Conformational Analysis Explores the Role of Electrostatic Nonclassical CF···HC Hydrogen Bonding Interactions in Selectively Halogenated Cyclohexanes.

The conformational equilibria of selectively halogenated cyclohexanes are explored both experimentally (VT-NMR) for 1,1,4,-trifluorocyclohexane 7 and by computational analysis (M06-2X/aug-cc-pVTZ level), with the latter approach extending to a wider range of more highly fluorinated cyclohexanes. Perhaps unexpectedly, 7ax is preferred over the 7eq conformation by ΔG = 1.06 kcal mol-1, contradicting the accepted norm for substituents on cyclohexanes. The axial preference is stronger again in 1,1,3,3,4,5,5,-heptafluorocyclohexane 9 (ΔG = 2.73 kcal mol-1) as the CF2 groups further polarize the isolated CH2 hydrogens. Theoretical decomposition of electrostatic and hyperconjugative effects by natural bond orbital analysis indicated that nonclassical hydrogen bonding (NCHB) between the C-4 fluorine and the diaxial hydrogens at C-2 and C-6 in cyclohexane 7 and 9 largely accounts for the observed bias. The study extended to changing fluorine (F) for chlorine (Cl) and bromine (Br) at the pseudoanomeric position in the cyclohexanes. Although these halogens do not become involved in NCHBs, they polarize the geminal -CHX- hydrogen at the pseudoanomeric position to a greater extent than fluorine, and consequent electrostatic interactions influence conformer stabilities.

Acid rain reduced soil carbon emissions and increased the temperature sensitivity of soil respiration: A comprehensive meta-analysis.

Soil respiration the second-largest carbon flux in terrestrial ecosystems, has been extensively studied across a wide range of biomes. Surprisingly, no consensus exist on how acid rain (AR) impacts the spatiotemporal pattern of soil respiration. Therefore, we conducted a meta-analysis using 318 soil respiration and 263 soil respiration temperature sensitivity (Q10) data points obtained from 48 studies to assess the impact of AR on soil respiration components and their Q10. The results showed that AR reduced soil total respiration (Rt) and soil autotrophic respiration (Ra) by 7.41 % and 20.75 %, respectively. As the H+ input increased, the response rates of Ra to AR (RR-Ra) and soil heterotrophic respiration (Rh) to AR (RR-Rh) decreased and increased, respectively. With increased AR duration, the RR-Ra increased, whereas the RR-Rh did not change. AR increased the Q10 of Rt (Rt-Q10) and Rh (Rh-Q10) by 1.92 % and 9.47 %, respectively, and decreased the Q10 of Ra (Ra-Q10) by 2.77 %. Increased mean annual temperature, mean annual precipitation, and initial soil organic carbon increased the response rate of Ra-Q10 to AR (RR-Ra-Q10) and decreased the response rate of Rh-Q10 to AR (RR-Rh-Q10). However, as the AR frequency and initial soil pH increased, both RR-Ra-Q10 and RR-Rh-Q10 also increased. In summary, AR decreased Rt but increased Q10, likely due to soil acidification (soil pH decreased by 7.84 %), reducing plant root biomass (decreased by 5.67 %) and soil microbial biomass (decreased by 5.67 %), changing microbial communities (increased fungi to bacteria ratio of 15.91 %), and regulated by climate, vegetation, soil and AR regimes. To the best of our knowledge, this is the first study to reveal the large-scale, varied response patterns of soil respiration components and their Q10 to AR. It highlights the importance of applying the reductionism theory in soil respiration research to enhance our understanding of soil carbon cycling processes with in the context of global climate change.

Single-atom Mn-embedded carbon nitride as highly efficient peroxymonosulfate catalyst for the harmful algal blooms control.

In recent years, water quality deterioration caused by harmful algal blooms (HABs) has become one of the global drinking water safety issues, and sulfate radical driven heterogeneous advanced oxidation technology has been widely used for algae removal. However, the shortages of low active site exposure, metal leaching, and secondary contamination limit its further application. Therefore, the single-atom Mn anchored on inorganic carbon nitride was constructed to enhance the oxidation and coagulation of algal cells while maintaining cell integrity in this study. The removal efficiency of Microcystis aeruginosa was as high as 100 % within 30 min under the optimal conditions of 400 mg/L single-atom Mn-embedded g-C3N4 (SA-MCN) and 0.32 mM peroxymonosulfate (PMS). Importantly, the K+ release, malondialdehyde concentration, floccules morphology and variation of algal organic matters further showed that the algal cells still maintained high integrity without severe rupture during the catalytic reaction. Furthermore, the catalytic mechanisms of algae removal by moderate oxidation and simultaneous coagulation in this system were explored by quenching experiments, EPR analysis, theoretical calculation, and Zeta potential. In brief, this study highlighted the single-atom heterogeneous catalyst with high-efficiency and environmental-friendliness in harmful algal blooms control.

Middle aged CAMKII-Cre:Cbsfl/fl mice: a new model for studying perioperative neurocognitive disorders.

Postoperative complications, such as perioperative neurocognitive disorders (PND), have become a major issue affecting surgical outcomes. However, the mechanism of PND remains unclear, and stable animal models of middle-aged PND are lacking. S-adenosylmethionine (SAM), a cystathionine beta-synthase (CBS) allosteric activator, can reduce the level of plasma homocysteine and prevent the occurrence of PND. However, the time and resource-intensive process of constructing models of PND in elderly animals have limited progress in PND research and innovative therapy development. The present study aimed to construct a stable PND model in middle-aged CAMKII-Cre:Cbsfl/fl mice whose Cbs was specifically knocked out in CAMKII positive neurons. Behavioral tests showed that these middle-aged mice displayed cognitive deficits which were aggravated by exploratory laparotomy under isoflurane anesthesia. Compared with typical PND mice which were 18-month-old, these middle-aged mice showed similar cognitive deficits after undergoing exploratory laparotomy under isoflurane anesthesia. Though there was no significant difference in the number of neurons in either the hippocampus or the cortex, a significant increase in numbers of microglia and astrocytes in the hippocampus was observed. These indicate that middle-aged CAMKII-Cre:Cbsfl/fl mice can be used as a new PND model for mechanistic studies and therapy development for PND.

A protocol to investigate the effects of lncRNAs on in vivo protein-protein interactions using proximity ligation assay.

A large variety of cellular signals are triggered and transmitted by protein-protein interactions (PPIs). Long noncoding RNAs regulate PPIs by enhancing or destabilizing these interactions. Here, we use the proximity ligation assay technique to determine PPIs between p53 and SET regulated by long intergenic noncoding RNA 324 (LINC00324). We detail procedures for establishing LINC00324 knockdown and overexpression U2OS and HepG2 cells followed by in situ PLA protocol. This approach has many potential applications for the study of cellular factors that regulate PPIs. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2023).1.

Divergent patterns and drivers of leaf functional traits of Robinia pseudoacacia and Pinus tabulaeformis plantations along a precipitation gradient in the Loess plateau, China.

Changes in precipitation patterns in arid and semi-arid regions can reshape plant functional traits and significantly affect ecosystem functions. However, the synchronous responses of leaf economical, anatomical, photosynthetic, and biochemical traits to precipitation changes and their driving factors have rarely been investigated, which hinders our understanding of plants' ecological adaptation strategies to drought tolerance in arid areas. Therefore, the leaf traits of two typical plantations (Robinia pseudoacacia, RP and Pinus tabulaeformis, PT) along the precipitation gradient in the Loess Plateau, including economical, anatomical, photosynthetic, and biochemical traits, were investigated in this study. The results show that the leaf photosynthetic traits of RP and PT increase along the precipitation gradient, whereas leaf biochemical traits decrease. The anatomical traits of PT decrease with increasing precipitation, whereas no significant variation was observed for RP. Random Forest analysis show that LNC, LDMC, Chl, and PRO are leaf traits that significantly vary with the precipitation gradient in both plantations. Correlation analysis reveals that the traits coordination of RP is better than that of PT. The LMG model was used to determine driving factors. The results suggest that MAP explains the variation of PT leaf traits better (30.38%-36.78%), whereas SCH and SPH contribute more to the variation of RP leaf traits (20.88%-41.76%). In addition, the piecewise Structural Equation Model shows that the climate and soil physical and chemical properties directly affect the selected leaf functional traits of RP, whereas only the soil chemical properties directly affect the selected leaf functional traits of PT. The results of this study contribute to the understanding of the ecological adaptation of plants to environmental gradients and highlight that correlations among leaf traits should be considered when predicting plant adaptation strategies under future global change scenarios.

Electrical Activity and Extremes of Individual Suspended ZnO Nanowires for 3D Nanoelectronic Applications.

We explored the electrical activity and extremes inside individual suspended zinc oxide (ZnO) nanowires (NWs) (diameter: 50-550 nm, length: 5-50 µm) subjected to high forward bias-induced Joule heating using two-terminal current-voltage measurements. NWs were isolated using a reproducible nanometrology technique, employing a nanomanipulator inside a scanning electron microscope. Schottky behavior is observed between installed tips and ZnO NW. The suspended ZnO NWs exhibited an average electrical resistivity ρ (approximately 2.3 × 10-2 Ω cm) and a high electron density n (exceeding 1.89 × 1018 cm-3), comparable to that of InP NWs, GaN NWs, and InAs NWs (1018∼1019 cm-3), suggesting the potential to drive advancements in high-performance NW devices. A maximum breakdown current density (JBD) of ∼0.14 MA/cm2 and a maximum breakdown power density (PBD) of 6.93 mW/µm3 were obtained, both of which are higher than substrate-bound ZnO NWs and consistent with previously reported results obtained from probed ZnO NWs grown vertically on the substrate. Moreover, we discovered that NWs experienced thermal breakdown due to Joule heating and exploited this breakdown mechanism to further investigate the temperature distribution along the ZnO NWs, as well as its dependence on the electrical properties and thermal conductance of contact electrodes. Thermal conductance was determined to be ∼0.4 nW K-1 and ∼1.66 pW K-1 at the tungsten(W)-ZnO NW and platinum(Pt)-ZnO NW contacts, respectively. In addition, we measured the elastic modulus (130-171 GPa), which closely approximated bulk values. We also estimated the nanoindentation hardness to be between 5 and 10 GPa. This work provides valuable insights into the electrical activity and extreme mechanisms, thus providing a better understanding of the potentials and limitations associated with utilizing suspended NWs in 3D nanodevices.

Construction of cubic CaTiO3 perovskite modified by highly-dispersed cobalt for efficient catalytic degradation of psychoactive pharmaceuticals.

Sulfate radical mediated advanced oxidation processes (SR-AOPs) have emerged as a promising alternative for emerging contaminants degradation. However, high activity and great stability are commonly difficult to juggle, and the structure-activity correlations are still ambiguous. This study constructed the cubic CaTiO3 perovskite modified by highly-dispersed cobalt for peroxymonosulfate (PMS) activation to improve the specific lattice plane exposure and reduce the metal leaching simultaneously. 98% of amitriptyline (AMT) degradation was achieved within 60 min under the condition of 200 mg/L Co0.1-CTO and 100 mg/L PMS. The results indicated that surface Co2+/Co3+ redox couple and lattice oxygen were responsible for PMS activation, and the evolution of ·OH, SO4·- and 1O2 were revealed. According to density functional theory (DFT) calculations, the highly-dispersed Co on cubic surface effectively captured PMS and promoted electron transfer for the generation of ·OH and SO4·-, while more oxygen atoms exposed on Co0.1-CTO(200) surface facilitated the generation of 1O2. Briefly, this study provides a novel strategy of catalyst synthesis in PMS activation for water treatment.

A p53/LINC00324 positive feedback loop suppresses tumor growth by counteracting SET-mediated transcriptional repression.

The p53 tumor suppressor exerts antitumor functions through its ability to regulate the transcription of its downstream targets. Long noncoding RNAs (lncRNAs) act as oncogenes or tumor suppressors implicated in tumorigenesis and tumor progression. Here, we identify the lncRNA LINC00324 (long intergenic noncoding RNA 00324) as a direct p53 transcriptional target. Knockdown of LINC00324 expression promotes tumor growth by reducing p53 transcriptional activity, whereas ectopic LINC00324 expression demonstrates a reverse effect. Notably, LINC00324 is present in the endogenous p53 complex in tumor cells and directly binds to the C-terminal domain of p53 in vitro. Mechanistically, LINC00324 enables p53 transactivation by competitively disrupting the p53-SET interaction, resulting in an increase of p300/CBP-mediated H3K18 and H3K27 acetylation on the p53 target promoters. Lower LINC00324 expression is associated with more aggressive disease status and predicts worse overall survival of patients with cancer. Our study identifies a p53/LINC00324 positive feedback loop that suppresses tumor growth by counteracting SET-mediated transcriptional repression.

Selective production of singlet oxygen for harmful cyanobacteria inactivation and cyanotoxins degradation: Efficiency and mechanisms.

Knowledge about the impact of singlet oxygen (1O2) on the characteristics and inactivation of harmful cyanobacterial organic matter is limited. In this study, the feasibility of using an improved single-iron doped graphite-like phase carbon nitride catalyst (FeCN) to activate peroxymonosulfate (PMS) catalytic production of 1O2 to inactivate four harmful cyanobacteria was investigated. The inactivation efficiencies at 30 min were 92.77%, 66.84%, 91.06%, and 93.45% for Microcystis aeruginosa (M. aeruginosa), Nodularia harveyana, Oscillatoria sp., and Nostoc sp., respectively. This was associated with adjusting experimental parameters, such as the FeCN and PMS doses and initial pH, to obtain the maximum 1O2 yield. The quenching experiment results and electron paramagnetic resonance spectra showed that 1O2 generated via the non-radical pathway might play a dominant role in inactivating harmful cyanobacteria and degrading harmful algal toxins (Microcystin-LR and Nodularin). In addition, the FeCN-PMS system not only effectively destroyed the integrity of harmful cyanobacterial cells but also effectively degraded cyanobacterial toxins, thereby preventing severe secondary contamination by cell rupture. A possible removal mechanism was proposed. This reveals the potential of 1O2 to simultaneously inactivate harmful cyanobacteria and degrade harmful cyanobacterial toxins.

The expression and clinical significance of STAMBP in breast cancer.

BACKGROUND: Breast cancer is the leading cause of death from cancer in women worldwide. STAMBP functions as a JAMM family deubiquitinating enzyme that modulates the stability of substrate proteins in cells by cleaving ubiquitin moieties. The expression of STAMBP and its clinical significance in breast cancer remain unclear. METHODS AND RESULTS: The level of the STAMBP protein in noncancerous and tumor tissues of breast cancer patients was examined by immunohistochemical staining. The expression of STAMBP mRNA in tissues based on healthy individual and breast cancer patient data in the TCGA database was evaluated. The association between the expression of STAMBP mRNA and clinical features and prognosis was evaluated using TCGA database. Cell growth was assessed by Cell Counting Kit-8 (CCK-8) assay, and cell migration and invasion were assessed by wound healing and Transwell assays. Activation of the ERK signaling was detected by Western blotting. The expression of STAMBP was markedly upregulated in the cytoplasm of tumor cells from breast cancer patients. The level of STAMBP was closely associated with the tumor subtype and size and the TNM stage of the breast cancer patients. Importantly, high expression of STAMBP predicted poor overall survival (OS) for breast cancer patients. Furthermore, knockdown of STAMBP expression reduced cell mobility and invasion of breast cancer cells. Notably, the phosphorylation of EGFR and ERK was markedly reduced in STAMBP-knockdown cells. CONCLUSION: STAMBP plays a critical role in the progression of breast cancer and may serve as a biomarker to monitor the progression of the disease.

Targeting neuroinflammation as a preventive and therapeutic approach for perioperative neurocognitive disorders.

Perioperative neurocognitive disorders (PND) is a common postoperative complication associated with regional or general anesthesia and surgery. Growing evidence in both patient and animal models of PND suggested that neuroinflammation plays a critical role in the development and progression of this problem, therefore, mounting efforts have been made to develop novel therapeutic approaches for PND by targeting specific factors or steps alongside the neuroinflammation. Multiple studies have shown that perioperative anti-neuroinflammatory strategies via administering pharmacologic agents or performing nonpharmacologic approaches exert benefits in the prevention and management of PND, although more clinical evidence is urgently needed to testify or confirm these results. Furthermore, long-term effects and outcomes with respect to cognitive functions and side effects are needed to be observed. In this review, we discuss recent preclinical and clinical studies published within a decade as potential preventive and therapeutic approaches targeting neuroinflammation for PND.

Peracetic acid activation by mechanochemically sulfidated zero valent iron for micropollutants degradation: Enhancement mechanism and strategy for extending applicability.

In this study, mechanically sulfidated microscale zero valent iron (S-ZVI) was found to effectively activate the peracetic acid (PAA) with a result of almost complete degradation of six micropollutants within 10 min under neutral conditions, and > 95% sulfamethoxazole (SMX) removal after six cycles. Reactive oxidized species (ROS) including HO•, carbon-centered radicals, and Fe(IV) were generated in the S-ZVI/PAA system, while HO• was the main contributor towards micropollutants degradation. This study clearly revealed that enhancement of the electron donating ability of ZVI by the formed conductive iron sulfides was crucial for promoted Fe(II) generation and subsequent PAA activation over several cycles, rather than the ability of sulfides to reduce Fe(III) for Fe(II) regeneration as reported previously. Interestingly, it's discovered that co-existence of Fe(III) would dramatically improve the contaminants removal efficiency of the S-ZVI/PAA system; transform the surfaced Fe(II) dominated ROS generation process to aqueous Fe(II) one; enhance the tolerance of the proposed system to water matrix. The promoting effect of predosed Fe(III) on PAA activation by S-ZVI should be mainly associated with: the greater ability of Fe(III) than H2O to accept electron from Fe0 for obtaining more active sites; slower Fe0 consumption and solid sulfur species release for elevated electron utilization efficiency and PAA activation. Considering the convenient and cost-effective access of Fe(III), the decrease of acute toxicity of treated SMX, excellent stability and good removal of various micropollutants fully demonstrate the superiority of S-ZVI/PAA system for practical application.

Selectively Fluorinated Citronellol Analogues Support a Hydrogen Bonding Donor Interaction with the Human OR1A1 Olfactory Receptor.

C-2 fluorinated and methylated stereoisomers of the fragrance citronellol 1 and its oxalate esters were prepared from (R)-pulegone 11 and explored as agonists of the human olfactory receptor OR1A1 and assayed also against site-specific mutants. There were clear isomer preferences and C-2 difluorination as in 18 led to the most active compound suggesting an important hydrogen bond donor role for citronellol 1. C-2 methylation and the corresponding oxalate ester analogues were less active.

Purification of Ubiquitinated p53 Proteins from Mammalian Cells.

Ubiquitination is a type of posttranslational modification that regulates not only the stability but also the localization and function of a substrate protein. The ubiquitination process occurs intracellularly in eukaryotes and regulates almost all basic cellular biological processes. Purification of ubiquitinated proteins aids the investigation of the role of ubiquitination in controlling the function of substrate proteins. Here, a step-by-step procedure to purify ubiquitinated proteins in mammalian cells is described with the p53 tumor suppressor protein as an example. Ubiquitinated p53 proteins were purified under stringent nondenaturing and denaturing conditions. Total cellular Flag-tagged p53 protein was purified with anti-Flag antibody-conjugated agarose under nondenaturing conditions. Alternatively, total cellular His-tagged ubiquitinated protein was purified using nickel-charged resin under denaturing conditions. Ubiquitinated p53 proteins in the eluates were successfully detected with specific antibodies. Using this procedure, the ubiquitinated forms of a given protein can be efficiently purified from mammalian cells, facilitating studies on the roles of ubiquitination in regulating protein function.

Destructing surfactant network in nanoemulsions by positively charged magnetic nanorods to enhance oil-water separation.

The separation of ultrafine oil droplets from wasted nanoemulsions stabilized with high concentration of surfactants is precondition for oil reuse and the safe discharge of effluent. However, the double barriers of the interfacial film and network structures formed by surfactants in nanoemulsions significantly impede the oil-water separation. To destroy these surfactant protective layers, we proposed a newly-developed polyethyleneimine micelle template approach to achieve simultaneous surface charge manipulation and morphology transformation of magnetic nanospheres to magnetic nanorods. The results revealed that positively charged magnetic nanospheres exhibited limited separation performance of nanoemulsions, with a maximum chemical oxygen demand (COD) removal of 50%, whereas magnetic nanorods achieved more than 95% COD removal in less than 30 s. The magnetic nanorods were also applicable to wasted nanoemulsions from different sources and exhibited excellent resistance to wide pH changes. Owing to their unique one-dimensional structure, the interfacial dispersion of magnetic nanorods was significantly promoted, leading to the efficient capture of surfactants and widespread destruction of both the interfacial film and network structure, which facilitated droplet merging into the oil phase. The easy-to-prepare and easy-to-tune strategy in this study paves a feasible avenue to simultaneously tailor surface charge and morphology of magnetic nanoparticles, and reveals the huge potential of morphology manipulation for producing high-performance nanomaterials to be applied in complex interfacial interaction process. We believe that the newly-developed magnetic-nanorods significantly contribute to hazardous oily waste remediation and advances technology evolution toward problematic oil-pollution control.

Xiaoxuming Decoction: A Traditional Herbal Recipe for Stroke With Emerging Therapeutic Mechanisms.

Xiaoxuming decoction (XXMD) has been traditionally used to manage stroke though debates on its clinical efficacy were present in the history. Till nowadays, it is still one of the most commonly used herbal recipes for stroke. One of the reasons is that a decent proportion of ischemic stroke patients still have residue symptoms even after thrombolysis with rt-PA or endovascular thrombectomy. Numerous clinical studies have shown that XXMD is an effective alternative therapy not only at the acute stage, but also at the chronic sequelae stage of ischemic stroke. Modern techniques have isolated groups of compounds from XXMD which have shown therapeutic effects, such as dilating blood vessels, inhibiting thrombosis, suppressing oxidative stress, attenuating nitric oxide induced damage, protecting the blood brain barrier and the neurovascular unit. However, which of the active compounds is responsible for its therapeutic effects is still unknown. Emerging studies have screened and tested these active compounds aiming to find individual compounds that can be used as drugs to treat stroke. The present study summarized both clinical evidence of XXMD in managing stroke and experimental evidence on its molecular mechanisms that have been reported recently using advanced techniques. A new perspective has also been discussed with an aim to provide new targets that can be used for screening active compounds from XXMD.

Identification of Hub Genes and Pathways Associated With Idiopathic Pulmonary Fibrosis via Bioinformatics Analysis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease whose etiology remains unknown. The purpose of this study was to explore hub genes and pathways related to IPF development and prognosis. Multiple gene expression datasets were downloaded from the Gene Expression Omnibus database. Weighted correlation network analysis (WGCNA) was performed and differentially expressed genes (DEGs) identified to investigate Hub modules and genes correlated with IPF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis were performed on selected key genes. In the PPI network and cytoHubba plugin, 11 hub genes were identified, including ASPN, CDH2, COL1A1, COL1A2, COL3A1, COL14A1, CTSK, MMP1, MMP7, POSTN, and SPP1. Correlation between hub genes was displayed and validated. Expression levels of hub genes were verified using quantitative real-time PCR (qRT-PCR). Dysregulated expression of these genes and their crosstalk might impact the development of IPF through modulating IPF-related biological processes and signaling pathways. Among these genes, expression levels of COL1A1, COL3A1, CTSK, MMP1, MMP7, POSTN, and SPP1 were positively correlated with IPF prognosis. The present study provides further insights into individualized treatment and prognosis for IPF.

Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma.

m6A RNA methylation regulators can regulate the growth, progression, and invasion of glioma cells by regulating their target genes, which provides a reliable support for the m6A regulator-target axes as the novel therapeutic targets and clinical prognostic signature in glioma. This study aimed to explore the role and prognostic value of m6A RNA methylation regulators and their targets. Expression profiles and clinicopathological data were obtained from the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteome Tumor Analysis Consortium (CPTAC) datasets. Differential expression and correlation analyses were performed between normal and glioma tissues at mRNA and protein levels. Univariate Cox regression, survival, and Lasso Cox regression analyses were conducted to identify and establish the prognostic gene signature. Kaplan-Meier curve, multivariate Cox regression analysis, and ROC were utilized to evaluate the prognostic capacity of the prognostic gene signature. The correlation analysis, systematic bioinformatics analysis, and cell experiment were performed to further understand the potential underlying molecular mechanisms and drug sensitivity. Our results suggested that IGF2BP2, KIAA1429, METTL16, and METTL3, as well as 208 targets are involved in the occurrence of glioma, GBM, and LGG. YTHDF1 and 78 targets involved the occurrence of glioma and GBM, not LGG, among which 181 genes were associated with overall survival. From other findings and our cell experiment results, we demonstrated that METTL3 can activate Notch pathway and facilitate glioma occurrence through regulating its direct targets NOTCH3, DLL3, and HES1, and Notch pathway genes may serve as the potential treatment targets for glioma. Our study established and validated a seven-gene signature comprising METTL3, COL18A1, NASP, PHLPP2, TIMP1, U2AF2, and VEGFA, with a good capability for predicting glioma survival, which may guide therapeutic customization and clinical decision-making. These genes were identified to influence 81 anticancer drug responses, which further contributes to the early phase clinical trials of drug development.

The Potential Mechanism of Cancer Patients Appearing More Vulnerable to SARS-CoV-2 and Poor Outcomes: A Pan-Cancer Bioinformatics Analysis.

To explore the potential mechanism of cancer patients appearing more vulnerable to SARS-CoV-2 infection and poor COVID-19 outcomes, we conducted an integrative bioinformatics analysis for SARS-CoV-2-required genes and host genes and variants related to SARS-CoV-2 susceptibility and COVID-19 severity. BLCA, HNSC, KIRC, KIRP, LGG, PCPG, PRAD, TGCT, and THCA patients carrying rs10774671-A (OAS1) genotype may be more likely to have poor COVID-19 outcomes relative to those who carry rs10774671-G, because individuals carrying rs10774671-A will have lower expression of OAS1, which serves as a protective factor against SARS-CoV-2 processes and poor COVID-19 outcomes. SARS-CoV-2-required genes were correlated with TME, immune infiltration, overall survival, and anti-cancer drug sensitivity. CHOL patients may have a higher risk of SARS-CoV-2 infection than healthy subjects. SARS-CoV-2-induced ACE2 and NPC1 elevation may have a negative influence on the immune responses of LUSC and CD8+T infiltration of LUAD, and negatively affect the sensitivity of anti-lung cancer drugs. LUSC and LUAD patients may have a varying degree of adverse outcomes if they are infected with SARS-CoV-2. miR-760 may target and inhibit ACE2 expression. Cancer patients appearing vulnerable to SARS-CoV-2 infection and having poor COVID-19 outcomes may be partly due to host genetic factors and dysregulation of SARS-CoV-2-required genes. OAS1, ACE2, and miR-760 could serve as the treatment and intervention targets for SARS-CoV-2.