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Abstract Background Although immune checkpoint blockade (ICB) therapy has brought survival benefits to patients with specific cancer types, most of cancer patients remain refractory to the ICB therapy, which is largely attributed to the immunosuppressive tumor microenvironment. Thereby, it is urgent to profile key molecules and signal pathways responsible for modification of tumor microenvironment. Methods Multiple databases of esophageal squamous cell carcinoma (ESCC) were integratively analyzed to screen candidate genes responsible for infiltration of CD8+ T cells. Expression of pescadillo ribosomal biogenesis factor 1 (PES1) in clinical ESCC samples was examined by qRT-PCR, western blotting, and immunohistochemistry. The mechanisms of PES1 were investigated via RNA sequencing and mass spectrometry followed by immunoprecipitation and proximity ligation assay. The clinical and therapeutic significance of PES1 in ESCC was comprehensively investigated using ESCC cells and mouse model. Results PES1 was significantly upregulated and correlated with poor prognosis in ESCC patients. PES1 knockdown decreased ESCC cell growth in vitro and in vivo and enhanced the efficacy of ICB therapy in mouse model, which was established through subcutaneous inoculation with ESCC cells. Analyses on RNA sequencing and mass spectrometry suggested that PES1 expression was negatively correlated with IL15 and ILF3 was one of the PES1-associated proteins. It has been known that ILF3 interacts with and stabilizes IL15 mRNA to increase IL15 protein level. Our data further indicated that PES1 interfered with the interaction between ILF3 and IL15 mRNA and impaired ILF3-mediated stabilization of IL15 mRNA, which eventually reduced the protein level of IL15. Interestingly, the inhibitory effect of ICB therapy boosted by PES1 knockdown dramatically antagonized by knockdown of IL15, which suppressed the tumor-infiltrated CD8+ T cells in ESCC. Finally, we confirmed the relationships among PES1, IL15, and CD8+ T cell infiltration in 10 locally advanced ESCC patients receiving ICB neoadjuvant therapy and demonstrated that ICB therapy would be more effective in those with low expression of PES1. Conclusions Altogether, our findings herein provided novel insights on biological function and clinical significance of PES1 and suggested that high expression of PES1 could suppress ILF3-IL15 axis-mediated immunosurveillance and promote resistance to ICB through restraining tumor-infiltrated CD8+ T cells.

Two-dimensional (2D) semiconductors with intrinsic dipole show glorious prospects in the fields of nanoelectronics. Herein, the possible applications of single-layer GaInO3 in the realms of optoelectronics and piezoelectricity are investigated via the first-principles study. We find that single-layer GaInO3 exhibits a large vertical dipole moment and a direct bandgap (1.53 eV). Its transport mobility for electrons and holes both surpasses 2000 cm2·V−1·s−1. The effective separation of charge carriers for single-layer GaInO3 is confirmed by the strong inside electric field and the spatially isolated conduction band minimum (CBM) and valence band maximum (VBM). The allowed optical transition makes single-layer GaInO3 a hopeful candidate for optical absorbers and detectors. Finally, we also find that single-layer GaInO3 holds a prominently stronger out-of-plane piezoelectric effect than that of previous 2D materials and will play a big role in modern top-bottom gate technologies. In summary, this work proves that single-layer GaInO3 is a promising candidate for atomic-thick optoelectronic and piezoelectric devices.

Two-dimensional optoelectronic materials with desirable bandgaps and high carrier separation efficiency are in urgent need. Herein, single-layer ZnGaInS4 is designed and thoroughly studied by first-principles calculations. Our calculations reveal the excellent stability of single-layer ZnGaInS4, and the small cleavage energy demonstrates the feasibility to exfoliate single-layer ZnGaInS4 from bulk counterparts. At the HSE06 level, single-layer ZnGaInS4 has a moderate bandgap of 2.05 eV, and its valence band maximum and conduction band minimum are spatially separated, thus impeding the electron-hole pair formation and enhancing the photoelectronic performance. In the visible region, single-layer ZnGaInS4 exhibits an optical absorption coefficient of ∼ 105 cm−1. Notably, single-layer ZnGaInS4 possesses high electron carrier mobility and low hole carrier mobility, further affirming the effective carrier separation. Another attractive characteristic is that single-layer ZnGaInS4 has anisotropic hole mobility. The desirable bandgap and high separation efficiency of generated carriers, together with abundant optical absorption, promise single-layer ZnGaInS4 is a hopeful candidate in atomic-thick optoelectronic devices.

The well-established cell-of-origin (COO) algorithm categorizes diffuse large B-cell lymphoma (DLBCL) into activated B-cell-like (ABC) and germinal center B-cell-like (GCB) subgroups through gene expression profiling. We aimed to develop and validate a qPCR-based gene expression assay to determine the COO subgroups of DLBCL with formalin-fixed paraffin-embedded (FFPE) tissue. We first established a DLBCL transcriptome database of 1,016 samples retrieved from three published datasets (GSE10846, GSE22470, and GSE31312). With this database, we identified a qPCR-based 32-gene expression signature (DLBCL-COO assay) that is significantly associated with the COO subgroups. The DLBCL-COO assay was further validated in a cohort of 160 Chinese DLBCL patients. Biopsy samples from DLBCL patients with paired FFPE and fresh frozen tissue were collected to assign COO subtypes based on the immunohistochemistry (IHC) algorithm (Han's algorithm), DLBCL-COO assay, and global gene expression profiling with RNA-seq. For 111 paired FFPE and fresh DLBCL samples, the concordance between the IHC, qPCR, and RNA-seq methods was 77.5% and 91.9%, respectively. The DLBCL-COO assay demonstrated a significantly superior concordance of COO determination with the “gold standard” RNA-seq compared with the IHC assignment with Han's algorithm (P = 0.005). Furthermore, the overall survival of GCB patients defined by the DLBCL-COO assay was significantly superior to that of ABC patients (P = 0.023). This effect was not seen when the tumors were classified by the IHC algorithm. The DLBCL-COO assay provides flexibility and accuracy in DLBCL subtype characterization. These findings demonstrated that the DLBCL-COO assay might serve as a useful tool for guiding prognostic and therapeutic options for DLBCL patients.

Abstract Cancer stem cells play an important role on tumor progression. Biomarkers of stem cell property and their relationship to extranodal involvement of malignant lymphocytes are undefined in diffuse large B-cell lymphoma (DLBCL). Here we showed that junctional adhesion molecule-A (JAM-A) was highly expressed in DLBCL patients with multiple extranodal lesions. JAM-A maintained B-lymphoma cell stemness and was associated with cell invasion and epithelial-to-mesenchymal transition both in vitro and in vivo. As mechanism of action, JAM-A overexpression selectively activated transforming growth factor-β (TGF-β)/NODAL signaling, thereby enhanced B-lymphoma cell aggressiveness and induced extranodal involvement to mesoendoderm-derived organs in DLBCL. Lenalidomide downregulated JAM-A and downstream NODAL expression, resulting in inhibition of B-lymphoma cell invasion and epithelial-to-mesenchymal transition. In a murine xenograft model established with subcutaneous injection of JAM-A-overexpressing B-lymphoma cells, lenalidomide retarded tumor growth and prevented cell invasion to mesoendoderm-derived organs, consistent with the downregulation of JAM-A and NODAL expression. Collectively, these findings indicated that JAM-A was related to extranodal involvement in DLBCL through modulating TGF-β/NODAL signaling. Identified as a biomarker of stem cell property, JAM-A indicated the sensitivity of B-lymphoma cells to lenalidomide. Therapeutic targeting of JAM-A/NODAL axis could thus be a promising clinical strategy to impede tumor progression in DLBCL.

PURPOSE: The tetraspanin CD151 acts as a promoter of metastasis and invasion in several tumors. However, the role of CD151 in human gastric cancer (HGC) remains unclear. METHODS: Twenty HGC specimens and matched nontumor samples, human gastric epithelial cells (HGEC), and four gastric cancer cell lines were used to analyze CD151 expression. Short hairpin RNA-mediated downregulation of CD151 expression in HGC cells was performed to examine the role of CD151 in the proliferation and metastasis/invasion of HGC cells in vivo and in vitro. The relationship of CD151 with integrin α3 in HGC cells was investigated by silencing integrin α3 followed by co-immunoprecipitation and immunofluorescence staining. Finally, the prognostic value of CD151 and integrin α3 was evaluated by immunohistochemistry in tissue microarrays of 76 HGC patients. RESULTS: CD151 was expressed at higher levels in HGC tissues and HGC cells than in nontumor tissues and HGEC cells. Down-regulation of CD151 by vshRNA-CD151 impaired metastasis and invasion of HGC-27 cells, but did not affect cell proliferation. CD151 formed a complex with integrin α3 in HGC cells. CD151-cDNA transfection rescued the metastatic potential and invasiveness of HGC-27-vshCD151 cells, but not those of HGC-27-vshintegrin α3 cells in vitro. Clinically, CD151 overexpression was significantly correlated with high TNM stage, depth of invasion and positive lymph node involvement (p

The complete molecule of the title compound, C16H14O3, is generated by crystallographic mirror symmetry, with two C atoms and one O atom lying on the mirror plane. The molecule adopts an E configuration about the C=C bond and the dihedral angle between the furan rings is 16.1 (2)°.

The title compound, C25H28O7, was prepared by the base-catalysed reaction of 3,4,5-trimethoxybenzaldehyde with cyclopentanone. The molecule has crystallographic twofold rotation symmetry and adopts an E-configuration about the central olefinic bonds. The two benzene rings and the central cyclopentanone ring are almost coplanar [dihedral angle = 4.7 (2)°].

The title Schiff base, C24H21N3O2, adopts an E configuration with respect to the central C=N bond. The pyrazole ring and the central benzene ring attached to the imino group are almost coplanar. The phenyl ring attached to the pyrazole unit is twisted by 39.3 (2)° with respect to the pyrazole ring plane. The phenoxy benzene ring makes a dihedral angle of 79.8 (2)° with the central benzene ring.

The title compound, C19H17NO5, was synthesized as part of a continuing project involving the structures of oxazolone derivatives. The molecule adopts a Z configuration about the central olefinic bond. The 2-phenyl ring is slightly twisted out of the plane of the oxazolone ring system by 11.2 (2)°. The crystal structure is stabilized by weak intermolecular C—H...O hydrogen bonds.

The title compound, C24H19N5OS·H2O, was synthesized by the reaction of 4-benzoyl-3-methyl-1-phenylpyrazol-5-one and 2-hydrazino-1,3-benzothiazole. Proton transfer leads to the formation of a zwitterionic structure and the molecule exists in the enolate form. The pyrazolone ring makes dihedral angles of 35.4 (3), 69.7 (3) and 40.1 (3)° with the 1-phenyl, indirectly bound phenyl and benzothiazole ring systems, respectively. The molecules are linked into one-dimensional chains by a combination of N—H...O, O—H...N and O—H...O hydrogen bonds.

In the title compound, C17H14N4O2·1.5H2O, the mean planes of the pyridine ring and quinoline group make a dihedral angle of 21.0 (2)°. One water molecule lies on a twofold rotation axis. The organic molecules and the three water molecules are linked into infinite chains by N—H...O, O—H...O and O—H...N hydrogen bonds.

This paper proposes an optimized LSB matching steganography based on Fisher Information. The embedding algorithm is designed to solve the optimization problem, in which Fisher information is the objective function and embedding transferring probabilities are variables to be optimized. Fisher information is the quadratic function of the embedding transferring probabilities, and the coefficients of quadratic term are determined by the joint probability distribution of cover elements. By modeling the groups of elements in a cover image as Gaussian mixture model, the joint probability distribution of cover elements for each cover image is obtained by estimating the parameters of Gaussian mixture distribution. For each sub-Gaussian distribution in Gaussian mixture distribution, the quadratic term coefficients of Fisher information are calculated, and the optimized embedding transferring probabilities are solved by quadratic programming. By maximum posteriori probability principle, cover pixels are classified as the categories corresponding to sub-Gaussian distributions. At last, in order to embed message bits, pixels chose to add or subtract one according to the optimized transferring probabilities of the category. The experiments show that the security performance of this new algorithm is better than the existing LSB matching. [ABSTRACT FROM AUTHOR]

The title compound, C20H17NO6, was synthesized by the reaction of syringaldehyde with hippuric acid. The molecule adopts a Z configuration about the central olefinic bond. The two benzene rings and the oxazolone ring are almost coplanar. The crystal structure is stabilized by weak intermolecular C—H...O hydrogen bonds. [ABSTRACT FROM AUTHOR]

In the title compound, C15H15N3O4·H2O, the organic molecule exists in the keto–imine tautomeric form. The benzene ring makes a dihedral angle of 49.9 (2)° with the pyridine ring. The molecules pack in a three-dimensional framework structure by a combination of O—H...O, O—H...N, N—H...O and N—H...N hydrogen bonds. The water molecule of hydration is disordered [ratio of components 0.758 (7):0.242 (7)]. [ABSTRACT FROM AUTHOR]

In the title compound, C24H18F3N3O, the molecule exists in the enamine–keto tautomeric form. The pyrazolone ring makes dihedral angles of 31.8 (2), 45.4 (2) and 71.2 (2)° with the 1-phenyl, aniline and methylene-bound phenyl rings, respectively. An intramolecular N—H...O hydrogen bond helps to stabilize the molecular conformation. [ABSTRACT FROM AUTHOR]

In the title compound, C21H26N2O3, the molecule adopts an E configuration about the central C=N double bond and exists in the phenol–imine tautomeric form. The two benzene rings make a dihedral angle of 38.5 (4)°. Intramolecular O—H...N hydrogen bonding is present. [ABSTRACT FROM AUTHOR]

The title compound, C18H17N3O4, was synthesized by the condensation of 2,3,4-trihydroxybenzaldehyde with 4-aminoantipyrine. The molecule adopts a trans configuration about the central C=N double bond and exists in the phenol–imine form. Molecules are linked into a two-dimensional framework by intermolecular O—H...O hydrogen bonds. [ABSTRACT FROM AUTHOR]

The title compound, C21H18N4O, was synthesized by condensation of quinoline-2-carbaldehyde and 4-aminoantipyrine. The mean planes of the pyrazole and phenyl rings make a dihedral angle of 55.7 (3)°. The crystal packing is stabilized by weak intermolecular C—H...O hydrogen bonds and π–π interactions. [ABSTRACT FROM AUTHOR]

The title compound, C19H22N2O7·H2O, was synthesized as part of a continuing project involving the structures of hydrazone derivatives. The molecules pack in a three-dimensional framework structure by a combination of O—H...O, O—H...N and N—H...O hydrogen bonds. [ABSTRACT FROM AUTHOR]

Molecules of the title compound, C19H16N4O2·H2O, are linked into a one-dimensional ladder structure by a combination of intermolecular O—H...O and N—H...O hydrogen bonds. [ABSTRACT FROM AUTHOR]

The title compound, C26H20N4O, was synthesized by the reaction of 1-phenyl-3-methyl-4-benzoylpyrazol-5-one and 8-aminoquinoline. The molecule exists in the enamine–keto tautomeric form. [ABSTRACT FROM AUTHOR]

In the title compound, C22H18N4O4·2H2O, the hydrazine molecule lies across a twofold rotation axis, the mean planes of the two quinoline ring systems forming a dihedral angle of 64.1 (2)°. The hydrazine molecules and two water molecules are linked into infinite chains by O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds. [ABSTRACT FROM AUTHOR]

The title compound, C20H19N3O3·1.5H2O, has two organic mol­ecules in the asymmetric unit which differ in conformation. The two independent mol­ecules and three water mol­ecules are linked into layers by O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds. [ABSTRACT FROM AUTHOR]

In the title compound, C23H28O6, the mean planes of the two benzene rings make a dihedral angle of 81.1 (2)°. A twofold rotation axis passes through the central C atom. The molecules are connected into chains via intermolecular O—H...O hydrogen bonds. [ABSTRACT FROM AUTHOR]