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In July to August 2022, Pakistan suffered historic flooding while record-breaking heatwaves swept southern China, causing severe socioeconomic impacts. Similar extreme events have frequently coincided between two regions during the past 44 years, but the underlying mechanisms remain unclear. Using observations and a suite of model experiments, here, we show that the upper-tropospheric divergent wind induced by convective heating over Pakistan excites a barotropic anomalous anticyclone over eastern China, which further leads to persistent heatwaves. Atmospheric model ensemble simulation indicates that this dynamic pathway linking Pakistan flooding and East Asian heatwaves is intrinsic to the climate system, largely independent of global sea surface temperature forcing. This dynamic connection is most active during July to August when convective variability is large over Pakistan and the associated divergent flow excites barotropic Rossby waves that propagate eastward along the upper troposphere westerly waveguide. This robust waveguide and the time delay offer hopes for improved subseasonal prediction of extreme events in East Asia.

This study analyzes the response of East Asian surface air temperature (SAT) to the quasi-biennial oscillation (QBO) in boreal winter using the JRA-55 reanalysis dataset and the CAM6 model. East Asian SAT patterns in response to the boreal winter QBO vertical profile are derived from singular value decomposition (SVD) analysis. The leading mode of SVD (SVD1) shows an evident cold center over East Asia, while warm and cold centers show an east–west dipole in the second mode of SVD (SVD2). The corresponding QBO pattern in SVD1 has two opposite centers, with an upper-stratospheric easterly phase and a lower-stratospheric westerly phase; however, there is only one middle-stratospheric westerly center in SVD2. The SVD1-like QBO tends to cause more significant East Asian SAT anomalies than the SVD2-like QBO pattern. This difference originates from the response of the stratospheric polar vortex and the North Pacific circulation to the QBO. The SVD1-like QBO forces a cyclonic anomaly over the midlatitude North Pacific and an anticyclonic anomaly over China via a subtropical path and polar path, leading to a zonal pressure gradient and meridional wind anomaly over East Asia. Temperature advection driven by this meridional wind affects cooling and warming over East Asia. By contrast, there are no significant responses to the SVD2-like QBO over the midlatitude North Pacific, and thus, the corresponding East Asian SAT response is weak. Significance Statement: East Asian surface air temperature (SAT) variation is often attributed to variations in lower-atmospheric dynamics and sea surface temperature. Few studies focus on the role of the QBO. In this study, we diagnose the influence of the stratospheric QBO on East Asian SAT during boreal winter. Both reanalysis and simulated results indicate that the response of East Asian SAT is sensitive to the selection of multilevel QBO indices. This sensitivity comes from the changes in QBO's subtropical and polar influencing path. Our results provide a new perspective on East Asian SAT changes. [ABSTRACT FROM AUTHOR]

Microvesicles (MVs) containing proteins, nucleic acid or organelles are shed from the plasma membrane. Although the mechanisms of MV budding are well elucidated, the connection between endosomal trafficking and MV formation remains poorly understood. In this report, RAB22A is revealed to be crucial for EGFR‐containing MVs formation by the RAB GTPase family screening. RAB22A recruits TBC1D2B, a GTPase‐activating protein (GAP) of RAB7A, to inactivate RAB7A, thus preventing EGFR from being transported to late endosomes and lysosomes. RAB22A also engages SH3BP5L, a guanine‐nucleotide exchange factor (GEF) of RAB11A, to activate RAB11A on early endosomes. Consequently, EGFR is recycled to the cell surface and packaged into MVs. Furthermore, EGFR can phosphorylate RAB22A at Tyr136, which in turn promotes EGFR‐containing MVs formation. Our findings illustrate that RAB22A acts as a sorter on early endosomes to sort EGFR to recycling endosomes for MV shedding by both activating RAB11A and inactivating RAB7A. Summary: This report reveals that RAB22A acts as a sorter: to sort EGFR from early endosomes to recycling endosomes. RAB22A promotes EGFR‐containing MVs formation via recruiting TBC1D2B to inactivate RAB7A and engaging SH3BP5L to activate RAB11A. In the meantime, EGFR can phosphorylate Tyr136 of RAB22A to enhance the release of EGFR‐containing MVs. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is one of the most common tumors characterized by a high rate of relapse and a lack of targeted therapy. Here, YEATS domain‐containing protein 4 (YEATS4) is an essential gene for BC cell viability using CRISPR‐Cas9 library screening is reported, and that HUWE1 is an E3 ligase responsible for YEATS4 ubiquitination and proteasomal degradation by the Protein Stability Regulators Screening Assay. KAT8‐mediated acetylation of YEATS4 impaired its interaction with HUWE1 and consequently prevented its ubiquitination and degradation. The protein levels of YEATS4 and KAT8 are positively correlated and high levels of these two proteins are associated with poor overall survival in BC patients. Importantly, suppression of YEATS4 acetylation with the KAT8 inhibitor MG149 decreased YEATS4 acetylation, reduced cell viability, and sensitized BC cells to cisplatin treatment. The findings reveal a critical role of the KAT8/YEATS4 axis in both tumor growth and cisplatin sensitivity in BC cells, potentially generating a novel therapeutic strategy for BC patients. [ABSTRACT FROM AUTHOR]