Enhancing osteogenesis and angiogenesis functions for Ti-24Nb-4Zr-8Sn scaffolds with methacrylated gelatin and deferoxamine.

Repair of large bone defects remains challenge for orthopedic clinical treatment. Porous titanium alloys have been widely fabricated by the additive manufacturing, which possess the elastic modulus close to that of human cortical bone, good osteoconductivity and osteointegration. However, insufficient bone regeneration and vascularization inside the porous titanium scaffolds severely limit their capability for repair of large-size bone defects. Therefore, it is crucially important to improve the osteogenic function and vascularization of the titanium scaffolds. Herein, methacrylated gelatin (GelMA) were incorporated with the porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds prepared by the electron beam melting (EBM) method (Ti2448-GelMA). Besides, the deferoxamine (DFO) as an angiogenic agent was doped into the Ti2448-GelMA scaffold (Ti2448-GelMA/DFO), in order to promote vascularization. The results indicate that GelMA can fully infiltrate into the pores of Ti2448 scaffolds with porous cross-linked network (average pore size: 120.2 ± 25.1 µm). Ti2448-GelMA scaffolds facilitated the differentiation of MC3T3-E1 cells by promoting the ALP expression and mineralization, with the amount of calcium contents ∼2.5 times at day 14, compared with the Ti2448 scaffolds. Impressively, the number of vascular meshes for the Ti2448-GelMA/DFO group (∼7.2/mm2) was significantly higher than the control group (∼5.3/mm2) after cultivation for 9 h, demonstrating the excellent angiogenesis ability. The Ti2448-GelMA/DFO scaffolds also exhibited sustained release of DFO, with a cumulative release of 82.3% after 28 days. Therefore, Ti2448-GelMA/DFO scaffolds likely provide a new strategy to improve the osteogenesis and angiogenesis for repair of large bone defects.

Allosteric regulation of nitrate transporter NRT via the signaling protein PII.

Coordinated carbon and nitrogen metabolism is crucial for bacteria living in the fluctuating environments. Intracellular carbon and nitrogen homeostasis is maintained by a sophisticated network, in which the widespread signaling protein PII acts as a major regulatory hub. In cyanobacteria, PII was proposed to regulate the nitrate uptake by an ABC (ATP-binding cassette)-type nitrate transporter NrtABCD, in which the nucleotide-binding domain of NrtC is fused with a C-terminal regulatory domain (CRD). Here, we solved three cryoelectron microscopy structures of NrtBCD, bound to nitrate, ATP, and PII, respectively. Structural and biochemical analyses enable us to identify the key residues that form a hydrophobic and a hydrophilic cavity along the substrate translocation channel. The core structure of PII, but not the canonical T-loop, binds to NrtC and stabilizes the CRD, making it visible in the complex structure, narrows the substrate translocation channel in NrtB, and ultimately locks NrtBCD at an inhibited inward-facing conformation. Based on these results and previous reports, we propose a putative transport cycle driven by NrtABCD, which is allosterically inhibited by PII in response to the cellular level of 2-oxoglutarate. Our findings provide a distinct regulatory mechanism of ABC transporter via asymmetrically binding to a signaling protein.

An Ultralow-concentration and Moisture-resistant Electrolyte of Lithium Difluoro(oxalato)borate in Carbonate Solvents for Stable Cycling in Practical Lithium-ion Batteries.

The electrolyte concentration not only impacts the battery performance but also affects the battery cost and manufacturing. Currently, most studies focus on high-concentration (>3 M) or localized high-concentration electrolytes (~1 M); however, the expensive lithium salt imposes a major concern. Most recently, ultralow concentration electrolytes (<0.3 M) have emerged as intriguing alternatives for battery applications, which feature low cost, low viscosity, and extreme-temperature operation. However, at such an early development stage, many works are urgently needed to further understand the electrolyte properties. Herein, we introduce an ultralow concentration electrolyte of 2 wt % (0.16 M) lithium difluoro(oxalato)borate (LiDFOB) in standard carbonate solvents. This electrolyte exhibits a record-low salt/solvent mass ratio reported to date, thus pointing to a superior low cost. Furthermore, this electrolyte is highly compatible with commercial Li-ion materials, forming stable and inorganic-rich interphases on the lithium cobalt oxide (LiCoO2) cathode and graphite anode. Consequently, the LiCoO2-graphite full cell demonstrates excellent cycling performance. Besides, this electrolyte is moisture-resistant and effectively suppresses the generation of hydrogen fluoride, which will markedly facilitate the battery assembly and recycling process under ambient conditions.

Transport mechanism of human bilirubin transporter ABCC2 tuned by the inter-module regulatory domain.

Bilirubin is mainly generated from the breakdown of heme when red blood cells reach the end of their lifespan. Accumulation of bilirubin in human body usually leads to various disorders, including jaundice and liver disease. Bilirubin is conjugated in hepatocytes and excreted to bile duct via the ATP-binding cassette transporter ABCC2, dysfunction of which would lead to Dubin-Johnson syndrome. Here we determine the structures of ABCC2 in the apo, substrate-bound and ATP/ADP-bound forms using the cryo-electron microscopy, exhibiting a full transporter with a regulatory (R) domain inserted between the two half modules. Combined with substrate-stimulated ATPase and transport activity assays, structural analysis enables us to figure out transport cycle of ABCC2 with the R domain adopting various conformations. At the rest state, the R domain binding to the translocation cavity functions as an affinity filter that allows the substrates of high affinity to be transported in priority. Upon substrate binding, the R domain is expelled from the cavity and docks to the lateral of transmembrane domain following ATP hydrolysis. Our findings provide structural insights into a transport mechanism of ABC transporters finely tuned by the R domain.

Synergistic Amelioration of Osseointegration and Osteoimmunomodulation with a Microarc Oxidation-Treated Three-Dimensionally Printed Ti-24Nb-4Zr-8Sn Scaffold via Surface Activity and Low Elastic Modulus.

Biomaterial scaffolds, including bone substitutes, have evolved from being primarily a biologically passive structural element to one in which material properties such as surface topography and chemistry actively direct bone regeneration by influencing stem cells and the immune microenvironment. Ti-6Al-4V(Ti6Al4V) implants, with a significantly higher elastic modulus than human bone, may lead to stress shielding, necessitating improved stability at the bone-titanium alloy implant interface. Ti-24Nb-4Zr-8Sn (Ti2448), a low elastic modulus ß-type titanium alloy devoid of potentially toxic elements, was utilized in this study. We employed 3D printing technology to fabricate a porous scaffold structure to further decrease the structural stiffness of the implant to approximate that of cancellous bone. Microarc oxidation (MAO) surface modification technology is then employed to create a microporous structure and a hydrophilic oxide ceramic layer on the surface and interior of the scaffold. In vitro studies demonstrated that MAO treatment enhances the proliferation, adhesion, and osteogenesis capabilities on the scaffold surface. The chemical composition of the MAO-Ti2448 oxide layer is found to enhance the transcription and expression of osteogenic genes in bone mesenchymal stem cells (BMSCs), potentially related to the enrichment of Nb2O5 and SnO2 in the oxide layer. The MAO-Ti2448 scaffold, with its synergistic surface activity and low stiffness, significantly activates the anti-inflammatory macrophage phenotype, creating an immune microenvironment that promotes the osteogenic differentiation of BMSCs. In vivo experiments in a rabbit model demonstrated a significant improvement in the quantity and quality of the newly formed bone trabeculae within the scaffold under the contact osteogenesis pattern with a matched elastic modulus. These trabeculae exhibit robust connections to the external structure of the scaffold, accelerating the formation of an interlocking structure between the bone and implant and providing higher implantation stability. These findings suggest that the MAO-Ti2448 scaffold has significant potential as a bone defect repair material by regulating osteoimmunomodulation and osteogenesis to enhance osseointegration. This study demonstrates an optional strategy that combines the mechanism of reducing the elastic modulus with surface modification treatment, thereby extending the application scope of ß-type titanium alloy.

Bilayer LDPC Codes Combined with Perturbed Decoding for MLC NAND Flash Memory.

This paper presents a coding scheme based on bilayer low-density parity-check (LDPC) codes for multi-level cell (MLC) NAND flash memory. The main feature of the proposed scheme is that it exploits the asymmetric properties of an MLC flash channel and stores the extra parity-check bits in the lower page, which are activated only after the decoding failure of the upper page. To further improve the performance of the error correction, a perturbation process based on the genetic algorithm (GA) is incorporated into the decoding process of the proposed coding scheme, which can convert uncorrectable read sequences into error-correctable regions of the corresponding decoding space by introducing GA-trained noises. The perturbation decoding process is particularly efficient at low program-and-erase (P/E) cycle regions. The simulation results suggest that the proposed bilayer LDPC coding scheme can extend the lifetime of MLC NAND flash memory up to 10,000 P/E cycles. The proposed scheme can achieve a better balance between performance and complexity than traditional single LDPC coding schemes. All of these findings indicate that the proposed coding scheme is suitable for practical purposes in MLC NAND flash memory.

Tandem Synergistic Effect of Cu-In Dual Sites Confined on the Edge of Monolayer CuInP2 S6 toward Selective Photoreduction of CO2 into Multi-Carbon Solar Fuels.

One-unit-cell, single-crystal, hexagonal CuInP2 S6 atomically thin sheets of≈0.81 nm in thickness was successfully synthesized for photocatalytic reduction of CO2 . Exciting ethene (C2 H4 ) as the main product was dominantly generated with the yield-based selectivity reaching ≈56.4 %, and the electron-based selectivity as high as ≈74.6 %. The tandem synergistic effect of charge-enriched Cu-In dual sites confined on the lateral edge of the CuInP2 S6 monolayer (ML) is mainly responsible for efficient conversion and high selectivity of the C2 H4 product as the basal surface site of the ML, exposing S atoms, can not derive the CO2 photoreduction due to the high energy barrier for the proton-coupled electron transfer of CO2 into *COOH. The marginal In site of the ML preeminently targets CO2 conversion to *CO under light illumination, and the *CO then migrates to the neighbor Cu sites for the subsequent C-C coupling reaction into C2 H4 with thermodynamic and kinetic feasibility. Moreover, ultrathin structure of the ML also allows to shorten the transfer distance of charge carriers from the interior onto the surface, thus inhibiting electron-hole recombination and enabling more electrons to survive and accumulate on the exposed active sites for CO2 reduction.

Synergistic effect of hierarchical topographic structure on 3D-printed Titanium scaffold for enhanced coupling of osteogenesis and angiogenesis.

The significance of the osteogenesis-angiogenesis relationship in the healing process of bone defects has been increasingly emphasized in recent academic research. Surface topography plays a crucial role in guiding cellular behaviors. Metal-organic framework (MOF) is an innovative biomaterial with nanoscale structural and topological features, enabling the modulation of scaffold physicochemical properties. This study involved the loading of varying quantities of UiO-66 nanocrystals onto alkali-heat treated 3D-printed titanium scaffolds, resulting in the formation of hierarchical micro/nano topography named UiO-66/AHTs. The physicochemical properties of these scaffolds were subsequently characterized. Furthermore, the impact of these scaffolds on the osteogenic potential of BMSCs, the angiogenic potential of HUVECs, and their intercellular communication were investigated. The findings of this study indicated that 1/2UiO-66/AHT outperformed other groups in terms of osteogenic and angiogenic induction, as well as in promoting intercellular crosstalk by enhancing paracrine effects. These results suggest a promising biomimetic hierarchical topography design that facilitates the coupling of osteogenesis and angiogenesis.

Placing steroid hormones within the human ABCC3 transporter reveals a compatible amphiphilic substrate-binding pocket.

The human ABC transporter ABCC3 (also known as MRP3) transports a wide spectrum of substrates, including endogenous metabolites and exogenous drugs. Accordingly, it participates in multiple physiological processes and is involved in diverse human diseases such as intrahepatic cholestasis of pregnancy, which is caused by the intracellular accumulation of bile acids and estrogens. Here, we report three cryogenic electron microscopy structures of ABCC3: in the apo-form and in complexed forms bound to either the conjugated sex hormones ß-estradiol 17-(ß-D-glucuronide) and dehydroepiandrosterone sulfate. For both hormones, the steroid nuclei that superimpose against each other occupy the hydrophobic center of the transport cavity, whereas the two conjugation groups are separated and fixed by the hydrophilic patches in two transmembrane domains. Structural analysis combined with site-directed mutagenesis and ATPase activity assays revealed that ABCC3 possesses an amphiphilic substrate-binding pocket able to hold either conjugated hormone in an asymmetric pattern. These data build on consensus features of the substrate-binding pocket of MRPs and provide a structural platform for the rational design of inhibitors.

Improving osteoinduction and osteogenesis of Ti6Al4V alloy porous scaffold by regulating the pore structure.

Titanium alloy scaffolds with a porous structure have attracted much attention in bone defect repair. However, which pore structure is more beneficial to bone defect repair is controversial. In the present research, the Ti6Al4V alloy porous scaffolds with gradient pore sizes were designed and fabricated. The microstructure characterization, tests of mechanical properties, and in vitro and in vivo experiments have been performed to systematically evaluate the effect of pore size on osteoinduction and osteogenesis. The results revealed that the contact angle with water, compressive strength, and elastic modulus of the Ti6Al4V alloy porous scaffolds decreased gradually with the increase of pore size. However, there were obvious drops when the pore size of the porous scaffold was around 600 µm. As the pore size increased, the proliferation and integrin ß1 of RAW 264.7 macrophages seeded on Ti6Al4V alloy porous scaffolds increased at first, reaching a maximum value at a pore size of around 600 µm, and then decreased subsequently. The proliferation, integrin ß1, and osteogenic gene-related expressions of Bone marrow mesenchymal stem cells (BMSCs) seeded on Ti6Al4V alloy porous scaffolds with different pore sizes all exhibited similar variations which rose with increased pore size firstly, obtaining the maximum value at pore size about 600 µm, and then declined. The in vivo experiments confirmed the in vitro results, and the Ti6Al4V alloy porous scaffold with a pore size of 600 µm possessed the better capability to induce new bone formation. Therefore, for the design of Ti6Al4V alloy with a regular porous scaffold, the surface morphology, porosity, strength, and elastic modulus should be considered systematically, which would determine the capability of osteoinduction and osteogenesis.

Repetitive transcranial magnetic stimulation enhances the neuronal excitability of mice by regulating dynamic characteristics of Granule cells' Ion channels.

This study aims to explore the effects of acute high-frequency repetitive transcranial magnetic stimulation (hf-rTMS) on neuronal excitability of granule cells in the hippocampal dentate gyrus, as well as the underlying intrinsic mediating mechanisms by which rTMS regulates neuronal excitability. First, high-frequency single TMS was used to measure the motor threshold (MT) of mice. Then, rTMS with different intensities of 0 MT (control), 0.8 MT, and 1.2 MT were applied to acute mice brain slices. Next, patch-clamp technique was used to record the resting membrane potential and evoked nerve discharge of granule cells, as well as the voltage-gated sodium current (I Na) of voltage-gated sodium channels (VGSCs), transient outward potassium current (I A) and delayed rectifier potassium current (I K) of voltage-gated potassium channels (Kv). Results showed that acute hf-rTMS in both 0.8 MT and 1.2 MT groups significantly activated I Na and inhibited I A and I K compared with control group, due to the changes of dynamic characteristics of VGSCs and Kv. Acute hf-rTMS in both 0.8 MT and 1.2 MT groups significantly increased membrane potential and nerve discharge frequency. Therefore, changing dynamic characteristics of VGSCs and Kv, activating I Na and inhibiting I A and I K might be one of the intrinsic mediating mechanisms by which rTMS enhanced the neuronal excitability of granular cells, and this regulatory effect increased with the increase of stimulus intensity.

Efficient continuous wave and passively Q switched Er:GdScO3 laser using Fe:ZnSe at 2.8 µm.

We report on diode-pumped continuous wave and passively Q switched Er:GdScO3 crystal lasers at around 2.8 µm. A continuous wave output power of 579 mW was obtained with a slope efficiency of 16.6%. Using Fe:ZnSe as a saturable absorber, a passively Q switched laser operation was realized. A maximum output power of 32 mW was generated with the shortest pulse duration of 286 ns at a repetition rate of 157.3 kHz, leading to a pulse energy of 204 nJ and a pulse peak power of 0.7 W.

[Effects of repetitive transcranial magnetic stimulation on neuronal excitability and ion channels in hindlimb unloading mice].

Weightlessness in the space environment affects astronauts' learning memory and cognitive function. Repetitive transcranial magnetic stimulation has been shown to be effective in improving cognitive dysfunction. In this study, we investigated the effects of repetitive transcranial magnetic stimulation on neural excitability and ion channels in simulated weightlessness mice from a neurophysiological perspective. Young C57 mice were divided into control, hindlimb unloading and magnetic stimulation groups. The mice in the hindlimb unloading and magnetic stimulation groups were treated with hindlimb unloading for 14 days to establish a simulated weightlessness model, while the mice in the magnetic stimulation group were subjected to 14 days of repetitive transcranial magnetic stimulation. Using isolated brain slice patch clamp experiments, the relevant indexes of action potential and the kinetic property changes of voltage-gated sodium and potassium channels were detected to analyze the excitability of neurons and their ion channel mechanisms. The results showed that the behavioral cognitive ability and neuronal excitability of the mice decreased significantly with hindlimb unloading. Repetitive transcranial magnetic stimulation could significantly improve the cognitive impairment and neuroelectrophysiological indexes of the hindlimb unloading mice. Repetitive transcranial magnetic stimulation may change the activation, inactivation and reactivation process of sodium and potassium ion channels by promoting sodium ion outflow and inhibiting potassium ion, and affect the dynamic characteristics of ion channels, so as to enhance the excitability of single neurons and improve the cognitive damage and spatial memory ability of hindlimb unloading mice.

Design of physical education teaching in colleges and universities based on emotional education under the environment of internet sharing information.

In the traditional teaching, the lack of emotional education for students leads to emotional indifference between teachers and students and low teaching quality. In this paper, from the perspective of emotional education. In college physical education teaching, information sharing through the Internet is compared with traditional education in terms of timeliness of communication, integrity of emotional education, teacher-student relationship, and teaching quality. The results show that the timeliness of communication has increased by 9.3%, the integrity of education has increased by 30%, and the relationship between teachers and students has also been significantly improved. In terms of teaching quality, students are more satisfied, and the teaching quality has also been improved. It also shows that emotional education in the Internet sharing information environment can better help students improve their learning, improve their learning efficiency, and learn better in happiness. Emotional education in a shared information environment can better enrich teaching content and enhance students' enthusiasm, which is of great significance.

Herbivore-induced tomato plant volatiles lead to the reduction of insecticides susceptibility in Spodoptera litura.

Herbivore-induced plant volatiles (HIPVs) have been associated with plant-plant-herbivorous-natural enemies communication and an enhanced response to the subsequent attack. Spodoptera litura is a serious cosmopolitan pest that has developed a high level of resistance to many insecticides. However, the underlying molecular and biochemical mechanism by which HIPV priming reduces S. litura larval sensitivity to insecticides remains largely unknown. This study was conducted to explore the potential of volatile from undamaged, or artificially damaged, or S. litura-damaged tomato plants on the susceptibility of S. litura to the insecticides beta-cypermethrin indoxacarb and chlorpyrifos. We found that larvae exposed to volatile from S. litura-damaged or artificially damaged tomato plants were significantly less susceptible to the three insecticides than those exposed to volatile from undamaged tomato plants. Elevated activities of detoxifying enzymes [cytochrome P450 monooxygenases (P450s), glutathione S-transferases (GSTs), and esterases (ESTs)], were expressed in S. litura larvae exposed to volatile from S. litura-damaged tomato plants than those exposed to volatile from undamaged tomato plants. Similarly, seven detoxification-related genes [GSTs (SlGSTe1, SlGSTo1, and SlGSTe3) and P450s (CYP6B48, CYP9A40, CYP321A7, and CYP321B1)] in the midgut and fat body of larvae were up-regulated under exposure to volatile from S. litura-damaged tomato plants. Increased volatile organic compounds emissions were detected in the headspace of tomato plants damaged by S. litura compared to the undamaged plants. Collectively, these findings suggest that HIPVs can considerably reduce caterpillar susceptibility to insecticides, possibly through induction-enhanced detoxification mechanisms, and provide valuable information for implementing an effective integrated pest management strategy.

Plastic structures for diverse substrates: A revisit of human ABC transporters.

ATP-binding cassette (ABC) superfamily is one of the largest groups of primary active transporters that could be found in all kingdoms of life from bacteria to humans. In humans, ABC transporters can selectively transport a wide spectrum of substrates across membranes, thus playing a pivotal role in multiple physiological processes. In addition, due to the ability of exporting clinic therapeutics, some ABC transporters were originally termed multidrug resistance proteins. Increasing investigations of human ABC transporters in recent years have provided abundant information for elucidating their structural features, based on the structures at distinct states in a transport cycle. This review focuses on the recent progress in human ABC structural analyses, substrate binding specificities, and translocation mechanisms. We dedicate to summarize the common features of human ABC transporters in different subfamilies, and to discuss the possibility to apply the fast-developing techniques, such as cryogenic electron microscopy, and artificial intelligence-assisted structure prediction, for future studies.

Improving Biological Functions of Three-Dimensional Printed Ti2448 Scaffolds by Decoration with Polydopamine and Extracellular Matrices.

Extracellular matrices (ECMs) provide important cues for cell proliferation and differentiation in the complex environment, which show a significant influence on cell functions. Herein, cell-derived ECMs were deposited on the polydopamine (PDA)-decorated porous Ti-24Nb-4Zr-8Sn (Ti2448) scaffolds fabricated by the electron beam melting method in order to improve biological functions. The influence of PDA-ECM coatings on cell functions was further investigated. The results demonstrated that the PDA-ECM coating facilitated adhesion, proliferation, and migration of MC3T3-E1 cells on Ti2448 scaffolds. Moreover, Ti2448-PDA-ECM scaffolds promoted osteogenesis differentiation of cells indicated by greater alkaline phosphatase activity and further mineralization, compared to the plain Ti2448 group. Meanwhile, Ti2448-PDA-ECM scaffolds enhanced bone growth after implantation for one month in rabbit femoral bone defects. Our findings suggest that the bioinspired PDA-ECM coating can be implemented on the porous Ti2448 scaffolds, which significantly improve the biological functions of orthopedic implants.

Effects of different additives and aerobic composting factors on heavy metal bioavailability reduction and compost parameters: A meta-analysis.

Additives are considered a promising approach to accelerate the composting process and alleviate the dissemination of pollutants to the environment. However, nearly all previous articles have focused on the impact of additive amounts on the reduction of HMs, which may not fully represent the main factor shaping HMs bioavailability status during composting. Simultaneously, previous reviews only explored the impacts, speciation, and toxicity mechanism of HMs during composting. Hence, a global-scale meta-analysis was conducted to investigate the response patterns of HMs bioavailability and compost parameters to different additives, composting duration, and composting factors (additive types, feedstock, bulking agents, and composting methods) by measuring the weighted mean values of the response ratio "[ln (RR)]" and size effect (%). The results revealed that additives significantly lessened HMs bioavailability by ≥ 40% in the final compost products than controls. The bioavailability decline rates were -40%, -60%, -57%, -55%, -42%, and -44% for Zn, Pb, Ni, Cu, Cr, and Cd. Simultaneously, additives significantly improved the total nitrogen (TN) (+16%), pH (+5%), and temperature (+5%), and decreased total organic carbon (TOC) (-17%), moisture content (MC) (-18%), and C/N ratio (-19%). Furthermore, we found that the prolongation of composting time significantly promoted the effect of additives on declining HMs bioavailability (p < 0.05). Nevertheless, increasing additive amounts revealed an insignificant impact on decreasing the HMs bioavailability (p > 0.05). Eventually, using zeolite as an additive, chicken manure as feedstock, sawdust as a bulking agent, and a reactor as composting method had the most significant reduction effect on HMs bioavailability (p < 0.05). The findings of this meta-analysis may contribute to the selection, modification, and application of additives and composting factors to manage the level of bioavailable HMs in the compost products.

Structural basis of substrate recognition and translocation by human very long-chain fatty acid transporter ABCD1.

Human ABC transporter ABCD1 transports very long-chain fatty acids from cytosol to peroxisome for ß-oxidation, dysfunction of which usually causes the X-linked adrenoleukodystrophy (X-ALD). Here, we report three cryogenic electron microscopy structures of ABCD1: the apo-form, substrate- and ATP-bound forms. Distinct from what was seen in the previously reported ABC transporters, the two symmetric molecules of behenoyl coenzyme A (C22:0-CoA) cooperatively bind to the transmembrane domains (TMDs). For each C22:0-CoA, the hydrophilic 3'-phospho-ADP moiety of CoA portion inserts into one TMD, with the succeeding pantothenate and cysteamine moiety crossing the inter-domain cavity, whereas the hydrophobic fatty acyl chain extends to the opposite TMD. Structural analysis combined with biochemical assays illustrates snapshots of ABCD1-mediated substrate transport cycle. It advances our understanding on the selective oxidation of fatty acids and molecular pathology of X-ALD.

Effects of Low-Concentration Graphene Oxide Quantum Dots on Improving the Proliferation and Differentiation Ability of Bone Marrow Mesenchymal Stem Cells through the Wnt/ß-Catenin Signaling Pathway.

Graphene oxide quantum dots (GOQDs) are considered to be a new method for regulating the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). However, there are few reports on such regulation with different concentrations of GOQDs, and the molecular mechanism has not been fully elucidated. The purposes of this study were, first, to explore the effects of GOQDs on the proliferation and differentiation of BMSCs in vitro and in vivo, and, second, to provide a theoretical basis for the repair of bone defects. Live/Dead staining, EdU staining, immunofluorescence staining, alkaline phosphatase (ALP), western blotting, and qT-PCR were used for detecting the proliferation and differentiation of BMSCs after coculture with GOQDs of different concentrations. Hematoxylin and eosin (HE) staining and Van Gieson (VG) staining were used to detect new bone regeneration in vivo. The results showed that low-concentration GOQDs (0.1 and 1 µg/mL) promoted the proliferation and differentiation of BMSCs. Compared with the 1 µg/mL GOQD group, the 0.1 µg/mL GOQD group had better ability to promote the proliferation and differentiation of BMSCs. HE and VG staining results showed the greatest proportion of new bone area on sandblasted, large-grit, and acid-etched (SLA)/GOQD scaffolds. Furthermore, the ratio of active ß-catenin and the phosphorylation level of GSK-3ß (p-GSK-3ß) increased after BMSCs treatment with 0.1 µg/mL GOQDs. Low concentrations of GOQDs improved the osteogenic differentiation ability of BMSCs by activating the Wnt/ß-catenin signaling pathway.