Strength-Plasticity Relationship and Intragranular Nanophase Distribution of Hybrid (GNS + SiCnp)/Al Composites Based on Heat Treatment.

The distribution of reinforcements and interfacial bonding state with the metal matrix are crucial factors in achieving excellent comprehensive mechanical properties for aluminum (Al) matrix composites. Normally, after heat treatment, graphene nanosheets (GNSs)/Al composites experience a significant loss of strength. Here, better performance of GNS/Al was explored with a hybrid strategy by introducing 0.9 vol.% silicon carbide nanoparticles (SiCnp) into the composite. Pre-ball milling of Al powders and 0.9 vol.% SiCnp gained Al flakes that provided a large dispersion area for 3.0 vol.% GNS during the shift speed ball milling process, leading to uniformly dispersed GNS for both as-sintered and as-extruded (0.9 vol.% SiCnp + 3.0 vol.% GNS)/Al. High-temperature heat treatment at 600 °C for 60 min was performed on the as-extruded composite, giving rise to intragranular distribution of SiCnp due to recrystallization and grain growth of the Al matrix. Meanwhile, nanoscale Al4C3, which can act as an additional reinforcing nanoparticle, was generated because of an appropriate interfacial reaction between GNS and Al. The intragranular distribution of both nanoparticles improves the Al matrix continuity of composites and plays a key role in ensuring the plasticity of composites. As a result, the work hardening ability of the heat-treated hybrid (0.9 vol.% SiCnp + 3.0 vol.% GNS)/Al composite was well improved, and the tensile elongation increased by 42.7% with little loss of the strength. The present work provides a new strategy in achieving coordination on strength-plasticity of Al matrix composites.

Effect of Particle Strength on SiCp/Al Composite Properties with Network Architecture Design.

Recent works have experimentally proven that metal matrix composites (MMCs) with network architecture present improved strength-ductility match. It is envisaged that the performance of architecturally designed composites is particularly sensitive to reinforcement strength. Here, reinforcing particles with various fracture strengths were introduced in numerical models of composites with network particle distribution. The results revealed that a low particle strength (1 GPa) led to early-stage failure and brittle fracture. Nevertheless, a high particle strength (5 GPa) delayed the failure behavior and led to ductile fracture at the SiC/Al-Al macro-interface areas. Therefore, the ultimate tensile strengths (UTS) of the network SiC/Al composites increased from 290 to 385 MPa, with rising particle strength from 1 to 5 GPa. Based on the composite property, different particle fracture threshold strengths existed for homogeneous (~2.7 GPa) and network (~3.7 GPa) composites. The higher threshold strength in network composites was related to the increased stress concentration induced by network architecture. Unfortunately, the real fracture strength of the commercial SiC particle is 1-2 GPa, implying that it is possible to select a high-strength particle necessary for efficient network architecture design.

Multifunctional MOF@COF Nanoparticles Mediated Perovskite Films Management Toward Sustainable Perovskite Solar Cells.

Although covalent organic frameworks (COFs) with high π-conjugation have recently exhibited great prospects in perovskite solar cells (PSCs), their further application in PSCs is still hindered by face-to-face stacking and aggregation issues. Herein, metal-organic framework (MOF-808) is selected as an ideal platform for the in situ homogeneous growth of a COF to construct a core-shell MOF@COF nanoparticle, which could effectively inhibit COF stacking and aggregation. The synergistic intrinsic mechanisms induced by the MOF@COF nanoparticles for reinforcing intrinsic stability and mitigating lead leakage in PSCs have been explored. The complementary utilization of π-conjugated skeletons and nanopores could optimize the crystallization of large-grained perovskite films and eliminate defects. The resulting PSCs achieve an impressive power conversion efficiency of 23.61% with superior open circuit voltage (1.20 V) and maintained approximately 90% of the original power conversion efficiency after 2000 h (30-50% RH and 25-30 °C). Benefiting from the synergistic effects of the in situ chemical fixation and adsorption abilities of the MOF@COF nanoparticles, the amount of lead leakage from unpackaged PSCs soaked in water (< 5 ppm) satisfies the laboratory assessment required for the Resource Conservation and Recovery Act Regulation.

Engineering of the AAV-Compatible Hair Cell-Specific Small-Size Myo15 Promoter for Gene Therapy in the Inner Ear.

Adeno-associated virus (AAV)-mediated gene therapy is widely applied to treat numerous hereditary diseases in animal models and humans. The specific expression of AAV-delivered transgenes driven by cell type-specific promoters should further increase the safety of gene therapy. However, current methods for screening cell type-specific promoters are labor-intensive and time-consuming. Herein, we designed a "multiple vectors in one AAV" strategy for promoter construction in vivo. Through this strategy, we truncated a native promoter for Myo15 expression in hair cells (HCs) in the inner ear, from 1,611 bp down to 1,157 bp, and further down to 956 bp. Under the control of these 2 promoters, green fluorescent protein packaged in AAV-PHP.eB was exclusively expressed in the HCs. The transcription initiation ability of the 2 promoters was further verified by intein-mediated otoferlin recombination in a dual-AAV therapeutic system. Driven by these 2 promoters, human otoferlin was selectively expressed in HCs, resulting in the restoration of hearing in treated Otof -/- mice for at least 52 weeks. In summary, we developed an efficient screening strategy for cell type-specific promoter engineering and created 2 truncated Myo15 promoters that not only restored hereditary deafness in animal models but also show great potential for treating human patients in future.

Large Cyclability of Elastocaloric Effect in Highly Porous Ni-Fe-Ga Foams.

Solid-state refrigeration based on elastocaloric materials (eCMs) requires reversibility and repeatability. However, the intrinsic intergranular brittleness of ferromagnetic shape memory alloys (FMSMAs) limits fatigue life and, thus, is the crucial bottleneck for its industrial applications. Significant cyclic stability of elastocaloric effects (eCE) via 53% porosity in Ni-Fe-Ga FMSMA has already been proven. Here, Ni-Fe-Ga foams (single-/hierarchical pores) with high porosity of 64% and 73% via tailoring the material's architecture to optimize the eCE performances are studied. A completely reversible superelastic behavior at room temperature (297 K) is demonstrated in high porosity (64-73%) Ni-Fe-Ga foams with small stress hysteresis, which is greatly conducive to durable fatigue life. Consequentially, hierarchical pore foam with 64% porosity exhibits a maximum reversible ∆Tad of 2.0 K at much lower stress of 45 MPa with a large COPmat of 34. Moreover, it shows stable elastocaloric behavior (ΔTad = 2.0 K) over >300 superelastic cycles with no significant deterioration. The enhanced eCE cyclability can be attributed to the pore hierarchies, which remarkably reduce the grain boundary constraints and/or limit the propagation of cracks to induce multiple stress-induced martensitic transformations (MTs). Therefore, this work paves the way for designing durable fatigue life FMSMAs as promising eCMs by manipulating the material architectures.

Interfacial Electron Transfer in PbI2@Single-Walled Carbon Nanotube van der Waals Heterostructures for High-Stability Self-Powered Photodetectors.

Acquiring a deep insight into the electron transfer mechanism and applications of one-dimensional (1D) van der Waals heterostructures (vdWHs) has always been a significant challenge. Herein, through direct observation using aberration-corrected transmission electron microscopy (AC-TEM), we verify the stable formation of a high-quality 1D heterostructure composed of PbI2@single-walled carbon nanotubes (SWCNTs). The phenomenon of electron transfer between PbI2 and SWCNT is elucidated through spectroscopic investigations, including Raman and X-ray photoelectron spectroscopy (XPS). Electrochemical testing indicates the electron transfer and enduring stability of 1D PbI2 within SWCNTs. Moreover, leveraging the aforementioned electron transfer mechanism, we engineer self-powered photodetectors that exhibit exceptional photocurrent and a 3-order-of-magnitude switching ratio. Subsequently, we reveal its unique electron transfer behavior using Kelvin probe force microscopic (KPFM) tests. According to KPFM, the average surface potential of SWCNTs decreases by 80.6 mV after filling. Theoretical calculations illustrate a charge transfer of 0.02 e per unit cell. This work provides an effective strategy for the in-depth investigation and application of electron transfer in 1D vdWHs.

Ni/Mg Dual Concentration-Gradient Surface Modification to Enhance Structural Stability and Electrochemical Performance of Li-Rich Layered Oxides.

Li-rich layered oxides (LRLOs), with the advantages of high specific capacity and low cost, are considered as candidates for the next-generation cathode of lithium-ion batteries (LIBs). Unfortunately, sluggish kinetics and interfacial degradation lead to capacity loss and voltage decay of the material during cycling. To address these issues, we propose a Ni/Mg dual concentration-gradient modification strategy for LRLOs. From the center to the surface of the modified materials, the contents of Ni and Mg are gradually increased while the content of Mn is decreased. The high Ni content on the surface increases the proportion of cationic redox, elevating the operating voltage and accelerating reaction kinetics. Moreover, the doped Mg on the surface of the material acting as a stabilizing pillar suppresses the migration of transition metals, stabilizing the layered structure. Therefore, the material with the Ni/Mg dual concentration-gradients delivers a superior electrochemical performance, exhibiting a suppressed voltage decay of 2.8 mV per cycle during 200 cycles (1 C, 2-4.8 V) and an excellent rate capability of 94.84 mAh/g at 7C. This study demonstrates a synergic design to construct high-performance LRLO cathode materials for LIBs.

Hair cell-specific Myo15 promoter-mediated gene therapy rescues hearing in DFNB9 mouse model.

Adeno-associated viral (AAV) vectors are increasingly used as vehicles for gene delivery to treat hearing loss. However, lack of specificity of the transgene expression may lead to overexpression of the transgene in nontarget tissues. In this study, we evaluated the expression efficiency and specificity of transgene delivered by AAV-PHP.eB under the inner ear sensory cell-specific Myo15 promoter. Compared with the ubiquitous CAG promoter, the Myo15 promoter initiates efficient expression of the GFP fluorescence reporter in hair cells, while minimizing non-specific expression in other cell types of the inner ear and CNS. Furthermore, using the Myo15 promoter, we constructed an AAV-mediated therapeutic system with the coding sequence of OTOF gene. After inner ear injection, we observed apparent hearing recovery in Otof-/- mice, highly efficient expression of exogenous otoferlin, and significant improvement in the exocytosis function of inner hair cells. Overall, our results indicate that gene therapy mediated by the hair cell-specific Myo15 promoter has potential clinical application for the treatment of autosomal recessive deafness and yet for other hereditary hearing loss related to dysfunction of hair cells.

Nanogap engineering of 3D nanoraspberries into 2D plasmonic nanoclusters toward improved SERS performance.

3D raspberry-like core/satellite nanostructures were prepared by controlled surface functionalization of silica spheres using crosslinked poly(4-vinylpyridine) (P4VP) chains with known binding affinity for gold nanoparticles (AuNPs). The 3D SiO2-g-P(4VP-co-DVB)/AuNP nanoraspberries can be further transformed into 2D plasmonic nanoclusters by etching the silica core with hydrofluoric acid (HF). After the transformation, the interparticle distance between the AuNPs dramatically reduced from a 10 nm scale to sub 2 nm. Owing to the strong electromagnetic field generated by the plasmonic coupling between AuNPs in very close proximity, the established P(4VP-co-DVB)/AuNP nanoclusters provided strong and undisturbed Raman signals as a SERS substrate. In addition, benefiting from the stabilizing effect of the crosslinked P(4VP-co-DVB) network, the prepared SERS substrate has the advantages of good uniformity, stability and reproducibility, as well as strong SERS enhancement, endowing it with great potential for rapid and efficient SERS detection.

Regulating Grind-Induced Lattice Distortion for Nickel-Rich Cathodes by Annealing.

The commercialization of high-performance nickel-rich cathodes always awaits a cost-effective, environmentally friendly, and large-scale preparation method. Despite a grinding process normally adopted in the synthesis of the nickel-rich cathodes, lattice distortion, rough surface, and sharp edge transformation inevitably occurr in the resultant samples. In this work, an additional annealing process is proposed that aims at regulating lattice distortion as well as achieving round and smoother morphologies without any structural or elemental modifications. Such a structural enhancement is favored for improved lithium diffusion and electrochemical stability during cycling. Consequently, the annealed cathodes demonstrate a considerable enhancement in capacity retention, escalating from 68.7% to 91.9% after 100 cycles at 1 C. Additionally, the specific capacity is significantly increased from 64 to 142 mAh g-1 at 5 C when compared to the unannealed cathodes. This work offers a straightforward and effective approach for reinforcing the electrochemical properties of nickel-rich cathodes.

The Key Role of Liraglutide in Preventing Autophagy of Vascular Smooth Muscle Cells in High Glucose Conditions

Background: The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LIRA) is a potential hypoglycemic drug with anti-atherosclerosis (AS) effects. Autophagy in the vascular smooth muscle cells (VSMCs) facilitates AS. However, the role of autophagy in the anti-AS mechanism of LIRA remains unclear. Aims: To examine the role and mechanisms of autophagy in LIRA's improvement of the biological characteristics of VSMCs in high glucose conditions. Study Design: Experimental animal study. Methods: VSMCs isolated from the thoracic aorta of male SD rats were subjected to a high glucose (HG) condition (25 mM) in Dulbecco's Modified Eagle's Medium with or without LIRA, the GLP-1 receptor antagonist exendin9-39 (Exe9-39), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), and autophagy inhibitors (3-methyladenine [3-MA] and bafilomycin A1 [Baf A1]). Acridine orange staining, western blotting, transmission electron microscopy, and mCherry-GFP-LC3 transfection were performed to evaluate the autophagy flux. Additionally, VSMC migration, calcification, proliferation, and apoptosis in HG conditions were observed. Results: Addition of LIRA alone or in combination with autophagy inhibitors significantly downregulated Beclin, increased the LC3-II/LC3-I ratio, and upregulated p62 in VSMCs in HG conditions. Furthermore, autophagolysosome formation was markedly curbed after treatment with LIRA and/or autophagy inhibitors. Inhibition of autophagy by LIRA and/or the autophagy inhibitors attenuated VSMC phenotype conversion, proliferation, migration, and calcification and promoted VSMC apoptosis in HG conditions. This protective role of LIRA was augmented by LY294002, but inhibited by Exe9-39. Conclusion: LIRA plays a significant role in the improvement of the biological features of VSMCs in HG conditions.

Consistent analysis of differentially expressed genes across 7 cell types in papillary thyroid carcinoma.

Single-cell transcriptome sequencing (scRNA-seq) provides a higher resolution of cellular differences than bulk RNA-seq, enabling the dissection of cell-type-specific responses to perturbations in papillary thyroid carcinoma (PTC). However, cellular genomic features are highly heterogeneous and have a large number of genes without any expression signals, which hinders the statistical power to identify differentially expressed genes and may generate many false-positive results. To overcome this challenge, we conducted an integrative analysis on two PTC scRNA-seq datasets and cross-validated consistent differential expression. By combining results from 32 common cell types in the two studies, we identified 31 consistently differentially expressed genes (DEGs) across seven cell types, including B cells, endothelial cells, epithelial cells, monocytes, NK cells, smooth muscle cells, and T cells. Functional enrichment analysis revealed that these genes are important for the adaptive immune response and autoimmune thyroid diseases. The additional disease-free survival analysis also confirmed that these 31 genes significantly affected patient survival time in large scale thyroid cancer cohort. Furthermore, we experimentally validated one of the top consistent DEGs as a potential biomarker gene of PTC epithelial cells, KRT7, which may be a upstream gene for the NF-κB signaling pathway. The result shows that KRT7 may promote thyroid cancer metastasis through the epithelial-mesenchymal transition and NF-κB signaling pathway. In summary, our single-cell transcriptome integration-based approach may provide insights into the important role of NF-κB in the underlying biology of the PTC.

Abnormal developmental trajectory and vulnerability to cardiac arrhythmias in tetralogy of Fallot with DiGeorge syndrome.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Ventricular dysfunction and cardiac arrhythmias are well-documented complications in patients with repaired TOF. Whether intrinsic abnormalities exist in TOF cardiomyocytes is unknown. We establish human induced pluripotent stem cells (hiPSCs) from TOF patients with and without DiGeorge (DG) syndrome, the latter being the most commonly associated syndromal association of TOF. TOF-DG hiPSC-derived cardiomyocytes (hiPSC-CMs) show impaired ventricular specification, downregulated cardiac gene expression and upregulated neural gene expression. Transcriptomic profiling of the in vitro cardiac progenitors reveals early bifurcation, as marked by ectopic RGS13 expression, in the trajectory of TOF-DG-hiPSC cardiac differentiation. Functional assessments further reveal increased arrhythmogenicity in TOF-DG-hiPSC-CMs. These findings are found only in the TOF-DG but not TOF-with no DG (ND) patient-derived hiPSC-CMs and cardiac progenitors (CPs), which have implications on the worse clinical outcomes of TOF-DG patients.

Heterogeneity and potential therapeutic insights for triple-negative breast cancer based on metabolic-associated molecular subtypes and genomic mutations.

Objective: Due to a lack of effective therapy, triple-negative breast cancer (TNBC) is extremely poor prognosis. Metabolic reprogramming is an important hallmark in tumorigenesis, cancer diagnosis, prognosis, and treatment. Categorizing metabolic patterns in TNBC is critical to combat heterogeneity and targeted therapeutics. Methods: 115 TNBC patients from TCGA were combined into a virtual cohort and verified by other verification sets, discovering differentially expressed genes (DEGs). To identify reliable metabolic features, we applied the same procedures to five independent datasets to verify the identified TNBC subtypes, which differed in terms of prognosis, metabolic characteristics, immune infiltration, clinical features, somatic mutation, and drug sensitivity. Results: In general, TNBC could be classified into two metabolically distinct subtypes. C1 had high immune checkpoint genes expression and immune and stromal scores, demonstrating sensitivity to the treatment of PD-1 inhibitors. On the other hand, C2 displayed a high variation in metabolism pathways involved in carbohydrate, lipid, and amino acid metabolism. More importantly, C2 was a lack of immune signatures, with late pathological stage, low immune infiltration and poor prognosis. Interestingly, C2 had a high mutation frequency in PIK3CA, KMT2D, and KMT2C and displayed significant activation of the PI3K and angiogenesis pathways. As a final output, we created a 100-gene classifier to reliably differentiate the TNBC subtypes and AKR1B10 was a potential biomarker for C2 subtypes. Conclusion: In conclusion, we identified two subtypes with distinct metabolic phenotypes, provided novel insights into TNBC heterogeneity, and provided a theoretical foundation for therapeutic strategies.

APLNR marks a cardiac progenitor derived with human induced pluripotent stem cells.

Cardiomyocytes can be readily derived from human induced pluripotent stem cell (hiPSC) lines, yet its efficacy varies across different batches of the same and different hiPSC lines. To unravel the inconsistencies of in vitro cardiac differentiation, we utilized single cell transcriptomics on hiPSCs undergoing cardiac differentiation and identified cardiac and extra-cardiac lineages throughout differentiation. We further identified APLNR as a surface marker for in vitro cardiac progenitors and immunomagnetically isolated them. Differentiation of isolated in vitro APLNR+ cardiac progenitors derived from multiple hiPSC lines resulted in predominantly cardiomyocytes accompanied with cardiac mesenchyme. Transcriptomic analysis of differentiating in vitro APLNR+ cardiac progenitors revealed transient expression of cardiac progenitor markers before further commitment into cardiomyocyte and cardiac mesenchyme. Analysis of in vivo human and mouse embryo single cell transcriptomic datasets have identified APLNR expression in early cardiac progenitors of multiple lineages. This platform enables generation of in vitro cardiac progenitors from multiple hiPSC lines without genetic manipulation, which has potential applications in studying cardiac development, disease modelling and cardiac regeneration.

Toughening of Ni-Mn-Based Polycrystalline Ferromagnetic Shape Memory Alloys.

Solid-state refrigeration technology is expected to replace conventional gas compression refrigeration technology because it is environmentally friendly and highly efficient. Among various solid-state magnetocaloric materials, Ni-Mn-based ferromagnetic shape memory alloys (SMAs) have attracted widespread attention due to their multifunctional properties, such as their magnetocaloric effect, elastocaloric effect, barocaloric effect, magnetoresistance, magnetic field-induced strain, etc. Recently, a series of in-depth studies on the thermal effects of Ni-Mn-based magnetic SMAs have been carried out, and numerous research results have been obtained. It has been found that poor toughness and cyclic stability greatly limit the practical application of magnetic SMAs in solid-state refrigeration. In this review, the influences of element doping, microstructure design, and the size effect on the strength and toughness of Ni-Mn-based ferromagnetic SMAs and their underlying mechanisms are systematically summarized. The pros and cons of different methods in enhancing the toughness of Ni-Mn-based SMAs are compared, and the unresolved issues are analyzed. The main research directions of Ni-Mn-based ferromagnetic SMAs are proposed and discussed, which are of scientific and technological significance and could promote the application of Ni-Mn-based ferromagnetic SMAs in various fields.

CoIn dual-atom catalyst for hydrogen peroxide production via oxygen reduction reaction in acid.

The two-electron oxygen reduction reaction in acid is highly attractive to produce H2O2, a commodity chemical vital in various industry and household scenarios, which is still hindered by the sluggish reaction kinetics. Herein, both density function theory calculation and in-situ characterization demonstrate that in dual-atom CoIn catalyst, O-affinitive In atom triggers the favorable and stable adsorption of hydroxyl, which effectively optimizes the adsorption of OOH on neighboring Co. As a result, the oxygen reduction on Co atoms shifts to two-electron pathway for efficient H2O2 production in acid. The H2O2 partial current density reaches 1.92 mA cm-2 at 0.65 V in the rotating ring-disk electrode test, while the H2O2 production rate is as high as 9.68 mol g-1 h-1 in the three-phase flow cell. Additionally, the CoIn-N-C presents excellent stability during the long-term operation, verifying the practicability of the CoIn-N-C catalyst. This work provides inspiring insights into the rational design of active catalysts for H2O2 production and other catalytic systems.

[Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway].

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

P2X7 receptor is required for the ototoxicity caused by aminoglycoside in developing cochlear hair cells.

Aminoglycoside antibiotics (AGAs) are widely used in life-threatening infections, but they accumulate in cochlear hair cells (HCs) and result in hearing loss. Increases in adenosine triphosphate (ATP) concentrations and P2X7 receptor expression were observed after neomycin treatment. Here, we demonstrated that P2X7 receptor, which is a non-selective cation channel that is activated by high ATP concentrations, may participate in the process through which AGAs enter hair cells. Using transgenic knockout mice, we found that P2X7 receptor deficiency protects HCs against neomycin-induced injury in vitro and in vivo. Subsequently, we used fluorescent gentamicin-Fluor 594 to study the uptake of AGAs and found fluorescence labeling in wild-type mice but not in P2rx7-/- mice in vitro. In addition, knocking-out P2rx7 did not significantly alter the HC count and auditory signal transduction, but it did inhibit mitochondria-dependent oxidative stress and apoptosis in the cochlea after neomycin exposure. We thus conclude that the P2X7 receptor may be linked to the entry of AGAs into HCs and is likely to be a therapeutic target for auditory HC protection.

Regulating Crystallization and Lead Leakage of Perovskite Solar Cell Via Novel Polyoxometalate-Based Metal-Organic Framework.

Despite the unprecedented progress in lead-based perovskite solar cells (PSCs), the toxicity and leakage of lead from degraded PSCs triggered by deep-level defects and poor crystallization quality increase environmental risk and become a critical challenge for eco-friendly PSCs. Here, a novel 2D polyoxometalate (POM)-based metal-organic framework (MOF) (C5 NH5 )4 (C3 N2 H5 )2 Zn3 (H8 P4 Mo6 O31 )2 ·2H2 O (POMOF) is ingeniously devised to address these issues. Note that the integration of POM endows POMOF with great advantages of electrical conductivity and charge mobility. Ordered POMOF induces the crystallization of high-quality perovskite film and eliminates lead-based defects to improve internal stability. The resultant PSCs achieve a superior power conversion efficiency (23.3%) accompanied by improved stability that maintains ≈90% of its original efficiency after 1600 h. Meanwhile, POMOF with phosphate groups effectively prevents lead leakage through in situ chemical anchoring and adsorption methods to reduce environmental risk. This work provides an effective strategy to minimize lead-based defects and leakage in sustainable PSCs through multi-functional POM-based MOF material.