Gravitational Waves from a Core g Mode in Supernovae as Probes of the High-Density Equation of State.

Using relativistic supernova simulations of massive progenitor stars with a quark-hadron equation of state (EOS) and a purely hadronic EOS, we identify a distinctive feature in the gravitational-wave signal that originates from a buoyancy-driven mode (g mode) below the proto-neutron star convection zone. The mode frequency lies in the range 200≲f≲800 Hz and decreases with time. As the mode lives in the core of the proto-neutron star, its frequency and power are highly sensitive to the EOS, in particular the sound speed around twice saturation density.

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics.

Dendrimers are polymers with well-defined 3D branched structures that are vastly utilized in various neurotheranostics and biomedical applications, particularly as nanocarrier vectors. Imaging agents can be loaded into dendrimers to improve the accuracy of diagnostic imaging processes. Likewise, combining pharmaceutical agents and anticancer drugs with dendrimers can enhance their solubility, biocompatibility, and efficiency. Practically, by modifying ligands on the surface of dendrimers, effective therapeutic and diagnostic platforms can be constructed and implemented for targeted delivery. Dendrimer-based nanocarriers also show great potential in gene delivery. Since enzymes can degrade genetic materials during their blood circulation, dendrimers exhibit promising packaging and delivery alternatives, particularly for central nervous system (CNS) treatments. The DNA and RNA encapsulated in dendrimers represented by polyamidoamine that are used for targeted brain delivery, via chemical-structural adjustments and appropriate generation, significantly improve the correlation between transfection efficiency and cytotoxicity. This article reports a comprehensive review of dendrimers' structures, synthesis processes, and biological applications. Recent progress in diagnostic imaging processes and therapeutic applications for cancers and other CNS diseases are presented. Potential challenges and future directions in the development of dendrimers, which provide the theoretical basis for their broader applications in healthcare, are also discussed.

Reactivation of Epstein-Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function.

Epstein-Barr nuclear antigen 1 (EBNA1) plays a vital role in the maintenance of the viral genome and is the only viral protein expressed in nearly all forms of Epstein-Barr virus (EBV) latency and EBV-associated diseases, including numerous cancer types. To our knowledge, no specific agent against EBV genes or proteins has been established to target EBV lytic reactivation. Here we report an EBNA1- and Zn2+-responsive probe (ZRL5P4) which alone could reactivate the EBV lytic cycle through specific disruption of EBNA1. We have utilized the Zn2+ chelator to further interfere with the higher order of EBNA1 self-association. The bioprobe ZRL5P4 can respond independently to its interactions with Zn2+ and EBNA1 with different fluorescence changes. It can selectively enter the nuclei of EBV-positive cells and disrupt the oligomerization and oriP-enhanced transactivation of EBNA1. ZRL5P4 can also specifically enhance Dicer1 and PML expression, molecular events which had been reported to occur after the depletion of EBNA1 expression. Importantly, we found that treatment with ZRL5P4 alone could reactivate EBV lytic induction by expressing the early and late EBV lytic genes/proteins. Lytic induction is likely mediated by disruption of EBNA1 oligomerization and the subsequent change of Dicer1 expression. Our probe ZRL5P4 is an EBV protein-specific agent that potently reactivates EBV from latency, leading to the shrinkage of EBV-positive tumors, and our study also suggests the association of EBNA1 oligomerization with the maintenance of EBV latency.

Enhancing Hybrid Upconversion Nanosystems via Synergistic Effects of Moiety Engineered NIR Dyes.

Hybrid upconversion nanosystems have been reported to improve the low absorption efficiency of lanthanide-doped upconversion nanoparticles (UCNPs). However, the low quantum yield and poor photostability of NIR dyes pose challenges for practical uses. Here, we introduce a bulky moiety, 4-(1,2,2-triphenylvinyl)-1,1'-biphenyl (TPEO), to enhance its quantum yield by suppressing the bond rotation and improve the stability by deactivating the photoinduced oxidization. Compared with the conventional IR806, the formed NIR dye, TPEO-Cy, has been characterized to deliver three times higher quantum yield and seven times better photostability. Moreover, we take advantage of the strong affinity of sulfonate chains on the TPEO-Cy to bind to the surface of UCNPs. Taking together the synergistic effect, we have achieved a 242-fold upconversion emission enhancement over the benchmark of IR806-sensitized system and an ∼800 000-fold increase than the bare UCNPs. Our design of the NIR dyes suggests a new scope to search for more efficient upconversion nanohybrids.

Erratum: Gravitational-Wave Signature of a First-Order Quantum Chromodynamics Phase Transition in Core-Collapse Supernovae [Phys. Rev. Lett. 125, 051102 (2020)].

This corrects the article DOI: 10.1103/PhysRevLett.125.051102.

Gravitational-Wave Signature of a First-Order Quantum Chromodynamics Phase Transition in Core-Collapse Supernovae.

A first-order quantum chromodynamics (QCD) phase transition (PT) may take place in the protocompact star (PCS) produced by a core-collapse supernova (CCSN). In this work, we study the consequences of such a PT in a nonrotating CCSN with axisymmetric hydrodynamic simulations. We find that the PT leads to the collapse of the PCS and results in a loud burst of gravitational waves (GWs). The amplitude of this GW burst is ∼30 times larger than the postbounce GW signal normally found for nonrotating CCSN. It shows a broad peak at high frequencies (∼2500-4000 Hz) in the spectrum, has a duration of ≲5 ms, and carries ∼3 orders of magnitude more energy than the other episodes. Also, the peak frequency of the PCS oscillation increases dramatically after the PT-induced collapse. In addition to a second neutrino burst, the GW signal, if detected by the ground-based GW detectors, is decisive evidence of the first-order QCD PT inside CCSNe and provides key information about the structure and dynamics of the PCS.

Identification of pulmonary edema in forensic autopsy cases of fatal anaphylactic shock using Fourier transform infrared microspectroscopy.

Anaphylaxis is a rapid allergic reaction that may cause sudden death. Currently, postmortem diagnosis of anaphylactic shock is sometimes difficult and often achieved through exclusion. The aim of our study was to investigate whether Fourier transform infrared (FTIR) microspectroscopy combined with pattern recognition methods would be complementary to traditional methods and provide a more accurate postmortem diagnosis of fatal anaphylactic shock. First, the results of spectral peak area analysis showed that the pulmonary edema fluid of the fatal anaphylactic shock group was richer in protein components than the control group, which included mechanical asphyxia, brain injury, and acute cardiac death. Subsequently, principle component analysis (PCA) was performed and showed that the anaphylactic shock group contained more turn and α-helix protein structures as well as less tyrosine-rich proteins than the control group. Ultimately, a partial least-square discriminant analysis (PLS-DA) model combined with a variables selection method called the genetic algorithm (GA) was built and demonstrated good separation between these two groups. This pilot study demonstrates that FTIR microspectroscopy has the potential to be an effective aid for postmortem diagnosis of fatal anaphylactic shock.

Reversible and Sensitive Hg2+ Detection by a Cell-Permeable Ytterbium Complex.

A cell-permeable ytterbium complex shows reversible binding with Hg2+ in aqueous solution and in vitroby off-on visible and NIR emission. The fast response and 150 nM sensitivity of Hg2+ detection is based upon FRET and the lanthanide antenna effect. The reversible Hg2+ detection can be performed in vitro, and the binding mechanism is suggested by NMR employing the motif structure in a La complex and by DFT calculations.

Unveiling Microscopic Structures of Charged Water Interfaces by Surface-Specific Vibrational Spectroscopy.

A sum-frequency spectroscopy scheme is developed that allows the measurement of vibrational spectra of the interfacial molecular structure of charged water interfaces. The application of this scheme to a prototype lipid-aqueous interface as a demonstration reveals an interfacial hydrogen-bonding water layer structure that responds sensitively to the charge state of the lipid headgroup and its interaction with specific ions. This novel technique provides unique opportunities to search for better understanding of electrochemistry and biological aqueous interfaces at a deeper molecular level.

Functionalized Nanomaterials Capable of Crossing the Blood-Brain Barrier.

The blood-brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.

Intranasal Delivery of Functionalized Polymeric Nanomaterials to the Brain.

Intravenous delivery of nanomaterials containing therapeutic agents and various cargos for treating neurological disorders is often constrained by low delivery efficacy due to difficulties in passing the blood-brain barrier (BBB). Nanoparticles (NPs) administered intranasally can move along olfactory and trigeminal nerves so that they do not need to pass through the BBB, allowing non-invasive, direct access to selective neural pathways within the brain. Hence, intranasal (IN) administration of NPs can effectively deliver drugs and genes into targeted regions of the brain, holding potential for efficacious disease treatment in the central nervous system (CNS). In this review, current methods for delivering conjugated NPs to the brain are primarily discussed. Distinctive potential mechanisms of therapeutic nanocomposites delivered via IN pathways to the brain are then discussed. Recent progress in developing functional NPs for applications in multimodal bioimaging, drug delivery, diagnostics, and therapeutics is also reviewed. This review is then concluded by discussing existing challenges, new directions, and future perspectives in IN delivery of nanomaterials.

Study on Strategic Interaction between Government and Farmers in Rural Passive Energy Transformation.

In the implementation of public environmental policies, the deviation between the behavioral intention of farmers and the results of policy implementation is widespread. To reveal the universality, and break through existing research perspectives, this paper, starting from the interaction between the government and farmers, builds a rural passive energy transformation mechanism conceptual model. Using the policy of "coal to gas" in northern China area as a case, a comprehensive analysis of the influencing factors of peasant household behavior response is presented, using a structural equation to compute the interaction strength between the two agents. The results of the study show that: (1) the standardized path coefficients of household behavioral intention and government policy characteristics on household behavioral response are 0.458 and 0.554, respectively. The effect of government is stronger than that of households, which highlights the change effect of government on household behavioral responses and explains the reason for the deviation between behavioral intention and behavioral response; and (2) The standardized correlation coefficient between government policy characteristics and farmers' behavioral intention is 0.858, indicating that the interaction between government and farmers has a significant impact on policy results, and verifies the important role of research on the interactions between government and farmers. Therefore, in order to improve the effect of rural energy transformation, it is necessary to strengthen the interactions between the government and farmers, to smooth the channels of farmers' demands, and to form a pattern of air pollution control with government guidance and full participation.

Biocompatible Porphyrin-Peptide Conjugates as Theranostic Agents Targeting the Epstein-Barr Virus.

Epstein-Barr virus (EBV) is a common human-infected virus related to many diseases and cancers. Recently, some peptides have been found to serve targeting and therapeutic roles by inhibiting EBNA1, an oncoprotein of the EBV. We herein report the conjugation of the EBNA1-targeting peptides and porphyrins which can bring synergistic effects by both introducing more specific treatments (photodynamic therapy) and improving the biocompatibility of the photosensitizer and the peptides. One of our compounds exhibited significant photo-cytotoxicity where the Lethal Concentration 50 (LC50 )=6.1 µM in EBV-positive cells. Besides, in vitro cell imaging and co-staining can also be achieved simultaneously and suggested the binding inside nucleus.

Sleep Staging Using Noncontact-Measured Vital Signs.

As a physiological phenomenon, sleep takes up approximately 30% of human life and significantly affects people's quality of life. To assess the quality of night sleep, polysomnography (PSG) has been recognized as the gold standard for sleep staging. The drawbacks of such a clinical device, however, are obvious, since PSG limits the patient's mobility during the night, which is inconvenient for in-home monitoring. In this paper, a noncontact vital signs monitoring system using the piezoelectric sensors is deployed. Using the so-designed noncontact sensing system, heartbeat interval (HI), respiratory interval (RI), and body movements (BM) are separated and recorded, from which a new dimension of vital signs, referred to as the coordination of heartbeat interval and respiratory interval (CHR), is obtained. By extracting both the independent features of HI, RI, and BM and the coordinated features of CHR in different timescales, Wake-REM-NREM sleep staging is performed, and a postprocessing of staging fusion algorithm is proposed to refine the accuracy of classification. A total of 17 all-night recordings of noncontact measurement simultaneous with PSG from 10 healthy subjects were examined, and the leave-one-out cross-validation was adopted to assess the performance of Wake-REM-NREM sleep staging. Taking the gold standard of PSG as reference, numerical results show that the proposed sleep staging achieves an averaged accuracy and Cohen's Kappa index of 82.42% and 0.63, respectively, and performs robust to subjects suffering from sleep-disordered breathing.

Dual-Targeting Peptide-Guided Approach for Precision Delivery and Cancer Monitoring by Using a Safe Upconversion Nanoplatform.

Using Epstein-Barr virus (EBV)-induced cancer cells and HeLa cells as a comparative study model, a novel and safe dual-EBV-oncoproteins-targeting pH-responsive peptide engineering, coating, and guiding approach to achieve precision targeting and treatment strategy against EBV-associated cancers is introduced. Individual functional peptide sequences that specifically bind to two overexpressed EBV-specific oncoproteins, EBNA1 (a latent cellular protein) and LMP1 (a transmembrane protein), are engineered in three different ways and incorporated with a pH-sensitive tumor microenvironment (TME)-cleavable linker onto the upconversion nanoparticles (UCNP) NaGdF4:Yb3+, Er3+@NaGdF4 (UCNP-P n , n = 5, 6, and 7). A synergistic combination of the transmembrane LMP1 targeting ability and the pH responsiveness of UCNP-P n is found to give specific cancer differentiation with higher cellular uptake and accumulation in EBV-infected cells, thus a lower dose is needed and the side effects and health risks from treatment would be greatly reduced. It also gives responsive UC signal enhancement upon targeted dual-protein binding and shows efficacious EBV cancer inhibition in vitro and in vivo. This is the first example of simultaneous imaging and inhibition of two EBV latent proteins, and serves as a blueprint for next-generation peptide-guided precision delivery nanosystem for the safe monitoring and treatment against one specific cancer.

Estimation of the age of human semen stains by attenuated total reflection Fourier transform infrared spectroscopy: a preliminary study.

Semen stain is one of the most important biological evidence at sexual crime scenes. Age estimation of human semen stains plays an important role in forensic work, and it is rarely studied due to lack of well-established methods. In this study, the technique called attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) coupled with advanced chemometric methods was employed to determine the age of semen stains on three different substrates: glass slides, tissues and fabric made of regenerated cellulose fibres up to 6 d. Partial least squares regression (PLSR) was used in conjunction with spectral analysis for age estimation, and the results generated high R 2 values (cross-validation: 0.81, external validation: 0.74) but a narrow margin of error for root mean square error (RMSE) (RMSE of cross-validation: 0.77 d, RMSE of prediction: 1.02 d). Additionally, our results indicated the robustness of PLSR model was not weaken by the influence of different substrates in this study. Our results indicate that ATR-FTIR, combined with chemometric methods, shows great potential as a convenient and efficient tool for age estimation of semen stains. Moreover, the method could be applied to routine forensic investigations in the future.

Responsive upconversion nanoprobe for monitoring and inhibition of EBV-associated cancers via targeting EBNA1.

Non-responsive emission enhancement is the disadvantage of upconversion nanomaterials (UCNM) when compared with conventional organic based agents for molecular imaging. We herein show a new strategy by conjugating NaGdF4:Yb3+,Er3+@NaGdF4 (UCNP) with peptides to achieve responsive UC emission enhancement upon binding to a targeted protein - EBNA1. EBNA1 is a well-known viral latent protein for the EBV-associated cancer. Peptide-coating of the functionalized core-shell nanoparticle diminishes upconverted emission intensity drastically. However, the peptide-coated UCNP shows selective and responsive UC emission enhancement via aggregation with the targeted protein. This phenomenon paves a new way for UCNM in molecular imaging.

Estimation of the late postmortem interval using FTIR spectroscopy and chemometrics in human skeletal remains.

Due to a lack of reliable and accurate methods, determining the postmortem interval (PMI) of human skeletal remains is one of the most important and challenging tasks in forensic medicine. In this paper, we studied the changes to bone chemistry with increasing PMI in two different experimental conditions using Fourier transform infrared (FTIR) spectroscopy in conjunction with chemometrics methods Paired bone samples collected from 56 human corpses were buried (placed in soil) and unburied (exposed to the air) for intervals between 76 and 552 days. The results of principle component analysis (PCA) showed the chemical differences of these two cases had a significant influence on the rate of decomposition of the remains. Meanwhile, satisfactory predictions were performed by the genetic algorithm combined with partial least-squares (GA-PLS) with the root mean square errors of prediction (RMSEP) of 50.93days for buried bones and 71.03days for unburied bones. Moreover, the amide I region of proteins and the area around 1390cm-1, which is associated with fatty acids, were identified with regular changes by GA-PLS and played an important role in estimating PMI. This study illustrates the feasibility of utilizing FTIR spectroscopy and chemometrics as an attractive alternative for estimating PMI of human remains and the great potential of these techniques in real forensic cases with natural conditions.

A luminescent lanthanide approach towards direct visualization of primary cilia in living cells.

We report a direct imaging tool, HGEu001, for primary cilia in living cells, which is specific, and based on the UV light or near infrared laser (via two-photon excitation) induced long-lived europium luminescence.

A Smart Europium-Ruthenium Complex as Anticancer Prodrug: Controllable Drug Release and Real-Time Monitoring under Different Light Excitations.

A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. Under evaluation-window irradiation (λirr = one-photon 350 nm or two-photon 700 nm), the drug delivery process can be quantitatively monitored in real-time because of the long-lived red europium emission. Linear relationships between released drug concentration and ESI-MS or luminescence responses are established. Finally, the efficiency of the new prodrug is demonstrated both in vitro RuEuL anticancer prodrug over some existing ones and open the way for decisive improvements in multipurpose prodrugs.