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1.
Fitoterapia ; 165: 105429, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36649761

RESUMO

Two previous unreported fusicoccane diterpenoids macrostines A and B, together with seven known compounds were isolated from an extract of the fungus Periconia macrospinosa WTG-10. Their structures were elucidated by detailed analysis of spectroscopic data, NMR calculations with DP4+, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or X-crystallography. Macrostines A and B showed no cytotoxicity, antimicrobial activity and inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages. Compound 9 showed moderate activity against Bacillus subtilis.

2.
Chemosphere ; 317: 137892, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36657581

RESUMO

It is still a big challenge for textile industry in improving fire resistance and reducing melt dripping with minimal loss on the physical properties of polyethylene terephthalate (PET) fabrics. In this work, a highly-effective hyperbranched flame retardant (DT) was first synthesized by ester exchange without using any organic solvent. Then, the DT foam was prepared and blade coated on PET fabric to improve the fire performance. The prepared PET fabric with only 2.7% weight gain of DT was self-extinguished and did not produce any molten dripping during the vertical flammable test. The peak heat release rate and total heat release of the PET fabric sample with 19.4% DT were decreased by 42.0% and 57.1%, respectively compared with that of the control PET. Besides, the as-prepared PET fabric sample showed better physical properties such as breaking strength, vapor permeability, air permeability, antistatic property, and softness than the control PET fabric sample. The DT foam finishing process did not involve any organic solvent and consumed less water and energy compared with conventional fabric treatments. It is expected that this work provides a facile and eco-friendly strategy for fabricating flame retardant PET fabric with excellent comprehensive performances.

3.
Molecules ; 28(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36677910

RESUMO

The important role of gasotransmitters in physiology and pathophysiology suggest employing gasotransmitters for biomedical treatment. Unfortunately, the difficulty in storage and controlled delivery of these gaseous molecules hindered the development of effective gasotransmitters-based therapies. The design of a safe, facile, and wide-scale method to delivery multiple gasotransmitters is a great challenge. Herein, we use an ultrasonic assisted preparation γ-cyclodextrin metal organic framework (γ-CD-MOF) as a broad-spectrum delivery vehicle for various gasotransmitters, such as SO2, NO, and H2S. The release rate of gasotransmitters could be tuned by modifying the γ-CD-MOF with different Pluronics. The biological relevance of the exogenous gasotransmitters produced by this method is evidenced by the DNA cleavage ability and the anti-inflammatory effects. Furthermore, the γ-CD-MOF composed of food-grade γ-CD and nontoxic metal salts shows good biocompatibility and particle size (180 nm). Therefore, γ-CD-MOF is expected to be an excellent tool for the study of co-delivery and cooperative therapy of gasotransmitters.


Assuntos
Ciclodextrinas , Gasotransmissores , Estruturas Metalorgânicas , Metais
4.
Respir Res ; 24(1): 25, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694200

RESUMO

BACKGROUND: Radiation-induced lung injury (RILI) is the most common and serious complication of chest radiotherapy. However, reported radioprotective agents usually lead to radiation resistance in tumor cells. The key to solving this problem is to distinguish between the response of tumor cells and normal lung epithelial cells to radiation damage. METHODS: RNA-Seq was used to recognize potential target of alleviating the progression of RILI as well as inhibiting tumor growth. The activation of NLRP3 inflammasome in lung epithelial cells was screened by qRT-PCR, western blotting, immunofluorescence, and ELISA. An in vivo model of RILI and in vitro conditioned culture model were constructed to evaluate the effect of NLRP3/interleukin-1ß on fibroblasts activation. ROS, ATP, and (NADP)+/NADP(H) level in lung epithelial cells was detected to explore the mechanism of NLRP3 inflammasome activation. The lung macrophages of the mice were deleted to evaluate the role of lung epithelial cells in RILI. Moreover, primary cells were extracted to validate the results obtained from cell lines. RESULTS: NLRP3 activation in epithelial cells after radiation depends on glycolysis-related reactive oxygen species accumulation. DPYSL4 is activated and acts as a negative regulator of this process. The NLRP3 inflammasome triggers interleukin-1ß secretion, which directly affects fibroblast activation, proliferation, and migration, eventually leading to lung fibrosis. CONCLUSIONS: Our study suggests that NLRP3 inflammasome activation in lung epithelial cells is essential for radiation-induced lung injury. These data strongly indicate that targeting NLRP3 may be effective in reducing radiation-induced lung injury in clinical settings.


Assuntos
Inflamassomos , Lesão Pulmonar , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-1beta/metabolismo , Lesão Pulmonar/metabolismo , NADP/metabolismo , NADP/farmacologia , Pulmão/metabolismo , Células Epiteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo
5.
Bone ; : 116680, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36702335

RESUMO

Breast cancer is the main lethal disease among females, and metastasis to lung and bone poses a serious threat to patients' life. Therefore, identification of novel molecular mediators that can potentially be exploited as therapeutic targets for treating osteolytic bone metastases is needed. A murine model of breast cancer bone metastasis was developed by injection of 4 T1.2 cells into the left ventricle and hence directly into the arterial system leading to bone. AEP (Asparagine endopeptidase) inhibitor combined with epirubicin or epirubicin alone was administered by intraperitoneal injection into animal model. The presence of bone metastatic and osteolytic lesions in bone were assessed by bioluminescent imaging and X-rays analysis. The expression of EMT (Epithelial-Mesenchymal Transition) relevant genes were examined by Western blotting. Cell migration and invasion were investigated with a transwell assay. Compound BIC-113, small molecule inhibitors of AEP, inhibited AEP enzymatic activity in breast cancer cell lines, and affected invasion and migration of cancer cells, but had no effect on cell growth. In animal model of breast cancer bone metastasis, compound BIC-113 combined with epirubicin inhibited breast cancer bone metastasis and attenuated breast cancer osteolytic lesions in bone by inhibiting osteoclast differentiation and EMT. These results indicate that compound BIC-113 combined with epirubicin has the potential to be used in breast cancer therapy by preventing bone metastasis via improving E-cadherin expression and inhibition of osteoclast formation.

6.
Dev Cell ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36696903

RESUMO

Chromothripsis is a catastrophic event of chromosomal instability that involves intensive fragmentation and rearrangements within localized chromosomal regions. However, its cause remains unclear. Here, we show that reduction and inactivation of Ran GTPase-activating protein 1 (RanGAP1) commonly occur in human osteosarcoma, which is associated with a high rate of chromothripsis. In rapidly expanding mouse osteoprogenitors, RanGAP1 deficiency causes chromothripsis in chr1q, instant inactivation of Rb1 and degradation of p53, consequent failure in DNA damage repair, and ultrafast osteosarcoma tumorigenesis. During mitosis, RanGAP1 anchors to the kinetochore, where it recruits PP1-γ to counteract the activity of the spindle-assembly checkpoint (SAC) and prevents TOP2A degradation, thus safeguarding chromatid decatenation. Loss of RanGAP1 causes SAC hyperactivation and chromatid decatenation failure. These findings demonstrate that RanGAP1 maintains mitotic chromosome integrity and that RanGAP1 loss drives tumorigenesis through its direct effects on SAC and decatenation and secondary effects on DNA damage surveillance.

7.
mSphere ; : e0051722, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622251

RESUMO

In the marine environment, surface-associated bacteria often produce an array of antimicrobial secondary metabolites, which have predominantly been perceived as competition molecules. However, they may also affect other hallmarks of surface-associated living, such as motility and biofilm formation. Here, we investigate the ecological significance of an antibiotic secondary metabolite, tropodithietic acid (TDA), in the producing bacterium, Phaeobacter piscinae S26. We constructed a markerless in-frame deletion mutant deficient in TDA biosynthesis, S26ΔtdaB. Molecular networking demonstrated that other chemical sulfur-containing features, likely related to TDA, were also altered in the secondary metabolome. We found several changes in the physiology of the TDA-deficient mutant, ΔtdaB, compared to the wild type. Growth of the two strains was similar; however, ΔtdaB cells were shorter and more motile. Transcriptome and proteome profiling revealed an increase in gene expression and protein abundance related to a type IV secretion system, and to a prophage, and a gene transfer agent in ΔtdaB. All these systems may contribute to horizontal gene transfer (HGT), which may facilitate adaptation to novel niches. We speculate that once a TDA-producing population has been established in a new niche, the accumulation of TDA acts as a signal of successful colonization, prompting a switch to a sessile lifestyle. This would lead to a decrease in motility and the rate of HGT, while filamentous cells could form the base of a biofilm. In addition, the antibiotic properties of TDA may inhibit invading competing microorganisms. This points to a role of TDA in coordinating colonization and adaptation. IMPORTANCE Despite the broad clinical usage of microbial secondary metabolites with antibiotic activity, little is known about their role in natural microbiomes. Here, we studied the effect of production of the antibiotic tropodithietic acid (TDA) on the producing strain, Phaeobacter piscinae S26, a member of the Roseobacter group. We show that TDA affects several phenotypes of the producing strain, including motility, cell morphology, metal metabolism, and three horizontal gene transfer systems: a prophage, a type IV secretion system, and a gene transfer agent. Together, this indicates that TDA participates in coordinating the colonization process of the producer. TDA is thus an example of a multifunctional secondary metabolite that can mediate complex interactions in microbial communities. This work broadens our understanding of the ecological role that secondary metabolites have in microbial community dynamics.

8.
ACS Biomater Sci Eng ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622761

RESUMO

Uncontrolled bleeding is one of the most important causes threatening human health, but quick hemostasis remains a challenge. We prepared porous cryogels with poly ß-cyclodextrin (Pß-CD) and quaternary ammoniated chitosan (QCs). Pß-CD acts as a "water-grabbing agent" to assist QCs' ability to absorb and concentrate blood rapidly. The rat-tail amputation model and liver injury model exhibited that cryogels had excellent hemostatic performance. Moreover, cryogels showed good antibacterial activity and biocompatibility. Therefore, these cryogels can be used as potential hemostatic materials.

9.
J Anim Sci Biotechnol ; 14(1): 15, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670458

RESUMO

BACKGROUND: Anthocyanins (AC) showed positive effects on improving the intestinal health and alleviating intestinal pathogen infections, therefore, an experiment was conducted to explore the protective effects of supplemented AC on Salmonella-infected chickens. METHODS: A total of 240 hatchling chickens were randomly allocated to 4 treatments, each with 6 replicates. Birds were fed a basal diet supplemented with 0 (CON, and ST), 100 (ACL) and 400 (ACH) mg/kg of AC for d 60, and orally challenged with PBS (CON) or 109 CFU/bird (ST, ACL, ACH) Salmonella Typhimurium at d 14 and 16. RESULTS: (1) Compared with birds in ST, AC supplementation increased the body weight (BW) at d 18 and the average daily gain (ADG) from d 1 to 18 of the Salmonella-infected chickens (P < 0.05); (2) AC decreased the number of Salmonella cells in the liver and spleen, the contents of NO in plasma and inflammatory cytokines in ileal mucosa of Salmonella-infected chickens (P < 0.05); (3) Salmonella infection decreased the ileal villi height, villi height to crypt depth (V/C), and the expression of zonulaoccludins-1 (ZO-1), claudin-1, occludin, and mucin 2 (MUC2) in ileal mucosa. AC supplementation relieved these adverse effects, and decreased ileal crypt depth (P < 0.05); (4) In cecal microbiota of Salmonella-infected chickens, AC increased (P < 0.05) the alpha-diversity (Chao1, Pd, Shannon and Sobs indexes) and the relative abundance of Firmicutes, and decreased (P < 0.05) the relative abundance of Proteobacteria and Bacteroidota and the enrichment of drug antimicrobial resistance, infectious bacterial disease, and immune disease pathways. CONCLUSIONS: Dietary AC protected chicken against Salmonella infection via inhibiting the Salmonella colonization in liver and spleen, suppressing secretion of inflammatory cytokines, up-regulating the expression of ileal barrier-related genes, and ameliorating the composition and function of cecal microbes. Under conditions here used, 100 mg/kg bilberry anthocyanin was recommended.

10.
Adv Sci (Weinh) ; : e2204826, 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36683247

RESUMO

Accumulation of obsolete biomolecules can accelerate cell senescence and organism aging. The two efficient intracellular systems, namely the ubiquitin-proteasome system and the autophagy-lysosome system, play important roles in dealing with cellular wastes. However, how multicellular organisms orchestrate the processing of obsolete molecules and delay aging remains unclear. Herein, it is shown that prevention of exosome release by GW4869 or Rab27a-/- accelerated senescence in various cells and mice, while stimulating exosome release by nutrient restriction delays aging. Interestingly, exosomes isolate from serum-deprived cells or diet-restricted human plasma, enriched with garbage biomolecules, including misfolded proteins, oxidized lipids, and proteins. These cellular wastes can be englobed by macrophages, eventually, for disintegration in vivo. Inhibition of nutrient-sensing mTORC1 signaling increases exosome release and delays senescence, while constitutive activation of mTORC1 reduces exosome secretion and exacerbates senescence in vitro and in mice. Notably, inhibition of exosome release attenuates nutrient restriction- or rapamycin-delayed senescence, supporting a key role for exosome secretion in this process. This study reveals a potential mechanism by which stimulated exosome release delays aging in multicellular organisms, by orchestrating the harmful biomolecules disposal via exosomes and macrophages.

11.
Plant Physiol Biochem ; 195: 144-154, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36638604

RESUMO

Nitrogen (N) is an essential nutrient for plant growth and development. Dioecious plants, especially perennial plants, are often faced with a shortage of N supply in nature. Poplar is one of the most important dioecious and perennials species. Due to the different ecological functions, female and male poplars adopt different adaptation strategies to N limitation. However, the regulation in epigenetic mechanism is poorly understood on sexes. Here, the integrative analysis of whole-genome bisulfite sequencing (WGBS), RNA sequencing, and plant physiological analysis on female and male Populus cathayana were performed. We found that N deficiency reprograms methylation in both sexes, and the CG and CHH methylation types played critical roles in female and male poplars, respectively. Induced by DNA methylation, N-deficient males had a stronger phenylpropanoid synthesis pathway and less anthocyanin accumulation than females, which not only strengthened the N cycle but also reduced the defense cost of males. In addition, compared with male poplars, females accumulated more starch to expend excess energy under N limited condition. Additionally, DNA methylation also mediated hormone signalling involved in anthocyanin synthesis and starch metabolism. Therefore, our study reveals new molecular evidences that male poplars are more tolerant to N deficiency than females, which provides a reference for ecological adaptability of forest trees.

12.
Evolution ; 77(1): 155-165, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36622778

RESUMO

Character displacement is considered a key driver of evolutionary divergence and adaptation. Few examples of reproductive character displacement with a narrow contact zone have been identified. We examined the genetic structure, body length variation, and genital morphology in the contact and allopatric areas of Platycerus takakuwai and P. viridicuprus to investigate character displacement and gene flow. In the contact area, the species identifications based on endophallic morphology and nuclear genes were identical, whereas mitochondrial gene did not exhibit a perfect match. This incongruence suggests that interspecific hybridization followed by the mitochondrial introgression has likely occurred during historical secondary contact. The species are essentially parapatric in contact area, co-occurring at only one of 28 adjacent sampling sites despite being flying species, and no hybrids based on morphology have been found, which indicates a strongly exclusive distribution. The results showed that the body length variation was consistent with character displacement after controlling for variation along geographic and environmental gradients. Interspecific body size differentiation may have evolved to reduce incorrect mating between the species. Moreover, selective pressure caused by reproductive interference between the two species may act on body size that have likely resulted in strongly exclusive distribution at the edge of their ranges.


Assuntos
Besouros , Animais , Evolução Biológica , Reprodução , Hibridização Genética , Tamanho Corporal
13.
Chem Commun (Camb) ; 59(8): 1094-1097, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36625183

RESUMO

Here, we report the simple construction of a supramolecular glycomaterial for the targeted delivery of antibiotics to P. aeruginosa in a photothermally-controlled manner. A galactose-pyrene conjugate (Gal-pyr) was developed to self-assemble with graphene nanoribbon-based nanowires via π-π stacking to produce a supramolecular glycomaterial, which exhibits a 1250-fold enhanced binding avidity toward a galactose-selective lectin when compared to Gal-pyr. The as-prepared glycomaterial when loaded with an antibiotic that acts as an inhibitor of the bacterial folic acid biosynthetic pathway eradicated P. aeruginosa-derived biofilms under near-infrared light irradiation due to the strong photothermal effect of the nanowires accelerating antibiotic release.


Assuntos
Grafite , Nanotubos de Carbono , Grafite/química , Antibacterianos , Galactose , Fototerapia
14.
Dalton Trans ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633156

RESUMO

Based on the bis-ß-diketonate-Dy2 metalloligand [Dy2(pbth)4]·2Et3N (1, pbth = (3z,3'z)-4,4'-(1,3-phenylene)bis(1,1,1-trifluoro-4-hydroxybut-3-en-2-one)), six dinuclear complexes with eight-coordinated geometries were synthesized solvothermally through different capping N-donor coligands or solvent systems. These complexes are namely [Dy2(pbth)3(Phen)2]·2C2H5OH (2), [Dy2(pbth)3(BPhen)2]·2C2H5OH (3), [Dy2(pbth)3(Dppz)2]·2C2H5OH (4), [Dy2(pbth)3(Dppz)2]·2CH3OH (4a), [Dy2(pbth)3(4-Dmbp)2]·CH3OH·C2H5OH (5) and [Dy2(pbth)3(5-Dmbp)2]·CH3OH (6) (Phen = 1,10-phenanthroline, BPhen = 4,7-diphenyl-1,10-phenanthroline, dppz = dipyrido [3,2-a:2',3'-c] phenazine, 4-Dmbp = 4,4'-dimethyl-2,2'-bipyridyl, 5-Dmbp = 5,5'-dimethyl-2,2'-bipyridyl), respectively. In the synthetic processes of 2-6, one of four bis-ß-diketonate ligands in the metalloligand is replaced by two capping N-donor coligands. The coordination geometries, metal distances and M-L-M torsion angles of the synthesized complexes are perceptibly fine-tuned by the modification of the capping N-donor coligands or the latticed solvent molecules. Systematic magnetic investigations indicate the different magnetic relaxation dynamics of 1-6. Complex 1 displays no characteristics of single-molecule magnets (SMMs), while complexes 2-6 exhibit SMM behaviours in the absence of a static magnetic field. Complexes 2 and 3 possess effective energy barriers (Ueff) of 110.18 (2) K and 133.21 (4) K, respectively. Theoretical analysis based on ab initio calculation provides some interpretations of experimental observation.

15.
J Crohns Colitis ; 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36682023

RESUMO

BACKGROUND AND AIMS: Ulcerative colitis [UC] is a complex heterogeneous disease. This study aims to reveal the underlying molecular features of UC using genome-scale transcriptomes of patients with UC and develop and validate a novel stratification scheme. METHODS: A normalized compendium was created using colon tissue samples [455 patients with UC and 147 healthy controls [HCs]], covering genes from 10 microarray datasets. Up-regulated differentially expressed genes [DEGs] were subjected to functional network analysis, wherein samples were grouped using unsupervised clustering. Additionally, the robustness of subclustering was further assessed by two RNA sequencing datasets [100 patients with UC and 16 HCs]. Finally, the Xgboost classifier was applied to the independent datasets to evaluate the efficacy of different biologics in patients with UC. RESULTS: Based on 267 up-regulated DEGs of the transcript profiles, UC patients were classified into three subtypes [subtype A-C] with distinct molecular and cellular signatures. Epithelial activation-related pathways were significantly enriched in subtype A [named epithelial proliferation], whereas subtype C was characterized as the immune activation subtype with prominent immune cells and proinflammatory signatures. Subtype B [named mixed] was modestly activated in all the signalling pathways. Notably, subtype A showed a stronger association with the superior response of biologics such as golimumab, infliximab, vedolizumab and ustekinumab compared to subtype C. CONCLUSIONS: We conducted a deep stratification of mucosal tissue using the most comprehensive microarray and RNA sequencing data, providing critical insights into pathophysiological features of UC, which could serve as a template for stratified treatment approaches.

16.
Opt Express ; 31(1): 442-451, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36606978

RESUMO

We theoretically present the waveform controls of terahertz (THz) radiations generated from homogeneous and rippled plasma within inhomogeneous external electrostatic field. The Particle-in-cell (PIC) simulations is implemented to demonstrate generation and controllability of three types of THz pulses: single frequency THz pulse in homogeneous plasma, broadband THz pulse and dual frequency THz pulse in rippled plasma. The single frequency THz pulse can be tuned via shifting the knob of electron density of homogeneous plasma. Waveform of broadband THz pulse can be regulated into an envelope-like shape by varying amplitude of electron density of rippled plasma. The two center frequencies' interval of dual frequency THz pulse can be controlled by wave numbers of density distribution of rippled plasma. This work provides a potential means to generate the dual frequency THz pulses with two harmonic frequencies (ω+Ωω, Ω=2) or incommensurate frequencies (ω+Ωω, Ω=1.7,1.8, 2.2…).

17.
Artigo em Inglês | MEDLINE | ID: mdl-36656379

RESUMO

PURPOSE: Oral squamous cell carcinomas (OSCCs) are primary head and neck malignant tumours with a high incidence and mortality. However, the molecular mechanisms involved in OSCC tumorigenesis are not fully understood. METHODS: OSCC and paired para-carcinoma samples were collected and used to perform multi-omics study. Transcriptomic analysis was used to reveal significant alterations in inflammatory and immune processes in OSCC. Ingenuity Pathway Analysis (IPA) combined with the LASSO Cox algorithm was used to identify and optimize a crucial gene signature. Metabolomics analysis was performed to identify the important metabolites which linked to the crucial gene signature. The public data TCGA-HNSCC cohort was used to perform the multiple bioinformatic analysis. RESULTS: These findings identified a FN1-mediated crucial network that was composed of immune-relevant genes (FN1, ACP5, CCL5, COL1A1, THBS1, BCAT1, PLAU, IGF2BP3, TNF, CSF2, CXCL1 and CXCL5) associated with immune infiltration and influences the tumour microenvironment, which may contribute to OSCC tumorigenesis and progression. Moreover, we integrated the relevant genes with altered metabolites identified by metabolic profiling and identified 7 crucial metabolites (Glu-Glu-Lys, Ser-Ala, Ser-Ala, N-(octadecanoyl) sphing-4-enine-1-phosphocholine, N-methylnicotinamide, pyrrhoxanthinol and xanthine) as potential downstream targets of the FN1-associated gene signature in OSCC. Importantly, FN1 expression is positively correlated with immune infiltration levels in HNSCC, which was confirmed at the single-cell level. CONCLUSIONS: Overall, these results revealed the differential genetic and metabolic patterns associated with OSCC tumorigenesis and identified an essential molecular network that plays an oncogenic role in OSCC by affecting amino acid and purine metabolism. These genes and metabolites might, therefore, serve as predictive biomarkers of survival outcomes and potential targets for therapeutic intervention in OSCC.

18.
Proc Natl Acad Sci U S A ; 120(4): e2214175120, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36649419

RESUMO

Copper is distinctive in electrocatalyzing reduction of CO2 into various energy-dense forms, but it often suffers from limited product selectivity including ethanol in competition with ethylene. Here, we describe systematically designed, bimetallic electrocatalysts based on copper/gold heterojunctions with a faradaic efficiency toward ethanol of 60% at currents in excess of 500 mA cm-2. In the modified catalyst, the ratio of ethanol to ethylene is enhanced by a factor of 200 compared to copper catalysts. Analysis by ATR-IR measurements under operating conditions, and by computational simulations, suggests that reduction of CO2 at the copper/gold heterojunction is dominated by generation of the intermediate OCCOH*. The latter is a key contributor in the overall, asymmetrical electrohydrogenation of CO2 giving ethanol rather than ethylene.

19.
Cancer Sci ; 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36642785

RESUMO

Radioresistance remains a major obstacle to efficacious radiotherapy in non-small cell lung cancer (NSCLC). DNA replication proteins are novel targets for radiosensitizers. POLQ is a DNA polymerase involved in DNA damage response and repair. We found that POLQ is overexpressed in NSCLC and is clinically correlated with high tumor stage, poor prognosis, increased tumor mutational burden, and ALK and TP53 mutation status; POLQ inhibition impaired lung tumorigenesis. Notably, POLQ expression was higher in radioresistant lung cancer cells than in wild type cancer cells. Moreover, POLQ expression was further increased in radioresistant cells after radiation. Enhanced radioresistance is through a prolonged G2/M phase and faster repair of DNA damage, leading to reduced radiation-induced apoptosis. Novobiocin (NVB), a POLQ inhibitor, specifically targeted cancer cells. Genetic knockdown of POLQ or pharmacological inhibition by NVB decreased radioresistance in lung adenocarcinoma while causing little toxicity to normal pulmonary epithelial cells. In conclusion, POLQ is a promising and practical cancer-specific target to impair tumorigenesis and enhance radiosensitivity in NSCLC.

20.
Clin Proteomics ; 20(1): 2, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609216

RESUMO

BACKGROUND: Spermatozoa have the task of delivering an intact paternal genome to the oocyte and supporting successful embryo development. The detection of sperm DNA fragmentation (SDF) has been emerging as a complementary test to conventional semen analysis for male infertility evaluation, but the mechanism leading to SDF and its impact on assisted reproduction remain unclear. Therefore, the study identified and analyzed the differentially expressed proteins of sperm with high and low SDF. METHODS: Semen samples from men attended the infertility clinic during June 2020 and August 2020 were analyzed, and sperm DNA fragmentation index (DFI) was detected by the sperm chromatin structure assay. Semen samples with low DFI (< 30%, control group) and high DFI (≥ 30%, experimental group) were optimized by density gradient centrifugation (DGC), and the differentially expressed proteins of obtained sperm were identified by the Sequential Window Acquisition of All Theoretical Mass Spectra Mass Spectrometry (SWATH-MS) and performed GO and KEGG analysis. RESULTS: A total of 2186 proteins were identified and 1591 proteins were quantified, of which 252 proteins were identified as differentially expressed proteins, including 124 upregulated and 128 downregulated. These differentially expressed proteins were involved in metabolic pathways, replication/recombination/repair, acrosomal vesicles, kinase regulators, fertilization, tyrosine metabolism, etc. Western blotting results showed that the expression levels of RAD23B and DFFA proteins and the levels of posttranslational ubiquitination and acetylation modifications in the experimental group were significantly higher than those in the control group, which was consistent with the results of proteomics analysis. CONCLUSIONS: Proteomic markers of sperm with high DNA fragmentation can be identified by the SWATH-MS and bioinformatic analysis, and new protein markers and posttranslational modifications related to sperm DNA damage are expected to be intensively explored. Our findings may improve our understanding of the basic molecular mechanism of sperm DNA damage.

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