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Objectives: Genetics have been shown to have a substantial impact on amyotrophic lateral sclerosis (ALS). The ALS process involves defects in axonal transport and cytoskeletal dynamics. It has been identified that KIF1A, responsible for encoding a kinesin-3 motor protein that carries synaptic vesicles, is considered a genetic predisposing factor for ALS. Methods: The analysis of whole-exome sequencing data from 1,068 patients was conducted to examine the genetic link between ALS and KIF1A. For patients with KIF1A gene mutations and a family history, we extended the analysis to their families and reanalyzed them using Sanger sequencing for cosegregation analysis. Results: In our cohort, the KIF1A mutation frequency was 1.31% (14/1,068). Thirteen nonsynonymous variants were detected in 14 ALS patients. Consistent with the connection between KIF1A and ALS, the missense mutation p.A1083T (c.3247G>A) was shown to cosegregate with disease. The mutations related to ALS in our study were primarily located in the cargo-binding region at the C-terminal, as opposed to the mutations of motor domain at the N-terminal of KIF1A which were linked to hereditary peripheral neuropathy and spastic paraplegia. We observed high clinical heterogeneity in ALS patients with missense mutations in the KIF1A gene. KIF5A is a more frequent determinant of ALS in the European population, while KIF1A accounts for a similar proportion of ALS in both the European and Chinese populations. Conclusion: Our investigation revealed that mutations in the C-terminus of KIF1A could increase the risk of ALS, support the pathogenic role of KIF1A in ALS and expand the phenotypic and genetic spectrum of KIF1A-related ALS. [ABSTRACT FROM AUTHOR]

Background: Upper motor neuron-dominant ALS (UMND ALS) is recognized to have early onset and good prognosis, but may have a rapid decline in motor function due to gait instability in the early stage. We investigated changes in lower extremity function in UMND ALS, particularly UMND ALS patients accompanied with postural instability or repeated falls (UMND ALS plus). Results: Among the 2,353 ALS patients reviewed, 211 (9.0%) had UMND ALS. UMND ALS had a longer diagnosis delay and restricted symptoms. Although UMND ALS patients had better lower extremity function and strength than matched classic ALS patients on first evaluation, there was no difference in the time of needing assistance or not being able to walk after disease onset. In contrast, UMND ALS plus has severe UMN symptoms and a more rapid decline in motor function. The lower extremity function was no better than that in the matched classic ALS. The prognosis of UMND ALS and UMND ALS plus were significantly better than those of overall ALS. Conclusion: UMND ALS has restricted symptoms but has a rapid decline in lower extremity function in the early stage of the disease. The motor function decline of UMND ALS plus is as fast as classic ALS. Whether these patients represent a distinct subgroup of ALS deserves further investigation. [ABSTRACT FROM AUTHOR]

Fluorine magnetic resonance imaging (19F-MRI) is particularly promising for biomedical applications owing to the absence of fluorine in most biological systems. However, its use has been limited by the lack of safe and water-soluble imaging agents with high fluorine contents and suitable relaxation properties. We report innovative 19F-MRI agents based on supramolecular dendrimers self-assembled by an amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic dendron. Specifically, this amphiphilic dendrimer bears multiple negatively charged terminals with high fluorine content, which effectively prevented intra- and intermolecular aggregation of fluorinated entities via electrostatic repulsion. This permitted high fluorine nuclei mobility alongside good water solubility with favorable relaxation properties for use in 19F-MRI. Importantly, the self-assembling 19F-MRI agent was able to encapsulate the near-infrared fluorescence (NIRF) agent DiR and the anticancer drug paclitaxel for multimodal 19F-MRI and NIRF imaging of and theranostics for pancreatic cancer, a deadly disease for which there remains no adequate early detection method or efficacious treatment. The 19F-MRI and multimodal 19F-MRI and NIRF imaging studies on human pancreatic cancer xenografts in mice confirmed the capability of both imaging modalities to specifically image the tumors and demonstrated the efficacy of the theranostic agent in cancer treatment, largely outperforming the clinical anticancer drug paclitaxel. Consequently, these dendrimer nanosystems constitute promising 19F-MRI agents for effective cancer management. This study offers a broad avenue to the construction of 19F-MRI agents and theranostics, exploiting self-assembling supramolecular dendrimer chemistry. [ABSTRACT FROM AUTHOR]

Background To establish topographic maps and determine fundus distribution patterns of ocular toxoplasmosis (OT) lesions. Methods In this retrospective study, patients who presented with OT to ophthalmology clinics from four countries (Argentina, Turkey, UK, USA) were included. Size, shape and location of primary (1°)/recurrent (2°) and active/inactive lesions were converted into a two-dimensional retinal chart by a retinal drawing software. A final contour map of the merged image charts was then created using a custom Matlab programme. Descriptive analyses were performed. Results 984 lesions in 514 eyes of 464 subjects (53% women) were included. Mean area of all 1° and 2° lesions was 5.96±12.26 and 5.21±12.77 mm2, respectively. For the subset group lesions (eyes with both 1° and 2° lesions), 1° lesions were significantly larger than 2° lesions (5.52±6.04 mm2 vs 4.09±8.90 mm2, p=0.038). Mean distances from foveola to 1° and 2° lesion centres were 6336±4267 and 5763±3491 µm, respectively. The majority of lesions were found in temporal quadrant (p<0.001). Maximum overlap of all lesions was at 278 µm inferotemporal to foveola. Conclusion The 1° lesions were larger than 2° lesions. The 2° lesions were not significantly closer to fovea than 1° lesions. Temporal quadrant and macular region were found to be densely affected underlining the vision threatening nature of the disease. [ABSTRACT FROM AUTHOR]

Objective: Charcot-Marie-Tooth (CMT) disease is the most common inherited neuromuscular disorder. Multi-echo Dixon MRI technique is a highly sensitive method for quantifying muscle fatty infiltration, which may provide excellent value for the assessment of CMT. Due to the rareness of the disease, its use in CMT disease has been rarely evaluated, especially in subtypes. Methods: Thirty-four CMT1 patients, 25 CMT2 patients, and 10 healthy controls were recruited. All of the recruited CMT1 patients are CMT1A with PMP22 duplication. Among CMT2 patients, 7 patients are CMT2A with MFN2 mutation, and 7 patients have SORD mutations. Multi-echo Dixon MRI imaging was performed. The fat fractions (FFs) of 5 muscle compartments of the leg were measured at proximal, middle, and distal levels by two specialized musculoskeletal radiologists. Comparisons between CMT1, CMT2, and genetically defined subtypes were conducted. Results: A proximal-distal gradient (27.6 ± 15.9, 29.9 ± 19.7, and 40.5 ± 21.4, p = 0.015) with a peroneal predominance (p = 0.001) in fat distribution was observed in CMT1. Significant differences in the soleus muscle FFs at proximal (19.1 ± 14.7 vs. 34.8 ± 25.1, p = 0.034) and medial levels (23.5 ± 21 vs. 38.0 ± 25.6, p = 0.044) were observed between CMT1 and CMT2 patients. Between PMP2 duplication and MFN2 mutation group, a significant difference in the soleus muscle FF was also observed (23.5 ± 21.0 vs. 54.7 ± 20.2, p = 0.039). Prominent correlations of calf muscle FFs with functional scores were observed. Discussion: Multi-echo Dixon MRI imaging is a valuable tool for assessing disease severity in CMT. The difference in patterns of fatty infiltration of CMT subtypes is first reported, which could provide references when making targeted training plans. [ABSTRACT FROM AUTHOR]

Global cropland expansion has been recognized as a key driver of food security. However, cropland expansion induced alterations in biophysical properties of the Earth's surface and greenhouse gas emissions may potentially impact the Earth's climate system. These changes could, in turn, affect cropland productivity and the potential distribution of croplands, although the underlying mechanisms remain relatively underexplored. In this study, a global climate model was employed to quantify the impact of global cropland expansion on cropping potential, utilizing observed and derived cropland expansion data. Our findings reveal that since 10000 BC, a 28% increase in cropland expansion has led to a 1.2% enhancement in global cropping potential, owing to more favorable precipitation and temperature conditions. This suggests that global cropland expansion yields dual benefits to crop production. However, in regions with low growth rates of cropping potential, cropland expansion proves to be an inefficient method for augmenting local crop potential yield. As croplands continue to expand worldwide, the capacity to support populations in different regions is altered, thereby reducing cropping potential inequality among nations. [ABSTRACT FROM AUTHOR]

Aims: To investigate the function and probable mechanism of Clostridium butyricum in the development of choledocholithiasis. Methods and results: The lithogenic diet group and the lithogenic diet + C. butyricum group were used to develop the choledocholithiasis model. During the experiment, C. butyricum suspension was administered to the rats in the lithogenic diet + C. butyricum group. The findings demonstrated that the C. butyricum intervention decreased the Firmicutes/Bacteroidetes ratio in the colon of experimental animals given a lithogenic diet. The relative levels of Desulfovibrio (0.93%) and Streptococcus (0.38%) fell, whereas Lactobacillus (22.36%), Prevotella (14.09%), and bacteria that produce short-chain fatty acids increased. Finally, 68 distinct metabolic products were found based on nontargeted metabonomics, and 42 metabolic pathways associated to the various metabolites were enriched. Conclusions: We found that C. butyricum decreased the development of choledocholithiasis. It keeps the equilibrium of the rat’s gut microbiome intact and lowers the danger of bacterial infections of the gastrointestinal and biliary systems. It is hypothesized that by controlling lipid metabolism, it may also have an impact on the development of cholelithiasis. [ABSTRACT FROM AUTHOR]

Background: Charcot-Marie-Tooth disease (CMT) is the most common inherited neurological disorder suffered in childhood. To date, the disease features have not been extensively characterized in the Chinese paediatric population. In this study, we aimed to analyse the clinical profiles and genetic distributions of a paediatric CMT cohort in China. Methods: A total of 181 paediatric CMT patients were enrolled. After preexcluding PMP22 duplication/deletion by multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, targeted next-generation sequencing (NGS) or whole-exome sequencing (WES) was performed to obtain a genetic diagnosis. Detailed information was collected to explore the spectrum of subtypes and genotype-phenotype correlations. Results: Pathogenic mutations were identified in 68% of patients in this study; with PMP22 duplication, MFN2 and GJB1 were the most frequent disease-causing genes. Of note, respect to the higher prevalence worldwide, CMT1A (18.2%) was relatively lower in our cohort. Besides, the mean age at onset (8.3 ± 5.7 years) was significantly older in our series. In genotype-phenotype analyse, PMP22 point mutations were considered the most severe genotypes and were mostly de novo. In addition, the de novo mutations were identified in up to 12.7% of all patients, which was higher than that in other studies. Conclusion: We identified a relatively lower detection rate of PMP22 duplication and a higher frequency of de novo variants among paediatric patients in China. We also identified the genetic and phenotypic heterogeneity of this cohort, which may provide clues for clinicians in directing genetic testing strategies for Chinese patients with early-onset CMT. [ABSTRACT FROM AUTHOR]

Background: Periaxins (encoded by PRX) play an important role in the stabilization of peripheral nerve myelin. Mutations in PRX can lead to Charcot-Marie-Tooth disease type 4F (CMT4F). Methods: In this study, we screened for PRX mutations using next-generation sequencing and whole-exome sequencing in a large Chinese CMT cohort consisting of 465 unrelated index patients and 650 healthy controls. Sanger sequencing was used for the validation of all identified variants. We also reviewed all previously reported PRX-related CMT cases and summarized the clinical manifestations and genetic features of PRX-related CMTs. Results: The hit rate for biallelic PRX variants in our cohort of Chinese CMT patients was 0.43% (2/465). One patient carried a previously unreported splice-site mutation (c.25_27 + 9del) compound heterozygous with a known nonsense variant. Compiling data on CMT4F cases and PRX variants from the medical literature confirmed that early-onset (95.2%), distal amyotrophy or weakness (94.0%), feet deformity (75.0%), sensory impairment or sensory ataxia (65.5%), delayed motor milestones (60.7%), and spinal deformity (59.5%) are typical features for CMT4F. Less frequent features were auditory impairments, respiratory symptoms, late onset, dysarthria or hoarseness, ophthalmic problems, and central nervous systeminvolvement. The two cases with biallelicmissensemutations have later onset age than those with nonsense or frameshiftmutations. We did not note clear correlations between the type and site of mutations and clinical severity or distinct constellations of symptoms. Conclusion: Consistent with observations in other countries and ethnic groups, PRX-related CMT is rare in China. The clinical spectrum is wider than previously anticipated. [ABSTRACT FROM AUTHOR]

Background/aims Anterior segment optical coherence tomography (AS-OCT) assessment of anterior chamber inflammation is an emerging tool. We describe the performance of AS-OCT in a paediatric population. Methods A mixed-methods prospective study, using routine clinical assessment as reference standard, and AS-OCT, with Tomey CASIA2 or Heidelberg Spectralis HS1, as index test, with data collected on patient perceptions of imaging. Repeatability, diagnostic indices, responsiveness to clinical change and clinical correlations of imaging-based metrics (image cell count, size, density and brightness) were assessed, with construction of receiver operated characteristic curves. Exploratory thematic analysis of responses from families was undertaken. Results A total of 90 children (180 eyes) underwent imaging. Bland Altman limits of agreement for CASIA2 repeatability ranged from +17 cells (95% CI 13.6 to 21.1) to −19 cells (95% CI −15.6 to −23.2) and HS1 from +1 (95% CI 0.9 to 1.2) to −1.0 (−1.2 to −0.8) cells. CASIA2 imaging had higher sensitivity of 0.92 (95% CI 0.78 to 0.97) vs HS1 imaging 0.17 (95% CI 0.07 to 0.34), with positive correlation between clinical grade and CASIA2 cell count (coefficient 12.8, p=0.02, 95% CI 2.2 to 23.4). Change in clinical grade at follow-up examinations correlated with change in image based ’cell’ count (r2=0.79, p<0.001). Patients reported a potential positive impact of seeing their disease activity. Conclusion Our findings suggest that OCT-based imaging holds the promise of deeper understanding of disease, improved patient experience and more granular monitoring of activity with resultant improved outcomes, but further work is needed to refine acquisition and analysis protocols. [ABSTRACT FROM AUTHOR]

Nucleic acid therapeutics are becoming an important drug modality, offering the unique opportunity to address "undruggable" targets, respond rapidly to evolving pathogens, and treat diseases at the gene level for precision medicine. However, nucleic acid therapeutics have poor bioavailability and are chemolabile and enzymolabile, imposing the need for delivery vectors. Dendrimers, by virtue of their well-defined structure and cooperative multivalence, represent precision delivery systems. We synthesized and studied bola-amphiphilic dendrimers for cargo-selective and on-demand delivery of DNA and small interfering RNA (siRNA), both important nucleic acid therapeutics. Remarkably, superior performances were achieved for siRNA delivery with the second-generation dendrimer, yet for DNA delivery with the third generation. We systematically studied these dendrimers with regard to cargo binding, cellular uptake, endosomal release, and in vivo delivery. Differences in size both of the dendrimers and their nucleic acid cargos impacted the cooperative multivalent interactions for cargo binding and release, leading to cargo-adaptive and selective delivery. Moreover, both dendrimers harnessed the advantages of lipid and polymer vectors, while offering nanotechnology-based tumor targeting and redox-responsive cargo release. Notably, they allowed tumor- and cancer cell-specific delivery of siRNA and DNA therapeutics for effective treatment in different cancer models, including aggressive and metastatic malignancies, outperforming the currently available vectors. This study provides avenues to engineer tailor-made vectors for nucleic acid delivery and precision medicine. [ABSTRACT FROM AUTHOR]

Background: Hereditary spastic paraplegia (HSP) constitutes a group of clinically and genetically rare neurodegenerative diseases characterized by progressive corticospinal tract degeneration. The phenotypes and genotypes of HSP are still expanding. In this study, we aimed to analyse the differential diagnosis, clinical features, and genetic distributions of a Chinese HSP patients in a 14-year cohort and to improve our understanding of the disease. Methods: The clinical data of patients with a primary diagnosis of HSP at the initial visit to the Department of the Neurology, Peking University Third Hospital, from 2008 to 2022 were retrospectively collected. Next-generation sequencing gene panels (NGS) combined with a multiplex ligation-amplification assay (MLPA) were conducted. Epidemiological and clinical features and candidate variants in HSPrelated genes were analyzed and summarized. Results: 54 cases (probands from 25 different pedigrees and 29 sporadic cases) from 95 patients with a primary diagnosis of HSP were finally confirmed to have a clinical diagnosis of HSP based on clinical criteria, including their clinical findings, family history and long-term follow-up. Earlier disease onset was associated with longer diagnostic delay and longer disease duration and was associated with a lower risk of loss of ability to walk independently. In addition, 20 candidate variants in reported HSP-related genes were identified in these clinically diagnosed HSP patients, including variants in SPAST, ALT1, WASHC5, SPG11, B4GALNT1, and REEP1. The genetic diagnostic rate in these 54 patients was 35.18%. Conclusion: Hereditary spastic paraplegia has high clinical and genetic heterogeneity and is prone to misdiagnosis. Long-term follow-up and genetic testing can partially assist in diagnosing HSP. Our study summarized the clinical features of Chinese HSP patients in a 14-year cohort, expanded the genotype spectrum, and improved our understanding of the disease. [ABSTRACT FROM AUTHOR]

A series of novel waterborne photosensitive resins were prepared successfully with poly(propylene oxide) bis(2-aminopropyl ether), tricyclodecane dimethanol diacrylate, 2-isocyanatoethyl acrylate, and hydrochloric acid by Michael addition reaction. The results show that with the increasing double bonds content, the double bonds conversion increases from 78.7, 85.6 to 92.8% in the photopolymerization, respectively, and the gel content of the UV-cured film increases from 48.05, 69.10 to 83.28%. In addition, the glass transition temperature and tensile strength of the UV-cured film follow the same increasing trend. Moreover, the content of hydrochloride has a great influence on the hydrophilicity of the waterborne photosensitive resins. The studies indicated that as the hydrochloride content decreases, the surface water contact angle of the UV-cured film increases from 10.8, 22.9 to 51.5°, and water absorption decreases from 26.55, 16.20 to 11.06%, respectively. Moreover, the waterborne photosensitive resins exhibited a high printing accuracy together with a good effect of washing and are promising for 3D printing [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is a commonmalignant tumor of the urinary system, which is highly invasive, metastatic, and insensitive to radiotherapy and chemotherapy. Chinese herbal medicine has always been an important source of anti-tumor drug development. Reineckia carnea Kunth is a traditional herb commonly used by the Miao nationality in southwest China. In this study, the extract of Reineckia carneawas isolated and purified by reverse phase preparative chromatography and other chromatographic techniques. According to the physicochemical properties and spectral data, the structure of the compound was identified, and a novel biflavone compound named Reineckia-biflavone A (RFA) was obtained. The result of antiproliferative activity showed that RFA had cytotoxicity on 786-O cells with an IC50 value of 19.34 μmol/L. The results of CCK-8 and hemolysis assays showed that RFA was not significantly cytotoxic to both red blood cells (RBC) and peripheral blood mononuclear cells (PBMC). By Hoechst 33258 apoptosis staining, typical apoptotic morphology was observed under fluorescence microscope. RFA could induce the apoptosis of 786-O cells with the increase of apoptosis rate. The cell cycle tests showed that the cell proportion was obviously arrested in the S phase. At the same time, RFA could decrease the mitochondrial membrane potential and increase the intracellular free Ca2+ concentration. Western blot showed that the expression levels of pro-apoptotic proteins (Bax, Caspase-3, Cleaved Caspase-3, and Cytochrome c) in cells rose, while the expression level of anti-apoptotic proteins (Bcl-2) declined significantly. In conclusion, this study suggests that the RFA is a new biflavone determined by SciFinder retrieval. The apoptosis may be triggered by RFA through the mitochondrial pathway, which is mediated by up-regulating the intracellular calcium ion, down-regulating the mitochondrial membrane potential, and changing the apoptosis-related proteins. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the possible associations between problematic smartphone use and brain functions in terms of both static and dynamic functional connectivity patterns. Materials and methods: Resting-state functional magnetic resonance imaging data were scanned from 53 young healthy adults, all of whom completed the Short Version of the Smartphone Addiction Scale (SAS-SV) to assess their problematic smartphone use severity. Both static and dynamic functional brain network measures were evaluated for each participant. The brain network measures were correlated the SAS-SV scores, and compared between participants with and without a problematic smartphone use after adjusting for sex, age, education, and head motion. Results: Two participants were excluded because of excessive head motion, and 56.9% (29/51) of the final analyzed participants were found to have a problematic smartphone use (SAS-SV scores ≥ 31 for males and ≥ 33 for females, as proposed in prior research). At the global network level, the SAS-SV score was found to be significantly positively correlated with the global efficiency and local efficiency of static brain networks, and negatively correlated with the temporal variability using the dynamic brain network model. Large-scale subnetwork analyses indicated that a higher SAS-SV score was significantly associated with higher strengths of static functional connectivity within the frontoparietal and cinguloopercular subnetworks, as well as a lower temporal variability of dynamic functional connectivity patterns within the attention subnetwork. However, no significant differences were found when directly comparing between the groups of participants with and without a problematic smartphone use. Conclusion: Our results suggested that problematic smartphone use is associated with differences in both the static and dynamic brain network organizations in young adults. These findings may help to identify at-risk population for smartphone addiction and guide targeted interventions for further research. Nevertheless, it might be necessary to confirm our findings in a larger sample, and to investigate if a more applicable SAS-SV cutoff point is required for defining problematic smartphone use in young Chinese adults nowadays. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (iCCA) patients had no obvious symptoms at early stage and poor postoperative survival. Therefore, the establishment of an iCCA prognostic prediction model to carry out refined management of iCCA patients is expected to improve the survival of the iCCA patient population. In this paper, we analyzed the expression profiling data of patients from 32 iCCA tissues and eight paracancerous tissues in The Cancer Genome Atlas (TCGA) database. Perl software was used to separate M6A-related genes and lncRNAs from expression matrix files obtained from the TCGA database. The differentially expressed lncRNAs in the iCCA samples and the normal samples were screened out by differential analysis using the R package limma, and the m6A-related lncRNAs were further screened by Pearson correlation analysis. WGCNA clustering analysis constructs a random network to extract the module genes most related to iCCA, and take the intersection of differentially expressed lncRNAs related to m6A. Univariate Cox screening was performed for the intersection lncRNAs that had significant influence on the prognosis of iCCA patients, and further screening was performed by LASSO method and multivariate Cox regression analysis. Risk model was constructed and prognostic ability was evaluated according to risk score. In conclusion, we identified four m6A-related lncRNAs with potential prognostic value in iCCA, and established a novel m6A-related lncRNA-based prognostic model, which can be used as an independent prognostic factor to predict the prognosis of clinical patients. [ABSTRACT FROM AUTHOR]

Heterozygous autosomal-dominant FIG4 mutations are associated with amyotrophic lateral sclerosis (ALS). Here, we describe a variant of the FIG4 gene (c.350dupC, p.Asp118GlyfsTer9) in a patient with rapidly progressive ALS that has not previously been reported in ALS or primary lateral sclerosis (PLS) patients before. Our study provides further information on the genotypes and phenotypes of patients with FIG4 mutations. [ABSTRACT FROM AUTHOR]

The digital archive of cultural heritage provides new opportunities for the protection of the cultural heritage and the development of online museums. One of the essential requirements for the digitization is to achieve accurate color reproduction. Taking the Imperial Chinese robes in the Qing Dynasty as an example, this study aims to develop a digital achieve system to digitize the robes using a high-end imaging system and accurately reproduce their color properties on a display. Currently, there has been very limited study focused on the color reproduction of silk fabrics or other textile materials. The conventional color management process using a traditional color chart, however, may not be suitable for the reproduction of silk fabrics because they have very high gloss. To address this difficulty, a unique “Qianlong Palette” color chart, consisting of 210 silk fabric samples, has been specifically produced for optimizing the color reproduction of silk fabrics and a color image reproduction system has been developed for the digitization and archiving of the clothing fabric for the royal court. Color characterization models using both the “Qianlong Palette” color chart and the traditional color chart, and different mapping methods, are compared and the model with highest accuracy used in a self-programmed interface for automatically processing textile images in the future. Finally, the digital archive system has been validated using six garments of silk fabric relics. The color differences after the color image reproduction are all less than 3.00ΛE ∗ ab, indicating acceptable color reproduction of the system. The images after color reproduction have also been evaluated subjectively by experts from the museum and the results are considered satisfactory. Our results show that the newly designed “Qianlong Palette” color chart exhibits superior performance over the conventional color chart in effectively predicting the color of the silk fabrics. The self-programmed graphical user interface for image color management can serve as a powerful tool to truly reproduce the color of various silk fabric relics in museums in the future and digitally archive those valuable cultural relics for different uses. [ABSTRACT FROM AUTHOR]

The main mechanism of virulence in Klebsiella pneumoniae is the acquisition of K. pneumoniae virulence plasmids (KpVPs), which include two dominant types, namely, KpVP-1 (carrying iuc1, iro1, rmpA, and rmpA2) and KpVP-2 (carrying iuc2, iro2, and rmpA). Both are non-conjugative and associated with different hypervirulent clones. In contrast to KpVP-1 reported in K1, K2, and other serotypes of K. pneumoniae, KpVP-2 was only reported in K2 strains and rarely characterized. In this study, we identified a conjugative KpVP-2-type virulence plasmid from a clinical hypervirulent K. pneumoniae strain. This plasmid was generated by the integration of conjugative transfer genes into the KpVP-2-type plasmid Kp52.145 II and could be readily conjugated to Escherichia coli strain EC600 and K. pneumoniae strains of various types which are clinically existing, mediating hypervirulence. Furthermore, this kind of conjugative KpVP-2-type virulence plasmid has been disseminated in clinical settings in Hong Kong and other regions of the world. The generation of conjugative virulence plasmid may promote its transmission and explain the evolution of this type of virulence plasmid. [ABSTRACT FROM AUTHOR]

Biodiversity conservation is the cornerstone for sustainable development. Bold conservation targets provide the last opportunities to halt the human-driven mass extinction. Recently, bold conservation targets have been proposed to protect 30% or 50% of Earth. However, little is known about its potential impacts on cropland. We identify potential cropland losses when 30% and 50% of global terrestrial area is given back to nature by 2030/2050, at three spatial scales (global, biome and country) and using two approaches (“nature-only landscapes” and “shared landscapes”). We find that different targets, applied scales and approaches will lead to different cropland losses: (1) At the global scale, it is possible to protect 50% of the Earth while having minimum cropland losses. (2) At biome scale, 0.64% and 8.54% cropland will be lost globally in 2030 and 2050 under the nature-only approach while by contrast, the shared approach substantially reduces the number of countries confronted by cropland losses, demanding only 0% and 2.59% of global cropland losses in 2030 and 2050. (3) At the national scale, the nature-only approach causes losses of 3.58% and 10.73% of global cropland in 2030 and 2050, while the shared approach requires 0.77% and 7.55% cropland in 2030 and 2050. Our results indicate that bold conservation targets could be considered, especially when adopting the shared approach, and we suggest adopting ambitious targets (protecting at least 30% by 2030) at the UN Biodiversity Conference (COP 15) to ensure a sustainable future for Earth. [ABSTRACT FROM AUTHOR]

The Northeast China Plain is one of the major grain-producing areas of China because of its fertile black soil and large fields adapted for agricultural machinery. It has experienced some land-use changes, such as urbanization, deforestation, and wetland reclamation in recent decades. A comprehensive understanding of these changes in terms of the total cropping land and its heterogeneity during this period is important for policymakers. In this study, we used a series of cropland products at the 30- m resolution for the period 1980-2015. The heterogeneity for dominant cropland decreased slowly over the three decades, especially for the large pieces of cropland, showing a general trend of increased cropland homogeneity. The spatial patterns of the averaged heterogeneity index were nearly the same, varying from 0.5 to 0.6, and the most heterogeneous areas were mainly located in some separate counties. Cropland expansion occurred across most of Northeast China, while cropland shrinking occurred only in the northern and eastern sections of Northeast China and around the capital cities, in the flat areas. Also, changes in land use away from cropland mainly occurred in areas with low elevation (50-200 m) and a gentle slope (less than 1 degree). The predominant changes in cropland were gross gain and homogeneity, occurring across most of the area except capital cities and boundary areas. Possible reasons for the total cropland heterogeneity changes were urbanization, restoration of cropland to forest, and some government land-use policies. Moreover, this study evaluates the effectiveness of cropland policies influencing in Northeast China. [ABSTRACT FROM AUTHOR]

Objective This study aims to evaluate the feasibility of retinal imaging in critical care using a novel mobile optical coherence tomography (OCT) device. The Heidelberg SPECTRALIS FLEX module (Heidelberg Engineering, Heidelberg, Germany) is an OCT unit with a boom arm, enabling ocular OCT assessment in less mobile patients. Design We undertook an evaluation of the feasibility of using the SPECTRALIS FLEX for undertaking ocular OCT images in unconscious and critically ill patients. Setting This study was conducted in the critical care unit of a large tertiary referral unit in the United Kingdom. Participants 13 systemically unwell patients admitted to the critical care unit were purposively sampled to enable evaluation in patients with a range of clinical states. Outcome measures The primary outcome was the feasibility of acquiring clinically interpretable OCT scans on a consecutive series of patients. The standardised scanning protocol included macula-focused OCT, OCT optic nerve head (ONH), OCT angiography (OCTA) of the macula and ONH OCTA. Results OCT images from 13 patients were attempted. The success rates of each scan type are 84% for OCT macula, 76% for OCT ONH, 56% for OCTA macula and 36% for OCTA ONH. The overall mean success rate of scans per patient was 64% (95% CI 46% to 81%). Clinicians reported clinical value in 100% scans which were successfully obtained, including both ruling in and ruling out relevant ocular complications such as corneal thinning, macular oedema and optic disc swelling. The most common causes of failure to achieve clinically interpretable scans were inadequately sustained OCT alignment in delirious patients and a compromised ocular surface due to corneal exposure. Conclusions This prospective evaluation indicates the feasibility and potential clinical value of the SPECTRALIS FLEX OCT system on the critical care unit. Portable OCT systems have the potential to bring instrument-based ophthalmic assessment to critically ill patients, enabling detection and micron-level monitoring of ocular complications. [ABSTRACT FROM AUTHOR]

Malaysia has enforced a nationwide smoking ban to the public at all eateries on the 1st of January 2019. A survey on the awareness and perception towards this ban among adults was carried out in Pedas, Negeri Sembilan. Preliminary findings were assuring. A total of 91.3% (n = 347, N = 380) of the respondents were aware of this ban. Among the respondents, a low percentage of them were smokers, 29.2% (n = 111). A median of 285.5 respondents (75.1%, IQR = 58.25), including the smokers, perceived that this ban brings about health benefits to self and their family when environmental tobacco smoke exposure is curbed. [ABSTRACT FROM AUTHOR]

Bioimaging plays an important role in cancer diagnosis and treatment. However, imaging sensitivity and specificity still constitute key challenges. Nanotechnology-based imaging is particularly promising for overcoming these limitations because nanosized imaging agents can specifically home in on tumors via the "enhanced permeation and retention" (EPR) effect, thus resulting in enhanced imaging sensitivity and specificity. Here, we report an original nanosystem for positron emission tomography (PET) imaging based on an amphiphilic dendrimer, which bears multiple PET reporting units at the terminals. This dendrimer is able to self-assemble into small and uniform nanomicelles, which accumulate in tumors for effective PET imaging. Benefiting from the combined dendrimeric multivalence and EPR-mediated passive tumor targeting, this nanosystem demonstrates superior imaging sensitivity and specificity, with up to 14-fold increased PET signal ratios compared with the clinical gold reference 2-fluorodeoxyglucose ([18F]FDG). Most importantly, this dendrimer system can detect imaging-refractory low-glucose-uptake tumors that are otherwise undetectable using [18F]FDG. In addition, it is endowed with an excellent safety profile and favorable pharmacokinetics for PET imaging. Consequently, this dendrimer nanosystem constitutes an effective and promising approach for cancer imaging. Our study also demonstrates that nanotechnology based on self-assembling dendrimers provides a fresh perspective for biomedical imaging and cancer diagnosis. [ABSTRACT FROM AUTHOR]

A novel UV-curable hyperbranched polyurethane acrylate (FHBPUA) with excellent flexibility is successfully synthesized based on a reaction of hydroxyl terminated hyperbranched polyurethane (regarded as core) with flexible semiadduct urethane monoacrylate (regarded as arms). The structure and property of FHBPUA is firstly analyzed and then utilized as functional additives to ameliorate the UV-curing and mechanical properties of epoxy acrylate resin. The degree of branching of FHBPUA turns out to be 0.82. Its thermal decomposition process consists of three different stages, and the glass transition temperature is around 65 °C. The freestanding FHBPUA film (~30 μm thickness) can be UV-cured within 3 s, and its flexibility is up to 1 mm. With the increase of FHBPUA content to 10 wt %, the UV-curing time of UV1000 film decreases from 6 to 3 s, flexibility strikingly increases from 10 to 1 mm, and adhesive force also improves from 5 to 3 grades, meanwhile its glossiness is not influenced by FHBPUA. In addition, a certain amount of FHBPUA can improve the tensile strength and elongation at break of UV1000 film. This novel FHBPUA can be used not only to develop flexible UV-curable freestanding films but also as functional additives to perfect other UV-curable compositions like coatings, inks and 3D printed parts. [ABSTRACT FROM AUTHOR]

The title compound, [Cu4(CH3COO) 6 (C16H23N2O)2], lies across a twofold rotation axis. The asymmetric unit contains two independent CuII ions. The symmetry-unique terminal CuII ion is O,N,N'-coordinated by a 2-{[(2,2,6,6-tetramethylpiperidin-4-yl)imino]meth-yl}phenolate ligand and an O atom from an acetate group in a slightly distorted square-planar coordination environment. The symmetry-unique central CuII ion is coordinated by a different O atom from the same acetate group and by four bridging acetate ligands, which connect the asymmetric unit into a dimeric complex and form a distorted square-pyramidal coordination environment. Within the complex there are two symmetry-equivalent intramolecular N--H⋯O hydrogen bonds. In the crystal, weak C--H⋯O hydrogen bonds link the complex molecules, forming a three-dimensional network. [ABSTRACT FROM AUTHOR]

Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy [ABSTRACT FROM AUTHOR]

A major challenge in cancer research field is to define molecular features that distinguish cancer stem cells from normal stem cells. In this study, we compared microRNA (miRNA) expression profiles in human glioblastoma stem cells and normal neural stem cells using combined microarray and deep sequencing analyses. These studies allowed us to identify a set of 10 miRNAs that are considerably up-regulated or down-regulated in glioblastoma stem cells. Among them, 5 miRNAs were further confirmed to have altered expression in three independent lines of glioblastoma stem cells by real-time RT-PCR analysis. Moreover, two of the miRNAs with increased expression in glioblastoma stem cells also exhibited elevated expression in glioblastoma patient tissues examined, while two miRNAs with decreased expression in glioblastoma stem cells displayed reduced expression in tumor tissues. Furthermore, we identified two oncogenes, NRAS and PIM3, as downstream targets of miR-124, one of the down-regulated miRNAs; and a tumor suppressor, CSMD1, as a downstream target of miR-10a and miR-10b, two of the up-regulated miRNAs. In summary, this study led to the identification of a set of miRNAs that are differentially expressed in glioblastoma stem cells and normal neural stem cells. Characterizing the role of these miRNAs in glioblastoma stem cells may lead to the development of miRNA-based therapies that specifically target tumor stem cells, but spare normal stem cells. [ABSTRACT FROM AUTHOR]