Salt adaptability in a halophytic soybean (Glycine soja) involves photosystems coordination

Background Glycine soja is a halophytic soybean native to saline soil in Yellow River Delta, China. Photosystem I (PSI) performance and the interaction between photosystem II (PSII) and PSI remain unclear in Glycine soja under salt stress. This study aimed to explore salt adaptability in Glycine soja in terms of photosystems coordination. Results Potted Glycine soja was exposed to 300 mM NaCl for 9 days with a cultivated soybean, Glycine max, as control. Under salt stress, the maximal photochemical efficiency of PSII (Fv/Fm) and PSI (oMR/MR0) were significantly decreased with the loss of PSI and PSII reaction center proteins in Glycine max, and greater PSI vulnerability was suggested by earlier decrease in oMR/MR0 than Fv/Fm and depressed PSI oxidation in modulated 820 nm reflection transients. Inversely, PSI stability was defined in Glycine soja, as oMR/MR0 and PSI reaction center protein abundance were not affected by salt stress. Consistently, chloroplast ultrastructure and leaf lipid peroxidation were not affected in Glycine soja under salt stress. Inhibition on electron flow at PSII acceptor side helped protect PSI by restricting electron flow to PSI and seemed as a positive response in Glycine soja due to its rapid recovery after salt stress. Reciprocally, PSI stability aided in preventing PSII photoinhibition, as the simulated feedback inhibition by PSI inactivation induced great decrease in Fv/Fm under salt stress. In contrast, PSI inactivation elevated PSII excitation pressure through inhibition on PSII acceptor side and accelerated PSII photoinhibition in Glycine max, according to the positive and negative correlation of oMR/MR0 with efficiency that an electron moves beyond primary quinone and PSII excitation pressure respectively. Conclusion Therefore, photosystems coordination depending on PSI stability and rapid response of PSII acceptor side contributed to defending salt-induced oxidative stress on photosynthetic apparatus in Glycine soja. Photosystems interaction should be considered as one of the salt adaptable mechanisms in this halophytic soybean

A One-Stone-Two-Birds Strategy of Targeting Microbubbles with “Dual” Anti-Inflammatory and Blood–Brain Barrier “Switch” Function for Ischemic Stroke Treatment

Inflammation is considered to be the main target of the development of new stroke therapies. There are three key issues in the treatment of stroke inflammation: the first one is how to overcome the blood–brain barrier (BBB) to achieve drug delivery, the second one is how to select drugs to treat stroke inflammation, and the third one is how to achieve targeted drug delivery. In this study, we constructed hydrocortisone-phosphatidylserine microbubbles and combined them with ultrasound (US)-targeted microbubble destruction technology to successfully open the BBB to achieve targeted drug delivery. Phosphatidylserine on the microbubbles was used for its “eat me” effect to increase the targeting of the microvesicles. In addition, we found that hydrocortisone can accelerate the closure of the BBB, achieving efficient drug delivery while reducing the entry of peripheral toxins into the brain. In the treatment of stroke inflammation, it was found that hydrocortisone itself has anti-inflammatory effects and can also change the polarization of microglia from the harmful pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype, thus achieving dual anti-inflammatory effects and enhancing the anti-inflammatory effects in ischemic areas after stroke, well reducing the cerebellar infarction volume by inhibiting the inflammatory response after cerebral ischemia. A confocal microendoscope was used to directly observe the polarization of microglial cells in living animal models for dynamic microscopic visualization detection showing the advantage of being closer to clinical work. Taken together, this study constructed a multifunctional targeted US contrast agent with the function of “one-stone-two-birds”, which can not only “on–off” the BBB but also have “two” anti-inflammatory functions, providing a new strategy of integrated anti-inflammatory targeted delivery and imaging monitoring for ischemic stroke treatment

SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer

Abstract Lymph node (LN) metastasis is one of the predominant metastatic routes of non-small cell lung cancer (NSCLC) and is considered as a leading cause for the unsatisfactory prognosis of patients. Although lymphangiogenesis is well-recognized as a crucial process in mediating LN metastasis, the regulatory mechanism involving lymphangiogenesis and LN metastasis in NSCLC remains unclear. In this study, we employed high-throughput sequencing to identify a novel circular RNA (circRNA), circTLCD4-RWDD3, which was significantly upregulated in extracellular vesicles (EVs) from LN metastatic NSCLC and was positively associated with deteriorated OS and DFS of patients with NSCLC from multicenter clinical cohort. Downregulating the expression of EV-packaged circTLCD4-RWDD3 inhibited lymphangiogenesis and LN metastasis of NSCLC both in vitro and in vivo. Mechanically, circTLCD4-RWDD3 physically interacted with hnRNPA2B1 and mediated the SUMO2 modification at K108 residue of hnRNPA2B1 by upregulating UBC9. Subsequently, circTLCD4-RWDD3-induced SUMOylated hnRNPA2B1 was recognized by the SUMO interaction motif (SIM) of ALIX and activated ALIX to recruit ESCRT-III, thereby facilitating the sorting of circTLCD4-RWDD3 into NSCLC cell-derived EVs. Moreover, EV-packaged circTLCD4-RWDD3 was internalized by lymphatic endothelial cells to activate the transcription of PROX1, resulting in the lymphangiogenesis and LN metastasis of NSCLC. Importantly, blocking EV-mediated transmission of circTLCD4-RWDD3 via mutating SIM in ALIX or K108 residue of hnRNPA2B1 inhibited the lymphangiogenesis and LN metastasis of NSCLC in vivo. Our findings reveal a precise mechanism underlying SUMOylated hnRNPA2B1-induced EV packaging of circTLCD4-RWDD3 in facilitating LN metastasis of NSCLC, suggesting that EV-packaged circTLCD4-RWDD3 could be a potential therapeutic target against LN metastatic NSCLC

Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.

SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution