Abstract
Nonnoble metal catalysts are low-cost alternatives to Pt for the oxygen reduction reactions (ORRs), which have been studied for various applications in electrocatalytic systems. Among them, ...transition metal complexes, characterized by a redox-active single-metal-atom with biomimetic ligands, such as pyrolyzed cobalt–nitrogen–carbon (Co–N
x
/C), have attracted considerable attention. Therefore, we reported the ORR mechanism of pyrolyzed Vitamin B12 using operando X-ray absorption spectroscopy coupled with electrochemical impedance spectroscopy, which enables operando monitoring of the oxygen binding site on the metal center. Our results revealed the preferential adsorption of oxygen at the Co
2+
center, with end-on coordination forming a Co
2+
-oxo species. Furthermore, the charge transfer mechanism between the catalyst and reactant enables further Co–O species formation. These experimental findings, corroborated with first-principle calculations, provide insight into metal active-site geometry and structural evolution during ORR, which could be used for developing material design strategies for high-performance electrocatalysts for fuel cell applications.
Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the ...underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e.g., Ara-C, DNR, 6-MP) induced the expression of niche-protecting cytokines (GDF15, CCL3 and CCL4) in both ALL cell lines and primary cells in vitro. The ATM and NF-κB pathways were activated after chemotherapy treatment, and the pharmacological or genetic inhibition of these pathways significantly reversed the cytokine upregulation. Besides, chemotherapy-induced NF-κB activation was dependent on ATM-TRAF6 signaling, and NF-κB transcription factor p65 directly regulated the cytokines expression. Furthermore, we found that both pharmacological and genetic perturbation of ATM and p65 significantly decreased the residual ALL cells after Ara-C treatment in ALL xenograft mouse models. Together, these results demonstrated that ATM-dependent NF-κB activation mediated the cytokines induction by chemotherapy and ALL resistance to chemotherapeutics. Inhibition of ATM-dependent NF-κB pathway can sensitize ALL to chemotherapeutics, providing a new strategy to eradicate residual chemo-resistant ALL cells.
Parkinson disease (PD)-associated alterations in the gut microbiome have been observed in clinical and animal studies. However, it remains unclear whether this association reflects a causal effect in ...humans.
We performed two-sample bidirectional Mendelian randomization using summary statistics from the international consortium MiBioGen (N = 18,340), the Framingham Heart Study (N = 2076), and the International Parkinson's Disease Genomics Consortium for PD (33,674 cases and 449,056 controls) and PD age at onset (17,996 cases).
Twelve microbiota features presented suggestive associations with PD risk or age at onset. Genetically increased Bifidobacterium levels correlated with decreased PD risk (odds ratio = 0.77, 95% confidence interval CI = 0.60-0.99, p = 0.040). Conversely, high levels of five short-chain fatty acid (SCFA)-producing bacteria (LachnospiraceaeUCG010, RuminococcaceaeUCG002, Clostridium sensustricto1, Eubacterium hallii group, and Bacillales) correlated with increased PD risk, and three SCFA-producing bacteria (Roseburia, RuminococcaceaeUCG002, and Erysipelatoclostridium) correlated with an earlier age at PD onset. Gut production of serotonin was associated with an earlier age at PD onset (beta = -0.64, 95% CI = -1.15 to -0.13, p = 0.013). In the reverse direction, genetic predisposition to PD was related to altered gut microbiota composition.
These results support a bidirectional relationship between gut microbiome dysbiosis and PD, and highlight the role of elevated endogenous SCFAs and serotonin in PD pathogenesis. Future clinical studies and experimental evidence are needed to explain the observed associations and to suggest new therapeutic approaches, such as dietary probiotic supplementation.
Hybrid manganese halide has attracted much attention in the field of environment friendly ferroelectric and photo‐responsive multifunctional materials. Here, the highly efficient photoluminescent ...inorganic framework MnBr42− is utilized to conceive and synthesize a series of hybrid manganese bromide compounds RQ2MnBr4 by introducing precisely designed quasi‐spherical cations RQ+ (R = H, Me, Et, FEt, Q = quinuclidine). The accurate and effective modification of cations not only achieves the satisfactory ferroelectricity, but also enhances the photoluminescence quantum yield from 38.7% to 83.65%. Moreover, FEtQ2MnBr4 shows a highly efficient X‐ray scintillator performance, including a large range of linear response to X‐ray dose rate from 0.3 to 414.2 μGyair s−1, a high light yield of 34 438 photons per MeV, and a low detection limit of 258 nGyair s−1. This work provides an efficient strategy for the preparation of hybrid manganese halide ferroelectrics with highly efficient light‐emission and X‐ray detection.
By coupling the design for high Curie temperature ferroelectrics and the modulation of photo‐responsive properties through precise modification of spherical cations, an A2MnBr4‐type hybrid ferroelectric with a high photoluminescence quantum yield of 83.65% is obtained. Moreover, the eco‐friendly crystal is promising for high performance X‐ray detectors compared with commercially available scintillators such as bismuth germanium oxide and lutetium yttrium oxyorthosilicate.
Mitophagy, which is a conserved cellular process for selectively removing damaged or unwanted mitochondria, is critical for mitochondrial quality control and the maintenance of normal cellular ...physiology. However, the precise mechanisms underlying mitophagy remain largely unknown. Prior studies on mitophagy focused on the events in the mitochondrial outer membrane. PHB2 (prohibitin 2), which is a highly conserved membrane scaffold protein, was recently identified as a novel inner membrane mitophagy receptor that mediates mitophagy. Here, we report a new signaling pathway for PHB2-mediated mitophagy. Upon mitochondrial membrane depolarization or misfolded protein aggregation, PHB2 depletion destabilizes PINK1 in the mitochondria, which blocks the mitochondrial recruitment of PRKN/Parkin, ubiquitin and OPTN (optineurin), leading to an inhibition of mitophagy. In addition, PHB2 overexpression directly induces PRKN recruitment to the mitochondria. Moreover, PHB2-mediated mitophagy is dependent on the mitochondrial inner membrane protease PARL, which interacts with PHB2 and is activated upon PHB2 depletion. Furthermore, PGAM5, which is processed by PARL, participates in PHB2-mediated PINK1 stabilization. Finally, a ligand of PHB proteins that we synthesized, called FL3, was found to strongly inhibit PHB2-mediated mitophagy and to effectively block cancer cell growth and energy production at nanomolar concentrations. Thus, our findings reveal that the PHB2-PARL-PGAM5-PINK1 axis is a novel pathway of PHB2-mediated mitophagy and that targeting PHB2 with the chemical compound FL3 is a promising strategy for cancer therapy.
AIFM1: apoptosis inducing factor mitochondria associated 1; ATP5F1A/ATP5A1: ATP synthase F1 subunit alpha; BAF: bafilomycin A
1
; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CCCP: chemical reagent carbonyl cyanide m-chlorophenyl hydrazine; FL3: flavaglines compound 3; HSPD1/HSP60: heat shock protein family D (Hsp60) member 1; LC3B/MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MEF: mouse embryo fibroblasts; MPP: mitochondrial-processing peptidase; MT-CO2/COX2: mitochondrially encoded cytochrome c oxidase II; MTS: mitochondrial targeting sequence; OA: oligomycin and antimycin A; OPTN: optineurin; OTC: ornithine carbamoyltransferase; PARL: presenilin associated rhomboid like; PBS: phosphate-buffered saline; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; PHB: prohibitin; PHB2: prohibitin 2; PINK1: PTEN induced kinase 1; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; Roc-A: rocaglamide A; TOMM20: translocase of outer mitochondrial membrane 20; TUBB: tubulin beta class I.
The phosphor‐converted light‐emitting diode (PC‐LED) has become an indispensable solid‐state lighting and display technologies in the modern society. Nevertheless, the use of scarce rare‐earth ...elements and the thermal quenching (TQ) behavior are still two most crucial issues yet to be solved. Here, this work successfully demonstrates a highly efficient and thermally stable green emissive MnI2(XanPO) crystals showing a notable photoluminescence quantum yield (PLQY) of 94% and a super TQ resistance from 4 to 623 K. This unprecedented superior thermal stability is attributed to the low electron–phonon coupling and the unique rigid crystal structure of MnI2(XanPO) over the whole temperature range based on the temperature‐dependent photoluminescence (PL) and single crystal X‐ray diffraction (SCXRD) analyses. Considering these appealing properties, green PC‐LEDs with a power efficacy of 102.5 lm W−1, an external quantum efficiency (EQE) of 22.7% and a peak luminance up to 7750 000 cd m−2 are fabricated by integrating MnI2(XanPO) with commercial blue LEDs. Moreover, the applicability of MnI2(XanPO) in both micro‐LEDs and organic light‐emitting diodes (OLEDs) is also demonstrated. In a nutshell, this study uncovers a candidate of highly luminescent and TQ resistant manganese halide suitable for a variety of emission applications.
A highly efficient and thermally stable manganese halide crystal, MnI2(XanPO) is demonstrated. The low electron–phono coupling along with rigid crystal structure contributes to excellent photoluminescent quantum yield of 94% with unprecedented near zero thermal quenching from 4 to 623 K. The crystals find their applications in light emitting diodes and micro light emitting diodes with excellent external quantum efficiency (EQE) up to 22.7% and power efficacy as high as 102.5 lm W−1.
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