Composited silk fibroins ensured adhesion stability and magnetic controllability of Fe3O4-nanoparticle coating on implant for biofilm treatment.

Magnetic propulsion of nano-/micro-robots is an effective way to treat implant-associated infections by physically destroying biofilm structures to enhance antibiotic killing. However, it is hard to precisely control the propulsion in vivo. Magnetic-nanoparticle coating that can be magnetically pulled off does not need precise control, but the requirement of adhesion stability on an implant surface restricts its magnetic responsiveness. Moreover, whether the coating has been fully pulled-off or not is hard to ensure in real-time in vivo. Herein, composited silk fibroins (SFMA) are optimized to stabilize Fe3O4 nanoparticles on a titanium surface in a dry environment; while in an aqueous environment, the binding force of SFMA on titanium is significantly reduced due to hydrophilic interaction, making the coating magnetically controllable by an externally-used magnet but still stable in the absence of a magnet. The maximum working distance of the magnet can be calculated using magnetomechanical simulation in which the yielding magnetic traction force is strong enough to pull Fe3O4 nanoparticles off the surface. The pulling-off removes the biofilms that formed on the coating and enhances antibiotic killing both in vitro and in a rat sub-cutaneous implant model by up to 100 fold. This work contributes to the practical knowledge of magnetic propulsion for biofilm treatment.

TMT-Based Proteomic Analysis Reveals the Molecular Mechanisms of Sodium Pheophorbide A against Black Spot Needle Blight Caused by Pestalotiopsis neglecta in Pinus sylvestris var. mongolica.

Black spot needle blight is a minor disease in Mongolian Scots pine (Pinus sylvestris var. mongolica) caused by Pestalotiopsis neglecta, but it can cause economic losses in severe cases. Sodium pheophorbide a (SPA), an intermediate product of the chlorophyll metabolism pathway, is a compound with photoactivated antifungal activity, which has been previously shown to inhibit the growth of P. neglecta. In this study, SPA significantly reduced the incidence and disease index and enhanced the chlorophyll content and antioxidant enzyme activities of P. sylvestris var. mongolica. To further study the molecular mechanism of the inhibition, we conducted a comparative proteomic analysis of P. neglecta mycelia with and without SPA treatment. The cellular proteins were obtained from P. neglecta mycelial samples and subjected to a tandem mass tag (TMT)-labelling LC-MS/MS analysis. Based on the results of de novo transcriptome assembly, 613 differentially expressed proteins (DEPs) (p < 0.05) were identified, of which 360 were upregulated and 253 downregulated. The 527 annotated DEPs were classified into 50 functional groups according to Gene Ontology and linked to 256 different pathways using the Kyoto Encyclopedia of Genes and Genomes database as a reference. A joint analysis of the transcriptome and proteomics results showed that the top three pathways were Amino acid metabolism, Carbohydrate metabolism, and Lipid metabolism. These results provide new viewpoints into the molecular mechanism of the inhibition of P. neglecta by SPA at the protein level and a theoretical basis for evaluating SPA as an antifungal agent to protect forests.

New Types of Magnetic Nanoparticles for Stimuli-Responsive Theranostic Nanoplatforms.

Magnetic nanomaterials have played a crucial role in promoting the application of nanotechnology in the biomedical field. Although conventional magnetic nanomaterials such as iron oxide nanoparticles (NPs) are used as biosensors, drug delivery vehicles, diagnostic and treatment agents for several diseases, the persistent pursuit of high-performance technologies has prompted researchers to continuously develop new types of magnetic nanomaterials such as iron carbide NPs. Considering their potential application in biomedicine, magnetic NPs responsive to exogenous or endogenous stimuli are developed, thereby enhancing their applicability in more complex versatile scenarios. In this review, the synthesis and surface modification of magnetic NPs are focused, particularly iron carbide NPs. Subsequently, exogenous and endogenous stimuli-responsive magnetic NP-based theranostic platforms are introduced, particularly focusing on nanozyme-based technologies and magnetic NP-mediated immunotherapy, which are emerging stimuli-responsive treatments. Finally, the challenges and perspectives of magnetic NPs to accelerate future research in this field are discussed.

LKB1 loss promotes colorectal cancer cell metastasis through regulating TNIK expression and actin cytoskeleton remodeling.

Colorectal cancer (CRC) is one of the most common malignant tumors. Approximately 5%-6% of CRC cases are associated with hereditary CRC syndromes, including the Peutz-Jeghers syndrome (PJS). Liver kinase B1 (LKB1), also known as STK11, is the major gene responsible for PJS. LKB1 heterozygotic deficiency is involved in intestinal polyps in mice, while the mechanism of LKB1 in CRC remains elusive. In this study, we generated LKB1 knockout (KO) CRC cell lines by using CRISPR-Cas9. LKB1 KO promoted CRC cell motility in vitro and tumor metastases in vivo. LKB1 attenuated expression of TRAF2 and NCK-interacting protein kinase (TNIK) as accessed by RNA-seq and western blots, and similar suppression was also detected in the tumor tissues of azoxymethane/dextran sodium sulfate-induced intestinal-specific LKB1-KO mice. LKB1 repressed TNIK expression through its kinase activity. Moreover, attenuating TNIK by shRNA inhibited cell migration and invasion of CRC cells. LKB1 loss-induced high metastatic potential of CRC cells was depended on TNIK upregulation. Furthermore, TNIK interacted with ARHGAP29 and further affected actin cytoskeleton remodeling. Taken together, LKB1 deficiency promoted CRC cell metastasis via TNIK upregulation and subsequently mediated cytoskeleton remodeling. These results suggest that LKB1-TNIK axis may play a crucial role in CRC progression.

An integrated RF energy-harvesting system with broad input voltage range and high power conversion efficiency.

By 2050, countries around the world are expected to be gradually phasing out fossil fuels and implementing greener energy technologies. In this work, we present a system employing Energy harvesting, a self-powered technology that can recycle energy from the surrounding environment. A high-efficiency radio frequency (RF) energy-harvesting chip was designed and fabricated. With an off-chip antenna and rectifier, the system scavenges ambient RF energy and converts it into usable energy, which is then stored in energy storage elements (such as a supercapacitor or a rechargeable battery). The system can further be implemented as an energy source for charging smart devices. The system-on-chip design consists of a cold start block, a boost converter with maximum power point tracking functionalities, and a charging block. The chip was fabricated using AMS 350 nm technology. Although the system was optimized for harvesting RF energy, it can be easily adapted to harvest other energy sources (i.e., mechanical and thermal energy sources). Using an optimized cold start architecture, the circuit has a cold start voltage of 380 mV. With an improved control strategy of power conversion, the system is capable of continuously charging up to 4.5 V with a broad input voltage range of 100 mV to 10 V and has a peak charging efficiency of 82%.

Identification, Culture Characteristics and Whole-Genome Analysis of Pestalotiopsis neglecta Causing Black Spot Blight of Pinus sylvestris var. mongolica.

Black spot needle blight is a serious conifer disease of Pinus sylvestris var. mongolica occurring in Northeast China, which is usually caused by the plant pathogenic fungus Pestalotiopsis neglecta. From the diseased pine needles collected in Honghuaerji, the P. neglecta strain YJ-3 was isolated and identified as the phytopathogen, and its culture characteristics were studied. Then, we generated a highly contiguous 48.36-Mbp genome assembly (N50 = 6.62 Mbp) of the P. neglecta strain YJ-3 by combining the PacBio RS II Single Molecule Real Time (SMRT) and Illumina HiSeq X Ten sequencing platforms. The results showed that a total of 13,667 protein-coding genes were predicted and annotated using multiple bioinformatics databases. The genome assembly and annotation resource reported here will be useful for the study of fungal infection mechanisms and pathogen-host interaction.

Phytic acid is a new substitutable plant-derived antifungal agent for the seedling blight of Pinus sylvestris var. mongolica caused by Fusarium oxysporum.

Phytic acid (PA) is a new substitutable plant-derived antifungal agent; however, few reports have been published regarding its antifungal effects on pathogenic fungi. The present study explored the in vitro antifungal activity of PA against four phytopathogenic fungi and found that PA was the most effective at inhibiting the growth of Fusarium oxysporum. This study aimed to investigate the in vivo and in vitro antifungal activities of PA against the seedling blight of Pinus sylvestris var. mongolica caused by F. oxysporum and to determine its possible mechanism of action. The results showed that PA inhibited spore germination and mycelial growth of F. oxysporum in a concentration-dependent manner and exhibited strong inhibition when its concentration exceeded 1000 mg/L. It mainly destroyed the integrity of the cell membrane, increasing its cell membrane permeability, causing the cell contents to spill out, and impairing fungal growth. In addition, the leakage of intercellular electrolytes and soluble proteins indicated that PA used at its EC20 and EC50 increased the membrane permeability of F. oxysporum. The increase in malondialdehyde and hydrogen peroxide content confirmed that PA treatment at its EC20 and EC50 damaged the cell membrane of the pathogen. Scanning electron microscopy revealed that PA affected the morphology of mycelia, causing them to shrivel, distort, and break. Furthermore, PA significantly reduced the activities of the antioxidant-related enzymes superoxide dismutase and catalase, as well as that of the pathogenicity-related enzymes polygalacturonase, pectin lyase, and endoglucanase (EG) in F. oxysporum (P < 0.05). In particular, EG enzyme activity was maximally inhibited in F. oxysporum treated with PA at its EC50. Moreover, PA significantly inhibited the incidence of disease, and growth indices in Pinus sylvestris var. mongolica seedling blight was determined. In summary, PA has a substantial inhibitory effect on F. oxysporum. Therefore, PA could serve as a new substitutable plant-derived antifungal agent for the seedling blight of P. sylvestris var. mongolica caused by F. oxysporum.

Lower Compositional Variation and Higher Network Complexity of Rhizosphere Bacterial Community in Constructed Wetland Compared to Natural Wetland.

Macrophyte rhizosphere microbes, as crucial components of the wetland ecosystem, play an important role in maintaining the function and stability of natural and constructed wetlands. Distinct environmental conditions and management practices between natural and constructed wetlands would affect macrophytes rhizosphere microbial communities and their associated functions. Nevertheless, the understanding of the diversity, composition, and co-occurrence patterns of the rhizosphere bacterial communities in natural and constructed wetlands remains unclear. Here, we used 16S rRNA gene high-throughput sequencing to characterize the bacterial community of the rhizosphere and bulk sediments of macrophyte Phragmites australis in representative natural and constructed wetlands. We observed higher alpha diversity of the bacterial community in the constructed wetland than that of the natural wetland. Additionally, the similarity of bacterial community composition between rhizosphere and bulk sediments in the constructed wetland was increased compared to that of the natural wetland. We also found that plants recruit specific taxa with adaptive functions in the rhizosphere of different wetland types. Rhizosphere samples of the natural wetland significantly enriched the functional bacterial groups that mainly related to nutrient cycling and plant-growth-promoting, while those of the constructed wetland-enriched bacterial taxa with potentials for biodegradation. Co-occurrence network analysis showed that the interactions among rhizosphere bacterial taxa in the constructed wetland were more complex than those of the natural wetland. This study broadens our understanding of the distinct selection processes of the macrophytes rhizosphere-associated microbes and the co-occurrence network patterns in different wetland types. Furthermore, our findings emphasize the importance of plant-microbe interactions in wetlands and further suggest P. australis rhizosphere enriched diverse functional bacteria that might enhance the wetland performance through biodegradation, nutrient cycling, and supporting plant growth.

Habitats modulate influencing factors shaping the spatial distribution of bacterial communities along a Tibetan Plateau riverine wetland.

The Tibetan Plateau riverine wetland is very sensitive to global climate change. Understanding the mechanisms that maintain the spatial patterns of bacterial communities provides insight into the dominant biogeochemical processes within the plateau riverine wetlands. Nonetheless, the spatial distribution of bacterial communities along these wetlands has rarely been explored. We investigated the spatial patterns of bacterial community within rhizosphere soil, bulk soil, and sediment samples collected along the Yarlung Tsangpo riverine wetland (YTRW), the longest plateau riverine wetland in China. Our results indicated that the diversity of bacterial communities in all three habitats increased significantly along the YTRW. The slope of the linear relationship between distance and bacterial community diversity in sediment was steeper than those for bulk and rhizosphere soils. Furthermore, bacterial communities in all three habitats showed significant distance-decay relationships. A combination of historical factors (geographical distance and climatic factors) and contemporary environmental heterogeneity (edaphic properties) controlled spatial distributions of bacterial communities in all three habitats, although climatic factors were predominant. Climatic factors affected rhizosphere bacterial communities more than those in bulk soil and sediment. Co-occurrence network analysis revealed that the potential interactions between bacterial taxa may decrease along the YTRW. This field investigation highlighted that the climatic factors strongly influenced the spatial distribution of bacterial communities along the YTRW; however, habitat differences among rhizosphere soil, bulk soil, and sediment samples affected the relative importance of climatic factors on spatial distributions of the associated bacterial communities. These findings would improve the understanding of biogeochemical processes in these typical habitats and potential alterations provoked by climate change.

Celastrol acts as a new histone deacetylase inhibitor to inhibit colorectal cancer cell growth via regulating macrophage polarity.

The tumorigenesis and progression of colorectal cancer are closely related to the tumor microenvironment, especially inflammatory response. Inhibitors of histone deacetylase (HDAC) have been reported as epigenetic regulators of the immune system to treat cancer and inflammatory diseases and our results demonstrated that Celastrol could act as a new HDAC inhibitor. Considering macrophages as important members of the tumor microenvironment, we further found that Celastrol could influence the polarization of macrophages to inhibit colorectal cancer cell growth. Specially, we used the supernatant of HCT116 and SW480 cells to induce Ana-1 cells in vitro and chose the spontaneous colorectal cancer model APCmin/+ mice as an animal model to validate in vivo. The results indicated that Celastrol could reverse the polarization of macrophages from M2 to M1 through impacting the colorectal tumor microenvironment both in vitro and in vivo. Furthermore, using bioinformatics analysis, we found that Celastrol might mechanistically polarize the macrophages through MAPK signaling pathway. In conclusion, our findings identified that Celastrol as a new HDAC inhibitor and suggested that Celastrol could modulate macrophage polarization, thus inhibiting colorectal cancer growth, which may provide some novel therapeutic strategies for colorectal cancer.

Biodegradable Ferrous Sulfide-Based Nanocomposites for Tumor Theranostics through Specific Intratumoral Acidosis-Induced Metabolic Symbiosis Disruption.

Abnormal metabolic symbiosis is a typical characteristic that differentiates the tumor regions from healthy tissues and meanwhile maintains tumor survival. It is of great potential to disrupt intratumoral metabolic symbiosis in tumor therapy. Herein, we report a specific tumor therapy strategy through inducing acidosis to disrupt intratumoral metabolic symbiosis for tumor elimination, which is based on carbonic anhydrase inhibitor (CAI)-modified ferrous sulfide nanoparticles (FeS-PEG-CAI NPs). The FeS-PEG-CAI NPs show the acid-responsive degradation capacity to release functional components, including CAI, Fe2+, and H2S, while remaining quite stable under normal physiological conditions. The generated CAI and H2S gas can not only disrupt the intracellular metabolic symbiosis to induce acidosis but also provide suitable circumstances for Fe2+-mediated Fenton reaction, producing abundant toxic hydroxyl radicals. Meanwhile, these NPs also show the dual-mode imaging capacity with photoacoustic and magnetic resonance imaging, which can dynamically monitor tumor location in the process of synergistic chemodynamic/photothermal/gas therapy. Overall, the developed FeS-PEG-CAI NPs exert their role of disrupting intratumoral metabolic symbiosis and other synergistic effects, which further enrich tumor treatment strategies.

Incontinentia pigmenti with intracranial arachnoid cyst: A case report.

BACKGROUND: Incontinentia pigmenti (IP) is a rare X-linked dominant genetic disorder that can be fatal in male infants. It is a disease that affects many systems of the human body. In addition to characteristic skin changes, patients may also have pathological features of the eyes, teeth, and central nervous system. Therefore, the lesions in these systems may be the first symptoms for which patients seek treatment. To date, no cases of IP complicated by intracranial arachnoid cyst (IAC) have been reported. This paper aims to report a case of IP with IAC in order to share the diagnosis and treatment experience of this rare case with other clinicians. CASE SUMMARY: An 11-year-old female patient suffered intermittent limb convulsions for five months and was sent to hospital. In the initial stage, the patient was considered to have primary epilepsy. Further investigation of the patient's medical history, physical examination and imaging examination led to the diagnosis of IP combined with intracranial space-occupying lesions, and secondary epilepsy. The patient was treated with craniotomy, and postoperative pathology revealed an IAC. The patient recovered well after craniotomy and had no obvious surgery-related complications. During the follow-up period, the patient did not have recurrent epilepsy symptoms. CONCLUSION: IP is a multi-system disease that presents with typical skin lesions at birth, but the long-term prognosis of this disease depends on the involvement of systems other than the skin, especially nervous system and ocular lesions.

A Catalytic Immune Activator Based on Magnetic Nanoparticles to Reprogram the Immunoecology of Breast Cancer from "Cold" to "Hot" State.

Triple-negative breast cancer (TNBC) as "cold" tumor is characterized by severe immunosuppression of the tumor microenvironment (TME). To effectively activate the immune response of TNBC, a new kind of therapy strategy called cancer catalytic immunotherapy is proposed based on magnetic nanoparticles (NPs) as immune activators. Utilizing the weak acidity and excessive hydrogen peroxide of TME, these magnetic NPs can release ferrous ions to promote Fenton reaction, leading to abundant ·OH and reactive oxygen species (ROS) for ultimately killing cancer cells. Mechanistically, these magnetic NPs activate the ROS-related signaling pathway to generate more ROS. Meanwhile, these magnetic NPs with unique immunological properties can promote the maturation of dendritic cells and the polarization of macrophages from M2 to M1, resulting in the infiltration of more T cells to reprogram the immunoecology of TNBC from "cold" to "hot" state. Besides directly affecting immune cells, these magnetic NPs can also affect the secretion of some immune-related cytokines by cancer cells, to further indirectly activate the immune response. In conclusion, these catalytic immune activators are designed to achieve the synergistic treatment of chemodynamic therapy-enhanced immunotherapy guided by computed tomography (CT)/near-infrared region-II (NIR-II) dual-mode imaging, providing a new strategy for TNBC treatment.

Biodegradable MnO-Based Nanoparticles with Engineering Surface for Tumor Therapy: Simultaneous Fenton-Like Ion Delivery and Immune Activation.

Immune checkpoint inhibitors have achieved significant clinical success but are still suffering from inadequate immune activation. It is worth noting that manganese as a nutritional inorganic trace element is closely associated with immune activation to fight against tumor growth and metastasis via the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. Herein, we designed hollow mesoporous silica-coated MnO nanoparticles (NPs), followed by conjugation of tumor homing peptide iRGD (CRGDKGPD). The obtained NPs (MnO@mSiO2-iRGD NPs) were applied to magnetic resonance imaging (MRI)-guided tumor immune-chemodynamic combination therapy, in which MnO NPs can be harnessed for cGAS-STING pathway-activated immunotherapy, Fenton-like reaction-induced reactive oxygen species upregulation, and T1-weighted MRI. The rough surface and large cavities of the mSiO2 shell promote cellular uptake and MnO NPs delivery. Meanwhile, it was found that MnO@mSiO2-iRGD NPs would dissociate under an acid environment, resulting in tumor specificity of MRI and exogenous Mn2+ release. Our results revealed that these pH-responsive biodegradable MnO@mSiO2-iRGD NPs synergized with α-PD-1 (PD-1 = programmed cell death-1) blocking antibody to highly elicit cytotoxic T lymphocyte infiltration and restrict melanoma progression and metastasis, which were envisioned as a promising candidate for tumor theranostics.

NosZI microbial community determined the potential of denitrification and nitrous oxide emission in river sediments of Qinghai-Tibetan Plateau.

Denitrification in river sediments is the hotspot of nitrogen removal and nosZI gene is essential for reducing nitrous oxide (N2O) emissions. However, few studies tried to link nosZI communities with variations of denitrification rates in sediments along the high-elevation rivers. Here, we investigated the spatial variation of potential denitrification rates of sediments along a section (hereafter YJ) of the middle reaches of the Yarlung Zangbo River in the Qinghai-Tibetan Plateau. We also used the real-time quantitative PCR (qPCR) and high-throughput sequencing techniques to evaluate the abundance and composition of nosZI-containing microbial groups. The influences of physicochemical factors and denitrifier communities on potential denitrification rates were further revealed through structural equation modeling. The obtained results indicated that potential denitrification rates and N2O/(N2O + N2) ratio in the sediments along YJ section were greatly different. Moreover, the alpha diversity and composition of nosZI-containing microbial community in river sediments differed remarkably, mainly driven by the ammonia nitrogen (NH4+-N), organic matter (OM) and pH in sediments. The relative abundances of Zoogloeaceae, Oxalobacteraceae, Rhodospirillaceae and Bradyrhizobiaceae significantly differed among five groups (P < 0.05). Structural equation modeling further suggested that nitrogen nutrients directly influenced the potential denitrification rates, while total phosphorus (TP) showed indirect effects on potential denitrification rates through modulating denitrifier abundances and nosZI community. The abundance and composition of nosZI community were powerful predictors in regulating denitrification rates and N2O/(N2O + N2) ratio. Our findings highlight that the nosZI-containing microbial groups play a non-negligible role in nitrogen removal and N2O mitigation in high-elevation river sediments.

Disentangling the assembly mechanisms of bacterial communities in a transition zone between the alpine steppe and alpine meadow ecosystems on the Tibetan Plateau.

Alpine meadows and alpine steppes are two major grassland types distributed on the Tibetan Plateau. Due in large part to the differences in hydrothermal and nutrient conditions following the thawing of lakeshore permafrost, alpine meadows and alpine steppes which are characterized by disparate above- and below-ground biomass, could emerge together in the grassland transition zone between meadows and steppes of the Tibetan Plateau. Bacterial communities are essential components of alpine grassland ecosystems and respond rapidly to environmental changes. Despite their ecological significance, it remains poorly elucidated whether and how the assembly patterns of bacterial communities differed between alpine meadows and alpine steppes. Here, to disentangle the assembly mechanisms of bacterial communities from alpine meadows and alpine steppes, we collected samples from three diverse habitats (i.e., sediments, rhizosphere soils and bulk soils) in both alpine meadow and steppe ecosystems on the Tibetan Plateau. Our results indicated that in both meadows and steppes, rhizosphere bacterial communities exhibited higher alpha-diversity but lower beta-diversity compared to the bacterial communities in sediments and bulk soils. However, the close relationships of bacterial communities between different habitats weakened from meadows to steppes. Null model analysis indicated that the importance of environmental selection shaping bacterial community assemblages in all habitats decreased from meadows to steppes, whereas the role of dispersal limitation showed an opposite pattern. Moreover, pH was the primary driver of phylogenetic turnover of bacterial communities in the steppes across all habitats, whereas the dominant drivers of phylogenetic turnover of bacterial communities in meadows varied with habitat types. Overall, our findings provide novel insights into understanding the differences in microbial communities between meadows and steppes in the grassland transition zone on the Tibetan Plateau.

Contrasting assembly mechanisms explain the biogeographic patterns of benthic bacterial and fungal communities on the Tibetan Plateau.

The Tibetan Plateau characterized by high altitude and low temperature, where a great number of lakes are located, is a hotspot of global biodiversity research. Both bacterial and fungal communities are vital participants of biogeochemical cycling in lake ecosystems. However, we know very little about the large-scale biogeographic patterns and the underlying assembly mechanisms of lake benthic microbial communities on the Tibetan Plateau. To investigate the biogeographic patterns and their underlying assembly mechanisms of benthic bacterial and fungal communities, we collected sediment samples from 11 lakes on the Tibetan Plateau (maximum geographic distance between lakes over 1100 km). Benthic community diversity and composition were determined using the high-throughput sequencing technique. Our results indicated that there were contrasting distance-decay relationships between benthic bacterial and fungal communities on a regional scale. Benthic bacterial communities showed a significant distance-decay relationship, whereas no significant relationship was observed for benthic fungal communities. Deterministic processes dominated the bacterial community assembly, whereas fungal community assembly was more stochastic. pH was a dominant factor in influencing the geographic distribution of benthic microbial communities. Co-occurrence network analysis revealed that bacterial communities showed higher complexity and greater stability than those of the fungal communities. Taken together, this study contributes to a novel understanding of the assembly mechanisms underlying the biogeographic distribution of plateau benthic bacterial and fungal communities at a large scale.

Amelioration of systemic antitumor immune responses in cocktail therapy by immunomodulatory nanozymes.

Nanozymes that mimic natural enzyme-like activities have gradually emerged in cancer therapy. To overcome the bottlenecks of single-mode nanozymes, including "off-target" toxicity and ineffectiveness toward metastatic cancers, we designed magnetic nanoparticle-based multifunctional visualized immunomodulatory nanozymes. Besides the partial initiation of the prime immune response by intrinsic immunogenicity, as a smart drug delivery system with a temperature- and pH-sensitive dual response to the tumor microenvironment, these nanozymes released immune agonists to boost enhanced systemic immune response, eventually ameliorating the cancer immune microenvironment through many aspects: activating dendritic cells, improving the function of CD8+ T cells, and decreasing the population of myeloid-derived suppressor cells, which inhibited both primary and metastatic cancers. Mechanistically, these nanozymes regulated the reactive oxygen species-related Akt signaling pathway and consequently activated cell apoptosis-related signaling pathways, which provided a deeper understanding of the synergistic mechanism of multifunctional nanozymes. Our findings offer a promising imaging-guided cocktail therapy strategy through immunomodulatory nanozymes.

First Report of Black Spot Needle Blight of Pinus sylvestris var. mongolica Litv. Caused by Heterotruncatella spartii in China.

Pinus sylvestris var. mongolica Litv. (Pinales: Pinaceae) is an excellent tree for soil and water conservation in Northeast China. The Honghua'erji area in Inner Mongolia is the "hometown of P. sylvestris var. mongolica", however, in recent years, coniferous diseases of P. sylvestris var. mongolica have frequently occurred here. During the investigation, it was found that some black spot needle blight had been observed in addition to the common blight caused by Sphaeropsis sapinea. From May to September 2020, black spot needle blight was found on hundreds of P. sylvestris var. mongolica trees in four forest farms, and the infection rate among the forests was 24.58 % (n=240). This disease first appeared on the upper part of the needles, and the needles then became withered and gradually showed light black spots, although they remained green. As the disease progressed, the needles eventually died and turned gray with many dark black spots. Fungal isolate named YJ-1 was obtained from infected needles of symptomatic pine trees, and a voucher specimen was deposited in Heilongjiang Province Key Laboratory of Forest Protection. Microscopic observation showed the conidia were 3-septate (4 cells) clavate spindles that measured 23.9 µm (20.8-25.9) × 5.9 µm (4.5-8.2) (n=50). The middle two cells were dark brown, and the septa were darker than the cells. Both apical and basal cells were hyaline. The apical cell had 2-4 appendages (mostly 3), and the basal cell had a truncate base (n=50). The cultural characteristics on potato dextrose agar medium were flat off-white and dense in 3-5 d. At approximately 5-7 d, the reverse side of the colony turned pale to slightly luteous. Superficial black acervuli were distributed in the center of the mature colonies after 10 d. Morphological, cultural and microscopic characteristics observed were similar of Heterotruncatella spartii (basionym: Truncatella spartii) reported by Hlaiem et al (2019). To further identify, total DNA was extracted and the internal transcribed spacer region (ITS-rDNA) was amplified by PCR using the primers ITS1/ITS4 and sequenced for BLASTn analysis and phylogenetic tree construction. The resulting 564 bp sequence (GenBank Accession No. OL662864) had 99.24% (521/525) to H. spartii MFLUCC 15-0537, with bootstrap support of at least 94% using the Neighbor-Joining algorithm by MEGA-X (Felsenstein, 1985). The fungus was identified as H. spartii based on morphology and molecular methods. A pathogenicity test was conducted by preparing a conidial suspension of 2.0 × 107 conidia/mL. The suspension was sprayed onto the needles of 20 pots of annual P. sylvestris ar. mongolica seedlings, and the control was sprayed with sterile water. Then the seedlings were placed in a constant temperature room at 25 °C. After 30 d, typical symptoms appeared on 11 inoculated needles, while the control needles remained symptomless. After 50 d, the re-isolation infection rate reached 66.7 %. The fungus present on the inoculated seedlings was morphologically identical to that originally observed on diseased pines, fulfilling Koch's postulates. The fungus was isolated from Spartium junceum for the first time and designated Truncatella spartii (Senanayake et al, 2015). It was then renamed H. spartii (Liu et al, 2019) and has been reported to infect P. pinea in Tunisia (Hlaiem et al, 2019). To our knowledge, this is the first report of H. spartii causing black spot needle blight on P. sylvestris var. mongolica in China and worldwide.

Magnetic Nanostructures: Rational Design and Fabrication Strategies toward Diverse Applications.

In recent years, the continuous development of magnetic nanostructures (MNSs) has tremendously promoted both fundamental scientific research and technological applications. Different from the bulk magnet, the systematic engineering on MNSs has brought a great breakthrough in some emerging fields such as the construction of MNSs, the magnetism exploration of multidimensional MNSs, and their potential translational applications. In this review, we give a detailed description of the synthetic strategies of MNSs based on the fundamental features and application potential of MNSs and discuss the recent progress of MNSs in the fields of nanomedicines, advanced nanobiotechnology, catalysis, and electromagnetic wave adsorption (EMWA), aiming to provide guidance for fabrication strategies of MNSs toward diverse applications.