Engineering customized nanovaccines for enhanced cancer immunotherapy.

Nanovaccines have gathered significant attention for their potential to elicit tumor-specific immunological responses. Despite notable progress in tumor immunotherapy, nanovaccines still encounter considerable challenges such as low delivery efficiency, limited targeting ability, and suboptimal efficacy. With an aim of addressing these issues, engineering customized nanovaccines through modification or functionalization has emerged as a promising approach. These tailored nanovaccines not only enhance antigen presentation, but also effectively modulate immunosuppression within the tumor microenvironment. Specifically, they are distinguished by their diverse sizes, shapes, charges, structures, and unique physicochemical properties, along with targeting ligands. These features of nanovaccines facilitate lymph node accumulation and activation/regulation of immune cells. This overview of bespoke nanovaccines underscores their potential in both prophylactic and therapeutic applications, offering insights into their future development and role in cancer immunotherapy.

Enhancing Adsorption Desulfurization Performance Using Enriched Cu(I) Sites over Microenvironment-Modulated HKUST-1.

High-efficiency adsorption of aromatic sulfur-containing compounds from liquid hydrocarbon fuels over metal-organic frameworks (MOFs) is challenging because of inert metal sites. A new method, the Ce-enhanced modulation of MOFs' microenvironment, is proposed to modulate the -COO···Cu(II)- coordination microenvironment of Hong Kong University of Science and Technology (HKUST-1) using Ce(III) as a molecular scalpel for fabricating abundant high-efficiency Cu(I) and Cu-coordination-unsaturated sites and improving the pore structures around adsorptive sites. The optimal CH-250 thus exhibits adsorptive capacities for 20.2, 28.0, and 58.3 mg S g-1 of thiophene, benzo-thiophene, and dibenzothiophene, respectively, which are superior to most reported MOFs, zeolites, and nanoporous carbons. The constructed Cu(I) sites show stronger affinity for dibenzothiophene (-0.86 eV) than the initial Cu(II) (-0.74 eV) for out-of-plane adsorption. Further, they are far stronger in-plane adsorption interactions in DBT/CH-250 (-0.90 eV) than those in DBT/HKUST-1 (-0.37 eV). Thus, molecular engineering for modulating the coordination microenvironment of MOFs shows great potential for adsorption desulfurization.

Magnetic Continuum Robot with Intraoperative Magnetic Moment Programming.

Magnetic continuum robots (MCRs), which are free of complicated structural designs for transmission, can be miniaturized and are therefore widely used in the medical field. However, the deformation shapes of different segments, including deflection directions and curvatures, are difficult to control simultaneously under an external programmable magnetic field. This is because the latest MCRs have designs with an invariable magnetic moment combination or profile of one or more actuating units. Therefore, the limited dexterity of the deformation shape causes the existing MCRs to collide readily with their surroundings or makes them unable to approach difficult-to-reach regions. These prolonged collisions are unnecessary or even hazardous, especially for catheters or similar medical devices. In this study, a novel magnetic moment intraoperatively programmable continuum robot (MMPCR) is introduced. By applying the proposed magnetic moment programming method, the MMPCR can deform under three modalities, that is, J, C, and S shapes. Additionally, the deflection directions and curvatures of different segments in the MMPCR can be modulated as desired. Furthermore, the magnetic moment programming and MMPCR kinematics are modeled, numerically simulated, and experimentally validated. The experimental results exhibit a mean deflection angle error of 3.3° and correspond well with simulation results. Comparisons between navigation capacities of the MMPCR and MCR demonstrate that the MMPCR has a higher capacity for dexterous deformation.

Studies on the Stability and Deactivation Mechanism of Immobilized Ionic Liquids in Catalytic Esterification Reactions.

Solid-supported ionic liquid catalysts (SILs) are the simplest form of a heterogenized ionic liquid and have attracted soaring attention because of the high catalytic activity as well as separation. Unfortunately, instability severely hinders their practical application, and the reason for the deactivation of SILs has not been investigated in detail. In the present study, the immobilized ionic liquid catalysts MIL-101-[IA-SO3H][HSO4] and MIL-101-[IA-COOH][HSO4] were prepared and used to study the stability in the esterification reaction. The results show that compared with MIL-101-[IA-COOH][HSO4], MIL-101-[IA-SO3H][HSO4] has a higher catalytic activity and a lower stability. The deactivation mechanism is discussed based on experiments and theoretical analysis: the protons on -SO3H dissociate in a polar solvent and combine with anion HSO4-, and then, the formative H2SO4 molecule will leach out into the solvent. Our discussion indicates that the stability of immobilized ionic liquids is determined by the substituents of ionic liquid cations and becomes the significant factor controlling the stability limits. The study presented here would be important for understanding the deactivation reason and can help in choosing the suitable cation to avoid leaching of the active site during the reaction.

Deep Reinforcement Learning Framework-Based Flow Rate Rejection Control of Soft Magnetic Miniature Robots.

Soft magnetic miniature robots (SMMRs) have potential biomedical applications due to their flexible size and mobility to access confined environments. However, navigating the robot to a goal site with precise control performance and high repeatability in unstructured environments, especially in flow rate conditions, still remains a challenge. In this study, drawing inspiration from the control requirements of drug delivery and release to the goal lesion site in the presence of dynamic biofluids, we propose a flow rate rejection control strategy based on a deep reinforcement learning (DRL) framework to actuate an SMMR to achieve goal-reaching and hovering in fluidic tubes. To this end, an SMMR is first fabricated, which can be operated by an external magnetic field to realize its desired functionalities. Subsequently, a simulator is constructed based on neural networks to map the relationship between the applied magnetic field and robot locomotion states. With minimal prior knowledge about the environment and dynamics, a gated recurrent unit (GRU)-based DRL algorithm is formulated by considering the designed history state-action and estimated flow rates. In addition, the randomization technique is applied during training to distill the general control policy for the physical SMMR. The results of numerical simulations and experiments are illustrated to demonstrate the robustness and efficacy of the presented control framework. Finally, in-depth analyses and discussions indicate the potentiality of DRL for soft magnetic robots in biomedical applications.

Benzylaminofentanyl derivates: Discovery of bifunctional µ opioid and σ1 receptor ligands as novel analgesics with reduced adverse effects.

To develop safer and potent analgesics, we designed, synthesized, and evaluated a new series of benzylaminofentanyl derivates as bifunctional µ opioid receptor (MOR) and σ1 receptor (σ1R) ligands. Compound 68 (Tao-191) showed desirable MOR agonism (Ki = 6.5 nΜ; EC50 = 48.5 nΜ, Emax = 66.3%) and σ1R antagonism (Ki = 35.7 nM) in vitro, and exerted powerful analgesic effects in the abdominal constriction test (ED50 = 0.32 mg/kg, in mice), formalin-induced pain test (phase II, ED50 = 2.26 mg/kg, in rats), and paclitaxel-induced neuropathic pain model (ED50 = 0.30 mg/kg, in mice). The contributions of MOR and σ1R to its antinociceptive effect were verified by combined administration with the MOR antagonist naloxone and the σ1R agonist PRE-084, respectively. At equianalgesic doses, compound 68 induced fewer MOR-related side effects-including physical and psychological dependence, respiratory depression, constipation, and acute hyperlocomotion-than fentanyl. The results provide a rationale for further exploration of the action and safety of dual MOR/σ1R ligands as a promising avenue for the development of potent and safe analgesics.

Transcription factor HOXB2 upregulates NUSAP1 to promote the proliferation, invasion and migration of nephroblastoma cells via the PI3K/Akt signaling pathway.

The transcription factor homeobox protein Hox­B2 (HOXB2) and its downstream factor nucleolar and spindle­associated protein 1 (NUSAP1) play important regulatory roles in cell proliferation, invasion and migration. However, their effects and specific mechanisms in nephroblastoma have not been previously investigated, to the best of our knowledge. Therefore, in the present study, the mRNA and protein expression levels of HOXB2 and NUSAP1 were determined in nephroblastoma cells using reverse transcription­quantitative PCR and western blot analyses, respectively. Furthermore, cell transfection experiments were carried out to knock down NUSAP1 and overexpress HOXB2 in nephroblastoma cell lines. The proliferative, invasive and migratory abilities of nephroblastoma cells were assessed by MTT, EdU, colony formation, wound healing and Transwell assays. In addition, the JASPAR website was used to predict the association between HOXB2 and NUSAP1, which was further verified by dual­luciferase reporter and chromatin immunoprecipitation assays. Finally, the expression levels of the PI3K/Akt signaling pathway­related proteins were measured by western blot analysis. The results showed that the expression of NUSAP1 was abnormally upregulated in nephroblastoma cell lines. However, NUSAP1 silencing attenuated the proliferation, invasion and migration abilities of nephroblastoma cells. The results also suggested that HOXB2 could transcriptionally activate NUSAP1. Therefore, HOXB2 overexpression abrogated the inhibitory effect of NUSAP1 silencing on the proliferation and metastasis of nephroblastoma cells, possibly via the PI3K/Akt signaling pathway. The aforementioned findings indicated that HOXB2 may upregulate NUSAP1 to promote the proliferation, invasion and migration of nephroblastoma cells via the PI3K/Akt signaling pathway.

Design, synthesis, and evaluation of phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents.

In this paper, we designed and synthesized a series of novel phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents. The best compound 10 had relatively high affinity for the GABAA receptor and low affinity for thirteen other off-target receptors. In three animal models (mice, rats, and rabbits), compound 10 exerted potent hypnotic effects (HD50 = 5.2 mg/kg in rabbits), comparable duration of the loss of righting reflex (LORR), and significant shorter recovery time (time to walk) than propanidid. Furthermore, compound 10 (TI = 18.1) showed higher safety profile than propanidid (TI = 14.7) in rabbits. Above results suggested that compound 10 may have predictable and rapid recovery profile in anesthesia.

Gut microbiome drives individual memory variation in bumblebees.

The potential of the gut microbiome as a driver of individual cognitive differences in natural populations of animals remains unexplored. Here, using metagenomic sequencing of individual bumblebee hindguts, we find a positive correlation between the abundance of Lactobacillus Firm-5 cluster and memory retention on a visual discrimination task. Supplementation with the Firm-5 species Lactobacillus apis, but not other non-Firm-5 bacterial species, enhances bees' memory. Untargeted metabolomics after L. apis supplementation show increased LPA (14:0) glycerophospholipid in the haemolymph. Oral administration of the LPA increases long-term memory significantly. Based on our findings and metagenomic/metabolomic analyses, we propose a molecular pathway for this gut-brain interaction. Our results provide insights into proximate and ultimate causes of cognitive differences in natural bumblebee populations.

Optomechanical Design and Application of Solar-Skylight Spectroradiometer.

Using a solar radiometer is an effective approach for improving the remote sensing of solar irradiance distribution and atmospheric composition. Long-term development of a solar scanning radiometer enables frequent and reliable measurement of atmospheric parameters such as the water vapor column and aerosol optical properties. However, the discrete wavelength radiometer has encountered a bottleneck with respect to its insufficient spectral resolution and limited observation waveband, and it has been unable to satisfy the needs of refined and intelligent on-site experiments. This study proposes a solar-skylight spectroradiometer for obtaining visible and near-IR fine spectrum with two types of measurement: direct-sun irradiance and diffuse-sky radiance. The instrument adopts distributed control architecture composed of the ARM-Linux embedded platform and sensor networks. The detailed design of the measuring light-path, two-axis turntable, and master control system will be addressed in this study. To determine all coefficients needed to convert instrument outputs to physical quantities, integrating sphere and Langley extrapolation methods are introduced for diffuse-sky and direct-sun calibration, respectively. Finally, the agreement of experimental results between spectroradiometers and measuring benchmarks (DTF sun-photometer, microwave radiometer, and Combined Atmospheric Radiative Transfer simulation) verifies the feasibility of the spectroradiometer system, and the radiation information of feature wavelengths can be used to retrieve the characteristics of atmospheric optics.

Isolation, structural characterization and quality control strategy of an unknown process-related impurity in sugammadex sodium.

Sugammadex sodium is the first selective relaxant binding agent (SRBA) indicated for reversal of neuromuscular blockade induced by rocuronium or vecuronium during surgery. The chemical synthesis of sugammadex involved the nucleophilic substitution reaction between 6-per-deoxy-6-per-halo-γ-cyclodextrin and 3-mercaptopropionic acid under basic conditions. During the manufacture of sugammadex sodium, an unknown process-related impurity was observed in pilot batches in the range of 0.21-1.9 % based upon HPLC analysis. The same impurity was also detected in commercial Bridion® samples at the levels of more than 0.1 %. Thus this unknown impurity was enriched from the mother liquor of reaction by preparative HPLC and characterized by LC-MS/QTOF, 1D-NMR (1H, 13C, DEPTQ) and 2D-NMR (1H-1H COSY, TOCSY, HSQC, HMBC, NOESY) techniques. Based on spectroscopic analysis and the synthetic route of sugammadex sodium, this new impurity was identified as monocyanoethyl sugammadex (impurity-I). The prospects to the formation mechanism and control strategy of impurity-I were discussed in detail. Moreover, the toxicological properties of impurity-I were evaluated using ADMET Predictor® software.

Probing and Manipulating Carrier Interlayer Diffusion in van der Waals Multilayer by Constructing Type-I Heterostructure.

van der Waals multilayer heterostructures have drawn increasing attention due to the potential for achieving high-performance photonic and optoelectronic devices. However, the carrier interlayer transportation behavior in multilayer structures, which is essential for determining the device performance, remains unrevealed. Here, we report a general strategy for studying and manipulating the carrier interlayer transportation in van der Waals multilayers by constructing type-I heterostructures, with a desired narrower bandgap monolayer acting as a carrier extraction layer. For heterostructures comprised of multilayer PbI2 and monolayer WS2, we find similar interlayer diffusion coefficients of ∼0.039 and ∼0.032 cm2 s-1 for electrons and holes in the PbI2 multilayer by fitting the time-resolved carrier dynamics based on the diffusion model. Because of the balanced carrier interlayer diffusion and the injection process at the heterointerface, the photoluminescence emission of the bottom WS2 monolayer is greatly enhanced by up to 106-fold at an optimized PbI2 thickness of the heterostructure. Our results provide valuable information on carrier interlayer transportation in van der Waals multilayer structures and pave the way for utilizing carrier behaviors to improve device performances.

Ultrahigh-Performance Optoelectronics Demonstrated in Ultrathin Perovskite-Based Vertical Semiconductor Heterostructures.

Two-dimensional (2D) atomic layered semiconductor (e.g., transition metal dichalcogenides, TMDCs) heterostructures display diverse novel interfacial carrier properties and have potential applications in constructing next generation highly compact electronics and optoelectronics devices. However, the optoelectronic performance of this kind of semiconductor heterostructures has difficulty reaching the expectations of practical applications, due to the intrinsic weak optical absorption of the atomic-thick component layers. Here, combining the extraordinary optoelectronic properties of quantum-confined organic-inorganic hybrid perovskite (PVK), we design an ultrathin PVK/TMDC vertical semiconductor heterostructure configuration and realize the controlled vapor-phase growth of highly crystalline few-nanometer-thick PVK layers on TMDCs monolayers. The achieved ultrathin PVKs show strong thickness-induced quantum confinement effect, and simultaneously form band alignment-engineered heterointerfaces with the underlying TMDCs, resulting in highly efficient interfacial charge separation and transport. Electrical devices constructed with the as-grown ultrathin PVK/WS2 heterostructures show ambipolar transport originating from p-type PVK and n-type WS2, and exhibit outstanding optoelectronic characteristics, with the optimized response time and photoresponsivity reaching 64 µs and 11174.2 A/W, respectively, both of which are 4 orders of magnitude better than the heterostructures with a thick PVK layer, and also represent the best among all previously reported 2D layered semiconductor heterostructures. This work provides opportunities for 2D vertical semiconductor heterostructures via incorporating ultrathin PVK layers in high-performance integrated optoelectronics.

Direct Vapor Growth of 2D Vertical Heterostructures with Tunable Band Alignments and Interfacial Charge Transfer Behaviors.

2D vertical van der Waals (vdW) heterostructures with atomically sharp interfaces have attracted tremendous interest in 2D photonic and optoelectronic applications. Band alignment engineering in 2D heterostructures provides a perfect platform for tailoring interfacial charge transfer behaviors, from which desired optical and optoelectronic features can be realized. Here, by developing a two-step chemical vapor deposition strategy, direct vapor growth of monolayer PbI2 on monolayer transition metal dichalcogenides (TMDCs) (WS2, WSe2, or alloying WS2(1- x )Se2 x ), forming bilayer vertical heterostructures, is demonstrated. Based on the calculated electron band structures, the interfacial band alignments of the obtained heterostructures can be gradually tuned from type-I (PbI2/WS2) to type-II (PbI2/WSe2). Steady-state photoluminescence (PL) and time-resolved PL measurements reveal that the PL emissions from the bottom TMDC layers can be modulated from apparently enhanced (for WS2) to greatly quenched (for WSe2) compared to their monolayer counterparts, which can be attributed to the band alignment-induced distinct interfacial charge transfer behaviors. The band alignment nature of the heterostructures is further demonstrated by the PL excitation spectroscopy and interlayer exciton investigation. The realization of 2D vertical heterostructures with tunable band alignments will provide a new material platform for designing and constructing multifunctional optoelectronic devices.

Van der Waals epitaxial growth and optoelectronics of large-scale WSe2/SnS2 vertical bilayer p-n junctions.

High-quality two-dimensional atomic layered p-n heterostructures are essential for high-performance integrated optoelectronics. The studies to date have been largely limited to exfoliated and restacked flakes, and the controlled growth of such heterostructures remains a significant challenge. Here we report the direct van der Waals epitaxial growth of large-scale WSe2/SnS2 vertical bilayer p-n junctions on SiO2/Si substrates, with the lateral sizes reaching up to millimeter scale. Multi-electrode field-effect transistors have been integrated on a single heterostructure bilayer. Electrical transport measurements indicate that the field-effect transistors of the junction show an ultra-low off-state leakage current of 10-14 A and a highest on-off ratio of up to 107. Optoelectronic characterizations show prominent photoresponse, with a fast response time of 500 µs, faster than all the directly grown vertical 2D heterostructures. The direct growth of high-quality van der Waals junctions marks an important step toward high-performance integrated optoelectronic devices and systems.

Synthesis and optoelectronic properties of quaternary GaInAsSb alloy nanosheets.

Quasi-one-dimensional (1D) nanostructures have been extensively explored for electronic and optoelectronic devices on account of their unique morphologies and versatile physical properties. Here, we report the successful synthesis of GaInAsSb alloy nanosheets by a simple chemical vapor deposition method. The grown GaInAsSb alloy nanosheets are pure zinc-blende single crystals, which show nanosize-induced extraordinary optoelectronic properties as compared with bulk materials. µ-Raman spectra exhibit a multi-mode phonon vibration behavior with clear frequency shifts under varied laser power. Photoluminescence measurements reveal a strong light emission in the near-infrared region (1985 nm), and the obtained Varshni thermal coefficients α and ß are smaller than those of the bulk counterparts due to the size confinement effect. In addition, photodetectors (PDs) based on these single-alloy nanosheets were constructed for the first time. The PDs show a strong response in the near-infrared region with the external quantum efficiency of 8.05 × 104%, and the responsivity of 0.675 × 103 A W-1. These novel nanostructures would make contributions to the study of fundamental physical phenomena in quasi-1D nanomaterial systems and can be potential building blocks for optoelectronic and quantum devices.