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In natural photosynthesis, the light-driven splitting of water into electrons, protons and molecular oxygen forms the first step of the solar-to-chemical energy conversion process. The reaction takes place in photosystem II, where the Mn4CaO5 cluster first stores four oxidizing equivalents, the S0 to S4 intermediate states in the Kok cycle, sequentially generated by photochemical charge separations in the reaction center and then catalyzes the O-O bond formation chemistry1-3. Here, we report room temperature snapshots by serial femtosecond X-ray crystallography to provide structural insights into the final reaction step of Kok's photosynthetic water oxidation cycle, the S3â[S4]âS0 transition where O2 is formed and Kok's water oxidation clock is reset. Our data reveal a complex sequence of events, which occur over micro- to milliseconds, comprising changes at the Mn4CaO5 cluster, its ligands and water pathways as well as controlled proton release through the hydrogen-bonding network of the Cl1 channel. Importantly, the extra O atom Ox, which was introduced as a bridging ligand between Ca and Mn1 during the S2âS3 transition4-6, disappears or relocates in parallel with Yz reduction starting at approximately 700 µs after the third flash. The onset of O2 evolution, as indicated by the shortening of the Mn1-Mn4 distance, occurs at around 1,200 µs, signifying the presence of a reduced intermediate, possibly a bound peroxide.
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Oxigênio , Fotossíntese , Complexo de Proteína do Fotossistema II , Oxirredução , Oxigênio/química , Oxigênio/metabolismo , Complexo de Proteína do Fotossistema II/química , Complexo de Proteína do Fotossistema II/metabolismo , Prótons , Água/química , Água/metabolismo , Manganês/química , Manganês/metabolismo , Cálcio/química , Cálcio/metabolismo , Peróxidos/metabolismoRESUMO
Enzymes catalyze biochemical reactions through precise positioning of substrates, cofactors, and amino acids to modulate the transition-state free energy. However, the role of conformational dynamics remains poorly understood due to poor experimental access. This shortcoming is evident with Escherichia coli dihydrofolate reductase (DHFR), a model system for the role of protein dynamics in catalysis, for which it is unknown how the enzyme regulates the different active site environments required to facilitate proton and hydride transfer. Here, we describe ligand-, temperature-, and electric-field-based perturbations during X-ray diffraction experiments to map the conformational dynamics of the Michaelis complex of DHFR. We resolve coupled global and local motions and find that these motions are engaged by the protonated substrate to promote efficient catalysis. This result suggests a fundamental design principle for multistep enzymes in which pre-existing dynamics enable intermediates to drive rapid electrostatic reorganization to facilitate subsequent chemical steps.
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Aminoácidos , Eletricidade , Catálise , Escherichia coli , Conformação Molecular , Tetra-Hidrofolato DesidrogenaseRESUMO
Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.
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COVID-19 , Receptor para Produtos Finais de Glicação Avançada , SARS-CoV-2 , Humanos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/complicações , COVID-19/virologia , Animais , Camundongos , Inflamação/metabolismo , Inflamação/patologia , Síndrome do Desconforto Respiratório/imunologia , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Proteínas de Grupo de Alta Mobilidade/genética , Masculino , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologia , FemininoRESUMO
Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the development and function of these circuits remain unresolved. Here, we show that midbrain-specific deletion of the transcription factor Brn3b causes a loss of neurons projecting to the lateral posterior nucleus of the thalamus. Brn3b deletion also down-regulates the expression of the neuropeptide tachykinin 2 (Tac2). Furthermore, Brn3b mutant mice display impaired defensive freezing responses to visual threat precipitated by social isolation. This behavioral phenotype could be ameliorated by overexpressing Tac2, suggesting that Tac2 acts downstream of Brn3b in regulating defensive responses to threat. Together, our experiments identify specific genetic components critical for the functional organization of midbrain fear-related visual circuits. Similar mechanisms may contribute to the development and function of additional long-range brain circuits underlying fear-associated behavior.
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Medo , Mesencéfalo , Animais , Camundongos , Medo/fisiologia , Mesencéfalo/fisiologia , Neurônios/fisiologia , TálamoRESUMO
Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances-such as deep phenotyping, real-time targeting, and artificial intelligence-to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.
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Países em Desenvolvimento , Neoplasias , Radioterapia (Especialidade) , Humanos , Países em Desenvolvimento/economia , Neoplasias/radioterapia , Radioterapia (Especialidade)/economia , Pesquisa Biomédica/economia , Radioterapia/economia , PobrezaRESUMO
BACKGROUND: Given the typical trajectory of glioblastoma, many patients lose decision-making capacity over time, which can lead to inadequate advance care planning (ACP) and end-of-life (EOL) care. We aimed to evaluate patients' current ACP and EOL care status. PATIENTS AND METHODS: We conducted a cohort study on 205 patients referred to oncologists at a Korean tertiary hospital between 2017 and 2022. We collected information on sociodemographic factors, cancer treatment, palliative care consultation, ACP, legal documents on life-sustaining treatment (LST) decisions, and aggressiveness of EOL care. RESULTS: With a median follow-up time of 18.3 months: 159 patients died; median overall survival: 20.3 months. Of the 159 patients, 11 (6.9%) and 63 (39.6%) had advance directive (AD) and LST plans, respectively, whereas 85 (53.5%) had neither. Among the 63 with LST plans, 10 (15.9%) and 53 (84.1%) completed their forms through self-determination and family determination, respectively. Of the 159 patients who died, 102 (64.2%) received palliative care consultation (median time: 44 days from the first consultation to death) and 78 (49.1%) received aggressive EOL care. Those receiving palliative care consultations were less likely to receive aggressive EOL care (83.3% vs 32.4%, Pâ <â .001), and more likely to use more than 3 days of hospice care at EOL (19.6% vs 68.0%, Pâ <â .001). CONCLUSIONS: The right to self-determination remains poorly protected among patients with glioblastoma, with nearly 90% not self-completing AD or LST plan. As palliative care consultation is associated with less aggressive EOL care and longer use of hospice care, physicians should promptly introduce patients to ACP conversations and palliative care consultations.
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Poly(ADP-ribose) polymerases (PARPs) are critical to regulating cellular activities, such as the response to DNA damage and cell death. PARPs catalyze a reversible post-translational modification (PTM) in the form of mono- or poly(ADP-ribosyl)ation. This type of modification is known to form a ubiquitin-ADP-ribose (Ub-ADPR) conjugate that depends on the actions of Deltex family of E3 ubiquitin ligases (DTXs). In particular, DTXs add ubiquitin to the 3'-OH of adenosine ribose' in ADP-ribose, which effectively sequesters ubiquitin and impedes ubiquitin-dependent signaling. Previous work demonstrates DTX function for ubiquitination of protein-free ADPR, mono-ADP-ribosylated peptides, and ADP-ribosylated nucleic acids. However, the dynamics of DTX-mediated ubiquitination of poly(ADP-ribosyl)ation remains to be defined. Here we show that the ADPR ubiquitination function is not found in other PAR-binding E3 ligases and is conserved across DTX family members. Importantly, DTXs specifically target poly(ADP-ribose) chains for ubiquitination that can be cleaved by PARG, the primary eraser of poly(ADP-ribose), leaving the adenosine-terminal ADPR unit conjugated to ubiquitin. Our collective results demonstrate the DTXs' specific ubiquitination of the adenosine terminus of poly(ADP-ribosyl)ation and suggest the unique Ub-ADPR conjugation process as a basis for PARP-DTX control of cellular activities.
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Adenosina Difosfato Ribose , Ubiquitina-Proteína Ligases , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Humanos , Adenosina Difosfato Ribose/metabolismo , Poli ADP Ribosilação , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Poli(ADP-Ribose) Polimerases/química , Poli(ADP-Ribose) Polimerases/genética , Ubiquitina/metabolismo , ADP-Ribosilação , Células HEK293RESUMO
BACKGROUND: Early selection in tree breeding could be achieved by addressing the longevity of tree improvement activities. Genetic parameter changes and age-age correlations are essential for determining the optimal timing of early selection. Practical tracking of genetic parameters of Pinus koraiensis, a major timber species with economic and ecological value, has become feasible as its progeny testing has entered the mid-term age in Korea. However, research on the age-age correlation of P. koraiensis as progeny trials approach rotation age is limited. This study aimed to investigate genetic parameter trends and age-age correlations in P. koraiensis progeny. P. koraiensis progeny were assessed at two sites using a linear mixed-effects model with two-dimensional spatial autoregressive structure. Height, diameter, and volume growth were measured in 11 assessments over 40 years. RESULTS: Genetic parameters, such as height and diameter, showed different patterns of change. The heritability ranged for the three growth traits in 0.083-0.710, 0.288-0.781, and 0.299-0.755 across the sites and age. Height heritability and its coefficient of variance decreased, whereas the diameter and volume estimates remained relatively constant. Correlations with Age 40 for phenotypic, genetic, and rank of breeding values ranged between 0.16 and 0.92, 0.594 and 0.988, and 0.412 and 0.965, respectively. These correlations generally increased as the age approached Age 40, with particularly high levels observed at Age 26 and Age 30. CONCLUSION: The observed genetic trends in P. koraiensis progeny testing offer valuable insights for early and precise selection. Notably, selecting superior genotypes at Ages 26-30 is supported by discernible genetic gains and robust correlations. Future research should integrate unbalanced data for selecting mother trees or families and conduct a comprehensive economic analysis of early selection to validate its practical benefits.
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Florestas , Pinus , Humanos , Adulto , Pinus/genética , Melhoramento Vegetal , Árvores , FenótipoRESUMO
This study introduces a hydrothermal synthesis method that uses glucose and Cu2+ ions to create a Cu-nanoparticle (NP)-decorated hydrothermal carbonaceous carbon hybrid material (Cu-HTCC). Glucose serves both as a reducing agent, efficiently transforming Cu2+ ions into elemental Cu nanostructures, and as a precursor for HTCC microstructures. An enhanced plasmon-induced electric field resulting from Cu NPs supported on microstructure matrices, coupled with a distinctive localized π-electronic configuration in the hybrid material, as confirmed by X-ray photoelectron spectroscopic analysis, lead to the heightened optical absorption in the visible-near-infrared range. Consequently, flexible nanocomposites of Cu-HTCC/PDMS and Cu-HTCC@PDMS (PDMS = polydimethylsiloxane) are designed as 2 and 3D structures, respectively, that exhibit broad-spectrum solar absorption. These composites promise efficient photo-assisted thermoelectric power generation and water evaporation, demonstrating commendable mechanical stability and flexibility. Notably, the Cu-HTCC@PDMS composite sponge simultaneously exhibits commendable efficiency in both water evaporation (1.47 kg m-2 h-1) and power generation (32.1 mV) under 1 sunlight illumination. These findings unveil new possibilities for innovative photothermal functional materials in diverse solar-driven applications.
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Functionality in molecular electronics relies on inclusion of molecular orbital energy level within a transmission window. This can be achieved by designing the active molecule with accessible energy levels or by widening the window. While many studies have adopted the first approach, the latter is challenging because defects in the active molecular component cause low breakdown voltages. Here, it is shown that control over the packing structure of monolayer via supramolecular mixing transforms an inert molecule into a highly tunable rectifier. Binary mixed monolayer composed of alkanethiolates with and without carboxylic acid head group as a proof of concept is formed via a surface-exchange reaction. The monolayer withstands high voltages up to |4.5 V| and shows a dynamic rectification-external bias relationship in magnitude and polarity. Sub-highest occupied molecular orbital (HOMO) levels activated by the widened transmission window account for these observations. This work demonstrates that simple supramolecular mixing can imbue new electrical properties in electro-inactive organic molecules.
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2D nanomaterials with ångström-scale thicknesses offer a unique platform for confining molecules at an unprecedentedly small scale, presenting novel opportunities for modulating material properties and probing microscopic phenomena. In this study, mesogen-tethered polyhedral oligomeric silsesquioxane (POSS) amphiphiles with varying numbers of mesogenic tails to systematically influence molecular self-assembly and the architecture of the ensuing supramolecular structures, are synthesized. These organic-inorganic hybrid amphiphiles facilitate precise spatial arrangement and directional alignment of the primary molecular units within highly ordered supramolecular structures. The correlation between molecular design and the formation of superlattices through comprehensive structural analyses, incorporating molecular thermodynamics and kinetics, is explored. The distinct intermolecular interactions of the POSS core and the mesogenic tails drive the preferential formation of a 2D inorganic sublattice while simultaneously guiding the hierarchical assembly of organic lamellae via soft epitaxy. The findings reveal the intricate balance between shape, size, and interaction strengths of the inorganic and organic components, and how these factors collectively influence the structural hierarchy of the superstructures, which consist of multiple sublattices. By controlling this unique molecular behavior, it is possible to modulate or maximize the anisotropy of optical, mechanical, and electrical properties at the sub-nanometer scale for nanotechnology applications.
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Neuregulin (NRG)-1 plays fundamental roles in several organ systems after binding to its receptors, ErbB2 and ErbB4. This study examines the role of NRG-1 in atopic dermatitis (AD), a chronic skin disease that causes dryness, pruritus, and inflammation. In mice administered Der p 38, the skin presents AD-like symptoms including filaggrin downregulation and infiltration of neutrophils and eosinophils. Noticeably, there is an increased expression of NRG-1, ErbB2, and ErbB4 in the skin. Upregulation of these proteins is significantly correlated to the clinical skin severity score. In human keratinocyte HaCaT cells, exposure to Der p 38 decreased filaggrin expression, and NRG-1 alone had no effect on the expression. However, co-treatment of Der p 38 with NRG-1 enhanced the filaggrin expression decreased by Der p 38. Pre-treatment with AG879 (an ErbB2 inhibitor) or ErbB4 siRNA blocked the recovery of filaggrin expression in the cells after co-treatment with Der p 38 and NRG-1. Der p 38 treatment enhanced the secretion of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1). Co-treatment of Der p 38 with NRG-1 lowered the cytokine secretion increased by Der p 38, although NRG-1 alone was not effective on cytokine alteration. Neutrophil apoptosis was not altered by NRG-1 or supernatants of cells treated with NRG-1, but the cell supernatants co-treated with Der p 38 and NRG-1 blocked the anti-apoptotic effects of Der p 38-treated supernatants on neutrophils, which was involved in the activation of caspase 9 and caspase 3. Taken together, we determined that NRG-1 has anti-inflammatory effects in AD triggered by Der p 38. These results will pave the way to understanding the functions of NRG-1 and in the future development of AD treatment.
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Dermatite Atópica , Camundongos , Animais , Humanos , Dermatite Atópica/genética , Proteínas Filagrinas , Neuregulina-1/farmacologia , Neuregulina-1/metabolismo , Neuregulina-1/uso terapêutico , Queratinócitos/metabolismo , Pele/metabolismo , Citocinas/metabolismo , Receptor ErbB-4/metabolismo , Receptor ErbB-4/farmacologia , Anti-Inflamatórios/farmacologiaRESUMO
BACKGROUND: A high expression pattern of minichromosome maintenance 2 (MCM2) has been observed in various cancers. MCM2 is a protein involved in the cell cycle and plays a role in cancer growth and differentiation by binding to six members of the MCM subfamily. The MCM protein family includes MCM2 through MCM7. METHODS: MCM2 has shown high expression in both lung cancer stem cells (LCSCs) and glioma stem cells (GSCs). We investigated the characteristics of CSCs and the regulation of the epithelial-to-mesenchymal transition (EMT) phenomenon in LCSCs and GSCs by MCM2. Additionally, we explored secreted factors regulated by MCM2. RESULTS: There was a significant difference in survival rates between lung cancer patients and brain cancer patients based on MCM2 expression. MCM2 was found to regulate both markers and regulatory proteins in LCSCs. Moreover, MCM2 is thought to be involved in cancer metastasis by regulating cell migration and invasion, not limited to lung cancer but also identified in glioma. Among chemokines, chemokine (C-X-C motif) ligand 1 (CXCL1) was found to be regulated by MCM2. CONCLUSIONS: MCM2 not only participates in the cell cycle but also affects cancer cell growth by regulating the external microenvironment to create a favorable environment for cells. MCM2 is highly expressed in malignant carcinomas, including CSCs, and contributes to the malignancy of various cancers. Therefore, MCM2 may represent a crucial target for cancer therapeutics.
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Neoplasias Pulmonares , Proteínas de Manutenção de Minicromossomo , Humanos , Quimiocina CXCL1 , Proteínas de Manutenção de Minicromossomo/genética , Proteínas , Células-Tronco Neoplásicas/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/genética , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Proteínas de Ciclo Celular/genética , Microambiente TumoralRESUMO
BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.
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Adenocarcinoma , Ampola Hepatopancreática , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Neoplasias do Ducto Colédoco , Oxaliplatina , Humanos , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Masculino , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Ampola Hepatopancreática/patologia , Feminino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adulto , Neoplasias do Ducto Colédoco/tratamento farmacológico , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/mortalidade , Estudos Retrospectivos , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).
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Niacinamida/análogos & derivados , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Irinotecano , Neoplasias Gástricas/patologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Antígeno B7-H1 , Camptotecina , Estudos Retrospectivos , Neoplasias Peritoneais/tratamento farmacológico , Fluoruracila , Leucovorina , República da Coreia/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
INTRODUCTION: The relationship between fat mass and osteoporosis, sarcopenia and osteosarcopenia is complex. While higher fat mass generally has a negative impact on bone and muscle health in the general population, the impact in peritoneal dialysis (PD) patients is less well understood. METHODS: In this study of 359 PD patients, sarcopenia was identified using appendicular skeletal muscle per square meter (ASM/m²), with cut-off values of <7.0 kg/m² for men and <5.5 kg/m² for women. Fat tissue index (FTI) and lean tissue index (LTI) were determined using body composition monitoring, with the lowest tertile classified as low FTI and low LTI. Bone mineral density (BMD) was measured, with a T-score below -2.5 indicating osteoporosis. RESULTS: The prevalence of osteoporosis, sarcopenia, and osteosarcopenia was 25%, 32%, and 15%, respectively. Notably, 60% of osteoporotic patients had sarcopenia, and about 45% of sarcopenic patients had osteoporosis. Patients with osteoporosis were older and had significantly lower LTI (15.3 vs. 12.7 kg/m², p<0.001) and ASM (7.3 vs. 5.8 kg/m2, p<0.001). Osteoporotic patients also had lower FTI, but this was more pronounced in men than in women. Patients with both sarcopenia and osteoporosis had the lowest LTI and FTI compared to those with only one or neither condition. Low FTI was a significant determinant for osteoporosis (OR, 2.34; 95% CI, 1.43-3.85; P = 0.001), sarcopenia (OR, 2.91; 95% CI, 1.82-4.64; P < 0.001), and osteosarcopenia (OR, 2.34; 95% CI, 1.30-4.24; P = 0.005) in univariate analysis, and these associations remained significant after adjustment for age and body mass index. CONCLUSION: Osteoporosis and sarcopenia are common and interrelated in PD patients. Low fat mass, but not normal/high fat mass, was significantly associated with these conditions, suggesting the importance of maintaining adequate fat mass in PD patients.
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Three Gram-reaction-positive bacterial strains, designated KSW-18T, KSW2-22, and KSW4-11T, were isolated from seawater, and two dried seaweed samples collected at Gwakji Beach in Jeju, Republic of Korea, respectively, and their taxonomic positions were examined by a polyphasic approach. The 16S rRNA gene phylogeny showed that strain KSW4-11T was tightly associated with Microbacterium oleivorans NBRC 103075T, while strains KSW-18T and KSW2-22 formed a distinctive subline at the base of a clade including the above two strains. The three isolates showed high sequence similarity with one another (99.7-99.9%; 1-4 nt differences) and Microbacterium oleivorans (99.8-99.9%; 1-3 nt differences). The chemotaxonomic features were typical for the genus Microbacterium; Lysine as the diagnostic diamino acid and N-glycolylated muramic acid of the peptidoglycans, the predominant menaquinones of MK-11, MK-10 and MK-12, the major fatty acids of anteiso-C15:0 and anteiso-C17:0, and the major polar lipids including diphosphatidylglycerol, phosphatidylglycerol, and two or three unidentified glycolipids. In core genome-based phylogenetic tree, strains KSW-18T and KSW2-22 were closely associated with Microbacterium oleivorans NBRC 103075T, while strain KSW4-11T formed a distinctive subline at the base of a clade including the above three strains, in contrast to the 16S rRNA gene tree. Strains KSW-18T and KSW2-22 shared an OrthoANIu of 98.6% and a digital DNA-DNA hybridization of 87.6% with each other, representing that they were strains of a species, while the OrthoANIu and digital DNA-DNA hybridization values between strains KSW-18T and KSW4-11T, and between both of these isolates and all members of the genus Microbacterium were ≤86.5% and ≤30.7%, respectively. The analyses of overall genomic relatedness indices and phenotypic distinctness support that the three isolates represent two new species of the genus Microbacterium. Based on the results obtained here, Microbacterium aquilitoris sp. nov. (type strain KSW-18T = KCTC 49623T = NBRC 115222T) and Microbacterium gwkjiense sp. nov. (type strain KSW4-11T = KACC 23321T = DSM 116380T) are proposed.
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Actinomycetales , Microbacterium , Filogenia , RNA Ribossômico 16S/genética , Actinomycetales/genética , DNARESUMO
Three actinobacterial strains, KSW2-21T, KSW2-29T and KSW4-17T, were isolated from dried seaweeds collected around Gwakji Beach in Jeju, Republic of Korea. Their taxonomic positions were determined based on genomic, physiological and morphological characteristics. The isolates were Gram-positive, aerobic, non-motile, rod-shaped bacteria characterized by the following chemotaxonomic features: ornithine as the cell wall diamino acid, the N-glycolyl type of murein, MK-11 as the predominant menaquinone, polar lipids including diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids and four unidentified phospholipids, with anteiso-C15â:â0, iso-C16â:â0 and anteiso-C17â:â0 as the the major fatty acids. The 16S rRNA gene phylogeny showed that the novel strains formed three distinct sublines within the genus Microbacterium. Strain KSW4-17T formed a tight cluster with the type strain of Microbacterium hydrothermale, while strains KSW2-21T and KSW2-29T occupied distinct positions between the type strains of M. hydrothermale and Microbacterium testaceum. Strains KSW4-17T and KSW2-29T showed 99.9â% rRNA gene sequence similarity to M. hydrothermale CGMCC 1.12512T, while strain KSW2-21T revealed 99.4â% 16S rRNA gene sequence similarity to the type strains of M. hydrothermale and M. testaceum. The genome sizes and genomic G+C contents of the three isolates ranged from 3.44 to 3.74 Mbp and from 70.3 to 70.8âmol%, respectively. The phylogenomic tree based on 92 core gene sequences exhibited similar topologies to the 16S rRNA gene phylogeny. The comparison of overall genomic relatedness indices, such as average nucleotide indentity and digital DNA-DNA hybridization, supported that the isolates represent three new species of the genus Microbacterium. Based on the results obtained here, Microbacterium algihabitans sp. nov. (type strain, KSW2-21T=KACC 23322T=DSM 116381T), Microbacterium phycohabitans sp. nov. (type strain KSW2-29T=KACC 22350T=NBRC 115221T) and Microbacterium galbum sp. nov. (type strain, KSW4-17T=KACC 23323T=DSM 116383T) are proposed.
Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Microbacterium , Filogenia , RNA Ribossômico 16S , Alga Marinha , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , Alga Marinha/microbiologia , República da Coreia , Ácidos Graxos/química , DNA Bacteriano/genética , Microbacterium/genética , Microbacterium/classificação , Fosfolipídeos , Hibridização de Ácido Nucleico , Vitamina K 2/análogos & derivadosRESUMO
Two Gram-stain-positive, aerobic, non-spore-forming, non-motile, irregular rod-shaped actinobacteria, designated as D2-41T and D3-21, were isolated from soil samples collected in a natural cave in Jeju, Republic of Korea. Both of the isolates were shown to share 100â% 16S rRNA sequence identity. The cell wall contained meso-diaminopimelic acid, arabinose and galactose. The predominant menaquinone was MK-8(H2). The polar lipids contained phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, an unidentified aminolipid, an unidentified aminoglycolipid, an unidentified phospholipid and two unidentified lipids. The predominant fatty acids were C16â:â0 and summed feature 3 (C16â:â1 ω7c and/or iso-C15â:â0 2-OH). Mycolic acids of C30-C38 were present. The 16S rRNA gene trees showed that the organisms occupied a distinct position remotely located from recognized genera within the order Mycobacteriales, albeit with the 16S rRNA gene similarities of 97.0-97.1â% with Rhodococcus olei, Rhodococcus rhodnii and Rhodococcus triatomae. The genome sizes and DNA G+C contents of strains D2-41T and D3-21 were 4.77-4.88 Mbp and 69.8âmol%, respectively. Both of the isolates shared an average nucleotide identity of 99.4â% and digital DNA-DNA hybridization of 95.2â% to each other, revealing that strains D2-41T and D3-21 belonged to the same species. In the core genome-based phylogenomic tree, both of the isolates were found to be closely associated with members of the genus Tomitella. However, strains D2-41T and D3-21 revealed the highest amino acid identity values (mean 66.5â%, range 66.2-67.0â% with the genus Prescottella of the family Nocardiaceae, followed by the genus Tomitella (mean 64.1â%, range 63.6-64.7â%) of the family Tomitellaceae. Based on the combined data obtained here, the novel isolates belong to a new genus of the new family for which the name Speluncibacter jeojiensis gen. nov. sp. nov. is proposed, with Speluncibacteraceae fam. nov. The type strain is strain D2-41T (=KACC 17930T=DSM 101875T).