Arildsenyang0352

Pebbles of millimeter sizes are abundant in protoplanetary discs around young stars. Chondrules inside primitive meteorites-formed by melting of dust aggregate pebbles or in impacts between planetesimals-have similar sizes. The role of pebble accretion for terrestrial planet formation is nevertheless unclear. Here, we present a model where inward-drifting pebbles feed the growth of terrestrial planets. The masses and orbits of Venus, Earth, Theia (which later collided with Earth to form the Moon), and Mars are all consistent with pebble accretion onto protoplanets that formed around Mars' orbit and migrated to their final positions while growing. The isotopic compositions of Earth and Mars are matched qualitatively by accretion of two generations of pebbles, carrying distinct isotopic signatures. Last, we show that the water and carbon budget of Earth can be delivered by pebbles from the early generation before the gas envelope became hot enough to vaporize volatiles.Cancer fibrosis serves as a major therapeutic barrier in desmoplastic tumors. Relaxin (RLN; a systemic hormone) is efficacious to decrease fibrosis, but the in vivo mechanism of action is not clear. Considering the localization of relaxin family peptide receptor type 1 (RXFP1), the receptor for RLN, on macrophages, we hypothesize that macrophages can be modulated by RLN to ameliorate cancer fibrosis. Using KPC mouse model of pancreatic ductal adenocarcinoma (PDAC), here, we report locally expressed RLN with targeted gene delivery induces increased F4/80+CD206+ macrophages originating from Ly6C+ monocytes, promoting fibrosis depletion and cytotoxic T cell infiltration. Moreover, RLN gene delivery synergizes with PD-L1 blockade for tumor inhibition by enhancing T cell-mediated tumor cell killing and macrophage phagocytosis. Collectively, our results reveal previously unidentified insights into the modulation of macrophages to regulate tumor-associated fibrosis, providing a feasible strategy to reverse the immunosuppressive environment and improve the therapeutic outcome of checkpoint immunotherapies.Loss-of-function mutations of DNAJC6, encoding HSP40 auxilin, have recently been identified in patients with early-onset Parkinson's disease (PD). To study the roles of DNAJC6 in PD pathogenesis, we used human embryonic stem cells with CRISPR-Cas9-mediated gene editing. Here, we show that DNAJC6 mutations cause key PD pathologic features, i.e., midbrain-type dopamine (mDA) neuron degeneration, pathologic α-synuclein aggregation, increase of intrinsic neuronal firing frequency, and mitochondrial and lysosomal dysfunctions in human midbrain-like organoids (hMLOs). In addition, neurodevelopmental defects were also manifested in hMLOs carrying the mutations. Transcriptomic analyses followed by experimental validation revealed that defects in DNAJC6-mediated endocytosis impair the WNT-LMX1A signal during the mDA neuron development. Furthermore, reduced LMX1A expression during development caused the generation of vulnerable mDA neurons with the pathologic manifestations. These results suggest that the human model of DNAJC6-PD recapitulates disease phenotypes and reveals mechanisms underlying disease pathology, providing a platform for assessing therapeutic interventions.

The thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed.

To compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth.

Multicentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals.

Infants with estimated birth weight <1500 g and/or gestational age <30

weeks.

Thermal management with or without a thermal servo-controlled system during stabilisation in the delivery room.

Proportion of normothermia at NICU admission (axillary temperature 36.5°C-37.5°C).

At NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C-36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01).

In very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge.

NCT03844204.

NCT03844204.Intermittent hypoxaemia (IH) events are well described in extremely preterm infants, but the occurrence of IH patterns in more mature preterm infants remains unclear. The objective of this study was to characterise the effect of gestational age on early postnatal patterns of IH in extremely ( less then 28 weeks), very (28- less then 32 weeks) and moderately (32- less then 34 weeks) preterm infants. Retinoic acid inhibitor As expected, extremely preterm infants had a significantly higher frequency of IH events of longer durations and greater time with hypoxaemia versus very and moderately preterm infants. In addition, the postnatal decrease in IH duration was comparable in the very and moderately preterm infants. This progression of IH events should assist clinicians and families in managing expectations for resolution of IH events during early postnatal life.

To determine the usefulness of video recordings for validating neonatal encephalopathy (NE) exams.

Population-based prospective cohort study. NE was assessed and recorded at 1, 3 and 5 hours after birth by the attending physician. Recordings were reviewed blindly after the recruitment period by two specialists. Outcome was assessed at 36 months of age.

Twelve intensive care units in Spain.

Infants of ≥35 weeks' gestational age with perinatal asphyxia.

Weighted kappa to measure disagreement between the two specialists and between the attending physician and the specialists' classification agreed on by consensus. Regression models to test the association of disagreement on NE assessment and outcome.

Of the 32 325 liveborn infants, 217 met the inclusion criteria. Video-recordings were not available for 43 infants (20%). Weighted kappa statistic was 0.74 (95% CI 0.67 to 0.81) between the specialists and the attending physicians. Disagreement occurred in 93 of the 417 (22%) videos, specifically in 39 (14%), 43 (47%), 11 (34%) and 0 exams categorised as no, mild, moderate and severe NE, respectively.