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Background In this study, an entomogenous, fungus was isolated from the Egyptian mealybug, Icerya aegyptiaca (J.) (Hemiptera: Monophlebidae) on the parasol leaf tree, Macaranga tanarius , in China where evaluated as a biocontrol fungus to reduce the population of the target insect. The strain was identified as Aspergillus parasiticus by morphological and phylogenetic analysisand named ZHKUAP1. The biological characteristics, pathogenicity, and field control effect of the strain were determined. Results The most suitable medium for the mycelial growth of strain ZHKUAP1 was PPDA medium, with an optimum temperature of 30 °C and pH 7, in addition to glucose and peptone as carbon and nitrogen sources. The optimum sporulation conditions were the PPDA medium at 30 °C and pH 6, using the soluble starch and beef extract as carbon and nitrogen sources. The mycelial growth and spore production of strain ZHKUAP1 were stopped at 70 °C and above, indicating that it was not resistant to high temperatures. High concentrations of spore suspension, against young insect age, resulted high corrected mortality, as well as decreased the median lethal time. When the spore concentration was 1 × 10 8 cfu/ml, the corrected mortality of the second nymph was 88.33%, and the LT 50 was 0.66 day. After 10 days of inoculation, the LC 50 of the second instar nymph was the smallest, reaching 4.07 × 10 4 cfu/ml. On the 10th day of the field experiment, the corrected mortality was 76.45%, indicating that the A. parasiticus strain ZHKUAP1 had strong pathogenicity on I. aegyptiaca population. Conclusions The indoor toxicity of the strain to I. aegyptiaca was determined, and the field control effect of the pathogen was explored on this basis. The results have important application prospects in the biological control of I. aegyptiaca.

The creation and development of classical multifunctional nanomaterials are crucial for the advancement of nanotherapeutic treatments for tumors. Currently, metal–organic frameworks (MOFs) modified with polydopamine (PDA) are at the forefront of nanomedicine research, particularly in tumor diagnostics and therapy, owing to their exceptional biocompatibility, expansive specific surface area, multifaceted functionalities, and superior photothermal properties, which led to significant advancements in anti-tumor research. Consequently, a range of anti-cancer strategies has been devised by leveraging the exceptional capabilities of MOFs, including intelligent drug delivery systems, photodynamic therapy, and photothermal therapy, which are particularly tailored for the tumor microenvironment. In order to gain deeper insight into the role of MOFs@PDA in cancer diagnosis and treatment, it is essential to conduct a comprehensive review of existing research outcomes and promptly analyze the challenges associated with their biological applications. This will provide valuable perspectives on the potential of MOFs@PDA in clinical settings.

Deep vein thrombosis is a common clinical peripheral vascular disease that occurs frequently in orthopaedic patients and may lead to pulmonary embolism (PE) if the thrombus is dislodged. pulmonary embolism can be prevented by placing an inferior vena cava filter (IVCF) to intercept the dislodged thrombus. Thus, IVCFs play an important role in orthopaedics. However, the occurrence of complications after inferior vena cava filter placement, particularly recurrent thromboembolism, makes it necessary to carefully assess the risk-benefit of filter placement. There is no accepted statement as to whether IVCF should be placed in orthopaedic patients. Based on the problems currently displayed in the use of IVCFs, an ideal IVCF is proposed that does not affect the vessel wall and haemodynamics and intercepts thrombi well. The biodegradable filters that currently exist come close to the description of an ideal filter that can reduce the occurrence of various complications. Currently available biodegradable IVCFs consist of various organic polymeric materials. Biodegradable metals have shown good performance in making biodegradable IVCFs. However, among the available experimental studies on degradable filters, there are no experimental studies on filters made of degradable metals. This article reviews the use of IVCFs in orthopaedics, the current status of filters and the progress of research into biodegradable vena cava filters and suggests possible future developments based on the published literature by an electronic search of PubMed and Medline databases for articles related to IVCFs searchable by October 2022 and a manual search for citations to relevant studies.

Gastric cancer (GC) is the most lethal malignancy in the digestive system. This study investigated an antibody-nanoparticle conjugate (ANC) constructed with trastuzumab (Herceptin®) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane®) (trastuzumab/nab-paclitaxel) as a novel strategy of targeted therapy for human epidermal growth factor receptor 2 (HER2) positive GC. The ANC was fabricated with trastuzumab and nab-paclitaxel by a 'one-step' synthesis using EDC/NHS. In vitro antitumor efficacy was evaluated by cell viability, apoptosis rate and cell cycle of HER2-positive GC NCI-N87 cells and compared with paclitaxel (Taxol®), nab-paclitaxel and trastuzumab/nab-paclitaxel. In addition, GC xenograft models were established to evaluate antitumor efficacy in vivo. These results demonstrated that trastuzumab/nab-paclitaxel was spherical with a suitable size (139.18±32.06 nm). The half-maximal inhibitory concentration (IC50) for NCI-N87 cells was 0.24±0.08, 0.13±0.03 and 0.048±0.01 µg/ml of paclitaxel, nab-paclitaxel and trastuzumab/nab-paclitaxel, respectively. Compared with paclitaxel and nab-paclitaxel, trastuzumab/nab-paclitaxel could induce a higher rate of apoptosis and significant G2/M arrest. At 4 weeks after treatment, tumor-bearing mice had a mean tumor volume of 233±24 mm3 treated by trastuzumab/nab-paclitaxel, 559±97 mm3 by nab-paclitaxel, 871±94 mm3 by paclitaxel and 1,576±190 mm3 by PBS as control, respectively, which showed that trastuzumab/nab-paclitaxel could surpass nab-paclitaxel and paclitaxel in antitumor effect. Furthermore, the NIR imaging indicated that trastuzumab/nab-paclitaxel labeled by NIR-797 could more precisely focus on tumor regions. In conclusion, trastuzumab/nab-paclitaxel could mediate targeted therapy and enhance antitumor efficacy, which could represent a novel therapeutic agent for HER2-positive GC.

Drug-induced acute kidney injury (AKI) with a high morbidity and mortality is poorly diagnosed in hospitals and deficiently evaluated in drug discovery. Here, we report the development of molecular renal probes (MRPs) with high renal clearance efficiency for in vivo optical imaging of drug-induced AKI. MRPs specifically activate their near-infrared fluorescence or chemiluminescence signals towards the prodromal biomarkers of AKI including the superoxide anion, N-acetyl-β-d-glucosaminidase and caspase-3, enabling an example of longitudinal imaging of multiple molecular events in the kidneys of living mice. Importantly, they in situ report the sequential occurrence of oxidative stress, lysosomal damage and cellular apoptosis, which precedes clinical manifestation of AKI (decreased glomerular filtration). Such an active imaging mechanism allows MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods. MRPs can also act as exogenous tracers for optical urinalysis that outperforms typical clinical/preclinical assays, demonstrating their clinical promise for early diagnosis of AKI.Chemiluminescent molecular renal probes have been developed and are shown to be capable of non-invasive real-time imaging of early-stage oxidative stress biomarkers of drug-induced acute kidney injury, and high renal clearance.

For improving manufacturing efficiency and minimizing costs, design for additive manufacturing (AM) has been accordingly proposed. The existing design for AM methods are mainly surrogate model based. Due to the increasingly available data nowadays, machine learning (ML) has been applied to medical diagnosis, image processing, prediction, classification, learning association, etc. A variety of studies have also been carried out to use machine learning for optimizing the process parameters of AM with corresponding objectives. In this paper, a ML integrated design for AM framework is proposed, which takes advantage of ML that can learn the complex relationships between the design and performance spaces. Furthermore, the primary advantage of ML over other surrogate modelling methods is the capability to model input–output relationships in both directions. That is, a deep neural network can model property–structure relationships, given structure–property input–output data. A case study was carried out to demonstrate the effectiveness of using ML to design a customized ankle brace that has a tunable mechanical performance with tailored stiffness.

Additive manufacturing (AM) is the process of joining materials layer by layer to fabricate products based on 3D models. Due to the layer-by-layer nature of AM, parts with complex geometries, integrated assemblies, customized geometry or multifunctional designs can now be manufactured more easily than traditional subtractive manufacturing. Path planning in AM is an important step in the process of manufacturing products. The final fabricated qualities, properties, etc., will be different when using different path strategies, even using the same AM machine and process parameters. Currently, increasing research studies have been published on path planning strategies with different aims. Due to the rapid development of path planning in AM and various newly proposed strategies, there is a lack of comprehensive reviews on this topic. Therefore, this paper gives a comprehensive understanding of the current status and challenges of AM path planning. This paper reviews and discusses path planning strategies in three categories: improving printed qualities, saving materials/time and achieving objective printed properties. The main findings of this review include: new path planning strategies can be developed by combining some of the strategies in literature with better performance; a path planning platform can be developed to help select the most suitable path planning strategy with required properties; research on path planning considering energy consumption can be carried out in the future; a benchmark model for testing the performance of path planning strategies can be designed; the trade-off among different fabricated properties can be considered as a factor in future path planning design processes; and lastly, machine learning can be a powerful tool to further improve path planning strategies in the future.

Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency and off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way to modulate protein homeostasis for cancer therapy; however, the always-on bioactivity of existing PROTACs potentially leads to uncontrollable protein degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPN pro ) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPN pro can remotely generate singlet oxygen ( 1 O 2 ) under NIR photoirradiation to eradicate tumor cells and induce immunogenic cell death (ICD) to enhance tumor immunogenicity. Moreover, the PROTAC function of SPN pro is specifically activated by a cancer biomarker (cathepsin B) to trigger targeted proteolysis of immunosuppressive indoleamine 2,3-dioxygenase (IDO) in the tumor of living mice. The persistent IDO degradation blocks tryptophan (Trp)-catabolism program and promotes the activation of effector T cells. Such a SPNpro-mediated in-situ immunometabolic intervention synergizes immunogenic phototherapy to boost the antitumor T-cell immunity, effectively inhibiting tumor growth and metastasis. Thus, this study provides a polymer platform to advance PROTAC in cancer therapy. Proteolysis targeting chimeras (PROTACs) is an effective alternative to modulate protein homeostasis but can lead to uncontrollable protein degradation and off-target side effects. Here, the authors developed semiconducting polymer nano-PROTACs with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy.

Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression. Due to tumour microenvironment, Fenton reactions have low therapeutic efficiency. Here the authors report on the application of NIR-II hybrid semiconducting nanozymes for combined photothermal therapy and enhanced ferrotherapy with photoacoustic imaging and show application in vivo in tumour models.