The heat shock factor 20-HSF4-cellulose synthase A2 module regulates heat stress tolerance in maize.

Temperature shapes the geographical distribution and behavior of plants. Understanding the regulatory mechanisms underlying the plant heat stress response is important for developing climate-resilient crops, including maize (Zea mays). To identify transcription factors (TFs) that may contribute to the maize heat stress response, we generated a dataset of short- and long-term transcriptome changes following a heat treatment time course in the inbred line B73. Co-expression network analysis highlighted several TFs, including the class B2a heat shock factor (HSF) ZmHSF20. Zmhsf20 mutant seedlings exhibited enhanced tolerance to heat stress. Furthermore, DNA affinity purification sequencing and Cleavage Under Targets and Tagmentation assays demonstrated that ZmHSF20 binds to the promoters of Cellulose synthase A2 (ZmCesA2) and three class A Hsf genes, including ZmHsf4, repressing their transcription. We showed that ZmCesA2 and ZmHSF4 promote the heat stress response, with ZmHSF4 directly activating ZmCesA2 transcription. In agreement with the transcriptome analysis, ZmHSF20 inhibited cellulose accumulation and repressed the expression of cell wall-related genes. Importantly, the Zmhsf20 Zmhsf4 double mutant exhibited decreased thermotolerance, placing ZmHsf4 downstream of ZmHsf20. We proposed an expanded model of the heat stress response in maize, whereby ZmHSF20 lowers seedling heat tolerance by repressing ZmHsf4 and ZmCesA2, thus balancing seedling growth and defense.

A Flexible, Adaptive, and Self-Powered Triboelectric Vibration Sensor with Conductive Sponge-Silicone for Machinery Condition Monitoring.

Vibration sensors for continuous and reliable condition monitoring of mechanical equipment, especially detection points of curved surfaces, remain a great challenge and are highly desired. Herein, a highly flexible and adaptive triboelectric vibration sensor for high-fidelity and continuous monitoring of mechanical vibration conditions is proposed. The sensor is entirely composed of flexible materials. It consists of a conductive sponge-silicone layer and a fluorinated ethylene propylene film. It can detect vibration acceleration of 5 to 50 m s-2 and vibration frequency of 10 to 100 Hz. It has strong robustness and stability, and the output performance barely changes after the durability test of 168 000 working cycles. Additionally, the flexible sensor can work even when the detection point of the mechanical equipment is curved, and the linear fit of the output voltage and acceleration is very close to that when the detection point is flat. Finally, it can be applied to monitoring the working condition of blower and vehicle engine, and can transmit vibration signal to mobile phone application through Wi-Fi module for real-time monitoring. The flexible triboelectric vibration sensor is expected to provide a practical paradigm for smart, green, and sustainable wireless sensor system in the era of Internet of Things.

Integrative single-cell analysis: dissecting CD8 + memory cell roles in LUAD and COVID-19 via eQTLs and Mendelian Randomization.

Lung adenocarcinoma exhibits high incidence and mortality rates, presenting a significant health concern. Concurrently, the COVID-19 pandemic has emerged as a grave global public health challenge. Existing literature suggests that T cells, pivotal components of cellular immunity, are integral to both antiviral and antitumor responses. Yet, the nuanced alterations and consequent functions of T cells across diverse disease states have not been comprehensively elucidated. We gathered transcriptomic data of peripheral blood mononuclear cells from lung adenocarcinoma patients, COVID-19 patients, and healthy controls. We followed a standardized analytical approach for quality assurance, batch effect adjustments, and preliminary data processing. We discerned distinct T cell subsets and conducted differential gene expression analysis. Potential key genes and pathways were inferred from GO and Pathway enrichment analyses. Additionally, we implemented Mendelian randomization to probe the potential links between pivotal genes and lung adenocarcinoma susceptibility. Our findings underscored a notable reduction in mature CD8 + central memory T cells in both lung adenocarcinoma and COVID-19 cohorts relative to the control group. Notably, the downregulation of specific genes, such as TRGV9, could impede the immunological efficacy of CD8 + T cells. Comprehensive multi-omics assessment highlighted genetic aberrations in genes, including TRGV9, correlating with heightened lung adenocarcinoma risk. Through rigorous single-cell transcriptomic analyses, this investigation meticulously delineated variations in T cell subsets across different pathological states and extrapolated key regulatory genes via an integrated multi-omics approach, establishing a robust groundwork for future functional inquiries. This study furnishes valuable perspectives into the etiology of multifaceted diseases and augments the progression of precision medicine.

DRL-RNP: Deep Reinforcement Learning-Based Optimized RNP Flight Procedure Execution.

The required navigation performance (RNP) procedure is one of the two basic navigation specifications for the performance-based navigation (PBN) procedure as proposed by the International Civil Aviation Organization (ICAO) through an integration of the global navigation infrastructures to improve the utilization efficiency of airspace and reduce flight delays and the dependence on ground navigation facilities. The approach stage is one of the most important and difficult stages in the whole flying. In this study, we proposed deep reinforcement learning (DRL)-based RNP procedure execution, DRL-RNP. By conducting an RNP approach procedure, the DRL algorithm was implemented, using a fixed-wing aircraft to explore a path of minimum fuel consumption with reward under windy conditions in compliance with the RNP safety specifications. The experimental results have demonstrated that the six degrees of freedom aircraft controlled by the DRL algorithm can successfully complete the RNP procedure whilst meeting the safety specifications for protection areas and obstruction clearance altitude in the whole procedure. In addition, the potential path with minimum fuel consumption can be explored effectively. Hence, the DRL method can be used not only to implement the RNP procedure with a simulated aircraft but also to help the verification and evaluation of the RNP procedure.

Construction of a competitive endogenous RNA network and analysis of potential regulatory axis targets in glioblastoma.

BACKGROUND: Glioblastoma is the most common primary malignant brain tumor. Because of the limited understanding of its pathogenesis, the prognosis of glioblastoma remains poor. This study was conducted to explore potential competing endogenous RNA (ceRNA) network chains and biomarkers in glioblastoma by performing integrated bioinformatics analysis. METHODS: Transcriptome expression data from The Cancer Genome Atlas database and Gene Expression Omnibus were analyzed to identify differentially expressed genes between glioblastoma and normal tissues. Biological pathways potentially associated with the differentially expressed genes were explored by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, and a protein-protein interaction network was established using the STRING database and Cytoscape. Survival analysis using Gene Expression Profiling Interactive Analysis was based on the Kaplan-Meier curve method. A ceRNA network chain was established using the intersection method to align data from four databases (miRTarBase, miRcode, TargetScan, and lncBace2.0), and expression differences and correlations were verified by quantitative reverse-transcription polymerase chain reaction analysis and by determining the Pearson correlation coefficient. Additionally, an MTS assay and the wound-healing and transwell assays were performed to evaluate the effects of complement C1s (C1S) on the viability and migration and invasion abilities of glioblastoma cells, respectively. RESULTS: We detected 2842 differentially expressed (DE) mRNAs, 2577 DE long non-coding RNAs (lncRNAs), and 309 DE microRNAs (miRNAs) that were dysregulated in glioblastoma. The final ceRNA network consisted of six specific lncRNAs, four miRNAs, and four mRNAs. Among them, four DE mRNAs and one DE lncRNA were correlated with overall survival (p < 0.05). C1S was significantly correlated with overall survival (p= 0.015). In functional assays, knockdown of C1S inhibited the proliferation and invasion of glioblastoma cell lines. CONCLUSIONS: We established four ceRNA networks that may influence the occurrence and development of glioblastoma. Among them, the MIR155HG/has-miR-129-5p/C1S axis is a potential marker and therapeutic target for glioblastoma. Knockdown of C1S inhibited the proliferation, migration, and invasion of glioblastoma cells. These findings clarify the role of the ceRNA regulatory network in glioblastoma and provide a foundation for further research.

A Multi-Dimensional Goal Aircraft Guidance Approach Based on Reinforcement Learning with a Reward Shaping Algorithm.

Guiding an aircraft to 4D waypoints at a certain heading is a multi-dimensional goal aircraft guidance problem. [d=Zu]In order to improve the performance and solve this problem, this paper proposes a multi-layer RL approach.To enhance the performance, in the present study, a multi-layer RL approach to solve the multi-dimensional goal aircraft guidance problem is proposed. The approach [d=Zu]enablesassists the autopilot in an ATC simulator to guide an aircraft to 4D waypoints at certain latitude, longitude, altitude, heading, and arrival time, respectively. To be specific, a multi-layer RL [d=Zu]approach is proposedmethod to simplify the neural network structure and reduce the state dimensions. A shaped reward function that involves the potential function and Dubins path method is applied. [d=Zu]Experimental and simulation results show that the proposed approachExperiments are conducted and the simulation results reveal that the proposed method can significantly improve the convergence efficiency and trajectory performance. [d=Zu]FurthermoreFurther, the results indicate possible application prospects in team aircraft guidance tasks, since the aircraft can directly approach a goal without waiting in a specific pattern, thereby overcoming the problem of current ATC simulators.

Amplitude randomness of spontaneous emission influence on the coherence properties of a laser.

Based on the randomness of spontaneous emission, the statistical characteristics of phase noise are discussed. A theoretical analysis model, focusing on the amplitude randomness of spontaneous emission, is established to calculate laser phase noise. Then, the coherence of a laser before and after phase-locked control is calculated when an ideal laser and nonideal laser are used as a reference light in an optical phase-locked loop (OPLL). The effects of the amplitude randomness of spontaneous emission on phase-locked laser coherence are analyzed in detail. The results show that phase noise randomness increases with the increase of the expectation or variance of spontaneous emission amplitude, which represents amplitude randomness. When an ideal light is used as reference light, if the expectation and the variance of spontaneous emission amplitude are about 10 and 100, respectively, the time constant of an OPLL should be set as 1 ns, while a favorable noise suppression result can be achieved. However, to achieve a favorable noise suppression result, the time constant of an OPLL should be set as 0.1 ns when a nonideal laser is used as reference light.

Dual-course dielectric barrier discharge with a novel hollow micro-holes electrode to efficiently mitigate NOx.

The effect of a novel hollow annular micro-hole electrode on the DBD de-NOx performance was investigated. The experimental results show that the hollow electrode allows the feed gas to take full advantage of the redundant heat of the electrode, thus reducing the energy consumption of the system. Subsequently, the micro-hole structure can improve the uniformity of feed gas in the plasma channel and prolong the residence time of the feed gas in the plasma channel. The reactor can also raise the temperature of the feed gas and enhance the plasma electric field. The optimum NOx removal efficiency of about 82.6% is achieved at 16 annular micro-holes. Compared to the rod electrode reactor, the novel electrode reactor shows 19.7% reduction in energy consumption and 13.2% enhancement in de-NOx efficiency. The calculations of de-NOx mechanism show that the NO2 concentration decays significantly as the feed gas residence time increases, accompanied by a slight increase in N2O concentration. The NO2 concentration marginally increases while N2O concentration slightly decreases as the increase of feed gas temperature. DBD de-NOx presents the mode of accelerated reduction of NO, essential removal of NO2, and gradual consumption of N2O with the reduced electric field increases.

Bacoside a inhibits the growth of glioma by promoting apoptosis and autophagy in U251 and U87 cells.

Bacoside A (gypenoside, Gyp) is a potent bioactive compound derived from Gynostemma pentaphyllum, known to exert inhibitory effects on various malignant tumors. However, the effects of Gyp on glioma as well as the underlying mechanisms remain unclear. In the present study, we first conducted a comprehensive investigation into the anti-glioma potential of gypenosides using network pharmacology to identify potential glioma-related targets. Protein-protein interaction networks were assembled, and GO and KEGG enrichment analyses were performed for shared targets. Experimental validation involved assessing the viability of U251 and U87 cell lines using the MTS method. Furthermore, trans-well and scratch migration assays evaluated the cell migration, while flow cytometry and Hoechst 33342 staining were utilized for apoptosis assessment. The study also monitored changes in autophagy flow through fluorescence microscopy. The expression levels of proteins pertinent to migration, apoptosis, and autophagy were tested using Western blotting. Findings revealed that Gyp upregulated apoptosis-related proteins (Bax and cleaved caspase-9), downregulated anti-apoptotic protein Bcl-2, and migration-associated matrix metalloproteinases (MMP-2 and MMP-9). Furthermore, autophagy-related proteins (Beclin1 and LC3 II) were upregulated, and p62 protein expression was downregulated. Gyp displayed considerable potential in suppressing glioma progression by inhibiting cell proliferation, invasion, and migration and promoting apoptosis and autophagy. Gyp may offer potential clinical therapeutic choices in glioma management.

Sevelamer reverses liver fibrosis by deactivation of hepatic stellate cells.

Liver fibrosis is a chronic liver disease characterized by a progressive wound healing response caused by chronic liver injury. Currently, there are no approved clinical treatments for liver fibrosis. Sevelamer is used clinically to treat hyperphosphatemia and has shown potential therapeutic effects on liver diseases. However, there have been few studies evaluating the therapeutic effects of sevelamer on liver fibrosis, and the specific mechanisms are still unclear. In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor ß (TGF-ß) expression in macrophages. In a rat model of liver fibrosis, oral administration of sevelamer significantly decreased blood phosphorus levels, improved liver function, reduced liver inflammation, and increased the antioxidant stress response in the liver. Our study revealed that the key mechanism by which sevelamer inhibited liver fibrosis involved binding to gastrointestinal phosphate, resulting in a decrease in blood phosphorus levels, the downregulation of TGF-ß expression in macrophages, and the inhibition of HSC migration and fibrosis-related protein expression. Therefore, our results suggest that sevelamer-induced low Pi stress can attenuate hepatic stellate cell activation and inhibit the progression of liver fibrosis, making it a potential option for the treatment of liver fibrosis and other refractory chronic liver diseases.

Progress of engineered bacteria for tumour therapy.

Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.

Roles of lncRNA-MALAT1 in the Progression and Prognosis of Gliomas.

Long noncoding RNAs (lncRNAs) represent a large subgroup of RNA transcripts that lack the function of coding proteins and may be essential universal genes involved in carcinogenesis and metastasis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNAMALAT1) is overexpressed in various human tumors, including gliomas. However, the biological function and molecular mechanism of action of lncRNA-MALAT1 in gliomas have not yet been systematically elucidated. Accumulating evidence suggests that the abnormal expression of lncRNA-MALAT1 in gliomas is associated with various physical properties of the glioma, such as tumor growth, metastasis, apoptosis, drug resistance, and prognosis. Furthermore, lncRNAs, as tumor progression and prognostic markers in gliomas, may affect tumorigenesis, proliferation of glioma stem cells, and drug resistance. In this review, we summarize the knowledge on the biological functions and prognostic value of lncRNA-MALAT1 in gliomas. This mini-review aims to deepen the understanding of lncRNA-MALAT1 as a novel potential therapeutic target for the individualized precision treatment of gliomas.

Heat Transfer Performance of a 3D-Printed Aluminum Flat-Plate Oscillating Heat Pipe Finned Radiator.

As electronic components progressively downsize and their power intensifies, thermal management has emerged as a paramount challenge. This study presents a novel, high-efficiency finned heat exchanger, termed Flat-Plate Oscillating Heat Pipe Finned Radiator (FOHPFR), which employs arrayed flat-plate oscillating heat pipes (OHP) as heat dissipation fins. Three-dimensional (3D)-printed techniques allow the internal microchannels of the FOHPFR to become rougher, providing excellent surface wettability and capillary forces, which in turn significantly improves the device's ability to dissipate heat. In this study, the 3D-printed FOHPFR is compared with traditional solid finned radiators made of identical materials and designs. The impacts of filling ratio, inclination angle, and cold-end conditions on the heat transfer performance of the 3D-printed FOHPFR are investigated. It is demonstrated by the results that compared to solid finned radiators, the FOHPFR exhibits superior transient heat absorption and steady-state heat transfer capabilities. When the heating power is set at 140 W, a decrease in thermal resistance from 0.32 °C/W in the solid type to 0.11 °C/W is observed in the FOHPFR, marking a reduction of 65.6%. Similarly, a drop in the average temperature of the heat source from 160 °C in the solid version to 125 °C, a decrease of 21.8%, is noted. An optimal filling ratio of 50% was identified for the vertical 3D-printed FOHPFR, with the minimal thermal resistance achieving 0.11 °C/W. Moreover, the thermal resistance of the 3D-printed FOHPFR is effectively reduced compared to that of the solid finned radiator at all inclination angles. This indicates that the FOHPFR possessed notable adaptability to various working angles.

Form-Stable Composite Phase Change Materials Based on Porous Copper-Graphene Heterostructures for Solar Thermal Energy Conversion and Storage.

Solar-thermal energy conversion and storage technology has attracted great interest in the past few decades. Phase change materials (PCMs), by storing and releasing solar energy, are able to effectively address the imbalance between energy supply and demand, but they still have the disadvantage of low thermal conductivity and leakage problems. In this work, new form-stable solar thermal storage materials by impregnating paraffin PCMs within porous copper-graphene (G-Cu) heterostructures were designed, which integrated high thermal conductivity, high solar energy absorption, and anti-leakage properties. In this new structure, graphene can directly absorb and store solar energy in the paraffin PCMs by means of phase change heat transfer. The porous structure provided good heat conduction, and the large surface area increased the loading capacity of solar thermal storage materials. The small pores and superhydrophobic surfaces of the modified porous G-Cu heterostructures effectively hindered the leakage issues during the phase change process. The experimental results exhibited that the thermal conductivity of the prepared form-stable PCM composites was up to 2.99 W/(m·K), and no leakage took place in the solar-thermal charging process. At last, we demonstrated that the PCM composites as an energy source were easily integrated with a thermoelectric chip to generate electric energy by absorbing and converting solar energy.

Budding uninhibited by benzimidazoles 1 overexpression is associated with poor prognosis and malignant phenotype: A promising therapeutic target for lung adenocarcinoma.

BACKGROUND: The budding uninhibited by benzimidazoles (BUB) family is involved in the cell cycle process as mitotic checkpoint components. Abnormal proliferation is a vital process in the development of lung adenocarcinoma (LUAD). Nevertheless, the roles of BUB1 in LUAD remain unclear. In this study, we evaluated the prognostic value and biological functions of BUB1 in LUAD using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), clinical LUAD samples, and in vitro experiments. METHODS: The expression, prognostic significance, functions, immune infiltration, and methylation of BUB1 in LUAD were comprehensively analyzed using TCGA, GEO, Gene Expression Profiling Interactive Analysis, Metascape, cBioPortal, MethSurv, and cancerSEA databases. Furthermore, we performed a battery of in vitro experiments and immunohistochemistry (IHC) to verify the bioinformatics results. RESULTS: Multivariate analysis revealed that BUB1 overexpression was an independent prognostic factor (hazard ratio = 1.499, p = 0.013). Functional enrichment analysis showed that BUB1 was correlated with cell cycle, proliferation, DNA repair, DNA damage, and invasion (p < 0.05). Finally, in vitro experiments showed that downregulation of BUB1 inhibited the proliferation, migration, and invasion of LUAD cells and promoted LUAD cell apoptosis. IHC also showed that BUB1 was overexpressed in LUAD (p < 0.001) and was significantly associated with poor prognosis (p < 0.001). CONCLUSIONS: Our bioinformatics and IHC analyses revealed that BUB1 overexpression was an adverse prognostic factor in LUAD. In vitro experiments demonstrated that BUB1 promoted tumor cell proliferation, migration, and invasion in LUAD. These results indicated that BUB1 was a promising biomarker and potential therapeutic target in LUAD.

Decapping enzyme 2 is a novel immune-related biomarker that predicts poor prognosis in glioma.

This study analyzed sequencing and clinical data from the Cancer Genome Atlas (TCGA) and gene expression synthesis, and used Chinese glioma Genome Atlas (CGGA) data for external validation. The expression of DCP2 in normal brain and tumor tissue was compared. We analyzed the clinical and molecular characteristics and prognostic value of DCP2 in glioma. In addition, DCP2 expression levels were evaluated in 30 glioma tissue samples and upregulated in glioma samples compared to normal brain tissue (p < 0.001). Multivariate data analysis from TCGA showed that increased DCP2 expression was an independent risk factor for overall survival and prognosis of glioma patients. As indicated by the analysis of the TCGA data set. The expression level of DCP2 is closely related to tumor immunity, including tumor immune cell infiltration, immune score, and co-expression of multiple immune-related genes. In addition, DCP2 was positively correlated with IL-6 and IL-7. Glioma cell proliferation and invasion were evaluated using cell viability, colony formation, wound healing, and transwell assays.Apoptosis and cell cycle were detected by flow cytometry. DCP2 promoted the proliferation, invasion and migration of glioma cells T98G and U251, inhibited apoptosis and blocked the S phase of the cell cycle. As a result of the altered expression of DCP2, a new prognostic biomarker may be identified that can improve patient survival.These findings suggest DCP2 as a potential biomarker for the prognosis of glioma and a candidate immunotherapy target.

Heat Transfer Performance of 3D-Printed Aluminium Flat-Plate Oscillating Heat Pipes for the Thermal Management of LEDs.

With the rapid development of electronic technologies towards high integration, high power and miniaturization, thermal management has become an increasingly important issue to guarantee the reliability and service life of electronic devices. The oscillating heat pipe (OHP), which was governed by thermally excited oscillating motion, was considered as a promising technology to dissipate high-density heat and had excellent application prospects in many important industrial processes. A flat-plate OHP, however, was fabricated by traditional welding methods, which were difficult and inefficient, resulting in increasing the cost and wasting the production time. In this work, we adopted a new metal 3D printing technology to develop an aluminum flat-plate OHP, which made it facile to build complex inner channels with high-precision molding at one time. AlSi10Mg powders, as raw materials, were selectively melted and solidified to form the container of the flat-plate OHP. The sintered inner surface presented excellent wettability to the working fluid, which facilitated the evaporation of the working fluid. Acetone was chosen as the working fluid, and the filling ratios with a range of 40-70% were loaded into the flat-plate oscillating heat pipe to analyze its effect on heat transfer performance. It was found that the 3D-printed flat-plate OHP with a 60% filling ratio had a better heat transfer performance and a lower thermal resistance, and it was able to work properly in both vertical and horizontal operation modes. The 3D-printed flat-plate OHP had been successfully applied for the thermal management of high-power LEDs, and the results showed that the temperature of LEDs was maintained within 60 °C, and its service life was prolonged.

High Expression of CKS2 Predicts Adverse Outcomes: A Potential Therapeutic Target for Glioma.

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a potential prognostic marker and is overexpressed in various cancers. This study analyzed sequencing and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus, with external validation using the Chinese Glioma Genome Atlas (CGGA) data. CKS2 expression in the normal brain and tumor tissue was compared. cBioPortal and MethSurv were utilized to scrutinize the prognostic value of CKS2 methylation. Gene set enrichment examination and single-sample gene set enrichment analysis were employed to explore the potential biological functions of CKS2. Cell viability, colony formation, and transwell assays were conducted to evaluate the influence of CKS2 on glioma cell proliferation and invasion. Compared with normal brain tissue, the expression of CKS2 was upregulated in glioma samples (p < 0.001). Multivariate data analysis from TCGA and CGGA indicated that increased expression of CKS2 was an independent risk factor for the prognosis of overall survival in glioma patients. CKS2 methylation was negatively associated with CKS2 expression. Patients with CKS2 hypomethylation had worse overall survival compared with patients with CKS2 methylation, as suggested by the analysis of both TCGA and CGGA datasets. The expression level of CKS2 is closely related to tumor immunity, including the correlation of tumor immune cell infiltration, immune score, and co-expression of multiple immune-related genes. In addition, CKS2 is associated with several immune checkpoints and responses to the chemotherapy drug cisplatin. CKS2 knockdown impeded the expansion and aggression of glioma cell lines. The changes in CKS2 expression may provide a novel prognostic biomarker that can be used to improve patient overall survival rates.

A Signature of N6-methyladenosine Regulator-Related Genes Predicts Prognoses and Immune Responses for Head and Neck Squamous Cell Carcinoma.

This study aimed to construct a signature of N6-methyladenosine (m6A) regulator-related genes that could be used for the prognosis of head and neck squamous cell carcinoma (HNSCC) and to clarify the molecular and immune characteristics and benefits of immune checkpoint inhibitor (ICI) therapy using the prognostic signature to define the subgroups of HNSCC. This study showed that eighteen m6A regulators were abnormally expressed in the Cancer Genome Atlas (TCGA) HNSCC tissues compared with those in normal tissues. We constructed a signature of 12 m6A regulator-related genes using the Cox risk model, combined with the least absolute shrinkage and selection operator (Lasso) variable screening algorithm. Based on the median of the signature risk score, the patients were divided into high- and low-risk groups. The Kaplan-Meier survival analyses showed that patients with high-risk scores demonstrated poorer overall survival (OS) than those with low-risk scores based on TCGA-HNSCC data (p <0.001). The OS of high-risk patients was significantly worse than that of low-risk patients in the GSE65858 (p <0.001) and International Cancer Genome Consortium (ICGC) oral cancer cohorts (p = 0.0089). Furthermore, immune infiltration analyses showed that 8 types of immune cell infiltration showed highly significant differences between the two risk groups (p <0.001). In the Imvigor210CoreBiologies dataset of patients who received ICIs, the objective response rate (ORR) of the low-risk group (32%) was significantly higher than that of the high-risk group (13%). Additionally, patients in the high-risk group presented with a more significant adverse OS than that of the low-risk group (p = 0.00032). GSE78220 also showed that the ORR of the low-risk group (64%) was higher than that of the high-risk group (43%) and the OS of low-risk patients was better than that of high-risk patients (p = 0.0064). The constructed prognostic signature, based on m6A regulator-related genes, could be used to effectively distinguish between prognoses for HNSCC patients. The prognostic signature was found to be related to the immune cell infiltration of HNSCC; it might help predict the responses and prognoses of ICIs during treatment.