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1.
Signal Transduct Target Ther ; 8(1): 30, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36693826

RESUMO

Passive immunotherapy is one of the most promising interventions for Alzheimer's disease (AD). However, almost all immune-modulating strategies fail in clinical trials with unclear causes although they attenuate neuropathology and cognitive deficits in AD animal models. Here, we showed that Aß-targeting antibodies including their lgG1 and lgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or FcγRIIb via the complex of Aß, antibody, and complement. Notably, anti-Aß antibodies without Fc fragment, or with blockage of CR3 or FcγRIIb, did not exert these adverse effects. Consistently, Aß-targeting antibodies, but not their Fab fragments, significantly induced acute microglial synapse removal and rapidly exacerbated cognitive deficits and neuroinflammation in APP/PS1 mice post-treatment, whereas the memory impairments in mice were gradually rescued thereafter. Since the recovery rate of synapses in humans is much lower than that in mice, our findings may clarify the variances in the preclinical and clinical studies assessing AD immunotherapies. Therefore, Aß-targeting antibodies lack of Fc fragment, or with reduced Fc effector function, may not induce microglial synaptic pruning, providing a safer and more efficient therapeutic alternative for passive immunotherapy for AD.

2.
Environ Dev Sustain ; : 1-29, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36687739

RESUMO

How heavily polluting enterprises achieve sustainable development has become an urgent issue to be solved. Based on the data of Chinese heavily polluting listed enterprises during the period of 2010-2020, this paper adopts the probit method to examine how heterogeneous environmental regulations affect green merger and acquisition (GMA) decision, and propensity score matching and difference-in-differences method to explore innovation performance of GMA. The findings are as follows: (1) Command-and-control environmental regulation (CMCER) can promote GMA, while there exists a U-shaped relationship between market-based environmental regulation (MBER) and GMA; (2) from a dynamic perspective, it turns out that GMA can promote green innovation (GI) in the first and second post-acquisition year, but this effect disappears in the third year; (3) compared with CMCER, MBER has a more pronounced positive effect on the relationship between GMA and GI; (4) heterogeneous analysis indicates that the above GMA performance is more persistent when the acquirer is state-owned, with high media attention, with high internal control or engages in vertical GMA. The findings further enrich the literature on GMA driver and performance and provide references for optimizing ER policies and promoting corporate sustainable development.

3.
Malar J ; 22(1): 21, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658578

RESUMO

BACKGROUND: Mass screening and treatment (MSAT) for malaria elimination lacks an ideal diagnostic tool to allow sensitive and affordable test of the target population in the field. This study evaluated whether Capture and Ligation Probe-PCR (CLIP-PCR) could be used in a field MSAT in Laiza City, Myanmar. METHODS: On day 0, two dried blood spots were collected from each participant. On day 1, all samples were screened for Plasmodium in a 20 m2 laboratory with workbench, a biosafety cabinet, a refrigerator, a benchtop shaking incubator and a qPCR machine, by four technicians using CLIP-PCR with sample pooling, at a health clinic of the Chinese bordering town of Nabang. On day 2, all positives were followed up and treated. RESULTS: Of 15,038 persons (65% of the total population) screened, 204 (1.36%) were CLIP-PCR positives. Among them, 188, 14, and 2 were infected with Plasmodium vivax, Plasmodium falciparum, and P. vivax/P. falciparum mix, respectively. The testing capacity was 538 persons/day, with a cost of US$0.92 /person. The proportion of submicroscopic infection was 64.7%. All positive individuals received treatment within 72 h after blood collection. CONCLUSION: Using CLIP-PCR in MSAT in low transmission settings can support the malaria elimination efforts in the China-Myanmar border region.


Assuntos
Malária Falciparum , Malária Vivax , Malária , Humanos , Mianmar , Malária/diagnóstico , Malária/prevenção & controle , Plasmodium falciparum/genética , Plasmodium vivax/genética , Reação em Cadeia da Polimerase/métodos , China/epidemiologia , Malária Vivax/diagnóstico , Malária Vivax/prevenção & controle , Malária Vivax/epidemiologia , Malária Falciparum/epidemiologia
4.
Adv Sci (Weinh) ; : e2204194, 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36683148

RESUMO

T cells play a crucial role in atherosclerosis, with its infiltration preceding the formation of atheroma. However, how T-cell infiltration is regulated in atherosclerosis remains largely unknown. Here, this work demonstrates that dipeptidyl peptidase-4 (DPP4) is a novel regulator of T-cell motility in atherosclerosis. Single-cell ribonucleic acid (RNA) sequencing and flow cytometry show that CD4+ T cells in atherosclerotic patients display a marked increase of DPP4. Lack of DPP4 in hematopoietic cells or T cells reduces T-cell infiltration and atherosclerotic plaque volume in atherosclerosis mouse models. Mechanistically, DPP4 deficiency reduces T-cell motility by suppressing the expression of microtubule associated protein midline-1 (Mid1) in T cells. Deletion of either DPP4 or Mid1 inhibits chemokine-induced shape change and motility, while restitution of Mid1 in Dpp4-/- T cell largely restores its migratory ability. Thus, DPP4/Mid1, as a novel regulator of T-cell motility, may be a potential inflammatory target in atherosclerosis.

5.
Microbiol Spectr ; : e0342622, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622170

RESUMO

SARS-CoV-2 has infected more than 600 million people. However, the origin of the virus is still unclear; knowing where the virus came from could help us prevent future zoonotic epidemics. Sequencing data, particularly metagenomic data, can profile the genomes of all species in the sample, including those not recognized at the time, thus allowing for the identification of the progenitor of SARS-CoV-2 in samples collected before the pandemic. We analyzed the data from 5,196 SARS-CoV-2-positive sequencing runs in the NCBI's SRA database with collection dates prior to 2020 or unknown. We found that the mutation patterns obtained from these suspicious SARS-CoV-2 reads did not match the genome characteristics of an unknown progenitor of the virus, suggesting that they may derive from circulating SARS-CoV-2 variants or other coronaviruses. Despite a negative result for tracking the progenitor of SARS-CoV-2, the methods developed in the study could assist in pinpointing the origin of various pathogens in the future. IMPORTANCE Sequences that are homologous to the SARS-CoV-2 genome were found in numerous sequencing runs that were not associated with the SARS-CoV-2 studies in the public database. It is unclear whether they are derived from the possible progenitor of SARS-CoV-2 or contamination of more recent SARS-CoV-2 variants circulated in the population due to the lack of information on the collection, library preparation, and sequencing processes. We have developed a computational framework to infer the evolutionary relationship between sequences based on the comparison of mutations, which enabled us to rule out the possibility that these suspicious sequences originate from unknown progenitors of SARS-CoV-2.

6.
Small ; : e2206807, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36592423

RESUMO

Conventional ion-selective membranes, that is ion-exchange and porous membranes, are unable to perform high conductivity and selectivity simultaneously due to the contradictions between their ion selecting and conducting mechanisms. In this work, a bifunctional ion-selective layer is developed via the combination of nanoporous boron nitride (PBN) and ion exchange groups from Nafion to achieve high ion conductivity through dual ion conducting mechanisms as well as high ion selectivity. A template-free method is adopted to synthesize flake-like PBN, which is further enmeshed with Nafion resin to form the bifunctional layer coated onto a porous polyetherimide membrane. The double-layer membrane exhibits excellent ion selectivity (1.49 × 108 mS cm-3  min), which is 22 times greater than that of the pristine porous polyetherimide membrane, with outstanding ion conductivity (64 mS cm-1 ). In a vanadium flow battery, the double-layer membrane achieves a high Coulombic efficiency of 97% and outstanding energy efficiency of 91% at 40 mA cm-2 with a stable cycling performance for over 700 cycles at 100 mA cm-2 . PBN with ion exchange groups may therefore offer a potential solution to the limitation between ion selectivity and conductivity in ion-selective membranes.

7.
Opt Lett ; 48(2): 359-362, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638457

RESUMO

We report, to the best of our knowledge, the first demonstration of a 1555-nm stepped-height ridge waveguide polarization mode converter monolithically integrated with a sidewall grating distributed-feedback (DFB) laser using the identical epitaxial layer scheme. The device shows stable single longitudinal mode (SLM) operation with the output light converted from TE to TM polarization with an efficiency of >94% over a wide range of DFB injection currents (IDFB) from 140 mA to 190 mA. The highest TM mode purity of 98.2% was obtained at IDFB = 180 mA. A particular advantage of this device is that only a single step of metalorganic vapor-phase epitaxy and two steps of III-V material dry etching are required for the whole integrated device fabrication, significantly reducing complexity and cost.

8.
Small Methods ; : e2201493, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36642856

RESUMO

The prospect of graphene-based shielding materials in the form of fillers is limited by the cumbersome preparation of graphene. Herein, defect-tunable porous graphene prepared by carbothermal shock using low-value sucrose as a precursor is proposed as an effective shielding filler. The resultant porous graphene exhibits 32.5 dB shielding efficiency (SE) and 2.5-18 GHz effective bandwidth at a mass loading of 20 wt%, competing with the shielding performance of graphene fillers prepared by other methods. Particularly, defect-rich graphene synthesized by increasing voltage and prolonging time shows increased electromagnetic (EM) wave absorption, echoing the current concept of green shielding. In addition, the strategy of controlling the discharge conditions to improve the absorption by the shield is developed in the terahertz band. The average SE and reflection loss of the samples in the THz band (0.2-1.2 THz) exhibit 40.7 and 15.9 dB at filler loading of 5 wt%, respectively, achieving effective shielding and absorption of THz waves. This work paves a new way for low-cost preparation of graphene for EM interference shielding fillers. Meanwhile, it supplies a reference for the shielding research of the upcoming applications integrating multiple EM bands (such as sixth-generation based integrated sensing and communication).

9.
Medicine (Baltimore) ; 102(2): e32673, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637955

RESUMO

Primary Sjögren syndrome (pSS) is a systemic autoimmue disease featured by excessive autoantibody production. It has been demonstrated that anti-carbonic anhydrase II (anti-CA II) antibody is correlated with renal tubular acidosis in pSS; however, no further details about urinary acidification defect have been reported, and the antibody's relationship with other organ impairments remains unknown. This case-control study aimed to examine anti-CA II antibody levels in relation to various systemic complications in pSS, and evaluate its potential role as a organ-specific biomarker in a Chinese cohort. Serum anti-CA II antibody levels were determined using ELISA in 123 patients with pSS and 72 healthy controls. The medical records of the patients were collected, and the correlation between serum anti-CA II antibody and clinical/immunological parameters was investigated. Serum anti-CA II antibody level and its positive rate were significantly increased in pSS patients compared with controls, and ANA-positive patients presented even higher titers of the antibody. In anti-CA II positive group, remarkably higher urine pH and bicarbonate, as well as lower urine titratable acid and serum potassium were observed, which indicated renal tubular acidification dysfunction both involving bicarbonate reabsorption and acid secretion. In addition, platelet count and complement 3, complement 4 levels decreased, whereas serum IgG, IgA and γ-globulin levels increased notably in accord with a higher EULAR SS disease activity index score in these patients. Further analysis showed that anti-CA II antibody was most elevated in patients with defect in bicarbonate reabsorption, reflecting proximal renal tubular injury, rather than in patients with distal renal tubular acidosis as previously reported. In conclusion, anti-CA II antibody reflects renal (especially proximal renal tubular) and hematologic impairment as well as increased disease activity in pSS. It may act as a serum biomarker of systemic damage of pSS.


Assuntos
Acidose Tubular Renal , Nefropatias , Síndrome de Sjogren , Humanos , Túbulos Renais Proximais , Síndrome de Sjogren/complicações , Bicarbonatos , Estudos de Casos e Controles , Concentração de Íons de Hidrogênio
10.
Int J Biol Macromol ; 230: 123133, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36621733

RESUMO

Lytic polysaccharide monooxygenase (LPMO) is known as an oxidatively cleaving enzyme in recalcitrant polysaccharide deconstruction. Herein, we report a novel AA10 LPMO derived from Bacillus subtilis (BsLPMO10A). A substrate specificity study revealed that the enzyme exhibited an extensive active-substrate spectrum, particularly for polysaccharides linked via ß-1,4 glycosidic bonds, such as ß-(Man1 â†’ 4Man), ß-(Glc1 â†’ 4Glc) and ß-(Xyl1 â†’ 4Xyl). HPAEC-PAD and MALDI-TOF-MS analyses indicated that BsLPMO10A dominantly liberated native oligosaccharides with a degree of polymerization (DP) of 3-6 and C1-oxidized oligosaccharides ranging from DP3ox to DP6ox from mixed linkage glucans and beechwood xylan. Due to its synergistic action with a variety of glycoside hydrolases, including glucanase IDSGLUC5-38, xylanase TfXYN11-1, cellulase IDSGLUC5-11 and chitinase BtCHI18-1, BsLPMO10A dramatically accelerated glucan, xylan, cellulose and chitin saccharification. After co-reaction for 72 h, the reducing sugars in Icelandic moss lichenan, beechwood xylan, phosphoric acid swollen cellulose and chitin yielded 3176 ± 97, 7436 ± 165, 649 ± 44, and 2604 ± 130 µmol/L, which were 1.47-, 1.56-, 1.44- and 1.25-fold higher than those in the GHs alone groups, respectively (P < 0.001). In addition, the synergy of BsLPMO10A and GHs was further validated by the degradation of natural feedstuffs, the co-operation of BsLPMO10A and GHs released 3266 ± 182 and 1725 ± 107 µmol/L of reducing sugars from Oryza sativa L. and Arachis hypogaea L. straws, respectively, which were significantly higher than those produced by GHs alone (P < 0.001). Furthermore, BsLPMO10A also accelerated the liberation of reducing sugars from Celluclast® 1.5 L, a commercial cellulase cocktail, on filter paper, A. hypogaea L. and O. sativa L. straws by 49.58 % (P < 0.05), 72.19 % (P < 0.001) and 54.36 % (P < 0.05), respectively. This work has characterized BsLPMO10A with a broad active-substrate scope, providing a promising candidate for lignocellulosic biomass biorefinery.

12.
Microb Pathog ; : 105993, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36657690

RESUMO

Edwardsiella tarda is a causative pathogen of edwardsiellosis in fish. Our previous studies on high (NUF251) and low (NUF194) virulent strains of E. tarda demonstrated that NUF251 strain induced significantly higher levels of NO and TNF-α from fish and mouse macrophages than NUF194 strain. Subsequent studies suggested that a flagellin-like protein secreted from E. tarda might be a responsible factor for the macrophage-stimulating activities. To evaluate the activities of flagellins of E. tarda, in this study, the flagellin genes of NUF251 and NUF194 strains were isolated by PCR and cloned into pQE-30 and pCold I expression vectors, and then the recombinant flagellins of two strains were overexpressed in E. coli JM109 and pG-Tf/BL21, respectively. The molecular weight of the purified recombinant flagellins of NUF251 and NUF194 strains were estimated to be 45 kDa and 37 kDa, respectively on SDS-PAGE analysis. Referring the three-dimensional structure of Salmonella flagellin, which has been reported to have 4 domains (D0, D1, D2, and D3), high sequence homology between two flagellins of E. tarda was observed at conservative domain (D0 and D1) regions, whereas the sequences equivalent to D2 and D3 domains were different, and even equivalent to 57 amino acids were deleted in NUF194. Both recombinant flagellins induced NO production, mRNA expression level of inducible NO synthase (iNOS), and intercellular ROS production in mouse macrophage cell line RAW264.7 cells. Also, the secretion of TNF-α and its mRNA expression level were increased by treatment of both recombinant flagellins. These results indicate that the recombinant flagellins from different virulent E. tarda strains can stimulate macrophages with nearly equal levels as judged by the parameters tested, even though they are differences in the structure and molecular weight, suggesting that conservative D0 and D1 domains are sufficient structural elements for the recombinant flagellins to induce a certain level of macrophage-stimulation in vitro. Further studies are necessary focusing on the role of D2 and D3 domain regions of the recombinant flagellins as macrophage-stimulating agent as well as their influence on host immune system in vivo.

13.
Medicina (Kaunas) ; 59(1)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36676745

RESUMO

Osteoporosis is mainly a geriatric disease with a high incidence, and the resulting spinal fractures and hip fractures cause great harm to patients. Anti-osteoporosis drugs are the main treatment for osteoporosis currently, but these drugs have potential clinical limitations and side effects, so the development of new therapies is of great significance to patients with osteoporosis. Electrical stimulation therapy mainly includes pulsed electromagnetic fields (PEMF), direct current (DC), and capacitive coupling (CC). Meanwhile, electrical stimulation therapy is clinically convenient without side effects. In recent years, many researchers have explored the use of electrical stimulation therapy for osteoporosis. Based on this, the role of electrical stimulation therapy in osteoporosis was summarized. In the future, electrical stimulation might become a new treatment for osteoporosis.


Assuntos
Terapia por Estimulação Elétrica , Magnetoterapia , Osteoporose , Humanos , Idoso , Osteoporose/terapia , Osteoporose/etiologia , Terapia por Estimulação Elétrica/efeitos adversos , Terapia por Estimulação Elétrica/métodos , Magnetoterapia/métodos , Estimulação Elétrica/efeitos adversos
14.
J Agric Food Chem ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36696156

RESUMO

It is well known that polyunsaturated fatty acids (PUFAs) in Schizochytrium sp. are mainly synthesized via the polyketide synthase (PKS) pathway. However, the specific mechanism of PKS in fatty acid synthesis is still unclear. In this work, the functions of ORFA, ORFB, ORFC, and their individual functional domain genes on fatty acid synthesis were investigated through heterologous expression in Yarrowia lipolytica. The results showed that the expression of ORFA, ORFB, ORFC, and their individual functional domains all led to the increase of the very long-chain PUFA content (mainly eicosapentaenoic acid). Furthermore, the transcriptomic analysis showed that except for the 3-ketoacyl-ACP synthase (KS) domain of ORFB, the expression of an individual functional domain, including malonyl-CoA: ACP acyltransferase, 3-hydroxyacyl-ACP dehydratase (DH), 3-ketoacyl-ACP reductase, and KS domains of ORFA, acyltransferase domains of ORFB, and two DH domains of ORFC resulted in upregulation of the tricarboxylic acid cycle and pentose phosphate pathway, downregulation of the triacylglycerol biosynthesis, fatty acid synthesis pathway, and ß-oxidation in Yarrowia lipolytica. These results provide a theoretical basis for revealing the function of PKS in fatty acid synthesis in Y. lipolytica and elucidate the possible mechanism for PUFA biosynthesis.

15.
J Org Chem ; 88(1): 513-524, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36545950

RESUMO

Herein, the efficient photoredox/nickel dual-catalyzed cyanoalkylation reaction of enamides is illustrated. A wide scope of enamides and cycloketone oxime esters was well-tolerated, affording the synthetically versatile and geometrically defined ß-cyanoalkylated enamide scaffolds. The synthetic practicality of this protocol was revealed by gram-scale reactions, further transformations of enamides, and late-stage modifications of biologically active molecules.


Assuntos
Amidas , Níquel , Estrutura Molecular , Catálise
16.
Inorg Chem ; 62(1): 266-274, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36548144

RESUMO

Multifunctional materials with switchable magnetic and dielectric properties are crucial for the development of memory and sensor devices. Herein, we report a methoxy-bridged dinuclear iron-pyridyl complex [Fe2(4-picoline)4(NCS)4(µ-OCH3)2] (1), which shows simultaneous thermal-induced magnetic and dielectric switchings. Within the phase-transition temperature range, both magnetic switching and the dielectric anomaly were detected, in which the thermal hysteresis loops were 23 and 21 K, respectively. Detailed structural analyses revealed that these simultaneous switchings were rooted in the flexible rotatable ligands, which were actuated by readjusting the π-π intermolecular interactions between the pyridine ligands in the trans positions of the metal centers. These results were comprehensively investigated both experimentally and theoretically. This study presents a new guideline to control both the magnetic and dielectric properties of molecular complexes by external stimuli.

17.
Appl Microbiol Biotechnol ; 107(2-3): 677-689, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36572830

RESUMO

Pectate lyases (Pels) have a vital function in degradation of the primary plant cell wall and the middle lamella and have been widely used in the industry. In this study, two pectate lyase genes, IDSPel16 and IDSPel17, were cloned from a sheep rumen microbiome. The recombinant enzymes were expressed in Escherichia coli and functionally characterized. Both IDSPel16 and IDSPel17 proteins had an optimal temperature of 60 ℃, and an optimal pH of 10.0. IDSPel16 was relatively stable below 60 °C, maintaining 77.51% residual activity after preincubation at 60 °C for 1 h, whereas IDSPel17 denatured rapidly at 60 °C. IDSPel16 was relatively stable between pH 6.0 and 12.0, after pretreatment for 1 h, retaining over 60% residual activity. IDSPel16 had high activity towards polygalacturonic acid, with a Vmax of 942.90 ± 68.11, whereas IDSPel17 had a Vmax of only 28.19 ± 2.23 µmol/min/mg. Reaction product analyses revealed that IDSPel17 liberated unsaturated digalacturonate (uG2) and unsaturated trigalacturonate (uG3) from the substrate, indicating a typical endo-acting pectate lyase (EC 4.2.2.2). In contrast, IDSPel16 initially generated unsaturated oligogalacturonic acids, then converted these intermediates into uG2 and unsaturated galacturonic acid (uG1) as end products, a unique depolymerization profile among Pels. To the best of our knowledge, the IDSPel16 discovered with both endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities. These two pectate lyases, particularly the relatively thermo- and pH-stable IDSPel16, will be of interest for potential application in the textile, food, and feed industries. KEY POINTS: • Two novel pectate lyase genes, IDSPel16 and IDSPel17, were isolated and characterized from the sheep rumen microbiome. • Both IDSPel16 and IDSPel17 are alkaline pectate lyases, releasing unsaturated digalacturonate and unsaturated trigalacturonate from polygalacturonic acid. • IDSPel16, a bifunctional pectate lyase with endo-Pel (EC 4.2.2.2) and exo-Pel (EC 4.2.2.9) activities, could be a potential candidate for industrial application.


Assuntos
Polissacarídeo-Liases , Rúmen , Animais , Ovinos , Rúmen/metabolismo , Polissacarídeo-Liases/metabolismo , Clonagem Molecular
18.
Neural Regen Res ; 18(3): 643-651, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018189

RESUMO

TMEM16F is involved in many physiological processes such as blood coagulation, cell membrane fusion and bone mineralization. Activation of TMEM16F has been studied in various central nervous system diseases. High TMEM16F level has been also found to participate in microglial phagocytosis and transformation. Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer's disease. However, few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer's disease. In this study, we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD. We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome. Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice. After TMEM16F knockdown in mice, spatial memory ability was improved, microglia polarization to the M2 phenotype was promoted, NLRP3 inflammasome activation was inhibited, cell apoptosis and Aß plaque deposition in brain tissue were reduced, and brain injury was alleviated. We used amyloid-beta (Aß25-35) to stimulate human microglia to construct microglia models of Alzheimer's disease. The levels of TMEM16F, inducible nitric oxide synthase (iNOS), proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aß25-35 treated group compared with that in the control group. TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3, reduced the release of proinflammatory factors interleukin-1, interleukin-6 and tumor necrosis factor-α, and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1ß and interleukin-18. This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin. Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer's disease through participating in polarization of microglia and activation of the NLRP3 inflammasome. These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer's disease treatment.

19.
J Agric Food Chem ; 71(1): 846-856, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36541832

RESUMO

Cadmium is a global ecological toxic pollutant; in animals, hepatotoxic fibrosis is caused by bioaccumulation of Cd through food chains. We determined the path of nano-Se antagonism in Cd-induced hepatocyte pyroptosis by targeting the APJ-AMPK-PGC1α pathway, using an in vivo model of hepatotoxicity. All 1-day-old chicks were treated with Cd (140 mg/kg BW/day) and/or nano-Se (0.3 or 0.6 mg/kg BW/day) for 90 days. The result showed that Cd (1.55 ± 0.148) activated NLRP3 inflammasome 49.903% as compared to the Con group (1.034 ± 0.008) to release the inflammasome as a result of hepatocyte pyroptosis (2.824 ± 0.057). Compared with the Con group (1.010 ± 0.021), Kupffer cells were 219.109% more to activate astrocytes through the APJ-AMPK-PGC1α pathway, resulting in 185.149% more hepatic fibrosis. However, the fibrosis degree of the H-Se + Cd group (1.252 ± 0.056) was 56.5278% (p < 0.001) lower than that of the Cd group (2.880 ± 0.124). Therefore, this study established that pyroptotic hepatocytes and Kupffer cells could be targeted for nano-Se antagonizing Cd toxicity, which reveals a potential new approach targeting astrocytes for the treatment of liver fibrosis triggered by Cd pollution.


Assuntos
Cádmio , Selênio , Animais , Cádmio/toxicidade , Galinhas , Selênio/farmacologia , Inflamassomos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Proteínas Quinases Ativadas por AMP , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Fígado
20.
ACS Appl Mater Interfaces ; 15(1): 1619-1628, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36574641

RESUMO

InP quantum dots (QDs) are the most competitive in terms of environmentally friendly QDs. However, the synthesis of InP QDs requires breakthroughs in low-cost and safe phosphorus precursors such as tri(dimethylamino)phosphine [(DMA)3P]. It is found that even if the oxygen is completely avoided, there are still oxidation state defects at the core/shell interface of InP QDs. Herein, the record-breaking (DMA)3P-based red InP QDs were synthesized with the assist of HF processing to eliminate the InPOx defect and improve the fluorescence efficiency. The maximum photoluminescence quantum yield was 97.7%, which is the highest of the red InP QDs synthesized by the aminophosphine. The external quantum efficiency and brightness of the QD light-emitting diode device are also improved accordingly from 0.6% and 1276 cd·m-2 to 3.5% and 2355 cd·m-2, respectively.

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