Driven by the persisting poor understanding of the sluggish kinetics of the hydrogen evolution reaction (HER) on Pt in alkaline media, a direct correlation of the interfacial water structure and ...activity is still yet to be established. Herein, using Pt and Pt–Ni nanoparticles we first demonstrate a strong dependence of the proton donor structure on the HER activity and pH. The structure of the first layer changes from the proton acceptors to the donors with increasing pH. In the base, the reactivity of the interfacial water varied its structure, and the activation energies of water dissociation increased in the sequence: the dangling O−H bonds < the trihedrally coordinated water < the tetrahedrally coordinated water. Moreover, optimizing the adsorption of H and OH intermediates can re‐orientate the interfacial water molecules with their H atoms pointing towards the electrode surface, thereby enhancing the kinetics of HER. Our results clarified the dynamic role of the water structure at the electrode–electrolyte interface during HER and the design of highly efficient HER catalysts.
On nickel–platinum alloy nanoparticles under alkaline conditions, the reactivity of interfacial water varies with its structure and the order of water dissociation. The inclusion of nickel re‐orientates interfacial water molecules with their hydrogen atoms pointing towards the electrode surface, thereby enhancing the kinetics of the hydrogen evolution reaction (HER).
Summary
In this study, we characterized the role of an apple cytosolic malate dehydrogenase gene (MdcyMDH) in the tolerance to salt and cold stresses and investigated its regulation mechanism in ...stress tolerance. The MdcyMDH transcript was induced by mild cold and salt treatments, and MdcyMDH‐overexpressing apple plants possessed improved cold and salt tolerance compared to wild‐type (WT) plants. A digital gene expression tag profiling analysis revealed that MdcyMDH overexpression largely altered some biological processes, including hormone signal transduction, photosynthesis, citrate cycle and oxidation–reduction. Further experiments verified that MdcyMDH overexpression modified the mitochondrial and chloroplast metabolisms and elevated the level of reducing power, primarily caused by increased ascorbate and glutathione, as well as the increased ratios of ascorbate/dehydroascorbate and glutathione/glutathione disulphide, under normal and especially stress conditions. Concurrently, the transgenic plants produced a high H2O2 content, but a low O2·− production rate was observed compared to the WT plants. On the other hand, the transgenic plants accumulated more free and total salicylic acid (SA) than the WT plants under normal and stress conditions. Taken together, MdcyMDH conferred the transgenic apple plants a higher stress tolerance by producing more reductive redox states and increasing the SA level; MdcyMDH could serve as a target gene to genetically engineer salt‐ and cold‐tolerant trees.
Proton transfer is crucial for electrocatalysis. Accumulating cations at electrochemical interfaces can alter the proton transfer rate and then tune electrocatalytic performance. However, the ...mechanism for regulating proton transfer remains ambiguous. Here, we quantify the cation effect on proton diffusion in solution by hydrogen evolution on microelectrodes, revealing the rate can be suppressed by more than 10 times. Different from the prevalent opinions that proton transport is slowed down by modified electric field, we found water structure imposes a more evident effect on kinetics. FTIR test and path integral molecular dynamics simulation indicate that proton prefers to wander within the hydration shell of cations rather than to hop rapidly along water wires. Low connectivity of water networks disrupted by cations corrupts the fast‐moving path in bulk water. This study highlights the promising way for regulating proton kinetics via a modified water structure.
Accumulating K+ cations break the water network connectivity, and confine protons in the cation hydration shell, thus slowing the proton diffusion kinetics.
Summary
Malate, the predominant organic acid in many fruits, is a crucial component of the organoleptic quality of fruit, including taste and flavor. The genetic and environmental mechanisms ...affecting malate metabolism in fruit cells have been studied extensively. However, the transcriptional regulation of malate‐metabolizing enzymes and vacuolar transporters remains poorly understood. Our previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and vacuolar acidification by directly activating vacuolar transporters, including MdVHA‐B1, MdVHA‐E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It was subsequently found that MdMYB73 protein bound directly to the promoters of MdALMT9 (aluminum‐activated malate transporter 9), MdVHA‐A (vacuolar ATPase subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating their expression and thereby enhancing their activities. Analyses of transgenic apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon downstream target genes. These findings help to elucidate how MdMYB73 directly modulates the vacuolar transport system to affect malate accumulation and vacuolar pH in apple.
Significance Statement
In this study we found that the R2R3‐MYB transcription factor MdMYB73 is involved in malate accumulation and vacuolar acidification in apple.
The existence of breast cancer stem cells (BCSCs) is a major reason underlying cancer metastasis and recurrence after chemotherapy and radiotherapy. Targeting BCSCs may ameliorate breast cancer ...relapse and therapy resistance. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) positively associates with breast cancer stemness and progression. Elevated TRIB3 expression supports BCSCs by interacting with AKT to interfere with the FOXO1-AKT interaction and suppress FOXO1 phosphorylation, ubiquitination, and degradation by E3 ligases SKP2 and NEDD4L. The accumulated FOXO1 promotes transcriptional expression of SOX2, a transcriptional factor for cancer stemness, which in turn, activates FOXO1 transcription and forms a positive regulatory loop. Disturbing the TRIB3-AKT interaction suppresses BCSCs by accelerating FOXO1 degradation and reducing SOX2 expression in mouse models of breast cancer. Our study provides insights into breast cancer development and confers a potential therapeutic strategy against TRIB3-overexpressed breast cancer.
• The plant hormone ethylene is critical for climacteric fruit ripening, while glucose and anthocyanins determine the fruit quality of climacteric fruits such as apple. Understanding the exact ...molecular mechanism for this process is important for elucidating the interconnection of ethylene and fruit quality.
• Overexpression of apple MdbHLH3 gene, an anthocyanin-related basic helix–loop–helix transcription factor (bHLH TF) gene, promotes ethylene production, and transgenic apple plantlets and trees exhibit ethylene-related root developmental abnormalities, premature leaf senescence, and fruit ripening. Biochemical analyses demonstrate that MdbHLH3 binds to the promoters of three genes that are involved in ethylene biosynthesis, including MdACO1, MdACS1, and MdACS5A, activating their transcriptional expression, thereby promoting ethylene biosynthesis.
• High glucose-inhibited U-box-type E3 ubiquitin ligase MdPUB29, the ortholog of Arabidopsis AtPUB29 in apple, influences the expression of ethylene biosynthetic genes and ethylene production by direct ubiquitination of the MdbHLH3 protein.
• Our findings provide new insights into the ubiquitination of MdbHLH3 by glucose-inhibited ubiquitin E3 ligase MdPUB29 in the regulation of ethylene biosynthesis as well as indicate that the regulatory module MdPUB29-MdbHLH3 connects ethylene biosynthesis with fruit quality in apple.
The development of C(sp3)−H functionalization reactions that use common protecting groups and practical oxidants remains a significant challenge. Herein we report a monoprotected aminoethyl thioether ...(MPAThio) ligand‐enabled β‐C(sp3)−H lactamization of tosyl‐protected aliphatic amides using tert‐butyl hydrogen peroxide (TBHP) as the sole oxidant. This protocol features exceedingly mild reaction conditions, reliable scalability, and the use of practical oxidants and protecting groups. Further derivatization of the β‐lactam products enables the synthesis of a range of biologically important motifs including β‐amino acids, γ‐amino alcohols, and azetidines.
PdII‐catalyzed β‐C(sp3)−H lactamization of aliphatic amides is reported. This protocol features the use of practical and inexpensive oxidants and protecting groups, mild conditions, and reliable scalability. Further derivatization of β‐lactam products enables synthesis of a range of biologically important motifs such as β‐amino acid, γ‐amino alcohol, and azetidine.
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and constitutes a major health threat globally. Intermediate HCC (Barcelona Clinic Liver Cancer Staging, stage B) encompasses a ...wide range of patients and is characterized by substantial heterogeneity with varying tumor burdens and liver functions. Therefore, it is paramount to evaluate the patient's overall conditions and to select the most appropriate therapy based on available evidence. Transarterial chemoembolization is the recommended first‐line therapy for intermediate HCC patients. However, in clinical practice, other treatment options are also used as alternative therapies, such as hepatic resection, percutaneous thermal ablation, radiotherapy (RT), systemic treatment, immunotherapy, and so forth. In this review, we will introduce current treatment strategies for intermediate HCC, discuss their advantages and disadvantages, and propose future directions.
Intermediate hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer Staging, stage B) encompasses a wide range of patients and is characterized by substantial heterogeneity with varying tumor burdens and liver functions. Transarterial chemoembolization is the recommended first‐line therapy for intermediate HCC patients. In clinic practice, other treatment options are also used as alternative therapies, such as hepatic resection, percutaneous thermal ablation, radiotherapy, systemic treatment, immunotherapy, and so forth.
Automatically extracting useful information from electronic medical records along with conducting disease diagnoses is a promising task for both clinical decision support(CDS) and neural language ...processing(NLP). Most of the existing systems are based on artificially constructed knowledge bases, and then auxiliary diagnosis is done by rule matching. In this study, we present a clinical intelligent decision approach based on Convolutional Neural Networks(CNN), which can automatically extract high-level semantic information of electronic medical records and then perform automatic diagnosis without artificial construction of rules or knowledge bases. We use collected 18,590 copies of the real-world clinical electronic medical records to train and test the proposed model. Experimental results show that the proposed model can achieve 98.67% accuracy and 96.02% recall, which strongly supports that using convolutional neural network to automatically learn high-level semantic features of electronic medical records and then conduct assist diagnosis is feasible and effective.
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