The multi-slit very small angle neutron scattering instrument at the China Spallation Neutron Source.

A multi-slit very small angle neutron scattering (MS-VSANS) instrument has been finally accepted at the China Spallation Neutron Source (CSNS). It is the first spallation neutron source based VSANS instrument. MS-VSANS has a good signal-to-noise ratio and can cover a wide scattering vector magnitude range from 0.00028 to 1.4 Å-1. In its primary flight path, a combined curved multichannel beam bender and sections of rotary exchange drums are installed to minimize the background downstream of the instrument. An exchangeable multi-slit beam focusing system is integrated into the primary flight path, enabling access to a minimum scattering vector magnitude of 0.00028 Å-1. MS-VSANS has three modes, namely conventional SANS, polarizing SANS and VSANS modes. In the SANS mode, three motorized high-efficiency 3He tube detectors inside the detector tank cover scattering angles from 0.12 to 35° simultaneously. In the polarizing SANS mode, a double-V cavity provides highly polarized neutrons and a high-efficiency 3He polarization analyser allows full polarization analysis. In the VSANS mode, an innovative high-resolution gas electron multiplier detector covers scattering angles from 0.016 to 0.447°. The absolute scattering intensities of a selection of standard samples are obtained using the direct-beam technique; the effectiveness of this method is verified by testing the standard samples and comparing the results with those from a benchmark instrument. The MS-VSANS instrument is designed to be flexible and versatile and all the design goals have been achieved.

Silicon modification improves biochar's ability to mitigate cadmium toxicity in tomato by enhancing root colonization of plant-beneficial bacteria.

Modification of biochar, such as impregnation with minerals, can improve biochar's efficacy to mitigate heavy metal toxicity in plants. Biochar amendments can alter plant rhizosphere microbiome, which has profound effects on plant growth and fitness. Here, we tested whether rhizosphere microbiome is involved in the ability of silicon (Si)-modified biochar to mitigate cadmium toxicity in tomato (Solanum lycopersicum L.). We demonstrated that Si modification altered biochar's physico-chemical properties and enhanced its ability to mitigate cadmium toxicity in tomato. Particularly, the Si-modified biochar contained higher content of Si and increased plant-available Si content in the soil. The rhizosphere microbiome transplant experiment showed that changes in rhizosphere microbiome contributed to the mitigation of cadmium toxicity by biochar amendments. The raw biochar and Si-modified biochar differently altered tomato rhizosphere bacterial community composition. Both biochars, especially the Si-modified biochar, promoted specific bacterial taxa (e.g., Sphingomonas, Lysobacter and Pseudomonas spp.). Subsequent culturing found these promoted bacteria could mitigate cadmium toxicity in tomato. Moreover, both biochars stimulated tomato to recruit plant-beneficial bacteria with Si-modified biochar having stronger stimulatory effects, indicating that the positive effects of biochar on plant-beneficial bacteria was partially mediated via the host plant. Overall, Si modification enhanced biochar's ability to mitigate cadmium toxicity, which was linked to the stimulatory effects on plant-beneficial bacteria.

Case report and literature review: Novel compound heterozygous FIG4 variants causing both of peripheral and central nervous system defects.

Background: Pathogenic variants in the FIG4 gene have been described to be associated with a diverse spectrum of syndromes, such as autosomal recessive bilateral temporooccipital polymicrogyria (OMIM 612691), autosomal dominant amyotrophic lateral sclerosis-11 (ALS11; OMIM 612577), autosomal recessive Charcot-Marie-Tooth disease, type 4J (CMT4J; OMIM 611228), and autosomal recessive Yunis-Varon syndrome (YVS; OMIM 216340). Heterozygous FIG4 variants are responsible for ALS11 characterized by progressive muscular weakness, atrophy, and bulbar palsy. CMT4J is a disorder of peripheral nervous system defects mainly presenting with a highly variable onset of proximal and/or distal muscle weakness. YVS is a disorder of severe neurological involvement with central nervous system (CNS) dysfunction and extensive skeletal anomalies. Case Presentation: We reported two Chinese siblings born with a weakness in all limbs. They experienced rapidly progressive weakness in distal limbs. At the age of 6 years, the elder brother presented with severe scoliosis and cervical kyphosis. They both had global developmental delay and a CNS involvement with cognitive deficits and swallowing problems. Genetic screening in the patients' family for inherited diseases was recommended. Novel compound heterozygous variants in the FIG4 gene (c.2148delTinsAA and c.317A > G) were found by whole-exome sequencing in the patients. These variants were confirmed by Sanger sequencing in family members. Conclusions: Herein, we reported two Chinese male patients with CMT4J who presented with abnormal CNS features. CMT4J with CNS involvement has been very rarely reported. We hoped this study could expand the phenotypic and genetic spectrum of FIG4-related diseases. And we helped physicians to understand the genotype-phenotype correlation.

Multiscale characterization reveals oligomerization dependent phase separation of primer-independent RNA polymerase nsp8 from SARS-CoV-2.

RNA replication and transcription machinery is an important drug target for fighting against coronavirus. Non-structure protein nsp8 was proposed harboring primase activity. However, the RNA primer synthesis mechanism of nsp8 is still largely unknown. Here, we purified dimer and tetramer forms of SARS-CoV-2 nsp8. Combined with dynamic light scattering, small-angle neutron scattering and thermo-stability analysis, we found that both dimer and tetramer become loosened and destabilized with decreasing salt concentration, and the dimer form is more stable than the tetramer form. Further investigation showed that nsp8 dimer and tetramer can undergo phase separation but exhibit different phase separation behaviors. Nsp8 dimer can form liquid-like droplets in the buffer with a low concentration of NaCl; phase separation of nsp8 tetramer depends on the assistance of RNA. Our findings on different phase separation behaviors of nsp8 dimer and tetramer may provide insight into the functional studies of nsp8 in coronavirus.

Structure and dynamics of supercooled water in the hydration layer of poly(ethylene glycol).

The statics and dynamics of supercooled water in the hydration layer of poly(ethylene glycol) (PEG) were studied by a combination of quasi-elastic neutron scattering (QENS) and molecular dynamics (MD) simulations. Two samples, that is, hydrogenated PEG/deuterated water (h-PEG/D2O) and fully deuterated PEG/hydrogenated water (d-PEG/H2O) with the same molar ratio of ethylene glycol (EG) monomer to water, 1:1, are compared. The QENS data of h-PEG/D2O show the dynamics of PEG, and that of d-PEG/H2O reveals the motion of water. The temperature-dependent elastic scattering intensity of both samples has shown transitions at supercooled temperature, and these transition temperatures depend on the energy resolution of the instruments. Therefore, neither one is a phase transition, but undergoes dynamic process. The dynamic of water can be described as an Arrhenius to super-Arrhenius transition, and it reveals the hydrogen bonding network relaxation of hydration water around PEG at supercooled temperature. Since the PEG-water hydrogen bond structural relaxation time from MD is in good agreement with the average relaxation time from QENS (d-PEG/H2O), MD may further reveal the atomic pictures of the supercooled hydration water. It shows that hydration water molecules form a series of pools around the hydrophilic oxygen atom of PEG. At supercooled temperature, they have a more bond ordered structure than bulk water, proceed a trapping sites diffusion on the PEG surface, and facilitate the structural relaxation of PEG backbone.

Biochar amendment reduces cadmium uptake by stimulating cadmium-resistant PGPR in tomato rhizosphere.

Biochar amendment in the soil can exert a positive effect in reducing heavy metal toxicity in plants. However, it remains unclear the extent to which this effect is associated with the modulation of plant growth-promoting rhizobacteria (PGPR). Here, we initially conducted a pot experiment using tomato (Solanum lycopersicum L.) as a model plant grown in soil spiked with cadmium. First, we found biochar amendment to result in reduced cadmium uptake in tomato plants and trackable changes in the tomato rhizosphere microbiome. Then, a rhizosphere transplant experiment validated the importance of this microbiome modulation for cadmium-toxicity amelioration. Sequence-based analyses targeted the isolation of representative isolates of PGPR, including Bacillus and Flavisolibacter spp. that displayed in vitro cadmium tolerance and biosorption capabilities (in addition to abilities to solubilize phosphate and produce indole acetic acid). Last, we performed a soil inoculation experiment and confirmed the effectiveness of these isolates in reducing cadmium toxicity in tomato plants. Besides, we found the inoculation of these taxa as single inoculant and in combination to result in increased activities of specific antioxidant enzymes in tomato tissues. Taken together, this study revealed the ecological and physiological mechanisms by which biochar amendment indirectly alleviate cadmium toxicity in tomato plants, in this case, via the modulation and activity of specific PGPR populations. This study provides new insights into strategies able to promote beneficial PGPR in the rhizosphere with potential application to ameliorate heavy metal toxicity in plants.

Neutron Total Scattering Investigation of the Dissolution Mechanism of Trehalose in Alkali/Urea Aqueous Solution.

The atomic picture of cellulose dissolution in alkali/urea aqueous solution is still not clear. To reveal it, we use trehalose as the model molecule and total scattering as the main tool. Three kinds of alkali solution, i.e., LiOH, NaOH and KOH are compared. The most probable all-atom structures of the solution are thus obtained. The hydration shell of trehalose has a layered structure. The smaller alkali ions can penetrate into the glucose rings around oxygen atoms to form the first hydration layer. The larger urea molecules interact with hydroxide groups to form complexations. Then, the electronegative complexation can form the second hydration layer around alkali ions via electrostatic interaction. Therefore, the solubility of alkali aqueous solution for cellulose decreases with the alkali cation radius, i.e., LiOH > NaOH > KOH. Our findings are helpful for designing better green solvents for cellulose.

The Relationship between Free Volume and Cooperative Rearrangement: From the Temperature-Dependent Neutron Total Scattering Experiment of Polystyrene.

Although many theories have been proposed to describe the nature of glass formation, its microscopic picture is still missing. Here, by a combination of neutron scattering and molecular dynamics simulation, we present the temperature-dependent atomic structure variation of polystyrene at the glass formation, free volume and cooperative rearrangement. When it is close to glass formation, the polymer is confined in tubes, whose diameter is the main chain-main chain distance, in a "static cage" from its neighbors. This definition can not only account for the kinetic pathway dependence of Williams-Landel-Ferry (WLF) free volume, but also be testified in a set of six polymers. However, the free volume which allows a monomer to move cannot be found in any frame of its real-space image. Monomers, thus, have to move cooperatively to be out of the cage. During glass formation, dynamic heterogeneity develops, and string-like cooperative rearrangement region (CRR) grows over a long range of time and length scales. All of these CRRs tend to walk through loose "static cages". Our observation unifies the concepts of free volume and cooperative rearrangement. The former is a statistical average leading to a polydisperse "static cage" formation; while a loose "static cage" provides the way that CRRs move.

Neutron total scattering investigation on the dissolution mechanism of trehalose in NaOH/urea aqueous solution.

Trehalose is chosen as a model molecule to investigate the dissolution mechanism of cellulose in NaOH/urea aqueous solution. The combination of neutron total scattering and empirical potential structure refinement yields the most probable all-atom positions in the complex fluid and reveals the cooperative dynamic effects of NaOH, urea, and water molecules in the dissolution process. NaOH directly interacts with glucose rings by breaking the inter- and intra-molecular hydrogen bonding. Na+, thus, accumulates around electronegative oxygen atoms in the hydration shell of trehalose. Its local concentration is thereby 2-9 times higher than that in the bulk fluid. Urea molecules are too large to interpenetrate into trehalose and too complex to form hydrogen bonds with trehalose. They can only participate in the formation of the hydration shell around trehalose via Na+ bridging. As the main component in the complex fluid, water molecules have a disturbed tetrahedral structure in the presence of NaOH and urea. The structure of the mixed solvent does not change when it is cooled to -12 °C. This indicates that the dissolution may be a dynamic process, i.e., a competition between hydration shell formation and inter-molecule hydrogen bonding determines its dissolution. We, therefore, predict that alkali with smaller ions, such as LiOH, has better solubility for cellulose.