Biology subjects

Wu, Z.-Q.

Publications and source records attributed to Wu, Z.-Q..

3 recordsLinked to original sources

bioRxiv2025

A non-canonical top-down pathway regulating relapse to opioid

The high relapse rates are major challenges in treating opioid addiction. However, it remains poorly understood the mechanisms underlying long-lasting vulnerability to relapse. Here, we identify the cortico-subthalamic projection from the granular retrosplenial cortex (RSG) to the zona incerta (ZI) as a key circuit for controlling relapse to opioid. We uncover that an ensemble of RSG glutamatergic neurons that locate in layer 5 and express B subtype cholecystokinin receptor (RSGGlu-Cckbr ensemble) are critically implicated in the encoding and retrieval of opioid-associated memories, leading to relapse to opioid via innervating ZI GABAergic (ZIGABA) rather than dopaminergic neurons. We further identify that the Cckergic neurons from anterodorsal nucleus of thalamus (AD thalamus) orchestrates RSGGlu-Cckbr-ZIGABA circuit function via release of cholecystokinin (Cck) in RSG. These results elucidate a previously unknown non-canonical top-down pathway regulating relapse to opioid and shed new light on the development of new therapeutic strategies to treat relapse to opioids.

neuroscience↗

bioRxiv2024

Arabidopsis EID1 E3 ubiquitin ligase regulates acquired thermotolerance by modulating HSBP translocation

Climate change is causing a rapid increase in global average temperatures and more frequent heatwaves, posing serious threats to agricultural production and global biodiversity. In response to heat stress (HS), plants can develop acquired thermotolerance (AT) by initiating a heat shock response (HSR) after mild HS priming, thereby enhancing their ability to withstand subsequent later lethal HS events. Central to this process are the HEAT SHOCK FACTORs (HSFs), which form trimeric complexes and activate the expression of HEAT SHOCK PROTEINs (HSPs) and other HSFs to maintain proper protein and cellular functionality. After heat stress subsides, the HSFs activities can be modulated to attenuate the negative effects of HSR during the heat. The SHOCK FACTOR BINDING PROTEIN (HSBP) is a conserved microprotein that plays a prominent role in modulating HSF activities. HSBP can translocate from the cytoplasm into the nucleus during heat stress to directly interact with HSFs and prevent the formation of HSF timers. However, the mechanism that regulates the HSBP cytoplasmic-nuclear shuttling remains unclear. Here, we identified an F-box E3 ubiquitin ligase, EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1), whose mutant form shows reduced thermotolerance in AT. We showed that EID1 interacts with HSBP to modulate HSBP cytoplasm-nuclear localization during heat stress, possibly through modulating the K41 of HSBP. The decreased thermotolerance in the eid1 mutant can be explained by alterations of some HSPs expression caused by the mis-localization of HSBP. This finding provided a novel example of E3 ubiquitin-mediated regulation of heat stress in plants.

plant biology↗

bioRxiv2024

Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treat low-burden metastases

Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-{gamma} production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors. Using a spontaneous metastasis mouse model of MHC-I+ breast cancer, we found that transfer of IL-15/IL-12-conditioned syngeneic NK cells after primary tumor resection promoted long-term survival of mice with low metastatic burden and induced a tumor-specific protective T cell response that is essential for the therapeutic effect. Furthermore, NK cell transfer augments activation of conventional dendritic cells (cDCs), Foxp3-CD4+ T cells and stem cell-like CD8+ T cells in metastatic lungs, to which IFN-{gamma} of the transferred NK cells contributes significantly. These results imply direct interactions between transferred NK cells and endogenous cDCs to enhance T cell activation. We conducted an investigator-initiated clinical trial of autologous NK cell therapy in six patients with advanced cancer and observed that the NK cell therapy was safe and showed signs of effectiveness. These findings indicate that autologous NK cell therapy is effective in treating established low burden metastases of MHC-I+ tumor cells by activating the cDC-T cell axis at metastatic sites.

immunology↗