Two novel polyoxometalate (POM)-based metal–organic frameworks (MOFs), TBA3ε-PMoV 8MoVI 4O36(OH)4Zn4BTB4/3·xGuest (NENU-500, BTB = benzene tribenzoate, TBA+ = tetrabutylammonium ion) and TBA3ε-PMoV ...8MoVI 4O37(OH)3Zn4BPT (NENU-501, BPT = 1,1′-biphenyl-3,4′,5-tricarboxylate), were isolated. In these compounds, the POM fragments serving as nodes were directly connected with organic ligands giving rise to three-dimensional (3D) open frameworks. The two anionic frameworks were balanced by TBA+ ions residing inside the open channels. They exhibit not only good stability in air but also tolerance to acidic and basic media. Furthermore, they were employed as electrocatalysts for the hydrogen evolution reaction (HER) owing to the combination of the redox activity of a POM unit and the porosity of a MOF. Meanwhile, the HER activities of ε(trim) 4/3 , NENU-5, and HKUST-1 were also studied for comparison. Remarkably, as a 3D hydrogen-evolving cathode operating in acidic electrolytes, NENU-500 exhibits the highest activity among all MOF materials. It shows an onset overpotential of 180 mV and a Tafel slope of 96 mV·dec–1, and the catalytic current density can approach 10 mA·cm–2 at an overpotential of 237 mV. Moreover, NENU-500 and NENU-501 maintain their electrocatalytic activities after 2000 cycles.
Nucleus accumbens (NAc) is involved in behaviors that depend on heightened wakefulness, but its impact on arousal remains unclear. Here, we demonstrate that NAc dopamine D1 receptor (D1R)-expressing ...neurons are essential for behavioral arousal. Using in vivo fiber photometry in mice, we find arousal-dependent increases in population activity of NAc D1R neurons. Optogenetic activation of NAc D1R neurons induces immediate transitions from non-rapid eye movement sleep to wakefulness, and chemogenetic stimulation prolongs arousal, with decreased food intake. Patch-clamp, tracing, immunohistochemistry, and electron microscopy reveal that NAc D1R neurons project to the midbrain and lateral hypothalamus, and might disinhibit midbrain dopamine neurons and lateral hypothalamus orexin neurons. Photoactivation of terminals in the midbrain and lateral hypothalamus is sufficient to induce wakefulness. Silencing of NAc D1R neurons suppresses arousal, with increased nest-building behaviors. Collectively, our data indicate that NAc D1R neuron circuits are essential for the induction and maintenance of wakefulness.
Summary
Post‐translational modification of proteins mediated by SIZ1, a small ubiquitin‐like modifier (SUMO) E3 ligase, regulates multiple biological processes in plants. However, its role in the ...regulation of lateral root formation remains unclear. Here, we demonstrate that the apple SUMO E3 ligase MdSIZ1 promotes lateral root formation.
Using a yeast‐two‐hybrid (Y2H) system, the auxin response factor MdARF8 was screened out as a protein–protein interaction partner of the SUMO‐conjugating E2 enzyme MdSCE1, indicating that MdARF8 may be a substrate for MdSIZ1. The interaction between MdARF8 and MdSCE1 was confirmed by pull‐down, Y2H and Co‐immunoprecipitation assays.
MdSIZ1 enhanced the conjugating enzyme activity of MdSCE1 to form a MdSCE1–MdSIZ1–MdARF8 complex, thereby facilitating SUMO modification. We identified two arginine substitution mutations at K342 and K380 in MdARF8 that blocked MdSIZ1‐mediated SUMOylation, indicating that K342 and K380 are the principal SUMOylation sites of the MdARF8 protein. Moreover, MdARF8 promoted lateral root formation in transgenic apple plants, and the phenotype of reduced lateral roots in the Arabidopsis siz1‐2 mutant was restored in siz1‐2/MdARF8 complementary plants.
Our findings reveal an important role for sumoylation in the regulation of lateral root formation in plants.
Extracellular vesicles (EVs) are nanovesicles released by various cell types. EVs are known for cell-to-cell communications and have potent biological activities. Despite great progress in recent ...years for studies exploring the potentials of EVs for early disease detection, therapeutic application and drug delivery, determination of the favorable storage conditions of EVs has been challenging. The understanding of the impact of storage conditions on EVs before and after isolation is still limited. Storage may change the size, number, contents, functions, and behaviors of EVs. Here, we summarized current studies about the stability of EVs in different conditions, focusing on temperatures, durations, and freezing and thawing cycles. -80 °C seems to remain the most favorable condition for storage of biofluids and isolated EVs, while isolated EVs may be stored at 4 °C shortly. Lyophilization is promising for storage of EV products. Challenges remain in the understanding of storage-mediated change in EVs and in the development of advanced preservation techniques of EVs.
An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a ...role in its pathogenesis. Among these, the specific effects of trimethylamine N‐oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO‐induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ‐free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO‐related POCD and improving the quality of life for elderly patients.
Background Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive ...statin‐based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high‐dose and moderate‐dose statins for patients who had experienced mild ischemic stroke during the acute period. Methods and Results This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high‐intensity and moderate‐intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow‐up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high‐intensity statin and moderate‐intensity statin groups (3 months: adjusted hazard ratio HR, 1.12 95% CI, 0.85–1.49; P =0.424; 12 months: adjusted HR, 1.08 95% CI, 0.86–1.34; P =0.519). High‐intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 95% CI, 1.00–3.25; P =0.048; 12 months: adjusted HR, 1.86 95% CI, 1.10–3.16; P =0.021). The results from the propensity score‐matched analyses were consistent with those from the Cox proportional hazards analysis. Conclusions Compared with moderate‐intensity statin therapy, high‐dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. Registration URL: www.chictr.org.cn/ . Unique Identifier: ChiCTR1900025214.
The MYB transcription factor family is one of the largest transcriptional factor families in plants and plays a multifaceted role in plant growth and development. However, MYB transcription factors ...involved in pathogen resistance in apple remain poorly understood.
We identified a new MYB family member from apple, and named it MdMYB30. MdMYB30 was localized to the nucleus, and was highly expressed in young apple leaves. Transcription of MdMYB30 was induced by abiotic stressors, such as polyethylene glycol and abscisic acid. Scanning electron microscopy and gas chromatograph-mass spectrometry analyses demonstrated that ectopically expressing MdMYB30 in Arabidopsis changed the wax content, the number of wax crystals, and the transcription of wax-related genes. MdMYB30 bound to the MdKCS1 promoter to activate its expression and regulate wax biosynthesis. MdMYB30 also contributed to plant surface properties and increased resistance to the bacterial strain Pst DC3000. Furthermore, a virus-based transformation in apple fruits and transgenic apple calli demonstrated that MdMYB30 increased resistance to Botryosphaeria dothidea. Our findings suggest that MdMYB30 plays a vital role in the accumulation of cuticular wax and enhances disease resistance in apple.
MdMYB30 bound to the MdKCS1 gene promoter to activate its transcription and regulate cuticular wax content and composition, which influenced the surface properties and expression of pathogenesis-related genes to resistance against pathogens. MdMYB30 appears to be a crucial element in the formation of the plant cuticle and confers apple with a tolerance to pathogens.
Natural selection endows animals with the abilities to store lipid when food is abundant and to synthesize lipid when it is limited. However, the relevant adaptive strategy of lipid metabolism has ...not been clearly elucidated in fish. This study examined the systemic metabolic strategies of Nile tilapia to maintain lipid homeostasis when fed with low‐ or high‐fat diets. Three diets with different lipid contents (1%, 7%, and 13%) were formulated and fed to tilapias for 10 weeks. At the end of the feeding trial, the growth rate, hepatic somatic index, and the triglyceride (TG) contents of serum, liver, muscle, and adipose tissue were comparable among three groups, whereas the total body lipid contents and the mass of adipose tissue increased with the increased dietary lipid levels. Overall quantitative PCR, western blotting and transcriptomic assays indicated that the liver was the primary responding organ to low‐fat (LF) diet feeding, and the elevated glycolysis and accelerated biosynthesis of fatty acids (FA) in the liver is likely to be the main strategies of tilapia toward LF intake. In contrast, excess ingested lipid was preferentially stored in adipose tissue through increasing the capability of FA uptake and TG synthesis. Increasing numbers, but not enlarging size, of adipocytes may be the main strategy of Nile tilapia responding to continuous high‐fat (HF) diet feeding. This is the first study illuminating the systemic adaptation of lipid metabolism responding to LF or HF diet in fish, and our results shed new light on fish physiology.
We illustrated the adaptive strategy of lipid metabolism responding to low or high fat diets in Nile tilapia. Briefly, the elevated glycolysis and accelerated biosynthesis of fatty acids in the liver were the main strategies of tilapia towards low fat intake. Increasing numbers, but not enlarging size, of adipocytes was the main strategy of Nile tilapia responding to continuous high‐fat diet feeding.
Novel luminescence‐functionalized metal–organic frameworks (MOFs) with superior electrogenerated chemiluminescence (ECL) properties were synthesized based on zinc ions as the central ions and ...tris(4,4′‐dicarboxylicacid‐2,2′‐bipyridyl)ruthenium(II) dichloride (Ru(dcbpy)32+) as the ligands. For potential applications, the synthesized MOFs were used to fabricate a “signal‐on” ECL immunosensor for the detection of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). As expected, enhanced ECL signals were obtained through a simple fabrication strategy because luminescence‐functionalized MOFs not only effectively increased the loading of Ru(dcbpy)32+, but also served as a loading platform in the ECL immunosensor. Furthermore, the proposed ECL immunosensor had a wide linear range from 5 pg mL−1 to 25 ng mL−1 and a relatively low detection limit of 1.67 pg mL−1 (signal/noise=3). The results indicated that luminescence‐functionalized MOFs provided a novel amplification strategy in the construction of ECL immunosensors and might have great prospects for application in bioanalysis.
Trap the light fantastic: Luminescence‐functionalized metal–organic frameworks (MOFs) were synthesized by using Zn2+ as the central ion and a Ru complex as the ligand. This provided a method to use a metallic complex instead of a small organic molecule as a ligand to prepare MOFs. Moreover, MOFs were applied to the construction of a sensitive electrogenerated chemiluminescence biosensor (see figure).
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