Counteracting TGM2 by a Fibroin peptide ameliorated Adriamycin-induced nephropathy via regulation of lipid metabolism through PANX1-PPAR α/PANK1 pathway.

Peptide drug discovery for the treatment of chronic kidney disease (CKD) has attracted much attention in recent years due to the urge to find novel drugs and mechanisms to delay the progression of the disease. In this study, we identified a novel short peptide (named YR-7, primary sequence 'YEVEDYR') from the natural Fibroin protein, and demonstrated that it significantly alleviated pathological renal changes in ADR-induced nephropathy. PANX1 was identified as the most notably upregulated component by RNA-sequencing. Further analysis showed that YR-7 alleviated the accumulation of lipid droplets via regulation of the lipid metabolism-related proteins PPAR α and PANK1. Using chemical proteomics, fluorescence polarization, microscale thermophoresis, surface plasmon resonance, and molecular docking, YR-7 was proven to directly bind to ß-barrel domains of TGM2 protein to inhibit lipid accumulation. TGM2 knockdown in vivo increased the protein levels of PPAR α and PANK1 while decreased the levels of fibrotic-related proteins to alleviate nephropathy. In vitro, overexpression TGM2 reversed the protective effects of YR-7. Co-immunoprecipitation indicated that TGM2 interacted with PANX1 to promote lipid deposition, and pharmacological inhibition or knockdown of PANX1 decreased the levels of PPAR α and PANK1 induced by ADR. Taken together, our findings revealed that TGM2-PANX1 interaction in promoting lipid deposition may be a new signaling in promoting ADR-induced nephropathy. And a novel natural peptide could ameliorate renal fibrosis through TGM2-PANX1-PPAR α/PANK1 pathway, which highlight the potential of it in the treatment of CKD.

Unraveling the mechanisms of NK cell dysfunction in aging and Alzheimer's disease: insights from GWAS and single-cell transcriptomics.

Background: Aging is an important factor in the development of Alzheimer's disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD. Methods: The study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes. Results: A correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD. Conclusion: We explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.

Suppression of Drosophila antifungal immunity by a parasite effector via blocking GNBP3 and GNBP-like 3, the dual receptors for ß-glucans.

The tactics used by animal pathogens to combat host immunity are largely unclear. Here, we report the depiction of the virulence-required effector Tge1 deployed by the entomopathogen Metarhizium robertsii to suppress Drosophila antifungal immunity. Tge1 can target both GNBP3 and GNBP-like 3 (GL3), and the latter can bind to ß-glucans like GNBP3, whereas the glucan binding by both receptors can be attenuated by Tge1. As opposed to the surveillance GNBP3, GL3 is inducible in Drosophila depending on the Toll pathway via a positive feedback loop mechanism. Losses of GNBP3 and GL3 genes result in the deregulations of protease cascade, Spätzle maturation, and antimicrobial gene expressions in Drosophila upon fungal challenges. Fly survival assays confirm that GL3 plays a more essential role than GNBP3 in combating fungal infections. In addition to evidencing the gene-for-gene interactions between fungi and insects, our data advance insights into Drosophila antifungal immunity.

Developing a universal and reliable temporomandibular joint reference system for quantifying morphological and positional changes.

OBJECTIVES: This study aimed to provide a universal and reliable reference system quantifying temporomandibular joint (TMJ) morphological and positional changes. METHODS: Large field-of-view (FOV) cone-beam computed tomography (CBCT) images (20 TMJs) from 10 preorthognathic surgery patients and limited FOV CBCT images (40 TMJs) from 20 splint therapy-treated patients with temporomandibular disorders were collected. TMJ-specific reference system including a TMJ horizontal reference plane (TMJHP) and a local coordinate system (TMJCS) was constructed with landmarks on cranial base. Its application for TMJ measurements and its spatial relationship to common Frankfort horizontal plane (FHP) and maxillofacial coordinate system (MFCS) were evaluated. RESULTS: Five relevant landmarks were selected to optimally construct TMJ-specific reference system. General parallelism between TMJHP and FHP was demonstrated by minimal angular and constant distance deviation (1.714 ±â€…0.811º; 2.925 ±â€…0.817 mm). Additionally, tiny axial orientational deviations (0.181 ±â€…6.805º) suggested TMJCS rivaled MFCS. Moreover, small deviations in orientations and distances (1.232 ±â€…0.609º; 0.310 ±â€…0.202 mm) indicated considerable reliability for TMJCS construction, with intraclass correlation coefficients (ICCs) ranging from 0.999 to 1.000. Lastly, slight discrepancies in translations and rotations revealed high reliability for condylar positional and morphological measurements (ICC, 0.918-0.999). LIMITATIONS: TMJ-specific reference system was merely tested in two representative FOVs. CONCLUSIONS: This study provides a universal and reliable reference system for TMJ assessment that is applicable to both limited and large FOV CBCT. It would improve comparability among diverse studies and enable comprehensive evaluations of TMJ positional and morphological changes during TMJ-related treatment follow-up such as splint therapy and disease progression.

The Effects of Radix isatidis Raw Material on Egg Quality, Serum Biochemistry, Gut Morphology and Gut Flora.

China produces more than 30 million tons of drug residues every year. Therefore, innovative solutions are needed to mitigate environmental damage. Certain plant compounds boost hens' health and performance. Radix isatidis is promising for layer production. This study elucidates the multidimensional impact of Radix isatidis residual material (RIHR) on laying hens, focusing on the egg quality, intestinal health and the microbial landscape. A total of 288 55-week-old Peking powder laying hens with similar laying rates and body weights were randomly divided into four groups, with eight replicates per group and nine hens per replicate. The groups were divided into a control group, an RIHR low-dose group, a medium-dose group and a high-dose group according to a single-factor, completely randomized design. For the three RIHR treatment groups, the added amounts were 5 kg/t, 10 kg/t and 15 kg/t, respectively. Liquid chromatography- mass spectrometry (LC-MS), molecular docking, fluorescence quantitative PCR and other methods were used. The results showed that three main anti-inflammatory and antiviral compounds were identified in RIHR-indirubin (0.21 µg/g), deoxyvasicinone (0.18 µg/g) and epigoitrin (0.39 µg/g). RIHR significantly increased the eggshell thickness, Haugh unit and protein height (p < 0.05). It also had significant antioxidant and anti-inflammatory effects on ilea and ceca (p < 0.05). The microbial analysis demonstrated that RIHR supplementation led to a significant reduction in foregut Lactobacillus levels (p < 0.05). In the hindgut, a significant increase in pathogenic bacteria was observed (p < 0.05). The study concludes that RIHR's anti-inflammatory compounds may directly act on the intestinal tract to modulate inflammation, highlighting its potential for targeted interventions in poultry health and nutrition.

The Lnc-HOTAIR/miR122/PPARγ signaling mediated the occurrence and continuous development of alcohol-induced Osteonecrosis of the femoral head.

This study aimed to explore the mechanism of alcohol-induced Osteonecrosis of the femoral head (ONFH) through in vivo and in vitro experiments. In vitro, the Oil Red O staining showed that ethanol promoted extracellular adipogenesis in a dose-dependent manner. ALP staining and alizarin red staining showed that ethanol inhibited the formation of extracellular mineralization in a dose-dependent manner. The Oil Red O staining showed that miR122 mimics and Lnc-HOTAIR SiRNA rescued extracellular adipogenesis induced by ethanol in BMSCs. Besides, we found that the high expression of PPARγ in BMSCs recruited histone deacetylase 3 (HDAC3) and histone methyltransferase (SUV39H1), which reduced the histone acetylation level and increased the histone methylation level in the miR122 promoter region, respectively. In vivo, the levels of H3K9ac, H3K14ac, and H3K27ac of miR122 promoter region in the ethanol group were significantly decreased compared to the control group, respectively. The levels of H3K9me2 and H3K9me3 of miR122 promoter region in the ethanol group were significantly increased compared to the control group. Lnc-HOTAIR/miR-122/PPARγ signaling mediated the alcohol-induced ONFH in the rat model. Furthermore, the persistent decrease of miR122 expression mediated the continuous progress of alcohol-induced ONFH after stopping alcohol consumption.

Sensing of a spore surface protein by a Drosophila chemosensory protein induces behavioral defense against fungal parasitic infections.

In addition to innate immunity in a physiological context, insects have evolved behavioral defenses against parasite attacks. Here, we report that Drosophila can sense the CFEM (common in fungal extracellular membrane) protein Mcdc9, which acts as a negative virulence factor of the entomopathogenic fungus Metarhizium robertsii. The individual deletions of 18 CFEM genes in Metarhizium followed by fly infection identified three null mutants that could kill the flies more quickly than the wild-type strain, among which Mcdc9 can coat fungal spores and interact with the fly chemosensory protein CheA75a. The deletion of Mcdc9 in the fungus or the knockdown of CheA75a in flies had a similar effect, in which a greater number of fungal spores were left on flies than on the respective controls after topical infection. Thus, similar to the accelerated death of the wild-type flies treated with ΔMcdc9, the CheA75aRNAi flies succumbed more quickly than the control insects topically challenged with the wild-type strain. The CheA75a gene is highly transcribed in fly legs and wings, and positive electrophysiological responses were evidenced in tarsal sensilla after stimulation with the Mcdc9 protein. The results imply that this CFEM protein could be sensed as a contact elicitor inducing the hygienic behavior of flies against fungal parasitic infection, which reveals a previously unsuspected mechanism of fungus-insect interactions.

Prevalence of Oral Exostoses in Northern China During the Past Six Millennia-From a Sex and Age Perspective.

This study is intended to investigate oral exostoses of 5 sample populations, spanning over 6000 years, from the same region of Northern China, to determine the significance of sex and age on the development of oral exostoses during each time period. The samples analyzed were 306 dry jaws from human skeletons, which were excavated from 4 archeological sites: Banpo (6700-5600 y BP), Shaolingyuan (3000 y BP), Shanren (2200 y BP), and Chang'an (1000-1300 y BP), as well as the modern Xi'an district. The sex and the age of the samples at death were estimated. The degree of buccal exostosis (BE), torus mandibularis (TM), and torus palatinus (TP) and the TP shape were recorded. The results showed BEs in the Banpo and Chang'an regions, TMs in the Banpo region were more often diagnosed in males than in females. Conversely, females in Shaolingyuan showed a higher prevalence and severity of TM than that in males. The occurrence of BEs in the Shanren and Xi'an regions, TMs in the Banpo, Chang'an, and Xi'an regions, as well as TPs in the Banpo region significantly increased with age at death. In conclusion, sex differences and increasing trends with age in relation to oral exostoses were found in samples from Northern China during the past six millennia.

Precise Design and Deliberate Tuning of Turn-On Fluorescence in Tetraphenylpyrazine-Based Metal-Organic Frameworks.

The manipulation on turn-on fluorescence in solid state materials attracts increasing interests owing to their widespread applications. Herein we report how the nonradiative pathways of tetraphenylpyrazine (TPP) units in metal-organic frameworks (MOFs) systems could be hindered through a topological design approach. Two MOFs single crystals of different topology were constructed via the solvothermal reaction of a TPP-based 4,4',4″,4‴-(pyrazine-2,3,5,6-tetrayl) tetrabenzoic acid (H4TCPP) ligand and metal cations, and their mechanisms of formation have been explored. Compared with the innate low-frequency vibrational modes of flu net Tb-TCPP-1, such as phenyl ring torsions and pyrazine twists, Tb-TCPP-2 adopts a shp net, so the dihedral angle of pyrazine ring and phenyl arms is larger, and the center pyrazine ring in TPP unit is coplanar, which hinders the radiationless decay of TPP moieties in Tb-TCPP-2. Thereby Tb-TCPP-2 exhibits a larger blue-shifted fluorescence and a higher fluorescence quantum yield than Tb-TCPP-1, which is consistent with the reduced nonradiative pathways. Furthermore, Density functional theory (DFT) studies also confirmed aforementioned tunable turn-on fluorescence mechanism. Our work constructed TPP-type MOFs based on a deliberately topological design approach, and the precise design of turn-on fluorescence holds promise as a strategy for controlling nonradiative pathways.

Significance of circRNAs as biomarkers for systemic lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: To comprehensively evaluate the significance of circular RNAs (circRNAs) as potential diagnostic biomarkers for systemic lupus erythematosus (SLE) via pooled analyses of data from published studies that focussed on the association between circRNAs and SLE. METHODS: The systematic review and meta-analysis protocol was registered in PROSPERO (registration No. CRD42021229383). Relevant studies published before 3 April 2022 were selected to verify the relationship between circRNA expression levels and SLE. Extracted data were analysed using a random-effects model with Meta-DiSc 1.4 and Stata 16 software. Transcription factors related to hsa_circ_0000479 and its parental gene were extracted from the TRCirc and hTFtarget databases, respectively. RESULTS: A total of 10 studies, involving 438 patients with SLE and 434 controls, were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio of circRNAs in detecting SLE were 0.66 (95% confidence interval [CI] 0.63, 0.70), 0.79 (95% CI 0.76, 0.82), and 10.80 (95% CI 6.58, 17.73), respectively. The area under the summary receiver operating characteristic curve was 0.8366. CONCLUSIONS: Meta-analysis of pooled data indicated a moderate accuracy of circRNAs in diagnosing SLE. The exact diagnostic value of circRNAs and the mechanisms of interaction between circRNAs and their parental genes should be confirmed in further studies.

Activating AhR alleviates cognitive deficits of Alzheimer's disease model mice by upregulating endogenous Aß catabolic enzyme Neprilysin.

Rationale: Neprilysin (NEP) is a major endogenous catabolic enzyme of amyloid ß (Aß). Previous studies have suggested that increasing NEP expression in animal models of Alzheimer's disease had an ameliorative effect. However, the underlying signaling pathway that regulates NEP expression remains unclear. The aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor. Recent studies have shown that AhR plays essential roles in the central nervous system (CNS), but its physiological and pathological roles in regulating NEP are not entirely known. Methods: Western blotting, immunofluorescence, quantitative RT-PCR and enzyme activity assay were used to verify the effects of AhR agonists on NEP in a cell model (N2a) and a mouse model (APP/PS1). Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were conducted to investigate the roles of AhR in regulating NEP transcription. Object recognition test and the Morris water maze task were performed to assess the cognitive capacity of the mice. Results: Activating AhR by the endogenous ligand L-Kynurenine (L-KN) or FICZ, or by the exogenous ligand diosmin or indole-3-carbinol (I3C) significantly increases NEP expression and enzyme activity in N2a cells and APP/PS1 mice. We also found that AhR is a direct transcription factor of NEP. Diosmin treatment effectively ameliorated the cognitive disorder and memory deficit of APP/PS1 transgenic mice. By knocking down AhR or using a small molecular inhibitor targeting AhR or NEP, we found that diosmin enhanced Aß degradation through activated AhR and increased NEP expression. Conclusions: These results indicate a novel pathway for regulating NEP expression in neurons and that AhR may be a potential therapeutic target for the treatment of Alzheimer's disease.

Vaspin regulated cartilage cholesterol metabolism through miR155/LXRα and participated in the occurrence of osteoarthritis in rats.

AIMS: This study intends to explore the role of Vaspin and cholesterol metabolism in the process of osteoarthritis (OA) and its mechanism in vitro and in vivo. MAIN METHODS: In vitro, chondrocytes were treated with interleukin-1ß (IL-1ß, 20 ng/mL) in combination with Vaspin at different concentrations for 48 h. The expressions of Aggrecan (ACAN), Collagen 2a1 (Col2a1), A Disintegrin And Metalloproteinase with Thrombo Spondin type 1 motifs 5 (ADAMTS 5), and Matrix metalloproteinase 13 (MMP13) were detected. In vivo, the expression of liver X receptor (LXRα) and other Cholesterol efflux related genes were detected in the rat OA knee cartilage-induced by papain. KEY FINDINGS: In vitro, in a concentration-dependent manner, Vaspin reversed the decreased expression of ACAN and Col2a1, and the increased expression of ADAMTS 5 and MMP13 caused by IL-1ß. Besides, Vaspin promoted the expression of LXRα and other Cholesterol efflux related genes in a concentration-dependent manner in chondrocytes. However, miR155 mimics reversed the Vaspin-induced expression changes of cholesterol efflux pathway in chondrocytes. In vivo, the expression of LXRα and other Cholesterol efflux related genes were decreased in the rat OA knee cartilage-induced by papain. Besides, the level of Vaspin was reduced and the miroRNA155 (miR155) expression was increased in OA knee cartilage of rats. SIGNIFICANCE: In conclusion, the decreased expression of Vaspin inhibited the expression of Cholesterol efflux pathway via miR155/LXRα. Finally, the inhibited Cholesterol efflux pathway led to the cholesterol accumulation and OA in cartilage.

Effect of Lignin Content on Properties of Flexible Transparent Poplar Veneer Fabricated by Impregnation with Epoxy Resin.

In this work, poplar veneer (PV) rotary-cut from fast-growing polar was delignified to prepare flexible transparent poplar veneer (TPV). Lignin was gradually removed from the PV and then epoxy resin filled into the delignified PV. The study mainly concerns the effect of lignin content on microstructure, light transmittance, haze, tensile strength, and thermal stability of the PVs impregnated with epoxy resin. The results indicate that the lignin could be removed completely from the PV when the delignification time was around 8 h, which was proved by FTIR spectra and chemical component detection. Moreover, according to SEM observation and XRD testing, the porosity and crystallinity of the PVs were gradually increased with the removal of lignin. Also, the optical properties measurement indicated that the light transmittance and haze of the TPVs gradually increased, and the thermal stability also became more stable as shown by thermogravimetric analysis (TG). However, the tensile strength of the TPVs declined due to the removal of lignin. Among them, TPV8 exhibited excellent optical properties, thermal stability, and tensile strength. Consequently, it has great potential to be used as a substrate in photovoltaics, solar cells, smart windows, etc.

Fabrication and Performance of Self-Supported Flexible Cellulose Nanofibrils/Reduced Graphene Oxide Supercapacitor Electrode Materials.

With the rapid development of portable and wearable electronic devices, self-supporting flexible supercapacitors have attracted much attention, and higher requirements have been put forward for the electrode of the device, that is, it is necessary to have good mechanical properties while satisfying excellent electrochemical performance. In this work, a facile method was invented to obtain excellent self-supported flexible electrode materials with high mechanical properties and outstanding electrochemical performance by combining cellulose nanofibrils (CNFs) and reduced graphene oxide (RGO). We focused on the effect of the ratio of the addition of CNFs and the formation process of the film on the electrochemical and mechanical properties. The results show that the CNFs/RGO12 (where the ratio of CNFs to GO is 1:2) film displayed outstanding comprehensive properties; its tensile strength and conductivity were up to 83 MPa and 202.94 S/m, respectively, and its CA value was as high as 146 mF cm-2 under the current density of 5 mA cm-2. Furthermore, the initial retention rate of the specific capacitance was about 83.7% when recycled 2000 times; moreover, its capacitance did not change much after perpendicular bending 200 times. Therefore, the films prepared by this study have great potential in the field of flexible supercapacitors.

A M35 family metalloprotease is required for fungal virulence against insects by inactivating host prophenoloxidases and beyond.

A diverse family of metalloproteases (MPs) is distributed in eukaryotes. However, the functions of MPs are still understudied. We report that seven MPs belonging to the M35 family are encoded in the genome of the insect pathogenic fungus Metarhizium robertsii. By gene deletions and insect bioassays, we found that one of the M35-family MPs, i.e. MrM35-4, is required for fungal virulence against insect hosts. MrM35-4 is a secretable enzyme and shows a proteolytic activity implicated in facilitating fungal penetration of insect cuticles. After gene rescue and overexpression, insect bioassays indicated that MrM35-4 contributes to inhibiting insect cuticular and hemocyte melanization activities. Enzymatic cleavage assays revealed that the recombinant prophenoloxidases PPO1 and PPO2 of Drosophila melanogaster could be clipped by MrM35-4 in a manner differing from a serine protease that can activate PPO activities. In addition, it was found that MrM35-4 is involved in suppressing antifungal gene expression in insects. Consistent with the evident apoptogenic effect of MrM35-4 on host cells, we found that the PPO mutant flies differentially succumbed to the infections of the wild-type and mutant strains of M. robertsii. Thus, MrM35-4 plays a multifaceted role beyond targeting PPOs during fungus-insect interactions, which represents a previously unsuspected strategy employed by Metarhizium to outmaneuver insect immune defenses.

Enhancing Oxygen Evolution Reaction through Modulating Electronic Structure of Trimetallic Electrocatalysts Derived from Metal-Organic Frameworks.

The construction of efficient, durable, and non-noble metal electrocatalysts for oxygen evolution reaction (OER) is of great value but challenging. Herein, a facile method is developed to synthesize a series of trimetallic (W/Co/Fe) metal-organic frameworks (MOFs)-derived carbon nanoflakes (CNF) with various Fe content, and an Fe-dependent volcano-type plot can be drawn out for WCoFex -CNF. The optimized WCoFe0.3 -CNF (when the feed ratio of Fe/Co is 0.3) demonstrates superior electrocatalytic performance with a low overpotential of only 254 mV@10 mA cm-2 and excellent durability of 100 h. Further researches show that appropriate amount of iron doping can regulate the electronic structure, resulting in a favorable synergistic environment. This method may stimulate the exploration of electrocatalysts by utilizing MOFs as precursors while realizing electronic modulation by multimetal doping.

Modulating the Electronic Structure of Porous Nanocubes Derived from Trimetallic Metal-Organic Frameworks to Boost Oxygen Evolution Reaction Performance.

The preparation of noble metal-free catalysts for water splitting is the key to low-cost, sustainable hydrogen generation. Herein, through a pyrolysis-oxidation process, we prepared a series of Co-Fe-Ni trimetallic oxidized carbon nanocubes (Co1-X FeX Ni-OCNC) with a continuously changeable Co/Fe ratio (X=0, 0.1, 0.2, 0.5, 0.8, 0.9, 1). The Co1-X FeX Ni-OCNC shows a volcano-type oxygen evolution reaction (OER) activity. The optimized Co0.1 Fe0.9 Ni-OCNC achieves a low overpotential of 268 mV at 10 mA cm-2 with a very low Tafel slope of 48 mV dec-1 in 1 m KOH. At the same time, the stability of the Co0.1 Fe0.9 Ni-OCNC is also outstanding; after 1000 CV cycles, the LSV plot is almost coincident. Moreover, the potential remains almost of the same value at 10 mA cm-2 after 12 h in comparison to the initial value. The excellent electrocatalytic properties can be attributed to the synergistic cooperation between each component. Therefore, the Co0.1 Fe0.9 Ni-OCNC is a promising candidate instead of precious metal-based electrocatalysts for OER.

Bimetallic Metal-Organic Framework-Derived Nanosheet-Assembled Nanoflower Electrocatalysts for Efficient Oxygen Evolution Reaction.

Non-noble metal-based metal-organic framework (MOF)-derived electrocatalysts have recently attracted great interest in the oxygen evolution reaction (OER). Here we report a facile synthesis of nickel-based bimetallic electrocatalysts derived from 2D nanosheet-assembled nanoflower-like MOFs. The optimized morphologies and large Brunauer-Emmett-Teller (BET) surface area endow FeNi@CNF with efficient OER performance, where the aligned nanosheets can expose abundant active sites and benefit electron transfer. The complex nanoflower morphologies together with the synergistic effects between two metals attributed to the OER activity of the Ni-based bimetallic catalysts. The optimized FeNi@CNF afforded an overpotential of 356 mV at a current density of 10 mA cm-2 with a Tafel slope of 62.6 mV dec-1 , and also exhibited superior durability with only slightly degradation after 24 hours of continuous operation. The results may inspire the use of complex nanosheet-assembled nanostructures to explore highly active catalysts for various applications.

The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway.

Trio, the Rho guanine nucleotide exchange factor (Rho-GEF), plays diverse roles in cell migration, cell axon guidance and cytoskeleton reorganization. Conserved during evolution, Trio encodes two guanine nucleotide exchange factor domains (GEFs) and activates small GTPases. The Rho-family small GTPases RhoA and Rac1, which are target molecules of Trio, have been described to engage in craniofacial development and tooth formation. However, the exact role of Trio in tooth development remains elusive. In this study, we generated Wnt1-cre;Triofl/fl mice to address the potential function of Trio in tooth development. Wnt1-cre;Triofl/fl mice showed short root deformity as well as decreased expression of odontogenic makers such as RUNX2, OSX, OCN, and OPN. In vitro, Trio was silenced in human stem cells of dental papilla (SCAPs). Compared with the control group, the proliferation and migration ability in the experimental group was disrupted. After knocking down Trio in SCAPs, the cells showed phenotypes of poor odontogenic differentiation and weak mineralized nodules. To study the underlying mechanism, we investigated the p38 MAPK pathway and found that loss of Trio blocked the cascade transduction of p38 MAPK signaling. In conclusion, we identified Trio as a novel coordinator in regulating root development and clarified its relevant molecular events.

Pax2 is essential for proliferation and osteogenic differentiation of mouse mesenchymal stem cells via Runx2.

Mesenchymal stem cells (MSCs) have been widely studied in the field of regenerative medicine with the potential to solve osteoporosis. Paired box 2 (Pax2), as a transcription factor, is the master regulator of embryogenesis and oncogenesis. However, the function of Pax2 in osteogenesis is unknown. Here, we reported for the first time that the expression of Pax2 gradually increased during osteogenic differentiation of mouse MSCs, and osteoprogenitor cells. However, detected in osteoblastic cells of mouse tibia, the expression of Pax2 in the embryonic stage was higher than that in adulthood. In C3H/10/T1/2 cells and compact bone-derived mouse MSCs (mMSCs), Pax2 knock-down inhibited the proliferation of these cells, down-regulated the expression of osteogenic marker genes, as well as repressed the ALP activity and mineralization. In addition, Pax2 enhanced the transcriptional activity of Runx2, and activated the MAPK pathway genes (ERK, JNK and p38). Furthermore, knock-down of Pax2 repressed the mMSCs-mediated bone regeneration in an ectopic bone formation model. In conclusion, Pax2 promotes osteogenesis of mouse MSCs, suggesting that Pax2 has a role in the pathophysiology of bone related diseases, and has potential application in bone tissue regeneration.