SIAH2 suppresses c-JUN pathway by promoting the polyubiquitination and degradation of HBx in hepatocellular carcinoma.

As an important protein encoded by hepatitis B virus (HBV), HBV X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). It has been shown that seven in absentia homologue 1 (SIAH1) could regulates the degradation of HBx through the ubiquitin-proteasome pathway. However, as a member of SIAH family, the regulatory effects of SIAH2 on HBx remain unclear. In this study, we first confirmed that SIAH2 could reduce the protein levels of HBx depending on its E3 ligase activity. Moreover, SIAH2 interacted with HBx and induced its K48-linked polyubiquitination and proteasomal degradation. Furthermore, we provided evidence that SIAH2 inhibits HBx-associated HCC cells proliferation by regulating HBx. In conclusion, our study identified a novel role for SIAH2 in promoting HBx degradation and SIAH2 exerts an inhibitory effect in the proliferation of HBx-associated HCC through inducing the degradation of HBx. Our study provides a new idea for the targeted degradation of HBx and may have great huge significance into providing novel evidence for the targeted therapy of HBV-infected HCC.

Long range topography by dispersion unmatched spectral-domain interferometry based on virtually imaged phased array modes.

We propose to realize a long range topography by dispersion unmatched spectral-domain interferometry based on virtually imaged phased array (VIPA) modes. By filtering the continuous spectrum of a supercontinuum source through a side-entrance Fabry-Perot etalon configured at two input angles, two groups of VIPA modes are generated. A method based on unmatched dispersion is proposed for non-aliasing reconstruction of the true depth from the interference spectrum under-sampled at two groups of VIPA modes. With the high spectral resolution provided by the VIPA modes instead of the grating-based spectrometer, only a 10 dB falloff in sensitivity over a range of 10 mm was demonstrated. The feasibility of the proposed method was confirmed by topography of a sample of gauge blocks and a model of three-dimensional (3D) printed tooth. The occlusal surface of the tooth model was further quantitatively evaluated, demonstrating its potential application in long range 3D topography.

Day-to-Night Street View Image Generation for 24-Hour Urban Scene Auditing Using Generative AI.

A smarter city should be a safer city. Nighttime safety in metropolitan areas has long been a global concern, particularly for large cities with diverse demographics and intricate urban forms, whose citizens are often threatened by higher street-level crime rates. However, due to the lack of night-time urban appearance data, prior studies based on street view imagery (SVI) rarely addressed the perceived night-time safety issue, which can generate important implications for crime prevention. This study hypothesizes that night-time SVI can be effectively generated from widely existing daytime SVIs using generative AI (GenAI). To test the hypothesis, this study first collects pairwise day-and-night SVIs across four cities diverged in urban landscapes to construct a comprehensive day-and-night SVI dataset. It then trains and validates a day-to-night (D2N) model with fine-tuned brightness adjustment, effectively transforming daytime SVIs to nighttime ones for distinct urban forms tailored for urban scene perception studies. Our findings indicate that: (1) the performance of D2N transformation varies significantly by urban-scape variations related to urban density; (2) the proportion of building and sky views are important determinants of transformation accuracy; (3) within prevailed models, CycleGAN maintains the consistency of D2N scene conversion, but requires abundant data. Pix2Pix achieves considerable accuracy when pairwise day-and-night-night SVIs are available and are sensitive to data quality. StableDiffusion yields high-quality images with expensive training costs. Therefore, CycleGAN is most effective in balancing the accuracy, data requirement, and cost. This study contributes to urban scene studies by constructing a first-of-its-kind D2N dataset consisting of pairwise day-and-night SVIs across various urban forms. The D2N generator will provide a cornerstone for future urban studies that heavily utilize SVIs to audit urban environments.

Single-cluster anchored on PC6 monolayer as high-performance electrocatalyst for carbon dioxide reduction reaction: First principles study.

Tremendous challenges remain to develop high-efficient catalysts for carbon dioxide reduction reaction (CO2RR) owing to the poor activity and low selectivity. However, the activity of catalyst with single active site is limited by the linear scaling relationship between the adsorption energy of intermediates. Motivated by the idea of multiple activity centers, triple metal clusters (M = Cr, Mn, Fe, Co, Ni, Cu, Pd, and Rh) doped PC6 monolayer (M3@PC6) were constructed in this study to investigate the CO2RR catalytic performance via density functional theory calculations. Results shows Mn3@PC6, Fe3@PC6, and Co3@PC6 exhibit high activity and selectivity for the reduction of CO2 to CH4 with limiting potentials of -0.32, -0.28, and -0.31 V, respectively. Analysis on the high-performance origin shows the more binding sites in M3@PC6 render the triple-atom anchored catalysts (TACs) high ability in regulating the binding strength with intermediates by self-adjusting the charges and conformation, leading to the improved performance of M3@PC6 than dual-atom doped PC6. This work manifests the huge application of PC6 based TACs in CO2RR, which hope to prove valuable guidance for the application of TACs in a broader range of electrochemical reactions.

Neem Leaf Extract Exhibits Anti-Aging and Antioxidant Effects from Yeast to Human Cells.

Neem leaves have long been used in traditional medicine for promoting longevity. However, the precise mechanisms underlying their anti-aging effects remain elusive. In this study, we investigated the impact of neem leaf extract (NLE) extracted from a 50% ethanol solution on the chronological lifespan of Saccharomyces cerevisiae, revealing an extension in lifespan, heightened oxidative stress resistance, and a reduction in reactive oxygen species. To discern the active compounds in NLE, LC/MS and the GNPS platform were employed. The majority of identified active compounds were found to be flavonoids. Subsequently, compound-target pharmacological networks were constructed using the STP and STITCH platforms for both S. cerevisiae and Homo sapiens. GOMF and KEGG enrichment analyses of the predicted targets revealed that "oxidoreductase activity" was among the top enriched terms in both yeast and human cells. These suggested a potential regulation of oxidative stress response (OSR) by NLE. RNA-seq analysis of NLE-treated yeast corroborated the anti-oxidative effect, with "oxidoreductase activity" and "oxidation-reduction process" ranking high in enriched GO terms. Notably, CTT1, encoding catalase, emerged as the most significantly up-regulated gene within the "oxidoreductase activity" cluster. In a ctt1 null mutant, the enhanced oxidative stress resistance and extended lifespan induced by NLE were nullified. For human cells, NLE pretreatment demonstrated a decrease in reactive oxygen species levels and senescence-associated ß-galactosidase activity in HeLa cells, indicative of anti-aging and anti-oxidative effects. This study unveils the anti-aging and anti-oxidative properties of NLE while delving into their mechanisms, providing novel insights for pharmacological interventions in aging using phytochemicals.

Oxygen Coordination Promotes Single-Atom Cu(II)-Catalyzed Azide-Alkyne Click Chemistry without Reducing Agents.

Unique active sites make single-atom (SA) catalysts promising to overcome obstacles in homogeneous catalysis but challenging due to their fixed coordination environment. Click chemistry is restricted by the low activity of more available Cu(II) catalysts without reducing agents. Herein, we develop efficient, O-coordinated SA Cu(II) directly catalyzed click chemistry. As revealed by theoretical calculations of the superior coordination structure to promote the click reaction, an organic molecule-assisted strategy is applied to prepare the corresponding SA Cu catalysts with respective O and N coordination. Although they both belong to Cu(II) centers, the O-coordinated one exhibits a 5-fold higher activity than the other and even much better activity than traditional homogeneous and heterogeneous Cu(II) catalysts. Control experiments further proved that the O-coordinated SA Cu(II) catalyst tends to be reduced by alkyne into Cu acetylide rather than the N-coordinated catalyst and thus facilitates click chemistry.

Unveiling the gastric microbiota: implications for gastric carcinogenesis, immune responses, and clinical prospects.

High-throughput sequencing has ushered in a paradigm shift in gastric microbiota, breaking the stereotype that the stomach is hostile to microorganisms beyond H. pylori. Recent attention directed toward the composition and functionality of this 'community' has shed light on its potential relevance in cancer. The microbial composition in the stomach of health displays host specificity which changes throughout a person's lifespan and is subject to both external and internal factors. Distinctive alterations in gastric microbiome signature are discernible at different stages of gastric precancerous lesions and malignancy. The robust microbes that dominate in gastric malignant tissue are intricately implicated in gastric cancer susceptibility, carcinogenesis, and the modulation of immunosurveillance and immune escape. These revelations offer fresh avenues for utilizing gastric microbiota as predictive biomarkers in clinical settings. Furthermore, inter-individual microbiota variations partially account for differential responses to cancer immunotherapy. In this review, we summarize current literature on the influence of the gastric microbiota on gastric carcinogenesis, anti-tumor immunity and immunotherapy, providing insights into potential clinical applications.

Association between oral microbiome and five types of respiratory infections: a two-sample Mendelian randomization study in east Asian population.

Objective: To explore the causal relationship between the oral microbiome and specific respiratory infections including tonsillitis, chronic sinusitis, bronchiectasis, bronchitis, and pneumonia, assessing the impact of genetic variations associated with the oral microbiome. Methods: Mendelian randomization was used to analyze genetic variations, leveraging data from genome-wide association studies in an East Asian cohort to identify connections between specific oral microbiota and respiratory infections. Results: Our analysis revealed that Prevotella, Streptococcus, Fusobacterium, Pauljensenia, and Capnocytophaga play crucial roles in influencing respiratory infections. Prevotella is associated with both promoting bronchitis and inhibiting pneumonia and tonsillitis, with a mixed effect on chronic sinusitis. Streptococcus and Fusobacterium show varied impacts on respiratory diseases, with Fusobacterium promoting chronic sinusitis, bronchiectasis, and bronchitis. Conversely, Pauljensenia and Capnocytophaga are linked to reduced bronchitis and tonsillitis, and inhibited pneumonia and bronchitis, respectively. Discussion: These findings underscore the significant impact of the oral microbiome on respiratory health, suggesting potential strategies for disease prevention and management through microbiome targeting. The study highlights the complexity of microbial influences on respiratory infections and the importance of further research to elucidate these relationships.

The effect of anxiety on sleep disorders in medical students: a moderated mediation model.

The relationship between anxiety and sleep disorders is a key research topic in the academic community. However, evidence on the mechanism through which anxiety influences sleep disorders remains limited. The purpose of this study was to investigate the roles of flourishing and neuroticism in the mechanism through which anxiety influences sleep disorders in medical students. We constructed a moderated mediation model and tested the mediating role of flourishing and the moderating role of neuroticism in medical college students. The results showed that: (1) anxiety was significantly and positively related to sleep disorders and significantly and negatively related to flourishing; flourishing was significantly and negatively related to sleep disorders; neuroticism was significantly and positively related to sleep disorders; (2) flourishing had a mediation effect on the relationship between anxiety and sleep disorders; (3) neuroticism moderated the process through which flourishing mediated the effect of anxiety on sleep disorders. Our research expands the literature on the mechanism underlying the effects of anxiety on sleep disorders and provides insights into the potential prevention and intervention of sleep and emotional problems in medical students.

B cells mediate lung ischemia/reperfusion injury by recruiting classical monocytes via synergistic B cell receptor/TLR4 signaling.

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We found that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborated our findings in reperfused human lungs, in which we observed a correlation between B cell infiltration and CM recruitment after transplantation. This study describes a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies.

The ever-lasting green tides: What can we do？.

Macroalgal blooms (Green tides) are occurring more frequently in many regions of the world because of the combined effects of increasingly intense human activity and climate change. In the last decade, the world's largest Ulva prolifera green tide has become a recurrent phenomenon, appearing every summer in the southern Yellow Sea, China. Green tides can hurt coastal tourism and eradicate aquaculture and artisanal fishing. Eutrophication in nearshore waters is the ultimate explanation for the explosive growth of the macroalgal biomass, but the specific course of each nearshore green tide is often complex and requires in-depth and extensive research to develop effective mitigation strategies. Researchers have undertaken extensive studies on the prevention, control and mitigation of large-scale green algal blooms, and felicitated the utilization of green tide harmful biomass through bio-refining, bioconversion and other measures. However, due to the large-scale and trans-regional nature of the green tide, the government's administrative coordination measures are also essential for effective control. Nevertheless, it is becoming increasingly urgent to prevent and control the bloom at the early stage, and efficiently salvage and use these valuable raw materials.

Efficacy of acupuncture therapy on cancer-related insomnia: a systematic review and network meta-analysis.

Objectives: Cancer-related insomnia (CRI) takes a toll on many cancer survivors, causing distressing symptoms and deteriorating the quality of life. Acupuncture therapy has been used for CRI already. However, it is still uncertain which acupuncture regime is best for CRI. The primary objective of this review is to conduct a comparative evaluation and ranking of the effectiveness of different acupuncture therapies for CRI. Methods: Randomized controlled trials (RCTs) that were published up to July 31, 2023, from 8 databases (PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc) were integrated in this study. Trials that met the inclusion criteria were evaluated the risk of bias. Pittsburgh sleep quality index (PSQI) was used to assess the efficacy of different acupuncture therapies as the primary outcome. Then, STATA 15, R, and OpenBUGS were applied to perform the network meta-analysis. PRISMA statements were followed in this network meta-analysis. Results: A total of 37 studies were included in this review, involving 16 interventions with 3,246 CRI participants. Auriculotherapy + moxibustion [surface under the cumulative ranking curve (SUCRA) 98.98%] and auriculotherapy (SUCRA 77.47%) came out top of the ranking, which were more effective than control, medicine, usual care and sham acupuncture. Conclusion: Auriculotherapy + moxibustion and auriculotherapy + acupuncture emerged as the top two acupuncture regimes for CRI and future studies should pay more attention to CRI. Clinical trial registration: https://clinicaltrials.gov/, identifier INPLASY202210095.

Sex-specific differences in the associations between adiposity indices and incident hyperuricemia among middle-aged and older adults: a nationwide longitudinal study.

Objective: Although obesity is a known risk for hyperuricemia (HUA), the associations between adiposity indices and incident HUA and whether sex-specific differences exist is still unknown. We aimed to investigate the associations between adiposity indices and incident HUA in a longitudinal study. Methods: Data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011-2012 and 2015-2016 were used to conduct a cohort study. Participants aged ≥45 years without HUA at baseline were included in this study. Adiposity indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio body roundness index (BRI), conicity index (CI), lipid accumulation product (LAP) index, waist-to-height ratio (WHtR), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI), were calculated. Logistic analysis was used to analyze the association between adiposity indices and incident HUA risk stratified by gender. Receiver operating characteristic curve analysis was performed to evaluate the power of predictions for incident HUA. Results: Of 5,873 participants aged 59.0 ± 8.7 years enrolled in this study, 578 (9.8%) participants developed HUA during the 4-year follow-up period. After adjusting for confounding variables, LAP, VAI, and CVAI showed significant association with incident HUA. BMI, WC, WHtR, BRI, and CI were significantly associated with incident HUA in women but not in men. LAP had the highest area under the curve (AUC) (0.612) followed by CVAI (0.596) in men, while CVAI had the highest AUC (0.707) followed by LAP (0.691) in women. All indices showed better predictive ability in women than in men. Conclusion: Our findings indicated that adiposity indices were effective predictors of incident HUA and showed better predictive power in women than men. In clinical practice, adiposity indices could be used to assess and prevent incident HUA among Chinese middle-aged and older adults.

Canagliflozin protects against hyperglycemia-induced cerebrovascular injury by preventing blood-brain barrier (BBB) disruption via AMPK/Sp1/adenosine A2A receptor.

Diabetes mellitus causes brain microvascular endothelial cell (MEC) damage, inducing dysfunctional angiogenic response and disruption of the blood-brain barrier (BBB). Canagliflozin is a revolutionary hypoglycemic drug that exerts neurologic and/or vascular-protective effects beyond glycemic control; however, its underlying mechanism remains unclear. In the present study, we hypothesize that canagliflozin ameliorates BBB permeability by preventing diabetes-induced brain MEC damage. Mice with high-fat diet/streptozotocin-induced diabetes received canagliflozin for 8 weeks. We assessed vascular integrity by measuring cerebrovascular neovascularization indices. The expression of specificity protein 1 (Sp1), as well as tight junction proteins (TJs), phosphorylated AMP-activated protein kinase (p-AMPK), and adenosine A2A receptors was examined. Mouse brain MECs were grown in high glucose (30 mM) to mimic diabetic conditions. They were treated with/without canagliflozin and assessed for migration and angiogenic ability. We also performed validation studies using AMPK activator (AICAR), inhibitor (Compound C), Sp1 small interfering RNA (siRNA), and adenosine A2A receptor siRNA. We observed that cerebral pathological neovascularization indices were significantly normalized in mice treated with canagliflozin. Increased Sp1 and adenosine A2A receptor expression and decreased p-AMPK and TJ expression were observed under diabetic conditions. Canagliflozin or AICAR treatment alleviated these changes. However, this alleviation effect of canagliflozin was diminished again after Compound C treatment. Either Sp1 siRNA or adenosine A2A receptor siRNA could increase the expression of TJs. Luciferase reporter assay confirmed that Sp1 could bind to the adenosine A2A receptor gene promoter. Our study identifies the AMPK/Sp1/adenosine A2A receptor pathway as a treatment target for diabetes-induced cerebrovascular injury.

Concentration, speciation and risk effects of multiple environmentally sensitive trace elements in respirable fine-grained fly ash.

Respirable fine-grained fly ash (RFA) is captured very inefficiently by existing air purification devices of power plant, leading to increasing concerns regarding their migration and subsequent interaction with body due to fine particle size and its complex toxic composition. Trace elements of RFA in three groups with five different sizes between 8-13 µm were analyzed in terms of available concentration, speciation and risk effects. The concentration, pollution level and ecological risk level of elements in RFA were related to particle sizes. Chronic non-carcinogenic effect risk (NER) and carcinogenic effect risk (CER) were negatively correlated with particle size. The individual weight of exposed subjects, corresponding trace elements concentration and ingestion rate in RFA were three significant variables influencing CER. NER and CER had a tenfold exaggerated effect when calculated using total element concentration of RFA. In addition to individual differences and exposure conditions, trace element properties, speciation and available concentration were the dominant factor responsible for ecological and environmental effects of trace elements in RFA, following the order As>Ni, Mn>Cr>Pb>Cu>Zn. Results of this work highlight the effects and differences of trace elements in RFA on ecology and health, and provide a basis for further pollution control and human health warning.

Calcaneal tuberosity avulsion fractures - A review.

Calcaneal tuberosity avulsion fracture, an extra-articular injury, is a rare fracture caused internally by Achilles tendon driven following intense contraction of gastrocnemius-soleus complex, and externally by low-energy (possibly high-energy). Moreover, the risk of injuries of the skin and Achilles tendon around calcaneal tuberosity is closely related to Lee classification and Carnero-Martín de Soto Classification of calcaneal tuberosity avulsion fracture. Although the diagnosis confirmed by X-ray, digital imaging and computed tomography (CT), magnetic resonance imaging (MRI) should also be used to evaluate soft tissue. In recent years, the understanding of this fracture has witnessed the development of different internal fixation devices and surgical procedures. These advances have been further elaborated scientifically in terms of their ability to provide stable fracture reduction ad resistance to Achilles tendon forces. In order to obtain a comprehensive knowledge of the disease, this article reviewed the new understanding of the anatomy, typing, risk factors, and treatment modalities of calcaneal tuberosity avulsion fracture in recent years.

Ubiquitin ligase NEDD4 promotes the proliferation of hepatocellular carcinoma cells through targeting PCDH17 protein for ubiquitination and degradation.

Neural precursor cell expressed developmentally downregulated 4 (NEDD4), an E3 ubiquitin ligase, is commonly upregulated in human hepatocellular carcinoma (HCC) and functions as an oncogenic factor in the progression of HCC, but the molecular mechanism needs be further explored. In this study, we found that NEDD4 could facilitate the proliferation of HCC cells, which was associated with regulating the ERK signaling. Further investigation showed that protocadherin 17 (PCDH17) was a potential substrate of NEDD4, and restoration of PCDH17 could block the facilitation of ERK signaling and HCC cells proliferation induced by NEDD4 overexpression. Whereafter, we confirmed that NEDD4 interacted with PCDH17 and promoted the Lys33-linked polyubiquitination and degradation of it via the proteasome pathway. Finally, NEDD4 protein level was found to be inversely correlated with that of PCDH17 in human HCC tissues. In conclusion, these results suggest that NEDD4 acts as an E3 ubiquitin ligase for PCDH17 ubiquitination and degradation thereby promoting the proliferation of HCC cells through regulating the ERK signaling, which may provide novel evidence for NEDD4 to be a promising therapeutic target for HCC.

CircTrim37 Ameliorates Intracerebral Hemorrhage Outcomes by Modulating Microglial Polarization via the miR-30c-5p/SOCS3 Axis.

Circular RNAs (circRNAs) have been progressively recognized as critical regulators in the pathology and pathophysiology of central nervous system disease. However, the potential role of circRNAs in intracerebral hemorrhage (ICH) is still largely unclear. Here, we demonstrate that circTrim37 expression was significantly upregulated at 3 days after ICH by circular RNA microarray and qPCR assays. Overexpression of circTrim37 could significantly ameliorate brain injury volume, brain edema, neurologic deficits, and inflammation in vivo after ICH. CircTrim37 promotes M2 polarization while restrains M1 polarization in vitro. Furthermore, circTrim37 acts as an endogenous sponge for miR-30c-5p, thereby inhibiting miR-30c-5p activity, leading to the upregulation of SOCS3 and making the balance of microglial response towards an M2 phenotype. Taken together, our results indicate the participation of circTrim37 and its coupling mechanism in ICH and provide a novel therapeutic target for ICH.

Effect of Pre-Rolling on Microstructure and Fatigue Crack Propagation Resistance of a Third-Generation Al-Li Alloy.

The effect of pre-rolling on the microstructure and fatigue crack (FC) propagation resistance of the Al-Cu-Li alloy was studied using tensile testing, fatigue testing, transmission electron microscopy (TEM), X-ray diffractometer (XRD), and scanning electron microscopy (SEM). The results revealed that reducing the alloy thickness through pre-rolling by up to 12% enhanced both tensile strength and yield strength, albeit at the expense of reduced elongation. In addition, the FC growth rate decreased by up to 9% pre-rolling, reaching the minimum, while the application of additional mechanical stress during the pre-rolling increases this parameter. Deformations in the Al-Cu-Li alloy with less than a 9% thickness reduction were confined to the surface layer and did not extend to the central layer. This non-uniform deformation induced a compressive stress gradient in the thickness direction and led to an inhomogeneous distribution of T1 phase, resembling the structure generated by shot peening. The superior FC propagation resistance in the 9% pre-rolled alloy could be primarily attributed to the optimum balance of compressive residual stress and work hardening.

Trichostatin A enhances the titanium rods osseointegration in osteoporotic rats by the inhibition of oxidative stress through activating the AKT/Nrf2 pathway.

The use of titanium implants as fixed supports following fractures in patients with OP can often result in sterile loosening and poor osseointegration. Oxidative stress has been shown to play a particularly important role in this process. While TSA has been reported to facilitate in vivo osteogenesis, the underlying mechanisms remain to be clarified. It also remains unclear whether TSA can improve the osseointegration of titanium implants. This study investigated whether TSA could enhance the osseointegration of titanium rods by activating AKT/Nrf2 pathway signaling, thereby suppressing oxidative stress. MC3T3-E1 cells treated with CCCP to induce oxidative stress served as an in vitro model, while an OVX-induced OP rat model was employed for in vivo analysis of titanium rod implantation. In vitro, TSA treatment of CCCP-treated MC3T3-E1 cells resulted in the upregulation of osteogenic proteins together with increased AKT, total Nrf2, nuclear Nrf2, HO-1, and NQO1 expression, enhanced mitochondrial functionality, and decreased oxidative damage. Notably, the PI3K/AKT inhibitor LY294002 reversed these effects. In vivo, TSA effectively enhanced the microstructural characteristics of distal femur trabecular bone, increased BMSCs mineralization capacity, promoted bone formation, and improved the binding of titanium implants to the surrounding tissue. Finally, our results showed that TSA could reverse oxidative stress-induced cell damage while promoting bone healing and improving titanium rods' osseointegration through AKT/Nrf2 pathway activation.