sj-docx-1-cre-10.1177_02692155241235336 - Supplemental material for Transcranial direct current stimulation for upper extremity motor dysfunction in poststroke patients: A systematic review and meta-analysis

Supplemental material, sj-docx-1-cre-10.1177_02692155241235336 for Transcranial direct current stimulation for upper extremity motor dysfunction in poststroke patients: A systematic review and meta-analysis by Xian Tang, Nan Zhang, Zhiyuan Shen, Xin Guo, Jun Xing, Shujuan Tian and Yuan Xing in Clinical Rehabilitation</p

Enhanced Tumor Retention Effect by Click Chemistry for Improved Cancer Immunochemotherapy

Because of the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce uptake by reticuloendothelial system and to enhance the permeability and retention effect. Herein, we demonstrated Cu­(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues. In addition, combined doxorubicin with the adjuvant monophosphoryl lipid A, an agonist of toll-like receptor4, generated immunogenic cell death, which further promoted maturity of dendritic cells, antigen presentation and induced strong effector T cells in vivo. Following combined with anti-PD-L1 therapy, substantial antitumor and metastasis inhibitory effects were achieved because of the reduced PD-L1 expression and regulatory T cells. In addition, effective long-term immunity from memory T cell responses protected mice from tumor recurrence

Increased Gold Nanoparticle Retention in Brain Tumors by <i>in Situ</i> Enzyme-Induced Aggregation

The treatment of brain tumors remains a challenge due to the limited accumulation of drugs and nanoparticles. Here, we triggered the aggregation of gold nanoparticles (AuNPs) using legumain to enhance the retention of chemotherapeutics in brain tumors. This nanoplatform, AuNPs-A&C, is comprised of Ala-Ala-Asn-Cys-Lys modified AuNPs (AuNPs-AK) and 2-cyano-6-aminobenzothiazole modified AuNPs (AuNPs-CABT). AuNPs-AK could be hydrolyzed to expose the 1,2-thiolamino groups on AuNPs-AK in the presence of legumain, which occurs by a click cycloaddition with the contiguous cyano group on AuNPs-CABT, resulting in formation of AuNPs aggregates. This strategy led to an enhanced retention of the AuNPs in glioma cells both <i>in vitro</i> and <i>in vivo</i> due to the blocking of nanoparticle exocytosis and minimizing nanoparticle backflow to the bloodstream. After conjugation of doxorubicin (DOX) <i>via</i> a pH-sensitive linker to AuNPs-A&C, the efficiency for treating glioma was improved. The median survival time for the DOX-linked AuNPs-A&C increased to 288% in comparison to the saline group. We further show the use of the AuNPs-A&C for optical imaging applications. In conclusion, we provide a strategy to increase nanoparticle tumor accumulation with the potential to improve therapeutic outcome

Phylogenetic neighbor-joining tree for HIV-1 pol sequences obtained from DBSs of MSM in Hong Kong.

<p>The reference sequences for classifying HIV-1 genotypes were included and were originally obtained from the NIH/NIAID–funded HIV Databases. The source of HIV-1 strains is color-coded. The horizontal branch was drawn in accordance with their relative genetic distances as indicated by the bar scale. The vertical lines are purely for clarity of the tree presentation.</p

Sexually transmitted diseases (STDs) among MSM in Hong Kong from March 2010 to February 2011.

<p>The unknown groups refer to the participants who had not been tested; these participants were excluded from the analysis.</p><p>‡Comparison of distribution between HIV-1 positive versus HIV-1 negative in each subcategory. Chi-square test when all cell frequency>10, otherwise Fisher’s exact test was employed. Bold numbers indicate statistical significance.</p><p>Sexually transmitted diseases (STDs) among MSM in Hong Kong from March 2010 to February 2011.</p

Vaccine protection against lethal challenge of pathogenic A/BhG/QH/1/05 virus.

<p>BALB/c mice were vaccinated twice with MVTT_HA-QH via intranasal, oral and intramuscular routes, respectively. The vaccinated animals were challenged with 100 MLD₅₀ A/BhG/QH/1/05 three weeks after the second immunization. Mice who received PBS were used as controls.</p

Sequence variation of HA gene of H5N1 influenza viruses at the indicated antigenic sites.

<p> Notes: The amino acid positions are based on mature H5 sequences. Three live viral strains that are included in this study are in bold.</p><p> Human isolates are in italic. The asterisk indicates a few WHO-recommended vaccine strains.</p><p> Abbreviations: RBS, receptor binding site; Gly, glycosylation site; BHG, bar-headed goose; Jpn-WE, Japanese white-eye.</p

The antibody level of immunized mice via HI and NT experiments.

<p>*, i.n.: intranasal. i.m.: intramuscular.</p>†<p>dpv: day post primary vaccination.</p>‡<p>the separated values represent different antibody levels were detected. N/A: not available.</p

The schematic representation of MVTT_-HA-QH and MVTT_-HA-AH construction and the expression of the HA protein in cells infected with MVTT_-HA-QH or MVTT_-HA-AH.

<p>(A) The HA gene was introduced, together with GFP gene or RFP gene, each under a separate promoter, into the genome of MVTT. The restriction enzymes Bam HI and Xho I were used for constructing MVTT_-HA-QH and MVTT_-HA-AH. The insertion region corresponds to the Del III region of MVA. (B) The HA protein was detected on Vero cells infected with MVTT_-HA-QH or MVTT_-HA-AH using mouse anti-HA serum in an immunohistochemical staining assay. No HA protein expression was detected on Vero cells infected with the control virus MVTT_SIV. (C) The full length HA gene was detected in the total DNA extracted from Vero cells infected MVTT_-HA-QH and MVTT_-HA-AH using specific primers for H5N1 Qinghai or Anhui strain. No H5 gene was detected in total DNA extracted from Vero cells infected control virus MVTT_SIV using both primers.</p

HA-specific Nab and IFN-γ-secreting CD8⁺ T-cell responses to MVTT_HA-QH or MVTT_HA-AH vaccinations.

<p>BALB/c mice were vaccinated three times or twice with MVTT_HA-QH (A) or MVTT_HA-AH (B, C), respectively, at three-week intervals via intranasal (I.N.) and intramuscular (I.M.) inoculations, respectively. The antiserum was collected at two weeks after each vaccination for analysis of HA-specific Nabs against H5N1 Qinghai strain (<b>A, C</b>) or Anhui strain (<b>B</b>), respectively. Control animals were given MVTT_S via the same corresponding routes. (<b>D</b>) Splenocytes of immunized mice were obtained after two immunizations and assessed by an ELIspot assay using a specific peptide (HA 9mer) or an irrelevant peptide (HIV Gag 9mer). <i>P</i><0.01, MVTT_HA-QH vs. MVTT_S.</p