Near-atomic structures of RHDV reveal insights into capsid assembly and different conformations between mature virion and VLP.

Rabbit hemorrhagic disease virus (RHDV) poses a significant threat to rabbits, causing substantial economic losses in rabbit farming. The virus also endangers wild populations of rabbit species and the predatory animals that rely on rabbits as a food source, thereby disturbing the ecological balance. However, the structural understanding of RHDV has been limited due to the lack of high-resolution structures. Here, we present the first high-resolution cryo-EM structures of the mature virion and virus-like particles (VLPs) derived from both full-length and N-terminal arm (NTA)-truncated VP60. These structures reveal intricate structural details of the icosahedral capsid and crucial NTA-mediated interactions essential for capsid assembly. In addition, dramatic conformational differences are unexpectedly observed between the mature virion and VLP. The protruding spikes of the A-B dimers adopt a "raised" state in the mature virion and a "resting" state in the VLP. These findings enhance our understanding of the structure, assembly, and conformational dynamics of the RHDV capsid, laying the essential groundwork for further virological research and therapeutic advancements.IMPORTANCERHDV is a pathogen with significant economic and ecological impact. By presenting the first high-resolution cryo-EM structures of RHDV, we have uncovered detailed interactions among neighboring VP60 subunits of the icosahedral capsid. The NTA of VP60 is uniquely clustered around the threefold axis of the capsid, probably play a critical role in dragging the six VP60 dimers around the threefold axis during capsid assembly. Additionally, we observed dramatic conformational differences between the mature virion and VLPs. VLPs are commonly used for vaccine development, under the assumption that their structure closely resembles that of the mature virion. Our findings significantly advance the understanding of the RHDV capsid structure, which may be used for developing potential therapeutic strategies against RHDV.

Nine months of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine chemotherapy for rifampicin/multidrug-resistant tuberculosis: a multicenter, randomized, open-label non-inferiority trial in China.

BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

In-Situ Construction of Atomic-Level Fe-O Bond Bridges within Fe2N/g-C3N4 Heterojunction for Efficient Visible-Light-Driven Photocatalytic H2 Production.

The limited active sites and faster photogenerated electron-hole pair recombination rate of g-C3N4 restrict its application in photocatalytic H2 production. Constructing heterojunctions has been shown to improve the spatial (directional) separation of photogenerated electrons and holes. However, due to interface mismatch in traditional heterojunction structures and a lack of precise electron transport channels, the photocatalytic efficiency is limited. Here, we developed a two-step calcination approach to create an Fe2N/g-C3N4 heterojunction linked by Fe-O bonds (named as Fe-OCN). The newly formed Fe-O bonds within the heterojunction can act as atomic-level interface electron transfer channels, directly transferring the photogenerated electrons of g-C3N4 to the reactive center Fe2N, significantly improving the charge transfer rate and utilization, thus promoting visible-light-driven photocatalytic H2 production. The optimal Fe-OCN achieved a H2 production rate of 5986.29 µmol g-1 h-1 under visible light, 13.44 times higher than that of the OCN due to efficient charge separation and transfer capabilities. This work provides a constructive reference for the design and synthesis of organic-inorganic heterojunction with chemically bonded interfaces, establishing quick electron transfer channels, and achieving targeted electron transfer.

Ba3Lu(BO3)3:Ce3+,Tb3+/Mn2+: Dual-Functional Material for WLEDs and Optical Pressure Sensing.

Ba3Lu(BO3)3(BLB):Ce3+,Tb3+/Mn2+ phosphors were designed to explore effective and multifunctional applications. Under the excitation of near-ultraviolet (n-UV) light, the BLB:Ce3+ phosphor showed broad-band blue emission. After codoping with Mn2+ ions, the single-phase white light phosphor is achieved through the energy transfer (ET) between Ce3+ and Mn2+. In addition, thermal stability is significantly enhanced by the addition of Tb3+ (BLB:0.02Ce3+,0.20Tb3+) compared to that codoped with Mn2+ (BLB:0.02Ce3+,0.10Mn2+). The light-emitting diode (LED) device with warm white light emission is fabricated with UV-chip-coated BLB:0.02Ce3+,0.05Tb3+ and Sr2Si5N8:Eu2+ phosphors, showing a good potential application value for LEDs. Additionally, the spectral properties of borate-based phosphors (BLB:0.02Ce3+) under high pressure were studied for the first time. Surprisingly, the change of pressure enabled the emission peak of BLB:0.02Ce3+ to be tuned from 485 to 552 nm, and dλ/dP is 3.51 nm GPa-1. The color changes from blue to yellow with an increase of pressure. Compared with the reported data, the pressure-sensing sensitivity based on the central peak shift in this work is the highest in all Ce3+ single-doped samples. In addition, the emitting color and intensity were gradually regained after decompression. The intensity can reach 80% of the initial intensity. All data demonstrate that the BLB:0.02Ce3+ phosphor has the potential to be utilized as an optical pressure sensor due to the high-pressure sensitivity and visible color tuning.

Ca9-yMgyNaGd0.667(PO4)7:Eu2+: A Single Eu2+-Doped Full-Spectrum White Light Emission Phosphor with High Color Rendering Index.

The multi-cationic site occupation control of rare earth doped phosphor materials is one of the key factors in achieving single-phase full-spectrum emission. In this work, the site distribution of Eu2+ in Ca9NaGd0.667(PO4)7 (CNGP):x%Eu2+ phosphors with multi-cationic sites was determined. Under 385 nm excitation, CNGP:x%Eu2+ samples exhibited a cyan emission composed of three sub-Gaussian components. The CNGP:1.5%Eu2+ phosphor was structurally modified through the partial substitution of Mg2+ for Ca2+ according to the crystallographic site engineering theory, and corresponding luminescent properties had been adjusted. When the concentration of Mg2+ changed, the Ca9-yMgyNaGd0.667(PO4)7:1.5%Eu2+ (CNGPE:yMg2+) phosphors exhibited a tunable emission from cyan to orange and achieved white light emission at y = 0.6. Based on the change of the crystal field environment, the mechanism of Mg2+ substitution affecting the luminescence characteristics of CNGP:x%Eu2+ phosphors was researched in detail. The light-emitting diode device consisted of a CNGPE:0.6Mg2+ phosphor and a 385 nm chip and had a high color rendering index (CRI = 91.9), low correlated color temperature (CCT = 4852 K), and excellent color stability. The optical performance of this device makes it promising to be used in full spectrum lighting.

3D/1D Fe3O4@TiO2/TC-TiO2/SiO2 Magnetic Inorganic-Framework Molecularly Imprinted Fibers for Targeted Photodegradation.

To achieve a selective degradation of pollutants in a water body, 3D/1D magnetic molecularly imprinted fibers Fe3O4@TiO2/TC-TiO2/SiO2 were fabricated by an electrospinning method. The molecularly imprinted layer was successfully prepared by a direct imprinting method using TiO2 as a functional monomer. Fe3O4 facilitates the catalyst recovery and light utilization. The as-prepared fibrous photocatalyst has a large specific surface area of 132.4 m2/g. The successful generation of imprinted sites was proven by various characterizations. The weak interaction between the inorganic functional monomer and tetracycline (TC) was determined to be van der Waals force and hydrogen bonds by the IGMH isosurface theory. The construction of the 3D/1D homojunction of molecularly imprinted materials is beneficial to charge transfer. The as-prepared photocatalyst exhibits a high selectivity coefficient α = 737.38 competing with RhB. The TC removal efficiency reached 100% within only 20 min. In addition, the possible degradation pathway and the degradation mechanism are reasonably proposed. This work not only provides an in-depth mechanism of the weak interaction between the inorganic molecularly imprinted functional monomer and pollutant molecules but also offers new thoughts on the fabrication of photocatalysts for the effective and selective treatment of pollutants in water bodies.

A Comparative Study of SiO2:Tb3+@Gd2O3:Eu3+ and Its Inverted Tb3+-Eu3+ Core-Shell Phosphors.

How to effectively improve energy transfer efficiency and luminous intensity inspired us to synthesize a series of SiO2:x%Tb3+@Gd2O3:y%Eu3+ samples, study their luminescence properties and interfacial energy transfer (IET), and compare with SiO2:x%Eu3+@Gd2O3:y%Tb3+. The results show that SiO2:x%Tb3+@Gd2O3:y%Eu3+ can exhibit adjustable multicolor luminescence from red to green at different concentrations of Eu3+ and Tb3+ or under different excitation wavelengths, and there exists efficient IET from Tb3+ to Eu3+ in SiO2:x%Tb3+@Gd2O3:y%Eu3+ and SiO2:x%Eu3+@Gd2O3:y%Tb3+, which improves the energy transfer efficiency and luminous intensity. In addition, the luminescence properties are different between SiO2:3%Tb3+@Gd2O3:3%Eu3+ and SiO2:3%Eu3+@Gd2O3:3%Tb3+, and the energy transfer efficiency of Tb3+ → Eu3+ in SiO2:3%Tb3+@Gd2O3:3%Eu3+ is obviously higher than that in SiO2:3%Eu3+@Gd2O3:3%Tb3+. The present study not only developed a kind of multicolor luminescent phosphor but also offered an important new strategy for improving the energy transfer efficiency and luminescent intensity.

Pressure-Triggered Fluorescence Intensity Ratio Variations of YNbO4:Bi3+/Ln3+ (Ln = Eu or Sm) for High-Sensitivity Optical Pressure Sensing.

Optical pressure sensing by phosphors is a growing area of research. However, the main pressure measurement methods rely on the movement of the central peak position, which has significant drawbacks for practical applications. This paper demonstrates the feasibility of using the fluorescence intensity ratio (FIR) of different emission peaks for pressure sensing. The FIR (IBi3+/ILn3+) values of the synthesized YNbO4:Bi3+/Ln3+ (Ln = Eu or Sm) phosphors are all first-order exponentially related to pressure, and YNbO4:Bi3+/Ln3+ (Ln = Eu or Sm) phosphors have high pressure-sensing sensitivities (Sp and Spr), which are 6 times higher than those from our previously reported work. In addition, the changes in FIR values during the decompression process were also calculated, and the trend was similar to that during the compression process. The YNbO4:Bi3+,Eu3+ phosphor has better pressure recovery performance. In summary, the YNbO4:Bi3+/Ln3+ (Ln = Eu or Sm) phosphors reported in this paper are expected to be applied in the field of optical pressure sensing, and this study provides a new approach and perspective for designing new phosphors for pressure measurement.

Synthesis Design and Properties of Ca5(BO3)3F: Bi3+/Eu3+: Insight into Luminescence, Temperature, and Pressure Sensing.

Nowadays, the utilization of noncontact temperature and pressure sensing is experiencing growing popularity. In this work, Bi3+, Eu3+-doped Ca5(BO3)3F (CBOF) phosphors were synthesized via an ionic liquid-assisted electrospinning approach. The effect of molecular weight of polyvinylpyrrolidone on the morphology of CBOF was investigated, and a comprehensive analysis of its formation mechanism was presented. The luminescence properties of CBOF: Bi3+, Eu3+ were studied systematically. The temperature-dependent emission of CBOF: Bi3+, Eu3+ phosphor was discussed, and it displayed thermal sensitivity, which can be attributed to the distinct thermal response emission behaviors of Bi3+ and Eu3+. The investigation of the pressure-dependent emission behavior of the CBOF: Bi3+ phosphor revealed an anomalous phenomenon: with the increase of pressure, the emission peak showed a trend of first a blue shift and then a red shift. This anomaly was discussed in detail. The phosphor exhibits visual color change (blue to cyan), remarkable pressure sensitivity (4.76 nm/GPa), and a high upper pressure limit (24.2 GPa), indicating its potential use as an optical pressure sensor. Consequently, this study presents an innovative synthetic approach for fabricating CBOF, presenting a bifunctional material with promising prospects in the fields of temperature and pressure sensing.

Identification a novel Ganoderma FIP gene from Ganoderma capense and its functional expression in Pichia pastoris.

Ganoderma capense is a precious medicinal fungus in China. In this study, a novel fungal immunomodulatory protein gene, named as FIP-gca, was cloned from G. capense by homologous cloning. Sequencing analysis indicated that FIP-gca was composed of 336 bp, which encoded a polypeptide of 110 amino acids. Protein sequence blasting and phylogenetic analysis showed that FIP-gca shared homology with other Ganoderma FIPs. FIP-gca was effectively expressed in Pichia pastoris GS115 at an expression level of 166.8 mg/L and purified using HisTrap™ fast-flow prepack columns. The immunomodulation capacity of rFIP-gca was demonstrated by that rFIP-gca could obviously stimulate cell proliferation and increase IL-2 secretion of murine spleen lymphocytes. Besides, antitumor activity of rFIP-gca towards human stomach cancer AGS cell line was evaluated in vitro. Cell wound scratch assay proved that rFIP-gca could inhibit migration of AGS cells. And flow cytometry assay revealed that rFIP-gca could significantly induce apoptosis of AGS cells. rFIP-gca was able to induce 18.12% and 22.29% cell apoptosis at 0.3 µM and 0.6 µM, respectively. Conclusively, the novel FIP-gca gene from G. capense has been functionally expressed in Pichia and rFIP-gca exhibited ideal immunomodulation and anti-tumour activities, which implies its potential application and study in future.

Eu2+-Doped Ca4Y3Si7O15N5 Phosphor with High Thermal Stability and Pressure Sensitivity for Dual-Functional Applications in W-LEDs and Pressure Sensors.

A novel green-light-emitting silicon-based oxynitride phosphor Ca4Y3Si7O15N5:Eu2+ with low thermal quenching and ideal pressure sensitivity is reported. The Ca3.99Y3Si7O15N5:0.01Eu2+ phosphor can be efficiently excited by 345 nm ultraviolet light and shows very low thermal quenching (integrated and peak emission intensities at 373 and 423 K were 96.17, 95.86, and 92.73, 90.66% of those at 298 K, respectively). The correlation between high thermal stability and structural rigidity is investigated in detail. The white-light-emitting diode (W-LED) is assembled by depositing the obtained green-light-emitting phosphor Ca3.99Y3Si7O15N5:0.01Eu2+ and commercial phosphors on a ultraviolet (UV)-emitting chip (λ = 365 nm). The CIE color coordinates, color rendering index (Ra), and corrected color temperature (CCT) of the obtained W-LED are (0.3724, 0.4156), 92.9, and 4806 K, respectively. In addition, when subjected to in situ high-pressure fluorescence spectroscopy, the phosphor exhibits an evident red shift of 40 nm with an increase in pressure from 0.2 to 32.1 GPa. The phosphor has the advantage of high-pressure sensitivity (dλ/dP = 1.13 nm GPa-1) and visualization with pressure changes. The possible reasons and mechanisms are deeply discussed in detail. Based on the above advantages, Ca3.99Y3Si7O15N5:0.01Eu2+ phosphor is expected to have potential applications in W-LEDs and optical pressure sensing.

Inhibitor of growth protein 3 epigenetically silences endogenous retroviral elements and prevents innate immune activation.

Endogenous retroviruses (ERVs) are subject to transcriptional repression in adult tissues, in part to prevent autoimmune responses. However, little is known about the epigenetic silencing of ERV expression. Here, we describe a new role for inhibitor of growth family member 3 (ING3), to add to an emerging group of ERV transcriptional regulators. Our results show that ING3 binds to several ERV promoters (for instance MER21C) and establishes an EZH2-mediated H3K27 trimethylation modification. Loss of ING3 leads to decreases of H3K27 trimethylation enrichment at ERVs, induction of MDA5-MAVS-interferon signaling, and functional inhibition of several virus infections. These data demonstrate an important new function of ING3 in ERV silencing and contributing to innate immune regulation in somatic cells.

A Triple-Doped Phosphor Strategy for the Conversion of Cool and Warm White Light.

This work proposes a new type of Eu2+, Ce3+, Mn2+ codoped strategy that can be adapted to both ultraviolet (UV) and blue chips to achieve high-quality white light illumination. Primarily, the target sample was confirmed by X-ray diffraction (XRD) and Rietveld refinement, and the surface morphology and element distribution were observed by scanning electron microscopy (SEM). Second, the energy transfer behavior and mechanism were determined by studying double-doped samples. Lu2Mg2Al2Si2O12: Eu2+,Ce3+ (LMAS: Eu2+,Ce3+) can realize an emission color adjustment from blue to yellow. The emission color of LMAS: Ce3+,Mn2+ can be adjusted from light yellow to orange yellow. Afterward, the triple-doped sample exhibits full-spectrum emission under the excitation at 365 nm, and yellow emission under the excitation at 450 nm. When combined with a 365 nm chip, the obtained light-emitting diode (LED) devices can achieve warm white light with a color rendering index (Ra) of 96.6, light emission (LE) of 1.79 lm/W, and correlated color temperature (CCT) of 4874 K. When this phosphor was combined with a 460 nm chip, cold white light with Ra = 70, LE = 13.57 lm/W, and CCT = 5782 K can be achieved. Finally, according to the properties of the phosphor, a conceptual diagram of a new type parallel device was designed, which can easily and effectively realize the conversion of cold and warm white light. This work provides a new idea for the design of single-substrate white light phosphor and proposes a new parallel device concept, which is expected to be applied in the field of lighting.

Multifunctional CaF2: Yb3+, Ho3+, Gd3+ Nanocrystals: Insight into Crystal Growth and Properties of Upconversion Luminescence, Magnetic, and Temperature Sensing Properties.

The upconversion (UC) emission intensity of Ln3+-doped CaF2 nanomaterials is not ideal, which limits their application in some advanced scientific fields. Hence, it is extremely imperative to enhance the emission intensity of UC nanocrystals. In this work, an ionic-liquid-assisted hydrothermal method based on an ethylene glycol (EG) and ionic liquid (IL) two-phase system was used to synthesize CaF2 doped with Yb3+ and Ho3+. The influence of the amount of IL and the reaction time as well as the concentration of Gd3+ doping on morphology and size was studied in detail, and the growth mechanism was proposed. Green UC luminescence materials were obtained through co-doping Yb3+ and Ho3+ ions. Furthermore, the luminescence of UC was increased monotonically with the introduction of Gd3+ ions. The effect mechanism of Gd3+ doping on the UC luminescence was put forward, which might provide a new method for the promotion of UC luminescence. In addition, the temperature sensing of CaF2: Yb3+/Ho3+/Gd3+ was investigated, which demonstrated that the phosphor has a potential application prospect in thermal sensing. Meanwhile, CaF2: Yb3+/Ho3+/Gd3+ also exhibited a paramagnetic property at room temperature. Therefore, these multifunctional nanocrystals may have prospective applications in optical bioimaging, magnetic resonance imaging, and temperature sensing.

Systematic Study on the Luminescent Properties, Thermal Stability, and Magnetic Behavior of GdOF: RE3+ (RE = Eu, Yb, and Er) Red Phosphors with Various Morphologies.

In this work, GdOF:RE3+ (RE = Eu, Yb, and Er) phosphors with high thermally stable luminescence were reported, which were synthesized by an ionic liquid-assisted two-phase system and subsequent calcination technique for the first time. Nanodisks, nanorod aggregates, nanoneedles, and stubby nanorods were obtained by simply regulating the pH value. The luminescent properties of precursors and products were discussed in detail. By carefully adjusting the calcination temperature and the pH value of the initial system, pure red emission was achieved in both GdOF:Eu3+ and GdOF:Yb3+, Er3+ phosphors. The reason for distinct luminescent properties of different products was discussed from various perspectives. Moreover, the temperature-dependent spectra were measured and the GdOF:Eu3+ and GdOF:Yb3+, Er3+ products both exhibited outstanding thermal stability. In addition, the as-prepared nanomaterials presented paramagnetic properties, indicating their potential application in both field-emission displays and magnetic resonance imaging technology.

CoMo layered double hydroxide equipped with carbon nanotubes for electrocatalytic oxygen evolution reaction.

To carry out effective resource reforming of sustainable electricity, hydrogen production by electrochemical water splitting provides an eco-friendly and economical way. Nevertheless, the oxygen evolution reaction (OER) at the anode is limited by the slow reaction process, which hinders the large-scale development and application of electrolysis technology. In this work, we present an electrocatalyst with superior OER performance, which attributed to the abundant active sites and good electronic conductivity. The two-dimensional CoMo Layered Double Hydroxide nanosheets are synthesized and deposited on conductive carbon nanotubes (CoMo LDH/CNTs), and then hybrid composites show better catalytic performance than their undecorated counterpart under identical conditions. Specifically, CoMo LDH/CNTs exhibit the low overpotential of 268 mV to obtain 10 mA cm-2and satisfactory stability (more than 40 h). We emphasize that this hybridization strategy with a conductive supporting framework could design more abundant and low-cost OER electrocatalysts to minimize electrical energy consumption, thereby achieving efficient conversion between energy sources.

Retinoic Acid and Lymphotoxin Signaling Promote Differentiation of Human Intestinal M Cells.

BACKGROUND & AIMS: Intestinal microfold (M) cells are a unique subset of intestinal epithelial cells in the Peyer's patches that regulate mucosal immunity, serving as portals for sampling and uptake of luminal antigens. The inability to efficiently develop human M cells in cell culture has impeded studies of the intestinal immune system. We aimed to identify signaling pathways required for differentiation of human M cells and establish a robust culture system using human ileum enteroids. METHODS: We analyzed transcriptome data from mouse Peyer's patches to identify cell populations in close proximity to M cells. We used the human enteroid system to determine which cytokines were required to induce M-cell differentiation. We performed transcriptome, immunofluorescence, scanning electron microscope, and transcytosis experiments to validate the development of phenotypic and functional human M cells. RESULTS: A combination of retinoic acid and lymphotoxin induced differentiation of glycoprotein 2-positive human M cells, which lack apical microvilli structure. Upregulated expression of innate immune-related genes within M cells correlated with a lack of viral antigens after rotavirus infection. Human M cells, developed in the enteroid system, internalized and transported enteric viruses, such as rotavirus and reovirus, across the intestinal epithelium barrier in the enteroids. CONCLUSIONS: We identified signaling pathways required for differentiation of intestinal M cells, and used this information to create a robust culture method to develop human M cells with capacity for internalization and transport of viruses. Studies of this model might increase our understanding of antigen presentation and the systemic entry of enteric pathogens in the human intestine.

Unique Dual-Sites Boosting Overall CO2 Photoconversion by Hierarchical Electron Harvesters.

Low selectivity and poor activity of photocatalytic CO2 reduction process are usually limiting factors for its applicability. Herein, a hierarchical electron harvesting system is designed on CoNiP hollow nano-millefeuille (CoNiP NH), which enables the charge enrichment on CoNi dual active sites and selective conversion of CO2 to CH4 . The CoNiP serves as an electron harvester and photonic "black hole" accelerating the kinetics for CO2 -catalyzed reactions. Moreover, the dual sites form from highly stable CoONiC intermediates, which thermodynamically not only lower the reaction energy barrier but also transform the reaction pathways, thus enabling the highly selective generation of CH4 from CO2 . As an outcome, the CoNiP NH/black phosphorus with dual sites leads to a tremendously improved photocatalytic CH4 generation with a selectivity of 86.6% and an impressive activity of 38.7 µmol g-1  h-1 .

Reverse Genetics Reveals a Role of Rotavirus VP3 Phosphodiesterase Activity in Inhibiting RNase L Signaling and Contributing to Intestinal Viral Replication In Vivo.

Our understanding of how rotavirus (RV) subverts host innate immune signaling has greatly increased over the past decade. However, the relative contribution of each virus-encoded innate immune antagonist has not been fully studied in the context of RV infection in vivo Here, we present both in vitro and in vivo evidence that the host interferon (IFN)-inducible 2'-5'-oligoadenylate synthetase (OAS) and RNase L pathway effectively suppresses the replication of heterologous RV strains. VP3 from homologous RVs relies on its 2'-5'-phosphodiesterase (PDE) domain to counteract RNase L-mediated antiviral signaling. Using an RV reverse-genetics system, we show that compared to the parental strain, VP3 PDE mutant RVs replicated at low levels in the small intestine and were shed less in the feces of wild-type mice, and such defects were rescued in Rnasel-/- suckling mice. Collectively, these findings highlight an important role of VP3 in promoting viral replication and pathogenesis in vivo in addition to its well-characterized function as the viral RNA-capping enzyme.IMPORTANCE Rotaviruses are significant human pathogens that result in diarrhea, dehydration, and deaths in many children around the world. Rotavirus vaccines have suboptimal efficacy in low- to middle-income countries, where the burden of the diseases is the most severe. With the ultimate goal of improving current vaccines, we aim to better understand how rotavirus interacts with the host innate immune system in the small intestine. Here, we demonstrate that interferon-activated RNase L signaling blocks rotavirus replication in a strain-specific manner. In addition, virus-encoded VP3 antagonizes RNase L activity both in vitro and in vivo These studies highlight an ever-evolving arms race between antiviral factors and viral pathogens and provide a new means of targeted attenuation for next-generation rotavirus vaccine design.

NF-κB and Keap1 Interaction Represses Nrf2-Mediated Antioxidant Response in Rabbit Hemorrhagic Disease Virus Infection.

The rabbit hemorrhagic disease virus (RHDV), which belongs to the family Caliciviridae and the genus Lagovirus, causes lethal fulminant hepatitis in rabbits. RHDV decreases the activity of antioxidant enzymes regulated by Nrf2 in the liver. Antioxidants are important for the maintenance of cellular integrity and cytoprotection. However, the mechanism underlying the regulation of the Nrf2-antioxidant response element (ARE) signaling pathway by RHDV remains unclear. Using isobaric tags for relative and absolute quantification (iTRAQ) technology, the current study demonstrated that RHDV inhibits the induction of ARE-regulated genes and increases the expression of the p50 subunit of the NF-κB transcription factor. We showed that RHDV replication causes a remarkable increase in reactive oxygen species (ROS), which is simultaneously accompanied by a significant decrease in Nrf2. It was found that nuclear translocation of Keap1 plays a key role in the nuclear export of Nrf2, leading to the inhibition of Nrf2 transcriptional activity. The p50 protein partners with Keap1 to form the Keap1-p50/p65 complex, which is involved in the nuclear translocation of Keap1. Moreover, upregulation of Nrf2 protein levels in liver cell nuclei by tert-butylhydroquinone (tBHQ) delayed rabbit deaths due to RHDV infection. Considered together, our findings suggest that RHDV inhibits the Nrf2-dependent antioxidant response via nuclear translocation of Keap1-NF-κB complex and nuclear export of Nrf2 and provide new insight into the importance of oxidative stress during RHDV infection.IMPORTANCE Recent studies have reported that rabbit hemorrhagic disease virus (RHDV) infection reduced Nrf2-related antioxidant function. However, the regulatory mechanisms underlying this process remain unclear. The current study showed that the NF-κB p50 subunit partners with Keap1 to form the Keap1-NF-κB complex, which plays a key role in the inhibition of Nrf2 transcriptional activity. More importantly, upregulated Nrf2 activity delayed the death of RHDV-infected rabbits, strongly indicating the importance of oxidative damage during RHDV infection. These findings may provide novel insights into the pathogenesis of RHDV.