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In this work, we study the dynamics of two less massive objects moving around a central massive object, which are all embedded within a thin accretion disc. In addition to the gravitational interaction between these objects, the disc–object interaction is also crucial for describing the long-term dynamics of the multibody system, especially in the regime of mean-motion resonances. We point out that near the resonance the density waves generated by the two moving objects generally coherently interfere with each other, giving rise to extra angular momentum fluxes. The resulting backreaction on the objects is derived within the thin-disc scenario, which explicitly depends on the resonant angle and sensitively depends on the smoothing scheme used in the two-dimensional theory. We have performed hydrodynamical simulations with planets embedded within a thin accretion disc and have found qualitatively agreement on the signatures of interfering density waves by measuring the torques on the embedded objects, for the cases of |$2:1$| and |$3:2$| resonance. By including in interference torque and the migration torques in the evolution of a pair of planets, we show that the chance of resonance trapping depends on the sign of the interference torque. For negative interference torques the pairs are more likely located at off-resonance regimes. The negative interference torques may also explain the |$1~{{\ \rm per\ cent}}-2~{{\ \rm per\ cent}}$| offset (for the period ratios) from the exact resonance values as observed in Kepler multiplanet systems. [ABSTRACT FROM AUTHOR]

Objective: PANoptosis, a new form of regulated cell death, concomitantly manifests hallmarks for pyroptosis, apoptosis, and necroptosis. It has been usually observed in macrophages, a class of widely distributed innate immune cells in various tissues, upon pathogenic infections. The second-generation curaxin, CBL0137, can trigger necroptosis and apoptosis in cancer-associated fibroblasts. This study aimed to explore whether CBL0137 induces PANoptosis in macrophages in vitro and in mouse tissues in vivo. Methods: Bone marrow-derived macrophages and J774A.1 cells were treated with CBL0137 or its combination with LPS for indicated time periods. Cell death was assayed by propidium iodide staining and immunoblotting. Immunofluorescence microscopy was used to detect cellular protein distribution. Mice were administered with CBL0137 plus LPS and their serum and tissues were collected for biochemical and histopathological analyses, respectively. Results: The results showed that CBL0137 alone or in combination with LPS induced time- and dose-dependent cell death in macrophages, which was inhibited by a combination of multiple forms of cell death inhibitors but not each alone. This cell death was independent of NLRP3 expression. CBL0137 or CBL0137 + LPS-induced cell death was characterized by simultaneously increased hallmarks for pyroptosis, apoptosis and necroptosis, indicating that this is PANoptosis. Induction of PANoptosis was associated with Z-DNA formation in the nucleus and likely assembly of PANoptosome. ZBP1 was critical in mediating CBL0137 + LPS-induced cell death likely by sensing Z-DNA. Moreover, intraperitoneal administration of CBL0137 plus LPS induced systemic inflammatory responses and caused multi-organ (including the liver, kidney and lung) injury in mice due to induction of PANoptosis in these organs. Conclusions: CBL0137 alone or plus inflammatory stimulation induces PANoptosis both in vitro and in vivo, which is associated with systemic inflammatory responses in mice. [ABSTRACT FROM AUTHOR]

Iodine acetonitrile (IAN) is an important halogenated acetonitrile (HANs) with potential toxic effect on organism. However, no in vivo toxicological study has been reported on IAN. To quantify the toxicity of IAN, we sought to use adult Drosophila as a model for studying IAN-induced neurotoxicity. Adult Drosophila flies were exposed to 1000 mg/L, 100 mg/L, 10 mg/L, and 1 mg/L IAN or dibromoacetonitrile (DBAN, used as positive control) for 4 days to observe fly survival rate, and for 7 days to study climbing behavior. One hundred percent lethality was observed at 1000 mg/L IAN or DBAN. Kaplan‒Meier survival curves demonstrated that the overall survival of flies treated with 1 mg/L IAN was significantly shorter than that of flies treated with 1 mg/L DBAN. The climbing assay showed that the 10 mg/L IAN and 100 mg/L DBAN conditions started to reduce the climbing ability of the flies, suggesting that IAN and DBAN are neurotoxicity. In conclusion, IAN is more toxic than DBAN. It is recommended that attention be paid to toxicity, and IAN be included in the water test criteria to limit its concentration. In addition, IAN exposure was associated with changes in climbing behavior in flies, which might be associated with neurotoxicity. [ABSTRACT FROM AUTHOR]

Itaconate is an unsaturated dicarboxylic acid that is derived from the decarboxylation of the Krebs cycle intermediate cis-aconitate and has been shown to exhibit anti-inflammatory and anti-bacterial/viral properties. But the mechanisms underlying itaconate's anti-inflammatory activities are not fully understood. Necroptosis, a lytic form of regulated cell death (RCD), is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) signaling. It has been involved in the pathogenesis of organ injury in many inflammatory diseases. In this study, we aimed to explore whether itaconate and its derivatives can inhibit necroptosis in murine macrophages, a mouse MPC-5 cell line and a human HT-29 cell line in response to different necroptotic activators. Our results showed that itaconate and its derivatives dose-dependently inhibited necroptosis, among which dimethyl itaconate (DMI) was the most effective one. Mechanistically, itaconate and its derivatives inhibited necroptosis by suppressing the RIPK1/RIPK3/MLKL signaling and the oligomerization of MLKL. Furthermore, DMI promoted the nuclear translocation of Nrf2 that is a critical regulator of intracellular redox homeostasis, and reduced the levels of intracellular reactive oxygen species (ROS) and mitochondrial superoxide (mtROS) that were induced by necroptotic activators. Consistently, DMI prevented the loss of mitochondrial membrane potential induced by the necroptotic activators. In addition, DMI mitigated caerulein-induced acute pancreatitis in mice accompanied by reduced activation of the necroptotic signaling in vivo. Collectively, our study demonstrates that itaconate and its derivatives can inhibit necroptosis by suppressing the RIPK1/RIPK3/MLKL signaling, highlighting their potential applications for treating necroptosis-associated diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phenolic endocrine‐disrupting chemicals (EDCs) are widespread and easily ingested through the food chain. They pose a serious threat to human health. Magnetic solid‐phase extraction (MSPE) is an effective sample pre‐treatment technology to determine traces of phenolic EDCs. RESULTS: Magnetic covalent organic framework (COF) (Fe3O4@COF) nanospheres were prepared and characterized. The efficient and selective extraction of phenolic EDCs relies on a large specific surface and the inherent porosity of COFs and hydrogen bonding, π–π, and hydrophobic interactions between COF shells and phenolic EDCs. Under optimal conditions, the proposed magnetic solid‐phase extraction‐high‐performance liquid chromatography–ultra violet (MSPE‐HPLC‐UV) based on the metallic covalent organic framework method for phenolic EDCs shows good linearities (0.002–6 μg mL−1), with R2 of 0.995 or higher, and low limits of detection (6–1.200 ng mL−1). CONCLUSION: Magnetic covalent organic frameworks (Fe3O4@COFs) with good MSPE performance for phenolic EDCs were synthesized by the solvothermal method. The magnetic covalent organic framework‐based MSPE‐HPLC‐UV method was applied successfully to determine phenolic EDCs in beverage and water samples with satisfactory recoveries (90.200%–123%) and relative standard deviations (2.100%–12.100%). © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Using first-principles calculations, we predict a new type of two-dimensional (2D) beryllium(Be)-decorated T-graphene named BeC2, where Be atoms are inserted into C–C bonds linking the carbon tetrarings of T-graphene. The band structure shows that BeC2 is metallic, thus, the possible phonon-mediated superconductivity is explored based on the Eliashberg equation. The calculated electron-phonon coupling (EPC) constant λ is up to 4.07, and the corresponding superconducting critical temperature (Tc) is 72.1 K, approaching the liquid nitrogen temperature. The reason for the high Tc is the strong EPC. And it is proved to be an anisotropic single-gap superconductor by analyzing the superconducting gap Δk of BeC2. The electronic susceptibility calculation shows strong nesting effect in BeC2. Since rare 2D superconductors show such a strong EPC constant λ which originates from the coupling between electrons in C–pz orbital and in-plane vibrations of Be and C atoms, the predicted BeC2 provides a new platform for investigating strong EPC 2D superconductor. [ABSTRACT FROM AUTHOR]

A new Zn(II) metal–organic framework (MOF) with the formula [Zn(BBIP)(2,6-NDC)]n (JXUST-44, BBIP = 3,5-bis(1H-benzo[d]imidazol-1-yl)pyridine and 2,6-H2NDC = 2,6-naphthalic acid) was synthesized under solvothermal conditions. The adjacent Zn(II) ions are connected by BBIP ligands to form one-dimensional (1D) chains, which are further linked by carboxylate groups of 2,6-NDC2− ligands to obtain a two-dimensional layer structure, resulting in a 2D → 3D polycatenated MOF. JXUST-44 can be simplified as a 4-connected sql topology and shows good chemical stability in a wide pH range from 2 to 12 at room temperature. The fluorescence experiments indicate that JXUST-44 presents sensitive and selective detection of salicylaldehyde (SA), acetylacetone (acac) and H2PO4− with the detection limits of 0.074, 10.311 and 0.011 ppm, respectively. It is worth noting that JXUST-44 shows turn-on fluorescence toward acac and H2PO4−, as well as good recyclability and stability for acac, SA and H2PO4−. Therefore, JXUST-44 can be considered as a good fluorescent sensor for acac, SA and H2PO4−. The sensing mechanism has also been studied in detail. [ABSTRACT FROM AUTHOR]

Studying a centi-parsec supermassive black hole binary (SMBHB) would allow us to explore a new parameter space in active galactic nuclei, and these objects are also potential sources of gravitational waves. We report evidence that an SMBHB with an orbital period of ∼30 yr may be resident in the nearby galactic nucleus M81. This orbital period and the known mass of M81 imply an orbital separation of ∼0.02 pc. The jet emanating from the primary black hole showed a short period of jet wobbling at ∼16.7 yr, superposing a long-term precession at a timescale of several hundred years. Periodic radio and X-ray outbursts were also found two times per orbital period, which could be explained by a double-peaked mass accretion rate variation per binary orbit. If confirmed, M81 would be one of the closest SMBHB candidates, providing a rare opportunity to study the final parsec problem. [ABSTRACT FROM AUTHOR]

Macrophages represent the first lines of innate defense against pathogenic infections and are poised to undergo multiple forms of regulated cell death (RCD) upon infections or toxic stimuli, leading to multiple organ injury. Triptolide, an active compound isolated from Tripterygium wilfordii Hook F., possesses various pharmacological activities including anti-tumor and anti-inflammatory effects, but its applications have been hampered by toxic adverse effects. It remains unknown whether and how triptolide induces different forms of RCD in macrophages. In this study, we showed that triptolide exhibited significant cytotoxicity on cultured macrophages in vitro, which was associated with multiple forms of lytic cell death that could not be fully suppressed by any one specific inhibitor for a single form of RCD. Consistently, triptolide induced the simultaneous activation of pyroptotic, apoptotic and necroptotic hallmarks, which was accompanied by the co-localization of ASC specks respectively with RIPK3 or caspase-8 as well as their interaction with each other, indicating the formation of PANoptosome and thus the induction of PANoptosis. Triptolide-induced PANoptosis was associated with mitochondrial dysfunction and ROS production. PANoptosis was also induced by triptolide in mouse peritoneal macrophages in vivo. Furthermore, triptolide caused kidney and liver injury, which was associated with systemic inflammatory responses and the activation of hallmarks for PANoptosis in vivo. Collectively, our data reveal that triptolide induces PANoptosis in macrophages in vitro and exhibits nephrotoxicity and hepatotoxicity associated with induction of PANoptosis in vivo, suggesting a new avenue to alleviate triptolide's toxicity by harnessing PANoptosis. [ABSTRACT FROM AUTHOR]

This study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC–MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aβ(1–42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aβ and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF's benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms. [ABSTRACT FROM AUTHOR]

This study differentiates myocardial infarction (MI) and strangulation death (STR) from the perspective of amino acid metabolism. In this study, MI mice model via subcutaneous injection of isoproterenol and STR mice model by neck strangulation were constructed, and were randomly divided into control (CON), STR, mild MI (MMI), and severe MI (SMI) groups. The metabolomics profiles were obtained by liquid chromatography-mass spectrometry (LC–MS)-based untargeted metabolomics. Principal component analysis, partial least squares-discriminant analysis, volcano plots, and heatmap were used for discrepancy metabolomics analysis. Pathway enrichment analysis was performed and the expression of proteins related to metabolomics was detected using immunohistochemical and western blot methods. Differential metabolites and metabolite pathways were screened. In addition, we found the expression of PPM1K was significantly reduced in the MI group, but the expression of p-mTOR and p-S6K1 were significantly increased (all P < 0.05), especially in the SMI group (P < 0.01). The expression of Cyt-C was significantly increased in each group compared with the CON group, especially in the STR group (all P < 0.01), and the expression of AMPKα1 was significantly increased in the STR group (all P < 0.01). Our study for the first time revealed significant differences in amino acid metabolism between STR and MI. [ABSTRACT FROM AUTHOR]

The discovery of highly crystalline two-dimensional (2D) superconductors provides a new alluring branch for exploring the fundamental significances. Based on first-principles calculations, we predict a new kind of 2D stable material W2C3, which is a semimetal but not a superconductor because of the weak electron–phonon coupling (EPC) strength. After hydrogenation, W2C3H2 possesses the intrinsic metallic properties with a large density of states (DOS) at the Fermi energy (EF). More interestingly, the EPC strength is greatly enhanced after hydrogenation and the calculated critical temperature (Tc) is 40.5 K. Furthermore, the compressive strain can obviously soften the low-frequency phonons and enhance the EPC strength. Then, the Tc of W2C3H2 can be increased from 40.5 K to 49.1 K with −4% compressive strain. This work paves the way for providing a new platform for 2D superconductivity. [ABSTRACT FROM AUTHOR]

Background: Trigger point (TrP) acupuncture is commonly used to treat chronic non-specific low back pain (CNLBP). Evidence for the efficacy of most TrP acupuncture modalities is weak or lacking. Objective: To assess the effect of TrP acupuncture on pain, disability, gait and muscle activation in patients with CNLBP. Methods: From May 2019 to February 2020, a randomised, single-blind clinical trial was carried out involving 33 participants with CNLBP, divided into one of two intervention groups or a control group (n = 11 per group). The intervention groups received TrP acupuncture or traditional acupuncture treatment three times a week for 4 weeks, and the control group remained on a waiting list and received no treatment. Pain, disability, gait and muscle activation were assessed at baseline and at 4 and 8 weeks of follow-up. Results: At baseline, the three groups showed no significant differences in age, gender, height, weight, body mass index (BMI) or disease course (p ⩾ 0.05). At 4 weeks, pain was relieved (measured by visual analogue scores, p = 0.036) and disability was improved (reflected by lower Oswestry disability index scores, p = 0.029) in TrP acupuncture versus waiting list groups. Moreover, lumbar extension range of motion was increased in TrP acupuncture versus both traditional acupuncture and waiting list groups (p = 0.029 and p = 0.027, respectively). At 8 weeks, there were no significant differences in any parameter between the three groups (p > 0.05). Conclusion: TrP acupuncture had a significant short-term effect on pain relief and disability in patients with CNLBP, but there was no evidence of a long-term influence (at 8 weeks following the intervention). Further high-quality randomised controlled trials are needed for verification in the future. Trial registration number: ChiCTR1900022838 (Chinese Clinical Trial Registry) [ABSTRACT FROM AUTHOR]

High-resolution near-infrared observations with GRAVITY instrument have revealed rapid orbital motions of a hotspot around Sagittarius A* (Sgr A*), the supermassive black hole in our Galactic Centre, during its three bright flares. The projected distances of the spot to the black hole are measured and seem to increase with time. The values of distance, combined with the measured orbiting time, imply that the spot is rotating with a super-Keplerian velocity. These results are hard to understand if the spot stays within the accretion flow thus provides strong constraints on theoretical models for flares. Previously we have proposed a 'CME' model for the flares by analogy with the coronal-mass-ejection model in solar physics. In that model, magnetic reconnection occurred at the surface of the accretion flow results in the formation of flux ropes, which are then ejected out. Energetic electrons accelerated in the current sheet flow into the flux rope region and their radiation is responsible for the flares. In this paper, we apply the model to the interpretation of the GRAVITY results by calculating the dynamics of the ejected flux rope, the evolution of the magnetic field and the energy distribution of accelerated electrons, and the radiation of the system. We find that the model can well explain the observed light curve of the flares, the time-dependent distance, and the super-Keplerian motion of the hotspot. It also explains why the light curve of some flares has double peaks. [ABSTRACT FROM AUTHOR]

Theoretically and experimentally, MXenes consisting of Mo and C have aroused much interest due to superconductivity in their films and even monolayer forms. Here, based on first-principles calculations, we systematically calculate the electronic structure, phonon dispersion, and electron–phonon coupling (EPC) of monolayer Mo2C (both T- and H-phases), Mo3C2, and Mo3C3. The results show that H-MoxCy (x = 2 or 3, y = 1–3) always have lower total energies than their corresponding T phase and other configurations. All these two-dimensional (2D) molybdenum carbides are metals and some of them display weak phonon-mediated superconductivity at different superconducting transition temperatures (Tc). The Mo 4d-orbitals play a critical role in their electronic properties and the Mo atomic vibrations play a dominant role in their low-frequency phonons, EPC, and superconductivity. By comparison, we find that increasing the Mo content can enhance the EPC and Tc. Besides, we further explore the impact of strain engineering on their superconducting related physical quantities. With increasing biaxial stretching, the phonon dispersions are gradually softened to form some soft modes, which can trigger some peaks of α2F(ω) in the low-frequency region and evidently increase the EPC λ. The Tc of H-Mo2C can be increased up to 11.79 K. Upon further biaxial stretching, charge density waves may appear in T-Mo2C, H-Mo3C2, and H-Mo3C3. [ABSTRACT FROM AUTHOR]

These years, two-dimensional (2D) superconductors have attracted more and more attentions. The critical temperature ( T c ) of superconductors can be modified by hole/electron doping, atom adsorption, strain and other means, so as to realize superconductivity with higher T c . In this paper, using first-principles calculations, we study the superconductivity of monolayer hexagonal boron phosphide (h-BP) by metal atoms adsorption. The electronic structure and electron-phonon coupling (EPC) of MBP (M=Li, Na, Ti) are studied. It is found that monolayer h-BP transforms from a semiconductor to a metal after metal atoms adsorption. Based on the conventional EPC mechanism, the coupling between electrons and the out-of-plane vibration of B atoms and P atoms contributes greatly to the EPC. For MBP (M=Li, Na, Ti), the calculated total EPC λ are 1.76, 0.64, and 1.54, and the corresponding T c are 26.38, 6.05, and 14.58 K, respectively. Thus, the predicted MBP (M=Li, Na, Ti) are new 2D superconductors which might be used in future superconducting electronic devices. [ABSTRACT FROM AUTHOR]

Objective To evaluate the accuracy of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in community or primary-care settings. Method We systematically searched the Web of Science, Embase, PubMed, and Cochrane Library databases. We conducted quality evaluation using ReviewManager software (version 5.0). We then used MetaDisc software (version 1.4) and Stata software (version 12.0) to build forest plots, along with a Deeks funnel plot and a bivariate boxplot for analysis. Result Overall, the sensitivity, specificity, and diagnostic odds ratio were 0.79, 0.97, and 328.18, respectively. The sensitivity for the subgroup with RNA extraction appeared to be higher, at 0.88 (0.86–0.90), compared to the subgroup without RNA extraction, at 0.50 (0.45–0.55), with no significant difference in specificity. Conclusion RT-LAMP assay exhibited high specificity regarding current SARS-CoV-2 infection. However, its overall sensitivity was relatively moderate. Extracting RNA was found to be beneficial in improving sensitivity. [ABSTRACT FROM AUTHOR]

The heart is the main organ of the circulatory system and requires fatty acids to maintain its activity. Stress is a contributor to aggravating cardiovascular diseases and even death, and exacerbates the abnormal lipid metabolism. The cardiac metabolism may be disturbed by stress. Cholecystokinin (CCK), which is a classical peptide hormone, and its receptor (CCKR) are expressed in myocardial cells and affect cardiovascular function. Nevertheless, under stress, the exact role of CCKR on cardiac function and cardiac metabolism is unknown and the mechanism is worth exploring. After unpredictable stress, a common stress-inducing model that induces the development of mood disorders such as anxiety and reduces motivated behavior, we found that the abnormal contraction and diastole of the heart, myocardial injury, oxidative stress and inflammation of mice were aggravated. Cholecystokinin A receptor and cholecystokinin B receptor knockout (CCK1R2R-/-) significantly reversed these changes. Mechanistically, fatty acid metabolism was found to be altered in CCK1R2R-/- mice. Differential metabolites, especially L-tryptophan, L-aspartic acid, cholesterol, taurocholic acid, ADP, oxoglutaric acid, arachidonic acid and 17-Hydroxyprogesterone, influenced cardiac function after CCK1R2R knockout and unpredictable stress. We conclude that CCK1R2R-/- ameliorated myocardial damage caused by unpredictable stress via altering fatty acid metabolism. [ABSTRACT FROM AUTHOR]

As an allotrope of graphene, T-graphene was predicted to be an intrinsic two-dimensional (2D) superconductor with a superconducting critical temperature (Tc) of about 20.8 K [Gu et al., Chin. Phys. Lett. 36, 097401 (2019)]. In this work, based on first-principles calculations, hole doping and biaxial tensile strain (BTS) are considered to modulate the electron–phonon coupling (EPC) and superconductivity of T-graphene. It is found that the EPC constant of T-graphene is 0.807 and the calculated critical temperature Tc is 28.2 K at a doping level of 0.5 hole per unit cell (3.31 × 1014 cm−2) and 12% BTS. Furthermore, when 0.8 hole per unit cell (5.43 × 1014 cm−2) doping and 10% BTS are applied, the EPC constant is 0.939, and the Tc can be boosted to 35.2 K, which is higher than those of the pristine T-graphene and many other 2D carbon-based superconductors. [ABSTRACT FROM AUTHOR]

Background: Exercise boosts the health of some brain parts, such as the hippocampus and hypothalamus. Several studies show that long-term exercise improves spatial learning and memory, enhances hypothalamic leptin sensitivity, and regulates energy balance. However, the effect of exercise on the hippocampus and hypothalamus is not fully understood. The study aimed to find epigenetic modifications or changes in gene expression of the hippocampus and hypothalamus due to exercise.Methods: Male C57BL/6 mice were randomly divided into sedentary and exercise groups. All mice in the exercise group were subjected to treadmill exercise 5 days per week for 1 h each day. After the 12-week exercise intervention, the hippocampus and hypothalamus tissue were used for RNA-sequencing or molecular biology experiments.Results: In both groups, numerous differentially expressed genes of the hippocampus (up-regulated: 53, down-regulated: 49) and hypothalamus (up-regulated: 24, down-regulated: 40) were observed. In the exercise group, increased level of N6-methyladenosine (m6A) was observed in the hippocampus and hypothalamus (p < 0.05). Furthermore, the fat mass and obesity-associated gene (FTO) of the hippocampus and hypothalamus were down-regulated in the exercise group (p < 0.001). In addition, the Fto co-expression genes of the mouse brain were studied and analyzed using database to determine the potential roles of exercise-downregulated FTO in the brain.Conclusion: The findings demonstrate that long-term exercise might elevates the levels of m6A-tagged transcripts in the hippocampus and hypothalamus via down-regulation of FTO. Hence, exercise might be an effective intervention for epigenetic modification. [ABSTRACT FROM AUTHOR]

LRP1, the low-density lipoprotein receptor 1, would be a novel candidate gene of epilepsy according to our bioinformatic results and the animal study. In this study, we explored the role of LRP1 in epilepsy and whether beta-hydroxybutyrate, the principal ketone body of the ketogenic diet, can treat epilepsy caused by LRP1 deficiency in drosophila. UAS/GAL4 system was used to establish different genotype models. Flies were given standard, high-sucrose, and ketone body food randomly. The bang-sensitive test was performed on flies and seizure-like behavior was assessed. In morphologic experiments, we found that LRP1 deficiency caused partial loss of the ellipsoidal body and partial destruction of the fan-shaped body. Whole-body and glia LRP1 defect flies had a higher seizure rate compared to the control group. Ketone body decreased the seizure rate in behavior test in all LRP1 defect flies, compared to standard and high sucrose diet. Overexpression of glutamate transporter gene Eaat1 could mimic the ketone body effect on LRP1 deficiency flies. This study demonstrated that LRP1 defect globally or in glial cells or neurons could induce epilepsy in drosophila. The ketone body efficaciously rescued epilepsy caused by LRP1 knockdown. The results support screening for LRP1 mutations as discriminating conduct for individuals who require clinical attention and further clarify the mechanism of the ketogenic diet in epilepsy, which could help epilepsy patients make a precise treatment case by case. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus can cause many diseases and even death. It's important to detect Staphylococcus aureus rapidly and reliably. The accuracy of a novel test named LAMP in detecting Staphylococcus aureus is unclear. Therefore, a systematic review and meta-analysis were conducted to evaluate the accuracy of the LAMP assay for Staphylococcus aureus detection. Methods: Four databases were searched for relevant studies. Meta-DiSc 1.4.0 and Stata 12.0 were used for statistical analysis. At the same time, we used QUADAS-2 to assess the studies we included. Two groups of subgroup analysis were done to differentiate the diagnostic effects of various LAMP tests and in cases of different gold standards. Results: 11 studies were identified and 19 2 × 2 contingency tables were extracted in our study. The results showed that both pooled sensitivity and specificity of the LAMP assay were 99% (95% CI 99–100). Conclusion: The LAMP assay demonstrated high sensitivity and specificity in diagnosing Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Background: GeneXpert enterovirus Assay is a PCR-based assay for Enterovirus meningitis diagnosis. However, there is currently no research about the performance of GeneXpert enterovirus assay in the diagnosis of enterovirus meningitis. Thus, a systematic review and meta-analysis is significant on the topic. Methods: Embase, Cochrane Library, Web of Science, and PubMed were systematically reviewed with retrieval types. Some criteria were used to filter the studies. Only studies published in English, that made a comparison between GeneXpert enterovirus assay and RT-PCR, and could be formulated in a 2*2 table, were included. The quality of the included studies was evaluated by QUADAS-2. The effect of the GeneXpert enterovirus assay was assessed by the Sensitivity, Specificity, Positive Likelihood Ratio, Negative Likelihood Ratio, Diagnosis Odds Ratio, and summary receiver operating characteristic (SROC) curve. Publication bias and heterogeneity were evaluated by the Deeks' funnel test and Bivariate Box plot respectively. Results: 7 studies were recruited in the analysis. The Pooled Sensitivity was 0.96 [95% CI (0.94–0.97)], Pooled Specificity was 0.99 [95% CI (0.98–0.99)], Positive Likelihood Ratio was 130.46 [95% CI (35.79–475.58)], Negative Likelihood Ratio was 0.04 [95% CI (0.02–0.10)], and Diagnostic Odds Ratio was 3648.23 (95% CI [963.99–13,806.72)]. In SROC Curve, Area Under Curve (AUC) was 0.9980, and Q*= 0.9849. In Deeks' funnel test, the P-value was 0.807 (P > 0.05), indicating no publication bias. The Bivariate Box plot indicated no evident heterogeneity. Conclusions: The GeneXpert enterovirus assay demonstrated high diagnostic accuracy in diagnosing enterovirus meningitis. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) superconductors have important potential applications in constructing nano superconducting devices, thus, 2D superconductors with high critical temperature (T c ) are highly desired. Till now, the T c of 2D superconductors are still relatively low. Based on density functional first-principles calculations, we predicted a new stable 2D transition metal molybdenum carbide 2H-Mo2C3. Based on the Eliashberg theory, we predict that it is not a superconductor. However, after hydrogenation, the hydrogen atoms increase the electronic density of states at the Fermi level, and strengthen the electron-phonon coupling. Accordingly, the hydrogenated 2H-Mo2C3, i.e., 2H-Mo2C3H2, is a 2D superconductor with T c of 53 K, exceeding the McMillan limit. Thus, hydrogenation is an important strategy for obtaining 2D high-temperature superconductors at atmosphere pressure. In view of the high superconducting T c of 2H-Mo2C3H2, it is highly expected to be synthesized in future experiments. [ABSTRACT FROM AUTHOR]

In recent years, three-dimensional (3D) high-temperature superconductors at ultrahigh pressure have been reported, typical examples are the polyhydrides H3S, LaH10, YH9, etc. To find high-temperature two-dimensional (2D) superconductors at atmospheric pressure is another research hotspot. Here, we investigated the possible superconductivity in a hydrogenated monolayer phosphorus carbide based on first-principles calculations. The results reveal that monolayer PC3 transforms from a semiconductor to a metal after hydrogenation. Interestingly, the C-π-bonding band contributes most to the states at the Fermi level. Based on the electron–phonon coupling mechanism, it is found that the electron–phonon coupling constant of HPC3 is 0.95, which mainly originates from the coupling of C-π electrons with the in-plane vibration modes of C and H. The calculated critical temperature Tc is 31.0 K, which is higher than those in most 2D superconductors. By further applying a biaxial tensile strain of 3%, the Tc can be boosted to 57.3 K, exceeding the McMillan limit. Thus, hydrogenation and strain are effective ways for increasing the superconducting Tc of 2D materials. [ABSTRACT FROM AUTHOR]

Quantum key distribution (QKD) allows authenticated parties to share secure keys. Its security comes from quantum physics rather than computational complexity. The previous work has been able to demonstrate the security of the BB84 protocol based on the uncertainty principle, entanglement purification and information theory. In the security proof method based on entanglement purification, it is assumed that the information of Calderbank–Shor–Steane (CSS) error correction code cannot be leaked, otherwise, it is insecure. However, there is no quantitative analysis of the relationship between the parameter of CSS code and the amount of information leaked. In the attack and defense strategy of the actual quantum key distribution system, especially in the application of the device that is easy to lose or out of control, it is necessary to assess the impact of the parameter leakage. In this paper, we derive the relationship between the leaked parameter of CSS code and the amount of the final key leakage based on the BB84 protocol. Based on this formula, we simulated the impact of different CSS code parameter leaks on the final key amount. Through the analysis of simulation results, the security of the BB84 protocol is inversely proportional to the value of n − k 1 and k 1 − k 2 in the case of the CSS code leak. [ABSTRACT FROM AUTHOR]

Background: Opportunistic Candida species causes severe infections when the human immune system is weakened, leading to high mortality. Methods: In our study, bioinformatics analysis was used to study the high-throughput sequencing data of samples infected with four kinds of Candida species. And the hub genes were obtained by statistical analysis. Results: A total of 547, 422, 415 and 405 differentially expressed genes (DEGs) of Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis groups were obtained, respectively. A total of 216 DEGs were obtained after taking intersections of DEGs from the four groups. A protein–protein interaction (PPI) network was established using these 216 genes. The top 10 hub genes (FOSB, EGR1, JUNB, ATF3, EGR2, NR4A1, NR4A2, DUSP1, BTG2, and EGR3) were acquired through calculation by the cytoHubba plug-in in Cytoscape software. Validated by the sequencing data of peripheral blood, JUNB, ATF3 and EGR2 genes were significant statistical significance. Conclusions: In conclusion, our study demonstrated the potential pathogenic genes in Candida species and their underlying mechanisms by bioinformatic analysis methods. Further, after statistical validation, JUNB, ATF3 and EGR2 genes were attained, which may be used as potential biomarkers with Candida species infection. [ABSTRACT FROM AUTHOR]

Background: This research aimed to explore the association between the RIG-I-like receptor (RIG-I and MDA5 encoded by DDX58 and IFIH1, respectively) pathways and the risk or severity of hand, foot, and mouth disease caused by enterovirus 71 (EV71-HFMD). In this context, we explored the influence of gene methylation and polymorphism on EV71-HFMD. Methodology/Principal findings: 60 healthy controls and 120 EV71-HFMD patients, including 60 mild EV71-HFMD and 60 severe EV71-HFMD patients, were enrolled. First, MiSeq was performed to explore the methylation of CpG islands in the DDX58 and IFIH1 promoter regions. Then, DDX58 and IFIH1 expression were detected in PBMCs using RT-qPCR. Finally, imLDR was used to detect DDX58 and IFIH1 single-nucleotide polymorphism (SNP) genotypes. Severe EV71-HFMD patients exhibited higher DDX58 promoter methylation levels than healthy controls and mild EV71-HFMD patients. DDX58 promoter methylation was significantly associated with severe HFMD, sex, vomiting, high fever, neutrophil abundance, and lymphocyte abundance. DDX58 expression levels were significantly lower in mild patients than in healthy controls and lower in severe patients than in mild patients. Binary logistic regression analysis revealed statistically significant differences in the genotype frequencies of DDX58 rs3739674 between the mild and severe groups. GeneMANIA revealed that 19 proteins displayed correlations with DDX58, including DHX58, HERC5, MAVS, RAI14, WRNIP1 and ISG15, and 19 proteins displayed correlations with IFIH1, including TKFC, IDE, MAVS, DHX58, NLRC5, TSPAN6, USP3 and DDX58. Conclusions/Significance: DDX58 expression and promoter methylation were associated with EV71 infection progression, especially in severe EV71-HFMD patients. The effect of DDX58 in EV71-HFMD is worth further attention. Author summary: EV71-HFMD is now prevalent in many Asia countries, including China, which caused a lot of death over the last few years. Therefore, it's important to distinguish patients with a severe tendency. In this research, we investigated the association between the epigenetic mechanisms of RIG-I-like pattern recognition receptors (DDX58 and IFIH1) and EV71-HFMD. It showed that children with higher level of DDX58 promoter methylation were related to severe EV71-HFMD and other clinical indicators. The DDX58 mRNA expression level was significantly lower in severe patients. Besides, DDX58 polymorphisms played an important role in the severity of EV71-HFMD. Therefore, various epigenetic biomarkers of DDX58 may be used as indicators to help clinicians identify EV71-HFMD patients with a tendency towards severity. [ABSTRACT FROM AUTHOR]

Background. West Africa has witnessed the unprecedented outbreak of Ebola virus disease (EVD). The Ebola virus (EBOV) can cause Ebola hemorrhagic fever, which is documented as the most deadly viral hemorrhagic fever in the world. RT-PCR had been suggested to be employed in the detection of Ebola virus; however, this method has high requirements for laboratory equipment and takes a long time to determine Ebola infection. Although Xpert Ebola is a fast and simple instrument for the detection of Ebola virus, its effect is still unclear. This study is aimed at evaluating the accuracy of Xpert Ebola in diagnosing Ebola virus infection. Methods. Using the keywords "Xpert" and "Ebola virus", relevant studies were retrieved from the database of PubMed, Embase, Web of Science, and Cochrane. RT-PCR was employed as a reference standard to evaluate whether the study is eligible to be included in the meta-analysis. Data from these included studies were extracted by two independent assessors and were then analyzed by the Meta-DiSc 1.4 software to produce the heterogeneity of sensitivity (SEN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) of the study. The results of pooled analysis were plotted, together with the summary receiver operating characteristic (SROC) curve plotted by calculating the area under the curve (AUC). Generated pooled summary estimates (95% CIs) were calculated for the evaluation of the overall accuracy of this study. Results. Five fourfold tables were made from the four studies that were included in the meta-analysis. The pooled sensitivity of Xpert Ebola was 0.98 (95% confidence interval (CI) (0.95, 0.99)), and the pooled specificity was 0.98 (95% CI (0.97, 0.99)). The pooled values of positive likelihood ratio was 53.91 (95% CI (12.82, 226.79)), with negative likelihood ratio being 0.04 (95% CI (0.02, 0.08)) and diagnostic odds ratio being 2649.45 (95% CI (629.61, 11149.02)). The AUC was 0.9961. Conclusions. Compared with RT-PCR, Xpert Ebola has high sensitivity and specificity. Therefore, it is a valued alternative method for the clinical diagnosis of Ebola virus infection. However, the Xpert Ebola test is a qualitative test that does not provide quantitative testing of EBOV concentration. Whether it can completely replace other methods or not calls for further evidences. [ABSTRACT FROM AUTHOR]

We perform a series of high-resolution 2D hydrodynamical simulations of equal-mass binary black holes (BBHs) embedded in active galactic nucleus (AGN) accretion disks to study whether these binaries can be driven to merger by the surrounding gas. We find that the gravitational softening adopted for the BBH has a profound impact on this result. When the softening is less than 10% of the binary separation, we show that, in agreement with recent simulations of isolated equal-mass binaries, prograde BBHs expand in time rather than contract. Eventually, however, the binary separation becomes large enough that the tidal force of the central AGN disrupts them. Only when the softening is relatively large do we find that prograde BBHs harden. We determine through detailed analysis of the binary torque, that this dichotomy is due to a loss of spiral structure in the circum-single disks orbiting each black hole when the softening is a significant fraction of the binary separation. Properly resolving these spirals—both with high resolution and small softening—results in a significant source of binary angular momentum. Only for retrograde BBHs do we find consistent hardening, regardless of softening, as these BBHs lack the important spiral structure in their circum-single disks. This suggests that the gas-driven inspiral of retrograde binaries can produce a population of compact BBHs in the gravitational-wave-emitting regime in AGN disks, which may contribute a large fraction to the observed BBH mergers. [ABSTRACT FROM AUTHOR]

Background: Currently, Chlamydia trachomatis–specific host defense mechanisms in humans remain poorly defined. To study the characteristics of host cells infected early with Chlamydia trachomatis, we used bioinformatics methods to analyze the RNA transcription profiles of the conjunctiva, fallopian tubes, and endometrium in humans infected with Chlamydia trachomatis. Method: The gene expression profiles of GSE20430, GSE20436, GSE26692, and GSE41075 were downloaded from the Gene Expression Synthesis (GEO) database. Then, we obtained the differentially expressed genes (DEGs) through the R 4.0.1 software. STRING was used to construct protein–protein interaction (PPI) networks; then, the Cytoscape 3.7.2 software was used to visualize the PPI and screen hub genes. GraphPad Prism 8.0 software was used to verify the expression of the hub gene. In addition, the gene–miRNA interaction was constructed on the NetworkAnalyst 3.0 platform using the miRTarBase v8.0 database. Results: A total of 600 and 135 DEGs were screened out in the conjunctival infection group and the reproductive tract infection group, respectively. After constructing a PPI network and verifying the hub genes, CSF2, CD40, and CSF3 in the reproductive tract infection group proved to have considerable statistical significance. Conclusion: In our research, the key genes in the biological process of reproductive tract infection with Chlamydia trachomatis were clarified through bioinformatics analysis. These hub genes may be further used in clinical treatment and clinical diagnosis. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB). An estimated 1.7 billion people worldwide are infected with Mycobacterium tuberculosis (LTBI) during the incubation period without any obvious symptoms. Because of MTB's high infection and mortality rates, there is an urgent need to develop a fast, portable, and sensitive diagnostic technology for its detection.Methods: We included research from PubMed, Cochrane Library, Web of Science, and Embase and extracted the data. MetaDisc and STATA were used to build forest plots, Deek's funnel plot, Fagan plot, and bivariate boxplot for analysis.Results: Forty-six articles were analyzed, the results of which are as follows: sensitivity and specificity were 0.92 (0.91-0.93) and 0.95 (0.94-0.95) respectively. The NLR and PLR were 0.04 (95% CI 0.03-0.07) and 25.32 (95% CI 12.38-51.78) respectively. DOR was 639.60 (243.04-1683.18). The area under the SROC curve (AUC) was 0.99.Conclusions: MPT64 exhibits good diagnostic efficiency for MTB. There is no obvious heterogeneity between the three commercial kits. [ABSTRACT FROM AUTHOR]

Severe hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection is associated with high mortality and disability. DC-SIGN, a receptor for EV71, is widely distributed in dendritic cells and may influence the severity of HFMD caused by EV71 infection. This observational study attempts to explore whether single-nucleotide polymorphisms (SNPs) in DC-SIGN are related to the severity of EV71-associated HFMD. Based on linkage disequilibrium and functional predictions, two DC-SIGN SNPs were selected and tested to explore their potential association with the severity of HFMD caused by EV71 infection. Two hundred sixteen Han Chinese children with HFMD caused by EV71 were enrolled to obtain clinical data, including the severity of HFMD, serum DC-SIGN levels, and DC-SIGN SNPs. We found a significant association between the rs7248637 polymorphism (A vs. G: OR = 0.644, 95% CI = 0.515-0.806) and the severity of HFMD caused by EV71 infection, as well as the rs4804800 polymorphism (A vs. G: OR = 1.539, 95% CI =1.229-1.928). These two DC-SIGN SNPs may have an effect on the severity of HFMD caused by EV71 infection. [ABSTRACT FROM AUTHOR]

The variability in multi-pulse gamma-ray bursts (GRBs) may help to reveal the mechanism of underlying processes from the central engine. To investigate whether the self-organized criticality (SOC) phenomena exist in the prompt phase of GRBs, we statistically study the properties of GRBs with more than 3 pulses in each burst by fitting the distributions of several observed physical variables with a Markov Chain Monte Carlo approach, including the isotropic energy Eiso, the duration time T, and the peak count rate P of each pulse. Our sample consists of 454 pulses in 93 GRBs observed by the CGRO/BATSE satellite. The best-fitting values and uncertainties for these power-law indices of the differential frequency distributions are: α E d = 1.54 ± 0.09 , α T d = 1.82 ± 0.15 + 0.14 a n d α P d = 2.09 − 019 + 0.18 , while the power-law indices in the cumulative frequency distributions are: α E c = 1.44 −s 0.10 + 0.08 , α T c = 1.75 − 0.13 + 0.141 a n d α P c = 1.99 − 019 + 0.16 . We find that these distributions are roughly consistent with the physical framework of a Fractal-Diffusive, Self-Organized Criticality (FD-SOC) system with the spatial dimension S = 3 and the classical diffusion β=1. Our results support that the jet responsible for the GRBs should be magnetically dominated and magnetic instabilities (e.g., kink model, or tearing-model instability) lead the GRB emission region into the SOC state. [ABSTRACT FROM AUTHOR]

After protoplanets have acquired sufficient mass to open partial gaps in their natal protostellar disks, residual gas continues to diffuse onto horseshoe streamlines under the effect of viscous dissipation, and to meander in and out of the planets' Hill sphere. Within the Hill sphere, the horseshoe streamlines intercept gas flow in circumplanetary disks. The host star's tidal perturbation induces a barrier across the converging streamlines' interface. Viscous transfer of angular momentum across this tidal barrier determines the rate of mass diffusion from the horseshoe streamlines onto the circumplanetary disks, and eventually the accretion rate onto the protoplanets. We carry out a series of numerical simulations to test the influence of this tidal barrier on superthermal planets. In weakly viscous disks, the protoplanets' accretion rate steeply decreases with their masses above the thermal limit. As their growth timescale exceeds the gas depletion timescale, their masses reach asymptotic values comparable to that of Jupiter. In relatively thick and strongly viscous disks, protoplanets' asymptotic masses exceed several times that of Jupiter. Two-dimensional numerical simulations show that such massive protoplanets strongly excite the eccentricity of nearby horseshoe streamlines, destabilize orderly flow, substantially enhance the diffusion rate across the tidal barrier, and elevate their growth rate until their natal disk is severely depleted. In contrast, eccentric streamlines remain stable in three-dimensional simulations. Based on the upper falloff in the observed mass distribution of known exoplanets, we suggest that their natal disks had relatively low viscosity (α ∼ 10−3) and modest thickness (H/R ∼ 0.03–0.05). [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) can lead to high morbidity and mortality, and genetic background plays an important role during the disease process. We investigated the association between the single‐nucleotide polymorphism (SNP) rs2564978 of the CD55 gene and susceptibility to and severity of HFMD using the SNPs can multiple SNP typing methods. Soluble CD55 (sCD55) expression was significantly lower in the EV71 HFMD group than in the control group and lower in severe cases than in mild cases (P <.001). Moreover, CD55 rs2564978 (C vs T OR = 1.300, 95% CI, 1.120‐1.509) was associated with the risk of EV71 infection, and genotype TC was related to the severity of the infection (TC vs TT OR = 4.523, 95% CI, 2.033‐10.066). Our results suggest that sCD55 expression and the CD55 polymorphism rs2564978 may influence the susceptibility to and severity of EV71 infection. Highlights: Serum CD55 expression was associated with susceptibility to and severity of HFMD caused by EV71.The CD55 polymorphism rs2564978 may influence the susceptibility to and severity of EV71 infection. [ABSTRACT FROM AUTHOR]

Background. The pathogenesis of invasive aspergillosis (IA) is still unknown, but its progression is rapid and mortality rate remains high. Bronchoalveolar lavage fluid (BALF) galactomannan (GM) analysis has been used to diagnose IA. This study is aimed at making an accurate estimate of the whole accuracy of BALF-GM in diagnosing IA. Methods. After a systematic review of the study, a bivariate meta-analysis was used to summarize the specificity (SPE), the sensitivity (SEN), the positive likelihood ratios (PLR), and the negative likelihood ratios (NLR) of BALF-GM in diagnosing IA. The overall test performance was summarized using a layered summary receiver operating characteristic (SROC) curve. Subgroup analysis was performed to explore the heterogeneity between studies. Results. A total of 65 studies that are in line with the inclusion criteria were included. The summary estimates of BALF-GM analysis are divided into four categories. The first is the proven+probable vs. possible+no IA, with an SPE, 0.87 (95% CI, 0.85-0.98); SEN, 0.81 (95% CI, 0.76-0.84); PLR, 9.78 (5.78-16.56); and NLR, 0.20 (0.14-0.29). The AUC was 0.94. The BALF-GM test for proven+probable vs. no IA showed SPE, 0.88 (95% CI, 0.87-0.90); SEN, 0.82 (95% CI, 0.78-0.85); PLR, 6.56 (4.93-8.75); and NLR, 0.24 (0.17-0.33). The AUC was 0.93. The BALF-GM test for proven+probable+possible vs. no IA showed SPE, 0.82 (95% CI, 0.79-0.95); SEN, 0.59 (95% CI, 0.55-0.63); PLR, 3.60 (2.07-6.25); and NLR, 0.31 (0.15-0.61). The AUC was 0.86. The analyses for others showed SPE, 0.85 (95% CI, 0.83-0.87); SEN, 0.89 (95% CI, 0.86-0.91); PLR, 6.91 (4.67-10.22); and NLR, 0.18 (0.13-0.26). The AUC was 0.94. Conclusions. The findings of this BALF-GM test resulted in some impact on the diagnosis of IA. The BALF-GM assay is considered a method for diagnosing IA with high SEN and SPE. However, the patients' underlying diseases may affect the accuracy of diagnosis. When the cutoff is greater than 1, the sensitivity will be higher. [ABSTRACT FROM AUTHOR]

To evaluate the epigenetic regulation of the VDR gene in enterovirus 71 (EV71)-associated severe hand, foot, and mouth disease (HFMD), a total of 116 patients with EV71-HFMD, including 58 with mild EV71-HFMD and 58 with severe EV71-HFMD, as well as 60 healthy controls, were enrolled in this study. Quantitative real-time PCR was used to measure the relative levels of VDR mRNA expression, and the methylation status of the VDR promoter was assessed using a MethylTarget™ assay. The DNA methylation levels of the VDR promoter in children with EV71-associated severe HFMD were lower than those in the healthy controls and in children with mild HFMD (P < 0.05). Hypomethylation at CpG site 133 and hypermethylation at the CpG 42 sites and 68 downregulated VDR expression. Moreover, the methylation level of VDR could be used for differential diagnosis of mild and severe EV71-associated HFMD (AUC56, 0.73; AUC68, 0.699; AUC42, 0.694; AUC66, 0.693). VDR expression and promoter methylation were associated with the progression of EV71 infection. Determining the VDR promoter status might help clinicians initiate the appropriate strategy for treatment of EV71-associated HFMD. [ABSTRACT FROM AUTHOR]

During their formation, emerging protoplanets tidally interact with their natal disks. Proto–gas giant planets, with Hill radii larger than the disk thickness, open gaps and quench gas flow in the vicinity of their orbits. It is usually assumed that their type II migration is coupled to the viscous evolution of the disk. Although this hypothesis provides an explanation for the origin of close-in planets, it also encounters a predicament on the retention of long-period orbits for most gas giant planets. Moreover, numerical simulations indicate that the planets' migrations are not solely determined by the viscous diffusion of their natal disk. Here we carry out a series of hydrodynamic simulations combined with analytic studies to examine the transition between different paradigms of type II migration. We find a range of planetary mass for which gas continues to flow through a severely depleted gap so that the surface density distribution in the disk region beyond the gap is maintained in a quasi-steady state. The associated gap profile modifies the location of corotation and Lindblad resonances. In the proximity of the planet's orbit, high-order Lindblad and corotation torque are weakened by the gas depletion in the gap, while low-order Lindblad torques near the gap walls preserve their magnitude. Consequently, the intrinsic surface density distribution of the disk delicately determines both the pace and direction of the planets' type II migration. We show that this effect might stall the inward migration of giant planets and preserve them in disk regions where the surface density is steep. [ABSTRACT FROM AUTHOR]

The omnipresence of super-Earths suggests that they are able to be retained in natal disks around low-mass stars, whereas exoplanets' mass distributions indicate that some cores have transformed into gas giants through runaway gas accretion at ≳1 au from solar-type stars. In this paper, we show that transition to runaway gas accretion by cores may be self-impeded by an increase of the grain opacity in their envelope after they have acquired sufficient mass (typically ∼ 10M⊕) to enter a pebble-isolation phase. The accumulation of approximately millimeter- to meter-sized pebbles in their migration barriers enhances their local fragmentation rates. The freshly produced submillimeter grains pass through the barrier, elevate the effective dust opacity, and reduce the radiative flux in the core's envelope. These effects alone are adequate to suppress the transition to runaway accretion and preserve super-Earths in the stellar proximity (∼0.1 au), albeit entropy advection between the envelope and the disk can further reduce the accretion rate. At an intermediate distance (∼1 au) from their host stars, the escalation in the dust opacity dominates over entropy advection in stalling the transition to runaway accretion for marginally pebble-isolated cores. Beyond a few astronomical unit, the transformation of more-massive cores to gas giants is reachable before severe depletion of disk gas. This requirement can be satisfied either in extended disks with large scale height via orderly accretion of migrating pebbles or through the mergers of oligarchic protoplanetary embryos, and can account for the correlated occurrence of long-period gas giants and close-in super-Earths. [ABSTRACT FROM AUTHOR]