Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, ...deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in
C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.
Great efforts have been made to convert renewable biomass into transportation fuels. Herein, we report the novel properties of NbOx‐based catalysts in the hydrodeoxygenation of furan‐derived adducts ...to liquid alkanes. Excellent activity and stability were observed with almost no decrease in octane yield (>90 % throughout) in a 256 h time‐on‐stream test. Experimental and theoretical studies showed that NbOx species play the key role in CO bond cleavage. As a multifunctional catalyst, Pd/NbOPO4 plays three roles in the conversion of aldol adducts into alkanes: 1) The noble metal (in this case Pd) is the active center for hydrogenation; 2) NbOx species help to cleave the CO bond, especially of the tetrahydrofuran ring; and 3) a niobium‐based solid acid catalyzes the dehydration, thus enabling the quantitative conversion of furan‐derived adducts into alkanes under mild conditions.
Fueling fuel production: Biomass conversion into liquid fuel depends on the design of multifunctional catalysts. In the direct conversion of furan‐based aldol adducts into liquid alkanes over a Pd/NbOPO4 catalyst under mild conditions (see scheme), NbOx species played an important role in CO bond cleavage.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The development of chemically recyclable polymers presents the most appealing solution to address the plastics’ end‐of‐use problem. Despite the recent advancements, it is highly desirable to develop ...chemically recyclable polymers from commercially available monomers to avoid the costly and time‐consuming commercialization. In this contribution, we achieve the controlled ring‐opening polymerization (ROP) of bio‐sourced δ‐caprolactone (δCL) using strong base/urea binary catalysts. The obtained PδCL is capable of chemical recycling to δCL in an almost quantitative yield by thermolysis. Sequential ROP of δCL and l‐lactide (l‐LA) affords well‐defined PLLA‐b‐PδCL‐b‐PLLA triblock copolymers, which behave as thermoplastic elastomers with excellent elastic recovery, tensile strength and ultimate elongation. The upcycling of PLLA‐b‐PδCL‐b‐PLLA to recover ethyl lactate and δCL with high yields is achieved by refluxing with ethanol and then distillation under reduced pressure.
This work presents the controlled ring‐opening polymerization (ROP) of δ‐caprolactone (δCL) to produce high‐molecular‐weight PδCL that was capable to recycle back to pristine monomer with an almost quantitative yield (≈99 %). Well‐defined PLLA‐b‐PδCL‐b‐PLLA triblock copolymers with excellent mechanical properties can be easily prepared by sequential ROP of δCL and l‐lactide.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional and translational regulation, and is involved in cancer. However, the regulatory ...circuitry between lncRNAs and microRNAs in tumorigenesis remains elusive. Here we demonstrate that a nuclear lncRNA LINC00336 is upregulated in lung cancer and functions as an oncogene by acting as a competing endogenous RNA (ceRNAs). LINC00336 bound RNA-binding protein ELAVL1 (ELAV-like RNA-binding protein 1) using nucleotides 1901-2107 of LINC00336 and the RRM interaction domain and key amino acids (aa) of ELAVL1 (aa 101-213), inhibiting ferroptosis. Moreover, ELAVL1 increased LINC00336 expression by stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) increased ELAVL1 expression through the p53 signaling pathway, further supporting the hypothesis that LSH promotes LINC00336 expression. Interestingly, LINC00336 served as an endogenous sponge of microRNA 6852 (MIR6852) to regulate the expression of cystathionine-β-synthase (CBS), a surrogate marker of ferroptosis. Finally, we found that MIR6852 inhibited cell growth by promoting ferroptosis. These data show that the network of lncRNA and ceRNA has an important role in tumorigenesis and ferroptosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ultrathin 2D porous carbon-based materials offer numerous fascinating electrical, catalytic, and mechanical properties, which hold great promise in various applications. However, it remains a ...formidable challenge to fabricate these materials with tunable morphology and composition by a simple synthesis strategy. Here, a facile one-step self-flowering method without purification and harsh conditions is reported for large-scale fabrication of high-quality ultrathin (≈1.5 nm) N-doped porous carbon nanosheets (NPC) and their composites. It is demonstrated that the layered tannic/oxamide (TA/oxamide) hybrid is spontaneously blown, exfoliated, bloomed, in situ pore-formed, and aromatized during pyrolysis to form flower-like aggregated NPC. This universal one-step self-flowering system is compatible with various precursors to construct multiscale NPC-based composites (Ru@NPC, ZnO@NPC, MoS
@NPC, Co@NPC, rGO@NPC, etc.). Notably, the programmable architecture enables NPC-based materials with excellent multifunctional performances, such as microwave absorption and hydrogen evolution. This work provides a facile, universal, scalable, and eco-friendly avenue to fabricate functional ultrathin porous carbon-based materials with programmability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Acyl‑CoA synthetase long‑chain family member 4 (ACSL4) is a member of the long chain family of acyl‑CoA synthetase proteins, which have recently been shown to serve an important role in ferroptosis. ...Previous studies have suggested that ferroptosis is involved in the occurrence of glioma; however, the role of ACSL4 in glioma remains unknown. In the present study, a reduction of ferroptosis in human glioma tissues and glioma cells was observed. Subsequently, it was demonstrated that the expression of ACSL4 was also downregulated in human glioma tissues and cells. A ferroptosis inhibitor and inducer were used to investigate the effects of ferroptosis on viability. The results showed that promoting ferroptosis inhibited the proliferation of glioma cells, and that the use of inducers had the reverse effect. Therefore, it was hypothesized that the reduction in ACSL4 expression may have been involved in ferroptosis and proliferation in glioma. Overexpression of ACSL4 decreased expression of glutathione peroxidase 4 and increased the levels of ferroptotic markers, including 5‑hydroxyeicosatetraenoic (HETE), 12‑HETE and 15‑HETE. Additionally, ACSL4 overexpression resulted in an increase in lactate dehydrogenase release and a reduction in cell viability. The opposite results were observed when ACSL4 was silenced. These findings suggest that ACSL4 regulates ferroptosis and proliferation of glioma cells. To further investigate the mechanism underlying ACSL4‑mediated regulation of proliferation in glioma cells, cells were treated with small interfering (si)‑ACSL4 and sorafenib, a ferroptosis inducer. sorafenib attenuated the ability of siRNA‑mediated silencing of ACSL4, thus improving cell viability. These results demonstrate that ACSL4 protects glioma cells and exerts anti‑proliferative effects by activating a ferroptosis pathway and highlight the pivotal role of ferroptosis regulation by ACSL4 in its protective effects on glioma. Therefore, ACSL4 may serve as a novel therapeutic target for the treatment of glioma.
Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in ...cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear.
Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5'tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5'tiRNA-His-GTG. The regulation of 5'tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments.
Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5'tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5'tiRNA-His-GTG in CRC and found that targeting 5'tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5'tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5'tiRNA-His-GTG, which renders 5'tiRNA-His-GTG to "turn off" hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes.
In summary, the findings revealed a specific 5'tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A 2D zinc(
ii
) metal-organic framework (Zn-MOF-
1
) formulated as Zn
2
(L)
2
(TPA)·2H
2
O, (L = 4-(tetrazol-5-yl)phenyl-4,2′:6′,4′′-terpyridine, TPA = terephthalic acid) was successfully obtained ...under solvothermal conditions. Zn-MOF-
1
shows a new 2D double-layered honeycomb structure containing Zn
2+
ions, ligand L and TPA, with uncoordinated nitrogen atoms (from pyridine rings and tetrazol rings) of L and uncoordinated carboxylate oxygen atoms of TPA, which easily form hydrogen bonds with analytes. Fluorescence analysis reveals that Zn-MOF-
1
generates strong blue luminescence, which can be assigned to ligand-centered emission. More importantly, it is the first reported recyclable multi-responsive Zn-MOF fluorescence sensor for pesticide 2,6-dichloro-4-nitroaniline, Fe(
iii
) and Cr(
vi
) (CrO
4
2−
/Cr
2
O
7
2−
ions) detection with high sensitivity, selectivity and low detection limit in methanol or water
via
fluorescence quenching. Furthermore, selective sensing by Zn-MOF-
1
of 2,6-dichloro-4-nitroaniline, Fe
3+
ions, and CrO
4
2−
or Cr
2
O
7
2−
ions can mainly be attributed to the absorption by the analytes of the excitation and/or emission light of Zn-MOF-
1
and the electronic interactions between Zn-MOF-
1
and the analytes.
A stable Zn-MOF acts as a multi-responsive luminescent sensor for efficient and recyclable detection of organochlorine pesticide 2,6-dichloro-4-nitroaniline, Fe(
iii
) and Cr(
vi
) with high selectivity and sensitivity.
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