CTLA-4 haplotype predicts HBsAg and HBcrAg levels and HBeAg seroconversion age in children with chronic HBV infection.

Background & Aim: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) attenuates cytotoxic T lymphocyte (CTL) activation. This study was performed to examine the relationships between CTLA-4 genotypes/haplotypes, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) levels, and their potential impact on the clinical course of chronic HBV infection. Methods: We recruited 145 treatment-naïve patients with genotype B or C chronic HBV infection who were initially hepatitis B e-antigen (HBeAg)-positive and had been followed from a mean age of 7.08 years for a total of 4,787 person-years in the study cohort. We also recruited another 69 treatment-naïve adults with genotype B or C chronic HBV infection as a validation cohort. We assessed the CTLA-4 gene single nucleotide polymorphisms rs4553808 (-A1661G)/rs5742909 (-C318T) in both cohorts, and the serum HBsAg and HBcrAg levels in the study cohort. Results: CTLA-4 promoter haplotypes were associated with HBsAg and HBcrAg levels at 10 and 15 years of age in the study cohort. Patients with the CTLA-4 AA/CC haplotype showed earlier spontaneous HBeAg seroconversion (hazard ratio = 1.58; p = 0.02), and a more rapid annual decline in the serum HBsAg level than other patients (0.09 vs. 0.03 log10 IU/ml/year, p = 0.02). The CTLA-4 AA/CC haplotype was also predictive of HBeAg seroconversion in the validation cohort (p = 0.01). Conclusions: Chronic HBV-infected patients with a CTLA-4 AA/CC haplotype had lower serum HBsAg and HBcrAg levels in childhood and earlier spontaneous HBeAg seroconversion. Impact and implications: The role of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in chronic HBV-infected children has not been studied previously. In a very long-term cohort followed from childhood to adulthood, we showed that CTLA-4 haplotypes are associated with HBV biomarker levels in childhood and are correlated with the clinical course of chronic HBV infection. CTLA-4 pathway may serve as a future target for the development of therapeutic agents against HBV infection.

Magnetotransport and magnetic properties of Cr-modified Mn2Sb epitaxial thin films.

High-quality Mn2-xCrxSb (x = 0.01, 0.04, and 0.1) epitaxial thin films were grown on SrTiO3 (STO) (001) single-crystal substrates using molecular beam epitaxy. Magnetotransport and magnetic measurements reveal that the x = 0.01 sample undergoes a quasi-ferrimagnetic (I) [Q-FIM(I)]-to-ferrimagnetic (II) [FIM(II)] spin reorientation (SR) transition and a giant magnetoresistance (MR) associated first-order ferrimagnetic(II)-to-antiferromagnetic (AFM) phase transition upon cooling, resulting in the AFM ground state with a weak in-plane net moment. Upon increasing the doping level from x = 0.01 to 0.1, both the SR transition and the first-order magnetic transition are suppressed. For x = 0.1, the former transition is suppressed, leaving only the Q-FIM(I)-to-AFM transition within the whole temperature region. TAFM-FIM shows almost similar changes upon the application of either in-plane or out-of-plane magnetic fields. TAFM-FIM values of the x = 0.01 and 0.04 samples are much higher than those of the Mn2-xCrxSb bulk with similar doping levels, which can be understood by the clamping effect from STO substrates. For each thin-film sample, the MR effect is observed near TAFM-FIM and disappears in the high temperature Q-FIM(I) phase and low temperature AFM phase, indicating that MR is related to the spin-dependent electron scattering during the first-order magnetic phase transition. Based on the magnetotransport and magnetic data, a magnetic phase diagram is established for the Mn2-xCrxSb films in the low doping level region.

Correction: Magnetotransport and magnetic properties of Cr-modified Mn2Sb epitaxial thin films.

Correction for 'Magnetotransport and magnetic properties of Cr-modified Mn2Sb epitaxial thin films' by Ting-Wei Chen et al., Phys. Chem. Chem. Phys., 2023, 25, 5785-5794, https://doi.org/10.1039/D2CP05442F.

The efficacy of a mindfulness-based exercise program in older residents of a long-term care facility in Taiwan.

Older people living in long-term care facilities remain largely inactive, and therefore promoting exercise in this population is necessary. This study evaluated the efficacy of a mindfulness-based exercise program in older residents of a long-term care facility in Taiwan. A convenience sample of 72 older residents of a long-term care facility were recruited and assigned to either an experimental group or a control group. The experimental group (n = 36) participated in an 8-week mindfulness-based exercise program, and the control group (n = 36) received routine care. The generalized estimating equation showed significantly larger improvements in a fear of falling, exercise self-efficacy, dynamic balance, and muscle strength in the experimental group than in the control group from baseline to the end of the intervention and 3 months after the end of the intervention. This study provides a reference for how to improve exercise practice in older people living in long-term care facilities.

Spontaneous giant vortices and circular supercurrents in a trapped exciton-polariton condensate.

We theoretically study an exciton-polariton condensate trapped in a harmonic potential with an annular pump. With a circular pump, predictions were made for a spontaneous rotating vortex lattice packed by singly quantized vortices. If the circular pump is replaced by an annular pump, singly quantized vortices are absorbed into the central hole and form a multiply quantized vortex. For a sufficiently narrow annular width, all vortices are absorbed into the central hole, ultimately forming a giant vortex with supersonic circular supercurrents flowing around it. Vortex-antivortex pairs can be generated if a defect is present in these supersonic circular supercurrents. We further discover that the motion of the vortex-antivortex pairs depends on the position at which they were generated. We suggest that this property can be used to control whether the velocity of the circular supercurrents is above or below the sound velocity.

Tyrosine 12 of human calcitonin modulates its amyloid formation, membrane binding, and bioactivity.

Irreversible aggregation greatly limits the bioavailability and therapeutic activity of peptide-based drugs, so preventing protein or peptide aggregation is a common issue in drug formulation. Human calcitonin (hCT), a peptide hormone secreted by thyroidal parafollicular cells, can regulate blood calcium levels and maintain bone structure. Hence, it can be used as a treatment for metabolic bone diseases, such as osteoporosis and Paget's disease. However, hCT has a relatively high propensity to form amyloid fibrils that hinder its biological function and limit its pharmaceutical potential. In previous studies, we demonstrated, along with other research groups, that modifying specific residues of hCT is sufficient to prevent hCT aggregation. We proceeded to find the key residues that regulate the aggregation of hCT for a better understanding of the mechanism of hCT aggregation. In this work, we used amyloid propensity prediction software and found that Tyr12 may play a key role in regulating hCT aggregation. Thus, we propose three human calcitonin variants (Y12E, Y12P, Y12R) for hCT non-amyloidogenic substituents and examined the aggregation characteristics of variants using multiple biophysical techniques. Y12E showed the best anti-aggregation propensity and can work as inhibitor of hCT aggregation. We also found this residue is crucial for membrane binding and receptor binding. The data presented herein provides an overview of Tyr12 that should be carefully considered in peptide design.

Aromatization as an Impetus to Harness Ketones for Metallaphotoredox-Catalyzed Benzoylation/Benzylation of (Hetero)arenes.

Herein we report ketones as feedstock materials in radical cross-coupling reactions under Ni/photoredox dual catalysis. In this approach, simple condensation first converts ketones into prearomatic intermediates that then act as activated radical sources for cross-coupling with aryl halides. Our strategy enables the direct benzylation/benzoylation of (hetero)arenes under mild reaction conditions with high functional group tolerance.

Half-skyrmions with higher topological quantum numbers in homogeneous exciton-polariton condensates.

We investigate the topological excitations of half-quantum vortices (HQVs) with higher topological quantum numbers in a homogeneous spinor exciton-polariton condensate pumped by a laser beam and an additional coherent light carrying orbital angular momentum. The spin texture and integrated topological charge can be controlled through the pump. Among these textures, the polaritonic half-skyrmions (or polaritonic merons) can be created with a suitable excitation condition. Moreover, when the pump polarization is in favor of the vortex component of the HQV, there is an inversion of circular polarization (spin flipping) from the center of the HQV towards the edge. The radial flipping position can be manipulated by the pump polarization or power. Finally, we demonstrate that the HQVs can stably exist from the linear stability analysis.

Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells.

Trytanthrin, found in Ban-Lan-Gen, is a natural product containing an indoloquinazoline moiety and has been shown to possess anti-inflammatory and anti-viral activities. Chronic inflammation and hepatitis B are known to be associated with the progression of hepatocellular carcinoma (HCC). In this study, a series of tryptanthrin derivatives were synthesized to generate potent anti-tumor agents against HCC. This effort yielded two compounds, A1 and A6, that exhibited multi-fold higher cytotoxicity in HCC cells than the parent compound. Flow cytometric analysis demonstrated that A1 and A6 caused S-phase arrest and downregulated the expression of cyclin A1, B1, CDK2, and p-CDC2. In addition to inducing caspase-dependent apoptosis, A1 and A6 exhibited similar regulation of the phosphorylation or expression of multiple signaling targets, including Akt, NF-κB, and mitogen-activated protein kinases. The anti-tumor activities of A1 and A6 were also attributable to the generation of reactive oxygen species, accompanied by an increase in p-p53 levels. Therefore, A1 and A6 have potential clinical applications since they target diverse aspects of cancer cell growth in HCC.

Ferroelectric 2D ice under graphene confinement.

We here report on the direct observation of ferroelectric properties of water ice in its 2D phase. Upon nanoelectromechanical confinement between two graphene layers, water forms a 2D ice phase at room temperature that exhibits a strong and permanent dipole which depends on the previously applied field, representing clear evidence for ferroelectric ordering. Characterization of this permanent polarization with respect to varying water partial pressure and temperature reveals the importance of forming a monolayer of 2D ice for ferroelectric ordering which agrees with ab-initio and molecular dynamics simulations conducted. The observed robust ferroelectric properties of 2D ice enable novel nanoelectromechanical devices that exhibit memristive properties. A unique bipolar mechanical switching behavior is observed where previous charging history controls the transition voltage between low-resistance and high-resistance state. This advance enables the realization of rugged, non-volatile, mechanical memory exhibiting switching ratios of 106, 4 bit storage capabilities and no degradation after 10,000 switching cycles.

Carbonic Anhydrase XII is a Clinically Significant, Molecular Tumor-Subtype Specific Therapeutic Target in Glioma with the Potential to Combat Invasion of Brain Tumor Cells.

BACKGROUND: The metabolic enzyme carbonic anhydrase 12 (CA12/CAXII) emerges as a promising cancer therapeutic target with drug development projects underway. Previous reports proposed the relevance of CA12 in the context of glioma but are limited in patient data quantity, ignore ethnic diversity of patients or rely on semi-quantitative, thereby out of date, methodology. Moreover, little is known on the association of CA12 to brain tumor stemness or on the effect of anti-CAXII-directed monotherapies on glioma stem cells (GSCs), in particular their response regarding mesenchymal differentiation status. METHODS: We performed in silico analysis on three independent, large-scale patient datasets interrogating state of the art molecular diagnostics alongside clinical outcomes. We analyzed CAXII abundance on a collection of GSCs and functionally tested their response to exposure to CAXII blocking antibody 6A10. RESULTS: CA12 is highly expressed in glial tumors compared with normal tissue and predicts for poor clinical course of tumor patients. CA12 expression in glioblastoma significantly correlates with clinically established, molecular markers of IDH1WT DNA, WHO grade IV or absence of 1p/19q chromosome arm co-deletion. Furthermore, tumors with elevated CA12 cluster into the mesenchymal transcription subclass of the disease. CAXII abundance in different GSCs ranges from almost absent to high levels and does not correlate to stem cell marker CD133/AC133 cell surface expression. Moreover, aiming to pharmacologically block CAXII in our cells with antibody 6A10 caused significant functional response only in one of the tested GSCs models, featuring suppression of cell invasion accompanied by reduction of ZEB1 protein and other stem cell markers. CONCLUSION: CA12 represents a clinically relevant and molecular brain tumor-subtype specific therapeutic target. Our correlative data from experimental and clinical samples does not support CA12/CAXII to be GSC specific. 6A10 possesses promising potential to impede the invasive capacity of glioma cells and supports the emerging concept that CAXII interacts with cancer EMT programs. However, further mechanistic studies are required to comprehensively assess the therapeutic potential of 6A10 and to identify different resistance mechanisms of GSCs.

Magnetotransport and magnetic properties of the layered noncollinear antiferromagnetic Cr2Se3 single crystals.

We report on the growth of high-quality stoichiometric layered Cr2Se3 single crystals with metallic and noncollinear antiferromagnetic ground state using the chemical vapor transport (CVT) method. The crystals show weak ferromagnetism in the in-plane and out-of-plane directions below the Neél temperature (T N), however, the field-cooled out-of-plane magnetization at 500 Oe and 10 K (∼0.24 µ B/f.u.) is approximately 15 times larger than that of the in-plane one, indicating strong c-axis easy uniaxial magnetic anisotropy, which is further supported by the in-plane and out-of-plane isothermal anisotropic magnetic hysteresis loops and the angular dependent magnetoresistance (MR). The latter also reveals a decrease of the coercive field of the crystal upon the tilting of the weak ferromagnetic easy axis away from the direction of the magnetic field. Further, the out-of-plane isothermal MR are negative below T N and show butterfly shapes for T < 10 K and couple with the magnetic hysteresis M(H) loop. These results may help researchers better understand the interplay between the weak ferromagnetism and the magnetotransport properties of 2D itinerant noncollinear antiferromagnetic systems.

Construction of hybrid DNAs@CP for the rapid synchronous sensing of multiplex microRNAs based on experimental studies and molecular simulation.

A water stable one-dimensional (1D) ladder-shaped coordination polymer (CP) has been synthesized and exhibits a strong affinity to two fluorescein-tagged single-stranded probe DNAs (P-DNAs), giving a sensing platform of P-DNAs@1. Such a hybrid sensing platform is capable of simultaneous detection of breast cancer related microRNA-221 (miRNA-221) and miRNA-222 in a specific and synchronous manner, without observable cross-reactions, as supported by experimental evidences. The interaction mode and the electronic energy between CP 1 with nucleic acid were confirmed by molecular simulation and the universal force field (UFF).

Nonvolatile and Reversible Ferroelectric Control of Electronic Properties of Bi2Te3 Topological Insulator Thin Films Grown on Pb(Mg1/3Nb2/3)O3-PbTiO3 Single Crystals.

Single-phase (00 l)-oriented Bi2Te3 topological insulator thin films have been deposited on (111)-oriented ferroelectric 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 (PMN-PT) single-crystal substrates. Taking advantage of the nonvolatile polarization charges induced by the polarization direction switching of PMN-PT substrates at room temperature, the carrier density, Fermi level, magnetoconductance, conductance channel, phase coherence length, and quantum corrections to the conductance can be in situ modulated in a reversible and nonvolatile manner. Specifically, upon the polarization switching from the positively poled Pr+ state (i.e., polarization direction points to the film) to the negatively poled Pr- (i.e., polarization direction points to the bottom electrode) state, both the electron carrier density and the Fermi wave vector decrease significantly, reflecting a shift of the Fermi level toward the Dirac point. The polarization switching from Pr+ to Pr- also results in significant increase of the conductance channel α from -0.15 to -0.3 and a decrease of the phase coherence length from 200 to 80 nm at T = 2 K as well as a reduction of the electron-electron interaction. All these results demonstrate that electric-voltage control of physical properties using PMN-PT as both substrates and gating materials provides a simple and a straightforward approach to realize reversible and nonvolatile tuning of electronic properties of topological thin films and may be further extended to study carrier density-related quantum transport properties of other quantum matter.

Integration of Oxide Semiconductor Thin Films with Relaxor-Based Ferroelectric Single Crystals with Large Reversible and Nonvolatile Modulation of Electronic Properties.

We report the fabrication of 0.71Pb(Mg1/3Nb2/3)O3-0.29PbTiO3 (PMN-0.29PT)-based ferroelectric field effect transistors (FeFETs) by the epitaxial growth of cobalt-doped tin dioxide (SnO2) semiconductor thin films on PMN-0.29PT single crystals. Using such FeFETs we realized in situ, reversible, and nonvolatile manipulation of the electron carrier density and achieved a large nonvolatile modulation of the resistance (∼330%) of the SnO2:Co films through the polarization switching of PMN-0.29PT at 300 K. Particularly, combining the ferroelectric gating with piezoresponse force microscopy, X-ray diffraction, Hall effect, and magnetoresistance (MR), we rigorously disclose that both sign and magnitude of the MR are intrinsically determined by the electron carrier density, which could modify the s-d exchange interaction of the SnO2:Co films. Furthermore, we realized multilevel resistance states of the SnO2:Co films by combining the ferroelectric gating with ultraviolet light illumination, demonstrating that the FeFETs have potential applications in multistate resistive memories and electro-optical devices.

Dark gap solitons in exciton-polariton condensates in a periodic potential.

We show that dark spatial gap solitons can occur inside the band gap of an exciton-polariton condensate (EPC) in a one-dimensional periodic potential. The energy dispersions of an EPC loaded into a periodic potential show a band-gap structure. Using the effective-mass model of the complex Gross-Pitaevskii equation with pump and dissipation in an EPC in a periodic potential, dark gap solitons are demonstrated near the minimum energy points of the band center and band edge of the first and second bands, respectively. The excitation energies of dark gap solitons are below these minimum points and fall into the band gap. The spatial width of a dark gap soliton becomes smaller as the pump power is increased.

Polariton solitons and nonlinear localized states in a one-dimensional semiconductor microcavity.

This paper presents numerical studies of cavity polariton solitons (CPSs) in a resonantly pumped semiconductor microcavity with an imbedded spatial defect. In the bistable regime of the well-known homogeneous polariton condensate, with proper incident wave vector and pump strength, bright and/or dark cavity solitons can be found in the presence of a spatially confined potential. The minimum pump strength required to observe the CPSs or nonlinear localized states in this parametric pump scheme is therefore reported.

Quantum fluctuations and stability of vortex lattices in a nonresonantly pumped exciton-polariton condensate.

The dynamics of an exciton-polariton condensate (EPC) subject to harmonic confinement can cause spontaneously formed vortices to arrange into a triangular vortex lattice. The stability of such a spontaneously formed vortex lattice is still unknown. We investigate the quantum fluctuations of vortex lattices in a rapidly rotating EPC with a rotation frequency close to the harmonic trap. In such a large condensate, we find that a vortex lattice with a triangular structure is stable, whereas one with a square structure becomes unstable. This result indicates that a driven-dissipative vortex array with strong quantum fluctuations can occur in an EPC.

Nonequilibrium and nonlinear defect states in microcavity-polariton condensates.

The nonequilibrium and nonlinear defect modes (NNDMs), localized by a defect in a nonequilibrium microcavity-polariton condensate (MPC), are studied. There are three analytic solutions of NNDMs in a point defect: the bright NNDM, a bound state with two dark solitons for an attractive potential, and a gray soliton bound by a defect for a repulsive potential. We find that the stable NNDMs in a nonequilibrium MPC are the bright NNDM and gray soliton bound by a defect. The bright NNDM, which has the hyperbolic cotangent form, is a bright localized state existing in a uniform MPC. The bright NNDM is a unique state occurring in a nonequilibrium MPC that has pump-dissipation and repulsive-nonlinearity characters. No such state can exist in an equilibrium system with repulsive nonlinearity.

Stable gray soliton pinned by a defect in a microcavity-polariton condensate.

We study the spatially localized dark state, called dark soliton, in a one-dimensional system of the non-resonantly pumped microcavity-polariton condensate (MPC). From the recent work by Xue and Matuszewski [Phys. Rev. Lett. 112, 216401 (2014)], we know that the dark soliton in the pure MPC system is unstable. But we find that a dark soliton pinned by a defect in the impure MPC becomes a gray soliton and can be stabilized by the presence of a defect. Moreover, the stable regime of the gray soliton is given in terms of the defect strength and pump parameter.