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1.
J Phys Chem Lett ; 15(23): 6183-6189, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38836642

ABSTRACT

Electrocatalytic oxidation of formaldehyde (FOR) is an effective way to prevent the damage caused by formaldehyde and produce high-value products. A screening strategy of a single-layer MnO2-supported transition metal catalyst for the selective oxidation of formaldehyde to formic acid was designed by high-throughput density functional calculation. N-MnO2@Cu and MnO2@Cu are predicted to be potential FOR electrocatalysts with potential-limiting steps (PDS) of 0.008 and -0.009 eV, respectively. Electronic structure analysis of single-atom catalysts (SACs) shows that single-layer MnO2 can regulate the spin density of loaded transition metal and thus regulate the adsorption of HCHO (Ead), and Ead is volcanically distributed with the magnetic moment descriptor -|mM - mH|. In addition, the formula quantifies Ead and |mM - mH| to construct a volcano-type descriptor α describing the PDS [ΔG(*CHO)]. Other electronic and structural properties of SACs and α are used as input features for the GBR method to construct machine learning models predicting the PDS (R2 = 0.97). This study hopes to provide some insights into FOR electrocatalysts.

2.
J Phys Chem A ; 128(27): 5243-5252, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38937149

ABSTRACT

Direct methanol fuel cells (DMFCs) have attracted increasing attention as a very promising and important energy source. In this paper, density functional theory (DFT) is used to study the structure and O-H fracture mechanism of methanol adsorption on PtnCu4-n (111) (n = 1, 2, 3) binary metal catalyst surfaces under different coverages. By comparing the adsorption energy and dehydrogenation energy barriers of methanol, it is found that the adsorption strength and dehydrogenation energy barriers of methanol on Pt and Cu sites decreased with increasing coverage. At the same Pt and Cu ratio, methanol is more easily adsorbed on Cu sites. When Pt/Cu = 3:1 and 1:3, the PtCu binary catalyst has a significant impact on the energy barrier of breaking the O-H bond in methanol with the increase of coverage. Especially when Pt/Cu = 1:3 and the coverage is 1/4 ML, the energy barriers of O-H bond breaking in methanol on Pt and Cu sites are 0.63 and 0.61 eV, respectively, which are lower than that on pure Pt. It means that the Cu sites played a very important role in reducing the O-H fracture energy barrier of methanol. When Pt/Cu = 1:1, the change in the dehydrogenation energy barrier of methanol on Pt sites and Cu sites is not significant, indicating that the coverage has little effect on it.

3.
Br J Anaesth ; 133(2): 296-304, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38839471

ABSTRACT

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).


Subject(s)
Anesthetics, Inhalation , Anesthetics, Intravenous , Cardiac Surgical Procedures , Desflurane , Postoperative Complications , Propofol , Humans , Propofol/adverse effects , Female , Male , Middle Aged , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/mortality , Anesthetics, Intravenous/adverse effects , Anesthetics, Inhalation/adverse effects , Aged , Postoperative Complications/mortality , Postoperative Complications/prevention & control , Adult , Sevoflurane/adverse effects , Anesthesia, Intravenous/methods , China/epidemiology , Length of Stay/statistics & numerical data , Anesthesia, Inhalation/methods , Anesthesia, Inhalation/adverse effects , Treatment Outcome
4.
Elife ; 122024 May 30.
Article in English | MEDLINE | ID: mdl-38814697

ABSTRACT

Almost all herbivorous insects feed on plants and use sucrose as a feeding stimulant, but the molecular basis of their sucrose reception remains unclear. Helicoverpa armigera as a notorious crop pest worldwide mainly feeds on reproductive organs of many plant species in the larval stage, and its adult draws nectar. In this study, we determined that the sucrose sensory neurons located in the contact chemosensilla on larval maxillary galea were 100-1000 times more sensitive to sucrose than those on adult antennae, tarsi, and proboscis. Using the Xenopus expression system, we discovered that Gr10 highly expressed in the larval sensilla was specifically tuned to sucrose, while Gr6 highly expressed in the adult sensilla responded to fucose, sucrose and fructose. Moreover, using CRISPR/Cas9, we revealed that Gr10 was mainly used by larvae to detect lower sucrose, while Gr6 was primarily used by adults to detect higher sucrose and other saccharides, which results in differences in selectivity and sensitivity between larval and adult sugar sensory neurons. Our results demonstrate the sugar receptors in this moth are evolved to adapt toward the larval and adult foods with different types and amounts of sugar, and fill in a gap in sweet taste of animals.


Subject(s)
Larva , Moths , Sensilla , Sucrose , Animals , Sucrose/metabolism , Sucrose/pharmacology , Larva/physiology , Moths/physiology , Moths/drug effects , Sensilla/physiology , Sensilla/metabolism , Taste/physiology , Taste Perception/physiology , Helicoverpa armigera
5.
Acta Pharmacol Sin ; 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38641746

ABSTRACT

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

6.
Leuk Res ; 139: 107483, 2024 04.
Article in English | MEDLINE | ID: mdl-38493755

ABSTRACT

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P<0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.


Subject(s)
Core Binding Factor Alpha 2 Subunit , Leukemia, Myeloid, Acute , Adult , Humans , Prognosis , Retrospective Studies , Prospective Studies , Core Binding Factor Alpha 2 Subunit/genetics , Mutation , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics
7.
Org Biomol Chem ; 22(14): 2824-2834, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38511321

ABSTRACT

An efficient, diversity-oriented synthesis of indole-1,2-fused 1,4-benzodiazepines, tetrahydro-ß-carbolines, and 2,2'-bis(indolyl)methanes was established starting from tosyl-protected tryptamine. These diverse privileged skeletons were controllably constructed by adjusting different hydride donors and Brønsted acids. A variety of indole-1,2-fused 1,4-benzodiazepines were facilely accessed using benzaldehydes bearing cyclic amines as hydride donors via a cascade N-alkylation/dehydration/[1,5]-hydride transfer/Friedel-Crafts alkylation sequence. The reaction site could be switched when benzaldehydes bearing an alkoxy moiety as hydride donors were used for the generation of tetrahydro-ß-carbolines. On the other hand, the switchable synthesis of 2,2'-bis(indolyl)methanes could be achieved as well by applying p-TsOH·H2O as a catalyst. The reactions feature mild conditions, simple and practical operation, excellent efficiency and the use of EtOH as a green solvent. Using the concept of diversity-oriented, reagent-based synthesis, the inexpensive feedstock tryptamine was efficiently converted to three different types of privileged scaffolds, which facilitates rapid compound library synthesis for accelerating drug discovery.

8.
Molecules ; 29(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38474524

ABSTRACT

The Sc(OTf)3-catalyzed dearomative [5+1] annulations between readily available 3-aminophenols and O-alkyl ortho-oxybenzaldehydes were developed for synthesis of spiro[chromane-3,1'-cyclohexane]-2',4'-dien-6'-ones. The "two-birds-with-one-stone" strategy was disclosed by the dearomatization of phenols and direct α-C(sp3)-H bond functionalization of oxygen through cascade condensation/[1,5]-hydride transfer/dearomative-cyclization process. In addition, the antifungal activity assay and derivatizations of products were conducted to further enrich the utility of the structure.

9.
Int Urol Nephrol ; 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38483736

ABSTRACT

Sirtuin 6 (SIRT6) can inhibit the fibrosis of many organs. However, the relationship between SIRT6 and peritoneal fibrosis (PF) in peritoneal dialysis (PD) remains unclear. We collected 110 PD patients with a duration of PD for more than 3 months and studied the influence of PD duration and history of peritonitis on SIRT6 levels in PD effluents (PDEs). We also analyzed the relationship between SIRT6 levels in PDEs and transforming growth factor beta 1 (TGF-ß1), IL-6, PD duration, peritoneal function, PD ultrafiltration (UF), and glucose exposure. We extracted human peritoneal mesothelial cells (HPMCs) from PDEs and measured the protein and gene expression levels of SIRT6, E-cadherin, vimentin, and TGF-ß1 in these cells. Based on the clinical results, we used human peritoneal mesothelial cells lines (HMrSV5) to observe the changes in SIRT6 levels and mesothelial-to-mesenchymal transition (MMT) after intervention with PD fluid. By overexpressing and knocking down SIRT6 expression, we investigated the effect of SIRT6 expression on E-cadherin, vimentin, and TGF-ß1 expression to elucidate the role of SIRT6 in mesothelial-to-epithelial transition in PMCs. Results: (1) With the extension of PD duration, the influence of infection on SIRT6 levels in PDEs increased. Patients with the PD duration of more than 5 years and a history of peritonitis had the lowest SIRT6 levels. (2) SIRT6 levels in PDEs were negatively correlated with PD duration, total glucose exposure, TGF-ß1, IL-6 levels, and the dialysate-to-plasma ratio of creatinine (Cr4hD/P), but positively correlated with UF. This indicates that SIRT6 has a protective effect on the peritoneum. (3) The short-term group (PD ≤ 1 year) had higher SIRT6 and E-cadherin gene and protein levels than the mid-term group (1 year < PD ≤ 5 years) and long-term group (PD > 5 years) in PMCs, while vimentin and TGF-ß1 levels were lower in the mid-term group and long-term group. Patients with a history of peritonitis had lower SIRT6 and E-cadherin levels than those without such a history. (4) After 4.25% PD fluid intervention for HPMCs, longer intervention time resulted in lower SIRT6 levels. (5) Overexpressing SIRT6 can lead to increased E-cadherin expression and decreased vimentin and TGF-ß1 expression in HPMCs. Knocking down SIRT6 expression resulted in decreased E-cadherin expression and increased vimentin and TGF-ß1 expression in HPMCs. This indicates that SIRT6 expression can inhibit MMT in HPMCs, alleviate PF associated with PD, and have a protective effect on the peritoneum.

10.
Int J Nanomedicine ; 19: 1431-1450, 2024.
Article in English | MEDLINE | ID: mdl-38371455

ABSTRACT

Introduction: Basic fibroblast growth factor (bFGF) shows great potential for preventing vascular dementia (VD). However, the blood‒brain barrier (BBB) and low bioavailability of bFGF in vivo limit its application. The present study investigated how nasal administration of bFGF-loaded nanoliposomes (bFGF-lips) affects the impaired learning and cognitive function of VD mice and the underlying mechanism involved. Methods: A mouse model of VD was established through repeated cerebral ischemia‒reperfusion. A Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess the learning and cognitive function of the mice. Hematoxylin and eosin (HE) staining, Nissl staining and TUNEL staining were used to evaluate histopathological changes in mice in each group. ELISA and Western blot analysis were used to investigate the molecular mechanism by which bFGF-lips improve VD incidence. Results: Behavioral and histopathological analyses showed that cognitive function was significantly improved in the bFGF-lips group compared to the VD and bFGF groups; in addition, abnormalities and the apoptosis indices of hippocampal neurons were significantly decreased. ELISA and Western blot analysis revealed that bFGF-lips nasal administration significantly increased the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), bFGF, B-cell lymphoma 2 (Bcl-2), phosphorylated protein kinase B (PAKT), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1) and haem oxygenase-1 (HO-1) in the hippocampus of bFGF-lips mice compared with the VD and bFGF groups. Furthermore, the concentrations of malondialdehyde (MDA), caspase-3 and B-cell lymphoma 2-associated X (Bax) were clearly lower in the bFGF-lips group than in the VD and bFGF groups. Conclusion: This study confirmed that the nasal administration of bFGF-lips significantly increased bFGF concentrations in the hippocampi of VD mice. bFGF-lips treatment reduced repeated I/R-induced neuronal apoptosis by regulating apoptosis-related protein concentrations and activating the phosphatidylinositol-3-kinase (PI3K)/(AKT)/Nrf2 signaling pathway to inhibit oxidative stress.


Subject(s)
Brain Ischemia , Dementia, Vascular , Mice , Animals , Dementia, Vascular/drug therapy , Dementia, Vascular/metabolism , Dementia, Vascular/pathology , Fibroblast Growth Factor 2/metabolism , NF-E2-Related Factor 2/metabolism , Administration, Intranasal , Oxidative Stress , Cerebral Infarction , Brain Ischemia/drug therapy , Cognition , Reperfusion , Neurons/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Apoptosis
12.
Ecotoxicol Environ Saf ; 270: 115813, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38113798

ABSTRACT

To investigate the impact of the ethanoic fractions of Periploca forrestii Schltr. (P. forrestii) in ameliorating the liver injury caused by fluoride ingestion and to explore the potential mechanisms. Initially, an in vitro fluorosis cell model was constructed using the human normal liver cell line (L-02) induced by fluoride. Cell viability was assessed using the CCK-8 assay kit. The lactate dehydrogenase (LDH) assay kit was utilized to measure LDH content in the cell supernatant, while the malonic dialdehyde (MDA) assay kit was employed to determine MDA levels within the cells. Subsequently, a fluorosis rat model was established, and LDH content in the cell supernatant was measured using the LDH assay kit. Various parameters, including MDA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and reactive oxygen species (ROS) content within the cells, were detected using appropriate assay kits. Additionally, cell apoptosis rate was determined using the Annexin V-FITC/PI cell apoptosis assay kit. The protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Cleaved Caspase-3, Caspase-9, and Cleaved Caspase-9 were analyzed through Western blotting. Compared to the model group, the ethanolic fraction D of P.forrestii (Fr.D) increased cell viability (P < 0.01) and decreased LDH and MDA levels (P < 0.01). In the high-dose Fr.D treatment group of fluoride-poisoned rats, serum ALT, AST, LDH and MDA levels significantly decreased (P < 0.01). Results from rat primary cells exhibited that the Fr.D administration group exhibited significantly higher cell survival rates than the fluoride group (P < 0.01). Similarly, primary rat cells treated with Fr.D showed enhanced cell viability (P < 0.05) and reduced apoptosis rate, LDH, MDA, SOD, GSH-Px, CAT, and ROS levels (P < 0.05) compared to the model group. Western blot analysis indicated that the Fr.D treatment group elevated the Bcl-2/Bax protein expression ratio and reduced Caspase-3 and Caspase-9 activation levels (P < 0.01) compared to the model group. The results suggest that components within the Fr.D from Periploca forrestii may alleviate fluoride-induced liver injury by potentially counteracting oxidative stress and cell apoptosis.


Subject(s)
Periploca , Rats , Humans , Animals , Reactive Oxygen Species/metabolism , Caspase 3/metabolism , Caspase 9/metabolism , Fluorides/toxicity , Fluorides/metabolism , Liver/metabolism , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolism , Superoxide Dismutase/metabolism , Oxidative Stress
13.
Org Lett ; 26(1): 332-337, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38153999

ABSTRACT

The Brønsted acid-controlled switchable synthesis of indoline-fused tetrahydroquinolines and indole-fused benzazepines was developed through hydride transfer-enabled formal [5 + 1] and [5 + 2] cyclization reactions from indoles and N-alkyl o-aminobenzoketones. Indoline, furanone, and tetrahydroquinoline hybridized pentacyclic products were unprecedentedly accessed via a cascade condensation/hydride transfer/dearomatization-cyclization/deethylation/nucleophilic addition process. In addition, the undeveloped hydride transfer-involved [5 + 2] cyclizations were also realized for direct construction of indole-fused benzazepines.

14.
Org Lett ; 26(1): 6-11, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38157254

ABSTRACT

The controllable synthesis of spirooxindole-dihydrofurans and spirooxindole-benzazepines was developed through formal [3 + 2] and [5 + 2] cyclization reactions from 2-(2-oxoindolin-3-yl)malononitriles and ortho-aminobenzaldehydes, respectively. A variety of spirooxindole-benzazepines were facilely constructed via a furan ring-open-involved hydride transfer/cyclization process. It is noteworthy that the application of the hydride-transfer-involved [5 + 2] cyclization strategy for construction of spirobenzazepines was unprecedented. In addition, the spiro N- and O-containing heterocycles were highly functionalized by amino, amide, and cyano groups, which were conducive to late-stage functionalization.

16.
Article in English | MEDLINE | ID: mdl-38018817

ABSTRACT

Manganese (Mn)-based layer-structured transition metal oxides are considered as excellent cathode materials for potassium ion batteries (KIBs) owing to their low theoretical cost and high voltage plateau. The energy density and cycling lifetime, however, cannot simultaneously satisfy the basic requirements of the market for energy storage systems. One of the primary causes results from the complex structural transformation and transition metal migration during the ion intercalation and deintercalation process. The orbital and electronic structure of the octahedral center metal element plays an important role for maintaining the octahedral structural integrity and improving the K+ diffusivity by the introduced heterogeneous [Me-O] chemical bonding. A multitransition metal oxide, P3-type K0.5Mn0.85Co0.05Fe0.05Al0.05O2 (KMCFAO), was synthesized and employed as a cathode material for KIBs. Beneficial from the larger layer spacing for K+ to better accommodate and effectively preventing the irreversible structural transformation in the insertion/extraction process, it can reach a superior capacity retention up to 96.8% after 300 cycles at a current density of 500 mA g-1. The full cell of KMCFAO//hard carbon exhibits an encouraging promising energy density of 113.8 W h kg-1 at 100 mA g-1 and a capacity retention of 72.6% for 500 cycles.

17.
Curr Biol ; 33(22): 4827-4843.e7, 2023 11 20.
Article in English | MEDLINE | ID: mdl-37848038

ABSTRACT

Food cues serve as pivotal triggers for eliciting physiological responses that subsequently influence food consumption. The magnitude of response induced by these cues stands as a critical determinant in the context of obesity risk. Nonetheless, the underlying neural mechanism that underpins how cues associated with edible food potentiate feeding behaviors remains uncertain. In this study, we revealed that corticotropin-releasing hormone (CRH)-expressing neurons in the lateral hypothalamic area played a crucial role in promoting consummatory behaviors in mice, shedding light on this intricate process. By employing an array of diverse assays, we initially established the activation of these neurons during feeding. Manipulations using optogenetic and chemogenetic assays revealed that their activation amplified appetite and promoted feeding behaviors, whereas inhibition decreased them. Additionally, our investigation identified downstream targets, including the ventral tegmental area, and underscored the pivotal involvement of the CRH neuropeptide itself in orchestrating this regulatory network. This research casts a clarifying light on the neural mechanism underlying the augmentation of appetite and the facilitation of feeding behaviors in response to food cues. VIDEO ABSTRACT.


Subject(s)
Corticotropin-Releasing Hormone , Hypothalamic Area, Lateral , Mice , Animals , Hypothalamic Area, Lateral/physiology , Corticotropin-Releasing Hormone/metabolism , Feeding Behavior/physiology , Neurons/physiology , Appetite
18.
Huan Jing Ke Xue ; 44(9): 5222-5230, 2023 Sep 08.
Article in Chinese | MEDLINE | ID: mdl-37699840

ABSTRACT

CuFeO2-modified biochars were prepared through co-precipitation and hydrothermal methods, and the composites had high efficiency removal for tetracycline (TC) from water. The CuFeO2-modified biochar with a 2:1 mass ratio of CuFeO2 to BC450 (CuFeO2/BC450=2:1) demonstrated the best adsorption performance. The kinetic process of TC adsorption by CuFeO2/BC450=2:1 was well fitted with the intraparticle diffusion model, suggesting that the adsorption process was controlled by film and pore diffusion. Under the condition of neutral pH and 298 K, the maximum adsorption capacity of the Langmuir model of CuFeO2/BC450=2:1 was 82.8 mg·g-1, which was much greater than that of BC450 (13.7 mg·g-1) and CuFeO2(14.8 mg·g-1). The thermodynamic data suggested that TC sorption onto CuFeO2/BC450=2:1 was a spontaneous and endothermic process. The removal of TC by CuFeO2/BC450=2:1 increased first and then decreased with increasing pH, and the maximum adsorption occurred under the neutral condition. The strong adsorption of TC by CuFeO2/BC450=2:1 could be attributed to better porosity, larger specific surface area, and more active sites (e.g., functional groups and charged surfaces). This work provided an efficient magnetic adsorbent for removing antibiotics.


Subject(s)
Anti-Bacterial Agents , Tetracycline , Adsorption , Thermodynamics
19.
Biochem Pharmacol ; 216: 115807, 2023 10.
Article in English | MEDLINE | ID: mdl-37716621

ABSTRACT

Small cell lung cancer (SCLC) is a highly lethal subtype of lung cancer with few therapeutic options; therefore, the identification of new targets and drugs with potent combination therapy is desirable. We previously screened BH3 mimetics from a natural product library, and in this study, we validated nobiletin as a BH3 mimetic. Specifically, we observed its combination potential and mechanism with vorinostat in SCLC in vitro and in vivo. The results showed that combination treatment with nobiletin and vorinostat reduced the proliferation of SCLC H82 cells and increased the levels of apoptotic proteins such as cleaved caspase-9 and cleaved PARP. The combination treatment increased LC3-II expression and induced autophagic cell death. In addition, this treatment significantly inhibited H82 cell xenograft SCLC tumor growth in nude mice. The combination treatment with nobiletin and vorinostat efficiently increased autophagy by inhibiting the PI3K-AKT-mTOR pathway and promoting dissociation of the BCL-2 and Beclin 1 complex, increasing the level of isolated Beclin 1 to stimulate autophagy. Molecular docking and surface plasmon resonance analysis showed that nobiletin stably bound to the BCL-2, BCL-XL and MCL-1 proteins with high affinity in a concentration-dependent manner. These results suggest that nobiletin is a BH3-only protein mimetic. Furthermore, the combination of nobiletin with vorinostat increased histone H3K9 and H3K27 acetylation levels in SCLC mouse tumor tissue and enhanced the expression of the BH3-only proteins BIM and BID. We conclude that nobiletin is a novel natural BH3 mimetic that can cooperate with vorinostat to induce apoptosis and autophagy in SCLC.


Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Animals , Mice , Vorinostat/pharmacology , Vorinostat/therapeutic use , Small Cell Lung Carcinoma/drug therapy , Beclin-1 , Mice, Nude , Phosphatidylinositol 3-Kinases , Molecular Docking Simulation , Apoptosis , Proto-Oncogene Proteins c-bcl-2/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Autophagy , Cell Line, Tumor
20.
Front Cell Dev Biol ; 11: 1268646, 2023.
Article in English | MEDLINE | ID: mdl-37771377

ABSTRACT

Pulmonary arterial hypertension (PAH) is a severe disease resulting from progressive increases in pulmonary vascular resistance and pulmonary vascular remodeling, ultimately leading to right ventricular failure and even death. Hypoxia, inflammation, immune reactions, and epigenetic modifications all play significant contributory roles in the mechanism of PAH. Increasingly, epigenetic changes and their modifying factors involved in reprogramming through regulation of methylation or the immune microenvironment have been identified. Among them, histone lactylation is a new post-translational modification (PTM), which provides a novel visual angle on the functional mechanism of lactate and provides a promising diagnosis and treatment method for PAH. This review detailed introduces the function of lactate as an important molecule in PAH, and the effects of lactylation on N6-methyladenosine (m6A) and immune cells. It provides a new perspective to further explore the development of lactate regulation of pulmonary hypertension through histone lactylation modification.

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