In-situ growth of metal-organic frameworks on cellulose nanofiber aerogels for rapid adsorption of heterocyclic aromatic amines.

Heterocyclic aromatic amines (HAAs) are the main carcinogens produced during thermal processing of protein-rich foods. In this paper, a composite aerogel (TOCNFCa) with a stabilized dual-network structure was prepared via a template for the in-situ synthesis of UiO-66 on cellulose for the adsorption of HAAs in food. The dual-network structure of TOCNFCa provides the composite aerogel with excellent wet strength, maintaining excellent compressive properties. With the in-situ grown UiO-66 content up to 71.89 wt%, the hierarchical porosity endowed TOCNFCa@UiO-66 with the ability to rapidly adsorb HAAs molecules with high capacity (1.44-5.82 µmol/g). Based on excellent thermal stability, adsorption capacity and anti-interference, TOCNFCa@UiO-66 achieved satisfactory recoveries of HAAs in the boiled marinade, which is faster and more economical than the conventional SPE method. Moreover, TOCNFCa@UiO-66 could maintain 84.55 % of the initial adsorption capacity after 5 times of reuse.

Defective UiO-66/cellulose nanocomposite aerogel for the adsorption of heterocyclic aromatic amines.

Heterocyclic aromatic amines (HAAs), arising as chemical derivatives during the high-temperature culinary treatment of proteinaceous comestibles, exhibit notable carcinogenic potential. In this paper, a composite aerogel (AGD-UiO-66) with high-capacity and fast adsorption of HAAs was made with anchoring defective UiO-66 (D-UiO-66) mediated by lauric acid on the backbone of cellulose nanofibers (CNF). AGD-UiO-66 with hierarchical porosity reduced the mass transfer efficiency for the adsorption of HAAs and achieved high adsorption amount (0.84-1.05 µmol/g) and fast adsorption (15 min). The isothermal adsorption model demonstrated that AGD-UiO-66 belonged to a multilayer adsorption mechanism for HAAs. Furthermore, AGD-UiO-66 was successfully used to adsorb 12 HAAs in different food (roasted beef, roasted pork, roasted salmon and marinade) with high recoveries of 94.65%-104.43%. The intrinsic potential of AGD-UiO-66 demonstrated that it could be widely applicable to the adsorption of HAAs in foods.

METTL14-mediated m6A epitranscriptomic modification contributes to chemotherapy-induced neuropathic pain by stabilizing GluN2A expression via IGF2BP2.

Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether N6-methyladenosine (m6A) specifically modified by methyltransferase-like 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-d-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP). Using dot blotting, immunofluorescence, gain/loss-of-function, and behavioral assays, we found that m6A levels were upregulated in L4-L6 DRG neurons in CINP in a DBP/METTL14-dependent manner, which was also confirmed in human DRGs. Blocking METTL14 reduced m6A methylation and attenuated pain hypersensitivity. Mechanistically, METTL14-mediated m6A modification facilitated the synaptic plasticity of DRG neurons by enhancing the GluN2A subunit of NMDAR, and inhibiting METTL14 blocked this effect. In contrast, overexpression of METTL14 upregulated m6A modifications, enhanced presynaptic NMDAR activity in DRG neurons, and facilitated pain sensation. Our findings reveal a previously unrecognized mechanism of METTL14-mediated m6A modification in DRG neurons to maintain neuropathic pain. Targeting these molecules may provide a new strategy for pain treatment.

Chronic Intermittent Hypobaric Hypoxia Reduces Hypothalamic N-Methyl-d-Aspartate Receptor Activity and Sympathetic Outflow in Spontaneously Hypertensive Rats.

Guo, Xinqi, Hongyu Ma, Ziye Cui, Qiyue Zhao, Ying Zhang, Lu Jia, Liping Zhang, Hui Guo, Xiangjian Zhang, Yi Zhang, Yue Guan, and Huijie Ma. Chronic intermittent hypobaric hypoxia reduces hypothalamic N-Methyl-d-Aspartate Receptor activity and sympathetic outflow in spontaneously hypertensive rats. High Alt Med Biol. 25:77-88, 2024. Objective: This study aims to determine the role of hypothalamic renin-angiotensin system (RAS) in the antihypertensive effect of chronic intermittent hypobaric hypoxia (CIHH). Methods: Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) received 35 days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h/day. The levels of RAS, blood pressure, and N-methyl-d-aspartate receptor (NMDAR) activities of hypothalamic paraventricular nucleus (PVN) presympathetic neurons from each group of rats were determined. Results: The systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure (MAP) of SHRs significantly decreased from the third week of CIHH treatment. This blood pressure reduction effect could be maintained for at least 2 weeks after stopping the CIHH treatment. CIHH treatment also attenuated the decrease in MAP and renal sympathetic nerve activity induced by hexamethonium administration in SHRs, but not in WKY rats. Furthermore, CIHH reversed the increase in serum angiotensin (Ang)II concentration and the expression of PVN angiotensin-converting enzyme (ACE) and AngII type 1 (AT1) receptors, as well as the decrease in serum Ang1-7 concentration and the expression of PVN ACE2 and Mas receptors in SHRs. In addition, the administration of CIHH resulted in a reduction in the frequency of miniature excitatory postsynaptic currents and amplitude of NMDAR current in PVN presympathetic neurons of SHRs, which means that CIHH decreased the pre- and postsynaptic NMDAR activity of PVN presympathetic neurons in SHRs. However, pretreatment with A779 (a Mas receptor blocker) or AngII abrogated the above effects. Meanwhile, Ang1-7 pretreatment mimicked the CIHH effect on pre- and postsynaptic NMDAR activity of presympathetic neurons in SHRs. Conclusions: Our data indicate that CIHH reduces pre- and postsynaptic NMDAR activity of PVN presympathetic neurons, sympathetic outflow, and blood pressure by decreasing the activity of the ACE/AngII/AT1 axis and increasing the activity of ACE2/Ang1-7/Mas axis in the hypothalamus in hypertension.

Rapid and large-capacity adsorption of heterocyclic aromatic amines on heat resistant two-dimensional metal organic layer/cellulose nanofiber aerogels constructed by a thawing cross-linking strategy.

Composite aerogels, formed by the combination of nanoscale polymers and highly efficient adsorbents, offer the potential to deploy adsorbent distinct separation properties into a processable matrix. This paper presents a method for the fabrication of low energy bio-aerogels with high ductility, excellent wet strength and favorable heat resistance, based on cellulose nanofibers (CNFs) bound by calcium carbonate particles (CaCO3) via a simple process of ice induction, cross-linking during freezing and freeze-drying. Due to induced defects, two-dimensional metal-organic layers (MOLs) were rich in mesoporous structure and embedded in the aerogel (AGCa-MOL), which exhibited a powerful adsorption capacity. AGCa-MOL could take full advantage of their hierarchical pores and available surface area to obtain high adsorption capacity (0.694-5.470 µmol/g) and rapid adsorption kinetics (5 min) for 14 heterocyclic aromatic amines (HAAs). Moreover, the CaCO3 particles and MOLs gave the AGCa-MOL excellent thermal stability, so that it could maintain excellent adsorption capacity at a high temperature (100 °C) and be applied as an adsorbent to remove HAAs in the boiling marinade. The intrinsic potential of composite aerogels was revealed due to the synergistic properties of the various components in the composite aerogel.

Unveiling the Quantitative Relationships between Electron Distribution and Steric Hindrance of Organic Amines and Their Reaction Rates with Carbonyl Sulfur: A Theoretical Calculation Investigation.

The removal of carbonyl sulfide (COS) commonly contained in natural gas is of great significance but still very challenging via a widely employed absorption process due to its low reactivity and solubility in various commercial solvents. Artificial intelligence (AI) is playing an increasingly important role in the exploration of desulfurization solvents. However, practically feasible AI models still lack a thorough understanding of the reaction mechanisms. Machine learning (ML) models established on chemical mechanisms exhibit enhanced chemical interpretability and prediction performance. In this study, we constructed a series of solvent molecules with varying functional groups, including linear aliphatic amines, cyclic aliphatic amines, and aromatic amines and proposed a three-step reaction pathway to dissect the effects of charge and steric hindrance of different substituents on their reaction rates with COS. Chemical descriptors, based on electrostatic potential (ESP), average local ionization energy (ALIE) theory, Hirshfeld charges, and Fukui functions, were used to correlate and predict the electrophilic reactivity of amine groups with COS. Substituents influence the reaction rate by changing the attraction interaction of amine groups to COS molecules and the electron rearrangement in the electrophilic reaction. Furthermore, they have more pronounced steric effects on the reaction rate in the linear amines. The descriptors N_ALIE and q(N) were found to be crucial in predicting the reactivity of amine groups with COS. Present study provides a comprehensive understanding of the reaction mechanisms of COS with amine compounds, offers specific chemical principles for the development of chemistry-driven ML models, sheds light on other types of electrophilic reactions occurring on amine and phosphine groups, and guides the development of chemical solvents in gas absorption processes.

Polydatin improves vascular endothelial function by maintaining mitochondrial homeostasis under high glucose conditions.

Previous studies have shown that polydatin (Poly) confer cardioprotective effects. However, its underlying mechanisms remain elusive. This study showed that Poly (10 µM) treatment reversed the high glucose (HG)-induced decrease in acetylcholine-elicited vasodilation in aortas. Poly also improved the acetylcholine-induced vasodilation of aortic vessels isolated from diabetic rats. Meanwhile, Poly ameliorated the morphological damage of the thoracic aorta and improved the viability of HUVECs under HG conditions. Furthermore, analysis of the vasoprotective effect of Poly under HG conditions by transmission electron microscopy, Western blotting, and qPCR revealed that Poly improved endothelial pyroptosis through the NLRP3/Caspase/1-IL-1ß pathway, enhanced dynamin-related protein 1-mediated mitochondrial fission, and increased the mitochondrial membrane potential under HG conditions. In conclusion, Poly restored acetylcholine-induced vasodilation impaired by HG incubation, which was associated with reduced oxidation, inflammation, and pyroptosis, the recovery of the mitochondrial membrane potential and maintenance of mitochondrial dynamic homeostasis of endothelial cells in the aortas.

Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats.

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.

Black Phosphorus/Ferroelectric P(VDF-TrFE) Field-Effect Transistors with High Mobility for Energy-Efficient Artificial Synapse in High-Accuracy Neuromorphic Computing.

The neuromorphic system is an attractive platform for next-generation computing with low power and fast speed to emulate knowledge-based learning. Here, we design ferroelectric-tuned synaptic transistors by integrating 2D black phosphorus (BP) with a flexible ferroelectric copolymer poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)). Through nonvolatile ferroelectric polarization, the P(VDF-TrFE)/BP synaptic transistors show a high mobility value of 900 cm2 V-1 s-1 with a 103 on/off current ratio and can operate with low energy consumption down to the femtojoule level (∼40 fJ). Reliable and programmable synaptic behaviors have been demonstrated, including paired-pulse facilitation, long-term depression, and potentiation. The biological memory consolidation process is emulated through ferroelectric gate-sensitive neuromorphic behaviors. Inspiringly, the artificial neural network is simulated for handwritten digit recognition, achieving a high recognition accuracy of 93.6%. These findings highlight the prospects of 2D ferroelectric field-effect transistors as ideal building blocks for high-performance neuromorphic networks.

Corticotropin-releasing factor potentiates glutamatergic input and excitability of presympathetic neurons in the hypothalamus in spontaneously hypertensive rats.

Hyperactivity of presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) plays a key role in generating excess sympathetic output in hypertension. However, the mechanisms driving hyperactivity of PVN presympathetic neurons in hypertension are unclear. In this study, we determined the role of corticotropin-releasing factor (CRF) in the PVN in augmented glutamatergic input, neuronal excitability and sympathetic outflow in hypertension. The number of CRF or c-Fos immunoreactive neurons and CRF/c-Fos double-labeled neurons in the PVN was significantly greater in spontaneously hypertensive rats (SHRs) than in normotensive Wistar-Kyoto (WKY) rats. Blocking glutamatergic input reduced the CRF-potentiated excitability of spinally projecting PVN neurons. Furthermore, CRF knockdown via Crispr/Cas9 in the PVN decreased the frequencies of spontaneous firing and miniature excitatory postsynaptic currents (mEPSCs) in spinally projecting PVN neurons in SHRs. In addition, the mRNA and protein levels of CRFR1, but not CRFR2, in the PVN were significantly higher in SHRs than in WKY rats. Blocking CRFR1 with NBI-35965, but not blocking CRFR2 with Antisauvagine-30, reduced the frequencies of spontaneous firing and mEPSCs of spinally projecting PVN neurons in SHRs. Also, microinjection of NBI-35965 into the PVN significantly reduced arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in anesthetized SHRs, but not in WKY rats. However, microinjection of Antisauvagine-30 into the PVN had no effect on ABP or RSNA in WKY rats and SHRs. Our findings suggest that endogenous CRF in the PVN potentiates glutamatergic input and firing activity of PVN presympathetic neurons via CRFR1, resulting in augmented sympathetic outflow in hypertension.

Hierarchical Porous Nanocellulose Aerogels Loaded with Metal-Organic Framework Particles for the Adsorption Application of Heterocyclic Aromatic Amines.

This work overcomes the long-standing challenge of cumbersome pretreatment methods in the detection of heterocyclic aromatic amines (HAAs). A UiO-66/nanocellulose composite aerogel (CMC-CNC-UiO-66) with layered pores and low density prepared by a self-cross-linking method is applied as a simple and rapid adsorbent for capturing 14 HAAs via strong electrostatic interactions, van der Waals force, and the steric effect. The adsorption capacity of CMC-CNC-UiO-66 to 14 HAAs reached 98.00-188.00 nmol/mg at equilibrium within 10 min. The adsorption and desorption abilities of CMC-CNC-UiO-66 were retained with values of 93.36 and 97.34% after two cycles. In the meantime, the kinetics study demonstrated the chemisorption between HAA molecules and CMC-CNC-UiO-66 due to the excellent agreement with the pseudo-second-order adsorption models. The fit with the Freundlich isotherm models suggested a multilayer adsorption mechanism between HAA molecules and materials with heterogeneous surfaces. Moreover, coupled with the ultrahigh-performance liquid chromatography-tandem mass spectrometry detection, the CMC-CNC-UiO-66 extraction process can be completed with a high average recovery ranging from 86.68 to 115.33%, indicating a potential application of CMC-CNC-UiO-66 in HAA adsorption for further quantitative analysis.

Efficacy and Prognostic Factors of Androgen Deprivation Therapy Combined with Radiation Therapy for Prostate Cancer.

OBJECTIVE: To analyze the efficacy of androgen deprivation therapy (ADT) combined with radiation therapy (also known as radiotherapy) for prostate cancer. METHODS: The clinical data of 94 prostate cancer patients treated in the Oncology Department of Xiangzhou People's Hospital from January 2017 to January 2018 were retrospectively analyzed, and the patients were divided into the combined group and the reference group according to their admission order, with 47 cases each. The patients in the reference group only received the radiotherapy, and on this basis, those in the combined group accepted ADT, so as to evaluate the efficacy of different treatment methods by comparing the patients' serum total prostate-specific antigen (T-PSA), vascular endothelial growth factor (VEGF), and other indicators and analyze the relevant factors affecting patients' prognosis by Cox single-factor and multi-factor regression models. RESULTS: Compared with the reference group after treatment, the patients in the combined group obtained significantly lower T-PSA and VEGF levels (P < 0.001), significantly higher objective remission rate and disease control rate (P < 0.05), and remarkably longer modified progression-free survival (mPFS) and overall survival (OS) (P < 0.001), and after the multi-factor research, it was found that the Gleason score of 8-10, positive lymphatic metastasis, and single radiotherapy were the factors affecting the clinical prognosis of prostate cancer. CONCLUSION: Combining ADT with radiotherapy ensures a better survival benefit for prostate cancer patients and has a fairly well efficacy. Further study will be conducive to establishing a better solution for such patients.

High throughput analysis and quantitation of α-dicarbonyls in biofluid by plasmonic nanoshells enhanced laser desorption/ionization mass spectrometry.

Advanced analytical platforms are required for accurate detection and quantification of small molecular substances exhibiting certain toxicity. Small molecules detection in complex biological fluids are challenged by the complexity of the samples and the low throughput of the existing methods. In the present study, to detect a batch of samples (50) in 1 h, the plasmonic nanoshell enhanced matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) was tested. The limit of quantification (LOQ) was determined as 0.01 µg/mL (for α-dicarbonyl compounds) by vortex-assisted liquid-liquid microextraction (VALLME). The developed method can be adopted to study the high-throughput metabolomics and employed for clinical precision diagnosis with MALDI-TOF MS.

High stability of bilayer nano-emulsions fabricated by Tween 20 and specific interfacial peptides.

To ensure emulsions to be continuously stable, the hydrolysates recovered from cod bones by papain acted as a natural surfactant to synthesize high-stability bilayer nano-emulsions. As assisted by Tween 20, the average diameter of synthesized nano-emulsion with enzymatic hydrolysate could exhibit stability between 300-400 nm under a broad range of pH (4-8), temperatures (30-90 °C) and salt concentration (25-250 mM). With the addition of the hydrolysates, the rate of increase of the TBARS value in the emulsion decreased. Moreover, the bilayer structure of the nano-emulsion was characterized under an atomic force microscopy and a cryo-scanning electron microscopy. Nano-LC-Q-TOF-MS was adopted to primarily identify peptides that contained hydrophobic and hydrophilic amino acids at the emulsion interface. Besides, the absorbed peptides on the interface of emulsion enhanced the stability of emulsion lipid oxidation.

Huoxue Jiedu Huayu Recipe Ameliorates Mesangial Cell Pyroptosis in Contralateral Kidney of UUO Rats.

OBJECTIVES: To observe the effects of the Huoxue Jiedu Huayu Recipe (HJHR) on pyroptosis of glomerular mesangial cells in the contralateral unobstructed kidney (CK) of unilateral ureteral obstruction (UUO) rats. METHODS: Sprague-Dawley rats were randomly divided into 4 groups: sham group, UUO group (10 days of left ureter ligation), UUO treated with eplerenone (EPL) (UUO + EPL) group, and UUO treated with HJHR (UUO + HJHR) group. The CKs of all rats were collected for studies. RESULTS: Cell pyroptosis and macrophage infiltration was found in contralateral glomeruli, and nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) and interleukin (IL)-1ß expression was upregulated in the CK of UUO rats. All of these changes were inhibited by HJHR and eplerenone. To determine how aldosterone (Aldo) activated the mineralocorticoid receptor (MR) and then induced mesangial cell pyroptosis with NLRP3-caspase-1-IL-1ß pathway, human mesangial cells (HMCs) were treated with HJHR and eplerenone, which were examined to detect the expression of NLRP3 inflammasome-associated proteins following treatment with Aldo. CONCLUSION: These results suggest that HJHR and eplerenone suppressed HMC pyroptosis via the MR/NLRP3 pathway.

Occurrence, Seasonal Variation and Risk Assessment of Antibiotics in the Surface Water of North China.

In this study, the occurrence, seasonal, and spatial variations of four classes antibiotics were investigated in the surface water of North China. Water samples were taken from 24 sampling sites along rivers in May and August and antibiotics in water samples were detected by SPE-UPLC-MS/MS. The occurrence of all antibiotics except for FLO in May were higher than in August. The mean concentrations of four classes antibiotics detected in May and August were in the following order respectively: quinolones (421.23 ng/L) > tetracyclines (28.37 ng/L) > amphenicols (20.38 ng/L) > sulfonamides (5.79 ng/L) and amphenicols (284.36 ng/L) > quinolones (15.74 ng/L) > tetracyclines (3.05 ng/L) > sulfonamides (0.20 ng/L). The results showed that quinolones and amphenicols were dominant antibiotics among four classes antibiotics. To explore the source of antibiotics from the fish ponds nearby, antibiotic concentration data, which was investigated in the sediment, fish feed and fish revealed a direct relationship between the main antibiotics and fish farms along the rivers. Risk assessment data indicated enrofloxacin and florfenicol could cause higher safety risks to aquatic organisms compared to other antibiotics.