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Objective: This study aims to disclose how loss of fucosyltransferase 2 (Fut2) impacts intestinal inflammation through cGAS-STING pathway that is closely associated with gut microbiota, and which microbial metabolite improves colitis in Fut2 deficiency., Methods: Chronic colitis was induced in intestinal epithelial Fut2 knock out mice (Fut2 △IEC ), whose intestinal inflammation and activity of cGAS-STING pathway were evaluated. 16S rRNA sequencing and metabolomics were performed using intestinal samples. 2-oxindole was used to treat RAW264.7 cells and Fut2 △IEC mice with colitis (Fut2 △IEC -DSS) to investigate the effect of 2-oxindole on cGAS-STING response and intestinal inflammation., Results: Fut2 loss exacerbated chronic colitis in mice, manifested by declined body weight, reduced colon length, increased disease activity index (DAI) and more colon injury in Fut2 △IEC -DSS mice compared with WT-DSS (wild type mice with colitis). Lack of Fut2 promoted activation of cGAS-STING pathway. Fut2 deficiency had a primary impact on colonic microbiota, as shown by alteration of microbial diversity and structure, as well as decreased Lactobacillus. Metabolic structure and tryptophan metabolism in colonic luminal microbiota were also influenced by Fut2 loss. Fut2 deficiency also led to decreased levels of aryl hydrocarbon receptor (AHR) and its ligand 2-oxindole derived from tryptophan metabolism. 2-oxindole compromised cGAS-STING response through activating AHR in macrophages, and protected against intestinal inflammation and overactive cGAS-STING pathway in Fut2 △IEC -DSS mice., Conclusion: Fut2 deficiency promotes cGAS-STING pathway through suppressing 2-oxindole-AHR axis, ultimately facilitating the susceptibility to chronic colitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary In most cases of malignant esophageal obstruction, esophageal stenting is efficacious in allowing peroral intake. However, in cases of complete esophageal obstruction, enteral nutrition via a feeding tube without the option for any peroral intake may be the only option for patients—a situation that is both morbid and dissatisfying. In this case, the authors describe a novel technique for recanalization of the esophagus in a patient with complete esophageal obstruction due to esophageal carcinoma. They describe clipping 2 magnets in place in the esophagus on either side of the obstruction, the distal side of the obstruction accessed by advancing an endoscope retrograde up the esophagus via a PEG tube orifice. Over several weeks, x-rays confirmed that the magnets were getting closer together and ultimately creating a channel through the stenosis, which could then be stented and allow for oral intake. Using magnets to create anastomoses or restore luminal integrity in the GI tract is an exciting potential therapeutic option for patients, especially those with no other means of peroral intake. Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Enhance performance in manufacturing carbon emission (MCE) reduction has become a widespread consensus and a necessary part, which cannot be achieved without the joint participation of manufacturing enterprises and supervisory departments. Accordingly, how to coordinate the interests of both sides and design a reasonable incentive-compatible mechanism becomes an urgent task at present. Considering the two subsidy funding channels of peer funds and government finance, this study applies the evolutionary game model to analyze feasible schemes for designing incentive-compatible mechanism of MCE supervision, discusses and simulates the realistic scenarios and influencing factors of incentive-compatible mechanism under the non-subsidized and subsidized schemes. The results show that MCE supervision is in an incentive-incompatible state under the non-subsidized incentive scheme, while in a constrained incentive-compatible state under the subsidized incentive scheme. With the increase of peer funds and penalty coefficient or the decrease of subsidy coefficient, the period of MCE supervision to reach an incentive-compatible state becomes shorter. However, a lower peer fund and penalty coefficient or a higher subsidy coefficient will contribute to a state of incentive-incompatible or a periodic cycle state of "incentive-compatible → incentive-incompatible →incentive-compatible→…" in the MCE supervision., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Liang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Supercapacitor is an important energy storage device widely used in the automobile industry, military production, and communication equipment because of its fast charge-discharge rate, and high power density. Herein, carbon quantum dots modified and Y 3+ doped Ni 3 (NO 3 ) 2 (OH) 4 (NiY@CQDs) nanospheres are prepared by a solvothermal method and used as an electrode material. The electrochemical properties of NiY@CQDs were measured in a three-electrode system. An asymmetric supercapacitor (ASC) cell was assembled with activated carbon (AC) as the anode and NiY@CQDs as the cathode. The electrochemical properties of the ASC device were measured in a two-electrode system. Experimental results show the shape of NiY@CQDs is petal-shaped and the introducing carbon quantum dots and doping Y 3+ significantly increases the specific surface area, conductivity, and specific capacitance of Ni 3 (NO 3 ) 2 (OH) 4 . The mass-specific capacitance of NiY@CQDs reaches up to 2944 F g -1 at a current density of 1 A g -1 . The asymmetric supercapacitor of NiY@CQDs//AC has a high energy density of 138.65 Wh kg -1 at a power density of 1500 W kg -1 , displaying a wide range of application prospects in the energy storage area., (© 2024 Wiley‐VCH GmbH.)

Metal-organic framework compounds are extensively utilized in various fields, such as electrode materials, owing to their distinctive porous structure and significant specific surface area. In this study, NiCoAl-MOF metal-organic framework precursors were synthesized by a solvothermal method, and NiAl 2 O 4 /NiCo 2 O 4 electrode materials were prepared by the subsequent calcination of the precursor. These materials were characterized by XRD, XPS, BET tests, and SEM, and the electrochemical properties of the electrode materials were tested by CV and GCD methods. BET tests showed that NiAl 2 O 4 /NiCo 2 O 4 has an abundant porous structure and a large specific surface area of up to 105 m 2 g -1 . The specific capacitance of NiAl 2 O 4 /NiCo 2 O 4 measured by the GCD method reaches up to 2870.83 F g -1 at a current density of 1 A g -1 . The asymmetric supercapacitor NiAl 2 O 4 /NiCo 2 O 4 //AC assembled with activated carbon electrodes has a maximum energy density of 166.98 W h kg -1 and a power density of 750.00 W kg -1 within a voltage window of 1.5 V. In addition, NiAl 2 O 4 /NiCo 2 O 4 materials have good cycling stability. These advantages make it a good candidate for the application of high-performance supercapacitors.

Chronic rhinosinusitis (CRS) is a highly heterogeneous disease characterized by inflammation in the nasal and sinus mucosa. The CRS phenotypes, based on the presence or absence of nasal polyps, are known as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). However, this classification has limitations in fully capturing the mechanisms and clinical manifestations of CRS. To address the heterogeneity of CRS, there has been a growing focus on classifying the condition into distinct endotypes. Endotype classification involves grouping patients based on specific molecular, immunological, and clinical characteristics, allowing for more personalized and targeted treatment approaches.This review delves into the current state of endotype classifications for CRS. It explores the role of geographic factors, microbiome, and subphenotype in shaping different endotypes. Additionally, the review examines how various clinical features are associated with specific endotypes, providing valuable insights into tailoring treatment options for better outcomes and transitions between different endotypes.Overall, this review offers a comprehensive and up-to-date perspective on the intricate realm of CRS endotype classifications. By unraveling the molecular and clinical intricacies, this review lays the foundation for more precise, effective, and individualized treatment strategies in the management of CRS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Molybdenum disulfide (MoS 2 ) has been deemed as one of the promising noble-metal-free electrocatalysts for hydrogen evolution reaction (HER), but it suffers from the inert basal plane and low electronic conductivity. Regulating the morphology of MoS 2 during the synthesis on conductive substrates is a synergistic strategy for enhancing the HER performance. In this work, vertical MoS 2 nanosheets were fabricated on carbon cloth (CC) using an atmospheric pressure chemical vapor deposition method. The growth process could be effectively tuned through introducing hydrogen gas during vapor deposition process, resulting in nanosheets with increased edge density. The mechanism for edge-enriching through controlling the growth atmosphere is systematically studied. The as-prepared MoS 2 exhibits excellent HER activity due to the combination of optimized microstructures and coupling with CC. Our findings provide new insights to design advanced MoS 2 -based electrocatalysts for HER., (© 2023 IOP Publishing Ltd.)

To understand the potential role of microglia in synaptic pruning following status epilepticus (SE), we examined the time course of expression of Iba-1, and immune and neuroinflammatory regulators, including CD86, CD206, and CX3CR1, and TLR4/NF-κB after SE induced by pilocarpine in rats. Behavioral tests, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, immunohistochemical staining, Western blotting, PCR, and fluorescence double staining assessments were performed. The expression of Iba-1 protein was lowest in the control group, and peaked after 2 days (p < 0.001). CD86 and CD206 mRNA levels increased gradually in the microglia of the epilepsy group after 12 hours, 1 day, 2 days, and 3 days; peak expression was on the second day. The expression of the chemokine receptor CX3CR1 in microglia increased to varying degrees after SE, and expression of the presynaptic protein synapsin decreased. The expression of TLR4/NF-κB in microglia positively correlated with Iba-1 protein expression. These findings indicate that the TLR4/NF-κB signaling pathway may be involved in the activation and polarization of microglia in epilepsy and in excess synaptic pruning, which could lead to an increase in brain injury., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Macrocyclic retinoic acid receptor-related orphan receptor C2 (RORC2) inverse agonists have been designed with favorable properties for topical administration. Inspired by the unanticipated bound conformation of an acyclic sulfonamide-based RORC2 ligand from cocrystal structure analysis, macrocyclic linker connections between the halves of the molecule were explored. Further optimization of analogues was accomplished to maximize potency and refine physiochemical properties (MW, lipophilicity) best suited for topical application. Compound 14 demonstrated potent inhibition of interleukin-17A (IL-17A) production by human Th17 cells and in vitro permeation through healthy human skin achieving high total compound concentration in both skin epidermis and dermis layers., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Co 3 O 4 /Bi 4 O 7 /Bi 2 O 3 (CBB) composites were prepared, in which Co 3 O 4 was synthesized from Co-MOF as precursor. The peroxymonosulfate (PMS) activated by CBB catalyst under visible light was used to degrade tetracycline (TC). Owing to the synergistic effect of photocatalysis and PMS activation, 98.4% of TC was removed within 60 min. The optimal loading of Co 3 O 4 was determined, and the influence of PMS dosage, initial pH, and disturbing anions on the degradation effect were investigated. The "CBB + Vis + PMS" system showed good reusability, and the degradation was only reduced by 1.7% after 5 cycles. This system also had a good degradation of other five pollutants. The quenching experiment showed that holes (h + ), superoxide radicals (·O 2 - ), and singlet oxygen ( 1 O 2 ) were the main active species. The degradation products of TC were determined by liquid chromatography-mass spectrometry, and the degradation pathway was proposed. Finally, a double Z-scheme degradation mechanism was proposed in the "CBB + Vis + PMS" system. The peroxymonosulfate activated by CBB under visible light to degrade organic pollutants has widespread application prospects in environmental remediation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Developing low-cost, environmentally friendly and efficient non-precious metal electrocatalysts as alternatives to noble metals for the hydrogen evolution reaction (HER) is highly essential for the sustainable advancement of green hydrogen energy. Herein, a novel heterostructured Ni 3 P/Ni nanoparticle anchored in nitrogen-doped mesoporous carbon nanofibers (Ni 3 P/Ni@N-CNFs) is prepared by a facile solid-phase calcination protocol. The results demonstrated that benefiting from the intensive electronic coupling effect at the interface of the Ni 3 P/Ni heterostructure, the electron configuration of the Ni active site is optimized and thus the favorable HER activity. Furthermore, the N-doped carbon nanofiber scaffold with an extensive mesoporous structure endows Ni 3 P/Ni@N-CNFs with abundant electrochemically active sites together with excellent conductivity and stability, contributing to fast electron/mass transport. As expected, the resultant Ni 3 P/Ni@N-CNF electrocatalyst exhibited exceptional HER catalytic properties under universal pH conditions, driving a current density of 10 mA cm -2 at pretty low overpotentials of 121 mV, 145 mV and 187 mV in acidic, basic and neutral solutions, respectively, and retaining the catalytic stability for over 60 h. This intriguing work represents a fresh perspective for designing and exploiting highly advanced phosphide electrocatalysts for green hydrogen fuel production.

A quantum gas microscope plays an important role in cold-atom experiments, which provides a high-resolution imaging of the spatial distributions of cold atoms. Here we design, build and calibrate an integrated microscope for quantum gases with all the optical components fixed outside the vacuum chamber. It provides large numerical aperture (NA) of 0.75, as well as good optical access from side for atom loading in cold-atom experiments due to long working distance (7 mm fused silica+6 mm vacuum) of the microscope objective. We make a special design of the vacuum viewport with a T-shape window, to suppress the window flatness distortion introduced by the metal-glass binding process, and protect the high-resolution imaging from distortions due to unflattened window. The achieved Strehl ratio is 0.9204 using scanning-near-field microscopy (SNOM) fiber coupling incoherent light as point light source.

Background: Controlled hypotension technique was usually used to reduce intraoperative bleeding, and it could improve visualization of the surgical field during total knee arthroplasty (TKA). However, inappropriate controlled hypotension, through reducing cerebral blood flow or cerebral perfusion pressure, may cause postoperative cognitive dysfunction (POCD), so it is important to identify the appropriate level of controlled hypotension. Objective: To investigate the effects of different levels of controlled hypotension on regional cerebral oxygen saturation and postoperative cognitive function in patients undergoing TKA., Methods: Patients meeting inclusion criteria were enrolled through preoperative visits and basic information was obtained. The patients were randomly divided into three groups: Group A, MAP was maintained at 90-100% of the baseline; Group B, MAP was maintained at 80-90% of the baseline; Group C, MAP was maintained at 70-80% of the baseline. The MAP, HR, and rSO 2 were observed and recorded during the operation. The C-reactive protein (CRP), hemoglobin (Hb) and MMSE score at 1, 3, and 7 days after operation were recorded. SPSS25.0 was used for data analysis., Result: When the MAP had a decrease among the three groups, rSO 2 did not decrease significantly, and none of the patients experienced POCD which was measured by MMSE. And there was no correlation between the decline in rSO 2 and that in MAP., Conclusion: No POCD was experienced in the three groups, and we recommend that the controlled hypotensive target indicated by MAP was maintained at 70-80% of the baseline which not only decreases intraoperative bleeding and improve the quality of the surgical field, but also is still within safe levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Zang, Ren, Fu, Liu, Zhou and Lang.)

Lipotoxicity and unresolved oxidative stress are key drivers of metabolic inflammation in nonalcoholic steatohepatitis (NASH). cAMP-response element binding protein H(CREBH) is a liver-specific transcription factor and regulates the glucose and lipid metabolism of NASH. However, its role in mitochondrial oxidative stress and its association with sirtuin 3 (SIRT3), a master regulator of deacetylation for mitochondrial proteins, remains elusive. In this study, AML-12 cells were treated with palmitic acid to imitate the pathological changes of NASH in vitro and 8-week-old male C57BL/6J mice were fed with a high-fat (HF) diet or a methionine-choline-deficient (MCD) diet to build the widely accepted in vivo model of NASH. We found that lipid overload induced mitochondrial oxidative stress and stimulated the expression of CREBH and SIRT3. CREBH overexpression alleviated the mitochondrial oxidative stress. Moreover, CREBH promoted SIRT3 expression, which regulated the deacetylation of manganese superoxide dismutase (MnSOD) and inhibited NOD-Like Receptor Pyrin Domain Containing 3 (Nlrp3) inflammasome activation whereas suppression of SIRT3 damaged the protecting ability of CREBH in mitochondrial oxidative stress. CREBH knockout mice were highly susceptible to HF and MCD diet-induced NASH with more severe oxidative stress. Collectively, our results firstly provided the support that CREBH could serve as a protective factor in the progression of NASH by regulating the acetylation of MnSOD and the activation of Nlrp3 inflammasome through SIRT3. These results suggest that CREBH might be a valuable therapeutic candidate for NASH., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Studies have long shown that uncontrolled inflammatory responses in the brain play a key role in epilepsy pathogenesis. Microglias play an important role in epileptic-induced neuroinflammation, but their role after epileptic seizures is still poorly understood. Alleviating epilepsy and its comorbidities has become a key area of interest for pediatricians., Methods: A pilocarpine-induced rat model of epilepsy was established. The rats were randomly divided into four groups: a control group, epilepsy group, TLR4 inhibitor group (epilepsy+TAK-242), and NF-κB antagonist group (epilepsy+BAY11-7082)., Results: 1. The results of TUNEL staining showed that the expression in rats in the epilepsy group was the most obvious and was significantly different from that in rats in the control, EP+BAY and EP+TAK groups. 2. The expression of TLR4 and NF-κB was highest in rats in the epilepsy group and was significantly different from that in rats in the control, EP+BAY and EP+TAK groups. 3. The fluorescence intensity and number of IBA-1-positive cells in rats in the epilepsy group were highest and significantly different from those in rats in the control, EP+BAY and EP+TAK groups. Western blot analysis of IBA-1 showed that the expression in rats in the epilepsy group was the highest and was statistically significant. 4. CD68 was the highest in rats in the epilepsy group and was statistically significant. 5. In the open-field experiment, the central region residence time of rats in the EP group was delayed, the central region movement distance traveled was prolonged, the total distance traveled was prolonged, and the average speed was increased. Compared with rats in the EP group, rats in the EP+BAY and EP+ TAK groups exhibited improvements to different degrees., Conclusion: At the tissue level, downregulation of the TLR4/NF-κB inflammatory pathway in epilepsy could inhibit microglial activation and the expression of the inflammatory factor CD68, could inhibit hyperphagocytosis, and inhibit the occurrence and exacerbation of epilepsy, thus improving cognitive and emotional disorders after epileptic seizures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Wang, Liu, Zhao and Zhang.)

Immature granulocytes (IGs) have significance for the diagnosis of myeloid neoplasms (MNs). The current study aims to use a hematology analyzer to evaluate the accuracy of IG parameters in MNs. Blood specimens from 388 patients with MN, 524 with non-hematological neoplasms (non-HNs), including 109 patients with inflammation and 68 undergoing G-CSF administration, and 500 healthy control subjects were analyzed. IG parameters was assayed by Sysmex XN-9000 (XN) and compared with manual assessments. A high level of agreement between IG% derived from XN and manual measurements for MN patients (r = 0.828, p < 0.0001) was revealed but only a moderate correlation for acute myeloid leukemia patients (AML; r = 0.597; p < 0.0001). Bland-Altman bias analysis was conducted, and the results showed that differences in IG% from XN and manual analysis for MN patients were considered clinically insignificant. ROC analysis demonstrated a good performance of IG# (AUC = 0.842) and IG% (AUC = 0.885) assessed by XN for MN patients with cut-off values of 0.200 × 10 9 /L and 1.95%, respectively. IG parameters from Sysmex XN analyzer are helpful for screening of MNs even though granulocyte morphological abnormalities may interfere with IG parameter accuracy., (© 2022. The Author(s).)

Periodontitis is the leading cause of tooth loss in adults, and psychological factors play an important role in the development of periodontitis. To elucidate the adverse effects of psychological stress on the inflammatory process and redox status of periodontitis tissue, fifty male Sprague-Dawley rats were divided into the control, experimental periodontitis, psychological stress, experimental periodontitis plus psychological stress, and experimental periodontitis plus psychological stress plus fluoxetine groups. Chronic unpredictable mild stress (CUMS) was used to establish psychological stress, and silk ligature was used to induce experimental periodontitis. Four weeks later, stressed rats showed altered behaviour, serum hormone levels, and sucrose preference. More obvious alveolar bone loss and attachment loss and higher protein expressions of inflammatory cytokines were observed in the experimental periodontitis plus psychological stress group. The combination of CUMS and periodontitis had synergistic effects on increasing hypoxia-inducible factor-1 α (HIF-1 α ) protein expression and reactive oxygen species (ROS) and malondialdehyde (MDA) contents and decreasing antioxidant enzyme activities compared with those in the stress or periodontitis groups. Moreover, psychological stress further increased p-I κ B α and p-NF- κ B p65 protein levels and decreased I κ B α protein levels in periodontitis rats. Fluoxetine administration alleviated the adverse effects of psychological stress on the progression of periodontitis in rats. These results hint us that psychological stress could aggravate inflammation in periodontitis tissues, which may be partly due to local worsening of oxidative damage and further activation of the nuclear factor kappa-B (NF- κ B) signalling pathway., Competing Interests: The authors declare no potential competing interests., (Copyright © 2022 Qiang Li et al.)

Background: Hepatocellular carcinoma (HCC) is the world's second most deadly cancer, and metabolic reprogramming is its distinguishing feature. Among metabolite profiling, variation in amino acid metabolism supports tumor proliferation and metastasis to the most extent, yet a systematic study on the role of amino acid metabolism-related genes in HCC is still lacking. An effective amino acid metabolism-related prediction signature is urgently needed to assess the prognosis of HCC patients for individualized treatment. Materials and Methods: RNA-seq data of HCC from the TCGA-LIHC and GSE14520 (GPL3921) datasets were defined as the training set and validation set, respectively. Amino acid metabolic genes were extracted from the Molecular Signature Database. Univariate Cox and LASSO regression analyses were performed to build a predictive risk signature. K-M curves, ROC curves, and univariate and multivariate Cox regression were conducted to evaluate the predictive value of this risk signature. Functional enrichment was analyzed by GSEA and CIBERSORTx software. Results: A nine-gene amino acid metabolism-related risk signature including B3GAT3, B4GALT2, CYB5R3, GNPDA1, GOT2, HEXB, HMGCS2, PLOD2, and SEPHS1 was constructed to predict the overall survival (OS) of HCC patients. Patients were separated into high-risk and low-risk groups based on risk scores and low-risk patients had lower risk scores and longer survival time. Univariate and multivariate Cox regression verified that this signature was an independent risk factor for HCC. ROC curves showed that this risk signature can effectively predict the 1-, 2-, 3- and 5-year survival times of patients with HCC. Additionally, prognostic nomograms were established based on the training set and validation set. These genes were closely correlated with the immune regulation. Conclusion: Our study identified a nine-gene amino acid metabolism-related risk signature and built predictive nomograms for OS in HCC. These findings will help us to personalize the treatment of liver cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Zhang, Wang, Jiang and Xu.)

Endothelial monocyte‑activating polypeptide II (EMAP II) is a sensitive marker of neurotoxic injury, the expression of which increases significantly under conditions of stress, such as hypoxia or apoptosis. Studies have confirmed the extensive apoptosis of nerve cells in the brain following status epilepticus (SE), and the occurrence of SE can confer a hypoxic state on cells. The purpose of the present study was to observe the changes in the expression of EMAP II, and in the numbers and tight junction protein levels of microvascular endothelial cells in the hippocampus of rats with pilocarpine‑induced SE. The protein expression levels of EMAP II, CD31, zonula occludens 1 (ZO‑1) and occludin in the hippocampus were determined by immunofluorescence and western blot analyses. It was found that almost 75.6% of the rats in the SE group developed Racine stage IV‑V seizures at approximately 44.7±18.8 min after the pilocarpine administration, and the 24‑h mortality rate was almost 10.4%. The weight of the rats in the SE group was significantly decreased within 24 h following SE. Immunofluorescence staining revealed a low EMAP II expression in the hippocampus of the rats in the control group; however, the numbers of EMAP II‑positive cells were significantly increased in the SE group from 2 h to 21 days. The trend of EMAP II protein expression was consistent with that obtained with immunofluorescence staining. The numbers of CD31‑positive microvascular endothelial cells were significantly increased from 24 h to 21 days compared with the levels in the control group. The protein expression of ZO‑1 and occludin was most significantly decreased in the SE group. On the whole, the present study demonstrated that the expression of EMAP II in the rat hippocampus was upregulated in the SE model, which may promote angiogenesis and alter the TJ integrity of brain microvascular endothelial cells, with an increased number of CD31‑positive microvascular endothelial cells and a decreased expression of ZO‑1 and occludin.

The homeostasis of mitochondrial functional state is intimately in relation with SIRT3 (sirtuin3). SIRT3, the deacetylase mainly anchored in mitochondria, acts as a modulator of metabolic regulation via manipulating the activity and function of downstream targets at post-translational modification levels. The features of energy sensing and ADP-ribose transference of SIRT3 have also been reported. Recently, accumulating SIRT3-focusing evidences have suggested its complicated role in a series of adverse events such as metabolic disorders, aging-related diseases, coupled with tumors, in which SIRT3 regulates the progress of corresponding biochemical reactions by targeting key mediators. By systematically summarizing the downstream deacetylated proteins of the SIRT3 axis, this review aims to give a comprehensive introduction to the main metabolic pathways and diseases of the molecules involved in acetylation modification, which is expected to provide a direction for further exploration of the pathogenesis and therapeutic targets of the above diseases., Competing Interests: Declaration of competing interest Authors declare no conflict of interests., (Copyright © 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Objective: To evaluate the relationship of the blood fibrinogen (FIB) degradation product (FDP) level and FDP/FIB ratio with seizure in young children with fever. Methods: A total of 35 children with simple febrile seizures and 80 children with fever but no seizure were selected. First, the differences in white blood cell (WBC), platelets (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), FIB, FDP, FDP/FIB ratio, and C-reactive protein (CRP) between 35 children with simple febrile seizures and 40 randomly selected children with fever but no seizure were retrospectively analyzed. Then, an ROC curve was used to determine the diagnostic utility of the FDP level, FDP/FIB ratio, and FDP+FDP/FIB ratio, and the best diagnostic cutoff points were selected. Finally, the diagnostic specificities of the three diagnostic indicators were verified by comparison with the results of all 80 children with fever but no seizure. Results: The FDP level and FDP/FIB ratio were significantly different between the two groups ( P < 0.0001) and there was a positive correlation between the FDP and FIB levels. Both the FDP level and FDP/FIB ratio had good diagnostic value. An FDP ≥ 2.0 mg/L and FDP/FIB ratio ≥ 0.5 had good diagnostic specificities. Combined application of an FDP ≥ 2.0 mg/L and FDP/FIB ratio ≥ 0.5 improved the diagnostic power. Conclusions: The blood FDP level and FDP/FIB ratio may be related to seizures after fever, and an FDP ≥ 2.0 mg/L + FDP/FIB ratio ≥ 0.5 has good diagnostic specificity., (Copyright © 2020 Li, Ma, Li, Zhao, Zhao and Wang.)

Objective Recently, there have been several studies on the clinical characteristics of patients with coronavirus disease 2019 (COVID-19); however, these studies have mainly been concentrated in Wuhan, China; the sample sizes of each article were different; and the reported clinical characteristics, especially blood biochemical indices, were quite different. This study aimed to summarize the blood biochemistry characteristics of COVID-19 patients by performing a systemic review and meta-analysis of published studies. Methods Comprehensive studies were screened from PubMed, Embase, and Cochrane Library through March 11, 2020. The inclusion criteria included studies investigating the biochemical indexes of patients with COVID-19. The statistical software R3.6.3 was used for meta-analysis. Results Ten studies including 1745 COVID-19 patients met the inclusion criteria for our meta-analysis. Meta-analysis showed that 16% and 20% of patients with COVID-19 had alanine transaminase (ALT) and aspartate aminotransferase (AST) levels higher than the normal range, respectively. Thirty-four percent of patients showed albumin (ALB) levels lower than the normal range, and 6% of patients showed abnormal total bilirubin (TBil) levels. The levels of creatinine (CRE) were increased in 8% of patients. The creatine kinase (CK) level of 13% of patients exceeded the normal range, and 52% of patients had elevated lactate dehydrogenase (LDH) levels. In addition, six studies met the inclusion criteria for the systemic review evaluating the relevance between LDH levels and the severity of COVID-19, and all six studies showed a positive association between these two factors. Conclusions Some patients with COVID-19 had different degrees of blood biochemical abnormalities, which might indicate multiple organ dysfunction. Some biochemical indexes, such as abnormal ALB and LDH, could reflect the severity of the disease to a certain extent. These blood biochemical indicators should be considered in the clinical management of the disease.

Simple febrile convulsion (SFC) is a common disease that is mainly caused by fever from extracranial infections. In this study, we used proteomic approaches involving discovery and validation cohorts to examine the proteomes of serum from children who were diagnosed with SFC, children with fever but without convulsion, and healthy children (normal controls). We identified 86 proteins involved in different biological pathways that were significantly different between the SFC and normal control groups. Of these 86 proteins, 35 had higher expression in the SFC group compared with the normal control group, whereas 51 had lower expression. Notably, fibrinogen-related proteins involved in the coagulation system pathway were markedly decreased in the SFC group. Targeted and absolute quantification of fibrinogen-related proteins was performed and validated the potential of these proteins as biomarkers. Thus, fibrinogen-related proteins may participate in the pathophysiological process of SFC and may be potential biomarkers for the diagnosis of SFC.

It is commonly accepted that psychological stress is closely associated with the occurrence and development of chronic orofacial pain. However, the pathogenesis underlying this process has not been fully elucidated. In the present study, we explored the role of N-methyl-D-aspartate receptors (NMDARs) and Jun N-terminal kinase (JNK) mediated intercellular communication between neurons and astrocytes in the spinal trigeminal nucleus caudalis (Vc) in the induction of masseter hyperalgesia by psychological stress in rats. We found that subjecting rats to 14 days of restraint stress (8 h/d) caused a significant decrease in body weight gain, behavioral changes and marked masseter hyperalgesia in the rats. We also found that exposure to restraint stress for 14 days caused the expression of pJNK in astrocytes in the Vc to significantly increase, and intrathecally infusing a JNK inhibitor significantly prevented restraint stress-induced masseter hyperalgesia in the rats. In addition, after exposure to restraint stress for 14 days, the stressed group exhibited a noticeably increased expression level of pNR2B in neurons in the Vc. Then, we intrathecally injected MK-801 (an NMDAR inhibitor) and ifenprodil (a selective NR2B subunit antagonist) and observed that the two types of inhibitors not only alleviated masseter hyperalgesia but also significantly inhibited the phosphorylation of JNK in the Vc after restraint stress; this indicates that the effect of NMDAR antagonists may influence the activation of astrocytic JNK. Furthermore, inhibitors of neuronal nitric oxide synthase (nNOS) activation and guanylate cyclase (GC) inhibitor could not only inhibit the expression of pJNK in the Vc, but also effectively alleviate masseter hyperalgesia induced by restraint stress. Taken together, our results suggest that NMDAR activation could increase JNK phosphorylation in astrocytes after restraint stress, which may depend on the nNOS-GC pathway. The intercellular communication between neurons and astrocytes in the Vc may play a key role in the induction of masseter muscle hyperalgesia by psychological stress in rats., (Copyright © 2019 Lin, Zhao, Cheng, Zhao, Miao, Li, Chen and Zhang.)

Tuning the coupling interface of a heterostructured catalyst is an effective approach to achieve abundant surface catalytic active sites and strong electronic interactions among active materials for improving electrocatalytic water splitting performance. Herein, we report a novel heterogeneous catalyst comprising Ni3S2 nanoparticles embedded in ultrathin NiV-layered double hydroxide nanosheet arrays supported on nickel foam, denoted as Ni3S2@NiV-LDH/NF. We demonstrate that the active edge-state length and the surface chemical state of such NiV-LDH-based heterostructures are well modulated by tailoring the coupling interfaces, resulting in the exposure of more catalytic reaction sites and enhancement of the electronic interactions between NiV-LDH and Ni3S2, thus greatly promoting the water dissociation kinetics. As expected, the optimized Ni3S2@NiV-LDH/NF heterostructures exhibit outstanding electrocatalytic activity for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), with an extremely low overpotential of 126 mV and 190 mV to deliver 10 mA cm-2 for the HER and OER without iR compensation in alkaline media, respectively. More importantly, Ni3S2@NiV-LDH/NF simultaneously functioned as both the anode and cathode for water splitting to yield a current density of 10 mA cm-2 at a cell voltage of only 1.53 V with an outstanding durability for 160 h. This work provides a new insight into the regulation of the coupling interface for obtaining highly active heterostructured catalysts for overall water splitting.

Purpose: B7-H3, a member of the B7 family of immune regulatory ligands, plays a critical role in the T cell-mediated immune response. It is broadly expressed in several human cancers and leads to poor prognosis. Nevertheless, the clinical significance of B7-H3 expression in colorectal cancer (CRC) remains unclear., Methods: The serum B7-H3, B7-H1, cancer-associated carbohydrate antigen-50 (CA-50) and carcinoembryonic antigen (CEA) expressions in patients with CRC, benign gastrointestinal diseases, and healthy controls were measured by ELISA. The miRNAs that target B7-H3 were predicted by using the miRTarBase. Real-time PCR was performed to examine their expressions in patients with CRC., Results: B7-H3, B7-H1, and CA-50 expressions were higher in patients with CRC than those in healthy controls and the patients with benign gastrointestinal diseases. B7-H3 expression was correlated with TNM stage and metastasis. It was predicted that B7-H3 was a target of miR-1301-3p, miR-335-5p, and miR-28-5p and its expression was negatively related to these three miRNAs expressions. Serum miR-1301-3p, miR-335-5p, and miR-28-5p expressions were also correlated with the TNM stage and metastasis., Conclusion: Our results indicated that serum miR-1301-3p, miR-28-5p, miR-335-5p, and B7-H3 expressions were correlated with pathological stages of CRC and metastasis and may therefore serve as novel biomarkers for CRC diagnosis and treatment.

Recent studies have revealed that circular RNAs (circRNAs) are involved in the development of various liver diseases. However, the regulatory role of circRNAs in nonalcoholic steatohepatitis (NASH) has not been fully elucidated. In the present study, the circRNA profiles in a NASH mouse model were investigated, and their functions in NASH were predicted using bioinformatics analysis, with the aim of providing novel clues for delineating the mechanisms of action. A NASH mouse model was established by feeding mice with a methionine and choline‑deficient diet. The liver circRNA profile was screened using a circRNA microarray, and the differentially expressed circRNAs were verified by reverse transcription‑quantitative polymerase chain reaction. Subsequently, circRNA‑microRNA (miRNA) interactions were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological functions of host linear transcripts of circRNA. A total of 450 circRNAs were revealed to be dysregulated, with 298 circRNAs upregulated and 152 circRNAs downregulated in the NASH model mice. circRNA&#95;29981 was identified as a significantly differentially expressed circRNA. The results from the circRNA‑miRNA pathway interaction analysis revealed that circRNA&#95;29981 was a potential regulator of hepatic stellate cell activation. The host linear transcripts were also analyzed, and the top 10 enriched GO entries and KEGG pathways were annotated. These findings suggested that circRNAs may be important regulators of NASH. Taken together, the results of the present study demonstrated that the circRNA profile in NASH may provide potential candidates for future studies aimed at elucidating the pathogenic mechanism(s) involved in the disease.

The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production of IL-17, a key proinflammatory cytokine. Through a high-throughput screening approach, we identified a molecule displaying promising binding affinity for RORC2, inhibition of IL-17 production in Th17 cells, and selectivity against the related RORA and RORB receptor isoforms. Lead optimization to improve the potency and metabolic stability of this hit focused on two key design strategies, namely, iterative optimization driven by increasing lipophilic efficiency and structure-guided conformational restriction to achieve optimal ground state energetics and maximize receptor residence time. This approach successfully identified 3-cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide as a potent and selective RORC2 inverse agonist, demonstrating good metabolic stability, oral bioavailability, and the ability to reduce IL-17 levels and skin inflammation in a preclinical in vivo animal model upon oral administration.

Single phase of Bi 3+ , Gd 3+ , Sm 3+ and Eu 3+ co-doped La 2 MgTiO 6 red phosphors were synthesized by high temperature solid-state method. The phase composition, morphology and fluorescent properties of the phosphors were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and fluorescence spectrometer. The La 2-x MgTiO 6 :xEu 3+ phosphors can be excited by UV (396 nm) and blue (465 nm) light-emitting diode (LED) chips and show a strong red emitting with dominated wavelength at 615 nm. The optimum doping concentration of Eu 3+ ion for La 2 MgTiO 6 is x = 0.5. The luminescent intensities of 5 D 0  →  7 F 2 transition of Eu 3+ in La 1.5-y MgTiO 6 :0.5Eu 3+ , yBi 3+ /Gd 3+ /Sm 3+ were 1.31 times, 1.32 times and 1.88 times that of La 1.5 MgTiO 6 :0.5Eu 3+ at y = 0.08, 0.06, 0.06 for Bi 3+ , Gd 3+ , or Sm 3+ sensitizer, respectively. The chromaticity coordinates of La 1.44 MgTiO 6 :0.5Eu 3+ , 0.06Sm 3+ , (0.6342, 0.3513) were very close to those of the National Television Standard Committee (NTSC) standard red light coordinates., (© 2018 John Wiley & Sons, Ltd.)

Background and Aim: Silybin is the major biologically active compound of silymarin, the standardized extract of the milk thistle (Silybum marianum). Increasing numbers of studies have shown that silybin can improve nonalcoholic steatohepatitis (NASH) in animal models and patients; however, the mechanisms underlying silybin's actions remain unclear., Methods: Male C57BL/6 mice were fed a methionine-choline deficient (MCD) diet for 8 weeks to induce the NASH model, and silybin was orally administered to the NASH mice. The effects of silybin on lipid accumulation, hepatic fibrosis, oxidative stress, inflammation-related gene expression and nuclear factor kappa B (NF-κB) activities were evaluated by biochemical analysis, immunohistochemistry, immunofluorescence, quantitative real-time PCR and western blot., Results: Silybin treatment significantly alleviated hepatic steatosis, fibrosis and inflammation in MCD-induced NASH mice. Moreover, silybin inhibited HSC activation and hepatic apoptosis and prevented the formation of MDBs in the NASH liver. Additionally, silybin partly reversed the abnormal expression of lipid metabolism-related genes in NASH. Further study showed that the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway played important roles in the silybin-derived antioxidant effect, as evidenced by the upregulation of Nrf2 target genes in the silybin treatment group. In addition, silybin significantly downregulated the expression of inflammation-related genes and suppressed the activity of NF-κB signaling., Conclusions: Silybin was effective in preventing the MCD-induced increases in hepatic steatosis, fibrosis and inflammation. The effect was related to alteration of lipid metabolism-related gene expression, activation of the Nrf2 pathway and inhibition of the NF-κB signaling pathway in the NASH liver.

Noninvasive serum markers for assessment of liver fibrosis in chronic hepatitis B (CHB) patients have not been well-studied. The present study was to evaluate the predictive value of serum interferon gamma-inducible protein-10 (IP-10/CXCL10) and the interferon (IFN)-γ/interleukin (IL)-4 ratio for liver fibrosis progression in CHB patients. A total of 180 CHB patients were categorized into four groups: no fibrosis, mild fibrosis, moderate fibrosis, and severe fibrosis. Serum and intrahepatic levels of IP-10, IFN-γ, and IL-4 were examined, from which the IFN-γ/IL-4 ratio was calculated. We found that the serum IP-10 levels were positively correlated with the severity of liver fibrosis, whereas the IFN-γ/IL-4 ratio was negatively associated with the progression of hepatic fibrosis. Multivariate logistic regression analysis revealed that the serum IP-10 was an independent predictor for significant fibrosis. For predicting significant fibrosis, the IP-10 cut-off value of 300 ng/mL had a sensitivity of 92.7% and a specificity of 68.6%. When the IP-10 level was combined with the IFN-γ/IL-4 ratio, the specificity and positive predictive value were 93.8% and 94.6%, respectively; thus, the discriminatory ability was much improved. In conclusion, the serum IP-10 level and the IFN-γ/IL-4 ratio have great potential to predict significant fibrosis among CHB patients.

PF-06651600, a newly discovered potent JAK3-selective inhibitor, is highly efficacious at inhibiting γc cytokine signaling, which is dependent on both JAK1 and JAK3. PF-06651600 allowed the comparison of JAK3-selective inhibition to pan-JAK or JAK1-selective inhibition, in relevant immune cells to a level that could not be achieved previously without such potency and selectivity. In vitro, PF-06651600 inhibits Th1 and Th17 cell differentiation and function, and in vivo it reduces disease pathology in rat adjuvant-induced arthritis as well as in mouse experimental autoimmune encephalomyelitis models. Importantly, by sparing JAK1 function, PF-06651600 selectively targets γc cytokine pathways while preserving JAK1-dependent anti-inflammatory signaling such as the IL-10 suppressive functions following LPS treatment in macrophages and the suppression of TNFα and IL-1β production in IL-27-primed macrophages. Thus, JAK3-selective inhibition differentiates from pan-JAK or JAK1 inhibition in various immune cellular responses, which could potentially translate to advantageous clinical outcomes in inflammatory and autoimmune diseases.

Ion beam sputtering deposition (IBSD) is used to synthesize high quality few-layer hexagonal boron nitride (h-BN) on copper foils. Compared to the conventional chemical vapor deposition, the IBSD technique avoids the use of unconventional precursors and is much easier to control, which should be very useful for the large-scale production of h-BN in the future., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The STAT6 (signal transducer and activator of transcription 6) protein facilitates T-helper cell 2 (Th2) mediated responses that control IgE-mediated atopic diseases such as asthma. We have identified compounds that bind to STAT6 and inhibit STAT6 tyrosine phosphorylation induced by IL-4. In the bronchial epithelial cell line BEAS-2B, compound (R)-84 inhibits the secretion of eotaxin-3, a chemokine eliciting eosinophil infiltration. (R)-84 appears to prevent STAT6 from assuming the active dimer configuration by directly binding the protein and inhibiting tyrosine phosphorylation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: The venom of spiders may inspire new drugs to treat carcinoma. The aim of this study was to investigate the effect of P38 MAPK on tumor necrosis factor-related apoptosis of lung adenocarcinoma cell line by spider venom., Methods: Lung adenocarcinoma A549 cells were cultured in PRMI-1640 medium and the apoptosis rate was observed after treatment with spider venom with a flow cytometer. The expression of P38 MAPK protein in lung cancer cells was analyzed using Western blot., Results: After targeting spider venom intervention, the expression of P38 MAPK in the cells compared to the control group was significantly down-regulated. The anticancer potency of spider venom is associated with decreased expression of P38 MAPK of lung adenocarcinoma cancer cells., (© Tianjin Lung Cancer Institute and Blackwell Publishing Asia Pty. Ltd.)

We measured the levels of pro- and anti-inflammatory cytokines in the cerebrospinal fluid (CSF) of 24 patients with West syndrome to clarify whether inflammatory cytokines were involved in the pathophysiology of West syndrome. There was no significant elevation of any of the three pro-inflammatory cytokines, interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha, in patients with West syndrome as compared with those in controls. However, level of anti-inflammatory cytokine, IL-1 receptor antagonist was significantly decreased in the CSF of patients with West syndrome. Further study is needed to elucidate whether an immune system disturbance is involved in the pathophysiology of West syndrome.

Cytosolic phospholipase A(2) alpha (cPLA(2)alpha, type IVA phospholipase) acts at the membrane surface to release free arachidonic acid, which is metabolized into inflammatory mediators, including leukotrienes and prostaglandins. Thus, specific cPLA(2)alpha inhibitors are predicted to have antiinflammatory properties. However, a key criterion in the identification and development of such inhibitors is to distinguish between compounds that bind stoichiometrically to cPLA(2)alpha and nonspecific membrane perturbants. In the current study, we developed a method employing isothermal titration calorimetry (ITC) to characterize the binding of several distinct classes of cPLA(2)alpha inhibitors. Thermodynamic parameters and the binding constants were obtained following titration of the inhibitor to the protein at 30 degrees C and pH 7.4. The compounds tested bound cPLA(2)alpha with a 1:1 stoichiometry, and the dissociation constant K(d) of the inhibitors calculated from the ITC experiments correlated well with the IC(50) values obtained from enzymatic assays. Interestingly, binding was observed only in the presence of a micellar surface, even for soluble compounds. The site of binding of these inhibitors within cPLA(2)alpha was analyzed by testing for binding in the presence of methyl arachidonyl fluorophosphonate (MAFP), an irreversible active site inhibitor of cPLA(2)alpha. Lack of binding of inhibitors in the presence of MAFP suggested that the compounds tested bound specifically at or near the active site of the protein. Furthermore, the effect of various detergents on the binding of certain inhibitors to cPLA(2)alpha was also tested. The results are discussed with reference to thermodynamic parameters such as changes in enthalpy (DeltaH), entropy (DeltaS), and free energy (DeltaG). The data obtained from these studies provide not only structure-activity relationships for compounds but also important information regarding mechanism of binding. This is the first example of ITC used for studying inhibitors of enzymes with interfacial kinetics.

This study has examined the immunological localization of platelet-derived growth factor (PDGF)-A, PDGF-B, and PDGF receptor (PDGFR) alpha and beta to clarify their role in the progression of muscular dystrophy. Biopsied frozen muscles from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy (CMD) were analysed immunohistochemically using antibodies raised against PDGF-A, PDGF-B, and PDGFR alpha and beta. Muscles from two dystrophic mouse models (dy and mdx mice) were also immunostained with antibodies raised against PDGFR alpha and beta. In normal human control muscle, neuromuscular junctions and vessels were positively stained with antibodies against PDGF-A, PDGF-B, PDGFR alpha and PDGFR beta. In human dystrophic muscles, PDGF-A, PDGF-B, PDGFR alpha and PDGFR beta were strongly immunolocalized in regenerating muscle fibres and infiltrating macrophages. PDGFR alpha was also immunolocalized to the muscle fibre sarcolemma and necrotic fibres. The most significant finding in this study was a remarkable overexpression of PDGFR beta and, to a lesser extent, PDGFR alpha in the endomysium of DMD and CMD muscles. PDGFR was also overexpressed in the interstitium of muscles from dystrophic mice, particularly dy mice. Double immunolabelling revealed that activated interstitial fibroblasts were clearly positive for PDGFR alpha and beta. However, DMD and CMD muscles with advanced fibrosis showed very poor reactivity against PDGF and PDGFR. Those findings were confirmed by immunoblotting with PDGFR beta. These findings indicate that PDGF and its receptors are significantly involved in the active stage of tissue destruction and are associated with the initiation or promotion of muscle fibrosis. They also have roles in muscle fibre regeneration and signalling at neuromuscular junctions in both normal and diseased muscle., (Copyright 2003 John Wiley & Sons, Ltd.)

Objective: A unique model of hypertension developed in our laboratory shows that neonatal degeneration of capsaicin-sensitive sensory nerves renders a rat responsive to salt load with a significant rise in blood pressure. Considering that capsaicin impairs the micturition reflex, increased retention of urine in the bladder of capsaicin-treated rats may lead to nephropathy and therefore to an increase in blood pressure. The present study was designed to test the hypothesis that abnormalities in renal function and blood pressure in this model are independent of urine retention, and are reversible when a high-salt diet is withdrawn., Design and Methods: Newborn Wistar rats were given either 50 mg/kg capsaicin subcutaneously or vehicle on the first and second days of life. After weaning, one set of male rats was treated for 3 weeks with: capsaicin pretreatment plus high-sodium diet (4%, CAP-HS), capsaicin plus normal-sodium diet (0.5%, CAP-NS), control plus high-sodium diet (CON-HS), and control plus normal sodium diet (CON-NS). The other set of male rats was given the same treatment for 4 weeks except that the two high-salt-treated groups were switched to normal salt (CAP-HS-NS and CON-HS-NS) for the last week. Chronic bladder catheterization was carried out in all rats to maintain free flow of urine. Western blot was used for measurement of the capsaicin (vanilloid) receptor levels in dorsal root ganglia. Radioimmunoassay was used for measurement of plasma renin activity and plasma aldosterone levels., Results: Capsaicin (vanilloid) receptor contents in dorsal root ganglia were markedly decreased in all capsaicin-treated groups. Plasma renin activity and plasma aldosterone levels were higher in CAP-HS rats than in CON-HS rats, but were not statistically different between CAP-HS-NS and CON-HS-NS rats. Urine Na excretion but not urine volume was decreased and water intake increased in CAP-HS compared with CON-HS, but these parameters were not statistically different between CAP-HS-NS and CON-HS-NS rats. Although systolic blood pressure and mean arterial pressure were higher in CAP-HS and CAP-HS-NS rats than in CON-HS and CON-HS-NS rats, they were higher in CAP-HS than in CAP-HS-NS rats., Conclusion: Despite elimination of urine retention, sensory denervation impairs renal function and leads to an increase in blood pressure in response to high salt intake. The abnormalities in renal function and blood pressure in sensory denervated rats are reversible, at least in part, when high salt intake is withdrawn. These data support the hypothesis that sensory innervation counterbalances the pro-hypertensive systems and serves as a modulator to control salt sensitivity and cardiovascular function.