Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.

F127-SE-tLAP thermosensitive hydrogel alleviates bleomycin-induced skin fibrosis via TGF-ß/Smad pathway.

BACKGROUND: Skin fibrosis affects the normal function of the skin. TGF-ß1 is a key cytokine that affects organ fibrosis. The latency-associated peptide (LAP) is essential for TGF-ß1 activation. We previously constructed and prepared truncated LAP (tLAP), and confirmed that tLAP inhibited liver fibrosis by affecting TGF-ß1. SPACE peptide has both transdermal and transmembrane functions. SPACE promotes the delivery of macromolecules through the stratum corneum into the dermis. This study aimed to alleviate skin fibrosis through the delivery of tLAP by SPACE. METHODS: The SPACE-tLAP (SE-tLAP) recombinant plasmid was constructed. SE-tLAP was purified by nickel affinity chromatography. The effects of SE-tLAP on the proliferation, migration, and expression of fibrosis-related and inflammatory factors were evaluated in TGF-ß1-induced NIH-3T3 cells. F127-SE-tLAP hydrogel was constructed by using F127 as a carrier to load SE-tLAP polypeptide. The degradation, drug release, and biocompatibility of F127-SE-tLAP were evaluated. Bleomycin was used to induce skin fibrosis in mice. HE, Masson, and immunohistochemistry were used to observe the skin histological characteristics. RESULTS: SE-tLAP inhibited the proliferation, migration, and expression of fibrosis-related and inflammatory factors in NIH-3T3 cells. F127-SE-tLAP significantly reduced ECM production, collagen deposition, and fibrotic pathological changes, thereby alleviating skin fibrosis. CONCLUSION: F127-SE-tLAP could increase the transdermal delivery of LAP, reduce the production and deposition of ECM, inhibit the formation of dermal collagen fibers, and alleviate the progression of skin fibrosis. It may provide a new idea for the therapy of skin fibrosis.

Minimalist Nanovaccine with Optimized Amphiphilic Copolymers for Cancer Immunotherapy.

Cancer vaccines with the ability to elicit tumor-specific immune responses have attracted significant interest in cancer immunotherapy. A key challenge for effective cancer vaccines is the spatiotemporal codelivery of antigens and adjuvants. Herein, we synthesized a copolymer library containing nine poly(ethylene glycol) methyl ether methacrylate-co-butyl methacrylate-co-2-(azepan-1-yl)ethyl methacrylate (PEGMA-co-BMA-co-C7AMA) graft copolymers with designed proportions of different components to regulate their properties. Among these polymers, C-25, with a C7AMA:BMA ratio at 1.5:1 and PEG wt % of 25%, was screened as the most effective nanovaccine carrier with enhanced ability to induce mouse bone marrow-derived dendritic cell (BMDC) maturation. Additionally, RNA-sequencing (RNA-Seq) analysis revealed that C-25 could activate dendritic cells (DCs) through multisignaling pathways to trigger potent immune effects. Then, the screened C-25 was used to encapsulate the model peptide antigen, OVA257-280, to form nanovaccine C-25/OVA257-280. It was found that the C-25/OVA257-280 nanovaccine could effectively facilitate DC maturation and antigen cross-presentation without any other additional adjuvant and exhibited excellent prophylactic efficacy in the B16F10-OVA tumor model. Moreover, in combination with antiprogrammed cell death protein-ligand 1 (anti-PD-L1), the C-25/OVA257-280 nanovaccine could significantly delay the growth of pre-existing tumors. Therefore, this work developed a minimalist nanovaccine with a simple formulation and high efficiency in activating tumor-specific immune responses, showing great potential for further application in cancer immunotherapy.

Superior energy storage properties in SrTiO3-based dielectric ceramics through all-scale hierarchical architecture.

The restricted energy density in dielectric ceramic capacitors is challenging for their integration with advanced electronic systems. Numerous strategies have been proposed to boost the energy density at different scales or combine those multiscale effects. Herein, guided by all-scale synergistic design, we fabricated Sr0.7Bi0.2TiO3 ceramics doped with (Bi0.5Na0.5)(Zr0.5Ti0.5)O3 by sintering the nanopowders by solution combustion synthesis, which demonstrate exceptional energy storage performance (ESP). Notably, an ultrahigh recoverable energy density of 11.33 J cm-3, accompanied by an impressive energy efficiency of 89.30%, was achieved at an extremely high critical electric field of 961 kV cm-1. These primary energy storage parameters outperform those of previously reported ceramic capacitors based on SrTiO3. Additionally, an excellent comprehensive performance is also realized, including a substantial power density of 156.21 MW cm-3 (at 300 kV cm-1), an extraordinarily short discharge time of 97 ns, a high Vickers hardness rating of approximately 8.23 GPa, and outstanding thermal and frequency stability. This enhancement can be attributed to the synergistic effect at all scales from atomic substitution, polar nano regions, submicrometer grain, and sample thickness. Consequently, this panoscopic approach has effectively demonstrated the potential to enhance the ESP of dielectric ceramics.

Global research trends in sexual health care: A bibliometric and visualized study.

No Patient or Public Contribution, because the relevant data of this article comes from the literature database. PURPOSE: The present study aimed to investigate the trends and research status of sexual healthcare. METHODS: We searched the Web of Science database for relevant articles concerning sexual healthcare, published between 2009 and 31 December 2022. Data collected include: the number of publications, authors, journals, countries, institutions, keywords. VOSviewer and CiteSpace were used to conduct the bibliometric study and visualise the analysis. RESULTS: A total of 1450 publications were included. The number of publications on sexual healthcare shows a fluctuating upward trend, and a stable core group of authors has been formed. The Journal of Clinical Nursing published the most articles on sexual healthcare (140 publications). The United States of America published the most articles (723, 49.86%). The research institution with the highest number of publications is the University of São Paulo. According to the keyword, timeline view and prominence mapping analysis, we believe that 'Female sexual health', 'HIV', 'LGBT' and 'Sexual Healthcare Services' may be new research hotspots in the field of sexual healthcare. CONCLUSION: This study describes the research status of sexual healthcare research over the past 14 years. The findings of this study can provide helpful reference and guidance for the development trend and research direction of sexual healthcare.

Delivery of short chain fatty acid butyrate to overcome Fusobacterium nucleatum-induced chemoresistance.

The gut microbiota is closely associated with the progression of colorectal cancer (CRC) in which Fusobacterium nucleatum (F. nucleatum) was found to induce cancer resistance to chemotherapeutics. To relieve F. nucleatum-induced drug resistance, herein, we found that short-chain fatty acid butyrate can inhibit the growth, enrichment and adhesion of F. nucleatum in colorectal cancer tissues by downregulating the expression of adhesion-associated outer membrane proteins, including RadD, FomA, and FadA, to reduce the colonization and invasion of F. nucleatum and relieve the chemoresistance induced by F. nucleatum. Leveraging the killing effect of butyrate on F. nucleatum, sodium butyrate (NaBu) was encapsulated in liposomes or prepared as NaBu tablets with Eudragit S100 coating and administered by intravenous injection or oral administration, respectively. Interestingly, both intravenous administration of NaBu liposomes and oral delivery of NaBu tablets could effectively inhibit the proliferation of F. nucleatum and significantly improve the therapeutic efficacy of oxaliplatin in mice with subcutaneous colorectal tumors, orthotopic colorectal tumors and even spontaneously formed colorectal tumors. Thus, our work provides a simple but effective formulation of NaBu to relieve F. nucleatum-induced chemoresistance, exhibiting ideal clinical application prospects.

Application of recombinant TGF-ß1 inhibitory peptide to alleviate isoproterenol-induced cardiac fibrosis.

Cardiac fibrosis is a remodeling process of the cardiac interstitium, characterized by abnormal metabolism of the extracellular matrix, excessive accumulation of collagen fibers, and scar tissue hyperplasia. Persistent activation and transdifferentiation into myofibroblasts of cardiac fibroblasts promote the progression of fibrosis. Transforming growth factor-ß1 (TGF-ß1) is a pivotal factor in cardiac fibrosis. Latency-associated peptide (LAP) is essential for activating TGF-ß1 and its binding to the receptor. Thus, interference with TGF-ß1 and the signaling pathways using LAP may attenuate cardiac fibrosis. Recombinant full-length and truncated LAP were previously constructed, expressed, and purified. Their effects on cardiac fibrosis were investigated in isoproterenol (ISO)-induced cardiac fibroblasts (CFs) and C57BL/6 mice. The study showed that LAP and tLAP inhibited ISO-induced CF activation, inflammation, and fibrosis, improved cardiac function, and alleviated myocardial injury in ISO-induced mice. LAP and tLAP alleviated the histopathological alterations and inhibited the elevated expression of inflammatory and fibrosis-related markers in cardiac tissue. In addition, LAP and tLAP decreased the ISO-induced elevated expression of TGF-ß, αvß3, αvß5, p-Smad2, and p-Smad3. The study indicated that LAP and tLAP attenuated ISO-induced cardiac fibrosis via suppressing TGF-ß/Smad pathway. This study may provide a potential approach to alleviate cardiac fibrosis. KEY POINTS: • LAP and tLAP inhibited ISO-induced CF activation, inflammation, and fibrosis. • LAP and tLAP improved cardiac function and alleviated myocardial injury, inflammation, and fibrosis in ISO-induced mice. • LAP and tLAP attenuated cardiac fibrosis via suppressing TGF-ß/Smad pathway.

Emerging trends of BCG immunotherapy for bladder cancer in last decade: a bibliometric and visualization analysis.

Background: One of the milestones in bacterial-mediated therapy for cancer, Bacillus Calmette-Guerin (BCG) has been used to treat bladder cancer (BC) for more than 30 years. BCG immunotherapy is now the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) following transurethral resection. Methods: We searched the Web of Science core collection (WoSCC) database and used bibliometric methods through CiteSpace (version 5.1.R6), VOSviewer (version 1.6.18) and R-Bibliometrix (version R 4.2.1) to analyze and discuss the current status and trends of BCG therapy of BC from 2012 to 2021 in terms of co-occurrence, co-polymerization and visualization. Results: A total of 2476 publications were found, with the majority coming from the United States and China. Over the last decade, overall yearly outputs have increased fivefold, from 117 papers in 2012 to 534 records in 2021. Most publications were produced by the University of Texas System. The authors, Ashish M. Kamat of the University of Texas-MD Anderson Cancer Center in the United States, and Shahrokh F. Shariat of Weill Cornell Medical College, were pioneers in this field with the most publications. The journals, Urologic Oncology Seminars and Original Investigations, Cancers and Frontiers in Oncology, have published a dramatic increase in the number of articles, and tumor and urology nephrology research directions have received the most attention from journals. Furthermore, recent research has concentrated on muscle-invasive bladder cancer (MIBC). BCG therapy mechanism, BCG dose and strains, targeted therapy and immune checkpoint inhibitors (ICIs) for BC were attractive research contents, with ICIs (PD-1, PD-L1) being the most popular study point in recent years. With more research on tumor immunology, screening for more reliable biomarkers for precision treatment, and the development of combination regimens of ICIs, targeted treatment of BC stem cells, and personalized BC therapies may be promising areas of immunotherapy research in the coming years. Conclusion: The results of this bibliometric study can provide the current status and research trends of BCG therapy for BC in the last decade, and also further complements the research content of bacterial-mediated cancer therapy.

A General Biomineralization Strategy to Synthesize Autologous Cancer Vaccines with cGAS-STING Activating Capacity for Postsurgical Immunotherapy.

Autologous cancer vaccines constructed by nonproliferative whole tumor cells or tumor lysates together with appropriate adjuvants represent a promising strategy to suppress postsurgical tumor recurrence. Inspired by the potency of cytosolic double-stranded DNA (dsDNA) in initiating anticancer immunity by activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, we herein report the concise synthesis of a cGAS-STING agonist through dsDNA-templated biomineralization growth of calcium carbonate (CaCO3) microparticles. The yielded DNA@CaCO3 can activate the intracellular cGAS-STING pathway of dendritic cells (DCs) by promoting endosomal escape of dsDNA, triggering their maturation and activation as a potent immune stimulator. Upon intratumoral injection, DNA@CaCO3 can reverse the immunosuppressive tumor microenvironment by simultaneously provoking innate and adaptive antitumor immunity, thereby effectively suppressing the growth of murine CT26 and B16-F10 tumors in mice. Furthermore, via CaCO3-based biomineralization of complete tumor lysates, we constructed a personalized autologous cancer vaccine with intrinsic cGAS-STING activation capacity that could provoke tumor-specific immune responses to not only delay the growth of challenged tumors but also synergize with anti-PD-1 immunotherapy to suppress postsurgical tumor recurrence. This study highlights a CaCO3-based biomineralization method to prepare autologous cancer vaccines in a concise manner, which is promising for personalized immunotherapy and clinical translation.

Regulating the Obesity-Related Tumor Microenvironment to Improve Cancer Immunotherapy.

Obesity usually induces systemic metabolic disturbances, including in the tumor microenvironment (TME). This is because adaptive metabolism related to obesity in the TME with a low level of prolyl hydroxylase-3 (PHD3) depletes the major fatty acid fuels of CD8+ T cells and leads to the poor infiltration and unsatisfactory function of CD8+ T cells. Herein, we discovered that obesity could aggravate the immunosuppressive TME and weaken CD8+ T cell-mediated tumor cell killing. We have thus developed gene therapy to relieve the obesity-related TME to promote cancer immunotherapy. An efficient gene carrier was prepared by modifying polyethylenimine with p-methylbenzenesulfonyl (abbreviated as PEI-Tos) together with hyaluronic acid (HA) shielding, achieving excellent gene transfection in tumors after intravenous administration. HA/PEI-Tos/pDNA (HPD) containing the plasmid encoding PHD3 (pPHD3) can effectively upregulate the expression of PHD3 in tumor tissues, revising the immunosuppressive TME and significantly increasing the infiltration of CD8+ T cells, thereby improving the responsiveness of immune checkpoint antibody-mediated immunotherapy. Efficient therapeutic efficacy was achieved using HPD together with αPD-1 in colorectal tumor and melanoma-bearing obese mice. This work provides an effective strategy to improve immunotherapy of tumors in obese mice, which may provide a useful reference for the immunotherapy of obesity-related cancer in the clinic.

Biosynthetic characterization of the antifungal fernane-type triterpenoid polytolypin for generation of new analogues via combinatorial biosynthesis.

Fernane-type triterpenoids are a small group of natural products mainly found in plants and fungi with a wide range of biological activities. Polytolypin is a representative fernane-type triterpenoid from fungi and possesses potent antifungal activity. So far, biosynthesis of fungal-derived fernane-type triterpenoids has not been characterized, which hinders the expansion of their structural diversity using biosynthetic approaches. Herein, we identified the biosynthetic gene cluster of polytolypin and elucidated its biosynthetic pathway through heterologous expression in Aspergillus oryzae NSAR1, which involves a new triterpene cyclase for the biosynthesis of the hydrocarbon skeleton motiol, followed by multiple oxidations via three P450 enzymes. Moreover, two new triterpene cyclases for the biosynthesis of two other fernane-type skeletons isomotiol and fernenol were identified from fungi, and were individually co-expressed with the three P450 enzymes involved in polytolypin biosynthesis. These studies led to the generation of 13 fernane-type triterpenoids including eight new compounds, and two of them showed stronger antifungal activity towards Candida albicans FIM709 than polytolypin.

Temperature-Dependent Affinity Changes in Substrate Binding Affect the Cleavage Activity of BthC2c1.

BACKGROUND: The CRISPR-Cas system is an adaptive immune mechanism for bacteria and archaea to resist foreign invasion. Currently, Cas9 and Cpf1 have been widely studied and applied in gene editing. C2c1 is a newly discovered CRISPR-Cas system endonuclease. It has broad application prospects due to its small molecular weight and high substrate recognition specificity. OBJECTIVES: Bacillus thermoamylovorans C2c1(BthC2c1) was expressed in E. coli C43 (DE3) competent cells, purified, and the BthC2c1-sgRNA-dsDNA complex was assembled. The effect of temperature on the cleavage ability of the BthC2c1 system was investigated. METHODS: The cDNA of BthC2c1 was cloned into the vector pGEX-6P-1. BthC2c1 was expressed in E. coli C43(DE3) cells and purified using a GST affinity column and FPLC. The sgRNAs were transcribed and purified in vitro, and the complexes were assembled by gel filtration chromatography. The enzyme cleavage activity of BthC2c1 at different temperatures was investigated using an in vitro cleavage assay. Microscale Thermophoresis detected the affinity of the BthC2c1-sgRNA complexes to substrate DNA. RESULTS: BthC2c1 proteins were prokaryotically expressed and purified. The complex of BthC2c1 with sgRNA and dsDNA was assembled. In vitro cleavage assay results showed that BthC2c1 cleaved the target DNA at temperatures ranging from 37°C to 67°C. The cleavage ability of BthC2c1 at 42oC was stronger than that at 37oC. The results of affinity detection showed that the affinity between the BthC2c1-sgRNA complex and ds36/36 at 42oC was stronger than that at 37oC. CONCLUSION: In this study, BthC2c1 was expressed, purified, and assembled into a complex with sgRNA and dsDNA. BthC2c1 cleaved DNA within the temperature range of 37oC to 67oC. The affinity of BthC2c1-sgRNA to DNA at 42°C was significantly enhanced than that at 37°C. It may be related to its stringent substrate recognition pattern, which differs from Cas9 and Cpf1. The temperature-dependent affinity changes of substrate binding may be part of the reason for the stronger cleavage activity of BthC2c1 at 42oC. This study may provide an experimental basis for optimizing and modifying the C2c1 gene editing system.

Fluoroalkane modified cationic polymers for personalized mRNA cancer vaccines.

Messenger RNA (mRNA) vaccines, while demonstrating great successes in the fight against COVID-19, have been extensively studied in other areas such as personalized cancer immunotherapy based on tumor neoantigens. In addition to the design of mRNA sequences and modifications, the delivery carriers are also critical in the development of mRNA vaccines. In this work, we synthesized fluoroalkane-grafted polyethylenimine (F-PEI) for mRNA delivery. Such F-PEI could promote intracellular delivery of mRNA and activate the Toll-like receptor 4 (TLR4)-mediated signaling pathway. The nanovaccine formed by self-assembly of F-PEI and the tumor antigen-encoding mRNA, without additional adjuvants, could induce the maturation of dendritic cells (DCs) and trigger efficient antigen presentation, thereby eliciting anti-tumor immune responses. Using the mRNA encoding the model antigen ovalbumin (mRNAOVA), our F-PEI-based mRNAOVA cancer vaccine could delay the growth of established B16-OVA melanoma. When combined with immune checkpoint blockade therapy, the F-PEI-based MC38 neoantigen mRNA cancer vaccine was able to suppress established MC38 colon cancer and prevent tumor reoccurrence. Our work presents a new tool for mRNA delivery, promising not only for personalized cancer vaccines but also for other mRNA-based immunotherapies.

ID-RDRL: a deep reinforcement learning-based feature selection intrusion detection model.

Network assaults pose significant security concerns to network services; hence, new technical solutions must be used to enhance the efficacy of intrusion detection systems. Existing approaches pay insufficient attention to data preparation and inadequately identify unknown network threats. This paper presents a network intrusion detection model (ID-RDRL) based on RFE feature extraction and deep reinforcement learning. ID-RDRL filters the optimum subset of features using the RFE feature selection technique, feeds them into a neural network to extract feature information and then trains a classifier using DRL to recognize network intrusions. We utilized CSE-CIC-IDS2018 as a dataset and conducted tests to evaluate the model's performance, which is comprised of a comprehensive collection of actual network traffic. The experimental results demonstrate that the proposed ID-RDRL model can select the optimal subset of features, remove approximately 80% of redundant features, and learn the selected features through DRL to enhance the IDS performance for network attack identification. In a complicated network environment, it has promising application potential in IDS.

Hierarchical core-shell-structured bimetallic nickel-cobalt phosphide nanoarrays coated with nickel sulfide for high-performance hybrid supercapacitors.

High-performance supercapacitors have attracted considerable interests due to their high-power density, fast charge/discharge process and long cycle life. However, the wide application of supercapacitors is limited by their low energy density. Herein, the hierarchical core-shell structured NiCoP@NiS nanoarrays have been successfully synthesized by using the vertically grown nickel-cobalt bimetallic phosphide (NiCoP) nanowire as the core and the nickel sulfide (NiS) by electrodeposition as the shell. As the "super channel" for electron transfer, the NiCoP core is coupled with the NiS shell to promote rapid diffusion of electrons and improve cycle stability of the electrode. Consequently, the optimized NiCoP@NiS nanoarrays display an extremely good specific capacitance (2128F g-1 at 1 A g-1) and a superior long cycle life (the capacitance retention of 90.36 % after 10,000 cycles). A hybrid supercapacitor (HSC) has been assembled using the NiCoP@NiS as the positive and the activated carbon (AC) as the negative, which displays a superior energy density of 30.47 Wh kg-1 at a remarkable power energy of 800 W kg-1. This study shows that the prepared hierarchical core-shell structured nanoarrays have great prospects as a novel electrode material in energy storage.

Recombinant truncated latency-associated peptide alleviates liver fibrosis in vitro and in vivo via inhibition of TGF-ß/Smad pathway.

BACKGROUND: Liver fibrosis is a progressive liver injury response. Transforming growth factor ß1 (TGF-ß1) is oversecreted during liver fibrosis and promotes the development of liver fibrosis. Therapeutic approaches targeting TGF-ß1 and its downstream pathways are essential to inhibit liver fibrosis. The N-terminal latency-associated peptide (LAP) blocks the binding of TGF-ß1 to its receptor. Removal of LAP is critical for the activation of TGF-ß1. Therefore, inhibition of TGF-ß1 and its downstream pathways by LAP may be a potential approach to affect liver fibrosis. METHODS: Truncated LAP (tLAP) plasmids were constructed. Recombinant proteins were purified by Ni affinity chromatography. The effects of LAP and tLAP on liver fibrosis were investigated in TGF-ß1-induced HSC-T6 cells, AML12 cells and CCl4-induced liver fibrosis mice by real time cellular analysis (RTCA), western blot, real-time quantitative PCR (RT-qPCR), immunofluorescence and pathological staining. RESULTS: LAP and tLAP could inhibit TGF-ß1-induced AML12 cells inflammation, apoptosis and EMT, and could inhibit TGF-ß1-induced HSC-T6 cells proliferation and fibrosis. LAP and tLAP could attenuate the pathological changes of liver fibrosis and inhibit the expression of fibrosis-related proteins and mRNAs in CCl4-induced liver fibrosis mice. CONCLUSION: LAP and tLAP could alleviate liver fibrosis in vitro and in vivo via inhibition of TGF-ß/Smad pathway. TLAP has higher expression level and more effective anti-fibrosis activity compared to LAP. This study may provide new ideas for the treatment of liver fibrosis.

Large-scale synthesis of ultrafine Fe3C nanoparticles embedded in mesoporous carbon nanosheets for high-rate lithium storage.

Fe3C modified by the incorporation of carbon materials offers excellent electrical conductivity and interfacial lithium storage, making it attractive as an anode material in lithium-ion batteries. In this work, we describe a time- and energy-saving approach for the large-scale preparation of Fe3C nanoparticles embedded in mesoporous carbon nanosheets (Fe3C-NPs@MCNSs) by solution combustion synthesis and subsequent carbothermal reduction. Fe3C nanoparticles with a diameter of ∼5 nm were highly crystallized and compactly dispersed in mesoporous carbon nanosheets with a pore-size distribution of 3-5 nm. Fe3C-NPs@MCNSs exhibited remarkable high-rate lithium storage performance with discharge specific capacities of 731, 647, 481, 402 and 363 mA h g-1 at current densities of 0.1, 1, 2, 5 and 10 A g-1, respectively, and when the current density reduced back to 0.1 A g-1 after 45 cycles, the discharge specific capacity could perfectly recover to 737 mA h g-1 without any loss. The unique structure could promote electron and Li-ion transfer, create highly accessible multi-channel reaction sites and buffer volume variation for enhanced cycling and good high-rate lithium storage performance.

Correction: Large-scale synthesis of ultrafine Fe3C nanoparticles embedded in mesoporous carbon nanosheets for high-rate lithium storage.

[This corrects the article DOI: 10.1039/D1RA08516F.].

Extensive expansion of the chemical diversity of fusidane-type antibiotics using a stochastic combinational strategy.

Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P1, are fungi-derived antimicrobials with little cross-resistance to commonly used antibiotics. Generation of new fusidane-type derivatives is therefore of great value, but this is hindered by available approaches. Here, we developed a stochastic combinational strategy by random assembly of all the post-tailoring genes derived from helvolic acid, fusidic acid, and cephalosporin P1 biosynthetic pathways in a strain that produces their common intermediate. Among a total of 27 gene combinations, 24 combinations produce expected products and afford 58 fusidane-type analogues, of which 54 are new compounds. Moreover, random gene combination can induce unexpected activity of some post-tailoring enzymes, leading to a further increase in chemical diversity. These newly generated derivatives provide new insights into the structure‒activity relationship of fusidane-type antibiotics. The stochastic combinational strategy established in this study proves to be a powerful approach for expanding structural diversity of natural products.

A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy.

Cancer metastases and recurrence after surgical resection remain an important cause of treatment failure. Here we demonstrate a general strategy to fabricate personalized nanovaccines based on a cationic fluoropolymer for post-surgical cancer immunotherapy. Nanoparticles formed by mixing the fluoropolymer with a model antigen ovalbumin, induce dendritic cell maturation via the Toll-like receptor 4 (TLR4)-mediated signalling pathway, and promote antigen transportation into the cytosol of dendritic cells, which leads to an effective antigen cross-presentation. Such a nanovaccine inhibits established ovalbumin-expressing B16-OVA melanoma. More importantly, a mix of the fluoropolymer with cell membranes from resected autologous primary tumours synergizes with checkpoint blockade therapy to inhibit post-surgical tumour recurrence and metastases in two subcutaneous tumour models and an orthotopic breast cancer tumour. Furthermore, in the orthotopic tumour model, we observed a strong immune memory against tumour rechallenge. Our work offers a simple and general strategy for the preparation of personalized cancer vaccines to prevent post-operative cancer recurrence and metastasis.