Direct Incorporation of Dinitrogen into an Aliphatic C-H Bond.

The activation of dinitrogen (N2) and direct incorporation of its N atom into C-H bonds to create aliphatic C-N compounds remains unresolved. Incompatible conditions between dinitrogen reduction and C-H functionalization make this process extremely challenging. Herein, we report the first example of dinitrogen insertion into an aliphatic Csp3-H bond on the ligand scaffold of a 1,3-propane-bridged [N2N]2--type dititanium complex. Mechanistic investigations on the behaviors of dinuclear and mononuclear Ti complexes indicated the intramolecular synergistic effect of two Ti centers at a C-N bond-forming step. Computational studies revealed the critical isomerization between the inactive side-on N2 complex and the active nitridyl complex, which is responsible for the Csp3-H amination. This strategy maps an efficient route toward the future synthesis of aliphatic amines directly from N2.

Nitrogen fixation and transformation with main group elements.

Nitrogen fixation is essential for the maintenance of life and development of society, however, the large bond dissociation energy and nonpolarity of the triple bond constitute a considerable challenge. The transition metals, by virtue of their combination of empty and occupied d orbitals, are prevalent in the nitrogen fixation studies and are continuing to receive a significant focus. The main group metals have always been considered incapable in dinitrogen activation owing to the absence of energetically and symmetrically accessible orbitals. The past decades have witnessed significant breakthroughs in the dinitrogen activation with the main group elements and compounds via either matrix isolation, theoretical calculations or synthetic chemistry. The successful reactions of the low-valent species of the main group elements with inert dinitrogen have been reported via the π back-donation from either the d orbitals (Ca, Sr, Ba) or p orbitals (Be, B, C…). Herein, the significant achievements have been briefly summarized, along with predicting the future developments.

(n-Bu)4NBr-Promoted N2 Splitting to Molybdenum Nitride.

Splitting of N2 via six-electron reduction and further functionalization to value-added products is one of the most important and challenging chemical transformations in N2 fixation. However, most N2 splitting approaches rely on strong chemical or electrochemical reduction to generate highly reactive metal species to bind and activate N2, which is often incompatible with functionalizing agents. Catalytic and sustainable N2 splitting to produce metal nitrides under mild conditions may create efficient and straightforward methods for N-containing organic compounds. Herein, we present that a readily available and nonredox (n-Bu)4NBr can promote N2-splitting with a Mo(III) platform. Both experimental and theoretical mechanistic studies suggest that simple X- (X = Br, Cl, etc.) anions could induce the disproportionation of MoIII[N(TMS)Ar]3 at the early stage of the catalysis to generate a catalytically active {MoII[N(TMS)Ar]3}- species. The quintet MoII species prove to be more favorable for N2 fixation kinetically and thermodynamically, compared with the quartet MoIII counterpart. Especially, computational studies reveal a distinct heterovalent {MoII-N2-MoIII} dimeric intermediate for the N≡N triple bond cleavage.

Potassium-Zincate-Catalyzed Benzylic C-H Bond Addition of Diarylmethanes to Styrenes.

Direct functionalization of the benzylic C-H bond of diarylmethanes is an important strategy for the synthesis of diarylmethine-containing compounds. However, the methods developed to date for this purpose require a stoichiometric amount (usually more) of either a strong base or an oxidant. Reported here is the first catalytic benzylic C-H bond addition of diarylmethanes to styrenes and conjugated dienes. A potassium zincate complex, generated from potassium benzyl and zinc amide, acts as a catalyst and displays good activity and chemoselectivity. Considering the atom economy of the reaction and the ready availability of the catalyst, this reaction constitutes a practical, efficient method for diarylalkane synthesis.

Potassium Amide-Catalyzed Benzylic C-H Bond Addition of Alkylpyridines to Styrenes.

The benzylic functionalization of alkylpyridines is an important pathway for pyridine derivatives synthesis. The reaction partners, however, were mostly limited to highly reactive polar electrophiles. Herein, we report a potassium amide-catalyzed selective benzylic C-H bond addition of alkylpyridines to styrenes. Potassium bis(trimethylsilyl)amide (KHMDS), a readily available Brønsted base, showed excellent catalytic activity and chemoselectivity. A series of alkylpyridine derivatives, including benzylic quaternary carbon substituted pyridines, were obtained in good to high yield. Preliminary mechanistic studies revealed that the deprotonation equilibrium is probably responsible for the excellent selectivity.

Three-Dimensional Electrodes for High-Performance Bioelectrochemical Systems.

Bioelectrochemical systems (BES) are groups of bioelectrochemical technologies and platforms that could facilitate versatile environmental and biological applications. The performance of BES is mainly determined by the key process of electron transfer at the bacteria and electrode interface, which is known as extracellular electron transfer (EET). Thus, developing novel electrodes to encourage bacteria attachment and enhance EET efficiency is of great significance. Recently, three-dimensional (3D) electrodes, which provide large specific area for bacteria attachment and macroporous structures for substrate diffusion, have emerged as a promising electrode for high-performance BES. Herein, a comprehensive review of versatile methodology developed for 3D electrode fabrication is presented. This review article is organized based on the categorization of 3D electrode fabrication strategy and BES performance comparison. In particular, the advantages and shortcomings of these 3D electrodes are presented and their future development is discussed.

Wiring Bacterial Electron Flow for Sensitive Whole-Cell Amperometric Detection of Riboflavin.

A whole-cell bioelectrochemical biosensing system for amperometric detection of riboflavin was developed. A "bioelectrochemical wire" (BW) consisting of riboflavin and cytochrome C between Shewanella oneidensis MR-1 and electrode was characterized. Typically, a strong electrochemical response was observed when riboflavin (VB2) was added to reinforce this BW. Impressively, the electrochemical response of riboflavin with this BW was over 200 times higher than that without bacteria. Uniquely, this electron rewiring process enabled the development of a biosensing system for amperometric detection of riboflavin. Remarkably, this amperometric method showed high sensitivity (LOD = 2.2 nM, S/N = 3), wide linear range (5 nM ∼ 10 µM, 3 orders of magnitude), good selectivity, and high resistance to interferences. Additionally, the developed amperometric method featured good stability and reusability. It was further applied for accurate and reliable determination of riboflavin in real conditions including food, pharmaceutical, and clinical samples without pretreatment. Both the cost-effectiveness and robustness make this whole-cell amperometric system ideal for practical applications. This work demonstrated the power of bioelectrochemical signal amplification with exoelectrogen and also provided a new idea for development of versatile whole-cell amperometric biosensors.

Enhanced power production from microbial fuel cells with high cell density culture.

Improvement of power production in a microbial fuel cell (MFC) with a high cell density culture strategy was developed. By using high cell density culture, the voltage output and power density output of the MFC were enhanced about 0.6 and 1.6 times compared to the control, respectively. Further analysis showed that riboflavin concentration in the MFC was dramatically increased from 0.1 mg/L to 1.2 mg/L by high cell density culture. Moreover, the biofilm formation on the anode surface was significantly enhanced by this new strategy. The increased accumulation of electron shuttle (riboflavin) as well as enhanced biofilm formation contributed to the improvement in anodic electrochemical activity and these factors were the underlying mechanism for MFC performance improvement by high cell density culture. This work demonstrated that high cell density culture would be a simple and practical strategy for MFC manipulation.

Microbial fuel cell-based biosensors for environmental monitoring: a review.

The microbial fuel cell (MFC) is an innovative technology that was initially designed to harness energy from organic waste using microorganisms. It is striking how many promising applications beyond energy production have been explored in recent decades. In particular, MFC-based biosensors are considered to be the next generation biosensing technology for environmental monitoring. This review describes recent advances in this emerging technology of MFC-based biosensors, with a special emphasis on monitoring of biochemical oxygen demand and toxicity in the environment. The progress confirms that MFC-based biosensors could be used as self-powered portable biosensing devices with great potential in long-term and remote environmental monitoring.

Caffeine in Hepatocellular Carcinoma: Cellular Assays, Animal Experiments, and Epidemiological Investigation.

The use of caffeine in treating various liver diseases has made substantial progress in the past decade owing to advances in science, technology, and medicine. However, whether caffeine has a preventive effect on hepatocellular carcinoma (HCC) and its mechanism are still worth further investigation. In this review, we summarize and analyze the efficacy and safety of caffeine in the prevention of HCC. We conducted a review of articles published in PubMed and Web of Science in the past 2 decades until December 6, 2023, which were searched for using the terms "Caffeine" and "Hepatocellular Carcinoma." Studies have found that coffee intake is negatively correlated with HCC risk, especially caffeinated coffee. Recent studies have found that caffeine has beneficial effects on liver health, decreasing levels of enzymes responsible for liver damaging and slowing the progression of hepatic fibrosis and cirrhosis. Caffeine also acts against liver fibrosis through adenosine receptors (ARs), which promote tissue remodeling by inducing fibrin and collagen production. Additionally, new studies have found that moderate consumption of caffeinated beverages can decrease various the levels of various collagens in patients with chronic hepatitis C. Furthermore, polyphenolic compounds in coffee can improve fat homeostasis, reduce oxidative stress, and prevent liver steatosis and fibrosis. Moreover, many in vitro studies have shown that caffeine can protect liver cells and inhibit the activation and proliferation of hepatic stellate cells. Taken together, we describe the benefits of caffeine for liver health and highlight its potential values as a drug to prevent various hepatic diseases. As a protective agent of liver inflammation, non-selective AR inhibitor caffeine can inhibit the growth of HCC cells by inhibiting adenosine and AR binding to initiate immune response, providing a basis for the future development of caffeine as an adjuvant drug against HCC.

Comparative Analysis of Main Agronomic Traits of Different Pleurotus giganteus Germplasm Resources.

Agronomic traits are key components in variety protection, cultivar development, and the formulation of DUS (distinct, uniform, and stable) test guidelines. P. giganteus is an increasingly popular and commercially promising edible macrofungi. In this study, both mycelial performance and fruiting body characters of 15 Pleurotus giganteus strains were investigated. The temperature gradient culture test indicated that, although most of the strains achieved optimal mycelial growth between 24 and 28 °C, a statistical difference in mycelial growth rates and temperature adaptability among strains were found, supporting that this trait has the potential to be adopted as an indicator in distinguishing strains. In the fruiting performance tests, the coefficient of variation (CV) of tested traits ranged from 5.30% (pileus diameter) to 18.70% (individual mushroom weight). The mushroom yields ranged from 103.37 g/bag (strain No. 15) to 275.76 g/bag (strain No. 9). The large divergence observed in individual mushroom weight tested strains, ranging from 40.88 g to 78.39 g (with median between 37.69 and 79.395 g), make it highly selective and a potential indicator in variety development. Strain No. 9 had the advantages of forming larger, heavier fruiting bodies and a more obvious funnel shape, which also exhibited the highest biological efficiency (15.61%). The results suggested some morphological traits showed high variety difference, such as pileus diameter (55.75 mm to 66.48 mm), stipe length (92.59 mm to 177.51 mm), stipe diameter (16.14 mm to 23.52 mm), and pileus thickness (13.38 mm to 19.75 mm). In the cluster analysis, the tested strains were grouped into four clusters based on agronomic traits: cluster Ⅰ comprised six strains (No. 6, No. 11, No. 8, No. 1, No. 14, and No. 9) with high mushroom yield; cluster Ⅱ included four strains (No. 3, No. 10, No. 7, and No. 4) with large pileus diameter and short stipe; cluster ⅡI consisted of four strains (No. 5, No. 12, No. 13, and No. 15) with relatively lower yields; and cluster Ⅳ included only strain No. 2 which was low in yield, individual mushroom weight, and biological efficiency, accompanied by smaller pileus size and shorter stipe. The results of the correlation analysis indicated three traits, including individual mushroom weight, stipe length, and pileus weight, were positively associated with high yield. This study suggested P. giganteus germplasm resources are of high abundance and their agronomic diversity is useful in distinguishing and developing different varieties. The findings of this work provide knowledge on the agronomic traits and cultivation performance of various P. giganteus strains, laying a foundation for the development of its DUS test guidelines and variety protection, as well as providing reference for the breeding and phenotype selection of high-quality cultivars.

Aversatile MOF as an electrochemical/fluorescence/colorimetric signal probe for the tri-modal detection of MMP-9 secretion in the extracellular matrix to identify the efficacy of chemotherapeutic drugs.

BACKGROUND: MMP-9 plays a crucial role in regulating the degradation of proteins within the extracellular matrix (ECM). This process closely correlates with the occurrence, development, invasion, and metastasis of various tumors, each exhibiting diverse levels of MMP-9 expression. However, the accuracy of detection results using the single-mode method is compromised due to the coexistence of multiple biologically active substances in the ECM. RESULTS: Therefore, in this study, a tri-modal detection system is proposed to obtain more accurate information by cross-verifying the results. Herein, we developed a tri-modal assay using the ZIF-8@Au NPs@S QDs composite as a multifunctional signal probe, decorated with DNA for the specific capture of MMP9. Notably, the probe demonstrated high conductivity, fluorescence response and mimicked enzyme catalytic activity. The capture segments of hybrid DNA specifically bind to MMP9 in the presence of MMP9, causing the signal probe to effortlessly detach the sensor interface onto the sample solution. Consequently, the sensor current performance is weakened, with the colorimetric and fluorescent signals becoming stronger with increasing MMP9 concentration. Notably, the detection range of the tri-modal sensor platform spans over 10 orders of magnitude, verifying notable observations of MMP-9 secretion in four tumor cell lines with chemotherapeutic drugs. Furthermore, the reliability of the detection results can be enhanced by employing pairwise comparative analysis. SIGNIFICANCE: This paper presents an effective strategy for detecting MMP9, which can be utilized for both the assessment of MMP-9 in cell lines and for analyzing the activity and mechanisms involved in various tumors.

Matrix metalloproteinases induce extracellular matrix degradation through various pathways to alleviate hepatic fibrosis.

Liver fibrosis is the common consequence of various chronic liver injuries and is mainly characterized by the imbalance between the production and degradation of extracellular matrix, which leads to the accumulation of interstitial collagen and other matrix components. Matrix metalloproteinases (MMPs) and their specific inhibitors, that is, tissue inhibitors of metalloproteinases (TIMPs), play a crucial role in collagen synthesis and lysis. Previous in vivo and in vitro studies of our laboratory found repressing extracellular matrix (ECM) accumulation by restoring the balance between MMPs and TIMPs can alleviate liver fibrosis. We conducted a review of articles published in PubMed and Science Direct in the last decade until February 1, 2023, which were searched for using these words "MMPs/TIMPs" and "Hepatic Fibrosis." Through a literature review, this article reviews the experimental studies of liver fibrosis based on MMPs/TIMPs, summarizes the components that may exert an anti-liver fibrosis effect by affecting the expression or activity of MMPs/TIMPs, and attempts to clarify the mechanism of MMPs/TIMPs in regulating collagen homeostasis, so as to provide support for the development of anti-liver fibrosis drugs. We found the MMP-TIMP-ECM interaction can result in better understanding of the pathogenesis and progression of hepatic fibrosis from a different angle, and targeting this interaction may be a promising therapeutic strategy for hepatic fibrosis. Additionally, we summarized and analyzed the drugs that have been found to reduce liver fibrosis by changing the ratio of MMPs/TIMPs, including medicine natural products.

New insights into fibrotic signaling in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) mostly occurs in the background of liver fibrosis, and activated hepatic stellate cells (HSCs) exist in HCC tissues and adjacent tissues. HSC activation is involved throughout the development of HCC precancerous lesions, which has gradually attracted the attention of related researchers. In addition, HCC can promote the activation of HSCs, which in turn accelerates the occurrence and development of HCC by promoting tumor angiogenesis. In this review, we reviewed 264 studies from PubMed and ScienceDirect to summarize and analyze current significant fibrotic signaling in HCC. As a result, we found 10 fibrotic signaling pathways that are closely related to the activation, proliferation, invasion, migration, and promotion of apoptosis of HCC cells. In addition, we found that crosstalk between various fibrotic signaling pathways of HCC, hypoxia-induced energy metabolic reprogramming of HCC cells, matrix stiffness and stemness of HCC cells, and ferroptosis of HCC cells and HSCs are the latest research hotspots. Furthermore, related drugs that have been found to target these 10 fibrotic signaling pathways of HCC are listed. Our study provides a new reference for developing anti-HCC drugs.

Transcriptome profiling and bioinformatic analysis of the effect of ganoderic acid T prevents Sendai virus infection.

Ganoderic acid T (GA-T) is an important triterpene of Ganoderma lucidum, which is utilized to treat viral infections. Sendai virus (SeV) is widely studied to determine the molecular biological characteristics of RNA viruses and employed to elucidate the mechanisms governing the innate immune response. However, the comprehensive mechanism governing the antiviral effects of GA-T against SeV infection remains unknown. In this study, SeV-infected host cells were treated with 16.3 µM GA-T, subsequently RNA-seq analysis was performed to screen the differentially expressed genes (DEGs). The RNA-seq data showed that GA-T treatment upregulated 934 DEGs and downregulated 1283 DEGs against viral infection, in particularly, IFNGR1, IL1A, and IL1R1 were upregulated, and mTOR, SMAD3, IFNL2 and IFNL3 were decreased. GO and KEGG analysis illustrated that DEGs were clustered in mTOR and IL-17 signalling pathways. Protein-protein interaction network analysis indicated the high degree of nodes, such as CXCL8, CSF2, CXCL1 and MYD88. Our results indicated that GA-T exerted its antiviral pharmacological effects through inhibition of the mTOR signalling pathway and adjustment of innate immunity system and the inflammatory response involving the IL-17 signalling pathway. Our results may help to elucidate the potential functions and underlying mechanisms governing the antiviral effects of GA-T.

Comparative analysis of proteomes and transcriptomes revealed the molecular mechanism of development and nutrition of Pleurotus giganteus at different fruiting body development stages.

Pleurotus giganteus is a commercially cultivated high-temperature mushroom. Investigating the molecular mechanism of fruiting body development will help us to better understand the regulation of substrates and energy in this process. However, little information has been reported on the development and nutrients of the P. giganteus fruiting body. In the present study, P. giganteus is cultivated in a climate chamber, and comparative transcriptome, proteome, and nutritional analysis of P. giganteus fruiting bodies were performed. Our results revealed that Cytochrome P450 monooxygenases and hydrophobin proteins play important roles during the differentiation in the elongation stage. Later, carbon metabolism dominate the fruiting body metabolism and genes related to the carbohydrate metabolic process, glycolytic process, and gluconeogenesis were up-regulated in the mature fruiting bodies. The up-regulation of carbohydrate substrates utilization CAZymes genes and inconsistent protein expression in pileus indicated a reverse transportation of mRNA from the fruiting body to vegetative mycelia. In addition, protein concentration in the pileus is higher than that in the stem, while the stem is the major nitrogen metabolic and amino acid synthetic location. The integrated transcriptomic, proteomic, and nutritional analysis indicated a two-way transportation of substrates and mRNAs in P. giganteus. Stem synthesizes amino acids and transported them to pileus with reducing sugars, while pileus induces the expression of substrate degradation mRNA according to the needs of growth and development and transports them in the other direction.

Jellyfish-type Dinuclear Hafnium Azido Complexes: Synthesis and Reactivity.

Di- and multinuclear hafnium complexes bridged by ligands have been rarely reported. In this article, a novel 3,5-disubstituted pyrazolate-bridged ligand LH5 with two [N2 N]2- -type chelating side arms was designed and synthesized, which supported a series of dinuclear hafnium complexes. Dinuclear hafnium azides [LHf2 (µ-1,1-N3 )2 (N3 )2 ][Na(THF)4 ] 3 and [LHf2 (µ-1,1-N3 )2 (N3 )2 ][Na(2,2,2-Kryptofix)] 4 were further synthesized and structurally characterized, featuring two sets of terminal and bridging azido ligands like jellyfishes. The reactivity of 3 under reduction conditions was conducted, leading to a formation of a tetranuclear hafnium imido complex [L1 Hf2 (µ1 -NH)(N3 ){µ2 -K}]2 5. DFT calculations revealed that the mixed imido azide 5 was generated via an intramolecular C-H insertion from a putative dinuclear HfIV -nitridyl intermediate.

New Drugs for Hepatic Fibrosis.

The morbidity and mortality of hepatic fibrosis caused by various etiologies are high worldwide, and the trend is increasing annually. At present, there is no effective method to cure hepatic fibrosis except liver transplantation, and its serious complications threaten the health of patients and cause serious medical burdens. Additionally, there is no specific drug for the treatment of hepatic fibrosis, and many drugs with anti-hepatic fibrosis effects are in the research and development stage. Recently, remarkable progress has been made in the research and development of anti-hepatic fibrosis drugs targeting different targets. We searched websites such as PubMed, ScienceDirect, and Home-ClinicalTrials.gov and found approximately 120 drugs with anti-fibrosis properties, some of which are in phase Ⅱ or Ⅲ clinical trials. Additionally, although these drugs are effective against hepatic fibrosis in animal models, most clinical trials have shown poor results, mainly because animal models do not capture the complexity of human hepatic fibrosis. Besides, the effect of natural products on hepatic fibrosis has not been widely recognized at home and abroad. Furthermore, drugs targeting a single anti-hepatic fibrosis target are prone to adverse reactions. Therefore, currently, the treatment of hepatic fibrosis requires a combination of drugs that target multiple targets. Ten new drugs with potential for development against hepatic fibrosis were selected and highlighted in this mini-review, which provides a reference for clinical drug use.

Caffeine in liver diseases: Pharmacology and toxicology.

We have previously shown that adenosine A1AR antagonists, adenosine A2aAR antagonists, and caffeine have significant inhibitory effects on the activation and proliferation of hepatic stellate cells in alcoholic liver fibrosis. Many recent studies have found that moderate coffee consumption is beneficial for various liver diseases. The main active ingredient of coffee is caffeine, which is a natural non-selective adenosine receptor antagonist. Moreover, numerous preclinical epidemiological studies and clinical trials have examined the association between frequent coffee consumption and the risk of developing different liver diseases. In this review, we summarize and analyze the prophylactic and therapeutic effects of caffeine on various liver diseases, with an emphasis on cellular assays, animal experiments, and clinical trials. To review the prevention and treatment effects of caffeine on different liver diseases, we searched all literature before 19 July 2022, using "caffeine" and "liver disease" as keywords from the PubMed and ScienceDirect databases. We found that moderate coffee consumption has beneficial effects on various liver diseases, possibly by inhibiting adenosine binding to its receptors. Caffeine is a potential drug for the prevention and treatment of various liver diseases.

Silylamido supported dinitrogen heterobimetallic complexes: syntheses and their catalytic ability.

Molybdenum dinitrogen complexes supported by monodentate arylsilylamido ligand, [Ar(Me3Si)N]3MoN2Mg(THF)2[N(SiMe3)Ar] (5) and [Ar(Me3Si)N]3MoN2SiMe3 (6) (Ar = 3,5-Me2C6H3) were synthesized and structurally characterized, and proved to be effective catalysts for the disproportionation of cyclohexadienes and isomerization of terminal alkenes. The 1H NMR spectrum suggested that the bridging nitrogen ligand remains intact during the catalytic reaction, indicating possible catalytic ability of the Mo-N=N motif.