Cancer-associated fibroblasts-secreted exosomal miR-92a-3p promotes tumor growth and stemness in hepatocellular carcinoma through activation of Wnt/ß-catenin signaling pathway by suppressing AXIN1.

Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in hepatocellular carcinoma (HCC). This study aimed to delve into the mechanisms underlying the tumor-promoting effects of CAFs in HCC. Small RNA sequencing was conducted to screen differential expressed microRNAs in exosomes derived from CAFs and normal fibroblasts (NFs). The miR-92a-3p expression was then measured using reverse transcriptase quantitative real-time PCR in CAFs, NFs, CAFs-derived exosomes (CAFs-Exo), and NF-derived exosomes (NFs-Exo). Compared to NFs or NF-Exo, CAFs and CAFs-Exo significantly promoted HCC cell proliferation, migration, and stemness. Additionally, compared to NFs or NF-Exo, miR-92a-3p level was notably higher in CAFs and CAFs-Exo, respectively. Exosomal miR-92a-3p was found to enhance HCC cell proliferation, migration, and stemness. Meanwhile, AXIN1 was targeted by miR-92a-3p. Exosomal miR-92a-3p could activate ß-catenin/CD44 signaling in HCC cells by inhibiting AXIN1 messenger RNA. Furthermore, in vivo studies verified that exosomal miR-92a-3p notably promoted tumor growth and stemness through targeting AXIN1/ß-catenin axis. Collectively, CAFs secreted exosomal miR-92a-3p was capable of promoting growth and stemness in HCC through activation of Wnt/ß-catenin signaling pathway by suppressing AXIN1. Therefore, targeting CAFs-derived miR-92a-3p may be a potential strategy for treating HCC.

Bi-Functional Electrolyte Additive Leading to a Highly Reversible and Stable Zinc Anode.

A stable stripping/plating process of the zinc anode is extremely critical for the practical application of aqueous zinc metal batteries. However, obstacles, including parasitic reactions and dendrite growth, notoriously deteriorate the stability and reversibility of zinc anode. Herein, Methyl l-α-aspartyl-l-phenylalaninate (Aspartame) is proposed as an effective additive in the ZnSO4 system to realize high stability and reversibility. Aspartame molecule with rich polar functional groups successfully participates in the solvation sheath of Zn2+ to suppress water-induced side reactions. The self-driven adsorption of Aspartame on zinc anode improves uniform deposition with a dose of 10 mm. These synergetic functions endow the zinc anode with a significantly long cycling lifespan of 4500 h. The cell coupled with a vanadium-based cathode also exhibited a high-capacity retention of 71.8% after 1000 cycles, outperforming the additive-free counterparts.

A Controllable Dual Interface Engineering Concept for Rational Design of Efficient Bifunctional Electrocatalyst for Zinc-Air Batteries.

Searching for bifunctional noble-free electrocatalysts with high activity and stability are urgently demanded for the commercial application of zinc-air batteries (ZABs). Herein, the authors propose a controllable dual interface engineering concept to design a noble-metal-free bifunctional catalyst with two well-designed interfaces (Ni3 FeN|MnO and MnO|CNTs) via a simple etching and wet chemical route. The heterointerface between MnO and Ni3 FeN facilitates the charge transfer rate during surface reaction, and heterointerface between MnO and carbon nanotubes (CNTs) support provides effective electron transfer path, while the CNTs matrix builds free diffusion channels for gas and electrolyte. Benefiting from the advantages of dual interfaces, Ni3 FeN/MnO-CNTs show superior oxygen reduction reaction and oxygen evolution reaction catalytic activity with an ultralow polarization gap (∆E) of 0.73 V, as well as preferable durability and rapid reaction kinetics. As proof of concept, the practical ZAB with Ni3 FeN/MnO-CNT exhibits high power density of 197 mW cm-2 and rate performance up to 40 mA cm-2 , as well as superior cycling stability over 600 cycles, outperforming the benchmark mixture of Pt/C and RuO2 . This work proposes a controllable dual interface engineering concept toward regulating the charge, electron, and gas transfer to achieve efficient bifunctional catalysts for ZABs.

Flexible, Flame-Resistant, and Dendrite-Impermeable Gel-Polymer Electrolyte for Li-O2 /Air Batteries Workable Under Hurdle Conditions.

Gel-polymer electrolytes are considered as a promising candidate for replacing the liquid electrolytes to address the safety concerns in Li-O2 /air batteries. In this work, by taking advantage of the hydrogen bond between thermoplastic polyurethane and aerogel SiO2 in gel polymer, a highly crosslinked quasi-solid electrolyte (FST-GPE) with multifeatures of high ionic conductivity, high mechanical flexibility, favorable flame resistance, and excellent Li dendrite impermeability is developed. The resulting gel-polymer Li-O2 /air batteries possess high reaction kinetics and stabilities due to the unique electrode-electrolyte interface and fast O2 diffusion in cathode, which can achieve up to 250 discharge-charge cycles (over 1000 h) in oxygen gas. Under ambient air atmosphere, excellent performances are observed for coin-type cells over 20 days and for prototype cells working under extreme bending conditions. Moreover, the FST-GPE electrolyte also exhibits durability to protect against fire, dendritic Li, and H2 O attack, demonstrating great potential for the design of practical Li-O2 /air batteries.

Characterization of cuproptosis signature in clear cell renal cell carcinoma by single cell and spatial transcriptome analysis.

Cuproptosis is a novel type to regulate cell death with copper-dependent manner, and has been reported to involve in the occurrence and development of various malignant tumors. However, the association between cuproptosis and the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remained unclear. To address this question, we integrated the single cell RNA sequencing (scRNA-seq) datasets of ccRCC across different stages, systematically examined the distinctive expression patterns of cuproptosis-related genes (CRGs) within the TME of ccRCC, and explored the crucial signatures using the spatial transcriptome sequencing (ST-seq) dataset. The cuproptosis activities reduced in cancer tissues along with the ccRCC development, and recovered after therapy. We identified HILPDA+ ccRCC1 subtype, characterized with hypoxia, as cuproptosis susceptible cells associated with a better prognosis. The main co-expression modules of HILPDA+ ccRCC1 subtype highlighted the role in anion transport, response to oxygen species and PD-L1-PD-1 pathway. Furthermore, the immunosuppressive cells might interact with HILPDA+ ccRCC1 subtype via HAVCR2-LGALS9, C3-C3AR1, HLA-A-CD8B and HLA-C-CD8A axises to shape the cuproptosis-related TME landscape. In summary, we anticipate that this study will offer valuable insights and potential strategies of cuproptosis for therapy of ccRCC.

Catalyst-Support Interaction in Polyaniline-Supported Ni3Fe Oxide to Boost Oxygen Evolution Activities for Rechargeable Zn-Air Batteries.

Catalyst-support interaction plays a crucial role in improving the catalytic activity of oxygen evolution reaction (OER). Here we modulate the catalyst-support interaction in polyaniline-supported Ni3Fe oxide (Ni3Fe oxide/PANI) with a robust hetero-interface, which significantly improves oxygen evolution activities with an overpotential of 270 mV at 10 mA cm-2 and specific activity of 2.08 mA cmECSA-2 at overpotential of 300 mV, 3.84-fold that of Ni3Fe oxide. It is revealed that the catalyst-support interaction between Ni3Fe oxide and PANI support enhances the Ni-O covalency via the interfacial Ni-N bond, thus promoting the charge and mass transfer on Ni3Fe oxide. Considering the excellent activity and stability, rechargeable Zn-air batteries with optimum Ni3Fe oxide/PANI are assembled, delivering a low charge voltage of 1.95 V to cycle for 400 h at 10 mA cm-2. The regulation of the effect of catalyst-support interaction on catalytic activity provides new possibilities for the future design of highly efficient OER catalysts.

Stabilizing Li Anodes in I2 Steam to Tackle the Shuttling-Induced Depletion of an Iodide/Triiodide Redox Mediator in Li-O2 Batteries with Suppressed Li Dendrite Growth.

Redox mediators (RMs) have become a significant point in the now-established Li-O2 battery system to reduce the charging overpotential in the oxygen evolution process. Nevertheless, a major inherent barrier of the RM is the redox shuttling between the Li metal anode and mobile RM, resulting in the corrosion of Li and depletion of RM. In this study, taking iodide/triiodide as a model RM, we propose an effective strategy by immersing the Li metal anode in I2 steam to create a 1.5 µm thick surface protective layer. The resultant ionic conductive LiI layer on the Li metal anode can not only suppress Li dendrite growth but also act as a buffer layer between the RM and bare Li. By combining the iodide/triiodide RM with the LiI protective layer, the Li-O2 battery shows low and steady charge voltage plateaus of ∼3.6 V over 70 cycles. Importantly, the symmetrical cell using the LiI-protected Li electrode exhibited small Li plating/stripping overpotentials (∼20 mV, 480 h), far superior to that of the bare Li electrode (∼70 mV, 300 h). The in situ interfacial observation shows that dendrite growth on the Li metal can be effectively suppressed by optimizing the LiI protective layer.

Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis.

Immunoglobulin γ-1 heavy chain constant region (IGHG1) is a functional isoform of immunoglobulins and plays an important role in the cytolytic activity of immune effector cells. Dysregulated IGHG1 was implicated in the occurrence and development of various tumors. Protoporphyrin IX (PpIX) is an endogenous fluorophore and is used in photodynamic therapy, which induces the generation of reactive oxygen species to initiate the death of tumor cells. However, the roles of IGHG1 in the colorectal cancer cell proliferation and PpIX accumulation have not been reported yet. Data from qRT-PCR and western blot analysis showed that IGHG1 was up-regulated in the colorectal cancer cells. Colorectal cancer cells were then transfected with shRNA targeting IGHG1 to down-regulate IGHG1 and conducted with Cell Counting Kit 8 (CCK8) and colony formation assays. Results demonstrated that shRNA-mediated down-regulation of IGHG1 decreased cell viability of colorectal cancer and suppressed cell proliferation. Moreover, PpIX accumulation was promoted and the hemin content was decreased by the silence of IGHG1. Interference of IGHG1 reduced the phosphorylated extracellular signal-regulated kinase (ERK) and ferrochelatase (FECH) expression, resulting in retarded cell proliferation in an MEK-FECH axis-dependent pathway.

Ultralong Cycle Life Li-O2 Battery Enabled by a MOF-Derived Ruthenium-Carbon Composite Catalyst with a Durable Regenerative Surface.

The cycling performance of Li-O2 batteries (LOBs), which is an important parameter determining the practical use of this advanced energy technology with ultrahigh energy density, is strongly affected by the nature of the oxygen electrocatalyst. As a good oxygen electrode, it should possess good activity for both the oxygen evolution reaction and the oxygen reduction reaction and superior stability under operating conditions. During the past, oxygen electrodes for LOBs were generally fabricated by loading noble metal nanoparticles on the surface of a porous carbon support. However, the nanoparticles could easily lose contact with the carbon support during the reversible liquid-gas-solid reactions that involve lithium ions, oxygen gas, and Li2O2. Herein, we reported a novel Ru-metal-organic framework (MOF)-derived carbon composite, characterized by stereoscopic Ru nanoparticle distribution within the carbon matrix, as an alternative oxygen catalyst of LOBs, enabling superior operational stability and favorable activity. More specifically, the battery demonstrated stable charge-discharge cycling for up to 800 times (∼107 days) at a current density of 500 mA g-1 with low discharge/charge overpotentials (∼0.2/0.7 V vs Li). A mechanism of regenerative surface was further proposed to explain the excellent cycling stability of the LOBs through the use of the Ru-MOF-C catalyst. These encouraging results imply an accessible solution to address issues related to the oxygen catalyst for the realization of practical LOBs.

A gel diffusion assay for visualization and quantification of chitinase activity.

Higher plants, bacteria, fungi, insects, and crustaceans all produce chitinases. Chitinase genes in many organisms are currently under investigation. Chitinase activity is usually assayed with radiolabeled or fluorogenic substrates. We developed a simple, inexpensive, nonradioactive gel-diffusion assay for chitinase that can be used to screen large numbers of samples. In this assay, chitinase diffuses from a small circular well cut in an agarose or agar gel containing the substrate glycol chitin, a soluble, modified form of chitin. Chitinase catalyzes the cleavage of glycol chitin as it diffuses through the gel, leaving a dark, unstained circular zone around the well, because the fluorescent dye calcofluor binds only to undigested chitin. Sample activities can be determined from linear regression of log-standard enzyme concentration versus the zone diameter of internal standards on each Petri dish used for a diffusion assay.