PSMD10/gankyrin induces autophagy to promote tumor progression through cytoplasmic interaction with ATG7 and nuclear transactivation of ATG7 expression.

Although autophagy is most critical for survival of cancer cells, especially in fast-growing tumors, the mechanism remains to be fully characterized. Herein we report that PSMD10/gankyrin promotes autophagy in hepatocellular carcinoma (HCC) in response to starvation or stress through 2 complementary routes. PSMD10 was physically associated with ATG7 in the cytoplasm, and this association was enhanced by initial nutrient deprivation. Subsequently, PSMD10 translocated into the nucleus and bound cooperatively with nuclear HSF1 (heat shock transcription factor 1) onto the ATG7 promoter, upregulated ATG7 expression in the advanced stage of starvation. Intriguingly, the type of PSMD10-mediated autophagy was independent of the proteasome system, although PSMD10 has been believed to be an indispensable chaperone for assembly of the 26S proteasome. A significant correlation between PSMD10 expression and ATG7 levels was detected in human HCC biopsies, and the combination of these 2 parameters is a powerful predictor of poor prognosis. The median survival of sorafenib-treated HCC patients with high expression of PSMD10 was much shorter than those with low expression of PSMD10. Furthermore, PSMD10 augmented autophagic flux to resist sorafenib or conventional chemotherapy, and inhibition of autophagy suppressed PSMD10-mediated resistance. We conclude that these results present a novel mechanism involving modulation of ATG7 by PSMD10 in sustaining autophagy, promoting HCC cell survival against starvation or chemotherapy. Targeting of PSMD10 might therefore be an attractive strategy in HCC treatment by suppressing autophagy and inducing HCC cell sensitivity to drugs

Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution.

The timely onset of female parturition is a critical determinant for pregnancy success. The highly heterogenous maternal decidua has been increasingly recognized as a vital factor in setting the timing of labor. Despite the cell type specific roles in parturition, the role of the uterine epithelium in the decidua remains poorly understood. This study uncovers the critical role of epithelial SHP2 in parturition initiation via COX1 and COX2 derived PGF2α leveraging epithelial specific Shp2 knockout mice, whose disruption contributes to delayed parturition initiation, dystocia and fetal deaths. Additionally, we also show that there are distinct types of epithelium in the decidua approaching parturition at single cell resolution accompanied with profound epithelium reformation via proliferation. Meanwhile, the epithelium maintains the microenvironment by communicating with stromal cells and macrophages. The epithelial microenvironment is maintained by a close interaction among epithelial, stromal and macrophage cells of uterine stromal cells. In brief, this study provides a previously unappreciated role of the epithelium in parturition preparation and sheds lights on the prevention of preterm birth

The ALMA-QUARKS survey: -- I. Survey description and data reduction

This paper presents an overview of the QUARKS survey, which stands for `Querying Underlying mechanisms of massive star formation with ALMA-Resolved gas Kinematics and Structures'. The QUARKS survey is observing 139 massive clumps covered by 156 pointings at ALMA Band 6 ($\lambda\sim$ 1.3 mm). In conjunction with data obtained from the ALMA-ATOMS survey at Band 3 ($\lambda\sim$ 3 mm), QUARKS aims to carry out an unbiased statistical investigation of massive star formation process within protoclusters down to a scale of 1000 au. This overview paper describes the observations and data reduction of the QUARKS survey, and gives a first look at an exemplar source, the mini-starburst Sgr B2(M). The wide-bandwidth (7.5 GHz) and high-angular-resolution (~0.3 arcsec) observations of the QUARKS survey allow to resolve much more compact cores than could be done by the ATOMS survey, and to detect previously unrevealed fainter filamentary structures. The spectral windows cover transitions of species including CO, SO, N$_2$D$^+$, SiO, H$_{30}\alpha$, H$_2$CO, CH$_3$CN and many other complex organic molecules, tracing gas components with different temperatures and spatial extents. QUARKS aims to deepen our understanding of several scientific topics of massive star formation, such as the mass transport within protoclusters by (hub-)filamentary structures, the existence of massive starless cores, the physical and chemical properties of dense cores within protoclusters, and the feedback from already formed high-mass young protostars.Comment: 9 figures, 4 tables, accepted by RA

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP). I. Detection of New Hot Corinos with the ACA

We report the detection of four new hot corino sources, G211.47-19.27S, G208.68-19.20N1, G210.49-19.79W, and G192.12-11.10, from a survey study of Planck Galactic Cold Clumps in the Orion Molecular Cloud Complex with the Atacama Compact Array. Three sources had been identified as low-mass Class 0 protostars in the Herschel Orion Protostar Survey. One source in the lambda Orionis region is first reported as a protostellar core. We have observed abundant complex organic molecules (COMs), primarily methanol but also other oxygen-bearing COMs (in G211.47-19.27S and G208.68-19.20N1) and the molecule of prebiotic interest NH2CHO (in G211.47-19.27S), signifying the presence of hot corinos. While our spatial resolution is not sufficient to resolve most of the molecular emission structure, the large line width and high rotational temperature of COMs suggest that they likely reside in the hotter and innermost region immediately surrounding the protostar. In G211.47-19.27S, the D/H ratio of methanol ([CH2DOH]/[CH3OH]) and the(12)C/C-13 ratio of methanol ([CH3OH]/[(CH3OH)-C-13]) are comparable to those of other hot corinos. Hydrocarbons and long-carbon-chain molecules such as c-C(3)H(2)and HCCCN are also detected in the four sources, likely tracing the outer and cooler molecular envelopes.Peer reviewe

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP) : Evidence for a Molecular Jet Launched at an Unprecedented Early Phase of Protostellar Evolution

Protostellar outflows and jets play a vital role in star formation as they carry away excess angular momentum from the inner disk surface, allowing the material to be transferred toward the central protostar. Theoretically, low-velocity and poorly collimated outflows appear from the beginning of the collapse at the first hydrostatic core (FHSC) stage. With growing protostellar core mass, high-density jets are launched, entraininf an outflow from the infalling envelope. Until now, molecular jets have been observed at high velocity (greater than or similar to 100 km s(-1)) in early Class 0 protostars. We, for the first time, detect a dense molecular jet in SiO emission with low velocity (similar to 4.2 km s(-1), deprojected similar to 24 km s(-1)) from source G208.89-20.04Walma (hereafter G208Walma) using ALMA Band 6 observations. This object has some characteristics of FHSCs, such as a small outflow/jet velocity, extended 1.3 mm continuum emission, and N2D+ line emission. Additional characteristics, however, are typical of early protostars: collimated outflow and SiO jet. The full extent of the outflow corresponds to a dynamical timescale of similar to 930(-100)(+200) yr. The spectral energy distribution also suggests a very young source having an upper limit of T-bol similar to 31 K and L-bol similar to 0.8 L-circle dot. We conclude that G208Walma is likely in the transition phase from FHSC to protostar, and the molecular jet has been launched within a few hundred years of initial collapse. Therefore, G208Walma may be the earliest object discovered in the protostellar phase with a molecular jet.Peer reviewe

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP). II. Survey Overview : A First Look at 1.3 mm Continuum Maps and Molecular Outflows

Planck Galactic Cold Clumps (PGCCs) are considered to be the ideal targets to probe the early phases of star formation. We have conducted a survey of 72 young dense cores inside PGCCs in the Orion complex with the Atacama Large Millimeter/submillimeter Array (ALMA) at 1.3 mm (band 6) using three different configurations (resolutions similar to 035, 10, and 70) to statistically investigate their evolutionary stages and substructures. We have obtained images of the 1.3 mm continuum and molecular line emission ((CO)-C-12, and SiO) at an angular resolution of similar to 035 (similar to 140 au) with the combined arrays. We find 70 substructures within 48 detected dense cores with median dust mass similar to 0.093 M and deconvolved size similar to 027. Dense substructures are clearly detected within the central 1000 au of four candidate prestellar cores. The sizes and masses of the substructures in continuum emission are found to be significantly reduced with protostellar evolution from Class 0 to Class I. We also study the evolutionary change in the outflow characteristics through the course of protostellar mass accretion. A total of 37 sources exhibit CO outflows, and 20 (>50%) show high-velocity jets in SiO. The CO velocity extents (Delta Vs) span from 4 to 110 km s(-1) with outflow cavity opening angle width at 400 au ranging from [Theta(obs)](400) similar to 06-39, which corresponds to 334-1257. For the majority of the outflow sources, the Delta Vs show a positive correlation with [Theta(obs)](400), suggesting that as protostars undergo gravitational collapse, the cavity opening of a protostellar outflow widens and the protostars possibly generate more energetic outflows.Peer reviewe

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP): How Do Dense Core Properties Affect the Multiplicity of Protostars?

During the transition phase from a prestellar to a protostellar cloud core, one or several protostars can form within a single gas core. The detailed physical processes of this transition, however, remain unclear. We present 1.3 mm dust continuum and molecular line observations with the Atacama Large Millimeter/submillimeter Array toward 43 protostellar cores in the Orion molecular cloud complex (λ Orionis, Orion B, and Orion A) with an angular resolution of ∼0.″35 (∼140 au). In total, we detect 13 binary/multiple systems. We derive an overall multiplicity frequency (MF) of 28% ± 4% and a companion star fraction (CSF) of 51% ± 6%, over a separation range of 300-8900 au. The median separation of companions is about 2100 au. The occurrence of stellar multiplicity may depend on the physical characteristics of the dense cores. Notably, those containing binary/multiple systems tend to show a higher gas density and Mach number than cores forming single stars. The integral-shaped filament of the Orion A giant molecular cloud (GMC), which has the highest gas density and hosts high-mass star formation in its central region (the Orion Nebula cluster), shows the highest MF and CSF among the Orion GMCs. In contrast, the λ Orionis GMC has a lower MF and CSF than the Orion B and Orion A GMCs, indicating that feedback from H ii regions may suppress the formation of multiple systems. We also find that the protostars comprising a binary/multiple system are usually at different evolutionary stages.T.L. acknowledges support from the National Natural Science Foundation of China (NSFC) through grants No. 12073061 and No. 12122307, the International Partnership Program of the Chinese Academy of Sciences (CAS) through grant No. 114231KYSB20200009, the Shanghai Pujiang Program (20PJ1415500), and science research grants from the China Manned Space Project with no. CMS-CSST-2021-B06. K.T. was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI (grant No. 20H05645). D.J. and J.d.F. are supported by NRC Canada and by NSERC Discovery Grants. C.-F.L. acknowledge grants from the Ministry of Science and Technology of Taiwan (MoST 107-2119-M-001-040-MY3 and 110-2112-M-001-021-MY3) and Academia Sinica (Investigator Award AS-IA-108-M01). This research was carried out in part at the Jet Propulsion Laboratory, which is operated by the California Institute of Technology under a contract with the National Aeronautics and Space Administration (80NM0018D0004). J.-E.L. was supported by a National Research Foundation of Korea grant funded by the Korean government (MSIT) (grant No. 2021R1A2C1011718). J.H. acknowledges the support of NSFC projects 11873086 and U1631237. This work is sponsored (in part) by the CAS, through a grant to the CAS South America Center for Astronomy in Santiago, Chile. S.-L.Q. is supported by the NSFC with grant No. 12033005. S.Z. acknowledges the support of the China Postdoctoral Science Foundation through grant No. 2021M700248. L.B. gratefully acknowledges support by the ANID BASAL projects ACE210002 and FB210003. P.S. was supported by a Grant-in-Aid for Scientific Research (KAKENHI No. 18H01259) of JSPS. V.-M.P. acknowledges support by the grant PID2020-115892GB-I00 funded by MCIN/AEI/10.13039/501100011033

PLANCK COLD CLUMPS IN THE lambda ORIONIS COMPLEX. I. DISCOVERY OF AN EXTREMELY YOUNG CLASS 0 PROTOSTELLAR OBJECT AND A PROTO-BROWN DWARF CANDIDATE IN THE BRIGHT-RIMMED CLUMP PGCC G192.32-11.88

We are performing a series of observations with ground-based telescopes toward Planck Galactic cold clumps (PGCCs) in the lambda Orionis complex in order to systematically investigate the effects of stellar feedback. In the particular case of PGCC G192.32-11.88, we discovered an extremely young Class 0 protostellar object (G192N) and a proto-brown dwarf candidate (G192S). G192N and G192S are located in a gravitationally bound brightrimmed clump. The velocity and temperature gradients seen in line emission of CO isotopologues indicate that PGCC G192.32-11.88 is externally heated and compressed. G192N probably has the lowest bolometric luminosity (similar to 0.8 L-circle dot) and accretion rate (6.3 x 10(-7) M-circle dot yr(-1)) when compared with other young Class 0 sources (e.g., PACS Bright Red Sources) in the Orion complex. It has slightly larger internal luminosity (0.21 +/- 0.01 L-circle dot) and outflow velocity (similar to 14 km s(-1)) than the predictions of first hydrostatic cores (FHSCs). G192N might be among the youngest Class 0 sources, which are slightly more evolved than an FHSC. Considering its low internal luminosity (0.08 +/- 0.01 L-circle dot) and accretion rate (2.8 x 10(-8) M-circle dot yr(-1)), G192S is an ideal proto-brown dwarf candidate. The star formation efficiency (similar to 0.3%-0.4%) and core formation efficiency (similar to 1%) in PGCC G192.32-11.88 are significantly smaller than in other giant molecular clouds or filaments, indicating that the star formation therein is greatly suppressed owing to stellar feedback.Peer reviewe

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP) : How Do Dense Core Properties Affect the Multiplicity of Protostars?

During the transition phase from a prestellar to a protostellar cloud core, one or several protostars can form within a single gas core. The detailed physical processes of this transition, however, remain unclear. We present 1.3 mm dust continuum and molecular line observations with the Atacama Large Millimeter/submillimeter Array toward 43 protostellar cores in the Orion molecular cloud complex (lambda Orionis, Orion B, and Orion A) with an angular resolution of similar to 0.'' 35 (similar to 140 au). In total, we detect 13 binary/multiple systems. We derive an overall multiplicity frequency (MF) of 28% +/- 4% and a companion star fraction (CSF) of 51% +/- 6%, over a separation range of 300-8900 au. The median separation of companions is about 2100 au. The occurrence of stellar multiplicity may depend on the physical characteristics of the dense cores. Notably, those containing binary/multiple systems tend to show a higher gas density and Mach number than cores forming single stars. The integral-shaped filament of the Orion A giant molecular cloud (GMC), which has the highest gas density and hosts high-mass star formation in its central region (the Orion Nebula cluster), shows the highest MF and CSF among the Orion GMCs. In contrast, the lambda Orionis GMC has a lower MF and CSF than the Orion B and Orion A GMCs, indicating that feedback from H ii regions may suppress the formation of multiple systems. We also find that the protostars comprising a binary/multiple system are usually at different evolutionary stages.Peer reviewe