A novel three-plasmid packaging system for chimeric SFV/SIN VRPs derived from Semliki Forest virus and Sindbis virus as a candidate gene delivery vector.

Semliki Forest virus (SFV) viral replicon particles (VRPs) have been frequently used in various animal models and clinical trials. Chimeric replicon particles offer different advantages because of their unique biological properties. We here constructed a novel three-plasmid packaging system for chimeric SFV/SIN VRPs. The capsid and envelope of SIN structural proteins were generated using two-helper plasmids separately, and the SFV replicon contained the SFV replicase gene, packaging signal of SIN, subgenomic promoter followed by the exogenous gene, and 3' UTR of SIN. The chimeric VRPs carried luciferase or eGFP as reporter genes. The fluorescence and electron microscopy results revealed that chimeric VRPs were successfully packaged. The yield of the purified chimeric VRPs was approximately 2.5 times that of the SFV VRPs (1.38 × 107 TU/ml vs. 5.41 × 106 TU/ml) (p < 0.01). Furthermore, chimeric VRPs could be stored stably at 4°C for at least 60 days. Animal experiments revealed that mice immunized with chimeric VRPs (luciferase) had stronger luciferase expression than those immunized with equivalent amount of SFV VRPs (luciferase) (p < 0.01), and successfully expressed luciferase for approximately 12 days. Additionally, the chimeric VRPs expressed the RBD of SARS-CoV-2 efficiently and induced robust RBD-specific antibody responses in mice. In conclusion, the chimeric VRPs constructed here met the requirements of a gene delivery tool for vaccine development and cancer therapy.

A pressure-induced superhard SiCN4 compound uncovered by first-principles calculations.

Silicon-carbon-nitride (Si-C-N) compounds are a family of potential superhard materials with many excellent chemical and physical properties; however, only SiCN, Si2CN4 and SiC2N4 were synthesized. Here, we theoretically report a new SiCN4 compound with P41212, Fdd2 and R3̄ structures by first-principles structural predictions based on the particle swarm optimization algorithm. Pressure-induced structural phase transitions from P41212 to Fdd2, and then to the R3̄ phase were determined at 2 GPa and 249 GPa. By comparing enthalpy differences with 1/3Si3N4 + C + 4/3N2, it was found that these structures tend to decompose at ambient pressure. However, with the increase of pressure, the enthalpy differences of Fdd2 and R3̄ structures turn to be negative and they can be stabilized at a pressure of more than 41 GPa. They are also dynamically stable as no imaginary frequencies were found in their stabilized pressure ranges. The calculated band gap is 4.37 eV for P41212, 3.72 eV for Fdd2 and 3.81 eV for the R3̄ phase by using the Heyd-Scuseria-Ernzerhof (HSE06) method and the estimated Vickers hardness values are higher than 40 GPa by adopting the elastic modulus based hardness formula, which confirmed their superhard characteristics. These results provide significant insights into Si-C-N systems and will inevitably promote the future experimental works.

Djsnon, a downstream gene of Djfoxk1, is required for the regeneration of the planarian central nervous system.

Regulators of adult neurogenesis are crucial targets for neuronal repair. Freshwater planarians are ideal model systems for studying neuronal regeneration as they can regenerate their entire central nervous system (CNS) using pluripotent adult stem cells. Here, we identified Djfoxk1 in planarian Dugesia japonica to be required for planarian CNS regeneration. Knockdown of Djfoxk1 inhibits the regeneration of the cephalic ganglia, resulting in the failure of eye regeneration. By RNAi screening of Djfoxk1 downstream genes, we identified Djsnon as another regulator of planarian neuronal regeneration. Inhibition of Djsnon with RNA interference (RNAi) results in similar phenotypes caused by Djfoxk1 RNAi without affecting cell proliferation and wound healing. Our findings show that Djsnon as a downstream gene of Djfoxk1 regulates the regeneration of the planarian CNS.

Actin restricts cell proliferation and promotes differentiation during planarian regeneration.

Actin is an integral component of the cytoskeleton, which plays an important role in various fundamental cellular processes, such as affecting the polarity of embryonic cells during embryonic development in various model organisms. Meanwhile, previous studies have demonstrated that the polymerization of the actin cytoskeleton can affect cell migration, proliferation, and differentiation. Actin polymerization state regulated osteogenic differentiation and affected cell proliferation. However, the function of actin in regenerative biology has not been thoroughly elucidated. The planarian flatworm, which contains a large number of adult somatic stem cells (neoblasts), is an ideal model organism to study regenerative biology. Here, we identified a homolog of actin in planarian Dugesia japonica and found that RNAi targeting actin during planarian regeneration results in the formation of protrusions on the dorsal side, where the division of phospho-H3 mitotic cells is increased. In addition, a decrease in differentiation is observed in regenerating tissues after Djactin RNAi. These results indicate that Djactin functions in proliferation and differentiation control in planarian regeneration.

Enhanced ultrathin ultraviolet detector based on a diamond metasurface and aluminum reflector.

Metasurface is a kind of sub-wavelength artificial electromagnetic structure, which can resonate with the electric field and magnetic field of the incident light, promote the interaction between light and matter, and has great application value and potential in the fields of sensing, imaging, and photoelectric detection. Most of the metasurface-enhanced ultraviolet detectors reported so far are metal metasurfaces, which have serious ohmic losses, and studies on the use of all-dielectric metasurface-enhanced ultraviolet detectors are rare. The multilayer structure of the diamond metasurface-gallium oxide active layer-silica insulating layer-aluminum reflective layer was theoretically designed and numerically simulated. In the case of gallium oxide thickness of 20 nm, the absorption rate of more than 95% at the working wavelength of 200-220 nm is realized, and the working wavelength can be adjusted by changing the structural parameters. The proposed structure has the characteristics of polarization insensitivity and incidence angle insensitivity. This work has great potential in the fields of ultraviolet detection, imaging, and communications.

Hardness and superconductivity in tetragonal LiB4 and NaB4.

Boron-based compounds have triggered substantial attention due to their multifunctional properties, incorporating excellent hardness and superconductivity. While tetragonal metal borides LiB4 and NaB4 with BaAl4-type structure and striking clathrate boron motif have been induced under compression, there is still a lack of deep understanding of their potential properties at ambient pressure. We herein conduct a comprehensive study on I4/mmm-structured LiB4 and NaB4 under ambient pressure via first-principles calculations. Remarkably, both LiB4 and NaB4 are found to possess high Vickers hardness of 39 GPa, which is ascribed to the robust boron framework with strong covalency. Furthermore, their high hardness values together with distinguished stability make them highly potential superhard materials. Meanwhile, electron-phonon coupling analysis reveals that both LiB4 and NaB4 are conventional phonon-mediated superconductors, with critical temperatures of 6 and 8 K at 1 atmosphere pressure (atm), respectively, mainly arising from the coupling of B 2p electronic states and the low-frequency phonon modes associated with Li-, Na-, and B-derived vibrations. This work provides valuable insights into the mechanical and superconducting behaviors of metal borides and will boost further studies of emergent borides with multiple functionalities.

Whole-genome sequence of the planarian Dugesia japonica combining Illumina and PacBio data.

Advances in stem cell biology have posed the challenges in revealing the mechanistic themes underlying whole tissues and organs formation during regeneration. The planarian Dugesia japonica is an ideal model organism for the study of regeneration and stem cell biology. However, the genome resources for this species are still limited. Here, we combined single-molecule real-time DNA sequencing platform Pacific Biosciences (PacBio) sequencing, Illumina paired-end sequencing and 10× Genomics linked reads data to obtain the whole-genome sequence of the planarian D. japonica. The final assembled D. japonica genome is 1.13G with contig N50 of 248.44 kb, and scaffold N50 of 652.52 kb. Repeat elements account for 64.92% of the genome, and 12,031 protein coding genes were annotated, of which 10,114 genes had at least one functional annotation, representing 84.07% of the total genes. We present a highly contiguous genome assembly of D. japonica. The D. japonica genome assembly, together with gene annotation and transcriptome data provide a valuable resource to investigate molecular mechanism of planarian and stem cell research.

Electrochemical immunosensor nanoarchitectonics with the Ag-rGO nanocomposites for the detection of receptor-binding domain of SARS-CoV-2 spike protein.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a grave threat to human life and health, it is essential to develop an efficient and sensitive detection method to identify infected individuals. This study described an electrode platform immunosensor to detect SARS-CoV-2-specific spike receptor-binding domain (RBD) protein based on a bare gold electrode modified with Ag-rGO nanocomposites and the biotin-streptavidin interaction system. The Ag-rGO nanocomposites was obtained by chemical synthesis and characterized by electrochemistry and scanning electron microscope (SEM). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to record the electrochemical signals in the electrode modification. The differential pulse voltammetry (DPV) results showed that the limit of detection (LOD) of the immunosensor was 7.2 fg mL-1 and the linear dynamic detection range was 0.015 ~ 158.5 pg mL-1. Furthermore, this sensitive immunosensor accurately detected RBD in artificial saliva with favorable stability, specificity, and reproducibility, indicating that it has the potential to be used as a practical method for the detection of SARS-CoV-2.

Meis1 Controls the Differentiation of Eye Progenitor Cells and the Formation of Posterior Poles during Planarian Regeneration.

As a member of TALE family, Meis1 has been proven to regulate cell proliferation and differentiation during cell fate commitment; however, the mechanism is still not fully understood. The planarian, which has an abundance of stem cells (neoblasts) responsible for regenerating any organ after injury, is an ideal model for studying the mechanisms of tissue identity determination. Here, we characterized a planarian homolog of Meis1 from the planarian Dugesia japonica. Importantly, we found that knockdown of DjMeis1 inhibits the differentiation of neoblasts into eye progenitor cells and results in an eyeless phenotype with normal central nervous system. Furthermore, we observed that DjMeis1 is required for the activation of Wnt signaling pathway by promoting the Djwnt1 expression during posterior regeneration. The silencing of DjMeis1 suppresses the expression of Djwnt1 and results in the inability to reconstruct posterior poles. In general, our findings indicated that DjMeis1 acts as a trigger for the activation of eye and tail regeneration by regulating the differentiation of eye progenitor cells and the formation of posterior poles, respectively.

4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody.

Exhaustion of chimeric antigen receptor (CAR) T cells is one of the limitations for CAR T efficacy in solid tumors and for tumor recurrence after initial CAR T treatment. Tumor treatment with a combination of programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockage and CD28-based CAR T cells has been intensively studied. However, it remains largely unclear whether autocrine single-chain variable fragments (scFv) PD-L1 antibody can improve 4-1BB-based CAR T cell anti-tumor activity and revert CAR T cell exhaustion. Here, we studied T cells engineered with autocrine PD-L1 scFv and 4-1BB-containing CAR. The antitumor activity and exhaustion of CAR T cells were investigated in vitro and in a xenograft cancer model using NCG mice. CAR T cells with autocrine PD-L1 scFv antibody demonstrate enhanced anti-tumor activity in solid tumors and hematologic malignancies by blocking the PD-1/PD-L1 signaling. Importantly, we found that CAR T exhaustion was largely diminished by autocrine PD-L1 scFv antibody in vivo. As such, 4-1BB CAR T with autocrine PD-L1 scFv antibody combined the power of CAR T cells and the immune checkpoint inhibitor, thereby increasing the anti-tumor immune function and CAR T persistence, providing a cell therapy solution for a better clinical outcome.

Multi-mode plasmonic resonance broadband LWIR metamaterial absorber based on lossy metal ring.

Broadband perfect infrared wave absorption of unpolarized light over a wide range of angles in an ultrathin film is critical for applications such as thermal emitters and imaging. Although many efforts have been made in infrared broadband absorption, it is still challenging to cover the perfect absorption of broadband in the long-wave infrared band. We propose a long-wave infrared broadband, polarization, and incident angle insensitivity metamaterial absorber based on the supercell with four rings of two sizes. Broadband absorption covering the long-wave infrared band is realized by combining four PSPRs and LSPRs absorption peaks excited by the supercell structure. The absorptivity of our absorber exceeds 90% in the wavelength range of 7.76∼14µm, and the average absorptivity reaches 93.8%. The absorber maintains more than 80% absorptivity as the incident angle of unpolarized light reaches 60°, which may have promising applications for thermal emitters, infrared imaging, thermal detection.

Polarization-selective absorptive and transmissive metamaterials.

A polarization sorting metamaterial with polarization filtering and absorption is proposed. When unpolarized incident light strikes the metamaterial, one polarization component is completely absorbed, and the other polarization component is completely transmitted. We achieved an absorption extinction ratio of up to 350 and a transmission extinction ratio of 425 simultaneously in the LWIR. Unlike the 50% energy utilization limit of other polarization absorbers due to the complete reflection of another polarization component, our proposed metamaterial can be composed of layered polarization selective absorption devices to achieve more than 90% energy utilization. Therefore our design can provide a new solution for real-time polarization detection.

TRIM25 Promotes TNF-α-Induced NF-κB Activation through Potentiating the K63-Linked Ubiquitination of TRAF2.

As an important effector in response to various intracellular or extracellular stimuli, the NF-κB family extensively participates in a wide spectrum of biological events, and its dysregulation may result in many pathological conditions, such as microbial infection, tumor progression, and neurodegenerative disorders. Previous investigations showed that multiple types of ubiquitination play critical roles in the modulation of the NF-κB signaling pathway, yet the molecular mechanisms are still poorly understood. In the current study, we identified TRIM25, an E3 ubiquitin ligase, as a novel positive regulator in mediating NF-κB activation in human embryonic kidney 293T (HEK293T), HeLa cells, THP-1 cells, and PBMCs. The expression of TRIM25 promoted TNF-α-induced NF-κB signaling, whereas the knockdown had the opposite effect. Furthermore, TRIM25 interacted with TRAF2 and enhanced the K63-linked polyubiquitin chains attached to TRAF2. Moreover, TRIM25 bridged the interaction of TRAF2 and TAK1 or IKKß. To our knowledge, our study has identified a previously unrecognized role for TRIM25 in the regulation of NF-κB activation by enhancing the K63-linked ubiquitination of TRAF2.

TBX2/3 is required for regeneration of dorsal-ventral and medial-lateral polarity in planarians.

The molecular mechanisms responsible for axis establishment during non-embryonic processes remain elusive. The planarian flatworm is an ideal model organism to study body axis polarization and patterning in vivo. Here, we identified a homolog of the TBX2/3 in the planarian Dugesia japonica. RNA interference (RNAi) knockdown of TBX2/3 results in the ectopic formation of protrusions in the midline of the dorsal surface which shows an abnormal expression of midline and ventral cell markers. Additionally, the TBX2/3 RNAi animals also show the duplication of expression of the boundary marker at the lateral edge. Furthermore, TBX2/3 is expressed in muscle cells and co-expressed with bmp4. Inhibition of bone morphogenetic protein (BMP) signaling reduces the expression of TBX2/3 at the midline. These results suggest that TBX2/3 RNAi results in phenotypic characters caused by inhibition of the BMP signal, indicating that TBX2/3 is required for DV and ML patterning, and might be a downstream gene of BMP signaling.

Emerging Yttrium Phosphides with Tetrahedron Phosphorus and Superconductivity under High Pressures.

Metal phosphides have triggered growing interest for their exotic structures and striking properties. Hence, within advanced structure search and first-principle calculations, several unprecedented Y-P compounds (e. g., Y3 P, Y2 P, Y3 P2 , Y2 P3 , YP2 , and YP3 ) were identified under compression. Interestingly, as phosphorus content increases, P atoms exhibit diverse behaviors corresponding to standalone anion, dumbbell, zigzag chain, planar sheet, crossing chain-like network, buckled layer, three-dimensional framework, and wrinkled layer. Particularly, Fd-3m YP2 can be viewed as assemblage of diamond-like Y structure and rare vertex-sharing tetrahedral P4  units. Impressively, electron-phonon coupling (EPC) calculations elucidate that Pm-3m Y3 P possesses the highest superconducting critical temperature Tc of 10.2 K among binary transition metal phosphides. Remarkably, the EPC of Pm-3m Y3 P mainly arises from the contribution of low-frequency soft phonon modes, whereas mid-frequency phonon modes of Fd-3m YP2 dominate. These results strengthen knowledge of metal phosphides and pave a way for seeking superconductive transition metal phosphides.

Crystal structures and superconductivity of lithium and fluorine implanted gold hydrides under high pressures.

The investigations on gold science have been capturing research interest due to its diverse physical and chemical properties. Gold hydrides in the solid state, as a member of the Au compound family, are rare since the reaction of Au with H is hindered in terms of their similar electronegativity. It is expected that Li and F can provide electrons and holes, respectively, to help stabilize gold hydrides under high pressure. Herein, by means of a crystal structural search based on particle swarm optimization methodology accompanied by first-principles calculations, four hitherto unknown Li-Au-H compounds (i.e., LiAuH, LiAu2H, Li2Au2H, and Li6AuH) are predicted to be stable under compression. Intriguingly, Au-H bonding is found in LiAuH, LiAu2H, and Li2Au2H. As the gold content increases, Au atom arrangements exhibit diverse forms, from the chain in Li6AuH, the square layer in LiAuH, the network in Li2Au2H, and eventually to the coexistence of square and pyramid layers in LiAu2H. Additionally, Li6AuH has a unique cage-type lithium structure. Furthermore, electron-phonon coupling calculations show that these Li-Au-H phases are phonon-modulated superconductors with a superconducting critical temperature of 1.3, 0.06, and 0.02 K at 25 GPa and 2.79 K at 100 GPa. In contrast, we also identified two solid F4AuH and F6AuH phases with unexpected semiconductivity. They have structural configurations of H-bridged AuF4 quasi-square components and distorted AuF6 octahedrons, respectively, and have no gold-to-hydrogen bonds. Our current results indicate that electron doping at suitable concentrations under pressure can stabilize unique gold hydrides, and provide deep insights into the structures, electron properties, bonding behavior, and stability mechanism of ternary Li-Au-H and F-Au-H compounds.

Red fluorescent nanoprobe based on Ag@Au nanoparticles and graphene quantum dots for H2O2 determination and living cell imaging.

A sensitive and turn-on fluorescence nanoprobe based on core-shell Ag@Au nanoparticles (Ag@AuNPs) as a fluorescence receptor and red emissive graphene quantum dots (GQDs) as a donor was fabricated. They were conjugated together through π-π stacking between the GQDs and single-strand DNA modified at the Ag@AuNPs surface. The absorption spectrum of the receptor significantly overlapped with the donor emission spectrum, leading to a strong Förster resonance energy transfer (FRET) and thus a dramatic quenching. The sensing mechanism relies on fluorescence recovery following DNA cleavage by •OH produced from Fenton-like reaction between the peroxidase-like Ag nanocore and H2O2. The red emissive feature (Ex/Em, 520 nm/560 nm) provides low background in physiological samples. The •OH production, great spectrum overlapping, and red emission together contributes to good sensitivity and living cell imaging capability. The fluorescence assay (intensity at 560 nm) achieves a low detection limit of 0.49 µM H2O2 and a wide linear range from 5 to 200 µM, superior to most of the reported fluorescent probes. The RSD value for 100 µM H2O2 was 1.4%. The nanoprobe exhibits excellent anti-interferences and shows low cytotoxicity. The recovery of 100 µM standard H2O2 in a cancer cell lysate was 85.8%. Most satisfactorily, it can realize monitoring and imaging H2O2 in living cells. This study not only presents a sensitive H2O2 probe but also provides a platform for detecting other types of reactive oxygen species.

Djnedd4L Is Required for Head Regeneration by Regulating Stem Cell Maintenance in Planarians.

SUMOylation and ubiquitylation are homologous processes catalyzed by homologous enzymes, and they are involved in nearly all aspects of eukaryotic biology. Planarians, which have the remarkable ability to regenerate their central nervous system (CNS), provide an excellent opportunity to investigate the molecular processes of CNS regeneration in vivo. In this study, we analyzed gene expression profiles during head regeneration with an RNA-seq-based screening approach and found that Djnedd4L and Djubc9 were required for head regeneration in planarians. RNA interference targeting of Djubc9 caused the phospho-H3 mitotic cells to decrease in quantity, or even become absent as a part of the Djubc9 RNAi phenotype, which also showed the collapse of the stem cell lineage along with the reduced expression of epidermal differentiation markers. Furthermore, we found that Djnedd4L RNAi induced increased cell division and promoted the premature differentiation during regeneration. Taken together, our findings show that Djubc9 and Djnedd4L are required for stem cell maintenance in the planarian Dugesia japonica, which helps to elucidate the role of SUMOylation and ubiquitylation in regulating the regeneration process.

Unconventional stable stoichiometry of vanadium peroxide.

Peroxides have attracted considerable attention due to their intriguing electronic properties and diverse applications. However, only a few transition metal peroxides have been known thus far, limiting the variety of peroxide examples. Here, we demonstrate the stabilization of peroxides in the O-rich V-O system through first-principles calculations coupled with a swarm-intelligence structure search. As well as reproducing the known stoichiometries of VO, V2O3, VO2, and V2O5, two hitherto unknown V2O and VO4 stoichiometries are predicted to be thermodynamically stable at megabar pressures. VO4 has the highest oxygen content among the known peroxides to date. More interestingly, its electronic band gap increases with pressure, originating from the pressure-induced decrease of O-O bonding length in the peroxide group. V-rich V2O exhibits superconductivity, becoming the first example in the V-O system. Our work not only unravels the unusual vanadium peroxide, but also provides further insight into the diverse electronic properties of vanadium oxides under high pressure.

Achieving high hydrogen evolution reaction activity of a Mo2C monolayer.

Two-dimensional Mo2C materials (1T and 2H phases) have emerged as promising electrocatalysts for the hydrogen evolution reaction (HER) due to their low cost, inherent metallicity, and high stability. Unfortunately, the catalytic activity of Mo2C is lower than that of Pt, and it needs to be substantially improved for practical applications. It is necessary and urgent to consider the effect of synergetic interactions among defects, functions, and strain on the HER activity. In this study, the geometric structures, electronic properties, and the HER activity of the Mo2C monolayer, with vacancy defects (i.e. Mo and C), oxygen functionalization, and strain, are studied by using first-principles calculations. According to our results, the combination of Mo vacancies, which can be obtained under C-rich conditions, and oxygen functionalization is the most effective way to improve the HER activity of 1T- and 2H-Mo2C. Considering the abundant active sites and optimal Gibbs free energy of hydrogen adsorption, the 1T phase we obtained shows excellent HER activity even at high H coverage and improves the utilization of active sites, for which the HER activity is comparable to that of Pt. This can be attributed to the fact that oxygen atoms gain more electrons from Mo2C, which weakens the strength of the O-H bond. Our work provides not only an opportunity to better understand the catalytic mechanism, but also a guide to achieving high HER activity of a Mo2C monolayer.