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1.
Nature ; 586(7830): 572-577, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32726802

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.


Assuntos
Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/imunologia , COVID-19 , Vacinas contra COVID-19 , Humanos , Macaca mulatta/imunologia , Macaca mulatta/virologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Modelos Animais , Modelos Moleculares , Domínios Proteicos , SARS-CoV-2 , Soro/imunologia , Baço/citologia , Baço/imunologia , Linfócitos T/imunologia , Vacinação
2.
Arch Toxicol ; 98(5): 1499-1513, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38480537

RESUMO

Cell senescence genes play a vital role in the pathogenesis of colorectal cancer, a process that may involve the triggering of genetic variations and reversible phenotypes caused by epigenetic modifications. However, the specific regulatory mechanisms remain unclear. Using CellAge and The Cancer Genome Atlas databases and in-house RNA-seq data, DNA methylation-modified cellular senescence genes (DMCSGs) were validated by Support Vector Machine and correlation analyses. In 1150 cases and 1342 controls, we identified colorectal cancer risk variants in DMCSGs. The regulatory effects of gene, variant, and DNA methylation were explored through dual-luciferase and 5-azacytidine treatment experiments, complemented by multiple database analyses. Biological functions of key gene were evaluated via cell proliferation assays, SA-ß-gal staining, senescence marker detection, and immune infiltration analyses. The genetic variant rs4558926 in the downstream of TACC3 was significantly associated with colorectal cancer risk (OR = 1.35, P = 3.22 × 10-4). TACC3 mRNA expression increased due to rs4558926 C > G and decreased DNA methylation levels. The CpG sites in the TACC3 promoter region were regulated by rs4558926. TACC3 knockdown decreased proliferation and senescence in colorectal cancer cells. In addition, subjects with high-TACC3 expression presented an immunosuppressive microenvironment. These findings provide insights into the involvement of genetic variants of cellular senescence genes in the development and progression of colorectal cancer.


Assuntos
Neoplasias Colorretais , Metilação de DNA , Epigênese Genética , Proteínas Associadas aos Microtúbulos , Humanos , Proteínas de Ciclo Celular/genética , Senescência Celular/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ilhas de CpG , DNA , Regulação Neoplásica da Expressão Gênica , Proteínas Associadas aos Microtúbulos/genética , Microambiente Tumoral
3.
Luminescence ; 39(10): e4909, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39344171

RESUMO

As a heavy metal ion, excessive aluminum ions pose a serious threat to human health and the ecological environment. Developing a simple, efficient, and fast detection method to detect the content of aluminum ions is of great significance, especially for ensuring human health and ecological safety. Herein, the mixed rare earth metal-organic framework (Ce0.74Eu0.26TPTC and Ce0.62Eu0.38TPTC) were prepared based on simple ligand 1,1':4',1″-Terphenyl-2',4,4″,5'-tetracarboxylic acid (H4TPTC). The Ce0.74Eu0.26TPTC and Ce0.62Eu0.38TPTC have dual luminescence centers, which can be used as ratio fluorescent probes to detect Al3+ ions, making the detection results more accurate and reliable. Therefore, this work can promote the further development of rare earth-based MOFs in the detection of heavy metal ions.


Assuntos
Alumínio , Cério , Európio , Estruturas Metalorgânicas , Alumínio/análise , Alumínio/química , Estruturas Metalorgânicas/química , Cério/química , Európio/química , Íons/análise , Corantes Fluorescentes/química , Espectrometria de Fluorescência , Medições Luminescentes , Estrutura Molecular
4.
Funct Integr Genomics ; 23(4): 316, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37789099

RESUMO

Immunogenic cell death (ICD), a type of cell death that activates the tumor-specific immune response and thus exerts anti-tumor effects, is an emerging target in tumor therapy, but research on ICD-related genes (ICDGs) in colorectal cancer (CRC) remains limited. This study aimed to identify the CRC-specific ICDGs and explore their potential roles. Through RNA sequencing for tissue samples from CRC patients and integration with The Cancer Genome Atlas (TCGA) data, we identified 33 differentially expressed ICDGs in CRC. We defined the ICD score based on these genes in single-cell data, where a high score indicated an immune-active microenvironment. Additionally, molecular subtypes identified in bulk RNA data showed distinct immune landscapes. The ICD-related signature constructed with machine learning effectively distinguished patients' prognosis. The summary data-based Mendelian randomization (SMR) and colocalization analysis prioritized CFLAR for its positive association with CRC risk. Molecular docking revealed its stable binding with chemotherapeutic drugs like irinotecan. Furthermore, experimental validation confirmed CFLAR overexpression in CRC samples, and its knockdown inhibited tumor cell proliferation. Overall, this study expands the understanding of the potential roles and mechanisms of ICDGs in CRC and highlights CFLAR as a promising target for CRC.


Assuntos
Neoplasias Colorretais , Morte Celular Imunogênica , Humanos , Análise da Randomização Mendeliana , Simulação de Acoplamento Molecular , Transcriptoma , Neoplasias Colorretais/genética , Microambiente Tumoral
5.
Respir Res ; 24(1): 154, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37301835

RESUMO

BACKGROUND: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most life-threatening diseases in the intensive care unit with high mortality and morbidity. Ferroptosis is a newly discovered immune related cell death that is associated with various lung diseases. However, the role of immune-mediated ferroptosis in ALI/ARDS has not been elucidated. METHOD: We analyzed two Gene Expression Omnibus (GEO) datasets (GSE2411 and GSE109913) and extracted characteristic ferroptosis-related genes (FRGs) between the control and ALI groups through bioinformatic analysis. Then, we prospectively collected bronchoalveolar lavage fluid (BALF) from patients with ARDS and verified the expression of characteristic FRGs. Lastly, we constructed the ALI/ARDS model induced by LPS and isolated the primary neutrophils of mice. Erastin, an ferroptosis inducer, was used at the cellular level to verify the effect of neutrophils on ferroptosis in lung epithelium cells. RESULT: We identified three characteristic FRGs, Cp, Slc39a14 and Slc7a11, by analyzing two gene expression profiling datasets. Immune infiltration analysis showed that the three characteristic genes were significantly positively correlated with the infiltration levels of neutrophils. We collected BALF from 59 ARDS patients to verify the expression of Cp, Slc7a11 and Slc39a14 in humans. The results showed that Cp was elevated in patients with severe ARDS (p = 0.019), Slc7a11 was significantly elevated in patients with moderate ARDS (p = 0.021) relative to patients with mild ARDS. The levels of neutrophils in the peripheral blood of ARDS patients were positively correlated with the expression levels of Slc7a11 (Pearson's R2 = 0.086, p = 0.033). Three characteristic FRGs were significantly activated after the onset of ferroptosis (6 h) early in LPS induced ALI model, and that ferroptosis was alleviated after the organism compensated within 12 to 48 h. We extracted primary activated neutrophils from mice and co-cultured them with MLE-12 in transwell, Slc7a11, Cp and Slc39a14 in MLE-12 cells were significantly upregulated as the number of neutrophils increased. The results showed that neutrophil infiltration alleviated erastin-induced MDA accumulation, GSH depletion, and divalent iron accumulation, accompanied by upregulation of Slc7a11 and Gpx4, implying the existence of a compensatory effect of lipid oxidation in neutrophils after acute lung injury in the organism. CONCLUSION: We identified three immune-mediated ferroptosis genes, namely, Cp, Slc7a11 and Slc39a14, which possibly regulated by neutrophils during the development of ALI, and their pathways may be involved in anti-oxidative stress and anti-lipid metabolism. Thus, the present study contributes to the understanding of ALI/ARDS and provide novel targets for future immunotherapeutic.


Assuntos
Lesão Pulmonar Aguda , Ferroptose , Síndrome do Desconforto Respiratório , Humanos , Animais , Camundongos , Ferroptose/genética , Lipopolissacarídeos , Pulmão/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo
6.
Ann Hematol ; 102(12): 3431-3444, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37550503

RESUMO

To investigate the possible risk factors for death at post-treatment in children with acute lymphoblastic leukemia (ALL). A multivariate competing risk analysis was performed to retrospectively analyze the data of children with ALL who died after treatment with CCCG-ALL-2015 in China and to determine the possible risk factors for death at post-treatment in children with ALL. Age at the first diagnosis of ≥10 years; final risk level of high-risk; D19 minimal residual disease (MRD) (≥0.01%) and D46 MRD (≥0.01%); genetic abnormalities, such as KMT2A-rearrangement, c-Myc rearrangement, and PDGFRB rearrangement; and the presence of CNS3 (all P values, <0.05) were identified as independent risk factors, whereas the risk level at the first diagnosis of low-risk (LR) and ETV6::RUNX1 positivity was considered as independent protective factors of death in children with ALL. Among the 471 cases of death, 45 cases were treated with CCCG-ALL-2015 only, and 163 (34.61%) were treatment-related, with 62.42% due to severe infections. 55.83% of treatment-related mortality (TRM) occurred in the early phase of treatment (induction phase). TRM has a significant impact on the overall survival of pediatric patients with ALL. Moreover, the CCCG-ALL-2015 regimen has a better safety profile for treating children with ALL, with rates close to those in developed countries (registration number: ChiCTR-IPR-14005706; date of registration: June 4, 2014).


Assuntos
População do Leste Asiático , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Causas de Morte , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
7.
J Chem Phys ; 158(6): 064105, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36792513

RESUMO

Utilizing localized orbitals, local correlation theory can reduce the unphysically high system-size scaling of post-Hartree-Fock (post-HF) methods to linear scaling in insulating molecules. The sparsity of the four-index electron repulsion integral (ERI) tensor is central to achieving this reduction. For second-order Møller-Plesset theory (MP2), one of the simplest post-HF methods, only the (ia|jb) ERIs are needed, coupling occupied orbitals i, j and virtuals a, b. In this paper, we compare the numerical sparsity (called the "ragged list") and two other approaches revealing the low-rank sparsity of the ERI. The ragged list requires only one set of (localized) virtual orbitals, and we find that the orthogonal valence virtual-hard virtual set of virtuals originally proposed by Subotnik et al. gives the sparsest ERI tensor. To further compress the ERI tensor, the pair natural orbital (PNO) type representation uses different sets of virtual orbitals for different occupied orbital pairs, while the occupied-specific virtual (OSV) approach uses different virtuals for each occupied orbital. Our results indicate that while the low-rank PNO representation achieves significant rank reduction, it also requires more memory than the ragged list. The OSV approach requires similar memory to that of the ragged list, but it involves greater algorithmic complexity. An approximation (called the "fixed sparsity pattern") for solving the local MP2 equations using the numerically sparse ERI tensor is proposed and tested to be sufficiently accurate and to have highly controllable error. A low-scaling local MP2 algorithm based on the ragged list and the fixed sparsity pattern is therefore promising.

8.
Langenbecks Arch Surg ; 408(1): 289, 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37515648

RESUMO

OBJECTIVES: Laparoscopic resection for rectal cancer is currently the predominant treatment modality for rectal tumors, with an ongoing focus on reducing the incidence of postoperative complications. In an effort to decrease the occurrence of anastomotic leakage, two additional steps worth considering are reinforcing the anastomosis with a barbed suture and retaining an anal drain as part of the procedure. The results of the operation were analyzed by comparing them to cases where the anastomosis was performed with a stapler alone. METHODS: This study retrospectively analyzed patients who underwent laparoscopic radical rectal cancer surgery between July 2020 and March 2023. The patients were categorized into three cohorts based on the postoperative management following instrumented anastomosis: cohort A, the instrumented anastomosis alone group; cohort B, the reinforced suture group; and cohort C, the reinforced suture and indwelling transanal drainage tube group. Propensity score matching was performed twice in a 1:1 ratio, comparing cohort B to cohort A and cohort C to cohort B. The objective was to compare the benefits and drawbacks among the different groups in terms of operative time, postoperative outcomes and operative costs. RESULTS: 529 patients with laparoscopic resection for rectal cancer were eligible for inclusion. the instrumented anastomosis alone group, reinforced suture group and the reinforced suture and indwelling transanal drainage tube group were performed in 205 patients, 198 patients and 126 patients, respectively. Cohort A and Cohort B differed in three variables after PSM: total operative time (p = 0.018), postoperative hospital stay (p < 0.001) and incidence of anastomotic leakage (p = 0.038). Cohort B had a longer total operative time, shorter postoperative hospital stay and a lower incidence of anastomotic leakage. Similarly, cohort C had less postoperative drainage (P = 0.01) and a longer postoperative hospital stay (P = 0.003) when cohort B and cohort C were matched for propensity scores. There was no significant difference in the cost of surgery between the three cohorts. CONCLUSIONS: The incorporation of barbed suture reinforcement significantly reduces the occurrence of postoperative anastomotic leakage in rectal cancer surgeries. On the other hand, although trans-anal drainage was used as an additional measure to the reinforcement suture of the anastomosis, the utilization of trans-anal drainage tubes does not demonstrate a significant improvement in surgical outcomes.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Anastomose Cirúrgica/métodos , Drenagem/métodos , Laparoscopia/efeitos adversos , Suturas/efeitos adversos
9.
J Virol ; 95(8)2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33472935

RESUMO

With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for Pseudomonas aeruginosa by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of P. aeruginosa with multi-drug resistance (MDR) both in vitro and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments.IMPORTANCE Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multi-drug resistant (MDR) Pseudomonas aeruginosa, and antibacterial capacity both in vitro and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, a mucoid phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria in vitro but also significantly reduce the infection symptom and disease progression in vivo, including lowered bug burdens, inflammatory responses and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR P. aeruginosa.

11.
Bioorg Med Chem Lett ; 41: 127956, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33744439

RESUMO

The production of ß-lactamases represents the main cause of resistance to clinically important ß-lactam antibiotics. Boron containing compounds have been demonstrated as promising broad-spectrum ß-lactamase inhibitors to combat ß-lactam resistance. Here we report a series of 3-aryl substituted benzoxaborole derivatives, which manifested broad-spectrum inhibition to representative serine-ß-lactamases (SBLs) and metallo-ß-lactamases (MBLs). The most potent inhibitor 9f displayed an IC50 value of 86 nM to KPC-2 SBL and micromolar inhibitory activity towards other tested enzymes. Cell-based assays further revealed that 9f was able to significantly reduce the MICs of meropenem in clinically isolated KPC-2-producing bacterial strains and it showed no apparent toxicity in HEK293T cells.


Assuntos
Compostos de Boro/farmacologia , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/farmacologia , Sítios de Ligação , Compostos de Boro/síntese química , Compostos de Boro/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Células HEK293 , Humanos , Concentração Inibidora 50 , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/metabolismo , Meropeném/farmacologia , Modelos Moleculares , Estrutura Molecular , Conformação Proteica , Inibidores de beta-Lactamases/química
12.
Antimicrob Agents Chemother ; 64(10)2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32718961

RESUMO

This study aimed to evaluate the antimicrobial activity of the novel monosulfactam 0073 against multidrug-resistant Gram-negative bacteria in vitro and in vivo and to characterize the mechanisms underlying 0073 activity. The in vitro activities of 0073, aztreonam, and the combination with avibactam were assessed by MIC and time-kill assays. The safety of 0073 was evaluated using 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and acute toxicity assays. Murine thigh infection and pneumonia models were employed to define in vivo efficacy. A penicillin-binding protein (PBP) competition assay and confocal microscopy were conducted. The inhibitory action of 0073 against ß-lactamases was evaluated by the half-maximal inhibitory concentration (IC50), and resistance development was evaluated via serial passage. The monosulfactam 0073 showed promising antimicrobial activity against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii isolates producing metallo-ß-lactamases (MBLs) and serine ß-lactamases. In preliminary experiments, compound 0073 exhibited safety both in vitro and in vivo In the murine thigh infection model and the pneumonia models in which infection was induced by P. aeruginosa and Klebsiella pneumoniae, 0073 significantly reduced the bacterial burden. Compound 0073 targeted several PBPs and exerted inhibitory effects against some serine ß-lactamases. Finally, 0073 showed a reduced propensity for resistance selection compared with that of aztreonam. The novel monosulfactam 0073 exhibited increased activity against ß-lactamase-producing Gram-negative organisms compared with the activity of aztreonam and showed good safety profiles both in vitro and in vivo The underlying mechanisms may be attributed to the affinity of 0073 for several PBPs and its inhibitory activity against some serine ß-lactamases. These data indicate that 0073 represents a potential treatment for infections caused by ß-lactamase-producing multidrug-resistant bacteria.


Assuntos
Antibacterianos , Compostos Azabicíclicos , beta-Lactamases/farmacologia , Animais , Antibacterianos/farmacologia , Aztreonam , Enterobacteriaceae , Camundongos , Testes de Sensibilidade Microbiana , Inibidores de beta-Lactamases
13.
J Antimicrob Chemother ; 75(11): 3248-3259, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32737484

RESUMO

BACKGROUND: Antimicrobial peptides are promising alternative antimicrobial agents to combat MDR. DP7, an antimicrobial peptide designed in silico, possesses broad-spectrum antimicrobial activities and immunomodulatory effects. However, the effects of DP7 against Pseudomonas aeruginosa and biofilm infection remain largely unexplored. OBJECTIVES: To assess (i) the antimicrobial activity of DP7 against MDR P. aeruginosa; and (ii) the antibiofilm activity against biofilm infection. Also, to preliminarily investigate the possible antimicrobial mode of action. METHODS: The MICs of DP7 for 104 clinical P. aeruginosa strains (including 57 MDR strains) and the antibiofilm activity were determined. RNA-Seq, genome sequencing and cell morphology were conducted. Both acute and chronic biofilm infection mouse models were established. Two mutants, resulting from point mutations associated with LPS and biofilms, were constructed to investigate the potential mode of action. RESULTS: DP7, at 8-32 mg/L, inhibited the growth of clinical P. aeruginosa strains and, at 64 mg/L, reduced biofilm formation by 43% to 68% in vitro. In acute lung infection, 0.5 mg/kg DP7 exhibited a 70% protection rate and reduced bacterial colonization by 50% in chronic infection. DP7 mainly suppressed gene expression involving LPS and outer membrane proteins and disrupted cell wall structure. Genome sequencing of the DP7-resistant strain DP7R revealed four SNPs controlling LPS and biofilm production. gshA44 and wbpJ139 mutants displayed LPS reduction and motility deficiency, conferring the reduction of LPS and biofilm biomass of strain DP7R and indicating that LPS was a potential target of DP7. CONCLUSIONS: These results demonstrate that DP7 may hold potential as an effective antimicrobial agent against MDR P. aeruginosa and related infections.


Assuntos
Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Antibacterianos/farmacologia , Biofilmes , Simulação por Computador , Camundongos , Testes de Sensibilidade Microbiana , Proteínas Citotóxicas Formadoras de Poros , Infecções por Pseudomonas/tratamento farmacológico
14.
Chemistry ; 26(67): 15558-15564, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32975862

RESUMO

The Periodic Table, and the unique chemical behavior of the first element in a column (group), were discovered simultaneously one and a half centuries ago. Half a century ago, this unique chemistry of the light homologs was correlated to the then available atomic orbital (AO) radii. The radially nodeless 1s, 2p, 3d, 4f valence AOs are particularly compact. The similarity of r(2s)≈r(2p) leads to pronounced sp-hybrid bonding of the light p-block elements, whereas the heavier p elements with n≥3 exhibit r(ns) ≪ r(np) of approximately -20 to -30 %. Herein, a comprehensive physical explanation is presented in terms of kinetic radial and angular, as well as potential nuclear-attraction and electron-screening effects. For hydrogen-like atoms and all inner shells of the heavy atoms, r(2s) ≫ r(2p) by +20 to +30 %, whereas r(3s)≳r(3p)≳r(3d), since in Coulomb potentials radial motion is more radial orbital expanding than angular motion. However, the screening of nuclear attraction by inner core shells is more efficient for s than for p valence shells. The uniqueness of the 2p AO is explained by this differential shielding. Thereby, the present work paves the way for future physical explanations of the 3d, 4f, and 5g cases.

15.
Phys Chem Chem Phys ; 21(3): 1514-1520, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30613835

RESUMO

Graphitic carbon nitride (g-C3N4) is a promising photocatalyst for the reduction of CO2 into fuels. However, the reduction mechanism of CO2 using g-C3N4 is not clear in the literature. In the present study, the fixation of CO2 and the formation of carbamate on the nitrogen atom at the edge of g-C3N4 were investigated using first-principles density functional theory. The calculated results shows that two adjacent bare nitrogen atoms at the edge of g-C3N4 could be the activation sites for the proton and CO2 molecule respectively, which are crucial to the formation of carbamate. The calculated energy barrier of carbamate formation is 0.95 eV for a preferential pathway. From studies on these micro processes, we propose a mechanism with proton assistance for the g-C3N4-catalyzed photoreduction of CO2 to CO.

16.
Bioorg Med Chem Lett ; 28(4): 834-838, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29402745

RESUMO

Staphylococcus aureus is a major and dangerous human pathogen that causes a range of clinical manifestations of varying severity, and is the most commonly isolated pathogen in the setting of skin and soft tissue infections, pneumonia, suppurative arthritis, endovascular infections, foreign-body associated infections, septicemia, osteomyelitis, and toxic shocksyndrome. Honokiol, a pharmacologically active natural compound derived from the bark of Magnolia officinalis, has antibacterial activity against Staphylococcus aureus which provides a great inspiration for the discovery of potential antibacterial agents. Herein, honokiol derivatives were designed, synthesized and evaluated for their antibacterial activity by determining the minimum inhibitory concentration (MIC) against S. aureus ATCC25923 and Escherichia coli ATCC25922 in vitro. 7c exhibited better antibacterial activity than other derivatives and honokiol. The structure-activity relationships indicated piperidine ring with amino group is helpful to improve antibacterial activity. Further more, 7c showed broad spectrum antibacterial efficiency against various bacterial strains including eleven gram-positive and seven gram-negative species. Time-kill kinetics against S. aureus ATCC25923 in vitro revealed that 7c displayed a concentration-dependent effect and more rapid bactericidal kinetics better than linezolid and vancomycin with the same concentration. Gram staining assays of S. aureus ATCC25923 suggested that 7c could destroy the cell walls of bacteria at 1×MIC and 4×MIC.


Assuntos
Antibacterianos/farmacologia , Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/química , Parede Celular/efeitos dos fármacos , Ciclização , Desenho de Fármacos , Escherichia coli/efeitos dos fármacos , Cinética , Lignanas/síntese química , Lignanas/química , Linezolida/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Vancomicina/farmacologia
17.
Inorg Chem ; 57(9): 5499-5506, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29687722

RESUMO

The periodic table provides a fundamental protocol for qualitatively classifying and predicting chemical properties based on periodicity. While the periodic law of chemical elements had already been rationalized within the framework of the nonrelativistic description of chemistry with quantum mechanics, this law was later known to be affected significantly by relativity. We here report a systematic theoretical study on the chemical bonding pattern change in the coinage metal dimers (Cu2, Ag2, Au2, Rg2) due to the relativistic effect on the superheavy elements. Unlike the lighter congeners basically demonstrating ns- ns bonding character and a 0g+ ground state, Rg2 shows unique 6d-6d bonding induced by strong relativity. Because of relativistic spin-orbit (SO) coupling effect in Rg2, two nearly degenerate SO states, 0g+ and 2u, exist as candidate of the ground state. This relativity-induced change of bonding mechanism gives rise to various unique alteration of chemical properties compared with the lighter dimers, including higher intrinsic bond energy, force constant, and nuclear shielding. Our work thus provides a rather simple but clear-cut example, where the chemical bonding picture is significantly changed by relativistic effect, demonstrating the modified periodic law in heavy-element chemistry.

18.
Inorg Chem ; 57(14): 8662-8672, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-29939723

RESUMO

Highly fluorescent nanomaterials have shown great potential application in optics area. However, further improving their fluorescence properties especially for nanomaterials still remains a challenge. Specifically, luminescence of lanthanide (Ln) ions doped two-dimensional (2D) nanosheets is seldom studied. Herein, MgWO4:Ln3+ (Ln = Eu, Tb) nanosheets were successfully synthesized via a simple hydrothermal method, and the luminescence properties of these nanosheets are obviously improved through incorporation of fluorescent carbon dots (CDs) onto the surface of MgWO4:Ln3+ (CDs@MgWO4:Ln3+) nanosheets. The obtained MgWO4:Ln3+ samples have a 2D nanosheet morphology with triclinic phase, and the morphology and phase structure can be maintained after incorporating CDs onto the nanosheets' surface. Under the excitation of UV light, the obtained MgWO4:Ln3+ nanosheets exhibit the characteristic emission of the doping ions, and the emission intensity of CDs@MgWO4:Eu3+ and CDs@MgWO4:Tb3+ nanosheets increases 2- and 7-fold compared to the corresponding samples without incorporation of CDs, respectively. This luminescent enhancement mechanism might be due to the capturing electrons by CDs and energy transfer from CDs to luminescent Ln3+. The fluorescence enhancement through incorporation of CDs provides a simple and environment-friendly strategy for further improving luminescence property of other lanthanide ions doped nanomaterials.

19.
Opt Express ; 25(2): 1495-1504, 2017 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-28158030

RESUMO

We theoretically investigate the coupling between molecular excitons and dipolar Fano-like cavity plasmon resonance in two-layered core-shell resonators consisting of a dielectric core with high refractive index and a thin metal outer shell gapped by a low refractive index thin dielectric layer containing molecules. We demonstrate that associated with the excitation of the dipolar Fano-like cavity plasmon, the electric fields can be highly localized within the dielectric gap shell, leading to very small mode volumes. By using the three-oscillator temporal coupled model to describe the proposed plasmon-exciton system, we are able to demonstrate that the coupling between molecular excitons and cavity plasmon resonance can reach the strong coupling regime. Furthermore, we also demonstrate that reducing the thickness or the refractive index of the dielectric gap shell layer can result in further compression of the mode volumes, and consequently decrease the minimum number of the coupled excitons that are required to fulfill the criteria for strong coupling.

20.
J Reprod Dev ; 63(5): 439-443, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28845020

RESUMO

Transcriptional activity is repressed due to the packaging of sperm chromatins during spermiogenesis. The detection of numerous transcripts in sperm, however, raises the question whether transcriptional events exist in sperm, which has been the central focus of the recent studies. To summarize the transcriptional activity during spermiogenesis and in sperm, we reviewed the documents on transcript differences during spermiogenesis, in sperm with differential motility, before and after capacitation and cryopreservation. This will lay a theoretical foundation for studying the mechanism(s) of gene expression in sperm, and would be invaluable in making better use of animal sires and developing reproductive control technologies.


Assuntos
Espermatogênese/genética , Espermatozoides/metabolismo , Transcrição Gênica/fisiologia , Animais , Cromatina/metabolismo , Criopreservação , Humanos , Masculino , Preservação do Sêmen/métodos , Capacitação Espermática/genética , Motilidade dos Espermatozoides/genética
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