ABSTRACT
Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is protective against type 2 diabetes, independent of body weight. The mechanism underlying this dissociation remains unclear. Here, we report that impaired mitochondrial catabolism of branched-chain amino acids (BCAAs) in BAT, by deleting mitochondrial BCAA carriers (MBCs), caused systemic insulin resistance without affecting energy expenditure and body weight. Brown adipocytes catabolized BCAA in the mitochondria as nitrogen donors for the biosynthesis of non-essential amino acids and glutathione. Impaired mitochondrial BCAA-nitrogen flux in BAT resulted in increased oxidative stress, decreased hepatic insulin signaling, and decreased circulating BCAA-derived metabolites. A high-fat diet attenuated BCAA-nitrogen flux and metabolite synthesis in BAT, whereas cold-activated BAT enhanced the synthesis. This work uncovers a metabolite-mediated pathway through which BAT controls metabolic health beyond thermogenesis.
Subject(s)
Adipose Tissue, Brown , Amino Acids, Branched-Chain , Insulin Resistance , Mitochondria , Nitrogen , Thermogenesis , Adipose Tissue, Brown/metabolism , Animals , Amino Acids, Branched-Chain/metabolism , Mice , Nitrogen/metabolism , Mitochondria/metabolism , Male , Humans , Energy Metabolism , Mice, Inbred C57BL , Oxidative Stress , Insulin/metabolism , Diet, High-Fat , Adipocytes, Brown/metabolism , Signal TransductionABSTRACT
Propionic acidemia (PA), arising from PCCA or PCCB variants, manifests as life-threatening cardiomyopathy and arrhythmias, with unclear pathophysiology. In this work, propionyl-CoA metabolism in rodent hearts and human pluripotent stem cell-derived cardiomyocytes was investigated with stable isotope tracing analysis. Surprisingly, gut microbiome-derived propionate rather than the propiogenic amino acids (valine, isoleucine, threonine, and methionine) or odd-chain fatty acids was found to be the primary cardiac propionyl-CoA source. In a Pcca-/-(A138T) mouse model and PA patients, accumulated propionyl-CoA and diminished acyl-CoA synthetase short-chain family member 3 impede hepatic propionate disposal, elevating circulating propionate. Prolonged propionate exposure induced significant oxidative stress in PCCA knockdown HL-1 cells and the hearts of Pcca-/-(A138T) mice. Additionally, Pcca-/-(A138T) mice exhibited mild diastolic dysfunction after the propionate challenge. These findings suggest that elevated circulating propionate may cause oxidative damage and functional impairment in the hearts of patients with PA.
ABSTRACT
PURPOSE: The study aimed to explore the mechanisms of luteolin in acquired sensorineural hearing loss (SNHL) through network pharmacology, molecular docking, molecular dynamics simulation, and experimental verification. METHODS: First, the practices of network pharmacology were used to obtain the intersecting targets of luteolin and acquired SNHL, construct the PPI (Protein-Protein Interaction) network, conduct GO and KEGG enrichments, and establish luteolin-acquired SNHL-target-pathway network, aiming to gain the core targets and pathways. Then, the affinity between the core targets and luteolin was verified by molecular docking. Moreover, molecular dynamics (MD) simulation was applied to simulate the binding between targets and luteolin. Finally, with the HEI-OC1 cell line, some molecular biology techniques were adopted to verify the pharmacological actions of luteolin and the significance of the pathway from KEGG enrichment in luteolin-protecting auditory cell damage related to acquired SNHL. RESULTS: 14 intersecting targets were obtained, and the 10 core targets were further verified through molecular docking and MD simulation to get 5 core targets. The JAK/STAT was selected as the critical pathway through KEGG enrichment. Luteolin could dose-dependently alleviate auditory cell apoptosis by inhibiting the JAK/STAT pathway, confirmed by a series of experiments in vitro. CONCLUSION: This study manifested that luteolin could reduce acquired SNHL-related auditory cell apoptosis through the JAK/STAT pathway, which provided a new idea for acquired SNHL pharmacological treatment.
Subject(s)
Drugs, Chinese Herbal , Molecular Dynamics Simulation , Molecular Docking Simulation , Janus Kinases , Luteolin/pharmacology , Network Pharmacology , STAT Transcription Factors , Signal Transduction , ApoptosisABSTRACT
The solar light-responsive Fe-doped Co-based coordination polymer (Fe@Co-CP) photocatalyst was synthesized under mild conditions. [Co(4-padpe)(1,3-BDC)]n (Co-CP) was first constructed using mixed ligands through the hydrothermal method. Then, Fe was introduced into the Co-CP framework to achieve the enhanced photocatalytic activity. The optimal Fe@Co-CP-2 exhibited excellent catalytic degradation performance for norfloxacin and ciprofloxacin under sunlight irradiation without auxiliary oxidants, and the degradation rates were 91.25 and 92.66% in 120 min. These excellent photocatalytic properties were ascribed to the generation of the Fe-O bond, which not only enhanced the light absorption intensity but also accelerated the separation efficiency of electrons and holes, and hence significantly improved the photocatalytic property of the composites. Meanwhile, Fe@Co-CP-2 displayed excellent stability and reusability. In addition, the degradation pathways and intermediates of antibiotic molecules were effectively analyzed. The free radical scavenging experiment and ESR results confirmed that â¢OH, â¢O2-, and h+ active species were involved in the catalytic degradation reaction; the corresponding mechanisms were deeply investigated. This study provides a fresh approach for constructing Fe-doped Co-CP-based composite materials as photocatalysts for degradation of antibiotic contaminants.
Subject(s)
Ciprofloxacin , Norfloxacin , Norfloxacin/chemistry , Norfloxacin/radiation effects , Anti-Bacterial Agents/chemistry , Light , CatalysisABSTRACT
To study the heavy metal accumulation and its impact on insect exterior and chromosome morphology, and reveal the molecular mechanism of insects adapting to long-term heavy metal compound pollution habitats, this study, in the Diaojiang river basin, which has been polluted by heavy metals(HMs) for nearly a thousand years, two Eucriotettix oculatus populations was collected from mining and non-mining areas. It was found that the contents of 7 heavy metals (As, Cd, Pb, Zn, Cu, Sn, Sb) in E. oculatus of the mining area were higher than that in the non-mining 1-11 times. The analysis of morphology shows that the external morphology, the hind wing type and the chromosomal morphology of E. oculatus are significant differences between the two populations. Based on the heavy metal accumulationï¼morphological change, and stable population density, it is inferred that the mining area population has been affected by heavy metals and has adapted to the environment of heavy metals pollution. Then, by analyzing the transcriptome of the two populations, it was found that the digestion, immunity, excretion, endocrine, nerve, circulation, reproductive and other systems and lysosomes, endoplasmic reticulum and other cell structure-related gene expression were suppressed. This shows that the functions of the above-mentioned related systems of E. oculatus are inhibited by heavy metal stress. However, it has also been found that through the significant up-regulation of genes related to the above system, such as ATP2B, pepsin A, ubiquitin, AQP1, ACOX, ATPeV0A, SEC61A, CANX, ALDH7A1, DLD, aceE, Hsp40, and catalase, etc., and the down-regulation of MAPK signalling pathway genes, can enhanced nutrient absorption, improve energy metabolism, repair damaged cells and degrade abnormal proteins, maintain the stability of cells and systems, and resist heavy metal damage so that E. oculatus can adapt to the environment of heavy metal pollution for a long time.
Subject(s)
Grasshoppers , Metals, Heavy , Water Pollutants, Chemical , Animals , Metals, Heavy/toxicity , Water Pollutants, Chemical/toxicity , Grasshoppers/drug effects , Grasshoppers/anatomy & histology , Environmental Monitoring/methods , Mining , China , Adaptation, Physiological/drug effects , Transcriptome/drug effects , Rivers/chemistryABSTRACT
BACKGROUND AND PURPOSE: To evaluate the effectiveness and safety of intravenous tirofiban before endovascular thrombectomy in subgroups of acute ischemic stroke patients with different degrees of leukoaraiosis (LA). METHODS: Patients of the RESCUE BT trial whose LA grade could be assessed were included. Eligible patients were dichotomized into two strata according to the van Swieten scale (VSS) score, absent-to-moderate LA (VSS score <3) and severe LA (VSS score ≥3). Furthermore, patients were divided into tirofiban and placebo groups in each stratum. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcome was radiological intracranial hemorrhage within 48 h. RESULTS: 861 patients were included, 439 patients with absent-to-moderate LA and 422 patients with severe LA. There were no significant differences in 90-day mRS score between the tirofiban and placebo groups in either stratum (absent-to-moderate LA: adjusted OR 0.92 (95%CI, 0.66-1.28), P = 0.62; severe LA: adjusted OR 0.99 (95% CI, 0.69-1.42), P = 0.96). In the severe LA stratum, the occurrence of radiologic intracranial hemorrhage was greater in the tirofiban group compared to the placebo group. (35.7% vs 26.4%; adjusted OR, 1.72 (95% CI, 1.12-2.66); P = 0.014). However, no difference was observed in the absent-to-moderate LA stratum (33.2% vs 29.3%; adjusted OR, 1.15 (95% CI, 0.76-1.75); P = 0.51). CONCLUSION: There was no significant difference in disability severity at 90 days when treating AIS patients using intravenous tirofiban before endovascular therapy, in either absent-to-moderate or severe LA strata. It should be noted that intravenous tirofiban before endovascular therapy increases the incidence of radiologic intracranial hemorrhage in patients with severe LA.
ABSTRACT
Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen and glycosamino-glycan in vitro. This study investigated the peptide mixture's pain relief and chondroprotective effect in a rat model of collagenase-induced osteoarthritis. Thirty-six adult male Sprague-Dawley rats were divided into three groups: control (saline), positive control (hyaluronic acid), and ex-perimental (peptides). Intra-articular collagenase injections were administered on days 1 and 4 to induce osteoarthritis in the left knees of the rats. Two injections of saline, hyaluronic acid, or the peptides were injected into the same knees of each corresponding group at the beginning of week one and two, respectively. Joint swelling, arthritic pain, and histopathological changes were evaluated. Injection of the peptides significantly reduced arthritic pain compared to the control group, as evidenced by the closer-to-normal weight-bearing and paw withdrawal threshold test results. Histological analyses showed reduced cartilage matrix loss and improved total cartilage degeneration score in the experimental versus the control group. Our findings suggest that intra-articular injection of synthetic deer antler peptides is a promising treatment for osteoarthritis.
Subject(s)
Antlers , Deer , Disease Models, Animal , Osteoarthritis, Knee , Peptides , Rats, Sprague-Dawley , Animals , Injections, Intra-Articular , Antlers/chemistry , Osteoarthritis, Knee/drug therapy , Osteoarthritis, Knee/pathology , Osteoarthritis, Knee/chemically induced , Male , Rats , Peptides/administration & dosage , Peptides/pharmacology , Peptides/therapeutic use , Hyaluronic Acid/administration & dosage , Cartilage, Articular/drug effects , Cartilage, Articular/pathology , Cartilage, Articular/metabolism , CollagenasesABSTRACT
BACKGROUND: Family-centered empowerment programs have been widely used in the pediatric field. Therefore, the current study investigated the effectiveness of family empowerment programs on caregiving ability and adverse mood among caregivers of children with acute leukemia. OBJECTIVE: To evaluate the effect of a family empowerment program on the caregiving ability and adverse mood of caregivers of children with acute leukemia. METHODS: Sixty-eight children with acute leukemia and their family caregivers admitted to our hospital were selected for the study. The control group received routine care during hospitalization, and the family empowerment program was implemented in the intervention group to compare the changes in caregiving capacity (FCTI), illness uncertainty (PPUS) and anxiety(SAS)of the caregivers of the two groups. RESULTS: After 8 weeks of intervention, the FCTI score of the intervention group was significantly lower than that of the control group (P < 0.001), and the difference between the scores before and after the intervention was statistically significant (P < 0.001); the PPUS score of the intervention group was significantly lower than that of the control group (P < 0.05), and the difference between the scores before and after the intervention was statistically significant (P < 0.001); the SAS score of the intervention group was lower than that of the control group after intervention(P < 0.05), and the score difference before and after intervention was statistically significant (P < 0.001). CONCLUSION: Family empowerment program is beneficial in improving caregiving capacity and reducing disease uncertainty and anxiety among caregivers of children with acute leukemia. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300073476 2023-07-12 Retrospectively registered.
ABSTRACT
Biosynthesis of atypical angucyclines involves unique oxidative B-ring cleavage and rearrangement reactions, which are catalyzed by AlpJ-family oxygenases, including AlpJ, JadG, and GilOII. Prior investigations established the essential requirement for FADH2/FMNH2 as cofactors when utilizing the quinone intermediate dehydrorabelomycin as a substrate. In this study, we unveil a previously unrecognized facet of these enzymes as cofactor-independent oxygenases when employing the hydroquinone intermediate CR1 as a substrate. The enzymes autonomously drive oxidative ring cleavage and rearrangement reactions of CR1, yielding products identical to those observed in cofactor-dependent reactions of AlpJ-family oxygenases. Furthermore, the AlpJ- and JadG-catalyzed reactions of CR1 could be quenched by superoxide dismutase, supporting a catalytic mechanism wherein the substrate CR1 reductively activates molecular oxygen, generating a substrate radical and the superoxide anion O2 â¢-. Our findings illuminate a substrate-controlled catalytic mechanism of AlpJ-family oxygenases, expanding the realm of cofactor-independent oxygenases. Notably, AlpJ-family oxygenases stand as a pioneering example of enzymes capable of catalyzing oxidative reactions in either an FADH2/FMNH2-dependent or cofactor-independent manner.
ABSTRACT
Text classification is a central part of natural language processing, with important applications in understanding the knowledge behind biomedical texts including electronic health records (EHR). In this article, we propose a novel heterogeneous graph convolutional network method for classifying EHR texts. Our method, called EHR-HGCN, is able to combine context-sensitive word and sentence embeddings with structural sentence-level and word-level relation information to perform text classification. EHR-HGCN reframes EHR text classification as a graph classification task to better capture structural information about the document using a heterogeneous graph. To mine contextual information from a document, EHR-HGCN first applies a bidirectional recurrent neural network (BiRNN) on word embeddings obtained via Global Vectors for word representation (GloVe) to obtain context-sensitive word-level and sentence-level embeddings. To mine structural relationships from the document, EHR-HGCN then constructs a heterogeneous graph over the word and sentence embeddings, where sentence-word and word-word relationships are represented by graph edges. Finally, a heterogeneous graph convolutional neural network is used to classify documents by their graph representation. We evaluate EHR-HGCN on a variety of standard text classification benchmarks and find that EHR-HGCN has higher accuracy and F1-score than other representative machine learning and deep learning methods. We also apply EHR-HGCN to the MedLit benchmark and find it performs with high accuracy and F1-score on the task of section classification in EHR texts. Our ablation experiments show that the heterogeneous graph construction and heterogeneous graph convolutional network are critical to the performance of EHR-HGCN.
Subject(s)
Electronic Health Records , Neural Networks, Computer , Humans , Machine Learning , Natural Language ProcessingABSTRACT
Objective: To explore the effect of NaOH on the surface morphology of three-dimensional (3D) printed poly- L-lactic acid (PLLA) mesh scaffolds. Methods: The 3D printed PLLA mesh scaffolds were prepared by fused deposition molding technology, then the scaffold surfaces were etched with the NaOH solution. The concentrations of NaOH solution were 0.01, 0.1, 0.5, 1.0, and 3.0 mol/L, and the treatment time was 1, 3, 6, 9, and 12 hours, respectively. There were a total of 25 concentration and time combinations. After treatment, the microstructure, energy spectrum, roughness, hydrophilicity, compressive strength, as well as cell adhesion and proliferation of the scaffolds were observed. The untreated scaffolds were used as a normal control. Results: 3D printed PLLA mesh scaffolds were successfully prepared by using fused deposition molding technology. After NaOH etching treatment, a rough or micro porous structure was constructed on the surface of the scaffold, and with the increase of NaOH concentration and treatment time, the size and density of the pores increased. The characterization of the scaffolds by energy dispersive spectroscopy showed that the crystal contains two elements, Na and O. The surface roughness of NaOH treated scaffolds significantly increased ( P<0.05) and the contact angle significantly decreased ( P<0.05) compared to untreated scaffolds. There was no significant difference in compressive strength between the untreated scaffolds and treated scaffolds under conditions of 0.1 mol/L/12 h and 1.0 mol/L/3 h ( P>0.05), while the compression strength of the other treated scaffolds were significantly lower than that of the untreated scaffolds ( P<0.05). After co-culturing the cells with the scaffold, NaOH treatment resulted in an increase in the number of cells on the surface of the scaffold and the spreading area of individual cells, and more synapses extending from adherent cells. Conclusion: NaOH treatment is beneficial for increasing the surface hydrophilicity and cell adhesion of 3D printed PLLA mesh scaffolds.
Subject(s)
Surgical Mesh , Tissue Scaffolds , Tissue Scaffolds/chemistry , Sodium Hydroxide , Cells, Cultured , Polyesters/chemistry , Lactic Acid , Printing, Three-Dimensional , Tissue EngineeringABSTRACT
BACKGROUND: Traditional biochemical screening for neonatal inherited metabolic diseases has high false-positive rates and low positive predictive values, which are not conducive to early diagnosis and increase parents' anxiety. This study analysed the relationship between gene variant carriers and their biochemical indicators in traditional biochemical screening, aiming to find explanations for false positives in newborns. RESULTS: This retrospective study included 962 newborns. Newborns underwent traditional biochemical screening at birth using blood staining and genomic sequencing of their stored blood staining using the NeoSeq Pro panel, which was able to detect 154 pathogenic genes and 86 diseases. A total of 632 newborns were carriers of gene variants. 56% of congenital hypothyroidism carriers had higher thyroid-stimulating hormone levels than normal newborns. Abnormal biochemical indices were detected in 71% of carriers of organic acid metabolic diseases, 69% of carriers of amino acid metabolic diseases, and 85% of carriers of fatty acid ß oxidation disorders. In carriers associated with organic acid metabolic diseases, the propionylcarnitine (C3), C3/acetylcarnitine (C2), and methylmalonylcarnitine (C4DC) + 3-hydroxyisovalerylcarnitine (C5OH) levels were higher than those in non-carriers (C3: 4.12 vs. 1.66 µmol/L; C3/C2: 0.15 vs. 0.09; C4DC + C5OH: 0.22 vs. 0.19 µmol/L). In carriers associated with amino acid metabolic diseases, phenylalanine levels were higher than those in non-carriers (68.00 vs. 52.05 µmol/L). For carriers of fatty acid ß oxidation disorders, butyrylcarnitine levels were higher than those in non-carriers (0.31 vs. 0.21 µmol/L), while the free carnitine levels were lower than those in non-carriers (14.65 vs. 21.87 µmol/L). There was a higher occurrence of carriers among newborns who received false-positive results for amino acid metabolic diseases compared to those who received negative results (15.52% vs. 6.71%). Similarly, there was a higher occurrence of carriers among newborns who received false-positive results for fatty acid ß oxidation disorders compared to those who received negative results (28.30% vs. 7.29%). CONCLUSIONS: This study showed that the carriers comprised a large number of newborns. Carriers had abnormal biochemical indicators compared with non-carriers, which could explain the false-positive rate for newborns using traditional newborn biochemical screening, especially in amino acid metabolic and fatty acid ß oxidation disorders.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Tandem Mass Spectrometry , Infant, Newborn , Humans , Retrospective Studies , Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acids , Neonatal Screening/methods , Fatty AcidsABSTRACT
A novel fluorescent "off" probe R-ß-D-1 containing a 1,2,3-triazole moiety was obtained by the Click reaction with azidoglucose using H8-BINOL as a substrate, and the structure was characterized by 1H NMR and 13C NMR and ESI-MS analysis. The fluorescence properties of R-ß-D-1 in methanol were investigated, and it was found that R-ß-D-1 could be selectively fluorescently quenched by Bi3+ in the recognition of 19 metal ions and basic cations. The recognition process of Bi3+ by R-ß-D-1 was also investigated by fluorescence spectroscopy, SEM, AFM, etc. The complex pattern of R-ß-D-1 with Bi3+ was determined by Job's curve as 1 + 1, and the binding constant Ka of R-ß-D-1 and Bi3+ was valued by the Benesi-Hildebrand equation as 1.01 × 104 M-1, indicating that the binding force of R-ß-D-1 and Bi3+ was medium. The lowest detection limit (LOD) of the self-assembled H8-BINOL derivative for Bi3+ was up to 0.065 µM. The mechanism for the recognition of Bi3+ by the sensor R-ß-D-1 may be the intramolecular charge transfer effect (ICT), which was attributed to the fact that the N-3 of the triazole readily serves as an electron acceptor while the incorporation of Bi3+ serves as an electron donor, and the two readily undergo coordination leading to the quenching of fluorescence. The recognition mechanism and recognition site could be verified by DFT calculation and CDD (Charge Density Difference).
ABSTRACT
Golden cuttlefish play a significant role in the food web of the East and Yellow Seas and are a valuable fishery resource in Chinese coastal waters. Samples of golden cuttlefish were obtained from the northern East China Sea between September 2021 and March 2022, and stable isotope methods were utilized in this study to examine the variations in the forage ecology of golden cuttlefish. Our findings reveal dynamic shifts in carbon and nitrogen stable isotopes (δ13C and δ15N), highlighting intricate foraging strategies tailored to growth and environmental changes. A notable trend emerges: an initial growth-linked rise in δ13C and δ15N enrichment, followed by seasonal fluctuations mirroring seasonal food availability. The ontogenetic niche evolution displays striking habitat shifts and trophic level escalation in small mantle length stages, transitioning to niche overlap and subtle trophic shifts later on. Sex-specific differences emerge, with females occupying higher trophic levels than males in most samples. This comprehensive study underscores the complexity and adaptability of golden cuttlefish feeding ecology, inviting further inquiry into their intricate relationships within the marine ecosystem.
ABSTRACT
The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a's diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.
Subject(s)
Circadian Clocks , Drosophila Proteins , Animals , Circadian Rhythm/physiology , Temperature , Sleep/physiology , Drosophila , Circadian Clocks/physiology , Drosophila Proteins/genetics , Drosophila melanogaster/physiologyABSTRACT
Controlled aggregation is of great significance in designing nanodevices with high electrochemical performance. In this study, an in situ aggregation strategy with cyclodextrin polymer (CDP) was employed to prepare polyaniline (PANI)/MXene (MX) composites. MXene served as a two-dimensional structure template. Due to supramolecular interactions, CDP could be controllably modified with PANI layers, effectively preventing the self-polymerization of PANI. As a result, this integration facilitated a more uniform growth of PANI on MXene and further improved the capacitance performance of CDP-MX/PA. In a three-electrode system, the specific capacitance of MX/PA at 1 A g-1 was 460.8 F g-1, which increased to 523.8 F g-1 after CDP-induced growth. CDP-MX/PA exhibited a high energy density of 27.7 W h kg-1 at a power density of 700 W kg-1. This suggests that the synthetic strategy employed in this study holds promise in providing robust support for the preparation of high-performance energy-storage device.
ABSTRACT
ABSTRACT: Although the secondary somatosensory cortex (SII) is known to be involved in pain perception, its role in pain modulation and neuropathic pain is yet unknown. In this study, we found that glutamatergic neurons in deep layers of the SII (SII Glu ) responded to bilateral sensory inputs by changing their firing with most being inhibited by contralateral noxious stimulation. Optical inhibition and activation of unilateral SII Glu reduced and enhanced bilateral nociceptive sensitivity, respectively, without affecting mood status. Tracing experiments revealed that SII Glu sent dense monosynaptic projections to the posterolateral nucleus (VPL) and the posterior nucleus (Po) of the thalamus. Optical inhibition and activation of projection terminals of SII Glu in the unilateral VPL and Po inhibited and facilitated pain on the contralateral side, respectively. After partial sciatic nerve ligation, SII Glu became hyperactive as evidenced by higher frequency of spontaneous firing, but the response patterns to peripheral stimulation remained. Optical inhibition of SII Glu alleviated not only bilateral mechanical allodynia and thermal hyperalgesia but also the negative affect associated with spontaneous pain. Inhibition of SII Glu terminals in the VPL and Po also relieved neuropathic pain. This study revealed that SII Glu and the circuits to the VPL and Po constitute a part of the endogenous pain modulatory network. These corticothalamic circuits became hyperactive after peripheral nerve injury, hence contributes to neuropathic pain. These results justify proper inhibition of SII Glu and associated neural circuits as a potential clinical strategy for neuropathic pain treatment.
Subject(s)
Neuralgia , Somatosensory Cortex , Rats , Animals , Rats, Sprague-Dawley , Thalamus , HyperalgesiaABSTRACT
Renewable, green, and safe natural biopolymer-derived materials are highly desired for the purification of pollutants, but significantly improving their performance without the introduction of additional harmful chemicals remains a huge challenge. Based on the concept of "structure optimization design", environment-friendly composite beads (named SA/PASP/RE) with excellent adsorption performance and recyclability were rationally constructed through a green ionic crosslinking route, using the completely green biopolymer sodium alginate (SA), sodium salt of polyaspartic acid (PASP), and the natural nanoclay rectorite (RE) as starting materials. The nano-layered RE was embedded in the polymer matrix to prevent the polymer chain from becoming over-entangled so that more adsorption sites inside the polymer network were exposed, which effectively improved the mass transfer efficiency of the adsorbent and the removal rate of contaminants. The composite beads embedded with 0.6% RE showed high adsorption capacities of 211.78, 197.13, and 195.69 mg/g for Pb(II) and 643.00, 577.80, and 567.10 mg/g for methylene blue (MB) in Yellow River water, Yangtze River water, and tap water, respectively. And the beads embedded with 43% RE could efficiently adsorb Pb(II) and MB with high capacities of 187.78 mg/g and 586.46 mg/g, respectively. This study provides a new route to design and develop a green, cost-effective, and efficient adsorbent for the decontamination of wastewater.
ABSTRACT
Immobilizing metal nanoparticles on a support is crucial for catalysts' stability and spatial distribution. MXenes are promising substrates for in situ growth engineering of various electrocatalysts owing to their merits. A stronger binding capacity can be achieved between the in situ-fabricated catalysts and MXenes compared to a common physical combination. Thus, synergistically utilizing morphology modulation, composition optimization, and the interfacial interaction between metal catalysts and supports will maximize the electrocatalytic activity. However, most reported in situ-formed catalysts on MXenes result in solid 0D nanoparticles and in situ growth of nanoalloy catalysts on MXenes with a precisely controlled morphology is still lacking. Herein, nanodendritic PdNi alloys are in situ grown on nitrogen-doped V2CTx, serving as efficient electrocatalysts toward the hydrogen evolution reaction (HER). Thanks to the synergistic effect of the unique nanodendritic structure of PdNi, the merits of N-TBA-V2CTx nanosheets, and the strong metal-support interaction between the PdNi and the N-TBA-V2CTx support, the in situ-formed Pd58Ni42/N-TBA-V2CTx electrocatalyst shows excellent HER performance with an ultralow overpotential of 44.1 mV to achieve 10 mA cm-2 and a lowest Tafel slope of 39.4 mV dec-1, which outperforms Pd58Ni42/TBA-V2CTx, Pd58Ni42, and Pd/C. Remarkably, the Pd58Ni42/N-TBA-V2CTx catalyst can maintain 92.3% of its initial activity even after 50 h of continuous operation.