High-Frequency Quartz Crystal Microbalance and Dual-Signaling Electrochemical Ratiometric Assays of PTP1B Activity Based on COF@Au@Fc Hybrids.

The abnormal expression of protein tyrosine phosphatase 1B (PTP1B) is highly related to several serious human diseases. Therefore, an accurate PTP1B activity assay is beneficial to the diagnosis and treatment of these diseases. In this study, a dual-mode biosensing platform that enabled the sensitive and accurate assay of PTP1B activity was constructed based on the high-frequency (100 MHz) quartz crystal microbalance (QCM) and dual-signaling electrochemical (EC) ratiometric strategy. Covalent-organic framework@gold nanoparticles@ferrocene@single-strand DNA (COF@Au@Fc-S0) was introduced onto the QCM Au chip via the chelation between Zr4+ and phosphate groups (phosphate group of the phosphopeptide (P-peptide) on the QCM Au chip and the phosphate group of thiol-labeled single-stranded DNA (S0) on COF@Au@Fc-S0) and used as a signal reporter. When PTP1B was present, the dephosphorylation of the P-peptide led to the release of COF@Au@Fc-S0 from the QCM Au chip, resulting in an increase in the frequency of the QCM. Meanwhile, the released COF@Au@Fc-S0 hybridized with thiol/methylene blue (MB)-labeled hairpin DNA (S1-MB) on the Au NPs-modified indium-tin oxide (ITO) electrode. This caused MB to be far away from the electrode surface and Fc to be close to the electrode, leading to a decrease in the oxidation peak current of MB and an increase in the oxidation peak current of Fc. Thus, PTP1B-induced dephosphorylation of the P-peptide was monitored in real time by QCM, and PTP1B activity was detected sensitively and reliably using this innovative QCM-EC dual-mode sensing platform with an ultralow detection limit. This platform is anticipated to serve as a robust tool for the analysis of protein phosphatase activity and the discovery of drugs targeting protein phosphatase.

Integrated metabolomic and transcriptomic analysis reveals variation in the metabolites of Dendrobium officinale, Dendrobium huoshanense, Dendrobium nobile.

INTRODUCTION: Dendrobium is a perennial herb of the genus Dendrobium in the orchid family. Generally, Dendrobium officinale (TP) and Dendrobium huoshanense (HS) are both considered to have the function of yin-nourishing, while Dendrobium nobile (JC) has better efficacy of heat-clearing. However, because of the wide variety of Dendrobium species, the classification and clinical application of Dendrobium are often confused clearly distinguished in different medicinal uses. OBJECTIVE: In order to compare the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) of the three Dendrobium. METHODS: We selected TP, HS, and JC cultivated on stone for metabolomic and transcriptomic analyses between 2 and 3 years. RESULTS: The results showed that a total of 489 metabolites were obtained, including 72 were DAMs. The 72 DAMs were mainly enriched in metabolic pathways and biosynthesis of secondary metabolites. Transcriptome analysis results showed that 1,038 annotated DEGs were identified among the three Dendrobium species. The comprehensive analysis showed that the three Dendrobium differed in the distribution of the content of four major active components: flavonoids, amino acids, alkaloids, and sugars and alcohols, among which the DAMs and DEGs were mainly enriched in metabolic pathways and secondary metabolite biosynthesis. CONCLUSION: In this study, metabolomics and transcriptomics were utilized to compare the differences among the three species of Dendrobium, to provide theoretical references for future research and selection of different species of Dendrobium based on different medicinal uses, and to lay the foundation for further research on the biosynthesis of flavonoids in Dendrobium.

Chromium-Mediated and Ligand-Dependent Activity Engineering of Boron-Doped g-C3N4 Photo-oxidative Nanozymes for Breaking the pH Limitation.

How to overcome the intrinsic low activity of most oxidase and peroxidase mimics at neutral pH has been extremely challenging. Herein, we represent a chromium-mediated and ligand-dependent strategy to activate the oxidase-like activity of boron-doped g-C3N4 (B-g-C3N4, denoted as BG), aiming at breaking the pH limitation. Cr (III) can be in situ oxidized to Cr (IV) by generated •O2- upon UV light irradiation, which then works as a catalysis mediator to oxidize TMB under a neutral environment. Excitingly, the TMB oxidation can be rationally modulated by ligands on the BG coordinating with chromium. We verify that the PEI-Cr3+ coordination outperformed Cit-PEI-Cr3+ on the oxidase-like activity through a more accelerated electron transfer, unveiled by the Gauss theoretical calculations. This study highlights a paradigm of tuning the coordination environment on nanozyme surface via the ligand engineering strategy for boosting the oxidase-mimicking activity and breaking the pH limitation. Meanwhile, the catalysis-based colorimetric assay for accurate and selective identification of Cr3+ was achieved.

A high-frequency QCM biosensing platform for label-free detection of the SARS-CoV-2 spike receptor-binding domain: an aptasensor and an immunosensor.

Herein, high-frequency quartz crystal microbalance biosensing platforms were constructed using an aptamer and antibody as bioreceptors for fast and label-free detection of the SARS-CoV-2 RBD.

Comparison of the effects of different doses of Glucocorticoids on distinct subtypes of Guillain-Barré syndrome in Southern China.

BACKGROUND: The effect of Glucocorticoids (GCs) on the treatment of Guillain-Barré syndrome (GBS) has been controversial. There is no information on whether specific subtypes of GBS respond differently to GCs. In this setting, we aimed to discuss whether GCs treating yield different effects in the distinct subtypes (acute inflammatory demyelinating polyneuropathy, AIDP; acute motor axonal neuropathy, AMAN). And further, we analyzed the impact of different doses on the outcome. METHODS: Medical records of 448 patients with a diagnosis of classic GBS admitted to 31 tertiary hospitals, located in 14 provinces of Southern China, from 1 January 2013 to 30 September 2016, were retrospectively collected. And 251 patients treated with GCs alone (AIDP=189, AMAN=62) were reviewed and analyzed. RESULTS: After GCs treatment, the Hughes score of AIDP patients was significantly lower than that of AMAN patients at discharge (P=0.005) and 3 months after onset (P<0.001). Further analysis revealed that among AIDP patients, the high-dose group had significantly shorter hospital stay (P=0.023), lower Hughes score at nadir (P<0.001), at discharge (P=0.005), and 3 months after onset (P<0.001), compared with the low-dose group. However, for AMAN patients, the outcome difference between groups was nonsignificant. CONCLUSION: Our data suggest that the high doses of GCs may result, at least in part, from the side of the duration of hospital stay and short-term outcome, favorable outcomes in AIDP patients. Therefore, we cannot completely deny the priority of GCs in the treatment of GBS, because the effect of different doses of GCs varies in treating different subtypes. More studies are needed in the future to further validate this issue. TRIAL REGISTRATION: ChiCTR-RRC-17014152 . Registered 26 December 2017- Retrospectively registered.

Clinical characteristics of central nervous system candidiasis due to Candida albicans in children: a single-center experience.

BACKGROUND: Central nervous system candidiasis due to Candida albicans (CNSC) in children is easily misdiagnosed and is associated with poor outcomes and a high mortality rate. There is no big data research or systematic review of CNSC. METHODS: Patients diagnosed as CNSC with positive culture results of Candida albicans in Beijing Children's Hospital affiliated to Capital Medical University from March 2010 to March 2019 were included. Patients receiving immunosuppressive therapy or transplantation, or with malignant tumours were excluded. We analysed the clinical characteristics, follow-up results, drug susceptibility tests and whole-exome sequencing (WES) results. RESULTS: Thirty-three definitive patients were enrolled, including 22 males and 11 females. Twenty-five patients suffered from CNSC when they were less than 1 year old, and a total of 29 patients had high-risk factors. The main clinical manifestations were fever, convulsions, and positive neurological signs. Twenty-two patients had CNS infections alone, and 11 patients had CNS infections combined with invasive infections involving multiple sites. Twenty-seven cases had a positive CSF and/or blood culture at our hospital. All strains were susceptible to fluconazole, and 2 strains had intermediate susceptibility to voriconazole. As for amphotericin B, all the strains were wild type (WT). WES of 16 patients revealed 2 cases with CARD9 mutations, who suffered from recurrent onychomycosis or thrush before. CONCLUSION: CNSC mostly existed in children younger than 1 year old, who all had underlying risk factors. CNSC patients with onset at an older age or with recurrent superficial fungal infections might have primary immunodeficiency.

The association of CYP2D6 gene polymorphisms in the full-length coding region with higher recurrence rate of vivax malaria in Yunnan Province, China.

BACKGROUND: Accumulating evidence suggest that compromised CYP2D6 enzyme activity caused by gene mutation could contribute to primaquine failure for the radical cure of vivax malaria. The current study aims to preliminarily reveal the association between the recurrence of vivax malaria in Yunnan Province and CYP2D6 gene mutation by analysing polymorphisms in the entire coding region of human CYP2D6 gene. METHODS: Blood samples were collected from patients with vivax malaria, who received "chloroquine and 8-day course of primaquine therapy" in Yunnan Province. The suspected relapsed cases were determined by epidemiological approaches and gene sequence alignment. PCR was conducted to amplify the CYP2D6 gene in the human genome, and the amplified products were then sequenced to compare with the non-mutation "reference" sequence, so as to ensure correct sequencing results and to determine 9 exon regions. Subsequently, the DNA sequences of 9 exons were spliced into the coding DNA sequence (CDS), which, by default, is known as maternal CDS. The paternal CDS was obtained by adjusting the bases according to the sequencing peaks. The mutation loci, haplotypes (star alleles), genotypes and odds ratios (OR) of all the CDSs were analysed. RESULTS: Of the119 maternal CDS chains in total with 1491 bp in length, 12 mutation sites in the 238 maternal and paternal CDS chains were detected. The c.408G > C mutation was most frequently detected in both suspected relapsed group (SR) and non-relapsed group (NR), reaching 85.2% (75/88) and 76.0% (114/150), respectively. The c.886C > T mutation was most closely related to the recurrence of vivax malaria (OR = 2.167, 95% CI 1.104-4.252, P < 0.05). Among the 23 haplotypes (Hap_1 ~ Hap_23), Hap_3 was non-mutant, and the sequence structure of Hap_9 was the most complicated one. Five star alleles, including *1, *2, *4, *10 and *39, were confirmed by comparison, and CYP2D6*10 allele accounted for the largest percentage (45.4%, 108/238). The frequency of CYP2D6*2 allele in the SR group was significantly higher than that in the NR group (Χ2 = 16.177, P < 0.05). Of the defined 24 genotypes, 8 genotypes, including *4/*4, *4/*o, *2/*39, *39/*m, *39/*x, *1/*r, *1/*n, and *v/*10, were detected only in the SR group. CONCLUSION: Mutation of CYP2D6*10 allele accounts for the highest proportion of vivax malaria cases in Yunnan Province. The mutations of c. 886C > T and CYP2D6*2 allele, which correspond to impaired PQ metabolizer phenotype, are most closely related to the relapse of vivax malaria. In addition, the genotype *4/*4 with null CYP2D6 enzyme function was only detected in the SR group. These results reveal the risk of defected CYP2D6 enzyme activity that diminishes the therapeutic effect of primaquine on vivax malaria.

Overall trend towards headache remission during the COVID-19 pandemic among Chinese patients with pre-existing headache highlights the role of family support.

BACKGROUND: The global status of the COVID-19 pandemic is not optimistic. This is a particularly vulnerable time for patients with pre-existing headache disorders. The present study aimed to investigate the impact of the COVID-19 pandemic on headache patients in China. METHODS: A survey was conducted through an online survey platform on June 6, 2020. Demographic characteristics, the PHQ-9, the ISI, a COVID-19 questionnaire and a headache profile survey were included in the online questionnaire. RESULTS: Eventually, a total of 15,000 participants from China completed the online questionnaire. Among them, 2806 participants had pre-existing headache disorders. Our analysis showed reductions in the duration of headaches (3.414 ± 6.859 vs 4.033 ± 7.325 h, P<0.001), number of headache days per month (1.788 ± 2.989 vs 2.092 ± 3.694, P<0.001), and headache intensity (4.110 ± 1.609 vs 4.290 ± 1.680, P<0.001) during the COVID-19 pandemic. Smoking (OR = 1.397, 95% CI 1.090 to 1.790, P = 0.008) and getting support from family members during social isolation (OR = 1.656, 95% CI 1.075 to 2.550, P = 0.022) were independent factors affecting the reduction in the duration of headaches. Education level (OR = 1.478, 95% CI 1.103 to 1.980, P = 0.009) and having a relative or acquaintance who contracted COVID-19 (OR = 0.643, 95% CI 0.458 to 0.902, P = 0.011) were the independent factors affecting the reduction in headache severity. Living in the Wuhan area, having symptoms or a diagnosis of COVID-19 and having relatives or acquaintances who had contracted COVID-19 were associated with the worsening of headaches. CONCLUSIONS: Participants experienced an overall trend towards the improvement of headaches during the COVID-19 pandemic. Family support might play an important role in the improvement of headaches.

Guillain-Barré syndrome triggered by surgery in a Chinese population: a multicenter retrospective study.

BACKGROUND: Surgery is a potential trigger of Guillain-Barré syndrome (GBS), a disorder which leads to an autoimmune-mediated attack of peripheral nerves. The present study was designed to explore clinical features of post-surgical GBS compared with those of general GBS in order to provide better clinical advice to patients undergoing surgery. METHODS: The medical records of GBS patients who were seen at 31 tertiary hospitals in southern China between January 1, 2013 and September 30, 2016 were retrospectively analyzed. Post-surgical GBS was defined as symptoms of GBS within 6 weeks after surgery. Clinical features of post-surgical GBS are described and are compared with general GBS. RESULTS: Among the 1001 GBS patient cases examined in this study, 45 (4.5%) patient cases exhibited symptoms of GBS within 6 weeks of undergoing surgery. Within this group, 36 (80.0%) patients developed initial symptoms of limb weakness. The average interval between surgery and symptom onset was 13.31 days. The most common type of surgery which triggered GBS was orthopedic surgery, followed by neurological surgery. Compared to general GBS, post-surgical GBS was characterized by a higher proportion of severe patients (Hughes functional grading scale (HFGS) score ≥ 3) upon admission and at nadir, higher HFGS scores at discharge, and longer hospital stays. Post-surgical GBS patients also had a significantly higher frequency of the acute motor axonal neuropathy subtype (37.9 vs. 14.2, respectively; P = 0.001). CONCLUSION: Surgery is probably a potential trigger factor for GBS, especially orthopedic surgery. Infections secondary to surgery may play a role. The possibility of preceding (post-operative) infections was not excluded in this study. Clinical presentation of post-surgical GBS is characterized by a more severe course and poorer prognosis, and should be closely monitored. TRIAL REGISTRATION: chicTR-RRc-17,014,152 .

Low serum calcium is associated with perioperative blood loss and transfusion rate in elderly patients with hip fracture: a retrospective study.

BACKGROUND: To investigate whether hypocalcemia influenced total blood loss and transfusion rate in elderly patients with hip fracture. METHODS: From our hip fracture database, patients were consecutively included between January 2014 and December 2020. Serum calcium level was corrected for albumin concentration, and hypocalcaemia was defined as corrected calcium < 2.11 mmol/L. Hemoglobin and hematocrit were obtained on admission day and postoperative day, and blood transfusions were collected. According to the combination formulas of Nadler and Gross, the total blood loss of each patient was calculated. Risk factors were further analyzed by multivariate linear regression. RESULTS: A total of 583 consecutive elderly hip fracture patients were finally included (mean age 79.32 ± 8.18 years, 68.61% female). On admission, the mean serum corrected calcium level was 2.17 ± 0.14 mmol/L, and the prevalence of hypocalcemia was 33.11% (95% CI: 29.42-37.02). When comparing patients with normal calcium, hypocalcemia patients exhibited a higher blood transfusion rate (7.69% vs 16.06%, P < 0.05), and significantly larger total blood loss (607.86 ± 497.07 ml vs 719.18 ± 569.98 ml, P < 0.05). Multivariate linear regression analysis showed that male, anemia on admission, time from injury to hospital, intertrochanteric fracture, blood transfusion and hypocalcemia were independently associated with increased total blood loss (P < 0.05). CONCLUSION: Hypocalcemia is common in elderly patients with hip fracture, and significantly associated with more total blood loss and blood transfusion. The other risk factors for increased total blood loss are male, anemia on admission, time from injury to hospital, intertrochanteric fracture, and blood transfusion. LEVEL OF EVIDENCE: Level III, retrospective study.

Photoelectrochemical detection of human epidermal growth factor receptor 2 (HER2) based on Co3O4-ascorbic acid oxidase as multiple signal amplifier.

A sensitive photoelectrochemical (PEC) sensor based on hexagonal carbon nitride tubes (HCNT) as photoactive material was prepared for the detection of human epidermal growth factor receptor 2 (HER2). Magnetic Fe3O4 nanospheres (MNs) modified with anti-HER2 antibodies were employed for highly efficient capture of HER2 from serum sample, and Co3O4 nanoparticles (Co3O4 NPs) modified with ascorbic acid oxidase (AAO) as well as HER2 aptamer were used for signal amplification. When the aptamer-Co3O4-AAO probe was captured onto the electrode surface through the specific binding of the aptamer with HER2, the photocurrent intensity decreased. This was because Co3O4 NPs competed with HCNT for consumption of the excitation energy. As a consequence AAO catalyzed the oxidation of the electron donor (AA), and the aptamer-Co3O4-AAO probe increased the steric hindrance at the electrode surface, leading to significant photocurrent intensity decrease, thus realizing multiple signal amplification. Based on this signal amplification strategy, at 0 V (vs Ag/AgCl), the PEC sensor shows a wide linear response ranging from 1 pg mL-1 to 1 ng mL-1 with a low detection limit of 0.026 pg mL-1 for HER2. Importantly, the prepared PEC sensor was applied for detection of HER2 in human serum samples with recoveries between 98.8 and 101%. Sensitive photoelectrochemical sensor based on Co3O4 nanoparticles modified with ascorbic acid oxidase for signal amplification is reported.

A Frequency-Multiplexed Coherent Electro-optic Memory in Rare Earth Doped Nanoparticles.

Quantum memories for light are essential components in quantum technologies like long-distance quantum communication and distributed quantum computing. Recent studies have shown that long optical and spin coherence lifetimes can be observed in rare earth doped nanoparticles, opening exciting possibilities over bulk materials, e.g., for enhancing coupling to light and other quantum systems, and material design. Here, we report on coherent light storage in Eu3+:Y2O3 nanoparticles using the Stark echo modulation memory (SEMM) quantum protocol. We first measure a nearly constant Stark coefficient of 50 kHz/(V/cm) across a bandwidth of 15 GHz, which is promising for broadband operation. Storage of light is then demonstrated with an effective coherence lifetime of 5 µs. Pulses with two different frequencies are also stored, confirming frequency-multiplexing capability, and are used to demonstrate the memory high phase fidelity. These results open the way to nanoscale optical quantum memories with increased efficiency, bandwidth, and processing capabilities.

Identification of differentially expressed miRNAs and mRNAs in synovial of osteoarthritis via RNA-sequencing.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. This study attempted to investigate the key mRNAs and miRNAs related to OA. PATIENTS AND METHODS: From April 17th, 2018 to May 17th, 2018, five patients with OA and three normal controls were enrolled in this present study. To identify the differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs) between patients with OA and normal controls, RNA-sequencing was performed. Then, DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. To validate the RNA-sequencing results, quantitative real time-PCR (RT-PCR) and western blot analysis were performed as well. RESULTS: A total of 1068 DEmRNAs, 21 DEmiRNAs and 395 DEmiRNA-DEmRNA pairs were identified in synovial tissues of patients with OA. The functional annotation of DEmiRNA-target DEmRNAs revealed that Pathways in cancer and PI3K-Akt signaling pathway were significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. QRT-PCR and western blot results revealed that except for TLR7, the expression level of the others was consistent with the RNA-sequencing results, generally. CONCLUSION: The findings of this present study may provide new clues for the roles of DEmRNAs and DEmiRNAs in the pathogenesis of OA.

Tritium diffusion in a Li2TiO3 crystal terminated with the (001) surface from first-principles calculations.

The tritium release behavior of the Li2TiO3 crystal has become an important index to evaluate its comprehensive performance as a solid breeder material in nuclear fusion reactors. The tritium diffusion on the surface (surface diffusion) and diffusion from the inside to the surface (hopping diffusion) in Li2TiO3 crystals with a 1/3-Li(001) surface are systematically investigated by the first-principles method. Possible adsorption sites, diffusion pathways and energy barriers of surface diffusion and hopping diffusion have been calculated and analyzed, respectively. Tritium atoms are found to diffuse preferentially along the [100] direction on the surface and two equivalent pathways across the surface were identified. The obtained activation energies are about 0.50 eV for surface diffusion and 1.56 eV for hopping diffusion. The local density of states and Bader charge for typical surface diffusion and hopping diffusion pathways are calculated and analyzed. The results reveal that the tritium (T) atom bonds with neighboring oxygen (O) atoms during the surface diffusion, while the T-O interaction is significantly weakened in the hopping diffusion which results in the higher activation energy than that of surface diffusion. In combination with our previous work, a complete tritium diffusion model for the Li2TiO3 crystal is proposed and the corresponding tritium diffusion coefficients are obtained. Our obtained activation energies are in the same range as previous experimental data and could provide theoretical support for the future related experiments.

Efficacy and Safety of Mechanical Thrombectomy for Acute Mild Ischemic Stroke with Large Vessel Occlusion.

BACKGROUND The suitability of mechanical thrombectomy (MT) for patients with acute mild ischemic stroke (AMIS) caused by large vessel occlusion (LVO) is controversial. This study evaluated MT in patients with AMIS and LVO. MATERIAL AND METHODS Forty-seven patients diagnosed as AMIS with LVO received MT or intravenous thrombolysis (IVT). Primary outcomes were National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale scores. Secondary outcomes were incidence of systemic complications and symptomatic intracranial hemorrhage. RESULTS There were no significant differences between IVT and MT groups for gender, age, risk factors of cerebrovascular disease, past history, NIHSS score at admission, blood pressure, and LVO sites. For all patients, the NIHSS scores at discharge were lower than those at admission. Patients with excellent outcomes were 66.6% (16/24) in the IVT group and 60.8% (14/23) in the MT group; favorable outcome rates were 75% (18/24) in the IVT group and 69.6% (16/23) in the MT group, with no significant differences between groups. Twelve patients (52.2%) in the MT group and 5 (20.8%) in the IVT group had systemic complications. Symptomatic intracranial hemorrhage was not detected in the IVT group, but manifested in 2 (8.7%) patients in the MT group. During 90-day follow-up, 1 patient died in each of the IVT and MT groups, with 4.2% and 4.4% mortality rates, respectively. CONCLUSIONS The efficacy of MT and IVT was comparable in AMIS patients with LVO. While MT had a higher incidence of systemic complications, its short- and long-term effects were equivalent to IVT.

The dynamic expression of canonical Wnt/ß-catenin signalling pathway in the pathologic process of experimental autoimmune neuritis.

Background: Guillain-Barré syndrome (GBS), an autoimmune disease and an acute inflammation disorder, is currently the most frequent cause of acute flaccid paralysis worldwide. EAN, an animal model of GBS, is a CD4+ T cell-mediated autoimmune disease of the PNS. Wnt/ß-catenin signals are critically important to several fundamental aspects of peripheral nerve development and play a crucial role in Schwann cell proliferation. Here, we investigate the role of Wnt/ß-catenin signalling cascades in EAN rats.Methods: 28 male Lewis rats weighing 170 ± 10 g were randomly divided into control group (n = 7) and EAN groups (Early group; Peak group and Recovery group. n = 7 per group). EAN rats were immunized with P257-81 peptide; weighed daily, and the neurologic signs of EAN were evaluated every day. The sciatic nerve was taken on the days 10, 17, and 30 p.i. for H&E staining, transmission electron microscopy and immunohistochemical staining; blood samples were collected weekly from caudal vein to detect IFN-γ, IL-4, TGF-ß1; and the sciatic nerve was taken to examinate the dynamics expression of Wnt/ß-catenin pathway molecules.Results: In our study, we chose tail-root injection to better model GBS. Moreover, we observed that IFN-γ levels paralleled clinical EAN, and the levels of TGF-ß1 and IL-4 gradually increased and peaked in the recovery phase. In addition, we have shown that canonical Wnt signalling is upregulated and reached a peak in the late recovery phase.Conclusion: Our findings suggest that Wnt/ß-catenin signalling is associated with the promotion of remyelination in EAN rats.

Gold nanoparticle-modified black phosphorus nanosheets with improved stability for detection of circulating tumor cells.

Gold nanoparticle (AuNP)-anchored BP nanosheets were synthesized through in situ growth of AuNPs onto BP. Due to the strong chelating ability of P or phosphorus oxides with AuNPs, the stability of BP is improved. As proof-of-concept demonstration of the functionalized BP, electrochemical detection of circulating tumor cells (CTCs) based on BP@AuNPs@aptamer as a probe combined with immunomagnetic separation is reported. The aptamer can specifically bind with CTCs, while the phosphorus oxides including phosphite ion and phosphate ion (PxOy species) on BP and aptamer can react with molybdate to generate an electrochemical current, leading to dual signal amplification. The biosensor is applied to MCF-7 cell detection and displays good analytical performance with a detection limit of 2 cell mL-1. Furthermore, the practicality of this biosensor was validated through sensitive determination of MCF-7 cells in human blood. Therefore, the reported biosensor could be applied to detect other biomarkers, offering an ultrasensitive strategy for clinical diagnostics. Graphical abstract Electrochemical detection of circulating tumor cells based on gold nanoparticle-modified black phosphorus nanosheets is reported.

LncRNA TP73-AS1 predicts poor prognosis and functions as oncogenic lncRNA in osteosarcoma.

TP73 antisense RNA 1 (TP73-AS1), a novel long noncoding RNA (lncRNA), has been suggested to be deregulated in various human cancers and serve as a tumor suppressor or promoter, depending on tumor types. The role of TP73-AS1 in osteosarcoma is still unknown. In our results, TP73-AS1 was highly expressed in osteosarcoma tissue samples and cell lines compared with matching adjacent nontumor tissue specimens and a normal human osteoblast cell line, respectively. Moreover, high expression of TP73-AS1 was statistically associated with advanced Enneking stage, large tumor size, present distant metastasis, and poor histological grade, while exhibiting no statistical association with age, sex, and tumor site. The survival analyses showed that patients with osteosarcoma with high expression of TP73-AS1 obviously had lower overall survival than osteosarcoma patients with low expression of TP73-AS1, and high expression of TP73-AS1 was an independent poor prognostic factor for osteosarcoma patients. The experiments in vitro indicated that inhibition of TP73-AS1 expression depressed osteosarcoma cell viability, migration, and invasion, and arrested cell cycle. In conclusion, TP73-AS1 serves as oncogenic lncRNA participated in osteosarcoma progression.

Electrochemical Detection of Circulating Tumor Cells Based on DNA Generated Electrochemical Current and Rolling Circle Amplification.

Circulating tumor cells (CTCs) are important indicators for tumor diagnosis and tumor metastasis. However, the extremely low levels of CTCs in peripheral blood challenges the precise detection of CTCs. Herein, we report DNA generated electrochemical current combined with rolling circle amplification (RCA) as well as magnetic nanospheres for highly efficient magnetic capture and ultrasensitive detection of CTCs. The antiepithelial cell adhesion molecule (EpCAM) antibody-modified magnetic nanospheres were used to capture and enrich CTCs. The following binding of an aptamer onto the CTC surface and the subsequent RCA assembled a significant amount of DNA molecules onto the electrode. The reaction of the DNA molecules with molybdate can then form redox molybdophosphate and produce an electrochemical current. Using the breast cancer cell MCF-7 as a model, the sensor displays good performances toward detection of MCF-7 that was spiked into peripheral blood. The signal amplification strategy integrated with a magnetic nanosphere platform exhibits good performance in the efficient capture and detection of CTCs, which may find wide potential in cancer diagnostics and therapeutics.

Genetic polymorphism of histidine rich protein 2 in Plasmodium falciparum isolates from different infection sources in Yunnan Province, China.

BACKGROUND: Failed diagnoses of some falciparum malaria cases by RDTs are constantly reported in recent years. Plasmodium falciparum histidine-rich protein 2 (pfhpr2) gene deficiency has been found to be the major reason of RDTs failure in many countries. This article analysed the deletion of pfhpr2 gene of falciparum malaria cases isolated in Yunnan Province, China. METHODS: Blood samples from falciparum malaria cases diagnosed in Yunnan Province were collected. Plasmodium genomic DNA was extracted and the pfhrp2 gene exon2 region was amplified via nested PCR. The haplotype of the DNA sequence, the nucleic acid diversity index (PI) and expected heterozygosity (He) were analyzed. Count PfHRP2 amino acid peptide sequence repeat and its times, and predict the properties of PfHRP2 peptide chain reaction to RDTs testing. RESULTS: A total of 306 blood samples were collected, 84.9% (259/306) from which pfhrp2 PCR amplification products (gene exon2) were obtained, while the remaining 47 samples were false amplification. The length of the 250 DNA sequences ranged from 345 - 927 bp, with 151 haplotypes, with PI and He values of 0.169 and 0.983, respectively. The length of the PfHRP2 peptide chain translated from 250 DNA sequences ranged from 115 to 309 aa. All peptide chains had more than an amino acid codon deletion. All 250 PfHRP2 strands ended with a type 12 amino acid repeat, 98.0% (245/250) started with a type 1 repetition and 2.0% (5/250) with a type 2 repetition. The detection rate for type 2 duplicates was 100% (250/250). Prediction of RDT sensitivity of PfHRP2 peptide chains based on type 2 and type 7 repeats showed that 9.60% (24/250), 50.0% (125/250), 13.20% (33/250) and 27.20.5% (68/250) of the 250 peptide chains were very sensitive, sensitive, borderline and non-sensitive, respectively. CONCLUSION: The diversified polymorphism of the pfhrp2 gene deletion from different infection sources in the Yunnan province are extremely complex. The cause of the failure of pfhrp2 exon2 amplification is still to be investigated. The results of this study appeal to Yunnan Province for a timely evaluation of the effectiveness and applicability of RDTs in the diagnosis of malaria.