The term inflammaging is now widely used to designate the inflammatory process of natural aging. During this process, cytokine balance is altered, presumably due to the loss of homeostasis, thus ...contributing to a greater predisposition to disease and exacerbation of chronic diseases. The aim of the study was to analyze the relationship between pro-inflammatory markers and age in the natural aging process of healthy individuals. One hundred and ten subjects were divided into 5 groups according to age (22 subjects/group). Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were quantified using the ELISA method. High-sensitivity C-reactive protein (hsCRP) was analyzed by turbidimetry according to laboratory procedures. The main findings of this study were: a positive correlation between hsCRP and IL-6 as a function of age (110 subjects); women showed stronger correlations; the 51-60 age group had the highest values for hsCRP and IL-6; women presented higher values for hsCRP in the 51-60 age group and higher values for IL-6 in the 61-70 age group; and men showed higher values in the 51-60 age group for hsCRP and IL-6. In conclusion, the natural aging process increased IL-6 and hsCRP levels, which is consistent with the inflammaging theory; however, women presented stronger correlations compared to men (IL-6 and hsCRP) and the 51-60 age range seems to be a key point for these increases. These findings are important because they indicate that early preventive measures may minimize the increase in these inflammatory markers in natural human aging.
Is there only one electric eel species? For two and a half centuries since its description by Linnaeus, Electrophorus electricus has captivated humankind by its capacity to generate strong electric ...discharges. Despite the importance of Electrophorus in multiple fields of science, the possibility of additional species-level diversity in the genus, which could also reveal a hidden variety of substances and bioelectrogenic functions, has hitherto not been explored. Here, based on overwhelming patterns of genetic, morphological, and ecological data, we reject the hypothesis of a single species broadly distributed throughout Greater Amazonia. Our analyses readily identify three major lineages that diverged during the Miocene and Pliocene-two of which warrant recognition as new species. For one of the new species, we recorded a discharge of 860 V, well above 650 V previously cited for Electrophorus, making it the strongest living bioelectricity generator.
A new family of distorted ribbon‐shaped nanographenes was designed, synthesized, and their optical and electrochemical properties were evaluated, pointing out an unprecedented correlation between ...their structural characteristics and the two‐photon absorption (TPA) responses and electrochemical band gaps. Three nanographene ribbons have been prepared: a seven‐membered‐ring‐containing nanographene presenting a tropone moiety at the edge, its full‐carbon analogue, and a purely hexagonal one. We have found that the TPA cross‐sections and the electrochemical band gaps of the seven‐membered‐ring‐containing compounds are higher and lower, respectively, than those of the fully hexagonal polycyclic aromatic hydrocarbon (PAH). Interestingly, the inclusion of additional curvature has a positive effect in terms of non‐linear optical properties of those ribbons.
The advantage of defects: The effect of a tropone moiety on the nonlinear optical properties of ribbon‐shaped nanographenes is unequivocally demonstrated. Curved edges created by the inclusion of heptagonal carbocycles enhance the two‐photon absorption on graphene molecules.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Source processes of injection‐induced earthquakes involve complex fluid‐rock interaction often elusive to regional seismic monitoring. Here we combine observations from a local seismograph array in ...the Montney Formation, northeast British Columbia, and stress modeling to examine the spatiotemporal evolution of the 30 November 2018 Mw 4.2 (ML 4.5) hydraulic fracturing‐induced earthquake sequence. The isolated occurrence of the mainshock at a depth of ∼4.5 km in the crystalline basement 2 days following injection onset at ∼2.5 km depth suggests direct triggering by rapid fluid pressure increase via a high‐permeability conduit. Most aftershocks are in the top 2 km sedimentary layers, with focal mechanisms indicating discrete slip along subvertical surfaces in an ∼1 km wide deformation zone. Aftershock distribution is consistent with static stress triggering from the Mw 4.2 coseismic slip. Our analysis suggests that complex hydraulic and stress transfer between fracture networks needs to be considered in induced seismic hazard assessment.
Plain Language Summary
Seismicity linked to hydraulic fracturing (HF) in shale gas exploration in western Canada has increased drastically over the last decade. However, details of induced seismicity sequence evolution and triggering mechanism(s) remain unclear. In this study, we integrate local seismic monitoring and numerical stress modeling for an Mw 4.2 (ML 4.5) HF‐induced earthquake sequence in northeast British Columbia, to reveal a two‐step stress transfer process. A nascent, near‐vertical fracture network in the sedimentary layers likely developed in the fault growth and basin infill of the Dawson Creek Graben Complex and hydraulically channeled injected fluids to a thrust fault in the basement, leading to a rapidly increased fluid pressure that initiated the mainshock rupture. Static Coulomb stress change from the coseismic slip subsequently triggered the aftershocks along subparallel slip surfaces within the overlying sedimentary sequences. Our results also suggest that the relative injection volumes and/or wellbore pressures required to create HF at each stage of neighboring wells may be diagnostic of the presence of hydraulic connectivity to the basement, which tends to promote large magnitudes events.
Key Points
Source parameter inversion and numerical modeling is performed for an Mw 4.2 hydraulic fracturing‐induced earthquake sequence in northeast BC
Mainshock is triggered by rapid fluid pressure increase via a hydraulic conduit channeling fluids from injection points to a basement fault
Most aftershocks are triggered by static Coulomb stress changes resulting from mainshock coseismic slip
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aim
This cross‐sectional study aimed to investigate the microbial profile and to quantify the levels of endotoxins (LPS) and lipoteichoic acid (LTA) present in periapical lesions associated with root ...filled teeth and those that had received root canal retreatment. It also aimed to investigate the association between microorganisms and their virulence factors with clinical and radiographic features.
Methodology
Patients with periapical lesions in teeth with post‐treatment endodontic disease following primary root canal treatment (n = 19) and unsuccessful root canal retreatment (n = 13) were treatment planned for endodontic microsurgery, where the periapical lesions were collected. Clinical and radiographic data were also collected. For microbiological analysis, nested polymerase chain reaction was used to detect 17 bacterial species. Levels of LPS and LTA were determined using limulus amebocyte lysate and enzyme‐linked immunosorbent assays, respectively. The Student t‐test or Wilcoxon–Mann–Whitney tests were applied to compare the data on LPS and LTA with clinical and radiographic features. The associations between the clinical and radiographic features and the bacterial species were analysed using the Fisher’s exact test. A significance level of 5% was adopted.
Results
Bacterial DNA, LPS and LTA were detected in all samples. Parvimonas micra was the most commonly detected species in all groups, followed by Enterococcus faecalis, Fusobacterium nucleatum and Porphyromonas endodontalis. The type of endodontic treatment, whether a primary root canal treatment or retreatment, was not associated with the presence of any bacterial species in periapical lesions. The levels of LPS and LTA in periapical lesions of root filled teeth were not significantly different from those that had been retreated. Associations between the levels of LPS and LTA with clinical signs and symptoms were found. No association was found between specific bacteria and clinical features.
Conclusion
Periapical lesions associated with teeth after primary root canal treatment and retreatment had similar polymicrobial composition. The levels of LPS and LTA in periapical lesions associated with teeth after primary root canal treatment and retreatment were similar, and both were associated with the same symptomatology.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
COVID-19 is affecting healthcare resources worldwide, with lower and middle-income countries being particularly disadvantaged to mitigate the challenges imposed by the disease, including the ...availability of a sufficient number of infirmary/ICU hospital beds, ventilators, and medical supplies. Here, we use mathematical modelling to study the dynamics of COVID-19 in Bahia, a state in northeastern Brazil, considering the influences of asymptomatic/non-detected cases, hospitalizations, and mortality. The impacts of policies on the transmission rate were also examined. Our results underscore the difficulties in maintaining a fully operational health infrastructure amidst the pandemic. Lowering the transmission rate is paramount to this objective, but current local efforts, leading to a 36% decrease, remain insufficient to prevent systemic collapse at peak demand, which could be accomplished using periodic interventions. Non-detected cases contribute to a ∽55% increase in R
. Finally, we discuss our results in light of epidemiological data that became available after the initial analyses.
We investigated the effect of increased glucose oxidase concentration as a technological option to decrease oxidative stress during the processing of probiotic yogurts. Probiotic yogurts were ...produced with increased concentrations of glucose oxidase (0, 250, 500, 750, or 1,000mg/kg) and submitted to physicochemical and microbiological analysis at 1, 15, and 30d of refrigerated storage. Higher concentrations of glucose oxidase (750 and 1,000mg/kg) and a longer storage time were found to have an influence on the characteristics of the probiotic yogurt, contributing to more extensive postacidification, an increase in the dissolved oxygen level, and higher proteolysis. In addition, increased production of aroma compounds (diacetyl and acetaldehyde) and organic acids (mainly lactic acid) and a decrease in the probiotic bacteria count were reported. The use of glucose oxidase was a feasible option to minimize oxidative stress in probiotic yogurts. However, supplementation with excessive amounts of the enzyme may be ineffective, because insufficient substrate (glucose) is present for its action. Consumer tests should be performed to evaluate changes in the sensory attributes of the probiotic yogurts with increased supplementation of glucose oxidase. In addition, packaging systems with different permeability to oxygen should be evaluated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present ground-based and Swift observations of iPTF16fnl, a likely tidal disruption event (TDE) discovered by the intermediate Palomar Transient Factory (iPTF) survey at 66.6 Mpc. The light curve ...of the object peaked at an absolute mag . The maximum bolometric luminosity (from optical and UV) was erg s−1, an order of magnitude fainter than any other optical TDE discovered so far. The luminosity in the first 60 days is consistent with an exponential decay, with , where t0 = 57631.0 (MJD) and days. The X-ray shows a marginal detection at erg s−1 (Swift X-ray Telescope). No radio counterpart was detected down to 3 , providing upper limits for monochromatic radio luminosities of erg s−1 and erg s−1 (Very Large Array, 6.1 and 22 GHz). The blackbody temperature, obtained from combined Swift UV and optical photometry, shows a constant value of 19,000 K. The transient spectrum at peak is characterized by broad He ii and H emission lines, with FWHMs of about 14,000 km s−1 and 10,000 km s−1, respectively. He i lines are also detected at λλ 5875 and 6678. The spectrum of the host is dominated by strong Balmer absorption lines, which are consistent with a post-starburst (E+A) galaxy with an age of ∼650 Myr and solar metallicity. The characteristics of iPTF16fnl make it an outlier on both luminosity and decay timescales, as compared to other optically selected TDEs. The discovery of such a faint optical event suggests a higher rate of tidal disruptions, as low-luminosity events may have gone unnoticed in previous searches.
Background
Cutaneous squamous‐cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) ...with anti‐programmed death receptor 1 (PD‐1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti‐PD‐1 agent nivolumab in patients with advanced CSCC (aCSCC).
Methods
CA209‐9JC was an open‐label, single‐arm, phase 2 study to evaluate the safety and/or efficacy of nivolumab in systemic treatment‐naive patients with aCSCC. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or 12 months of treatment. The primary end point was the best objective response rate (BORR) as per RECIST 1.1 criteria. Secondary end points included safety, progression‐free survival (PFS), and overall survival (OS).
Results
Twenty‐four patients with aCSCC were enrolled with a median age of 74 years (range, 48–93). Among the 24 patients evaluable for response, the BORR was 58.3% (14/24); there were no complete responses. With a median follow‐up of 17.6 months, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 months, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p = .035, univariate analysis). Treatment‐related adverse events of any grade and grade ≥ 3 occurred in 21 (87.5%) and six (25%) patients, respectively, and one patient discontinued nivolumab due to toxicities.
Conclusions
Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment‐naive patients with aCSCC. These data provide further evidence to support the use of ICI as the standard treatment of aCSCC.
In CA209‐9JC, a single‐arm, phase 2 study, 24 systemic treatment‐naive patients with advanced cutaneous squamous‐cell carcinoma were treated with nivolumab (3 mg/kg every 2 weeks) until disease progression, unacceptable toxicity, or 12 months of treatment. Nivolumab resulted in significant antitumor activity, prolonged responses, and a good tolerability in patients with advanced cutaneous squamous‐cell carcinoma in the first‐line setting.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The monocyte chemoattractant protein 1 (MCP-1) belongs to the CC chemokine family and acts in the recruitment of C–C motif chemokine receptor 2 (CCR2)-positive immune cell types to inflammation ...sites. In testis, the MCP-1/CCR2 axis has been associated with the macrophage population’s functional regulation, which presents significant functions supporting germ cell development. In this context, herein, we aimed to investigate the role of the chemokine receptor CCR2 in mice testicular environment and its impact on male sperm production. Using adult transgenic mice strain that had the CCR2 gene replaced by a red fluorescent protein gene, we showed a stage-dependent expression of CCR2 in type B spermatogonia and early primary spermatocytes. Several parameters related to sperm production were reduced in the absence of CCR2 protein, such as Sertoli cell efficiency, meiotic index, and overall yield of spermatogenesis. Daily sperm production decreased by almost 40%, and several damages in the seminiferous tubules were observed. Significant reduction in the expression of important genes related to the Sertoli cell function (Cnx43, Vim, Ocln, Spna2) and meiosis initiation (Stra8, Pcna, Prdm9, Msh5) occurred in comparison to controls. Also, the number of macrophages significantly decreased in the absence of CCR2 protein, along with a disturbance in Leydig cell steroidogenic activity. In summary, our results show that the non-activation of the MCP-1/CCR2 axis disturbs the testicular homeostasis, interfering in macrophage population, meiosis initiation, blood–testis barrier function, and androgen synthesis, leading to the malfunction of seminiferous tubules, decreased testosterone levels, defective sperm production, and lower fertility index.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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