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Alphaherpesvirus infection results in severe health consequences in a wide range of hosts. USPs are the largest subfamily of deubiquitinating enzymes that play critical roles in immunity and other cellular functions. To investigate the role of USPs in alphaherpesvirus replication, we assessed 13 USP inhibitors for PRV replication. Our data showed that all the tested compounds inhibited PRV replication, with the USP14 inhibitor b-AP15 exhibiting the most dramatic effect. Ablation of USP14 also influenced PRV replication, whereas replenishment of USP14 in USP14 null cells restored viral replication. Although inhibition of USP14 induced the K63-linked ubiquitination of PRV VP16 protein, its degradation was not dependent on the proteasome. USP14 directly bound to ubiquitin chains on VP16 through its UBL domain during the early stage of viral infection. Moreover, USP14 inactivation stimulated EIF2AK3/PERK- and ERN1/IRE1-mediated signaling pathways, which were responsible for VP16 degradation through SQSTM1/p62-mediated selective macroautophagy/autophagy. Ectopic expression of non-ubiquitinated VP16 fully rescued PRV replication. Challenge of mice with b-AP15 activated ER stress and autophagy and inhibited PRV infection in vivo. Our results suggested that USP14 was a potential therapeutic target to treat alphaherpesvirus-induced infectious diseases. Abbreviations ATF4: activating transcription factor 4; ATF6: activating transcription factor 6; ATG5: autophagy related 5; ATG12: autophagy related 12; CCK-8: cell counting kit-8; Co-IP: co-immunoprecipitation; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR associated system 9; DDIT3/CHOP: DNA-damage inducible transcript 3; DNAJB9/ERdj4: DnaJ heat shock protein family (Hsp40) member B9; DUBs: deubiquitinases; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EP0: ubiquitin E3 ligase ICP0; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; FOXO1: forkhead box O1; FRET: Förster resonance energy transfer; HSPA5/BiP: heat shock protein 5; HSV: herpes simplex virus; IE180: transcriptional regulator ICP4; MAP1LC3/LC3: microtube-associated protein 1 light chain 3; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; PPP1R15A/GADD34: protein phosphatase 1, regulatory subunit 15A; PRV: pseudorabies virus; PRV gB: PRV glycoprotein B; PRV gE: PRV glycoprotein E; qRT-PCR: quantitative real-time polymerase chain reaction; sgRNA: single guide RNA; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID50: tissue culture infective dose; UB: ubiquitin; UBA: ubiquitin-associated domain; UBL: ubiquitin-like domain; UL9: DNA replication origin-binding helicase; UPR: unfolded protein response; USPs: ubiquitin-specific proteases; VHS: virion host shutoff; VP16: viral protein 16; XBP1: X-box binding protein 1; XBP1s: small XBP1; XBP1(t): XBP1-total. [ABSTRACT FROM AUTHOR]

A new 3 D polyoxometalate, H7K3[Na2Cu3(H2O)(B-α-SbW9O33)2]·8H2O (1), has been hydrothermally made and characterized by IR spectroscopy, thermogravimetric analyses, powder X-ray diffraction and single crystal X-ray diffraction analysis. 1 crystallizes in the tetragonal system, space group P-421m, with a = 16.7532(7) Å, b = 16.7532(7) Å, c = 13.8335(11) Å and Z = 2. Structure analysis reveals that the polyanion in 1 consists of two B-α-SbW9O33 ({SbW9}) units sandwiched by a U-shaped {Na2Cu3} cluster made by two Na+ and three Cu2+ ions. The most prominent structural feature of 1 is that the [Na2Cu3(H2O)(B-α-SbW9O33)2]10– ({Na2Cu3(SbW9)2}) units are connected to construct a 2 D network through Cu–O = W bridges. To the best of our knowledge, 1 represents the first sample with an unclosed central belt between two {SbW9} fragments. Furthermore, neighboring 2 D networks connect by K+ cations to form a 3 D framework. The semiconductor behavior, electrochemical properties and photocatalytic activities have been investigated, showing excellent photocatalytic and electrocatalytic activities for the photodegradation of MB/RhB and bromate reduction. [ABSTRACT FROM AUTHOR]

Some new methods, such as air oxidation, catalytic oxidation, and solvent-free synthesis, are developed for the synthesis of 3-methyl-1-phenylchromeno[4,3-c]pyrazol-4(1H)-ones(2) from the cyclization of 3-[1-(phenyl-hydrazono)ethyl]-chromen-2-ones(1). Compared with air oxidation, catalytic oxidation can increase the rate of the cyclization of compound1, and the solvent-free synthesis showed advantages of no organic solvent pollution, elevated reaction rate, and higher selectivity. [ABSTRACT FROM AUTHOR]

The hydrothermal reaction of Co(COO)2 · 4H2O, MoO3, H3PO4 and 4,4'-bipyridine yields bipyridine-ligated cobalt dimolybdate [CoMo2O7(4,4'-bipy)1.5] (1) (4,4'-bipy = 4,4'-bipyridine) in the triclinic system with space group of P 1 and cell parameters of a = 7.1951(8) Å, b = 11.1708(17) Å, c = 11.4514(11) Å, α = 98.545(7)°, β = 90.315(2)°, γ = 105.777(5)°, V = 874.88(19) Å3, and Z = 2. Its structure consists of Co/Mo/O bimetal oxide layers with {Mo2O7} building blocks, linked by the coordination of 4,4'-bipy ligand with Co and Mo atoms, into a 3D porous hybrid framework. [ABSTRACT FROM AUTHOR]

Two novel cadmium polymeric complexes, [Cd 2 (btec)·6H 2 O] n ( 1 ), and [Cd 2 (btec)] n ( 2 ) (H 4 btec = 1,2,4,5-benzenetetracarboxylic acid), were obtained by assembly of Cd(NO 3 ) 2 ·4H 2 O and Cd(OH) 2 with H 4 btec at different pH values and characterized by elemental analysis, IR spectra, X-ray single-crystal diffraction, TGA and fluorescent spectra. Complex 1 crystallizes in the triclinic system with space group , a = 5.595(1), b = 7.770(2), c = 9.685(2) Å, α = 111.93(2), β = 101.78(2), γ = 98.28(2)° and complex 2 crystallizes in the monoclinic system with space group C 2/m, a = 6.588(2), b = 18.038(5), c = 4.728(2) Å, β = 116.49(1)°. Complex 1 contains a novel step-like 2D layered network and complex 2 possesses a 3D pillared-layered structure. These two complexes exhibit strong fluorescent emission bands at 363.5 and 486.5 nm (λ ex = 215 nm) for complex 1 , 386.5 nm (λ ex = 335 nm) for complex 2 in the solid state at room temperature. [ABSTRACT FROM AUTHOR]