Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

PBAT/lignin-ZnO composite film for food packaging: Photo-stability, better barrier and antibacterial properties.

When PBAT used as film, stability deteriorates under sunlight exposure, the poor barrier and antibacterial properties are also limiting its application. In this work, lignin-ZnO nanoparticles were prepared by hydrothermal method, as additives to fill the PBAT matrix. In addition, PBAT-lignin-ZnO composite films were successfully prepared by melting and hot-pressing method. It is found that lignin could well dispersed the ZnO when its implantation into PBAT films, and lignin-ZnO not only maintaining tensile strength and thermal stability, but also could prompt PBAT's crystallinity. Especially, P-L-ZnO-2 composite films have good photostability. After 60 h aging, it can still maintain good molecular weight, chemical structure and mechanical properties. Besides, these composite films have improved hydrophobicity, barrier and antibacterial properties, could prevent mildew and significantly reduce the weight loss rate, color difference and hardness changes of strawberries during storage. This work provides a potential film material for outdoor applications and food packaging.

Rapidly-manufactured CD276 CAR-T cells exhibit enhanced persistence and efficacy in pancreatic cancer.

BACKGROUND: Pancreatic cancer is one of the most lethal malignancies and the lack of treatment options makes it more deadly. Chimeric Antigen Receptor T-cell (CAR-T) immunotherapy has revolutionized cancer treatment and made great breakthroughs in treating hematological malignancies, however its success in treating solid cancers remains limited mainly due to the lack of tumor-specific antigens. On the other hand, the prolonged traditional manufacturing process poses challenges, taking 2 to 6 weeks and impacting patient outcomes. CD276 has recently emerged as a potential therapeutic target for anti-solid cancer therapy. Here, we investigated the efficacy of CD276 CAR-T and rapidly-manufactured CAR-T against pancreatic cancer. METHODS: In the present study, CD276 CAR-T was prepared by CAR structure carrying 376.96 scFv sequence, CD8 hinge and transmembrane domain, 4-1BB and CD3ζ intracellular domains. Additionally, CD276 rapidly-manufactured CAR-T (named CD276 Dash CAR-T) was innovatively developed by shortening the duration of ex vitro culture to reduce CAR-T manufacturing time. We evaluated the anti-tumor efficacy of CD276 CAR-T and further compared the functional assessment of Dash CAR-T and conventional CAR-T in vitro and in vivo by detecting the immunophenotypes, killing ability, expansion capacity and tumor-eradicating effect of CAR-T. RESULTS: We found that CD276 was strongly expressed in multiple solid cancer cell lines and that CD276 CAR-T could efficiently kill these solid cancer cells. Moreover, Dash CAR-T was successfully manufactured within 48-72 h and the functional validation was carried out subsequently. In vitro, CD276 Dash CAR-T possessed a less-differentiated phenotype and robust proliferative ability compared to conventional CAR-T. In vivo xenograft mouse model, CD276 Dash CAR-T showed enhanced anti-pancreatic cancer efficacy and T cell expansion. Besides, except for the high-dose group, the body weight of mice was maintained stable, and the state of mice was normal. CONCLUSIONS: In this study, we proved CD276 CAR-T exhibited powerful activity against pancreatic cancer cells in vitro and in vivo. More importantly, we demonstrated the manufacturing feasibility, acceptable safety and superior anti-tumor efficacy of CD276 Dash CAR-T generated with reduced time. The results of the above studies indicated that CD276 Dash CAR-T immunotherapy might be a novel and promising strategy for pancreatic cancer treatment.

Electric Field Effects in Hybrid Perovskites Studied via Picosecond Kerr Microscopy.

We present time-resolved Kerr rotation (TRKR) spectra in thin films of CH3NH3PbI3 (MAPI) hybrid perovskite using a unique picosecond microscopy technique at 4 K having a spatial resolution of 2 µm and temporal resolution of 1 ps, subjected to both an in-plane applied magnetic field up to 700 mT and an electric field up to 104 V/cm. We demonstrate that the obtained TRKR dynamics and spectra are substantially inhomogeneous across the MAPI films with prominent resonances at the exciton energy and interband transition of this compound. From the obtained quantum beating response as a function of magnetic field in the Voigt configuration, we also extract the inhomogeneity of the electron and hole Lande g-values and spin coherence time, T2*. We also report the TRKR dependence on both the applied magnetic field and electric field. From the change in the quantum beating dynamics, we found that T2* substantially decreases upon the application of an electric field. At the same time, from the induced spatial TRKR changes, we show that the electric field induced effects are caused by ion migration in the MAPI films.

Simulating multiple variability in spatially resolved transcriptomics with scCube.

A pressing challenge in spatially resolved transcriptomics (SRT) is to benchmark the computational methods. A widely-used approach involves utilizing simulated data. However, biases exist in terms of the currently available simulated SRT data, which seriously affects the accuracy of method evaluation and validation. Herein, we present scCube ( https://github.com/ZJUFanLab/scCube ), a Python package for independent, reproducible, and technology-diverse simulation of SRT data. scCube not only enables the preservation of spatial expression patterns of genes in reference-based simulations, but also generates simulated data with different spatial variability (covering the spatial pattern type, the resolution, the spot arrangement, the targeted gene type, and the tissue slice dimension, etc.) in reference-free simulations. We comprehensively benchmark scCube with existing single-cell or SRT simulators, and demonstrate the utility of scCube in benchmarking spot deconvolution, gene imputation, and resolution enhancement methods in detail through three applications.

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-ß1/Smad3 Signaling Pathway.

OBJECTIVE: Intestinal fibrosis is a refractory complication of inflammatory bowel disease (IBD). Tumor necrosis factor ligand-related molecule-1A (TL1A) is important for IBD-related intestinal fibrosis in a dextran sodium sulfate (DSS)-induced experimental colitis model. This study aimed to explore the effects of TL1A on human colonic fibroblasts. METHODS: A trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic (Tg) or wild-type (WT) mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis. The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell (PBMC) supernatant. The proliferation and activation of CCD-18Co cells were detected by BrdU assays, flow cytometry, immunocytochemistry and Western blotting. Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The level of collagen metabolism in the TNBS+ethyl alcohol (EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group. Transforming growth factor-ß1 (TGF-ß1) and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group. The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A, and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4% at 24 h. TL1A promoted cell activation and increased the levels of COL1A2, COL3A1, and TIMP-1 in CCD-18Co cells. Treatment of CCD-18Co cells with TL1A increased the expression of TGF-ß1 and p-Smad3. CONCLUSION: TL1A promotes TGF-ß1-mediated intestinal fibroblast activation, proliferation, and collagen deposition and is likely related to an increase in the TGF-ß1/Smad3 signaling pathway.

Admission Left-Arm Systolic Blood Pressure and In-Hospital Mortality After Acute Type A Aortic Dissection Repair.

AIM: Admission systolic blood pressure is a significant predictor of in-hospital mortality in patients with acute type A aortic dissection (ATAAD). While previous studies have focussed on recording the highest blood pressure value from both arms, this study aimed to evaluate the associations between blood pressure in bilateral arms and in-hospital mortality. METHODS: Data were analysed from 262 patients with ATAAD treated at a single centre. The relationship between bilateral arm blood pressure upon admission and in-hospital mortality was assessed in a logistic regression model. To comprehensively evaluate potential non-linear relationships, the association between admission bilateral systolic blood pressure (SBP) and the risk of in-hospital mortality was analysed using restricted cubic splines on a continuous scale. RESULTS: Mean age was 53.6±12.5 years and 194 (74.0%) were male. Baseline and operative data showed that ages, body mass index, smoking, left-arm SBP, left-arm diastolic blood pressure (DBP), right-arm SBP, right-arm DBP, syncope, cerebral/cardiac ischaemia, retrograde brain perfusion, Bentall procedure, coronary artery bypass grafting, and aortic valve replacement significantly differed among the left-arm SBP tertiles. In-hospital mortality was 17.6% (46 of 262). Restricted cubic splines demonstrated that the relationship between presenting left-arm SBP and in-hospital mortality followed a U-shaped curve, whereas non-linearity was not detected in the right arm. CONCLUSION: This study found a U-shaped association between admission left-arm SBP and in-hospital mortality in ATAAD surgery patients, whereas a non-linearity relationship was not detected for right-arm SBP. Low left-arm SBP independently correlated with increased in-hospital mortality, underscoring the significance of bilateral blood pressure differences in ATAAD prognosis.

Ce-4f as an electron-modulation reservoir weakening Fe-O bond to induce iron vacancies in CeFevNi hydroxide for enhancing oxygen evolution reaction.

Designing novel rare-earth-transition metal composites is at the forefront of electrocatalyst research. However, the modulation of transition metal electronic structures by rare earths to induce vacancy defects and enhance electrochemical performance has rarely been reported. In this study, we systematically investigate the mechanism by which Ce-4f electron modulation weakens the Fe-O bond, thereby altering the electronic structure in CeFevNi hydroxide to improve oxygen evolution reaction (OER) performance. Theoretical calculations and experimental characterizations reveal that Ce-4f orbitals function as electron-modulation reservoirs, capable not only of retaining or donating electrons but also of influencing the material's electronic structure. Moreover, Ce-4f bands optimize the Fe lower Hubbard bands (LHB) and O-2p bands, leading to weakened Fe-O bonds and the formation of cationic vacancies. This change results in the upshift of the d-band center at the active sites, favoring the reaction energy barrier for oxygen intermediates in the OER process. The synthesized catalyst demonstrated an overpotential of 201 mV at 10 mA cm-2 and a lifetime exceeding 200 h at 100 mA cm-2 under alkaline conditions. This work offers a proof-of-concept for the application of the mechanism of rare earth-induced transition metal vacancy defects, providing a general guideline for the design and development of novel highly efficient catalysts.

Preliminary analysis on the characteristics of light absorption coefficients in typical rivers of different river basins across China.

As a vital constituent of water's optical properties, the absorption coefficients influence the distribution of underwater light field, consequently impacting the structures and functional patterns of riverine ecosystems. In this study, the light absorption of non-algal particulates (ad(λ), m-1), phytoplankton (aph(λ), m-1) and CDOM (ag(λ), m-1) of 380 water samples collected from 133 rivers in eight external river basins across China from 2013 to 2023 were examined to determine the optical absorption characteristics. Results showed significant differences in ad(λ), aph(λ) and ag(λ) across different basins. ① The water bodies of eight basins can be categorized into 5 dominant types of absorption coefficients. ② In eastern China, ag(440) exhibited a northeast-high and southwest-low spatial distribution pattern. The Songliao River Basin had the highest ag(440) than other basins. The higher slope S of ag(λ) in rivers compared to lakes and reservoirs confirm river water primarily derive CDOM from external sources, distinguishing them from lakes and reservoirs. ③ The Huaihe and Haihe River Basins had higher ad(440) and aph(440) values, primarily due to lower terrain and human activities, leading to the accumulation of suspended particles and nutrients. And soil erosion from the Loess Plateau caused significant differences in ad(440) between the upper and middle reaches of the Yellow River Basin. These findings hold significant implications for understanding the optical characteristics of rivers in China.

Emergence of novel hypervirulent Acinetobacter baumannii strain and herpes simplex type 1 virus in a case of community-acquired pneumonia in China.

BACKGROUND: A. baumannii is an important and common clinical pathogen, especially in the intensive care unit (ICU). This study aimed to characterize one hypervirulent A. baumannii strain in a patient with community-acquired pneumonia and herpes simplex type 1 virus infection. METHODS: Minimum inhibitory concentrations (MICs) were determined using the Kirby-Bauer (K-B) and broth microdilution methods. Galleria mellonella infection model experiment was conducted. Whole-genome sequencing (WGS) was performed using the Illumina and Nanopore platforms. The resistance and virulence determinants were identified using the ABRicate program with ResFinder and the VFDB database. The capsular polysaccharide locus (K locus) and lipooligosaccharide outer core locus (OC locus) were identified using Kleborate with Kaptive. Phylogenetic analyses were conducted using the BacWGSTdb server. RESULTS: A. baumannii XH2146 strain belongs to ST10Pas and ST447Oxf. The strain was resistant to cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole (TMP-SMX). Bautype and Kaptive analyses showed that XH2146 contains OCL2 and KL49. WGS analysis revealed that the strain harbored blaADC-76, blaOXA-68, ant(3'')-IIa, tet(B), and sul2. Notably, tet(B) and sul2, both were located within a 114,700-bp plasmid (designated pXH2146-1). Virulence assay revealed A. baumannii XH2146 possessed higher virulence than A. baumannii AB5075 at 12 h. Comparative genomic analysis showed that A. baumannii ST447 strains were mainly isolated from the USA and exhibited a relatively close genetic relationship. Importantly, 11 strains were observed to carry blaOXA-58; blaOXA-23 was identified in 11 isolates and three ST447 A. baumannii strains harbored blaNDM-1. CONCLUSIONS: Early detection of community-acquired hypervirulent Acinetobacter baumannii strains is recommended to prevent their extensive spread in hospitals.

Amphiphilic AIE Fluorescent Probe: A Dual-Functionality Strategy for Efficient Antibacterial Therapy Fluorescence Bioimaging against Staphylococcus aureus.

Drug-resistant bacteria present a grave threat to human health. Fluorescence imaging-guided photodynamic antibacterial therapy holds enormous potential as an innovative treatment in antibacterial therapy. However, the development of a fluorescent material with good water solubility, large Stokes shift, bacterial identification, and high photodynamic antibacterial efficiency remains challenging. In this study, we successfully synthesized an amphiphilic aggregation-induced emission (AIE) fluorescent probe referred to as NPTPA-QM. This probe possesses the ability to perform live-bacteria fluorescence imaging while also exhibiting antibacterial activity, specifically against Staphylococcus aureus (S. aureus). We demonstrate that NPTPA-QM can eliminate S. aureus at a very low concentration (2 µmol L-1). Moreover, it can effectively promote skin wound healing. Meanwhile, this NPTPA-QM exhibits an excellent imaging ability by simple mixing with S. aureus. In summary, this research presents a straightforward and highly effective method for creating "amphiphilic" AIE fluorescent probes with antibacterial properties. Additionally, it offers a rapid approach for imaging bacteria utilizing red emission.

Dual-trait genomic analysis in highly stratified Arabidopsis thaliana populations using genome-wide association summary statistics.

Genome-wide association study (GWAS) is a powerful tool to identify genomic loci underlying complex traits. However, the application in natural populations comes with challenges, especially power loss due to population stratification. Here, we introduce a bivariate analysis approach to a GWAS dataset of Arabidopsis thaliana. We demonstrate the efficiency of dual-phenotype analysis to uncover hidden genetic loci masked by population structure via a series of simulations. In real data analysis, a common allele, strongly confounded with population structure, is discovered to be associated with late flowering and slow maturation of the plant. The discovered genetic effect on flowering time is further replicated in independent datasets. Using Mendelian randomization analysis based on summary statistics from our GWAS and expression QTL scans, we predicted and replicated a candidate gene AT1G11560 that potentially causes this association. Further analysis indicates that this locus is co-selected with flowering-time-related genes. The discovered pleiotropic genotype-phenotype map provides new insights into understanding the genetic correlation of complex traits.

Acid etching-induced nanocutting of LaNiO3 transplanting self-assembled photodiode array-like LaNiO3/N,P-RGO nanoreactor for efficient photocatalytic hydrogen evolution.

Nanoscale graphene-semiconductor composite photocatalysts with fascinating properties in the photocatalytic hydrogen evolution have inspired numerous interests in broad research fields. The architectures with efficient light response and promoting charge separation at the interface between reduced graphene oxide (RGO) and semiconductor are critical, yet synthesizing them remains a formidable challenge. Herein, the photodiode array-like LaNiO3/N,P-RGO (LNO/N,P-RGO) nanoreactor was constructed using an innovative strategy of acid etching-induced nanocutting self-assembly. Ammonium dihydrogen phosphate working as both a nitrogen phosphorus co-dopant and an acid etching reagent, cuts perovskite LaNiO3 (LNO) nanoparticles into nanorods, which are bonded evenly on the nitrogen phosphorus co-doped reduced graphene oxide (N,P-RGO) to form an n-n semiconductor heterojunction LNO/N,P-RGO as a photodiode array-like nanoreactor via hydrothermal treatment. The photodiode array-like nanostructure exposes more active sites that are conducive to light absorption. The robust Ni-C and P-O bonds promote the narrowing of space-charge region at the interface by UV irradiation, thereby improving the transport of photogenerated carriers by visible light irradiation. The LNO/N,P-RGO nanoreactor exhibits excellent photocatalytic hydrogen evolution performance with a yield of up to 354 µmol g-1 h-1 under UV-visible light, which is 50 times higher than that of pure perovskite LNO, and it also displays favorable recycling stability.

Genetic analysis of seven patients with inherited ichthyosis and Nagashima­type palmoplantar keratoderma.

Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using whole­exome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosis­like but distinct clinical manifestations. Genetic analysis identified diagnostic variations in the FLG, STS, KRT10 and SERPINB7 genes and clarified the carrying status of each variant in the respective family members. The two residues affected by the detected missense variants remained conserved across multiple species. Of note, the two variants, namely STS: c.452C>T(p.P151L) and c.647_650del(p.L216fs) are novel. In conclusion, a clear genetic differential diagnosis was made for the enrolled ichthyosis­associated patients; the study findings also extended the mutation spectrum of ichthyosis and provided solid evidence for the counseling of the affected families.

Drymariamides A-J, Antiadipogenic Cyclopeptides Incorporating Noncanonical Amino Acids from Drymaria cordata.

Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata, which led to the isolation of ten new orbitides, named drymariamides A-J (1-10). Compounds 2, 3, and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey's method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1-10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC50 value of 1.17 ± 0.19 µM.

An Experimental Study on the Mechanical Properties and Microstructure of the Cemented Paste Backfill Made by Coal-Based Solid Wastes and Nanocomposite Fibers under Dry-Wet Cycling.

The mechanical properties and microstructure of the cemented paste backfill (CPB) in dry-wet cycle environments are particularly critical in backfill mining. In this study, coal gangue, fly ash, cement, glass fiber, and nano-SiO2 were used to prepare CPB, and dry-wet cycle tests on CPB specimens with different curing ages were conducted. The compressive, tensile, and shear strength of CPB specimens with different curing ages under different dry-wet cycles were analyzed, and the microstructural damage of the specimens was observed by scanning electron microscopy (SEM). The results show that compared with the specimens without dry-wet cycles, the uniaxial compressive strength, tensile strength, and shear strength of the specimens with a curing age of 7 d after seven dry-wet cycles were the smallest, being reduced by 40.22%, 58.25%, and 66.8%, respectively. After seven dry-wet cycles, the compressive, tensile, and shear strength of the specimens with the curing age of 28 d decreased slightly. The SEM results show that with the increasing number of dry-wet cycles, the internal structure of the specimen becomes more and more loose and fragile, and the damage degree of the structural skeleton gradually increases, leading to the poor mechanical properties of CPB specimens. The number of cracks and pores on the specimen surface is relatively limited after a curing age of 28 d, while the occurrence of internal structural damage within the specimen remains insignificant. Therefore, the dry-wet cycle has an important influence on the both mechanical properties and microstructure of CPB. This study provides a reference for the treatment of coal-based solid waste and facilitates the understanding of the mechanical properties of backfill materials under dry-wet cycling conditions.

Role of co­inhibitory molecules in the treatment of psoriasis (Review).

Psoriasis is a common chronic inflammatory skin disease characterized by abnormal activation and infiltration of T-cells and excessive proliferation of keratinocytes (KCs). Its pathogenesis is complex and frequently accompanied by the imbalance of T-cell subpopulations, contributing to its development and further exacerbation. Therefore, the immune system, especially T-cells, is mainly involved in the pathogenesis of psoriasis. While T-cell activation not only requires the first recognition of T-cell receptor and major histocompatibility complex peptide, co-stimulatory and co-inhibitory pathways are reported to promote or dampen T-cell responses through a variety of mechanisms. In recent years, immuno-related agents have been applied in the treatment of numerous clinical diseases, including psoriasis, and are starting to show promising and potential therapy prospects in autoimmune skin diseases. The present review outlined the role of co-inhibitory molecules in the pathogenesis of psoriasis and their application in the treatment of psoriasis.

Recent progress in marine chondroitin sulfate, dermatan sulfate, and chondroitin sulfate/dermatan sulfate hybrid chains as potential functional foods and therapeutic agents.

Chondroitin sulfate (CS), dermatan sulfate (DS), and CS/DS hybrid chains are natural complex glycosaminoglycans with high structural diversity and widely distributed in marine organisms, such as fish, shrimp, starfish, and sea cucumber. Numerous CS, DS, and CS/DS hybrid chains with various structures and activities have been obtained from marine animals and have received extensive attention. However, only a few of these hybrid chains have been well-characterized and commercially developed. This review presents information on the extraction, purification, structural characterization, biological activities, potential action mechanisms, and structure-activity relationships of marine CS, DS, and CS/DS hybrid chains. We also discuss the challenges and perspectives in the research of CS, DS, and CS/DS hybrid chains. This review may provide a useful reference for the further investigation, development, and application of CS, DS, and CS/DS hybrid chains in the fields of functional foods and therapeutic agents.

Ir-Doped CuPd Single-Crystalline Mesoporous Nanotetrahedrons for Ethylene Glycol Oxidation Electrocatalysis: Enhanced Selective Cleavage of C-C Bond.

The development of highly efficient electrocatalysts for complete oxidation of ethylene glycol (EG) in direct EG fuel cells is of decisive importance to hold higher energy efficiency. Despite some achievements, their progress, especially electrocatalytic selectivity to complete oxidated C1 products, is remarkably slower than expected. In this work, we developed a facile aqueous synthesis of Ir-doped CuPd single-crystalline mesoporous nanotetrahedrons (Ir-CuPd SMTs) as high-performance electrocatalyst for promoting oxidation cleavage of C-C bond in alkaline EG oxidation reaction (EGOR) electrocatalysis. The synthesis relied on precise reduction/co-nucleation and epitaxial growth of Ir, Cu and Pd precursors with cetyltrimethylammonium chloride as the mesopore-forming surfactant and extra Br- as the facet-selective agent under ambient conditions. The products featured concave nanotetrahedron morphology enclosed by well-defined (111) facets, single-crystalline and mesoporous structure radiated from the center, and uniform elemental composition without any phase separation. Ir-CuPd SMTs disclosed remarkably enhanced electrocatalytic activity and excellent stability as well as superior selectivity of C1 products for alkaline EGOR electrocatalysis. Detailed mechanism studies demonstrated that performance improvement came from structural and compositional synergies, which kinetically accelerated transports of electrons/reactants within active sites of penetrated mesopores and facilitated oxidation cleavage of high-energy-barrier C-C bond of EG for desired C1 products. More interestingly, Ir-CuPd SMTs performed well in coupled electrocatalysis of anode EGOR and cathode nitrate reduction, highlighting its high potential as bifunctional electrocatalyst in various applications.

Naringenin attenuated airway cilia structural and functional injury induced by cigarette smoke extract via IL-17 and cAMP pathways.

BACKGROUND: Cigarette smoke impairs mucociliary clearance via mechanisms such as inflammatory response and oxidative injury, which in turn induces various respiratory diseases. Naringenin, a naturally occurring flavonoid in grapes and grapefruit, has exhibited pharmacological properties such as anti-inflammatory, expectorant, and antioxidant properties. However, it is still unclear whether naringenin protects airway cilia from injury caused by cigarette smoke. PURPOSE: This study aimed to investigate the effect of naringenin on cigarette smoke extract (CSE)-induced structural and functional abnormalities in airway cilia and highlight the potential regulatory mechanism. METHODS: Initially, network pharmacology was used to predict the mechanism of action of naringenin in ciliary disease. Next, HE staining, immunofluorescence, TEM, qRT-PCR, western blot, and ELISA were performed to assess the effects of naringenin on airway cilia in tracheal rings and air-liquid interface (ALI) cultures of Sprague Dawley rats after co-exposure to CSE (10% or 20%) and naringenin (0, 25, 50, 100 µM) for 24 h. Finally, transcriptomics and molecular biotechnology methods were conducted to elucidate the mechanism by which naringenin protected cilia from CSE-induced damage in ALI cultures. RESULTS: The targets of ciliary diseases regulated by naringenin were significantly enriched in inflammation and oxidative stress pathways. Also, the CSE decreased the number of cilia in the tracheal rings and ALI cultures and reduced the ciliary beat frequency (CBF). However, naringenin prevented CSE-induced cilia damage via mechanisms such as the downregulation of cilia-related genes (e.g., RFX3, DNAI1, DNAH5, IFT88) and ciliary marker proteins such as DNAI2, FOXJ1, and ß-tubulin IV, the upregulation of inflammatory factors (e.g., IL-6, IL-8, IL-13), ROS and MDA. IL-17 signaling pathway might be involved in the protective effect of naringenin on airway cilia. Additionally, the cAMP signaling pathway might also be related to the enhancement of CBF by naringenin. CONCLUSION: In this study, we first found that naringenin reduces CSE-induced structural disruption of airway cilia in part via modulation of the IL-17 signaling pathway. Furthermore, we also found that naringenin enhances CBF by activating the cAMP signaling pathway. This is the first report to reveal the beneficial effects of naringenin on airway cilia and the potential underlying mechanisms.