Multiresponsive Behavior of the Pickering Emulsifier and Its Application for Collecting Small Oil Droplets in Water.

Responsive Pickering emulsions, with unique nanoparticle interfaces and sensitivity to external stimuli, significantly enhanced the stability and applicability of Pickering emulsions. Multifunctional composite material poly((2-(dimethylaminoethyl methacrylate)-b-(acrylate cyclodextrin))/Fe3O4 nanoparticles, namely P(DMAEMA-b-A-CD)/Fe3O4, with both multiresponsive characteristics and emulsifying capabilities had been designed to remove small oil droplets from water. Using the reversible addition-fragmentation chain transfer (RAFT) method, diblock polymers P(DMAEMA-b-A-CD) were grown in a controlled manner on the surface of Fe3O4. The Fe3O4 core showed responsiveness to a magnetic field, and the block copolymers prepared via the RAFT method demonstrated reactivity to both pH and CO2. The P(DMAEMA-b-A-CD)/Fe3O4 nanoparticles exhibited the capability to form Pickering/Oxford emulsions with exceptional stabilization properties. It could be observed that the introduction of CO2, acid, and a magnetic field led to the breakage of the emulsion, while the emulsion could be restabilized by removing the CO2 and the magnetic field or by adding alkali. Measurements of interfacial tension, ζ-potential, and contact angle demonstrated that the emulsification/breakdown mechanisms associated with pH and CO2/N2 were related to the surface wettability of the nanoparticles. In addition, the emulsifier had an excellent cycling capacity with at least 10 cycles by CO2/N2. Additionally, P(DMAEMA-b-A-CD)/Fe3O4 nanoparticles exhibited excellent stability in oil phases with large polarity differences and various real oil phases with different viscosities. Importantly, the P(DMAEMA-b-A-CD)/Fe3O4 nanoparticles could serve as functional materials for efficiently separating small oil droplets from water through the application of a magnetic field. Therefore, P(DMAEMA-b-A-CD)/Fe3O4 nanoparticles held promising potential as materials with economic and commercial value for oil-water separation applications.

An integrated analysis revealing the angiogenic function of TP53I11 in tumor microenvironment.

Despite growing evidence suggesting an important contribution of Tumor Protein P53 Inducible Protein 11 (TP53I11) in cancer progression, the role of TP53I11 remains unclear. Our first pan-cancer analysis of TP53I11 showed some tumor tissues displayed reduced TP53I11 expression compared to normal tissues, while others exhibited high TP53I11 expression. Meanwhile, TP53I11 expression carries a particular pan-cancer risk, as high TP53I11 expression levels are detrimental to survival for BRCA, KIRP, MESO, and UVM, but to beneficial survival for KIRC. We demonstrated that TP53I11 expression negatively correlates with DNA methylation in most cancers, and the S14 residue of TP53I11 is phosphorylated in several cancer types. Additionally, TP53I11 was found to be associated with endothelial cells in pan-cancer, and functional enrichment analysis provided strong evidence for its role in tumor angiogenesis. In vitro angiogenesis assays confirmed that TP53I11 can promote angiogenic function of human umbilical vein endothelial cells (HUVECs) in vitro. Mechanistic investigations reveal that TP53I11 is transcriptionally up-regulated by HIF2A under hypoxia.

Physicochemical properties and antibacterial property of pickering emulsion stabilized by smart Janus nanospheres.

In this study, responsive Janus nanospheres were prepared by grafting LMA and DMAEMA monomers on both sides of SiO2 nanospheres using the Pickering emulsion stencil method and RAFT polymerization. The successful synthesis was verified through infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA), scanning electron microscopy (SEM) characterizations. Subsequently, Pickering emulsion was formulated using Janus nanospheres as emulsifiers. The particle size of the emulsion droplets was systematically investigated by manipulating factors such as pH, nanosphere dosage, water to oil ratio, and oil phase polarity. Notably, the Pickering emulsion exhibited responsive properties to pH, temperature, and CO2. Furthermore, Janus nanospheres exhibited excellent emulsification property for real oil phases, including canola oil, kerosene, gasoline, and diesel oil. Building upon this, a smart antibacterial Pickering emulsion was developed using Janus nanospheres, and its inhibition rate against E. coli could reach 100% within 4 h, which would be beneficial for its application in the food field.

VIX constant maturity futures trading strategy: A walk-forward machine learning study.

This study employs seven advanced machine learning approaches to conduct numerical predictions of the next-day returns of VIX constant-maturity futures (VIX CMFs) using the term structure information derived from VIX CMFs. Based on precise numerical predictions, this study proposes a new Constrained-Mean-Variance Portfolio Optimization (C-MVO) trading strategy and tests it against a benchmark long-short trading strategy to evaluate the profitability of the machine learning numerical predictions. This study applies three unique feature sets, each incrementally incorporating the VIX CMFs' term structure features, to individually examine the predictive ability of the seven machine learning models and their backtesting performance. Over a comprehensive 11-year period, the experiment adheres to a strict walk-forward expanding-window methodology for both training and backtesting. The predictive and backtesting results show that four of the seven machine learning models attain a prediction information ratio greater than 0.02, with an average prediction information ratio of 0.037. This result suggests that the VIX CMFs term structure features have predictive power for the next-day returns of VIX CMFs. Moreover, the average C-MVO information ratio is 0.623, and the long-short strategy information ratio is 0.404. This increase in the information ratio under the C-MVO strategy validates the effectiveness of the machine learning models and the C-MVO strategy.

Controllable Regulation of Diesel Oil-in-Water Pickering Emulsion Stability by Multiresponsive Recyclable Magnetic Polymer Brush Microvessels.

To ensure safety and efficiency in the production and transportation of fuel oil, there is an urgent demand to develop intelligent emulsifiers to deal with this challenge. Fe3O4@PDA-P(NIPAM-b-MAA-b-LMA) (MNPDNML) microspheres were prepared by modifying polydopamine and the triblock polymer brush P(NIPAM-b-MAA-b-LMA) on the surface of Fe3O4 nanoparticles via oxidative autopolymerization and SI-RAFT polymerization. Therefore, the MNPDNML microspheres exhibited sensitive stimulus-responsive behavior to pH, temperature, near-infrared (NIR) laser radiation, and magnetic fields. The stability state of the emulsion could be modulated by changing pH, temperature, magnetic field, and NIR radiation, and the reversible switching of emulsification/breaking behavior could be reached at least 10 times. This "intelligent emulsifier" exhibited high emulsification efficiency, long-term stability, and on-demand emulsification/breaking properties. It was notable that MNPDNML microspheres showed excellent emulsification ability for olive oil, kerosene, gasoline, and crude oil, which allowed the material to be widely used in the controlled transportation and separation of fuel oil.

G protein subunit alpha i2's pivotal role in angiogenesis.

Here we explored the potential role of Gαi2 (G protein subunit alpha i2) in endothelial cell function and angiogenesis. Methods: Genetic methodologies such as shRNA, CRISPR/Cas9, dominant negative mutation, and overexpression were utilized to modify Gαi2 expression or regulate its function. Their effects on endothelial cell functions were assessed in vitro. In vivo, the endothelial-specific Gαi2 shRNA adeno-associated virus (AAV) was utilized to silence Gαi2 expression. The impact of this suppression on retinal angiogenesis in control mice and streptozotocin (STZ)-induced diabetic retinopathy (DR) mice was analyzed. Results: Analysis of single-cell RNA sequencing data revealed Gαi2 (GNAI2) was predominantly expressed in retinal endothelial cells and expression was increased in retinal endothelial cells following oxygen-induced retinopathy (OIR) in mice. Moreover, transcriptome analysis linking Gαi2 to angiogenesis-related processes/pathways, supported by increased Gαi2 expression in experimental OIR mouse retinas, highlighted its possible role in angiogenesis. In various endothelial cell types, shRNA-induced silencing and CRISPR/Cas9-mediated knockout (KO) of Gαi2 resulted in substantial reductions in cell proliferation, migration, invasion, and capillary tube formation. Conversely, Gαi2 over-expression in endothelial cells induced pro-angiogenic activities, enhancing cell proliferation, migration, invasion, and capillary tube formation. Furthermore, our investigation revealed a crucial role of Gαi2 in NFAT (nuclear factor of activated T cells) activation, as evidenced by the down-regulation of NFAT-luciferase reporter activity and pro-angiogenesis NFAT-targeted genes (Egr3, CXCR7, and RND1) in Gαi2-silenced or -KO HUVECs, which were up-regulated in Gαi2-overexpressing endothelial cells. Expression of a dominant negative Gαi2 mutation (S48C) also down-regulated NFAT-targeted genes, slowing proliferation, migration, invasion, and capillary tube formation in HUVECs. Importantly, in vivo experiments revealed that endothelial Gαi2 knockdown inhibited retinal angiogenesis in mice, with a concomitant down-regulation of NFAT-targeted genes in mouse retinal tissue. In contrast, Gαi2 over-expression in endothelial cells enhanced retinal angiogenesis in mice. Single-cell RNA sequencing data confirmed increased levels of Gαi2 specifically in retinal endothelial cells of mice with streptozotocin (STZ)-induced diabetic retinopathy (DR). Importantly, endothelial Gαi2 silencing ameliorated retinal pathological angiogenesis in DR mice. Conclusion: Our study highlights a critical role for Gαi2 in NFAT activation, endothelial cell activation and angiogenesis, offering valuable insights into potential therapeutic strategies for modulating these processes.

Identification of circular RNA-Dcaf6 as a therapeutic target for optic nerve crush-induced RGC degeneration.

The death of retinal ganglion cells (RGCs) can cause irreversible injury in visual function. Clarifying the mechanism of RGC degeneration is critical for the development of therapeutic strategies. Circular RNAs (circRNAs) are important regulators in many biological and pathological processes. Herein, we performed circRNA microarrays to identify dysregulated circRNAs following optic nerve crush (ONC). The results showed that 221 circRNAs were differentially expressed between ONC retinas and normal retinas. Notably, the levels of circular RNA-Dcaf6 (cDcaf6) expression in aqueous humor of glaucoma patients were higher than that in cataract patients. cDcaf6 silencing could reduce oxidative stress-induced RGC apoptosis in vitro and alleviate retinal neurodegeneration in vivo as shown by increased neuronal nuclei antigen (NeuN, neuronal bodies) and beta-III-tubulin (TUBB3, neuronal filaments) staining and reduced glial fibrillary acidic protein (GFAP, activated glial cells) and vimentin (activated glial cells) staining. Collectively, this study identifies a promising target for treating retinal neurodegeneration.

Food Security and Land Use under Sustainable Development Goals: Insights from Food Supply to Demand Side and Limited Arable Land in China.

The conflict between economic growth and the arable land demand poses a significant challenge to maintaining food security and achieving the Sustainable Development Goals. Meanwhile, substantial regional disparities in food consumption contribute to variations in land demand, further exacerbating constraints on food security. However, few studies have delved into regional differences in land demand related to food consumption. To bridge these gaps, this study estimated the arable land demand and associated pressures, considering food consumption patterns and the land footprint across 31 provincial districts in China. The findings reveal that grains remain the primary crop consumed by Chinese residents. Notably, the food consumption pattern exhibits substantial disparities among provincial districts, particularly concerning livestock products. Given China's vast population and escalating consumption of livestock, the country demonstrates heightened land demands. While China does not face a national-level food security threat, regional disparities are evident, with eight provincial districts facing potential food security risks. This study explored the challenges and pathways in maintaining food security and the visions to achieve it, emphasizing the importance of sustaining a balanced food consumption pattern, reducing food waste, improving environmentally friendly agriculture practices, formulating effective and continuous laws and regulations, and exploring potential land resource development to alleviate the pressure on arable land and ensure food security.

Macrophage/microglia polarization for the treatment of diabetic retinopathy.

Macrophages/microglia are immune system defense and homeostatic cells that develop from bone marrow progenitor cells. According to the different phenotypes and immune responses of macrophages (Th1 and Th2), the two primary categories of polarized macrophages/microglia are those conventionally activated (M1) and alternatively activated (M2). Macrophage/microglial polarization is a key regulating factor in the development of inflammatory disorders, cancers, metabolic disturbances, and neural degeneration. Macrophage/microglial polarization is involved in inflammation, oxidative stress, pathological angiogenesis, and tissue healing processes in ocular diseases, particularly in diabetic retinopathy (DR). The functional phenotypes of macrophages/microglia affect disease progression and prognosis, and thus regulate the polarization or functional phenotype of microglia at different DR stages, which may offer new concepts for individualized therapy of DR. This review summarizes the involvement of macrophage/microglia polarization in physiological situations and in the pathological process of DR, and discusses the promising role of polarization in personalized treatment of DR.

Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.

We here tested the potential activity and the underlying mechanisms of neuroligin-3 (NLGN3) against ischemia-reperfusion-induced neuronal cell injury. In SH-SY5Y neuronal cells and primary murine cortical neurons, NLGN3 activated Akt-mTOR and Erk signalings, and inhibited oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced cytotoxicity. Akt activation was required for NLGN3-induced neuroprotection. Gαi1/3 mediated NLGN3-induced downstream signaling activation. NLGN3-induced Akt-S6K1 activation was largely inhibited by Gαi1/3 silencing or knockout. Significantly, NLGN3-induced neuroprotection against OGD/R was almost abolished by Gαi1/3 silencing or knockout. In vivo, the middle cerebral artery occlusion (MCAO) procedure induced NLGN3 cleavage and secretion, and increased its expression and Akt activation in mouse brain tissues. ADAM10 (A Disintegrin and Metalloproteinase 10) inhibition blocked MCAO-induced NLGN3 cleavage and secretion, exacerbating ischemic brain injury in mice. Neuronal silencing of NLGN3 or Gαi1/3 in mice also inhibited Akt activation and intensified MCAO-induced ischemic brain injury. Conversely, neuronal overexpression of NLGN3 increased Akt activation and alleviated MCAO-induced ischemic brain injury. Together, NLGN3 activates Gαi1/3-Akt signaling to protect neuronal cells from ischemia-reperfusion injury.

Efficient removal of both heavy metal ion and dyes from wastewater using magnetic response adsorbent of block polymer brush-grafted N-doped biochar.

The recovery of biomass from agricultural and forestry waste could realize effective utilization of waste and synthesis of novel adsorbent. Herein, porous biochar was prepared from waste ginkgo biloba leaves and modified by Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT). And the prepared adsorbent exhibited excellent adsorption capacity owing to its abundant functional groups and porous structure. In addition, the adsorption capacities of the prepared adsorbent for Malachite Green (MG), Amaranth (AM) and Cr (Ⅵ) were 422.59, 373.75 and 368.82 mg/g, respectively, surpassing those of many previously reported materials. Subsequently, the influence of various factors on adsorption performance was studied. The results showed that adsorption of MG, AM and Cr (Ⅵ) on adsorbent followed pseudo-second-order and Langmuir models and the adsorbent also displayed excellent cycling performance. The experimental results of application in various water samples showed that the adsorbent had outstanding adsorption performance in real water samples, further proving that the adsorbent had wide application and practicability. Finally, a simple adsorption column was used for filtration experiments to simulate industrial application. The results were exhibited that the adsorbent had great potential in treating wastewater containing MG, AM and Cr (Ⅵ).

Gαi1/3 mediate Netrin-1-CD146-activated signaling and angiogenesis.

Netrin-1 binds to the high-affinity receptor CD146 to activate downstream signaling and angiogenesis. Here, we examine the role and underlying mechanisms of G protein subunit alpha i1 (Gαi1) and Gαi3 in Netrin-1-induced signaling and pro-angiogenic activity. In mouse embryonic fibroblasts (MEFs) and endothelial cells, Netrin-1-induced Akt-mTOR (mammalian target of rapamycin) and Erk activation was largely inhibited by silencing or knockout of Gαi1/3, whereas signaling was augmented following Gαi1/3 overexpression. Netrin-1 induced Gαi1/3 association with CD146, required for CD146 internalization, Gab1 (Grb2 associated binding protein 1) recruitment and downstream Akt-mTOR and Erk activation. Netrin-1-induced signaling was inhibited by CD146 silencing, Gab1 knockout, or Gαi1/3 dominant negative mutants. Netrin-1-induced human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation were inhibited by Gαi1/3 short hairpin RNA (shRNA), but were potentiated by ectopic Gαi1/3 overexpression. In vivo, intravitreous injection of Netrin-1 shRNA adeno-associated virus (AAV) significantly inhibited Akt-mTOR and Erk activation in murine retinal tissues and reduced retinal angiogenesis. Endothelial knockdown of Gαi1/3 significantly inhibited Netrin1-induced signaling and retinal angiogenesis in mice. Netrin-1 mRNA and protein expression were significantly elevated in retinal tissues of diabetic retinopathy (DR) mice. Importantly, silence of Netrin-1, by intravitreous Netrin-1 shRNA AAV injection, inhibited Akt-Erk activation, pathological retinal angiogenesis and retinal ganglion cells degeneration in DR mice. Lastly, Netrin-1 and CD146 expression is significantly increased in the proliferative retinal tissues of human proliferative diabetic retinopathy patients. Together, Netrin-1 induces CD146-Gαi1/3-Gab1 complex formation to mediate downstream Akt-mTOR and Erk activation, important for angiogenesis in vitro and in vivo.

Advances in artificial intelligence models and algorithms in the field of optometry.

The rapid development of computer science over the past few decades has led to unprecedented progress in the field of artificial intelligence (AI). Its wide application in ophthalmology, especially image processing and data analysis, is particularly extensive and its performance excellent. In recent years, AI has been increasingly applied in optometry with remarkable results. This review is a summary of the application progress of different AI models and algorithms used in optometry (for problems such as myopia, strabismus, amblyopia, keratoconus, and intraocular lens) and includes a discussion of the limitations and challenges associated with its application in this field.

SCF/c-Kit-activated signaling and angiogenesis require Gαi1 and Gαi3.

The stem cell factor (SCF) binds to c-Kit in endothelial cells, thus activating downstream signaling and angiogenesis. Herein, we examined the role of G protein subunit alpha inhibitory (Gαi) proteins in this process. In MEFs and HUVECs, Gαi1/3 was associated with SCF-activated c-Kit, promoting c-Kit endocytosis, and binding of key adaptor proteins, subsequently transducing downstream signaling. SCF-induced Akt-mTOR and Erk activation was robustly attenuated by Gαi1/3 silencing or knockout (KO), or due to dominant negative mutations but was strengthened substantially following ectopic overexpression of Gαi1/3. SCF-induced HUVEC proliferation, migration, and capillary tube formation were suppressed after Gαi1/3 silencing or KO, or due to dominant negative mutations. In vivo, endothelial knockdown of Gαi1/3 by intravitreous injection of endothelial-specific shRNA adeno-associated virus (AAV) potently reduced SCF-induced signaling and retinal angiogenesis in mice. Moreover, mRNA and protein expressions of SCF increased significantly in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. SCF silencing, through intravitreous injection of SCF shRNA AAV, inhibited pathological retinal angiogenesis and degeneration of retinal ganglion cells in DR mice. Finally, the expression of SCF and c-Kit increased in proliferative retinal tissues of human patients with proliferative DR. Taken together, Gαi1/3 mediate SCF/c-Kit-activated signaling and angiogenesis.

Multifunctional pH-responsive carbon-based hydrogel adsorbent for ultrahigh capture of anionic and cationic dyes in wastewater.

An environmental friendly hydrogel adsorbent (DEC@GEL) was successfully manufactured by a facile free-radical polymerization method. Multiple characterizations demonstrated that the adsorbent was rich in functional groups and porous structures. The batch and multisystem adsorption experiments were applied to systematically investigate the adsorption properties of methylene blue (MB), malachite green (MG), indigo sodium dimethyl sulfonate (IC) and tartrazine (TR) in wastewater. The experimental results proved that the kinetic and isotherms of four dyes were more consistent with the pseudo-second-order and Langmuir model, respectively. Notably, the maximum adsorption capacities of MB, MG, TR and IC at 318 K were 2186.85, 2302.53, 1766.13 and 2301.75 mg/g, respectively, which were higher than many adsorbents that had been reported. Recycle experiment demonstrated the high reusability of the DEC@GEL. The selectivity and adsorption column experiments proved that DEC@GEL was not only widely applicable to various dyes, but also provided a positive start for the industrial application. Moreover, the simulated adsorption experiments further demonstrate that DEC@GEL had the prospect of application in real industrial conditions. Finally, four adsorption mechanisms had been proposed. Various adsorption experiments had shown that DEC@GEL was not only efficient in processing dyes, but also had great potential for practical industrial applications.

Long Noncoding RNA LINC00909 Induces Epithelial-Mesenchymal Transition and Contributes to Osteosarcoma Tumorigenesis and Metastasis.

Background: Osteosarcoma (OS) is a malignant tumor that is highly metastatic with a high mortality rate. Although mounting evidence suggests that LINC00909 is strongly associated with the malignant progression of various tumors, the exact role of LINC00909 in OS remains unknown. Therefore, the current study was designed to investigate the relationship between LINC00909 and the malignant progression of OS. Methods: LINC00909 expression was measured in OS cell lines and clinical specimens using RT-qPCR assays. The effects of LINC00909 on OS proliferation, invasion, and migration were calculated both in vitro and in vivo. Apart from that, bioinformatics analyses, FISH, RIP, and luciferase reporter assays were carried out to investigate the downstream target of LINC00909. Rescue experiments were also conducted to investigate the potential mechanisms of action of competitive endogenous RNAs (ceRNAs). Results: In this study, we found that LINC00909 was highly expressed in OS cell lines and clinical specimens. In vivo and in vitro experiments demonstrated that LINC00909 induces epithelial-to-mesenchymal transition (EMT) and contributes to OS tumorigenesis and metastasis. FISH, RIP, and luciferase assays indicated that miR-875-5p is a direct target of LINC00909. Moreover, HOXD9 was validated as the downstream target of miR-875-5p in a luciferase reporter assay and western blotting experiments. Rescue experiments revealed that HOXD9 reversed the effect of LV-sh-LINC00909 on OS cells by positively regulating the PI3K/AKT/mTOR signaling pathway. Conclusion: Collectively, LINC00909 induces EMT and contributes to OS tumorigenesis and metastasis through the PI3K/AKT/mTOR pathway by binding to miR-875-5p to upregulate HOXD9 expression. Targeting the LINC00909/miR-875-5p/HOXD9 axis may have potential in treating OS.

Jujuboside A Exhibits an Antiepileptogenic Effect in the Rat Model via Protection against Traumatic Epilepsy-Induced Oxidative Stress and Inflammatory Responses.

Traumatic brain injuries (TBI) are the greatest source of death in trauma, and post-traumatic epilepsy (PTE) is one of the common complications of TBI. Oxidative stress and inflammatory responses play an important role in the process of PTE. Many studies have shown that Jujuboside A has powerful antioxidant and anti-inflammatory properties. However, it is not known whether Jujuboside A has an anti-epileptic effect. The influences of Jujuboside A in the experimental FeCl3-induced model of PTE were tested by estimating the grade of seizures and performing behavioral tests. Following that, we detected oxidative stress indicators and inflammatory factors. Additionally, western blotting was used to test the protein levels of signaling molecules in MAPK pathways. In this study, Jujuboside A was found to have improved the recognition deficiency and epilepsy syndromes in the experimental rat model. Moreover, oxidative stress and inflammatory responses induced by FeCl3 injection were relieved by Jujuboside A. In addition, Jujuboside A was found to be capable of reducing the increased expression of p-P38 and p-ERK1/2 caused by iron ions. Collectively, our results demonstrated that Jujuboside A exhibits an antiepileptogenic effect by alleviating oxidative stress and inflammatory responses via the p38 and ERK1/2 pathways.

Nrf2 signaling activation by a small molecule activator compound 16 inhibits hydrogen peroxide-induced oxidative injury and death in osteoblasts.

We explored the potential activity of compound 16 (Cpd16), a novel small molecule Nrf2 activator, in hydrogen peroxide (H2O2)-stimulated osteoblasts. In the primary murine/human osteoblasts and MC3T3-E1 murine osteoblastic cells, Cpd16 treatment at micro-molar concentrations caused disassociation of Keap1-Nrf2 and Nrf2 cascade activation. Cpd16 induced stabilization of Nrf2 protein and its nuclear translocation, thereby increasing the antioxidant response elements (ARE) reporter activity and Nrf2 response genes transcription in murine and human osteoblasts. Significantly, Cpd16 mitigated oxidative injury in H2O2-stimulited osteoblasts. H2O2-provoked apoptosis as well as programmed necrosis in osteoblasts were significantly alleviated by the novel Nrf2 activator. Cpd16-induced Nrf2 activation and osteoblasts protection were stronger than other known Nrf2 activators. Dexamethasone- and nicotine-caused oxidative stress and death in osteoblasts were attenuated by Cpd16 as well. Cpd16-induced osteoblast cytoprotection was abolished by Nrf2 short hairpin RNA or knockout, but was mimicked by Keap1 knockout. Keap1 Cys151S mutation abolished Cpd16-induced Nrf2 cascade activation and osteoblasts protection against H2O2. Importantly, weekly Cpd16 administration largely ameliorated trabecular bone loss in ovariectomy mice. Together, Cpd16 alleviates H2O2-induced oxidative stress and death in osteoblasts by activating Nrf2 cascade.