Preliminary study of the homeostatic regulation of osseointegration by nanotube topology.

The ideal implant surface plays a substantial role in maintaining bone homeostasis by simultaneously promoting osteoblast differentiation and limiting overactive osteoclast activity to a certain extent, which leads to satisfactory dynamic osseointegration. However, the rational search for implant materials with an ideal surface structure is challenging and a hot research topic in the field of tissue engineering. In this study, we constructed titanium dioxide titanium nanotubes (TNTs) by anodic oxidation and found that this structure significantly promoted osteoblast differentiation and inhibited osteoclast formation and function while simultaneously inhibiting the total protein levels of proline-rich tyrosine kinase 2 (PYK2) and focal adhesion kinase (FAK). Knockdown of the PYK2 gene by siRNA significantly suppressed the number and osteoclastic differentiation activity of mouse bone marrow mononuclear cells (BMMs), while overexpression of PYK2 inhibited osteogenesis and increased osteoclastic activity. Surprisingly, we found for the first time that neither knockdown nor overexpression of the FAK gene alone caused changes in osteogenesis or osteoclastic function. More importantly, compared with deletion or overexpression of PYK2/FAK alone, coexpression or cosilencing of the two kinases accelerated the effects of TNTs on osteoclastic and osteogenic differentiation on the surface of cells. Furthermore, in vivo experiments revealed a significant increase in positiveexpression-PYK2 cells on the surface of TNTs, but no significant change in positiveexpression -FAK cells was observed. In summary, PYK2 is a key effector molecule by which osteoblasts sense nanotopological mechanical signals and maintain bone homeostasis around implants. These results provide a referable molecular mechanism for the future development and design of homeostasis-based regulatory implant biomaterials.

Fast and high-precision tracking technology for image-based closed-loop cascaded control system with a Risley prism and fast steering mirror.

The Risley prism's compact structure, dynamic responsiveness, and high tracking accuracy make it ideal for photoelectric image tracking. To realize fast and high-precision tracking of the target, we propose an image-based closed-loop tracking cascade control (IBCLTCR-F) system using a single image detector that integrates the Risley prism and fast steering mirror (FSM). Firstly, We propose a cascade control input-decoupling method (CCIDM) for the IBCLTCR-F system to solve the complex problem of coarse-fine control input decoupling in traditional single detector cascaded control systems. Moreover, the CCIDM method ensures that the FSM deflection angle is small and does not exceed its range during the fine tracking process, by using the Risley prism to compensate for the FSM deflection angle. Next, we design the image-based closed-loop tracking controllers of the Risley prism system and FSM system and analyze the stability of the IBCLTCR-F system. Finally, we track static and moving targets through experiments. The experimental results verify the feasibility of the IBCLTCR-F system, the effectiveness of the decoupling method, and the fast and high-precision tracking of the targets.

Identification of HIST1H2BH as the hub gene associated with multiple myeloma using integrated bioinformatics analysis.

OBJECTIVES: Identifying the specific biomarkers and molecular signatures of MM might provide novel evidence for MM prognosis and targeted therapy. METHODS: Bioinformatic analyses were performed through GEO and TCGA datasets. The differential expression of HIST1H2BH in MM sample was validated by the qRT-PCR. And the CCK-8 assay was performed to detect the proliferation activity of HIST1H2BH on MM cell lines. RESULTS: A total of 793 DEGs were identified between bone marrow plasma cells from newly diagnosed myeloma and normal donors in GSE6477. Among them, four vital genes (HIST1H2AC, HIST1H2BH, CCND1 and TCF7L2) modeling were constructed. The increased HIST1H2BH expression was correlated with worse survival of MM based on TCGA datasets. The transcriptional expression of HIST1H2BH was significantly up-regulated in primary MM patients. And knockdown HIST1H2BH decreased the proliferation of MM cell lines. CONCLUSIONS: We have identified up-regulated HIST1H2BH in MM patients associated with poor prognosis using integrated bioinformatical methods.

Exploring the regulated effects of solid-state fortified Jiuqu and liquid-state fortified agent on Chinese Baijiu brewing.

Zaopei is the direct source of Chinese liquor (Baijiu). Adding functional strains to Zaopei is a potential strategy to regulate Baijiu brewing, mainly including the two ways of solid-state fortified Jiuqu (SFJ) and liquid-state fortified agent (LFA). Here, to explore their regulated details, the response patterns of Zaopei microecosystem and the changes in the product features were comprehensively investigated. The results showed that SFJ more positively changed the physicochemical properties of Zaopei and improved its ester content, from 978.57 mg/kg to 1078.63 mg/kg over the fermentation of 30 days, while LFA decreased the content of esters, alcohols, and acids. Microbial analysis revealed that SFJ significantly increased Saccharomycopsis and Aspergillus from the start of fermentation and induced a positive interaction cluster driven by the added functional Paenibacillus, while LFA exhibited a community structure near that of the original microecosystem and led to a simpler network with the reduced microbial nodes and correlations. Metabolism analysis found that both SFJ and LFA weakened the flavor-producing metabolism by suppressing some key enzyme pathways, such as EC 3.2.1.51, EC 4.2.1.47, EC 1.1.1.27, EC 1.1.1.22, EC 1.5.1.10, EC 1.14.11.12. As a result, SFJ improved the raw liquor yield by 28.5 % and endowed the final product with a more fragrant aroma, mainly through ethyl (E)-cinnamate, ethyl isovalerate, ethyl phenacetate with the higher odor activity values, while LFA promoted the yield by 13.2 % and resulted in a purer and less intense aroma through the aroma-active ß-damascenone, ethyl heptoate, ethyl phenacetate. These results facilitated the regulated mechanism of SFJ and LFA on Baijiu brewing and indicated that the used functional strains in this study could be applicated in SFJ way for the further industrial-scale application.

The Effect of Co-Culture with Different Pichia kluyveri and Saccharomyces cerevisiae on Volatile Compound and Characteristic Fingerprints of Mulberry Wine.

In this study, changes in volatile compounds co-fermented by different Pichia kluyveri with Saccharomyces cerevisiae were analyzed using GC-IMS and compared with S. cerevisiae fermentation, to investigate the production of aroma in mulberry wine during the fermentation process. A total of 61 compounds were accurately identified, including 21 esters, 10 alcohols, 8 aldehydes, 6 ketones, and 19 other volatiles. Compared with the single strain fermentation (S. cerevisiae), the content of 2-methylpropyl acetate, allyl Isothiocyanate, ethyl crotonate, isobutyl propanoate, and butyl 2-methylbutanoate, co-fermentation groups (S. cerevisiae with different P. kluyveri) showed a significant decrease. Alcohols, aldehydes, ketones, and organic acid were lower in both the F(S-P1) and F(S-P2) groups than in the F(S) group throughout fermentation. The 2-methylpentanoic acid only was contained in the F(S) group. The co-fermentation with different P. kluyveri could also be well distinguished. The content of Benzaldehyde and 4-methylphenol in the F(S-P1) group was significantly lower than that in the F(S-P2) group. The PCA results revealed effective differentiation of mulberry wine fermented by different fermentation strains from GC-IMS. The result showed that P. kluyveri could establish a new flavor system for mulberry wine, which plays a crucial role in enhancing the flavor of fruit wine.

How does ultrasound-assisted ionic liquid treatment affect protein? A comprehensive review of their potential mechanisms, safety evaluation, and physicochemical and functional properties.

Proteins are essential to human health with enormous food applications. Despite their advantages, plant and animal proteins often exhibit limited molecular flexibility and poor solubility due to hydrogen bonds, hydrophobic interactions, and ionic interactions within their molecular structures. Thus, there is an urgent need to modify the rigid structure of proteins to enhance their stability and functional properties. Ultrasound-assisted ionic liquid (UA-IL) treatment for developing compound modification and producing proteins with excellent functional properties has received interest. However, no review specifically addresses the interactions between UA-ILs and proteins. Hence, this review focused on recent research advancements concerning the effects and potential reaction mechanisms of UA-ILs on the physicochemical properties (including particle size; primary, secondary, and tertiary structure; and surface morphology) as well as the functionality (such as solubility, emulsifying properties, and foaming ability) of proteins. Moreover, the safety evaluation of modified proteins was also discussed from various perspectives, such as acute and chronic toxicity, genotoxicity, cytotoxicity, and environmental and microbial toxicity. This review demonstrated that UA-IL treatment-induced protein structural changes significantly impact the functional characteristics of proteins. This treatment approach efficiently promotes protein structure stretching and spatial rearrangement through cavitation, thermal effects, and ionic interactions. As a result, the functional properties of modified proteins exhibited an obvious enhancement, thereby bringing more opportunities to utilize modified protein products in the food industry. Potential future directions for protein modification using UA-ILs were also proposed.

Instructive Synergistic Effect of Coordinating Phosphorus in Transition-Metal-Doped ß-Phosphorus Carbide Guiding the Design of High-Performance CO2RR Electrocatalysts.

Developing efficient electrocatalysts for the CO2 reduction reaction (CO2RR) is the key and difficult point to alleviate energy and climate issues. The synergistic catalytic effects between metal and nonmetal elements have gained attention for the design of the CO2RR electrocatalysts. The realization of this effect requires a suitable combination of metal and nonmetal elements, as well as the support of suitable substrates. Based on this, the transition-metal-doped ß-phosphorus carbide (TM-PC) (TM = 4d and 5d transition metals except Tc) catalysts are designed, and their structures, electronic properties, and CO2RR catalytic performances are studied in depth via first-principle calculations. The strong bonding ability and high reactivity brought by the moderate electronegativity and abundant electrons and orbitals of phosphorus are the key to the excellent catalytic performance of TM-PCs. Coordinating phosphorus atoms improve the catalyst activity in two ways: (1) regulating the electron transfer of the TM active site, and (2) acting as the active site and changing the reaction mechanism. With the participation of coordinating P atoms, the "relay" of active sites reduces the limiting potential values for the reduction from CO2 to CH4 catalyzed by Cr-PC and Mo-PC by 0.27 and 0.23 V, respectively, compared with pathways where only the TM atom is the active site, reaching -0.55 and -0.63 V, respectively. Regarding the coordinating P atom as the second active site, Cr-PC and Mo-PC can catalyze the production of CH3CH2OH at limiting potential values of -0.54 and -0.67 V, respectively. This study demonstrates the dramatic enhancement of catalytic activity caused by suitable nonmetal coordinating atoms such as P and provides a reference for the design of high-performance CO2RR electrocatalysts based on metal-nonmetal coordinating active centers.

Efficacy and toxicity of drugs targeting KRASG12C mutation in non-small cell lung cancer: a meta-analysis.

OBJECTIVE: To systematically analyze the efficacy and toxicity of drugs targeting KRASG12C mutation in non-small cell lung cancer (NSCLC). METHODS: The candidate studies were identified in PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases up to 1 June 2023. Data on efficacy, prognosis, and adverse events (AEs) were extracted and calculated by meta-analysis. RESULTS: Six eligible prospective studies were included in this meta-analysis, including 563 patients with advanced or metastatic NSCLC. For patients with NSCLC, the objective response rate (ORR) of drugs targeting KRASG12C mutation was 37% (95%CI 31-43), median duration of response (DOR) was 8.89 months (95%CI 7.96-9.83), and median progression-free survival (PFS) was 6.40 months (95%CI 5.86-6.93). The overall incidence of AEs was 88% (95%CI 79-96) and the incidence of grade ≥3 AEs was 44% (95%CI 24-64). The most common AEs were diarrhea, nausea, fatigue, and vomiting. The most common grade ≥3 AEs were Alaninetransaminase (ALT) or Aspartatetransaminase (AST) increased and diarrhea. CONCLUSION: Sotorasib, Adagrasib, and Garsorasib as the drugs of choice for patients with KRASG12C mutation NSCLC, have definite efficacy and acceptable safety, especially for patients with advanced or metastatic disease and within posterior line therapy.

EpiMCI: Predicting Multi-Way Chromatin Interactions from Epigenomic Signals.

The recently emerging high-throughput Pore-C (HiPore-C) can identify whole-genome high-order chromatin multi-way interactions with an ultra-high output, contributing to deciphering three-dimensional (3D) genome organization. However, it also brings new challenges to relevant data analysis. To alleviate this problem, we proposed the EpiMCI, a model for multi-way chromatin interaction prediction based on a hypergraph neural network with epigenomic signals as the input. The EpiMCI integrated separate hyperedge representations with coupling hyperedge information and obtained AUCs of 0.981 and 0.984 in the GM12878 and K562 datasets, respectively, which outperformed the current available method. Moreover, the EpiMCI can be applied to denoise the HiPore-C data and improve the data quality efficiently. Furthermore, the vertex embeddings extracted from the EpiMCI reflected the global chromatin architecture accurately. The principal component analysis suggested that it was well aligned with the activities of genomic regions at the chromatin compartment level. Taken together, the EpiMCI can accurately predict multi-way chromatin interactions and can be applied to studies relying on chromatin architecture.

Engineered Escherichia coli Consortia Function in a Programmable Pattern for Multiple Enzymatic Biosynthesis.

Coordinating microbial consortia to realize complex synthetic pathways is an area of great interest in the rapidly growing field of biomanufacturing. This work presents a programmable method for assembling living cells based on the surface display of affinity groups, enabling whole-cell catalysis with optimized catalytic efficiency through the rational arrangement of cell assemblies and enzymes. In the context of d-phenyllactic acid (d-PLA) synthesis, four enzymes were rationally arranged considering substrate channeling and protein expression levels. The production efficiencies of d-PLA catalyzed by engineered microbial consortia were 1.31- and 2.55-fold higher than those of biofilm and whole-cell catalysts, respectively. Notably, substrate channeling was identified between the coimmobilized rate-limiting enzymes, resulting in a 3.67-fold improvement in catalytic efficiency compared with hybrid catalysts (free enzymes coupled with whole-cell catalysts). The highest yield of d-PLA catalyzed by microbial consortia was 102.85 ± 3.39 mM with 140 mM benzaldehyde as the substrate. This study proposes a novel approach to cell enzyme assembly for coordinating microbial consortia in multiple enzymatic biosynthesis processes.

The active synergetic microbiota with Aspergillus as the core dominates the metabolic network of ester synthesis in medium-high temperature Daqu.

The active ester-synthesis microorganisms in medium-high temperature Daqu (MHT-Daqu) largely impact the strong-flavor Baijiu quality, while their actual composition and metabolic mechanism remain unclear. Here, to explore how the active microbiota contributes to MHT-Daqu ester biosynthesis, metatranscriptomic and metaproteomic analyses coupled with experimental verification were performed. The results showed that the MHT-Daqu microbiota with the higher ester-forming ability exhibited a more active dynamic alteration from transcription to translation. The genera Aspergillus, Bacillus, Leuconostoc, and Pediococcus could transcribe and translate obviously more ester-forming enzymes. In the ester-synthesis metabolic network, the synergetic microbiota confirmed by interaction analysis, containing Eurotiales, Bacillales, and Saccharomycetales, played an essential role, in which the Eurotiales and its representative genus Aspergillus contributed the highest transcript and protein abundance in almost every metabolic process, respectively. The recombined fermentation verified that their corresponding genera could produce the ester and precursor profiles very close to that of the original MHT-Daqu active microbiota, while the microbiota without Aspergillus caused a polar separation. These results indicated that the synergetic microbiota with Aspergillus as the core dominated the metabolic network of ester synthesis in MHT-Daqu. Our study provides a detailed framework of the association between the active synergetic microbiota and ester synthesis in MHT-Daqu.

Transition metals anchored on two-dimensional p-BN support with center-coordination scaling relationship descriptor for spontaneous visible-light-driven photocatalytic nitrogen reduction.

Solar energy has the potential to revolutionize the production of ammonia, as it could provide a reliable and uninterrupted source of energy for the chemical reaction involved. However, improving the catalytic performance of catalysts often leads to a reduction in their band gaps, which results in insufficient photogenerated electron potential to realize the nitrogen reduction reaction (NRR), and thus the development of NRR efficient photocatalysts remains a great challenge. Herein, based on the density functional theory (DFT), a series of single-atom photocatalysts with transition metals (TMs) doped on porous boron nitride (p-BN) nanosheet are proposed for NRR. Among them, Re-B3@p-BN could effectively catalyze gas-phase N2 through the corresponding pathways with limiting potentials of 0.31 V. Meanwhile, it exhibits excellent light absorption efficiency under illumination and could spontaneously catalyse nitrogen fixation reactions due to the suitable forbidden band and high photogenerated electron potential. Moreover, a linear relationship descriptor based on the intrinsic properties has been established, using a machine learning approach by considering the combined effects of the central metal atom and the coordination atoms. This descriptor could help accelerate the development of rational and improved 2D NRR photocatalysts with high catalytic activity and high selectivity.

Effects of six commercially available koji (Chinese Xiaoqu) on the production of ethyl acetate, ethyl lactate, and higher alcohols in Chinese Baijiu (distilled spirit) brewing.

Commercial koji has been increasingly used in Chinese Baijiu brewing; however, there are only few studies comparing different koji and their relationship with key components of Chinese Baijiu such as ethyl acetate, ethyl lactate, and higher alcohols. Here, we studied six commercially available koji and showed that the microbial communities in the individual koji varied in composition, with Rhizopus, Aspergillus, and Bacillus primarily associated with starch hydrolysis and Saccharomyces mainly associated with alcohol production. In the brewing processes using the six koji, Saccharomyces was undoubtedly the most abundant fungus and Weissella, Bacillus, and Acinetobacter were the predominant bacterial groups. The levels of ethyl acetate, ethyl lactate, and higher alcohols in all brewing processes using the koji exhibited rapid increase in the early stages of fermentation, which stabilized in the later stages, followed by substantial increase after distillation. The results of metagenomic and redundancy analyses of samples taken during the brewing processes indicated that Saccharomyces from the koji was closely related to the production of ethyl acetate, ethyl lactate, and higher alcohols. This study provides a basis for the quality improvement and application of commercial koji.

Contrasting the microbial community and non-volatile metabolites involved in ester synthesis between Qing-flavor Daqu and Nong-flavor Daqu.

Daqu, a fermentation starter, was important source of key flavors of Chinese Baijiu. The quality of Chinese Baijiu could be significantly affected by the ester-synthesis microorganisms. In order to clarify the microbial community that promoted the ester formation in Daqu, the dynamic changes of microbial community and non-volatile profiles of Qing-flavor Daqu and Nong-flavor Daqu samples through the whole making process were investigated by Illumina MiSeq platform and liquid chromatograph-mass spectrometry (LC-MS). The non-volatile compounds related to ester synthesis were identified by comparing with ester synthesis pathway and partial least squares discriminant analysis (PLS-DA). Correlations between microbial community and non-volatile metabolites involved in ester synthesis of two types of Daqu were disclosed by Pearson correlation analysis. Results showed that a total of 50 key compounds involved in ester synthesis were identified and 25 primary functional microorganisms were screened in 39 samples. Among them, in Qing-flavor Daqu, the top three primary functional microorganisms that had strong correlations with ester-formation precursors were Lactobacillus, Pantoea, and Sphingomonas; Lactobacillus and Pantoea had significantly positive interactions with various microorganisms, but Sphingomonas did not interact with others. In Nong-flavor Daqu, the top three primary functional microorganisms that had strong correlations with ester-formation precursors were Candida, Apiotrichum, and Cutaneotrichosporon. Candida showed strong positive correlation with other microorganisms, whereas Apiotrichum and Cutaneotrichosporon had no interaction with other microorganisms. The study could help our understanding of the microbial metabolism process in Daqu and provided a scientific basis for a controllable and feasible fermentation system.

Long-term effect of Helicobacter pylori eradication on colorectal cancer incidences.

Background: There is evidence supporting the association between Helicobacter pylori infection and colorectal cancer (CRC), but whether H. pylori eradication reduces the risk of CRC is still unknown. Objectives: To compare the incidence of CRC in subjects who had received H. pylori eradication therapy with general population. Design: A population-based retrospective cohort study. Methods: This study included all H. pylori-infected subjects who had received their first course of clarithromycin-containing triple therapy in 2003-2015 in Hong Kong. We compared the observed incidences of CRC in this H. pylori eradicated cohort with the expected incidences in the age- and sex-matched general population. The standardized incidence ratio (SIR) with 95% confidence interval (CI) was computed. Results: Among 96,572 H. pylori-eradicated subjects with a median follow-up of 9.7 years, 1417 (1.5%) developed CRC. Primary analysis showed no significant difference in the observed and expected incidences of CRC (SIR: 1.03, 95% CI: 0.97-1.09). However, when stratified according to the follow-up period, higher incidence of CRC was only observed in the first 5 years after eradication (SIR: 1.47, 95% CI: 1.39-1.55), but it was lower (SIR: 0.85, 95% CI: 0.74-0.99) than general population after 11 years. When stratified by tumor location, the observed incidence was higher for colon (SIR: 1.20, 95% CI: 1.12-1.29) but lower for rectal cancer (SIR: 0.90, 95% CI: 0.81-0.999) among H. pylori-eradicated subjects. Conclusions: H. pylori-infected subjects appeared to have a higher incidence of CRC initially, which declined progressively to a level lower than general population 10 years after H. pylori eradication, particularly for rectal cancer.

Integrating metabolomics and metatranscriptomics to explore the formation pathway of aroma-active volatile phenolics and metabolic profile during industrial radish paocai fermentation.

The aroma profile of industrial Sichuan paocai is formed and regulated by complex physiological and biochemical reactions and microbial metabolism, but little is known so far. In this study, we comprehensively analyzed the changes of metabolic profile and gene expression profile, mainly explored the formation pathways of two skeleton aroma-active compounds, 4-ethylphenol and 4-ethylguaiacol, and verified the pathways at multiple levels. The results showed that a total of 136 volatile metabolites and 560 non-volatile metabolites were identified in the whole fermentation process. The types and concentrations of metabolites in paocai were higher than those in brine, and gradually converged with fermentation. Differential analysis of metabolism and transcription levels were both enriched in three pathways: amino acid metabolism, phenylpropanoid metabolism and lipid metabolism. Among them, 4-ethylphenol and 4-ethylguaiacol, the products of the phenylpropanoid metabolism, were converted from p-coumaric acid and ferulic acid in plant cell walls, respectively. Under the action of decarboxylase produced by yeast (such as Debaryomyces Hansenii) and lactic acid bacteria (such as Lactobacillus versmoldensis), intermediate metabolites vinylphenols were produced, and the intermediate metabolites further produce the final products under the action of vinylphenol reductase. The key gene copy number, enzyme activity, and metabolite concentration in the pathways were detected to provide stronger evidence for the formation pathways. This study provided meaningful new insights for the development of aroma-producing enzymes and further guidance for the flavor improvement of industrial paocai.

Promising application of a novel biomaterial, light chain of silk fibroin combined with NT3, in repairment of rat sciatic nerve defect injury.

Autologous nerve transplantation is the gold standard for treating peripheral nerve defects, but it is associated with defects such as insufficient donor and secondary injury. Artificial nerve guidance conduits (NGCs) are now considered promising alternatives for bridging long nerve gaps, although exploring new biomaterials to construct NGCs remains challenging. Silk fibroin (SF) has good biocompatibility and can self-assemble in aqueous solutions. However, the lack of proximal neurotrophic factors after nerve injury is a major concern, leading to incomplete nerve regeneration. In this study, NT-3, a neurotrophin that promotes neuronal survival and differentiation, was bound to the light chain of silk fibroin (FIBL) in two ways: one was directly bound to FIBL (FIBL-NT3) and the other was a polypeptides-linker (FIBL-Linker-NT3). The design aimed to take advantage of silk fiber's character of self-assembly of heavy-light chains and test whether a flexible linker with NT3 molecule is easy to be a NT3 dimer, the active form. In vitro studies indicated that FIBL-Linker-NT3 combined with SF membranes promoted axon growth in adult rat dorsal root ganglion (DRG) neurons. Then we tested if FIBL-Linker-NT3 could self-assemble with the SF heavy chain (SFH). DTT (Dithiothreitol) was used to break the disulfide bonds between the SF light and heavy chains, and the light-chain protein was removed via dialysis. SFH was assembled using FIBL-Linker-NT3, as evidenced by the western blotting results that showed a high molecular band corresponding to SFH-FIBL-Linker-NT3. Chitosan scaffolds have been identified to provide a suitable microenvironment, so a chitosan/SF-FIBL-Linker-NT3 conduit was also constructed. Nerve transplantation of this conduit was evaluated in vivo in a rat sciatic nerve defect model. Immunohistochemical assays showed that the chitosan/SF-FIBL-Linker-NT3 group was superior to the chitosan/PBS, SF, PBS + FIBL-Linker-NT3 groups in nerve regeneration. In addition, the chitosan/SF-FIBL-Linker-NT3 conduit-transplanted group exhibited better recovery in terms of neurite length, sciatic functional index value, sensitivity to heat, time on the rotarod, wet weight ratio, cross-sectional area, compound muscle action potential, number of myelin layers, and myelin thickness in the nerve. Taking together, our study identified that FIBL-Linker-NT3 could promote axonal growth and regeneration in vivo and in vitro and is a promising candidate biomaterial for artificial NGCs.

The effects of short-term dietary exposure to SiO2 nanoparticle on the domesticated lepidopteran insect model silkworm (Bombyx mori): Evidence from the perspective of multi-omics.

Silicon dioxide nanoparticles (nSiO2) are one of the widely utilized nanoparticle (NPSs) materials, and exposure to nSiO2 is ubiquitous. With the increasing commercialization of nSiO2, the potential risk of nSiO2 release to the health and the ecological environment have been attracted more attention. In this study, the domesticated lepidopteran insect model silkworm (Bombyx mori) was utilized to evaluate the biological effects of dietary exposure to nSiO2. Histological investigations showed that nSiO2 exposure resulted in midgut tissue injury in a dose-dependent manner. Larval body mass and cocoon production were reduced by nSiO2 exposure. ROS burst was not triggered, and the activities of antioxidant enzymes were induced in the midgut of silkworm exposure to nSiO2. RNA-sequencing revealed that the differentially expressed genes induced by nSiO2 exposure were predominantly enriched into xenobiotics biodegradation and metabolism, lipid, and amino acid metabolism pathways. 16 S rDNA sequencing revealed that nSiO2 exposure altered the microbial diversity in the gut of the silkworm. Metabolomics analysis showed that the combined uni- and multivariate analysis identified 28 significant differential metabolites from the OPLS-DA model. These significant differential metabolites were predominantly enriched into the metabolic pathways, including purine metabolism and tyrosine metabolism and so. Spearman correlation analysis and the Sankey diagram established the relationship between microbe and metabolites, and some genera may play crucial and pleiotropic functions in the interaction between microbiome and host. These findings indicated that nSiO2 exposure could impact the dysregulation of genes related to xenobiotics metabolism, gut dysbiosis, and metabolic pathways and provided a valuable reference for assessing nSiO2 toxicity from a multi-dimensional perspective.

The activation of gastric inhibitory peptide/gastric inhibitory peptide receptor axis via sonic hedgehog signaling promotes the bridging of gapped nerves in sciatic nerve injury.

Schwann cells play an essential role in peripheral nerve regeneration by generating a favorable microenvironment. Gastric inhibitory peptide/gastric inhibitory peptide receptor (GIP/GIPR) axis deficiency leads to failure of sciatic nerve repair. However, the underlying mechanism remains elusive. In this study, we surprisingly found that GIP treatment significantly enhances the migration of Schwann cells and the formation of Schwann cell cords during recovery from sciatic nerve injury in rats. We further revealed that GIP and GIPR levels in Schwann cells were low under normal conditions, and significantly increased after injury demonstrated by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Wound healing and Transwell assays showed that GIP stimulation and GIPR silencing could affect Schwann cell migration. In vitro and in vivo mechanistic studies based on interference experiment revealed that GIP/GIPR might promote mechanistic target of rapamycin complex 2 (mTORC2) activity, thus facilitating cell migration; Rap1 activation might be involved in this process. Finally, we retrieved the stimulatory factors responsible for GIPR induction after injury. The results indicate that sonic hedgehog (SHH) is a potential candidate whose expression increased upon injury. Luciferase and chromatin immunoprecipitation (ChIP) assays showed that Gli3, the target transcription factor of the SHH pathway, dramatically augmented GIPR expression. Additionally, in vivo inhibition of SHH could effectively reduce GIPR expression after sciatic nerve injury. Collectively, our study reveals the importance of GIP/GIPR signaling in Schwann cell migration, providing a therapeutic avenue toward peripheral nerve injury.