RESUMO
Nucleotide excision repair removes DNA lesions caused by ultraviolet light, cisplatin-like compounds and bulky adducts1. After initial recognition by XPC in global genome repair or a stalled RNA polymerase in transcription-coupled repair, damaged DNA is transferred to the seven-subunit TFIIH core complex (Core7) for verification and dual incisions by the XPF and XPG nucleases2. Structures capturing lesion recognition by the yeast XPC homologue Rad4 and TFIIH in transcription initiation or DNA repair have been separately reported3-7. How two different lesion recognition pathways converge and how the XPB and XPD helicases of Core7 move the DNA lesion for verification are unclear. Here we report on structures revealing DNA lesion recognition by human XPC and DNA lesion hand-off from XPC to Core7 and XPA. XPA, which binds between XPB and XPD, kinks the DNA duplex and shifts XPC and the DNA lesion by nearly a helical turn relative to Core7. The DNA lesion is thus positioned outside of Core7, as would occur with RNA polymerase. XPB and XPD, which track the lesion-containing strand but translocate DNA in opposite directions, push and pull the lesion-containing strand into XPD for verification.
Assuntos
Dano ao DNA , Reparo do DNA , Proteínas de Ligação a DNA , DNA , Fator de Transcrição TFIIH , Proteína de Xeroderma Pigmentoso Grupo A , Humanos , DNA/química , DNA/metabolismo , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fator de Transcrição TFIIH/metabolismo , Proteína de Xeroderma Pigmentoso Grupo A/metabolismo , Especificidade por Substrato , RNA Polimerases Dirigidas por DNA/metabolismoRESUMO
Advancements in next-generation sequencing (NGS) technologies have led to a substantial increase in the availability of population genetic variant data, thus prompting the development of various population analysis tools to enhance our understanding of population structure and evolution. The tools that are currently used to analyze population genetic variant data generally require different environments, parameters, and formats of the input data, which can act as a barrier preventing the wide-spread usage of such tools by general researchers who may not be familiar with bioinformatics. To address this problem, we have developed an automated and comprehensive pipeline called PAPipe to perform nine widely used population genetic analyses using population NGS data. PAPipe seamlessly interconnects and serializes multiple steps, such as read trimming and mapping, genetic variant calling, data filtering, and format converting, along with nine population genetic analyses such as principal component analysis, phylogenetic analysis, population tree analysis, population structure analysis, linkage disequilibrium decay analysis, selective sweep analysis, population admixture analysis, sequentially Markovian coalescent analysis, and fixation index analysis. PAPipe also provides an easy-to-use web interface that allows for the parameters to be set and the analysis results to be browsed in intuitive manner. PAPipe can be used to generate extensive results that provide insights that can help enhance user convenience and data usability. PAPipe is freely available at https://github.com/jkimlab/PAPipe.
Assuntos
Biologia Computacional , Software , Filogenia , Biologia Computacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Genética PopulacionalRESUMO
A nanographene-fused expanded carbaporphyrin (5) and its BF2 complex (6) were synthesized. Single-crystal X-ray structures revealed that 5 and 6 are connected by two hexa-peri-hexabenzocoronene (HBC) units and two dipyrromethene or BODIPY units, respectively. As prepared, 5 and 6 both show nonaromatic character with figure-of-eight carbaoctaphyrin (1.1.1.0.1.1.1.0) cores and adopt tweezers-like conformations characterized by a partially confined space between the two constituent HBC units. The distance between the HBC centers is >10 Å, while the dihedral angles between the two HBC planes are 30.5 and 35.2° for 5 and 6, respectively. The interactions between 5 and 6 and fullerene C60 were studied both in organic media and in the solid state. Proton NMR spectral titrations of 5 and 6 with C60 revealed a 1:1 binding mode for both macrocycles. In toluene-d8, the corresponding binding constants were determined to be 1141 ± 17 and 994 ± 10 M-1 for 5 and 6, respectively. Single-crystal X-ray diffraction structural analyses confirmed the formation of 1:1 fullerene inclusion complexes in the solid state. The C60 guests in both complexes are found within triangular pockets composed of two HBC units from the tweezers-like receptor most closely associated with the bound fullerene, as well as an HBC unit from an adjacent host. Femtosecond transient absorption measurements revealed subpicosecond ultrafast charge separation between 5 (and 6) and C60 in the complexes. To the best of our knowledge, the present report provides the first example wherein a nanographene building block is incorporated into the core of a porphyrinic framework.
RESUMO
Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C2O, which mainly consists of carbon and oxygen in a 2:1 molar ratio and features crown ether holes in its skeletal structure. The covalent-frameworked 2D crown ether can be synthesized on a gram-scale and exhibits fine chemical stability in various environments, including acid, base, and different organic solvents. The C2O efficiently activates KI through the strong coordination of K+ with crown ether holes in a rigid framework, which enhances the nucleophilicity of I- and significantly improves its catalytic activity for CO2 fixation with epoxides. The presence of C2O with KI results in remarkable increases in CO2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C2O possesses both electrophilic and nucleophilic sites at the edge of its framework, allowing for the customization of physicochemical properties by a diverse range of chemical modifications. Specifically, incorporating allyl glycidyl ether (AGE) as an electrophile or ethoxyethylamine (EEA) as a nucleophile into C2O enables the synthesis of C2O-AGE or C2O-EEA, respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO2 fixation with allyl glycidyl ether, outperforming unmodified C2O showing a conversion of 74.2%. This newly developed scalable, durable, and customizable covalent framework holds tremendous potential for the design and preparation of outstanding materials with versatile functionalities, rendering them highly attractive for a wide range of applications.
RESUMO
BACKGROUND: Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODS: We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTS: A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONS: Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).
Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. METHODS: In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. RESULTS: At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. CONCLUSIONS: HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.
Assuntos
Infecções Respiratórias , Humanos , Feminino , Masculino , Lactente , Pré-Escolar , Prevalência , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/diagnóstico , Criança , República da Coreia/epidemiologia , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/virologia , Infecções por Paramyxoviridae/diagnóstico , AdolescenteRESUMO
Stacked-ring aromaticity arising from the close stacking of antiaromatic π-systems has recently received considerable attention. Here, we realize stacked-ring aromaticity via a rational supramolecular approach. A nanocapsule composed of bent polyaromatic amphiphiles was employed to encapsulate several antiaromatic norcorrole Ni(II) complexes (NCs) in water. The resulting micellar capsules display high stability toward heating and concentration change. The encapsulation resulted in the appearance of a broad absorption band in the near-infrared region, which is characteristic of norcorroles with close face-to-face stacking. Importantly, a meso-isopropyl NC, which does not exhibit π-stacking even in a concentrated solution or the crystalline phase, adopted π-stacking with stacked-ring aromaticity in the supramolecular micellar capsule.
RESUMO
Excited-state aromatization dynamics in the photochemical ring opening of dihydroazulene (DHA) is investigated by nonadiabatic molecular dynamics simulations in connection with the mixed-reference spin-flip (MRSF)-TDDFT method. It is found that, in the main reaction channel, the ring opening occurs in the excited state in a sequence of steps with increasing aromaticity. The first stage lasting ca. 200 fs produces an 8π semiaromatic S1 minimum (S1, min) through an ultrafast damped bond length alternation (BLA) movement synchronized with a partial planarization of the cycloheptatriene ring. An additional ca. 200 fs are required to gain the vibrational energy needed to overcome a ring-opening transition state characterized by an enhanced Baird aromaticity. Unlike other BLA motions of ππ* state, it was shown that their damping is a characteristic feature of aromatic bond-equalization process. In addition, some minor channels of the reaction have also been discovered, where noticeably higher barriers of the S1 non/antiaromatic transition structures must be surmounted. These anti-Baird channels led to reformation of DHA or other closed-ring products. The observed competition between the Baird and anti-Baird channels suggests that the quantum yield of photochemical products can be controllable by tipping their balance. Hence, here we suggest including the concept of anti-Baird, which would expand the applicability of Baird rule to much broader situations.
RESUMO
The relationship between the overall electronic structure of π-conjugated molecules and the arrangement of their constituent elements is of fundamental importance. Establishing rational design guidelines for conjugated hydrocarbons with narrow HOMO-LUMO gaps is useful to develop near-infrared (NIR) responsive dyes and redox-active materials. This study describes the synthesis and properties of three conjugated hydrocarbons, i. e., an indenonaphthoperylene, an indenoterrylene, and a diindenoterrylene. These molecules exhibit NIR absorption despite the absence of significant antiaromaticity and diradical character. Notably, the indenonaphthoperylene exhibits red-to-NIR emission in the 620-850â nm region. The indenoterrylene and the diindenoterrylene exhibit NIR absorption tailing to 870 and 940â nm, respectively. Moreover, the effect of the π-extension of indenoperylene is disclosed in order to propose guidelines for achieving a narrow HOMO-LUMO gap with negligible antiaromaticity and diradical character.
RESUMO
Recently, Baird (anti)aromaticity has been referred to as a description of excited-state (anti)aromaticity. With the term of Baird's rule, recent studies have intensively verified that the Hückel aromatic [4n + 2]π (or antiaromatic [4n]π) molecules in the ground state are reversed to give Baird aromatic [4n]π (or Baird antiaromatic [4n + 2]π) molecules in the excited states. Since the Hückel (anti)aromaticity has great influence on the molecular properties and reaction mechanisms, the Baird (anti)aromaticity has been expected to act as a dominant factor in governing excited-state properties and processes, which has attracted intensive scientific investigations for the verification of the concept of reversed aromaticity in the excited states. In this scientific endeavor, porphyrinoids have recently played leading roles in the demonstration of the aromaticity reversal in the excited states and its conceptual development. The distinct structural and electronic nature of porphyhrinoids depending on their (anti)aromaticity allow the direct observation of excited-state aromaticity reversal, Baird's rule. The explicit experimental demonstration with porphyrinoids has contributed greatly to its conceptual development and application in novel functional organic materials. Based on the significant role of porphyrinoids in the field of excited-state aromaticity, this review provides an overview of the experimental verification of the reversal concept of excited-state aromaticity by porphyrinoids and the recent progress on its conceptual application in novel functional molecules.
RESUMO
In organometallic complexes containing π-conjugated macrocyclic chelate ligands, conformational change significantly affects metal-ligand electronic interactions, hence tuning properties of the complexes. In this regard, we investigated the metal-ligand interactions in hexaphyrin mono-Pd(II) complexes Pd[28]M and Pd[26]H, which exhibit a redox-induced switching of Hückel-Möbius aromaticity and subsequent molecular conformation, and their effect on the electronic structure and photophysical behaviors. In Möbius aromatic Pd[28]M, the weak metal-ligand interaction leads to the π electronic structure of the hexaphyrin ligand remaining almost intact, which undergoes efficient intersystem crossing (ISC) assisted by the heavy-atom effect of the Pd metal. In Hückel aromatic Pd[26]H, the significant metal-ligand interaction results in ligand-to-metal charge-transfer (LMCT) in the excited-state dynamics. These contrasting metal-ligand electronic interactions have been revealed by time-resolved electronic and vibrational spectroscopies and time-dependent DFT calculations. This work indicates that the conspicuous modulation of metal-ligand interaction by Hückel-Möbius aromaticity switching is an appealing approach to manipulate molecular properties of metal complexes, further enabling the fine-tuning of metal-ligand interactions and the novel design of functional organometallic materials.
RESUMO
Noroviruses cause acute gastroenteritis with symptoms of diarrhoea and vomiting, and their high infectivity allows outbreaks to readily occur. Quickly identifying and isolating potential contaminants is an effective method to prevent the spread of outbreaks. A total of 376 samples collected from nine outbreaks were categorized as either patient, asymptomatic individual, cook or environmental samples, according to the source of contamination. Using real-time PCR and sequencing analysis, norovirus GII genotypes were detected in 34·9% of samples from patients, 19·2% from asymptomatic individuals, 2·4% from the environment and 1·4% from cooks. Our findings showed contrasting results in samples categories quantified based on the limit of blank and detection limit by reverse transcription droplet digital PCR, which is a more sensitive testing method than real-time-PCR.
Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Fezes , Gastroenterite/epidemiologia , Genótipo , Humanos , Norovirus/genética , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
BIII subporphyrins are the legitimate ring-contracted porphyrins consisting of three pyrroles and three meso-carbons and their chemistry has been extensively developed since the first synthesis in 2006. However, subporphyrin free bases have never been synthesized, despite tremendous attempts to remove the BIII ion. Here we report that Suzuki-Miyaura coupling between α,α'-diborylated tripyrrane 1 and tetrabromide 5 gave subporphyrin free bases 6, 6 A, and free base dimer 7 in 6 %, 4 %, and 2 % yields as the first examples. Subporphyrin free bases exhibit curved bowl-like structures and distinct 14π-aromaticity. Steady-state and time-resolved spectroscopy revealed that the excited-state behaviors of the subporphyrin free bases are comparable with those of the corresponding BIII subporphyrins. Rotational relaxation processes in the excited states have been revealed, which enhance the electronic interactions with the meso-aryl substituents and between the two subporphyrins.
RESUMO
The corrole derivative meso-oxoisocorrole has been theoretically predicted to be antiaromatic, despite its formally cross conjugated electronic system. In this study, this prediction has been experimentally proven by the facile preparation of meso-oxoisocorrole via the oxidation of a meso free corrole with MnO2 and its comprehensive characterization using NMR, UV/vis absorption, FT-IR, and transient-absorption spectroscopy, cyclic voltammetry, and X-ray diffraction analysis. Furthermore, the free base meso-oxoisocorrole was metalated by treatment with Ni(acac)2, PdCl2(PhCN)2, and Zn(OAc)2 to give the corresponding metal complexes. These complexes are more strongly antiaromatic, and their degree of paratropicity depends on their planarity. Thus, fine tuning of their antiaromaticity was achieved with concomitant modulation of their HOMO-LUMO gaps. In the presence of tris(pentafluorophenyl)borane, their antiaromaticity is significantly enhanced due to the elongation of the CâO bond, which promotes the polarized C+-O- resonance state. Furthermore, a distinct frequency shift of the CâO vibrational mode in the triplet state was observed in the time-resolved IR spectra in accordance with the Baird rule, which indicates aromaticity reversal in the excited state.
RESUMO
Microelectrodes are widely used for neural signal analysis because they can record high-resolution signals. In general, the smaller the size of the microelectrode for obtaining a high-resolution signal, the higher the impedance and noise value of the electrodes. Therefore, to improve the signal-to-noise ratio (SNR) of neural signals, it is important to develop microelectrodes with low impedance and noise. In this research, an Au hierarchical nanostructure (AHN) was deposited to improve the electrochemical surface area (ECSA) of a microelectrode. Au nanostructures on different scales were deposited on the electrode surface in a hierarchical structure using an electrochemical deposition method. The AHN-modified microelectrode exhibited an average of 80% improvement in impedance compared to a bare microelectrode. Through electrochemical impedance spectroscopy analysis and impedance equivalent circuit modeling, the increase in the ECSA due to the AHN was confirmed. After evaluating the cell cytotoxicity of the AHN-modified microelectrode through an in vitro test, neural signals from rats were obtained in in vivo experiments. The AHN-modified microelectrode exhibited an approximate 9.79 dB improvement in SNR compared to the bare microelectrode. This surface modification technology is a post-treatment strategy used for existing fabricated electrodes, so it can be applied to microelectrode arrays and nerve electrodes made from various structures and materials.
Assuntos
Nanoestruturas , Animais , Espectroscopia Dielétrica , Impedância Elétrica , Microeletrodos , Ratos , Razão Sinal-RuídoRESUMO
BACKGROUND: The independent role of pericardial adipose tissue (PAT) as an ectopic fat associated with cardiovascular disease (CVD) remains controversial. This study aimed to determine whether PAT is associated with left ventricular (LV) structure and function independent of other markers of general obesity. METHODS: We studied 2471 participants (50.9 % women) without known CVD from the Korean Genome Epidemiology Study, who underwent 2D-echocardiography with tissue Doppler imaging (TDI) and computed tomography measurement for PAT. RESULTS: Study participants with more PAT were more likely to be men and had higher cardiometabolic indices, including blood pressure, glucose, and cholesterol levels (all P < 0.001). Greater pericardial fat levels across quartiles of PAT were associated with increased LV mass index and left atrial volume index (all P < 0.001) and decreased systolic (P = 0.015) and early diastolic (P < 0.001) TDI velocities, except for LV ejection fraction. These associations remained after a multivariable-adjusted model for traditional CV risk factors and persisted even after additional adjustment for general adiposity measures, such as waist circumference and body mass index. PAT was also the only obesity index independently associated with systolic TDI velocity (P < 0.001). CONCLUSIONS: PAT was associated with subclinical LV structural and functional deterioration, and these associations were independent of and stronger than with general and abdominal obesity measures.
Assuntos
Tecido Adiposo/fisiopatologia , Adiposidade , Hipertrofia Ventricular Esquerda/fisiopatologia , Obesidade/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Tecido Adiposo/diagnóstico por imagem , Idoso , Doenças Assintomáticas , Estudos Transversais , Ecocardiografia Doppler , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Obesidade/epidemiologia , Pericárdio , República da Coreia/epidemiologia , Fatores de Risco , Tomografia Computadorizada por Raios X , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologiaRESUMO
Given the unsatisfactory survival in patients who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for peripheral T-cell lymphomas (PTCLs), we conducted a prospective trial of busulfan (Bu), etoposide (E), cytarabine (A), and melphalan (M) (BuEAM), including IV Bu instead of carmustine (BCNU) as in standard BEAM, as a high-dose regimen in such patients. This study evaluated the efficacy and toxicity of BuEAM as a high-dose regimen for ASCT in patients with T-cell lymphomas. The high-dose chemotherapy at seven centers in Korea included Bu (3.2 mg/kg IV qd from day 6 to day 5), E (200 mg/m2 IV bid on day 4 and day 3), A (1 g/m2 IV qd on day 4 and day 3), and M (140 mg/m2 IV qd on day 2). Eighty-one patients were enrolled in this study. The main subtypes were peripheral T-cell lymphoma, not other specified (n = 32, 39.5%), NK/T-cell lymphoma (n = 22, 27.5%), and angioimmunoblastic T-cell lymphoma (n = 12, 14.8%). Upfront and salvage ASCTs were performed in 65 (80.2%) and 16 (19.8%) patients, respectively. The disease status of the patients before ASCT was 54 patients (66.7%) with complete response and 27 patients (33.3%) with partial response. The common grade-III toxicities were anorexia (8.6%), diarrhea (7.4%), and stomatitis (4.9%). No veno-occlusive disorder was noted. Fifty-six (69.1%) and seven (8.6%) patients achieved complete and partial response, respectively, after ASCT, although 17 patients (21.0%) showed progressive disease. At a median follow-up duration of 49.3 months, the estimated 3-year progression-free survival and overall survival were 55.2% and 68.2% in all patients. The BuEAM high-dose regimen for ASCT was well tolerated and seemed to be effective in patients with T-cell lymphomas.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células T Periférico/tratamento farmacológico , Melfalan/administração & dosagem , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adulto JovemRESUMO
BACKGROUND: Urinary chloride is regulated by kidney transport channels, and high urinary chloride concentration in the distal tubules can trigger tubuloglomerular feedback. However, little attention has been paid to urinary chloride as a biomarker of clinical outcomes. Here, we studied the relationship between urinary chloride concentration and chronic kidney disease (CKD) progression. METHODS: We included 2086 participants with CKD from the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease. Patients were categorized into three groups, according to baseline urinary chloride concentration tertiles. The study endpoint was a composite of ≥50% decrease in estimated glomerular filtration rate from baseline values, or end-stage kidney disease. RESULTS: During a median follow-up period of 3.4 years (7452 person-years), 565 participants reached the primary endpoint. There was a higher rate of CKD progression events in the lowest and middle tertiles than in the highest tertile. Compared with the lowest tertile, the highest tertile was associated with 33% [95% confidence interval (CI) 0.49-0.90] lower risk for the primary outcome in a cause-specific hazard model after adjustment for confounding variables. In addition, for every 25 mEq/L increase in urinary chloride concentration, there was 11% (95% CI 0.83-0.96) lower risk for CKD progression. This association was consistent in a time-varying model. Urinary chloride concentration correlated well with tubule function and kidney injury markers, and its predictive performance for CKD progression was comparable to that of these markers. CONCLUSIONS: In this hypothesis-generating study, low urinary chloride concentration was associated with a higher risk for CKD progression.
Assuntos
Biomarcadores/urina , Cloretos/urina , Insuficiência Renal Crônica/patologia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/urina , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
Dragonet fishes (Callionymidae) are benthic inhabitants of shallow waters, even in tidal pools, down to depths below 900 m in all subtropical, tropical and temperate oceans. The family comprises 200 species in 20 genera worldwide, of which 18 species in 6 genera occur in Korea. Classification within the family Callionymidae has been controversial because of the differing proposals of Fricke and Nakabo (Fishes of Japan with pictorial keys to the species, 1983). For example, Fricke suggested genus Repomucenus and Bathycallionymus, whose genera contains most callionymid species in Korean waters, as junior synonym of genus Callionymus while Nakabo (Fishes of Japan with pictorial keys to the species, 1983) suggested as valid. In such cases, when classifications of adults have taxonomic contention, examination of larval characters may prove informative. Therefore, in this study, the authors conducted comprehensive molecular and morphological analyses on larvae and juveniles of five species in the genus Repomucenus and discussed their taxonomic status within the family Callionymidae. Larval and juvenile callionymids show high morphological similarities during their ontogenetic development. Nonetheless, the following morphological differences were observed in melanophore distribution and preopercular spine development: (a) stellate or punctate melanophores in Bathycallionymus kaianus vs. branched melanophores in genus Repomucenus, (b) melanophores on the abdominal cavity gradually disappearing in B. kaianus vs. gradually becoming prominent in Repomucenus and (c) preopercular spine development giving rise to one perpendicular spine in B. kaianus vs. two or three spines in Repomucenus. Molecular analysis based on 16S ribosomal RNA showed similar results to the morphological analysis. Genera Bathycallionymus and Repomucenus showed significant genetic distance (d = 0.113-0.120); moreover, genus Callionymus, which was suggested as a senior synonym of genus Bathycallionymus and Repomucenus by Fricke (Journal of Natural History, 2014, 48, 2419-2448), also showed considerable difference (d = 0.226-0.246). In the present study, the monophyly of genus Repomucenus seemed well supported by the results of morphological and molecular analyses of larval stage Callionymidae.
Assuntos
Perciformes , Animais , Peixes/genética , Japão , Larva , Filogenia , RNA Ribossômico 16S/genéticaRESUMO
3,7,23,27-Tetrabromo[36]octaphyrin 2 was synthesized as a novel octaphyrin bearing two meso-free positions. Surprisingly, its ZnII and NiII complexation reactions produced a directly fused porphyrin(2.1.1.1) dimer 6, and a meso-α fused N-confused porphyrin (NCP) dimer 7, as the first example of NCP tape, respectively, via transannular C-C bond formation. While 6 exhibits a diatropic ring-current effect owing to the global 36π Möbius aromaticity, 7 shows a paratropic ring-current effect due to the global Hückel 36π antiaromaticity. In addition, the oxidation of 7 with PbO2 allowed for formation of its two-electron oxidized species 9 that exhibited a diatropic ring-current effect due to the global Hückel 34π aromaticity. This work has demonstrated that meso-free large expanded porphyrins can be a promising platform to produce novel fused porphyrinoids.