Helicid (4-formylphenyl-O-β-D-allopyranoside), an active component found in seeds from the Chinese herb Helicia nilagirica, has been reported to exert sedative, analgesic, hypnotic and antidepressant ...effects. The present study was designed to evaluate the antidepressant, learning and cognitive improvement effects of helicid in a chronic unpredictable mild stress (CUMS) model of depression in rats and to explore cAMP/protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway. Sprague-Dawley rats were randomly assigned to six groups (n = 10): control; CUMS; CUMS + fluoxetine (5 mg/kg) and CUMS + helicid at 8, 16 and 32 mg/kg. All rats were subjected to 12 weeks of CUMS protocols and drug administration during the last 6 weeks of CUMS. Our results showed that helicid, at a dose of 32 mg/kg, significantly reversed decreases in body weight and sucrose consumption, increased the distance and number of crossings in the open-field test (OFT), reduced immobility times in the forced swimming test (FST) and improved spatial memory in the Morris water maze (MWM); all of these effects had been induced by CUMS paradigm. Immunohistochemistry showed that administration of helicid could promoted the proliferation of neurons in the hippocampal CA1 and dentate gyrus (DG) regions. CUMS rats treated with helicid had dramatically decreased protein levels of serotonin transporters (SERTs). In addition, CUMS resulted in a significant reduction in the expression of cAMP, PKA C-α and p-CREB, each of which were partially attenuated by helicid administration. These results indicated that helicid could improve depressive behaviors, learning and cognitive deficits and increase hippocampal neurogenesis, which may be mediated by the regulation of SERTs, activation of the cAMP/PKA/CREB signaling pathway and upregulation of p-CREB levels in hippocampal.
Solid state potassium (K) metal batteries are intriguing in grid‐scale energy storage, benefiting from the low cost, safety, and high energy density. However, their practical applications are impeded ...by poor K/solid electrolyte (SE) interfacial contact and limited capacity caused by the low K self‐diffusion coefficient, dendrite growth, and intrinsically low melting point/soft features of metallic K. Herein, a fused‐modeling strategy using potassiophilic carbon allotropes molted with K is demonstrated that can enhance the electrochemical performance/stability of the system via promoting K diffusion kinetics (2.37 × 10−8 cm2 s−1), creating a low interfacial resistance (≈1.3 Ω cm2), suppressing dendrite growth, and maintaining mechanical/thermal stability at 200 °C. A homogeneous/stable K stripping/plating is consequently implemented with a high current density of 2.8 mA cm−2 (at 25 °C) and a record‐high areal capacity of 11.86 mAh cm−2 (at 0.2 mA cm−2). The enhanced K diffusion kinetics contribute to sustaining intimate interfacial contact, stabilizing the stripping/plating at high current densities. Full cells coupling ultrathin K–C composite anodes (≈50 µm) with Prussian blue cathodes and β/β″‐Al2O3 SEs deliver a high energy density of 389 Wh kg−1 with a retention of 94.4% after 150 cycles and fantastic performances at −20 to 120 °C.
An ultrathin K–10% reduced graphene oxide anode is constructed, delivering promoted K diffusion kinetics and mechanical/thermal stability at 200 °C, which creates an interfacial resistance (≈1.3 Ω cm2) with a current density of 2.8 mA cm−2 at 25 °C and an areal capacity of 11.86 mAh cm−2, enabling solid state potassium metal batteries operating at −20 to 120 °C.
Abstract
One of the best ways to control COVID-19 is vaccination. Among the various SARS-CoV-2 vaccines, inactivated virus vaccines have been widely applied in China and many other countries. To ...understand the underlying protective mechanism of these vaccines, it is necessary to systematically analyze the humoral responses that are triggered. By utilizing a SARS-CoV-2 microarray with 21 proteins and 197 peptides that fully cover the spike protein, antibody response profiles of 59 serum samples collected from 32 volunteers immunized with the inactivated virus vaccine BBIBP-CorV were generated. For this set of samples, the microarray results correlated with the neutralization titers of the authentic virus, and two peptides (S1-5 and S2-22) were identified as potential biomarkers for assessing the effectiveness of vaccination. Moreover, by comparing immunized volunteers to convalescent and hospitalized COVID-19 patients, the N protein, NSP7, and S2-78 were identified as potential biomarkers for differentiating COVID-19 patients from individuals vaccinated with the inactivated SARS-CoV-2 vaccine. The comprehensive profile of humoral responses against the inactivated SARS-CoV-2 vaccine will facilitate a deeper understanding of the vaccine and provide potential biomarkers for inactivated virus vaccine-related applications.
High-performance pervaporation membranes have potential in industrial separation applications, but overcoming the permeability-selectivity trade-off is a challenge. We report a strategy to create ...highly flexible metal-organic framework nanosheet (MOF-NS) membranes with a faveolate structure on polymer substrates for alcohol-water separation. The controlled growth followed by a surface-coating method effectively produced flexible and defect-free superhydrophobic MOF-NS membranes. The reversible deformation of the flexible MOF-NS and the vertical interlamellar pathways were captured with electron microscopy. Molecular simulations confirmed the structure and revealed transport mechanism. The ultrafast transport channels in MOF-NS exhibited an ultrahigh flux and a separation factor of 8.9 in the pervaporation of 5 weight % ethanol-water at 40°C, which can be used for biofuel recovery. MOF-NS and polydimethylsiloxane synergistically contribute to the separation performance.
Honeycomb channels enhance separations
Pervaporation membranes use a combination of permeation and evaporation for energy-efficient separations of volatile compounds from solutions. Xu
et al
. designed a strategy to fabricate defect-free superhydrophobic metal-organic framework (MOF) nanosheet membranes. Instead of dispersing the MOFs into a polydimethylsiloxane (PDMS) matrix, the authors grew a continuous and uniform layer of embedded MOF seeds on polymeric substrates that were then sealed with PDMS. This procedure results in a honeycomb-like structure with high flexibility and fast molecular transport channels, thus enhancing the separation of alcohols from water. —MSL
Flexible metal-organic framework honeycombed nanosheet membranes are applied for alcohol-water separations.
Rational utilization of the rich light‐bio‐matter interplay taking place in single‐cell analysis represents a new technological direction in the field. The light‐fueled operation is expected to ...achieve advanced photoelectrochemical (PEC) single‐cell analysis with unknown possibilities. Here, a PEC nanoreactor capable of single‐cell sampling and near zero‐background Faradaic detection of intracellular microRNA (miR) is devised by the construction of a small reaction chamber accommodating the target‐triggered hybridization chain reaction for binding the metallointercalator of Ru(bpy)2(dppz)2+ as the signal reporter. Light stimulation of the dsDNA/metallointercalator adduct will induce the generation of photocurrents, underpinning a zero‐biased and near zero‐background PEC method toward Faradaic detection of non‐electrogenic miR at the single‐cell level. Using this nanotool, lower miR concentration in the near‐nucleus region than that in the main cytosol was revealed.
A photoelectrochemical nanoreactor was devised for single‐cell sampling and near zero‐background faradic detection of intracellular microRNA. This platform provided a new perspective for exploring light‐biomatter interplay toward single‐cell studies.
To avoid large open surgery using scaffold transplants, small‐sized cell carriers are employed to repair complexly shaped tissue defects. However, most cell carriers show poor cell adherences and ...viability. Therefore, polyhydroxyalkanoate (PHA), a natural biopolymer, is used to prepare highly open porous microspheres (OPMs) of 300–360 µm in diameter, combining the advantages of microspheres and scaffolds to serve as injectable carriers harboring proliferating stem cells. In addition to the convenient injection to a defected tissue, and in contrast to poor performances of OPMs made of polylactides (PLA OPMs) and traditional less porous hollow microspheres (PHA HMs), PHA OPMs present suitable surface pores of 10–60 µm and interconnected passages with an average size of 8.8 µm, leading to a high in vitro cell adhesion of 93.4%, continuous proliferation for 10 d and improved differentiation of human bone marrow mesenchymal stem cells (hMSCs). PHA OPMs also support stronger osteoblast‐regeneration compared with traditional PHA HMs, PLA OPMs, commercial hyaluronic acid hydrogels, and carrier‐free hMSCs in an ectopic bone‐formation mouse model. PHA OPMs protect cells against stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues. They function like a micro‐Noah's Ark to safely transport cells to a defect tissue.
Combining the advantages of microspheres and scaffolds, highly open porous microspheres (OPMs) made of polyhydroxyalkanoate (PHA) are developed as injectable carriers harboring growing stem cells. The PHA OPMs protect the stem cells from stresses during injection, allowing more living cells to proliferate and migrate to damaged tissues, functioning like a micro‐Noah's Ark to safely transport cells to a designated tissue location for regeneration.
The examination of circulating nucleic acids (CNAs) is an emerging noninvasive diagnostic technique. However, it is unclear if serum long noncoding RNAs (lncRNAs) represent a novel marker to detect ...gastric cancer (GC). In this study, we measured 39 candidate cancer‐associated lncRNAs by reverse transcription and quantitative polymerase chain reaction (RT‐qPCR) in sera from 110 patients with GC, 106 age‐ and sex‐matched healthy subjects and 15 patients with gastric peptic ulcer, markers were validated and assessed by RT‐qPCR. The correlation of the expression levels of the candidate serum lncRNAs with clinical parameters of GC patients was performed. A three‐lncRNA signature, including CUDR, LSINCT‐5 and PTENP1, was identified that may be potential diagnostic marker for GC. The areas under the receiver operating characteristic (ROC) curve for this serum three‐lncRNA signature were 0.920 and 0.829 for the two sets of serum samples. Moreover, a risk model for the serum three‐lncRNA signature demonstrated that healthy samples can be distinguished from early GC samples. Three‐lncRNA signature in serum was identified as diagnostic marker for GC. This work may facilitate the detection of GC and serve as the basis for further studies of the clinical value of serum lncRNAs in maintaining surveillance and forecasting prognosis.
What's new?
Certain long noncoding RNAs (lncRNAs) may be involved in oncogenesis or tumor suppression, raising questions about their potential service as cancer biomarkers. The authors of the present study systematically assessed the diagnostic value of serum‐detectable lncRNAs for gastric cancer (GC) patients. Reverse transcription, quantitative PCR resulted in the identification of a GC‐associated three‐lncRNA signature centering on CUDR, LSINCT‐5 and PTENP1. The three‐lncRNA signature successfully distinguished between early‐stage GC patients and healthy subjects. The findings warrant further investigation of the clinical utility of serum lncRNAs in the detection of early‐stage GC.
Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, ...randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.
Objective:
Stroke is a leading cause of mortality and disability. Nicotinamide phosphoribosyltransferase (Nampt) is the rate‐limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD)+ ...biosynthesis and contributes to cell fate decisions. However, the role of Nampt in brain and stroke remains to be investigated.
Methods:
We used lentivirus‐mediated Nampt overexpression and knockdown to manipulate Nampt expression and explore the effects of Nampt in neuronal survival on ischemic stress both in vivo and in vitro. We also used adenosine monophosphate (AMP)‐activated kinase‐α2 (AMPKα2) and silent mating type information regulation 2 homolog 1 (SIRT1) knockout mice to investigate the underlying mechanisms of Nampt neuroprotection.
Results:
Nampt inhibition by a highly‐specific Nampt inhibitor, FK866, aggravated brain infarction in experimentally cerebral ischemia rats, whereas Nampt overexpression in local brain and Nampt enzymatic product nicotinamide mononucleotide (NMN) reduced ischemia‐induced cerebral injuries. Nampt overexpression and knockdown regulated neuron survival via the AMPK pathway. Neuroprotection of Nampt was abolished in AMPKα2−/− neurons. In neurons, Nampt positively modulated NAD+ levels and thereby controlled SIRT1 activity. SIRT1 coprecipitated with serine/threonine kinase 11 (LKB1), an upstream kinase of AMPK, and promoted LKB1 deacetylation in neurons. Nampt‐induced LKB1 deacetylation and AMPK activation disappeared in SIRT1−/− neurons. In contrast, Ca2+/calmodulin‐dependent protein kinase kinase‐β (CaMKK‐β), another upstream kinase of AMPK, was not involved in the neuroprotection of Nampt. More important, Nampt overexpression‐induced neuroprotection was abolished in SIRT1+/− and AMPKα2−/− mice.
Interpretation:
Our findings reveal that Nampt protects against ischemic stroke through rescuing neurons from death via the SIRT1‐dependent AMPK pathway and indicate that Nampt is a new therapeutic target for stroke. Ann Neurol 2011.
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