AimFetal bowel dilatation (FBD) in the late trimester of pregnancy can be related with varies of prognosis. Our aims were to obtain antenatal factors that might have relevance for the distinct prognosis with FBD.MethodsSeven features of 68 pregnancies presented with FBD were assessed. The best cut‐off value to predict intestinal outcomes was selected using receiver‐operating characteristics curves, and the effective variables were included into a logistic regression model.ResultsThe best cut‐off valves to predict intestinal pathologies were 14.5 mm of fetus dilated loop and 37.7 weeks of gestational age at delivery, respectively. The congenital gastrointestinal tract anomalies included 24 cases (92.3%) of intestine atresia, 1 case (3.85%) of small intestine volvulus and 1 case (3.85%) of midgut malrotation.ConclusionFetal dilated loops and gestational age at delivery are both an independent risk factor for predicting intestinal pathologies of newborns, which should arouse high attention.
Autophagy is elevated in colorectal cancer (CRC) and is generally associated with poor prognosis. However, the role of autophagy core-protein Beclin 1 remains controversial in CRC development. Here, we show that the expression of nuclear Beclin 1 protein is upregulated in CRC with a negative correlation to retinoblastoma (RB) protein expression. Silencing of BECN1 upregulates RB resulting in cell cycle G1 arrest and growth inhibition of CRC cells independent of p53. Furthermore, ablation of BECN1 inhibits xenograft tumor growth through elevated RB expression and reduced autophagy, while simultaneous silencing of RB1 restores tumor growth but has little effect on autophagy. Mechanistically, knockdown of BECN1 promotes the complex formation of MDM2 and MDMX, resulting in MDM2-dependent MDMX instability and RB stabilization. Our results demonstrate that nuclear Beclin 1 can promote cell cycle progression through modulation of the MDM2/X-RB pathway and suggest that Beclin 1 promotes CRC development by facilitating both cell cycle progression and autophagy.
Ac onvenient and divergenta pproach was developed to prepare diverse bacterial 3-deoxy-d-manno-oct-2ulosonic acid (Kdo) oligosaccharides containing aK do-a-(2!4)-Kdo fragment. The orthogonal protected a-(2!4) linked Kdo-Kdo disaccharide 3,s erving as ac ommon precursor,w as divergently transformed into the corresponding 8-, 8'-, and4 '-hydroxy disaccharides 5, 7,a nd 14,r espectively.Then, these alcohols were glycosylated, respectively,w ith the 5,7-O-di-tert-butylsilylene (DTBS) protected Kdo thioglycoside donors 1 or 2 in an a-stereoselective and high-yielding manner to afford ar ange of Kdo oligosaccharides. Finally,r emoval of all protecting groupso ft he newly formed glycosides resulted in the desired freeK do oligomer.
Non-small cell lung cancers (NSCLC) frequently contain KRAS mutation but retain wild-type TP53. Abundant senescent cells are observed in premalignant but not in malignant tumors derived from the Kras-driven mouse model, suggesting that KRAS oncogenic signaling would have to overcome the intrinsic senescence burden for cancer progression. Here, we show that the nuclear Beclin 1-mediated inhibition of p53-dependent senescence drives Kras-mediated tumorigenesis. KRAS activates USP5 to stabilize nuclear Beclin 1, leading to MDM2-mediated p53 protein instability. KrasG12D mice lacking Beclin 1 display retarded lung tumor growth. Knockdown of USP5 or knockout of Becn1 leads to increased senescence and reduced autophagy. Mechanistically, KRAS elevates ROS to induce USP5 homodimer formation by forming the C195 disulfide bond, resulting in stabilization and activation of USP5. Together, these results demonstrate that activation of the USP5-Beclin 1 axis is pivotal in overriding intrinsic p53-dependent senescence in Kras-driven lung cancer development.
ObjectivesTo investigate twin reversed arterial perfusion (TRAP) sequence for the prediction of TRAP-related adverse pregnancy outcomes at the gestational age of 11-14 weeks.
MethodsPregnant women in the rst trimester diagnosed with TRAP were recruited at West China Second University Hospital from January 2015 to June 2018. Systematic screening for the pump twin's crownrump length (CRL) and acardiac twin's upper pole-rump length (URL) was conducted using ultrasonic detection. The (CRL-URL)/CRL and URL/CRL ratios were used to assess the pregnancy outcomes for the pump twin.
ResultsTwenty-one pregnant women aged 21-39 years with a gestation of 11-14 weeks were recruited. TRAP was diagnosed on average (± standard deviation [SD]) at pregnancy week 13.1 ± 0.18. The pump twins' mean (± SD) CRL was 6.65 ± 1.1 cm. The incidence of intrauterine death for the pump twins was 19.0% (n=4), the miscarriage rate was 14.3% (n=3), and the live birth rate was 66.7% (n=14). The (CRL-URL)/CRL ratios between the non-survival (intrauterine death and miscarriage) and survival groups signi cantly differed (0.33 ± 0.08 vs. 0.58 ± 0.08, p < 0.05). Similarly, the URL/CRL ratios between the non-survival and survival groups signi cantly differed (0.67 ± 0.08 vs. 0.42 ± 0.08, p < 0.05).
ConclusionsThe (CRL-URL)/CRL and URL/CRL ratios were valuable indicators for determining pregnancy outcomes of pump twins with TRAP at an early gestational age.
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