621 research outputs found
Skeletal muscles and gut microbiota-derived metabolites: novel modulators of adipocyte thermogenesis
Obesity occurs when overall energy intake surpasses energy expenditure. White adipose tissue is an energy storage site, whereas brown and beige adipose tissues catabolize stored energy to generate heat, which protects against obesity and obesity-associated metabolic disorders. Metabolites are substrates in metabolic reactions that act as signaling molecules, mediating communication between metabolic sites (i.e., adipose tissue, skeletal muscle, and gut microbiota). Although the effects of metabolites from peripheral organs on adipose tissue have been extensively studied, their role in regulating adipocyte thermogenesis requires further investigation. Skeletal muscles and intestinal microorganisms are important metabolic sites in the body, and their metabolites play an important role in obesity. In this review, we consolidated the latest research on skeletal muscles and gut microbiota-derived metabolites that potentially promote adipocyte thermogenesis. Skeletal muscles can release lactate, kynurenic acid, inosine, and ÎČ-aminoisobutyric acid, whereas the gut secretes bile acids, butyrate, succinate, cinnabarinic acid, urolithin A, and asparagine. These metabolites function as signaling molecules by interacting with membrane receptors or controlling intracellular enzyme activity. The mechanisms underlying the reciprocal exchange of metabolites between the adipose tissue and other metabolic organs will be a focal point in future studies on obesity. Furthermore, understanding how metabolites regulate adipocyte thermogenesis will provide a basis for establishing new therapeutic targets for obesity
Impairment in acquisition of conditioned fear in people with depressive symptoms
BackgroundDepression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored.MethodsWe used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response.ResultsThe findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms.ConclusionThe study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems
Chromogranin A (CgA) as Poor Prognostic Factor in Patients with Small Cell Carcinoma of the Cervix: Results of a Retrospective Study of 293 Patients
BACKGROUND: Small cell carcinoma of the cervix (SCCC) is a very rare tumor. Due to its rarity and the long time period, there is a paucity of information pertaining to prognostic factors associated with survival. The objective of this study was to determine whether clinicopathologic finings or immunohistochemical presence of molecular markers predictive of clinical outcome in patients with SCCC. METHODOLOGY AND FINDINGS: We retrospectively reviewed a total of 293 patients with SCCC (47 patients from Cancer Center of Sun Yat-sen University in china, 71 patients from case report of china journal, 175 patients from case report in PubMed database). Of those 293 patients with SCCC, the median survival time is 23 months. The 3-year overall survival rates (OS) and 3-year disease-free survival rates (DFS) for all patients were 34.5% and 31.1%, respectively. Univariate and multivariate analysis showed that FIGO stage (IIb-IV VS I-IIa, Hazard Ratio (HR) = 3.08, 95% confidence interval (CI) of ratio = [2.05, 4.63], P<0.001), tumor mass size (â„ 4 cm VS <4 cm, HR = 2.37, 95% CI = [1.28, 4.36], P = 0.006) and chromogranin A (CgA) (Positive VS Negative, HR = 1.81, 95% CI = [1.12, 2.91], P = 0.015) were predictive of poor prognosis. CgA stained positive was found to be highly predictive of death in early-stage (FIGO I-IIa) patient specifically. CONCLUSIONS: Patients with SCCC have poor prognosis. FIGO stage, tumor mass size and CgA stained positive may act as a surrogate for factors prognostic of survival. CgA may serve as a useful marker in prognostic evaluation for early-stage patients with SCCC
ESPGHAN Revised Porto Criteria for the Diagnosis of Inflammatory Bowel Disease in Children and Adolescents.
BACKGROUND:: The diagnosis of pediatric-onset IBD (PIBD) can be challenging in choosing the most informative diagnostic tests and correctly classifying PIBD into its different subtypes. Recent advances in our understanding of the natural history and phenotype of PIBD, increasing availability of serological and fecal biomarkers, and the emergence of novel endoscopic and imaging technologies taken together have made the previous Porto criteria for the diagnosis of PIBD obsolete. METHODS:: We aimed to revise the original Porto criteria utilizing an evidence-based approach and consensus process to yield specific practice recommendations for the diagnosis of PIBD. These revised criteria are based on the Paris classification of PIBD and the original Porto criteria whilst incorporating novel data, such as for serum and fecal biomarkers. A consensus of at least 80% of participants was achieved for all recommendations and the summary algorithm. RESULTS:: The revised criteria depart from existing criteria by defining two categories of ulcerative colitis (UC; typical and atypical); atypical phenotypes of UC should be treated as UC. A novel approach based on multiple criteria for diagnosing IBD-unclassified (IBDU) is proposed. Specifically, these revised criteria recommend upper GI endoscopy and ileocolonscopy for all suspected PIBD patients, with small bowel imaging (unless typical UC after endoscopy and histology) by magnetic resonance enterography (MRE) or wireless capsule endoscopy. CONCLUSIONS:: These revised Porto criteria for the diagnosis of PIBD have been developed to meet current challenges and developments in PIBD and provide up to date guidelines for the definition and diagnosis of the IBD spectrum
The DArk Matter Particle Explorer mission
The DArk Matter Particle Explorer (DAMPE), one of the four scientific space
science missions within the framework of the Strategic Pioneer Program on Space
Science of the Chinese Academy of Sciences, is a general purpose high energy
cosmic-ray and gamma-ray observatory, which was successfully launched on
December 17th, 2015 from the Jiuquan Satellite Launch Center. The DAMPE
scientific objectives include the study of galactic cosmic rays up to
TeV and hundreds of TeV for electrons/gammas and nuclei respectively, and the
search for dark matter signatures in their spectra. In this paper we illustrate
the layout of the DAMPE instrument, and discuss the results of beam tests and
calibrations performed on ground. Finally we present the expected performance
in space and give an overview of the mission key scientific goals.Comment: 45 pages, including 29 figures and 6 tables. Published in Astropart.
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Direct detection of a break in the teraelectronvolt cosmic-ray spectrum of electrons and positrons
High energy cosmic ray electrons plus positrons (CREs), which lose energy
quickly during their propagation, provide an ideal probe of Galactic
high-energy processes and may enable the observation of phenomena such as
dark-matter particle annihilation or decay. The CRE spectrum has been directly
measured up to TeV in previous balloon- or space-borne experiments,
and indirectly up to TeV by ground-based Cherenkov -ray
telescope arrays. Evidence for a spectral break in the TeV energy range has
been provided by indirect measurements of H.E.S.S., although the results were
qualified by sizeable systematic uncertainties. Here we report a direct
measurement of CREs in the energy range by the
DArk Matter Particle Explorer (DAMPE) with unprecedentedly high energy
resolution and low background. The majority of the spectrum can be properly
fitted by a smoothly broken power-law model rather than a single power-law
model. The direct detection of a spectral break at TeV confirms the
evidence found by H.E.S.S., clarifies the behavior of the CRE spectrum at
energies above 1 TeV and sheds light on the physical origin of the sub-TeV
CREs.Comment: 18 pages, 6 figures, Nature in press, doi:10.1038/nature2447
Multiphoton Quantum Optics and Quantum State Engineering
We present a review of theoretical and experimental aspects of multiphoton
quantum optics. Multiphoton processes occur and are important for many aspects
of matter-radiation interactions that include the efficient ionization of atoms
and molecules, and, more generally, atomic transition mechanisms;
system-environment couplings and dissipative quantum dynamics; laser physics,
optical parametric processes, and interferometry. A single review cannot
account for all aspects of such an enormously vast subject. Here we choose to
concentrate our attention on parametric processes in nonlinear media, with
special emphasis on the engineering of nonclassical states of photons and
atoms. We present a detailed analysis of the methods and techniques for the
production of genuinely quantum multiphoton processes in nonlinear media, and
the corresponding models of multiphoton effective interactions. We review
existing proposals for the classification, engineering, and manipulation of
nonclassical states, including Fock states, macroscopic superposition states,
and multiphoton generalized coherent states. We introduce and discuss the
structure of canonical multiphoton quantum optics and the associated one- and
two-mode canonical multiphoton squeezed states. This framework provides a
consistent multiphoton generalization of two-photon quantum optics and a
consistent Hamiltonian description of multiphoton processes associated to
higher-order nonlinearities. Finally, we discuss very recent advances that by
combining linear and nonlinear optical devices allow to realize multiphoton
entangled states of the electromnagnetic field, that are relevant for
applications to efficient quantum computation, quantum teleportation, and
related problems in quantum communication and information.Comment: 198 pages, 36 eps figure
Reversed-engineered human alveolar lung-on-a-chip model
Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung
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