Microbial community assemblage altered by coprecipitation of artificial humic substances and ferrihydrite: Implications for carbon fixation pathway transformation.

The suppression of soil carbon mineralization has been demonstrated to be effectively facilitated by carbon­iron interactions, yet the specific mechanisms by which artificial humic substances (A-HS) coupled with ferrihydrite influence this process remain insufficiently explored. This study is to investigate how the A-HS, specifically artificial fulvic acid (A-FA) and artificial humic acid (A-HA), coupled with ferrihydrite, affect carbon mineralization under anaerobic system that simulates paddy flooding conditions. The object is to investigate trends in carbon emissions and to delineate microbial community structure and functional pathways. The findings indicate that A-HA and A-FA substantially reduce CO2 and CH4 emissions, with A-FA having a particularly pronounced effect on carbon fixation, halving CO2 concentrations. The low concentration of Fe(II) observed suggest that A-FA and A-HA impede the dissimilatory iron reduction (DIR) process. Detailed 16S rDNA sequencing and gene prediction analyses reveal changes in microbial community structures and functions, highlighting Methanobacterium as the dominant hydrogenotrophic methanogens. The reductive citric acid cycle, predominantly utilized by Clostridium carboxidivorans, was identified as the principal carbon fixation pathway. This work provides a novel insight into the microbial mechanisms of carbon sequestration and highlights the potential of A-HS in improving soil fertility and contributing to climate change mitigation through enhancing soil carbon storage.

SHP2 as a primordial epigenetic enzyme expunges histone H3 pTyr-54 to amend androgen receptor homeostasis.

Mutations that decrease or increase the activity of the tyrosine phosphatase, SHP2 (encoded by PTPN11), promotes developmental disorders and several malignancies by varying phosphatase activity. We uncovered that SHP2 is a distinct class of an epigenetic enzyme; upon phosphorylation by the kinase ACK1/TNK2, pSHP2 was escorted by androgen receptor (AR) to chromatin, erasing hitherto unidentified pY54-H3 (phosphorylation of histones H3 at Tyr54) epigenetic marks to trigger a transcriptional program of AR. Noonan Syndrome with Multiple Lentigines (NSML) patients, SHP2 knock-in mice, and ACK1 knockout mice presented dramatic increase in pY54-H3, leading to loss of AR transcriptome. In contrast, prostate tumors with high pSHP2 and pACK1 activity exhibited progressive downregulation of pY54-H3 levels and higher AR expression that correlated with disease severity. Overall, pSHP2/pY54-H3 signaling acts as a sentinel of AR homeostasis, explaining not only growth retardation, genital abnormalities and infertility among NSML patients, but also significant AR upregulation in prostate cancer patients.

Photothermal driven BMSCs osteogenesis and M2 macrophage polarization on polydopamine-coated Ti3C2 nanosheets/poly(vinylidene fluoride trifluoroethylene) nanocomposite coatings.

Mild thermal stimulation plays an active role in bone tissue repair and regeneration. In this work, a bioactive polydopamine/Ti3C2/poly(vinylidene fluoride trifluoroethylene) (PDA/Ti3C2/P(VDF-TrFE)) nanocomposite coating with excellent near-infrared light (NIR)-triggered photothermal effect was designed to improve the osteogenic ability of implants. By incorporating dopamine (DA)-modified Ti3C2 nanosheets into the P(VDF-TrFE) matrix and combining them with alkali initiated in situ polymerization, the resulting PDA/Ti3C2/P(VDF-TrFE) nanocomposite coating gained high adhesion strength on Ti substrate, excellent tribological and corrosion resistance properties, which was quite important for clinical application of implant coatings. Cell biology experiments showed that NIR-triggered mild thermal stimulation on the coating surface promoted cell spreading and growth of BMSCs, and also greatly upregulated the osteogenic markers, including Runt-Related Transcription Factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN). Simultaneously, the synthesis of heat shock protein 47 (HSP47) was significantly promoted by the mild thermal stimulation, which strengthened the specific interaction between HSP47 and collagen Ⅰ (COL-Ⅰ), thereby activating the integrin-mediated MEK/ERK osteogenic differentiation signaling pathway. In addition, the results also showed that the mild thermal stimulation induced the polarization of macrophages towards M2 phenotype, which can attenuate the inflammatory response of injured bone tissue. Antibacterial results indicated that the coating exhibited an outstanding antibacterial ability against S. aureus and E. coli. Conceivably, the versatile implant bioactive coatings developed in this work will show great application potential for implant osseointegration.

Synergistic enhancement of cadmium immobilization and soil fertility through biochar and artificial humic acid-assisted microbial-induced calcium carbonate precipitation.

Microbially induced carbonate precipitation (MICP) is emerging as a favorable alternative to traditional soil remediation techniques for heavy metals, primarily due to its environmental friendliness. However, a significant challenge in using MICP for farmland is not only to immobilize heavy metals but also to concurrently enhance soil fertility. This study explores the innovative combination of artificial humic acid (A-HA), biochar (BC), and Sporosarcina pasteurii (S. pasteurii) to mitigate the bioavailability of cadmium (Cd) in contaminated agricultural soils through MICP. X-ray diffraction (XRD) and scanning electron microscope (SEM) analyses revealed that the integration of BC and A-HA significantly enhances Cd immobilization efficiency by co-precipitating with CaCO3. Moreover, this treatment also improved soil fertility and ecological functions, as evidenced by increases in total nitrogen (TN, 9.0-78.2 %), alkaline hydrolysis nitrogen (AN, 259.7-635.5 %), soil organic matter (SOM, 18.1-27.9 %), total organic carbon (TOC, 43.8-48.8 %), dissolved organic carbon (DOC, 36.0-88.4 %) and available potassium (AK, 176.2-193.3 %). Additionally, the relative abundance of dominant phyla such as Proteobacteria and Firmicutes significantly increased with the introduction of BC and A-HA in MICP. Consequently, the integration of BC and A-HA with MICP offers a promising solution for remediating Cd-contaminated agricultural soil and synergistically enhancing soil fertility.

Comparative study of [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p as novel PD-L1 targeting PET probes for tumor imaging.

PD-L1 is expressed in many tumors but rarely in normal tissues, therefore, it can be a target of PET imaging. In this work, we developed new peptide-based PET probes [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p with yields of 20-25 % and 40-55 %, respectively. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p were synthesized within 30 min with high molar activities. [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p showed good stability in vivo and in vitro. In vitro cell studies showed [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p target PD-L1 specifically, with high uptake of 61.52 ± 4.39 and 19.29 ± 2.17 %ID/1 million cells in B16F10 cells at 60 min, respectively. Biodistribution results showed that both [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1p had lower liver accumulation. In vivo PET imaging results showed that [18F]AlF-PAI-PDL1p had a high tumor uptake of 4.23 ± 0.81 %ID/g at 2 h and increased uptake of 6.60 ± 1.01 %ID/g at 12 h. [68Ga]Ga-PAI-PDL1p also showed high tumor uptake of 2.30 ± 0.20 %ID/g at 2 h and slightly increased uptake of 3.80 ± 0.26 %ID/g at 6 h. In conclusion, [18F]AlF-PAI-PDL1p and [68Ga]Ga-PAI-PDL1 seemed to be potential tracers for PET imaging of PD-L1 expression.

Investigation of the impact of planar microelectrodes on macrophage-mediated mesenchymal stem cell osteogenesis.

Osseointegration commences with foreign body inflammation upon implant placement, where macrophages play a crucial role in the immune response. Subsequently, during the intermediate and late stages of osseointegration, mesenchymal stem cells (MSCs) migrate and initiate their osteogenic functions, while macrophages support MSCs in osteogenesis. The utilization of ferroelectric P(VDF-TrFE) covered ITO planar microelectrodes facilitated the simulation of various surface charge to investigate their effects on MSCs' osteogenic differentiation and macrophage polarization and the results indicated a parabolic increase in the promotional effect of both with the rise in piezoelectric coefficient. Furthermore, the surface charge with a piezoelectric coefficient of -18 exhibited the strongest influence on the promotion of M1 polarization of macrophages and the promotion of MSCs' osteogenic differentiation. The impact of macrophage polarization and MSC osteogenesis following the interaction of macrophages affected by surface charge and MSC was ultimately investigated. It was observed that macrophages affected by the surface charge of -18 piezoelectric coefficient still exerted the most profound induced osteogenic effect, validating the essential role of M1-type macrophages in the osteogenic differentiation of MSCs.

Do bubbles matter amid PBC for trigeminal neuralgia?

BACKGROUND: As a simple and safe alternative intervention, percutaneous balloon compression (PBC) has been gradually adopted by a growing number of neurosurgeons to treat trigeminal neuralgia. A pear-shaped opacity observed fluoroscopically, which indicates full suffusion of Meckel's cave conducting sufficient pressure against Gasserian ganglion, is believed to be the key to its success. Sometimes, a bitten pear may appear due to bubbles in the balloon but is usually ignored. OBJECTIVE: This study aims to investigate the effects of the bubbles on postoperative outcomes. METHODS: Patient data were obtained from the consecutive cases undergoing PBCs in our department between 2019 and 2021. Among them, pain and numbness were used to assess the efficacy of PBC based on Barrow Neurology Institute (BNI) scoring system. It was defined as an effective outcome if the postoperative pain intensity grade was lower than II. And those with numbness grade > II were regarded as numb incidence. RESULTS: We eventually recruited 59 cases, including 42 in full pear and 17 in bitten pear groups with follow-up time up to 44 months. The early effective rates were 95.2% and 82.4%, respectively (p > 0.05), which turned to 88.1% and 52.9% during the last follow-up period (p < 0.01). This result indicated that the bitten pear gave rise to a significantly higher recurrence. In terms of numbness, there was no significant difference. CONCLUSION: Gas does not yield enough pressure as liquid, and cannot exert enough pressure to the semilunar ganglion. Therefore, air evacuation should not be ignored before injection.

Enzyme-responsive design combined with photodynamic therapy for cancer treatment.

Photodynamic therapy (PDT) is a noninvasive cancer treatment that has garnered significant attention in recent years. However, its application is still hampered by certain limitations, such as the hydrophobicity and low targeting of photosensitizers (PSs) and the hypoxia of the tumor microenvironment. Nevertheless, the fusion of enzyme-responsive drugs with PDT offers novel solutions to overcome these challenges. Utilizing the attributes of enzyme-responsive drugs, PDT can deliver PSs to the target site and selectively release them, thereby enhancing therapeutic outcomes. In this review, we spotlight recent advances in enzyme-responsive materials for cancer treatment and primarily delineate their application in combination with PDT.

Artificial Humic Acid Mediated Carbon-Iron Coupling to Promote Carbon Sequestration.

Fe (hydr)oxides have a substantial impact on the structure and stability of soil organic carbon (SOC) pools and also drive organic carbon turnover processes via reduction-oxidation reactions. Currently, many studies have paid much attention to organic matter-Fe mineral-microbial interactions on SOC turnover, while there is few research on how exogenous carbon addition abiotically regulates the intrinsic mechanisms of Fe-mediated organic carbon conversion. The study investigated the coupling process of artificial humic acid (A-HA) and Fe(hydr)oxide, the mechanism of inner-sphere ligands, and the capacity for carbon sequestration using transmission electron microscopy, thermogravimetric, x-ray photoelectron spectroscopy, and wet-chemical disposal. Furthermore, spherical aberration-corrected scanning transmission electron microscopy-electron energy loss spectroscopy and Mössbauer spectra have been carried out to demonstrate the spatial heterogeneity of A-HA/Fe (hydr)oxides and reveal the relationship between the increase in Fe-phase crystallinity and redox sensitivity and the accumulation of organic carbon. Additionally, the dynamics of soil structures on a microscale, distribution of carbon-iron microdomains, and the cementing-gluing effect can be observed in the constructing nonliving anthropogenic soils, confirming that the formation of stable aggregates is an effective approach to achieving organic carbon indirect protection. We propose that exogenous organic carbon inputs, specifically A-HA, could exert a substantial but hitherto unexplored effect on the geochemistry of iron-carbon turnover and sequestration in anoxic water/solid soils and sediments.

Heterocyclic-Modified Imidazoquinoline Derivatives: Selective TLR7 Agonist Regulates Tumor Microenvironment against Melanoma.

Immunotherapy targeting the toll-like receptor 7 (TLR7) is a promising strategy for cancer treatment. Herein, we describe the design and synthesis of a series of imidazoquinoline-based TLR7 agonists and assess NF-κB pathway activation using HEK-Blue hTLR7 cells to identify the most potent small-molecule TLR7 agonist, SMU-L11 (EC50 = 0.024 ± 0.002 µM). In vitro experiments demonstrated that SMU-L11 specifically activated TLR7, resulting in recruitment of the MyD88 adaptor protein and activation of the NF-κB and MAPK signaling pathways. Moreover, SMU-L11 was found to exert immune-enhancing effects by significantly inducing the secretion of proinflammatory cytokines in murine dendritic cells, macrophages, and human peripheral blood mononuclear cells while promoting M1 macrophage polarization. In vivo studies using a B16-F10 mouse tumor model showed that SMU-L11 significantly enhanced immune cell activation and augmented CD4+ T and CD8+ T-cell proliferation, directly killing tumor cells and inhibiting tumor growth.

Discovery of an ellipticine derivative as TLR3 inhibitor against influenza A virus and SARS-CoV-2.

Influenza and COVID-19 continue to pose global threats to public health. Classic antiviral drugs have certain limitations, coupled with frequent viral mutations leading to many drugs being ineffective, the development of new antiviral drugs is urgent. Meanwhile, the invasion of influenza virus can cause an immune response, and an excessive immune response can generate a large number of inflammatory storms, leading to tissue damage. Toll-like receptor 3 (TLR3) recognizes virus dsRNA to ignite the innate immune response, and inhibit TLR3 can block the excess immune response and protect the host tissues. Taking TLR3 as the target, SMU-CX1 was obtained as the specific TLR3 inhibitor by high-throughput screening of 15,700 compounds with IC50 value of 0.11 µM. Its anti-influenza A virus activity with IC50 ranged from 0.14 to 0.33 µM against multiple subtypes of influenza A virus and also showed promising anti-SARS-CoV-2 activity with IC50 at 0.43 µM. Primary antiviral mechanism study indicated that SMU-CX1 significantly inhibited PB2 and NP protein of viruses, it can also inhibit inflammatory factors in host cells including IFN-ß, IP-10 and CCL-5. In conclusion, this study demonstrates the potential of SMU-CX1 in inhibiting IAV and SARS-CoV-2 activity, thereby offering a novel approach for designing antiviral drugs against highly pathogenic viruses.

Overview of epigenetic degraders based on PROTAC, molecular glue, and hydrophobic tagging technologies.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.

Artificial humic acid coated ferrihydrite strengthens the adsorption of phosphate and increases soil phosphate retention.

Phosphorus (P) leaching loss from farmland soils is one of the main causes of water eutrophication. Thus, effective methods must be developed to maintain sustainability in agricultural soils. Herein, we design artificial humic acid (A-HA) coated ferrihydrite (Fh) particles for fixing P in soil. The experiments in water and soil are successively conducted to explore the phosphate adsorption mechanism and soil P retention performance of A-HA coated ferrihydrite particles (A-Fh). Compared with unmodified ferrihydrite (Fh), the phosphate adsorption capacity of A-Fh is increased by 15 %, the phosphate adsorption speed and selectivity are also significantly improved. The ligand exchange, electrostatic attraction and hydrogen bonding are the dominant mechanisms of phosphate adsorption by A-Fh. In soil experiments, the addition of 2 % A-Fh increases the soil P retention performance from 0.15 to 0.7 mg/kg, and A-Fh are able to convert more phosphate adsorbed by itself into soil available P to improve soil fertility. Overall, this work highlights the importance of this a highly effective amendment for improving poor soils.

Effects of Fe3+ on Hydrothermal Humification of Agricultural Biomass.

Hydrothermal humification technology for the preparation of artificial humic matters provides a new strategy, greatly promoting the natural maturation process. Iron, as a common metal, is widely used in the conversion of waste biomass; however, the influence of Fe3+ on hydrothermal humification remains unknown. In this study, FeCl3 is used to catalyze the hydrothermal humification of corn straw, and the influence of Fe3+ on the hydrothermal humification is explored by a series of characterization techniques. Results show that Fe3+ as the catalyst can promote the decomposition of corn straw, shorten the reaction time from 24 h to 6 h, and increase the yield from 6.77 % to 14.08 %. However, artificial humic acid (A-HA) obtained from Fe3+ -catalysis hydrothermal humification contains more unstable carbon and low amount of aromatics, resulting in a significantly decreased stability of the artificial humic acid. These results provide theoretical guidance for regulating the structure and properties of artificial humic acid to meet various maintenance needs.

Effect of humic substances on nitrogen cycling in soil-plant ecosystems: Advances, issues, and future perspectives.

Nitrogen (N) cycle is one of the most significant biogeochemical cycles driven by soil microorganisms on the earth. Exogenous humic substances (HS), which include composted-HS and artificial-HS, as a new soil additive, can improve the water retention capacity, cation exchange capacity and soil nutrient utilization, compensating for the decrease of soil HS content caused by soil overutilization. This paper systematically reviewed the contribution of three different sources of HS in the soil-plant system and explained the mechanisms of N transformation through physiological and biochemical pathways. HS convert the living space and living environment of microorganisms by changing the structure and condition of soil. Generally, HS can fix atmospheric and soil N through biotic and abiotic mechanisms, which improved the availability of N. Besides, HS transform the root structure of plants through physiological and biochemical pathways to promote the absorption of inorganic N by plants. The redox properties of HS participate in soil N transformation by altering the electron gain and loss of microorganisms. Moreover, to alleviate the energy crisis and environmental problems caused by N pollution, we also illustrated the mechanisms reducing soil N2O emissions by HS and the application prospects of artificial-HS. Eventually, a combination of indoor simulation and field test, molecular biology and stable isotope techniques are needed to systematically analyze the potential mechanisms of soil N transformation, representing an important step forward for understanding the relevance between remediation of environmental pollution and improvement of the N utilization in soil-plant system.

Mitochondrial metabolic flexibility is critical for CD8+ T cell antitumor immunity.

Mitochondria use different substrates for energy production and intermediatory metabolism according to the availability of nutrients and oxygen levels. The role of mitochondrial metabolic flexibility for CD8+ T cell immune response is poorly understood. Here, we report that the deletion or pharmacological inhibition of protein tyrosine phosphatase, mitochondrial 1 (PTPMT1) significantly decreased CD8+ effector T cell development and clonal expansion. In addition, PTPMT1 deletion impaired stem-like CD8+ T cell maintenance and accelerated CD8+ T cell exhaustion/dysfunction, leading to aggravated tumor growth. Mechanistically, the loss of PTPMT1 critically altered mitochondrial fuel selection-the utilization of pyruvate, a major mitochondrial substrate derived from glucose-was inhibited, whereas fatty acid utilization was enhanced. Persistent mitochondrial substrate shift and metabolic inflexibility induced oxidative stress, DNA damage, and apoptosis in PTPMT1 knockout cells. Collectively, this study reveals an important role of PTPMT1 in facilitating mitochondrial utilization of carbohydrates and that mitochondrial flexibility in energy source selection is critical for CD8+ T cell antitumor immunity.

AMPK activator-treated human cardiac spheres enhance maturation and enable pathological modeling.

BACKGROUND: Cardiac pathological outcome of metabolic remodeling is difficult to model using cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) due to low metabolic maturation. METHODS: hiPSC-CM spheres were treated with AMP-activated protein kinase (AMPK) activators and examined for hiPSC-CM maturation features, molecular changes and the response to pathological stimuli. RESULTS: Treatment of hiPSC-CMs with AMPK activators increased ATP content, mitochondrial membrane potential and content, mitochondrial DNA, mitochondrial function and fatty acid uptake, indicating increased metabolic maturation. Conversely, the knockdown of AMPK inhibited mitochondrial maturation of hiPSC-CMs. In addition, AMPK activator-treated hiPSC-CMs had improved structural development and functional features-including enhanced Ca2+ transient kinetics and increased contraction. Transcriptomic, proteomic and metabolomic profiling identified differential levels of expression of genes, proteins and metabolites associated with a molecular signature of mature cardiomyocytes in AMPK activator-treated hiPSC-CMs. In response to pathological stimuli, AMPK activator-treated hiPSC-CMs had increased glycolysis, and other pathological outcomes compared to untreated cells. CONCLUSION: AMPK activator-treated cardiac spheres could serve as a valuable model to gain novel insights into cardiac diseases.

A simplified network topology for fruit detection, counting and mobile-phone deployment.

The complex network topology, deployment unfriendliness, computation cost, and large parameters, including the natural changeable environment are challenges faced by fruit detection. Thus, a Simplified network topology for fruit detection, tracking and counting was designed to solve these problems. The network used common networks of Conv, Maxpool, feature concatenation and SPPF as new backbone and a modified decoupled head of YOLOv8 as head network. At the same time, it was validated on a dataset of images encompassing strawberry, jujube, and cherry fruits. Having compared to YOLO-mainstream variants, the params of Simplified network is 32.6%, 127%, and 50.0% lower than YOLOv5n, YOLOv7-tiny, and YOLOv8n, respectively. The results of mAP@50% tested using test-set show that the 82.4% of Simplified network is 0.4%, -0.2%, and 0.2% respectively more accurate than 82.0% of YOLOv5n, 82.6% of YOLOv7-tiny, and 82.2% of YOLOv8n. Furthermore, the Simplified network is 12.8%, 17.8%, and 11.8% respectively faster than YOLOv5n, YOLOv7-tiny, and YOLOv8n, including outperforming in tracking, counting, and mobile-phone deployment process. Hence, the Simplified network is robust, fast, accurate, easy-to-understand, fewer in parameters and deployable friendly.

Discovery of novel aporphine alkaloid derivative as potent TLR2 antagonist reversing macrophage polarization and neutrophil infiltration against acute inflammation.

Toll-like receptor 2 (TLR2) mediated macrophages regulate the protective immune response to infectious microorganisms, but the aberrant activation of macrophages often leads to pathological inflammation, including tissue damage. In this study, we identified antagonists of TLR2 by screening 2100 natural products and subsequently identified Taspine, an aporphine alkaloid, as an excellent candidate. Furthermore, analysis of the 10 steps chemical synthesis route and structural optimization yielded the Taspine derivative SMU-Y6, which has higher activity, better solubility, and improved drug-feasible property. Mechanistic studies and seq-RNA analysis revealed that SMU-Y6 inhibited TLR2 over other TLRs, hindered the formation of TLR2/MyD88 complex, and blocked the downstream NF-κB and MAPK signaling pathway, thus suppressing the release of inflammatory cytokines. SMU-Y6 could stabilize TLR2 and bind to TLR2 protein with a Kd of 0.18 µmol/L. Additionally, SMU-Y6 could efficiently reverse the M1 phenotype macrophage polarization, reduce the production of cytokines as well as infiltration of neutrophiles and alleviate the local inflammation in mice with acute paw edema and colitis. Collectively, we reported the first aporphine alkaloid derivative that selectively inhibits TLR2 with high binding affinity and superior drug-feasible property, thus providing an urgently-needed molecular probe and potential drug candidate for inflammatory and autoimmune disease therapy.

Accelerated Bone Regeneration on the Metal Surface through Controllable Surface Potential.

Surface potential is rarely investigated as an independent factor in influencing tissue regeneration on the metal surface. In this work, the surface potential on the titanium (Ti) surface was designed to be tailored and adjusted independently, which arises from the ferroelectricity and piezoelectricity of poled poly(vinylidene fluoride-trifluoroethylene) (PVTF). Notably, it is found that such controllable surface potential on the metal surface significantly promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro as well as bone regeneration in vivo. In addition, the intracellular calcium ion (Ca2+) concentration measurement further proves that such controllable surface potential on the metal surface could activate the transmembrane calcium channels and allow the influx of extracellular Ca2+ into the cytoplasm. That might be the reason for improved osteogenic differentiation of BMSCs and bone regeneration. These findings reveal the potential of the metal surface with improved bioactivity for stimulation of osteogenesis and show great prospects for fabricable implantable medical devices with adjustable surface potential.