Transition-Metal-Free Hydrodefluoroamination of Trifluoromethyl Enones for the Synthesis of α-Fluoroenamides.

A three-component strategy was developed to enable hydrodefluoroamination of ß-trifluoromethyl enones by selectively activating two C(sp3)-F bonds in the trifluoromethyl group. The method involved a sequence of carbonyl reduction, hydrodefluorination, and defluoroamination under transition-metal-free conditions. Synthetically useful (E)-stereospecific α-fluoroenamides were obtained in good yields with diverse functional group tolerance, which could be easily transformed into valuable organofluorides and heterocycles. The carbonyl auxiliary exerts both electronic and steric impacts on the CF3-alkenes, allowing for controllable and selective defluorination.

Tailoring the spectro-temporal mode of photon pairs generated from interspatial-mode four-wave mixing.

We investigate the spectro-temporal mode property of the photon pairs generated via interspatial-mode spontaneous four-wave mixing (FWM) in a few-mode fiber (FMF) that supports two linearly polarized spatial modes in the 1550 nm telecom band. The two pulsed pumps for the process are in distinct spatial modes, while the created signal and idler photon pairs are also occupying different spatial modes. By exploiting the unique inter-mode phase matching condition in the FMF, we can tailor the spectro-temporal mode structure of the photon pairs by changing the pulse duration (spectral bandwidth) of the two pumps. Especially, photon pairs with a nearly round-shaped factorable joint spectrum are experimentally realized. The techniques are valuable for generating and manipulating quantum states in multi-mode waveguides and exploiting the spatial degree of freedom in quantum information processing.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Silver-promoted ceramic conversion treatment of Ti6Al4V alloy and its mechanical performance.

In this paper, the Ti6Al4V alloy surface was modified via ceramic conversion treatment (CCT) with or without a pre-deposited silver layer. After characterizing the surface morphologies, microstructure and phase constituents of the ceramic oxide layer formed at 620 °C, we investigated the surface hardness and the cross-sectional nano-hardness profile under the oxide layer. The static load-bearing capacity of the oxide layers was examined by applying discrete loads via a Vickers indenter and observing the indentations. A scratch test was used to evaluate the load-bearing capacity and the adhesion/cohesion of the oxide layers. The wettability of the surface changed due to the incorporation of silver and the change of surface morphology. Reciprocating friction and wear test was used to assess the tribological properties. Small and dispersed silver nanoparticles and clusters were found in the oxide layer of the Ag pre-deposited Ti6Al4V samples, and they had much better tribological properties in terms of reduced coefficient of friction and wear volume. With the assistance of silver, the efficiency of the CCT was significantly improved.

Genotypic and phenotypic characteristics of sodium channel-associated epilepsy in Chinese population.

Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein's pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.

The Development of Novel Cu/GO Nano-Composite Coatings by Brush Plating with High Wear Resistance for Potential Brass Sliding Bearing Application.

Low friction and high wear resistance are critical properties for sliding bearings. In this research, advanced Cu/GO nanocomposite coatings have been developed by a brush plating method to improve the tribological performance of brass-based sliding bearings. A series of brush plating studies under voltages from 2 to 6 V with different GO concentrations (0.2-0.8 g/L) was conducted, and the coating microstructures were characterised by SEM, EDX, GDOES and XRD and the tribological behaviour of the Cu/GO composite coatings were evaluated using dry ball-on-plane tribological tests The experimental results have demonstrated that GO can be successfully introduced into the whole composite coating layer; the Cu/GO composite coatings can reduce the friction of brass and increase its wear resistance by two orders of magnitude, mainly due to the self-lubricating GO added into the coatings.

Seed physiological traits and environmental factors influence seedling establishment of vegetable soybean (Glycine max L.).

Edamame (Glycine max (L.) Merr.), a specialty soybean prized for its nutritional value and taste, has witnessed a surge in demand within the U.S. However, subpar seedling stands have hindered its production potential, necessitating increased inputs for farmers. This study aims to uncover potential physiological factors contributing to low seedling emergence in edamame. We conducted comprehensive assessments on thirteen prominent edamame genotypes alongside two food-grade and two grain-type soybean genotypes, focusing on germination and emergence speed in both laboratory and field settings. Additionally, we employed single electrical conductivity tests and identified and quantified seed leachate components to distinguish among soybean types. Furthermore, using a LabField™ simulation table, we examined seed emergence across a wide soil temperature range (5°C to 45°C) for edamame and other soybean types. All seeds were produced under the same environmental conditions, harvested in Fall 2020, and stored under uniform conditions to minimize quality variations. Our findings revealed minimal divergence in emergence percentages among the seventeen genotypes, with over 95% germination and emergence in laboratory conditions and over 70% emergence in the field. Nonetheless, edamame genotypes typically exhibited slower germination speeds and higher leachate exudates containing higher soluble sugars and amino acids. Seed size did not significantly impact total emergence but was negatively correlated with germination and emergence speed, although this effect could be mitigated under complex field conditions. Furthermore, this study proposed differences that distinguish edamame from other soybean types regarding ideal and base temperatures, as well as thermal time. The finds offer valuable insights into edamame establishment, potentially paving the way for supporting local edamame production in the U.S.

Correction: A Multilabel Text Classifier of Cancer Literature at the Publication Level: Methods Study of Medical Text Classification.

[This corrects the article DOI: 10.2196/44892.].

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

miR-181d targets BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to Cryptosporidium parvum infection via the intrinsic apoptosis pathway.

Cryptosporidium parvum is an important zoonotic pathogen that is studied worldwide. MicroRNAs (miRNAs) act as post-transcriptional regulators and may play a key role in modulating host epithelial responses following Cryptosporidium infection. Our previous study has shown that C. parvum downregulates the expression of miR-181d through the p50-dependent TLRs/NF-κB pathway. However, the mechanism by which miR-181d regulates host cells in response to C. parvum infection remains unclear. The present study found that miR-181d downregulation inhibited cell apoptosis and increased parasite burden in HCT-8 cells after C. parvum infection. Bioinformatics analysis and luciferase reporter assays have shown that BCL2 was a target gene for miR-181d. Moreover, BCL2 overexpression and miR-181d downregulation had similar results. To further investigate the mechanism by which miR-181d regulated HCT-8 cell apoptosis during C. parvum infection, the expression of molecules involved in the intrinsic apoptosis pathway was detected. Bax, caspase-9, and caspase-3 expression was decreased at 4, 8, 12, and 24 hpi and upregulated at 36 and 48 hpi. Interfering with the expression of miR-181d or BCL2 significantly affected the expression of molecules in the intrinsic apoptosis pathway. These data indicated that miR-181d targeted BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to C. parvum infection via the intrinsic apoptosis pathway. These results allowed us to further understand the regulatory mechanisms of host miRNAs during Cryptosporidium infection, and provided a theoretical foundation for the design and development of anti-cryptosporidiosis drugs.

Tailoring Stress-Relieved Structure for SnSe Toward High Performance Potassium Ion Batteries.

Metal chalcogenides as an ideal family of anode materials demonstrate a high theoretical specific capacity for potassium ion batteries (PIBs), but the huge volume variance and poor cyclic stability hinder their practical applications. In this study, a design of a stress self-adaptive structure with ultrafine SnSe nanoparticles embedded in carbon nanofiber (SnSe@CNF) via the electrospinning technology is presented. Such an architecture delivers a record high specific capacity (272 mAh g-1 at 50 mA g-1) and high-rate performance (125 mAh g-1 at 1 A g-1) as a PIB anode. It is decoded that the fundamental understanding for this great performance is that the ultrafine SnSe particles enhance the full utilization of the active material and achieve stress relief as the stored strain energy from cycling is insufficient to drive crack propagation and thus alleviates the intrinsic chemo-mechanical degradation of metal chalcogenides.

Mn(II)-Aloe-Emodin Nanoscale Coordination Polymer Enhances Ferroptosis by Synergistically Enhancing Reactive Oxygen Species Generation via the Nrf2-GPX4 Axis.

Ferroptosis induction is particularly promising for cancer therapy when the apoptosis pathway is compromised. Current strategies in nanomedicine for inducing ferroptosis primarily focus on promoting the accumulation of reactive oxygen species (ROS). However, the presence of intracellular antioxidants, such as nuclear factor erythroid 2-related factor 2 (Nrf2), can limit the effectiveness of such therapy by activating detoxification systems and eliminating ROS. To overcome this challenge, we developed a synergistic ferroptosis-inducing agent by modifying manganese (Mn2+)-1,8-dihydroxy-3-hydroxymethyl-anthraquinone (aloe-emodin, AE) with polyvinyl pyrrolidone (PVP) to create nanoparticles (MAP NPs). In the tumor microenvironment, these NPs degraded and released AE and Mn(II), facilitating the generation of ROS and Mn(IV) through a Fenton-like reaction between hydrogen peroxide (H2O2) and Mn(II). Mn(IV) subsequently interacts with glutathione (GSH) to induce a cyclic catalytic effect, and the depletion of GSH diminished the activation of glutathione-dependent peroxidase 4 (GPX4). Furthermore, AE inhibits the activity of Nrf2 and depleted GSH, thereby synergistically enhancing antitumor efficacy. Here it is demonstrated that MAP NPs effectively generate a robust ROS storm within tumor cells, suggesting that high-performance ferroptosis therapy is effective. Additionally, the inclusion of Mn(II) in the MAP NPs enables real-time monitoring of therapeutic efficacy via magnetic resonance T1-weighted contrast imaging.

Dietary intervention rescues a bone porosity phenotype in a murine model of Neurofibromatosis Type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a complex genetic disorder that affects a range of tissues including muscle and bone. Recent preclinical and clinical studies have shown that Nf1 deficiency in muscle causes metabolic changes resulting in intramyocellular lipid accumulation and muscle weakness. These can be subsequently rescued by dietary interventions aimed at modulating lipid availability and metabolism. It was speculated that the modified diet may rescue defects in cortical bone as NF1 deficiency has been reported to affect genes involved with lipid metabolism. Bone specimens were analyzed from wild type control mice as well as Nf1Prx1-/- (limb-targeted Nf1 knockout mice) fed standard chow versus a range of modified chows hypothesized to influence lipid metabolism. Mice were fed from 4 weeks to 12 weeks of age. MicroCT analysis was performed on the cortical bone to examine standard parameters (bone volume, tissue mineral density, cortical thickness) and specific porosity measures (closed pores corresponding to osteocyte lacunae, and larger open pores). Nf1Prx1-/- bones were found to have inferior bone properties to wild type bones, with a 4-fold increase in the porosity attributed to open pores. These measures were rescued by dietary interventions including a L-carnitine + medium-chain fatty acid supplemented chow previously shown to improve muscle histology function. Histological staining visualized these changes in bone porosity. These data support the concept that lipid metabolism may have a mechanistic impact on bone porosity and quality in NF1.

2024 Chinese Expert Consensus Guidelines on the Diagnosis and Treatment of Atrial Fibrillation in the Elderly, Endorsed by Geriatric Society of Chinese Medical Association (Cardiovascular Group) and Chinese Society of Geriatric Health Medicine (Cardiovascular branch): Executive Summary.

The consensus guidelines of the Geriatric Society of Chinese Medical Association on the management of atrial fibrillation (AF) in the elderly was first published in 2011 and updated in 2016, with endorsement by Chinese Society of Geriatric Health Medicine. Since then, many important studies regarding the screening and treatment in the elderly population have been reported, necessitating this updated expert consensus guideline. The writing committee members comprehensively reviewed updated evidence pertaining to elderly patients with AF, and formulated this 2024 update. The highlighted issues focused on the following: screening for AF, geriatric comprehensive assessment, use of the Atrial fibrillation Better Care (ABC) pathway for the elderly patients, and special clinical settings related to elderly patients with AF. New recommendations addressing smart technology facilitated AF screening, ABC pathway based management, and optimal anticoagulation were developed, with a focus on the elderly.

Tirzepatide for Weight Reduction in Chinese Adults With Obesity: The SURMOUNT-CN Randomized Clinical Trial.

Importance: Obesity has become a global public health concern and China has the largest number of affected people worldwide. Objective: To assess the efficacy and safety of treatment with tirzepatide for weight reduction in Chinese adults with obesity or overweight and weight-related comorbidities. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 29 centers in China from September 2021 to December 2022 included Chinese adults (aged ≥18 years) with a body mass index (BMI) greater than or equal to 28 or greater than or equal to 24 and at least 1 weight-related comorbidity, excluding diabetes. Interventions: Participants were randomly assigned (1:1:1) to receive once-weekly, subcutaneous 10-mg (n = 70) or 15-mg (n = 71) tirzepatide or placebo (n = 69), plus a lifestyle intervention, for 52 weeks. Main Outcomes and Measures: Co-primary end points were the percent change in body weight from baseline and weight reduction of at least 5% at week 52. Efficacy and safety analyses were performed on an intention-to-treat population. Results: Of 210 randomized participants (103 [49.0%] female; mean [SD] age, 36.1 [9.1] years; body weight, 91.8 [16.0] kg; BMI, 32.3 [3.8]), 201 (95.7%) completed the trial. The mean change in body weight at week 52 was -13.6% (95% CI, -15.8% to -11.4%) with tirzepatide 10 mg, -17.5% (95% CI, -19.7% to -15.3%) with tirzepatide 15 mg, and -2.3% with placebo (difference between 10 mg and placebo, -11.3% [95% CI, -14.3% to -8.3%; P < .001]; difference between 15 mg and placebo, -15.1% [95% CI, -18.2% to -12.1%; P < .001]). The percentage of participants achieving body weight reductions of 5% or greater was 87.7% with tirzepatide 10 mg, 85.8% with tirzepatide 15 mg, and 29.3% with placebo (P < .001 for comparisons with placebo). The most frequent treatment-emergent adverse events with tirzepatide were gastrointestinal. Most were mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Conclusions and Relevance: In Chinese adults with obesity or overweight, once-weekly treatment with tirzepatide 10 mg or 15 mg resulted in statistically significant and clinically meaningful weight reduction with an acceptable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT05024032.

Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress.

Apigenin (API) is a natural flavonoid compound with antioxidant, anti fibrotic, anti-inflammatory and other effects, but there is limited research on the effect of API on liver fibrosis. This study aims to explore the effect and potential mechanism of API on liver fibrosis induced by CCl4 in mice. The results indicate that API reduces oxidative stress levels, inhibits hepatic stellate cell (HSC) activation, and exerts anti liver fibrosis effects by regulating the PKM2-HIF-1α pathway. We observed that API alleviated liver tissue pathological damage and collagen deposition in CCl4 induced mouse liver fibrosis model, promoting the recovery of liver function in mice with liver fibrosis. In addition, the API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer formation by regulating the EGFR-MEK1/2-ERK1/2 pathway, thereby preventing dimer from entering the nucleus and blocking PKM2-HIF-1α access. This change leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of liver fibrosis mice. At the same time, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis, inhibited the activation of HSC, and reduced collagen deposition. These results indicate that API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress, laying an important foundation for the development and clinical application of API as a novel drug for treating liver fibrosis.

The role of dietary fats on cognition and sarcopenia in the elderly.

BACKGROUND AND OBJECTIVES: To elucidate the role of dietary fats on the relationship between mild cognitive impairment and sarcopenia and help identifying and preventing the decline of cognitive and muscle function in elderly individuals. METHODS AND STUDY DESIGN: The study conducted involving a group of 1812 individuals between the ages of 61 and 92. Body composition and BMR were assessed by bioelectrical impedance analysis. Cognitive function and dietary nutrition were evaluated by neuropsychological assessments and questionnaire of food intake frequency. Lipidomics analysis was performed using UHPLC-Qtrap-MS/MS. RESULTS: MCI and SA are mutual influencing factors, lower intake of MUFA, PUFA and higher intake of fat was associated with cognitive dysfunction and/or SA (p < 0.05). PUFA was important for MCI combined with SA (Compared with Q1, Q4 OR: 0.176, 95%CI: 0.058,0.533). Lipidomics analysis revealed that triacylglycerol (TAG) contain more carbon chains with saturated double bonds may be closely related to cognitive impairment and the progression of SA (p < 0.05). While, DAG with carbon chains of unsaturated double bonds is opposite. CONCLUSIONS: Insufficient intake of unsaturated fatty acids was associated with the development of cognitive decline and the progression of SA. MUFA affecting muscle health, fats and PUFA has a greater impact on MCI combined with SA. Less MUFA intake and increasing saturated double-bonded fatty acid intake might be the key factors on promoting cognitive impairment and SA in the elderly. They have the potential to serve as prospective biomarkers indicating a higher risk of cognitive decline and/or SA in the elderly population.

Associations between dietary macronutrient quality and asthenozoospermia risk: a hospital-based case-control study.

Background & aims: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). Methods: A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. Results: No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers (Ptrend < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; Ptrend < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk (P < 0.05). Conclusions: Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.

Xanthohumol Promotes Skp2 Ubiquitination Leading to the Inhibition of Glycolysis and Tumorigenesis in Ovarian Cancer.

Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells.

Moxibustion ameliorates chronic inflammatory visceral pain via spinal circRNA-miRNA-mRNA networks: a central mechanism study.

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion's analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.