The m6A reader SlYTH2 negatively regulates tomato fruit aroma by impeding the translation process.

N6-methyladenosine (m6A) is a fundamentally important RNA modification for gene regulation, whose function is achieved through m6A readers. However, whether and how m6A readers play regulatory roles during fruit ripening and quality formation remains unclear. Here, we characterized SlYTH2 as a tomato m6A reader protein and profiled the binding sites of SlYTH2 at the transcriptome-wide level. SlYTH2 undergoes liquid-liquid phase separation and promotes RNA-protein condensate formation. The target mRNAs of SlYTH2, namely m6A-modified SlHPL and SlCCD1B associated with volatile synthesis, are enriched in SlYTH2-induced condensates. Through polysome profiling assays and proteomic analysis, we demonstrate that knockout of SlYTH2 expedites the translation process of SlHPL and SlCCD1B, resulting in augmented production of aroma-associated volatiles. This aroma enrichment significantly increased consumer preferences for CRISPR-edited fruit over wild type. These findings shed light on the underlying mechanisms of m6A in plant RNA metabolism and provided a promising strategy to generate fruits that are more attractive to consumers.

RNA-protein interactions reveals the pivotal role of lncRNA1840 in tomato fruit maturation.

Long non-coding RNAs (lncRNAs) play crucial roles in various biological processes in plants. However, the functional mechanism of lncRNAs in fruit ripening, particularly the transition from unripe to ripe stages, remains elusive. One such lncRNA1840, reported by our group, was found to have important role in tomato fruit ripening. In the present study, we gain insight into its functional role in fruit ripening. CRISPR-Cas9 mediated lncRNA1840 mutants caused the delayed tomato fruit ripening. Notably, loss function of lncRNA1840 did not directly impact ethylene signaling but rather delay ethylene synthesis. Transcriptomic analysis revealed differences in the expression of ripening related genes in lncRNA1840 mutants, suggesting that it is involved in gene regulation of fruit ripening. We used Chromatin Isolation by RNA Purification (ChIRP)-Seq to identify lncRNA1840 binding sites on chromatin. ChIRP-seq suggested that lncRNA1840 had occupancy on 40 genes, but none of them is differentially expressed genes in transcriptomic analysis, which indicated lncRNA1840 might indirectly modulate the gene expression. ChIRP-mass spectrometry analysis identified potential protein interactors of lncRNA1840, Pre-mRNA processing splicing factor 8, highlighting its involvement in post-transcriptional regulatory pathways. In summary, lncRNA1840 is key player in tomato plant growth and fruit ripening, with multifaceted roles in gene expression and regulatory networks.

The kiwifruit amyloplast proteome (kfALP): a resource to better understand the mechanisms underlying amyloplast biogenesis and differentiation.

The biogenesis and differentiation (B&D) of amyloplasts contributes to fruit flavor and color. Here, remodeling of starch granules, thylakoids and plastoglobules was observed during development and ripening in two kiwifruit (Actinidia spp.) cultivars - yellow-fleshed 'Hort16A' and green-fleshed 'Hayward'. A protocol was developed to purify starch-containing plastids with a high degree of intactness, and amyloplast B&D was studied using label-free-based quantitative proteomic analyses in both cultivars. Over 3000 amyloplast-localized proteins were identified, of which >98% were quantified and defined as the kfALP (kiwifruit amyloplast proteome). The kfALP data were validated by Tandem-Mass-Tag (TMT) labeled proteomics in 'Hort16A'. Analysis of the proteomic data across development and ripening revealed: 1) a conserved increase in the abundance of proteins participating in starch synthesis/degradation during both amyloplast B&D; 2) up-regulation of proteins for chlorophyll degradation and of plastoglobule-localized proteins associated with chloroplast breakdown and plastoglobule formation during amyloplast differentiation; 3) constitutive expression of proteins involved in ATP supply and protein import during amyloplast B&D. Interestingly, two different pathways of amyloplast B&D were observed in the two cultivars. In 'Hayward', significant increases in abundance of photosynthetic- and tetrapyrrole metabolism-related proteins were observed, but the opposite trend was observed in 'Hort16A'. In conclusion, analysis of the kfALP provides new insights into the potential mechanisms underlying amyloplast B&D with relevance to key fruit quality traits in contrasting kiwifruit cultivars.

SlRBP1 promotes translational efficiency via SleIF4A2 to maintain chloroplast function in tomato.

Many glycine-rich RNA-binding proteins (GR-RBPs) have critical functions in RNA processing and metabolism. Here, we describe a role for the tomato (Solanum lycopersicum) GR-RBP SlRBP1 in regulating mRNA translation. We found that SlRBP1 knockdown mutants (slrbp1) displayed reduced accumulation of total chlorophyll and impaired chloroplast ultrastructure. These phenotypes were accompanied by deregulation of the levels of numerous key transcripts associated with chloroplast functions in slrbp1. Furthermore, native RNA immunoprecipitation-sequencing (nRIP-seq) recovered 61 SlRBP1-associated RNAs, most of which are involved in photosynthesis. SlRBP1 binding to selected target RNAs was validated by nRIP-qPCR. Intriguingly, the accumulation of proteins encoded by SlRBP1-bound transcripts, but not the mRNAs themselves, was reduced in slrbp1 mutants. Polysome profiling followed by RT-qPCR assays indicated that the polysome occupancy of target RNAs was lower in slrbp1 plants than in wild-type. Furthermore, SlRBP1 interacted with the eukaryotic translation initiation factor SleIF4A2. Silencing of SlRBP1 significantly reduced SleIF4A2 binding to SlRBP1-target RNAs. Taking these observations together, we propose that SlRBP1 binds to and channels RNAs onto the SleIF4A2 translation initiation complex and promotes the translation of its target RNAs to regulate chloroplast functions.

A plant-specific module for homologous recombination repair.

Homologous recombination repair (HR) is an error-free DNA damage repair pathway to maintain genome stability and a basis of gene targeting using genome-editing tools. However, the mechanisms of HR in plants are still poorly understood. Through genetic screens for DNA damage response mutants (DDRM) in Arabidopsis, we find that a plant-specific ubiquitin E3 ligase DDRM1 is required for HR. DDRM1 contains an N-terminal BRCT (BRCA1 C-terminal) domain and a C-terminal RING (really interesting new gene) domain and is highly conserved in plants including mosses. The ddrm1 mutant is defective in HR and thus is hypersensitive to DNA-damaging reagents. Biochemical studies reveal that DDRM1 interacts with and ubiquitinates the transcription factor SOG1, a plant-specific master regulator of DNA damage responses. Interestingly, DDRM1-mediated ubiquitination promotes the stability of SOG1. Consistently, genetic data support that SOG1 functions downstream of DDRM1. Our study reveals that DDRM1-SOG1 is a plant-specific module for HR and highlights the importance of ubiquitination in HR.

Advancing H2O2 electrosynthesis: enhancing electrochemical systems, unveiling emerging applications, and seizing opportunities.

Hydrogen peroxide (H2O2) is a highly desired chemical with a wide range of applications. Recent advancements in H2O2 synthesis center on the electrochemical reduction of oxygen, an environmentally friendly approach that facilitates on-site production. To successfully implement practical-scale, highly efficient electrosynthesis of H2O2, it is critical to meticulously explore both the design of catalytic materials and the engineering of other components of the electrochemical system, as they hold equal importance in this process. Development of promising electrocatalysts with outstanding selectivity and activity is a prerequisite for efficient H2O2 electrosynthesis, while well-configured electrolyzers determine the practical implementation of large-scale H2O2 production. In this review, we systematically summarize fundamental mechanisms and recent achievements in H2O2 electrosynthesis, including electrocatalyst design, electrode optimization, electrolyte engineering, reactor exploration, potential applications, and integrated systems, with an emphasis on active site identification and microenvironment regulation. This review also proposes new insights into the existing challenges and opportunities within this rapidly evolving field, together with perspectives on future development of H2O2 electrosynthesis and its industrial-scale applications.

Multiscale Regulation of Ordered PtCu Intermetallic Electrocatalyst for Highly Durable Oxygen Reduction Reaction.

Transforming the Pt-M alloy into an ordered intermetallic is an effective strategy to improve the electrocatalytic activity and stability toward the oxygen reduction reaction (ORR). However, the synthesis of nanosized intermetallics remains challenging. Herein, we report an efficient ORR electrocatalyst, consisting of a monodisperse nanosized PtCu intermetallic on hollow mesoporous carbon spheres (HMCS). As predicted by theoretical calculations, PtCu intermetallics exhibit beneficial electronic structure, with a low theoretical overpotential of 0.33 V and enhanced Cu stability. Resulting from the multiscale modulation of catalyst structure, the O-PtCu/HMCS catalyst delivers a high mass activity of 2.73 A cm-2Pt at 0.9 V and remarkable stability. Identical location transmission electron microscopy (IL-TEM) investigations demonstrate that the rate of carbon corrosion is alleviated on HMCS, which contributes to the long-term durability. This work provides a promising design strategy for an ORR electrocatalyst, and the IL-TEM investigations offer new perspectives for the performance enhancement mechanism.

Pd 4d Orbital Overlapping Modulation on Au@Pd Nanowires for Efficient H2O2 Production.

Isolating Pd atoms has been shown to be crucial for the design of a Pd-based electrocatalyst toward 2e- oxygen reduction reaction (ORR). However, there are limited studies focusing on the systematic compositional design that leads to an optimal balance between activity and selectivity. Herein, we design a series of Au@Pd core@shell structures to investigate the influence of the Pd 4d orbital overlapping degree on 2e- ORR performance. Density functional theory (DFT) calculations indicate that enhanced H2O2 selectivity and activity are achieved at Pdn clusters with n ≤ 3, and Pd clusters larger than Pd3 should be active for 4e- ORR. However, experimental results show that Au@Pd nanowires (NWs) with Pd4 as the primary structure exhibit the optimal H2O2 performance in an acidic electrolyte with a high mass activity (7.05 A mg-1 at 0.4 V) and H2O2 selectivity (nearly 95%). Thus, we report that Pd4, instead of Pd3, is the upper threshold of Pd cluster size for an ideal 2e- ORR. It results from the oxygen coverage on the catalyst surface during the ORR process, and such an oxygen coverage phenomenon causes electron redistribution and weakened *OOH binding strength on active sites, leading to enhanced activity of Pd4 with only 0.06 V overpotential in acidic media.

EGR1 and EGR2 positively regulate plant ABA signaling by modulating the phosphorylation of SnRK2.2.

During abscisic acid (ABA) signaling, reversible phosphorylation controls the activity and accumulation of class III SNF1-RELATED PROTEIN KINASE 2s (SnRK2s). While protein phosphatases that negatively regulate SnRK2s have been identified, those that positively regulate ABA signaling through SnRK2s are less understood. In this study, Arabidopsis thaliana mutants of Clade E Growth-Regulating 1 and 2 (EGR1/2), which belong to the protein phosphatase 2C family, exhibited reduced ABA sensitivity in terms of seed germination, cotyledon greening, and ABI5 accumulation. Conversely, overexpression increased these ABA-induced responses. Transcriptomic data revealed that most ABA-regulated genes in egr1 egr2 plants were expressed at reduced levels compared with those in Col-0 after ABA treatment. Abscisic acid up-regulated EGR1/2, which interact directly with SnRK2.2 through its C-terminal domain I. Genetic analysis demonstrated that EGR1/2 function through SnRK2.2 during ABA response. Furthermore, SnRK2.2 de-phosphorylation by EGR1/2 was identified at serine 31 within the ATP-binding pocket. A phospho-mimic mutation confirmed that phosphorylation at serine 31 inhibited SnRK2.2 activity and reduced ABA responsiveness in plants. Our findings highlight the positive role of EGR1/2 in regulating ABA signaling, they reveal a new mechanism for modulating SnRK2.2 activity, and provide novel insight into how plants fine-tune their responses to ABA.

Decoding plant adaptation: deubiquitinating enzymes UBP12 and UBP13 in hormone signaling, light response, and developmental processes.

Ubiquitination, a vital post-translational modification in plants, plays a significant role in regulating protein activity, localization, and stability. This process occurs through a complex enzyme cascade that involves E1, E2, and E3 enzymes, leading to the covalent attachment of ubiquitin molecules to substrate proteins. Conversely, deubiquitinating enzymes (DUBs) work in opposition to this process by removing ubiquitin moieties. Despite extensive research on ubiquitination in plants, our understanding of the function of DUBs is still emerging. UBP12 and UBP13, two plant DUBs, have received much attention recently and are shown to play pivotal roles in hormone signaling, light perception, photoperiod responses, leaf development, senescence, and epigenetic transcriptional regulation. This review summarizes current knowledge of these two enzymes, highlighting the central role of deubiquitination in regulating the abundance and activity of critical regulators such as receptor kinases and transcription factors during phytohormone and developmental signaling.

Case report of penile squamous cell carcinoma continuous treatment with BRCA2 mutation.

BACKGROUND: Penile squamous cell carcinoma (PSCC) is a highly aggressive malignancy with a poor prognosis. BRCA1/2 mutations are associated with impaired DNA double-strand break repair and are among the common mutations in penile cancer, potentially paving the way for poly ADP-ribose polymerase inhibitor therapy. CASE PRESENTATION: We report a 65-year-old male with PSCC who progressed to thigh metastasis at 10 months after partial penectomy. Next-generation sequencing showed that the penis primary lesion and metastatic thigh lesion harboured a BRCA2 mutation. Chemotherapy plus immunotherapy was used for treatment, and the thigh metastasis was found to involve no tumour. Progression-free survival (PFS) lasted for 8 months until the appearance of lung metastasis. Afterwards, the patient benefited from second-line therapy of olaparib with pembrolizumab and anlotinib, and his disease was stable for 9 months. The same BRCA2 was identified in the lung biopsy. Given the tumour mutation burden (TMB, 13.97 mutation/Mb), the patient received third-line therapy with nivolumab plus ipilimumab, but PFS only lasted for 3 months, with the appearance of right frontal brain metastasis. Then, the patient was treated with radiation sequential fluzoparib therapy as fourth-line treatment, and the treatment efficacy was evaluated as PR. Currently, this patient is still alive. CONCLUSIONS: This is the first report of penile cancer with BRCA2 mutation, receiving a combination treatment with olaparib and experiencing a benefit for 9 months. This case underscores the pivotal role of BRCA2 in influencing treatment response in PSCC, providing valuable insights into the application of targeted therapies in managing recurrent PSCC with BRCA2 alterations. This elucidation establishes a crucial foundation for further research and clinical considerations in similar cases.

Integrated transcriptome and metabolome analyses shed light on the defense mechanisms in tomato plants after (E)-2-hexenal fumigation.

Tomato is a widely cultivated fruit and vegetable and is valued for its flavor, colour, and nutritional value. C6-aldehydes, such as (E)-2-hexenal, not only have antibacterial and antifungal properties but also function as signaling molecules that control the defense mechanisms of plants, including tomatoes. In this study, we used liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing techniques to generate metabolome and transcriptome datasets that elucidate the molecular mechanisms regulating defense responses in tomato leaves exposed to (E)-2-hexenal. A total of 28.27 Gb of clean data were sequenced and assembled into 23,720 unigenes. In addition, a non-targeted metabolomics approach detected 739 metabolites. There were 233 significant differentially expressed genes (DEGs) (158 up-regulated, 75 down-regulated) and 154 differentially expressed metabolites (DEMs) (86 up-regulated, 69 down-regulated). Most nucleotides and amino acids (L-Phenylalanine, L-Asparagine, L-Histidine, L-Arginine, and L-Tyrosine) and their derivatives were enriched. The analyses revealed that mitogen-activated protein kinase (MPK), pathogenesis-related protein (PR), and endochitinase (CHIB) were primarily responsible for the adaptation of plant defense responses. Therefore, the extensive upregulation of these genes may be associated with the increased plant defense response. These findings help us comprehend the defense response of plants to (E)-2-hexenal and improve the resistance of horticultural plants.

A Highly Active and Durable Hierarchical Electrocatalyst for Large-Current-Density Water Splitting.

Designing bifunctional catalysts with high current densities under industrial circumstances is crucial to propelling hydrogen energy with a boost from fundamental to practical application. In this work, heterojunction nanowire arrays consisting of manganese oxide and cobalt phosphide (denoted as MnO-CoP/NF) are designed to meet the industrial demand by regulating the synergic mass transport and electronic structure coupling with numerous nano-heterogeneous interfaces. The optimal MnO-CoP/NF electrode exhibits remarkable bifunctional electrocatalytic performance with overpotentials of 259.5 mV for hydrogen evolution at a large current density of 1000 mA cm-2 and 392.2 mV for oxygen evolution at 1500 mA cm-2. Moreover, the MnO-CoP/NF electrode demonstrates superior durability and an ultralow voltage of 1.76 V at 500 mA cm-2, outperforming that of a commercial RuO2||Pt/C electrode. This work sheds light on the design of metallic heterostructures with optimized interfacial electronic structures and a high abundance of active sites for practical industrial water splitting applications.

Competitive Coordination Structure Regulation in Deep Eutectic Electrolyte for Stable Zinc Batteries.

Rechargeable zinc-based batteries are finding their niche in energy storage applications where cost, safety, scalability matter, yet they are plagued by rapid performance degradation due to the lack of suitable electrolytes to stabilize Zn anode. Herein, we report a competitive coordination structure to form unique quaternary hydrated eutectic electrolyte with ligand-cation-anion cluster. Unraveled by experiment and calculation results, the competing component can enter initial primary coordination shell of Zn2+ ion, partially substituting Lewis basic eutectic ligands and reinforcing cation-anion interaction. The hydration-deficient complexes induced between competing eutectic as hydrogen bond donor-accepter and water also broaden the electrochemical window and confine free water activity. The altered coordination further leads to robust hybrid organic-inorganic enriched solid electrolyte interphase, enabling passivated surface and suppressed dendrite growth. Noticeably, stable Zn plating/stripping for 8000 cycles with high Coulombic efficiencies of 99.6 % and long cycling life of 10000 cycles for Zn-organic batteries are obtained. Even under harsh conditions (small N/P ratio, low temperature), the profits brought by the competitive eutectic electrolyte are still very prominent. This design principle leveraged by eutectic electrolytes with competitive coordination offers a new approach to improve battery performance.

Stabilizing Diluted Active Sites of Ultrasmall High-Entropy Intermetallics for Efficient Formic Acid Electrooxidation.

The poisoning of undesired intermediates or impurities greatly hinders the catalytic performances of noble metal-based catalysts. Herein, high-entropy intermetallics i-(PtPdIrRu)2FeCu (HEI) are constructed to inhibit the strongly adsorbed carbon monoxide intermediates (CO*) during the formic acid oxidation reaction. As probed by multiple-scaled structural characterizations, HEI nanoparticles are featured with partially negative Pt oxidation states, diluted Pt/Pd/Ir/Ru atomic sites and ultrasmall average size less than 2 nm. Benefiting from the optimized structures, HEI nanoparticles deliver more than 10 times promotion in intrinsic activity than that of pure Pt, and well-enhanced mass activity/durability than that of ternary i-Pt2FeCu intermetallics counterpart. In situ infrared spectroscopy manifests that both bridge and top CO* are favored on pure Pt but limited on HEI. Further theoretical elaboration indicates that HEI displayed a much weaker binding of CO* on Pt sites and sluggish diffusion of CO* among different sites, in contrast to pure Pt that CO* bound more strongly and was easy to diffuse on larger Pt atomic ensembles. This work verifies that HEIs are promising catalysts via integrating the merits of intermetallics and high-entropy alloys.

Improving Alkaline Hydrogen Oxidation through Dynamic Lattice Hydrogen Migration in Pd@Pt Core-Shell Electrocatalysts.

Tracking the trajectory of hydrogen intermediates during hydrogen electro-catalysis is beneficial for designing synergetic multi-component catalysts with division of chemical labor. Herein, we demonstrate a novel dynamic lattice hydrogen (LH) migration mechanism that leads to two orders of magnitude increase in the alkaline hydrogen oxidation reaction (HOR) activity on Pd@Pt over pure Pd, even ≈31.8 times mass activity enhancement than commercial Pt. Specifically, the polarization-driven electrochemical hydrogenation process from Pd@Pt to PdHx @Pt by incorporating LH allows more surface vacancy Pt sites to increase the surface H coverage. The inverse dehydrogenation process makes PdHx as an H reservoir, providing LH migrates to the surface of Pt and participates in the HOR. Meanwhile, the formation of PdHx induces electronic effect, lowering the energy barrier of rate-determining Volmer step, thus resulting in the HOR kinetics on Pd@Pt being proportional to the LH concentration in the in situ formed PdHx @Pt. Moreover, this dynamic catalysis mechanism would open up the catalysts scope for hydrogen electro-catalysis.

DNA and coding/non-coding RNA methylation analysis provide insights into tomato fruit ripening.

Ripening is the last, irreversible developmental stage during which fruit become palatable, thus promoting seed dispersal by frugivory. In Alisa Craig fruit, mRNAs with increasing m5C levels, such as STPK and WRKY 40, were identified as being involved in response to biotic and abiotic stresses. Furthermore, two mRNAs involved in cell wall metabolism, PG and EXP-B1, also presented increased m5C levels. In the Nr mutant, several m5C-modified mRNAs involved in fruit ripening, including those encoding WRKY and MADS-box proteins, were found. Targets of long non-coding RNAs and circular RNAs with different m5C sites were also found; these targets included 2-alkenal reductase, soluble starch synthase 1, WRKY, MADS-box, and F-box/ketch-repeat protein SKIP11. A combined analysis of changes in 5mC methylation and mRNA revealed many differentially expressed genes with differentially methylated regions encoding transcription factors and key enzymes related to ethylene biosynthesis and signal transduction; these included ERF084, EIN3, AP2/ERF, ACO5, ACS7, EIN3/4, EBF1, MADS-box, AP2/ERF, and ETR1. Taken together, our findings contribute to the global understanding of the mechanisms underlying fruit ripening, thereby providing new information for both fruit and post-harvest behavior.

Transcriptomic and proteomic analysis reveals (E)-2-hexenal modulates tomato resistance against Botrytis cinerea by regulating plant defense mechanism.

In a previous study, we observed that (E)-2-hexenal stimulated systemic resistance against B. cinerea in tomato plants. However, the molecular mechanisms underlying (E)-2-hexenal-mediated regulation of systemic immunity against B. cinerea remained unclear. In the current study, the global mechanism underlying (E)-2-hexenal-meidated regulation of biotic stress tolerance in tomato was investigated using RNA-seq- and LC-MS/MS- integrated transcriptomic and proteomic analyses. Compared to control plants, (E)-2-hexenal-treated plants exhibited reduced susceptibility to B. cinerea, with a 50.51% decrease in lesion diameters. Meanwhile, (E)-2-hexenal vapor fumigation significantly increased total phenolic content and activities of various antioxidant enzymes peroxidase (POD), phenylalanine ammonia lyase (PAL), and lipoxygenase (LOX). A total of 233 differentially expressed genes (DEGs) and 400 differentially expressed proteins (DEPs), respectively, were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that (E)-2-hexenal treatment markedly affected the expression of genes involved in multiple metabolic pathways, especially glutathione metabolism, phenylpropanoid biosynthesis, plant hormone signal transduction, and MAPK signaling pathway. Notably, proteomic analysis revealed modulation of the activities of several defense response proteins, such as pathogenesis-related (PR) proteins (Solyc02g031950.3.1, Solyc02g031920.4.1, and Solyc04g064870.3.1), peroxidases (Solyc06g050440.3.1, Solyc01g105070.3.1, Solyc01g015080.3.1, Solyc03g025380.3.1 and Solyc06g076630.3.1). Our results provide a comprehensive analysis of the effects of (E)-2-hexenal treatment on the transcriptome and proteome of tomato plants, which might be used as a reference in further studies on plant defense responses against pathogens.

Pseudo-Pt Monolayer for Robust Hydrogen Oxidation.

Heteroepitaxial core-shell structure is conducive to combining the advantages of the epilayer and the substrate, creating a novel multifunctionality for catalysis application. Herein, we report a pseudomorphic-Pt atomic layer (PmPt) epitaxially growing on an IrPd-core matrix (PmPt@IrPd/C) as an efficient and stable catalyst for alkaline hydrogen oxidation reaction that exhibits ∼29.2 times more mass activity enhancement than that of benchmark Pt/C. The PmPt@IrPd/C catalyst also gives rise to ∼25.0 times more enhancement than Pt/C during a 50,000-cycle accelerated stability test. This robust stability originates from the resistance to carbon corrosion owing to the stronger H2O interaction instead of carbon oxide (COx) poison species, and the modulated hydroxyl (OH*) adsorption could inhibit the OH* species from shuffling the surface Pt atoms away from the substrate. Moreover, the anion-exchange membrane fuel cells assembled by PmPt@IrPd/C with an ultralow Pt loading of 0.009 mgPt cm-2 in the anode can deliver a power density of 1.27 W cm-2.

Cbl induced ubiquitination of HER2 mediate immune escape from HER2-targeted CAR-T.

Breast cancer (BC) with high HER2 expression has higher recurrence rate and worse prognosis, and its immunotherapy is promising. Based on the high expression of HER2, develop Chimeric Antigen Receptor T-cell (CAR-T) and PDL-1 immunotherapy, and study the molecular pathways of related immune cells and recurrence. HER2-CAR-T cells were constructed using retroviruses, and their specific recognition and immune effects on HER2+ BC cells were verified by in vivo and in vitro experiments. PDL-1 was used as adjuvant immunotherapy, knocking down PDL-1 in tumor cells or dendritic cells, or depleted macrophages to study immune pathways. The negative regulation of HER2 by cbl was determined by IP, ubiquitination experiments, and segmented plasmids, elucidating the molecular mechanism of HER2+ BC recurrence after immunotherapy. HER2-CAR-T specifically recognizes HER2-positive tumor cells and inhibits tumor growth in vivo and in vitro, and anti-PDL1 treatment enhances the therapeutic effect of HER2-CAR-T on tumors. HER2-CART therapy eradicated solid tumors after PDL1 knockdown in dendritic cells. Immunotherapy of relapsed tumors lost HER2 expression by upregulating cbl. HER2-CAR-T shows specific recognition of HER2+ cells and can mediate immune response therapy with the cooperation of PDL-1.