TRIM44 Promotes Rabies Virus Replication by Autophagy-Dependent Mechanism.

Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host-virus interactions through specific pathways, but their involvement in response to rabies virus (RABV) infection remains poorly understood. Here, we identified that several TRIM proteins are upregulated in mouse neuroblastoma cells (NA) after infection with the rabies virus using RNA-seq sequencing. Among them, TRIM44 was found to regulate RABV replication. This is supported by the observations that downregulation of TRIM44 inhibits RABV replication, while overexpression of TRIM44 promotes RABV replication. Mechanistically, TRIM44-induced RABV replication is brought about by activating autophagy, as inhibition of autophagy with 3-MA attenuates TRIM44-induced RABV replication. Additionally, we found that inhibition of autophagy with rapamycin reverses the TRIM44-knockdown-induced decrease in LC3B expression and autophagosome formation as well as RABV replication. The results suggest that TRIM44 promotes RABV replication by an autophagy-dependent mechanism. Our work identifies TRIM44 as a key host factor for RABV replication, and targeting TRIM44 expression may represent an effective therapeutic strategy.

Single-nucleus RNA-seq identifies one galanin neuronal subtype in mouse preoptic hypothalamus activated during recovery from sleep deprivation.

The preoptic area of the hypothalamus (POA) is essential for sleep regulation. However, the cellular makeup of the POA is heterogeneous, and the molecular identities of the sleep-promoting cells remain elusive. To address this question, this study compares mice during recovery sleep following sleep deprivation to mice allowed extended sleep. Single-nucleus RNA sequencing (single-nucleus RNA-seq) identifies one galanin inhibitory neuronal subtype that shows upregulation of rapid and delayed activity-regulated genes during recovery sleep. This cell type expresses higher levels of growth hormone receptor and lower levels of estrogen receptor compared to other galanin subtypes. single-nucleus RNA-seq also reveals cell-type-specific upregulation of purinergic receptor (P2ry14) and serotonin receptor (Htr2a) during recovery sleep in this neuronal subtype, suggesting possible mechanisms for sleep regulation. Studies with RNAscope validate the single-nucleus RNA-seq findings. Thus, the combined use of single-nucleus RNA-seq and activity-regulated genes identifies a neuronal subtype functionally involved in sleep regulation.

Influence of Interlayer Cation Ordering on Na Transport in P2-Type Na0.67-xLiy Ni0.33-zMn0.67+zO2 for Sodium-Ion Batteries.

P2-type Na2/3Ni1/3Mn2/3O2 (PNNMO) has been extensively studied because of its desirable electrochemical properties as a positive electrode for sodium-ion batteries. PNNMO exhibits intralayer transition-metal ordering of Ni and Mn and intralayer Na+/vacancy ordering. The Na+/vacancy ordering is often considered a major impediment to fast Na+ transport and can be affected by transition-metal ordering. We show by neutron/X-ray diffraction and density functional theory (DFT) calculations that Li doping (Na2/3Li0.05Ni1/3Mn2/3O2, LFN5) promotes ABC-type interplanar Ni/Mn ordering without disrupting the Na+/vacancy ordering and creates low-energy Li-Mn-coordinated diffusion pathways. A structure model is developed to quantitatively identify both the intralayer cation mixing and interlayer cationic stacking fault densities. Quasielastic neutron scattering reveals that the Na+ diffusivity in LFN5 is enhanced by an order of magnitude over PNNMO, increasing its capacity at a high current. Na2/3Ni1/4Mn3/4O2 (NM13) lacks Na+/vacancy ordering but has diffusivity comparable to that of LFN5. However, NM13 has the smallest capacity at a high current. The high site energy of Mn-Mn-coordinated Na compared to that of Ni-Mn and higher density of Mn-Mn-coordinated Na+ sites in NM13 disrupts the connectivity of low-energy Ni-Mn-coordinated diffusion pathways. These results suggest that the interlayer ordering can be tuned through the control of composition, which has an equal or greater impact on Na+ diffusion than the Na+/vacancy ordering.

Gold(I)-Thiolate Coordination Polymers as Multifunctional Materials: The Case of Au(I)-p-Fluorothiophenolate.

Gold-sulfur interaction has vital importance in nanotechnologies and material chemistry to design functional nanoparticles, self-assembled monolayers, or molecular complexes. In this paper, a mixture of only two basic precursors, such as the chloroauric acid (HAu(III)Cl4) and a thiol molecule (p-fluorothiophenol (p-HSPhF)), are used for the synthesis of gold(I)-thiolate coordination polymers. Under different conditions of synthesis and external stimuli, five different functional materials with different states of [Au(I)(p-SPhF)]n can be afforded. These gold-thiolate compounds are (i) red emissive, flexible, and crystalline fibers; (ii) composite materials made of these red emissive fibers and gold nanoparticles; (iii) amorphous phase; (iv) transparent glass; and (v) amorphous-to-crystalline phase-change material associated with an ON/OFF switch of luminescence. The different functionalities of these materials highlight the great versatility of the gold(I) thiolate coordination polymers with easy synthesis and diverse shaping that may have great potential as sustainable phosphors, smart textiles, sensors, and phase change memories.

Bioinspired Collective Total Synthesis of (±)-Rhynchines A-E.

Herein, we present the first racemic total synthesis of the structurally complex monoterpene indole alkaloids rhynchines A-E, starting from commercially available methyl nicotinate and 3-(2-bromoethyl)-1H-indole. The success of our synthesis is attributed to the utilization of a bioinspired synthetic strategy, which facilitated the rapid construction of the pentacyclic core skeleton of the target molecules through biomimetic skeletal rearrangement and late-stage C-H oxidative cyclization. Additionally, silica-gel-promoted tautomerization played a crucial role as a strategic element in the chemical synthesis of rhynchines A and B.

Tailoring the d-band center on Ru1Cu single-atom alloy nanotubes for boosting electrochemical non-enzymatic glucose sensing.

The development of cost-effective and highly efficient electrocatalysts is critical to help electrochemical non-enzymatic sensors achieve high performance. Here, a new class of catalyst, Ru single atoms confined on Cu nanotubes as a single-atom alloy (Ru1Cu NTs), with a unique electronic structure and property, was developed to construct a novel electrochemical non-enzymatic glucose sensor for the first time. The Ru1Cu NTs with a diameter of about 24.0 nm showed a much lower oxidation potential (0.38 V) and 9.0-fold higher response (66.5 µA) current than Cu nanowires (Cu NWs, oxidation potential 0.47 V and current 7.4 µA) for glucose electrocatalysis. Moreover, as an electrochemical non-enzymatic glucose sensor, Ru1Cu NTs not only exhibited twofold higher sensitivity (54.9 µA mM-1 cm-2) and wider linear range (0.5-8 mM) than Cu NWs, but also showed a low detection limit (5.0 µM), excellent selectivity, and great stability. According to theoretical calculation results, the outstanding catalytic and sensing performance of Ru1Cu NTs could be ascribed to the upshift of the d-band center that helped promote glucose adsorption. This work presents a new avenue for developing highly active catalysts for electrochemical non-enzymatic sensors.

Modeling and optimization of a novel multi-DOF electromagnetic driven spherical motion generator.

This paper introduces a new spherical motion generator and presents a method for modeling its magnetic field and analyzing its moments. The generator employs an electromagnetic drive of a spherical motor as its driving method and utilizes a spherical parallel manipulator to execute the spherical motion. The combination of these two technologies offers several advantages, including a large workspace and high motion accuracy. The equivalent magnetizing current method is used in the magnetic field modeling and the average air-gap flux density is optimized to achieve a better magnetic field distribution, and the accuracy of the analytical model is verified by finite element simulations and experiments.

Tailoring the Coordination Micro-Environment in Nanotraps for Efficient Platinum/Palladium Separation.

Recovering platinum group metals from secondary resources is crucial to meet the growing demand for high-tech applications. Various techniques are explored, and adsorption using porous materials has emerged as a promising technology due to its efficient performance and environmental beingness. However, the challenge lies in effectively recovering and separating individual platinum group metals (PGMs) given their similar chemical properties. Herein, a breakthrough approach is presented by sophisticatedly tailoring the coordination micro-environment in a series of aminopyridine-based porous organic polymers, which enables the creation of platinum-specific nanotraps for efficient separation of binary PGMs (platinum/palladium). The newly synthesized POP-o2NH2-Py demonstrates record uptakes and selectivity toward platinum over palladium, with the amino groups adjacent to the pyridine moieties being vital in improving platinum binding performance. Further breakthrough experiments underline its remarkable ability to separate platinum and palladium. Spectroscopic analysis reveals that POP-o2NH2-Py offers a more favorable coordination fashion to platinum ions compared to palladium ions owing to the greater interaction between N and Pt4+ and stronger intramolecular hydrogen bonding between the amino groups and four coordinating chlorines at platinum. These findings underscore the importance of fine-tuning the coordination micro-environment of nanotraps through subtle modifications that can greatly enhance the selectivity toward the desired metal ions.

The cytosolic DNA-sensing cGAS-STING pathway in neurodegenerative diseases.

BACKGROUND: With the widespread prevalence of neurodegenerative diseases (NDs) and high rates of mortality and disability, it is imminent to find accurate targets for intervention. There is growing evidence that neuroimmunity is pivotal in the pathology of NDs and that interventions targeting neuroimmunity hold great promise. Exogenous or dislocated nucleic acids activate the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS), activating the stimulator of interferon genes (STING). The activated STING triggers innate immune responses and then the cGAS-STING signaling pathway links abnormal nucleic acid sensing to the immune response. Recently, numerous studies have shown that neuroinflammation regulated by cGAS-STING signaling plays an essential role in NDs. AIMS: In this review, we summarized the mechanism of cGAS-STING signaling in NDs and focused on inhibitors targeting cGAS-STING. CONCLUSION: The cGAS-STING signaling plays an important role in the pathogenesis of NDs. Inhibiting the cGAS-STING signaling may provide new measures in the treatment of NDs.

Bioinspired Total Synthesis of Cephalotaxus Diterpenoids and Their Structural Analogues.

Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one-carbon introduction and ring expansion operations, we have successfully converted cephalotane-type C18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid-type C19 norditerpenoids and intact cephalotane-type C20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13-oxo-cephinoid H, 7-oxo-cephinoid H, fortalpinoid C, 7-epi-fortalpinoid C, cephanolide E, and 13-epi-cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between ß-oxo esters and ß-substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family.

Phonon softening induced phase transition of CeSiO4: a density functional theory study.

Density functional theory plus Hubbard U (DFT+U) methodology was used to calculate the structures and energetic landscapes of CeSiO4, including its stetindite and scheelite phases from ambient pressure to ∼24 GPa. To ensure accurate simulations of the high-pressure structures, assessments of strain-stress methods and stress-strain methods were conducted in prior, with the former found to have a better agreement with the experimental result. From DFT calculations the equation of states (EOS) of both stetindite and scheelite were further obtained, with the fitted bulk moduli being 182(2) GPa and 190.0(12) GPa, respectively. These results were found to be consistent with the experimental values of 177(5) GPa and 222(40) GPa. Furthermore, the calculated energetics suggest that the stetindite structure is more thermodynamically stable than the scheelite structure at a pressure lower than 8.35 GPa. However, the stetindite → scheelite phase transition was observed experimentally at a much higher pressure of ∼15 GPa. A further phonon spectra investigation by the density functional perturbation theory (DFPT) indicated the Eg1 mode is being softened with pressure and becomes imaginary after 12 GPa, which is a sign of the lattice instability. Consequently, it was concluded that the stetindite → scheelite transition is predominantly initiated by the lattice instability under high-pressure.

[Analysis of a case of Kabuki syndrome due to a novel variant of KMT2D gene].

OBJECTIVE: To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene. METHODS: A child diagnosed with KS at the Fujian Children's Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c.6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.6285dup variant of the KMT2D gene probably underlay the KS in this child.

A mitochondria-targeted ratiometric fluorescent sensor based on naphthalimide derivative-functionalized silica-based nanodots for imaging formaldehyde in living cells and zebrafish.

A mitochondria-targeted ratiometric fluorescent sensor (Mito-Si-NA) for formaldehyde (FA) has been constructed by functionalizing silica-based nanodots (silica-based ND). As the fluorescence reference and carrier, the silica-based ND conjugate with small molecule probe for FA via covalent. Further modifying with mitochondria targeting moiety enables the sensor to specifically target mitochondria. In the presence of FA, the emission of silica-based ND remain constant to act as an internal reference (445 nm) while the response signal of small molecule probe was gradually enhanced (545 nm). This sensor exhibits excellent selectivity towards FA with great changes of fluorescence intensity ratio values (I545/I445). The FA ratiometric fluorescence imaging in mitochondria was achieved successfully. In addition, the sensor was also successfully used for imaging FA in zebrafish. The good performance of Mito-Si-NA for FA bioimaging confirms that Mito-Si-NA is an appealing imaging tool to monitor FA in mitochondria and shows great potential to study the functions of FA on mitochondria.

Surface thermodynamics of yttrium titanate pyrochlore nanomaterials.

Nanocrystalline pyrochlore materials have been investigated for their enhanced radiation tolerance as ceramic nuclear waste hosts. In this work, we study the thermodynamic driving force of nano-scale materials for radiation resistance. The size dependent thermodynamic properties of a series of Y2Ti2O7 nanoparticles were investigated. Samples were synthesized by a sol-gel method and characterized by synchrotron X-ray diffraction, BET analysis, and thermogravimetric analysis. The surface and interface enthalpies of Y2Ti2O7 were determined by high temperature oxide melt drop solution calorimetry to be 4.07 J m-2 and 3.04 J m-2, respectively. The experimentally obtained surface energy is in good agreement with computationally derived average surface energies for yttrium and other rare-earth titanate pyrochlores. Theoretical links between nanoparticle stability, surface energy, and radiation resistance of pyrochlore materials were then explored.

A Comprehensive View on the Protein Functions of Porcine Epidemic Diarrhea Virus.

Porcine epidemic diarrhea (PED) virus (PEDV) is one of the main pathogens causing diarrhea in piglets and fattening pigs. The clinical signs of PED are vomiting, acute diarrhea, dehydration, and mortality resulting in significant economic losses and becoming a major challenge in the pig industry. PEDV possesses various crucial structural and functional proteins, which play important roles in viral structure, infection, replication, assembly, and release, as well as in escaping host innate immunity. Over the past few years, there has been progress in the study of PEDV pathogenesis, revealing the crucial role of the interaction between PEDV viral proteins and host cytokines in PEDV infection. At present, the main control measure against PEDV is vaccine immunization of sows, but the protective effect for emerging virus strains is still insufficient, and there is no ideal safe and efficient vaccine. Although scientists have persistently delved their research into the intricate structure and functionalities of the PEDV genome and viral proteins for years, the pathogenic mechanism of PEDV remains incompletely elucidated. Here, we focus on reviewing the research progress of PEDV structural and nonstructural proteins to facilitate the understanding of biological processes such as PEDV infection and pathogenesis.

A new methodology for measuring the enthalpies of mixing and heat capacities of molten chloride salts using high temperature drop calorimetry.

Molten salt reactors (MSRs) are a promising alternative to conventional nuclear reactors as they may offer more efficient fuel utilization, lower waste generation, and improved safety. The state of knowledge of the properties of liquid salts is far from complete. In order to develop the MSR concept, it is essential to develop a fundamental understanding of the thermodynamic properties, including the heat capacities (Cp) and enthalpies of mixing (ΔHmix), of molten salts at MSR operating conditions. Historically, the Cp values of molten salts were determined by drop-calorimetry or differential scanning calorimetry, whereas their ΔHmix values were typically measured using specialized high temperature calorimeters. In this work, a new methodology for measuring both the Cp and the ΔHmix of molten chloride salts was developed. This novel method involves sealing a chloride salt sample in a nickel capsule and performing conventional transposed temperature drop calorimetry using a commercially available Setaram AlexSYS-800 Tian-Calvet twin microcalorimeter. This methodology may be applied to calorimetric measurements of more complex salt mixtures, especially mixtures containing actinides and fission products.

Autophagy and Apoptosis in Rabies Virus Replication.

Rabies virus (RABV) is a single-stranded negative-sense RNA virus belonging to the Rhabdoviridae family and Lyssavirus genus, which is highly neurotropic and can infect almost all warm-blooded animals, including humans. Autophagy and apoptosis are two evolutionarily conserved and genetically regulated processes that maintain cellular and organismal homeostasis, respectively. Autophagy recycles unnecessary or dysfunctional intracellular organelles and molecules in a cell, whereas apoptosis eliminates damaged or unwanted cells in an organism. Studies have shown that RABV can induce both autophagy and apoptosis in target cells. To advance our understanding of pathogenesis of rabies, this paper reviews the molecular mechanisms of autophagy and apoptosis induced by RABV and the effects of the two cellular events on RABV replication.

TRIM28 promotes porcine epidemic diarrhea virus replication by mitophagy-mediated inhibition of the JAK-STAT1 pathway.

Porcine epidemic diarrhea virus (PEDV) infection causes immunosuppression and clinical symptoms such as vomiting, watery diarrhea, dehydration, and even death in piglets. TRIM28, an E3 ubiquitin ligase, is involved in the regulation of autophagy. However, the role of TRIM28 in PEDV infection is unknown. This study aimed to determine whether TRIM28 acts as a host factor for PEDV immune escape. We found that depletion of TRIM28 inhibited PEDV replication, whereas overexpression of TRIM28 promoted the viral replication in host cells. Furthermore, knockdown of TRIM28 reversed PEDV-induced downregulation of the JAK/STAT1 pathway. Treatment with the mitophagic activator carbonyl cyanide 3-chlorophenylhydrazone (CCCP) attenuated the activating effect of TRIM28 depletion on the expression of the STAT1 pathway-related proteins. Treatment with CCCP also reduced the nuclear translocation of pSTAT1. Moreover, TRIM28, via its RING domain, interacted with PEDV N. Overexpression of TRIM28 induced mitophagy, which could be enhanced by co-expression with PEDV N. The results indicate that PEDV infection upregulates the expression of TRIM28, which induces mitophagy, leading to inhibition of the JAK-STAT1 pathway. This research unveils a new mechanism by which PEDV can hijack host cellular TRIM28 to promote its own replication.

Tumour-associated macrophages and Schwann cells promote perineural invasion via paracrine loop in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently accompanied by perineural invasion (PNI), which is associated with excruciating neuropathic pain and malignant progression. However, the relationship between PNI and tumour stromal cells has not been clarified. METHODS: The dorsal root ganglia or sciatic nerves nerve model was used to observe the paracrine interaction and the activation effect among Schwann cells, tumour-associated macrophages (TAMs), and pancreatic cancer cells in vitro. Next generation sequencing, enzyme-linked immunosorbent assay and chromatin immunoprecipitation were used to explore the specific paracrine signalling between TAMs and Schwann cells. RESULTS: We demonstrated that more macrophages were expressed around nerves that have been infiltrated by pancreatic cancer cells compared with normal nerves in murine and human PNI specimens. In addition, high expression of CD68 or GFAP is associated with an increased incidence of PNI and indicates a poor 5-year survival rate in patients with PDAC. Mechanistically, tumour-associated macrophages (TAMs) activate Schwann cells via the bFGF/PI3K/Akt/c-myc/GFAP pathway. Schwann cells secrete IL-33 to recruit macrophages into the perineural milieu and facilitate the M2 pro-tumourigenic polarisation of macrophages. CONCLUSIONS: Our study demonstrates that the bFGF/IL-33 positive feedback loop between Schwann cells and TAMs is essential in the process of PNI of PDAC. The bFGF/PI3K/Akt/c-myc/GFAP pathway would open potential avenues for targeted therapy of PDAC.

The effect of heat-moisture treatment changed the binding of starch, protein and lipid in rice flour to affect its hierarchical structure and physicochemical properties.

This study investigated the effect of removing proteins, lipids and starch on the structure, physicochemical properties and digestion properties of rice flour (with 30% moisture) treated with heat moisture treatment (HMT). According to the results, HMT caused the adhesion and agglomeration of the rice flour, promoted the binding between starch, protein and lipid molecular chains and led to the formation of complexes (especially starch-lipid complexes), which hindered the removal of non-starch components. Compared to the untreated rice flour, the HMT treated lipid-removal rice flour had small changes in their crystallinity, gelatinization temperature and viscosity property. After removing protein, the crystallinity, peak viscosity, final viscosity, breakdown and starch digestibility were sharply increased. In particular, the peak viscosity increased from 811 cP to 1746 cP and the enthalpy change increased from 5.33 J/g to 10.18 J/g. These findings are helpful in understanding the contribution of removing endogenous proteins and lipids to the physicochemical changes of HMT treated rice flour during its heating process and thus can be helpful in controlling the quality of rice flour through HMT.