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The combination of photothermal therapy and chemical drug therapy shows good prospects in cancer treatment, but there are also some limitations such as low permeability of therapeutic agents and uneven photothermal therapy. Here, we synthesized a walnut-shaped polydopamine (PDA) nanomotor driven by near infrared (NIR) light. The nanomotor was modified by methoxy polyethylene glycol amine (mPEG-NH

Background The mitochondrial tRNA translation optimization 1 (MTO1) gene, which is closely related to defective mitochondrial oxidative phosphorylation, is an evolutionarily conserved protein expressed in high energy-demanding tissues and is associated with complex oxidative phosphorylation deficiency type 10 (COXPD10) in humans. Related cases and studies are still scarce and have not been reported in the Chinese region. Materials and methods Detailed clinical assessment was applied to the patient. Based on next-generation sequencing technology, we performed whole-exome sequencing of the patient and the parents. Sanger sequencing was used for validation. Bioinformatics software and protein simulations were used to predict the pathogenicity of the variants. Results The patient was diagnosed with a possible association with mitochondrial disease according to the clinical manifestations and physical examination. A novel frameshift mutation c.344delA (p. Asn115Thrfs*11) and a novel point mutation c.1055C > T (p. Thr352Met) in the MTO1 gene were identified. They were found to cause abnormal changes in amino acids and the protein by biochemical tools, indicating it may be pathogenic. Conclusion We present two novel and possibly pathogenic variants in the MTO1 gene in a Chinese Han family.

Myristic acid-palmitic acid-tetradecanol/expanded graphite (MA-PA-TD/EG) and myristic acid-stearic acid-lauric acid/ expanded graphite (MA-SA-LA/EG) were obtained. MA-PA-TD/EG and MA-SA-LA/EG for the optimum mass ratio of 8:1 were investigated by DSC, FT-IR, TG, and SEM, and it was shown that MA-PA-TD and MA-SA-LA phase change materials were evenly distributed in expanded graphite through capillary force. Phase transition temperatures of MA-PA-TD/EG and MA-SA-LA/EG before and after cooling and heating cycles were 34.14, 34.39 °C and 30.21, 30.33 °C, respectively, and MA-PA-TD/EG and MA-SA-LA/EG had good stability. On the other hand, MA-PA-TD/EG was 67% faster than that of MA-PA-TD during solid-liquid phase change, and MA-SA-LA/EG was 63% faster than that of MA-SA-LA. Meanwhile, MA-PA-TD/EG and MA-SA-LA/EG had good thermal stability and heat storage according to thermogravimetric experiments. Therefore, MA-PA-TD/EG and MA-SA-LA/EG are suitable for practical application in buildings.

Bioinspired strategies have recently emerged as novel approaches for designing a functionalized nanovector with enhanced tumor targeting and therapeutic efficacy. Herein, a virus-like Fe3O4/Au@C nanovector is described for programmable drug delivery via hierarchical targeting. Specifically, the virus-like Fe3O4/Au@C nanovector is synthesized via a simple hydrothermal process, and then the spiky surface of which is camouflaged via doxorubicin (DOX)-conjugated polyethylene glycol (PEG), constructing an innovative virus-like core/spherical shell biomimetic nanomedicine (Fe3O4/Au@C-DOX-PEG), which is conducive to improve bioavailability and reduce adverse effects. After systemic administration, the as-prepared nanomedicine is capable of facilitating effective tumor accumulation and deep tumor penetration with the assistance of an external magnetic field and endogenous pH stimuli. Simultaneously, in response to the acidic tumor microenvironment, Fe3O4/Au@C-DOX nanocomposites are released and exhibit excellent performance in cellular internalization through a virus-mimetic rough surface. Furthermore, the in vivo experiments identify that the unique nanomedicine is bestowed with an effective targeting tumor, prominent antitumor efficacy, and reduced systemic toxicity. Such a bioinspired hierarchical targeting nanoplatform holds promising potential for enhanced chemotherapeutic intracellular delivery and tumor theranostics.

Cancer is one of the main diseases threatening human health. Immunotherapy, in which cancer is treated by activating immune cells and inducing the body's immune response, has rapidly developed. Photothermal therapy (PTT), a new treatment method that ablates tumors by light irradiation, has attracted great attention for its good therapeutic effect and low toxic side effects. In the present study, we combined photothermal and immunotherapy to design a novel nanoparticle delivery system by loading indoleamine 2,3-dioxygenase (IDO) inhibitors and toll-like receptor (TLR) agonists into polydopamine (PDA) nanoparticles coated with polyethylene imine (PEI). This delivery system has the advantages of high homogeneity, good stability, excellent biocompatibility, and low toxicity.

Sclerotial development is a vital stage in the life cycles of many fungal plant pathogens. In this study, the protein Ss-CAD, which contains three conserved domains of cinnamyl alcohol dehydrogenase (CAD), was found to be required for sclerotial development in Sclerotinia sclerotiorum. Ss-CAD was significantly upregulated during early stage of sclerotial development. In Ss-CAD-silenced strains, sclerotial development was abnormal. In these silenced strains, formation of sclerotia was delayed or sclerotia yield was reduced, whereas hyphal growth and virulence were normal. Nox1, Nox2, and NoxR, which encode reactive oxygen species (ROS)-generating NADPH oxidases, were downregulated in Ss-CAD-silenced strains. NoxR-silenced strains displayed similar defects during sclerotial formation as Ss-CAD-silenced strains. Treatment of Ss-CAD-silenced strains with exogenous oxidants or NADPH restored normal sclerotial development. Sclerogenesis in Ss-CAD-silenced strains could also be recovered through Nox1 overexpression. The results suggest that Ss-CAD is linked to the NADPH oxidase pathways to affect sclerotial development in S. sclerotiorum.

Photodynamic therapy (PDT) is strongly O2 dependent. Therefore, its therapeutic effects are seriously hindered in hypoxic tumors. Red blood cells are responsible for delivering O2 in the blood. In this manuscript, biomimetic red blood cells (BRBCs) were exploited using a layer-by-layer assembly method, using Fe3O4@CuO, oxyhemoglobin (OxyHb), a photosensitizer and a photo-cross linked acrylate modified hyaluronic acid (HA) gel shell. The Fe3O4@CuO core has very high OxyHb loading efficiency (the adsorption capacity of Fe3O4@CuO for OxyHb is derived to be 0.99 mg mg-1) to ensure a sufficient O2 supply. OxyHb was protected well by the HA shell in order to avoid O2 release during the delivery process in blood before arrival at the tumor tissue. The HA shell protection can be eliminated in position at the tumor to trigger O2 release through hyaluronidase (HAase) triggered HA degradation. Furthermore, Fe3O4 in the nanosystem can provide magnetic field assisted tumor targeting and magnetic resonance imaging of the tumor. Therefore, this work presents a highly efficient all-in-one biomimetic nanomedicine approach to overcome hypoxia and achieve tumor targeting theranostics.

Multimode sensing has attracted extensive attention because they provide more than one transduction channel, thus improving accuracy and sensitivity. Due to the structural diversity, MnO2 nanosheets and nanoneedles were successively obtained via one-step redox reaction and different self-assembly methods. MnO2 nanosheets possess outstanding optical properties including extremely strong resonance Rayleigh scattering (RRS) and absorbance signal, and were selected as a dual-mode sensing material. Inspired by the selectivity of alkaline phosphatase (ALP) towards dephosphorylate ascorbic acid 2-phosphate (AAP) to generate ascorbic acid (AA), which has the ability to decompose MnO2 nanosheets along with optical signals and colour change, a dual-mode optical ALP sensing platform has been designed. Therefore, MnO2 nanosheets can serve as colorimetric probes by directly visualizing the colour variation with bare eyes. Moreover, the detection limit obtained by the RRS sensing mode can be as low as 0.17 mU L−1, which is far superior to that obtained by previously reported methods. The strategy not only has good feasibility and sensitivity, but also shows good prospects for a series of ALP-extended sensing applications.

The common existence of hypoxia within the tumor microenvironment severely restricts the efficacy of photodynamic therapy (PDT), which is attributed to the fact that the PDT process is strongly oxygen (O2) dependent. Here, a multifunctional composite (named CPCG), which combines polyethylene glycol (PEG) functionalized cerium oxide nanoparticles (CeO2) with photosensitizer chlorin e6 (Ce6) and glucose oxidase (GOx), is reported for generating O2 within the tumor microenvironment by the dual-path hydrogen peroxide (H2O2)-modulated ways to ameliorate hypoxia, thereby enhancing the PDT efficiency. This process is realized based on the dual enzyme-like activity of CeO2. The first modulated way is to transform the superoxide anion (O2˙-) into H2O2 by the superoxide dismutase-like activity of CeO2. The second modulated way is to decompose glucose into H2O2 through the catalysis of GOx. Subsequently, H2O2 generated from the above dual modulated ways can further produce O2via the catalase-like activity of CeO2. Additionally, the depletion of glucose could impede the nutrient supply to obtain starvation therapy. Both in vitro and in vivo experiments indicate that the CPCG composite could enhance the efficacy of photodynamic/starvation synergistic therapy. Therefore, this strategy offers great potential to modulate the O2 level in the tumor microenvironment for better therapeutic outcomes, and can act as a promising candidate in photodynamic/starvation synergistic therapy.

Bioinspired strategies have recently emerged as novel approaches for designing a functionalized nanovector with enhanced tumor targeting and therapeutic efficacy. Herein, a virus-like Fe

Docker is the de-facto container technology for software system deployment and delivery. A Dockerfile specifies how to containerize a system into a Docker image. However, creating a Dockerfile is not trivial since resolving the dependencies (e.g., third-party libraries) of diverse software requires comprehensive domain knowledge. In this paper, we propose DockerGen to containerize software packages automatically. DockerGen constructs a knowledge graph containing rich knowledge of building Docker images by analyzing nearly 220 thousand Dockerfiles. DockerGen exploits the knowledge graph to containerize the target software by creating a Dockerfile specifying the base image, dependencies, and the operation workflow. We evaluate DockerGen on 100 software packages of various categories. DockerGen achieves a 73% build success rate and a 59% configuration success rate. The experimental result indicates it is viable to automate software containerization based on a domain knowledge graph.

The tumor microenvironment (TME) is composed of tumor cells, blood vessels, cancer-associated fibroblasts (CAFs), tumor extracellular matrix (ECM), et al. The TME is closely related to anticancer treatment outcome. In this manuscript, a multifunctional nanomedicine (denoted as ZDCMH NP), combining multiple TME destruction strategies into one delivery system, has been designed and fabricated. In brief, zinc phthalocyanine (ZnPc, a photosensitizer), bromopentacarbonylmanganese(I) (COMn, a CO donor), and losartan (Dup, a CAF inhibitor) were coloaded inside mesoporous silica nanoparticles (MSNs). After that, a cross-linked hyaluronic acid (HA) gel shell was encapsulated onto the surface of the MSNs to form ZDCMH NPs. After arriving at the tumor tissue, the HA gel shell could be degraded by hyaluronidase (HAase) in the ECM to trigger encapsulated drug release. After light irradiation, ZnPc generated abundant reactive oxygen species (ROS), which could provide photodynamic therapy (PDT) activity and induce COMn to release CO, which could improve the enhanced permeability and retention (EPR) effect to promote ZDCMH NP accumulation in tumor tissue. The released Dup could inhibit CAF activity and downregulate the collagen fiber concentration in the TME to promote the deep penetration of ZDCMH NPs inside solid tumors. In vitro and in vivo anticancer studies have indicated that the destruction of the TME by multiple strategies is very helpful for ZnPc to obtain satisfactory PDT efficiency.

The cancer cell membrane (CCM) is widely used for nanomedicine encapsulation to improve their tumor-targeting ability. However, few researches are focused on drug release process and mechanism of these composite. Cell membrane fusion (two separate lipid membranes merge into a single continuous bilayer), one of the most fundamental processes in biology could be promoted by heating. Thus, in this manuscript, CCM was exploited as the gate keeper and tumor-targeting moiety of anticancer drug-loaded mesoporous silica nanoparticles (MSN). In addition, the drug release process and mechanism based on cell membrane fusion were studied. The loaded drugs included indocyanine green (ICG), a FDA-approved near-infrared photothermal agent for clinical applications, and doxorubicin (DOX), a chemotherapy drug. By coating CCM on drug-loaded MSN, the keeper could prevent unexpected drug leaking during the circulation and provide tumor targeting based on its specific recognition function. After arriving tumor tissue post-tail vein injection, the tumor position is irradiated by 808 nm light to trigger light–thermal conversion process of ICG to heat the composite (DOX-ICG@MSN@CCM) and promote cell membrane fusion between the encapsulated CCM and targeted tumor cell membrane. Such process can enhance the uptake efficacy of DOX-ICG@MSN@CCM to tumor cells. Furthermore, ICG could provide a synergistic photothermal therapy activity with DOX.

Generalized pustular psoriasis (GPP) is a rare and severe auto-inflammatory skin disease that is characterized by recurrent, acute onset, and generalized pustular eruptions on erythematous, inflamed skin. GPP is traditionally classified as a variant of psoriasis vulgaris, even though recent clinical, histological and genetic evidence suggests that it is a heterogeneous disease and requires a separate diagnosis. In recent years, variants of IL36RN, CARD14, AP1S3 and MPO genes have been identified as causative or contributing to genetic defects in a proportion of patients affected by GPP. These disease-related genes are involved in common inflammatory pathways, in particular in the IL-1/IL-36-chemokines-neutrophil pathogenic axis. At present, no standard therapeutic guidelines have been established for GPP management, and there is a profound need for novel efficacious treatments of GPP. Among them, biological agents antagonizing the IL-36 pathway are promising therapeutics. The aim of the present review is to provide the most recent updates on the genetics, genotype-phenotype correlation and pathological basis of GPP, as well as on biologic treatments available for GPP and relative clinical courses.

The low depth of tissue penetration by therapeutic light sources severely restricts photodynamic therapy (PDT) in treating deep-seated tumors. Using a luciferase/d-luciferin bioluminescence system to artificially create internal light sources in cells instead of external light sources is an effective means of solving the above problems. However, high-efficiency bioluminescence requires a higher concentration of luciferase in the cell, which poses a considerable challenge to the existing system of enzyme loading, delivery, activity and retention of drugs, and dramatically increases the cost of treatment. We loaded the substrate D-luciferin, and the photosensitizer hypericin into a polyethyleneimine (PEI)-modified nano-calcium phosphate (CaP) to solve this problem. Subsequently, the plasmid DNA containing the luciferase gene was loaded onto it using the high-density positive charge characteristic of PEI from the nanodrug (denoted DHDC). After the DHDC enters the tumor cell, it collapses and releases the plasmid DNA, which uses the intracellular protein synthesis system to continuously and massively express luciferase. Using endogenous ATP, Mg2+ , and O2 in cells, luciferase oxidizes d-luciferin and produces luminescence. The luminescence triggers hypericin excitation to generate ROS and kill cancer cells. This study provides a new strategy for the application of bioluminescence in PDT treatment.

Base-pairing is stable under physiological temperature but broken by heating, which is the basic mechanism for nucleic acid amplification in biology. In this manuscript, a simple controlled-drug-release system was prepared on the basis of this rule and its in vivo activity was studied. Poly adenine (poly A), the tail of the synthesized RNA chain, was exploited as gatekeeper of thymine (T)-modified mesoporous silica nanoparticles (MSN-T) based on the simple A-T base-pairing rules. The gate keeper maintains stability to avoid drug (chemotherapy and photothermal therapy drugs) release during the delivery process but is effectively removed by a photothermal effect to trigger drug release at the tumor tissue by near-infrared (NIR) laser irradiation. In vitro and in vivo experiments indicated that the prepared nanomedicine could effectively suppress tumor growth and activate antitumor immunity.

Ti-based immobilized metal affinity chromatography (IMAC) nanomaterial has shown high potential in phosphoproteome mass-spectrometric (MS) analysis. However, the limited surface area and poor solubility will greatly restrict its use in phosphoproteome research. To overcome these two key drawbacks, a novel Ti-based IMAC nanomaterial was prepared by Ti-bonded β-cyclodextrin (β-CD) anchored on the surface of carbon nanotubes (CNTs) (denoted as COOH-CNTs-CD-Ti) and successfully applied as a biofunctional adsorbent for selectively enriching trace phosphopeptides. In the selective enrichment process, CNTs provided greater surface area for the absorption of phosphopeptides, while β-CD also offered a greater opportunity for the interaction between phosphopeptides and Ti4+. COOH-CNTs-CD-Ti with the aforementioned properities exhibited higher selectivity for phosphopeptides from the standard protein digests, the tryptic digests of nonfat milk and human serum, showing a great selective enrichment capability towards complex biological samples.

To enhance affinity to their hosts, many organisms have evolved to be spiky. This strategy has been inspiring in many fields, but in drug delivery, the feasibility has not yet been extensively explored due to the lack of suitable nanocarriers. Herein, viruslike mesoporous FeSe

Virus-like nanostructures could involve their interaction with biological hosts, as well as adaptive immune responses. Herein, imitating the intrinsic structure of virus, we formulated novel virus-like hollow mesoporous silica nanoparticles (VH-MSNs) by using self-consuming perovskite template. The unique topological structure on the surface of nanoparticles could enhance cellular uptake and amplify the immune response. By loading doxorubicin (DOX) on nanoparticles, we achieved a combination of chemotherapy and immunotherapy. This study provides a promising platform with superior cellular uptake property for drug delivery and a basis for the study of the effect of surface physical structure on the nanocarriers.