Construction of Thiadiazole-Bridged sp2-Carbon-Conjugated Covalent Organic Frameworks with Diminished Excitation Binding Energy Toward Superior Photocatalysis.

Sp2-carbon-conjugated covalent organic frameworks (sp2c-COFs) have emerged as promising platforms for phototo-chemical energy conversion due to their tailorable optoelectronic properties, in-plane π-conjugations, and robust structures. However, the development of sp2c-COFs in photocatalysis is still highly hindered by their limited linkage chemistry. Herein, we report a novel thiadiazole-bridged sp2c-COF (sp2c-COF-ST) synthesized by thiadiazole-mediated aldol-type polycondensation. The resultant sp2c-COF-ST demonstrates high chemical stability under strong acids and bases (12 M HCl or 12 M NaOH). The electro-deficient thiadiazole together with fully conjugated and planar skeleton endows sp2c-COF-ST with superior photoelectrochemical performance and charge-carrier separation and migration ability. As a result, when employed as a photocathode, sp2c-COF-ST exhibits a significant photocurrent up to ∼14.5 µA cm-2 at 0.3 V vs reversible hydrogen electrode (RHE) under visible-light irradiation (>420 nm), which is much higher than those analogous COFs with partial imine linkages (mix-COF-SNT ∼ 9.5 µA cm-2) and full imine linkages (imi-COF-SNNT ∼ 4.9 µA cm-2), emphasizing the importance of the structure-property relationships. Further temperature-dependent photoluminescence spectra and density functional theory calculations demonstrate that the sp2c-COF-ST has smaller exciton binding energy as well as effective mass in comparison to mix-COF-SNT and imi-COF-SNNT, which suggests that the sp2c-conjugated skeleton enhances the exciton dissociation and carrier migration under light irradiation. This work highlights the design and preparation of thiadiazole-bridged sp2c-COFs with promising photocatalytic performance.

Investigating the Role of Extracellular Matrix Stiffness in Modulating the Ferroptosis Process in Hepatocellular Carcinoma Cells via Scanning Electrochemical Microscopy.

Extracellular matrix (ECM) stiffness modulates a variety of cellular processes, including ferroptosis, a process with significant potential implications for hepatocellular carcinoma (HCC) fibrosis and cirrhosis. However, the exact relationship between ECM stiffness and HCC ferroptosis is yet unclarified, partially due to the lack of in situ information on key parameters of the ferroptosis process of living HCC cells. This study pioneers the use of in vitro mechanical microenvironment models of HCC and the scanning electrochemical microscopy (SECM) technique for understanding this interplay. We first cultured HuH7 cells on 4.0, 18.0, and 44.0 kPa polyacrylamide (PA) gels to simulate early, intermediate, and advanced HCC ECM stiffness, respectively. Then, we used SECM to in situ monitor changes in cell membrane permeability, respiratory activity, and reactive oxygen species (ROS) levels of erastin-induced HuH7 cells on PA gels, finding that increasing ECM stiffness potentiates ferroptosis, including increased membrane permeabilization and H2O2 release as well as reduced respiratory activity. Through further transcriptome sequencing and molecular biology measurements, we identified a critical role for focal adhesion kinase (FAK)-mediated yes-associated protein (YAP) in regulating the ferroptosis process dependent on ECM stiffness, which provides novel insights into the mechanical regulation of ferroptosis in HCC cells and may pave the way for innovative therapeutic strategies.

Single-cell insights: pioneering an integrated atlas of chromatin accessibility and transcriptomic landscapes in diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM's unique cell states and molecular landscape for targeted therapeutic interventions. METHODS: Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings. RESULTS: This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation. CONCLUSION: Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.

Effect of extracellular matrix stiffness on efficacy of Dapagliflozin for diabetic cardiomyopathy.

BACKGROUND: Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive. MATERIALS AND METHODS: This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained. RESULTS: The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin ß1, but without significant impact on piezo 1. CONCLUSIONS: Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.

Simultaneous Determination of Fragmentation Functions and Test on Momentum Sum Rule.

We perform a simultaneous global analysis of hadron fragmentation functions (FFs) to various charged hadrons (π^{±}, K^{±}, and p/p[over ¯]) at next-to-leading order in QCD. The world data include results from electron-positron single-inclusive annihilation, semi-inclusive deep inelastic scattering, as well as proton-proton collisions including jet fragmentation measurements for the first time, which lead to strong constraints on the gluon fragmentations. By carefully selecting hadron kinematics to ensure the validity of QCD factorization and the convergence of perturbative calculations, we achieve a satisfying best fit with χ^{2}/d.o.f.=0.90. The total momentum of u, d quarks and gluon carried by light charged hadrons have been determined precisely, urging precision determinations of FFs to neutral hadrons for a test of fundamental sum rules in QCD fragmentation.

The association between the triglyceride-glucose index and vitamin D status: a systematic review and meta-analysis.

OBJECTIVE: This study aims to explore the association between the triglyceride-glucose (TyG) index and vitamin D status to enhance our understanding of how vitamin D status relates to metabolic health and to provide evidence for the early diagnosis of vitamin D deficiency (VDD) using the TyG index. METHODS: We conducted a comprehensive search in various databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc, China Science and Technology Journal Database, and Wanfang Data to gather articles published from the inception of these databases until February 19, 2024. We assessed the quality of included studies using the Newcastle-Ottawa Scale (NOS) for case-control studies and the Agency for Healthcare Research and Quality (AHRQ) methodology checklist for cross-sectional studies. Statistical analyses in this study were conducted using conversion methods for non-standard data formats and consolidation techniques for combining multiple groups. The Fisher transformation method was used for correlation coefficients. We used a random-effects model considering the inherent clinical heterogeneity among the studies, and assessed statistical heterogeneity with the Cochrane Q test and I2 statistic, complemented by subgroup analyses and sensitivity analysis. RESULTS: Our meta-analysis selected a total of nine studies. The analysis revealed that patients with vitamin D deficiency (VDD group) exhibited a significantly higher TyG index than those without deficiency (no-VDD group), with a mean difference (MD) of 0.16 (95% CI: 0.10 to 0.23, I2 = 93%). This association was particularly pronounced among patients with type 2 diabetes (T2DM), showing an MD of 0.15 (95% CI: 0.05 to 0.26, I2 = 55%). Additionally, a negative correlation was observed between the TyG index and vitamin D levels, with a correlation coefficient (r) of -0.236 (95% CI: -0.310 to -0.159, I2 = 91%). Excluding each study sequentially in the sensitivity analyses did not significantly alter the outcomes. CONCLUSIONS: Our findings demonstrate a significant association between the TyG index and vitamin D status across diverse populations, including those with T2DM, subclinical hypothyroidism (SCH), and metabolic associated fatty liver disease (NAFLD). Our results reveal a notable disparity in the TyG index between vitamin D deficient and non-deficient groups, suggesting that vitamin D may play a critical role in metabolic health. These findings highlight the need for further research to explore the underlying mechanisms and clinical implications of vitamin D in the context of various metabolic disorders.

ΔNp63α promotes cigarette smoke-induced renal cancer stem cell activity via the Sonic Hedgehog pathway.

Cigarette smoke (CS) has been generally recognized as a chief carcinogenic factor in renal cell carcinoma (RCC). The stimulative effect of CS on renal cancer stem cells (RCSCs) has been described previously. The Sonic Hedgehog (SHH) pathway plays an essential role in self-renewal, cell growth, drug resistance, metastasis, and recurrence of cancer stem cells (CSCs). Renal cancer-related gene ΔNp63α is highly expressed in renal epithelial tissues and contributes to the RCSCs characteristics of tumors. The aim of this study was to elucidate the role of ΔNp63α and the SHH pathway on the activity of RCSCs induced by CS through a series of in vivo and in vitro studies. It was shown that in renal cancer tissues, ΔNp63α and RCSCs markers in smokers are expressed higher than that in non-smokers. RCSCs were effectively enriched by tumor sphere formation assay. Besides, CS increased the expression of RCSCs markers and the capability of sphere-forming in vitro and in vivo. Moreover, the SHH pathway was activated, and the specialized inhibitor alleviated the promotion of CS on RCSCs. ΔNp63α activated the SHH pathway and promoted CS-induced enhancement of RCSCs activity. These findings indicate that ΔNp63α positively regulates the activity of CS-induced RCSCs via the SHH pathway.

Effect of Exogenous Electric Stimulation on the Cardiac Tissue Function In Situ Monitored by Scanning Electrochemical Microscopy.

Cardiac tissue is sensitive to and can be easily damaged by exogenous electric stimulation. However, due to the thermal-electric coeffect and the limitation of in situ and quantitative information on the cardiac tissue function under electric stimulation, the detailed effect and the underlying mechanism of exogenous electric stimulation on the cardiac tissue remain elusive. To address this, in this work, we first constructed an in vitro cardiac tissue model and established a thermal-electric coupled theoretical model for simulating the electric field and temperature distributions around the cardiac tissue, from which we selected the electric field strengths (1.19, 2.37, and 3.39 kV cm-1) and electrical energies (0.001, 0.005, and 0.011 J) for electric stimulations without inducing a thermal effect. Then, we applied electric field stimulations on the cardiac tissue using these parameters and scanning electrochemical microscopy (SECM) to in situ and quantitatively monitor the dynamic changes in the key parameters of the cardiac tissue function, including respiratory activity, membrane permeability, and contraction frequency, after electric field stimulations. The SECM results showed that the oxygen consumption, cell membrane permeability coefficient, and contraction frequency of the cardiac tissue were strongly dependent on electrical energy, especially when the electrical energy was higher than 0.001 J. Our work, for the first time, achieves the in situ and quantitative monitoring of the cardiac tissue function under electric stimulation using SECM, which would provide important references for designing an electric stimulation regime for cardiac tissue engineering and clinical application of electrotherapy.

In Situ and Quantitatively Monitoring the Dynamic Process of Ferroptosis in Single Cancer Cells by Scanning Electrochemical Microscopy.

Ferroptosis, as a promising therapeutic strategy for cancers, has aroused great interest. Quantifying the quick dynamic changes in key parameters during the early course of ferroptosis can provide insights for understanding the underlying mechanisms of ferroptosis and help the development of therapies targeting ferroptosis. However, in situ and quantitatively monitoring the quick responses of living cancer cells to ferroptosis at the single-cell level remains technically challenging. In this work, we selected HuH7 cells (hepatocellular carcinoma (HCC) cells) as a cell model and Erastin as a typical ferroptosis inducer. We utilized scanning electrochemical microscopy (SECM) to quantitatively and in situ monitor the early course of ferroptosis in HuH7 cells by characterizing the three key parameters of cell ferroptosis (i.e., cell membrane permeability, respiratory activity, and the redox state). The SECM results show that the membrane permeability of ferroptotic HuH7 cells continuously increased from 0 to 8.1 × 10-5 m s-1, the cellular oxygen consumption was continuously reduced by half, and H2O2 released from the cells exhibited periodic bursts during the early course of ferroptosis, indicating the gradually destroyed cell membrane structure and intensified oxidative stress. Our work realizes, for the first time, the in situ and quantitative monitoring of the cell membrane permeability, respiratory activity, and H2O2 level of the early ferroptosis process of a single living cancer cell with SECM, which can contribute to the understanding of the physiological process and underlying mechanisms of ferroptosis.

Mechanisms and research advances in mRNA antibody drug-mediated passive immunotherapy.

Antibody technology is widely used in the fields of biomedical and clinical therapies. Nonetheless, the complex in vitro expression of recombinant proteins, long production cycles, and harsh storage conditions have limited their applications in medicine, especially in clinical therapies. Recently, this dilemma has been overcome to a certain extent by the development of mRNA delivery systems, in which antibody-encoding mRNAs are enclosed in nanomaterials and delivered to the body. On entering the cytoplasm, the mRNAs immediately bind to ribosomes and undergo translation and post-translational modifications. This process produces monoclonal or bispecific antibodies that act directly on the patient. Additionally, it eliminates the cumbersome process of in vitro protein expression and extends the half-life of short-lived proteins, which significantly reduces the cost and duration of antibody production. This review focuses on the benefits and drawbacks of mRNA antibodies compared with the traditional in vitro expressed antibodies. In addition, it elucidates the progress of mRNA antibodies in the prevention of infectious diseases and oncology therapy.

Deterministic Effect of pH on Shaping Soil Resistome Revealed by Metagenomic Analysis.

Soil is recognized as the major reservoir of antibiotic resistance genes (ARGs), harboring the most diverse naturally evolved ARGs on the planet. Multidrug resistance genes are a class of ARGs, and their high prevalence in natural soil ecosystems has recently raised concerns. Since most of these genes express proton motive force (PMF) driven efflux pumps, studying whether soil pH is a determinant for the selection of multidrug efflux pump genes and thus shaping the soil resistome are of great interest. In this study, we collected 108 soils with pH values ranging from 4.37 to 9.69 from multiple ecosystems and profiled the composition of ARGs for metagenomes and metagenome-assembled genomes. We observed the multidrug efflux pump genes enriched in the acidic soil resistome, and their abundances have significant soil pH dependence. This reflects the benefits of high soil proton activity on the multidrug efflux pump genes, especially for the PMF-driven inner membrane transferase. In addition, we preliminary indicate the putative microbial participants in pH shaping the soil resistome by applying ecological analyzing tools such as stepwise regression and random forest model fitting. The decisive influence of proton activity on shaping the resistome is more impactful than any other examined factors, and as the consequence, we revisited the influence of edaphic factors on the soil resistome; i.e., the deterministic selection of resistance mechanisms by edaphic factors could lead to the bottom-up shaping of the ARG composition. Such natural developing mechanisms of the resistome are herein suggested to be considered in assessing human-driven ARG transmissions.

c-Myc protects hepatocellular carcinoma cell from ferroptosis induced by glutamine deprivation via upregulating GOT1 and Nrf2.

BACKGROUND: Glutamine metabolism is critical for development of hepatocellular carcinoma (HCC), which makes it a novel promising treatment target. However, clinical evidence suggested glutamine withdrawal therapy does not achieved the desired tumor suppression. Therefore, it is valuable to investigate the survival mechanisms of tumors with glutamine deprivation. METHODS: The HCC cells were cultured in glutamine-free medium or supplemented with glutamine metabolites or ferroptosis inhibitors. The parameters related to ferroptosis and the activity of GSH synthesis-related enzymes of the HCC cells were detected by corresponding kits. The expressions of glutamate oxaloacetate transaminase 1 (GOT1), c-Myc and Nrf2 were detected by western blot and qRT-PCR. The chromatin immunoprecipitation and luciferase reporter assays were performed to investigate the correlation between c-Myc and GOT1. The siRNAs of c-Myc and GOT1 were used to explore their roles in GSH (GSH) synthesis and ferroptosis in vitro and in vivo. RESULTS: Glutamine deprivation-induced ferroptosis did not completely inhibit HCC cells proliferation. Glutamine deprivation activated the expression of c-Myc, which promoted the transcription of GOT1 and Nrf2, consequently maintaining the GSH synthesis and inhibiting ferroptosis. In addition, combined inhibition of GOT1 with glutamine deprivation could result in better inhibition of HCC in vitro and in vivo. CONCLUSIONS: In our work, the results indicate that GOT1 induced by c-Myc may play an important role in combating ferroptosis due to glutamine deprivation, making it a significant target in glutamine withdrawal therapy. This study provides a theoretical foundation for the clinical targeted therapy for HCC.

Identification of Potential Factors for the Promotion of Fucoxanthin Synthesis by Methyl Jasmonic Acid Treatment of Phaeodactylum tricornutum.

Fucoxanthin, a vital secondary metabolite produced by marine diatoms, has great economic value and research potential. However, its popularization and application have been greatly restricted due to its low content, difficult extraction, and high production cost. Methyl jasmonic acid (MeJA) exerts similar inductive hormones in the growth and development as well as metabolic processes of plants. In Phaeodactylum tricornutum (P. tricornutum), MeJA treatment can increase fucoxanthin content. In this study, the effects of different concentrations of MeJA on the cell growth and the fucoxanthin content of P. tricornutum were explored. Meanwhile, this study used high-throughput sequencing technology for transcriptome sequencing of P. tricornutum and subsequently performed differential gene expression analysis, gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and weighted gene co-expression network analysis (WGCNA) for screening the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum. On this basis, the functions of the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum were further analyzed. The results revealed that the carotenoid synthesis-related genes PHATRDRAFT_54800 and PHATRDRAFT_20677 were the hub genes for the promotion of fucoxanthin synthesis with MeJA-treated P. tricornutum. PHATRDRAFT_54800 may be a carotenoid isomerase, while PHATRDRAFT_20677 may be involved in the MeJA-stimulated synthesis of fucoxanthin by exerting the role of SDR family NAD(P)-dependent oxidoreductases.

Time-Series Representation Learning in Topology Prediction for Passive Optical Network of Telecom Operators.

The passive optical network (PON) is widely used in optical fiber communication thanks to its low cost and low resource consumption. However, the passiveness brings about a critical problem that it requires manual work to identify the topology structure, which is costly and prone to bringing noise to the topology logs. In this paper, we provide a base solution firstly introducing neural networks for such problems, and based on that solution we propose a complete methodology (PT-Predictor) for predicting PON topology through representation learning on its optical power data. Specifically, we design useful model ensembles (GCE-Scorer) to extract the features of optical power with noise-tolerant training techniques integrated. We further implement a data-based aggregation algorithm (MaxMeanVoter) and a novel Transformer-based voter (TransVoter) to predict the topology. Compared with previous model-free methods, PT-Predictor is able to improve prediction accuracy by 23.1% in scenarios where data provided by telecom operators is sufficient, and by 14.8% in scenarios where data is temporarily insufficient. Besides, we identify a class of scenarios where PON topology does not follow a strict tree structure, and thus topology prediction cannot be effectively performed by relying on optical power data alone, which will be studied in our future work.

An All-Natural Wood-Inspired Aerogel.

The oriented pore structure of wood endows it with a variety of outstanding properties, among which the low thermal conductivity has attracted researchers to develop wood-like aerogels as excellent thermal insulation materials. However, the increasing demands of environmental protection have put forward new and strict requirements for the sustainability of aerogels. Here, we report an all-natural wood-inspired aerogel consisting of all-natural ingredients and develop a method to activate the surface-inert wood particles to construct the aerogel. The obtained wood-inspired aerogel has channel structure similar to that of natural wood, endowing it with superior thermal insulation properties to most existing commercial sponges. In addition, remarkable fire retardancy and complete biodegradability are integrated. With the above outstanding performances, this sustainable wood-inspired aerogel will be an ideal substitute for the existing commercial thermal insulation materials.

In Situ and Quantitative Monitoring of Cardiac Tissues Using Programmable Scanning Electrochemical Microscopy.

In vitro cardiac tissue model holds great potential as a powerful platform for drug screening. Respiratory activity, contraction frequency, and extracellular H2O2 levels are the three key parameters for determining the physiological functions of cardiac tissues, which are technically challenging to be monitored in an in situ and quantitative manner. Herein, we constructed an in vitro cardiac tissue model on polyacrylamide gels and applied a pulsatile electrical field to promote the maturation of the cardiac tissue. Then, we built a scanning electrochemical microscopy (SECM) platform with programmable pulse potentials to in situ characterize the dynamic changes in the respiratory activity, contraction frequency, and extracellular H2O2 level of cardiac tissues under both normal physiological and drug (isoproterenol and propranolol) treatment conditions using oxygen, ferrocenecarboxylic acid (FcCOOH), and H2O2 as the corresponding redox mediators. The SECM results showed that isoproterenol treatment induced enhanced oxygen consumption, accelerated contractile frequency, and increased released H2O2 level, while propranolol treatment induced dynamically decreased oxygen consumption and contractile frequency and no obvious change in H2O2 levels, suggesting the effects of activation and inhibition of ß-adrenoceptor on the metabolic and electrophysiological activities of cardiac tissues. Our work realizes the in situ and quantitative monitoring of respiratory activity, contraction frequency, and secreted H2O2 level of living cardiac tissues using SECM for the first time. The programmable SECM methodology can also be used to real-time and quantitatively monitor electrochemical and electrophysiological parameters of cardiac tissues for future drug screening studies.

Ruthenium Complex of sp2 Carbon-Conjugated Covalent Organic Frameworks as an Efficient Electrocatalyst for Hydrogen Evolution.

It is still a great challenge to explore hydrogen evolution reaction (HER) electrocatalysts with both lower overpotential and higher stability in acidic electrolytes. In this work, an efficient HER catalyst, Ru@COF-1, is prepared by complexation of triazine-cored sp2 carbon-conjugated covalent organic frameworks (COFs) with ruthenium ion. Ru@COF-1 possesses high crystallinity and porosity, which are beneficial for electrocatalysis. The large specific surface area and regular porous channels of Ru@COF-1 facilitate full contact between reactants and catalytic sites. The nitrogen atoms of triazines are protonated in the acidic media, which greatly improve the conductivity of Ru@COF-1. This synergistic effect makes the overpotential of Ru@COF-1 about 200 mV at 10 mA cm-2 , which is lower than other reported COFs-based electrocatalysts. Moreover, Ru@COF-1 exhibits exceptionally electrocatalytic durability in the acidic electrolytes. It is particularly stable and remains highly active after 1000 cyclic voltammetry cycles. Density functional theory calculations demonstrate that tetracoordinated Ru-N2 Cl2 moieties are the major contributors to the outstanding HER performance. This work provides a new idea for developing protonated HER electrocatalysts in acidic media.

Enantioselective Total Synthesis of Spirotryprostatin A.

In this paper, we disclosed a novel enantioselective total synthesis of spirotryprostatin A (1) in 15 steps with a 7.4% total yield from commercially available 2-iodo-5-methoxyaniline and γ-butyrolactone. The key step features of this synthesis include the copper-catalyzed cascade reaction of o-iodoaniline derivatives with alkynone to introduce the quaternary carbon stereocenter and an aza-Michael tandem reaction to construct the spiro[pyrrolidine-3,3'-oxindole] moiety.

Multi-omics analyses revealed key factors involved in fluorescent carbon-dots-regulated secondary metabolism in Tetrastigma hemsleyanum.

BACKGROUND: Luminescent nanomaterials (LNMs), especially newly-exploited fluorescent carbon-dots (CDs), have demonstrated promising candidates for sunlight harvesting and enhanced photosynthesis efficiency of crops. However, most of the studies focus on the design and synthesis of LNMs and primary metabolism in biomass acceleration, secondary metabolism that closely associated with the quality ingredients of plants is rarely mentioned. RESULTS: UV-absorptive and water-soluble NIR-CDs were harvested via a facile microwave-assisted carbonization method. The effect and regulatory mechanism of NIR-CDs on the secondary metabolism and bioactive ingredients accumulation in Tetrastigma hemsleyanum were explored. A total of 191 differential secondary metabolites and 6874 differentially expressed genes were identified when the NIR-CDs were adopted for enhancing growth of T. hemsleyanum. The phenolic acids were generally improved, but the flavonoids were more likely to decrease. The pivotal differentially expressed genes were involved in biosynthesis of secondary metabolites, flavonoid biosynthesis, porphyrin and chlorophyll metabolism, etc. The gene-metabolite association was constructed and 44 hub genes highly related to quality ingredients accumulation and growth were identified, among which and the top 5 genes of the PPI network might be the key regulators. CONCLUSION: This research provided key regulatory genes and differentially accumulating quality ingredients under NIR-CDs-treatment, which could provide a theoretical basis for expanding the applications of nanomaterial in industrial crop agriculture.

Reduced sensitivity of lager brewing yeast to premature yeast flocculation via adaptive evolution.

Malt-induced premature yeast flocculation (PYF) is a sporadic problem within the brewing industry. The use of PYF malts is concomitant with a number of negative impacts on beer quality, including incomplete fermentation and/or flavor defects. Although malt-induced PYF is widely acknowledged, actions taken so far have proved insufficient to solve the PYF-related issues. To limit the detrimental effects of PYF malts on beer production, an adaptive laboratory evolution (ALE) process was applied in this study to an industrial lager brewing yeast strain (TT02), in an attempt to generate variant strains with improved fermentation performance in PYF wort. Through a batch fermentation-based adaptation process, evolved variants were isolated and screened for their phenotypic and metabolic traits. The investigation focused mainly on the tendency to remain in suspension, fermentation capacity and final acetaldehyde concentration. We successfully obtained a variant (TT02-30 T) with improved fermentation properties. The improvement was seen in worts prepared from different types of PYF malt as well as normal malt. Furthermore, ALE of lager brewing yeast in PYF wort yielded a wide array of mutations. Several changes in the genomes (copy number variation in flocculin encoding gene FLO1 and a missense SNP in a putative mitochondrial membrane protein coding gene FMP10) of the variant strains relative to the original strain were observed. These could potentially contribute to the improved yeast suspension during fermentation. Importantly, mutational enrichment in genes related to ion binding in PYF-evolved strains suggests the involvement of the yeast ion transportation process in dealing with the PYF stress. Our study demonstrates the possibility of attenuating yeast sensitivity to PYF malts over time through adaptive laboratory evolution via spontaneous mutation.