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1.
ACS Nano ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35575066

RESUMO

In artificial van der Waals (vdW) layered devices, twisting the stacking angle has emerged as an effective strategy to regulate the electronic phases and optical properties of these systems. Along with the twist registry, the lattice reconstruction arising from vdW interlayer interaction has also inspired significant research interests. The control of twist angles is significantly important because the moiré periodicity determines the electron propagation length on the lattice and the interlayer electron-electron interactions. However, the moiré periodicity is hard to be modified after the device has been fabricated. In this work, we have demonstrated that the moiré periodicity can be precisely modulated with a localized laser annealing technique. This is achieved with regulating the interlayer lattice mismatch by the mismatched lattice constant, which originates from the variable density of sulfur vacancy generated during laser modification. The existence of sulfur vacancy is further verified by excitonic emission energy and lifetime in photoluminescence measurements. Furthermore, we also discover that the mismatched lattice constant has the equivalent contribution as the twist angle for determining the lattice mismatch. Theoretical modeling elaborates the moiré-wavelength-dependent energy variations at the interface and mimics the evolution of moiré morphology.

2.
J Cell Mol Med ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35567290

RESUMO

Obesity, which has unknown pathogenesis, can increase the frequency and seriousness of acute myocardial infarction (AMI). This study evaluated effect of Huayu Qutan Recipe (HQR) pretreatment on myocardial apoptosis induced by AMI by regulating mitochondrial function via PI3K/Akt/Bad pathway in rats with obesity. For in vivo experiments, 60 male rats were randomly divided into 6 groups: sham group, AMI group, AMI (obese) group, 4.5, 9.0 and 18.0 g/kg/d HQR groups. The models fed on HQR with different concentrations for 2 weeks before AMI. For in vitro experiments, the cardiomyocytes line (H9c2) was used. Cells were pretreated with palmitic acid (PA) for 24 h, then to build hypoxia model followed by HQR-containing serum for 24 h. Related indicators were also detected. In vivo, HQR can lessen pathohistological damage and apoptosis after AMI. In addition, HQR improves blood fat levels, cardiac function, inflammatory factor, the balance of oxidation and antioxidation, as well as lessen infarction in rats with obesity after AMI. Meanwhile, HQR can diminish myocardial cell death by improving mitochondrial function via PI3K/Akt/Bad pathway activation. In vitro, HQR inhibited H9c2 cells apoptosis, improved mitochondrial function and activated the PI3K/Akt/Bad pathway, but effects can be peripeteiad by LY294002. Myocardial mitochondrial dysfunction occurs following AMI and can lead to myocardial apoptosis, which can be aggravated by obesity. HQR can relieve myocardial apoptosis by improving mitochondrial function via the PI3K/Akt/Bad pathway in rats with obesity.

3.
Environ Res ; 212(Pt C): 113284, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35504342

RESUMO

Greenhouse gas (GHG) mitigation in wastewater treatment sector is indispensable in China's carbon neutral target. As an important component of wastewater system, sludge generation is rapidly increased with the acceleration of urbanization in China. It is crucial to investigate the carbon footprint of various sludge management strategies and quantify the potential optimization of GHG reduction effect at national scale. Therefore, this study conducted a comprehensive analysis of sludge distribution and GHG profiles of various sludge systems. The overall dry sludge generation in China is 12.15 Mt, with spatial resolution at city level. Different sludge treatment options were categorized into four types: energy recovery, nutrient recovery (e.g. phosphorus and nitrogen), material valorisation (e.g. brick, biochar) and conventional disposal. With various sludge treatment options, the GHG profile of annual sludge management in China ranges from -35.86 Mt/year to 57.11 Mt/year. The best GHG mitigation can be achieved through energy recovery by co-incineration system and the greatest reduction opportunity is concentrated in highly urbanized regions, such as Yangtze River Delta, Pearl River Delta, and Beijing-Tianjin-Hebei urban agglomerations.

4.
mSystems ; : e0029722, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35491831

RESUMO

Clostridium inhabiting pit mud (PM) is one of the important bacterial populations for synthesizing flavor compounds of Chinese strong-flavor baijiu. The long-term cereal fermentation with sorghum as the main raw material creates an environment rich in starch, ethanol, and organic acids (mainly lactic acid). However, the genetic factors underpinning Clostridium's adaptation to PM remain poorly understood. Here, we performed comparative genomic analysis between 30 pit mud-associated (PMA) and 100 non-pit mud-associated (NPMA) Clostridium strains. Comparison analysis of the enrichment of KEGG pathways between PMA and NPMA Clostridium strains showed two-component system, flagellar assembly, and bacterial chemotaxis pathways related to environmental adaptation were enriched in PMA strains. The number of genes encoding alcohol dehydrogenase and l-lactate dehydrogenase in PMA Clostridium strains was significantly higher than that in NPMA, which is helpful for them to adapt to the ethanol- and lactic acid-rich environment. The analysis of carbohydrate-active enzymes demonstrated that glycoside hydrolases (GHs) was the most abundant family in all Clostridium strains, and genes encoding GH4 and GH13, involved in starch and sucrose metabolism, were enriched in PMA Clostridium. Horizontal gene transfer analysis revealed that multiple genes encoding the enzymes involved in carbohydrate and amino acid metabolism were transferred from Bacillus to Clostridium in pit mud. Most of the PMA Clostridium strains had good potential for butyric acid synthesis from ethanol, lactic acid, and starch. Collectively, this study furthers our understanding of the habitat adaptation and metabolic potential of PMA Clostridium strains. IMPORTANCE Pit mud is a typical artificial ecosystem for Chinese liquor production. Clostridium inhabiting pit mud plays essential roles in the flavor formation of strong-flavor baijiu. The relative abundance of Clostridium increased with pit mud quality, further influencing the quality of baijiu. So far, the ecological adaptation of Clostridium to a pit mud-associated lifestyle is largely unknown. Here, comparative genomic analysis of pit mud-associated (PMA) and non-pit mud-associated (NPMA) Clostridium strains was performed. We found genes related to the metabolism of starch, ethanol, and lactic acid were enriched in PMA Clostridium strains, which facilitated their adaptation to the unique brewing environment. In addition, horizontal gene transfer contributed to the adaptation of Clostridium to pit mud. Our findings provide genetic insights on PMA Clostridium strains' ecological adaptation and metabolic characteristics.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35543248

RESUMO

Acinetobacter baumannii  is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii  LPS, four Kdo-containing inner core glycans from A. baumannii  strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7- O -di- tert -butylsilylene or 5- O -benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against  A. baumannii.

6.
BMC Nephrol ; 23(1): 179, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538439

RESUMO

BACKGROUND: Tripterygium Wilfordii Hook F (TwHF) preparation has been widely used in the treatments of IgA nephropathy (IgAN) in China. However, the effectiveness and safety of the new generation of TwHF preparation, KuxXian capsule, on the treatment of IgAN remains unknown. METHODS: Here, we retrospectively describe our experience treating 55 consecutive IgAN patients with KunXian. We defined complete remission as proteinuria < 0.5 g/24 h and partial remission as proteinuria < 1 g/24 h, each also having > 50% reduction in proteinuria from baseline. RESULTS: At first follow-up after KunXian treatment (5.7 weeks, IQR 4.7-7.9), all but two patients (96%) showed a reduction in proteinuria. The overall median proteinuria decreased from 2.23 g/day at baseline to 0.94 g/day (P < 0.001) at the first follow-up. During a median follow-up of 28 weeks after KunXian administration, 25(45.5%) patients achieved complete remission, 34 (61.8%) patients achieved complete/partial remission. Of the 12 patients discontinued KunXian treatment during the follow-up, the median proteinuria was increased from 0.97 g/24 h to 2.74 g/24 h after a median of 10.9 weeks (P = 0.004). Multivariable Cox models showed that female, treatment switching from previous generation of TwHF preparation, lower initial KunXian dosage, and higher proteinuria at baseline were independently associated proteinuria remission. Of the 20 pre-menopausal females, 12 of them developed oligomenorrhea or menstrual irregularity and ten of them developed amenorrhea. CONCLUSION: KunXian is effectiveness and safety for the treatment of IgA nephropathy. Woman of childbearing age to be informed of the risk of ovarian failure after being treated with TwHF preparations.


Assuntos
Glomerulonefrite por IGA , Medicamentos de Ervas Chinesas , Feminino , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Masculino , Proteinúria/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Tripterygium
7.
Anal Chem ; 94(20): 7164-7168, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35543580

RESUMO

Exosomes are small extracellular vesicles (EVs) secreted by all cells and found in biological fluids, which can serve as minimally invasive liquid biopsies with extremely high therapeutic and diagnostic potential. Mass spectrometry (MS)-based proteomics is a powerful technique to profile and quantify the protein content in exosomes, but the current methods require laborious and time-consuming multistep sample preparation that significantly limit throughput. Herein, we report a one-pot exosome proteomics method enabled by a photocleavable surfactant, Azo, to simplify exosomal lysis, effectively extract proteins, and expedite digestion. We have applied this method to exosomes derived from isolated mammary fibroblasts and confidently identified 3466 proteins and quantified 2288 proteins using a reversed-phase liquid chromatography coupled to trapped ion mobility spectrometry (TIMS) quadrupole time-of-flight mass spectrometer. Here, 3166 (91%) of the identified proteins are annotated in the exosome/EVs databases, ExoCarta and Vesiclepedia, including important exosomal markers, CD63, PDCD6IP, and SDCBP. This method is fast, simple, and highly effective at extracting exosomal proteins with high reproducibility for deep exosomal proteome coverage. We envision that this method could be generally applicable for exosome proteomics applications in biomedical research, therapeutic interventions, and clinical diagnostics.

8.
Small ; 18(18): e2107199, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35373497

RESUMO

Na metal anode (NMA) is one of the most promising candidate materials for next-generation low-cost sodium metal batteries. However, the preferred deposition of Na metal at the anode/separator interface increases the risk of dendrite penetration of the separator, consequently, reduces safety and life of batteries with NMA. In this study, a Na deposition-regulating strategy is shown by designing a gradiently graphitized 3D carbon fiber (CF) framework as host (grad-CF), whereby Na is guided to deposit preferentially at the bottom of the anode, safely away from the separator. The obtained Na anode significantly reduces the probability of dendrite-induced short circuits. The grad-CF host enables NMA stable cycling at a high current density of 6 mA cm-2 . When the Na@grad-CF is applied as anode in full cells pared with Na3 V2 (PO4 )3 (NVP) cathode, it exhibits a reversible capacity of 73 mA h g-1 after 500 cycles with a low decay rate of 0.13%.


Assuntos
Fontes de Energia Elétrica , Sódio , Eletrodos , Íons
10.
Small ; 18(18): e2200395, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35384295

RESUMO

Carbon-based single metal atom catalysts (SACs) are being extensively investigated to improve the kinetics of the Li-S redox reaction, which is greatly important for batteries with cell-level energy densities >500 W h kg-1 . However, there are contradictory reports regarding the electrocatalytic activities of the different metal atoms and the role of the metal atom in LiS chemistry still remains unclear. This is due to the complex relationship between the catalytic behavior and the structure of carbon-based SACs. Here, the catalytic behavior and active-site geometry, oxidation state, and the electronic structure of different metal centers (Fe/Co/Ni) embedded in nitrogen-doped graphene, and having similar physicochemical characteristics, are studied. Combining X-ray absorption spectroscopy, density functional theory calculations, and electrochemical analysis, it is revealed that the coordination-geometry and oxidation state of the metal atoms are modified when interacting with sulfur species. This interaction is strongly dependent on the hybridization of metal 3d and S p-orbitals. A moderate hybridization with the Fermi level crossing the metal 3d band is more favorable for LiS redox reactions. This study thus provides a fundamental understanding of how metal atoms in SACs impact LiS redox behavior and offers new guidelines to develop highly active catalytic materials for high-performance LiS batteries.


Assuntos
Carbono , Metais , Carbono/química , Catálise , Metais/química , Nitrogênio/química , Oxirredução
11.
Plant Biotechnol J ; 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35403801

RESUMO

Grain size is one of the essential determinants of rice yield. Our previous studies revealed that ethylene plays an important role in grain-size control; however, the precise mechanism remains to be determined. Here, we report that the ethylene response factor OsERF115 functions as a key downstream regulator for ethylene-mediated grain development. OsERF115 encodes an AP2/ERF-type transcriptional factor that is specifically expressed in young spikelets and developing caryopses. Overexpression of OsERF115 significantly increases grain length, width, thickness and weight by promoting longitudinal elongation and transverse division of spikelet hull cells, as well as enhancing grain-filling activity, whereas its knockout mutations lead to the opposite effects, suggesting that OsERF115 positively regulates grain size and weight. OsERF115 transcription is strongly induced by ethylene, and OsEIL1 directly binds to the promoter to activate its expression. OsERF115 acts as a transcriptional repressor to directly or indirectly modulate a set of grain-size genes during spikelet growth and endosperm development. Importantly, haplotype analysis reveals that the SNP variations in the EIN3-binding sites of OsERF115 promoter are significantly associated with the OsERF115 expression levels and grain weight, suggesting that natural variations in the OsERF115 promoter contribute to grain-size diversity. In addition, the OsERF115 orthologues are identified only in grass species, implying a conserved and unique role in the grain development of cereal crops. Our results provide insights into the molecular mechanism of ethylene-mediated grain-size control and a potential strategy based on the OsEIL1-OsERF115-target gene regulatory module for genetic improvement of rice yield.

12.
Bioorg Chem ; 123: 105780, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35395448

RESUMO

Swietelinins A - C (1-3) and swieteliacates F - R (4-16), sixteen new limonoids and 18 known limonoids (17-34) were isolated from Swietenia macrophylla. The absolute configurations of these compounds were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. Swieteliacate J (10) is the first limonoid possessing an unusual 8ß, 9ß-epoxy ring system. All of the compounds were tested for cytotoxicity against four human tumor cell lines (SMMC-7721, SW620, A549, and A375). Compounds 10, 11, and 19 exhibited selectively moderate cytotoxicity against four tumor cell lines, especially 19 exhibited significant cytotoxic effects against A375 with IC50 an value of 9.8 µM and was more active than the positive control, dacarbazine with an IC50 value of 22.4 µM. Compound 19 effectively induced apoptosis of A375, which was associated with G2/M-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 19 significantly induced A375 cell apoptosis in a dose-dependent manner.


Assuntos
Limoninas , Melanoma , Meliaceae , Apoptose , Linhagem Celular Tumoral , Humanos , Limoninas/química , Limoninas/farmacologia , Meliaceae/química
13.
Cell Death Dis ; 13(4): 384, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35444236

RESUMO

Chronic myeloid leukemia (CML) are initiated and sustained by self-renewing malignant CD34+ stem cells. Extensive efforts have been made to reveal the metabolic signature of the leukemia stem/progenitor cells in genomic, transcriptomic, and metabolomic studies. However, very little proteomic investigation has been conducted and the mechanism regarding at what level the metabolic program was rewired remains poorly understood. Here, using label-free quantitative proteomic profiling, we compared the signature of CD34+ stem/progenitor cells collected from CML individuals with that of healthy donors and observed significant changes in the abundance of enzymes associated with aerobic central carbonate metabolic pathways. Specifically, CML stem/progenitor cells expressed increased tricarboxylic acid cycle (TCA) with decreased glycolytic proteins, accompanying by increased oxidative phosphorylation (OXPHOS) and decreased glycolysis activity. Administration of the well-known OXPHOS inhibitor metformin eradicated CML stem/progenitor cells and re-sensitized CD34+ CML cells to imatinib in vitro and in patient-derived tumor xenograft murine model. However, different from normal CD34+ cells, the abundance and activity of OXPHOS protein were both unexpectedly elevated with endoplasmic reticulum stress induced by metformin in CML CD34+ cells. The four major aberrantly expressed protein sets, in contrast, were downregulated by metformin in CML CD34+ cells. These data challenged the dependency of OXPHOS for CML CD34+ cell survival and underlined the novel mechanism of metformin. More importantly, it suggested a strong rationale for the use of tyrosine kinase inhibitors in combination with metformin in treating CML.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Metformina , Animais , Antígenos CD34/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Metformina/farmacologia , Camundongos , Células-Tronco Neoplásicas/metabolismo , Fosforilação Oxidativa , Inibidores de Proteínas Quinases/farmacologia , Proteômica
14.
Front Cardiovasc Med ; 9: 821672, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35391838

RESUMO

Backgrounds and Objectives: Drug-coated balloons (DCBs) have shown promising benefits in improving the outcomes for patients with peripheral artery disease. Several randomized clinical trials have reported that paclitaxel-coated balloon significantly reduce the rates of restenosis and the need for reintervention in comparison with regular balloon angioplasty. Due to the differences in excipients, paclitaxel dose, and coating techniques, variable clinical outcomes have been observed with different DCBs. In this study, we aimed to evaluate the safety and efficacy of a novel ZENFlow carrier-free DCB in the treatment of femoropopliteal artery occlusive disease. Methods: In this randomized controlled trial conducted at 15 sites, 192 patients with Rutherford class 3-5 were randomly assigned into two groups: drug-coated balloon group and percutaneous transluminal angioplasty group. The primary endpoint was a late lumen loss at 6 months based on blinded angiographic core laboratory evaluations, and the secondary endpoints included primary patency rate, binary restenosis, clinically driven target lesion revascularization, ankle-brachial index, Rutherford class change, and major adverse events. Results: In this multicenter trial, 93 patients received DCB angioplasty, whereas 99 patients underwent regular balloon angioplasty. The late lumen loss at 6-month follow-up was 0.50 ± 0.82 and 1.69 ± 0.87 mm in the drug-coated balloon and percutaneous transluminal angioplasty groups, respectively (p < 0.001). During the 12-month follow-up period, the drug-coated balloon group showed a significantly higher primary patency rate (54 vs. 31.3%, p = 0.009) and markedly lower rates of target vessel restenosis (22.1 vs. 64.3%, p < 0.001) and clinically driven target lesion revascularization rate (5.4 vs. 19.2%, p = 0.006) than the percutaneous transluminal angioplasty group. Compared with the percutaneous transluminal angioplasty group, the drug-coated balloon group had significant improvements in the ankle-brachial index and Rutherford class. The all-cause mortality rate was comparable, and no device-related deaths occurred in either groups. Conclusions: Balloon angioplasty using a ZENFlow carrier-free drug-coated balloon is a safe and effective treatment method for femoropopliteal artery lesions. This novel drug-coated balloon catheter achieved satisfactory early and 1-year outcomes in this trial. Clinical Trial Registration: https://clinicaltrials.gov, identifier: NCT03844724.

15.
ACS Nano ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35420784

RESUMO

With the potential to circumvent the need for scarce and cost-prohibitive platinum-based catalysts in proton-exchange membrane fuel cells, anion-exchange membrane fuel cells (AEMFCs) are emerging as alternative technologies with zero carbon emission. Numerous noble metal-free catalysts have been developed with excellent catalytic performance for cathodic oxygen reduction reaction in AEMFCs. However, the anodic catalysts for hydrogen oxidation reaction (HOR) still rely on noble metal materials. Since the kinetics of HOR in alkaline media is 2-3 orders of magnitude lower than that in acidic media, it is a major challenge to either improve the performance of noble metal catalysts or to develop high-performance noble metal-free catalysts. Additionally, the mechanisms of alkaline HOR are not yet clear and still under debate, further hampering the design of electrocatalysts. Against this backdrop, this review starts with the prevailing theories for alkaline HOR on the basis of diverse activity descriptors, i.e., hydrogen binding energy theory and bifunctional theory. The design principles and recent advances of HOR catalysts employing the aforementioned theories are then summarized. Next, the strategies and recent progress in improving the antioxidation capability of HOR catalysts, a thorny issue which has not received sufficient attention, are discussed. Moreover, the significance of correlating computational models with real catalyst structure and the electrode/electrolyte interface is further emphasized. Lastly, the remaining controversies about the alkaline HOR mechanisms as well as the challenges and possible research directions in this field are presented.

16.
Proc Natl Acad Sci U S A ; 119(15): e2120787119, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35385357

RESUMO

SignificanceWe provide transcriptomic insights into differences between pediatric and adult T cell acute lymphoblastic leukemia (T-ALL) patients through an international collaborative effort integrating RNA-sequencing data of 707 patients. Ten subtypes were identified, each characterized by distinct gene mutation profiles and dysregulated expression signatures of leukemogenic factors, and associated with T cell development stages. Adult T-ALL tends to have characteristics of early T cell precursor ALL, mostly corresponding to the mixed phenotype acute leukemia, whereas pediatric T-ALL shows a wide spectrum of aberrant molecular features, from early T cell precursor to mature T cell compartments. Our findings have important implications for disease mechanism of T-ALL that differs between pediatric and adult patients, facilitating further refined targeted therapy.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Transcriptoma , Criança , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética
17.
Acta Neurobiol Exp (Wars) ; 82(1): 96-105, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35451427

RESUMO

Studies on rodents and nonhuman primates suggest that exposure to anesthetics, particularly in the young brain, is associated with neuronal apoptosis as well as hippocampal­dependent cognitive dysfunction. Disruption of the development of dentate gyrus may play an important role in anesthetics­induced neurotoxicity. However, the anesthetics triggered molecular events in the dentate gyrus of the developing brain are poorly understood. By integrating two independent data sets obtained from miRNA­seq and mRNA­seq respectively, this study aims to profile the network of miRNA and potential target genes, as well as relevant events occurring in the dentate gyrus of isoflurane exposed 7­day­old mice. We found that a single four hours exposure to isoflurane yielded 1059 pairs of differently expressed miRNAs/target genes in the dentate gyrus. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further indicates that dysregulated miRNAs/target genes have far­reaching effects on the cellular pathophysiological events, such as cell apoptosis, axon development, and synaptic transmission. Our results would greatly broaden our functional understanding of the role of miRNA/target gene in the context of anesthetics­induced neurotoxicity.


Assuntos
Anestésicos , Isoflurano , MicroRNAs , Anestésicos/farmacologia , Animais , Giro Denteado , Hipocampo , Isoflurano/toxicidade , Camundongos , MicroRNAs/genética
18.
J Hazard Mater ; 435: 128954, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35462189

RESUMO

Zn2+ is largely discharged from many industries and poses a severe threat to the environment, making its remediation crucial. Encapsulins, proteinaceous nano-compartments, may protect cells against environmental stresses by sequestering toxic substances. To determine whether hemerythrin-containing encapsulins (cEnc) from anammox bacteria Ca. Brocadia fulgida can help cells deal with toxic substances such as Zn2+, we transferred cEnc into E.coli by molecular biology technologies for massive expression and then cultured them in media with increasing Zn2+ levels. The engineered bacteria (with cEnc) grew better and entered the apoptosis phase later, while wild bacteria showed poor survival. Furthermore, tandem mass tag-based quantitative proteomic analysis was used to reveal the underlying regulatory mechanism by which the genetically-engineered bacteria (with cEnc) adapted to Zn2+ stress. When Zn2+ was sequestered in cEnc as a transition, the engineered bacteria presented a complex network of regulatory systems against Zn2+-induced cytotoxicity, including functions related to ribosomes, sulfur metabolism, flagellar assembly, DNA repair, protein synthesis, and Zn2+ efflux. Our findings offer an effective and promising stress control strategy to enhance the Zn2+ tolerance of bacteria for Zn2+ remediation and provide a new application for encapsulins.

19.
bioRxiv ; 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35475171

RESUMO

The SARS-CoV-2 Omicron (B.1.1.529) variant possesses numerous spike (S) mutations particularly in the S receptor-binding domain (S-RBD) that significantly improve transmissibility and evasion of neutralizing antibodies. But exactly how the mutations in the Omicron variant enhance viral escape from immunological protection remains to be understood. The S-RBD remains the principal target for neutralizing antibodies and therapeutics, thus new structural insights into the Omicron S-RBD and characterization of the post-translational glycosylation changes can inform rational design of vaccines and therapeutics. Here we report the molecular variations and O-glycoform changes of the Omicron S-RBD variant as compared to wild-type (WA1/2020) and Delta (B.1.617.2) variants using high-resolution top-down mass spectrometry (MS). A novel O-glycosite (Thr376) unique to the Omicron variant is identified. Moreover, we have directly quantified the Core 1 and Core 2 O-glycan structures and characterized the O-glycoform structural heterogeneity of the three variants. Our findings reveal high resolution detail of Omicron O-glycoforms and their utilization to provide direct molecular evidence of proteoform alterations in the Omicron variant which could shed light on how this variant escapes immunological protection.

20.
Int J Clin Exp Pathol ; 15(3): 145-151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35414842

RESUMO

Cardiac hypertrophy is a common myocardial structural abnormality which may cause heart failure. Many studies have shown that cardiac hypertrophy can be induced by hyperthyroidism. Ligand-gated potassium channels have been reported to be involved in various biological processes in the cardiovascular system, such as GPCR coupled KACh and metabolism sensor KATP channel. It is unclear whether the gene expression of KACh and KATP was altered in hyperthyroid rabbit atria. We aimed to investigate the expression of KACh and KATP genes in rabbit atria in our experimental model. We established an effective hyperthyroidism-induced cardiac hypertrophy animal model through an injection of T4. H&E staining and RT-PCR were used to observe the histomorphological damages and alteration of gene expression. The results showed that the heart weight, heart rate significantly increased in T4-treated rabbits. The systolic pressure increased from 115.60 mmHg to 152.6 mmHg in T4-treated rabbits. The expression of KACh and KATP genes was decreased in the atria of hyperthyroidism-induced cardiac hypertrophied rabbits. These findings indicated that the decreased gene expression of KACh and KATP may be related to hyperthyroidism-induced cardiac hypertrophy and atrial fibrillation.

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