CARMIL1 regulates liver cancer cell proliferation by activating the ERK/mTOR pathway through the TRIM27/p53 axis.

Capping protein regulatory factor and myosin 1 linker 1 is termed CARMIL1. CARMIL1 is involved in several physiological processes; it forms an actin filament network and plasma membrane-bound cellular projection tissues and positively regulates the cellular components and tissues. CARMIL1 exhibits important biological functions in cancer; nonetheless, these functions have not been completely explored. We aimed to investigate the novel functions of CARMIL1 in liver cancer, particularly in cell proliferation. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Component A experiments, and subcutaneous tumor formation model suggest that CARMIL1 is central to the proliferation of liver cancer cells both in vivo and in vitro. We extracted CARMIL1 samples from The Cancer Genome Atlas Program and analyzed its enrichment. CARMIL1 regulated the pathway activity by affecting the expression of star molecular proteins of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Moreover, it influenced the proliferation ability of liver cancer cells. Western blotting suggested that CARMIL1 downregulation could affect ERK and mTOR phosphorylation. Results of the co-immunoprecipitation demonstrated that CARMIL1 binds to tripartite motif (TRIM)27, which in turn binds to p53. Subsequently, CARMIL1 can regulate p53 stability and promote its degradation through TRIM27. Additionally, CARMIL1 inhibition enhanced the sensitivity of liver cancer cells to sorafenib. Tumor growth was significantly inhibited in the group treated with sorafenib and CARMIL1, compared with the group treated with CARMIL1 alone. Sorafenib is a first-line targeted chemotherapeutic drug for hepatocellular carcinoma treatment. It increases the long-term survival of hepatocellular carcinoma by 44%. In this study, downregulated CARMIL1 combined with sorafenib significantly reduced the tumor volume and weight of the mouse subcutaneous tumor model, indicating the potential possibility of combining CARMIL1 with sorafenib in hepatocellular carcinoma treatment. In summary, CARMIL1 promotes liver cancer cell proliferation by regulating the TRIM27/p53 axis and activating the ERK/mTOR pathway.

NAP1L5 facilitates pancreatic ductal adenocarcinoma progression via TRIM29-mediated ubiquitination of PHLPP1.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most aggressive solid tumours in humans. Despite its high mortality rate, effective targeted therapeutic strategies remain limited due to incomplete understanding of the underlying biological mechanisms. The NAP1L gene family has been implicated in the development and progression of various human tumours. However, the specific function and role of NAP1L5 (nucleosome assembly protein-like 5) in PDAC have not been fully elucidated. Therefore, in this study, we aimed to investigate the role of NAP1L5 in PDAC and explore the regulatory relationship between NAP1L5 and its potential downstream molecule PHLPP1 (PH domain Leucine-rich repeat Protein Phosphatase 1) in PDAC. Our study revealed that NAP1L5 is notably upregulated in PDAC. Moreover, both in vivo and in vitro experiments demonstrated that knockdown of NAP1L5 suppressed the proliferation of PDAC cells. Mechanistically, NAP1L5 was found to promote PDAC progression by activating the AKT/mTOR signalling pathway in a PHLPP1-dependent manner. Specifically, NAP1L5 binds to PHLPP1 and facilitates the ubiquitination-mediated degradation of PHLPP1, ultimately resulting in reduced PHLPP1 expression. Notably, TRIM29, recruited by NAP1L5, was found to be involved in facilitating K48-linked ubiquitination of PHLPP1. Our findings indicate that NAP1L5 overexpression promotes the proliferation of PDAC cells by inhibiting PHLPP1 expression. These novel insights suggest that NAP1L5 may serve as a potential therapeutic target for PDAC.

ZrO2-Promoted Cu-Co, Cu-Fe and Co-Fe Catalysts for Higher Alcohol Synthesis.

The development of efficient catalysts for the direct synthesis of higher alcohols (HA) via CO hydrogenation has remained a prominent research challenge. While modified Fischer-Tropsch synthesis (m-FTS) systems hold great potential, they often retain limited active site density under operating conditions for industrially relevant performance. Aimed at improving existing catalyst architectures, this study investigates the impact of highly dispersed metal oxides of Co-Cu, Cu-Fe, and Co-Fe m-FTS systems and demonstrates the viability of ZrO2 as a general promoter in the direct synthesis of HA from syngas. A volcano-like composition-performance relationship, in which 5-10 mol % ZrO2 resulted in maximal HA productivity, governs all catalyst families. The promotional effect resulted in a 2.5-fold increase in HA productivity for the optimized Cu1Co4@ZrO2-5 catalyst (Cu:Co = 1:4, 5 mol % ZrO2) compared to its ZrO2-free counterpart and placed Co1Fe4@ZrO2-10 among the most productive systems (345 mgHA h-1 gcat-1) reported in this category under comparable operating conditions, with stable performance for at least 300 h. ZrO2 assumes an amorphous and defective nature on the catalysts, leading to enhanced H2 and CO activation, facilitated formation of metallic and carbide phases, and structural stabilization.

TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC.

TM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, the effect of TM4SF1 on cancer stemness in hepatocellular carcinoma (HCC) and its molecular basis are yet to be reported. We found through abundant in vitro and in vivo experiments which the expression of TM4SF1 was positively correlated with the progression and cancer stemness of HCC. We identified the downstream protein MYH9 of TM4SF1 and its final regulatory target NOTCH pathway using bioinformatics analysis and protein mass spectrometry. We cultivated a Lenvatinib-resistant strain from HCC cells to examine the relationship between cancer stemness and tumor drug resistance. The study confirmed that TM4SF1 could regulate the NOTCH pathway by upregulating MYH9, thus promoting cancer stemness and Lenvatinib resistance in HCC. This study not only provided a new idea for the pathogenesis of HCC but also confirmed that TM4SF1 might become a new intervention point to improve the clinical efficacy of Lenvatinib in treating HCC.

NAP1L5 targeting combined with MYH9 Inhibit HCC progression through PI3K/AKT/mTOR signaling pathway.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Nucleosome assembly protein 1-like 5 (NAP1L5) is a protein-coding gene that encodes a protein similar to nucleosome assembly protein 1 (NAP1). It is a histone chaperone that plays an important role in gene transcription in organisms. However, the role of NAP1L5 in the pathogenesis of hepatocellular carcinoma remains to be elucidated. In this study, low expression of NAP1L5 was found in hepatocellular carcinoma, and the downregulation of NAP1L5 was related to shorter survival and disease-free survival. In addition, its expression is also related to the tumor size and recurrence of hepatocellular carcinoma. The overexpression and knockdown of NAP1L5 by plasmid and siRNA showed that NAP1L5 inhibited the proliferation, migration and invasion and induced apoptosis of hepatoma cells. In vivo experiments confirmed that NAP1L5 can inhibit the growth and metastasis of hepatocellular carcinoma cells. In the mechanistic study, we found that NAP1L5 affects the occurrence and development of hepatocellular carcinoma by regulating MYH9 to inhibit the PI3K/AKT/mTOR signaling pathway. As a functional tumor suppressor, NAP1L5 is expressed at low levels in HCC. NAP1L5 inhibits the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma by regulating MYH9. It may be a new potential target for liver cancer treatment.

Aerobic glycolysis and tumor progression of hepatocellular carcinoma are mediated by ubiquitin of P53 K48-linked regulated by TRIM37.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. In malignant liver cancer, the increase of aerobic glycolysis indicates that the possibility of tumorigenesis is greatly enhanced. TRIM37 is a member of the TRIM family of proteins that possesses E3 ubiquitin ligase activity and has been implicated in the occurrence and prognosis of many different tumors. However, the stability of P53 plays an important role in preventing tumorigenesis. The mechanism by which TRIM37 regulates the stability of P53 through ubiquitin in the progression of hepatocellular carcinoma is still unclear. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the expression of mRNA and protein in HCC cells. Lactic acid production, glucose uptake, and ATP levels were measured by BioVision kit. The following were used to assess the in vitro function of TRIM37 in HCC cells: cell counting kit-8 (CCK-8), colony formation assay, cell migration and invasion assay, and flow cytometry. We observed the effect of TRIM37 on the growth of transplanted tumors in nude mice. Co-Immunoprecipitation (Co-IP) revealed a binding relationship between TRIM37 and P53. RESULTS: The expression of TRIM37 in hepatocellular carcinoma (HCC) tissues was higher than that of normal tissues according to an analysis of The Cancer Genome Atlas (TCGA) database.Loss-of-function assays indicated that TRIM37 inhibited the proliferation, colony formation, migration, and invasion of liver cancer cells. The mechanism is as follows: TRIM37 interacts with the P53 protein to induce E3 ligase activity, ubiquitination, and degradation, further promoting the malignant characteristics of hepatocellular carcinoma, thus promoting the process of glycolysis. Genetic knockdown of P53 reversed the promoting function of TRIM37 on the growth and metastasis of hepatocellular carcinoma cells. CONCLUSIONS: Our study showed that the TRIM37-P53 axis plays a role in the progression of liver cancer, and thus is a potential target for the treatment of liver cancer.

DNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with ß-catenin to promote its ubiquitin degradation pathway.

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic ß-catenin destruction complex (GSK-3ß and Axin), promotes the ubiquitination degradation of ß-catenin, and inhibits its nuclear transfer, thus, decreasing c-Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

Atomically dispersed Ir/α-MoC catalyst with high metal loading and thermal stability for water-promoted hydrogenation reaction.

Synthesis of atomically dispersed catalysts with high metal loading and thermal stability is challenging but particularly valuable for industrial application in heterogeneous catalysis. Here, we report a facile synthesis of a thermally stable atomically dispersed Ir/α-MoC catalyst with metal loading as high as 4 wt%, an unusually high value for carbide supported metal catalysts. The strong interaction between Ir and the α-MoC substrate enables high dispersion of Ir on the α-MoC surface, and modulates the electronic structure of the supported Ir species. Using quinoline hydrogenation as a model reaction, we demonstrate that this atomically dispersed Ir/α-MoC catalyst exhibits remarkable reactivity, selectivity and stability, for which the presence of high-density isolated Ir atoms is the key to achieving high metal-normalized activity and mass-specific activity. We also show that the water-promoted quinoline hydrogenation mechanism is preferred over the Ir/α-MoC, and contributes to high selectivity towards 1,2,3,4-tetrahydroquinoline. The present work demonstrates a new strategy in constructing a high-loading atomically dispersed catalyst for the hydrogenation reaction.

Heterogeneous Catalysis in Water.

Heterogeneous catalytic processes produce the majority of the fuels and chemicals in the chemical industry and have kept improving the welfare of human beings for centuries. Although most of the heterogeneous catalytic reactions occur at the gas-solid interface, numerous cases have demonstrated that the condensed water near the active site and/or the aqueous phase merging the catalysts play positive roles in enhancing the performance of heterogeneous catalysts and creating novel catalytic conversion routes. We enumerate the traditional heterogeneous catalytic reactions that enable significant rate/selectivity promotion in the aqueous phase or adsorbed micro water environment and discuss the role of water in specific systems. Some of the novel heterogeneous reactions achieved with only the assistance of the aqueous phase have been summarized. The development of reactions with the participation of the aqueous phase/water and the investigation of the role of water in the heterogeneous catalytic reactions will open new horizons for catalysts with better activity, improved selectivity, and novel processes.

Controllable Synthesis of Supported PdAu Nanoclusters and Their Electronic Structure-Dependent Catalytic Activity in Selective Dehydrogenation of Formic Acid.

We report the design and synthesis of uniform PdAu alloy nanoclusters immobilized on diamine and graphene oxide-functionalized silica nanospheres. The structure-dependent activity for selectively catalytic dehydrogenation of formic acid (FA) has been evaluated and optimized by controlling the Pd/Au mole ratio and the carrier components. The relationship between the catalyst structure and activity has been investigated via both experiments and characterization. High-resolution transmission electron microscopy (TEM) and X-ray diffraction (XRD) proved the formation of PdAu alloy nanoclusters. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), X-ray photoelectron spectroscopy (XPS), and X-ray absorption fine structure (XAFS) analyses verified the electron transfer between Au, Pd, and the support. An outstanding turnover frequency (TOF) value of 16 647 h-1 at 323 K, which is among the highest activity for FA dehydrogenation ever reported, can be achieved at optimized conditions and ascribed to the combination of the bimetallic synergistic effect and the carrier effect.

Maximizing the Synergistic Effect of CoNi Catalyst on α-MoC for Robust Hydrogen Production.

We report the syntheses of highly dispersed CoNi bimetallic catalysts on the surface of α-MoC based on the strong metal support interaction (SMSI) effect. The interaction between the nearly atomically dispersed Co and Ni atoms was observed for the first time by the real-space chemical mapping at the atomic level. Combined with the ability of α-MoC to split water at low temperatures, the as-synthesized CoNi/α-MoC catalysts exhibited robust and synergistic performance for the hydrogen production from hydrolysis of ammonia borane. The metal-normalized activity of the bimetallic 1.5Co1.5Ni/α-MoC catalyst reached 321.1 molH2·mol-1CoNi·min-1 at 298 K, which surpasses all the noble metal-free catalysts ever reported and is four times higher than that of the commercial Pt/C catalyst.

Primulina hochiensis var. ochroleuca (Gesneriaceae), a new variety from a limestone area of Guangxi, China, and errata on five new species of Primulina.

Primulina hochiensis var. ochroleuca, a new variety from a limestone hill of karst areas, Guangxi, China is described with color photographs. It resembles P. hochiensis var. hochiensis, P. hochiensis var. ovata and P. hochiensis var. rosulata, but can be easily distinguished by a combination of characteristics, especially by its corolla color. We found only one population with approx. 3000 mature individuals at the type locality. This variety is provisionally assessed as vulnerable [VU C1] using IUCN criteria.

Molybdenum Carbide: Controlling the Geometric and Electronic Structure of Noble Metals for the Activation of O-H and C-H Bonds.

In the field of heterogeneous catalysis, transition metal carbides (TMCs) have attracted growing and extensive attention as a group of important catalytic materials for a variety of energy-related reactions. Due to the incorporation of carbon atoms at the interstitial sites, TMCs possess much higher density of states near the Fermi level, endowing the material with noble-metal-like electron configuration and catalytic behaviors. Crystal structure, site occupancies, surface termination, and metal/carbon defects in the bulk phase or at the surface are the structural factors that influence the behavior of the TMCs in catalytic reactions. In the early studies of heterogeneous catalytic applications of TMCs, the carbide itself was used individually as the catalytically active site, which exhibited unique catalytic performance comparable to precious metal catalysts toward hydrogenation, dehydrogenation, isomerization, and hydrodeoxygenation. To promote the catalytic performance, the doping of secondary transition metals into the carbide lattice to form bimetallic carbides was extensively studied. As a recent development, the utilization of TMCs as functionalized catalyst supports has achieved a series of significant breakthroughs in low-temperature catalytic applications, including the reforming of alcohols, water-gas shift reactions, and the hydrogenation of functional groups for chemical production and biomass conversion. Generally, the excellence of TMCs as supports is attributed to three factors: the modulation of geometric and electronic structures of the supported metal centers, the special reactivity of TMC supports that accelerates certain elementary step and influences the surface coverage of intermediates, and the special interfacial properties at the metal-carbide interface that enhance the synergistic effect. In this Account, we will review recent discoveries from our group and other researchers on the special catalytic properties of face-centered cubic MoC (α-MoC) as both a special catalyst and a functional support that enables highly efficient low-temperature O-H bond activation for several important energy-related catalytic applications, including hydrogen evolution from aqueous phase methanol reforming, ultralow temperature water-gas shift reaction, and biomass conversion. In particular, α-MoC has been demonstrated to exhibit unprecedented strong interaction with the supported metals compared with other TMCs, which not only stabilizes the under-coordinated metal species (single atoms and layered clusters) under strong thermal perturbation and harsh reaction conditions but also tunes the charge density at the metal sites and modifies their catalytic behavior in C-H activation and CO chemisorption. We will discuss how to exploit the metal/α-MoC interaction and interfacial properties to construct CO-tolerant selective hydrogenation catalysts for nitroarene derivatives. Several examples of constructing bifunctional tandem catalytic systems using molybdenum carbides that enable hydrogen extraction and utilization in one-pot conversion of biomass substrates and Fischer-Tropsch synthesis are also highlighted.

PtNi/NiO Clusters Coated by Hollow Sillica: Novel Design for Highly Efficient Hydrogen Production from Ammonia-Borane.

Ammonia-borane (NH3·BH3; AB) has been considered as an excellent chemical material for hydrogen storage. However, developing highly efficient catalysts for continuous hydrogen generation from AB is still a challenge for future fuel cell applications. The combination of Pt with Ni is an effective strategy to achieve active bimetallic nanocatalyst, and the particle size has proved to play a crucial role in determining its final activity. However, the synthesis of PtNi bimetallic catalyst in the size of highly dispersed clusters has always been a challenge. In this report, PtNi/NiO clusters coated by small-sized hollow silica (R-PtNi/NiO@SiO2) were designed for efficient hydrogen generation from the hydrolysis of ammonia-borane. The newly designed catalysis system showed extremely high activity with the initial turnover frequency value reaching 1240.3 mol of H2·mol-1 of Pt·min-1, which makes it one the most active Pt-based catalysts for this reaction. Detailed characterization by means of scanning transmission electron microscopy, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy element mapping, etc. revealed that the excellent performance of R-PtNi/NiO@SiO2 is derived from the highly dispersed PtNi/NiO clusters and the reduction of extra Pt4+ on the surface of PtNi/NiO clusters to Pt0 at relatively low temperature.

Highly efficient silica coated CuNi bimetallic nanocatalyst from reverse microemulsion.

Silica protected CuNi bimetallic nanoparticles (CuNi@SiO2) were successfully prepared by a modified co-reduction method. Typically, ammoniacal Cu(II) and Ni(II) were firstly dispersed and encapsulated inside silica by the method of reverse microemulsion. Then, ultra small CuO and NiO particles were in-situ formed during calcination under air. CuNi bimetallic nanoparticles were obtained by the co-reduction of CuO and NiO under H2 at high temperature. The composition and size of CuNi bimetallic nanoparticles was tuned simply by varying the concentration of precursor solutions. The samples were characterized by FT-IR, TEM, XPS, XRD and ICP-OES. The reduction of p-nitrophenol by NaBH4 was chosen as model reaction to evaluate the catalytic activity. The results indicate that CuNi bimetallic nanoparticles prepared by our method show size and composition dependent catalytic activity. The activation energy of Cu54Ni46@SiO2 for the same reaction was calculated as to be 16.6kJ/mol which was much lower than that of Cu@SiO2 (29.0kJ/mol) and Ni@SiO2 (39.5kJ/mol).

Chloride capping of CdTiO3 for higher crystallinity and enhanced photocatalytic activity.

The crystallinity of cadmium titanate (CdTiO3) was greatly improved when synthesized under mild reaction conditions, in the presence of chloride. The highly crystalline CdTiO3 showed much enhanced photodegradation of methyl orange (MO) under simulated sunlight. CdTiO3 was characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), N2 adsorption/desorption, photoluminescence (PL), and UV/vis spectrometry. The enhanced photodegradation was attributed to the better charge separation owing to its higher crystallinity.

In Situ Encapsulation of Ultrasmall CuO Quantum Dots with Controlled Band-Gap and Reversible Thermochromism.

Silica encapsulated ultrasmall CuO quantum dots (QDs; CuO@SiO2) were synthesized by reverse microemulsion. The CuO QDs with sizes ranging from 2.0 to 1.0 nm with corresponding band gaps of 1.4 to 2.6 eV were prepared simply by varying the concentration of the Cu(2+) precursor. The samples were characterized by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and UV-vis spectroscopy. The CuO@SiO2 composite displayed reversible thermochromism which resulted from the strong electron-phonon coupling of ultrasmall CuO in the confined space of SiO2 and the enhanced band-gap shift in the visible light region depending on temperature. Besides, the as synthesized CuO@SiO2 was found to be highly stable for reversible thermochromism due to the micropore structure of silica matrix and local confinement of the QDs.