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This paper proposes an optimization strategy using competitive particle swarm algorithm for the anti-reconnaissance problem in the near-range game scenario of spacecraft. Firstly, the constraint analysis is carried out for the anti-reconnaissance game scenario, and game model are designed. Then, an adaptive sliding mode pointing controller is designed, and the effectiveness of the controller is verified through simulation examples. For the survival game, the two-point boundary value problem is derived. To facilitate the solution, it is further transformed into a single-objective optimization problem, and solved by using competitive particle swarm optimization algorithm. The simulation results verify the effectiveness of the solution method.

Atherosclerosis, driven by chronic inflammation in the artery walls, underlies several severe cardiovascular diseases. However, currently available anti-inflammatory-based strategies for atherosclerosis treatment suffer from compromised therapeutic efficacy and undesirable therapeutic outcome. Herein, a distinct tetrapod needle-like PdH nanozyme was designed and engineered for efficient atherosclerosis treatment by the combinatorial reactive oxygen species (ROS) scavenging, hydrogen anti-inflammation, and autophagy activation. After loading into macrophages and targeted delivery to arterial plaques, these multifunctional nanozymes efficiently decreased the ROS levels and significantly suppressed the inflammation-related pathological process, exerting the distinct antioxidation and anti-inflammatory performance for alleviating atherosclerosis development. Especially and importantly, the specific spiky morphology of the PdH nanoenzyme further triggered a strong autophagy response in macrophages, synergistically maintaining the cellular homeostasis and alleviating atherosclerosis development. Both in vitroand in vivoresults confirmed the synergy among the antioxidation, anti-inflammatory, and autophagy activation, suggesting that the combinatorial engineering of nanomedicines with intrinsic multiple therapeutic functions and topology-induced biological effects is highly preferable and effective for achieving the high therapeutic performance and desirable therapeutic outcome on atherosclerosis management and therapy.

Despite the merits of high tissue-penetrating depth, no ionizing radiation, and low cost, sonodynamic therapy (SDT) still suffers from a low quantum yield of reactive oxygen species (ROS), limited delivery efficiency, and potential toxicity of sonosensitizers. Different from the direct delivery of sonosensitizers into tumor tissue for SDT, this work reports the fabrication of two-dimensional (2D) nanosonosensitizers/nanocatalysts (Ti3C2/CuO2@BSA) for the in situgeneration of nanosonosensitizers by responding to the tumor microenvironment, achieving the high-performance and synergistic sonodynamic/chemodynamic tumor therapy. CuO2nanoparticle integration on 2D Ti3C2MXene achieved in situH2O2generation in an acidic tumor microenvironment for oxidizing Ti3C2to produce TiO2nanosonosensitizers, accompanied by the enhanced separation of electrons (e–) and holes (h+) by the carbon matrix after oxidation, further augmenting the SDT efficacy. Ultrasound irradiation during the sonodynamic process also enhanced the Cu-initiated Fenton-like reaction to produce more ROS for synergizing the sonodynamic tumor therapy. The experimental results confirm and demonstrate the synergistic therapeutic effects of chemodynamic and sonodynamic nanotherapy both in vitroand in vivo. The antitumor mechanisms of synergistic chemodynamic and sonodynamic therapies are associated with the upregulation of oxidative phosphorylation, ROS generation, and apoptosis as demonstrated by RNA sequencing. This work thus provides a distinct paradigm of 2D MXene-originated in situnanosonosensitizer generation for augmented and synergistic sonodynamic tumor nanotherapy.

Tumor oxygenation level has been regarded as an attractive target to elevate the efficiency of photodynamic therapy (PDT). Cyanobacterial photosynthesis-mediated reversal of tumor hypoxia could enable an oxygen-boosted PDT, but is limited by scant penetration depth and efficiency of external light. Herein, aiming at the dual purposes of reducing biological toxicity induced by long-term light irradiation and alleviating hypoxia, we here introduce a novel-designed CaAl2O4:Eu,Nd blue persistent luminescence material (PLM) as the in vivolight source after pre-excited in vitro. The ingenious construction of blue-emitting PLM with “optical battery” characteristics activates cyanobacterial cells and verteporfin simultaneously, which performs the successive oxygen supply and singlet oxygen generation without the long-term external excitation, resulting in the modulated tumor hypoxic microenvironment and enhanced photodynamic tumor proliferation inhibition efficiency. Both in vitrocellular assessment and in vivotumor evaluation results affirm the advantages of self-produced oxygen PDT system and evidence the notable antineoplastic outcome. This work develops an irradiation-free photosynthetic bacteria-based PDT platform for the optimization of both oxygen production capacity and light utilization efficiency in cancer treatment, which is expected to promote the clinical progress of microbial-based photonic therapy.

ABSTRACTThe sclerotia of Pachyma hoelenare one of the traditional Chinese medicines and foods that are widely used in East Asian countries. The strains used for cultivation showed bad performance in recent years, and breeding of superior strains has become increasingly important for this fungus. Nevertheless, the mating system and life cycle of P. hoelenwere still ambiguous. In this study, the methods for distinguishing between homokaryotic offspring with different mating types were established, as well as confirmation of strain hybridization based on allelic polymorphism at a locus of the rpb2gene. The bipolar mating system was confirmed according to the mating results of homokaryotic SSIs. The fact that heterokaryotic parents produce homokaryotic meiospores proves that the life cycle is heterothallic. Combining scanning electron microscope observation and DAPI (4′,6-diamidino-2-phenylindole) fluorescent staining of hymenium and basidiospores in situand ex situ, nuclear migration pattern from basidia to spores was revealed. The heterothallic life cycle was verified, revised, and supplemented step by step. This is the first report of systematic research on the mating system, life cycle, and outcrossing of homokaryotic offspring in P. hoelen. It will be helpful for the biological research, strain improvement, and development of the P. hoelenindustry.

Endogenic tumor chemodynamic therapy (CDT) is emerging as a tumor-therapeutic strategy featuring in situ treatments with high efficiency and specificity based on the Fenton reaction principle. Considering the limitation of monotherapy and relatively insufficient intracellular level of endogenous hydrogen peroxide (H2O2) in tumor tissues, a mitochondria-specific nanocatalyst composed of cisplatin prodrug and gallic acid-ferrous (GA-Fe(II)) nanocomposites is successfully fabricated to fulfill chemotherapy-augmented sequential chemoreactive tumor therapy. The bioactive cisplatin elevates the level of endogenous H2O2through the activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX)-related cascaded reactions, and the GA-Fe(II) nanocomposites possessing sustainable Fenton catalytic activity subsequently catalyzes H2O2into highly reactive and toxic hydroxyl radicals to substantially inhibit tumor progression. Especially, this mitochondria-specific nanocatalyst amplifies oxidative stress, stimulates mitochondrial dysfunction, downregulates AKT/mTOR signaling and finally induces cell autophagic death. Both in vitro and in vivo measurements verify that the chemotherapy-augmented sequential chemoreactive nanotherapy based on the mitochondria-specific nanocatalyst implements excellent anticancer efficiency and avoids undesired side effects. This work reveals the enormous potential of chemotherapy-augmented CDT for combating tumors. The therapeutic modality of “chemotherapy-augmented sequential chemoreactive therapy” based on the designed mitochondria-specific nanocatalyst composed of cisplatin prodrug and gallic acid-ferrous (GA-Fe(II)) nanocomposites achieves distinct catalytic cancer-therapeutic performance. The bioactive cisplatin elevates the endogenous H2O2level through the cascaded reactions, and the GA-Fe(II) nanocomposites with sustainable Fenton catalytic activity subsequently catalyzes H2O2into hydroxyl radicals to substantially inhibit tumor progression.

ABSTRACTAcanthocytes are special cells with a distinct spiky shape produced exclusively by the fungi of Strophariaand can be used to defend against nematodes. In the present study, the ultrastructure and development of acanthocytes were revealed by scanning electron microscopy (SEM) and cryo-SEM in S. rugosoannulata, a popular cultivated mushroom both in China and Europe. The acanthocytes were abundant on the surface of rhizomorph, casing soils, and vegetative mycelia of homokaryotic and heterokaryotic strains in S. rugosoannulata. The development of the acanthocyte was investigated with cryo-SEM, which has distinct advantage for observation of the ultrastructure of live, hydrated structures. Three distinct stages, including formation of lateral branch that was covered with patches, spiky structure formation, and maturation of acanthocytes, were identified and described. The irregular patches deposited on the surface of lateral branches and the holes in the spiky branches of the acanthocytes were reported for the first time. The environmental nitrogen level showed impact on acanthocyte production, but it seemed not to be the indispensable factor. Acid medium could delay the initiation of the acanthocyte formation but did not affect the overall morphology and structure, indicating that the central deposit of acanthocytes should be acid soluble. Acanthocytes of S. rugosoannulatahave similar hydrophobicity to mycelia. The observation of ultrastructure and development process of acanthocytes provides insights into the ecological function and evolution of this special structure.

Recent studies have underscored the unique biological activities of oligosaccharides derived from edible-medicinal mushrooms, highlighting their superiority over polysaccharides due to their simpler structures and increased bioavailability. Investigating the structure-activity relationship of oligosaccharides could help overcome the technical challenges associated with the intricate structural analysis of polysaccharides. Despite numerous studies on oligosaccharide compounds, our understanding of oligosaccharides from edible-medicinal mushrooms remains limited. This review aims to outline current trends in oligosaccharide research and clarify the health-promoting characteristics of oligosaccharides derived from edible-medicinal mushrooms. It offers a comprehensive analysis of the glycan chain structures and biological activities of oligosaccharides and advocates for the establishment of an oligosaccharide compound library specific to edible-medicinal mushrooms. This approach might expedite the high-throughput screening of active oligosaccharides, thus stimulating the development of related health foods and products, and facilitating industrial advancement.

This paper contains errors in the authors’ affiliations. Wenjia Li, is a Ph.D. candidate in the University of Chinese Academy of Sciences, Jiangchun Wei and Xingzhong Liu are professors in the University of Chinese Academy of Sciences, which is missing in the original version. The affiliations have been corrected.

Fungal disease of mushroomCordyceps militaris(CM) caused byCalcarisporium cordycipiticola(CC) is destructive to fruiting body cultivation, resulting in significant economic loss and potential food safety risks. CRISPR/Cas9 genome editing has proven to be a powerful tool for crop improvement but seldom succeeded in mushrooms. Here, the first genomic safe-harbor site, CmSH1locus, was identified in the CM genome. A safe-harbor-targeted CRISPR/Cas9 system based on an autonomously replicating plasmid was designed to facilitate alien gene integration at the CmSH1locus. Cmhyd1, one of the hydrophobin genes, was confirmed as a defensive factor against CC infection, and Cmhyd1overexpression by this system showed enhancement of disease resistance with negligible effect on the agronomic traits of CM. No off-target events and residues of plasmid sequence were tested by PCR and genome resequencing. This study provided the first safe harbor site for genetic manipulations, a safe harbor-targeted CRISPR/Cas9 system, and the first disease-resistant gene-editing breeding system in mushrooms.

Reactive oxygen species (ROS) has been employed as a powerful therapeutic agent for eradicating tumor via oxidative stress. As an emerging ROS‐involving noninvasive anticancer therapeutic modality, sonodynamic therapy (SDT) with high tissue penetration depth and benign remote spatiotemporal selectivity has been progressively utilized as the distinct alternative for ROS‐based tumor treatment. However, the hypoxic tumor microenvironment substantially restricts the sonodynamic effect. In this work, an oxygen self‐sufficient hybrid sonosensitizer on the basis of photosynthetic microorganisms cyanobacteria (Cyan) integrated with ultrasmall oxygen‐deficient bimetallic oxide Mn1.4WOxnanosonosensitizers, termed as M@C, is designed and engineered to overcome the critical issue of hypoxia‐induced tumor resistance and strengthen the SDT effect. The sustained photosynthetic oxygen production by Cyan under light illumination can promote Mn1.4WOxnanosonosensitizers to produce more ROS against cancer cells both in vitro and in vivo under ultrasound (US) irradiation. Especially, the sustained oxygen evolution for suppressing the gene expression of hypoxia‐inducible factor 1alpha (HIF‐1α) further boosts and augments the SDT efficiency. Thus, this work provides the paradigm that the rationally engineered biohybrid microorganism‐based multifunctional sonosensitizers can serve as an effective bioplatform for augmenting the therapeutic efficiency of SDT, particularly for the treatment of hypoxic tumors. Based on tumor hypoxia microenvironment for achieving tumor sonodynamic therapy, a photosynthetic oxygenation system is designed and constructed by engineering a biohybrid sonosensitizer on the combination of Cyan as the oxygen self‐supplier with ultrasmall oxygen‐deficient bimetallic oxide Mn1.4WOxnanoparticles (NPs) as nanosonosensitizers, termed as M@C, to augment the sonodynamic therapy (SDT) efficacy in hypoxic tumors.

Hypoxia, the typical and conspicuous characteristic of most solid tumors, worsens the tumor invasiveness and metastasis. Here, we engineered a sequential ultrasound (US)/hypoxia-sensitive sonochemotherapeutic nanoprodrug by initially synthesizing the hypoxia-activated azo bond-containing camptothecin (CPT) prodrug (CPT2-Azo) and then immobilizing it into the mesopores of sonosensitizer-integrated metal organic frameworks (MOF NPs). Upon entering the hypoxic tumor microenvironment (TME), the structure of CPT2-Azo immobilized MOFs (denoted as MCA) was ruptured and the loaded nontoxic CPT2-Azo prodrug was released from the MOF NPs. Under US actuation, this sonochemotherapeutic nanoprodrug not only promoted sonosensitizer-mediated sonodynamic therapy (SDT) via the conversion of oxygen into cytotoxic reactive oxygen species (ROS) but also aggravated hypoxia in the TME by elevating oxygen consumption. The exacerbated hypoxia in turn served as a positive amplifier to boost the activation of CPT2-Azo, and the controllable release of toxic chemotherapeutic drug (CPT), and compensated the insufficient treatment efficacy of SDT. In vitroand in vivoevaluations confirmed that sequential SDT and tumor hypoxia-activated sonochemotherapy promoted the utmost of tumor hypoxia and thereby contributed to the augmented antitumor efficacy, resulting in conspicuous apoptotic cell death and noteworthy tumor suppression in vivo. Our work provides a distinctive insight into the exploitation of the hypoxia-activated sonochemotherapeutic nanoprodrug that utilizes the hypoxic condition in TME, a side effect of SDT, to initiate chemotherapy, thus causing a significantly augmented treatment outcome compared to conventional SDT.

The local hypoxic tumor environment substantially hampers the therapeutic efficiency of radiotherapy, which typically requires the large X-ray doses for tumor treatment but induces the serious side effects. Herein, a biomimetic radiosensitized platform based on a natural in-situoxygen-evolving photosynthetic cyanobacteria combined with two-dimensional (2D) bismuthene with high atomic-number (Z) components, is designed and engineered to effectively modulate the radiotherapy-resistant hypoxic tumor environment and achieve sufficient radiation energy deposition into tumor. Upon the exogenous sequential irradiation of 660 nm laser and X-ray beam, continuous photosynthetic oxygen evolution by the cyanobacteria and considerable generation of reactive oxygen species by the 2D bismuthene radiosensitizer substantially augmented the therapeutic efficacy of radiotherapy and suppressed the in vivotumor growth, as demonstrated on both LLC-lung tumor xenograft-bearing C57/B6 mice model and 4T1-breast tumor xenograft-bearing Balb/c mice model, further demonstrating the photosynthetic hypoxia-alleviation capability and radiosensitization performance of the engineered biomimetic radiosensitized platform. This work exemplifies a distinct paradigm on the construction of microorganism-enabled tumor-microenvironment modulation and nanoradiosensitizer-augmented radiotherapy for efficient tumor treatment.

Ultrasound-activated therapies have been regarded as the efficient strategy for tumor treatment, among which sonosensitizer-enabled sonodynamic oxidative tumor therapy features intrinsic advantages as compared to other exogenous trigger-activated dynamic therapies. Nanomedicine-based nanosonosensitizer design has been extensively explored for improving the therapeutic efficacy of sonodynamic therapy (SDT) of tumor. This review focuses on solving two specific issues, i.e., precise and enhanced sonodynamic oxidative tumor treatment, by rationally designing and engineering multifunctional composite nanosonosensitizers. This multifunctional design can augment the therapeutic efficacy of SDT against tumor by either improving the production of reactive oxygen species or inducing the synergistic effect of SDT-based combinatorial therapies. Especially, this multifunctional design is also capable of endowing the nanosonosensitizer with bioimaging functionality, which can effectively guide and monitor the therapeutic procedure of the introduced sonodynamic oxidative tumor treatment. The design principles, underlying material chemistry for constructing multifunctional composite nanosonosensitizers, intrinsic synergistic mechanism, and bioimaging guided/monitored precise SDT are summarized and discussed in detail with the most representative paradigms. Finally, the existing critical issues, available challenges, and potential future developments of this research area are also discussed for promoting the further clinical translations of these multifunctional composite nanosonosensitizers in SDT-based tumor treatment.

Sonodynamic therapy (SDT), relying on the generation of reactive oxygen species (ROS), is a promising clinical therapeutic modality for the treatment of hepatocellular carcinoma (HCC) due to its noninvasiveness and high tissue-penetration depth, whereas the oxidative stress and antioxidative defense system in cancer cells significantly restrict the prevalence of SDT. Herein, we initially identified that NFE2L2was immediately activated during SDT, which further inhibited SDT efficacy. To address this intractable issue, an ultrasound remote control of the cluster regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) release system (HMME@Lip-Cas9) was meticulously designed and constructed, which precisely knocks down NFE2L2to alleviate the adverse effects and augment the therapeutic efficiency of SDT. The hematoporphyrin monomethyl ether (HMME) in this system yielded abundant ROS to damage cancer cells under ultrasound irradiation, and meanwhile the generated ROS could induce lysosomal rupture to release Cas9/single guide RNA ribonucleoprotein (RNP) and destroy the oxidative stress-defensing system, significantly promoting tumor cell apoptosis. This study provides a new paradigm for HCC management and lays the foundation for the widespread application of CRISPR/Cas9 with promising clinical translation, meanwhile developing a synergistic therapeutic modality in the combination of SDT with gene editing.