Ndufa8 promotes white fat Browning by improving mitochondrial respiratory chain complex I function to ameliorate obesity by in vitro and in vivo.

Obesity and its complications have become a global health problem that needs to be addressed urgently. White adipose tissue (WAT) browning contributes to consuming excess energy in WAT, which is important for improving obesity and maintaining a healthy energy homeostasis. Mitochondria, as the energy metabolism center of cells, are extensively involved in many metabolic processes, including the browning of WAT. NADH: Ubiquinone oxidoreductase subunit A8 (NDUFA8) is a constituent subunit of respiratory chain complex I (CI), which has been found to participate in a wide range of physiological processes by affecting the activity of respiratory CI. However, the regulatory effect of Ndufa8 on the browning of WAT has not been reported. Here, we used ß3-adrenergic agonis CL316, 243 to construct WAT browning models in vivo and in vitro to investigate the role and mechanism of Ndufa8 in the regulation of WAT browning. Briefly, Ndufa8 significantly increased CI activity and suppressed mitochondrial ROS levels in vitro, thereby improving mitochondrial function. Ndufa8 also increased the transcriptional levels and protein levels of UCP1 in vitro and in vivo, which promoted WAT browning. Our findings provide a new molecular approach for the research of browning of WAT in animals, as well as a new target for animal metabolism improvement and obesity treatments.

In-situ construction of integrated asymmetric micro-supercapacitors achieving monolithic hundred-volt output.

Asymmetric micro-supercapacitors (MSCs) exhibit higher energy density while face significant challenges in power density as well as cycling life and large dimensions. The key factors contributing to these dilemmas include the match of electrode materials and electrolytes, poor uniformity of device, and complicated while low-precise fabrication processes. Herein we develop a laser scribing-engraving (LSE) strategy to fabricate MSCs with monolithic high-voltage output and scalable array integration. Utilizing this strategy, we induce the conversion of the majority of Ti3C2Tx-MXene into TiO2 and graphene oxide into laser-scribed graphene (LSG), yielding asymmetric MSCs with laser-induced MXene/graphene oxide as the negative electrode and MXene/graphene oxide as the positive electrode. A single asymmetric micro-supercapacitor exhibits a high voltage window of 1.8 V, delivering an outstanding energy density (240 mWh cm-3) and power density (9503 mW cm-3), coupled with excellent cycling stability. Moreover, the LSE strategy enables monolithically integrated 64 devices to achieve a high-voltage output of 115.2 V. Our approach showcases the potential for integrating micro-energy storage devices into various microsystems, increasing the practicality of asymmetric micro-supercapacitors.

Effectiveness of utilizing step-monitoring devices to prevent and treat obesity in children and adolescents: A systematic review and meta-analysis.

Background: Children and adolescents who are overweight and obese represent a growing public health issue. The use of step-monitoring devices as an intervention tool may be a simple, cost-effective, and easily replicable solution for addressing obesity in children and adolescents. No prior systematic reviews have evaluated the effectiveness of utilizing step-monitoring devices as an intervention method for obesity in children and adolescents. Methods: Previous studies on using step-monitoring devices to prevent and treat obesity in children and adolescents were identified in the following databases: Web of Science, EMBASE, PubMed, Cochrane Library, SPORTDiscus, and SCOPUS. The search period for each database ranged from the year of their inception to 8 March 2023 (updated in June 2024). Meta-analyses were performed for mean differences (MDs) in body mass index (BMI), BMI z-score (BMI-Z), body fat, waist circumference, and body weight. Results: From 12,907 relevant records, 23 studies were included in this meta-analysis. The included studies were mainly at low risk of bias, except for blinding. Step-monitoring device-based interventions had significant effects in reducing BMI-Z (MD -0.06; 95% CI -0.10 to -0.02), body fat (MD -0.95%; 95% CI -1.35 to -0.54), and body weight (MD -1.23 kg; 95% CI -2.36 to -0.10). However, there was no significant effect on BMI (MD -0.16 kg/m2; 95% CI -0.55 to 0.22) and waist circumference (MD -0.33 cm; 95% CI -1.23 to 0.58). Subgroup analyses indicated that participants who were overweight or obese showed greater intervention effects on BMI and BMI-Z compared to participants with normal weight. The programs with an intervention duration of ≤6 months presented a greater intervention effect on BMI-Z than those with an intervention duration of more than 6 months. The programs that established goals had a greater intervention effect on body fat than those that did not. Conclusions: Step-monitoring devices may be an effective and generalizable intervention tool for the prevention and treatment of obesity in children and adolescents. Future studies should further explore how to set step goals and the duration of interventions to achieve better intervention effects.

Diffusion-based virtual MR elastography for predicting recurrence of solitary hepatocellular carcinoma after hepatectomy.

BACKGROUND: To explore the capability of diffusion-based virtual MR elastography (vMRE) in the preoperative prediction of recurrence in hepatocellular carcinoma (HCC) and to investigate the underlying relevant histopathological characteristics. METHODS: Between August 2015 and December 2016, patients underwent preoperative MRI examination with a dedicated DWI sequence (b-values: 200,1500 s/mm2) were recruited. The ADC values and diffusion-based virtual shear modulus (µdiff) of HCCs were calculated and MR morphological features were also analyzed. The Cox proportional hazards model was used to identify the risk factors associated with tumor recurrence. A preoperative radiologic model and postoperative model including pathological features were built to predict tumor recurrence after hepatectomy. RESULTS: A total of 87 patients with solitary surgically confirmed HCCs were included in this study. Thirty-five patients (40.2%) were found to have tumor recurrence after hepatectomy. The preoperative model included higher µdiff and corona enhancement, while the postoperative model included higher µdiff, microvascular invasion, and histologic tumor grade. These factors were identified as significant prognostic factors for recurrence-free survival (RFS) (all p < 0.05). The HCC patients with µdiff values > 2.325 kPa showed poorer 5-year RFS after hepatectomy than patients with µdiff values ≤ 2.325 kPa (p < 0.001). Moreover, the higher µdiff values was correlated with the expression of CK19 (3.95 ± 2.37 vs. 3.15 ± 1.77, p = 0.017) and high Ki-67 labeling index (4.22 ± 1.63 vs. 2.72 ± 2.12, p = 0.001). CONCLUSIONS: The µdiff values related to the expression of CK19 and Ki-67 labeling index potentially predict RFS after hepatectomy in HCC patients.

Efficacy and safety of radical cystectomy with ileal conduit for muscle-invasive bladder cancer in the elderly: a multicenter retrospective study.

Objective: Radical cystectomy with ileal conduit is the current mainstay of treatment for muscle-invasive bladder cancer and is also a high-risk procedure. Existing studies have limited targeted assessment of the efficacy and safety of this procedure, and the patient population appropriate for this procedure is still poorly defined. We sought to longitudinally analyze differences in the efficacy and safety of radical cystectomy with ileal conduit by age subgroups to assess whether the age factor should be used as an exclusion criterion when selecting this procedure. Materials and methods: We retrospectively examined the clinicopathological data of patients with MIBC treated with RC with IC at the Cancer Hospital of Harbin Medical University between February 2014 and October 2023. Additionally, we utilized clinical and pathological data from the SEER database (2000-2020) for external validation of our findings. Patients were categorized into elderly (≥70 years at diagnosis) and non-elderly (<70 years) groups. Statistical analyses included t-tests, non-parametric tests for continuous data, chi-square tests for categorical data, and Kaplan-Meier survival analysis. Results: In this study, 152 patients were included: 119 were categorized as non-elderly and 33 as elderly. For external validation, data from 416 patients in the SEER database were analyzed, with 172 classified as non-elderly and 244 as elderly. The results indicated that elderly patients were more likely to require ICU transfer postoperatively but exhibited a lower incidence of stoma inflammation. Additionally, both the data from our center and the external validation from the SEER database showed a concordance in cancer-specific survival (CSS) between the elderly and non-elderly groups. The efficacy of RC with IC was comparable in both elderly and non-elderly patients. Conclusion: For longitudinal age subgroups, RC with IC for both elderly and non-elderly MIBC had good efficacy and safety, and good quality of life after surgery. Although there are surgical and perioperative risks in elderly patients, there is no significant difference compared with non-elderly patients. In elderly patients requiring RC for bladder cancer, IC should remain the preferred mode of urinary diversion, and old age should not be used as an absolute exclusion criterion for IC.

Effects of starch filling on physicochemical properties, functional activities, and release characteristics of PBAT-based biodegradable active films loaded with tea polyphenols.

In this work, the modification of poly(butylene adipate-co-terephthalate) (PBAT) was combined with the development of active packaging films. PBAT, starch, plasticizer, and tea polyphenols (TP) were compounded and extrusion-blown into thermoplastic starch (TPS)/PBAT-TP active films. Effects of TPS contents on physicochemical properties, functional activities, biodegradability, and release kinetics of PBAT-based active films were explored. Starch interacted strongly with TP through hydrogen bonding and induced the formation of heterogeneous structures in the films. With the increase in TPS contents, surface hydrophilicity and water vapor permeability of the films increased, while mechanical properties decreased. Blending starch with PBAT greatly accelerated degradation behavior of the films, and the T30P70-TP film achieved complete degradation after 180 days. As TPS contents increased, swelling degree of the films increased and TP release were improved accordingly, resulting in significantly enhanced antioxidant and antimicrobial activities. This work demonstrated that filling starch into PBAT-based active films could achieve different antioxidant and antimicrobial activities of the films by regulating film swelling and release behavior.

Comparison of liver venous deprivation with portal vein embolization alone in patients undergoing major liver resection: a systematic review and meta-analysis.

BACKGROUND: The clinical efficacy and safety between liver venous deprivation (LVD) and portal vein embolization (PVE) prior to major hepatectomy is still unclear. METHODS: Studies comparing LVD and PVE were obtained by systemically searching PubMed, Embase, and Cochrane Library Central databases through 22 December 2023. RESULTS: Ten studies including 588 patients were reviewed. Compared with PVE group, LVD group exhibited an increased liver resection rate (OR, 1.89; 95% CI, 1.13-3.15; P = 0.01), a faster KGR (MD, 1.37; 95% CI, 0.31-2.42; P = 0.01), and a shorter time to hepatectomy (MD, -6.66; 95% CI, -8.03 to -5.30; P < 0.0001). The pooled results showed that post-embolization complications (OR, 1.35; 95% CI, 0.66-2.74), overall postoperative complications (OR, 1.09; 95% CI, 0.68-1.75), severe complications (Clavien-Dindo ≥ III) (OR, 0.70; 95% CI, 0.43-1.14), and 90-day mortality (OR, 0.38; 95% CI, 0.13-1.09) were not significantly different in both groups. LVD group had significantly lower post-hepatectomy liver failure (PHLF) than PVE group (OR, 0.45; 95% CI, 0.22-0.91; P = 0.03). CONCLUSION: LVD outperforms PVE regarding liver resection rate and future liver remnant (FLR) hypertrophy and shows comparable safety to PVE. In addition, LVD allowed for major hepatectomy with lower incidence of PHLF.

Phycosphere bacterial composition and function in colony and solitary Phaeocystis globosa strains providing novel insights into the algal blooms.

Phycosphere bacteria can regulate the dynamics of different algal blooms that impact marine ecosystems. Phaeocystis globosa can alternate between solitary free-living cells and colonies and the latter morphotype is dominate during blooms. The mechanisms underlying the formation of these blooms have received much attention. High throughput sequencing results showed that the bacterial community composition differed significantly between colony and solitary strains in bacterial composition and function. It was found that the genera SM1A02 and Haliea were detected only among the colony strains and contribute to ammonium accumulation in colonies, and the genus Sulfitobacter was abundant among the colony strains that were excellent at producing DMS. In addition, the bacterial communities of the two colony strains exhibited stronger abilities for carbon and sulfur metabolism, energy metabolism, vitamin B synthesis, and signal transduction, providing inorganic and organic nutrients and facilitating tight communication with the host algae, thereby promoting growth and bloom development.

Effects of Commonly used Surfactants, Poloxamer 188 and Tween 80, on the Drug Transport Capacity of Intestinal Glucose Transporters.

Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC(0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect.

Risk factors for unsuccessful reduction of chronic Monteggia fractures in children treated surgically.

Aims: To investigate the risk factors for unsuccessful radial head reduction (RHR) in children with chronic Monteggia fractures (CMFs) treated surgically. Methods: A total of 209 children (mean age 6.84 years (SD 2.87)), who underwent surgical treatment for CMFs between March 2015 and March 2023 at six institutions, were retrospectively reviewed. Assessed risk factors included age, sex, laterality, dislocation direction and distance, preoperative proximal radial metaphysis width, time from injury to surgery, reduction method, annular ligament reconstruction, radiocapitellar joint fixation, ulnar osteotomy, site of ulnar osteotomy, preoperative and postoperative ulnar angulation, ulnar fixation method, progressive ulnar distraction, and postoperative cast immobilization. Independent-samples t-test, chi-squared test, and logistic regression analysis were used to identify the risk factors associated with unsuccessful RHR. Results: Redislocation occurred during surgery in 48 patients (23%), and during follow-up in 44 (21.1%). The mean follow-up of patients with successful RHR was 13.25 months (6 to 78). According to the univariable analysis, time from injury to surgery (p = 0.002) and preoperative dislocation distance (p = 0.042) were identified as potential risk factors for unsuccessful RHR. However, only time from injury to surgery (p = 0.007) was confirmed as a risk factor by logistic regression analysis. Receiver operating characteristic curve analysis and chi-squared test confirmed that a time from injury to surgery greater than 1.75 months increased the rate of unsuccessful RHR above the cutoff (p = 0.002). Conclusion: Time from injury to surgery is the primary independent risk factor for unsuccessful RHR in surgically treated children with CMFs, particularly in those with a time from injury to surgery of more than 1.75 months. No other factors were found to influence the incidence of unsuccessful RHR. Surgical reduction of paediatric CMFs should be performed within the first two months of injury whenever possible.

The role of cholesterol-modified prognostic nutritional index in nutritional status assessment and predicting survival after liver resection for hepatocellular carcinoma.

Malnutrition, which is often underestimated in patients with hepatocellular carcinoma (HCC), has a proven adverse effect on survival rates. The purpose of this study was to verify the effectiveness of the cholesterol-modified prognostic nutritional index (CPNI) in determining the nutritional status and predicting overall survival (OS) and recurrence-free survival (RFS) in patients with HCC by comparing it with several other nutritional indicators. This retrospective single-center study enrolled 1450 consecutive HCC patients who underwent curative liver resection from January 2015 to November 2019. We evaluated the prognostic significance of several nutritional indicators, including CPNI, the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI), by applying time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. Among several objective nutrition evaluations (including CPNI, CONUT, NRI, and PNI), CPNI demonstrated the greatest prognostic predictive power for predicting OS. Meanwhile, CPNI demonstrated marginally higher accuracy in predicting RFS compared to PNI, and significantly outperformed CONUT and NRI. Univariate and multivariate analyses suggested that CPNI was an independent risk factor for the OS and RFS of patients with HCC undergoing curative liver resection. In most subgroups, malnutrition as identified by CPNI demonstrates strong stratification ability in predicting both OS and RFS. CPNI serves as an accurate and stable instrument for evaluating nutritional status and forecasting survival outcomes in HCC patients following liver resection, which has the potential to markedly influence clinical decision-making processes and the management of patient care.

Modulating the Moderate d-Band Center of Indium in InVO4 Nanobelts by Synergizing MnOx and Oxygen Vacancies for High-Efficiency CO2 Photoreduction.

Modulating the electronic properties of transition metal sites in photocatalysts at the atomic level is essential for achieving high-activity carbon dioxide photoreduction (CO2PR). An electronic strategy is herein proposed to engineer In-d-band center of InVO4 by incorporating MnOx nanoparticles and oxygen vacancies (VO) into holey InVO4 nanobelts (MnOx/VO-InVO4), which synergistically modulates the In-d-band center to a moderate level and consequently leads to high-efficiency CO2PR. The MnOx/VO-InVO4 catalyst with optimized electronic property exhibits a single carbon evolution rate of up to 145.3 µmol g-1 h-1 and a carbon monoxide (CO) product selectivity of 92.6%, coming out in front of reported InVO4-based materials. It is discovered that the modulated electronic property favors the interaction between the In sites and their intermediates, which thereby improves the thermodynamics and kinetics of the CO2PR-to-CO reaction. This work not only demonstrates the effective engineering of the d orbital of the low-coordination In atoms to promote CO2PR, but also paves the way for the application of tuning d-band center to develop high-efficiency catalysts.

Factors influencing contractors' low-carbon construction behaviors in China: a LDA-DEMATEL-ISM approach.

Contractors' low-carbon construction behaviors (CLCB) are pivotal in advancing decarbonization during the construction phase. However, there exists a notable gap in the comprehensive exploration of the multifaceted factors and mechanisms influencing CLCB. Therefore, this study aims to systematically identify the factors influencing CLCB in China, examine the interrelationships among these factors, and pinpoint the key determinants. Based on topic modeling of Latent Dirichlet Allocation (LDA), influencing factors are identified firstly from the pertinent literature. Subsequently, the causality degree and centrality degree between these factors are assessed by the Decision-Making Trial and Evaluation Laboratory (DEMATEL), followed by the establishment of a hierarchical structure using the Interpretive Structural Modeling (ISM) method, culminating in the identification of pivotal factors. Findings reveal that (1) 21 influential factors influencing CLCB are identified. (2) "Incentive policies for relevant stakeholders" and "Low-carbon regulation and supervision" emerge as key influences. (3) CLCB should be guided by policy and subjective awareness, fortified by market and management support, underpinned by technology, and directly driven by economic considerations. This research furnishes valuable insights for promoting low-carbon development during the construction phase, thereby assisting the construction sector in achieving carbon peak and carbon neutrality.

Effects of Three Kinds of Carbohydrate Pharmaceutical Excipients-Fructose, Lactose and Arabic Gum on Intestinal Absorption of Gastrodin through Glucose Transport Pathway in Rats.

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.

FAT10 induces immune suppression by upregulating PD-L1 expression in hepatocellular carcinoma.

The upregulation of programmed death ligand 1 (PD-L1) plays a crucial role in facilitating cancer cells to evade immune surveillance through immunosuppression. However, the precise regulatory mechanisms of PD-L1 in hepatocellular carcinoma (HCC) remain undefined. The correlation between PD-L1 and ubiquitin-like molecules (UBLs) was studied using sequencing data from 20 HCC patients in our center, combined with TCGA data. Specifically, the association between FAT10 and PD-L1 was further validated at both the protein and mRNA levels in HCC tissues from our center. Subsequently, the effect of FAT10 on tumor progression and immune suppression was examined through both in vivo and in vitro experiments. Utilizing sequencing data, qPCR, and Western blotting assays, we confirmed that FAT10 was highly expressed in HCC tissues and positively correlated with PD-L1 expression. Additionally, in vitro experiments demonstrated that the overexpression of FAT10 fostered the proliferation, migration, and invasion of HCC cells. Furthermore, the overexpression of FAT10 in HCC cells led to an increase in PD-L1 expression, resulting in the inhibition of T cell proliferation and the enhancement of HCC cell resistance to T cell-mediated cytotoxicity. Moreover, in vivo experiments utilizing the C57BL/6 mouse model revealed that overexpression of FAT10 effectively suppressed the infiltration of CD8 + GZMB + and CD8 + Ki67 + T cells, as well as reduced serum levels of TNF-α and IFN-γ. Mechanistically, we further identified that FAT10 upregulates PD-L1 expression via activating the PI3K/AKT/mTOR pathway, but not in a ubiquitin-like modification. In conclusion, our findings indicate that FAT10 promotes immune evasion of HCC via upregulating PD-L1 expression, suggesting its potential as a novel target to enhance the efficiency of immunotherapy in HCC.

Identification of coagulation diagnostic biomarkers related to the severity of spinal cord injury.

BACKGROUND: Blood always shows coagulation changes after spinal cord injury (SCI), and identifying these blood changes may be helpful for diagnosis and treatment of SCI. Nevertheless, studies to date on blood coagulation changes after SCI in humans are not comprehensive. Therefore, this study aims to identify blood coagulation diagnostic biomarkers and immune changes related to SCI and its severity levels. METHODS: Human blood sequencing datasets were obtained from public databases. Differentially expressed coagulation-related genes were analyzed (DECRGs). Enrichment analysis and assessment of immune changes were conducted. Weighted gene co-expression network analysis, least absolute shrinkage and selection operator logistic regression were used to identify biomarkers. Validation for these biomarkers was performed. The correlation between biomarkers and immune cells was evaluated. Transcription factors, miRNA, lncRNA, and drugs that can regulate biomarkers were analyzed. RESULTS: DECRGs associated with SCI and its different grades were identified, showing enrichment in altered coagulation and immune-related signaling pathways. ADAM9, CD55, and STAT4 were identified as coagulation diagnostic biomarkers for SCI. IRF4 and PABPC4 were identified as coagulation diagnostic biomarkers for American Spinal Injury Association Impairment Scale (AIS) A grade of SCI. GP9 was designated as a diagnostic biomarker for AIS D grade of SCI. Immune changes in blood of SCI and its different grades were observed. Correlation between diagnostic biomarkers and immune cells were identified. Transcription factors, miRNA, lncRNA, and drugs that can regulate diagnostic biomarker expression were discovered. CONCLUSION: Therefore, detecting the expression of these putative diagnostic biomarkers and related immune changes may be helpful for predicting the severity of SCI. Uncovering potential regulatory mechanisms for biomarkers may be beneficial for further research.

Red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain through stimulating the expressions of TNF-α and IL-1ß.

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1ß in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1ß. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1ß, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1ß. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

Key biogeochemical processes and source apportionment of nitrate in the Bohai Sea based on nitrate stable isotopes.

Excessive nitrate input is one of the primary factors causing nearshore eutrophication. This study applied the nitrate stable isotope techniques to analyse the biogeochemical processes and sources of nitrate in the Bohai Sea (BHS). The results showed that intensive NO3- assimilation probably occurred at surface in summer, while nitrification primarily occurred in the Yellow River diluted water. In autumn, regional assimilation and nitrification were still identified. For avoiding the interference from assimilation, the isotopic fractionations were further calculated as correction data for the quantitative analysis of nitrate sources. The river inputs were identified as the primary source of nitrate in the BHS in summer and autumn, accounting for >50 %, and the atmospheric deposition was the secondary source. This study provides quantitative data for evaluating the significance of river inputs to the nearshore nitrate, which will be beneficial to policy formulation on the BHS eutrophication control.