Photo-Assisted Li-N2 Batteries with Enhanced Nitrogen Fixation and Energy Conversion.

Li-N2 batteries have received widespread attention for their potential to integrate N2 fixation, energy storage, and conversion. However, because of the low activity and poor stability of cathode catalysts, the electrochemical performance of Li-N2 batteries is suboptimal, and their electrochemical reversibility has rarely been proven. In this study, a novel bifunctional photo-assisted Li-N2 battery system was established by employing a plasmonic Au nanoparticles (NPs)-modified defective carbon nitride (Au-Nv -C3 N4 ) photocathode. The Au-Nv -C3 N4 exhibits strong light-harvesting, N2 adsorption, and N2 activation abilities, and the photogenerated electrons and hot electrons are remarkably beneficial for accelerating the discharge and charge reaction kinetics. These advantages enable the photo-assisted Li-N2 battery to achieve a low overpotential of 1.32 V, which is the lowest overpotential reported to date, as well as superior rate capability and prolonged cycle stability (≈500 h). Remarkably, a combination of theoretical and experimental results demonstrates the high reversibility of the photo-assisted Li-N2 battery. The proposed novel strategy for developing efficient cathode catalysts and fabricating photo-assisted battery systems breaks through the overpotential bottleneck of Li-N2 batteries, providing important insights into the mechanism underlying N2 fixation and storage.

Polyoxometalate Li3 PW12 O40 and Li3 PMo12 O40 Electrolytes for High-energy All-solid-state Lithium Batteries.

Solid-state lithium (Li) batteries promise both high energy density and safety while existing solid-state electrolytes (SSEs) fail to satisfy the rigorous requirements of battery operations. Herein, novel polyoxometalate SSEs, Li3 PW12 O40 and Li3 PMo12 O40 , are synthesized, which exhibit excellent interfacial compatibility with electrodes and chemical stability, overcoming the limitations of conventional SSEs. A high ionic conductivity of 0.89 mS cm-1 and a low activation energy of 0.23 eV are obtained due to the optimized three-dimensional Li+ migration network of Li3 PW12 O40 . Li3 PW12 O40 exhibits a wide window of electrochemical stability that can both accommodate the Li anode and high-voltage cathodes. As a result, all-solid-state Li metal batteries fabricated with Li/Li3 PW12 O40 /LiNi0.5 Co0.2 Mn0.3 O2 display a stable cycling up to 100 cycles with a cutoff voltage of 4.35 V and an areal capacity of more than 4 mAh cm-2 , as well as a cost-competitive SSEs price of $5.68 kg-1 . Moreover, Li3 PMo12 O40 homologous to Li3 PW12 O40 was obtained via isomorphous substitution, which formed a low-resistance interface with Li3 PW12 O40 . Applications of Li3 PW12 O40 and Li3 PMo12 O40 in Li-air batteries further demonstrate that long cycle life (650 cycles) can be achieved. This strategy provides a facile, low-cost strategy to construct efficient and scalable solid polyoxometalate electrolytes for high-energy solid-state Li metal batteries.

An In Situ Chemotherapy Drug Combined with Immune Checkpoint Inhibitor for Chemoimmunotherapy.

Clinically, cancer chemotherapy still faces unsatisfactory efficacy due to drug resistance and severe side effects, including tiredness, hair loss, feeling sick, etc. The clinical benefits of checkpoint inhibitors have revived hope for cancer immunotherapy, but the objective response rate of immune checkpoint inhibitors remains around 10-40%. Herein, two types of copper-doped mesoporous silica nanoparticles (MS-Cu-1 with a diameter of about 30 nm and MS-Cu-2 with a diameter of about 200 nm) were synthesized using a one-pot method. Both MS-Cu-1 and MS-Cu-2 nanoparticles showed excellent tumor microenvironment regulation properties with elevated extracellular and intracellular ROS generation, extracellular and intracellular oxygenation, and intracellular GSH depletion. In particular, MS-Cu-2 nanoparticles demonstrated a better microenvironment modulation effect than MS-Cu-1 nanoparticles. The DSF/MS-Cu composites with disulfiram (DSF) and copper co-delivery characteristics were prepared by a straightforward method using chloroform as the solvent. Cell survival rate and live/dead staining results showed that DSF and MS-Cu alone were not toxic to LLC cells, while a low dose of DSF/MS-Cu (1-10 µg/mL) showed a strong cell-killing effect. In addition, MS-Cu-2 nanoparticles released more Cu2+ in a weakly acidic environment (pH = 5) than in a physiological environment (pH = 7.4), and the Cu2+ released was 41.72 ± 0.96 mg/L in 1 h under weakly acidic conditions. UV-visible absorption spectrometry confirmed the production of tumor-killing drugs (CuETs). The intratumoral injection of DSF/MS-Cu significantly inhibited tumor growth in vivo by converting nontoxic DSF/MS-Cu into toxic CuETs. The combination of DSF/MS-Cu and anti-CTLA-4 antibody further inhibited tumor growth, showing the synergistic effect of DSF/MS-Cu and immune checkpoint inhibitors.

Effects of Zinc and Strontium Doping on In Vitro Osteogenesis and Angiogenesis of Calcium Silicate/Calcium Phosphate Cement.

Based on multiple biological functions (mainly osteogenesis and angiogenesis) of bioactive ions, Zn/Sr-doped calcium silicate/calcium phosphate cements (Zn/Sr-CS/CPCs, including 10Zn-CS/CPC, 20Sr-CS/CPC, and 10Zn/20Sr-CS/CPC) were prepared by the addition of Zn and Sr dual active ions into CS/CPC to further accelerate its bone regeneration in this study. The physicochemical and biological properties of the Zn/Sr-CS/CPCs were systematically investigated. The results showed that the setting time was slightly prolonged, the compressive strength and porosity did not change much, and all groups maintained good injectability after the doping of Zn and Sr. Besides, the doping of Zn and Sr had little effect on the phase and microstructure of hydrated products of CS/CPC. The degradation rate of Zn/Sr-CS/CPCs decreased after doping with Zn and Sr. In mouse bone marrow mesenchymal stem cells (mBMSC) experiments, all Zn/Sr-CS/CPCs stimulated the viability, adhesion, proliferation, and alkaline phosphatase (ALP) activity together with osteogenesis-related genes (ALP, Runx2, Col-I, OCN, and OPN). The further addition of Zn and Sr played better and synergistic roles in in vitro osteogenesis. Thereinto, 10Zn/20Sr-CS/CPC manifested the optimum in vitro osteogenic performance. As for human umbilical vein endothelial cell (HUVEC) experiments, the incorporation of CS doped with Zn and Sr into CPC possessed good vascularization properties of proliferation, NO secretion, tube formation, and the expression of angiogenesis-related genes (VEGF, bFGF, and eNOS). In conclusion, the doping of Zn and Sr into CS/CPC could exhibit excellent osteogenesis and good angiogenesis potentials and 10Zn/20Sr-CS/CPC could be considered as a promising candidate in bone repair.

Preparation of lithium-containing magnesium phosphate-based composite ceramics having high compressive strength, osteostimulation and proangiogenic effects.

Fairly high concentrations of magnesium and lithium are conducive to improving the osteogenic and angiogenic capacities. In the current study, lithium-containing magnesium phosphate-based ceramics (AMP/LMPGs) were prepared from amorphous magnesium phosphate (AMP) at a low sintering temperature (650 °C), and the lithium/magnesium-containing phosphate glasses (LMPGs) were utilized as sintering additives. During the sintering procedure of AMP/LMPGs, the AMP reacted with LMPGs, producing new compounds. The AMP/LMPGs displayed nano-size grains and plentiful micropores. The addition of LMPGs noticeably increased the porosity as well as compressive strength of the AMP/LMPGs ceramics. The AMP/LMPGs sustainedly released Mg, P and Li ions, forming Mg-rich ionic microenvironment, which ameliorated cellular proliferation, osteogenic differentiation and proangiogenic capacities. The AMP/LMPGs ceramics with considerably high compressive strength, osteostimulation and proangiogenic effects were expected to efficiently regenerate the bone defects.

3D-plotted zinc silicate/ß-tricalcium phosphate ceramic scaffolds enable fast osteogenesis by activating the p38 signaling pathway.

Biomaterials in combination with multiple bioactive ions could create a favorable microenvironment for bone remolding. Herein, zinc silicate/ß-tricalcium phosphate (ZS/ß-TCP) composite ceramic scaffolds with different amounts of ZS (5, 10, and 15 wt%) were constructed using a three-dimensional fiber deposition (3DF) technique. The physicochemical, osteogenic and angiogenic properties of these interconnected macroporous scaffolds were investigated systematically. Simultaneously, GeneChip, alkaline phosphatase (ALP), western blot (WB) and polymerase chain reaction (PCR) were utilized to elucidate the underlying mechanism of the enhancement in osteogenic differentiation. The results showed that the incorporation of ZS significantly improved the mechanical performance by more than 5 fold in comparison with the ß-TCP ceramic scaffold (4.79 ± 0.99 MPa). The ZS modified ß-TCP scaffolds greatly supported the cytoactivity, adhesion, proliferation of mouse bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs). The expression levels of osteogenic genes and proteins as well as angiogenic genes were markedly upregulated by the sustained release of bioactive ions (mainly Si and Zn) from the composite scaffolds. The 10ZS/ß-TCP demonstrated the best overall performance in vitro. Moreover, the 10ZS/ß-TCP displayed a high bone volume fraction, bone maturity and angiogenesis after implantation in the rat skull defects for 6 weeks. It was further verified that ZS/ß-TCP scaffolds stimulated the osteogenic differentiation of mBMSCs by activating the p38 signaling pathway directly. The 10ZS/ß-TCP ceramic scaffold holds great potential for the fast repair of bone defects, and deep understanding of the mechanism will facilitate the formulation of new strategies for bone repair.

Zinc-doped calcium silicate additive accelerates early angiogenesis and bone regeneration of calcium phosphate cement by double bioactive ions stimulation and immunoregulation.

Calcium phosphate cement (CPC), a popular injectable bone defect repairing material, has deficiencies in stimulating osteogenesis and angiogenesis. To overcome the weaknesses of CPC, zinc-doped calcium silicate (Zn-CS) which can release bioactive silicon (Si) and zinc (Zn) ions was introduced to CPC. The physicochemical and biological properties of CPC and its composites were evaluated. Firstly, the most effective addition content of calcium silicate (CaSiO3, CS) in promoting the in vitro osteogenesis was first sorted out. On this basis, the most effective Zn doping content in CS for improving osteogenic differentiation of CPC-based composites was screened out. Finally, the immunoregulation of CS/CPC and Zn-CS/CPC in promoting angiogenesis and osteogenesis was studied. The results showed that the most effective incorporation content of CS was 10 wt%. Zn at a doping content of 30 mol% in CS (30Zn-CS) further enhanced the osteogenic capacity of CS/CPC and simultaneously maintained excellent proangiogenic activity. CS/CPC and 30Zn-CS/CPC promoted the recruitment of macrophages and enhanced M2 polarization while inhibiting M1 polarization, which was beneficial to the early vascularization as well as subsequent new bone formation. When implanted into the femoral condylar defects of rabbits, 30Zn-CS/CPC showed high in vivo materials degradation rate, angiogenesis and osteogenesis, due to the synergistic effects of Si and Zn on bio-stimulation and immunoregulation. This study shed light on the synergistic effects of Si and Zn on regulating the angiogenic, osteogenic, and immunoregulatory activity, and 30Zn-CS/CPC is expected to repair the lacunar bone defects effectively.

Preparation and characterization of novel lithium magnesium phosphate bioceramic scaffolds facilitating bone generation.

Both magnesium and lithium are able to stimulate osteogenic and angiogenic activities. In this study, lithium magnesium phosphate (Li0.5Mg2.75(PO4)2, Li1Mg2.5(PO4)2 and Li2Mg2(PO4)2) biomaterials were synthesized by a solid-state reaction method, and their bioceramic blocks and scaffolds were fabricated by compression molding and 3D printing, respectively. The results indicated that the lithium magnesium phosphates consisted of the Mg3(PO4)2 phase and/or LiMgPO4 phase. Compared with the lithium-free Mg3(PO4)2 bioceramics, the lithium magnesium phosphate bioceramics showed a lower porosity and consequently a higher compressive strength, and stimulated in vitro cellular proliferation, osteogenic differentiation and proangiogenic activity. In vivo results manifested that the Li2Mg2(PO4)2 bioceramic scaffolds efficiently promoted bone regeneration of critical-size calvarial defects in rats. Benefiting from the high compressive strength and capacity of stimulating osteogenesis and angiogenesis, the Li2Mg2(PO4)2 bioceramic scaffolds are considered promising for efficiently repairing the bone defects.

Enhancing the bioactivity of hydroxyapatite bioceramic via encapsulating with silica-based bioactive glass sol.

Although hydroxyapatite (HA) bioceramic has excellent biocompatibility and osteoconductivity, its high chemical stability results in slow degradation which affects osteogenesis, angiogenesis and clinical applications. Silica-based bioglass (BG) with superior biological performance has been introduced into HA bioceramic to overcome this insufficiency; however, the composite bioceramics are usually prepared by traditional mechanical mixture of HA and BG powders, which tremendously weakens their mechanical performance. In this research, BG-modified HA bioceramics were prepared by the use of BG sol encapsulated HA powders. The results showed that introducing 1 and 3 wt% BG allowed the HA-based bioceramics to maintain the high compressive strength (>300 MPa), improved the apatite mineralization activity, and played an important role in cellular response. The bioceramic modified with 1 wt% BG (1BG/HA) remarkably enhanced in vitro cell proliferation, osteogenic and angiogenic activities. This present work provides a new strategy to improve the biological performance of bioceramics and the HA-based bioceramics with 1 wt% BG can be as a promising candidate material for bone repair.

Enhanced osteogenesis and angiogenesis of calcium phosphate cement incorporated with zinc silicate by synergy effect of zinc and silicon ions.

Calcium phosphate cement (CPC) with good injectability and osteoconductivity plays important roles in bone grafting application. Much attention has been paid to achieve multifunctionality through incorporating trace elements into CPC. Silicon and zinc can be used as additives to endow CPC with biological functions of osteogenesis, angiogenesis and anti-osteoclastogenesis. In this study, zinc and silicate ions were co-incorporated into CPC through mixing with submicron zinc silicate (Zn2SiO4, ZS) to obtain zinc silicate-modified CPCs (ZS/CPCs) with different contents. The results revealed that the addition of ZS increased the compressive strength, prolonged the setting time, and densified the structure of CPC. Low addition content of ZS facilitated the formation of surface apatite layer in the early mineralization stage. Incorporating ZS significantly induced osteogenesis of mouse bone marrow stromal cells (mBMSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs), and moreover, restricted osteoclastogenesis of Raw 264.7 in vitro. Silicate and zinc ions could be steadily released from ZS/CPCs into the culture medium. With the synergistic effect of silicate and zinc ions, ZS/CPCs provided an appropriate microenvironment for the immune cells to facilitate the osteogenesis of mBMSCs and angiogenesis of HUVECs further. Taken together, it can be concluded that incorporating ZS is an effective way to endow CPC with multifunctionality and better bone regeneration for bone defect repair.

NIR-Responsive Ti3 C2 MXene Colloidal Solution for Curing Purulent Subcutaneous Infection through the "Nanothermal Blade" Effect.

Pathogenic microorganisms' infections have always been a difficult clinical challenge and lead to serious health problems. Thus, a new strategy is urgently needed. In this study, a simple preparation method for Ti3 C2 MXene colloidal solution is proposed. In vitro, Staphylococcus aureus is treated with 250 µg mL-1 of Ti3 C2 colloidal solution under 5 min of 808 nm near-infrared (NIR) laser irradiation twice. Staphylococcus aureus is eliminated by the "nanothermal blade" effect from Ti3 C2 combined with NIR; the antibacterial rate is 99%, which is higher than the antibacterial rate of pure Ti3 C2 alone 78%. The antibacterial mechanism underlying this treatment may be that the thermal Ti3 C2 nanosheets first transfer heat to the cell membrane, disrupting the membrane structure, disturbing the metabolism and causing leakage of bacterial protein and deoxyribonucleic acid, consequently leading to bacterial death. In vivo results indicate that Ti3 C2 colloidal solution under NIR can effectively kill Staphylococcus aureus and prevent inflammation. Moreover, 250 µg mL-1 Ti3 C2 colloidal solution is nontoxic to mouse organs during the therapeutic process. Therefore, Ti3 C2 colloidal solution can be an ideal candidate for subcutaneous infection application. The antibacterial mechanism proposed in this study aids the investigation of other MXenes as antibacterial agents.

Cancer killers in the human gut microbiota: diverse phylogeny and broad spectra.

Cancer as a large group of complex diseases is believed to result from the interactions of numerous genetic and environmental factors but may develop in people without any known genetic or environmental risks, suggesting the existence of other powerful factors to influence the carcinogenesis process. Much attention has been focused recently on particular members of the intestinal microbiota for their potential roles in promoting carcinogenesis. Here we report the identification and characterization of intestinal bacteria that exhibited potent anti-malignancy activities on a broad range of solid cancers and leukemia. We collected fecal specimens from healthy individuals of different age groups (preschool children and university students), inspected their effects on cancer cells, and obtained bacteria with potent anti-malignancy activities. The bacteria mostly belonged to Actinobacteria but also included lineages of other phyla such as Proteobacteria and Firmicutes. In animal cancer models, sterile culture supernatant from the bacteria highly effectively inhibited tumor growth. Remarkably, intra-tumor administration of the bacterial products prevented metastasis and even cleared cancer cells at remote locations from the tumor site. This work demonstrates the prevalent existence of potent malignancy-killers in the human intestinal microbiota, which may routinely clear malignant cells from the body before they form cancers.