Messenger RNA (mRNA) vaccine is a promising candidate in cancer immunotherapy as it can encode tumorassociated antigens with an excellent safety profile. Unfortunately, the inherent instability of RNA and translational efficiency are major limitations of RNA vaccine. Here, we report an injectable hydrogel formed with graphene oxide (GO) and polyethylenimine (PEI), which can generate mRNA (ovalbumin, a model antigen) and adjuvants (R848)-laden nanovaccines for at least 30 days after subcutaneous injection. The released nanovaccines can protect the mRNA from degradation and confer targeted delivering capacity to lymph nodes. The data show that this transformable hydrogel can significantly increase the number of antigen-specific CD8 + T cells and subsequently inhibit the tumor growth with only one treatment. Meanwhile, this hydrogel can generate an antigen specific antibody in the serum which in turn prevents the occurrence of metastasis. Collectively, these results demonstrate the potential of the PEI-functionalized GO transformable hydrogel for effective cancer immunotherapy.

The successful control of coronavirus disease 2019 (COVID-19) pandemic is not only relying on the development of vaccines, but also depending on the storage, transportation, and administration of vaccines. Ideally, nucleic acid vaccine should be directly delivered to proper immune cells or tissue (such as lymph nodes). However, current developed vaccines are normally treated through intramuscular injection, where immune cells do not normally reside. Meanwhile, current nucleic acid vaccines must be stored in a frozen state that may hinder their application in developing countries. Here, we report a separable microneedle (SMN) patch to deliver polymer encapsulated spike (or nucleocapsid) protein encoding DNA vaccines and immune adjuvant for efficient immunization. Compared with intramuscular injection, SMN patch can deliver nanovaccines into intradermal for inducing potent and durable adaptive immunity. IFN-γ + CD4/8 + and IL-2 + CD4/8 + T cells or virus specific IgG are significantly increased after vaccination. Moreover, in vivo results show the SMN patches can be stored at room temperature for at least 30 days without decreases in immune responses. These features of nanovaccines-laden SMN patch are important for developing advanced COVID-19 vaccines with global accessibility.

Circulating tumor DNA (ctDNA) is a promising noninvasive biomarker for the early diagnosis of cancers. However, it is challenging for accurate and sensitive detection of pico-to-femtomolar serum concentration of ctDNA, especially in the presence of its analogues that produce strong background noise. Herein, a DNA-rN1-DNA-mediated surface-enhanced Raman scattering frequency shift assay is developed, which enables sensitive detection of ctDNA with one single base pair mutation (KARS G12D mutation) from the normal ones (KARS G12D normal) of lung cancer. This sensing platform features in both the designed hairpin DNA-rN1-DNA probe for specific ctDNA recognition and the employed RNase HII enzyme that specifically hydrolyzes the DNA-rN1-DNA/ctDNA hybrid and thus allows ctDNA recycling in the system to realize signal amplification. The detection system shows sub-femtomolar-level sensitivity in the phosphate-buffered saline solution and is demonstrated to function well in both fetal bovine serum and human physiological media. In particular, the sensitive assay of ctDNA in serum samples from lung cancer patients is achieved, suggesting its high potential applications in clinical settings for early diagnosis and prognosis of lung cancer.

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The overall water splitting for hydrogen production is an effective strategy to resolve the environmental and energy crisis. Here, we report a facile approach to synthesize the Ir-based multimetallic, hierarchical, double-coreshelled architecture (HCSA) assisted by oil bath reaction for boosting overall water splitting in acidic environment. The IrNiCu HCSA shows superior electrocatalytic activity for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), which are comparable to commercial Pt/C and better than IrO 2. The IrNiCu HCSA exhibits remarkably catalytic efficiency as bifunctional catalyst for overall water splitting where a low cell voltage of 1.53 V is enough to drive a current density of 10 mA cm −2 and maintains stable for at least 20 h. The presented work for the design and synthesis of novel Ir-based multimetallic architecture paves the way for highperformance overall water splitting catalysis.

We provided an ultrasensitive sensing strategy for microRNA detection by first employing branched DNA. With the aid of microcontact printing, we realized the multiplex sensing of different kinds of liver cancer biomarkers: microRNA and protein simultaneously. Delicately designed branched DNA included multiple complementary sticky ends as probe to microRNA capture and the double-stranded rigid branched core to increase the active sticky-ends distance and expose more DNA probes for sensitivity. The branched DNA enables 2 orders of magnitude increase in sensitivity for microRNA detection over single-stranded DNA. The limit of detection reaches as low as 10 attomolar (S/N = 3) for miR-223 and 10–12 M for α-fetoprotein. In addition, this system shows high selectivity and appropriate reproducibility (the relative standard deviation is less than 20%) in physiological media. Serum samples are tested and the results of α-fetoprotein are in good agreement with the current gold-standard method, electrochemiluminescence immunoassay analyzer. The results suggest the reliability of this approach in physiological media and show high potential in the sensing of low abundant microRNA in serum, especially for early diagnosis of primary liver cancers.

To address the issues of low electrical conductivity, sluggish lithiation kinetics and dramatic volume variation in FeO anodes of lithium ion battery, herein, a double carbon-confined three-dimensional (3D) nanocomposite architecture was synthesized by an electrostatically assisted self-assembly strategy. In the constructed architecture, the ultrafine FeO subunits (∼10 nm) self-organize to form nanospheres (NSs) that are fully coated by amorphous carbon (AC), formatting core-shell structural FeO/AC NSs. By further encapsulation by reduced graphene oxide (rGO) layers, a constructed 3D architecture was built as dual carbon-confined rGO/FeO/AC. Such structure restrains the adverse reaction of the electrolyte, improves the electronic conductivity and buffers the mechanical stress of the entire electrode, thus performing excellent long-term cycling stability (99.4% capacity retention after 465 cycles relevant to the second cycle at 5 A g). Kinetic analysis reveals that a dual lithium storage mechanism including a diffusion reaction mechanism and a surface capacitive behavior mechanism coexists in the composites. Consequently, the resulting rGO/FeO/AC nanocomposite delivers a high reversible capacity (835.8 mA h g for 300 cycles at 1 A g), as well as remarkable rate capability (436.7 mA h g at 10 A g).

The solubility of l-alanyl-l-glutamine (Ala-Gln) in pure water and ethanol–water mixed solvents was measured using a synthetic method from 283.15 to 313.15 K. Molecular dynamics simulation was carried out to explain the effect of ethanol content on the solubility of Ala-Gln. The radial distribution function was used to evaluate the interactions between solute molecules and solvent molecules. The solubility data was correlated by four thermodynamic models, including the hybrid model, Wilson model, NRTL model, and UNIQUAC model. It was found that the NRTL model could give better correlation results than the other models. The dissolution properties of Ala-Gln solutions, including the free Gibbs energy, the dissolution enthalpy, and the dissolution entropy, were calculated by using the modified van’t Hoff equation.