Injectable and Self-Healing Thermosensitive Magnetic Hydrogel for Asynchronous Control Release of Doxorubicin and Docetaxel to Treat Triple-Negative Breast Cancer

Integration of two or more drugs into a multiagent delivery system has been considered to have profound impact on both in vitro and in vivo cancer treatment due to their efficient synergistic effect. This study presents a cheap and simple chitosan hydrogel cross-linked with telechelic difunctional poly­(ethylene glycol) (DF-PEG-DF) for synthesis of an injectable and self-healing thermosensitive dual-drug-loaded magnetic hydrogel (DDMH), which contains both doxorubicin (DOX) and docetaxel (DTX) for chemotherapy and iron oxide for magnetic hyperthermia induced stimuli responsive drug release. The as-prepared DDMH not only have good biocompatibility but also exhibit unique self-healing, injectable, asynchronous control release properties. Meanwhile, it shows an excellent magnetic field responsive heat-inducing property, which means that DDMH will produce a large amount of heat to control the surrounding temperature under the alternative magnetic field (AMF). A remarkably improved synergistic effect to triple negative breast cancer cell line is obtained by comparing the therapeutic effect of codelivery of DOX and DTX/PLGA nanoparticles (DTX/PLGA NPs) with DOX or DTX/PLGA NPs alone. In vivo results showed that DDMH exhibited significant higher antitumor efficacy of reducing tumor size compared to single drug-loaded hydrogel. Meanwhile, the AMF-trigger control release of drugs in codelivery system has a more efficient antitumor effect of cancer chemotherapy, indicating that DDMH was a promising multiagent codelivery system for synergistic chemotherapy in the cancer treatment field

Association Study of Gene LPP in Women with Polycystic Ovary Syndrome

<div><h3>Background</h3><p>Previous genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in Han Chinese population has found that SNPs in <em>LPP</em> gene were nominally significant in PCOS patients (P around 10E-05). Replication of the GWAS was applied to further confirm the relationship between <em>LPP</em> gene and PCOS.</p> <h3>Methods</h3><p>Three polymorphisms of <em>LPP</em> gene (rs715790, rs4449306, rs6782041) were selected and replicated in additional 1132 PCOS cases and 1142 controls. Genotyping of <em>LPP</em> gene was carried out by Taqman-MGB method.</p> <h3>Results</h3><p>In rs715790, the allele frequency is significantly different between the PCOS group and the control group. Meta-analysis showed that the allele frequencies of the three SNPs rs715790 (P_meta = 1.89E-05, OR = 1.23), rs4449306 (P_meta = 3.0E-04, OR = 1.10), rs6782041 (P_meta = 2.0E-04, OR = 1.09), were significantly different between PCOS cases and controls.</p> <h3>Conclusions</h3><p>Our results suggest that <em>LPP</em> gene might be a novel candidate for PCOS.</p> </div

Allele frequencies in PCOS cases and controls.

<p>Risk allele is shown in bold type.</p><p>GWAS: Genome-Wide Association Study.</p><p>OR: odds ratio.</p><p>The GWAS data and Replication data were combined.</p><p>Meta-analysis was performed to analyze the combined data.</p><p>OR_meta: odds ratio by meta-analysis.</p><p>P_meta: P value by meta-analysis.</p

Characteristics comparison in PCOS cases using dominant model of rs715790.

<p>Risk allele group is TT plus TC, and the non-risk allele group is CC.</p><p>Characteristics were presented by mean±Std.</p><p>P_adjusted is calculated by logistic regression analysis taking BMI as covariant.</p><p>BMI: body mass index; T: testosterone; GLU: glucose; INS: insulin; HOMA-IR: homeostasis model assessment-insulin resistance.</p

Genotype frequencies in PCOS cases and controls.

<p>Risk allele is shown in bold type.</p><p>P_add: P value of additive model (three genotypes).</p><p>P_dom: P value of dominant model [(homozygotes of risk allele + heterozygotes) vs. homozygotes of non-risk allele].</p><p>P_rec : P value of recessive model [homozygotes of risk allele vs.(heterozygotes+ homozygotes of non-risk allele)].</p

Controllability of the Conductive Filament in Porous SiO_<i>x</i> Memristors by Humidity-Mediated Silver Ion Migration

Oxide-based memristors composed of Ag/porous SiOx/Si stacks are fabricated using different etching time durations between 0 and 90 s, and the memristive properties are analyzed in the relative humidity (RH) range of 30–60%. The combination of humidity and porous structure provides binding sites to control silver filament formation with a confined nanoscale channel. The memristive properties of devices show high on/off ratios up to 108 and a dispersion coefficient of 0.1% of the high resistance state (CHRS) when the RH increases to 60%. Humidity-mediated silver ion migration in the porous SiOx memristors is investigated, and the mechanism leading to the synergistic effects between the porous structure and environmental humidity is elucidated. The artificial neural network constructed theoretically shows that the recognition rate increases from 60.9 to 85.29% in the RH range of 30–60%. The results and theoretical understanding provide insights into the design and optimization of oxide-based memristors in neuromorphic computing applications

Foliar Exposure of Cu(OH)₂ Nanopesticide to Basil (<i>Ocimum basilicum</i>): Variety-Dependent Copper Translocation and Biochemical Responses

In this study, low and high anthocyanin basil (<i>Ocimum basilicum</i>) varieties (LAV and HAV) were sprayed with 4.8 mg Cu/per pot from Cu­(OH)₂ nanowires, Cu­(OH)₂ bulk (CuPro), or CuSO₄ and cultivated for 45 days. In both varieties, significantly higher Cu was determined in leaves of CuSO₄ exposed plants (691 and 672.6 mg/kg for LAV and HAV, respectively); however, only in roots of HAV, Cu was higher, compared to control (<i>p</i> ≤ 0.05). Nanowires increased <i>n</i>-decanoic, dodecanoic, octanoic, and nonanoic acids in LAV, but reduced <i>n</i>-decanoic, dodecanoic, octanoic, and tetradecanoic acids in HAV, compared with control. In HAV, all compounds reduced eugenol (87%), 2-methylundecanal (71%), and anthocyanin (3%) (<i>p</i> ≤ 0.05). In addition, in all plant tissues, of both varieties, nanowires and CuSO₄ reduced Mn, while CuPro increased chlorophyll contents, compared with controls (<i>p</i> ≤ 0.05). Results suggest that the effects of Cu­(OH)₂ pesticides are variety- and compound-dependent

Transcriptional activity of <i>PLCz</i> promoter with recombinant haplotypes in MLTC-1 cells.

<p><b>A.</b> 5′-flanking region of bovine <i>PLCz</i> gene, as identified using the NCBI database. The base numbers are relative to the A of TSS. The red box color represents exon 1. g.−456 G>A and g. +65 T>C are located in the 5′-flanking region (−2290 nt to +112 nt) of <i>PLCz</i>. Other numbers represent primer positions for the cloning reporter constructs. <b>B.</b> TA1 fragments with different haplotypes (H2, H3, H4, and H1) were amplified by PCR to generate the reporter constructs; the various recombinant haplotypes are shown above the line. Each fragment was cloned into the pGL3 basic vector and transfected into MLTC-1 cells. <b>C.</b> Transcriptional activities of the <i>PLCz</i> promoter with various haplotypes were measured by dual luciferase assays. For each construct, individual plasmid DNA extracted from 6 to 9 colonies was used. Results are presented as the average fold change of firefly luciferase activity versus the <i>Renilla</i> control vector (mean±S.D., <i>n</i> = 6 to 9) (* indicates <i>P</i><0.05, ** indicates <i>P</i><0.01 vs. H2).</p

Genetic variation in the 5′-flanking sequence and PCR-RFLP patterns of the two bovine <i>PLCz</i> loci.

<p>Patterns for g. −456 G>A: genotypes CC, TC, and TT; patterns for g. +65 T>C: genotypes AA, GA, and GG. Digested products smaller than 50 bp are not shown. M: Marker.</p

Performance of prostate cancer diagnostic models.

The lack of accuracy in the current prostate specific antigen (PSA) test for prostate cancer (PCa) screening causes around 60–75% of unnecessary prostate biopsies. Therefore, alternative diagnostic methods that have better accuracy and can prevent over-diagnosis of PCa are needed. Researchers have examined various potential biomarkers for PCa, and of those fatty acids (FAs) markers have received special attention due to their role in cancer metabolomics. It has been noted that PCa metabolism prefers FAs over glucose substrates for continued rapid proliferation. Hence, we proposed using a urinary FAs based model as a non-invasive alternative for PCa detection. Urine samples collected from 334 biopsy-designated PCa positive and 232 biopsy-designated PCa negative subjects were analyzed for FAs and lipid related compounds by stir bar sorptive extraction coupled with gas chromatography/mass spectrometry (SBSE-GC/MS). The dataset was split into the training (70%) and testing (30%) sets to develop and validate logit models and repeated for 100 runs of random data partitioning. Over the 100 runs, we confirmed the stability of the models and obtained optimal tuning parameters for developing the final FA based model. A PSA model using the values of the patients’ PSA test results was constructed with the same cohort for the purpose of comparing the performances of the FA model against PSA test. The FA final model selected 20 FAs and rendered an AUC of 0.71 (95% CI = 0.67–0.75, sensitivity = 0.48, and specificity = 0.83). In comparison, the PSA model performed with an AUC of 0.51 (95% CI = 0.46–0.66, sensitivity = 0.44, and specificity = 0.71). The study supports the potential use of urinary FAs as a stable and non-invasive alternative test for PCa diagnosis.</div