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Soil salinity is detrimental to plant growth and remains a major threat to crop productivity of the world. Plants employ various physiological and molecular mechanisms to maintain growth under salt stress. Identification of genes and genetic loci underlying plant salt tolerance holds the key to breeding salt tolerant crops. CIPK-CBL pathways regulate adaptive responses of plants (especially ion transport) to abiotic stresses via fine-tuned Ca2+ signal transduction. In this study, we showed that over-expression of OsCIPK17 in Arabidopsis enhanced primary root elongation under salt stress, which is in a Ca2+ dependent manner. Further investigation revealed that, under salt stress, OsCIPK17 transcript level was significantly induced and its protein moved from the cytosol to the tonoplast. Using both Y2H and BiFC, tonoplast-localised OsCBL2 and OsCBL3 were shown to interact with OsCIPK17. Interestingly, over-expressing salt-induced OsCBL2 or OsCBL3 in Arabidopsis led to enhanced primary root elongation under salt stress. In this process, OsCIPK17 was shown recruited to the tonoplast (similar to the effect of salt stress). Furthermore, transgenic Arabidopsis lines individually over-expressing OsCIPK17, OsCBL2 and OsCBL3 all demonstrated larger biomass and less Na + accumulation in the shoot under salt stress. All data combined suggest that OsCIPK17- OsCBL2/3 module is a major component of shoot Na+ exclusion and therefore plant salt tolerance, which is through enhanced Na + compartmentation into the vacuole in the root. OsCIPK17 and OsCBL2/3 are therefore potential genetic targets that can be used for delivering salt tolerant rice cultivars.
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Arabidopsis , Oryza , Proteínas de Plantas , Brotos de Planta , Plantas Geneticamente Modificadas , Tolerância ao Sal , Sódio , Arabidopsis/genética , Arabidopsis/metabolismo , Oryza/genética , Oryza/metabolismo , Tolerância ao Sal/genética , Brotos de Planta/genética , Brotos de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sódio/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/genética , Raízes de Plantas/metabolismoRESUMO
[This retracts the article DOI: 10.1016/j.omtn.2021.11.012.].
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A novel bacterial strain, designated DW002T, was isolated from the sea ice of Cape Evans, McMurdo Sound, Antarctica. Cells of the strain were Gram-negative, obligate anaerobic, motile, non-flagellated, and short rod-shaped. The strain DW002T grew at 4-32 â (optimum at 22-28 â) and thrived best at pH 7.0, NaCl concentration of 2.5% (w/v). The predominant isoprenoid quinone of strain DW002T was menaquinone-7 (MK-7). The major fatty acids (> 10%) of DW002T were iso-C15:0, anteiso-C15:0 and iso-C17:1ω9c. The predominant polar lipids of strain DW002T contained two phosphatidylethanolamines, one unidentified glycolipid, one unidentified aminolipid and four unidentified lipids. The DNA G + C content of the strain DW002T was 34.8%. Strain DW002T encoded 237 carbohydrate-active enzymes. The strain DW002T had genes associated with dissimilatory nitrate reduction and assimilatory sulfate reduction metabolic pathways. Based on distinct physiological, chemotaxonomic, genome analysis and phylogenetic differences compared to other members of the phylogenetically related genera in the family Marinifilaceae, strain DW002T is proposed to represent a novel genus within the family. Therefore, the name Paralabilibaculum antarcticum gen. nov., sp. nov. is proposed. The type strain is DW002T (=KCTC 25274T=MCCC 1K06067T).
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Composição de Bases , DNA Bacteriano , Ácidos Graxos , Camada de Gelo , Filogenia , RNA Ribossômico 16S , Regiões Antárticas , RNA Ribossômico 16S/genética , Ácidos Graxos/metabolismo , Camada de Gelo/microbiologia , DNA Bacteriano/genética , Anaerobiose , Técnicas de Tipagem Bacteriana , Fosfolipídeos/análiseRESUMO
Subarachnoid hemorrhage (SAH) induced acute impairment of the glymphatic system, but few have investigated the dysfunction of the meningeal lymphatic system and their contribution to the pathophysiology of SAH. In addition, most studies were conducted in rodent animals. We aimed to investigate the impact of SAH on glymphatic and meningeal lymphatic function in a large animal model using beagles and to evaluate the effects of intermittent cistern magna CSF drainage on these systems. Methods: The SAH model was created in beagles via endovascular perforation using a digital subtraction angiography machine. Intermittent cistern magna CSF drain was performed daily from 1 d to 3 d after SAH. We examined CSF pressure, neuronal death, enlargement of perivascular space (PVS), hydrocephalus, and neurological and cognitive deficits before and after SAH. The dynamics of glymphatic and meningeal lymphatic functions were analyzed by quantifying the signal intensity of dimeglumine gadopentetate (Gd-DTPA) using T1-weighted magnetic resonance imaging (MRI). Measurements were taken before SAH and at 1 h, 1 week, and 2 weeks post-SAH. Results: SAH in beagles caused significant blood clots, neuronal death, increased CSF pressure, hydrocephalus, and neurological and cognitive deficits. MRI revealed dilated ventricles and enlarged PVS post-SAH. The glymphatic system's function, assessed by Gd-DTPA distribution, showed reduced CSF influx and glymphatic impairment after SAH, particularly in the ipsilateral hemisphere, persisting for a week with partial recovery at 2 weeks. For lymphatic clearance, Gd-DTPA rapidly filled the olfactory bulbs, optic nerves, facial and vestibulocochlear nerves, and spinal nerves under normal conditions. SAH caused delayed and reduced Gd-DTPA efflux outflow in these areas, disrupting lymphatic clearance. Despite initial dysfunction, increased hemoglobin levels in cervical lymph nodes indicated active blood clearance post-SAH, with recovery by 2 weeks. Treatment with intermittent cistern magna CSF drain significantly ameliorated the glymphatic and meningeal lymphatic dysfunction after SAH. Conclusion: SAH impaired both glymphatic and meningeal lymphatic functions in beagles, with better restoration of lymphatic function post-SAH, which may contribute to functional recovery after SAH. External CSF drain is an effective therapeutic approach to facilitate the recovery of glymphatic and meningeal lymphatic function following SAH.
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Modelos Animais de Doenças , Sistema Glinfático , Sistema Linfático , Meninges , Hemorragia Subaracnóidea , Animais , Cães , Sistema Glinfático/fisiopatologia , Hemorragia Subaracnóidea/fisiopatologia , Meninges/fisiopatologia , Sistema Linfático/fisiopatologia , Masculino , Imageamento por Ressonância Magnética/métodos , Cisterna Magna , Gadolínio DTPA/administração & dosagemRESUMO
Pseudorabies virus (PRV) infection causes systemic inflammatory responses and inflammatory damages in infected animals, which are associated with the activation of inflammasome and pyroptosis in infected tissues. Here, we identified a critical function of PRV non-structural protein UL4 that enhanced ASC-dependent inflammasome activation to promote pyroptosis. Whereas, the deficiency of viral UL4 was able to reduce ASC-dependent inflammasome activation and the occurrences of pyroptosis. Mechanistically, the 132-145 aa of UL4 permitted its translocation from the nucleus to the cytoplasm to interact with cytoplasmic ASC to promote the activation of NLRP3 and AIM2 inflammasome. Further research showed that UL4 promoted the phosphorylation levels of SYK and JNK to enhance the ASC phosphorylation, which led to the increase of ASC oligomerization, thus promoting the activation of NLRP3 and AIM2 inflammasome and enhanced GSDMD-mediated pyroptosis. In vivo experiments further showed that PRV UL4 (132DVAADAAAEAAAAE145) mutated strain (PRV-UL4mut) infection did not lead to a significant decrease in viral titers at 12 h. p. i, but it induced lower levels of IL-1ß, IL-18, and GSDMD-NT, which led to an alleviated inflammatory infiltration and pathological damage in the lungs and brains, and a lower death rate compared with wild-type PRV strain infection. Taken together, our findings unravel that UL4 is an important viral regulator to manipulate the inflammasome signaling and pyroptosis of host cells to promote the pathogenicity of PRV, which might be further exploited as a new target for live attenuated vaccines or therapeutic strategies against pseudorabies in the future.
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Proteínas Adaptadoras de Sinalização CARD , Herpesvirus Suídeo 1 , Inflamassomos , Inflamação , Pseudorraiva , Piroptose , Animais , Inflamassomos/metabolismo , Inflamassomos/imunologia , Camundongos , Herpesvirus Suídeo 1/imunologia , Inflamação/metabolismo , Pseudorraiva/virologia , Pseudorraiva/metabolismo , Pseudorraiva/imunologia , Pseudorraiva/patologia , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas Virais/metabolismo , Proteínas Virais/genética , Camundongos Endogâmicos C57BLRESUMO
Background: Acute myeloid leukemia (AML) is the most common type of acute leukemia among adults with the recommend therapy of combination of cytarabine and idarubicin in the induction phase. The uncoordinated pharmacokinetics prevent adequate control of drug ratio following systemic administration. Therefore, the dual-loaded liposomes containing cytarabine and idarubicin for synergistic effects were proposed and investigated. Methods: The molar ratio of cytarabine and idarubicin for synergistic effects was investigated. The dual-loaded liposomes were prepared and characterized by particle size, zeta potential, encapsulation efficiency, cryo-Transmission electron microscopy (cryo-TEM), and in vitro stability. The in vitro cytotoxicity and cell uptake of liposomes were determined within CCRF-CEM cells. The PK experiments was carried out in male SD rats. The in vivo antitumor effect was carried out within CD-1 nude female mice. The antitumor mechanism of liposomes was investigated. Results: The synergistic molar ratios were found to be in the range of 20:1~40:1. The size distribution of the dual-loaded liposomes was approximately 100 nm with PDI ≤ 0.1, a zeta potential of approximately -30 mV, an entrapment efficiency of cytarabine and idarubicin of >95% with spherical structure and uniform distribution, and in vitro stability for 21 d. The drugs in the liposomes can be quickly uptaken by the leukemia cells. The PK experiments showed that the molar ratio of cytarabine to idarubicin in plasma was maintained at 30:1 within 4 h. The efficacy of liposomes was significantly enhanced. Conclusions: The dual-loaded liposomes containing cytarabine and idarubicin showed enhanced antitumor efficacy.
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The multimode assay based on multiple response mechanisms has received great attention to effectively improve the accuracy of a sensing platform. However, multifunctional sensing materials for simultaneously satisfying the multiple-mode detections are still in shortage due to the incompatibility of the signal transduction mechanisms in different modes. Here, taking human papillomavirus 16 (HPV-16) DNA (TDNA) as the model due to its important role in cervical cancer, a novel multifunctional material, ethyl violet (EV)@NH2-MIL-88B(Fe) (ENM) hybrids, have been successfully prepared, which could simultaneously satisfy CRISPR-Cas12a-assisted photoelectrochemical (PEC)-fluorescent (FL)-colorimetric (CL) triple-mode detection of TDNA. Based on the TDNA-induced trans-cleavage ability of CRISPR-Cas12a and efficient separation of magnetic beads, ENM was obtained from the single-stranded DNA-surrounded streptavidin-modified magnetic beads-ENM (SMB-ssDNA-ENM) and decomposed by pyrophosphate to get free EV, 2-aminoterephthalic acid (NH2-BDC), and Fe3+. Thus, TDNA was sensitively detected based on the EV-enhanced PEC signal of SnS2 nanosheets (PEC mode), fluorescent signal of NH2-BDC (FL mode), and characteristic absorption peak at about 720 nm of Fe3+-induced Prussian blue (PB) (CL mode). The designed PEC-FL-CL triple-mode biosensing platform had good performance for the detection of TDNA with a wide linear range (0.1 fM-100 nM) and ultralow detection limits (0.07 fM for PEC, 0.03 fM for FL and 0.09 fM for CL). Additionally, the developed PEC-FL-CL triple-mode biosensing platform has great potential for applications in early disease diagnosis and bioanalysis, as it can be easily extended to other DNA assays through modification of the crRNA sequence within the CRISPR-Cas12a system.
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Sistemas CRISPR-Cas , Papillomavirus Humano 16 , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Sistemas CRISPR-Cas/genética , Técnicas Eletroquímicas/métodos , DNA Viral/análise , DNA Viral/genética , Humanos , Colorimetria/métodos , Técnicas Biossensoriais/métodos , Limite de Detecção , Corantes Fluorescentes/químicaRESUMO
BACKGROUND: Relative fat mass (RFM) is a newly developed, sex-specific anthropometric formula designed to estimate total body fat percentage. However, research investigating the correlation between RFM and the risk of non-alcoholic fatty liver disease (NAFLD) remains limited. This study evaluates the association between RFM and the risk of NAFLD within the Japanese population. METHODS: This study including 14,250 Japanese adults who underwent physical examinations at Murakami Memorial Hospital between 2004 and 2015. We employed binary logistic regression to elucidate the direct relationship between RFM levels and the incidence of NAFLD. Additionally, a generalized additive model (GAM) coupled with smooth curve fitting techniques was utilized to map the non-linear association. RESULTS: The cohort had an average age of 43.53 ± 8.89 years, with a male majority of 52.00%. NAFLD was identified in 17.59% of the participants. After adjusting for confounding factors, a significant positive correlation between RFM and NAFLD risk was observed (OR: 1.15, 95%CI: 1.10-1.21, P < 0.0001 for females; OR: 1.15, 95%CI: 1.10-1.19, P < 0.0001 for males). Additionally, a non-linear relationship between RFM and the incidence of NAFLD was detected in both genders. The RFM threshold was identified as 34.95 for women and 23.40 for men. RFM was positively associated with the risk of NAFLD when RFM was below the respective threshold (OR: 1.29, 95%CI: 1.19-1.40, P < 0.0001 for females; OR: 1.23, 95%CI: 1.17-1.29, P < 0.0001 for males), whereas no significant association was found when RFM was above the threshold (OR: 1.05, 95%CI: 0.98-1.12, P = 0.1829 for females; OR: 1.01, 95%CI: 0.95-1.08, P = 0.7392 for males). CONCLUSION: Our findings suggest a positive, nonlinear relationship between RFM and the risk of NAFLD, with a saturation effect. These results imply that maintaining RFM at a lower level may be advantageous in mitigating the risk of NAFLD.
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Advancing the compositional space of a compound class can result in intriguing superconductors, such as LaH10. Herein, we performed a comprehensive first-principles structural search on a binary B-C system with various chemical compositions. The identified diamond-like BC15, named d-BC15, is thermodynamically superior to the synthesized BC3 and BC5. Interestingly, d-BC15 shows anisotropic superconductivity resulting from three distinct Fermi surfaces. Its predicted critical temperature (Tc) is 43.6 K at ambient pressure, beyond the McMillan limit. d-BC15 reaches a maximum of around 75 K at 0.43% hole doping due to the substantially enhanced density of states at the Fermi level. Additionally, d-BC15 demonstrates superhard characteristics with a Vickers hardness of 75 GPa. The calculated tensile and shear stresses are 72 and 73 GPa, respectively. The combination of high superconductivity and superhardness in d-BC15 offers new insights into the design of multifunctional materials.
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Objective: It has been recognized that there is a nexus among Trisomy 8 (T8), Behcet's disease (BD), and myelodysplastic syndrome (MDS). We reported a series of inflammatory features in 2 children with T8 without hematological involvement. Methods: 2 children with trisomy 8 who were excluded from MDS were retrospectively collected from the Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing. Results: Patients developed a range of inflammatory manifestations before a diagnosis of T8. The clinical manifestations of T8 patients vary from normal to severely disabled. Glucocorticoids and thalidomide can effectively relieve inflammation in patients with T8. Conclusion: The early clinical manifestations of T8 in children lack specificity, and the diagnosis is mainly based on karyotype analysis, gastrointestinal endoscopy and bone marrow aspiration findings. Active and effective immunoregulatory therapy and long-term follow-up can improve the prognosis of patients with T8.
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PURPOSE: To evaluate the therapeutic efficacy of intravenous amoxicillin clavulanate potassium combined with nebulized budesonide and ambroxol hydrochloride in pediatric community-acquired pneumonia (CAP) and its impact across various microbial strains and clinical symptoms. The primary objective of this study is to evaluate the efficacy of intravenous amoxicillin-clavulanate combined with nebulized budesonide and ambroxol hydrochloride in the treatment of pediatric community-acquired pneumonia (CAP), and to analyze their impact on different microbial strains and clinical symptoms. Secondary objectives include assessing the treatment's effect on the improvement of clinical symptoms, hospital stay duration, and the levels of inflammatory markers. DESIGN: Prospective, single-center study. METHODS: Fifty-six children with CAP, aged under 6 years, from Affiliated Maternity and Child Health Care Hospital of Nantong University were included. Patients were treated with conventional therapy and the study medication. Clinical characteristics, microbiological data, symptom improvement, and hospitalization times were analyzed. FINDINGS: Young children, particularly under 1 year, exhibited a higher incidence of multiple microbial infections and severe clinical manifestations. Treatment with budesonide and ambroxol hydrochloride led to significant clinical improvement across all age groups, with notable efficacy against various pathogens. CONCLUSIONS: Nebulized budesonide and ambroxol hydrochloride are effective in treating pediatric CAP, offering a promising therapeutic option, particularly for young children with severe presentations.
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Ambroxol , Budesonida , Infecções Comunitárias Adquiridas , Nebulizadores e Vaporizadores , Humanos , Ambroxol/administração & dosagem , Ambroxol/uso terapêutico , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Feminino , Masculino , Pré-Escolar , Lactente , Estudos Prospectivos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Resultado do Tratamento , Administração por Inalação , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Criança , Pneumonia/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Expectorantes/administração & dosagem , Expectorantes/uso terapêutico , Biomarcadores/sangue , Quimioterapia Combinada , Tempo de InternaçãoRESUMO
Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.
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Desenho de Fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1 , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Animais , Humanos , Camundongos , Relação Estrutura-Atividade , Masculino , Hipoglicemiantes/farmacologia , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Receptores de Glucagon/agonistas , Receptores de Glucagon/metabolismoRESUMO
BACKGROUND: We aimed to evaluate the trajectory of skin barrier properties in full-term newborns during the first four days after birth. METHODS: Based on the MKNFOAD cohort (NCT02889081), transepidermal water loss (TEWL), stratum corneum hydration (SCH), skin pH, and sebum content at five anatomical sites (cheek, forehead, volar forearm, abdomen, and dorsal lower leg) were examined once within 96 h after birth in 384 full-term infants. Multivariable linear regression analysis was performed to assess variations in these skin barrier parameters with age adjusted for gestational age, neonate's sex, parents' allergy history, delivery mode, amniotic fluid characteristics, and birth weight. The regression coefficient (ß) and 95% confidence interval were reported. RESULTS: We analyzed a total of 384 neonates including 198 (51.6%) boys. TEWL values remained stable and showed no significant association with age (days). pH values exhibited a declining trend with age (p for trend <0.001). Both SCH values and sebum content grew with age (p for trend <0.001). CONCLUSION: During the first four days after birth, the skin TEWL remained stable, pH decreased, and the SCH and sebum content increased over time. These findings provide insights into the neonatal skin physiological development at the beginning of life. IMPACT: From birth to 96 h, TEWL was stable, pH showed a steep decline, SCH and sebum content increased. This study provides the first evidence of skin adaptation in the newborn due to changes in utero to after birth in the first 4 days of life in an Asian population. These findings will provide a new theoretical basis for neonatal skin physiology and clinical strategies for guiding newborn skin care.
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Coral reefs rely heavily on reef fish for their health, yet overfishing has resulted in their decline, leading to an increase in fast-growing algae and changes in reef ecosystems, a phenomenon described as the phase-shift. A clearer understanding of the intricate interplay between herbivorous, their food, and their gut microbiomes could enhance reef health. This study examines the gut microbiome and isotopic markers (δ13C and δ15N) of four key nominally herbivorous reef fish species (Acanthurus chirurgus, Kyphosus sp., Scarus trispinosus, and Sparisoma axillare) in the Southwestern Atlantic's Abrolhos Reef systems. Approximately 16.8 million 16S rRNA sequences were produced for the four fish species, with an average of 317,047 ± 57,007 per species. Bacteria such as Proteobacteria, Firmicutes, and Cyanobacteria were prevalent in their microbiomes. These fish show unique microbiomes that result from co-diversification, diet, and restricted movement. Coral-associated bacteria (Endozoicomonas, Rhizobia, and Ruegeria) were found in abundance in the gut contents of the parrotfish species Sc. trispinosus and Sp. axillare. These parrotfishes could aid coral health by disseminating such beneficial bacteria across the reef. Meanwhile, Kyphosus sp. predominantly had Pirellulaceae and Rhodobacteraceae. Four fish species had a diet composed of turf components (filamentous Cyanobacteria) and brown algae (Dictyopteris). They also had similar isotopic niches, suggesting they shared food sources. A significant difference was observed between the isotopic signature of fish muscular gut tissue and gut contents, pointing to the role that host genetics and gut microbes play in differentiating fish tissues.
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Bactérias , Recifes de Corais , Peixes , Microbioma Gastrointestinal , RNA Ribossômico 16S , Animais , RNA Ribossômico 16S/genética , Peixes/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Herbivoria , Especificidade da Espécie , Isótopos de Carbono/análise , Isótopos de Nitrogênio/análise , Perciformes/microbiologia , Dieta/veterináriaRESUMO
OBJECTIVE: The relationship between body fat mass and bone mineral density (BMD) remains controversial. This research aimed to explore the linear or non-linear relationship between body fat mass and BMD among adults in the United States. METHODS: This cross-sectional study identified adults aged 18 years or older in the National Health and Nutrition Examination Survey from 2011 to 2018. After adjusting for covariates, linear relationships between body fat mass and BMD in different genders were tested by generalized linear models, and potential non-linear relationships were explored by generalized additive models and piecewise linear regression models. RESULTS: The research included 4691 (57.9% of the total sample) males and 3417 (42.1% the of total sample) females. In both males and females, we found a negative association between android or total body fat mass and lumbar spine BMD and a positive association between appendicular, android, gynoid, or total body fat mass and whole body BMD (all P < 0.05). The relationships between body fat mass in all regions and lumbar spine BMD were U-shaped in males and inverted U-shaped in females (all Pnon-linear < 0.05). Inverted U-shaped relationships existed between body fat mass in all regions and whole body BMD in females (all Pnon-linear < 0.05). CONCLUSIONS: Body fat mass was negatively and linearly associated with lumbar spine BMD, but positively associated with whole body BMD. Body fat mass had a U-shaped relationship with lumbar spine BMD in males and an inverted U-shaped association with lumbar spine and whole body BMD in females.
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Densidade Óssea , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Densidade Óssea/fisiologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Estados Unidos , Distribuição da Gordura Corporal , Vértebras Lombares/fisiologia , Idoso , Tecido AdiposoRESUMO
Hydrogen sulfide (H2S), methanethiol (MeSH) and dimethylsulfide (DMS) are abundant sulfur gases with roles in biogeochemical cycling, chemotaxis and/or climate regulation. Catabolism of the marine osmolyte dimethylsulfoniopropionate (DMSP) is a major source of DMS and MeSH, but both also result from S-methylation of H2S via MddA, an H2S and MeSH S-methyltransferase whose gene is abundant in soil but scarce in marine environments. Here we identify the S-adenosine methionine (SAM)-dependent MeSH and H2S S-methyltransferase 'MddH', which is widespread in diverse marine bacteria and some freshwater and soil bacteria. mddH is predicted in up to ~5% and ~15% of seawater and coastal sediment bacteria, respectively, which is considerably higher than mddA. Furthermore, marine mddH transcript levels are similar to those for the most abundant DMSP lyase gene dddP. This study implies that the importance of H2S and MeSH S-methylation pathways in marine environments is significantly underestimated.
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Bactérias , Sulfeto de Hidrogênio , Metiltransferases , Água do Mar , Sulfetos , Compostos de Sulfônio , Bactérias/genética , Bactérias/metabolismo , Bactérias/enzimologia , Bactérias/classificação , Sulfetos/metabolismo , Água do Mar/microbiologia , Metiltransferases/metabolismo , Metiltransferases/genética , Compostos de Sulfônio/metabolismo , Sulfeto de Hidrogênio/metabolismo , Filogenia , Metilação , Compostos de Sulfidrila/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Sedimentos Geológicos/microbiologiaRESUMO
In the era of personalized/precision health care, additional effort is being expended to understand the biology and molecular mechanisms of disease processes. How these mechanisms are affected by individual genetics, environmental exposures, and behavioral choices will encompass an expanding role in the future of optimally preventing and treating diseases. Considering saliva as an important biological fluid for analysis to inform oral disease detection/description continues to expand. This review provides an overview of saliva as a diagnostic fluid and the features of various biomarkers that have been reported. We emphasize the use of salivary biomarkers in periodontitis and transport the reader through extant literature, gaps in knowledge, and a structured approach toward validating and determine the utility of biomarkers in periodontitis. A summation of the findings support the likelihood that a panel of biomarkers including both host molecules and specific microorganisms will be required to most effectively identify risk for early transition to disease, ongoing disease activity, progression, and likelihood of response to standard periodontal therapy. The goals would be to develop predictive algorithms that serve as adjunctive diagnostic tools which provide the clinician and patient important information for making informed clinical decisions.
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Biomarcadores , Saliva , Humanos , Saliva/química , Saliva/microbiologia , Biomarcadores/análise , Periodontite/diagnóstico , Doenças da Boca/diagnóstico , Doenças Periodontais/diagnósticoRESUMO
Vitexin is a natural flavonoid glycoside compound extracted from the leaves and seeds of Vitex negundo. It is widely distributed in the leaves and stems of numerous plants and exhibites remarkable anti-tumor, anti-inflammatory, and anti-hypertensive properties. However, whether vitexin presents the anti-aging and senescence prevention effect has not been fully elucidated. The purpose of this study is to investigate the effect of vitexin on progeria mice and cellular senescence, as well as its underlying molecular mechanisms. To generate a premature aging/senescence model in vivo and in vitro, we used D-galactose (D-gal), hydrogen peroxide (H2O2), and adriamycin (ADR), respectively. Our findings demonstrated that vitexin potentially delays D-gal-induced progeria mice; similar effects were observed in stress-induced premature senescent fibroblasts in culture. Interestingly, this effect of vitexin is closely correlated with the reduction of the senescence-associated secretory phenotype (SASP) and the inhibition of the SASP-related JAK2/STAT3 pathway. Furthermore, we determined that vitexin meets the pharmacological parameters using the freely available ADMET web tool. Collectively, our findings demonstrate that vitexin possesses anti-senescence and anti-aging properties due to the inhibition of SASP and suppression of JAK2/STAT3 signaling pathway.
Assuntos
Apigenina , Senescência Celular , Galactose , Janus Quinase 2 , Progéria , Fator de Transcrição STAT3 , Animais , Apigenina/farmacologia , Apigenina/uso terapêutico , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Senescência Celular/efeitos dos fármacos , Camundongos , Progéria/tratamento farmacológico , Progéria/patologia , Progéria/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Senilidade Prematura/induzido quimicamente , Senilidade Prematura/tratamento farmacológico , Senilidade Prematura/metabolismo , Senilidade Prematura/patologia , Modelos Animais de Doenças , Fenótipo Secretor Associado à Senescência/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismoRESUMO
Objective: To observe the effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the prognosis and the incidence of lymphatic leakage in patients undergoing radical cystectomy (RC). Method: A total of 129 patients who underwent RC in Lanzhou University Second Hospital from 2013 to 2022 were enrolled in this study. They were divided into 43 patients treated with PA-MSHA and 86 patients in the control group. Inverse probability of treatment weighting (IPTW) was applied to reduce potential selection bias. Kaplan-Meier method and Cox regression analysis were used to analyze the effect of PA-MSHA on the survival of patients and the incidence of postoperative lymphatic leakage. Results: The PA-MSHA group exhibited improved overall survival (OS) and cancer-specific survival (CSS) rates compared to the control group. The 3-year and 5-year overall survival (OS) rates for the PA-MSHA group were 69.1% and 53.2%, respectively, compared to 55.6% and 45.3% for the control group (Log-rank=3.218, P=0.072). The 3-year and 5-year cancer-specific survival (CSS) rates for the PA-MSHA group were 73.3% and 56.5%, respectively, compared to 58.0% and 47.3% for the control group (Log-rank=3.218, P=0.072). Additionally, the 3-year and 5-year progression-free survival (PFS) rates for the PA-MSHA group were 74.4% and 56.8%, respectively, compared to 57.1% and 52.2% for the control group (Log-rank=2.016, P=0.156). Multivariate Cox regression analysis indicates that lymph node metastasis and distant metastasis are poor prognostic factors for patients, while the use of PA-MSHA can improve patients' OS (HR: 0.547, 95%CI: 0.304-0.983, P=0.044), PFS (HR: 0.469, 95%CI: 0.229-0.959, P=0.038) and CSS (HR: 0.484, 95%CI: 0.257-0.908, P=0.024). The same trend was observed in the cohort After IPTW adjustment. Although there was no significant difference in the incidence of postoperative lymphatic leakage [18.6% (8/35) vs. 15.1% (84.9%), P=0.613] and pelvic drainage volume [470 (440) ml vs. 462.5 (430) ml, P=0.814] between PA-MSHA group and control group, PA-MSHA could shorten the median retention time of drainage tube (7.0 d vs 9.0 d) (P=0.021). Conclusion: PA-MSHA may improve radical cystectomy in patients with OS, PFS, and CSS, shorten the pelvic drainage tube retention time.
Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Masculino , Cistectomia/métodos , Cistectomia/efeitos adversos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Prognóstico , Idoso , Pseudomonas aeruginosaRESUMO
A Gram-staining-negative, facultative aerobic, motile strain, designated strain ZSDE20T, was isolated from the surface seawater of Qingdao offshore. Phylogenetic analysis of the 16S rRNA gene of strain ZSDE20T, affiliated it to the genus Photobacterium. It was closely related to Photobacterium lutimaris DF-42 T (98.92% 16S rRNA gene sequence similarity). Growth occurred at 4-28ºC (optimum 28ºC), pH 1.0-7.0 (optimum 7.0) and in the presence of 1-7% (w/v) NaCl (optimum 3%). The dominant fatty acids were summed feature 3 (C16:1 ω7c or/and C16:1 ω6c, 34.23%), summed feature 8 (C18:1 ω7c and C18:1 ω6c, 10.36%) and C16:0 (20.05%). The polar lipids of strain ZSDE20T comprised phosphatidylethanolamine, phosphatidylcholine, lyso-phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol dimannoside, phosphatidylinositol mannosides and two unknown lipids. The major respiratory quinone was ubiquinone-8 (Q-8). The DNA G + C content of strain ZSDE20T was 45.6 mol%. Average nucleotide identity (ANI) values between ZSDE20T and its reference species were lower than the threshold for species delineation (95-96%); in silico DNA-DNA hybridization further showed that strain ZSDE20T had less than 70% similarity to its relatives. Based on the polyphasic evidences, strain ZSDE20T is proposed as representing a novel species of the genus Photobacterium, for which the name Photobacterium pectinilyticum sp. nov. is proposed. The type strain is ZSDE20T (= MCCC 1K06283T = KCTC 82885 T).