Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres.

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.

Deciphering the Superior Electronic Transmission Induced by the Li-N Ligand Pairs Boosted Photocatalytic Hydrogen Evolution.

Atomic level decoration route is designated as one of the attractive methods to regulate both the charge density and band structure of photocatalysts. Moreover, to enable more efficient separation and transport of photocarriers, the construction of novel active sites can enhance both the reactivity and electrical conductivity of the crystal. Herein, an Li-N ligand is constructed via co-doping lithium and nitrogen atoms into ZnIn2 S4 lattice, which achieves a promoted photocatalytic H2 evolution at 9737 µmol g-1 h-1 . The existence of Li-N ligand pairs and the behaviors of photocarriers on L40 N5 ZIS are determined systematically, which also provides a unique insight into the mechanism of the improved photocarrier migration rate. With the introduction of Li-N dual sites, the vacancy form of ZnIn2 S4 has changed and the photocatalytic stability is significantly improved. Interestingly, the change of charge density around Li-N ligand in ZnIn2 S4 is determined by theoretical simulations, as well as the regulated energy barrier of photocatalytic water splitting caused by Li-N dual sites, which act as both adsorption site for H2 O and stronger reactive sites. This work helps to extend the understanding of ZnIn2 S4 and offers a fresh perspective for the creation of a Li-N co-doped photocatalyst.

Isolated Electron Trap-Induced Charge Accumulation for Efficient Photocatalytic Hydrogen Production.

The solar-driven evolution of hydrogen from water using particulate photocatalysts is considered one of the most economical and promising protocols for achieving a stable supply of renewable energy. However, the efficiency of photocatalytic water splitting is far from satisfactory due to the sluggish electron-hole pair separation kinetics. Herein, isolated Mo atoms in a high oxidation state have been incorporated into the lattice of Cd0.5 Zn0.5 S (CZS@Mo) nanorods, which exhibit photocatalytic hydrogen evolution rate of 11.32 mmol g-1 h-1 (226.4 µmol h-1 ; catalyst dosage 20 mg). Experimental and theoretical simulation results imply that the highly oxidized Mo species lead to mobile-charge imbalances in CZS and induce the directional photogenerated electrons transfer, resulting in effectively inhibited electron-hole recombination and greatly enhanced photocatalytic efficiency.

Reversely Trapping Isolated Atoms in High Oxidation State for Accelerating the Oxygen Evolution Reaction Kinetics.

Developing efficient electrocatalysts for the oxygen evolution reaction (OER) is paramount to the energy conversion and storage devices. However, the structural complexity of heterogeneous electrocatalysts makes it a great challenge to elucidate the dynamic structural evolution and OER mechanisms. Here, we develop a controllable atom-trapping strategy to extract isolated Mo atom from the amorphous MoOx -decorated CoSe2 (a-MoOx @CoSe2 ) pre-catalyst into Co-based oxyhydroxide (Mo-CoOOH) through an ultra-fast self-reconstruction process during the OER process. This conceptual advance has been validated by operando characterizations, which reveals that the initially rapid Mo leaching can expedite the dynamic reconstruction of pre-catalyst, and simultaneously trap Mo species in high oxidation state into the lattice of in situ generated CoOOH support. Impressively, the OER kinetics of CoOOH has been greatly accelerated after the reverse decoration of Mo species, in which the Mo-CoOOH affords a markedly decreased overpotential of 297 mV at the current density of 100 mA cm-2 . Density functional theory (DFT) calculations demonstrate that the Co species have been greatly activated via the effective electron coupling with Mo species in high oxidation state. These findings open new avenues toward directly synthesizing atomically dispersed electrocatalysts for high-efficiency water splitting.

MECP2 Duplication Causes Aberrant GABA Pathways, Circuits and Behaviors in Transgenic Monkeys: Neural Mappings to Patients with Autism.

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene-circuit-behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced ß-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene-circuit-behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2 However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.

Slr0151 in Synechocystis sp. PCC 6803 is required for efficient repair of photosystem II under high-light condition.

Cyanobacteria are ancient photosynthetic prokaryotes that have adapted successfully to adverse environments including high-light irradiation. Although it is known that the repair of photodamaged photosystem II (PSII) in the organisms is a highly regulated process, our knowledge of the molecular components that regulate each step of the process is limited. We have previously identified a hypothetical protein Slr0151 in the membrane fractions of cyanobacterium Synechocystis sp. PCC 6803. Here, we report that Slr0151 is involved in PSII repair of the organism. We generated a mutant strain (Δslr0151) lacking the protein Slr0151 and analyzed its characteristics under normal and high-light conditions. Targeted deletion of slr0151 resulted in decreased PSII activity in Synechocystis. Moreover, the mutant exhibited increased photoinhibition due to impairment of PSII repair under high-light condition. Further analysis using in vivo radioactive labeling and 2-D blue native/sodium dodecylsulfate polyacrylamide gel electrophoresis indicated that the PSII repair cycle was hindered at the levels of D1 synthesis and disassembly and/or assembly of PSII in the mutant. Protein interaction assays demonstrated that Slr0151 interacts with D1 and CP43 proteins. Taken together, these results indicate that Slr0151 plays an important role in regulating PSII repair in the organism under high-light stress condition.

Electrochemical nitrogen reduction reaction on anchored SnS2 nanosheets with TM2 dimers.

The design of efficient, high-stability nitrogen fixation catalysts remains a great challenge to achieve electrochemical nitrogen reduction reaction (NRR) under ambient conditions. Herein, the high-throughput first-principles calculations are performed to obtain potential electrochemical NRR catalysts from transition metal (TM) dimers anchored on SnS2 nanosheets. The selected W2/SnS2 behaves as a promising NRR candidate possessing -0.27 V limiting potential and 0.81 eV maximum kinetic potential, and it exhibits the adsorption advantages of *N2 over other small molecules (*H2O, *O, *OH, *H). More importantly, the moderate d orbital valence electron number and electronegativity of TM atom could obtain better NRR activity, and a new descriptor φ considering the effects of coordination environments and adsorbates is proposed to achieve the fast pre-screening among various candidates. This work presents practical insights into the fast screening of TM2/SnS2 candidates for efficient nitrogen fixation and further streamlining the design of electrochemical NRR catalysts.

Noncoding transcripts are linked to brain resting-state activity in non-human primates.

Brain-derived transcriptomes are known to correlate with resting-state brain activity in humans. Whether this association holds in nonhuman primates remains uncertain. Here, we search for such molecular correlates by integrating 757 transcriptomes derived from 100 macaque cortical regions with resting-state activity in separate conspecifics. We observe that 150 noncoding genes explain variations in resting-state activity at a comparable level with protein-coding genes. In-depth analysis of these noncoding genes reveals that they are connected to the function of nonneuronal cells such as oligodendrocytes. Co-expression network analysis finds that the modules of noncoding genes are linked to both autism and schizophrenia risk genes. Moreover, genes associated with resting-state noncoding genes are highly enriched in human resting-state functional genes and memory-effect genes, and their links with resting-state functional magnetic resonance imaging (fMRI) signals are altered in the brains of patients with autism. Our results highlight the potential for noncoding RNAs to explain resting-state activity in the nonhuman primate brain.

Brain-wide and cell-specific transcriptomic insights into MRI-derived cortical morphology in macaque monkeys.

Integrative analyses of transcriptomic and neuroimaging data have generated a wealth of information about biological pathways underlying regional variability in imaging-derived brain phenotypes in humans, but rarely in nonhuman primates due to the lack of a comprehensive anatomically-defined atlas of brain transcriptomics. Here we generate complementary bulk RNA-sequencing dataset of 819 samples from 110 brain regions and single-nucleus RNA-sequencing dataset, and neuroimaging data from 162 cynomolgus macaques, to examine the link between brain-wide gene expression and regional variation in morphometry. We not only observe global/regional expression profiles of macaque brain comparable to human but unravel a dorsolateral-ventromedial gradient of gene assemblies within the primate frontal lobe. Furthermore, we identify a set of 971 protein-coding and 34 non-coding genes consistently associated with cortical thickness, specially enriched for neurons and oligodendrocytes. These data provide a unique resource to investigate nonhuman primate models of human diseases and probe cross-species evolutionary mechanisms.

Proteomic study of the impact of Hik33 mutation in Synechocystis sp. PCC 6803 under normal and salt stress conditions.

Cyanobacteria are the only prokaryotes possessing plasma, thylakoid, and outer membranes. The plasma membrane of a cyanobacterial cell is essential for the biogenesis of cyanobacterial photosystems and serves as a barrier against environmental stress. We previously identified dozens of salt-responsive proteins in the plasma membrane of Synechocystis sp. PCC 6803. Five histidine kinases (Hiks) including Hik33 were also proposed to be involved in the perception of salt stress in Synechocystis. In this study, we analyzed proteomic profiles of the plasma membrane from a hik33-knockout mutant (ΔHik33) under normal and salt-stress conditions. Using 2D-DIGE followed by mass spectrometry analysis, we identified 26 differentially expressed proteins in ΔHik33 mutant cells. Major changes, due to the Hik33 mutation, included the substrate-binding proteins of ABC transporters, such as GgtB and FutA1, regulatory proteins including MorR and Rre13, as well as several hypothetical proteins. Under salt-stress conditions, the Hik33 mutation reduced levels of 7 additional proteins, such as NrtA, nitrate/sulfonate/bicarbonate-binding protein and LexA, and enhanced levels of 9 additional proteins including SphX. These observations suggest a substantial rearrangement in the plasma membrane proteome of Synechocystis due to the loss of hik33. Furthermore, a comprehensive molecular network was revealed in ΔHik33 mutant coping with salt stress.

Bacillus nematocida B16 Enhanced the Rhizosphere Colonization of Pochonia chlamydosporia ZK7 and Controlled the Efficacy of the Root-Knot Nematode Meloidogyne incognita.

Pochonia chlamydosporia is widely applied in many countries as a biocontrol fungus against parasitic nematodes in plants. In a field experiment, the combined use of Bacillus nematocida B16 increased the biocontrol efficiency of P. chlamydosporia ZK7 against Meloidogyne incognita. Further study indicated that the colonization of P. chlamydosporia ZK7 in the rhizosphere soil and the roots of tomatoes was significantly higher in the combined use group than in the control group. Gas chromatography was conducted to determine the effects of signaling substances. Five compounds, hexanal, (E)-2-hexenal, furfural, benzaldehyde, and 2-nonanone, were found to be highly altered in the volatile compounds produced in the soil under the combined application. The changes in benzaldehyde and 2-nonanone were the main factors that resulted in an increase in the colonization of fungi P. chlamydosporia ZK7 in the tomato roots. Furfural was the main volatile substance that affected the colonization of fungi P. chlamydosporia ZK7 in the soil. The combined use of B. nematocida B16 and P. chlamydosporia ZK7 altered the volatile ranges and resulted in increased colonization of biocontrol fungi and improved biocontrol efficiency against nematodes. This combined model could be used to promote the ability of biocontrol fungi to control root-knot nematodes.

AWA and ASH Homologous Sensing Genes of Meloidogyne incognita Contribute to the Tomato Infection Process.

The AWA neurons of Caenorhabditis elegans mainly perceive volatile attractive odors, while the ASH neurons perceive pH, penetration, nociception, odor tropism, etc. The perceptual neurons of Meloidogyne incognita have been little studied. The number of infestations around and within tomato roots was significantly reduced after RNA interference for high-homology genes in AWA and ASH neurons compared between M. incognita and C. elegans. Through in situ hybridization, we further determined the expression and localization of the homologous genes Mi-odr-10 and Mi-gpa-6 in M. incognita. In this study, we found that M. incognita has neuronal sensing pathways similar to AWA and ASH perception of C. elegans for sensing chemical signals from tomato roots. Silencing the homologous genes in these pathways could affect the nematode perception and infestation of tomato root systems. The results contribute to elucidating the process of the plant host perception of M. incognita.

Mapping brain-wide excitatory projectome of primate prefrontal cortex at submicron resolution and comparison with diffusion tractography.

Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here, we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic, and subcortical areas, relatively weak projections to parietal and insular regions but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative green fluorescent protein-labeled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.

In the brain is a web of interconnected nerve cells that send messages to one another via spindly projections called axons. These axons join together at junctions called synapses to create circuits of nerve cells which connect neighboring or distant brain regions. Notably, long-range neural connections underpin higher-order cognitive skills (such as planning and emotion regulation) which make humans distinct from our primate relatives. Only by untangling these far-reaching networks can researchers begin to delineate what sets the human brain apart from other species. Researchers deploy a range of imaging techniques to map neural networks: scanning entire brains using MRI machines, or imaging thin slices of fluorescently labelled brain tissue using powerful microscopes. However, tracing long-range axons at a high resolution is challenging, and has stirred up debate about whether some neural tracts, such as the inferior fronto-occipital fasciculus, are present in all primates or only humans. To address these discrepancies, Yan, Yu et al. employed a two-pronged approach to map neural circuits in the brains of macaques. First, two techniques ­ called viral tracing and two-photon microscopy ­ were used to create a three-dimensional, fine-grain map showing how the ventrolateral prefrontal cortex (vlPFC), which regulates complex behaviors, connects to the rest of the brain. This revealed prominent axons from the vlPFC projecting via a single synapse to distant brain regions involved in higher-order functions, such as encoding memories and processing emotion. However, there were no direct, monosynaptic connections between the vlPFC and the occipital lobe, the brain's visual processing center at the back of the head. Next, Yan, Yu et al. used a specialized MRI scanner to create an atlas of neural circuits connected to the vlPFC, and compared these results to a technique tracing axons stained with a fluorescent dye. In general, there was good agreement between the two methods, except for major differences in the rear-end projections that typically form the inferior fronto-occipital fasciculus. This suggests that this long-range neural pathway exists in monkeys, but it connects via multiple synapses instead of a single junction as was previously thought. The findings of Yan, Yu et al. provide new insights on the far-reaching neural pathways connecting distant parts of the macaque brain. It also suggests that atlases of neural circuits from whole brain scans should be taken with caution and validated using neural tracing experiments.

Reversal of Functional Brain Activity Related to Gut Microbiome and Hormones After VSG Surgery in Patients With Obesity.

CONTEXT: Vertical sleeve gastrectomy (VSG) is becoming a prioritized surgical intervention for obese individuals; however, the brain circuits that mediate its effective control of food intake and predict surgical outcome remain largely unclear. OBJECTIVE: We investigated VSG-correlated alterations of the gut-brain axis. METHODS: In this observational cohort study, 80 patients with obesity were screened. A total of 36 patients together with 26 normal-weight subjects were enrolled and evaluated using the 21-item Three-Factor Eating Questionnaire (TFEQ), MRI scanning, plasma intestinal hormone analysis, and fecal sample sequencing. Thirty-two patients underwent VSG treatment and 19 subjects completed an average of 4-month follow-up evaluation. Data-driven regional homogeneity (ReHo) coupled with seed-based connectivity analysis were used to quantify VSG-related brain activity. Longitudinal alterations of body weight, eating behavior, brain activity, gastrointestinal hormones, and gut microbiota were detected and subjected to repeated measures correlation analysis. RESULTS: VSG induced significant functional changes in the right putamen (PUT.R) and left supplementary motor area, both of which correlated with weight loss and TFEQ scores. Moreover, postprandial levels of active glucagon-like peptide-1 (aGLP-1) and Ghrelin were associated with ReHo of PUT.R; meanwhile, relative abundance of Clostridia increased by VSG was associated with improvements in aGLP-1 secretion, PUT.R activity, and weight loss. Importantly, VSG normalized excessive functional connectivities with PUT.R, among which baseline connectivity between PUT.R and right orbitofrontal cortex was related to postoperative weight loss. CONCLUSION: VSG causes correlated alterations of gut-brain axis, including Clostridia, postprandial aGLP-1, PUT.R activity, and eating habits. Preoperative connectivity of PUT.R may represent a potential predictive marker of surgical outcome in patients with obesity.