diabetic drugs is imperative for type 2 diabetes mellitus (T2DM) therapy. AIM: To evaluate the risk of infection in patients with T2DM treated with dipeptidyl-peptidase 4 (DPP-4) inhibitors. METHODS: Electronic databases were searched. The selection criteria included randomized controlled trials focused on cardiovascular outcomes. In these studies, the effects of DPP-4 inhibitors were directly compared to those of either other active anti-diabetic treatments or placebo. Six trials involving 53616 patients were deemed eligible. We calculated aggregate relative risks employing both random-effects and fixed-effects approaches, contingent upon the context. RESULTS: The application of DPP-4 inhibitors showed no significant link to the overall infection risk [0.98 (0.95, 1.02)] or the risk of serious infections [0.96 (0.85, 1.08)], additionally, no significant associations were found with opportunistic infections [0.69 (0.46, 1.04)], site-specific infections [respiratory infection 0.99 (0.96, 1.03), urinary tract infections 1.02 (0.95, 1.10), abdominal and gastrointestinal infections 1.02 (0.83, 1.25), skin structure and soft tissue infections 0.81 (0.60, 1.09), bone infections 0.96 (0.68, 1.36), and bloodstream infections 0.97 (0.80, 1.18)]. CONCLUSION: This meta-analysis of data from cardiovascular outcome trials revealed no heightened infection risk in patients undergoing DPP-4 inhibitor therapy compared to control cohorts.

Triceps skinfold thickness trajectories and the risk of all-cause mortality: A prospective cohort study.

BACKGROUND: The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated. AIM: To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality. METHODS: This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors. RESULTS: Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort. CONCLUSION: In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

Optimizing Ionomer Distribution in Anode Catalyst Layer for Stable Proton Exchange Membrane Water Electrolysis.

The high cost of proton exchange membrane water electrolysis (PEMWE) originates from the usage of precious materials, insufficient efficiency, and lifetime. In this work, an important degradation mechanism of PEMWE caused by dynamics of ionomers over time in anode catalyst layer (ACL), which is a purely mechanical degradation of microstructure, is identified. Contrary to conventional understanding that the microstructure of ACL is static, the micropores are inclined to be occupied by ionomers due to the localized swelling/creep/migration, especially near the ACL/PTL (porous transport layer) interface, where they form transport channels of reactant/product couples. Consequently, the ACL with increased ionomers at PTL/ACL interface exhibit rapid and continuous degradation. In addition, a close correlation between the microstructure of ACL and the catalyst ink is discovered. Specifically, if more ionomers migrate to the top layer of the ink, more ionomers accumulate at the ACL/PEM interface, leaving fewer ionomers at the ACL/PTL interface. Therefore, the ionomer distribution in ACL is successfully optimized, which exhibits reduced ionomers at the ACL/PTL interface and enriches ionomers at the ACL/PEM interface, reducing the decay rate by a factor of three when operated at 2.0 A cm-2 and 80 °C. The findings provide a general way to achieve low-cost hydrogen production.

Multi-Omics Analysis Reveals the Distinct Features of Metabolism Pathways Supporting the Fruit Size and Color Variation of Giant Pumpkin.

Pumpkin (Cucurbita maxima) is an important vegetable crop of the Cucurbitaceae plant family. The fruits of pumpkin are often used as directly edible food or raw material for a number of processed foods. In nature, mature pumpkin fruits differ in size, shape, and color. The Atlantic Giant (AG) cultivar has the world's largest fruits and is described as the giant pumpkin. AG is well-known for its large and bright-colored fruits with high ornamental and economic value. At present, there are insufficient studies that have focused on the formation factors of the AG cultivar. To address these knowledge gaps, we performed comparative transcriptome, proteome, and metabolome analysis of fruits from the AG cultivar and a pumpkin with relatively small fruit (Hubbard). The results indicate that up-regulation of gene-encoded expansins contributed to fruit cell expansion, and the increased presence of photoassimilates (stachyose and D-glucose) and jasmonic acid (JA) accumulation worked together in terms of the formation of large fruit in the AG cultivar. Notably, perhaps due to the rapid transport of photoassimilates, abundant stachyose that was not converted into glucose in time was detected in giant pumpkin fruits, implying that a unique mode of assimilate unloading is in existence in the AG cultivar. The potential molecular regulatory network of photoassimilate metabolism closely related to pumpkin fruit expansion was also investigated, finding that three MYB transcription factors, namely CmaCh02G015900, CmaCh01G018100, and CmaCh06G011110, may be involved in metabolic regulation. In addition, neoxanthin (a type of carotenoid) exhibited decreased accumulation that was attributed to the down-regulation of carotenoid biosynthesis genes in AG fruits, which may lead to pigmentation differences between the two pumpkin cultivars. Our current work will provide new insights into the potential formation factors of giant pumpkins for further systematic elucidation.

Efficient and Stable Proton Exchange Membrane Water Electrolysis Enabled by Stress Optimization.

Proton exchange membrane water electrolysis (PEMWE) is a promising solution for the conversion and storage of fluctuating renewable energy sources. Although tremendously efficient materials have been developed, commercial PEMWE products still cannot fulfill industrial demands regarding efficiency and stability. In this work, we demonstrate that the stress distribution, a purely mechanical parameter in electrolyzer assembly, plays a critical role in overall efficiency and stability. The conventional cell structure, which usually adopts a serpentine flow channel (S-FC) to deliver and distribute reactants and products, resulted in highly uneven stress distribution. Consequently, the anode catalyst layer (ACL) under the high stress region was severely deformed, whereas the low stress region was not as active due to poor electrical contact. To address these issues, we proposed a Ti mesh flow channel (TM-FC) with gradient pores to reduce the stress inhomogeneity. Consequently, the ACL with TM-FC exhibited 27 mV lower voltage initially and an 8-fold reduction in voltage degradation rate compared to that with S-FC at 2.0 A/cm2. Additionally, the applicability of the TM-FC was demonstrated in cross-scale electrolyzers up to 100 kW, showing a voltage increase of only 20 mV (accounting for less than 2% of overall voltage) after three orders of magnitude scaleup.

METTL3 as a novel diagnosis and treatment biomarker and its association with glycolysis, cuproptosis and ceRNA in oesophageal carcinoma.

METTL3 has been shown to be involved in regulating a variety of biological processes. However, the relationship between METTL3 expression and glycolysis, cuproptosis-related genes and the ceRNA network in oesophageal carcinoma (ESCA) remains unclear. ESCA expression profiles from databases were obtained, and target genes were identified using differential analysis and visualization. Immunohistochemistry (IHC) staining assessed METTL3 expression differences. Functional enrichment analysis using GO, KEGG and GSEA was conducted on the co-expression profile of METTL3. Cell experiments were performed to assess the effect of METTL3 interference on tumour cells. Correlation and differential analyses were carried out to assess the relationship between METTL3 with glycolysis and cuproptosis. qRT-PCR was used to validate the effects of METTL3 interference on glycolysis-related genes. Online tools were utilized to screen and construct ceRNA networks based on the ceRNA theory. METTL3 expression was significantly higher in ESCA compared to the controls. The IHC results were consistent with the above results. Enrichment analysis revealed that METTL3 is involved in multiple pathways associated with tumour development. Significant correlations were observed between METTL3 and glycolysis-related genes and cuproptosis-related gene. Experiments confirmed that interfered with METTL3 significantly inhibited glucose uptake and lactate production in tumour cells, and affected the expression of glycolytic-related genes. Finally, two potential ceRNA networks were successfully predicted and constructed. Our study establishes the association between METTL3 overexpression and ESCA progression. Additionally, we propose potential links between METTL3 and glycolysis, cuproptosis and ceRNA, presenting a novel targeted therapy strategy for ESCA.

Constructing Robust 3D Ionomer Networks in the Catalyst Layer to Achieve Stable Water Electrolysis for Green Hydrogen Production.

The widespread application of proton exchange membrane water electrolyzers (PEMWEs) is hampered by insufficient lifetime caused by degradation of the anode catalyst layer (ACL). Here, an important degradation mechanism has been identified, attributed to poor mechanical stability causing the mass transfer channels to be blocked by ionomers under operating conditions. By using liquid-phase atomic force microscopy, we directly observed that the ionomers were randomly distributed (RD) in the ACL, which occupied the mass transfer channels due to swelling, creeping, and migration properties. Interestingly, we found that alternating treatments of the ACL in different water/temperature environments resulted in forming three-dimensional ionomer networks (3D INs) in the ACL, which increased the mechanical strength of microstructures by 3 times. Benefitting from the efficient and stable mass transfer channels, the lifetime was improved by 19 times. A low degradation rate of approximately 3.0 µV/h at 80 °C and a high current density of 2.0 A/cm2 was achieved on a 50 cm2 electrolyzer. These data demonstrated a forecasted lifetime of 80 000 h, approaching the 2026 DOE lifetime target. This work emphasizes the importance of the mechanical stability of the ACL and offers a general strategy for designing and developing a durable PEMWE.

TRIP6 a potential diagnostic marker for colorectal cancer with glycolysis and immune infiltration association.

Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.

A compact multi-pixel superconducting nanowire single-photon detector array supporting gigabit space-to-ground communications.

Classical and quantum space-to-ground communications necessitate highly sensitive receivers capable of extracting information from modulated photons to extend the communication distance from near-earth orbits to deep space explorations. To achieve gigabit data rates while mitigating strong background noise photons and beam drift in a highly attenuated free-space channel, a comprehensive design of a multi-functional detector is indispensable. In this study, we present an innovative compact multi-pixel superconducting nanowire single-photon detector array that integrates near-unity detection efficiency (91.6%), high photon counting rate (1.61 Gcps), large dynamic range for resolving different photon numbers (1-24), and four-quadrant position sensing function all within one device. Furthermore, we have constructed a communication testbed to validate the advantages offered by such an architecture. Through 8-PPM (pulse position modulation) format communication experiments, we have achieved an impressive maximum data rate of 1.5 Gbps, demonstrating sensitivities surpassing previous benchmarks at respective speeds. By incorporating photon number information into error correction codes, the receiver can tolerate maximum background noise levels equivalent to 0.8 photons/slot at a data rate of 120 Mbps-showcasing a great potential for daylight operation scenarios. Additionally, preliminary beam tracking tests were conducted through open-loop scanning techniques, which revealed clear quantitative dependence indicating sensitivity variations based on beam location. Based on the device characterizations and communication results, we anticipate that this device architecture, along with its corresponding signal processing and coding techniques, will be applicable in future space-to-ground communication tasks.

The crosstalk between enteric nervous system and immune system in intestinal development, homeostasis and diseases.

The gut is the largest digestive and absorptive organ, which is essential for induction of mucosal and systemic immune responses, and maintenance of metabolic-immune homeostasis. The intestinal components contain the epithelium, stromal cells, immune cells, and enteric nervous system (ENS), as well as the outers, such as gut microbiota, metabolites, and nutrients. The dyshomeostasis of intestinal microenvironment induces abnormal intestinal development and functions, even colon diseases including dysplasia, inflammation and tumor. Several recent studies have identified that ENS plays a crucial role in maintaining the immune homeostasis of gastrointestinal (GI) microenvironment. The crosstalk between ENS and immune cells, mainly macrophages, T cells, and innate lymphoid cells (ILCs), has been found to exert important regulatory roles in intestinal tissue programming, homeostasis, function, and inflammation. In this review, we mainly summarize the critical roles of the interactions between ENS and immune cells in intestinal homeostasis during intestinal development and diseases progression, to provide theoretical bases and ideas for the exploration of immunotherapy for gastrointestinal diseases with the ENS as potential novel targets.

A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

Auxin homeostasis is maintained by sly-miR167-SlARF8A/B-SlGH3.4 feedback module in the development of locular and placental tissues of tomato fruits.

The locular gel, produced by the placenta, is important for fruit flavor and seed development in tomato. However, the mechanism underlying locule and placenta development is not fully understood yet. Here, we show that two SlARF transcription factors, SlARF8B and SlARF8A (SlARF8A/B), promote the development of locular and placenta tissues. The expression of both SlARF8A and SlARF8B is repressed by sly-microRNA167 (sly-miR167), allowing for the activation of auxin downstream genes. In slarf8a, slarf8b, and slarf8a/b mutants, the auxin (IAA) levels are decreased, whereas the levels of inactive IAA conjugates including IAA-Ala, IAA-Asp, and IAA-Glu are increased. We further find that SlARF8B directly inhibits the expression of SlGH3.4, an acyl acid amino synthetase that conjugates the amino acids to IAA. Disruption of such auxin balance by the increased expression of SlGH3.4 or SlGH3.2 results in defective locular and placental tissues. Taken together, our findings reveal an important regulatory module constituted by sly-miR167-SlARF8A/B-SlGH3.4 during the development of locular and placenta tissues of tomato fruits.

University MOOC should be added with farmer interested sections and provide individualized service to adapt to farmer training.

Vegetables represent an important agricultural industry in China. New farmers and new technologies for vegetable production have emerged in recent years, which makes farmer training very necessary. On the other hand, massive open online courses (MOOCs) are currently widely used in universities. The purpose of this study is to investigate the importance of different sections of a university MOOC focused on olericulture to farmers with different demographic characteristics and provide a basis to improve university MOOCs for farmer training. The survey results suggest that the age, education level, gender, farmer scale, facility type and profit of farmer learners are important factors determining evaluations of the importance of different MOOC sections, indicating that services customized to different farmer populations are necessary. Among different sections of MOOC "Olericulture", farmers with younger age, higher education, larger farm, more advanced facility and more profit were more interesting in sections include cultural, social and theoretical knowledge, and less interesting in practical skill sections. Based on the survey, eight new sections including one marketing subsection (new agricultural supplies and market news), one social subsection (laws and regulations), two practical subsections (practice videos, photos and videos from other farms), and three comprehensive subsections (discussion of practical issues, mechanization, and smart olericulture) were added to the original MOOC, and the results indicate that this improvement is efficient in enhancing the importance evaluations and profits of all farmer learners, especially among those with high education levels.

Transcription Factor Id1 Plays an Essential Role in Th9 Cell Differentiation by Inhibiting Tcf3 and Tcf4.

T helper type 9 (Th9) cells play important roles in immune responses by producing interleukin-9 (IL-9). Several transcription factors are responsible for Th9 cell differentiation; however, transcriptional regulation of Th9 cells is not fully understood. Here, it is shown that Id1 is an essential transcriptional regulator of Th9 cell differentiation. Id1 is induced by IL-4 and TGF-ß. Id1-deficient naïve CD4 T cells fail to differentiate into Th9 cells, and overexpression of Id1 induce expression of IL-9. Mass spectrometry analysis reveals that Id1 interacts with Tcf3 and Tcf4 in Th9 cells. In addition, RNA-sequencing, chromatin immunoprecipitation, and transient reporter assay reveal that Tcf3 and Tcf4 bind to the promoter region of the Il9 gene to suppress its expression, and that Id1 inhibits their function, leading to Th9 differentiation. Finally, Id1-deficient Th9 cells ameliorate airway inflammation in an animal model of asthma. Thus, Id1 is a transcription factor that plays an essential role in Th9 cell differentiation by inhibiting Tcf3 and Tcf4.

[Regulation effect of serum IFN-γ and IL-4 expression on immune response in patients with oral lichen planus].

PURPOSE: To investigate the regulation effect of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in the serum of patients with oral lichen planus (OLP) on immune response. METHODS: A total of 83 OLP patients in Wangfujing Branch of Beijing Stomatological Hospital, Capital Medical University from January 2019 to December 2021 were selected as the experimental group, and another 61 healthy volunteers who came to the hospital during the same period were included as the control group. The expression levels of IFN-γ and IL-4 in the serum and the expression of immune function indexes of the two groups were compared. The relationship between the expression levels of IFN-γ, IL-4 and immune function indicators in the experimental group was analyzed. SPSS 22.0 software package was used to analyze the data. RESULTS: The levels of IFN-γ and IL-4 in the experimental group were significantly higher than those in the control group(P＜0.05). There was no significant difference in the levels of IFN-γ between patients with reticulated OLP and erosive OLP in the experimental group (P＞0.05). The level of IL-4 in patients with erosive OLP in the experimental group was significantly higher than that in patients with reticulated OLP(P＜0.05). The levels of CD3+, CD4, CD16++CD56+ and CD4+/CD8+ in the experimental group were significantly lower than those in the control group(P＜0.05), the levels of CD8+ and CD19+ in the experimental group were significantly higher than those in the control group(P＜0.05). The levels of IgG, IgM and CH50 in the experimental group were significantly higher than those in the control group(P＜0.05), and the levels of IgA, C3 and C4 in the experimental group were significantly lower than those in the control group(P＜0.05). Pearson correlation analysis showed that the level of IFN-γ in the experimental group was negatively correlated with CD16++CD56+ and CD4+/CD8+ (P＜0.05), the level of IL-4 in the experimental group was negatively correlated with CD16++CD56+ and CD4+/CD8+(P＜0.05), and the level of IL-4 in the experimental group was positively correlated with IgG (P＜0.05). CONCLUSIONS: Serum IFN-γ and IL-4 in OLP patients are abnormally high, and IL-4 expression is significantly higher in erosive OLP patients. The cellular and humoral immune functions of OLP patients are disordered and related to the regulation of CD16++CD56+, CD4+/CD8+, and IgG immune responses.

A novel fluorescent dye selectively images and kills cancer stem cells by targeting mitochondria: Evidence from a cell line­based zebrafish xenograft model.

Numerous agents such as near-infrared dyes that are characterized by specialized cancer imaging and cytotoxicity effects have key roles in cancer diagnosis and therapy via molecularly targeting special biological tissues, organelles and processes. In the present study, a novel fluorescent compound was demonstrated to inhibit cancer cell proliferation in a zebrafish model with slight in vivo toxicity. Further studies demonstrated selective staining of cancer cells and even putative cancer stem cells via accumulation of the dye in the mitochondria of cancer cells, compared with normal cells. Moreover, this compound was also used to image cancer cells in vivo using a zebrafish model. The compound displayed no apparent toxicity to the host animal. Overall, the data indicated that this compound was worthy of further evaluation due to its low toxicity and selective cancer cell imaging and killing effects. It could be a useful tool in cancer research.