Heterogeneous-Structure-Based AuNBs@TiO2 Nano-Photosensitizers for Computed Tomography Imaging Guided NIR-II Photodynamic Therapy and Cancer Metastatic Prevention.

Photodynamic therapy (PDT) is a minimally invasive cancer treatment that, despite its significant attention, faces limitations in penetration depth, which restrict its effectiveness. Herein, it is found that gold nanobipyramid (AuNBs) coated with TiO2 can form a core-shell heterogeneous structure (AuNBs@TiO2) with strong absorption at second near infrared (NIR-II) region. A substantial quantity of reactive oxygen species (ROS), including singlet oxygen (1O2), superoxide anion radicals, and hydroxyl radicals, can be rapidly generated when subjecting the AuNBs@TiO2 aqueous suspension to 1064 nm laser irradiation. The quantum yield for sensitization of 1O2 by AuNBs@TiO2 is 0.36 at 1064 nm light excitation. In addition, the Au element as high-Z atoms in the nanosystem can improve the ability of computed tomographic (CT) imaging. As compared to commercial iohexol, the AuNBs@TiO2 nanoparticle exhibits significantly better CT imaging effect, which can be used to guide PDT. In addition, the nano-photosensitizer shows a remarkable therapeutic effect against established solid tumors and prevents tumor metastasis and potentiates immune checkpoint blockade therapy. More importantly, here the great potentials of AuNBs@TiO2 are highlighted as a theranostic platform for CT-guided cancer photodynamic immunotherapy.

A potential bivalent mRNA vaccine candidate protects against both RSV and SARS-CoV-2 infections.

As the world continues to confront severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV) is also causing severe respiratory illness in millions of infants, elderly individuals, and immunocompromised people globally. Exacerbating the situation is the fact that co-infection with multiple viruses is occurring, something which has greatly increased the clinical severity of the infections. Thus, our team developed a bivalent vaccine that delivered mRNAs encoding SARS-CoV-2 Omicron spike (S) and RSV fusion (F) proteins simultaneously, SF-LNP, which induced S and F protein-specific binding antibodies and cellular immune responses in BALB/c mice. Moreover, SF-LNP immunization effectively protected BALB/c mice from RSV infection and hamsters from SARS-CoV-2 Omicron infection. Notably, our study pointed out the antigenic competition problem of bivalent vaccines and provided a solution. Overall, our results demonstrated the potential of preventing two infectious diseases with a single vaccine and provided a paradigm for the subsequent design of multivalent vaccines.

In-based coordination polymer-derived carbon nanoribbons with abundant CoP nanoparticles in carbon nanotubes for water oxidation.

The sluggish oxygen evolution reaction (OER) in overall electrocatalytic water splitting poses a significant challenge in hydrogen production. A series of transition metal phosphides are emerging as promising electrocatalysts, effectively modulating the charge distribution of surrounding atoms for OER. In this study, a highly efficient OER electrocatalyst (CoP-CNR-CNT) was successfully synthesized through the pyrolysis and phosphatization of a Co-doped In-based coordination polymer, specifically InOF-25. This process resulted in evenly dispersed CoP nanoparticles encapsulated in coordination polymer-derived carbon nanoribbons. The synthesized CoP-CNR-CNT demonstrated a competitive OER activity with a smaller overpotential (η10) of 295.7 mV at 10 mA cm-2 and a satisfactory long-term stability compared to the state-of-the-art RuO2 (η10 = 353.7 mV). The high OER activity and stability can be attributed to the high conductivity of the carbon network, the abundance of CoP particles, and the intricate nanostructure of nanoribbons/nanotubes. This work provides valuable insights into the rational design and facile preparation of efficient non-precious metal-based OER electrocatalysts from inorganic-organic coordination polymers, with potential applications in various energy conversion and storage systems.

Breaking through the basement membrane barrier to improve nanotherapeutic delivery to tumours.

An effective nanotherapeutic transport from the vasculature to the tumour is crucial for cancer treatment with minimal side effects. Here we demonstrate that, in addition to the endothelial barrier, the tumour vascular basement membrane surrounding the endothelium acts as a formidable mechanical barrier that entraps nanoparticles (NPs) in the subendothelial void, forming perivascular NP pools. Breaking through this basement membrane barrier substantially increases NP extravasation. Using inflammation triggered by local hyperthermia, we develop a cooperative immunodriven strategy to overcome the basement membrane barrier that leads to robust tumour killing. Hyperthermia-triggered accumulation and inflammation of platelets attract neutrophils to the NP pools. The subsequent movement of neutrophils through the basement membrane can release the NPs entrapped in the subendothelial void, resulting in increased NP penetration into deeper tumours. We show the necessity of considering the tumour vascular basement membrane barrier when delivering nanotherapeutics. Understanding this barrier will contribute to developing more effective antitumour therapies.

Long-term immune response to Omicron-specific mRNA vaccination in mice, hamsters, and nonhuman primates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and its subvariants (such as BQ.1, XBB and the latest variants, including XBB.1.16, EG.5, and BA.2.86), as the dominant variants, currently account for almost all new infections in the world due to their high transmissibility and immune escape ability. Omicron-specific mRNA vaccines showed great potential to protect against Omicron infections. However, whether the vaccine could provide long-term protection is unknown. Toward this goal, we evaluated the immunogenicity of a preclinical Omicron (BA.1)-specific mRNA vaccine (SOmicron-6P) in different animal models. SOmicron-6P induced the highest levels of antibody titers at 1-2 weeks in different animals after the second dose. Even 9 months after the immunization, we observed modest neutralizing activity against Omicron subvariants in macaques. In addition, immunological memory cells can be rapidly reactivated upon stimulation. SOmicron-6P at concentrations higher than 10 µg effectively protected hamsters from BA.1 challenge 253 days after the first immunization, which could be attributed to the reactivation of immune systems. In addition, the toxicity tests conducted in rats revealed a highly favorable biosafety profile for SOmicron-6P, even at high dosages. Our data suggest that the Omicron-specific mRNA vaccine is highly effective and safe in animal models and provides long-term immunologic protection against SARS-CoV-2 Omicron infections.

Highly thermostable mixed lanthanide organic frameworks with high quantum yield for warm white light-emitting diodes.

A mixed lanthanide organic framework was prepared via hydrothermal methods using m-phthalic acid (m-H2BDC), 1,10-phenanthroline (1,10-Phen), and Ln3+ ions, formulated as [HNMe2][Eu0.095Tb1.905(m-BDC)3(phen)2] (ZTU-6). The structure and stability of ZTU-6 were characterised by X-ray diffraction (XRD) and thermogravimetric analysis (TGA), which revealed a three-dimensional pcu topology with high thermal stability. Fluorescence tests showed that ZTU-6 emitted orange light with a high quantum yield of 79.15%, and it can be effectively encapsulated in a light-emitting diode (LED) device emitting orange light. In addition, ZTU-6 was found to be compatible with BaMgAl10O17:Eu2+ (BAM) blue powder and [(Sr,Ba)2SiO4:Eu2+] silicate yellow and green powder to create a warm white LED with a high colour rendering index (CRI) of 93.4, a correlated colour temperature (CCT) of 3908 K, and CIE coordinates of (0.38, 036).

Gut microbiota enhance energy accumulation of black-necked crane to cope with impending migration.

Less is known about the role of gut microbiota in overwintering environmental adaptation in migratory birds. Here, we performed metagenomic sequencing on fresh fecal samples (n = 24) collected during 4 periods of overwintering (Dec: early; Jan: middle I; Feb: middle II; Mar: late) to characterize gut microbial taxonomic and functional characteristics of black-necked crane (Grus nigricollis). The results demonstrated no significant change in microbial diversity among overwintering periods. Analysis of compositions of microbiomes with bias correction (ANCOM-BC) determined 15 Proteobacteria species enriched in late overwintering period. Based on previous reports, these species are associated with degradation of chitin, cellulose, and lipids. Meanwhile, fatty acid degradation and betalain biosynthesis pathways are enriched in late overwintering period. Furthermore, metagenomic binning obtained 91 high-quality bins (completeness >70% and contamination <10%), 5 of which enriched in late overwintering period. Carnobacterium maltaromaticum, unknown Enterobacteriaceae, and Yersinia frederiksenii have genes for chitin and cellulose degradation, acetate, and glutamate production. Unknown Enterobacteriaceae and Y. frederiksenii hold genes for synthesis of 10 essential amino acids required by birds, and the latter has genes for γ-aminobutyrate production. C. maltaromaticum has genes for pyridoxal synthesis. These results implied the gut microbiota is adapted to the host diet and may help black-necked cranes in pre-migratory energy accumulation by degrading the complex polysaccharide in their diet, supplying essential amino acids and vitamin pyridoxal, and producing acetate, glutamate, and γ-aminobutyrate that could stimulate host feeding. Additionally, enriched Proteobacteria also encoded more carbohydrate-active enzymes (CAZymes) and antibiotic resistance genes (ARGs) in late overwintering period. KEY POINTS: • Differences in gut microbiota function during overwintering period of black-necked cranes depend mainly on changes in core microbiota abundance • Gut microbiota of black-necked crane adapted to the diet during overwintering period • Gut microbiota could help black-necked cranes to accumulate more energy in the late overwintering period.

Robust DUT-67 material for highly efficient removal of the Cr(VI) ion from an aqueous solution.

Robust DUT-67 was synthesized by the hydrothermal method and characterized by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). To systematically study the removal of Cr(VI) ion by DUT-67, single-factor, competition ion, material regeneration, kinetic, and thermodynamic experiments were designed. The experimental results show that DUT-67 had a maximum removal rate of 96.1% and a maximum adsorption capacity of 105.42 mg g-1 with material regeneration and outstanding selective adsorption. In addition, the process of removal of the Cr(VI) ion from an aqueous solution by DUT-67, which accorded with the pseudo-second-order kinetics model and Langmuir model, was studied, and its adsorption mechanism was reasonably explained by the theoretical calculation.

Preparation of Highly Stable DUT-52 Materials and Adsorption of Dichromate Ions in Aqueous Solution.

Highly stable DUT-52 materials were synthesized by the hydrothermal method and well-characterized by X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, and X-ray photoelectron spectroscopy (XPS). In order to systematically study the adsorption of dichromate ions in aqueous solution by the DUT-52 materials, a single factor experiment, kinetic experiment, thermodynamic experiment, competition ion experiment, and material regeneration experiment were designed. Based on the H-bond interaction between the dichromate ions and the H atoms of a NDC2- ligand, the DUT-52 materials showed a maximum removal rate of 96.4% and a maximum adsorption capacity of 120.68 mg·g-1 with excellent selective adsorption and material regeneration. In addition, the process of adsorption of dichromate ions by the DUT-52 materials is in accordance with the pseudo second-order kinetics and Langmuir models, and the adsorption mechanism and the important role of the H-bond interaction were reasonably explained using the XPS pattern and theoretical calculation. Accordingly, DUT-52 can be regarded as a multifunctional material for efficiently removing dichromate ions from the wastewater.

Phototherapy Facilitates Tumor Recruitment and Activation of Natural Killer T cells for Potent Cancer Immunotherapy.

Adoptively transferred natural killer T (NKT) cells confer distinct cancer surveillance without causing obvious side effects, making them a promising candidate for cancer immunotherapy. However, their therapeutic efficacy is limited by inefficient tumor infiltration and inadequate activation in an immunosuppressive tumor microenvironment. To overcome these obstacles, we develop a strategy of using photothermal therapy (PTT) to promote the antitumor ability of adoptively transferred NKT cells. The transferred NKT cells are efficiently recruited to PTT-treated tumors in response to PTT-created inflammation. Moreover, PTT treatment promotes the activation of NKT cells and enhances the NKT cell-initiated immune cascade. As a consequence, the combined therapy of PTT plus NKT cell transfer exhibits excellent growth inhibition of local tumors. Moreover, it efficiently rejects distant tumors and elicits long-term immunological memory to prevent tumor recurrence. Overall, the current study opens new paths to the clinical translation of NKT cells for cancer immunotherapy.

Pseudoneutrophil Cytokine Sponges Disrupt Myeloid Expansion and Tumor Trafficking to Improve Cancer Immunotherapy.

Myeloid-derived suppressor cells (MDSCs) promote tumor immune escape through multiple mechanisms including suppressing antitumor activities of T lymphocytes. However, therapeutic abrogation of MDSCs often causes severe adverse effects, compensatory recruitment of alternative cell populations, and the multiplicity and complexity of relevant cytokines/receptors. Alternatively, suppressing the expansion and tumor trafficking of MDSCs may be a proficient and safe way for cancer treatment. Here we report that pseudoneutrophil cytokine sponges (pCSs) can disrupt expansion and tumor trafficking of MDSCs and reverse immune tolerance. Coated with plasma membranes of neutrophils phenotypically and morphologically similar to polymorphonuclear MDSCs (PMN-MDSCs), the nanosized pCSs inherited most membrane receptors from the "parental" neutrophils, enabling the neutralization of MDSC-related cytokines. Upon pCSs administration, the expansion of MDSCs and their enrichment in peripheral lymphoid organs and tumors were reduced without the compensatory influx of alternative myeloid subsets. In murine breast cancer and melanoma syngeneic models, pCSs treatment dramatically increased the number of tumor-infiltrating T lymphocytes and restored their antitumor functions. In addition, when pCSs were combined with the programmed cell death protein 1 (PD-1), the immune checkpoint blockade synergistically suppressed tumor progression and prolonged animal survival. Overall, the pseudocell nanoplatform opens up new paths toward effective cancer immunotherapy.

Antiviral chromones from the stem of Cassia siamea.

Seven new chromones, siamchromones A-G (1-7), and 12 known chromones (8-19) were isolated from the stems of Cassia siamea. Compounds 1-19 were evaluated for their antitobacco mosaic virus (anti-TMV) and anti-HIV-1 activities. Compound 6 showed antitobacco mosaic virus (anti-TMV) activity with an inhibition rate of 35.3% and IC50 value of 31.2 µM, which is higher than that of the positive control, ningnamycin. Compounds 1, 10, 13, and 16 showed anti-TMV activities with inhibition rates above 10%. Compounds 4, 6, 13, and 19 showed anti-HIV-1 activities with therapeutic index values above 50.