A novel vector for magnetic resonance imaging-guided chemo-photothermal therapy for cancer.

As an effective strategy for oncotherapy, developing efficacious drug delivery systems for cancer combination therapy remains a major challenge. To improve nanodrug biocompatibility and composite function facilitating their clinical conversion application, a novel nanocarrier was presented by a facile method through conjugating humic acid with gadolinium ions to synthesize HA-Gd with good biocompatibility and dispersity. HA-Gd exhibited high photothermal conversion efficiency up to 38%, excellent photothermal stability, and high doxorubicin (DOX) loading capacity (93%) with pH-responsive release properties. HA-Gd loading DOX showed a combined chemo-photothermal inhibitory effect on tumor cells. Compared with lipid-DOX, HA-Gd-DOX had a more significant inhibitory effect on tumor growth and fewer side effects. T1-weighted MRI contrast toward tumor tissue provided HA-Gd with an MRI-based cancer diagnosis. This study revealed the great potential of humic acids as a novel vector for developing more drug carriers with desirable functions for clinical anticancer therapy.

Lung transcriptome analysis for the identification of genes involved in the hypoxic adaptation of plateau pika (Ochotona curzoniae).

The plateau pika, a typical hypoxia-tolerant mammal lives 3000-5000 m above sea level on the Qinghai-Tibet Plateau, has acquired many physiological and morphological characteristics and strategies in its adaptation to sustained, high-altitude hypoxia. Blunted hypoxic pulmonary vasoconstriction is one such strategy, but the genes involved in this strategy have not been elucidated. Here, we investigated the genes involved and their expression profiles in the lung transcriptome of plateau pikas subjected to different hypoxic conditions (using low-pressure oxygen cabins). A slight, right ventricular hypertrophy was observed in pikas of the control group (altitude: 3200 m) vs. those exposed to 5000 m altitude conditions for one week. Our assembly identified 67,774 genes; compared with their expression in the control animals, 866 and 8364 genes were co-upregulated and co-downregulated, respectively, in pikas subjected to 5000 m altitude conditions for 1 and 4 w. We elucidated pathways that were associated with pulmonary vascular arterial pressure, including vascular smooth muscle contraction, HIF-1 signalling, calcium signalling, cGMP-PKG signalling, and PI3K-Akt signalling based on the differentially expressed genes; the top-100 pathway enrichments were found between the control group and the group exposed to 5000 m altitude conditions for 4 w. The mRNA levels of 18 candidate gene showed that more than 83% of genes were expressed and the number of transcriptome The up-regulated genes were EPAS1, Hbα, iNOS, CX40, CD31, PPM1B, HIF-1α, MYLK, Pcdh12, Surfactant protein B, the down-regulated genes were RYR2, vWF, RASA1, CLASRP, HIF-3α. Our transcriptome data are a valuable resource for future genomic studies on plateau pika.

Testosterone-retinoic acid signaling directs spermatogonial differentiation and seasonal spermatogenesis in the Plateau pika (Ochotona curzoniae).

During evolution, animals optimize their reproductive strategies to increase offspring survival. Seasonal breeders reproduce only during certain times of the year. In mammals, reproduction is tightly controlled by hypothalamus-pituitary-gonad axis. Although pathways regulating gametogenesis in non-seasonal model species have been well established, molecular insights into seasonal reproduction are severely limited. Using the Plateau pika (Ochotona curzoniae), a small rodent animal species native to the Qinghai-Tibetan plateau, as a model, here we report that seasonal spermatogenesis is governed at the level of spermatogonial differentiation. In testis of the reproductively dormant animals, undifferentiated spermatogonia failed to differentiate and accumulated in the seminiferous tubules. RNA-seq analyses of the active and dormant testes revealed that genes modulating retinoic acid biogenesis and steriodogenesis were differentially regulated. A single injection of all-trans retinoic acid (ATRA) reinitiated spermatogenesis and inhibition the function of RA-degrading enzyme CYP26B1 for 10 days induced spermatogonial differentiation. Strikingly, testosterone injection reinitiated spermatogenesis in short day adapted animals. Testosterone provides a permissive environment of RA biogenesis and actions in testis, therefore, indirectly controls spermatogonial differentiation. Collectively, these findings provide a key mechanistic insight regarding the molecular regulation of seasonal reproduction in mammals.

[Study on the relationship between 22q11 microdeletion and congenital heart disease].

To investigate if microdeletion of chromosome 22q11 is an epidemiologically important cause of congenital heart disease (CHD), we studied 25 cases with CHD phenotypes. Venous blood samples were tested by fluorescence in situ hybridization (FISH) for microdeletion of 22q11. Among 23 cases with simple CHD, 19 were shown not to have microdeletion of 22q11 and the other 4 cases were shown to have 22q11 microdeletion. Microdeletion of 22q11 was found in 2 cases with Tetralogy of Fallot (TOF) accompanied by multiple malformations. The results suggested that microdeletion of 22q11 was associated with CHD.