Two two‐dimensional supramolecular copper(II) and cobalt(III) complexes, Cu(L1)2 (1; HL1 = 2‐hydroxy‐3‐methoxybenzaldehyde oxime) and Co(L2)22⋅2CH3COOCH2CH3 (2; HL2 = ...1‐(2‐{(E)‐3‐methoxy‐2‐hydroxybenzylideneamino}phenyl)ethanone oxime), have been synthesized via complexation of Cu(II) nitrate trihydrate and Co(II) acetate tetrahydrate with HL. A plausible reaction mechanism for the formation of HL1 is proposed. HL was synthesized and characterized using infrared, 1H NMR and 13C NMR spectra, as well as elemental analysis. Complexes 1 and 2 were investigated using single‐crystal X‐ray diffraction and have a 2:1 ligand‐to‐metal ratio. Different geometric features of both complexes are observed. In their crystal structures, 1 and 2 form infinite two‐dimensional structures and 2 forms a three‐dimensional supramolecular framework. Electron paramagnetic resonance spectra of 1 and 2 were also investigated. Moreover, thermal and electrochemical properties and antimicrobial activity of 2 were also studied. In addition, the calculated HOMO and LUMO energies show the character of complex 1.
Two‐dimensional supramolecular copper(II) and cobalt(III) complexes were synthesized from a quinazoline‐type ligand. EPR spectra of the complexes were investigated. Thermal and electrochemical properties and antimicrobial activity of the Co(III) complex were also studied. The calculated HOMO and LUMO energies show the character of the Cu(II) complex.
Visible-light-responsive ternary metal tungstate (MWO
4
) photocatalysts are being increasingly investigated for energy conversion and environmental purification applications owing to their striking ...features, including low cost, eco-friendliness, and high stability under acidic and oxidative conditions. However, rapid recombination of photoinduced electron–hole pairs and a narrow light response range to the solar spectrum lead to low photocatalytic activity of MWO
4
-based materials, thus significantly hampering their wide usage in practice. To enable their widespread practical usage, significant efforts have been devoted, by developing new concepts and innovative strategies. In this review, we aim to provide an integrated overview of the fundamentals and recent progress of MWO
4
-based photocatalysts. Furthermore, different strategies, including morphological control, surface modification, heteroatom doping, and heterojunction fabrication, which are employed to promote the photocatalytic activities of MWO
4
-based materials, are systematically summarized and discussed. Finally, existing challenges and a future perspective are also provided to shed light on the development of highly efficient MWO
4
-based photocatalysts.
Parkinson's disease (PD) is a prevalent neurodegenerative disorder with pathological features including death of dopaminergic neurons in the substantia nigra and intraneuronal accumulations of Lewy ...bodies. As the main component of Lewy bodies, α-synuclein is implicated in PD pathogenesis by aggregation into insoluble filaments. However, the detailed mechanisms underlying α-synuclein induced neurotoxicity in PD are still elusive. MicroRNAs are ~20nt small RNA molecules that fine-tune gene expression at posttranscriptional level. A plethora of miRNAs have been found to be dysregulated in the brain and blood cells of PD patients. Nevertheless, the detailed mechanisms and their in vivo functions in PD still need further investigation. By using Drosophila PD model expressing α-synuclein A30P, we examined brain miRNA expression with high-throughput small RNA sequencing technology. We found that five miRNAs (dme-miR-133-3p, dme-miR-137-3p, dme-miR-13b-3p, dme-miR-932-5p, dme-miR-1008-5p) were upregulated in PD flies. Among them, miR-13b, miR-133, miR-137 are brain enriched and highly conserved from Drosophila to humans. KEGG pathway analysis using DIANA miR-Path demonstrated that neuroactive-ligand receptor interaction pathway was most likely affected by these miRNAs. Interestingly, miR-137 was predicted to regulate most of the identified targets in this pathway, including dopamine receptor (DopR, D2R), γ-aminobutyric acid (GABA) receptor (GABA-B-R1, GABA-B-R3) and N-methyl-D-aspartate (NMDA) receptor (Nmdar2). The validation experiments showed that the expression of miR-137 and its targets was negatively correlated in PD flies. Further experiments using luciferase reporter assay confirmed that miR-137 could act on specific sites in 3' UTR region of D2R, Nmdar2 and GABA-B-R3, which downregulated significantly in PD flies. Collectively, our findings indicate that α-synuclein could induce the dysregulation of miRNAs, which target neuroactive ligand-receptor interaction pathway in vivo. We believe it will help us further understand the contribution of miRNAs to α-synuclein neurotoxicity and provide new insights into the pathogenesis driving PD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As an indigenous breed, the Tibetan chicken is found in highland regions and shows physiological adaptations to high altitude; however, the genetic changes that determine these adaptations remain ...elusive. We assumed that the microevolution of the Tibetan chicken occurred from lowland to highland regions with a continuous elevation range. In this study, we analyzed the genome of 188 chickens from lowland areas to the high‐altitude regions of the Tibetan plateau with four altitudinal levels. Phylogenetic analysis revealed that Tibetan chickens are significantly different from other altitude chicken populations. Reconstruction of the demographic history showed that the migration and admixture events of the Tibetan chicken occurred at different times. The genome of the Tibetan chicken was also used to analyze positive selection pressure that is associated with high‐altitude adaptation, revealing the well‐known candidate gene that participates in oxygen binding (HBAD), as well as other novel potential genes (e.g., HRG and ANK2) that are related to blood coagulation and cardiovascular efficiency. Our study provides novel insights regarding the evolutionary history and microevolution mechanisms of the high‐altitude adaptation in the Tibetan chicken.
Resistance to proteasome inhibitors (PIs) is a major obstacle to the successful treatment of multiple myeloma (MM). Many mechanisms have been proposed for PI resistance; however, our mechanistic ...understanding of how PI resistance is inevitably acquired and reversed remains incomplete.
MM patients after bortezomib relapse, MM cell lines and mouse models were used to generate matched resistant and reversed cells. RNA sequencing and bioinformatics analyses were employed to assess dysregulated epigenetic regulators. In vitro and in vivo procedures were used to characterise PI-tolerant cells and therapeutic efficacy.
Upon PI treatment, MM cells enter a slow-cycling and reversible drug-tolerant state. This reversible phenotype is associated with epigenetic plasticity, which involves tolerance rather than persistence in patients with relapsed MM. Combination treatment with histone deacetylase inhibitors and high-dosage intermittent therapy, as opposed to sustained PI monotherapy, can be more effective in treating MM by preventing the emergence of PI-tolerant cells. The therapeutic basis is the reversal of dysregulated epigenetic regulators in MM patients.
We propose an alternative non-mutational PI resistance mechanism that explains why PI relapse is inevitable and why patients regain sensitivity after a 'drug holiday'. Our study also suggests strategies for epigenetic elimination of drug-tolerant cells.
Schistosomiasis is one of the world's major public health problems in terms of morbidity and mortality, causing granulomatous inflammation and cumulative fibrosis. This study explored in vivo and ...vitro effects of miR‐29b‐3p in granulomatous liver fibrosis by targeting COL1A1 and COL3A1 in Schistosoma japonicum infection. Thirty male Balb/c mice were assigned to normal control and model (percutaneous infection of cercariae of S. japonicum) groups. NIH‐3T3 mouse embryonic fibroblasts were designated into blank, NC, miR‐29b‐3p mimic, TGF‐β1, TGF‐β1 + NC, and TGF‐β1 + miR‐29b‐3p mimic groups. HE and Masson staining were employed to observe the pathological changes and collagenous fibrosis. The expression of α‐SMA, COL1A1, COL3A1, TIMP‐1 was determined by immunohistochemistry. The RT‐qPCR, Western blotting and immunofluorescence staining were conducted to determine expression of miR‐29b‐3p, COL1A1, and COL3A1. CCK‐8 assay and flow cytometry were performed to evaluate viability and apoptosis. The relative expression of miR‐29b‐3p decreased in the model group. The model group showed marked fibrosis in liver tissues. The expression of α‐SMA, COL1A1, COL3A1, TIMP‐1 was higher in the model group than that in the normal control group. Dual luciferase reporter gene assay revealed that miR‐29b‐3p directly targeted COL1A1 and COL3A1. Compared with the blank, NC, TGF‐β1 and TGF‐β1 + NC groups, the miR‐29b‐3p mimic group exhibited up‐regulated expression of miR‐29b‐3p and MMP‐9 but down‐regulated expression of TIMP‐1, HSP47, α‐SMA, COL1A1, and COL3A1; while lower cell viability but higher apoptosis rate showed. It indicated that miR‐29b‐3p prevents S. japonicum‐induced liver fibrosis by inhibiting COL1A1 and COL3A1.
It indicated that miR‐29b‐3p prevents Schistosoma japonicum‐induced liver fibrosis by inhibiting COL1A1 and COL3A1.
This paper focuses on revealing the thermal decomposition behaviors of a self‐intumescent flame retardant (IFR) epoxy (EP) resin (EP/15%APP‐Cu2O) employing 12 wt% ammonium polyphosphate (APP) as a ...halogen‐free flame retardant and 3 wt% copper (I) oxide (Cu2O) as char forming rate regulator. Initially, the thermal stability of EP/15%APP‐Cu2O was analyzed and compared to virgin EP resin and flame retardant EP (EP/15%APP) containing 15 wt% APP as flame retardant by thermogravimetric analysis test at different heating rates under nitrogen atmosphere. It was shown that the incorporation of APP altered the decomposition pathway of EP and decreased the onset decomposition temperature. Luckily, compared to EP/15%APP, the onset decomposition temperature of EP/15%APP‐Cu2O was just slightly reduced from 300.4 to 292.8°C. Then, the thermal degradation kinetics of EP, EP/15%APP and EP/15%APP‐Cu2O were further evaluated by Kissinger and Flynn‐Wall‐Ozawa methods. It was worth noted that the addition of APP or APP‐Cu2O enhanced the thermal degradation activation energies of EP, which contributed to the protective effect of the char formation. Particularly, the incorporation of 3 wt% Cu2O significantly decreased the thermal degradation activation energies at the early decomposition stage of EP. This may be the main contribution for intumescent char formation, which resulted in higher fire safety of EP/15%APP‐Cu2O compared to EP/15%APP. These information can potentially help to develop alternative IFR systems.
Background： Accumulating evidence indicates that attention deficit hyperactivity disorder （ADHD） is associated with core deficits in executive function （EF） which predicts poorer academic and ...occupational functioning. This makes early intervention targeting EF impairments important to prevent long-term negative outcomes. Cognitive training is a potential ADHD treatment target. The present study aimed to explore the efficacy, feasibility, and acceptability of a cognitive training program （targeting child＇s multiple EF components and involving parent support in daily life）, as a nonpharmacological intervention for children with ADHD. Methods： Forty-four school-age children with ADHD and their parents participated in 12 sessions of EF training （last for 12 weeks） and 88 health controls （HC） were also recruited. Training effects were explored using both neuropsychological tests （Stroop color-word test, Rey-Osterrieth complex figure test, trail making test, tower of Hanoi, and false-belief task） and reports of daily life （ADHD rating scale-IV, Conners＇ parent rating scale, and behavior rating inventory of executive function BRIEF） by analysis of paired sample t-test and Wilcoxon signed-rank test. The differences on EF performances between children with ADHD after training and HC were explored using multivariate analysis. Results： The results （before vs. after EF training） showed that after intervention, the children with ADHD presented better performances of EF both in neuropsychological tests （word interference of Stroop： 36.1 ± 14.6 vs. 27.1 ± 11.1, t = 4.731, P 〈 0.001 ; shift time of TMT： 194.9 ± 115.4 vs. 124.8 ± 72.4, Z = -4.639, P 〈 0.001 ; false-belief task： χ^2 = 6.932, P = 0.008） and reports of daily life （global executive composite of BRIEF： 148.9 ± 17.5 vs. 127.8 ± 17.5, t =6.433, P 〈 0.001）. The performances on EF tasks for children with ADHD after EF training could match with the level of HC children. The ADHD symptoms （ADHD rating scale total score： 32.4 ± 8.9 vs. 22.9 ± 8.2, t = 6.331, P 〈 0.001） and behavioral problems of the children as reported by parents also reduced significantly after the intervention. Participants reported that the EF training program was feasible to administer and acceptable. Conclusions： The EF training program was feasible and acceptable to children with ADH D and parents. Although replication with a larger sample and an active control group are needed, EF training program with multiple EF focus and parent involving in real-life activities could be a potentially promising intervention associated with significant EF （near transfer） and ADHD symptoms improvement （far transfer）.
Abstract
Cardiac fibrosis is a common feature of chronic heart failure. Iroquois homeobox (IRX) family of transcription factors plays important roles in heart development; however, the role of IRX2 ...in cardiac fibrosis has not been clarified. Here we report that IRX2 expression is significantly upregulated in the fibrotic hearts. Increased IRX2 expression is mainly derived from cardiac fibroblast (CF) during the angiotensin II (Ang II)-induced fibrotic response. Using two CF-specific
Irx2
-knockout mouse models, we show that deletion of
Irx2
in CFs protect against pathological fibrotic remodelling and improve cardiac function in male mice. In contrast,
Irx2
gain of function in CFs exaggerate fibrotic remodelling. Mechanistically, we find that IRX2 directly binds to the promoter of the early growth response factor 1 (EGR1) and subsequently initiates the transcription of several fibrosis-related genes. Our study provides evidence that IRX2 regulates the EGR1 pathway upon Ang II stimulation and drives cardiac fibrosis.
Multidrug-resistant bacterial infections mediated by metallo-β-lactamases (MβLs) have grown into an emergent health threat, and development of novel antimicrobials is an ideal strategy to combat the ...infections. Herein, a novel vancomycin derivative
was constructed by conjugation of triazolylthioacetamide and vancomycin molecules, characterized by reverse-phase high performance liquid chromatography (HPLC) and confirmed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The biological assays revealed that
effectively inhibited
and methicillin-resistant
(MRSA), gradually increased the antimicrobial effect of β-lactam antibiotics (cefazolin, meropenem and penicillin G) and exhibited a dose-dependent synergistic antibacterial effect against eight resistant strains tested, which was confirmed by the time-kill curves determination. Most importantly,
increased the antimicrobial effect of meropenem against the clinical isolates EC08 and EC10 and
producing ImiS and CcrA, resulting in a 4- and 8-fold reduction in MIC values, respectively, at a dose up to 32 μg/mL. This work offers a promising scaffold for the development of MβLs inhibitors, specifically antimicrobials for clinically drug-resistant isolates.
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