Simulating the Kibble-Zurek mechanism of the Ising model with a superconducting qubit system

The Kibble-Zurek mechanism (KZM) predicts the density of topological defects produced in the dynamical processes of phase transitions in systems ranging from cosmology to condensed matter and quantum materials. The similarity between KZM and the Landau-Zener transition (LZT), which is a standard tool to describe the dynamics of some non-equilibrium physics in contemporary physics, is being extensively exploited. Here we demonstrate the equivalence between KZM in the Ising model and LZT in a superconducting qubit system. We develop a time-resolved approach to study quantum dynamics of LZT with nano-second resolution. By using this technique, we simulate the key features of KZM in the Ising model with LZT, e.g., the boundary between the adiabatic and impulse regions, the freeze-out phenomenon in the impulse region, especially, the scaling law of the excited state population as the square root of the quenching rate. Our results supply the experimental evidence of the close connection between KZM and LZT, two textbook paradigms to study the dynamics of the non-equilibrium phenomena.Comment: Title changed, authors added, and some experimental data update

MAPK-dependent hormonal signaling plasticity contributes to overcoming Bacillus thuringiensis toxin action in an insect host

The arms race between entomopathogenic bacteria and their insect hosts is an excellent model for decoding the intricate coevolutionary processes of host-pathogen interaction. Here, we demonstrate that the MAPK signaling pathway is a general switch to trans-regulate differential expression of aminopeptidase N and other midgut genes in an insect host, diamondback moth (Plutella xylostella), thereby countering the virulence effect of Bacillus thuringiensis (Bt) toxins. Moreover, the MAPK cascade is activated and fine-tuned by the crosstalk between two major insect hormones, 20-hydroxyecdysone (20E) and juvenile hormone (JH) to elicit an important physiological response (i.e. Bt resistance) without incurring the significant fitness costs often associated with pathogen resistance. Hormones are well known to orchestrate physiological trade-offs in a wide variety of organisms, and our work decodes a hitherto undescribed function of these classic hormones and suggests that hormonal signaling plasticity is a general cross-kingdom strategy to fend off pathogens

Highly accurate and reliable ultrasonic focusing capability in heterogeneous media using a spherical cavity transducer

Introduction: Focused ultrasound ablation surgery (FUAS) has been emerging to treat a wide range of conditions non-invasively and effectively with promising therapeutic outcomes. The focusing capability of an ultrasound transducer (i.e., focus shift, beam distortion, and acoustic pressure at the focus) determines the ablation effects. However, the focus shift and focal beam distortion after ultrasound propagating through multi-layered heterogeneous viscoelastic biological tissues become significant and are found to deteriorate the performance of FUAS in clinics.Methods: To achieve an accurate and reliable focal field among patients with large variations in the anatomical structures and properties, a spherical cavity transducer with open ends and sub-wavelength focal size (Li et al., APL, 2013,102:204102) was applied here. Both experimental measurements and numerical simulations were performed to characterize the acoustic fields of the spherical cavity transducer in water, the multi-layered concentric cylindrical phantom, and the heterogeneous tissue model (an adult male pelvis enclosed by porcine skin, fat, and muscle) and then compared with those of a conventional concave transducer at the same electrical power output.Results: It is found that standing-wave focusing using the spherical cavity transducer results in much less focus shift (0.25λ vs. 1.67λ) along the transducer axis and focal beam distortion (−6 dB beam area of 0.71 mm2vs. 4.72 mm2 in water and 2.55 mm2vs. 17.30 mm2 in tissue) in the focal plane but higher pressure focusing gain (40.05 dB vs. 33.61 dB in tissue).Discussion: Such a highly accurate and reliable focal field is due to the excitation at an appropriate eigen-frequency of the spherical cavity with the varied media inside rather than the reverberation from the concave surface. Together with its sub-wavelength focal size, the spherical cavity transducer is technically advantageous in comparison to the concave one. The improved focusing capability would benefit ultrasound exposure for not only safer and more effective FUAS in clinics, but also broad acoustic applications

Fisetin Inhibited Growth and Metastasis of Triple-Negative Breast Cancer by Reversing Epithelial-to-Mesenchymal Transition via PTEN/Akt/GSK3β Signal Pathway

Triple negative breast cancer (TNBC), characterized by its highly aggressive and metastatic features, is associated with poor prognosis and high mortality partly due to lack of effective treatment. Fisetin, a natural flavonoid compound, has been demonstrated to possess anti-cancer effects in various cancers. However, the effects and mechanisms of fisetin on metastasis of TNBC remain uncovered. In this study, we found that fisetin dose-dependently inhibited cell proliferation, migration and invasion in TNBC cell lines MDA-MB-231 and BT549 cells. In addition, fisetin reversed epithelial to mesenchymal transition (EMT) as evaluated by cell morphology and EMT markers in MDA-MB-231 and BT549 cells. Furthermore, fisetin suppressed phosphoinositol 3-kinase (PI3K)-Akt-GSK-3β signaling pathway but upregulated the expression of PTEN mRNA and protein in a concentration-dependent manner. Further, silence of PTEN by siRNA abolished these benefits of fisetin on proliferation and metastasis of TNBCs. In vivo, using the metastatic breast cancer xenograft model bearing MDA-MB-231 cells, we found that fisetin dramatically inhibited growth of primary breast tumor and reduced lung metastasis, meanwhile, the expression of EMT molecules and PTEN/Akt/GSK-3β in primary and metastatic tissues changed in the same way as those in vitro experiments. In conclusion, all these results indicated that fisetin could effectively suppress proliferation and metastasis of TNBC and reverse EMT process, which might be mediated by PTEN/Akt/GSK-3β signaling pathway

Influenza vaccine uptake among children and older adults in China: a secondary analysis of a quasi-experimental study.

BACKGROUND: Influenza vaccination is the key to prevent influenza-related disease, especially among high-risk populations. However, influenza vaccine uptake in China is low. This secondary analysis of a quasi-experimental trial aimed to understand factors associated with influenza vaccine uptake among children and older people stratified by funding context. METHODS: A total of 225 children (aged 0.5-8 years) and 225 older people (aged 60 years or above) were recruited from three clinics (rural, suburban and urban) in Guangdong Province. Participants were allocated into two groups based on funding contexts: a self-paid group (N = 150, 75 children and 75 older adults) in which participants paid full price for their vaccination; and a subsidized group (N = 300, 150 children and 150 older adults) in which varying levels of financial support was provided. Univariate and multivariable logistic regressions were conducted stratified by funding contexts. RESULTS: Overall, 75.0% (225/300) of participants in the subsidized group and 36.7% (55/150) in the self-paid group got vaccinated. Older adults had lower vaccination rates than children in both funding groups, while both age groups showed much higher uptake in the subsidized group than in the self-paid group (aOR = 5.96, 95% CI: 3.77-9.42, p = 0.001). In the self-paid group, having prior influenza vaccination history of children (aOR:2.61, 95%CI: 1.06-6.42) or older people (aOR:4.76, 95%CI: 1.08-20.90) was associated with increased influenza vaccine uptake compared to those who had no prior vaccination experiences in the family. While in the subsidized group, participants who got married or lived with partners (aOR = 0.32, 0.10-0.98) had lower vaccination uptake than single ones. Trust in providers' advice (aOR = 4.95, 95%CI:1.99, 12.43), perceived effectiveness of the vaccine (aOR: 12.18, 95%CI: 5.21-28.50), and experienced influenza-like illnesses in the family in the past year (aOR = 46.52, 4.10, 533.78) were associated with higher vaccine uptake. CONCLUSIONS: Older people had suboptimal vaccine uptake compared to children in both contexts and need more attention to enhance influenza vaccination. Tailoring interventions to different vaccine funding contexts may help improve influenza vaccination: In self-paid context, motivating people to accept their first ever influenza vaccination may be a promising strategy. In subsidized context, improving public confidence in vaccine effectiveness and providers' advice would be useful

Author Correction: The flying spider-monkey tree fern genome provides insights into fern evolution and arborescence (Nature Plants, (2022), 8, 5, (500-512), 10.1038/s41477-022-01146-6)

Correction to: Nature Plantshttps://doi.org/10.1038/s41477-022-01146-6, published online 9 May 2022. In the version of the article initially published, Dipak Khadka, who collected the samples in Nepal, was thanked in the Acknowledgements instead of being listed as an author. His name and affiliation (GoldenGate International College, Tribhuvan University, Battisputali, Kathmandu, Nepal) have been added to the authorship in the HTML and PDF versions of the article

A Phase Ib Study of the Simmitecan Single Agent and in Combination With 5-Fluorouracil/Leucovorin or Thalidomide in Patients With Advanced Solid Tumor

Background: Simmitecan is a potent inhibitor of topoisomerase I with anti-tumor activity. This phase Ib trial was conducted to investigate the safety and anti-tumor effect of simmitecan alone or in combination with other drugs.Methods: Eligible patients with advanced solid tumor had no further standard treatment options. Patients were allocated to receive simmitecan alone, simmitecan in combination with 5-fluorouracil (5-FU)/leucovorin (LV), or simmitecan in combination with thalidomide, 14 days a cycle, until disease progression or unacceptable toxicity occurred.Results: A total of 41 patients were enrolled, with a median age of 55 (range 29–69) years. Among them, 13 patients received simmitecan monotherapy, 10 received simmitecan + 5-FU/LV, and 18 received simmitecan + thalidomide. No dose-limiting toxicity occurred. Overall, the most common grade 3/4 adverse event (AE) was neutropenia (46.2, 70.0, and 88.9%, respectively, in simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts), and treatment-related severe AEs included anemia and febrile neutropenia (7.7% each in simmitecan cohort), diarrhea (10% in simmitecan +5-FU/LV cohort), and febrile neutropenia (5.6% in simmitecan + thalidomide cohort). The majority of patients (24/41, 58.3%) had progressed on prior irinotecan; nevertheless, partial response was achieved in one colorectal cancer patients treated with simmitecan + thalidomide. The disease control rates of simmitecan, simmitecan + 5-FU/LV, and simmitecan + thalidomide cohorts were 46.2, 80.0, and 61.1%, respectively.Conclusion: This study demonstrated a manageable safety profile of simmitecan as a single agent or as part of a combination therapy. There have not been any safety concerns with simmitecan in combination when compared to simmitecan alone. Simmitecan + 5-FU/LV regimen seemed to have a better efficacy. Nonetheless, the efficacy of this regimen needs to be further explored in the subsequent study

Biomarkers for Early Diagnostic of Mild Cognitive Impairment in Type-2 Diabetes Patients: A Multicentre, Retrospective, Nested Case–Control Study

AbstractBackgroundBoth type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are common age-associated disorders and T2DM patients show an increased risk to suffer from AD, however, there is currently no marker to identify who in T2DM populations will develop AD. Since glycogen synthase kinase-3β (GSK-3β) activity, ApoE genotypes and olfactory function are involved in both T2DM and AD pathogenesis, we investigate whether alterations of these factors can identify cognitive impairment in T2DM patients.MethodsThe cognitive ability was evaluated using Minimum Mental State Examination (MMSE) and Clinical Dementia Rating (CDR), and the mild cognitive impairment (MCI) was diagnosed by Petersen's criteria. GSK-3β activity in platelet, ApoE genotypes in leucocytes and the olfactory function were detected by Western/dot blotting, the amplification refractory mutation system (ARMS) PCR and the Connecticut Chemosensory Clinical Research Center (CCCRC) test, respectively. The odds ratio (OR) and 95% confidence intervals (95% CI) of the biomarkers for MCI diagnosis were calculated by logistic regression. The diagnostic capability of the biomarkers was evaluated by receiver operating characteristics (ROC) analyses.FindingsWe recruited 694 T2DM patients from Jan. 2012 to May. 2015 in 5 hospitals (Wuhan), and 646 of them met the inclusion criteria and were included in this study. 345 patients in 2 hospitals were assigned to the training set, and 301 patients in another 3 hospitals assigned to the validation set. Patients in each set were randomly divided into two groups: T2DM without MCI (termed T2DM-nMCI) or with MCI (termed T2DM-MCI). There were no significant differences for sex, T2DM years, hypertension, hyperlipidemia, coronary disease, complications, insulin treatment, HbA1c, ApoE ε2, ApoE ε3, tGSK3β and pS9GSK3β between the two groups. Compared with the T2DM-nMCI group, T2DM-MCI group showed lower MMSE score with older age, ApoE ε4 allele, higher olfactory score and higher rGSK-3β (ratio of total GSK-3β to Ser9-phosphorylated GSK-3β) in the training set and the validation set. The OR values of age, ApoE ε4 gene, olfactory score and rGSK-3β were 1.09, 2.09, 1.51, 10.08 in the training set, and 1.06, 2.67, 1.47, 7.19 in the validation set, respectively. The diagnostic accuracy of age, ApoE ε4 gene, olfactory score and rGSK-3β were 0.76, 0.72, 0.66, 0.79 in the training set, and 0.70, 0.68, 0.73, 0.79 in the validation set, respectively. These four combined biomarkers had the area under the curve (AUC) of 82% and 86%, diagnostic accuracy of 83% and 81% in the training set and the validation set, respectively.InterpretationAging, activation of peripheral circulating GSK-3β, expression of ApoE ε4 and increase of olfactory score are diagnostic for the mild cognitive impairment in T2DM patients, and combination of these biomarkers can improve the diagnostic accuracy

Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists

The roots and rhizomes of Valeriana jatamansi have long been used as folk medicine in Asia and usually named as “Zhizhuxiang” in Chinese for the treatment of abdominal distention and pain. However, its active ingredients and molecular targets for treatment of abdominal pain remain unrevealed. Inhibitors of Cav2.2 N-type voltage-gated calcium channels (VGCCs) are actively sought after for their potential in treating pain, especially chronic pain. As far as we know, the method used for seeking analgesic active ingredient from plant material has rarely been reported. The analgesic potentials of the EtOH extract (0.01 mg/ml) of the roots and rhizomes of V. jatamansi and its EtOAc, n-BuOH and H2O soluble parts (0.01 mg/ml, respectively) were tested herein on Cav2.2, using whole-oocyte recordings in vitro by tow-electrode voltage clamp. The results indicated that the EtOAc-soluble part exhibited the most potent inhibition of Cav2.2 peak current (20 mv). The EtOAc-soluble part was then subjected to silica gel column chromatography (CC) and giving 9 fractions. Phytochemical studies were carried out by repeated CC and extensive spectroscopic analyses after the fraction (0.01 mg/ml) was identified to be active and got seventeen compounds (1–17). All isolates were then sent for further bioactive verification (1 and 3 at concentration of 10 μM, others at 30 μM). In addition, the selectivity of the active compounds 1 and 3 were tested on various ion channels including Cav1.2, Cav2.1 and Cav3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. The results indicated that compound 1 and 3 (an abundant compound) inhibited Cav2.2 with an EC50 of 3.3 and 4.8 μM, respectively, and had weaker or no effect on Cav1.2, Cav2.1 and Cav3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. Compounds 1 and 3 appear to act as allosteric modulators rather than pore blockers of Cav2.2, which may play crucial role in attenuating nociception. The results of present research indicated that the ethnopharmacological utilization of V. jatamansi for relieving the abdominal distention and pain may mediate through Cav2.2 channel. Our work is the first demonstration of inhibition of Cav2.2 by iridoids, which may provide a fresh source for finding new analgesics