The J bs-5YP peptide can alleviate dementia in senile mice by restoring the transcription of Slc40a1 to secrete the excessive iron from brain.

INTRODUCTION: With age and ATP decrease in the body, the transcription factors hypophosphorylation weakens the transcription of Slc40a1 and hinders the expression of the iron discharger ferroportin. This may lead to iron accumulation in the brain and the catalysis of free radicals that damage cerebral neurons and eventually lead to Alzheimer's disease (AD). OBJECTIVES: To prevent AD caused by brain iron excretion disorders and reveal the mechanism of J bs-5YP peptide restoring ferroportin. METHODS: We prepared J bs-YP peptide and administered it to the senile mice with dementia. Then, the intelligence of the mice was tested using a Morris Water Maze. The ATP content in the body was detected using the ATP hydrophysis and Phosphate precipitation method. The activation of Slc40a1 transcription was assayed with ATAC seq and the ferroportin, as well as the phosphorylation levels of Ets1 in brain were detected by Western Blot. RESULTS: The phosphorylation level of Ets1in brain was enhanced, and subsequently, the transcription of Slc40a1 was activated and ferroportin was increased in the brain, the levels of iron and free radicals were reduced, with the neurons protection, and the dementia was ultimately alleviated in the senile mice. CONCLUSION: J bs-5YP can recover the expression of ferroportin to excrete excessive iron in the brain of senile mice with dementia by enhancing the transcription of Slc40a1 via phosphorylating Ets1, revealing the potential of J bs-5YP as a drug to alleviate senile dementia.

(3,3)-Connected Triazine-Based Covalent Organic Frameworks for Efficient CO2 Separation over N2 and Dye Adsorption.

Covalent organic frameworks (COFs) are a promising class of adsorption and separation materials that can meet the needs of ecological sustainability, such as the removal of carbon dioxide and organic dyes. The two synthesized (3,3)-connected triazine-based COFs demonstrate high specific surface area and good thermal and chemical stability. COFZ1 shows good CO2 adsorption selectivities for different CO2 and N2 volume percentage systems at 273 K and 1 bar, with an ideal adsorbed solution theory (IAST) CO2 selectivity (i.e., separation factor) of 35.09 for the simulated flue gas component and a CO2 adsorption capacity of 24.21 cm3 g-1. In the aqueous dye solutions, both COFs present good adsorption performance for the selected dyes, and the maximum adsorption capacities of COFZ1 for methylene blue (MB) and gentian violet (GV) reach 510 and 564 mg g-1, respectively. Each of the two COFs shows a high anti-interference performance and excellent recyclability. The adsorption capacities of two COFs for RhB (Rhodamine B), MB, and GV hardly vary with pH values and salt concentrations. The adsorption behaviors of the two COFs for dyes follow Langmuir isothermal adsorption and quasi-secondary kinetic adsorption, approaching monolayer adsorption and chemisorption.

Investigation of seawater electrolyte on hydrogen evolution reaction from the perspective of kinetics and energy consumption using an Ni-based electrocatalyst supported on carbon nanotubes.

In this study, a Ni-based composite incorporating Ni4N and La2O3 supported on carbon nanotubes (Ni-La-Ni4N/CNT) was synthesized as an efficiency electrocatalyst towards the hydrogen evolution reaction in different electrolytes with the kinetics and energy consumption investigated in detail. The Ni-La-Ni4N/CNT exhibits overpotentials of 124 mV and 200 mV at the current density of 10 mA cm-2 in 1.0 M KOH and alkaline seawater, respectively. As quantitative comparison, the exchange current density (j°) based on Volmer-Heyrovsky-Tafel mechanism was calculated from various polarization curves, which indicated that the addition of NaCl in alkaline medium or using seawater alone reduced the reactivity of the catalyst. The activity of Ni-La-Ni4N/CNT in alkaline seawater was equal to 91% of that in 1.0 M KOH. Furthermore, dynamic polarization resistance and corresponding current were obtained by the analysis of the equivalent circuit model with the extended Kalman filter algorithm. The analysis of the resistance power at 1 mW also shows that the current between the conditions in KOH and in seawater is 2.76 times. Adding alkaline substances to seawater can narrow it to 1.19 times. These strategies provide novel approaches for inspecting the activity changes of materials in different electrochemical environments.

Data on cloning, expression and biochemical characteristics of a chondroitin sulfate/dermatan sulfate 4-O-endosulfatase.

The data shown in this article are related to the published paper entitled "A novel 4-O-endosulfatase with high potential for the structure-function studies of chondroitin sulfate/dermatan sulfate" in Carbohydrate Polymers. In this article, the phylogenetic analysis, cloning, expression, purification, specificity and biochemical characteristics of the identified chondroitin sulfate/dermatan sulfate 4-O-endosulfatase (endoBI4SF) are described in detail. The recombinant endoBI4SF with a molecular mass of 59.13 kDa can can specifically hydrolyze the 4-O- but not 2-O- and 6-O-sulfate groups in the oligo-/polysaccharides of chondroitin sulfate/dermatan sulfate and show the maximum reaction rate in 50 mM Tris-HCl buffer (pH 7.0) at 50°C, which can be a very useful tool for the structural and functional studies of chondroitin sulfate/dermatan sulfate.

Enzymatic comparison of two homologous enzymes reveals N-terminal domain of chondroitinase ABC I regulates substrate selection and product generation.

Chondroitinase ABC-type I (CSase ABC I), which can digest both chondroitin sulfate (CS) and dermatan sulfate (DS) in an endolytic manner, is an essential tool in structural and functional studies of CS/DS. Although a few CSase ABC I have been identified from bacteria, the substrate-degrading pattern and regulatory mechanisms of them have rarely been investigated. Herein, two CSase ABC I, IM3796 and IM1634, were identified from the intestinal metagenome of CS-fed mice. They show high sequence homology (query coverage: 88.00%, percent identity: 90.10%) except for an extra peptide (Met1-His109) at the N-terminus in IM1634, but their enzymatic properties are very different. IM3796 prefers to degrade 6-O-sulfated GalNAc residue-enriched CS into tetra- and disaccharides. In contrast, IM1634 exhibits nearly a thousand times more activity than IM3796 and can completely digest CS/DS with various sulfation patterns to produce disaccharides, unlike most CSase ABC I. Structure modeling showed that IM3796 did not contain an N-terminal domain composed of two ß-sheets, which is found in IM1634 and other CSase ABC I. Furthermore, deletion of the N-terminal domain (Met1-His109) from IM1634 caused the enzymatic properties of the variant IM1634-T109 to be similar to those of IM3796, and conversely, grafting this domain to IM3796 increased the similarity of the variant IM3796-A109 to IM1634. In conclusion, the comparative study of the new CSase ABC I provides two unique tools for CS/DS-related studies and applications and, more importantly, reveals the critical role of the N-terminal domain in regulating the substrate binding and degradation of these enzymes.

Soluble CD206 levels correlate with disease deterioration and predict prognosis of anti-MDA5 antibody-positive dermatomyositis related interstitial lung disease.

INTRODUCTION: The prognosis of anti-MDA5 antibody-positive dermatomyositis/clinically amyopathic dermatomyositis-associated interstitial lung disease (MDA5-DM/CADM-ILD) is poor. This study was to evaluate the effect of serum soluble CD206 (sCD206), a biomarker of macrophage activation, on predicting the interstitial lung disease (ILD) deterioration and prognosis for MDA5-DM/CADM-ILD. METHODS: Forty-one patients diagnosed with MDA5-DM/CADM-ILD were retrospectively included. The clinical data were analyzed. Serum sCD206 levels were measured in 41 patients and 30 healthy controls. The relation between sCD206 levels and ILD deterioration was assessed. Receiver operating characteristic (ROC) curve was generated to determine the optimal cut-off value of sCD206 for predicting outcome. The association between sCD206 and survival was examined. RESULTS: The median serum sCD206 level in patients was significantly higher than healthy controls (464.1 ng/mL vs. 349.1 ng/mL, P = 0.002). In DM/CADM patients, the sCD206 level was significantly higher in patients with acute/subacute interstitial lung disease (AILD/SILD) than those with chronic interstitial lung disease (CILD) (539.2 ng/mL vs. 309.4 ng/mL, P = 0.005). The AUC of sCD206 was 0.885 for predicting mortality (95% CI 0.779-0.990). Patients were divided into two groups: sCD206 high level group (≥400 ng/mL) and sCD206 low level group (<400 ng/mL). Patients with sCD206 high level had significantly decreased survival rate than those with low level (25% vs. 88%, P < 0.001). The adjusted hazard ratio of sCD206 for mortality was 1.003 (adjusted for age and gender, P < 0.001), with sCD206 high level associated with higher death risk (HR 4.857, P = 0.006). CONCLUSION: Serum sCD206 might be a potential predictor of ILD deterioration and prognosis for Chinese patients with MDA5-DM/CADM-ILD.

A novel 4-O-endosulfatase with high potential for the structure-function studies of chondroitin sulfate/dermatan sulfate.

The sulfation patterns of chondroitin sulfate (CS)/dermatan sulfate (DS), which encode unique biological information, play critical roles in the various biological functions of CS/DS chains. CS/DS sulfatases, which can specifically hydrolyze sulfate groups, could potentially be essential tools for deciphering and changing the biological information encoded by these sulfation patterns. However, endosulfatase with high activity to efficiently hydrolyze the sulfate groups inside CS/DS polysaccharides have rarely been identified, which hinders the practical applications of CS/DS sulfatases. Herein, a novel CS/DS 4-O-endosulfatase (endoBI4SF) with a strong ability to completely remove 4-O-sulfated groups inside various CS/DS polysaccharides was identified and successfully used to investigate the biological roles of 4-O-sulfated CS/DS in vitro and in vivo. This study provides a much-needed tool to tailor the sulfation patterns and explore the related functions of 4-O-sulfated CS/DS chains in vitro and in vivo.

Quantitative chest CT assessment of pulmonary alveolar proteinosis with deep learning: a real-world longitudinal study.

Background: High-resolution computed tomography (HRCT) plays an important role in accessing the severity of pulmonary alveolar proteinosis (PAP). Visual evaluation of changes between two HRCT scans is subjective. This study was conducted to quantitatively evaluate lung burden changes in patients with PAP using HRCT-based automated deep-learning method following 12 months of statin therapy. Methods: In this prospective real-world observational study, patients with PAP who underwent chest HRCT were evaluated from November 28, 2018, to April 12, 2021. Oral statin administration was initiated as therapy for these PAP patients with 12 months of follow-up. HRCT-derived lung ground-glass opacification percentage of the whole lung and 5 lobes and the percentage of different densities of ground glass were automatically quantified with deep-learning software. Longitudinal changes of the HRCT quantitative parameter were also compared. Results: The study enrolled 50 patients with PAP, including 25 mild-moderate PAP cases and 25 severe PAP cases. The percentage of lung ground-glass opacification of the whole lung and 5 lobes and the percentage of different densities of ground glass were significantly different among the 2 different clinical types at baseline (all P values <0.05). Overall, the percentage of whole-lung ground-glass opacification significantly decreased between the baseline HRCT and the HRCT results after 12 months of follow-up (P=0.023; 95% CI: 1.384-18.684). Changes in the total opacification of the whole lung were positively correlated with changes in partial pressure of arterial oxygen (PaO2; r=0.716; P<0.001) and percentage of predicted diffusion capacity for carbon monoxide (DLCO%pred; r=0.664; P<0.001). Conclusions: A quantitative image parameter automatically generated by a deep-learning tool from chest HRCT scans may be used to evaluate the severity of PAP and may help to evaluate and quantify the response to statin therapy.

A mutated glycosaminoglycan-binding domain functions as a novel probe to selectively target heparin-like epitopes on tumor cells.

The high heterogeneity and mutation rate of cancer cells often lead to the failure of targeted therapy, and therefore, new targets for multitarget therapy of tumors are urgently needed. Aberrantly expressed glycosaminoglycans (GAGs) have been shown to be involved in tumorigenesis and are promising new targets. Recently, the GAG-binding domain rVAR2 of the Plasmodium falciparum VAR2CSA protein was identified as a probe targeting cancer-associated chondroitin sulfate A-like epitopes. In this study, we found that rVAR2 could also bind to heparin (Hep) and chondroitin sulfate E. Therefore, we used rVAR2 as a model to establish a method based on random mutagenesis of the GAG-binding protein and phage display to identify and optimize probes targeting tumor GAGs. We identified a new probe, VAR2HP, which selectively recognized Hep by interacting with unique epitopes consisting of a decasaccharide structure that contains at least three HexA2S(1-4)GlcNS6S disaccharides. Moreover, we found that these Hep-like epitopes were overexpressed in various cancer cells. Most importantly, our in vivo experiments showed that VAR2HP had good biocompatibility and preferentially localizes to tumors, which indicates that VAR2HP has great application potential in tumor diagnosis and targeted therapy. In conclusion, this study provides a strategy for the discovery of novel tumor-associated GAG epitopes and their specific probes.

The bs-YHEDA peptide protects the brains of senile mice and thus recovers intelligence by reducing iron and free radicals.

Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood-brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named "bs-YHEDA"). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease.

Clinical Results of Acetabular Fracture via the Pararectus versus Ilioinguinal Approach.

OBJECTIVE: To compare the clinical efficacy of pararectus and ilioinguinal approach in the treatment of acetabular fractures. METHODS: A retrospective analysis of the clinical data of 60 patients with acetabular fractures treated by the pararectus approach or the ilioinguinal approach from January 2016 to January 2019 was performed to record all data by comparing the length of the surgical incision, the time to expose the fracture and the amount of blood loss during the operation. Patients were routinely followed up at 1, 6 and 12 months postoperatively. The function of the hip joint after the operation (Improved Merle d' Aubigne and Postel scores) and the complications postoperation were recorded. RESULTS: There was a significant difference (mean ± SD) in the length of surgical incision [(11.2 ± 1.5) cm vs.(23.8 ± 2.1) cm], and in surgical exposure time [(10.8 ± 1.7) min vs.(19.9 ± 1.9) min] (P < 0.05) between the two approaches; there was no significant difference (mean ± SD) in intraoperative blood loss [(591.8 ± 131.4) mL vs. (614.6 ± 132.7) mL] or in hip function scores at the last follow-up between the two groups (P > 0.05). In the pararectus approach group, there was one patient (3.3%) with postoperative wound fat liquefaction, and the wound completely improved by secretion culture, enhanced dressing and effective antibiotics, one patient (3.3%) developed lateral femoral cutaneous nerve injury; One case (3.3%) of postoperative myositis ossificans occurred in the ilioinguinal approach group, and there were no obvious symptoms. CONCLUSIONS: These data suggest that for patients with acetabular fractures, both the pararectus approach and the ilioinguinal approach can achieve satisfactory surgical results, but the former has relatively simple operation and small incision length, which is in line with the modern concept of the minimally invasive pelvis.

Therapeutic Effect of Acetabular Fractures Using the Pararectus Approach Combined with 3D Printing Technique.

OBJECTIVE: To explore the clinical efficacy of pararectus approach combined with 3D printing technique for the surgical treatment of partial acetabular fractures. METHODS: We retrospectively evaluated 33 (20 males and 13 females) patients with acetabular fractures in the period of June 2017 to December 2018. According to Judet and Letournel classification: 11 cases were of anterior column fracture, 10 cases were of double column fracture, seven fractures were of the anterior column with posterior half transverse, three fractures were of transverse fracture, and two cases were of "T" fracture. For all cases, 3D printing is used to print the acetabular model. Pre-bent reconstruction plates from the model were placed to fixate fractures via the pararectus approach. RESULTS: Thirty-three patients (mean age 48 years; range, 35-63 years), included 20 men and 13 women, were treated successfully with open reduction and internal fixation by the pararectus approach. Surgery duration was 203 min on average (range: 135-245 min), and intra-operative bleeding was 1030 mL on average (range: 450-1400 mL). All patients were followed-up for 12-18 months (average,14 months); two patients (6.0%) developed postoperative ossifying myositis, and there are no obvious symptoms at present; one patient (3.0%) developed postoperative wound infection, and the wound completely improved by secretion culture, enhanced dressing, and effective antibiotics; all the acetabular fractures united after 12 to 16 weeks (average,13 weeks). According to the modified Merle d'Aubigne and Postel scoring system to assess the hip function: excellent in 22 cases (66.7%), good in seven cases (21.2%), and fair in four cases (12.1%). CONCLUSIONS: In the treatment of partial acetabular fractures, the pararectus approach combined with 3D printing technique can achieve effective reduction and fixation, decrease intraoperative hemorrhage, shorten operation time, and the internal fixation position can be properly adjusted during the operation by looking directly at the model.

Clavicle Shaft Fracture After Surgery for Bipolar Dislocation of the Clavicle.

BACKGROUND Bipolar dislocation of the clavicle is a rare disease that is often associated with some high-energy injuries. It refers to concomitant dislocation of the ipsilateral acromioclavicular joint and sternoclavicular joint. Because of its rarity, the diagnosis of bipolar dislocation of the clavicle is often difficult. Additionally, few reports are available on its treatment. Here, we describe a case of bipolar dislocation of the clavicle in which a secondary operation was needed because of a missed diagnosis. However, after surgery for bipolar dislocation of the clavicle, the clavicle shaft had a fracture that required reoperation. CASE REPORT A 58-year-old woman presented at our hospital with left shoulder pain. The patient had a history of sternoclavicular joint (SCJ) reconstruction and had a plate for left SCJ dislocation inserted 1 month ago at another hospital. Plain radiography images revealed that the left acromioclavicular joint (ACJ) was dislocated. We performed ACJ reconstruction with a hook plate. However, 4 weeks after the operation, the patient fell and visited to our hospital with left shoulder pain again. Plain radiography images revealed a left clavicle shaft fracture. We removed the plates from both ends of the clavicle and performed an open reduction and internal fixation using the long clavicular plate for clavicle shaft fracture. CONCLUSIONS Bipolar dislocation of the clavicle is frequently missed at the first diagnostic imaging examination; therefore, careful attention is required when SCJ or ACJ dislocation is observed. This case suggested that clavicle shaft fracture can occur after reconstruction of the SCJ and ACJ for bipolar dislocation of the clavicle. We conducted a literature review of this related case, highlighting the treatment of such cases.

Fabrication of ZIF-67@three-dimensional reduced graphene oxide aerogel nanocomposites and their electrochemical applications for rutin detection.

Three-dimensional reduced graphene oxide aerogel (3D rGA) was synthesized by hydrothermal method and cobalt imidazolate framework-67 (ZIF-67) was further grown in situ on the 3D rGA matrix directly. The resultant ZIF-67@3D rGA nanocomposite was checked by different techniques including scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and thermo-gravimetric analysis (TGA). The presence of 3D rGA acted as the backbone for the loading of ZIF-67, and the resultant ZIF-67@3D rGA nanocomposite exhibited an interconnected porous structure with large surface area and high conductivity due to synergistic effects, which was applied to the electrode modification and used for rutin detection. The developed method showed excellent performance with a wider linear range (0.05-200.0 µmol/L) and lower detection limit (0.028 ± 0.0016 µmol/L, S/N=3). Various samples including the compounded rutin tablets and onions were analyzed by this modified electrode with satisfactory results.

Associations of Serological Biomarkers of sICAM-1, IL-1ß, MIF, and su-PAR with 3-Month Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis.

OBJECTIVE: To investigate prognostic values of serum biomarkers of soluble intercellular adhesion molecule 1 (sICAM-1), macrophage migration inhibitor factor (MIF), interleukin 1ß (IL-1ß), and soluble urokinase plasminogen activator receptor (su-PAR) in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). METHODS: From August 2017 to November 2019, 122 consecutive IPF patients treated in our center were classified as stable IPF and AE-IPF based on the newly published international guidelines. Serum levels of four biomarkers at admission were measured by the enzyme-linked immunosorbent assay (ELISA). The primary endpoint was 3-month mortality. The log-rank test and logistic regression analysis were used to evaluate the effects of these biomarkers for survival in patients with AE-IPF. Cox proportional hazards analysis was performed to evaluate the prognostic values of serological biomarkers and clinical data. RESULTS: Eighty-one patients were diagnosed with stable IPF, and 41 AE-IPF patients were enrolled in the study. Serum levels of sICAM-1 (p < 0.001), IL-1ß (p < 0.001), MIF (p < 0.001), and su-PAR (p < 0.001) in patients with IPF were significantly increased compared to those in healthy controls. All the four biomarkers were elevated in patients with AE-IPF compared to those with stable IPF. The 3-month mortality in AE-IPF was 56.1% (23/41). Increased levels of MIF (p = 0.01) and IL-1ß (>5 pg/mL, p = 0.033) were independent risk factors for 3-month mortality in patients with AE-IPF. CONCLUSIONS: We showed the higher serum levels of IL-1ß, and MIF had prognostic values for 3-month mortality in AE-IPF. This study provided a clue to promote our understanding in the pathogenesis of the disease.

Association of serum macrophage-mannose receptor CD206 with mortality in idiopathic pulmonary fibrosis.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is attracting considerable attention due to disease acceleration and substantial mortality. Macrophages are known to regulate the fibrotic process in idiopathic pulmonary fibrosis. OBJECTIVE: We investigated if two new macrophage-specific serum biomarkers, soluble mannose receptor (MR, sCD206) and soluble CD163 (sCD163), increased in serum obtained from patients with AE-IPF compared to stable IPF (S-IPF). METHODS: A total of 36 IPF patients with AE status, 54 IPF patients with stable status, and 27 normal controls were enrolled in this study. The levels of serum sCD206 and sCD163 were compared among the three groups and analysed with the clinical features and mortality of IPF. RESULTS: The serum concentrations of both markers were higher in patients with AE-IPF than in those with S-IPF (580.0 ng/ml vs 335 ng/ml for sCD206 and 69.2 ng/ml vs 37.9 ng/ml for sCD163). The level of sCD206 was related to an increased risk of mortality (HR = 1.002, p < 0.001). The best separation between decedents and survivors was obtained by sCD206 (area under the receiver operating characteristic curve [AUC] 0.712 and 95% confidence interval 0.595-0.830). CONCLUSION: Our data demonstrated that the macrophage-related markers sCD206 and sCD163 were significantly higher in patients with IPF, especially sCD206 in AE-IPF patients. The high level of serum sCD206 was associated with mortality in idiopathic pulmonary fibrosis.

Voltammetric sensing performances of a carbon ionic liquid electrode modified with black phosphorene and hemin.

A black phosphorene (BPE) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) hybrid was used for the immobilization of hemin on a carbon ionic liquid electrode (CILE). BPE inside the PEDOT:PSS film was stable without adverse effects of water and oxygen. The hemin-modified electrode facilitates electrochemical communication with a couple of well-shaped and enhanced redox waves. Therefore BPE exhibits an accelerating function to the electron movement. This sensor exhibits excellent electrocatalytic effects on the reduction of various substrates including trichloroacetic acid (TCA), nitrite and H2O2. As for TCA, the reduction current at -0.36 V (vs. Ag/AgCl) increases linearly in the concentration range from 2.0 to 180 mmol·L-1 with a detection limit of 0.67 mmol·L-1 (at 3σ). As for nitrite, the reduction current at -0.59 Vis linear in the 1.0 to 10.5 mmol·L-1 concentration range, and the detection limit is 0.33 mmol·L-1 (at 3σ). As for H2O2, the reduction current at -0.033 V (vs. Ag/AgCl) is linear in the concentration range from 4.0 to 35.0 mmol·L-1 and the detection limit is 1.3 mmol·L-1 (at 3σ). The real sample was analyzed with satisfactory results, which indicated that BPE had potential applications in the field of electrochemical biosensor. Graphical abstract Photos of (a) black phosphorene (BPE) solution, (b) poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS), (c) BPE-PEDOT:PSS (1:5) dispersion, and the fabrication procedure of this electrochemical sensor. It was applied to the determination of trichloroacetic acid, nitrite and hydrogen peroxide.

Linking the low-density lipoprotein receptor-binding segment enables the therapeutic 5-YHEDA peptide to cross the blood-brain barrier and scavenge excess iron and radicals in the brain of senescent mice.

INTRODUCTION: Iron accumulates in the brain during aging, which catalyzes radical formation, causing neuronal impairment, and is thus considered a pathogenic factor in Alzheimer's disease (AD). To scavenge excess iron-catalyzed radicals and thereby protect the brain and decrease the incidence of AD, we synthesized a soluble pro-iron 5-YHEDA peptide. However, the blood-brain barrier (BBB) blocks large drug molecules from entering the brain and thus strongly reduces their therapeutic effects. However, alternative receptor- or transporter-mediated approaches are possible. METHODS: A low-density lipoprotein receptor (LDLR)-binding segment of Apolipoprotein B-100 was linked to the 5-YHEDA peptide (bs-5-YHEDA) and intracardially injected into senescent (SN) mice that displayed symptoms of cognitive impairment similar to those of people with AD. RESULTS: We successfully delivered 5-YHEDA across the BBB into the brains of the SN mice via vascular epithelium LDLR-mediated endocytosis. The data showed that excess brain iron and radical-induced neuronal necrosis were reduced after the bs-5-YHEDA treatment, together with cognitive amelioration in the SN mouse, and that the senescence-associated ferritin and transferrin increase, anemia and inflammation reversed without kidney or liver injury. DISCUSSION: bs-5-YHEDA may be a mild and safe iron remover that can cross the BBB and enter the brain to relieve excessive iron- and radical-induced cognitive disorders.

Gold Nanocage-Based Electrochemical Sensing Platform for Sensitive Detection of Luteolin.

A simple and sensitive electrochemical sensor was developed for the detection of tracelevels of luteolin. The sensoris based on a novel type of chemically modified electrode: gold nanocage (AuNCs)-modified carbon ionic liquid electrode (CILE). To construct this electrochemical sensing platform for luteolin, CILE is initially prepared by using 1-hexylpyridinium hexafluorophosphate as the binder and then AuNCs are coated on the surface of CILE to fabricate AuNCs-modified CILE (AuNCs/CILE). Electrochemical studies have shown that AuNCs/CILE can exhibit enhanced electrocatalytic activity toward the redox reaction of luteolin, therefore, the redox peak current of luteolin can be greatly improved, resulting in the high sensitivity of the developed sensor. Under the optimal conditions, the oxidation peak currents of the sensor increase linearly with an increase in the luteolin concentration in a range from 1 to 1000 nM with a detection limit of 0.4 nM, which is lower than those of most reported electrochemical luteolin sensors. Moreover, the reproducibility, precision, selectivity, and stability of this sensor are excellent. Finally, the sensing system was applied to the analysis of luteolin-spiked drug samples and the recovery in all cases was 95.0⁻96.7%, indicating the potential application of this simple, facile, and sensitive sensing system in pharmaceutical analysis.

miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression.

MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR-495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR-495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol-doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre-treatment with miR-495 before chemotherapy could improve the curative effect on MDR1-based MDR cancer.