L-茶氨酸对H2O2致L02细胞损伤的保护作用及其机制研究

研究L-茶氨酸对肝细胞损伤的保护作用及其机制。利用H2O2诱导的LO2肝细胞损伤模型,分别用MTT法检测细胞存活率、测定LDH、流式细胞术检测细胞凋亡率、Western blot法检测Caspase-3和PARP蛋白表达7LBax／Bcl-2比值的变化,评价L-茶氨酸是否能保护H2O2诱导的肝细胞损伤。结果表明,L-茶氨酸能提高H2O2损伤的L02细胞存活率,减少LDH的渗漏,降低肝细胞凋亡,且L-茶氨酸通过抑制caspase-3的激活和PARP的切割及Bax／Bcl-2比值的升高而发挥抗凋亡的作用。L-茶氨酸对肝细胞损伤有一定的治疗和保护作用。     

秤锤树属与长果安息香属植物的地理分布及其濒危现状

秤锤树属(SinojackiaHu)和长果安息香属(ChangiostyraxC.T.Chen)是安息香科的少种属,这两属在我国共记录有7个种。本文通过野外调查,分析了中国这两属植物的地理分布、濒危现状及其迁地保护状况。结果表明:秤锤树属植物地理分布较广,但是每个物种的居群数量和居群大小均很小。其中秤锤树(Sinojackiaxylocarpa)和狭果秤锤树(S.rehderiana)已经在其模式标本产地灭绝;棱果秤锤树(S.henryi)在过去的近70年内没有采到过标本,该物种可能存在同物异名现象或已经灭绝;细果秤锤树(S.microcarpa)由于人为破坏严重,居群大小急剧下降;肉果秤锤树(S.sarcocarpa)和怀化秤锤树(S.oblongicarpa)呈零星分布且个体数量很少,处于极濒危状态。另外本次调查发现秤锤树属的一个新的分类群(待鉴定种)。秤锤树属的大多数种和长果安息香属植物的居群更新能力差:虽然结果率较高,但是结籽率较低;坚硬的内果皮阻碍了种子的萌发,这是其居群更新的最大障碍;另外人为破坏对其居群更新的影响也较大。作者建议应该把秤锤树属的所有物种和长果安息香属植物都纳入保护的范围并讨论了这两属植物的保护策略。     

Comparing Protein Expression in Erwinia amylovora Strain TS3128 Cultured under Three Sets of Environmental Conditions

Erwinia amylovora, the causal agent of fire-blight disease in apple and pear trees, was first isolated in South Korea in 2015. Although numerous studies, including omics analyses, have been conducted on other strains of E. amylovora, studies on South Korean isolates remain limited. In this study, we conducted a comparative proteomic analysis of the strain TS3128, cultured in three media representing different growth conditions. Proteins related to virulence, type III secretion system, and amylovoran production, were more abundant under minimal conditions than in rich conditions. Additionally, various proteins associated with energy production, carbohydrate metabolism, cell wall/membrane/envelope biogenesis, and ion uptake were identified under minimal conditions. The strain TS3128 expresses these proteins to survive in harsh environments. These findings contribute to understanding the cellular mechanisms driving its adaptations to different environmental conditions and provide proteome profiles as reference for future studies on the virulence and adaptation mechanisms of South Korean strains.     

MicroRNA-363-3p/sphingosine-1-phosphate receptor 1 axis inhibits sepsis-induced acute lung injury via the inactivation of nuclear factor kappa-B ligand signaling

Infection-associated inflammation and coagulation are critical pathologies in sepsis-induced acute lung injury (ALI). This study aimed to investigate the effects of microRNA-363-3p (miR-363-3p) on sepsis-induced ALI and explore the underlying mechanisms. A cecal ligation and puncture-induced septic mouse model was established. The results of this study suggested that miR-363-3p was highly expressed in lung tissues of septic mice. Knockdown of miR-363-3p attenuated sepsis-induced histopathological damage, the inflammation response and oxidative stress in lung tissues. Furthermore, knockdown of miR-363-3p reduced the formation of platelet-derived microparticles and thrombin generation in blood samples of septic mice. Downregulation of miR-363-3p suppressed sphingosine-1-phosphate receptor 1 (S1PR1) expression in lung tissues and subsequently inactivated the nuclear factor kappa-B ligand (NF-κB) signaling. A luciferase reporter assay confirmed that miR-363-3p directly targeted the 3’-untranslated region of the mouse S1pr1 mRNA. Collectively, our study suggests that inactivation of NF-κB signaling is involved in the miR-363-3p/S1PR1 axis-mediated protective effect on septic ALI.     

AvrRps4 effector family processing and recognition in lettuce

During pathogenesis, effector proteins are secreted from the pathogen to the host plant to provide virulence activity for invasion of the host. However, once the host plant recognizes one of the delivered effectors, effector‐triggered immunity activates a robust immune and hypersensitive response (HR). In planta, the effector AvrRps4 is processed into the N‐terminus (AvrRps4^N) and the C‐terminus (AvrRps4^C). AvrRps4^C is sufficient to trigger HR in turnip and activate AtRRS1/AtRPS4‐mediated immunity in Arabidopsis; on the other hand, AvrRps4^N induces HR in lettuce. Furthermore, AvrRps4^N‐mediated HR requires a conserved arginine at position 112 (R112), which is also important for full‐length AvrRps4 (AvrRps4^F) processing. Here, we show that effector processing and effector recognition in lettuce are uncoupled for the AvrRps4 family. In addition, we compared effector recognition by lettuce of AvrRps4 and its homologues, HopK1 and XopO. Interestingly, unlike for AvrRps4 and HopK1, mutation of the conserved R111 in XopO by itself was insufficient to abolish recognition. The combination of amino acid substitutions arginine 111 to leucine with glutamate 114 to lysine abolished the XopO‐mediated HR, suggesting that AvrRps4 family members have distinct structural requirements for perception by lettuce. Together, our results provide an insight into the processing and recognition of AvrRps4 and its homologues.     

KxVPO4F (x∼0): A New High-Voltage and Low-Stain Cathode Material for Ultrastable Calcium Rechargeable Batteries

The utilization of high-voltage intercalation cathodes in calcium-ion batteries (CIBs) is impeded by the substantial size and divalent character of Ca²⁺ ions, which result in pronounced volume alterations and sluggish ion mobility, consequently causing inferior reversibility and low energy/power densities. To tackle these issues, polyanionic K-vacant K_xVPO₄F (x∼0, designated as K₀VPF) is proposed as high-voltage and ultra-stable cathode material in CIBs. The K₀VPF demonstrates a decent calcium storage capacity of 75 mAh g⁻¹ at 10 mA g⁻¹ and remarkable capacity retention of 84.2% over 1000 cycles. The average working voltage of the K₀VPF is 3.85 V versus Ca²⁺/Ca, representing the highest value reported for CIB cathodes to date. The combined experimental and theoretical investigations revealed that the low volume changes and hopping diffusion barriers contribute to the extraordinary stability and high-power capabilities, respectively, of K₀VPF. The distribution of Ca ions into polyanionic frameworks with pronounced spatial separation effectively attenuates the Ca²⁺–Ca²⁺ repulsive force and thus augmenting the Ca migration kinetics. The high voltage of K₀VPF is attributed to the inductive effect from the largely electronegative fluorine. In conjunction with a calcium metal anode and a compatible electrolyte, Ca metal full cells featured a record-high energy density of ≈300 Wh kg⁻¹.     

Design of Star-Shaped Trimer Acceptors for High-Performance (Efficiency > 19%), Photostable,and Mechanically Robust Organic Solar Cells

High power conversion efficiency (PCE), long-term stability, and mechanical robustness are prerequisites for the commercial applications of organic solar cells (OSCs). In this study, a new star-shaped trimer acceptor (TYT-S) is developed and high-performance OSCs with a PCE of 19.0%, high photo-stability (t_80% lifetime = 2600 h under 1-sun illumination), and mechanical robustness with a crack-onset strain (COS) of 21.6% are achieved. The isotropic molecular structure of TYT-S affords efficient multi-directional charge transport and high electron mobility. Furthermore, its amorphous structure prevents the formation of brittle crystal-to-crystal interfaces, significantly enhancing the mechanical properties of the OSC. As a result, the TYT-S-based OSCs demonstrate a significantly higher PCE (19.0%) and stretchability (COS = 21.6%) than the linear-shaped trimer acceptor (TYT-L)-based OSCs (PCE = 17.5% and COS = 6.4%) and the small-molecule acceptor (MYT)-based OSCs (PCE = 16.5% and COS = 1.3%). In addition, the increased molecular size of TYT-S, relative to that of MYT and dimer (DYT), suppresses the diffusion kinetics of the acceptor molecules, substantially improving the photostability of the OSCs. Finally, to effectively demonstrate the potential of TYT-S, intrinsically stretchable (IS)-OSCs are constructed. The TYT-S-based IS-OSCs exhibit high device stretchability (strain at PCE_80% = 31%) and PCE of 14.4%.     

A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers

Mutations of the RAS oncogene are found in around 30% of all human cancers yet direct targeting of RAS is still considered clinically impractical except for the KRAS^G12C mutant. Here we report that RAS-ON (RASON), a novel protein encoded by the long intergenic non-protein coding RNA 00673 (LINC00673), is a positive regulator of oncogenic RAS signaling. RASON is aberrantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) patients, and it promotes proliferation of human PDAC cell lines in vitro and tumor growth in vivo. CRISPR/Cas9-mediated knockout of Rason in mouse embryonic fibroblasts inhibits KRAS-mediated tumor transformation. Genetic deletion of Rason abolishes oncogenic KRAS-driven pancreatic and lung cancer tumorigenesis in LSL-Kras^G12D; Trp53^R172H/+ mice. Mechanistically, RASON directly binds to KRAS^G12D/V and inhibits both intrinsic and GTPase activating protein (GAP)-mediated GTP hydrolysis, thus sustaining KRAS^G12D/V in the GTP-bound hyperactive state. Therapeutically, deprivation of RASON sensitizes KRAS mutant pancreatic cancer cells and patient-derived organoids to EGFR inhibitors. Our findings identify RASON as a critical regulator of oncogenic KRAS signaling and a promising therapeutic target for KRAS mutant cancers.Subject terms: Gastrointestinal cancer, Cancer therapy     

Neuroprotection of exercise: P2X4R and P2X7R regulate BDNF actions

The neurotrophin brain-derived neurotrophic factor (BDNF), which acts as a transducer, is responsible for improving cerebral stroke, neuropathic pain, and depression. Exercise can alter extracellular nucleotide levels and purinergic receptors in central nervous system (CNS) structures. This inevitably activates or inhibits the expression of BDNF via purinergic receptors, particularly the P2X receptor (P2XR), to alleviate pathological progression. In addition, the significant involvement of sensitive P2X4R in mediating increased BDNF and p38-MAPK for intracerebral hemorrhage and pain hypersensitivity has been reported. Moreover, archetypal P2X7R blockade induces mouse antidepressant-like behavior and analgesia by BDNF release. This review summarizes BDNF-mediated neural effects via purinergic receptors, speculates that P2X4R and P2X7R could be priming molecules in exercise-mediated changes in BDNF, and provides strategies for the protective mechanism of exercise in neurogenic disease.     

Dorsal root ganglia P2X4 and P2X7 receptors contribute to diabetes-induced hyperalgesia and the downregulation of electroacupuncture on P2X4 and P2X7

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2’,3’-O-(2,4,6-trinitrophenyl)-adenosine 5’-triphosphate), a nonspecific P2X1–7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4–L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.