Biology subjects

Li, S.-Q.

Publications and source records attributed to Li, S.-Q..

4 recordsLinked to original sources

bioRxiv2026

Elevated procoagulant platelets driven by necroptosis and pyroptosis aggravate pulmonary thrombosis via suppressing monocyte efferocytosis in severe pneumonia

BACKGROUND: Severe influenza pneumonia with secondary bacterial infection is complicated by progressive pulmonary thrombus exacerbation, a key contributor to respiratory failure, yet anticoagulant therapies show limited efficacy and bleeding risks. Although platelet-monocyte crosstalk initiates thrombosis, whether and how it drives thrombus exacerbation via procoagulant platelets and monocyte efferocytosis remains unclear. METHODS: Clinical samples, mouse models, and isolated platelets challenged with influenza A virus followed by methicillin-resistant Staphylococcus aureus (MRSA) were analyzed. Procoagulant platelet, platelet programmed cell death and monocyte efferocytosis were assessed, and pharmacological inhibition, platelet depletion and systemic/platelet-specific Gsdmd knockout were used. Platelet proteomics and exogenous C1qa supplementation identified C1qa as a key mediator. RESULTS: We showed that elevated procoagulant platelet-driven thrombus exacerbation, rather than initial thrombus formation, was a critical driver of disease progression in influenza pneumonia with secondary bacterial infection, whereas influenza alone caused milder illness. Procoagulant platelet formation was induced via MLKL-mediated necroptosis and GSDMD-mediated pyroptosis. These platelets exacerbated pulmonary thrombosis and lung injury by inhibiting monocyte efferocytosis via complement C1qa. Platelet depletion reduced monocyte efferocytosis and worsened pneumonia, while pharmacological inhibition or platelet-specific Gsdmd knockout decreased procoagulant platelet levels, restored monocyte efferocytosis, and alleviated thrombotic and pulmonary injury. Mechanistically, C1qa impaired efferocytosis both by directly suppressing monocyte function and by reducing the proportion of reparative (M2-like) monocytes. Clinical relevance was confirmed by detection of MLKL/GSDMD-dependent procoagulant platelets and reduced efferocytosis receptor levels on monocytes in bronchoalveolar lavage fluid from severe pneumonia patients. CONCLUSIONS: Necroptosis/pyroptosis-driven procoagulant platelets exacerbate pulmonary thrombosis by suppressing monocyte efferocytosis in a C1qa-dependent manner. These findings extend platelet-monocyte crosstalk from thrombus initiation to thrombus exacerbation, identifying modulation of the interaction between procoagulant platelets and monocyte efferocytosis as a potential therapeutic strategy for thrombus-exacerbating diseases, especially in subpopulations of patients with severe pneumonia and progressive pulmonary thrombosis.

cell biology↗

bioRxiv2026

Catalase 2-dependent regulation of autophagy in response to carbon starvation in Arabidopsis

Reactive oxygen species (ROS) are fundamental regulators of plant development and stress acclimation. However, their roles in carbon starvation tolerance remain largely unresolved. We therefore dissected the dynamics of redox regulation in carbon-starved Arabidopsis leaves. We present data showing the presence of an early ROS wave that activates autophagy, followed by a sustained, accumulation of hydrogen peroxide (H2O2) that leads to programmed cell death. We show that catalase 2 (CAT2) constitutively binds and sequesters the autophagy initiators ATG1a and ATG13a, a process that prevents the activation of autophagy under carbon-replete conditions. The accumulation of H2O2 in response to carbon starvation leads to oxidation of the Cys-370 and Cys-413 residues on the CAT2 protein and dissociation from ATG1a/13a, thereby allowing ATG1-kinase complex assembly and autophagosome formation. The expression of CAT2-C370S or CAT2-C413S variants in the cat2-1 mutant significantly enhanced carbon starvation tolerance, because both variants retain catalase activity but fail to bind ATG1a/13a. We conclude that CAT2 functions as a redox-sensitive regulator of autophagy.

plant biology↗

bioRxiv2021

Cypripedium wardii (Orchidaceae) employs pseudopollen with both reward and deception to attract both flis and bees as pollinators

O_LIFlowering plants always attract animals providing rewards or deceptive signals to gain reproductive success. However, there is no well-documented reporting about a pollination mechanism with both rewards and deceptive signals by a same object. We found Cypripedium wardii flowers seem to attract visitors by the white pseudopollenlike trichomes on labella in our preliminary field observation. C_LIO_LITo explore the pollination mechanism of Cypripedium wardii, especially, the ecological function of the pseudopollen-like trichomes, we conducted field observations, analyses of the traits of visitors and flowers, and breeding system experiments. C_LIO_LIThe white trichomes composed by multicellular moniliform hairs on the floral labella played a crucial role to attract pollinators, causing a high natural fruit set ratio in C. wardii. We established the direct connection of the white trichomes and real pollen. C_LIO_LIWe propose that flowers of C. wardii provide pseudopollen to attract suitable bees and hoverflies as pollinators. And our evidence indicate that the pseudopollen owns both deceptive and rewarding ecological functions. Our study provide a clear pollination mechanism with both rewards and deceptive signals by a same object in angiosperm for the first time. However, an inbreeding depression seem to be caused by this strategy. And we speculated that the pollen mimicry strategy with both rewarding and deceptive functions in C. wardii may be an adaptation to the habitat fragmentation of this species to gain a reproductive assurance. C_LI

plant biology↗

bioRxiv2020

Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer

Estrogen receptor positive (ER+) breast cancer is a leading cause of cancer-related death globally. Resistance to standard of care endocrine treatment occurs in at least 30% of ER+ breast cancer patients resulting in ~40,000 deaths every year in the US alone. Preclinical studies strongly implicate activation of growth factor receptor, HER2 in endocrine treatment resistance of ER+ breast cancer that is HER2- at diagnosis1,2. However, clinical trials of pan-HER inhibitors in ER+/HER2- patients have disappointed, likely due to a lack of predictive biomarkers3-6. Here we demonstrate that loss of MLH1, a principal mismatch repair gene, causally activates HER2 in ER+/HER2- breast cancer upon endocrine treatment. Additionally, we show that HER2 activation is indispensable for endocrine treatment resistant growth of MLH1- cells in vitro and in vivo. Consequently, inhibiting HER2 restores sensitivity to endocrine treatment in multiple experimental models including patient-derived xenograft tumors. Patient data from multiple clinical datasets (TCGA, METABRIC, Alliance (Z1031) and E-GEOD-28826) supports an association between MLH1 loss, HER2 upregulation, and sensitivity to trastuzumab in endocrine treatment-resistant ER+/HER2- patients. These results provide strong rationale that MLH1 could serve as a first-in-class predictive marker of sensitivity to combinatorial treatment with endocrine drugs and HER inhibitors in endocrine treatment-resistant ER+/HER2- breast cancer patients. Implications of this study extend beyond breast cancer to Lynch Syndrome cancers. One Sentence SummaryDefective mismatch repair activates HER2 in HER2-negative breast cancer cells and renders them susceptible to HER2 inhibitors.

cancer biology↗