Portraying on-road CO2 concentrations using street view panoramas and ensemble learning.

A significant reduction in carbon dioxide (CO2) emissions caused by transportation is essential for attaining sustainable urban development. Carbon concentrations from road traffic in urban areas exhibit complex spatial patterns due to the impact of street configurations, mobile sources, and human activities. However, a comprehensive understanding of these patterns, which involve complex interactions, is still lacking due to the human perspective of road interface characteristics has not been taken into account. In this study, a mobile travel platform was constructed to collect both on-road navigation Street View Panoramas (OSVPs) and the corresponding CO2 concentrations. >100 thousand sample pairs that matched "street view-CO2 concentration" were obtained, covering 675.8 km of roads in Shenzhen, China. In addition, four ensemble learning (EL) models were utilized to establish nonlinear connections between the semantic and object features of streetscapes and CO2 concentrations. After performing EL fusion modeling, the predictive R2 in the test set exceeded 90 %, and the mean absolute error (MAE) was <3.2 ppm. The model was applied to Baidu Street View Panoramas (BSVPs) in Shenzhen to generate a map of average on-road CO2 with a 100 m resolution, and the Local Indicator of Spatial Association (LISA) was then used to identify high CO2 intensity spatial clusters. Additionally, the Light Gradient Boost-SHapley Additive exPlanation (LGB-SHAP) analysis revealed that vertically planted trees can reduce CO2 emissions from on-road sources. Moreover, the factors that affect on-road CO2 exhibit interaction and threshold effects. Street View Panoramas (SVPs) and Artificial Intelligence (AI) were adopted here to enhance the spatial measurement of on-road CO2 concentrations and the understanding of driving factors. Our approach facilitates the assessment and design of low-emission transportation in urban areas, which is critical for promoting sustainable traffic development.

Benzoate glycosides from Gentiana scabra Bge. and their lipid-lowering activity.

Seven undescribed benzoate glycosides (1-7) and five known ones (8-12) were isolated from the rhizomes of Gentiana scabra Bge. Their structures were characterized by comprehensive NMR and MS spectroscopic data analysis. The lipid-lowering effects of these compounds were evaluated by measuring the triglyceride (TG) contents and intracellular lipid droplets (LDs) in oleic acid (OA)-treated HepG2 cells. The results showed that compounds 1, 5, 7, and 11 significantly reduced the TG content at 20 µM, and the Bodipy staining displayed that OA enhanced the levels of LDs in the cell, while these compounds reversed the lipid accumulation caused by OA. These findings provide a basis for further development and utilization of G. scabra as a natural source of potential lipid-lowering agents.

Modulation of Alzheimer's Disease Aß40 Fibril Polymorphism by the Small Heat Shock Protein αB-Crystallin.

Deposition of amyloid plaques in the brains of Alzheimer's disease (AD) patients is a hallmark of the disease. AD plaques consist primarily of the beta-amyloid (Aß) peptide but can contain other factors such as lipids, proteoglycans, and chaperones. So far, it is unclear how the cellular environment modulates fibril polymorphism and how differences in fibril structure affect cell viability. The small heat-shock protein (sHSP) alpha-B-Crystallin (αBC) is abundant in brains of AD patients, and colocalizes with Aß amyloid plaques. Using solid-state NMR spectroscopy, we show that the Aß40 fibril seed structure is not replicated in the presence of the sHSP. αBC prevents the generation of a compact fibril structure and leads to the formation of a new polymorph with a dynamic N-terminus. We find that the N-terminal fuzzy coat and the stability of the C-terminal residues in the Aß40 fibril core affect the chemical and thermodynamic stability of the fibrils and influence their seeding capacity. We believe that our results yield a better understanding of how sHSP, such as αBC, that are part of the cellular environment, can affect fibril structures related to cell degeneration in amyloid diseases.

Characterization of Sesquiterpene Dimers from the Flowers of Inula japonica and the Structural Revisions of Related Compounds.

Sesquiterpene dimers are mainly found in the Asteraceae family. However, conflicting reports on the structures of these compounds can be found in the literature. Herein, we describe ten sesquiterpene dimers isolated from the flowers of Inula japonica, including configurational revisions of japonicone H (1-1), japonicone D (2-1), inulanolide A (4-1), japonicone X (5-1), and inulanolide F (5-2) to compounds 1, 2, 4, and 5, respectively. Five new related metabolites (3 and 6-9) are also described. Application of GIAO NMR/DP4+ analyses and ECD/OR calculations enabled us to revise the absolute configurations of an additional 13 sesquiterpene dimers isolated from plants of the genus Inula. Compounds 1, 2, 4, and 6 exhibited inhibition of nitric oxide production in lipopolysaccharide activated RAW264.7 macrophages with IC50 values of 4.07-10.00 µM.

Metal-Organic Frameworks-Based Frustrated Lewis Pairs for Selective Reduction of Nitroolefins to Nitroalkanes.

Nitroalkanes serve as essential intermediates in the synthesis of pharmaceuticals, agrochemicals, and functional materials. To date, nitroalkanes are mainly prepared from homogeneous catalysts such as noble transition metal catalysts with poor recyclability. Herein, we propose a metal-organic framework-frustrated Lewis pair (MOF-FLP) heterogeneous catalyst for selectively reducing nitroolefins to nitroalkanes under moderate reaction conditions. MOF enrichment effect can significantly improve the catalytic efficiency compared to homogeneous FLP catalysts. Benefiting from the strong interaction between FLP and MOF, the MOF-FLP catalyst exhibits outstanding recyclability. This work not only provides a convenient route for nitroalkane synthesis but also showcases the potential of porous heterogeneous FLP catalysts, offering inspiration for future catalytic design strategies.

Aggregation mechanisms and molecular structures of amyloid-ß in Alzheimer's disease.

Amyloid plaques are a major pathological hallmark involved in Alzheimer's disease and consist of deposits of the amyloid-ß peptide (Aß). The aggregation process of Aß is highly complex, which leads to polymorphous aggregates with different structures. In addition to aberrant aggregation, Aß oligomers can undergo liquid-liquid phase separation and form dynamic condensates. It has been hypothesized that these amyloid liquid droplets affect and modulate amyloid fibril formation. In this review, we briefly introduce the relationship between stress granules and amyloid protein aggregation that is associated with neurodegenerative diseases. Then we highlight the regulatory role of liquid-liquid phase separation in Aß aggregation and discuss the potential relationship between Aß phase transition and aggregation. Furthermore, we summarize the current structures of Aß oligomers and amyloid fibrils, which have been determined using nuclear magnetic resonance and cryo-electron microscopy. The structural variations of Aß aggregates provide an explanation for the different levels of toxicity, shed light on the aggregation mechanism and may pave the way towards structure-based drug design for both clinical diagnosis and treatment.

Trim14-IκBα Signaling Regulates Chronic Inflammatory Pain in Rats and Osteoarthritis Patients.

Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain.

Aggregation and phase separation of α-synuclein in Parkinson's disease.

The deposition of α-synuclein (α-Syn) in Lewy bodies serves as a prominent pathological hallmark of Parkinson's disease (PD). Recent research has revealed that α-Syn can undergo liquid-liquid phase separation (LLPS) during its fibrillization. Over time, the maturation of the resulting condensates leads to a liquid-to-solid phase transition (LSPT) ultimately resulting in the amyloid deposition in cells which is linked to the pathogenesis and development of PD. Herein, we summarize the understanding of α-Syn aggregation which can be described by nucleation and elongation steps to obtain insights into the correlation of protein aggregation, structural polymorphism, and PD progression. Additionally, we discuss the LLPS phenomena of α-Syn and heterotypic cross-amyloid interactions with a focus on aberrant LSPT in the aggregation process. Exploring the underlying mechanisms and interplay between α-Syn aberrant aggregation, pathological phase transitions, and PD pathogenesis will shed light on potential therapeutic interventions.

Bifunctional Metal-Organic Nanoballs Featuring Lewis Acidic and Basic Sites as a New Platform for One-Pot Tandem Catalysis.

The design and synthesis of polyhedra using coordination-driven self-assembly has been an intriguing research area for synthetic chemists. Metal-organic polyhedra are a class of intricate molecular architectures that have garnered significant attention in the literature due to their diverse structures and potential applications. Hereby, we report Cu-MOP, a bifunctional metal-organic cuboctahedra built using 2,6-dimethylpyridine-3,5-dicarboxylic acid and copper acetate at room temperature. The presence of both Lewis basic pyridine groups and Lewis acidic copper sites imparts catalytic activity to Cu-MOP for the tandem one-pot deacetalization-Knoevenagel/Henry reactions. The effect of solvent system and time duration on the yields of the reactions was studied, and the results illustrate the promising potential of these metal-organic cuboctahedra, also known as nanoballs for applications in catalysis.

An asymptomatic perforation of the gastrointestinal tract caused by ingestion of foreign body: A case report.

Ingestion of foreign bodies is very common in clinical practice. However, gastrointestinal perforation caused by a foreign body is rare, as most foreign bodies can pass the alimentary tract spontaneously or be removed endoscopically. Ingesting a foreign body causes gastrointestinal tract perforation in less than 1% of cases that require surgery. In the past, the literature about gastrointestinal tract perforation caused by foreign bodies had been widely reported worldwide. However, the case of foreign bodies causing gastrointestinal perforation without significant abdominal infection was rarely documented. A 47-year-old woman presented with intermittent left lower abdominal pain associated with a mass for 1 month and had no other symptoms. Laparotomy was performed after clinical assessment. During the operation, a local inflammatory mass that adhered to the abdominal wall, part of the small intestine, and sigmoid colon was found in the left lower quarter of the abdominal cavity. The surrounding intestinal wall was edematous. There were two bony foreign bodies in it. Postoperative pathology suggested an inflammatory mass. A foreign body rarely migrates into the abdominal cavity without symptoms that may be related to the omentum's slow perforation process and good function. The best treatment is surgery and using appropriate antibiotics.

Associations of Whole Blood Zinc Levels with Coronary Artery Calcification and Future Cardiovascular Events in CKD Patients.

This study was conducted to compare the differences of the whole blood zinc concentration in patients with chronic kidney disease (CKD) as compared to healthy controls, and to explore the correlations of the whole blood zinc level with coronary artery calcification (CAC) and cardiovascular event (CVE) in CKD patients. A total of 170 CKD patients and 62 healthy controls were recruited. The whole blood zinc concentration was determined in using atomic absorption spectroscopy (AAS) method. The degrees of CAC were evaluated by Agatston score based on computed tomography (CT). Regular follow-up visits were performed to record the incidence of CVE, and risk factors were analyzed by COX proportional hazard model and Kaplan-Meier survival curve. There were statistically significant lower zinc levels in CKD patients than in healthy population. The prevalence of CAC was 58.82% in CKD patients. Correlation analysis showed that dialysis duration, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), 25-hydroxyvitamin D3 (25(OH)D3), neutrophil-lymphocyte ratio (NLR), total cholesterol (TC), and high-sensitive C-reactive protein (Hs-CRP) were positively correlated with CAC, while albumin (ALB), hemoglobin (Hb), and zinc levels were negatively associated with CAC. Further COX proportional hazard model demonstrated that moderate to severe CAC, NLR, phosphate, 25(OH)D3, iPTH, and high-density lipoprotein (HDL) were associated with an increased risk for CVE, while zinc levels, Hb, and ALB were inversely associated with a reduced risk for CVE. Kaplan-Meier curve showed that low zinc (zinc < 86.62 µmol/L) patients and moderate to severe CAC patients had lower survival respectively. Our study found the lower levels of zinc and higher prevalence of CAC in CKD patients; the low zinc is involved in the high incidence rate of moderate to severe CAC and CVE in CKD patients.

Pemetrexed alleviates piglet diarrhea by blocking the interaction between porcine epidemic diarrhea virus nucleocapsid protein and Ezrin.

Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that causes high mortality in piglets, thus posing a serious threat to the world pig industry. Porcine epidemic diarrhea (PED) is related to the imbalance of sodium absorption by small intestinal epithelial cells; however, the etiology of sodium imbalanced diarrhea caused by PEDV remains unclear. Herein, we first proved that PEDV can cause a significant decrease in Na+/H+ exchanger 3 (NHE3) expression on the cell membrane, in a viral dose-dependent manner. Further study showed that the PEDV nucleocapsid (N) protein participates in the regulation of NHE3 activity through interacting with Ezrin. Flame atomic absorption spectroscopy results indicated a serious imbalance in Na+ concentration inside and outside cells following overexpression of PEDV N. Meanwhile, molecular docking technology identified that the small molecule drug Pemetrexed acts on the PEDV N-Ezrin interaction region. It was confirmed that Pemetrexed can alleviate the imbalanced Na+ concentration in IPEC-J2 cells and the diarrhea symptoms of Rongchang pigs caused by PEDV infection. Overall, our data suggest that the interaction between PEDV N and Ezrin reduces the level of phosphorylated Ezrin, resulting in a decrease in the amount of NHE3 protein on the cell membrane. This leads to an imbalance of intracellular and extracellular Na+, which causes diarrhea symptoms in piglets. Pemetrexed is effective in relieving diarrhea caused by PEDV. Our results provide a reference to screen for anti-PEDV targets and to develop drugs to prevent PED.IMPORTANCEPorcine epidemic diarrhea (PED) has caused significant economic losses to the pig industry since its initial outbreak, and the pathogenic mechanism of porcine epidemic diarrhea virus (PEDV) is still under investigation. Herein, we found that the PEDV nucleocapsid protein interacts with Ezrin to regulate Na+/H+ exchanger 3 activity. In addition, we screened out Pemetrexed, a small molecule drug, which can effectively alleviate pig diarrhea caused by PEDV. These results provide support for further exploration of the pathogenesis of PEDV and the development of drugs to prevent PED.

Prognostic and clinicopathological effect of the prognostic nutritional index (PNI) in patients with cervical cancer: a meta-analysis.

BACKGROUND: Numerous studies have explored whether the prognostic nutritional index (PNI) can predict the prognosis of cervical cancer (CC); however, their findings remain controversial. This meta-analysis focused on evaluating the relationship between the PNI and the prognosis of patients with CC. METHODS: Relevant articles were collected from specific databases up to March 16, 2023. The relationship between the PNI and survival outcomes in patients with CC was estimated using combined hazard ratios (HRs) and associated 95% confidence intervals (CIs). The association of the PNI with clinicopathological features in patients with CC was assessed by combining odds ratios (ORs) and associated 95% CIs. RESULTS: Nine articles with 2508 cases were included in the meta-analysis. According to our pooled findings, a decreased PNI showed a significant association with worse overall survival (OS) (HR = 2.98, 95% CI = 2.22-3.99, p < .001) as well as progression-free survival (PFS) (HR = 2.43, 95% CI = 1.92-3.07, p < .001) in patients with CC. The subgroup analysis indicated that the results were reliable. Moreover, the decreased PNI showed a significant association with the presence of lymph node metastasis (LN metastasis, OR = 1.53, 95% CI = 1.04-82.24, p = .030) and maximum tumor size >4 cm (OR = 1.73, 95% CI = 1.21-2.46, p = .002). However, the PNI was not significantly associated with histology, differentiation, or FIGO stage. CONCLUSION: In this study, a low PNI predicted dismal OS and PFS in patients with CC, who also tend to suffer from LN metastasis and larger tumor size. PNI is a promising biomarker for predicting the prognosis of patients with CC in clinical practice.

To our knowledge, the present meta-analysis is the first to explore whether the PNI can be used to predict the prognosis of patients with CC.In this study, a low PNI predicted dismal OS and PFS in patients with CC, who also tend to suffer from LN metastasis and larger tumor size.PNI is a promising biomarker for predicting the prognosis of patients with CC in clinical practice.

Phylogenomic analyses reveal reticulate evolution between Neomicrocalamus and Temochloa (Poaceae: Bambusoideae).

Neomicrocalamus and Temochloa are closely related to bamboo genera. However, when considered with newly discovered and morphologically similar material from China and Vietnam, the phylogenetic relationship among these three groups was ambiguous in the analyses based on DNA regions. Here, as a means of investigating the relationships among the three bamboo groups and exploring potential sources of genomic conflicts, we present a phylogenomic examination based on the whole plastome, single-nucleotide polymorphism (SNP), and single-copy nuclear (SCN) gene datasets. Three different phylogenetic hypotheses were found. The inconsistency is attributed to the combination of incomplete lineage sorting and introgression. The origin of newly discovered bamboos is from introgressive hybridization between Temochloa liliana (which contributed 80.7% of the genome) and Neomicrocalamus prainii (19.3%), indicating that the newly discovered bamboos are closer to T. liliana in genetics. The more similar morphology and closer distribution elevation also imply a closer relationship between Temochloa and newly discovered bamboos.

Porcine epidemic diarrhea virus causes diarrhea by activating EGFR to regulates NHE3 activity and mobility on plasma membrane.

As part of the genus Enteropathogenic Coronaviruses, Porcine Epidemic Diarrhea Virus (PEDV) is an important cause of early diarrhea and death in piglets, and one of the most difficult swine diseases to prevent and control in the pig industry. Previously, we found that PEDV can block Na+ absorption and induce diarrhea in piglets by inhibiting the activity of the sodium-hydrogen ion transporter NHE3 in pig intestinal epithelial cells, but the mechanism needs to be further explored. The epidermal growth factor receptor (EGFR) has been proved to be one of the co-receptors involved in many viral infections and a key protein involved in the regulation of NHE3 activity in response to various pathological stimuli. Based on this, our study used porcine intestinal epithelial cells (IPEC-J2) as an infection model to investigate the role of EGFR in regulating NHE3 activity after PEDV infection. The results showed that EGFR mediated viral invasion by interacting with PEDV S1, and activated EGFR regulated the downstream EGFR/ERK signaling pathway, resulting in decreased expression of NHE3 and reduced NHE3 mobility at the plasma membrane, which ultimately led to decreased NHE3 activity. The low level of NHE3 expression in intestinal epithelial cells may be a key factor leading to PEDV-induced diarrhea in newborn piglets. This study reveals the importance of EGFR in the regulation of NHE3 activity by PEDV and provides new targets and clues for the prevention and treatment of PEDV-induced diarrhea in piglets.

Mechanism of Lactiplantibacillus plantarum regulating Ca2+ affecting the replication of PEDV in small intestinal epithelial cells.

Porcine epidemic diarrhea virus (PEDV) mainly invades the small intestine and promotes an inflammatory response, eventually leading to severe diarrhea, vomiting, dehydration, and even death of piglets, which seriously threatens the economic development of pig farming. In recent years, researchers have found that probiotics can improve the intestinal microenvironment and reduce diarrhea. At the same time, certain probiotics have been shown to have antiviral effects; however, their mechanisms are different. Herein, we aimed to investigate the inhibitory effect of Lactiplantibacillus plantarum supernatant (LP-1S) on PEDV and its mechanism. We used IPEC-J2 cells as a model to assess the inhibitory effect of LP-1S on PEDV and to further investigate the relationship between LP-1S, Ca2+, and PEDV. The results showed that a divalent cation chelating agent (EGTA) and calcium channel inhibitors (Bepridil hydrochloride and BAPTA-acetoxymethylate) could inhibit PEDV proliferation while effectively reducing the intracellular Ca2+ concentration. Furthermore, LP-1S could reduce PEDV-induced loss of calcium channel proteins (TRPV6 and PMCA1b), alleviate intracellular Ca2+ accumulation caused by PEDV infection, and promote the balance of intra- and extracellular Ca2+ concentrations, thereby inhibiting PEDV proliferation. In summary, we found that LP-1S has potential therapeutic value against PEDV, which is realized by modulating Ca2+. This provides a potential new drug to treat PEDV infection.

Prognostic and clinicopathological impacts of Controlling Nutritional Status (CONUT) score on patients with gynecological cancer: a meta-analysis.

BACKGROUND: The Controlling Nutritional Status (CONUT) score has proven to be a potential biomarker for determining the prognosis of patients with various types of cancer. Its value in determining the prognosis of patients with gynecological cancer, however, remains unknown. The present study was a meta-analysis that aimed to evaluate the prognostic and clinicopathological significance of the CONUT score in gynecological cancer. METHODS: The Embase, PubMed, Cochrane Library, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched through November 22, 2022. A pooled hazard ratio (HR), together with a 95% confidence interval (CI), was used to determine whether the CONUT score had prognostic value in terms of survival outcomes. Using odds ratios (ORs) and 95% CIs, we estimated the relationship between the CONUT score and clinicopathological characteristics of gynecological cancer. RESULTS: We evaluated 6 articles, involving a total of 2,569 cases, in the present study. According to the results of our analyses, higher CONUT scores were significantly correlated with decreased overall survival (OS) (n = 6; HR = 1.52; 95% CI = 1.13-2.04; P = 0.006; I2 = 57.4%; Ph = 0.038) and progression-free survival (PFS) (n = 4; HR = 1.51; 95% CI = 1.25-1.84; P < 0.001; I2 = 0; Ph = 0.682) in gynecological cancer. Moreover, higher CONUT scores were significantly correlated with a histological grade of G3 (n = 3; OR = 1.76; 95% CI = 1.18-2.62; P = 0.006; I2 = 0; Ph = 0.980), a tumor size ≥ 4 cm (n = 2; OR = 1.50; 95% CI = 1.12-2.01; P = 0.007; I2 = 0; Ph = 0.721), and an advanced International Federation of Gynecology and Obstetrics (FIGO) stage (n = 2; OR = 2.52; 95% CI = 1.54-4.11; P < 0.001; I2 = 45.5%; Ph = 0.175). The correlation between the CONUT score and lymph node metastasis, however, was not significant. CONCLUSIONS: Higher CONUT scores were significantly correlated with decreased OS and PFS in gynecological cancer. The CONUT score, therefore, is a promising and cost-effective biomarker for predicting survival outcomes in gynecological cancer.

An aliphatic MOF with a molecular sieving effect for efficient C2H2/C2H4 separation.

A metal-organic framework, SDMOF-1, with rigid pores of about 3.4 Å, which is appropriate for accommodating C2H2 molecules, exhibits high C2H2 adsorption capacity and great separation capability of the C2H2/C2H4 mixture. This work provides a new method to design aliphatic MOFs with a molecular sieving effect to realize efficient gas separation.

Introducing Frustrated Lewis Pairs to Metal-Organic Framework for Selective Hydrogenation of N-Heterocycles.

Hydrogenated nitrogen heterocyclic compounds play a critical role in the pharmaceutical, polymer, and agrochemical industries. Recent studies on partial hydrogenation of nitrogen heterocyclic compounds have focused on costly and toxic precious metal catalysts. As an important class of main-group catalysts, frustrated Lewis pairs (FLPs) have been widely applied in catalytic hydrogenation reactions. In principle, the combination of FLPs and metal-organic framework (MOF) is anticipated to efficiently enhance the recyclability performance of FLPs; however, the previously studied MOF-FLPs showed low reactivity in the hydrogenation of N-heterocycles compounds. Herein, we offer a novel P/B type MOF-FLP catalyst that was achieved via a solvent-assisted linker incorporation approach to boost catalytic hydrogenation reactions. Using hydrogen gas under moderate pressure, the proposed P/B type MOF-FLP can serve as a highly efficient heterogeneous catalyst for selective hydrogenation of quinoline and indole to tetrahydroquinoline and indoline-type drug compounds in high yield and excellent recyclability.

TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats.

Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4-6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4-6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4-6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4-6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain.