Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing ...resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose‐stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM)). Mutations of beta cell ion channels involved in insulin secretion regulation also alter glucose sensing. Activating or inactivating mutations of ATP‐dependent potassium (KATP) channel genes result in severe but completely opposite clinical phenotypes, including PNDM and CHI. Mutations of the other ion channels, including voltage‐gated potassium channels (Kv7.1) and voltage‐gated calcium channels, also lead to abnormal glucose sensing and CHI. Furthermore, amino acids can stimulate insulin secretion in a glucose‐independent manner in some forms of CHI, including activating mutations of the glutamate dehydrogenase gene, HDAH deficiency, and inactivating mutations of KATP channel genes. These genetic defects have provided insight into a better understanding of the complicated nature of beta cell fuel‐sensing mechanisms.
During insulin-resistant states such as type II diabetes mellitus (T2DM), insulin fails to suppress hepatic glucose production (HGP) yet promotes lipid synthesis. This metabolic state has been termed ...“selective insulin resistance” to indicate a defect in one arm of the insulin-signaling cascade, potentially downstream of Akt. Here we demonstrate that Akt-dependent activation of mTORC1 and inhibition of Foxo1 are required and sufficient for de novo lipogenesis, suggesting that hepatic insulin signaling is likely to be intact in insulin-resistant states. Moreover, cell-nonautonomous suppression of HGP by insulin depends on a reduction of adipocyte lipolysis and serum FFAs but is independent of vagal efferents or glucagon signaling. These data are consistent with a model in which, during T2DM, intact liver insulin signaling drives enhanced lipogenesis while excess circulating FFAs become a dominant inducer of nonsuppressible HGP.
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•Insulin autonomously regulates hepatic lipid synthesis in vivo•Activation of mTORC1 is not sufficient to induce lipogenesis in the absence of Akt•Inhibition of Foxo1 and activation of mTORC1 are sufficient to drive lipogenesis•Foxo1 controls adipocyte lipolysis to nonautonomously regulate glucose production
During diabetes, both gluconeogenesis and lipogenesis occur in the liver. Titchenell et al. (2016) address the issue of selective insulin resistance to show that direct liver insulin signaling is required for lipogenesis, while liver insulin signaling only indirectly suppresses glucose production by reducing serum free fatty acids coming from adipocytes.
Kinetically stabilized inflation Li, Changhong; Gong, Hao; Cheung, Yeuk-kwan Edna
The journal of high energy physics,
01/2023, Letnik:
2023, Številka:
1
Journal Article
Recenzirano
Odprti dostop
A
bstract
In this work, we propose a string-inspired two fields inflation model to address the fine-tuning problem that the standard inflation model suffers. The fast-rolling tachyon
T
originated ...from the D-brane and anti-D-brane pair annihilation locks the inflaton
φ
slowly rolling on a Higgs-like potential
V
φ
=
−
m
φ
2
φ
2
+
λ
φ
4
and drives a kinetically stabilized (KS) inflation. Our numerical simulation confirms such a solution is a dynamic attractor. In particular, for
λ <
0
.
8 × 10
−
3
, the e-folding number contributed by the KS inflation phase can be larger than 62 to solve the horizon and flatness problems of Big Bang theory. Notably, this KS inflation generates a nearly scale-invariant primordial curvature perturbations spectrum consistent with current cosmic microwave background (CMB) observations. It predicts a low tensor-to-scalar ratio, which the current primordial gravitational wave background (the B-modes in CMB) searches favor.
To realize the design of a medical sensor with excellent comprehensive performance indexes, herein, a plasma concentration sensing model satisfying the Parity-Time (PT) symmetric condition is ...proposed. In this paper, the transfer matrix method was used to simulate the transmittance spectrum of the structure, according to the amplification effect on defect mode transmission and various detection performance indexes of the structure. We numerically optimized the parameters of the structure, such as the number of PT-symmetry unit cell N, the sample layer thickness dD as well as the macroscopic Lorentz oscillation intensity α in the PT-symmetry unit cell. The calculation results demonstrate that when the sample concentration changes from 0 g/L to 50 g/L, the wavelength of defect peak shifts from 1538 nm to 1561 nm, and the average quality factor, sensitivity, average figure of merit, average detection limit and average resolution of the structure can reach 78,564, 0.4409 nm/(g/L) (or 227.05 nm/RIU), 11,515 RIU−1, 5.1 × 10−6 RIU and 0.038 g/L, respectively. Not only the sensitivity and resolution of the PT-symmetry structure are better than that of the similar sensors, but it also has excellent comprehensive detection performance, which indicates that the developed sensor can be used in high-precision biomedical detection devices.
Recently, China's Ministry of Education has established a new department to regulate extracurricular tutoring for the purpose of reducing students' excessive academic burden. In this paper, we ...provide empirical evidence that academic competitiveness among students is a key driver of the extracurricular tutoring fever. Using the China Education Panel Survey (CEPS) data, we show that when their competitors attend extracurricular tutoring, students keep up with the actions of competitors, generating the peer effect of extracurricular tutoring. This effect is more pronounced for students with stronger competitive preferences. However, this irrational imitation behavior does not improve students' academic performance.
Rocks in underground works usually experience rather complex stress disturbance. For this, their fracture mechanism is significantly different from rocks subjected to conventional triaxial ...compression conditions. The effects of stress disturbances on rock geomechanical behaviors under fatigue loading conditions and triaxial unloading conditions have been reported in previous studies. However, little is known about the dependence of the unloading rate on fatigue loading and confining stress unloading (FL-CSU) conditions that influence rock failure. In this paper, we aimed at investigating the fracture behaviors of marble under FL-CSU conditions using the post-test X-ray computed tomography (CT) scanning technique and the GCTS RTR 2000 rock mechanics system. Results show that damage accumulation at the fatigue stage can influence the final fracture behaviors of marble. The stored elastic energy for rock samples under FL-CSU tests is relatively larger compared to those under conventional triaxial tests, and the dissipated energy used to drive damage evolution and crack propagation is larger for FL-CSU tests. In FL-CSU tests, as the unloading rate increases, the dissipated energy grows and elastic energy reduces. CT scanning after the test reveals the impacts of the unloading rate on the crack pattern and a fracture degree index is therein defined in this context to represent the crack dimension. It shows that the crack pattern after FL-CSU tests depends on the unloading rate, and the fracture degree is in agreement with the analysis of both the energy dissipation and the amount of energy released. The effect of unloading rate on fracture evolution characteristics of marble is revealed by a series of FL-CSU tests.
Abstract
Background
For ischaemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs or reducing the dose of antiplatelet drugs was a conventional clinical therapy method. ...But not a study to prove which way was better. And the machinery learning methods could help to obtain which way more suit for some patients.
Methods
Data from consecutive ischaemic stroke patients with gastrointestinal haemorrhage were prospectively collected. The outcome was a recurrent stroke rate, haemorrhage events, mortality and favourable functional outcome (FFO). We analysed the data using conventional logistic regression methods and a supervised machine learning model. We used unsupervised machine learning to group and analyse data characters.
Results
The patients of stopping antiplatelet drugs had a lower rate of bleeding events (
p
= 0.125), mortality (
p
= 0.008), rate of recurrence of stroke (
p
= 0.161) and distribution of severe patients (mRS 3–6) (
p
= 0.056). For Logistic regression, stopping antiplatelet drugs (OR = 2.826,
p
= 0.030) was related to lower mortality. The stopping antiplatelet drugs in the supervised machine learning model related to mortality (AUC = 0.95) and FFO (AUC = 0.82). For group by unsupervised machine learning, the patients of better prognosis had more male (
p
< 0.001), younger (
p
< 0.001), had lower NIHSS score (
p
< 0.001); and had a higher value of serum lipid level (
p
< 0.001).
Conclusions
For ischemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs had a better prognosis. Patients who were younger, male, with lesser NIHSS scores at admission, with the fewest history of a medical, higher value of diastolic blood pressure, platelet, blood lipid and lower INR could have a better prognosis.
In the field of modern optical communication systems and photoelectric detection, new components with complex functions and excellent performance are urgently needed. In this paper, a graphene-based ...parity–time (PT) symmetry structure is proposed, which is achieved by preparing the graphene layer on the top of a PT-symmetry photonic crystal. The transfer matrix method was used to calculate the absorptance of graphene, and a unique amplified absorption effect was found. Meanwhile, the peak value and wavelength position of the absorption can be modulated via the applied electric field. The results show that by adjusting the negative square-wave electric field from −3.5 × 10−5 to −13.5 × 10−5 V/nm (or the positive square-wave electric field from 2 × 10−5 to 11 × 10−5 V/nm), the proposed structure can achieve in-phase (or out-phase) enhanced absorption for the communication wavelength 1550 nm, with the absorption of graphene from 17 to 28 dB (or 30 to 15 dB) corresponding to the square-wave modulation electric field change. The modulable absorption properties of graphene in the structure have potential in optoelectronic devices and optical communication systems.
Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance, both involved in the development of metabolic syndrome (MS). We aimed to investigate whether ...leptin/adiponectin ratio (L/A), as a marker of these two adipokines imbalance, may improve diagnosis of MS in children and adolescents, and determined its cut-off value in the diagnosis of MS.
A total of 3,428 subjects aged 6-18 years were selected from Beijing Child and Adolescent Metabolic Syndrome study. Adipokine leptin and adiponectin were measured using enzyme-linked immunosorbent assay. Odds ratio of MS per 1 z-score of adipokine was examined using logistic regression. Diagnosis accuracy was assessed using c-statistics (AUC) and net reclassification index.
The levels of leptin and L/A increased with number of positive MS components, while the levels of adiponectin declined in both boys and girls (all P <0.001). AUCs for diagnosis of MS in girls were 0.793, 0.773, and 0.689 using L/A, leptin and adiponectin, respectively; and AUCs in boys were 0.822, 0.798, and 0.697 for L/A, leptin and adiponectin, respectively. Notably, L/A outperformed individual leptin or adiponectin in discriminating a diagnosis of MS (all P < 0.02 in AUC comparisons). In addition, the optimal cut-offs of L/A by ROC curve differed by genders and pubertal stages, which were 1.63, 1.28, 1.95 and 1.53 ng/ug for total, pre-, mid- and postpubertal boys, respectively and 2.19, 0.87,1.48 and 2.27 ng/ug for total, pre-, mid- and postpubertal girls, respectively, yielding high sensitivity and moderate specificity for a screening test.
In this pediatric population, leptin-adiponectin imbalance, as reflected by an increase in L/A level, was found to be a better diagnostic biomarker for MS than leptin or adiponectin alone. Future longitudinal studies are needed to further validate the gender-specific cutoff values.
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