RNA Methyltransferase FTSJ3 Regulates the Type I Interferon Pathway to Promote Hepatocellular Carcinoma Immune Evasion.

Immunotherapies such as immune checkpoint blockade have achieved remarkable success in treating cancer. Unfortunately, response rates have been limited in multiple cancers including hepatocellular carcinoma (HCC). The critical function of epigenetics in tumor immune evasion and antitumor immunity supports harnessing epigenetic regulators as a potential strategy to enhance the efficacy of immunotherapy. Here, we discovered a tumor-promoting function of FTSJ3, an RNA 2'-O-methyltransferase, in HCC by suppressing antitumor immune responses. FTSJ3 was upregulated in hepatocellular carcinoma, and high FTSJ3 expression correlated with reduced patient survival. Deletion of FTSJ3 blocked HCC growth and induced robust antitumor immune responses. Mechanistically, FTSJ3 suppressed double-stranded RNA (dsRNA)-induced IFNß signaling in a 2'-O-methyltransferase manner. Deletion of RNA sensors in HCC cells or systemic knockout of type I IFN receptor IFNAR in mice rescued the in vivo tumor growth defect caused by FTSJ3 deficiency, indicating that FTSJ3 deletion suppresses tumor growth by activating the RNA sensor-mediated type I IFN pathway. Furthermore, FTSJ3 deletion significantly enhanced the efficacy of programmed cell death protein 1 (PD-1) immune checkpoint blockade. The combination of FTSJ3 deficiency and anti-PD-1 antibody treatment effectively eradicated tumors and increased the survival time. In conclusion, this study reveals an epigenetic mechanism of tumor immune evasion and, importantly, suggests FTSJ3-targeting therapies as potential approach to overcome immunotherapy resistance in patients with HCC. SIGNIFICANCE: Hepatocellular carcinoma cells use 2'-O-methylation catalyzed by FTSJ3 for immune evasion by suppressing abnormal dsRNA-mediated type I IFN responses, providing a potential target to activate antitumor immunity and enhance immunotherapy efficacy.

Lokatt: a hybrid DNA nanopore basecaller with an explicit duration hidden Markov model and a residual LSTM network.

BACKGROUND: Basecalling long DNA sequences is a crucial step in nanopore-based DNA sequencing protocols. In recent years, the CTC-RNN model has become the leading basecalling model, supplanting preceding hidden Markov models (HMMs) that relied on pre-segmenting ion current measurements. However, the CTC-RNN model operates independently of prior biological and physical insights. RESULTS: We present a novel basecaller named Lokatt: explicit duration Markov model and residual-LSTM network. It leverages an explicit duration HMM (EDHMM) designed to model the nanopore sequencing processes. Trained on a newly generated library with methylation-free Ecoli samples and MinION R9.4.1 chemistry, the Lokatt basecaller achieves basecalling performances with a median single read identity score of 0.930, a genome coverage ratio of 99.750%, on par with existing state-of-the-art structure when trained on the same datasets. CONCLUSION: Our research underlines the potential of incorporating prior knowledge into the basecalling processes, particularly through integrating HMMs and recurrent neural networks. The Lokatt basecaller showcases the efficacy of a hybrid approach, emphasizing its capacity to achieve high-quality basecalling performance while accommodating the nuances of nanopore sequencing. These outcomes pave the way for advanced basecalling methodologies, with potential implications for enhancing the accuracy and efficiency of nanopore-based DNA sequencing protocols.

The Prognostic Value and the Oncogenic and Immunological Roles of Vacuolar Protein Sorting Associated Protein 26 A in Pancreatic Adenocarcinoma.

The identification of the prognostic markers and therapeutic targets might benefit the diagnosis and treatment of pancreatic adenocarcinoma (PAAD), one of the most aggressive malignancies. Vacuolar protein sorting associated protein 26 A (VPS26A) is a candidate prognosis gene for hepatocellular carcinoma, but its expression and function in PAAD remain unknown. The mRNA and protein expression of VPS26A in PAAD was explored and validated by bioinformatics and immunohistochemical analysis. The correlation between VPS26A expression and various clinical parameters, genetic status, diagnostic and prognostic value, survival and immune infiltration were evaluated, and the co-expressed gene-set enrichment analysis for VPS26A was performed. Cytologic and molecular experiments were further carried out to investigate the role and potential mechanism of VPS26A in PAAD. The mRNA and protein levels of VPS26A were elevated in PAAD tissues. High VPS26A expression was associated with the advanced histological type, tumor stage simplified, smoking status and tumor mutational burden score, and the poor prognosis of PAAD patients. VPS26A expression was significantly correlated with immune infiltration and immunotherapy response. VPS26A-co-expressed genes were mainly enriched in the regulation of cell adhesion and actin cytoskeleton and the immune-response-regulating signaling pathway. Our experiments further demonstrated that VPS26A promoted the proliferation, migration and invasion potentials of PAAD cell lines through activating the EGFR/ERK signaling. Our study suggested that VPS26A could be a potential biomarker and a therapeutic target for PAAD through comprehensive regulation of its growth, migration and immune microenvironment.

[Association between single nucleotides polymorphism of catalase gene and susceptibility to noise-induced hearing loss in occupational population].

OBJECTIVE: To investigate the relationship between single nucleotides polymorphism of catalase(CAT) gene and susceptibility to noise-induced hearing loss(NIHL) in occupational noise exposed population. METHODS: A case-control study of 1∶1 was conducted to select 286 workers with binaural high frequency average hearing threshold ≥40 dB(HL), from 2006 to 2015 in a cohort study of occupational noise exposure workers in Henan Province. According to the type of work, the age difference was not more than 5 years and the length of exposure to noise was not more than 2 years. The polymorphism of 8 single nucleotides in CAT gene was detected by medium SNPscanTM, and the relationship between 8 single nucleotides polymorphism of CAT gene and NIHL susceptibility was analyzed by multivariate conditional logistic regression. RESULTS: Under the dominant model of rs208679 locus of CAT gene [(GA GG)/AA], the risk of NIHL in individuals carrying GA or GG genotype was 1. 431 times higher than that in individuals carrying AA genotype(95%CI 1. 020-2. 009), and P=0. 038. CONCLUSION: G, a mutant at rs208679 site of CAT gene, may be one of the risk factors for NIHL susceptibility.

A multiporous carbon family with superior stability, tunable electronic structures and amazing hydrogen storage capability.

The traditional view that natural allotropes are more stable than artificially synthesized structures is widely accepted. For instance, graphite and diamond are more energetically favorable than other new carbon allotropes no matter whether they are experimentally prepared or theoretically predicted. Surprisingly, we find that a family of multiporous carbon (N-diaphenes) could be thermodynamically more stable than natural diamond with the increase of its feature size parameter N. Multiporous N-diaphenes exhibit extremely strong anisotropic mechanical properties and their ideal strength linearly depends on the corresponding yield strain. Density functional theory (DFT) calculations reveal that the bandgap hierarchy of N-diaphenes is inherited from their precursors. In addition, N-diaphenes exhibit superior capability for hydrogen storage due to their large specific surface areas.

Multiporous sp2-hybridized boron nitride (d-BN): stability, mechanical properties, lattice thermal conductivity and promising application in energy storage.

All-solid-state lithium-sulfur (Li-S) batteries offer the possibility of high theoretical energy densities and long cycle lifetime. Finding new multiporous insulating materials or wide bandgap semiconductors suitable for the transportation of Li-ions is a key problem for the application of solid state lithium-sulfur (Li-S) batteries. In this study, an sp2-hybridized multiporous boron nitride (d-BN) is found to be able to be used as a solid electrolyte or filter in Li-S batteries due to the lower energy barriers of Li-ion diffusion along its [110] direction. By means of density functional theory (DFT) calculations, it is also found that the d-BN is more stable than most reported BN polymorphs. In addition, the elastic properties, ideal tensile strength, electronic structure, lattice thermal conductivity and phonon lifetime of d-BN are also investigated.

A new metallic π-conjugated carbon sheet used for the cathode of Li-S batteries.

Lithium-sulfur (Li-S) batteries are considered as the most promising next generation high density energy storage devices. However, the commercialization of Li-S batteries is hindered by the shuttle effect of polysulfides, the low electronic conductivity of the sulfur cathode and a large volume expansion during lithiation. Herein, we predict a new two dimensional sp2 hybridized carbon allotrope (PHE-graphene) and prove its thermodynamic and kinetic stability. If it is utilized to encapsulate the cathode of Li-S batteries, not only will the shuttle effect be avoided but also the electronic conductivity of the sulfur cathode will be improved significantly owing to its metallic electronic band structure. The thermal conductivity of PHE-graphene was found to be very high and even comparable with graphene, which is helpful for the heat dissipation of cathodes. In addition, PHE-graphene also exhibited superior mechanical properties including ideal tensile strength and in-plane stiffness.

Luminescence and energy-transfer properties of color-tunable Ca2Mg0.25Al1.5Si1.25O7:Ce(3+)/Eu(2+)/Tb(3+) phosphors for ultraviolet light-emitting diodes.

A series of Ca2Mg0.25Al1.5Si1.25O7:Ce(3+)/Eu(2+)/Tb(3+) phosphors was been prepared via a conventional high temperature solid-state reaction and their luminescence properties were studied. The emission spectra of Ca2Mg0.25Al1.5Si1.25O7:Ce(3+),Eu(2+) and Ca2Mg0.25Al1.5Si1.25O7:Ce(3+),Tb(3+) phosphors show not only a band due to Ce(3+) ions (409 nm) but also as a band due to Eu(2+) (520 nm) and Tb(3+) (542 nm) ions. More importantly, the effective energy transfer from Ce(3+) to Eu(2+) and Tb(3+) ions was confirmed and investigated by emission/excitation spectra and luminescent decay behaviors. Furthermore, the energy level scheme and energy transfer mechanism were investigated and were demonstrated to be of resonant type via dipole-dipole (Ce(3+) to Eu(2+)) and dipole-quadrupole (Ce(3+) to Tb(3+)) reactions, respectively. Under excitation at 350 nm, the emitting color could be changed from blue to green by adjusting the relative doping concentration of Ce(3+) and Eu(2+) ions as well as Ce(3+) and Tb(3+) ions. The above results indicate that Ca2Mg0.25Al1.5Si1.25O7:Ce(3+),Eu(2+)/Tb(3+) are promising single-phase blue-to-green phosphors for application in phosphor conversion white-light-emitting diodes.

Chirality control of nonplanar lead phthalocyanine (PbPc) and its potential application in high-density storage: a theoretical investigation.

On single-crystal surfaces, achiral molecules may become chiral owing to confinement in two dimensions (2D). Metal phthalocyanines (MPcs) on Cu(001) and Ag(100) surfaces have exhibited a chiral electronic state. However, the chirality is not always desirable since crystal defects (grain boundaries) inevitably occur between two different chiral domains during the self-assembly of single layers. In this theoretical study, we propose to utilize metal(001) substrates with different electron configurations to mediate the azimuthal orientations of nonplanar PbPc. The results show that PbPc is chiral on Cu(001) with a partially filled s orbital (3d(10)4s(1)) but achiral on Pd(001) with a completely filled d orbital (4d(10)). The mechanism that PbPc prefers achiral azimuthal orientation rather than chiral orientation on Pd(001) is clarified. In addition, we predict that PbPc can form a (3 × 4) surface reconstruction. While it is used for data storage, the capacity is almost three orders of magnitude higher than the present storage materials.

Photoluminescence properties and energy transfer in Ce(3+) /Dy(3+) co-doped Sr(3) MgSi(2) O(8) phosphors for potential application in ultraviolet white light-emitting diodes.

Sr(3) MgSi(2) O(8) :Ce(3+) , Dy(3+) phosphors were prepared by a solid-state reaction technique and the photoluminescence properties were investigated. The emission spectra show not only a band due to Ce(3+) ions (403 nm) but also as a band due to Dy(3+) ions (480, 575 nm) (UV light excitation). The photoluminescence properties reveal that effective energy transfer occurs in Ce(3+) /Dy(3+) co-doped Sr(3) MgSi(2) O(8)phosphors, and the co-doping of Ce(3+) could enhance the emission intensity of Dy(3+) to a certain extent by transferring its energy to Dy(3+) . The Ce(3+) /Dy(3+) energy transfer was investigated by emission/excitation spectra, and photoluminescence decay behaviors. In Sr2.94 MgSi2 O8 :0.01Ce(3+) , 0.05Dy(3+) phosphors, the fluorescence lifetime of Dy(3+) (from 3.35 to 27.59 ns) is increased whereas that of Ce(3+) is greatly decreased (from 43.59 to 13.55 ns), and this provides indirect evidence of the Ce(3+) to Dy(3+) energy transfer. The varied emitted color of Sr(3) MgSi(2) O(8):Ce(3+) , Dy(3+) phosphors from blue to white were achieved by altering the concentration ratio of Ce(3+) and Dy(3+) . These results indicate Sr(3) MgSi(2) O(8):Ce(3+) , Dy(3+) may be as a candidate phosphor for white light-emitting diodes.