A New Class of Multiple-rate Codes Based on Block Markov Superposition Transmission

Hadamard transform~(HT) as over the binary field provides a natural way to implement multiple-rate codes~(referred to as {\em HT-coset codes}), where the code length $N=2^p$ is fixed but the code dimension $K$ can be varied from $1$ to $N-1$ by adjusting the set of frozen bits. The HT-coset codes, including Reed-Muller~(RM) codes and polar codes as typical examples, can share a pair of encoder and decoder with implementation complexity of order $O(N \log N)$. However, to guarantee that all codes with designated rates perform well, HT-coset coding usually requires a sufficiently large code length, which in turn causes difficulties in the determination of which bits are better for being frozen. In this paper, we propose to transmit short HT-coset codes in the so-called block Markov superposition transmission~(BMST) manner. At the transmitter, signals are spatially coupled via superposition, resulting in long codes. At the receiver, these coupled signals are recovered by a sliding-window iterative soft successive cancellation decoding algorithm. Most importantly, the performance around or below the bit-error-rate~(BER) of $10^{-5}$ can be predicted by a simple genie-aided lower bound. Both these bounds and simulation results show that the BMST of short HT-coset codes performs well~(within one dB away from the corresponding Shannon limits) in a wide range of code rates

A Molecular-Splicing Strategy for Constructing a Near-Infrared Fluorescent Probe for UDP-Glucuronosyltransferase 1A1

UDP-glucuronosyltransferase 1A1 (UGT1A1) is a vital metabolic enzyme responsible for the clearance of endogenous substances and drugs. Hitherto, the development of fluorescent probes for UGTs was severely restricted due to the poor isoform selectivity and on–off or blue-shifted fluorescence response. Herein, we established a novel “molecular-splicing” strategy to construct a highly selective near-infrared (NIR) fluorescent probe, HHC, for UGT1A1, which exhibited a NIR signal at 720 nm after UGT1A1 metabolism. HHC was then successfully used for the real-time imaging of endogenous UGT1A1 in living cells and animals and to monitor the bile excretion function. In summary, an isoform-specific NIR fluorescent probe has been developed for monitoring UGT1A1 activity in living systems, high-throughput screening of novel UGT1A1 inhibitors and visual evaluation of bile excretion function.</p

Visual identification of gut bacteria and determination of natural inhibitors using a fluorescent probe selective for PGP-1

PGP-1 is a bacterial hydrolase that can hydrolyze the amide bond of the L-pyroglutamate (L-pGlu) residue at the amino terminus of proteins and peptides. Guided by the biological function of PGP-1, an off-on NIR fluorescent probe DDPA was developed for the visual sensing of PGP-1 by conjugating pyroglutamic acid (recognition group) and DDAN (fluorophore). Using intestinal bacteria cultivation, eight bacteria strains with active PGP-1 were identified and cultivated efficiently using DDPA. In addition, three natural inhibitors against PGP-1 were isolated from the medical herb Psoralea corylifolia, which could be used to interfere with bacterial metabolism in the gut. As such, the fluorescent probe DDPA provides an efficient method and potential tool for the investigation of intestinal microbiota.</p

Visual High-Throughput Screening for Developing a Fatty Acid Amide Hydrolase Natural Inhibitor Based on an Enzyme-Activated Fluorescent Probe

Fatty acid amide hydrolase (FAAH) is an important drug target for the treatment of many disease related conditions such as pain, inflammation, and mood disorders due to its vital role in the metabolism of endocannabinoid. In our present work, a FAAH-activated fluorescent probe named THPO was developed, which possessed high selectivity and excellent sensitivity for FAAH in complex systems. Critically, its metabolite 7-amino-3H-phenoxazin-3-one (AHPO) has long excitation and emission wavelengths and high fluorescence quantum yield, which are necessary for monitoring the activity of FAAH in living systems. In addition, a visual high-throughput screening method for FAAH inhibitors was established using THPO, which resulted in the discovery of an efficient natural inhibitor Neobavaisoflavone that was identified from 68 traditional herbal medicines. These results indicated that THPO can be used as a molecular tool for the rapid evaluation of FAAH activity in complex systems as well as providing an effective approach to screen FAAH inhibitors and providing a boost for the discovery of therapeutic agents toward FAAH related diseases. </p

Rational Design of a Two-Photon Fluorescent Probe for Human Cytochrome P450 3A and the Visualization of Mechanism-Based Inactivation

Mechanism-based inactivation (MBI) can mediate adverse reactions and hepatotoxicity from drugs, which is a result of their conversion into highly reactive metabolites catalyzed by enzymes such as cytochrome P450 3A (CYP3A). In the present research, we optimized the key interaction domain of the fluorophore with the target protein to develop a two-photon fluorescent probe for CYP3A that is involved in the metabolism of more than half of all clinical drugs. The developed BN-1 probe exhibited appropriate selectivity and sensitivity for the semi-quantitative detection and imaging of endogenous CYP3A activity in various living systems, thereby providing a high-throughput screening system enabling evaluation of MBI-associated hepatotoxicity by CYP3A. Using BN-1 as a fluorescent molecular tool facilitates the efficient discovery and characterization of CYP3A-induced MBI in natural systems.</p

Hybrid Nanosecond Laser Processing and Heat Treatment for Rapid Preparation of Super-Hydrophobic Copper Surface

The super-hydrophobic copper surface was obtained by using a nanosecond pulsed laser. Different micro- and nano-structures were fabricated by changing the laser scanning interval and scanning speed, before heating in an electric heater at 150 °C for two hours to explore the effect of laser parameters and heat treatment on the wettability of the copper surface. It was found that the laser-treated copper surface is super-hydrophilic, and then, after the heat treatment, the surface switches to hydrophobic or even super-hydrophobic. The best super-hydrophobic surface’s apparent contact angle (APCA) was 155.6°, and the water sliding angle (WSA) was 4°. Super-hydrophobic copper is corrosion-resistant, self-cleaning, and dust-proof, and can be widely used in various mechanical devices

Effects of Sublethal Concentrations of Chlorpyrifos on Olfactory Learning and Memory Performances in Two Bee Species, Apis mellifera and Apis cerana

Chlorpyrifos is a widely used organophosphorus insecticide. The acute oral 24 h median lethal dose (LD50) value of chlorpyrifos in Apis mellifera and in Apis cerana was estimated to assess differential acute chlorpyrifos toxicity in both bee species. The LD50 values of chlorpyrifos in A. mellifera and in A. cerana are 103.4 ng/bee and 81.8 ng/bee, respectively, which suggests that A. cerana bees are slightly more sensitive than A. mellifera bees to the toxicity of chlorpyrifos. Doses half the acute LD50 of chlorpyrifos were selected to study behavioral changes in both bee species using proboscis extension response assay. A. mellifera foragers treated with chlorpyrifos showed significantly lower response to the 10% sucrose solution compared to control bees after 2, 24 and 48 h. Chlorpyrifos significantly impaired the olfactory learning abilities and 2 h memory retention of forager bees regardless of honey bee species, which may affect the foraging success of bees exposed to chlorpyrifos

A novel Pseudorabies virus vaccine developed using HDR-CRISPR/Cas9 induces strong humoral and cellular immune response in mice

Outbreaks of Pseudorabies (PR) by numerous highly virulent and antigenic variant Pseudorabies virus (PRV) strains have been causing severe economic losses to the pig industry in China since 2011. However, current commercial vaccines are often unable to induce thorough protective immunity. In this study, a TK/gI/gE deleted recombinant PRV expressing GM-CSF was developed by using the HDR-CRISPR/Cas9 system. Here, a four-sgRNA along with the Cas9D10A targeting system was utilized for TK/gI/gE gene deletion and GM-CSF insertion. Our study showed that the four-sgRNA targeting system appeared to have higher knock-in efficiency for PRVs editing. The replication of the recombinant PRVs were slightly lower than that of the parental strain, but they appeared to have similar properties in terms of growth curves and plaque morphology. The mice vaccinated with the recombinant PRV expressing GM-CSF via intramuscular injection showed no obvious clinical symptoms, milder pathological lesions, and were completely protected against wild-type PRV challenge. When compared to the triple gene-deleted PRV, the gB antibodies and neutralizing antibody titers were improved and the immunized mice appeared to have lower viral load and higher mRNA levels of IL-2, IL-4, IL-6, and IFN-γ in spleens. Our study offers a novel approach for recombinant PRV construction, and the triple gene-deleted PRV expressing GM-CSF could serve as a promising vaccine candidate for PR control

Dopamine depletion and subcortical dysfunction disrupt cortical synchronization and metastability affecting cognitive function in Parkinson's disease

Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic cells and atrophy in subcortical regions. However, the impact of these pathological changes on large‐scale dynamic integration and segregation of the cortex are not well understood. In this study, we investigated the effect of subcortical dysfunction on cortical dynamics and cognition in PD. Spatiotemporal dynamics of the phase interactions of resting‐state blood‐oxygen‐level‐dependent signals in 159 PD patients and 152 normal control (NC) individuals were estimated. The relationships between subcortical atrophy, subcortical–cortical fiber connectivity impairment, cortical synchronization/metastability, and cognitive performance were then assessed. We found that cortical synchronization and metastability in PD patients were significantly decreased. To examine whether this is an effect of dopamine depletion, we investigated 45 PD patients both ON and OFF dopamine replacement therapy, and found that cortical synchronization and metastability are significantly increased in the ON state. The extent of cortical synchronization and metastability in the OFF state reflected cognitive performance and mediates the difference in cognitive performance between the PD and NC groups. Furthermore, both the thalamic volume and thalamocortical fiber connectivity had positive relationships with cortical synchronization and metastability in the dopaminergic OFF state, and mediate the difference in cortical synchronization between the PD and NC groups. In addition, thalamic volume also reflected cognitive performance, and cortical synchronization/metastability mediated the relationship between thalamic volume and cognitive performance in PD patients. Together, these results highlight that subcortical dysfunction and reduced dopamine levels are responsible for decreased cortical synchronization and metastability, further affecting cognitive performance in PD. This might lead to biomarkers being identified that can predict if a patient is at risk of developing dementia