Bismuth Sulfide Nanoflowers Facilitated miR339 Delivery to Overcome Stemness and Radioresistance through Ubiquitin-Specific Peptidase 8 in Esophageal Cancer.

Despite the superior efficacy of radiotherapy in esophageal squamous cell carcinoma (ESCC), radioresistance by cancer stem cells (CSCs) leads to recurrence, metastasis, and treatment failure. Therefore, it is necessary to develop CSC-based therapies to enhance radiotherapy. miR-339-5p (miR339) is involved in stem cell division and DNA damage checkpoint signaling pathways based on ESCC cohort. miR339 inhibited ESCC cell stemness and enhanced radiation-induced DNA damage by targeting USP8, suggesting that it acts as a potential CSC regulator and radiosensitizer. Considering the limited circulating periods and poor tumor-targeting ability of miRNA, a multifunctional nanoplatform based on bismuth sulfide nanoflower (Bi@PP) is developed to efficiently deliver miR339 and improve radioresistance. Intriguingly, Bi@PP encapsulates more miR339 owing to their flower-shaped structure, delivering more than 1000-fold miR339 into cells, superior to free miR339 alone. Besides being used as a carrier, Bi@PP is advantageous for dynamically monitoring the distribution of delivered miR339 in vivo while simultaneously inhibiting tumor growth. Additionally, Bi@PP/miR339 can significantly enhance radiotherapy efficacy in patient-derived xenograft models. This multifunctional platform, incorporating higher miRNA loading capacity, pH responsiveness, hypoxia relief, and CT imaging, provides another method to promote radiosensitivity and optimize ESCC treatment.

A two-site Kitaev chain in a two-dimensional electron gas.

Artificial Kitaev chains can be used to engineer Majorana bound states (MBSs) in superconductor-semiconductor hybrids1-4. In this work, we realize a two-site Kitaev chain in a two-dimensional electron gas by coupling two quantum dots through a region proximitized by a superconductor. We demonstrate systematic control over inter-dot couplings through in-plane rotations of the magnetic field and via electrostatic gating of the proximitized region. This allows us to tune the system to sweet spots in parameter space, where robust correlated zero-bias conductance peaks are observed in tunnelling spectroscopy. To study the extent of hybridization between localized MBSs, we probe the evolution of the energy spectrum with magnetic field and estimate the Majorana polarization, an important metric for Majorana-based qubits5,6. The implementation of a Kitaev chain on a scalable and flexible two-dimensional platform provides a realistic path towards more advanced experiments that require manipulation and readout of multiple MBSs.

Crossed Andreev Reflection and Elastic Cotunneling in Three Quantum Dots Coupled by Superconductors.

The formation of a topological superconducting phase in a quantum-dot-based Kitaev chain requires nearest neighbor crossed Andreev reflection and elastic cotunneling. Here, we report on a hybrid InSb nanowire in a three-site Kitaev chain geometry-the smallest system with well-defined bulk and edge-where two superconductor-semiconductor hybrids separate three quantum dots. We demonstrate pairwise crossed Andreev reflection and elastic cotunneling between both pairs of neighboring dots and show sequential tunneling processes involving all three quantum dots. These results are the next step toward the realization of topological superconductivity in long Kitaev chain devices with many coupled quantum dots.

Highly selective photoelectrochemical CO2 reduction by crystal phase-modulated nanocrystals without parasitic absorption.

Photoelectrochemical (PEC) carbon dioxide (CO2) reduction (CO2R) holds the potential to reduce the costs of solar fuel production by integrating CO2 utilization and light harvesting within one integrated device. However, the CO2R selectivity on the photocathode is limited by the lack of catalytic active sites and competition with the hydrogen evolution reaction. On the other hand, serious parasitic light absorption occurs on the front-side-illuminated photocathode due to the poor light transmittance of CO2R cocatalyst films, resulting in extremely low photocurrent density at the CO2R equilibrium potential. This paper describes the design and fabrication of a photocathode consisting of crystal phase-modulated Ag nanocrystal cocatalysts integrated on illumination-reaction decoupled heterojunction silicon (Si) substrate for the selective and efficient conversion of CO2. Ag nanocrystals containing unconventional hexagonal close-packed phases accelerate the charge transfer process in CO2R reaction, exhibiting excellent catalytic performance. Heterojunction Si substrate decouples light absorption from the CO2R catalyst layer, preventing the parasitic light absorption. The obtained photocathode exhibits a carbon monoxide (CO) Faradaic efficiency (FE) higher than 90% in a wide potential range, with the maximum FE reaching up to 97.4% at -0.2 V vs. reversible hydrogen electrode. At the CO2/CO equilibrium potential, a CO partial photocurrent density of -2.7 mA cm-2 with a CO FE of 96.5% is achieved in 0.1 M KHCO3 electrolyte on this photocathode, surpassing the expensive benchmark Au-based PEC CO2R system.

Triplet correlations in Cooper pair splitters realized in a two-dimensional electron gas.

Cooper pairs occupy the ground state of superconductors and are typically composed of maximally entangled electrons with opposite spin. In order to study the spin and entanglement properties of these electrons, one must separate them spatially via a process known as Cooper pair splitting (CPS). Here we provide the first demonstration of CPS in a semiconductor two-dimensional electron gas (2DEG). By coupling two quantum dots to a superconductor-semiconductor hybrid region we achieve efficient Cooper pair splitting, and clearly distinguish it from other local and non-local processes. When the spin degeneracy of the dots is lifted, they can be operated as spin-filters to obtain information about the spin of the electrons forming the Cooper pair. Not only do we observe a near perfect splitting of Cooper pairs into opposite-spin electrons (i.e. conventional singlet pairing), but also into equal-spin electrons, thus achieving triplet correlations between the quantum dots. Importantly, the exceptionally large spin-orbit interaction in our 2DEGs results in a strong triplet component, comparable in amplitude to the singlet pairing. The demonstration of CPS in a scalable and flexible platform provides a credible route to study on-chip entanglement and topological superconductivity in the form of artificial Kitaev chains.

Understanding global changes of the mouse brain proteome after vaginal infection with HSV-2 using a label-free shotgun approach.

Herpes simplex virus type 2 (HSV-2) is a common human pathogen that establishes lifelong latency in neurons of the nervous system. The number of severe central nervous system infections caused by the virus has increased recently. However, the pathogenesis of HSV-2 infection in the nervous system is not fully understood. Here, we demonstrated global proteomic changes in the brain tissue in BALB/c mice vaginally infected with HSV-2. Data are available via ProteomeXchange with identifier PXD034186. A total of 249 differentially expressed proteins were identified in infected brain tissue. The GO and KEGG enrichment analysis of these proteins indicated that they were mainly involved in the regulation of synapse formation and synaptic excitability. In addition, genes affecting autophagy, the development of other neurodegenerative diseases, and signaling pathways relevant to other neurologic diseases were identified. Additional experiments, comparing the brain tissue of asymptomatic and symptomatic mice showed a differential expression of proteins involved in synapse formation and synaptic transmission. Others were involved in autophagy, addiction, and signaling pathways of other neurologic diseases. These results suggest that changes in synaptic structure and function, as well as autophagy, may be related to the development of neurologic abnormalities that follow HSV-2 infection. We also identified a protein GluN2A encoded by Grin2a was continuously expressed at high levels after infection. We propose that GluN2A may be a key molecule in the pathogenesis of HSV-2-induced neurologic diseases.

Enhanced Glioblastoma Selectivity of Harmine via the Albumin Carrier.

Glioblastoma, the most common tumor in the brain, has witnessed very little clinical progress over the last decades. Exploring and discovering new therapeutic strategies for glioblastoma has become a critical problem. Harmine (HM), belonging to the beta-carboline alkaloid, is a natural product and isolated from the seeds of Peganum harmala L., which own notable antitumor activity in vitro. However, the poor water solubility and less selectivity of HM severely limit its clinical use. For enhancing its selective ability to tumor cells, we fabricated a kind of protein nanoparticles (BSA-HM NPs), composed of the modified bovine serum albumin (BSA) and HM. It was substantiated through in vitro and in vivo experiment that BSA-HM NPs could predominantly accumulate in tumor tissues and exhibited remarkably enhanced antitumor efficacy. This study provides a promising strategy to improve the bioavailability and avoid side effects of HM as antitumor agents by choosing BSA as carriers.

Validation of the predictive accuracy of "clinical + morphology nomogram" for the rebleeding risk of ruptured intracranial aneurysms after admission.

BACKGROUND: Rebleeding can cause a catastrophic outcome after aneurysmal subarachnoid hemorrhage. A clinical + morphology nomogram was promoted in our previous study to assist in discriminating the rupture intracranial aneurysms (RIAs) with a high risk of rebleeding. The aim of this study was to validate the predictive accuracy of this nomogram model. METHOD: The patients with RIAs in two medical centers from December 2020 to September 2021 were retrospectively reviewed, whose clinical and morphological parameters were collected. The Cox regression model was employed to identify the risk factors related to rebleeding after their admission. The predicting accuracy of clinical + morphological nomogram, ELAPSS score and PHASES score was compared based on the area under the curves (AUCs). RESULTS: One hundred thirty-eight patients with RIAs were finally included in this study, 20 of whom suffering from rebleeding after admission. Hypertension (hazard ratio (HR), 2.54; a confidence interval of 95% (CI), 1.01-6.40; P = 0.047), bifurcation (HR, 3.88; 95% CI, 1.29-11.66; P = 0.016), and AR (HR, 2.68; 95% CI, 1.63-4.41; P < 0.001) were demonstrated through Cox regression analysis as the independent risk factors for rebleeding after admission. The clinical + morphological nomogram had the highest predicting accuracy (AUC, 0.939, P < 0.01), followed by the bifurcation (AUC, 0.735, P = 0.001), AR (AUC, 0.666, P = 0.018), and ELAPSS score (AUC, 0.682, P = 0.009). Hypertension (AUC, 0.693, P = 0.080) or PHASES score (AUC, 0.577, P = 0.244) could not be used to predict the risk of rebleeding after admission. The calibration curve for the probability of rebleeding showed a good agreement between the prediction through clinical + morphological nomogram and actual observation. CONCLUSION: Hypertension, bifurcation site, and AR were independent risk factors related to the rebleeding of RIAs after admission. The clinical + morphological nomogram could help doctors to identify the high-risk RIAs with a high predictive accuracy.

InSbAs Two-Dimensional Electron Gases as a Platform for Topological Superconductivity.

Topological superconductivity can be engineered in semiconductors with strong spin-orbit interaction coupled to a superconductor. Experimental advances in this field have often been triggered by the development of new hybrid material systems. Among these, two-dimensional electron gases (2DEGs) are of particular interest due to their inherent design flexibility and scalability. Here, we discuss results on a 2D platform based on a ternary 2DEG (InSbAs) coupled to in situ grown aluminum. The spin-orbit coupling in these 2DEGs can be tuned with the As concentration, reaching values up to 400 meV Å, thus exceeding typical values measured in its binary constituents. In addition to a large Landé g-factor of ∼55 (comparable to that of InSb), we show that the clean superconductor-semiconductor interface leads to a hard induced superconducting gap. Using this new platform, we demonstrate the basic operation of phase-controllable Josephson junctions, superconducting islands, and quasi-1D systems, prototypical device geometries used to study Majorana zero modes.

Efficient CO2 electroreduction on facet-selective copper films with high conversion rate.

Tuning the facet exposure of Cu could promote the multi-carbon (C2+) products formation in electrocatalytic CO2 reduction. Here we report the design and realization of a dynamic deposition-etch-bombardment method for Cu(100) facets control without using capping agents and polymer binders. The synthesized Cu(100)-rich films lead to a high Faradaic efficiency of 86.5% and a full-cell electricity conversion efficiency of 36.5% towards C2+ products in a flow cell. By further scaling up the electrode into a 25 cm2 membrane electrode assembly system, the overall current can ramp up to 12 A while achieving a single-pass yield of 13.2% for C2+ products. An insight into the influence of Cu facets exposure on intermediates is provided by in situ spectroscopic methods supported by theoretical calculations. The collected information will enable the precise design of CO2 reduction reactions to obtain desired products, a step towards future industrial CO2 refineries.

New Application of Waste Citrus Maxima Peel-Derived Carbon as an Oxygen Electrode Material for Lithium Oxygen Batteries.

Recently, lithium oxygen battery has become a promising candidate to satisfy the current large-energy-storage devices demand because of its amazing theoretical energy density. However, it still faces problems such as poor reversibility and short cycle life. Here, citrus maxima peel (CMP) was used as a precursor to prepare activated and Fe-loading carbon (CMPACs and CMPACs-Fe, respectively) via pyrolysis in nitrogen atmosphere at 900 °C, in which KOH was added as an activator. Electrochemical measurements show that CMPAC-based Li-O2 battery possesses high specific capacity of 7800 mA h/g, steady cycling performance of 466 cycles with a corresponding Coulombic efficiency of 92.5%, good rate capability, and reversibility. Besides, CMPACs-Fe-based O2 electrode delivers even lower overpotential in both charge and discharge processes. We conclude that these excellent electrochemical performances of CMPACs and CMPACs-Fe-based O2 electrode benefit from their cellular porous structure, plenty of active sites, and large specific surface area (900 and 768 m2/g), which suggest that these biomass-derived porous carbons might become promising candidates to achieve efficient lithium oxygen battery.

Ultralong Cycle Life Achieved by a Natural Plant: Miscanthus × giganteus for Lithium Oxygen Batteries.

Large energy-storage systems and electric vehicles require energy devices with high power and high energy density. Lithium oxygen (Li-O2) batteries could achieve high energy density, but they are still facing problems such as low practical capacity and poor cyclability. Here, we prepare activated carbons (MGACs) based on the natural plant Miscanthus × giganteus (MG) through slow pyrolysis. It possesses a large surface area, plenty of active sites, and high porosity, which are beneficial to the utilization of oxygen electrode in Li-O2 batteries. The MGACs-based oxygen electrode delivers a high specific capacity of 9400 mAh/g at 0.02 mA/cm2, and long cycle life of 601 cycles (with a cutoff capacity of 500 mAh/g) and 295 cycles (with a cutoff capacity of 1000 mAh/g) at 0.2 mA/cm2, respectively. Additionally, the material exhibits high rate capability and high reversibility, which is a promising candidate for the application in Li-O2 batteries.