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[Display omitted] Neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain, with a high incidence and complex pathogenesis, is one of the most significant areas of clinical medicine and basic research. Currently, prescribed treatments are still unsatisfactory or have limited effectiveness. A medicinal preparation is required that relieves the neuropathic pain and prolongs action time, which has not yet been discovered. In this study, MIL-101 (Fe) was employed as a drug carrier to regulate the release of diclofenac sodium, thereby achieving the effect of analgesia and sustained release. The release curves demonstrated that diclofenac sodium could be continuously released from MIL-101 (Fe) for more than 48 h. There was no toxicity in vitro and in vivo, and the safety of MIL-101 (Fe) was confirmed by hematoxylin and eosin as well as ELISA tests in vivo. The results of behavioral testing, pharmacokinetics, and RNA sequencing analysis showed that MIL-101 (Fe) loaded with diclofenac sodium could enhance the mechanical withdrawal threshold and alleviate cold allodynia induced by Spared Nerve Injury, prolonging the work time by three days. The results indicated that MIL-101 (Fe) exhibited excellent biocompatibility, while the MIL-101 (Fe)-DS demonstrated analgesic and controlled-release properties. These findings provide a scientific foundation for the clinical management of neuropathic pain and the development of a novel formulation. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a debilitating psychiatric disorder which is common and endangers human physical and mental health. Studies have shown that hesperidin could improve the symptoms of depression with unclear mechanisms. In this study, hesperidin was administered to chronic unpredictable mild stress (CUMS) depressed mice before behavioral test, network pharmacology analysis, RNA expression microarray analysis, pathway validation and molecular docking experiments. we found that hesperidin intervention could significantly improve the depressive symptoms and downregulate the expression level of pyroptosis pathway including caspase 1 (Casp1), interleukin 18 (IL18), interleukin-1β (IL-1β) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). In addition, we found that hesperidin could possibly bind to NLRP3. Our study demonstrated that hesperidin had huge potential as anti-depressive neuroprotectant, and may play a role in treating MDD by regulating NLRP3-mediated pyroptosis. [ABSTRACT FROM AUTHOR]

Fresh lotus seeds are gaining favor with consumers for their crunchy texture and natural sweetness. However, the intricacies of sugar accumulation in lotus seeds remain elusive, which greatly hinders the quality improvement of fresh lotus seeds. This study endeavors to elucidate this mechanism by identifying and characterizing the sucrose synthase (SUS) gene family in lotus. Comprising five distinct members, namely NnSUS1 to NnSUS5 , each gene within this family features a C-terminal glycosyl transferase1 (GT1) domain. Among them, NnSUS1 is the predominately expressed gene, showing high transcript abundance in the floral organs and cotyledons. NnSUS1 was continuously up-regulated from 6 to 18 days after pollination (DAP) in lotus cotyledons. Furthermore, NnSUS1 demonstrates co-expression relationships with numerous genes involved in starch and sucrose metabolism. To investigate the function of NnSUS1 , a transient overexpression system was established in lotus cotyledons, which confirmed the gene's contribution to sugar accumulation. Specifically, transient overexpression of NnSUS1 in seed cotyledons leads to a significant increase in the levels of total soluble sugar, including sucrose and fructose. These findings provide valuable theoretical insights for improving sugar content in lotus seeds through molecular breeding methods. • Five sucrose synthase (SUS) genes were identified and characterized in lotus. • NnSUS1 is the predominately expressed gene in lotus. • A transient overexpression system was successfully established in cotyledon. • NnSUS1 plays a positive role in sugar accumulation in seed cotyledons. [ABSTRACT FROM AUTHOR]

Originating in the subtropics, cucumbers require warm weather and plenty of light, low light inhibits the growth of cucumbers. For cucumbers to efficiently absorb light energy in low light, chlorophyll synthesis is necessary. Oxygenase for chlorophyllate is encoded by CsCAO. RNA interference (RNAi) was used to reduce CsCAO expression in cucumber, reduced chlorophyll b content and Fv/Fm (maximal photochemical efficiency of photosystem II) were found in RNAi- CsCAO lines. The Arabidopsis Atcao mutant lacks chlorophyll b and has a low Fv/Fm, but overexpressing CsCAO restored the mutant's phenotype. CsCAO gene expression was found to be upregulated in the presence of low light. The Y1H screening assay revealed that CsHsfA6b and CsBLH4 were potential CsCAO expression regulators. The results of the Y1H, LUC/REN, and EMSA assays confirmed that only CsBLH4 can bind to the CsCAO promoter. Furthermore, like Atcao , the Atblh4 mutant had low chlorophyll b content and Fv/Fm. CsCAO overexpression in the Atblh4 mutant increased the content of chlorophyll b and Fv/Fm, especially under low light conditions. CsBLH4 targeting CsCAO was found to positively regulate chlorophyll b synthesis and photosynthetic capacity in cucumber under low light conditions in our study. • Low light promoted the accumulation of chlorophyll b by up-regulating the transcription level of CsCAO. • It clarified the regulatory mechanism of BLH family member involved in chlorophyll b synthesis. • The synthesis of chlorophyll plays an important role in the response of cucumber to low light stress. [ABSTRACT FROM AUTHOR]

• By inhibiting SLC7A11/xCT with the inhibitor sulfasalazine and nanoreactors with tetrasulfide bond (-s-s-s-s-)- as the backbone, tumor cell glutathione synthesis is suppressed and its consumption is promoted. • Decreased glutathione content inhibits GPX4 synthesis, promotes intracellular lipid peroxide accumulation, and induces ferroptosis in tumor cells. • The photosensitizer DVDMS produces ROS under ultrasound, which, together with Fe3+, promotes lipid peroxide generation. • Targeted delivery of USP39 shRNA can efficiently silence USP39 gene expression under ultrasound stimulation, inhibiting cell proliferation and selectively inducing autophagy-dependent ferroptosis. The promotion of cellular ferroptosis through ultrasound (US)-assisted Fenton chemistry has emerged as a promising strategy for tumor therapy. To enhance the therapeutic effect, we designed a GSH-responsive ultrasound-driven nanoreactor for RNA interference (RNAi)-intensified ferroptosis in synergistic sono-chemodynamic therapy. Our nanoreactor comprises Fe3+/tetrasulfide bond (-s-s-s-s-) enriched dendritic organosilica encapsulating USP39 shRNA, along with co-loading of sinophoryrin sodium (DVDMS) and sulfasalazine (SAS). Hyaluronic acid surface functionalization ensures high tumor accumulation for active targeting of tumor cells. Upon internalization into tumor cells, the nanoreactor degrades upon the triggering of intracellular overproduced GSH. Ultrasound-triggered release of DVDMS generates large amounts of ROS, synergizing with Fe-catalyzed Fenton chemistry. The simultaneous depletion of glutathione peroxidase 4 and GSH by SAS and Fe3+ weakens the ROS-scavenging system, leading to tumoral redox dyshomeostasis via oxidative stress amplification. This results in the accumulation of lipid peroxide in tumor cells, efficiently inducing ferroptosis. Additionally, USP39 shRNA effectively silences the expression of the USP39 gene in cells, inhibiting tumor cell proliferation, while promoting ATG5 gene expression to intensify ferroptosis. Our work provides a promising nanoreactor for high-efficiency synergistic tumor therapy via RNAi-intensified ferroptosis, highlighting the potential of sono-chemodynamic therapy in cancer treatment. [ABSTRACT FROM AUTHOR]

Cucumber (Cucumis sativus L.) is a high water-demanding and drought-susceptible vegetable crop. Basic leucine zipper (bZIP) transcription factors (TFs) have been linked to drought stress response in plants. Here we characterized a G subfamily gene in cucumber, CsbZIP50 , which was strongly induced by drought stress and an exogenous abscisic acid (ABA) treatment. Under drought stress, CsbZIP50 -overexpressing plants exhibited enhanced drought tolerance compared with wild-type plants, as indicated by the higher antioxidant enzyme activities but lower reactive oxygen species (ROS) and malondialdehyde contents. In addition, overexpression of CsbZIP50 enhanced cucumber's sensitivity to exogenously applied ABA, and up-regulated the expression of its stress-related genes. Moreover, we found that CsbZIP50 activated CsRD29 expression by directly binding to the G-box/ABRE cis-acting element in its promoter, both in vitro and in vivo. Yeast two-hybrid, luciferase complementation imaging, and pull-down assays showed that CsbZIP50 physically interacted with two IQ domain-containing proteins, CsIQD1 and CsIQD4, both of which promoted the ability of CsbZIP50 to activate the expression of CsRD29. Taken together, our results show that CsbZIP50 enhances drought stress tolerance in cucumber by regulating drought-responsive gene expression and ROS levels. • CsbZIP50 is a G subfamily of the bZIP TF, which was induced by drought stress and exogenous ABA treatment. • Expression of CsbZIP50 positively regulates drought tolerance by improving stomata closure and ROS scavenging. • CsbZIP50 targeted CsRD29A and the expression activation effect was enhanced by interacting with CsIQD1 and CsIQD4. [ABSTRACT FROM AUTHOR]