Automatic grading evaluation of winter wheat lodging based on deep learning.

Lodging is a crucial factor that limits wheat yield and quality in wheat breeding. Therefore, accurate and timely determination of winter wheat lodging grading is of great practical importance for agricultural insurance companies to assess agricultural losses and good seed selection. However, using artificial fields to investigate the inclination angle and lodging area of winter wheat lodging in actual production is time-consuming, laborious, subjective, and unreliable in measuring results. This study addresses these issues by designing a classification-semantic segmentation multitasking neural network model MLP_U-Net, which can accurately estimate the inclination angle and lodging area of winter wheat lodging. This model can also comprehensively, qualitatively, and quantitatively evaluate the grading of winter wheat lodging. The model is based on U-Net architecture and improves the shift MLP module structure to achieve network refinement and segmentation for complex tasks. The model utilizes a common encoder to enhance its robustness, improve classification accuracy, and strengthen the segmentation network, considering the correlation between lodging degree and lodging area parameters. This study used 82 winter wheat varieties sourced from the regional experiment of national winter wheat in the Huang-Huai-Hai southern area of the water land group at the Henan Modern Agriculture Research and Development Base. The base is located in Xinxiang City, Henan Province. Winter wheat lodging images were collected using the unmanned aerial vehicle (UAV) remote sensing platform. Based on these images, winter wheat lodging datasets were created using different time sequences and different UAV flight heights. These datasets aid in segmenting and classifying winter wheat lodging degrees and areas. The results show that MLP_U-Net has demonstrated superior detection performance in a small sample dataset. The accuracies of winter wheat lodging degree and lodging area grading were 96.1% and 92.2%, respectively, when the UAV flight height was 30 m. For a UAV flight height of 50 m, the accuracies of winter wheat lodging degree and lodging area grading were 84.1% and 84.7%, respectively. These findings indicate that MLP_U-Net is highly robust and efficient in accurately completing the winter wheat lodging-grading task. This valuable insight provides technical references for UAV remote sensing of winter wheat disaster severity and the assessment of losses.

Electrochemistry-assisted in-situ regeneration of oxygen vacancies and Ti(III) active sites for persistent uranium recovery at a low potential.

Electrochemical uranium extraction (EUE) from seawater is a very promising strategy, but its practical application is hindered by the high potential for electrochemical system, as well as the low selectivity, efficiency, and poor stability of electrode. Herein, we developed creatively a low potential strategy for persistent uranium recovery by electrochemistry-assisted in-situ regeneration of oxygen vacancies and Ti(III) active sites coupled with indirect reduction of uranium, finally achieving high selectivity, efficient and persistent uranium recovery. As-designed titanium dioxide rich in oxygen vacancies (TiO2-VO) electrode displayed an EUE efficiency of ∼99.9 % within 180 min at a low potential of 0.09 V in simulated seawater with uranium of 5∼20 ppm. Moreover, the TiO2-VO electrode also showed high selectivity (89.9 %) to uranium, long-term cycling stability and antifouling activity in natural seawater. The excellent EUE property was attributed to the fact that electrochemistry-assisted in-situ regeneration of oxygen vacancies and Ti(III) active sites enhanced EUE cycling process and achieved persistent uranium recovery. The continuous regeneration of oxygen vacancies not only reduced the adsorption energy of U(VI)O22+ but also serve as a storage and transportation channel for electrons, accelerating electron transfer from Ti(III) to U(VI) at solid-liquid interface and promoting EUE kinetic rate.

Computational investigation of the inhibitory interaction of IRF3 and SARS-CoV-2 accessory protein ORF3b.

ORF3b is one of the SARS-CoV-2 accessory proteins. Previous experimental study suggested that ORF3b prevents IRF3 translocating to nucleus. However, the biophysical mechanism of ORF3b-IRF3 interaction is elusive. Here, we explored the conformation ensemble of ORF3b using all-atom replica exchange molecular dynamics simulation. Disordered ORF3b has mixed α-helix, ß-turn and loop conformers. The potential ORF3b-IRF3 binding modes were searched by docking representative ORF3b conformers with IRF3, and 50 ORF3b-IRF3 complex poses were screened using molecular dynamics simulations ranging from 500 to 1000 ns. We found that ORF3b binds IRF3 predominantly on its CBP binding and phosphorylated pLxIS motifs, with CBP binding site has the highest binding affinity. The ORF3b-IRF3 binding residues are highly conserved in SARS-CoV-2. Our results provided biophysics insights into ORF3b-IRF3 interaction and explained its interferon antagonism mechanism.

Mesoscale size-promoted targeted therapy for acute kidney injury through combined RONS scavenging and inflammation alleviation strategy.

Acute kidney injury (AKI) is a heterogeneous, high-mortality clinical syndrome with diverse pathogenesis and prognosis, but it lacks the effective therapy clinically. Its pathogenesis is associated with production of reactive oxygen/nitrogen species and infiltration of inflammatory cells. To overcome these pathogenic factors and improve the therapeutic efficiency, we synthesized triptolide-loaded mesoscale polydopamine melanin-mimetic nanoparticles (MeNP4TP) as the antioxidant plus anti-inflammatory therapeutic platform to synergistically scavenge reactive oxygen/nitrogen species (RONS), inhibit the activity of macrophages and dendritic cells, and generate Treg cells for AKI therapy. It was demonstrated that mesoscale size was beneficial for MeNP4TP to specifically accumulate at renal tubule cells, and MeNP4TP could significantly attenuate oxidative stress, reduce proinflammatory immune cells in renal, and repair renal function in cisplatin-induced AKI mouse model. MeNP4TP might be a potential candidate to inhibit oxidative damages and inflammatory events in AKI.

Continuous-wave operation of 1550 nm low-threshold triple-lattice photonic-crystal surface-emitting lasers.

Benefitting from narrow beam divergence, photonic crystal surface-emitting lasers are expected to play an essential role in the ever-growing fields of optical communication and light detection and ranging. Lasers operating with 1.55 µm wavelengths have attracted particular attention due to their minimum fiber loss and high eye-safe threshold. However, high interband absorption significantly decreases their performance at this 1.55 µm wavelength. Therefore, stronger optical feedback is needed to reduce their threshold and thus improve the output power. Toward this goal, photonic-crystal resonators with deep holes and high dielectric contrast are often used. Nevertheless, the relevant techniques for high-contrast photonic crystals inevitably complicate fabrication and reduce the final yield. In this paper, we demonstrate the first continuous-wave operation of 1.55 µm photonic-crystal surface-emitting lasers by using a 'triple-lattice photonic-crystal resonator', which superimposes three lattice point groups to increase the strength of in-plane optical feedback. Using this geometry, the in-plane 180° coupling can be enhanced threefold compared to the normal single-lattice structure. Detailed theoretical and experimental investigations demonstrate the much lower threshold current density of this structure compared to 'single-lattice' and 'double-lattice' photonic-crystal resonators, verifying our design principles. Our findings provide a new strategy for photonic crystal laser miniaturization, which is crucial for realizing their use in future high-speed applications.

Photocatalytic selective synthesis of (E)-ß-aminovinyl sulfones and (E)-ß-amidovinyl sulfones using Ru(bpy)3Cl2 as the catalyst.

Selectively producing a variety of valuable compounds using controlled chemical reactions starting from a common material is an appealing yet complex concept. Herein, a photocatalytic approach for the selective synthesis of (E)-ß-aminovinyl sulfones and (E)-ß-amidovinyl sulfones from allenamides and sodium sulfinates was established. This reaction exhibits the traits of an eco-friendly solvent and adjustable amide cleavage, and can accommodate a diverse range of substrates with exceptional functional group tolerance. Based on control experiments and deuterium labeling experiments, a plausible radical reaction pathway is proposed.

Cleavage and Noncleavage Chemistry in Reactive Oxygen Species (ROS)-Responsive Materials for Smart Drug Delivery.

The design and development of advanced drug delivery systems targeting reactive oxygen species (ROS) have gained significant interest in recent years for treating various diseases, including cancer, psychiatric diseases, cardiovascular diseases, neurological diseases, metabolic diseases, and chronic inflammations. Integrating specific chemical bonds capable of effectively responding to ROS and triggering drug release into the delivery system is crucial. In this Review, we discuss commonly used conjugation linkers (chemical bonds) and categorize them into two groups: cleavable linkers and noncleavable linkers. Our goal is to clarify their unique drug release mechanisms from a chemical perspective and provide practical organic synthesis approaches for their efficient production. We showcase numerous significant examples to demonstrate their synthesis routes and diverse applications. Ultimately, we strive to present a comprehensive overview of cleavage and noncleavage chemistry, offering insights into the development of smart drug delivery systems that respond to ROS.

Selective Anchoring by Surface Sulfur Species Coupled with Rapid Interface Electron Transfer for Ultrahigh Capacity Extraction of Uranium from Seawater.

Improving the adsorption selectivity, enhancing the extraction capacity, and ensuring the structural stability of the adsorbent are the key to realize the high efficiency recovery of uranium. In this work, we utilized the strong Lewis acid-base interaction between S2- and U(VI)O22+ coupling rapid electron transfer at the MnS/U(VI)O22+ solid-liquid interface to achieve excellent selectivity, high adsorption capacity, and rapid extraction of uranium. The as-synthesized MnS adsorbent exhibited an ultrahigh uranium extraction capacity (2457.05 mg g-1) and a rapid rate constant (K = 9.11 × 10-4 g h-1 mg-1) in seawater with 100.7 ppm of UO2(NO3)2 electrolyte. The kinetic simulation reveals that this adsorption process is a chemical adsorption process and conforms to a pseudo-second-order kinetic model, indicating electron transfer at the MnS/U(VI)O22+ solid-liquid interface. The relevant (quasi) in situ spectroscopic characterization and theoretical calculation results further revealed that the outstanding uranium extraction property of MnS could be attributed to the highly selective UO22+ adsorption of MnS with lower adsorption energy as a result of the strong interaction between S2- and UO22+ and the rapid mass transfer and interface electron transfer from S2- and low-valent Mn(II) to U(VI)O22+.

[Establishment of a quantitative method for GC analysis of polyoxyethylene (35) castor oil in microemulsion extracts].

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.

Advances in Drug Design and Development for Human Therapeutics Using Artificial Intelligence-II.

Building on our 2021-2022 Special Issue, "Advances in Drug Design and Development for Human Therapeutics Using Artificial Intelligence [...].

Exploring microproteins from various model organisms using the mip-mining database.

Microproteins, prevalent across all kingdoms of life, play a crucial role in cell physiology and human health. Although global gene transcription is widely explored and abundantly available, our understanding of microprotein functions using transcriptome data is still limited. To mitigate this problem, we present a database, Mip-mining ( https://weilab.sjtu.edu.cn/mipmining/ ), underpinned by high-quality RNA-sequencing data exclusively aimed at analyzing microprotein functions. The Mip-mining hosts 336 sets of high-quality transcriptome data from 8626 samples and nine representative living organisms, including microorganisms, plants, animals, and humans, in our Mip-mining database. Our database specifically provides a focus on a range of diseases and environmental stress conditions, taking into account chemical, physical, biological, and diseases-related stresses. Comparatively, our platform enables customized analysis by inputting desired data sets with self-determined cutoff values. The practicality of Mip-mining is demonstrated by identifying essential microproteins in different species and revealing the importance of ATP15 in the acetic acid stress tolerance of budding yeast. We believe that Mip-mining will facilitate a greater understanding and application of microproteins in biotechnology. Moreover, it will be beneficial for designing therapeutic strategies under various biological conditions.

Data Mining Suggests That CXCL14 Gene Silencing in Colon Cancer Is Due to Promoter Methylation.

CXCL14 is one of the most evolutionarily conserved members of the chemokine family and is constitutionally expressed in multiple organs, suggesting that it is involved in the homeostasis maintenance of the system. CXCL14 is highly expressed in colon epithelial cells and shows obvious gene silencing in clinical colon cancer samples, suggesting that its silencing is related to the immune escape of cancer cells. In this paper, we analyzed the expression profiles of multiple human clinical colon cancer datasets and mouse colon cancer models to reveal the variation trend of CXCL14 expression during colitis, colon polyps, primary colon cancer, and liver metastases. The relationship between CXCL14 gene silencing and promoter hypermethylation was revealed through the colorectal carcinoma methylation database. The results suggest that CXCL14 is a tumor suppressor gene in colorectal carcinoma which is activated first and then silenced during the process of tumor occurrence and deterioration. Promoter hypermethylation is the main cause of CXCL14 silencing. The methylation level of CXCL14 is correlated with the anatomic site of tumor occurrence, positively correlated with patient age, and associated with prognosis. Reversing the hypermethylation of CXCL14 may be an epigenetic therapy for colon cancer.

Photocatalytic Radical Cascade Dehalogenation/Carbo-cyclization/Sulfonylation Leading to Indole- and Benzofuran-Based Benzylic Sulfones.

This study presents a convenient approach to the synthesis of indole- and benzofuran-based benzylic sulfones using unactivated alkynes containing aryl iodides and sodium sulfinates under visible light irradiation. The procedure involves a sequential series of dehalogenation, carbo-cyclization, and radical sulfonylation. Plausible insights into the reaction mechanism are derived from control experiments, leading to the proposal of a radical cascade reaction pathway.

Strengthening Fe(II)/Fe(III) Dynamic Cycling by Surface Sulfation to Achieve Efficient Electrochemical Uranium Extraction at Ultralow Cell Voltage.

Electrochemically mediated Fe(II)/Fe(III) redox-coupled uranium extraction can efficiently reduce the cell voltage of electrochemical uranium extraction (EUE). How to regulate the surface structure to enhance the uranium acyl ion adsorption capacity and strengthen the Fe(II)/Fe(III) redox cycle process is crucial for EUE. In this work, we developed surface sulfated nanoreduced iron (S-NRI) for EUE and exhibited improved properties for EUE at an ultralow cell voltage (-0.1 V). Compared with a nanoreduced iron (NRI) adsorbent, S-NRI displayed faster electrochemical extraction kinetics properties and higher extraction efficiency and capacity for uranium. In a more complex seawater electrolyte containing uranyl ion concentration ranging from 1 to 20 ppm, the removal efficiency could reach almost ∼100% after EUE for 24 h. At a higher 50 ppm uranium acyl ion concentration in a seawater electrolyte, S-NRI exhibited higher extraction capacity (755.03 mg/g), which is better than 528.53 mg/g of NRI at a cell voltage of -0.1 V. Outstanding EUE property could be attributed to the fact that sulfate species (M-SO42-) on the S-NRI surface not only enhanced selective adsorption of uranyl ions but also strengthened the Fe(II)/Fe(III) redox cycle, which accelerated electron transfer between Fe(II) and U(VI), promoted the regeneration of Fe(II) active sites, and finally enhanced the EUE property.

Inhibition of cMYC-MAX transcription factors hetero-dimerization with structurally engineered omoMYC to downregulate oncogenic pathways in renal carcinoma.

In the current study, we employed, structural informatics, and molecular simulation-based methods to engineer OmoMyc, a c-Myc dominant negative protein, to design novel mutants that could abrogate the c-MYC-MAX complex in Renal Carcinoma (RC). Among the total 472 mutations, only six mutations A61Q, Q64E, Q64K, N77R, Q64E-N77R, and Q64K-N77R were reported to increase the binding affinity and subjected to subsequent analysis such as protein-protein docking. The docking results revealed that the predicted mutants improve the functionality of the OmoMyc by not only increasing the binding affinity but also vdW and electrostatic energy in each complex that consequently increase the binding of the engineered OmoMyc by establishing extra hydrogen bonds, salt-bridges, and non-bonded contacts. Molecular simulation revealed a more stable behavior by the mutant complexes in contrast to the native OmoMyc however structural perturbations were reported in the regions, DBD (DNA-binding domain), loop region, and minor deviations at CTD (C terminal domain). Moreover, the hydrogen bonding and binding free energy results further validated the promising activity of our predicted mutants of OmoMyc. The results for TBE (total binding energy) revealed that the for each complex the TBE was calculated to be -87.88 ± 0.16 kcal/mol (WT OmoMyc-MAX), -91.89 ± 0.21 kcal/mol (A61Q OmoMyc-MAX), -91.55 ± 0.20 kcal/mol (Q64E OmoMyc-MAX), -95.17 ± 0.24 kcal/mol (Q64K OmoMyc-MAX), -96.49 ± 0.22 kcal/mol (N77R OmoMyc-MAX), -97.76 ± 0.22 kcal/mol (Q64E-N77R OmoMyc-MAX), and -95.31 ± 0.20 kcal/mol (Q64K-N77R OmoMyc-MAX) respectively. The results for TBE revealed promising results that allow the mutants to competitively inhibit the c-Myc-MAX complex more swiftly. Additionally, the internal motion and energy landscape were altered. These findings provide important insights into the potential of the mutants of OmoMyc as a therapeutic candidate for cancer treatment, particularly renal carcinoma, and could pave the way for the development of more effective clinical versions of OmoMyc.

Bacterial Magnetosome-Hitchhiked Quick-Frozen Neutrophils for Targeted Destruction of Pre-Metastatic Niche and Prevention of Tumor Metastasis.

Premetastatic niche (PMN) is a prerequisite for tumor metastasis. Destruction of PMN can significantly suppress the tumor metastasis. Bone marrow-derived cells are usually recruited into the premetastatic organs to support PMN formation, which can be orchestrated by tumor-derived secreted factors. Neutrophils can chemotactically migrate towards the inflammatory sites and consume tumor-derived secreted factors, capable of acting as therapeutic agents for a broad-spectrum suppression of PMN formation and metastasis. However, neutrophils in response to inflammatory signals can release neutrophil extracellular traps (NETs), promoting the tumor metastasis. Herein, live neutrophils are converted into dead neutrophils (C NE) through a quick-frozen process to maintain PMN-targeting and tumor-derived secreted factor-consuming abilities but eliminate NET-releasing shortcomings. Considering macrophages-regulated remodeling of the extracellular matrix in PMN, bacterial magnetosomes (Mag) are further hitchhiked on the surface of C NE to form C NEMag , which can repolarize macrophages from M2 to M1 phenotype for further disruption of PMN formation. A series of in vitro and in vivo assessments have been applied to confirm the effectiveness of C NEMag in suppression of PMN formation and metastasis. This study presents a promising strategy for targeted anti-metastatic therapy in clinics.

Development of FAP-Targeted Chimeric Antigen Receptor NK-92 Cells for Non-Small Cell Lung Cancer.

OBJECTIVES: Over the past two decades, great progress has been made in advancing the early detection and multimodal treatment of non-small cell lung cancer (NSCLC). However, overall cure rates and survival rates of NSCLC are still not satisfactory, and research into new therapies is needed. This study attempted to construct human Fibroblast Activation Protein-Chimeric Antigen Receptor Natural killer (NK)-92 cells (hFAP-CAR-NK-92 cells) and explore their potential therapeutic effects in NSCLC. METHODS: Immunohistochemistry analysis was carried out to examine fibroblast activation protein (FAP) and Gasdermin E (GSDME) expression in clinical specimens of lung adenocarcinoma and squamous cell carcinoma tissue. Then the engineered hFAP-CAR-NK-92 cells efficiency was determined in vitro with lactate dehydrogenase (LDH) cytotoxicity assay and the cell morphology of A549, H226, and cancer-related fibroblast (CAF) was observed by electron microscopy. After the co-culture of target cells and effect cells, flow cytometry was employed for examining the CD107a expression in the effect cells, and western blotting was conducted for the cleavage levels of Caspase 3 and GSDME proteins in the target cells. The safety and efficacy of hFAP-CAR-NK-92 cells adoptive transfer immunotherapy in a tumor-bearing mouse were evaluated. RESULTS: Clinical studies have shown FAP positivity in patients with NSCLC. Compared with A549 or H226 cells alone, FAP expression was notably raised in A549+CAF cells or H226+CAF cells in nude mice, respectively (p < 0.05). The killing efficiency of K562 cells was not significantly different between hFAP-CAR-NK-92 and NK-92 cells (p > 0.05). The hFAP-CAR-NK-92 cells presented a higher killing efficiency against the hFAP-target (A549-hFAP, H226-hFAP and CAF-hFAP) cells than the NK-92 cells (p < 0.05). The degranulation of CD107a and cleavage levels of GSDME and Caspase 3 protein in the hFAP-CAR-NK-92 group were higher than those in the NK-92 group (p < 0.05). The 300 nM Granzyme B also induced pyroptosis in hFAP- or GSDME-positive cells (p < 0.05). In vivo experiments revealed that hFAP-CAR-NK-92 cells inhibited tumor progression of hFAP-positive NSCLC (p < 0.05). CONCLUSIONS: In this study, we successfully constructed hFAP-CAR-NK-92 cells and confirmed that hFAP-CAR-NK-92 cells could target hFAP-positive NSCLC to inhibit the progression of NSCLC by activating the Caspase-3/GSDME pyroptosis pathway.

Preharvest Application of Sodium Nitroprusside Alleviates Yellowing of Chinese Flowering Cabbage via Modulating Chlorophyll Metabolism and Suppressing ROS Accumulation.

Chinese flowering cabbage is prone to senescence and yellowing after harvest, leading to a huge postharvest loss. Nitric oxide (NO) is a multifunctional plant growth regulator, but the effect of preharvest application of NO on the storage quality of Chinese flowering cabbage remains unclear. Preharvest application of 50 mg L-1 sodium nitroprusside (SNP, a NO donor) to the roots obviously reduced leaf yellowing in Chinese flowering cabbage during storage. Proteomic analysis reveals 198 differentially expressed proteins (DEPs) in SNP-treated plants compared to the control. The main DEPs were significantly enriched in chlorophyll metabolisms, phenylpropanoid synthesis, and antioxidant pathways. SNP treatment enhanced chlorophyll biosynthesis and suppressed chlorophyll-degradation-related proteins and genes. It also modulated flavonoid-biosynthesis-related genes, and 21 significantly regulated flavonoids were identified in SNP-treated plants. The enhanced antioxidant capacity in SNP-treated plants was able to decrease chlorophyll catabolism by inhibiting peroxidase-mediated chlorophyll bleaching. Collectively, preharvest SNP treatment modulated chlorophyll metabolism and preserved chlorophyll content in leaves during storage. Moreover, SNP treatment enhanced flavonoid synthesis, suppressed reactive oxygen species accumulation, and delayed the senescence process, thereby maintaining leaf greening in Chinese flowering cabbage. These findings highlight the role of exogenous NO in alleviating yellowing of leafy vegetables.

Targeted hollow pollen silica nanoparticles for enhanced intravesical therapy of bladder cancer.

Bladder cancer (BC), such as non-muscle invasive bladder cancer (NMIBC), has a significantly high recurrence rate even after intravesical therapy because traditional intravesical chemotherapeutic drugs have short retention time in the bladder and lack efficient uptake in BC cells. Pollen structure usually shows potent adhesion ability to tissue surfaces, different from traditional electronic interaction or covalent binding. 4-Carboxyphenylboric acid (CPBA) has high affinity to sialic acid residues that are overexpressed on BC cells. In the present study, hollow pollen silica (HPS) nanoparticles (NPs) were prepared and modified with CPBA to form CHPS NPs, which could be further loaded with pirarubicin (THP) to form THP@CHPS NPs. THP@CHPS NPs showed high adhesion to skin tissues and could be more efficiently internalized by a mouse bladder cancer cell line (MB49) than THP, inducing more significant apoptotic cells. After intravesical instillation into a BC mouse model through an indwelling catheter, THP@CHPS NPs could more significantly accumulate at the bladder than THP at 24 h post-instillation, and after 8 days of intravesical treatments, magnetic resonance imaging (MRI) revealed that the bladders treated with THP@CHPS NPs showed more smooth bladder lining and more reduction in size and weights than those with THP. Moreover, THP@CHPS NPs exhibited excellent biocompatibility. THP@CHPS NPs hold great potential for intravesical treatment of bladder cancer.

Bacteria engineered with intracellular and extracellular nanomaterials for hierarchical modulation of antitumor immune responses.

Induction of immunogenic cell death (ICD) by hyperthermia can initiate adaptive immune responses, emerging as an attractive strategy for tumor immunotherapy. However, ICD can induce proinflammatory factor interferon-γ (IFN-γ) production, leading to indoleamine 2,3-dioxygenase 1 (IDO-1) activation and an immunosuppressive tumor microenvironment, which dramatically reduces the ICD-triggered immunotherapeutic efficacy. Herein, we developed a bacteria-nanomaterial hybrid system (CuSVNP20009NB) to systematically modulate the tumor immune microenvironment and improve tumor immunotherapy. Attenuated Salmonella typhimurium (VNP20009) that can chemotactically migrate to the hypoxic area of the tumor and repolarize tumor-associated macrophages (TAMs) was employed to intracellularly biosynthesize copper sulfide nanomaterials (CuS NMs) and extracellularly hitchhike NLG919-embedded and glutathione (GSH)-responsive albumin nanoparticles (NB NPs), forming CuSVNP20009NB. After intravenous injection into B16F1 tumor-bearing mice, CuSVNP20009NB could accumulate in tumor tissues and repolarize TAMs from the immunosuppressive M2 to immunostimulatory M1 phenotype and release NLG919 from extracellular NB NPs to inhibit IDO-1 activity. Under further near infrared laser irradiation, intracellular CuS NMs of CuSVNP20009NB could photothermally induce ICD including calreticulin (CRT) expression and high mobility group box 1 (HMGB-1) release, promoting intratumoral infiltration of cytotoxic T lymphocytes. Finally, CuSVNP20009NB with excellent biocompatibility could systematically augment immune responses and significantly inhibit tumor growth, holding great promise for tumor therapy.