A universal growth strategy for DNA-programmed quantum dots on graphene oxide surfaces.

The emerging materials of semiconductor quantum dots/graphene oxide (QDs/GO) hybrid composites have recently attracted intensive attention in materials science and technology due to their potential applications in electronic and photonic devices. Here, a simple and universal strategy to produce DNA-programmed semiconductor quantum dots/graphene oxide (QDs/GO) hybrid composites with controllable sizes, shapes, compositions, and surface properties is reported. This proof-of-concept work successfully demonstrates the use of sulfhydryl modified single-stranded DNA (S-ssDNA) as a 'universal glue' which can adsorb onto GO easily and provide the growth sites to synthesize CdS QDs, CdSe QDs, CdTe QDs and CdTeSe QDs with distinctive sizes, shapes and properties. Also, adapting this method, other graphene oxide-based hybrid materials which are easily synthesized in aqueous solution, including oxides, core-shell structure QDs and metal nanocrystals, would be possible. This method provided a universal strategy for the synthesis and functional realization of graphene -based nanomaterials.

V-set and immunoglobulin domain containing 4 inhibits oxidative stress, mitochondrial dysfunction, and inflammation to attenuate Parkinson's disease progression by activating the JAK2/STAT3 pathway.

OBJECTIVE: V-set and immunoglobulin domain containing 4 (VSIG4) inhibits neurological dysfunction, microglial M1 polarization, and inflammation to participate in the progression of neurological disorders, but evidence regarding Parkinson's disease (PD) is scarce. The present study intended to investigate the engagement of VSIG4 in PD progression, and the potential mechanism. METHODS: BV-2 cells were treated with 1-Methyl-4-phenylpyridinium (MPP+) to establish PD model. MPP+ treated BV-2 cells were infected with VSIG4 overexpression adenovirus-associated virus (AAV) (oeVSIG4) and negative control AAV (oeNC), and AZD1480 (JAK2 inhibitor) was added to these cells. RESULTS: MPP+ reduced VSIG4 mRNA (P < 0.05) and protein (P < 0.05) in BV-2 cells. Interestingly, VSIG4 reduced malondialdehyde (P < 0.01), reactive oxygen species (P < 0.01), NOD-like receptor family pyrin domain containing 3 (P < 0.05), cleaved-caspase1 (P < 0.05), tumor necrosis factor-α (P < 0.05), and interleukin-1ß (P < 0.05), but increased glutathione (P < 0.05), mitochondrial membrane potential (P < 0.05), phosphorylation (p)-JAK2 (P < 0.05), and p-STAT3 (P < 0.01) in MPP+ treated BV-2 cells, which indicated that VSIG4 inhibited oxidative stress, mitochondrial dysfunction, and inflammation, as well as activated the JAK2/STAT3 pathway in PD model. Moreover, AZD1480 inhibited the JAK2/STAT3 pathway and aggravated oxidative stress, mitochondrial dysfunction, and inflammation in PD model (all P < 0.05). Importantly, AZD1480 attenuated the influence of VSIG4 on oxidative stress, mitochondrial dysfunction, inflammation, and the JAK2/STAT3 pathway in PD model (all P < 0.05). CONCLUSION: VSIG4 suppresses oxidative stress, mitochondrial dysfunction, and inflammation by activating the JAK2/STAT3 pathway, which may be helpful in attenuating PD progression.

Role of epithelial cell-mesenchymal transition regulators in molecular typing and prognosis of colon cancer.

Background: Despite advances in colon cancer screening, diagnosis, chemotherapy, and targeted therapy, the prognosis remains poor once colon cancer develops distant metastasis or local recurrence. To further improve the prognosis of colon cancer patients, researchers or clinicians may need to identify new indicators for predicting the prognosis and treatment of colon cancer. Methods: In order to discover the new mechanism of epithelial-mesenchymal transition (EMT) promoting tumor progression and to find new indicators of colon cancer diagnosis, targeted therapy and prognosis, this study conducted The Cancer Genome Atlas (TCGA) analysis, differential gene analysis, prognostic analysis, protein-protein interaction (PPI), enrichment analysis, molecular typing, and a machine algorithm were combined with data from TCGA and Gene Expression Omnibus (GEO) databases and EMT-related genes. Results: Our study identified 22 EMT-related genes with clinical prognostic value in colon cancer. On the basis of 22 EMT-related genes, we divided colon cancer into 2 different molecular subtypes by non-negative matrix factorization (NMF) model using 14 differentially expressed genes (DEGs), and the DEGs were enriched in multiple signaling pathways related to tumor metastasis process. Further analysis of EMT DEGs revealed that the PCOLCE2 and CXCL1 genes were characteristic genes for clinical prognosis of colon cancer. Conclusions: In this study, 22 prognostic genes were screened out from 200 EMT-related genes, and then the PCOLCE2 and CXCL1 molecules were finally focused on through the combination of the NMF molecular typing model and machine learning screening feature genes, suggesting that PCOLCE2 and CXCL1 may have good application potential. The findings provide a theoretical basis for the next clinical transformation in the treatment of colon cancer.

Construction of multifunctional carboxymethyl cellulose nanohydrogel carriers based on near-infrared DNA-templated quantum dots for tumor theranostics.

Multifunctional therapeutic platforms with targeted delivery, fast diagnosis, and efficient therapy could effectively reduce side effects and improve treatment in the clinical therapy of tumors. Near-infrared DNA-templated CdTeSe quantum dots (DNA-CdTeSe QDs) were developed as building blocks to construct a multifunctional carboxymethyl cellulose (CMC)-based nanohydrogel as a nanocarrier to address the challenges of serious side effects and precise treatment in cancer theranostics, including active tumor targeting, fluorescence tracking, controlled drug release, chemotherapy and gene regulation. Single-stranded DNA containing the complementarity sequence of miRNA and cystine, as co-crosslinkers, initiated hybridization between the DNA-CdTeSe QD-modified CMC chain with the anti-nucleolin aptamer DNA (AS1411)-modified CMC chain to form the hydrogels. DOX, as a model drug, was successfully incorporated into the hydrogels. The synthesized multifunctional hydrogel nanocarriers with an average diameter of 150 nm could be taken up through targeting and achieved the controlled release of DOX by triggering both glutathione (GSH) and miRNA in the tumor microenvironment. The CdTeSe QDs trapped in nanohydrogels acted as fluorophores for bioimaging in the diagnosis and treatment process. The proposed multifunctional delivery system provided a potential platform for tumor imaging and precise therapy.

Value of Lumbar MRI Parameters in the Evaluation of Postoperative Curative Effect on Patients with Lumbar Disc Herniation and Analysis of Risk Factors.

OBJECTIVE: For exploring the value of magnetic resonance imaging (MRI) parameters in the evaluation of postoperative curative effect on patients with lumbar disc herniation (LDH) and analyzing risk factors. METHODS: Totally 60 patients confirmed with LDH in our hospital between Jan. 2018 and Jan. 2020 were enrolled into the observation group (Obs group) given transforaminal endoscopic discectomy (TED). In addition, 60 individuals with low back pain but no LDH over the same time span were enrolled into the control group (Con group). The two groups were given lumbar MRI, and the cross-sectional area differences of bilateral psoas major muscle (BPMM) and multifidus muscle of the patients before and after therapy were evaluated. The visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) scores of the two groups before and after therapy were compared, and the associations of the cross-sectional area differences of BPMM and multifidus muscle with efficacy, VAS score, and JOA score were analyzed. According to MacNab criteria, the clinical efficacy on the patients was evaluated, on which the patients were grouped. In addition, logistic regression analysis was performed for analyzing risk factors of clinical efficacy, and receiver operating characteristic (ROC) curves were drawn for analyzing the value of risk factors with differences in clinical efficacy evaluation. RESULTS: The Obs group presented larger cross-sectional area differences of BPMM and multifidus muscle than the Con group (both P < 0.05). At 6 months after surgery, the Obs group showed a superior rate of 83.33%. In this group, patients with a superior efficacy showed smaller cross-sectional area differences of BPMM and multifidus muscle before surgery and at 6 months after surgery and got lower VAS scores and higher JOA scores than those without a superior efficacy (all P < 0.05). According to Pearson's correlation analysis, the cross-sectional area differences of BPMM and multifidus muscle before surgery and at 6 months after surgery were positively associated with VAS score and negatively associated with JOA score (both P < 0.05). According to logistic regression analysis, the cross-sectional area differences of BPMM and multifidus muscle were risk factors impacting the patients' prognosis. ROC curve-based analysis revealed that the cross-sectional area differences could be adopted as evaluation indexes for clinical efficacy on patients. CONCLUSION: The cross-sectional area differences of BPMM and multifidus muscle can serve as reference indexes for evaluating the postoperative efficacy on patients with LDH.

Changes of DCE-MRI Parameters in Patients with Rheumatoid Arthritis before and after Therapy and Their Value for the Efficacy Evaluation of Patients.

OBJECTIVE: To explore the changes of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in patients with rheumatoid arthritis (RA) before and after therapy and their value for the efficacy evaluation of patients. METHODS: Totally, 90 patients with RA confirmed in our hospital between January 2018 and January 2020 were enrolled. All of them were examined with a Siemens Magnetom Avanto 1.5T imaging system, and data about the rate of enhancement in early stage (REE) and steep slope maximum (SSmax) were obtained. Then, the disease activity score in 28 joints (DAS-28), REE, and SSmax were analyzed, and the associations of SSmax and REE with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and DAS-28 were investigated. Additionally, the patients were assigned to the acute-stage group and the chronic-stage group according to their time-signal intensity curves after therapy, and the two groups were compared in SSmax, REE, ESR, CRP, and DAS-28. Corresponding receiver operating characteristic (ROC) curves were drawn for the analysis of potential markers for efficacy improvement in patients. RESULTS: After therapy, REE, SSmax, ESR, DAS-28, and CRP in the synovium of all patients declined greatly (all P < 0.05), with higher levels observed in the acute-stage group than those in the chronic-stage group (all P < 0.05). SSmax and REE of patients were positively bound up with their ESR, CRP, and DAS-28 (all P < 0.05). Additionally, according to ROC curve-based analysis, both SSmax and REE can be adopted as biological indexes for distinguishing between patients at the acute phase from those at the chronic stage, and joint detection of them can boost the sensitivity of DAS-28. CONCLUSION: The SSmax and REE levels in RA patients after treatment were significantly decreased, and the levels in patients in the chronic phase were lower than those in patients in the acute phase. SSmax and REE are highly expressed in RA patients, and the combined detection can enhance the value of DAS-28 in the assessment of RA, and it is worthy of clinical promotion.

Aptamer-DNA concatamer-quantum dots based electrochemical biosensing strategy for green and ultrasensitive detection of tumor cells via mercury-free anodic stripping voltammetry.

A electrochemical biosensing strategy was developed for green and ultrasensitive detection of tumor cells by combining aptamer-DNA concatamer-CdTe quantum dots (QDs) signal amplification probe with mercury-free anodic stripping voltammetry (ASV). First, aptamer-DNA concatamer- CdTe QDs probes were designed by DNA hybridization and covalent assembling, which contained specific recognition of aptamer and signal amplification incorporating the DNA concatamer with QDs. Meanwhile, the capture electrode, glassy carbon electrode (GCE)/Graphene oxide (GO)/Polyaniline (PANI) / Glutaraldehyde (GA) / concanavalin A (Con A) was fabricated by a layer-by-layer assembling technique. K562 cells, as model cancer cells were detected to demonstrate the feasibility of this sensing strategy. Then, novel composite, graphene (GR)- Poly diallyldimethylammonium chloride (PDDA)/L-Cysteine (L- Cys), was explored in ASV which replaced mercury electrodes using for determination of tumor cells. The proposed electrochemical biosensor showed high sensitivity with the detection limit of 60 cells mL-1. More importantly, this novel design of signal amplification probes and the exploration of new composites in mercury-free ASV analysis would provide a promising method for ultrasensitive biosensor preparation and green electrochemical detection of tumor cells.

MicroRNA­25/ATXN3 interaction regulates human colon cancer cell growth and migration.

The present study aimed to investigate the function of microRNA­25 (miR­25) in human colon cancer cell viability and migration in addition to the underlying possible mechanisms. miR­25 expression was upregulated in patients with colon cancer compared with the control group. Reverse transcription­quantitative polymerase chain reaction and gene chip technology were used to analyze the alterations of miR­25 in patients with colon cancer. Cell viability and cell migration were analyzed using MTT and wound healing assays, respectively, apoptosis was analyzed using flow cytometry, and western blot analysis was conducted to determine the protein expression of ataxin­3 (ATXN3), apoptosis regulator Bax (Bax) and cyclin D1. Overexpression of miR­25 increased cell viability and migration, decreased apoptosis, decreased caspase­3/9 activity level in addition to decreased Bax protein expression, and increased cyclin D1 protein expression in colon cancer cells. Furthermore, miR­25 was demonstrated to target ATXN3 and suppress ATXN3 protein expression. Downregulation of miR­25 induced apoptosis of colon cancer cells via increased expression ATXN3. Small interfering­ATXN3 inhibited the anti­cancer effects of miR­25 downregulation in colon cancer. Collectively, the present results demonstrated that miR­25 promoted human colon cancer cell viability and migration by regulating ATXN3 expression.

Ultrasensitive electrochemical detection of tumor cells based on multiple layer CdS quantum dots-functionalized polystyrene microspheres and graphene oxide - polyaniline composite.

In this work, a novel ultrasensitive electrochemical biosensor was developed for the detection of K562 cell by a signal amplification strategy based on multiple layer CdS QDs functionalized polystyrene microspheres(PS) as bioprobe and graphene oxide(GO) -polyaniline(PANI) composite as modified materials of capture electrode. Due to electrostatic force of different charge, CdS QDs were decorated on the surface of PS by PDDA (poly(diallyldimethyl-ammonium chloride)) through a layer-by-layer(LBL) assemble technology, in which the structure of multiple layer CdS QDs increased the detection signal intensity. Moreover, GO-PANI composite not only enhanced the electron transfer rate, but also increased tumor cells load ratio. The resulting electrochemical biosensor was used to detect K562 cells with a lower detection limit of 3 cellsmL-1 (S/N = 3) and a wider linear range from 10 to 1.0 × 107 cellsmL-1. This sensor was also used for mannosyl groups on HeLa cells and Hct116 cells, which showed high specificity and sensitivity. This signal amplification strategy would provide a novel approach for detection, diagnosis and treatment for tumor cells.

Pharmacokinetics and cerebrospinal fluid penetration of norvancomycin in Chinese adult patients.

Norvancomycin is an antibiotic that has been approved for the treatment of infections caused by antibiotic-resistant Gram-positive bacteria and has been used in China for more than a decade. However, the cerebrospinal fluid (CSF) penetration of norvancomycin has not been evaluated. The aims of the study were (i) to investigate the pharmacokinetics and CSF penetration of norvancomycin in meningitis and non-meningitis patients and (ii) to recommend favourable dosing regimens in meningitis patients. Twenty adult patients (ten with meningitis and ten without meningitis) requiring norvancomycin treatment were enrolled. All patients received a norvancomycin regimen of 800 mg every 12 h. Blood and CSF samples were consecutively collected up to 12 h after the end of the fourth 60-min infusion. Norvancomycin concentrations both in serum and CSF were measured using a high-performance liquid chromatography (HPLC) assay. CSF penetration of norvancomycin was evaluated by calculating the CSF/serum ratio. Mean norvancomycin serum trough levels were 9.9 ± 1.44 µg/mL in patients with meningitis and 10.08 ± 1.12 µg/mL in patients without meningitis (P > 0.05). In addition, norvancomycin penetrated into the inflamed meninges, with mean CSF concentrations of 3.93-10.52 µg/mL and mean CSF/serum ratios of 0.18-0.43, both of which were significantly higher than in patients without meningitis (P <0.05). These results suggest that norvancomycin has higher CSF penetration in patients with meningitis compared with other groups and that norvancomycin is effective in treating patients with purulent meningitis at a comparably low dose.

[The effect of sandfly control on the transmission of visceral leishmaniasis].

OBJECTIVE: To observe the effect of Phlebotomus chinensis control including insecticide residual spraying in the habitats and bathing for dogs on the transmission of visceral leishmaniasis in Nanping of Sichuan Province. METHODS: Alpha-methrin with a dosage of 50 mg/m2 was sprayed in the wild caves and 2.5% deltamethrin wettable power at a concentration of 250 mg/L was applied for dog bathing in the villages. The density of sandflies in the natural caves was examined and data on the incidence of visceral leishmaniasis were collected from epidemiological survey following the sandfly control measures. RESULTS: The density of sandflies has been considerably reduced after the chemical spraying in caves, the important habitats of the sandflies. By both the cave spraying and bathing for dogs since 1993, the reported human cases of leishmaniasis also decreased. CONCLUSION: Measures for sandfly control including insecticide spraying in the habitats and bathing for dogs with insecticide solution can significantly reduce the sandfly density, and can contain the transmission of visceral leishmaniasis in the endemic area.