The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria ...and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of invading plasmids and viruses. Here, we studied the effects of the CRISPR/CRISPR-associated Cas9 system that was targeted to the surface antigen (HBsAg)-encoding region of HBV, both in a cell culture system and in vivo. The HBsAg levels in the media of the cells and in the sera of mice were analyzed by a quantitative enzyme-linked immunosorbent assay. The HBV DNA levels were assessed by quantitative PCR and HBsAg expression in mouse livers was assessed by an immunohistochemical assay. The amount of HBsAg secreted in the cell culture and mouse serum was reduced by CRISPR/Cas9 treatment. Immunohistochemistry analyses showed almost no HBsAg-positive cells in the liver tissue of CRISPR/Cas9-S1+X3-treated mice. The CRISPR/Cas9 system efficiently produced mutations in HBV DNA. Thus, CRISPR/Cas9 inhibits HBV replication and expression in vitro and in vivo and may constitute a new therapeutic strategy for HBV infection.
Large-scale, highly integrated and low-power-consuming hardware is becoming progressively more important for realizing optical neural networks (ONNs) capable of advanced optical computing. ...Traditional experimental implementations need N
units such as Mach-Zehnder interferometers (MZIs) for an input dimension N to realize typical computing operations (convolutions and matrix multiplication), resulting in limited scalability and consuming excessive power. Here, we propose the integrated diffractive optical network for implementing parallel Fourier transforms, convolution operations and application-specific optical computing using two ultracompact diffractive cells (Fourier transform operation) and only N MZIs. The footprint and energy consumption scales linearly with the input data dimension, instead of the quadratic scaling in the traditional ONN framework. A ~10-fold reduction in both footprint and energy consumption, as well as equal high accuracy with previous MZI-based ONNs was experimentally achieved for computations performed on the MNIST and Fashion-MNIST datasets. The integrated diffractive optical network (IDNN) chip demonstrates a promising avenue towards scalable and low-power-consumption optical computational chips for optical-artificial-intelligence.
Various adsorbents have been used to remove different types of dyes and heavy metal ions from wastewater especially those that are harmful to mankind. Activated carbons, plant or lignocellulosic ...wastes, clays and biopolymers are among the common adsorbents used. Chitosan, a type of biopolymer, is a good adsorbent to remove various kinds of anionic and cationic dyes as well as heavy metal ions. Chemical modifications that lead to the formation of chitosan derivatives, grafting chitosan and chitosan composites have gained much attention, extensively studied and widely reported in the literatures. This review provides relevant literature of the past ten years on the application of chitosan composites for removing dyes and heavy metal ions. A list of chitosan composites with their adsorption capacity and the experimental conditions has been compiled. This review also includes the mechanisms that might be involved during adsorption process.
Splicing of precursor messenger RNA (pre-mRNA) in yeast is executed by the spliceosome, which consists of five small nuclear ribonucleoproteins (snRNPs), NTC (nineteen complex), NTC-related proteins ...(NTR), and a number of associated enzymes and cofactors. Here, we report the three-dimensional structure of a Schizosaccharomyces pombe spliceosome at 3.6-angstrom resolution, revealed by means of single-particle cryogenic electron microscopy. This spliceosome contains U2 and U5 snRNPs, NTC, NTR, U6 small nuclear RNA, and an RNA intron lariat. The atomic model includes 10,574 amino acids from 37 proteins and four RNA molecules, with a combined molecular mass of approximately 1.3 megadaltons. Spp42 (Prp8 in Saccharomyces cerevisiae), the key protein component of the U5 snRNP, forms a central scaffold and anchors the catalytic center. Both the morphology and the placement of protein components appear to have evolved to facilitate the dynamic process of pre-mRNA splicing. Our near-atomic-resolution structure of a central spliceosome provides a molecular framework for mechanistic understanding of pre-mRNA splicing.
To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) ...rats.
RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies.
No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells.
Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies.
This paper investigates an electricity time-of-use (TOU) tariff problem with the consideration of consumer behavior. Under the TOU tariff, we consider two periods: the peak and base periods. A ...two-level model is established to solve the TOU tariff problem: in the upper level, the producer determines the TOU tariff with the consideration of consumer behavior; in the lower level, the consumers respond to the TOU tariff through shifting some electricity consumption in the peak period to the base period. Using the traditional flat-rate (FR) tariff as a baseline, we verify the conditions under which the producer has incentives to adopt the TOU tariff. With the adoption of a general consumer transfer cost, we solve for the optimal TOU tariff under different situations. Our results demonstrate that proper adoption of the TOU tariff can create a win–win situation for both the producer and the consumers: the producer can increase its profit and the consumers can save their electricity cost. We further evaluate the effectiveness of the TOU tariff in terms of the peak demand reduction. Using a quadratic transfer cost, we obtain some managerial insights into the TOU tariff problem, and illustrate that the TOU tariff is always beneficial to the producer and the consumers under the quadratic transfer cost.
•This paper investigates a new electricity time-of-use (TOU) tariff problem with the consideration of consumer behavior.•We verify the conditions under which the producer has incentives to adopt the TOU tariff.•We solve for the optimal TOU tariff under different situations.•Our results show that proper adoption of the TOU tariff can create a win–win situation.•We obtain some managerial insights into the TOU tariff problem.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term ...adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
Unlike the studies of freshmen entrants, the learning experiences of community college transfer (CCT) students in the receiving university is a topic that has only started to gain attention in recent ...decades. Little is known about the differences between CCT and freshmen entrants with regard to their study workload stress and its relationship with their perceptions of the teaching and learning environment, approaches to learning, self-efficacy and generic skills. The purpose of our study was to address this gap. This was a cross-sectional survey study conducted from April 2018 to November 2018 in a university in Hong Kong. The HowULearn questionnaire was adapted to local usage and validated for data collection. In total, 841 CCT students and 978 freshmen entrants completed the survey. The respondents were aged between 19 and 52 years (mean = 21.6, SD = 1.92), and 66.0% were women. The HowULearn questionnaire was determined by factor analyses to have eight factors. The reliabilities of the eight factors were found to be acceptable (Cronbach alphas = 0.709-0.918). The CCT students scored significantly higher than the freshmen entrants for perceived study workload stress and surface approaches to learning, but lower on teaching for understanding & encouraging learning, peer support, and self-efficacy beliefs. The surface approach to learning, deep & organized studying, alignment & constructive feedback, and generic skills were found to be predictors of study workload stress in both groups of students, and in the overall student data. This study has shown that CCT students and freshmen entrants differed with regard to their study workload stress and learning experiences. Our findings provide a message, both for educators in higher education and policy makers in the government-there is not a one-size-fits-all approach to different student populations when it comes to enhancing their learning experiences.
Gold nanohexapods represent a novel class of optically tunable nanostructures consisting of an octahedral core and six arms grown on its vertices. By controlling the length of the arms, their ...localized surface plasmon resonance peaks could be tuned from the visible to the near-infrared region for deep penetration of light into soft tissues. Herein we compare the in vitro and in vivo capabilities of Au nanohexapods as photothermal transducers for theranostic applications by benchmarking against those of Au nanorods and nanocages. While all these Au nanostructures could absorb and convert near-infrared light into heat, Au nanohexapods exhibited the highest cellular uptake and the lowest cytotoxicity in vitro for both the as-prepared and PEGylated nanostructures. In vivo pharmacokinetic studies showed that the PEGylated Au nanohexapods had significant blood circulation and tumor accumulation in a mouse breast cancer model. Following photothermal treatment, substantial heat was produced in situ and the tumor metabolism was greatly reduced for all these Au nanostructures, as determined with 18F-flourodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Combined together, we can conclude that Au nanohexapods are promising candidates for cancer theranostics in terms of both photothermal destruction and contrast-enhanced diagnosis.
Grain length in rice plays an important role in determining rice appearance, milling, cooking and eating quality. In this study, the genetic basis of grain length was dissected into six main-effect ...quantitative trait loci (QTLs) and twelve pairs of epistatic QTLs. The stability of these QTLs was evaluated in four environments using an F7 recombinant inbred line (RIL) population derived from the cross between a Japonica variety, Asominori, and an Indica variety, IR24. Moreover, chromosome segment substitution lines (CSSLs) harboring each of the six main-effect QTLs were used to evaluate gene action of QTLs across eight environments. A major QTL denoted as qGL-3a, was found to express stably not only in the isogenic background of Asominori but also in the recombinant background of Asominori and IR24 under multiple environments. The IR24 allele at qGL-3a has a positive effect on grain length. Based on the test of advanced backcross progenies, qGL-3a was dissected as a single Mendelian factor, i.e., long rice grain was controlled by a recessive gene gl-3. High-resolution genetic and physical maps were further constructed for fine mapping gl-3 by using 11 simple sequence repeat (SSR) markers designed using sequence information from seven BAC/PAC clones and a BC4F2 population consisting of 2,068 individuals. Consequently, the gl-3 gene was narrowed down to a candidate genomic region of 87.5 kb long defined by SSR markers RMw357 and RMw353 on chromosome 3, which provides a basis for map-based cloning of this gene and for marker-aided QTL pyramiding in rice quality breeding.
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