Aerobic glycolysis has pleiotropic roles in the pathogenesis of hepatocellular carcinoma (HCC). Emerging studies revealed key promoters of aerobic glycolysis, however, little is known about its negative regulators in HCC. In this study, an integrative analysis identifies a repertoire of differentially expressed genes (DNASE1L3, SLC22A1, ACE2, CES3, CCL14, GYS2, ADH4, and CFHR3) that are inversely associated with the glycolytic phenotype in HCC. ACE2, a member of the rennin-angiotensin system, is revealed to be downregulated in HCC and predicts a poor prognosis. ACE2 overexpression significantly inhibits the glycolytic flux as evidenced by reduced glucose uptake, lactate release, extracellular acidification rate, and the expression of glycolytic genes. Opposite results are noticed in loss-of-function studies. Mechanistically, ACE2 metabolizes Ang II to Ang-(1-7), which activates Mas receptor and leads to the phosphorylation of Src homology 2-containing inositol phosphatase 2 (SHP-2). SHP2 activation further blocks reactive oxygen species (ROS)-HIF1α signaling. Addition of Ang-(1-7) or the antioxidant N-acetylcysteine compromises in vivo additive tumor growth and aerobic glycolysis induced by ACE2 knockdown. Moreover, growth advantages afforded by ACE2 knockdown are largely glycolysis-dependent. In clinical settings, a close link between ACE2 expression and HIF1α or the phosphorated level of SHP2 is found. Overexpression of ACE2 significantly retards tumor growth in patient-derived xenograft model. Collectively, our findings suggest that ACE2 is a negative glycolytic regulator, and targeting the ACE2/Ang-(1-7)/Mas receptor/ROS/HIF1α axis may be a promising therapeutic strategy for HCC treatment.

Because current mainstream anti-glycolipid GD2 therapeutics for neuroblastoma (NB) have limitations, such as severe adverse effects, improved therapeutics are needed. In this study, we developed a GD2 aptamer (DB99) and constructed a GD2-aptamer-mediated multifunctional nanomedicine (ANM) with effective, precise, and biocompatible properties, which functioned both as chemotherapy and as gene therapy for NB. DB99 can bind to GD2⁺ NB tumor cells but has minimal cross-reactivity to GD2⁻ cells. Furthermore, ANM is formulated by self-assembly of synthetic aptamers DB99 and NB-specific MYCN small interfering RNA (siRNA), followed by self-loading of the chemotherapeutic agent doxorubicin (Dox). ANM is capable of specifically recognizing, binding, and internalizing GD2⁺, but not GD2⁻, NB tumor cells in vitro. Intracellular delivery of ANM activates Dox release for chemotherapy and MYCN-siRNA-induced MYCN silencing. ANM specifically targets, and selectively accumulates in, the GD2⁺ tumor site in vivo and further induces growth inhibition of GD2⁺ tumors in vivo; in addition, ANM generates fewer or no side effects in healthy tissues, resulting in markedly longer survival with fewer adverse effects. These results suggest that the GD2-aptamer-mediated, targeted drug delivery system may have potential applications for precise treatment of NB.

Increased cortisol has been shown to be negatively correlated with infant motor development. Sunlight help decrease the level of cortisol. Vitamin D is associated with infant motor development. The present study aimed to determine whether natural sunlight exposure plus vitamin D supplements could ameliorate delayed early motor development in little infants from maternal perinatal depression. The term pregnant women waiting for delivery from the department of gynecology and obstetrics were assessed depressive symptoms by Hamilton Rating Scale for Depression (HAMD). 120 normal and 229 depressed subjects were recruited. During 2 days postpartum, infant motor development were assessed by Neonatal Behavioral Assessment Scale (NBAS). Infants of 2-day-old in maternal depression group were divided into four groups: control group, conventional vitamin D supplements (400IU/d) group, high dose of vitamin D supplements group (1000IU/d), sunlight plus conventional vitamin D supplement group (400IU/d). Serum and hair cortisol (HairF) in mothers and infants were measured. The infants of perinatal depressed mothers displayed early motor developmental delay accompanied by increased cortisol. Sunlight plus conventional vitamin D supplement (400IU/d) were better than exclusive vitamin D supplements for the amelioration delayed early motor development in infants (p < 0.05). The infants exposure to sunlight 7-14 h/week plus conventional vitamin D supplement reached the best scores of motor development and the lowest HairF (p < 0.05). We should have measured the serum 25OH-vitamin D concentrations. Sunlight plus vitamin D supplements could ameliorate delayed early motor development in little infants by decreasing cortisol from perinatal depression.

To investigate the effect and safety of endovascular embolization of tiny aneurysms (≤3 mm) within 72 h of subarachnoid hemorrhage compared with larger ones. Patients with intracranial aneurysms treated with endovascular embolization within 72 h were retrospectively enrolled and divided into group A (n = 33) with ruptured tiny aneurysms (≤3 mm) and group B (n = 244) with ruptured larger aneurysms (>3 mm). The clinical and angiographic data before and after embolization were analyzed. Most tiny aneurysms were located at the posterior communicating artery (36.4%) followed by anterior communicating artery (18.2%). The stent-assisted coiling technique was used mostly in group A with 18 stents deployed (51.5%), but only 24 (9.8%) patients had stent-assisted coiling in group B, with the stent-assisted coiling technique more significantly (P < 0.001) frequently used in group A. No significant (P > 0.05) difference existed in the total, subtotal and incomplete occlusion of aneurysms in two groups. The procedure-related complication rate was not significantly (P > 0.05) different between groups A (24.2%) and B (17.0%). At discharge, no significant (P > 0.05) difference existed in the neurological abnormality between the two groups. Follow-up was performed in 64.5% (20/31) in group A and 75.6% (177/234) in group B. No significant (P > 0.05) difference existed in the aneurysm recurrence rate, deaths, and prognosis. Early embolization of tiny cerebral aneurysms within 72 h of subarachnoid hemorrhage is safe and effective compared with ruptured large aneurysms treated in the same manner.