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Over the past few decades, understandings and evidences concerning the role of endoplasmic reticulum (ER) stress in deciding the cell fate have been constantly growing. Generally, during ER stress, the signal transductions are mainly conducted by three ER stress transducers: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring kinase 1 (IRE1) and activating transcription factor 6 (ATF6). Consequently, the harmful stimuli from the ER stress transducers induce apoptosis and autophagy, which share several crosstalks and eventually decide the cell fate. The dominance of apoptosis or autophagy induced by ER stress depends on the type and degree of the stimuli. When ER stress is too severe and prolonged, apoptosis is induced to eliminate the damaged cells; however, when stimuli are mild, cell survival is promoted to maintain normal physiological functions by inducing autophagy. Although all the three pathways participate in ER stress-induced apoptosis and autophagy, PERK shows several unique characteristics by interacting with some specific downstream effectors. Notably, there are some preliminary findings on PERK-dependent mechanisms switching autophagy and apoptosis. In this review, we particularly focused on the novel, intriguing and complicated role of PERK in ER stress-decided cell fate, and also discussed more roles of PERK in restoring cellular homeostasis. However, more in-depth knowledge of PERK in the future would facilitate our understanding about many human diseases and benefit in searching for new molecular therapeutic targets.

Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. In the study we demonstrated that CD133 expression was the highest in triple-negative (TN) breast cancer specimens. Importantly, VM showed statistical correlation with CD133 + expression. The presence of the close relationship between VM and CD133 + expression might be central for TN tumor relapse and progression. The TN breast cancer cell line, MDA-MB-231 cells developed a range of colony morphologies paralleling the holoclone, meroclone and paraclone morphologies produced by normal keratinocytes and other epithelial cancer cell lines when plated at clonal densities. Holoclone cells were capable of forming more colonies on soft agar than meroclone cells and paraclone cells, suggesting that holoclone cells had higher self-renew potential and might harbors cancer stem cells (CSCs) subpopulation. Strikingly, it was holoclone that displayed CD133 + phenotype and formed VM. In addition, holoclone acquired endothelial cell marker vascular endothelial-cadherin expression and upregulated VM mediators matrix metalloproteinase (MMP)-2 and MMP-9 expression. The subpopulation with holoclone morphology, CD133 + phenotype and CSCs characteristics might have the capacity of transdifferentiation and contributed to VM in TN breast cancer. The related molecular pathways may be used as novel therapeutic targets for the inhibition of angiogenesis and metastasis in TN breast carcinoma.

A period of cooling about 13,000 years ago interrupted about 2,000 years of deglacial warming. Known as the Younger Dryas (YD), the event is thought to have resulted from a slowdown of the Atlantic meridional overturning circulation in response to a sudden flood of Laurentide Ice Sheet meltwater that reached the Nordic Seas. Oxygen isotope evidence for a local source of meltwater to the open western North Atlantic from the Gulf of St Lawrence has been lacking. Here we report that the eastern Beaufort Sea contains the long-sought signal of 18O-depleted water. Beginning at ~12.94 ± 0.15 thousand years ago, oxygen isotopes in the planktonic foraminifera from two sediment cores as well as sediment and seismic data indicate a flood of meltwater, ice and sediment to the Arctic via the Mackenzie River that lasted about 700 years. The minimum in the oxygen isotope ratios lasted ~130 years. We suggest that the floodwater travelled north along the Canadian Archipelago and then through the Fram Strait to the Nordic Seas, where freshening and freezing near sites of deep-water formation would have suppressed convection and caused the YD cooling by reducing the meridional overturning.

In August 2022, the Tohoku region of Japan suffered three major heavy rainfall events, while one was related to an anticyclone, and the others were induced by a “Baiu‐like” stationary front. By using the Lagrangian backward trajectories, we found the moisture sources of the three events varied much due to the rapidly changing atmospheric conditions. In general, moisture from the Sea of Japan contributed the most in all events, while the western Pacific also played a certain role. Surprisingly, moisture from tropical storms and the East China Sea did not contribute much due to the along‐transport precipitation. But, based on forward‐traced trajectories, we confirmed that tropical storms did enhance moisture transport from subtropical regions via their southerly wind. Overall, this study highlights the role of the moisture gains nearby and the outer flows of tropical storms during heavy rainfalls in a northern region. Plain Language Summary Heavy rainfalls hit northern Japan (i.e., the Tohoku region) from early‐ to mid‐August 2022, which were caused by a moving high‐pressure system, a rare north‐located “Baiu‐like” stationary front, and tropical storms. The highly accumulated moisture over Tohoku was supplied by the moistening over the marginal seas and the subtropical western Pacific, while the inland region also supplied a certain amount. Surprisingly, moisture carried by tropical storms (Songda, Trases, and Meari) and that from the East China Sea did not contribute much, because they were lost due to the precipitation during the transport. Most of the moisture was obtained nearby over the Sea of Japan. On the other hand, although storms did not contribute much moisture, their related wind fields did enhance moisture transport from moist‐rich regions to the Tohoku region. Key Points Three heavy rainfalls occurred over the Tohoku region with varied moisture sources Moisture gains from the nearby Sea of Japan contributed the most, while the western Pacific played a secondary role Moisture that was carried by tropical storms did not contribute much to the events but the storm‐induced southerly wind did

Liu R, Chen G, Zhao N, Yue W. Neuropsychiatr Dis Treat. 2025;21:129-140. The authors have advised there is an error in affiliation 1 and the correspondence address on page 129 of the published paper. The text \"Tianjin Medical University, Tianjin Huanhu Hospital\" should read \"Tianjin Huanhu Hospital, Tianjin Medical University\". The authors apologize for this error.

Estuaries have been sites of intensive human activities during the past century. Tracing the evolution of subaqueous topography in estuaries on a decadal timescale enables us to understand the effects of human activities on estuaries. Bathymetric data from 1955 to 2010 show that land reclamation decreased the subaqueous area of Lingding Bay, in the Pearl River estuary, by ~170 km 2 and decreased its water volume by 615 × 10 6  m 3 , representing a net decrease of 11.2 × 10 6  m 3 per year and indicating the deposition of approximately 14.5 Mt/yr of sediment in Lingding Bay during that period. Whereas Lingding Bay was mainly governed by natural processes with slight net deposition before 1980, subsequent dredging and large port engineering projects changed the subaqueous topography of the bay by shallowing its shoals and deepening its troughs. Between 2012 and 2013, continuous dredging and a surge of sand excavation resulted in local changes in water depth of ± 5 m/yr, far exceeding the magnitude of natural topographic evolution in Lingding Bay. Reclamation, dredging, and navigation-channel projects removed 8.4 Mt/yr of sediment from Lingding Bay, representing 29% of the sediment input to the bay, and these activities have increased recently.

Engineered defects in the diamond lattice hold promise for the storage and manipulation of quantum information. Entanglement between the electron and nuclear spins of two such defects is demonstrated at room temperature. Entanglement is the central yet fleeting phenomenon of quantum physics. Once being considered a peculiar counter-intuitive property of quantum theory 1 , it has developed into the most central element of quantum technology. Consequently, there have been a number of experimental demonstrations of entanglement between photons 2 , atoms 3 , ions 4 and solid-state systems such as spins or quantum dots 5 , 6 , 7 , superconducting circuits 8 , 9 and macroscopic diamond 10 . Here we experimentally demonstrate entanglement between two engineered single solid-state spin quantum bits (qubits) at ambient conditions. Photon emission of defect pairs reveals ground-state spin correlation. Entanglement (fidelity = 0.67±0.04) is proved by quantum state tomography. Moreover, the lifetime of electron spin entanglement is extended to milliseconds by entanglement swapping to nuclear spins. The experiments mark an important step towards a scalable room-temperature quantum device being of potential use in quantum information processing as well as metrology.

The growth behavior of intermetallic compounds (IMCs) at the liquid-solid interfaces in Cu/Sn/Cu interconnects during reflow at 250 °C and 280 °C on a hot plate was investigated. Being different from the symmetrical growth during isothermal aging, the interfacial IMCs showed clearly asymmetrical growth during reflow, i.e., the growth of Cu 6 Sn 5 IMC at the cold end was significantly enhanced while that of Cu 3 Sn IMC was hindered especially at the hot end. It was found that the temperature gradient had caused the mass migration of Cu atoms from the hot end toward the cold end, resulting in sufficient Cu atomic flux for interfacial reaction at the cold end while inadequate Cu atomic flux at the hot end. The growth mechanism was considered as reaction/thermomigration-controlled at the cold end and grain boundary diffusion/thermomigration-controlled at the hot end. A growth model was established to explain the growth kinetics of the Cu 6 Sn 5 IMC at both cold and hot ends. The molar heat of transport of Cu atoms in molten Sn was calculated as + 11.12 kJ/mol at 250 °C and + 14.65 kJ/mol at 280 °C. The corresponding driving force of thermomigration in molten Sn was estimated as 4.82 × 10 −19 N and 6.80 × 10 −19 N.

The layered rock masses with structural planes are widely distributed, among which the transverse isotropy caused by the bedding structural plane has a great influence on the stability of the slope and surrounding rock. Construct a beam-particle model (BPM) to reveal the layered slate fracture characteristics is of great significance. This paper takes the layered carbonaceous slate of the Muzhailing tunnel in Shanxi as the research specimens, carries out the Brazilian split test and uniaxial compression test of the layered slate with different bedding inclination angles, and conducts out a systematic numerical analysis based on the BPM solver. The test and numerical results show that: (1) In the Brazilian split test, the load–displacement curve of the layered slate has the development trend of the initial stage, the rock specimens compaction, nearly linear elasticity, and finally complete collapse. As the bedding inclination angle changes from 0∘ to 90∘, the tensile strength of slate decreases successively. (2) In the uniaxial compression test, when the bedding inclination angle is 0∘ and 90∘, the compressive strength is greater, and the bedding inclination angle is 30∘, 45∘ and 60∘, the compressive strength is small and the value is close, showing a “U”-shaped change as a whole. (3) With the change of bedding inclination angle and the comprehensive influence of matrix and bedding, the split failure mode of layered slate is complex and changeable, and roughly presents split tensile failure, shear slip failure and comprehensive tensile shear failure. (4) Through the comparative analysis of test load–displacement response and failure mode, the BPM solver can better reproduce the split evolution process of layered slate under different bedding inclination angles, and prove the robustness and stability of the program. The BPM solver can provide a new numerical research method for the widespread engineering practice of layered rock masses.

Continental breakup represents the successful process of rifting and thinning of the continental lithosphere, leading to plate rupture and initiation of oceanic crust formation. Magmatism during breakup seems to follow a path of either excessive, transient magmatism (magma-rich margins) or of igneous starvation (magma-poor margins). The latter type is characterized by extreme continental lithospheric extension and mantle exhumation prior to igneous oceanic crust formation. Discovery of magma-poor margins has raised fundamental questions about the onset of ocean-floor type magmatism, and has guided interpretation of seismic data across many rifted margins, including the highly extended northern South China Sea margin. Here we report International Ocean Discovery Program drilling data from the northern South China Sea margin, testing the magma-poor margin model outside the North Atlantic. Contrary to expectations, results show initiation of Mid-Ocean Ridge basalt type magmatism during breakup, with a narrow and rapid transition into igneous oceanic crust. Coring and seismic data suggest that fast lithospheric extension without mantle exhumation generated a margin structure between the two endmembers. Asthenospheric upwelling yielding Mid-Ocean Ridge basalt-type magmatism from normal-temperature mantle during final breakup is interpreted to reflect rapid rifting within thin pre-rift lithosphere.