Magnetic aptamer copper nanoclusters fluorescent biosensor for the visual detection of zearalenone based on docking-aided rational tailoring.

To address the food safety issues caused by toxins, we established a fluorescent copper nanocluster biosensor based on magnetic aptamer for the visual and quantitative detection of ZEN. Specifically, we utilized the docking-aided rational tailoring (DART) strategy to analyze intermolecular force and interaction sites between zearalenone (ZEN) and the aptamer, and optimize the long-chain aptamer step by step to enhance the binding affinity by 3.4 times. The magnetic bead-modified aptamer underwent conformational changes when competing with complementary sequences to bind with ZEN. Then, the released complementary sequences will be amplified in template-free mode with the presence of the terminal deoxynucleotidyl transferase (TdT), and generating T-rich sequences as the core sequences for the luminescence of copper nanoclusters. The luminescence could be visualized and quantitatively detected through ultraviolet irradiation. The proposed label-free aptasensor exhibited high sensitivity and specificity, with a low limit of detection (LOD) of 0.1 ng/mL.

Effects of ferric derisomaltose on postoperative anaemia in adult spinal deformity surgery: a study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative anaemia is prevalent in adult spinal deformity (ASD) surgery in association with unfavourable outcomes. Ferric derisomaltose, a novel iron supplement, offers a promising solution in rapidly treating postoperative anaemia. However, the clinical evidence of its effect on patients receiving spinal surgery remains inadequate. This randomised controlled trial aims to evaluate the safety and efficacy of ferric derisomaltose on postoperative anaemia in ASD patients. METHODS AND ANALYSIS: This single-centre, phase 4, randomised controlled trial will be conducted at Department of Orthopaedics at Peking Union Medical College Hospital and aims to recruit adult patients who received ASD surgery with postoperative anaemia. Eligible participants will be randomly assigned to receive ferric derisomaltose infusion or oral ferrous succinate. The primary outcome is the change in haemoglobin concentrations from postoperative days 1-14. Secondary outcomes include changes in iron parameters, reticulocyte parameters, postoperative complications, allogeneic red blood cell infusion rates, length of hospital stay, functional assessment and quality-of-life evaluation. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of Peking Union Medical College Hospital and registered at ClinicalTrials.gov. Informed consent will be obtained from all participants prior to enrolment and the study will be conducted in accordance with the principles of the Declaration of Helsinki. The results of this study are expected to be disseminated through peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT05714007.

Buyang Huanwu Decoction promotes neurovascular remodeling by modulating astrocyte and microglia polarization in ischemic stroke rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction (BYHWD), one of the most commonly utilized traditional Chinese medicine prescription for treatment of cerebral ischemic stroke. However, the understanding of BYHWD on neurovascular repair following cerebral ischemia is so far limited. AIM OF THE STUDY: This research investigated the influence of BYHWD on neurovascular remodeling by magnetic resonance imaging (MRI) technology and revealed the potential neurovascular repair mechanism underlying post-treatment with BYHWD after ischemic stroke. MATERIALS AND METHODS: Male Sprague-Dawley rats were utilized as an ischemic stroke model by permanent occlusion of the middle cerebral artery (MCAO). BYHWD was intragastrically administrated once daily for 30 days straight. Multimodal MRI was performed to detect brain tissue injuries, axonal microstructural damages, cerebral blood flow and intracranial vessels on the 30th day after BYHWD treatment. Proangiogenic factors, axonal/synaptic plasticity-related factors, energy transporters and adenosine monophosphate-activated protein kinase (AMPK) signal pathway were evaluated using western blot. Double immunofluorescent staining and western blot were applied to evaluate astrocytes and microglia polarization. RESULTS: Administration of BYHWD significantly alleviated infarct volume and brain tissue injuries and ameliorated microstructural damages, accompanied with improved axonal/synaptic plasticity-related factors, axonal growth guidance factors and decreased axonal growth inhibitors. Meanwhile, BYHWD remarkably improved cerebral blood flow, cerebral vascular signal and promoted the expression of proangiogenic factors. Particularly, treatment with BYHWD obviously suppressed astrocytes A1 and microglia M1 polarization accompanied with promoted astrocyte A2 and microglia M2 polarization. Furthermore, BYHWD effectively improved energy transporters. Especially, BYHWD markedly increased expression of phosphorylated AMPK, cyclic AMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) accompanied by inactivation of the NF-κB. CONCLUSION: Taken together, these findings identified that the beneficial roles of BYHWD on neurovascular remodeling were related to AMPK pathways -mediated energy transporters and NFκB/CREB pathways.

Effect of manual lymphatic drainage combined with targeted rehabilitation therapies on the recovery of upper limb function in patients with modified radical mastectomy: A randomized controlled trial.

Objectives: This study aimed to evaluate the effect of manual lymphatic drainage (MLD) combined with targeted rehabilitation therapies on the recovery of upper limb function in patients with breast cancer after modified radical mastectomy. Patients and methods: In the randomized controlled study conducted between October 2019 and June 2020, 104 eligible breast cancer patients who underwent modified radical mastectomy were randomly divided into two groups. The routine functional exercise group (Group RF) received regular functional exercise guidance. In addition, the MLD combined with targeted rehabilitation therapies group (Group MLDT) received MLD, targeted rehabilitation therapies, and regular functional exercise guidance. The primary endpoints were shoulder range of motion, arm circumference and the incidence of axillary web syndrome (AWS). The secondary endpoints included the duration of axillary drainage, the duration of chest wall drainage, and complications. Results: One hundred participants (mean age: 51.9±8.0 years; range, 28 to 72 years) were included in the final analysis as four patients could not complete the study. A significant improvement in shoulder range of motion was observed in Group MLDT compared to Group RF (p<0.05). Additionally, in Group MLDT, the duration of chest wall drainage was reduced (p=0.037). The frequency of AWS in Group RF was twice that in Group MLDT (p=0.061), but there was no significant difference in arm circumference (p>0.05) or the duration of axillary drainage (p=0.519). Regarding complications, there was one case of necrosis in the MLDT group and four cases in the RF group, including wound infection and seroma. Conclusion: Manual lymphatic drainage combined with targeted rehabilitation therapies is an effective strategy to improve shoulder function, shorten the duration of chest wall drainage, reduce complications, and partly lower the incidence of AWS.

A Bridge-Linked Phosphorus-Containing Flame Retardant for Endowing Vinyl Ester Resin with Low Fire Hazard.

The high flammability of vinyl ester resin (VE) significantly limits its widespread application in the fields of electronics and aerospace. A new phosphorus-based flame retardant 6,6'-(1-phenylethane-1,2 diyl) bis (dibenzo[c,e][1,2]oxaphosphinine 6-oxide) (PBDOO), was synthesized using 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) and acetophenone. The synthesized PBDOO was further incorporated with VE to form the VE/PBDOO composites, which displayed an improved flame retardancy with higher thermal stability. The structure of PBDOO was investigated using Fourier transformed infrared spectrometry (FTIR) and nuclear magnetic resonances (NMR). The thermal stability and flame retardancy of VE/PBDOO composites were investigated by thermogravimetric analysis (TGA), vertical burn test (UL-94), limiting oxygen index (LOI), and cone calorimetry. The impacts of PBDOO weight percentage (wt%) on the flame-retardant properties of the formed VE/PBDOO composites were also examined. When applying 15 wt% PBDOO, the formed VE composites can meet the UL-94 V-0 rating with a high LOI value of 31.5%. The peak heat release rate (PHRR) and the total heat release (THR) of VE loaded 15 wt% of PBDOO decreased by 76.71% and 40.63%, respectively, compared with that of untreated VE. In addition, the flame-retardant mechanism of PBDOO was proposed by analyzing pyrolysis behavior and residual carbon of VE/PBDOO composites. This work is expected to provide an efficient method to enhance the fire safety of VE.

[Mechanism of oxymatrine in treatment of collagen-induced arthritis in mice].

Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type Ⅱ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.

In Vivo Study on the Effects of Xiaoaiping on the Stemness of Hepatocellular Carcinoma Cells.

AIMS: The aim of this study was to examine the effects of Xiaoaiping on the stemness of hepatocellular carcinoma (HCC) cells in vivo and to investigate the underlying molecular mechanism. METHODS: A subcutaneous xenograft nude mouse model was established using Hep3B-derived HCC cells. The mice were randomly assigned to the 100 mg/kg Xiaoaiping or 100 µL/20 g normal saline (control) groups (n =3/sex/group) for daily intragastric administration for 14 days. The tumor size was closely monitored during the dosing phase. After the treatment period, the tumor tissues were weighed and harvested for mRNA and protein isolation. qPCR and Western blotting were used to evaluate the expression of cancer stemness markers (epithelial cell adhesion molecule [EpCAM], cluster of differentiation [CD13], CD90, aldehyde dehydrogenase 1 [ALDH1], CD44, and CD45), totipotency factors (sex determining region Y-box 2 [Sox2], Nanog, and octamer-binding transcription factor 4 [Oct4]), and genes involved in the Notch, Wnt/ß-catenin, Hedgehog, and Hippo signaling pathways. KEY FINDINGS: The tumor size and weight were significantly reduced in the nude mice treated with 100 mg/kg Xiaoaiping when compared with the controls. The Xiaoaiping effects on the stemness markers and totipotency factors included decreased expression of EpCAM, CD24, CD47, Sox2, Oct4, and sal-like protein 4 (SALL4), as well as increased expression of CD13 and ALDH1. In addition, Xiaoaiping inhibited the Hippo, Wnt, and Hedgehog signaling pathways. CONCLUSION: Xiaoaiping significantly inhibited the growth of HCC xenograft in nude mice. These antitumor effects may be mediated by modulating the expression of multiple stemness markers and totipotency factors and inhibition of the Hippo, Wnt, and Hedgehog signaling pathways.

Pectin reduces environmental pollutant-induced obesity in mice through regulating gut microbiota: A case study of p,p'-DDE.

BACKGROUND: The prevalence of obesity has raised global concerns. Environmental pollutants are one of the main causes of obesity. Many studies have demonstrated that dietary fiber could reduce obesity induced by high-fat diets, but whether environmental pollutant-induced obesity can be reversed is still unknown. OBJECTIVES: This study aimed to investigate the effects of pectin on obesity induced by a typical environmental pollutant p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and explore the underlying mechanism by which pectin reversed p,p'-DDE-induced obesity. METHODS: p,p'-DDE was used to induce obesity in C57BL/6J mice and pectin was supplied during and after cessation of p,p'-DDE exposure. Body and fat weight gain, plasma lipid profile and insulin resistance of mice were assessed. Gut microbiota composition and the levels of short-chain fatty acids (SCFAs) as well as the receptor proteins and hormones in the SCFAs-related signaling pathway were analyzed. Moreover, p,p'-DDE levels in various tissues of mice were detected. RESULTS: Pectin supplementation reversed body and fat weight gain, dyslipidemia, hyperglycemia and insulin resistance in p,p'-DDE-exposed mice. Furthermore, pectin apparently altered the p,p'-DDE-induced microbial composition and then promoted the levels of SCFAs in colonic feces as well as the expression of G-protein coupled receptors and the concentration of hormone peptide YY (PYY) and glucagon like peptide-1 (GLP-1). Pectin treatment also significantly reduced p,p'-DDE accumulation in mice tissues during p,p'-DDE exposure but did not change p,p'-DDE metabolism after termination of p,p'-DDE exposure. CONCLUSIONS: Pectin had a good effect on reducing p,p'-DDE-induced obesity through regulating gut microbiota and provided a potential strategy for the treatment of environmental pollutant-caused health problems.

Detection of Aß oligomers based on magnetic-field-assisted separation of aptamer-functionalized Fe3O4 magnetic nanoparticles and BaYF5:Yb,Er nanoparticles as upconversion fluorescence labels.

A sensitive and stable bioassay for the detection of Aß oligomer (Aßo), a potentially promising candidate biomarker for Alzheimer's disease (AD) diagnosis, was developed using Fe3O4 magnetic nanoparticles (MNPs) as the recognition and concentration elements and BaYF5:Yb,Er upconversion nanoparticles (UCNPs) as highly sensitive labels, conjugated with the Aßo aptamer (DNA1) and the complementary oligonucleotide of the Aßo aptamer (DNA2), respectively. The DNA1 hybridized with DNA2 to form the duplex structure on the surface of the MNPs/UCNPs nanocomposites probe. When the target Aßo was introduced, the aptamer DNA1 preferentially bound with Aßo and caused the dissociation of some complementary DNA2, liberating some UCNP-labeled complementary DNA2 and leading to a decreased upconversion fluorescent intensity on the surface of MNPs. The decreased fluorescence intensity of UCNPs was related to the concentration of Aßo in the range of 0.2-15nM with a detection limit of 36 pM. The developed method then was successfully applied to measure Aßo in artificial cerebrospinal fluid. Benefiting from the magnetic separation and concentration effect of MNPs, the high sensitivity of UCNPs, as well as the selectivity and stability of the aptamer, the present strategy offered valuable information related to early diagnosis of AD process.

[In vivo study of Chuankezhi metabolism in rat].

To study the metabolic products of main compounds of Chuankezhi injection in rat, 12 Sprague Dawley rats were classed into 2 groups, a blank control group and an intermuscular administration group, respectively. Rat feces and urine samples were collected from 0−24 h and 24−48 h after administration. All the samples were ultrasonically treated with methanol and then analyzed using LC-LTQ Orbitrap MSn. By comparison with the total ion chromatogram of samples from the blank control group, the metabolites in the samples of drug-treated group were screened. These metabolites were further analyzed by multistage product ion scanning and comparison of retention time with reference substances. As a result, a total of 12 flavonoid metabolites were tentatively identified from the rat feces and no metabolite was discovered in the rat urine. Epimedin C and icariin were detected in the rat blood samples after 30 min of administration, but their metabolites and other original flavones were not detected. Furthermore, no original flavones and their metabolites were detected in rat blood samples after 2 and 4 h of administration. The potential metabolism paths were further characterized and the principal in vivo transformation of flavones from Chuankezhi injection were deglycosylation, dehydration, methylation, oxidation and isomerization in rats.

[Phosphate solubilization of Aureobasidium pullulan F4 and its mechanism].

The Aureobasidium pullulans F4 was isolated from the rhizosphere of Hippochaete ramosissimum in Tongguanshan mine wasteland in Tongling City, Anhui Province. Liquid culture was conducted with four kinds of phosphorus sources, calcium phosphate, aluminum phosphate, ferric phosphate and rock phosphate to determine the pH, dissolved phosphorus, phosphorus in the bacteria and organic acid in the solution. The results showed that the phosphate solubilization by A. pullulans F4 varied with phosphorus sources, which decreased in order of aluminum phosphate > ferric phosphate, calcium phosphate > rock phosphate. The amounts of dissolved phosphorus in the different treatments were all higher than 200 mg x L(-1). The pH of the medium dropped immediately in 48 h, and the aluminum phosphate and ferric phosphate treatments showed a greater decrease in pH than the calcium phosphate and rock phosphate treatments. The organic acid synthesized by A. pullulans F4 included oxalic acid, citric acid and tartaric acid, and oxalic acid, among which oxalic acid was the dominated component. The phosphate dissolving capacity of A. pullulans F4 showed no significant correlation with organic acid, but significantly correlated with the pH. The available phosphorus was significantly improved with the combined application of A. pullulans F4 and glucose, suggesting A. pullulans F4 was a potent candidate for remediation of copper mine wastelands.

Overexpression of TaSTRG gene improves salt and drought tolerance in rice.

High salt and drought are the main factors affecting agricultural production. Thus, cloning stress-tolerance-related genes and identifying their functions are essential to enhancing crop tolerance to stresses. In this study, a salt-induced unknown wheat (Triticum aestivum L.) gene was identified and cloned according to microarray analysis of salt-tolerant wheat mutant RH8706-49 under salt stress. The gene was named Triticum aestivum salt tolerance-related gene (TaSTRG) and submitted to Genbank (Accession number: EF599631). TaSTRG expression in wheat is induced by multiple stresses including salt, polyethylene glycol (PEG), abscisic acid (ABA), and cold. Transgenic rice plants overexpressing TaSTRG gene showed higher salt and drought tolerance than the control. Under salt stress, the transgenic rice had a lower intracellular Na(+)/K(+) ratio than the control. Under salt and PEG treatments, these TaSTRG overexpressing rice plants had higher survival rate, fresh weight and chlorophyll content, accumulated higher proline and soluble sugar contents, and had significantly higher expression levels of putative proline synthetase and transporter genes than the control plants. These results indicate that the wheat TaSTRG gene could enhance plant tolerance to multiple types of stresses.

[Increasing the content of active constituents in Polygonum cuspidatum hairy root by gene transformation technology].

To increase the content of active constituent--RE and PD of Polygonum cuspidatum hairy root, through Ri-mediated gene transformation technology, modified high salt low pH method was used to distill genome DNA of grapevine (Vitis raparia). Primer was designed according to sequence of Genebank (AF128861). Through PCR amplification obtain RS gene sequence was obtained. Binary vector pCAMBIA1300-35S-RS was constructed. Frost thawing method was used to transform Agrobacterium rhizogenes ATCC11325. Scratched aseptic seedling leaf of Polygonum cuspidatum was contaminated subsequently. DNA conformity and mRNA expression of RS gene were investigated by PCR and RT-PCR respectively. RE and PD in transgenic hairy root were determined by HPLC. For the first time successfully inducement acquires transformed RS gene hairy root of Polygonum cuspidatum. Content of active constituents--RE and PD were 17 - 187 microg x g(-1) DW and 836 - 1 970 microg x g(-1) DW, respectively, the non-transgenic hairy root was 0 - 130 microg x g(-1) DW and 190 - 320 microg x g(-1) DW. In the different root selected, the content of PD was much higher than that in non-transformed hairy roots of Polygonum cuspidatum, the highest content is 5 times, but the content of RE has not increased apparently.

Increasing the content of active constituents in Polygonum cuspidatum hairy root by gene transformation technology / 药学学报

To increase the content of active constituent--RE and PD of Polygonum cuspidatum hairy root, through Ri-mediated gene transformation technology, modified high salt low pH method was used to distill genome DNA of grapevine (Vitis raparia). Primer was designed according to sequence of Genebank (AF128861). Through PCR amplification obtain RS gene sequence was obtained. Binary vector pCAMBIA1300-35S-RS was constructed. Frost thawing method was used to transform Agrobacterium rhizogenes ATCC11325. Scratched aseptic seedling leaf of Polygonum cuspidatum was contaminated subsequently. DNA conformity and mRNA expression of RS gene were investigated by PCR and RT-PCR respectively. RE and PD in transgenic hairy root were determined by HPLC. For the first time successfully inducement acquires transformed RS gene hairy root of Polygonum cuspidatum. Content of active constituents--RE and PD were 17 - 187 microg x g(-1) DW and 836 - 1 970 microg x g(-1) DW, respectively, the non-transgenic hairy root was 0 - 130 microg x g(-1) DW and 190 - 320 microg x g(-1) DW. In the different root selected, the content of PD was much higher than that in non-transformed hairy roots of Polygonum cuspidatum, the highest content is 5 times, but the content of RE has not increased apparently.