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Hepatocellular carcinoma (HCC) is frequently characterized by metabolic and immune remodeling in the tumor microenvironment. We previously discovered that liver-specific deletion of fructose-1, 6-bisphosphatase 1 (FBP1), a gluconeogenic enzyme ubiquitously suppressed in HCC tissues, promotes liver tumorigenesis and induces metabolic and immune perturbations closely resembling human HCC. However, the underlying mechanisms remain incompletely understood. Here, we reported that FBP1-deficient livers exhibit diminished amounts of natural killer (NK) cells and accelerated tumorigenesis. Using the diethylnitrosamine-induced HCC mouse model, we analyzed potential changes in the immune cell populations purified from control and FBP1-depleted livers and found that NK cells were strongly suppressed. Mechanistically, FBP1 attenuation in hepatocytes derepresses an zeste homolog 2 (EZH2)-dependent transcriptional program to inhibit PKLR expression. This leads to reduced levels of PKLR cargo proteins sorted into hepatocyte-derived extracellular vesicles (EVs), dampened activity of EV-targeted NK cells, and accelerated liver tumorigenesis. Our study demonstrated that hepatic FBP1 depletion promotes HCC-associated immune remodeling, partly through the transfer of hepatocyte-secreted, PKLR-attenuated EVs to NK cells.

As a newly emerging approach for surface-enhanced Raman spectroscopy (SERS), pressure-induced SERS (PI-SERS) has been attracting increasing interest for its applications in Raman signal enhancement at extreme conditions. However, how to efficiently realize the PI-SERS enhancement and elucidate the corresponding mechanism remain open questions. Herein, we demonstrate the PI-SERS enhancement up to 8.04 GPa using monolayer molybdenum disulfide (ML-MoS2) as a SERS substrate and three organic molecules with similar energy levels but different symmetries as probes. The combined theory and experiment results show that a pressure-induced increase in the Fermi level of the ML-MoS2 substrate and a decrease in the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap of probe molecules lead to a transition from the multiple resonance-related SERS enhancement to charge transfer (CT)-dominated PI-SERS selective enhancement, depending on the incident laser energy and the pressure applied. Such PI-SERS selective enhancement has been discussed in the framework of CT-induced strengthening of electron-phonon coupling, as well as a possible match of the structural symmetries between probe molecules and the substrate. This study provides deep insights into our understanding of PI-SERS enhancement, and the revealed mechanism can be extended to other molecules for SERS at extreme conditions.

Creation of the hybrid nanostructures with superior properties that combine the advantages of hardest diamond and flexible graphite remains challenging in experiment. Here we report a new strategy for the synthesis of diamond-graphite hybrid nanocomposite from multi-walled carbon nanotubes fibers by laser heating diamond anvil cell. A combined theory experiment approach confirms the formation of diamond-graphite hybrid structure with the coherent interface consisted of covalent bonds between diamond and graphite. This opens an avenue for the synthesis of diamond-graphite hybrid structure, which may be extended to generate new carbon nanocomposites using other suitable carbon precursors by high pressure.

According to the laws of thermodynamics, materials normally exhibit contraction or expansion along the directions of the applied pressure or tension. Here, we show that a man-made cocrystal of a me ...

Suppression of gluconeogenesis elevates glycolysis and is commonly observed in tumors derived from gluconeogenic tissues including liver and kidney, yet the definitive regulatory mechanism remains elusive. Here, we screened an array of transcription regulators and identified the enhancer of zeste homolog 2 (EZH2) as a key factor that inhibits gluconeogenesis in cancer cells. Specifically, EZH2 repressed the expression of a rate-limiting gluconeogenic enzyme fructose-1, 6-bisphosphatase 1 (FBP1) and promoted tumor growth primarily through FBP1 suppression. Furthermore, EZH2 was upregulated by genotoxins that commonly induce hepatic and renal tumorigenesis. Genotoxin treatments augmented EZH2 acetylation, leading to reduced association between EZH2 and its E3 ubiquitin ligase SMURF2. Consequently, EZH2 became less ubiquitinated and more stabilized, promoting FBP1 attenuation and tumor formation. Intriguingly, FBP1 physically interacted with EZH2, competed for EZH2 binding, and dissembled the polycomb complex. Therefore, FBP1 suppresses polycomb-initiated transcriptional responses and constitutes a double-negative feedback loop indispensable for EZH2-promoted tumorigenesis. Finally, EZH2 and FBP1 levels were inversely correlated in tumor tissues and accurately predicted patient survival. This work reveals an unexpected cross-talk between epigenetic and metabolic events, and identifies a new feedback circuitry that highlights EZH2 inhibitors as liver and kidney cancer therapeutics. Significance: A novel feedback loop involving EZH2 and suppression of the gluconeogenesis enzyme FBP1 promotes hepatocellular cancer growth. See related commentary by Leithner, p. 657

Here, we report a high-pressure study on corannulene up to 27.6 GPa using the diamond cell technique assisted by Raman and infrared spectroscopic measurements. The intermolecular interactions betwe...

MYCN amplification is tightly associated with the poor prognosis of pediatric neuroblastoma (NB). The regulation of NB cell death by MYCN represents an important aspect, as it directly contributes to tumor progression and therapeutic resistance. However, the relationship between MYCN and cell death remains elusive. Ferroptosis is a newly identified cell death mode featured by lipid peroxide accumulation that can be attenuated by GPX4, yet whether and how MYCN regulates ferroptosis are not fully understood. Here, we report that MYCN-amplified NB cells are sensitive to GPX4-targeting ferroptosis inducers. Mechanically, MYCN expression reprograms the cellular iron metabolism by upregulating the expression of TFRC, which encodes transferrin receptor 1 as a key iron transporter on the cell membrane. Further, the increased iron uptake promotes the accumulation of labile iron pool, leading to enhanced lipid peroxide production. Consistently, TFRC overexpression in NB cells also induces selective sensitivity to GPX4 inhibition and ferroptosis. Moreover, we found that MYCN fails to alter the general lipid metabolism and the amount of cystine imported by System Xc(−) for glutathione synthesis, both of which contribute to ferroptosis in alternative contexts. In conclusion, NB cells harboring MYCN amplification are prone to undergo ferroptosis conferred by TFRC upregulation, suggesting that GPX4-targeting ferroptosis inducers or TFRC agonists can be potential strategies in treating MYCN-amplified NB.

Diamond aerogel, a special kind of carbon aerogel made by sp3 carbon atoms, has been attracting intensive research interest due to its potential applications since it is first synthesized by the conversion of amorphous carbon. Despite of many expectations in diamond aerogel, the study on its synthesis is still not adequate compared with other carbon aerogel. Here we report the synthesis of diamond aerogel by laser heating graphene aerogel (GA) under high pressure in a diamond anvil cell. The results suggest that the density and microstructure of GA, as well as the heating duration obviously affect the diamond aerogel growth. When heating GA with lower laser power, we also observe a transparent carbon phase in experiment, which transforms into graphite and amorphous carbon upon decompression. These results present new insights into our understanding on the transformation from ultralow density carbon to sp3 carbon under high pressure and high temperature. It is possible to tune the microstructures of diamon...

Carbon nitride (C-N) materials have been attracting great interest because of their extraordinary performance in photocatalysis and energy conversion. However, developing an effective strategy for achieving band-gap engineering of C-N materials to satisfy practical applications remains highly desired. Here we report an efficient way to tune the band gap and control the nitrogen stoichiometry in carbon nitride compounds by using high pressure and high temperature (HPHT) treatment. It is found that treating a g-C3N4 precursor at relatively low temperature (630oC and below) under pressure can efficiently narrow the band gap even down to the red light region (~600 nm), increase the crystallinity, and significantly improve the charge carrier separation efficiency (by two orders of magnitude), almost without changing their stoichiometry. When increasing the treatment temperature under pressure, nitrogen-doped graphene/graphite materials with weak ferromagnetism were obtained. We thus obtained C-N materials with tunable band gaps, ranging from semiconducting to metallic states. XPS measurements show that pyridinic nitrogen is preferentially eliminated under such HPHT conditions while graphitic nitrogen is preserved in the C-N network. Our results thus provide an efficient strategy for tuning the structure and physical properties of C-N materials for applications. Supplementary information available at the journal website.

The efficacy of traditional chemotherapy often suffers from rapid clearance and off-target toxicity. Drug delivery systems and controlled release are applied to improve the therapeutic efficiencies of small-molecule drugs. In this work, two novel oxidative/reductive (Ox/Re) -sensitive and one non-sensitive Paclitaxel (PTX) prodrugs were synthesized with a maleimide group, which rapidly conjugates with albumin in vivo. Albumin serves as a good vehicle to deliver more prodrug to tumors due to the enhanced permeation and retention (EPR) effect. PTX was then released from the prodrugs in glutathione(GSH)/ reactive oxygen species(ROS)-rich tumor microenvironments. This bioresponsive prodrug strategy demonstrates potent chemotherapeutic efficiency in vivo and may be utilized in clinical cancer therapy.

Li3V2(PO4)3 (LVP) has been highlighted as a promising cathode material for lithium ion batteries, but it suffers from poor rate capability and rapid capacity decay due to sluggish electrode kinetics and vigorous electrode/electrolyte side reactions at high voltage. In this study, an inexpensive aqueous lithium poly-acrylic acid (LiPAA) binder was developed to deftly solve the shortcomings of the LVP material by tailoring the functional groups in the binder. The good adhesion and cohesion properties of the LiPAA binder ensured a close linkage between the active LVP particles, conductive additives and current collector, which formed a stable and conductive network in the electrode. In addition, the reversible H+/Li+ exchange in LiPAA effectively assisted the transport of Li+ ions at the electrode interface, which allowed the establishment of a Li+ conductive pathway without considerable degradation of the electrolyte. Due to these advantages, the LVP electrode containing the LiPAA binder exhibited significantly improved electrochemical performance compared to the electrode that employed the traditional polyvinylidene fluoride binder. The new electrode configuration showed a large specific capacity of 107 mA h g−1 at 70C rate and a high capacity retention of 91% was obtained after 1400 cycles at 10C rate, showcasing the great potential of this aqueous binder in lithium ion batteries.

Nanostructured carbon is a low-cost, economic, and elementally abundant candidate for manufacturing high-conductivity counter electrodes of organic photoelectric devices. Herein, we prepare onion-like carbon nanosphere:silver (OLCNS:Ag) composite electrodes for efficient, inverted-architecture polymer solar cells (PSCs) via a simple, solution-processed approach. The optical electric field distribution from the OLCNS:Ag nanocomposite layer opens up the possibility of additional light harvesting of the entire visible spectrum resulting from synergies between both components. The large effective specific surface area and high conductivity of OLCNS allow significant charge transfer and collection, resulting in a remarkably enhanced power conversion efficiency (PCE) of 9.81% in PTB7:PC71BM PSCs and 6.95% in PCDTBT:PC71BM PSCs, compared with control devices with PCEs of 7.76 and 5.31%, respectively. These consequences indicate that OLCNS:Ag composite electrodes constitute a valid and versatile method for realiz...

To overcome the intrinsic chemical-reduction-activity of highly p-doped PEDOT:PSS and improve the open-circuit voltage (Voc) of planar inverted perovskite solar cells, a kind of oxidized carbon nanorods (OCNRs) is developed by a ball-milling/chemical-oxidation method and incorporated into PEDOT:PSS hole transport layer (HTL). The incorporation of OCNRs can increase the work function of the PEDOT:PSS layer, which avoids the energy-level mismatch between the PEDOT:PSS HTL and the HOMO level of the CH3NH3PbI3 perovskite layer, leading to a relatively high Voc of 1.01 V (vs. 0.92 V for the PEDOT:PSS device). Moreover, the introduction of OCNRs into the PEDOT:PSS HTL increases the grain size and uniformity of the perovskite layer, accompanied by the improved charge transport ability. As a result, the fill factor of perovskite solar cells is increased from 75.4% to 81.7%, and the best power conversion efficiency of 19.02% is achieved.

The fabrication of silicon (Si) anode materials derived from high silica-containing plants enables effective utilization of subsidiary agricultural products. However, the electrochemical performances of synthesized Si materials still require improvement and thus need further structural design and morphology modifications, which inevitably increase preparation time and economic cost. Here, the conversion of corn leaves into Si anode materials is reported via a simple aluminothermic reduction reaction without other modifications. The obtained Si material inherits the structural characteristics of the natural corn leaf template and has many inherent advantages, such as high porosity, amorphous/crystalline mixture structure, and high-valence SiOx residuals, which significantly enhance the material's structural stability and electrode adhesive strength, resulting in superior electrochemical performances. Rate capability tests show that the material delivers a high capacity of 1200 mA h g-1 at 8 A g-1 current density. After 300 cycles at 0.5 A g-1 , the material maintains a high specific capacity of 2100 mA h g-1 , with nearly 100% capacity retention during long-term cycling. This study provides an economical route for the industrial production of Si anode materials for Lithium-Ion batteries.

In order to build the fusion models, the high performance liquid chromatographic (HPLC) fingerprints of scutellariae radix (SR), rhei radix et rhizoma (RRR), coptidis rhizoma (CR) and their synthesizing fingerprints were developed in this study. After exploring the consistency between the fingerprints of compound synthesizing fingerprints (CSF) and the sample, the quality of traditional Chinese medicine preparation was predicted intelligently using CSF. HPLC coupled with diode array detector was used to obtain chromatograms of SR, RRR, CR and Yi Qing Tablet (YQT) samples at 268 nm. Meanwhile, the quality of CSF and the 15 batches of YQT samples was evaluated by systematically quantified fingerprint method (SQFM) qualitatively and quantitatively. The chromatograms showed that CSF covered the main fingerprints' information of each herb and the 55 common peaks of CSF covered the main information of the 50 common peaks in YQT sample. The evaluation results showed that among the 15 batches of YQT samples, only YQT-S01 was grade 5 and the others were all above grade 3. Most of the CSFs were grade 2 or grade 1 except CSF-2 which was grade 6. The fingerprints of Chinese herba preparation could be replaced by CSF to achieve a novel pattern for predicting the quality of TCM preparation intelligently by studying the relationship between the standard fingerprints and the CSF, and simultaneously developing first-class evaluation software.

Onion-like carbon nanospheres (OCNSs) with an average diameter of 43 nm were produced on a large scale via a combustion method and examined as an anode material for lithium ion batteries. The OCNSs exhibit a remarkable electrochemical cycling behavior and a capacity much higher than that of graphite. The capacity increases significantly with increasing charge-discharge cycles and reaches a value of 178% of the initial value (from 586 mA h g-1to 1045 mA h g-1) after 200 cycles. Further investigation provides unambiguous experimental evidence that such a remarkable capacity increase is related to the stable onion-like structure of the OCNSs and to the existence of large numbers of disordered/short graphitic fragments, which gradually provide more active sites for Li ion storage. The unique electrochemical performance of OCNSs provides a new way to design a high-performance anode material for rechargeable batteries.

As a new category of solids, crystalline materials constructed with amorphous building blocks expand the structure categorization of solids, for which designing such new structures and understanding the corresponding formation mechanisms are fundamentally important. Unlike previous reports, new amorphous carbon clusters constructed ordered carbon phases are found here by compressing C8H8/C60 cocrystals, in which the highly energetic cubane (C8H8) exhibits unusual roles as to the structure formation and transformations under pressure. The significant role of C8H8 is to stabilize the boundary interactions of the highly compressed or collapsed C60 clusters which preserves their long‐range ordered arrangement up to 45 GPa. With increasing time at high pressure, the gradual random bonding between C8H8 and carbon clusters, due to “energy release” of highly compressed cubane, leads to the loss of the ability of C8H8 to stabilize the carbon cluster arrangement. Thus a transition from short‐range disorder to long‐range disorder (amorphization) occurs in the formed material. The spontaneous bonding reconstruction most likely results in a 3D network in the material, which can create ring cracks on diamond anvils.

Carbon nano-onions (CNOs) with an average diameter of 43 nm have been studied under pressure. The interlayer d-spacings of the CNOs are expanded by about 3% compared to those of the larger CNOs with average diameter of 150 nm studied earlier. High pressure study on the G-band of the small CNOs indicates that a bonding change was initiated at 23.4 GPa, which is higher than that of the larger CNOs. The small CNOs were destroyed into amorphous fragments at above 48 GPa with a large applied deviatoric stress, showing a lower high pressure stability compared with the larger CNOs. These features are qualitatively similar to the size effects observed in the compression behavior of some nanocrystalline materials, showing that a reduced cluster size gives similar physical effects in the two classes of materials. The present results for CNOs can be rationalized by the interlayer expansion and the highly turbostratic layer structure of the studied material. The fact that CNOs with different diameters behave differently upon compression is important when selecting materials for applications.