For many regenerative electrochemical energy‐conversion systems, hybrid electrocatalysts comprising transition metal (TM) oxides and heteroatom‐doped (e.g., nitrogen‐doped) carbonaceous materials are ...promising bifunctional oxygen reduction reaction/oxygen evolution reaction electrocatalysts, whose enhanced electrocatalytic activities are attributed to the synergistic effect originated from the TM–N–C active sites. However, it is still ambiguous which configuration of nitrogen dopants, either pyridinic or pyrrolic N, when bonded to the TM in oxides, predominately contributes to the synergistic effect. Herein, an innovative strategy based on laser irradiation is described to controllably tune the relative concentrations of pyridinic and pyrrolic nitrogen dopants in the hybrid catalyst, i.e., NiCo2O4 NPs/N‐doped mesoporous graphene. Comparative studies reveal the dominant role of pyridinic‐NCo bonding, instead of pyrrolic‐N bonding, in synergistically promoting reversible oxygen electrocatalysis. Moreover, density functional theory calculations provide deep insights into the corresponding synergistic mechanism. The optimized hybrid, NiCo/NLG‐270, manifests outstanding reversible oxygen electrocatalytic activities, leading to an overpotential different ΔE among the lowest value for highly efficient bifunctional catalysts. In a practical reversible Zn–air battery, NiCo/NLG‐270 exhibits superior charge/discharge performance and long‐term durability compared to the noble metal electrocatalysts.
An innovative strategy based on laser irradiation is developed to selectively regulate relative contents of pyridinic and pyrrolic nitrogen in NiCo2O4/N‐graphene hybrids. Strong chemical bonding forms between nitrogen and cobalt, and pyridinic‐NCo bonds, instead of pyrrolic‐NCo bonds, are identified to predominantly contribute to synergistic catalysis, leading to substantially enhanced oxygen electrocatalytic activities, outperforming a combination of benchmark noble metal catalysts.
Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting the interaction between the serotonin transporter (SERT) ...and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased the SERT-nNOS complex in the DRN in mice. Augmentation of SERT-nNOS interactions in the DRN caused a depression-like phenotype and accounted for the CMS-induced depressive behaviors. Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects. This compound, or analogous reagents, may serve as a new, rapidly acting treatment for MDD.
Recent studies have identified a class of small non‐coding RNA molecules, named microRNA (miRNA), that is dysregulated in malignant brain glioblastoma. Substantial data have indicated that miRNA‐16 ...(miR‐16) plays a significant role in tumors of various origins. This miRNA has been linked to various aspects of carcinogenesis, including cell apoptosis and migration. However, the molecular functions of miR‐16 in gliomagenesis are largely unknown. We have shown that the expression of miR‐16 in human brain glioma tissues was lower than in non‐cancerous brain tissues, and that the expression of miR‐16 decreased with increasing degrees of malignancy. Our data suggest that the expression of miR‐16 and nuclear factor (NF)‐κB1 was negatively correlated with glioma levels. MicroRNA‐16 decreased glioma malignancy by downregulating NF‐κB1 and MMP9, and led to suppressed invasiveness of human glioma cell lines SHG44, U87, and U373. Our results also indicated that upregulation of miR‐16 promoted apoptosis by suppressing BCL2 expression. Finally, the upregulation of miR‐16 in a nude mice model of human glioma resulted in significant suppression of glioma growth and invasiveness. Taken together, our experiments have validated the important role of miR‐16 as a tumor suppressor gene in glioma growth and invasiveness, and revealed a novel mechanism of miR‐16‐mediated regulation in glioma growth and invasiveness through inhibition of BCL2 and the NF‐κB1/MMP‐9 signaling pathway. Therefore, our experiments suggest the possible future use of miR‐16 as a therapeutic target in gliomas.
We first report that miR‐16 and NF‐κB1expression were inversely correlated to glioma levels in the same patient samples. We further identified the miR‐16 as a negative regulator of tumor growth and invasion, both in vitro and in vivo. Mechanistically the tumor‐suppressive role of miR‐16 can be attributed to inhibition of BCL‐2 and NF‐kappaB1/MMP9 signaling pathways.
Bismuth-halide-based inorganic-organic hybrid materials (Bi-IOHMs) are desirable in luminescence-related applications due to their advantages such as low toxicity and chemical stability. Herein, two ...Bi-IOHMs of BpyBiCl
(Phen) (
, Bpy =
-butylpyridinium, Phen = 1,10-phenanthroline) and PP14BiCl
(Phen)·0.25H
O (
, PP14 =
-butyl-
-methylpiperidinium), containing different ionic liquid cations and same anionic units, have been synthesized and characterized. Single-crystal X-ray diffraction reveals that compounds
and
crystallize in the monoclinic space group of
2
/
and
2
, respectively. They both possess zero-dimensional ionic structures and exhibit phosphorescence at room temperature upon excitation of UV light (375 nm for
, 390 nm for
), with microsecond lifetime (24.13 μs for
and 95.37 μs for
). Hirshfeld surface analysis has been utilized to visually exhibit the different packing motifs and intermolecular interactions in
and
. The variation in ionic liquids makes compound
have a more rigid supramolecular structure than
, resulting in a significant enhancement in photoluminescence quantum yield (PLQY), that is, 0.68% for
and 33.24% for
. In addition, the ratio of the emission intensities for compounds
and
shows a correlation with temperature. This work provides new insight into luminescence enhancement and temperature sensing applications involving Bi-IOHMs.
Manganese‐based oxides have exhibited high promise as noncoinage alternatives to Pt/C for catalyzing oxygen reduction reaction (ORR) in basic solution and a mix of Mn3+/4+ valence is believed to be ...vital in achieving optimum ORR performance. Here, it is proposed that, distinct from the most studied perovskites and spinels, Mn‐based mullites with equivalent molar ratio of Mn3+ and Mn4+ provide a unique platform to maximize the role of Mn valence in facile ORR kinetics by introducing modest content of oxygen deficiency, which is also beneficial to enhanced catalytic activity. Accordingly, amorphous mullite SmMn2O5−δ nanoparticles with finely tuned concentration of oxygen vacancies are synthesized via a versatile top‐down approach and the modest oxygen‐defective sample with an Mn3+/Mn4+ ratio of 1.78, i.e., Mn valence of 3.36 gives rise to a superior overall ORR activity among the highest reported for the family of Mn‐based oxides, comparable to that of Pt/C. Altogether, this study opens up great opportunities for mullite‐based catalysts to be a cost‐effective alternative to Pt/C in diverse electrochemical energy storage and conversion systems.
Amorphous mullite SmMn2O5−δ nanoparticles with finely tuned content of oxygen vacancies and Mn valence are synthesized via a simple and versatile top‐down approach. The modest oxygen‐defective sample with appropriate Mn3+/Mn4+ ratio (i.e., 1.78) possesses a superior overall catalytic performance for electrochemical oxygen reduction among the highest reported for the family of Mn‐based oxides and comparable to that of Pt/C.
•Indirubin is a natural compound with a wide range of clinical applications.•A de novo indirubin biosynthetic pathway was constructed.•E. coli was engineered to produce indirubin directly from ...glucose.•Fermentative production of indirubin directly from glucose was demonstrated.
Indirubin is an indole alkaloid that can be used to treat various diseases including granulocytic leukemia, cancer, and Alzheimer’s disease. Microbial production of indirubin has so far been achieved by supplementation of rather expensive substrates such as indole or tryptophan. Here, we report the development of metabolically engineered Escherichia coli strain capable of producing indirubin directly from glucose. First, the Methylophaga aminisulfidivorans flavin-containing monooxygenase (FMO) and E. coli tryptophanase (TnaA) were introduced into E. coli in order to complete the biosynthetic pathway from tryptophan to indirubin. Further engineering was performed through rational strategies including disruption of the regulatory repressor gene trpR and removal of feedback inhibitions on AroG and TrpE. Then, combinatorial approach was employed by systematically screening eight genes involved in the common aromatic amino acid pathway. Moreover, availability of the aromatic precursor substrates, phosphoenolpyruvate and erythrose-4-phosphate, was enhanced by inactivating the pykF (pyruvate kinase I) and pykA (pyruvate kinase II) genes, and by overexpressing the tktA gene (encoding transketolase), respectively. Fed-batch fermentation of the final engineered strain led to production of 0.056 g/L of indirubin directly from glucose. The metabolic engineering and synthetic biology strategies reported here thus allows microbial fermentative production of indirubin from glucose.
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Constructing Fe-Cu bimetal catalysts is an efficient strategy to promote Fe(III)/Fe(II) cycle, whereas there is still a long way to go before fully understanding the role of the Cu in ...the catalysts. Herein, a new Fe-MOF namely BUC-96(Fe) was fabricated from FeSO4·7H2O, 4,4′-bipyridine (bpy) and 2,5-dihydroxyterephthalic acid (H4dhtp) by both hydrothermal reaction and microwave-assisted method. Also, bimetal BUC-96(FeCu-x) were obtained when the CuSO4 was added into the system identical to the synthesis process of BUC-96(Fe). Series BUC-96 MOFs showed good organics elimination performance via Fenton-like process, where 88.1% (k = 0.0672 min−1) of chloroquine phosphate (CQ, 20 mg/L) was decomposed over pristine BUC-96(Fe) within 30 min. Interestingly, nearly 100% CQ was degraded over BUC-96(FeCu-5) as catalyst under the identical conditions within 5 min, whose reaction rate (1.3527 min−1) was 20.1-fold higher than that of BUC-96. Additionally, BUC-96(FeCu-5) exhibited excellent Fenton-like oxidation degradation performance for 10 selected emerging organic pollutants. The reaction mechanism was studied in detail by experiments, and density functional theory (DFT) calculation. The results revealed that the introduced Cu not only accelerated Fe(III)/Fe(II) cycles, hydroxyl radical (·OH) generation, electron transfer, but also lowered H2O2 dissociated energy barrier. This work advanced the bimetal MOFs construction and application in wastewater treatment via Fenton-like process.
Abstract
Background
Oblique lumbar interbody fusion (OLIF) is an important surgical modality for the treatment of degenerative lumbar spine disease. Various supplemental fixations can be co-applied ...with OLIF, increasing OLIF stability and reducing complications. However, it is unclear whether osteoporosis affects the success of supplemental fixations; therefore, this study analyzed the effects of osteoporosis on various supplemental fixations co-applied with OLIF.
Methods
We developed and validated an L3-S1 finite element (FE) model; we assigned different material properties to each component and established models of the osteoporotic and normal bone lumbar spine. We explored the outcomes of OLIF combined with each of five supplemental fixations: standalone OLIF; OLIF with lateral plate fixation (OLIF + LPF); OLIF with translaminar facet joint fixation and unilateral pedicle screw fixation (OLIF + TFJF + UPSF); OLIF with unilateral pedicle screw fixation (OLIF + UPSF); and OLIF with bilateral pedicle screw fixation (OLIF + BPSF). Under the various working conditions, we calculated the ranges of motion (ROMs) of the normal bone and osteoporosis models, the maximum Mises stresses of the fixation instruments (MMSFIs), and the average Mises stresses on cancellous bone (AMSCBs).
Results
Compared with the normal bone OLIF model, no demonstrable change in any segmental ROM was apparent. The MMSFIs increased in all five osteoporotic OLIF models. In the OLIF + TFJF + UPSF model, the MMSFIs increased sharply in forward flexion and extension. The stress changes of the OLIF + UPSF, OLIF + BPSF, and OLIF + TFJF + UPSF models were similar; all stresses trended upward. The AMSCBs decreased in all five osteoporotic OLIF models during flexion, extension, lateral bending, and axial rotation. The average stress change of cancellous bone was most obvious under extension. The AMSCBs of the five OLIF models decreased by 14%, 23.44%, 21.97%, 40.56%, and 22.44% respectively.
Conclusions
For some supplemental fixations, the AMSCBs were all reduced and the MMSFIs were all increased in the osteoporotic model, compared with the OLIF model of normal bone. Therefore, the biomechanical performance of an osteoporotic model may be inferior to the biomechanical performance of a normal model for the same fixation method; in some instances, it may increase the risks of fracture and internal fixation failure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Phateacid esters (PAEs), such as dibutyl phthalate (DBP), have been widely used and human exposure results into serious toxic effects; such as the development of fatty liver disease. In the present ...study, SD rat models for in vivo study (normal and fatty liver model group) and hepatocytes for in vitro study (normal and abnormal lipid metabolism model group) were established to determine the effects of DBP on liver function and discover the possible mechanisms. Meanwhile, the peroxisome proliferator activated receptor (PPARα) blocker, GW6471, with the Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activator, AICAR, were applied in vitro study to clarify the role of PPARα/SREBP-1c/FAS/GPAT/AMPK signal pathway in the process. Results suggested that DBP could activate PPARα signaling pathway and affected the protein expression of SREBP, FAS and GPAT to cause hyperlipidemia and abnormal liver function. DBP also could inhibit the phosphorylation and activation of AMPK to inhibit the decomposition and metabolism of lipids. Interestingly, the effects of DBP could be alleviated by GW6471 and AICAR. Our experimental results provide reliable evidence that DBP exposure could further induce liver lipid metabolism disorder and other hepatic toxicity through PPARα/SREBP-1c/FAS/GPAT/AMPK signal pathway.
•DBP could cause hepatotoxicity in normal body.•Metabolic abnormal bodies are more sensitive to the toxicity of DBP.•Firstly put forward the toxicity mechanism of DBP based on the PPARα/SREBP-1c/FAS/GPAT/AMPK signaling pathway.•The dose of DBP herein was close to normal exposure.
Identification of stably expressed gene(s) as internal reference(s) for different experimental conditions is key to the accurate normalization and quantification of target transcripts. Previously, ...our RNA‐seq study showed that Hprt1, Actb, and 18S rRNA abundances were all significantly altered in porcine immature Sertoli cells (iSCs) during acute heat stress (HS). In the current study, we aimed to identify stable reference gene(s) to study the gene expression dynamics of quick and delayed responses after acute HS treatment of porcine iSCs. A total of six genes previously used in pig testis or Sertoli cells (Hprt1, Top2b, Actb, Rpl32, Gapdh, and 18S rRNA) were chosen to perform RT‐qPCR for the control (before acute HS), HS0.5 (acute HS at 43°C for 0.5 h), and HS0.5‐R36 (36 h recovery following acute HS) groups. The stability of candidate reference genes was examined by the GeNorm, NormFinder, BestKeeper and Comparative ΔCt methods, and RefFinder to obtain the final rank. Rpl32 and Actb were the two most stable internal reference genes as found by all methods, whereas Hprt1 and 18S rRNA were the two most unstable as ranked by RefFinder. Moreover, expression of six target mRNAs (Ccn1, Ccnb1, Eif4g1, Hdac6, Plk2, and Ptma) was normalized using Rpl32, Actb, or the combination of Rpl32 and Actb, respectively. Therefore, our findings that the most suitable internal references are Rpl32 and Actb provide useful information for further functional investigation on genes regulating the acute HS of porcine iSCs.
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