Subclinical hypothyroidism (SCH) has been shown to be associated with microbiota. However, the association between SCH and oral microbiota has not yet been elucidated. The results of our previous ...clinical studies showed that Prevotella intermedia was abundant in the oral microbiota of SCH patients. This study aimed to investigate the relationship between SCH and oral microbiota, verify the pathogenicity of P. intermedia in SCH, and preliminarily explore the possible mechanism. The SCH mouse model with oral application of P. intermedia was established, and the variance in the mouse oral microbiota and changes in thyroid function and metabolism were detected in mice. Student’s t test and analysis of variance were used for statistical analysis. Oral application of P. intermedia changed the composition of the oral microbiota of SCH mice, which enhanced the damage to the thyroid and decreased the expression of functional genes of the thyroid. Moreover, P. intermedia decreased oxygen consumption and aggravated glucose and lipid metabolism disorders in SCH mice. Glucose tolerance and insulin tolerance decreased, and the triglyceride content of the liver and inflammatory infiltration in adipose tissue increased in SCH mice after P. intermedia stimulation. Mechanistically, P. intermedia increased the proportion of CD4+ T cells in cervical lymph nodes and thyroids in SCH mice. Th1 cells were suggested to play an important role in the pathogenesis of SCH involving P. intermedia. In conclusion, P. intermedia aggravated SCH manifestations, including thyroid dysfunction and glucose and lipid metabolism disorders, by causing immune imbalance in mice. This study sheds new light on the pathogenesis of SCH from the perspective of oral microbiota.
The explosion process of the flake aluminum powder–air two-phase flow is experimentally studied in a large-scale long straight horizontal tube with a length of 32.4 m and an inner diameter of ...0.199 m. The deflagration-to-detonation transition (DDT) of the aluminum powder–air mixture is analyzed after being ignited by a 40-J electric spark, and the DDT of the mixture at different mass concentrations is compared. The results show that self-sustained detonation can be achieved in the range of 286–532 g/m
3
of the flake aluminum powder concentration, and the DDT process of the aluminum powder–air mixture at the concentration of aluminum particles 409 g/m
3
(optimal concentration) is analyzed in detail. The detonation velocity and detonation pressure at the optimal concentration are 1690 m/s and 58 bar, respectively. During the self-sustained detonation stage, the detonation overpressure of the multiphase fuel–air mixture exhibits a typical constant oscillation characteristic, while the detonation velocity remains stable. In addition, a double-headed mode helical detonation phenomenon is observed in the detonation wave front of the aluminum powder–air mixture. The structure of the detonation wave, the flow field parameters, and the interaction between the shock wave and the three-wave point trajectory are analyzed. The detonation cell size at the optimal concentration is approximately 486 mm.
We investigate the thermodynamics of Schwarzschild–Tangherlini black hole in the context of the generalized uncertainty principle (GUP). The corrections to the Hawking temperature, entropy and the ...heat capacity are obtained via the modified Hamilton–Jacobi equation. These modifications show that the GUP changes the evolution of the Schwarzschild–Tangherlini black hole. Specially, the GUP effect becomes susceptible when the radius or mass of the black hole approaches the order of Planck scale, it stops radiating and leads to a black hole remnant. Meanwhile, the Planck scale remnant can be confirmed through the analysis of the heat capacity. Those phenomena imply that the GUP may give a way to solve the information paradox. Besides, we also investigate the possibilities to observe the black hole at the Large Hadron Collider (LHC), and the results demonstrate that the black hole cannot be produced in the recent LHC.
Focal chromosomal amplification contributes to the initiation of cancer by mediating overexpression of oncogenes
, and to the development of cancer therapy resistance by increasing the expression of ...genes whose action diminishes the efficacy of anti-cancer drugs. Here we used whole-genome sequencing of clonal cell isolates that developed chemotherapeutic resistance to show that chromothripsis is a major driver of circular extrachromosomal DNA (ecDNA) amplification (also known as double minutes) through mechanisms that depend on poly(ADP-ribose) polymerases (PARP) and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Longitudinal analyses revealed that a further increase in drug tolerance is achieved by structural evolution of ecDNAs through additional rounds of chromothripsis. In situ Hi-C sequencing showed that ecDNAs preferentially tether near chromosome ends, where they re-integrate when DNA damage is present. Intrachromosomal amplifications that formed initially under low-level drug selection underwent continuing breakage-fusion-bridge cycles, generating amplicons more than 100 megabases in length that became trapped within interphase bridges and then shattered, thereby producing micronuclei whose encapsulated ecDNAs are substrates for chromothripsis. We identified similar genome rearrangement profiles linked to localized gene amplification in human cancers with acquired drug resistance or oncogene amplifications. We propose that chromothripsis is a primary mechanism that accelerates genomic DNA rearrangement and amplification into ecDNA and enables rapid acquisition of tolerance to altered growth conditions.
Background
Acupuncture is used to treat chronic functional constipation (CFC) in China, despite limited evidence. We aim to assess the effectiveness and safety of acupuncture in managing CFC.
Methods
...A multicenter randomized controlled trial was performed involving 684 patients with CFC; the patients were randomly allocated to receive He acupuncture (n = 172), Shu‐mu acupuncture (n = 171), He‐shu‐mu acupuncture (n = 171), or oral administration of mosapride (n = 170). Sixteen sessions of acupuncture were given in the treatment duration of 4 weeks. The primary outcome was the change in spontaneous bowel movements (SBMs) at week 4 (at the end of treatment) compared to baseline. The secondary outcomes included stool consistency (Bristol scale), the degree of straining during defecation, and adverse events.
Key Results
The SBMs increased in all the four groups at week 4, and the magnitude of increase was equivalent in the four groups (He acupuncture, 2.7 95% CI, 2.3‐3.1; Shu‐mu acupuncture, 2.7 95% CI, 2.3‐3.0; He‐shu‐mu acupuncture, 2.2 95% CI, 1.9‐2.5; and mosapride, 2.4 95% CI, 2.0‐2.9; P = .226). However, the change in SBMs at week 8 was significantly smaller in mosapride group (1.4 95% CI, 1.0‐1.8) than the three acupuncture groups (2.4 95% CI, 2.1‐2.7, 2.3 95% CI, 1.9‐2.7, 2.1 95% CI, 1.7‐2.5 in He, Shu‐mu, and He‐shu‐mu group, respectively, P = .005).
Conclusions & Interferences
The three acupuncture treatments were as effective as mosapride in improving stool frequency and stool consistency in CFC, but the magnitude of the treatment effect is unknown due to the lack of sham acupuncture control.
The effectiveness of acupuncture in the treatment of chronic functional constipation is unknown. Our study result showed that acupuncture treatments are as effective as mosapride in improving stool frequency and stool consistency.
Dysbiotic oral microbiota has been associated with multiple sclerosis. However, the role and mechanism of oral microbiota in the development of multiple sclerosis are still elusive. Here, we ...demonstrated that ligature-induced periodontitis (LIP) aggravated experimental autoimmune encephalomyelitis (EAE) in mice, and this was likely dependent on the expansion of T helper 17 (Th17) cells. LIP increased the splenic richness of Enterobacter sp., which was able to induce the expansion of splenic Th17 cells and aggravate EAE in mice. LIP also led to enrichment of Erysipelotrichaceae sp. in the gut and increased Th17 cells in the large intestinal lamina propria of EAE mice. Fecal microbiota transplantation from EAE mice with LIP also promoted EAE symptoms. In conclusion, periodontitis exacerbates EAE, likely through ectopic colonization of oral pathobionts and expansion of Th17 cells.
Abstract
Nickel-based complex oxides have served as a playground for decades in the quest for a copper-oxide analog of the high-temperature superconductivity. They may provide clues towards ...understanding the mechanism and an alternative route for high-temperature superconductors. The recent discovery of superconductivity in the infinite-layer nickelate thin films has fulfilled this pursuit. However, material synthesis remains challenging, direct demonstration of perfect diamagnetism is still missing, and understanding of the role of the interface and bulk to the superconducting properties is still lacking. Here, we show high-quality Nd
0.8
Sr
0.2
NiO
2
thin films with different thicknesses and demonstrate the interface and strain effects on the electrical, magnetic and optical properties. Perfect diamagnetism is achieved, confirming the occurrence of superconductivity in the films. Unlike the thick films in which the normal-state Hall-coefficient changes signs as the temperature decreases, the Hall-coefficient of films thinner than 5.5 nm remains negative, suggesting a thickness-driven band structure modification. Moreover, X-ray absorption spectroscopy reveals the Ni-O hybridization nature in doped infinite-layer nickelates, and the hybridization is enhanced as the thickness decreases. Consistent with band structure calculations on the nickelate/SrTiO
3
heterostructure, the interface and strain effect induce a dominating electron-like band in the ultrathin film, thus causing the sign-change of the Hall-coefficient.
The fundamental features of one kind of rarely known stratocumulus, which was termed as “Millipede Cloud,” occurred over the Eastern Pacific Ocean in 2017 were first documented by using Moderate ...Resolution Imaging Spectroradiometer (MODIS) satellite imagery. These clouds had long and meandering “central axes” extending from several hundreds to thousands kilometers, and a number of “radical cloud arms” extending several tens of kilometers in its two sides. Total 59 “Millipede Clouds,” 4 and 55 of them, were formed over the Northern and the Southern Hemispheres, respectively. Their environmental backgrounds were analyzed by using ERA5 reanalysis data and MODIS sensor Level‐2 data. The cloud top pressures of these “Millipede Clouds” were between 850 and 800 hPa, and their top heights were about 1–2 km. There existed “inversion layer” of air temperature near the cloud tops at 800 hPa, which strongly suggested that these clouds were lower stratocumulus in essence.
Plain Language Summary
“Millipede Cloud,” one kind of rarely known stratocumulus which looks like “Millipede” shape, is termed for the first time in this paper. It has an obvious “central axis” and a number of well‐organized “radial cloud arms” in two sides of the “central axis” extending in several tens of kilometers length. This paper introduces the fundamental features of “Millipede Clouds” occurred over the Eastern Pacific Ocean in 2017 from the perspective of satellite image. Totally, 59 “Millipede Clouds” were found to occur over the Eastern Pacific Ocean. Their geographic distribution, cloud top features and vertical structure of one typical case on 16 July 2017 were documented.
Key Points
The fundamental features of “Millipede Clouds” over the Eastern Pacific Ocean in 2017 were documented by using Moderate Resolution Imaging Spectroradiometer (MODIS) satellite imagery
The environmental backgrounds of these “Millipede Clouds” were analyzed by using ERA5 reanalysis data and MODIS data
The cloud top pressures of these “Millipede Clouds” are between 850 and 800 hPa, and their top heights are about 1–2 km
We present a novel surface-enhanced Raman scattering (SERS) substrate based on graphene oxide/silver nanoparticles/silicon pyramid arrays structure (GO/Ag/PSi). The SERS behaviors are discussed and ...compared by the detection of R6G. Based on the contrast experiments with PSi, GO/PSi, Ag/PSi and GO/AgA/PSi as SERS substrate, the perfect bio-compatibility, good homogeneity and chemical stability were confirmed. We also calculated the electric field distributions using Finite-difference time-domain (FDTD) analysis to further understand the GO/Ag/PSi structure as a perfect SERS platform. These experimental and theoretical results imply that the GO/Ag/PSi with regular pyramids array is expected to be an effective substrate for label-free sensitive SERS detections in areas of medicine, food safety and biotechnology.
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