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Abstract Background This study aimed to investigate the difference between cycloplegic and noncycloplegic refraction and evaluate the pseudomyopia prevalence in Chinese preschool children during the outbreak of COVID-19. Methods A cross-sectional study was conducted in the Tongzhou District of Beijing, China. Refractive error was measured under both noncycloplegic and cycloplegic conditions with autorefraction. The difference between noncycloplegic and cycloplegic spherical equivalent refraction (SER) and pseudomyopia prevalence were analyzed. Pseudomyopia was defined as SER ≤-0.50D in precycloplegic assessments and >-0.50D in post-cycloplegic assessments. Results Out of the 1487 participants who were enrolled in the study, 1471 individuals (98.92%) between the ages of 3–6 years completed all required procedures. A statistically significant difference in refraction was observed between noncycloplegic and cycloplegic measurements, the median of difference in spherical equivalent refraction (SER) of 0.88D (dioptre)(0.50,1.38). There was a high intraclass correlation (ICC) between these two methods for cylinders (ICC = 0.864; 95% CI, 0.850–0.877). The median DSE for myopia, emmetropia and hyperopia were 0.25D (0.00, 0.38),0.25D (0.06, 0.50) and 1.00D (0.62, 1.38), an hypermetropes showed considerably greater differences than myopes and emmetropes (Kruskal-Wallis test, H = 231.023, P = 0.000). Additionally, girls displayed a greater DSE than boys. Furthermore, when comparing against-the-rule (ATR) and oblique astigmatism, it was found that with-the-rule (WTR) astigmatism had the largest DSE. The study found varying prevalence rates of myopia, emmetropia, and hyperopia with and without cycloplegia, which were 1.90% vs. 10.06%, 11.49% vs. 50.31%, and 86.61% vs. 39.63%, respectively. Additionally, the overall prevalence of pseudomyopia was determined to be 8.29%. Participants with pseudomyopia had a significantly higher mean difference in SER (DSE) compared to non-pseudomyopic participants. Conclusions Cycloplegic refraction is more sensitive than a noncycloplegic one for measuring refractive error in preschool children. Pseudomyopia is prevalent in preschool children during the COVID-19 outbreak period. Our study indicates the possibility that cycloplegic refraction should be performed in preschool children routinely.

As the most common internal modification of mRNA, N6-methyladenosine (m6A) and its regulators modulate gene expression and play critical roles in various biological and pathological processes including tumorigenesis. It was reported previously that m6A methyltransferase (writer), methyltransferase-like 3 (METTL3) adds m6A in primary microRNAs (pri-miRNAs) and facilitates its processing into precursor miRNAs (pre-miRNAs). However, it is unknown whether m6A modification also plays a role in the maturation process of pre-miRNAs and (if so) whether such a function contributes to tumorigenesis. Here, we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia (AML) patients, especially in relapsed patients, and plays an oncogenic role in AML. Moreover, YTHDF2 promotes expression of miR-126-3p (also known as miR-126, as it is the main product of precursor miR-126 (pre-miR-126)), a miRNA that was reported as an oncomiRNA in AML, through facilitating the processing of pre-miR-126 into mature miR-126. Mechanistically, YTHDF2 recognizes m6A modification in pre-miR-126 and recruits AGO2, a regulator of pre-miRNA processing, to promote the maturation of pre-miR-126. YTHDF2 positively and negatively correlates with miR-126 and miR-126's downstream target genes, respectively, in AML patients, and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis, indicating that miR-126 is a functionally important target of YTHDF2 in AML. Overall, our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the therapeutic potential of targeting this axis for AML treatment, but also suggest that m6A plays a role in pre-miRNA processing that contributes to tumorigenesis.

Abstract Recombinant proteins are gaining increasing popularity for treating human diseases. The clinical effectiveness of recombinant proteins is directly related to their biological activity, which is an important indicator in drug development and quality control. However, certain recombinant proteins have unclear or complex signal pathways, making detecting their activity in vitro difficult. For instance, recombinant human endostatin (endostatin), a new antitumor drug developed in China, lacks a sensitive and stable assay for its biological activity since being market approval. To address this issue, we performed a genome‐wide screening of immortalized human umbilical vein endothelial cells (HUVECs) using a CRISPR/Cas9 knockout library containing 20,000 targeted genes. We identified two potential endostatin‐resistant genes, NEPSPP and UTS2, and successfully constructed a highly sensitive cell line, HUVEC‐UTS2‐3#, by knocking down the UTS2 gene. Based on the optimized parameters of HUVEC‐UTS2‐3# cells, we established a new method for detecting the biological activity of endostatin. The method was validated, and it produced results consistent with primary HUVEC cells but with higher sensitivity and more stable data. The use of gene‐editing technology provides a novel solution for detecting the biological activity of recombinant proteins that other methods cannot detect.

This study considers the superior mechanical properties of carbon nanotube concrete (CNC) and conducts corrosion tests over varying durations to investigate key aspects such as corrosion depth, strength loss, ion migration patterns, and microscopic morphological changes in CNC under the influence of stray current in a salt brine environment. Through compressive strength test, chloride ion color test, ion content titration test, microscopic detection test and molecular dynamics simulation, the results show that in an environment where multiple erosive ions coexist, sulfate ions are the most erosive ions to CNC, and are easily combined with calcium ions. The electric field speeds up the transmission of ions, especially chloride ions. Carbon nanotube has a certain adsorption effect on sulfate ions. The main corrosion products are ettringite, gypsum and magnesium hydroxide. Among them, ettringite and gypsum mainly cause expansion and corrosion.

This paper proposes the design of the Zhejiang opera culture gene map using the Zhejiang opera culture gene and gene map. Secondly, it focuses on the application of data mining algorithms in managing opera culture resources, including indexing and querying of dissemination track data and mining Zhejiang opera culture data resources. Finally, the application effect of data mining in Zhejiang opera culture gene mapping is demonstrated through an example analysis. The results show that for the multi-valued attribute dataset of trajectory data of Zhejiang opera culture, the execution time of the optimized algorithm is reduced by 848 ms under a 1% support rate and 88 ms under a 10% support rate compared with the Apriori algorithm. This paper reveals the inner connections and characteristics of Zhejiang opera culture through a data mining algorithm for cultural gene mapping, providing a scientific basis.

Abstract Background Prevention of myopia should begin before school age. However, few population-based cohort studies have investigated refractive status in preschool children with cycloplegia. This study aimed to investigate the post-COVID-19 refraction and ocular biometric parameters of preschool children in Beijing Tongzhou District. Methods A population-based cohort study of kindergarten children in Tongzhou District, Beijing, commenced in November 2021. The present study reports data from the first year of the aforementioned population-based study. We selected children aged 3–6 years from nine kindergartens. Biometric parameters, including axial length (AL), anterior chamber depth (ACD), and corneal radius of curvature (CR), were collected before cycloplegia. Cycloplegic refraction was also measured. The spherical equivalent (SE), lens power (LP), and AL-to-CR ratio were calculated. Multiple linear regression analysis was used to analyse the correlation between refraction and ocular biometric parameters. Results A total of 1,505 children completed the examination, and a mean SE of 1.24 ± 0.91 D was found. The overall prevalence of myopia was 1.93%. The mean AL, ACD, CR, LP, and AL-to-CR ratio were 22.24 ± 0.70 mm, 3.28 ± 0.26 mm, 7.77 ± 0.26 mm, 26.01 ± 1.56 D, and 2.86 ± 0.07, respectively. Longer AL, deeper ACD, larger AL-to-CR ratio, and lower LP were associated with older age; the CR was not significantly different among different ages. In the multiple linear regression analysis, after adjusting for sex and age, the model that included AL, CR, and LP explained 87% of the SE variation. No differences were observed in the prevalence of myopia or the SE in this particular age range. Conclusion The findings of this study suggest that a large proportion of preschool children in Beijing are mildly hyperopic, with a considerably low prevalence of myopia. In preschool children, refractive development was found to present mild hyperopia rather than emmetropia or myopia, a phenomenon that is characteristic of this age range.

Recombinant adeno-associated virus (rAAV) has emerged as a prominent vector for in vivo gene therapy, owing to its distinct advantages. Accurate determination of the rAAV genome titer is crucial for ensuring the safe and effective administration of clinical doses. The evolution of the rAAV genome titer assay from quantitative PCR (qPCR) to digital PCR (dPCR) has enhanced accuracy and precision, yet practical challenges persist. This study systematically investigated the impact of various operational factors on genome titration in a single-factor manner, aiming to address potential sources of variability in the quantitative determination process. Our findings revealed that a pretreatment procedure without genome extraction exhibits superior precision compared with titration with genome extraction. Additionally, notable variations in titration results across different brands of dPCR instruments were documented, with relative standard deviation (RSD) reaching 23.47% for AAV5 and 11.57% for AAV8. Notably, optimal operations about DNase I digestion were identified; we thought treatment time exceeding 30 min was necessary, and there was no need for thermal inactivation after digestion. And we highlighted that thermal capsid disruption before serial dilution substantially affected AAV genome titers, causing a greater than ten-fold decrease. Conversely, this study found that additive components of dilution buffer are not significant contributors to titration variations. Furthermore, we found that repeated freeze–thaw cycles significantly compromised AAV genome titers. In conclusion, a comprehensive dPCR titration protocol, incorporating insights from these impact factors, was proposed and successfully tested across multiple serotypes of AAV. The results demonstrate acceptable variations, with the RSD consistently below 5.00% for all tested AAV samples. This study provides valuable insights to reduce variability and improve the reproducibility of AAV genome titration using dPCR.

The complexity of finite element analysis for composite structures can be significantly reduced by representing the connector and adjacent concrete as a macroscopic element. Nevertheless, the prevailing macroscopic models for shear connections predominantly employ nonlinear elastic theory. This approach introduces inaccuracies in estimating structural stiffness and load-bearing capabilities, primarily due to its inability to precisely capture the cumulative effects of plastic damage. In response, this study introduces a novel macroscopic elastoplastic model grounded in plasticity theory, aimed at accurately characterizing the nonlinear behavior of stud connections subjected to concurrent shear and tensile forces. This paper meticulously delineates the implementation of the elastoplastic constitutive model using the backward Euler method for numerical integration. It further articulates the derivation of the consistent tangent stiffness, which aligns with the convergence efficiency of the Newton–Raphson iterative approach. The computation of the element stiffness matrix for a two-node element is executed via the governing equation inherent to the finite element method. An exemplar macroelement test conducted in ABAQUS affirms the implicit backward Euler scheme’s stability and consistency across varying tolerances. Validation of the elastoplastic model against empirical test outcomes corroborates its efficacy, demonstrating the model’s precision in predicting the load–displacement behavior of stud connections under the influence of shear and tensile forces.

Two-dimensional semiconductors simultaneously having suitable electronic properties and high carrier motilities are highly required in next-generation photoelectronic devices. Herein, we propose a new single-layer semiconductor, CdIn2S4, and investigate its photoelectronic properties utilizing first-principles calculations. Interestingly, we find that single-layer CdIn2S4 holds a quasi-direct moderate bandgap of 1.73 eV. Its valence band maximum and conduction band minimum are located at different atomic regions, which hinders the recombination of generated electrons and holes. Hence, single-layer CdIn2S4 has a suitable electronic structure for optoelectronics. The suitable electronic property also exists under the biaxial strains of −4%, −2%, 2 %, and 4 %, while the electron mobility ranges from ∼3000 to ∼11,000 cm2·V−1·s−1, revealing its potential application in high-speed electronics. In addition, its strong visible absorption and much-reduced exciton binding energy render abundant photogenerated electrons and holes. Summarily, the suitable electronic property, ultrahigh carrier mobility, and abundant visible absorption demonstrate that single-layer CdIn2S4 is a hopeful candidate for high-speed optoelectronics.

Background The Rhizophoraceae family comprises crucial mangrove plants that inhabit intertidal environments. In China, eight Rhizophoraceae mangrove species exist. Although complete chloroplast (Cp) genomes of four Rhizophoraceae mangrove plants have been reported, the Cp genomes of the remaining four species remain unclear, impeding a comprehensive understanding of the evolutionary history of this family. Methods Illumina high-throughput sequencing was employed to obtain the DNA sequences of Rhizophoraceae species. Cp genomes were assembled by NOVOPlasty and annotated using CpGAVAS software. Phylogenetic and divergence time analyses were conducted using MEGA and BEAST 2 software. Results Four novel Cp genomes of Rhizophoraceae mangrove species (Bruguiera sexangula, Bruguiera gymnorrhiza, Bruguiera × rhynchopetala and Rhizophora apiculata) were successfully assembled. The four Cp genomes ranged in length from 163,310 to 164,560 bp, with gene numbers varying from 124 to 128. The average nucleotide diversity (Pi) value of the eight Rhizophoraceae Cp genomes was 0.00596. Phylogenetic trees constructed based on the complete Cp genomes supported the monophyletic origin of Rhizophoraceae. Divergence time estimation based on the Cp genomes of representative species from Malpighiales showed that the origin of Rhizophoraceae occurred at approximately 58.54–50.02 million years ago (Mya). The divergence time within the genus Rhizophora (∼4.51 Mya) was much earlier than the divergence time within the genus Bruguiera (∼1.41 Mya), suggesting recent speciation processes in these genera. Our data provides new insights into phylogenetic relationship and evolutionary history of Rhizophoraceae mangrove plants.

Two-dimensional (2D) semiconductors with intrinsic dipole show glorious prospects in the fields of nanoelectronics. Herein, the possible applications of single-layer GaInO3 in the realms of optoelectronics and piezoelectricity are investigated via the first-principles study. We find that single-layer GaInO3 exhibits a large vertical dipole moment and a direct bandgap (1.53 eV). Its transport mobility for electrons and holes both surpasses 2000 cm2·V−1·s−1. The effective separation of charge carriers for single-layer GaInO3 is confirmed by the strong inside electric field and the spatially isolated conduction band minimum (CBM) and valence band maximum (VBM). The allowed optical transition makes single-layer GaInO3 a hopeful candidate for optical absorbers and detectors. Finally, we also find that single-layer GaInO3 holds a prominently stronger out-of-plane piezoelectric effect than that of previous 2D materials and will play a big role in modern top-bottom gate technologies. In summary, this work proves that single-layer GaInO3 is a promising candidate for atomic-thick optoelectronic and piezoelectric devices.

Recombinant human interferon α2b (rhIFNα2b) is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C. The current identification test for rhIFNα2b is complex. In this study, an anti-rhIFNα2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNα2b. RhIFNα2b was used to immunize an alpaca, which established a phage nanobody library. After five steps of enrichment, the nanobody I22, which specifically bound rhIFNα2b, was isolated and inserted into the prokaryotic expression vector pET28a. After subsequent purification, the physicochemical properties of the nanobody were determined. A semiquantitative detection and rapid identification assay of rhIFNα2b was developed using this novel nanobody. To develop a rapid test, the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips. The developed rhIFNα2b detection assay had a limit of detection of 1 μg/mL. The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products. The principle of this novel assay is generally applicable for the rapid testing of other commercial products, with a great potential for routine use in detecting counterfeit recombinant protein products.

A high-sensitivity plasmonic photonic crystal fiber (PCF) sensor is designed and a metal thin film is embedded for achieving surface plasmon resonance (SPR), which can detect the magnetic field and temperature simultaneously. Within the plasmonic PCF sensor, the SPR sensing is accomplished by coating both the upper sensing channel (Ch1) and the lower sensing channel (Ch2) with gold film. In addition, the temperature-sensitive medium polydimethylsiloxane (PDMS) is chosen to fill in Ch1, allowing the sensor to respond to the temperature. The magnetic field-sensitive medium magnetic fluid (MF) is chosen to fill in Ch2, allowing this sensor to respond to the magnetic field. During these processes, this proposed SPR-PCF sensor can achieve dual-parameter sensing. The paper also investigates the electrical field characteristics, structural parameters and sensing performance using COMSOL. Finally, under the magnetic field range of 50–130 Oe, this sensor has magnetic field sensing sensitivities of 0 pm/Oe (Ch1) and 235 pm/Oe (Ch2). In addition, this paper also investigates the response of temperature. Under the temperature range of 20–40 °C, Ch1 and Ch2 have temperature sensitivities of −2000 pm/°C and 0 pm/°C, respectively. It is noteworthy that the two sensing channels respond to only a single physical parameter; this sensing performance is not common in dual-parameter sensing. Due to this sensing performance, it can be found that the magnetic field and temperature can be detected by this designed SPR-PCF sensor simultaneously without founding and calculating a sensing matrix. This sensing performance can solve the cross-sensitivity problem of magnetic field and temperature, thus reducing the measurement error. Since it can sense without a matrix, it further can solve the ill-conditioned matrix and nonlinear change in sensitivity problems in dual-parameter sensing. These excellent sensing capabilities are very important for carrying out multiparameter sensing in complicated environments.

Electrochemical oxygen evolution reaction (OER) always plays an important role in many electrochemical energy storage and conversion systems. Owing to the slow kinetics mainly brought from multiple proton-coupled electron transfer steps, the design and exploit low-cost, highly active, durable OER electrocatalysts are of significant importance. Although the black phosphorus (BP) shows good electrocatalytic OER performance, it still faces the problems of poor intrinsic activity and low stability due to its instability under ambient conditions. The NiFe-LDH was assembled onto the surfaces of exfoliated BP (EBP) nanoflakes to realize the interfacial coupling between them, achieving an effective improvement in electrocatalytic activity and stability. Benefitting from the interfacial P-O bonding, the NiFe-LDH@EBP hybrid shows high OER activity with a low overpotential of ∼240 mV@10 mA cm−2 toward OER under alkaline conditions, as well as the good stability. Density functional theory (DFT) calculations proved that the interface-coupling of NiFe-LDH on BP promotes charge transfer kinetics and balances the adsorption/desorption of reaction intermediates, ultimately imparting excellent OER electrocatalytic activity.

To achieve the global temperature control target under the background of climate warming, it is necessary to establish a systematic carbon dioxide (CO2) emission accounting method system in the field of water resources as soon as possible. In this study, the carbon dioxide emission equivalent analysis (CEEA) method for different water resource behaviors (WRBs) is proposed from four dimensions of development, allocation, utilization, and protection, and a function table of CEEA (FT-CEEA) for WRBs is constructed. The FT-CEEA includes CEEA formulae for 16 aspects in four categories of water resource development, allocation, utilization, and protection. The CEEA method is applied to 31 provinces in China. The results reveal that: (1) There are significant spatial differences in the carbon dioxide emission equivalent (CEE) of WRBs in different provinces of China under the influence of various factors such as water supply structure and natural conditions. (2) Reservoir storage, tap water allocation, and wastewater treatment are the main contributors to CEE in the categories of water resource development, allocation, and protection behaviors, respectively. (3) The water resource utilization behavior category has the most significant CO2 emission and absorption effects, and industrial and domestic water utilization behaviors are the main sources of emission effects. (4) The overall CO2 emission effect of WRBs is greater than the absorption effect. Measures such as increasing the proportion of hydroelectric power generation, improving ecological water security capacity, and strengthening the level of wastewater treatment and reclaimed water reuse are effective ways to promote the goal of carbon neutrality in the field of water resources.

Owing to the outbreak of the novel coronavirus (SARS-CoV-2) worldwide at the end of 2019, the development of a SARS-CoV-2 vaccine became an urgent need. In this study, we developed a type 9 adeno-associated virus vectored vaccine candidate expressing a dimeric receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S protein) and evaluated its immunogenicity in a murine model. The vaccine candidate, named AAV9-RBD virus, was constructed by inserting a signal peptide to the N-terminus of two copies of RBD, spaced by a linker, into the genome of a type 9 adeno-associated virus. In vitro assays showed that HeLa cells infected by the recombinant AAV virus expressed high levels of the recombinant RBD protein, mostly found in the cell culture supernatant. The recombinant AAV9-RBD virus was cultured and purified. The genome titer of the purified recombinant AAV9-RBD virus was determined to be 2.4 × 1013 genome copies/mL (GC/mL) by Q-PCR. Balb/c mice were immunized with the virus by intramuscular injection or nasal drip administration. Eight weeks after immunization, neutralizing antibodies against the new coronavirus pseudovirus were detected in the sera of all mice; the mean neutralizing antibody EC50 values were 517.7 ± 292.1 (n=10) and 682.8 ± 454.0 (n=10) in the intramuscular injection group and nasal drip group, respectively. The results of this study showed that the recombinant AAV9-RBD virus may be used for the development of a SARS-CoV-2 vaccine.

AIM: To study the correlation of β-amyloid(Aβ)plaques in retinas from Alzheimer's model mice in different months and progression of disease. METHODS: Six-month(n=6)and twelve-month(n=6)old Alzheimer's model mice, together with six-month(n=6)and twelve-month(n=6)old C57 mice were in this experiment. Morris water maze test was to assess the spatial memory. After intragastrical administration of curcumin for consecutive three days, the Aβ plaques in retinas(n=48)from all mice(n=24)were detected by noninvasive in vivo optical imaging. RESULTS: Morris water maze test: compared with the six-month control group(C6), six-month model mice(AD6)swam longer(PP>0.05); compared with the twelve-month control group(C12), twelve-month model mice(AD12)swam longer, swam longer distance(PP>0.05); compared with the six-month model mice(AD6), twelve-month model mice(AD12)swam longer, swam longer distance and experienced more crossing times(PPCONCLUSION: Six-month model mice(AD6)had already a decline of cognition; and the illness gradually increased with the extension of the disease, and the positive rate of retinal Aβ plaques is increasing with progression of Alzheimer's disease.

Abstract Background Human saliva is a protein-rich, easily accessible source of potential biomarkers for the diagnosis of oral and systemic diseases. However, little is known about the changes in salivary proteome associated with aging of patients with dental caries. Here, we applied isobaric tags for relative and absolute quantitation (iTRAQ) in combination with multiple reaction monitoring mass spectrometry (MRM-MS) to characterize the salivary proteome profiles of subjects of different ages, presenting with and without caries, with the aim of identifying age-related biomarkers for dental caries. Methods Unstimulated whole saliva samples were collected from 40 caries-free and caries-susceptible young adults and elderly individuals. Salivary proteins were extracted, reduced, alkylated, digested with trypsin and then analyzed using iTRAQ-coupled LC–MS/MS, followed by GO annotation, biological pathway analysis, hierarchical clustering analysis, and protein–protein interaction analysis. Candidate verification was then conducted using MRM-MS. Results Among 658 salivary proteins identified using tandem mass spectrometry, 435 proteins exhibited altered expression patterns in different age groups with and without caries. Of these proteins, 96 displayed age-specific changes among caries-susceptible adults and elderly individuals, and were mainly associated with salivary secretion pathway, while 110 age-specific proteins were identified among healthy individuals. It was found that the age factor caused significant variations and played an important role in both healthy and cariogenic salivary proteomes. Subsequently, a total of 136 target proteins with complex protein–protein interactions, including 14 age-specific proteins associated with caries, were further successfully validated using MRM analysis. Moreover, non-age-specific proteins (histatin-1 and BPI fold-containing family B member 1) were verified to be important candidate biomarkers for common dental caries. Conclusions Our proteomic analysis performed using the discovery-through-verification pipeline revealed distinct variations caused by age factor in both healthy and cariogenic salivary proteomes, highlighting the significance of age in the great potential of saliva for caries diagnosis and biomarker discovery.

This paper concerns on two types of integral boundary value problems of a nonlinear fractional differential system, i.e., nonlocal strip integral boundary value problems and coupled integral boundary value problems. With the aid of the monotone iterative method combined with the upper and lower solutions, the existence of extremal system of solutions for the above two types of differential systems is investigated. In addition, a new comparison theorem for fractional differential system is also established, which is crucial for the proof of the main theorem of this paper. At the end, an example explaining how our studies can be used is also given.

The Huashan Rock Art site is a cultural tourism site of considerable importance in the development of domestic tourism focusing on heritage and history. As a previously peripheral part of Chinese society, Huashan has a significant role in explaining to Chinese people the extent and complexity of their history. Yet development of the research site has been hampered by the lack of tourism infrastructure (e.g. managerial capacity, accommodation, transportation, integrated services and so forth) and the private sector is not well-positioned to make up for the shortfall. The situation compares unfavourably with other destinations in neighbouring provinces. Under these circumstances, a program of qualitative research was launched using in-depth personal interviews to investigate the means by which Huashan Rock Art site is being presented and promoted currently and how can that presentation lead to an emotional and ideological response. It was found that there is some interaction between the type and nature of presentation and the success of the site in terms of destination management and this interaction is explored.

Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.

Investigation of exotic electron–nucleon interactions with few-micrometers range requires micrometer-scale, highly-sensitive and well-isolated sensors. Here, the authors use an NV center to set limits on the monopole–dipole interaction between its electron spin and the nucleons of a half-ball lens.

Ten-eleven translocation 1 (TET1) is a critical oncoprotein in AML. Here, the authors identify 2 compounds that target the binding of STAT3/5 specifically to the TET1 promoter, inhibiting its expression and AML cell viability.

Alzheimer's disease(AD), a neurodegenerative disease, can result in memory loss,cognitive and behavioral deficits. The pathological hallmarkes are β amyloid plaques and neurofibrillary tangles which lead loss of neurons in brain. As the extension of the central nervous system, retina has a similar tissue anatomy with central nervous system. The β amyloid plaques have also been detected in retina of AD. Furthermore, according to eye examinations of AD patients, we have found the loss of retinal ganglion cells, the attenuation of retinal nerve fiber layer thickness, the smaller changes of macula lutea, the decline of vascular density and so on. And then, there occurs the visual field loss and the decline of contrast sensitivity and so on in AD patients. Thus, the retina has occurred nerve degenerative changes in AD. Meanwhile, there has been proved that the retina nerve degeneration is even earlier than senile plaques formation in brain. In addition,curcumin, a natural and safe fluorescent dye, can be used to label β amyloid plaques in retina. The above suggests that retina can be a window for the early diagnosis of AD.

Abstract MLL-rearranged acute myeloid leukemia (AML) remains a fatal disease with a high rate of relapse and therapeutic failure due to chemotherapy resistance. In analysis of our Affymetrix microarray profiling and chromatin immunoprecipitation (ChIP) assays, we found that ALOX5 is especially down-regulated in MLL-rearranged AML, via transcription repression mediated by Polycomb repressive complex 2 (PRC2). Colony forming/replating and bone marrow transplantation (BMT) assays showed that Alox5 exhibited a moderate anti-tumor effect both in vitro and in vivo. Strikingly, leukemic cells with Alox5 overexpression showed a significantly higher sensitivity to the standard chemotherapeutic agents, i.e., doxorubicin (DOX) and cytarabine (Ara-C). The drug-sensitizing role of Alox5 was further confirmed in human and murine MLL-rearranged AML cell models in vitro, as well as in the in vivo MLL-rearranged AML BMT model coupled with treatment of “5 + 3” (i.e. DOX plus Ara-C) regimen. Stat and K-Ras signaling pathways were negatively correlated with Alox5 overexpression in MLL-AF9-leukemic blast cells; inhibition of the above signaling pathways mimicked the drug-sensitizing effect of ALOX5 in AML cells. Collectively, our work shows that ALOX5 plays a moderate anti-tumor role and functions as a drug sensitizer, with a therapeutic potential, in MLL-rearranged AML.

Importance. Psychological factors and glaucoma knowledge are closely related to the effects of glaucoma treatment. Background. Studies comparing anxiety and depression levels and glaucoma knowledge between glaucoma day-case patients and inpatients are limited. Design. Randomized clinical trial. Participants. Consecutive patients undergoing surgery were prospectively enrolled. Methods. Patients were randomized into the day-case group or the inpatient group. All of the patients underwent corresponding procedures for treatment, care, and education. All participants were asked to complete the General Condition Questionnaire, the Hospital Anxiety and Depression Scale (HADS), and the Gray Glaucoma Knowledge Questionnaire (GGKQ) at admission and the HADS and GGKQ at discharge. Main Outcome Measures. The scores for the General Condition Questionnaire, the HADS, and the GGKQ. Results. In total, 216 patients were enrolled in this study, including 119 day ward patients and 97 inpatients. There were no significant differences between the two groups in terms of their baseline demographic and clinical data (P>0.05). The baseline HADS-anxiety (HADS-A), HADS-depression (HADS-D), and GGKQ scores were similar in both groups (P>0.05). Before discharge, the difference in HADS-A scores between the two groups was not significant; however, the HADS-D scores of the day-case inpatients were significantly lower (α = 0.05, P

Soluble glycoprotein 130 kDa (sgp130)-Fc fusion protein, an innovative therapeutic bio-macromolecular drug specifically targeting IL-6 trans-signaling, proved to have good potential for application in the treatment of chronic inflammatory diseases. A simple and quick bioassay for sgp130-Fc was developed in this study. First, a stable reporter cell line was obtained by transfecting CHO-K1 cells with a sis-inducible element (SIE)-driving luciferase reporter gene (CHO/SIE-Luc). Sgp130-Fc could inhibit the expression of luciferase induced by IL-6/sIL-6Rα complex, and the dose−response curve fitted the four-parameter logistic model, with 50% inhibitive concentration (IC50) being about 500 ng/mL and detection range between 40 and 5000 ng/mL. Both the intra-assay and inter-assay coefficient of variation (CV) were below 10.0%, and the accuracy estimates ranged from 94.1% to 106.2%. The assay indicated a good linearity (R² = 0.99) in the range of 50% to 150% of optimized initial concentration. No significant difference was found between the test results of new assay and BAF3/gp130 proliferation assay (unpaired t test, p = 0.4960, n = 6). The dose-response effect and copy number of the luciferase gene was basically unchanged after long-term culture (up to passage 60), demonstrating the stability of CHO/SIE-Luc cells. These results suggested that the new reporter assay was suited to routine potency determination of therapeutic sgp130-Fc.

The long-acting growth hormone (LAGH) is a promising alternative biopharmaceutical to treat growth hormone (GH) deficiency in children, and it was developed using a variety of technologies by several pharmaceutical companies. Most LAGH preparations, such as Fc fusion protein, are currently undergoing preclinical study and clinical trials. Accurate determination of bioactivity is critical for the efficacy of quality control systems of LAGH. The current in vivo rat weight gain assays used to determine the bioactivity of recombinant human GH (rhGH) in pharmacopoeias are time-consuming, expensive, and imprecise, and there are no recommended bioassays for LAGH bioactivity in pharmacopoeias. Therefore, we developed a cell-based bioassay for bioactivity determination of therapeutic long-acting Fc-fusion recombinant human growth hormone (rhGH-Fc) based on the luciferase reporter gene system, which is involved in the full-length human GH receptor (hGHR) and the SG (SIE and GAS) response element. The established bioassay was comprehensively validated according to the International Council for Harmonization (ICH) Q2 (R1) guidelines and the Chinese Pharmacopoeia, and is highly precise, time-saving, simple, and robust. The validated bioassay could be qualified for bioactivity determination during the research, development, and manufacture of rhGH-Fc, and other LAGH formulations.

The therapeutic recombinant human keratinocyte growth factor 1 (rhKGF-1) was approved by the FDA for oral mucositis resulting from hematopoietic stem cell transplantation for hematological malignancies in 2004. However, no recommended bioassay for rhKGF-1 bioactivity has been recorded in the U.S. Pharmacopoeia. In this study, we developed an rhKGF-1-dependent bioassay for determining rhKGF-1 bioactivity based on HEK293 and HaCat cell lines that stably expressed the luciferase reporter driven by the serum response element (SRE) and human fibroblast growth factor receptor (FGFR2) IIIb. A good responsiveness to rhKGF-1 and rhKGF-2 shared by target HEK293/HaCat cell lines was demonstrated. Our stringent validation was completely focused on specificity, linearity, accuracy, precision, and robustness according to the International Council for Harmonization (ICH) Q2 (R1) guidelines, AAPS/FDA Bioanalytical Workshop and the Chinese Pharmacopoeia. We confirmed the reliability of the method in determining rhKGF bioactivity. The validated method is highly timesaving, sensitive, and simple, and is especially valuable for providing information for quality control during the manufacture, research, and development of therapeutic rhKGF.

The membranes of a pillared-layer structure Metal-Organic Framework (MOF), [Ni(HBTC)(4,4′-bipy)] (HBTC = 1,3,5-Benzenetricarboxylic acid, 4,4′-bipy = 4,4′-bipyridine), have been in situ fabricated on Nickel foam substrate. The orientations of MOF crystals in the membranes can be controlled by the molar ratio of ligand H3BTC to 4,4′-bipyridine. Scanning electron microscope images and powder X-ray diffraction patterns were used to characterize the membranes and confirm the orientations of their MOF layers. Control experiments have revealed that the presence of homologous metal element Nickel in both the MOF and the substrate and the presence of the neutral 4,4′-bipyridine in the reaction system are necessary for in situ growth of the well-intergrown MOF membranes. This work provides a successful example of directly growing continuous MOF layers on porous metallic substrate with desired orientations by a facile approach.

The original version of this Article contained an error in the spelling of the author James C. Mulloy, which was incorrectly given as James Mulloy. This has now been corrected in both the PDF and HTML versions of the Article.