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1.
Opt Express ; 32(3): 2929-2941, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297529

RESUMO

Developing from transient absorption (TA) spectroscopy, two-dimensional (2D) spectroscopy with pump-probe geometry has emerged as a versatile approach for alleviating the difficulty in implementing 2D spectroscopy with other geometries. However, the presence of cross-phase modulation (XPM) in TA spectroscopy introduces significant spectral distortions, particularly when the pump and probe pulses overlap. We demonstrate that this phenomenon is extended to the 2D spectroscopy with pump-probe geometry and the XPM is induced by the interference of the two pump pulses. We present the oscillatory behavior of XPM in the 2D spectrum and its displacement with respect to the waiting time delay through both experimental measurements and numerical simulations. Additionally, we explore the influence of probe pulse chirp on XPM and discover that by compressing the chirp, the impact of XPM on the desired signal can be reduced.

2.
Acta Pharmacol Sin ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060523

RESUMO

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

3.
Plant Cell ; 32(9): 2878-2897, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32641349

RESUMO

Casein kinase 1 (CK1) family members are conserved Ser/Thr protein kinases that regulate important developmental processes in all eukaryotic organisms. However, the functions of CK1 in plant immunity remain largely unknown. Barley yellow striate mosaic virus (BYSMV), a plant cytorhabdovirus, infects cereal crops and is obligately transmitted by the small brown planthopper (SBPH; Laodelphax striatellus). The BYSMV phosphoprotein (P) exists as two forms with different mobilities corresponding to 42 kD (P42) and 44 kD (P44) in SDS-PAGE gels. Mass spectrometric analyses revealed a highly phosphorylated serine-rich (SR) motif at the C-terminal intrinsically disordered region of the P protein. The Ala-substitution mutant (PS5A) in the SR motif stimulated virus replication, whereas the phosphorylation-mimic mutant (PS5D) facilitated virus transcription. Furthermore, PS5A and PS5D associated preferentially with nucleocapsid protein-RNA templates and the large polymerase protein to provide optimal replication and transcription complexes, respectively. Biochemistry assays demonstrated that plant and insect CK1 protein kinases could phosphorylate the SR motif and induce conformational changes from P42 to P44. Moreover, overexpression of CK1 or a dominant-negative mutant impaired the balance between P42 and P44, thereby compromising virus infections. Our results demonstrate that BYSMV recruits the conserved CK1 kinases to achieve its cross-kingdom infection in host plants and insect vectors.


Assuntos
Caseína Quinase I/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Proteínas de Plantas/metabolismo , Rhabdoviridae/fisiologia , Proteínas Virais/metabolismo , Motivos de Aminoácidos , Caseína Quinase I/genética , Genoma Viral , Proteínas de Insetos/metabolismo , Espectrometria de Massas , Mutação , Fosfoproteínas/metabolismo , Fosforilação , Doenças das Plantas/virologia , Rhabdoviridae/patogenicidade , Serina , Nicotiana/virologia , Replicação Viral/fisiologia
4.
J Chem Inf Model ; 63(15): 4780-4790, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37486605

RESUMO

The sirtuin enzyme family members, SIRT1 and SIRT2, play both tumor-promoting and tumor-suppressing roles, depending on the context and experimental conditions. Compounds that inhibit either SIRT1 or SIRT2 show promising antitumor effects in several types of cancer models, both in vitro and in vivo. The simultaneous inhibition of SIRT1 and SIRT2 is helpful in treating cancer by completely blocking p53 deacetylation, leading to cell death. However, only a few SIRT1/2 dual inhibitors have been developed. Here, we report the discovery of a novel series of SIRT1/2 dual inhibitors via a rational drug design that involved virtual screening and a substructure search. Eleven of the derived compounds exhibited high inhibitory activities, with IC50 < 5 µM and high specificity for both SIRT1 and SIRT2. Compounds hsa55 and PS9 strongly induced apoptosis and showed antiproliferative effects against human leukemia cell lines, which could be due to their ability to increase of p53 and α-tubulin acetylation, as we observed in MOLM-13 cells. Therefore, the new scaffolds of these compounds and their efficacy in leukemia cell lines provide important clues for the further development of novel anti-leukemia drugs.


Assuntos
Neoplasias , Sirtuína 2 , Humanos , Sirtuína 2/química , Sirtuína 1 , Proteína Supressora de Tumor p53/metabolismo , Apoptose
5.
Am J Epidemiol ; 190(9): 1961-1968, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33878172

RESUMO

Monitoring survival in cancer is a common concern for patients, physicians, and public health researchers. The traditional cohort approach for monitoring cancer prognosis has a timeliness problem. In this paper, we propose a survivorship-period-cohort (SPC) model for examining the effects of survivorship, period, and year-of-diagnosis cohort on cancer prognosis and for predicting future trends in cancer survival. We used the developed SPC model to evaluate the relative survival (RS) of patients with liver cancer in Taiwan (diagnosed from 1997 to 2016) and to predict future trends in RS by imputing incomplete follow-up data for recently diagnosed patient cohorts. We used cross-validation to select the extrapolation method and bootstrapping to estimate the 95% confidence interval for RS. We found that 5-year cumulative RS increased for both men and women with liver cancer diagnosed after 2003. For patients diagnosed before 2010, the 5-year cumulative RS rate for men was lower than that for women; thereafter, the rates were better for men than for women. The SPC model can help elucidate the effects of survivorship, period, and year-of-diagnosis cohort effects on cancer prognosis. Moreover, the SPC model can be used to monitor cancer prognosis in real time and predict future trends; thus, we recommend its use.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias Hepáticas/mortalidade , Modelos Estatísticos , Análise de Sobrevida , Fatores Etários , Estudos de Coortes , Humanos , Masculino , Prognóstico , Reprodutibilidade dos Testes , Fatores Sexuais , Taiwan/epidemiologia , Fatores de Tempo
6.
Chemistry ; 27(51): 12998-13008, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34288149

RESUMO

A series of dicyano-imidazole-based molecules with thermally activated delayed fluorescence (TADF) properties were synthesized to obtain pure blue-emitting organic light-emitting diodes (OLEDs). The targeted molecules used dicyano-imidazole with a short-conjugated system as the electron acceptor to strong intermolecular π-π interactions, and provide a relatively shallow energy level of the lowest unoccupied molecular orbital (LUMO). The cyano group was selected to improve imidazole as an electron acceptor due to its prominent electron-transporting characteristics. Four different electron donors, that is, 9,9-dimethyl-9,10-dihydroacridine (DMAC), 10H-spiro(acridine-9,9'-fluoren) (SPAC), and 9,9-diphenyl-9,10-dihydroacridine (DPAC), were used to alternate the highest occupied molecular orbital (HOMO) energy level to tune the emission color further. The crowded molecular structure in space makes the electron donor and acceptor almost orthogonal, reducing the energy gap (ΔEST ) between the first excited singlet (S1 ) and the triplet (T1 ) states and introducing significant TADF property. The efficiencies of the blue-emissive devices with imM-SPAC and imM-DMAC obtained in this work are the highest among the reported imidazole-based TADF-OLEDs, which are 13.8 % and 13.4 %, respectively. Both of Commission Internationale de l'Eclairage (CIE) coordinates are close to the saturated blue region at (0.17, 0.18) and (0.16, 0.19), respectively. Combining these tailor-made TADF compounds with specific device architectures, electroluminescent (EL) emission from sky-blue to deep-blue could be achieved, proving their great potential in EL applications.

7.
Fish Shellfish Immunol ; 98: 551-563, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31981776

RESUMO

Hepcidin, a multifunctional hormone oligopeptide, not only exhibits a regulatory role in iron metabolism, but also participates in the regulation of teleostean immunity. In this study, ORF sequence of WR-hepcidin was 258 bp and encoded 85 amino acid residues. Tissue-specific analysis revealed that the highest expression of WR-hepcidin was observed in liver. Aeromonas hydrophila challenge can sharply increased WR-hepcidin mRNA expression in liver, trunk kidney and spleen. The purified WR-hepcidin fusion peptide can directly bind to A. hydrophila and Streptococcus agalactiae, reduce the relative bacterial activity, limit bacterial growth and attenuate their dissemination to tissues in vivo. In addition, the treatment of WR-hepcidin fusion protein can diminish the production of pro-inflammatory cytokines. These results indicated that WR-hepcidin can play a negative regulatory role in bacteria-stimulated pro-inflammatory cytokines production and MyD88-IRAK4 activation.


Assuntos
Doenças dos Peixes/microbiologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica/imunologia , Carpa Dourada/genética , Infecções por Bactérias Gram-Negativas/veterinária , Hepcidinas/química , Aeromonas hydrophila , Animais , Feminino , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Hibridização Genética , Masculino
8.
PLoS Pathog ; 13(7): e1006522, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28727810

RESUMO

Shoot apical meristems (SAM) are resistant to most plant viruses due to RNA silencing, which is restrained by viral suppressors of RNA silencing (VSRs) to facilitate transient viral invasion of the SAM. In many cases chronic symptoms and long-term virus recovery occur, but the underlying mechanisms are poorly understood. Here, we found that wild-type Cucumber mosaic virus (CMVWT) invaded the SAM transiently, but was subsequently eliminated from the meristems. Unexpectedly, a CMV mutant, designated CMVRA that harbors an alanine substitution in the N-terminal arginine-rich region of the coat protein (CP) persistently invaded the SAM and resulted in visible reductions in apical dominance. Notably, the CMVWT virus elicited more potent antiviral silencing than CMVRA in newly emerging leaves of infected plants. However, both viruses caused severe symptoms with minimal antiviral silencing effects in the Arabidopsis mutants lacking host RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) or SUPPRESSOR OF GENE SILENCING 3 (SGS3), indicating that CMVWT induced host RDR6/SGS3-dependent antiviral silencing. We also showed that reduced accumulation of the 2b protein is elicited in the CMVWT infection and consequently rescues potent antiviral RNA silencing. Indeed, co-infiltration assays showed that the suppression of posttranscriptional gene silencing mediated by 2b is more severely compromised by co-expression of CPWT than by CPRA. We further demonstrated that CPWT had high RNA binding activity leading to translation inhibition in wheat germ systems, and CPWT was associated with SGS3 into punctate granules in vivo. Thus, we propose that the RNAs bound and protected by CPWT possibly serve as templates of RDR6/SGS3 complexes for siRNA amplification. Together, these findings suggest that the CMV CP acts as a central hub that modulates antiviral silencing and VSRs activity, and mediates viral self-attenuation and long-term symptom recovery.


Assuntos
Arabidopsis/virologia , Proteínas do Capsídeo/metabolismo , Cucumovirus/metabolismo , Doenças das Plantas/virologia , Proteínas Virais/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/imunologia , Proteínas do Capsídeo/genética , Cucumovirus/genética , Inativação Gênica , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Folhas de Planta/genética , Folhas de Planta/imunologia , Folhas de Planta/virologia , Interferência de RNA , Nicotiana/genética , Nicotiana/imunologia , Nicotiana/virologia , Proteínas Virais/genética
9.
New Phytol ; 223(4): 2120-2133, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31059138

RESUMO

Plant viruses have been used as rapid and cost-effective expression vectors for heterologous protein expression in genomic studies. However, delivering large or multiple foreign proteins in monocots and insect pests is challenging. Here, we recovered a recombinant plant cytorhabdovirus, Barley yellow striate mosaic virus (BYSMV), for use as a versatile expression platform in cereals and the small brown planthopper (SBPH, Laodelphax striatellus) insect vector. We engineered BYSMV vectors to provide versatile expression platforms for simultaneous expression of three foreign proteins in barley plants and SBPHs. Moreover, BYSMV vectors could express the c. 600-amino-acid ß-glucuronidase (GUS) protein and a red fluorescent protein stably in systemically infected leaves and roots of cereals, including wheat, barley, foxtail millet, and maize plants. Moreover, we have demonstrated that BYSMV vectors can be used in barley to analyze biological functions of gibberellic acid (GA) biosynthesis genes. In a major technical advance, BYSMV vectors were developed for simultaneous delivery of CRISPR/Cas9 nuclease and single guide RNAs for genomic editing in Nicotiana benthamiana leaves. Taken together, our results provide considerable potential for rapid screening of functional proteins in cereals and planthoppers, and an efficient approach for developing other insect-transmitted negative-strand RNA viruses.


Assuntos
Grão Comestível/genética , Grão Comestível/virologia , Genoma de Planta , Genômica , Hemípteros/virologia , Vírus de Plantas/fisiologia , Rhabdoviridae/fisiologia , Animais , Sequência de Bases , DNA Complementar/genética , Edição de Genes , Vetores Genéticos/metabolismo , Glucuronidase/metabolismo , Hordeum/ultraestrutura , Hordeum/virologia , Folhas de Planta/virologia , Vírus de Plantas/ultraestrutura , RNA Guia de Cinetoplastídeos/metabolismo , Rhabdoviridae/ultraestrutura , Nicotiana/ultraestrutura , Nicotiana/virologia
10.
J Exp Bot ; 70(15): 4049-4062, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31020313

RESUMO

As obligate parasites, plant viruses usually hijack host cytoskeletons for replication and movement. Rhabdoviruses are enveloped, negative-stranded RNA viruses that infect vertebrates, invertebrates, and plants, but the mechanisms of intracellular trafficking of plant rhabdovirus proteins are largely unknown. Here, we used Barley yellow striate mosaic virus (BYSMV), a plant cytorhabdovirus, as a model to investigate the effects of the actin cytoskeleton on viral intracellular movement and viral RNA synthesis in a mini-replicon (MR) system. The BYSMV P protein forms mobile inclusion bodies that are trafficked along the actin/endoplasmic reticulum network, and recruit the N and L proteins into viroplasm-like structures. Deletion analysis showed that the N terminal region (aa 43-55) and the remaining region (aa 56-295) of BYSMV P are essential for the mobility and formation of inclusions, respectively. Overexpression of myosin XI-K tails completely abolishes the trafficking activity of P bodies, and is accompanied by a significant reduction of viral MR RNA synthesis. These results suggest that BYSMV P contributes to the formation and trafficking of viroplasm-like structures along the ER/actin network driven by myosin XI-K. Thus, rhabdovirus P appears to be a dynamic hub protein for efficient recruitment of viral proteins, thereby promoting viral RNA synthesis.


Assuntos
Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Hordeum/metabolismo , Hordeum/virologia , RNA Viral/metabolismo , Rhabdoviridae/metabolismo , Rhabdoviridae/patogenicidade , Citoesqueleto de Actina/genética , Actinas/genética , Hordeum/genética , Transporte Proteico/genética , Transporte Proteico/fisiologia , RNA Viral/genética
11.
Arch Virol ; 163(6): 1455-1461, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29429036

RESUMO

Hand, foot and mouth disease (HFMD) is a serious public health problem, and coxsackievirus A6 (CVA6) and coxsackievirus A10 (CVA10) are two of the major causative pathogens, in addition to enterovirus 71 (EV71) and coxsackievirus A16 (CVA16). A simple and rapid reverse transcription recombinase-aided amplification assay (RT-RAA) was developed for the detection of CVA10 and CVA6 in this study. The analytical sensitivity for detection of CVA10 and CVA6 at 95% probability by probit regression analysis was 35 copies per reaction and 38 copies per reaction, respectively, with 100% specificity. Compared with commercial RT-qPCR assays, when testing 455 fecal specimens, the kappa value of the RT-RAA assay for CVA10 and CVA6 was 0.920 (p < 0.001) and 0.952 (p < 0.001), respectively. Moreover, four samples that were positive for CVA10 and five that were positive for CVA6 by RT-RAA but negative by RT-qPCR were further determined to be true positives. These results demonstrate that the proposed RT-RAA assays are very valuable tools for the detection of CVA10 and CVA6 and have potential for use in resource-limited settings.


Assuntos
Enterovirus/genética , Doença de Mão, Pé e Boca/diagnóstico , RNA Viral/genética , Recombinases/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Criança , Pré-Escolar , Primers do DNA/química , Primers do DNA/genética , Enterovirus/classificação , Enterovirus/isolamento & purificação , Fezes/virologia , Feminino , Doença de Mão, Pé e Boca/virologia , Humanos , Lactente , Masculino , Plasmídeos/química , Plasmídeos/metabolismo , Recombinases/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Sensibilidade e Especificidade
12.
BMC Infect Dis ; 18(1): 450, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30176819

RESUMO

BACKGROUND: Diarrhea is a major source of morbidity and mortality among young children in low-income and middle-income countries. Human adenoviruses (HAdV), particular HAdV species F (40, 41) has been recognized as important causal pathogens, however limited data exist on molecular epidemiology of other HAdV associated with acute gastroenteritis. METHODS: In the present preliminary study, we performed a case-control study involving 273 children who presented diarrheal disease and 361 healthy children matched control in Children's hospital of Hebei Province (China) to investigate the relationship between non-enteric HAdV and diarrhea. HAdV were detected and quantified using quantitative real-time PCR (qPCR) and serotyped by sequencing and phylogenetic analysis. Odds ratio (OR) was used to assess the risk factor of HAdV. RESULTS: HAdV were detected in 79 (28.94%) of 273 children with diarrhea including 7 different serotypes (HAdV 40, 41, 3, 2,1,5 and 57) with serotypes 40, 41 and 3 being the most dominant and in 26 (7.20%) of 361 healthy children containing 9 serotypes (HAdV 40, 41, 3, 2,1,5,57,6 and 31). A majority (91.14%) of HAdV positives occurred in diarrhea children and 65.38% in controls< 3 years of age. No significant difference in the viral load was found between case and control groups or between Ad41-positive patients and healthy controls. In addition to HAdV 40 and 41, HAdV 3 was also associated with diarrhea (OR = 17.301, adjusted OR = 9.205, p < 0.001). CONCLUSIONS: Our results demonstrate a high diversity of HAdV present among diarrhea and healthy children and implicate that non-enteric HAdV3 may lead to diarrhea.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , Diarreia/epidemiologia , Diarreia/virologia , Infecções por Adenovirus Humanos/complicações , Adenovírus Humanos/genética , Adenovírus Humanos/isolamento & purificação , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/virologia , Humanos , Lactente , Masculino , Epidemiologia Molecular , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Sorotipagem , Carga Viral
14.
Eur J Obstet Gynecol Reprod Biol ; 299: 54-61, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838387

RESUMO

OBJECTIVE: To evaluate the effect of insulin resistance (IR) on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: PubMed, Google Scholar,Web of Science, Embase, Scopus and the Cochrane Library were searched to identify relevant studies. A total of 6,137 PCOS women undergoing IVF/ICSI with or without IR were included in the systematic review and meta-analysis. RESULTS: The systematic review and meta-analysis included twelve observational studies that were free from inherent bias. When comparing PCOS women undergoing IVF/ICSI, the IR and non-IR groups did not show significant differences in oocytes retrieved (WMD = -0.63, 95 % CI: -2.37 to 1.12, P = 0. 483), fertilization rate (WMD = 1.01, 95 % CI: -0.66 to 2.67, P = 0.236; OR = 0.97, 95 % CI: 0.79 to 1.19, P = 0.783), and live birth rate (OR = 1.02, 95 % CI: 0.78 to 1.33, P = 0.892). However, the group with IR had a lower number of MII oocytes (WMD = -1.07, 95 % CI: -1.54 to -0.59, P < 0.001), total embryos (WMD = -1.37, 95 % CI: -1. 78 to -0.95, P < 0.001), and clinical pregnancy rate (OR = 0.77, 95 % CI: 0.59 to 0.99, P = 0.042), as well as a higher miscarriage rate (OR = 1.11, 95 % CI: 1.02 to 1.22, P = 0.017) compared to the non-IR group. CONCLUSION: In women with PCOS, IR had a negative impact on IVF/ICSI outcomes. To obtain more favourable empirical support, larger studies are necessary.


Assuntos
Fertilização in vitro , Resistência à Insulina , Síndrome do Ovário Policístico , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia , Feminino , Gravidez , Fertilização in vitro/métodos , Infertilidade Feminina/terapia
15.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38497835

RESUMO

Two-dimensional electronic spectroscopy (2DES) can be implemented with different geometries, e.g., BOXCARS, collinear, and pump-probe geometries. The pump-probe geometry has the advantage of overlapping only two beams and reducing phase cycling steps. However, its applications are typically limited to observing the dynamics with single-quantum coherence and population, leaving the challenge to measure the dynamics of the double-quantum (2Q) coherence, which reflects the many-body interactions. We demonstrate an experimental technique in 2DES under pump-probe geometry with a designed pulse sequence and the signal processing method to extract 2Q coherence. In the designed pulse sequence, with the probe pulse arriving earlier than the pump pulses, our measured signal includes the 2Q signal as well as the zero-quantum signal. With phase cycling and data processing using causality enforcement, we extract the 2Q signal. The proposal is demonstrated with rubidium atoms. We observe the collective resonances of two-body dipole-dipole interactions in both the D1 and D2 lines.

16.
JMIR Public Health Surveill ; 10: e46737, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819904

RESUMO

BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality globally, with late diagnoses often resulting in poor prognosis. In response, the Lung Ambition Alliance aims to double the 5-year survival rate by 2025. OBJECTIVE: Using the Taiwan Cancer Registry, this study uses the survivorship-period-cohort model to assess the feasibility of achieving this goal by predicting future survival rates of patients with lung cancer in Taiwan. METHODS: This retrospective study analyzed data from 205,104 patients with lung cancer registered between 1997 and 2018. Survival rates were calculated using the survivorship-period-cohort model, focusing on 1-year interval survival rates and extrapolating to predict 5-year outcomes for diagnoses up to 2020, as viewed from 2025. Model validation involved comparing predicted rates with actual data using symmetric mean absolute percentage error. RESULTS: The study identified notable improvements in survival rates beginning in 2004, with the predicted 5-year survival rate for 2020 reaching 38.7%, marking a considerable increase from the most recent available data of 23.8% for patients diagnosed in 2013. Subgroup analysis revealed varied survival improvements across different demographics and histological types. Predictions based on current trends indicate that achieving the Lung Ambition Alliance's goal could be within reach. CONCLUSIONS: The analysis demonstrates notable improvements in lung cancer survival rates in Taiwan, driven by the adoption of low-dose computed tomography screening, alongside advances in diagnostic technologies and treatment strategies. While the ambitious target set by the Lung Ambition Alliance appears achievable, ongoing advancements in medical technology and health policies will be crucial. The study underscores the potential impact of continued enhancements in lung cancer management and the importance of strategic health interventions to further improve survival outcomes.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Taiwan/epidemiologia , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Taxa de Sobrevida/tendências , Adulto , Sistema de Registros/estatística & dados numéricos , Previsões , Idoso de 80 Anos ou mais , Análise de Sobrevida
17.
Front Mol Biosci ; 10: 1157186, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065444

RESUMO

Serine protease inhibitors (Serpins) are the most widely distributed protease inhibitors in nature and have been identified from all kingdoms of life. Eukaryotic serpins are most abundant with their activities often subject to modulation by cofactors; however, little is known about the regulation of prokaryotic serpins. To address this, here we prepared a recombinant bacteria serpin, termed chloropin, derived from green sulfur bacteria Chlorobium limicola and solved its crystal structure at 2.2 Å resolution. This showed a canonical inhibitory serpin conformation of native chloropin with a surface-exposed reactive loop and a large central beta-sheet. Enzyme activity analysis showed that chloropin could inhibit multiple proteases, such as thrombin and KLK7 with second order inhibition rate constants at 2.5×104 M-1s-1 and 4.5×104 M-1s-1 respectively, consistent with its P1 arginine residue. Heparin could accelerate the thrombin inhibition by ∼17-fold with a bell-shaped dose-dependent curve as seen with heparin-mediated thrombin inhibition by antithrombin. Interestingly, supercoiled DNA could accelerate the inhibition of thrombin by chloropin by 74-fold, while linear DNA accelerated the reaction by 142-fold through a heparin-like template mechanism. In contrast, DNA did not affect the inhibition of thrombin by antithrombin. These results indicate that DNA is likely a natural modulator of chloropin protecting the cell from endogenous or exogenous environmental proteases, and prokaryotic serpins have diverged during evolution to use different surface subsites for activity modulation.

18.
Virology ; 577: 91-98, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36332529

RESUMO

All RNA viruses produce and use RNA-dependent RNA polymerases (RdRPs) for their genome replication. Efficient viral genome replication also requires host factors which often function as co-factors of viral RdRP. To identify host factors required for nodavirus genome replication, we carried out an unbiased genetic screen in Caenorhabditis elegans mutants defective in antiviral RNA interference. This genetic screen utilized a self-replicating GFP-tagged viral replicon, derived from flock house virus, as a reporter for the loss of viral genome replication. Upon completing the screen, 16 candidate alleles were isolated and assigned to 14 candidate genes through genetic complementation. Interestingly, 4 of the candidate genes were also found to be required for the genome replication of Orsay virus, a nodavirus that naturally infects C. elegans. Our unbiased genetic screen therefore has led to the identification of a set of worm genes conserved for nodavirus genome replication.

19.
Ageing Res Rev ; 79: 101665, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35690383

RESUMO

Sexual function which comprises of desire, arousal, orgasm and satisfaction and pain, involves coordinated physiologic responses from multiple different pathways. Sexual dysfunction (SD) occurs when these domains of the sexual response cycle are affected. SD is a common but under-recognized non-motor feature in Parkinson's disease (PD), a common age-related neurodegenerative disorder. SD significantly affects the quality of life of PD patients and their partners. Advanced age, gender, hormone deficiency, neuropsychiatric and medical comorbidities contribute to SD in PD. Possible potential pathological mechanisms include vasculogenic, endocrinologic, neurogenic and psychogenic factors. Various therapeutic interventions, both pharmacological and non-pharmacological modalities have been suggested to improve SD in PD. However, erectile dysfunction (ED) is the only SD with evidence-based treatment available. Non-pharmacological therapies are also offering promising evidence in the improvement of SD. A multidisciplinary approach in the assessment, investigation, and treatment is needed to address the real life complex issues (gender and comorbidities, neurobiological, vasoactive, hormonal as well as psychosocial aspects). Future clinical studies with validated and standardized methods in assessing SD as well as experimental models will be necessary for better insight into the pathophysiology. This would facilitate appropriate therapy and improve sexual rehabilitation in PD patients.


Assuntos
Doença de Parkinson , Disfunções Sexuais Fisiológicas , Comorbidade , Humanos , Masculino , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Qualidade de Vida/psicologia , Comportamento Sexual/psicologia , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/terapia
20.
ACS Appl Mater Interfaces ; 14(46): 52289-52300, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36349361

RESUMO

Environmental contamination and energy shortage are among the most critical global issues that require urgent solutions to ensure sustainable ecological balance. Rapid and ultrasensitive monitoring of water quality against pollutant contaminations using a low-cost, easy-to-operate, and environmentally friendly technology is a promising yet not commonly available solution. Here, we demonstrate the effective use of plasma-converted natural bioresources for environmental monitoring. The energy-efficient microplasmas operated at ambient conditions are used to convert diverse bioresources, including fructose, chitosan, citric acid, lignin, cellulose, and starch, into heteroatom-doped graphene quantum dots (GQDs) with controlled structures and functionalities for applications as fluorescence-based environmental nanoprobes. The simple structure of citric acid enables the production of monodispersed 3.6 nm averaged-size GQDs with excitation-independent emissions, while the saccharides including fructose, chitosan, lignin, cellulose, and starch allow the synthesis of GQDs with excitation-dependent emissions due to broader size distribution. Moreover, the presence of heteroatoms such as N and/or S in the chemical structures of chitosan and lignin coupled with the highly reactive species generated by the plasma facilitates the one-step synthesis of N, S-codoped GQDs, which offer selective detection of toxic environmental contaminants with a low limit of detection of 7.4 nM. Our work provides an insight into the rapid and green fabrication of GQDs with tunable emissions from natural resources in a scalable and sustainable manner, which is expected to generate impact in the environmental safety, energy conversion and storage, nanocatalysis, and nanomedicine fields.


Assuntos
Quitosana , Grafite , Pontos Quânticos , Pontos Quânticos/química , Grafite/química , Lignina , Nitrogênio/química , Ácido Cítrico/química , Amido , Frutose
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