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Background and Purpose: This study sought to explore dynamic degree centrality (DC) variability in particular regions of the brain in patients with poststroke Broca aphasia (BA) using a resting-state functional magnetic resonance imaging (rs-fMRI) approach, comparing differences between Uyghur and Chinese BA patients., Methods: This study investigated two factors, language and BA status, and divided patients into four groups: Uyghur aphasia patients (UA), Uyghur normal control subjects (UN), Chinese aphasia patients (CA), and Chinese normal subjects (CN) who underwent rs-fMRI analysis. Two-way analysis of variance (ANOVA) was used to calculate the comprehensive differences in dynamic DC among these four groups. Correlations between DC and language behavior were assessed with partial correlation analyses., Results: Two-way ANOVA revealed comparable results for the results of pairwise comparisons of dynamic DC variability among the four groups in the right middle frontal gyrus/orbital part (ORBmid.R), right superior frontal gyrus/dorsolateral, and right precuneus (PCUN.R), with results as follows: UA < UN, CA > CN, UA < CA, and UN > CN (p < .05, with the exception of the p-values for UA and UN in superior frontal gyrus/dorsolateral). In contrast, the opposite results were observed for the right calcarine fissure and surrounding cortex (CAL.R, p < .05)., Conclusion: The observed enhancement of dynamic DC variability in ORBmid.R and PCUN.R among Chinese BA patients and in CAL.R in Uyghur BA patients may be attributable to language network restructuring. Overall, these results suggest that BA patients who use different language families may exhibit differences in the network mechanisms that characterize observed impairments of language function., (© 2024 The Author(s). Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Background: Prior research has shown that granulin precursor (GRN, also termed PGRN) is closely linked to aphasia. However, there has been little research on the mechanism of action of GRN in post-stroke aphasia (PSA)., Methods: In this study, RT-qPCR was used to identify variations in gene expression, while RNA sequencing (RNA-seq) was utilized to acquire transcriptional profiles. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were employed for bioinformatics analysis., Results: GRN was considerably more active in PSA subjects. After silencing the GRN, 197 transcripts had differential expression, and 237 alternative splicing events (ASEs) were substantially affected. The analysis of differentially expressed genes (DEGs) using GO and KEGG approaches showed that these genes have various molecular functions and are significantly enriched in metabolic signaling pathways. Regarding Alternative Splicing (AS), the GO and KEGG analyses revealed numerous functional genes involved in transcription and metabolism., Conclusions: The knockdown of GRN has been shown to be associated with alterations in transcription, metabolism, and ASEs, potentially impacting transcriptional and metabolic pathways through its involvement in AS. Furthermore, GRN knockdown is associated with nervous system disease-related gene transcription and AS processes, as well as its involvement in G protein-coupled receptor (GPCR) and wingless/integrated (Wnt) signaling pathways, which impact the initiation and resolution of PSA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Highly fluoroquinolone-resistant Salmonella enterica serovar Kentucky ( S. Kentucky) of sequence type (ST) 198 has emerged as a global multidrug-resistant (MDR) clone, posing a threat to public health., Methods: Whole genome sequencing and antibiotic susceptibility testing was used to characterize the population structure and evolutionary history of 54 S. Kentucky isolates recovered from food and human clinical cases in Beijing from 2016 to 2023., Results: All 54 S. Kentucky ST198 isolates exhibited resistance to quinolones, carrying point mutations in the quinolone resistance-determining regions ( gyrA &#95;S83F and parC &#95;S80I). Resistance to other antibiotics (folate pathway inhibitors, cephems, aminoglycosides, phenicols, rifamycin, fosfomycin, macrolides, and tetracyclines), mediated by the sul1 , sul2 , dfrA14 , bla CTX-M , bla TEM-1B , aac(3)-Id , aadA2 , aadA7 , aph(3')-I , aph(3'')-Ib , rmtB , floR , arr-2 , fosA , mph(A) , and tet(A) genes, was also observed in different combinations. The Beijing S. Kentucky ST198 evolutionary tree was divided into clades 198.2-1 and 198.2-2, which were further differentiated into three subclades: 198.2-2A, 198.2-2B, and 198.2-2C. Compared with the extended-spectrum β-lactamase-encoding gene bla CTX-M-14b in 198.2-1, the co-existence of bla CTX-M-55 and bla TEM-1B , as well as chromosomally located qnrS1 , was detected in most 198.2-2 isolates, which showed more complex MDR phenotypes. S. Kentucky ST198 outbreak isolates derived from two predominant clonal sources: 198.2-1 with cgST236434 and 198.2-2A with cgST296405., Conclusions: The S. Kentucky population in Beijing is genetically diverse, consisting of multiple co-circulating lineages that have persisted since 2016. Strengthening surveillance of food and humans will aid in implementing measures to prevent and control the spread of AMR., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

When faced with salinity stress, plants typically exhibit a slowdown in their growth patterns. Boron (B) is an essential micronutrient for plants that are known to play a critical role in controlling cell wall properties. In this study, we used the model plant Arabidopsis thaliana Col-0 and relevant mutants to explore how the difference in B availability may modulate plant responses to salt stress. There was a visible root growth suppression of Col-0 with the increased salt levels in the absence of B while this growth reduction was remarkably alleviated by B supply. Pharmacological experiments revealed that orthovanadate (a known blocker of H + -ATPase) inhibited root growth at no B condition, but had no effect in the presence of 30 μM B. Salinity stress resulted in a massive K + loss from mature zones of A. thaliana roots; this efflux was attenuated in the presence of B. Supplemental B also increased the magnitude of net H + pumping by plant roots. Boron availability was also essential for root halotropism. Interestingly, the aha2Δ57 mutant with active H + -ATPase protein exhibited the same halotropism response as Col-0 while the aha2-4 mutant had a stronger halotropism response (larger bending angle) compared with that of Col-0. Overall, the ameliorative effect of B on the A. thaliana growth under salt stress is based on the H + -ATPase stimulation and a subsequent K + retention, involving auxin- and ROS-pathways.

Soil salinity is a major environmental constraint affecting the sustainability and profitability of agricultural production systems. Salinity stress tolerance has been present in wild crop relatives but then lost, or significantly weakened, during their domestication. Given the genetic and physiological complexity of salinity tolerance traits, agronomical solutions may be a suitable alternative to crop breeding for improved salinity stress tolerance. One of them is optimizing fertilization practices to assist plants in dealing with elevated salt levels in the soil. In this review, we analyse the causal relationship between the availability of boron (an essential metalloid micronutrient) and plant's adaptive responses to salinity stress at the whole-plant, cellular, and molecular levels, and a possibility of using boron for salt stress mitigation. The topics covered include the impact of salinity and the role of boron in cell wall remodelling, plasma membrane integrity, hormonal signalling, and operation of various membrane transporters mediating plant ionic and water homeostasis. Of specific interest is the role of boron in the regulation of H + -ATPase activity whose operation is essential for the control of a broad range of voltage-gated ion channels. The complex relationship between boron availability and expression patterns and the operation of aquaporins is also discussed., (© 2024 The Author(s). Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

Diffuse cystic lung diseases (DCLDs) are a group of heterogeneous lung diseases that are characterized by inflated spaces or cysts within the lung parenchyma. They also exhibit similar imaging characteristics and clinical manifestations compared with those of cystic lesions, such as pulmonary cavities, emphysema, bronchiectasis and honeycomb lung. The most common DCLDs encountered in the clinic include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, Langerhans cell histiocytosis and lymphocytic interstitial pneumonia. In particular, accurate diagnosis of DCLDs in terms of the different lesions found is important, because their clinical courses, prognoses and treatment strategies vary widely. However, because DCLDs usually have overlapping clinical presentations, diagnosis typically requires a combination of clinical considerations that take into account characteristics of the cyst, its distribution, organ of origin and background parenchymal findings. The present report documents the case of a 73-year-old man diagnosed with desquamative interstitial pneumonia (DIP). The patient was admitted to the hospital due to chest tightness, shortness of breath and intermittent fever. The patient had been a smoker for >60 years and had stopped smoking for 6 months before being admitted. A transbronchial lung biopsy, bronchoscopy and alveolar lavage cytopathogen culture were performed to confirm the diagnosis of desquamative interstitial pneumonia (DIP). The patient was treated with hormonal therapy and advised to abstain from smoking. The diagnosis of DIP in comparison with other DCLDs was summarized for the purpose of providing a clinical basis for the accurate clinical diagnosis of DIP and the development of evidence-based practice guidelines., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Zhang et al.)

Background: T cell exhaustion (TEX) signifies a condition of T cell disorder which implicate the therapeutic benefits and prognostic significance in patients with cancer. However, its role in the Head and Neck Squamous Carcinoma (HNSCC) remains incompletely understood., Methods: The detailed data of HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) database and two Gene Expression Omnibus (GEO) datasets. We computed the expression scores of four TEX-related pathways and detected gene modules closely linked to these pathways, indicating prognostic significance. Following this, regression analyses were performed to select eight genes for the development of a predictive signature. The predictive capacity of this signature was evaluated. Additionally, we examined the relationships between TEX-related signature risk scores and the effectiveness of immunotherapy as well as drug sensitivity., Results: A novel prognostic model, comprising eight TEX-related genes, was established for patients with HNSCC. The prognostic value was further confirmed using additional GEO datasets: GSE65858 and GSE27020. This signature enables the stratification of patients into high- and low- risk groups, each showing distinct survival outcomes and responsiveness to immunotherapy. The low-risk group demonstrated improved prognosis and enhanced efficacy of immunotherapy. In addition, AZD6482, TAF1, Ribociclib, LGK974, PF4708671 and other drugs showed increased sensitivity in the high-risk group based on drug sensitivity values, offering tailored therapeutic recommendations for individuals with various risks profiles., Conclusion: In conclusion, we developed a novel T cell exhaustion-associated signature, which holds considerable predictive value for both the prognosis of patients with HNSCC and the effectiveness of tumor immunotherapy., (© 2024. The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear., Aim: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats., Methods: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence., Results: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased ( P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced ( P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1β and IL-6. DJB surgery significantly reduced ( P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated ( P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats., Conclusion: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Luban locks with mortise and tenon structure have structural diversity and architectural stability, and it is extremely challenging to synthesize Luban lock-like structures at the molecular level. In this work, we report the cocrystallization of two structurally related atom-precise fcc silver nanoclusters Ag 110 (SPhF) 48 (PPh 3 ) 12 (Ag 110 ) and Ag 14 (μ 6 -S)(SPhF) 12 (PPh 3 ) 8 (Ag 14 ). It is worth noting that the Ag 110 cluster is the first compound to simulate the complex Luban lock structure at the molecular level. Meanwhile, Ag 110 is the largest known fcc-based silver nanocluster, so far, there is no precedent for fcc silver nanocluster with more than 100 silver atoms. DFT calculations show that Ag 110 is a 58-electron superatom with an electronically closed shell1S 2 1P 6 1D 10 2S 2 1F 14 2P 6 1G 18 . Ag 110 ⋅Ag 14 can rapidly catalyze the reduction of 4-nitrophenol within 4 minutes. In addition, Ag 110 presents clear structural evidence to reveal the critical size and mechanism of the transformation of metal core from fcc stacking to quasi-spherical superatom. This research work provides an important structural model for studying the nucleation mechanism and structural assembly of silver nanoclusters., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: There is increasing evidence that abnormal expression of microRNAs is involved in the occurrence and progression of tumors. In previous experiments, we found that the content of hsa-miR-1301-3p in tumor tissues of patients with nonsmall cell lung cancer (NSCLC) showed an obvious upward trend compared with that in normal tissues. We performed a detailed study on the impact and underlying mechanism of hsa-miR-1301-3p in NSCLC cells. Methods: The impact of hsa-miR-1301-3p on NSCLC cell proliferation, apoptosis, migration, and invasion was examined using colony formation, flow cytometry, modified Boyden chamber, and wound healing assays. Different doses of radiation were applied to NSCLC cells to investigate their sensitivity to radiotherapy. The potential target gene of hsa-miR-1301-3p was determined by dual-luciferase reporter assay and immunoblotting. Result: hsa-miR-1301-3p was upregulated in NSCLC tissues and cells. hsa-miR-1301-3p effectively promoted the rapid proliferation, migration, and invasion of NSCLC cells, while inhibiting apoptosis. It also induced radioresistance in NSCLC cells. hsa-miR-1301-3p targeted the homeodomain-only protein homeobox (HOPX) mRNA 3' untranslated region and inhibited its transcription in NSCLC cells. Exogenous HOPX overexpression antagonized the mechanism by which hsa-miR-1301-3p regulates NSCLC cell proliferation, metastasis, and apoptosis. Conclusions: hsa-miR-1301-3p plays an oncogenic role in the occurrence and development of NSCLC. By targeting HOPX, hsa-miR-1301-3p can not only promote the proliferation and metastasis of NSCLC cells, but also alleviate apoptosis and reduce radiosensitivity.

Drought is among the most common abiotic constraints of crop growth, development, and productivity. Integrating different omics approaches offers a possibility for deciphering the metabolic pathways and fundamental mechanisms involved in abiotic stress tolerance. Here, we explored the transcriptional and post-transcriptional changes in drought-stressed tomato plants using transcriptomic and proteomic profiles to determine the molecular dynamics of tomato drought stress responses. We identified 22467 genes and 5507 proteins, among which the expression of 3765 genes and 294 proteins was significantly changed under drought stress. Furthermore, the differentially expressed genes (DEGs) and differentially abundant proteins (DAPs) showed a good correlation (0.743). The results indicated that integrating different omics approaches is promising in exploring the multilayered regulatory mechanisms of plant drought resistance. Gene ontology (GO) and pathway analysis identified several GO terms and pathways related to stress resistance, including response to stress, abiotic stimulus, and oxidative stress. The plant hormone abscisic acid (ABA) plays pivotal roles in response to drought stress, ABA-response element binding factor ( AREB ) is a key positive regulator of ABA signaling. Moreover, our analysis indicated that drought stress increased the abscisic acid (ABA) content, which activated AREB1 expression to regulate the expression of TAS14 , GSH-Px-1 , and Hsp , ultimately improving tomato drought resistance. In addition, the yeast one-hybrid assay demonstrated that the AREB1 could bind the Hsp promoter to activate Hsp expression. Thus, this study involved a full-scale analysis of gene and protein expression in drought-stressed tomato, deepening the understanding of the regulatory mechanisms of the essential drought-tolerance genes in tomato., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Zhao, Huang, Pan, Chen, Qu, Ouyang, Yu and Shabala.)

As a clinical emergency with a high mortality rate, the treatment of acute liver failure has been paid attention to by society. At present, liver transplantation is the most effective treatment for acute liver failure, but there is still an insufficient supply of liver sources and a poor prognosis. In view of the current therapeutic development of this disease, more researchers have turned their attention to the research of drugs related to the NF-κB pathway. The NF-κB canonical pathway has been proven to play a role in a variety of diseases, regulating inflammation, apoptosis, and other physiological processes. More and more evidence shows that the NF-κB canonical pathway regulates the pathogenesis of acute liver failure. In this review, we will summarize the regulation process of the NF-κB canonical pathway on acute liver failure, and develop a new way to treat acute liver failure by targeting the components of the pathway.

Introduction: Campylobacter jejuni ( C. jejuni ) is the leading cause of human bacterial gastroenteritis worldwide and has a major impact on global public health. The objective of the present study was to conduct whole genome sequencing (WGS) to determine the genetic diversity, virulence factors, and determinants of antimicrobial resistance of C. jejuni during a 3-year surveillance period in Beijing, China., Methods: A total of 184 clinical isolates were obtained from sentinel hospital surveillance between 2019 and 2021. Antimicrobial susceptibility testing was conducted using the agar dilution method. WGS was employed to characterize the 184 C. jejuni strains., Results: Multilocus sequence typing analysis revealed high genetic diversity among the 184 C. jejuni strains, identifying 71 sequence types (STs) and 19 clonal complexes (CCs). The most prevalent ST was ST760 (6.5%), and the most common CC was CC21 (24.5%), consisting of 11 STs. High resistance rates were observed for ciprofloxacin (76.6%), nalidixic acid (76.1%), and tetracycline (71.2%). A total of 77 C. jejuni isolates (41.8%) exhibited multidrug resistance with 43 resistance patterns. Virulome analysis disclosed the differential distribution of virulence factors related to adherence, colonization, chemotaxis, as well as lipo-oligosaccharide and capsular polysaccharide biosynthesis. Resistome analysis demonstrated widespread resistance to quinolones and tetracycline, but low rates of macrolides resistance. The phylogeny, based on whole genome single nucleotide polymorphisms, indicated a high degree of clonality and grouped the C. jejuni strains into six clades. Closely related isolates that were part of a genetic cluster mostly shared a homogenous clonal complex., Conclusions: The present study emphasizes the rising resistance to quinolones and tetracycline, as well as the virulence potential and diverse genotypes identified among C. jejuni strains isolated from diarrheal patients in Beijing., Competing Interests: No conflicts of interest. Table S1Distribution of CCs and STs in 184 C. jejuni strains.CC typeST typeNo. of isolates (%)CC typeST typeNo. of isolates (%)CC typeST typeNo. of isolates (%)Abbreviation: CC=clonal complex; ST=sequence type; C. jejuni=Campylobacterjejuni.CC21ST214 (2.2)CC52ST1611 (0.5)CC574ST3052 (1.1)ST504 (2.2)CC206ST1223 (1.6)ST28951 (0.5)ST2982 (1.1)ST5723 (1.6)ST88801 (0.5)ST76012 (6.5)ST22821 (0.5)ST106821 (0.5)ST18115 (2.7)CC257ST2573 (1.6)CC658ST69002 (1.1)ST35974 (2.2)ST8241 (0.5)CC828ST15861 (0.5)ST65003 (1.6)ST9902 (1.1)CC1034ST23141 (0.5)ST82614 (2.2)ST99513 (1.6)unassignedST1313 (1.6)ST98731 (0.5)CC353ST52 (1.1)ST18561 (0.5)ST99602 (1.1)ST21321 (0.5)ST21232 (1.1)ST100754 (2.2)CC354ST3545 (2.7)ST21332 (1.1)CC22ST2210 (5.4)ST6533 (1.6)ST22742 (1.1)CC42ST65324 (2.2)ST29883 (1.6)ST23281 (0.5)ST79241 (0.5)ST99801 (0.5)ST35781 (0.5)CC45ST452 (1.1)CC403ST4034 (2.2)ST42681 (0.5)ST1375 (2.7)ST17751 (0.5)ST43272 (1.1)ST5382 (1.1)ST80031 (0.5)ST66071 (0.5)ST5832 (1.1)ST92551 (0.5)ST78661 (0.5)ST13261 (0.5)CC443ST517 (3.8)ST79261 (0.5)ST34561 (0.5)ST72081 (0.5)ST90791 (0.5)CC48ST9185 (2.7)CC460ST1131 (0.5)ST99612 (1.1)ST69592 (1.1)CC464ST4646 (3.3)ST100211 (0.5)CC49ST4911 (6.0)ST72684 (2.2)ST117111 (0.5)ST46241 (0.5)ST74692 (1.1)Figure S1MDR patterns of 184 C. jejuni strains to various antibiotic combinations.Abbreviation: MDR=multidrug resistance; C. jejuni=Campylobacter jejuni., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2023.)

Photochromic viologen-based materials have emerged as one of the most promising candidates for the development of X-ray light detection applications, including medical diagnosis and treatment, environmental radiation inspection, and industrial crack detection. However, the design and construction of low-dose X-ray-sensitive complexes remains an immense challenge, especially for the in-depth dissection of their response mechanisms. Herein, by using N , N '-4,4'-bipyridiniodipropionate (CV) as functional sensitive structural units and cadmium as heavy atoms, two cadmium-viologen complexes with one-dimensional chained structures, namely, [Cd 2 Cl 4 (CV)(H 2 O) 2 ] n ( 1 ) and [CdBr 2 (CV)] n ( 2 ), have been constructed, which exhibit a remarkable and selective photochromic response to low-dose X-ray radiation detection. Compound 1 is visually sensitive to both X-ray and UV light due to the more accessible photoinduced electron transfer (ET) pathways, while compound 2 only shows a slight color-changing process in response to UV light, in conformity with UV-vis absorbance analyses and kinetic studies. Surprisingly, compound 2 has longer ET pathways than 1 , but not in response to high-energy X-ray light, seeming to contradict the previous phenomena. On further analysis, the key point in achieving X-ray-sensitive behavior should be a good balance among the electron donor-acceptor distance, intermolecular interaction, and X-ray absorbing capacity, as verified by density functional theory (DFT) and X-ray absorption strength calculations, X-ray photoelectron spectra, electron paramagnetic resonance measurements, and independent gradient model analysis. In particular, compound 1 is unprecedentedly sensitive to soft X-ray radiation, accompanied by an X-ray detection limit of as low as 2.91 Gy. These findings push forward the further development of low-dose X-ray sensing materials.

The treatment of agricultural waste plays an important role in the sustainability of agricultural production and the well-being of rural communities. The present study analyzes the existing sources of agricultural waste in rural communities, their current disposal, and the farmers' attitudes towards waste management. The data is based on a survey in 21 communities in agricultural areas in Shaanxi (N = 359 farmers interviewed). The results provide a description of the main agricultural waste in the region based on empirical data. The responses highlight the farmers' experience, reputation, and engagement at recycling domestic waste as the main variables shaping their attitudes towards agricultural waste disposal. Farmers prefer treating primarily biowaste, mostly used for biogas generation or crop fertilizer at the farms. Improving waste management facilities, accessibility and economic incentives are identified as the main factors that could increase recycling rates, as well as the importance of training campaigns and instructions related to waste handling and recycling. The analysis captured the general trends in agricultural waste treatment and future directions and provides a basis for better designing waste and management alternatives., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rural residents are the main agents of rural domestic waste-sorting; their level of sorting directly relates to the improvement of their rural living environment and the construction of "beautiful countryside". Considering the data of 943 rural residents in Shaanxi Province, China, this study incorporates the factors at the individual and group levels and explores how personal norms and mianzi , which is the individual's reputation and social status, at the individual level and social capital at the group level impact the level of rural residents' domestic waste-sorting through an Ordered Probit model. The results show that personal norms and mianzi at the individual level play an important role in improving the level of rural residents' domestic waste-sorting. Meanwhile, social capital (i.e., social networking, social trust, social participation, and social norms) at the group level has significant positive impacts on the level of rural residents' domestic waste-sorting. Furthermore, mianzi plays a moderating role between personal norms, social capital, and the level of rural residents' domestic waste-sorting, respectively. These findings are useful for the Chinese government to formulate a policy about enhancing the level of rural residents' domestic waste-sorting to ease the rural environmental problem.

A 3D-printed all-dielectric metasurface is presented in this Letter which can generate an accelerating beam with a circularly symmetric non-spreading transverse profile that can propagate along arbitrary convex trajectories. The curved trajectory is mapped to the corresponding direct-space spatial phases by the basic cube units with different geometrical heights. The required phase distribution is derived in detail based on the enveloping theory of differential geometry and the Bessel beam generation method. A metasurface with a preset trajectory is simulated and measured to demonstrate the validity of the phase distribution calculated by the proposed theory. The full-wave simulation and measurement results verify that the Bessel-like beam whose intensity follows a curved (off-axis) trajectory can be produced by the proposed metasurface. The generated hybrid beam merges the advantages of non-accelerating and accelerating diffractive-free beams. Therefore, the proposed metasurface has great potential in ultrahigh-speed communication, secure communication, near-field imaging, wireless energy transmission applications, and so on. The all-dielectric characteristic provides the proposed metasurface with the competitive advantages of low cost and easy large-scale processing.

Introduction: Vibrio parahaemolyticus ( V. parahaemolyticus ) is a common foodborne pathogen which causes gastroenteritis in humans, especially the O3:K6 pandemic clone which is still a prominent serotype in Beijing, China. In this study, we observed a novel serotype O10:K4 isolated from clinical diarrhea cases, which became the most prevalent clone in 2021., Methods: 73 clinical isolates were collected through sentinel hospitals' surveillance in 2021. Serum agglutination testing and antimicrobial susceptibility testing were conducted. Whole genome sequencing was applied to characterize 73 V. parahaemolyticus strains and complete phylogenetic analysis., Results: Seven serotypes were identified among 73 strains. O10:K4 was the most common serotype (83.6%), followed by O2:KUT, O4:KUT, and O1:KUT. Multilocus sequence typing divided the 73 isolates into 10 sequence types (STs) with ST3 as the most prevalent, which covered all O10:K4 strains. Most isolates were sensitive to common antimicrobial agents apart from colistin. All the O10:K4 isolates were positive for the thermostable direct hemolysin gene, toxRS/new , and orf8 , and negative for the TDH-related hemolysin gene. The whole genome sequencing-single nucleotide polymorphism phylogenetic analysis revealed O10:K4 strains formed a main genetic lineage, which was genetically distinct from other serotypes. We also demonstrated the presence of two type III secretion system genes (T3SS1 and T3SS2) and β lactamase resistance gene blaCARB-22 in all O10:K4 strains., Conclusions: The study confirmed the emergence of V. parahaemolyticus O10:K4 possessing virulence factors similar to the O3:K6 pandemic clone, which may have enabled them to become prevalent in Beijing, China., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2022.)

Boron (B) deficiency and aluminum (Al) toxicity are two major constraints on plants grown in acidic soils. B supply mitigates Al toxicity; however, the underlying mechanisms of this process remain elusive. In this work, Pisum sativum plants were used to address this issue. In the absence of pH buffers, B supply had a better mitigation effect on Al-induced root inhibition at pH 4.0 than pH 4.8. However, in MES buffered solution, mitigating effects of B on Al-induced root inhibition were more pronounced at pH 4.8, indicating a strong pH dependency of this process. Quantification of pH-dependent accumulation of Al in various root zones, modification of root pH by an exogenous addition of rapid alkalization factor (RALF), and measuring changes in the rhizosphere pH by fluorescent dyes have revealed operation of two concurrent mechanisms to explain alleviation of the inhibition of root elongation induced by Al toxicity by boron: (1) via enhancing rhizosphere pH under strong acidic stress (pH4.0), and (2) via stabilizing of cell wall by cross-linking with RGII at relatively higher pH (4.8). These findings provide scientific basis and support for the application of B fertilizers in the regions with inherited soil acidity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Although gastric surgery can significantly improve blood glucose homeostasis in type 2 diabetes mellitus (T2DM), its mechanism remains unclear. This study evaluated the role of intestinal glucose sensing, glucose transport, and metabolism in the alimentary limb (A limb) of T2DM rats after duodenal jejunal bypass (DJB) surgery., Methods: A T2DM rat model was induced via a high-glucose high-fat diet and low-dose streptozotocin injection. The diabetic rats were divided into two groups: the DJB surgery (T2DM-DJB) group and the sham surgery (T2DM-Sham) group. Wistar rats were used as wild-type control (Control). Small animal PET was used to assess the change in glucose metabolic status in the intestine. The intestinal villi height and the number of EECs after DJB were evaluated. The expressions of sweet taste receptors (T1R2/T1R3), glucose transporters (SGLT1/GLUT2), and key enzymes involved in glucose metabolism (HK2, PFK2, PKM2, G6Pase, and PCK1) in the A limb after DJB was detected by Western blot and qRT-PCR., Results: Small animal PET analysis showed the intestinal glucose metabolism increased significantly 6 weeks after DJB surgery. The intestinal villi height and the number of EECs in the A limb 6 weeks after surgery increased significantly in T2DM-DJB rats comparing to T2DM-Sham rats. The mRNA and protein expression of T1R1/T1R3 and SGLT1/GLUT2 were downregulated in DJB-T2DM rats, while enzymes involved in glucose metabolism was upregulated in the A limb in T2DM-DJB rats., Conclusion: Proximal intestinal glucose sensing and metabolism play an important role in blood glucose homeostasis by DJB., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

What Is Already Known About This Topic?: Typhoid fever remains a major public health problem in developing countries. Waterborne typhoid fever affects an estimated 27 million people worldwide each year. Decades of indiscriminate antibiotic usage has driven the emergence and spread of multidrug-resistant (MDR) and even extensively drug-resistant (XDR) Salmonella Typhi ( S. Typhi) strains., What Is Added by This Report?: By combining the epidemiological investigations, bacterial isolation from patients and household water, whole genome sequencing and drug resistance analysis, we identified a waterborne typhoid fever outbreak caused by XDR S. Typhi in Beijing municipality. This was the first report of the XDR S . Typhi triggered outbreak in Beijing, which was also rare in China., What Are the Implications for Public Health Practice?: This report highlights the importance of ensuring access to affordable and safe drinking water, improved sanitation, and waste management systems for resource-constrained urban populations. Typhoid fever caused by XDR S . Typhi is still a severe public health threat., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2022.)

Solasodine, a major ingredient in Solanaceae family, has various biological functions such as inducing neurogenesis, anticonvulsant and anti-tumor. Its risk assessment has also drawn public attention. However, little is known about its oral bioavailability and metabolic process. In this study, an liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of solasodine in mice dried blood spot (DBS) samples. To block nonspecific adsorption, DBS samples were pretreated with bovine serum albumin (BSA) and then extracted with ethyl acetate. This method was applied to a pharmacokinetic and bioavailability study of solasodine. The absolute bioavailability was only 1.28%. Thereafter, its metabolites in mice were characterized using an ultra-performance liquid chromatography Q-Exactive high-resolution mass spectrometer (UHPLC-QE-HRMS). Several isomeric metabolites were well separated and differentiated using their retention time, fragmentation pathways and correspondingly fragmentation rules of solasodine. As a result, 21 metabolites were characterized including 16 phase I and 5 phase II metabolites. The proposed metabolic pathways showed that solasodine mainly experienced oxidation, dehydration, dehydrogenation and sulfation. These results could help us to better understand the efficacy and safety of solasodine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The growing interest of policy-makers, environmental stakeholders, and academics in rural domestic waste treatment has made it a recent focus of research in the field of rural human settlements. Many studies have been conducted to understand the related factors; however, their results are inconsistent. Therefore, different from previous studies, the study systematically analyzed and summarized empirical studies on rural domestic waste treatment and explored the key factors that fostered and impeded it. It also examined the reasons for differences in research level and trends in key factors over time. A random-effects meta-analysis of 24 studies revealed that education, political status, perceived value, behavioral attitude, subjective norm, garbage collection facilities and services, environmental knowledge and propaganda, and government policy and regulation had a significant positive correlation with rural domestic waste treatment; perceived value had the highest impact, followed by behavioral attitude. All of the variables had significant heterogeneity. Some of the heterogeneity can be explained by differences in research methods, sample size, and variable measurement methods. An increasing trend was observed in the effects of perceived value, behavioral attitude, and subjective norm. Finally, based on these results, the study provided suggestions on policy and academic aspects., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Prediction and early diagnosis of Parkinson's disease (PD) and Parkinson's disease with depression (PDD) are essential for the clinical management of PD. Objectives: The present study aimed to develop a plasma Family with sequence similarity 19, member A5 (FAM19A5) and MRI-based radiomics nomogram to predict PD and PDD. Methods: The study involved 176 PD patients and 181 healthy controls (HC). Sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure FAM19A5 concentration in the plasma samples collected from all participants. For enrolled subjects, MRI data were collected from 164 individuals (82 in the PD group and 82 in the HC group). The bilateral amygdala, head of the caudate nucleus, putamen, and substantia nigra, and red nucleus were manually labeled on the MR images. Radiomics features of the labeled regions were extracted. Further, machine learning methods were applied to shrink the feature size and build a predictive radiomics signature. The resulting radiomics signature was combined with plasma FAM19A5 concentration and other risk factors to establish logistic regression models for the prediction of PD and PDD. Results: The plasma FAM19A5 levels (2.456 ± 0.517) were recorded to be significantly higher in the PD group as compared to the HC group (2.23 ± 0.457) ( P < 0.001). Importantly, the plasma FAM19A5 levels were also significantly higher in the PDD subgroup (2.577 ± 0.408) as compared to the non-depressive subgroup (2.406 ± 0.549) ( P = 0.045 < 0.05). The model based on the combination of plasma FAM19A5 and radiomics signature showed excellent predictive validity for PD and PDD, with AUCs of 0.913 (95% CI: 0.861-0.955) and 0.937 (95% CI: 0.845-0.970), respectively. Conclusion: Altogether, the present study reported the development of nomograms incorporating radiomics signature, plasma FAM19A5, and clinical risk factors, which might serve as potential tools for early prediction of PD and PDD in clinical settings., Competing Interests: A-bM was employed by Shanghai Xunshi Technology Co., Ltd. as a data engineer and directly participated in data analysis of this study. This study did not receive any financial support from the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Hao, Qu, Zhang, Ma, Pan and Ma.)

Wide bandgap oxide semiconductors constitute a unique class of materials that combine properties of electrical conductivity and optical transparency. They are being widely used as key materials in optoelectronic device applications, including flat-panel displays, solar cells, OLED, and emerging flexible and transparent electronics. In this article, an up-to-date review on both the fundamental understanding of materials physics of oxide semiconductors, and recent research progress on design of new materials and high-performing thin film transistor (TFT) devices in the context of fundamental understanding is presented. In particular, an in depth overview is first provided on current understanding of the electronic structures, defect and doping chemistry, optical and transport properties of oxide semiconductors, which provide essential guiding principles for new material design and device optimization. With these principles, recent advances in design of p-type oxide semiconductors, new approaches for achieving cost-effective transparent (flexible) electrodes, and the creation of high mobility 2D electron gas (2DEG) at oxide surfaces and interfaces with a wealth of fascinating physical properties of great potential for novel device design are then reviewed. Finally, recent progress and perspective of oxide TFT based on new oxide semiconductors, 2DEG, and low-temperature solution processed oxide semiconductor for flexible electronics will be reviewed., (© 2021 Wiley-VCH GmbH.)

In this Letter, a metasurface combined with emerging 3D printing technology is proposed. The proposed metasurface regards the simple cube as the unit cell, and the height of the cube is the only variable. A nearly linear transmission phase range covering 360° operating at 20 GHz is obtained when the height is regulated in [2.26 mm, 11.20 mm]. Therefore, the proposed unit cell can be adopted to any metasurface with various functions. Taking the generation of a non-diffractive Bessel beam as an example, two metasurfaces composed of 30×30 units with different focusing directions are designed based on non-diffractive theory and the generalized law of refraction. Two prototypes are 3D printed and measured by a near-field scanning system. The measured results validate our design with satisfactory focusing and beam deflection performance. Additionally, the 3D printed metasurface has lower cost and a shorter processing cycle, and avoids metal loss. Therefore, a 3D printed metasurface is an excellent candidate that can be applied in millimeter wave or even higher frequency bands.

One-dimensional (1D) organic-inorganic hybrid lead halides with unique core-shell quantum wire structures and splendid photoluminescence properties have been considered one of the most promising high-efficiency broadband emitters. However, studies on the broadband emissions in 1D purely face-shared lead iodide hybrids are still rare so far. Herein, we report on a new 1D lead iodide hybrid, (2cepyH)PbI 3 (2cepy = 1-(2-chloroethyl)pyrrolidine), characterized with face-sharing PbI 6 octahedral chains. Upon UV photoexcitation, this material shows broadband yellow emissions originating from the self-trapped excitons associated with distorted Pb-I lattices on account of the strong exciton-phonon coupling, as proved by variable-temperature emission spectra. Moreover, experimental and calculated results reveal that (2cepyH)PbI 3 is an indirect bandgap semiconductor, the band structures of which are governed by inorganic parts. Our work represents the first broadband emitter based on a 1D face-shared lead iodide hybrid and opens a new way to obtain the novel broadband emission materials.

Exosomes show diagnostic and therapeutic promise as carriers of ncRNAs in diseases. LncRNAs in exosomes have been identified as being stable and avoided degradation by nucleolytic enzymes. Although lncRNAs have been confirmed to be important in cancers, no studies for exo-lncRNAs have been reported in LAA stroke. High-throughput sequencing was performed to detect the differential expression profiles of lncRNAs in five paired plasma-derived exosome samples from patients with LAA stroke and controls (matched on vascular risk factors). Exo-lncRNA-associated networks were predicted with a combination of multiple databases. The expression of the selected genes in the networks was confirmed by qRT-PCR in a validation set (LAA vs. controls = 30:30). Furthermore, ROC analysis was used to evaluate the diagnostic performance of the lncRNA-related networks. A total of 1,020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. qRT-PCR confirmed that the expression trend of differential expressed genes was consistent with RNA-seq. Furthermore, the AUCs of the lnc&#95;002015-related network and lnc&#95;001350-related network were 0.959 and 0.97, respectively, in LAA stroke. Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic networks for LAA stroke for the first time. The results suggested that exosomal lncRNA-related networks could be potential diagnostic tools in LAA stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Wang, Qu, Wang, Ma, Pan and Zhu.)

Differentiation therapy with all-trans-retinoic acid (ATRA) in acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), has been extremely successful in inducing clinical remission in APL patients. However, the differentiation therapy of ATRA-based treatment has not been effective in other subtypes of AML. In this study, we evaluated a small molecule of ent -kaurene diterpenoid, Jiyuan oridonin A (JOA), on the differentiation blockade in AML cells with the mixed lineage leukemia (MLL) gene rearrangements (MLLr) in MV4-11, MOLM-13 and THP-1 cells. We found that JOA could significantly inhibit the proliferation of MOLM-13, MV4-11 and THP-1 cells. Moreover, JOA promoted cell differentiation coupled with cell-cycle exit at G0/G1 and inhibited the colony- forming capacity of these cells. We showed that the anti-proliferative effect of JOA attributed to cell differentiation is most likely through the martens tretinoin response up pathway in the MOLM-13 cell line, and the hematopoietic cell lineage pathway by the inhibition of c-KIT expression and cell adhesion pathway in the THP-1 cell line. Our findings suggest that JOA could be a novel therapeutic agent against human MLLr acute myeloid leukemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qu, Duan, Zhao, Wang, Zhao, Zhao, Wang, Ke, Liu, Liu, Wei and Hu.)

Acute myelogenous leukemia (AML) is characterized by blockage of cell differentiation leading to the accumulation of immature cells, which is the most prevalent form of acute leukemia in adults. It is well known that all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are the preferred drugs for acute promyelocytic leukemia (APL). However, they can lead to irreversible resistance which may be responsible for clinical failure after complete remission (CR). Moreover, the differentiation therapy of ATRA-based treatment has not been effective against AML with t(8;21) translocation. Here we aimed to identify the differentiation effect of OGP46 on AML cell lines (HL-60, NB4, and Kasumi-1) and explore its possible mechanisms. We found that OGP46 has significant inhibitory activity against these cells by triggering cell differentiation with cell-cycle exit at G1/G0 and inhibited the colony-formation capacity of the AML cells. It was shown that OGP46 induced the differentiation of NB4 cells via the transcriptional misregulation in cancer signaling pathway by PML-RARα depletion, while it was attributed to the hematopoietic cell lineage and phagosome pathway in Kasumi-1 cells, which are all critical pathways in cell differentiation. These results highlight that OGP46 is an active agent not only in the APL cell line NB4 but also in AML-M2 cell lines, especially Kasumi-1 with t(8;21) translocation. Therefore, OGP46 may be a potential compound for surmounting the differentiation blockage in AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Wang, Qu, Zhao, Wang, Ke, Liu, Lei, Liu, Hu, Wei and Chen.)

After the economy enters a "new normal" era in China, resource-based cities are under pressure in terms of transformation, upgrading and sustainable development. This paper uses the panel data of 33 resource-based cities from 2008 to 2018 to empirically analyze the impact of environmental regulation and innovation compensation on scientific and technological competitiveness. The results show that there is a positive U-shaped relation between environmental regulation and scientific and technological competitiveness. This means that when environmental regulations exceed a certain level, continuing to increase regulations will significantly enhance technological competitiveness, but most samples are still on the left side of the turning point. At the same time, the labor productivity and fiscal capacity of non-agricultural industries in the region may have a strong regulatory effect. In a region with higher labor productivity in non-agricultural industries or stronger local fiscal capacity, environmental regulation is more likely to reflect the attribute of "innovation compensation" and advance scientific and technological competitiveness. At this stage, we should optimize the trans-regional compensation mechanism for resource-rich regions, increase investment in pollution management and ecological protection and impose stricter admission standards on industrial projects. Besides, skilled laborers should be cultivated and innovation and entrepreneurship be supported to realize the green and sustainable development of resource-based cities in the new era.

The sorting of domestic waste is the most effective way to alleviate the problem of mass garbage accumulation around the villages of rural China. Farmers are the creators of rural domestic waste as well as the direct beneficiaries of effective waste management. However, few studies have been conducted on the psychological determinants of farmers' intentions to sort domestic waste. This paper applies planned behavior theory (TPB) and normative activation theory (NAM), to analyze the domestic waste sorting intentions of rural residents in Guanzhong, China. Based on the micro-data of 327 rural households in Guanzhong, structural equation models of the factors influencing farmers' domestic waste sorting intentions were estimated. The results demonstrate the following. (1) Farmers' attitudes, perceived behavioral control, and personal norms have significant positive direct impacts on their domestic waste sorting intentions, with personal norms having the greatest direct impact. (2) Subjective norms have no direct impact on farmers' domestic waste sorting intentions but do have an indirect impact on them through personal norms, behavioral attitudes, and perceived behavior control. This article increases scholarly understanding of the psychosocial determinants of the environmentally friendly behavioral intention to sort domestic waste. The study also provides academic and theoretical support to policy makers in implementing relevant policy recommendations.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the adult central nervous system (CNS), however, it causes excitation in the immature CNS neurons. The shift from GABA-induced depolarization to hyperpolarization in postnatal brain is primarily due to progressive decrease in the expression of the Na + -K + -2Cl - symporter 1 (NKCC1) and increased expression of the K + -Cl - cotransporter 2 (KCC2). Unlike CNS neurons, both immature and mature neurons in the enteric nervous system (ENS) are depolarized by GABA. Molecular mechanisms by which GABA excites ENS neurons are unclear. It is understood, however, that the excitatory action depends on elevated intraneuronal Cl - . We aimed to test a hypothesis that high intracellular Cl - in ENS neurons is maintained by activity of the NKCCs. We found that NKCC2 immunoreactivity (IR) was expressed in the ENS of the rat colon on postnatal day 1 (P1). The expression level of NKCC2 continuously increased and reached a steady high level on P14 and maintained at that level in adulthood. NKCC1 IR appeared in ENS on P14 and maintained through adulthood. KCC2 IR was not detectable in the ENS in any of the developmental stages. Both NKCC1 IR and NKCC2 IR were co-expressed with GABA A receptors in ENS neurons. Exogenous GABA (1 mmol/L) caused membrane depolarization in the ENS neurons. The reversal potential of GABA-induced depolarization was about -16 mV. Blockade of NKCC by bumetanide (50 μmol/L) or furosemide (300 μmol/L) suppressed the depolarizing responses to GABA. Bumetanide (50 μmol/L) shifted the reversal potential of GABA-induced depolarization in the hyperpolarizing direction. Neither the KCC blocker DIOA (20 μmol/L) nor the Cl - /HCO 3 - exchanger inhibitor DIDS (200 μmol/L) suppressed GABA-evoked depolarization. The results suggest that ENS neurons continuously express NKCC2 since P1 and NKCC1 since P14, which contribute to the accumulation of Cl - in ENS neurons and GABA-evoked depolarization in neonate and adult ENS neurons. These results provide the first direct evidence for the contribution of both NKCC2 and NKCC1 to the GABA A -mediated depolarization.

Chronic myeloid leukemia (CML) is caused by the Philadelphia (Ph + ) chromosome carrying the BCR-ABL oncogene, a constitutively active tyrosine kinase. The discovery of imatinib represents a major success story in the treatment against CML. However, mutations in the BCR-ABL kinase domain are a major cause of resistance to imatinib, demonstrating that BCR-ABL remains a critical drug target. Here, we investigate a novel small molecule inhibitor, OGP46, for its inhibitory activity against K562, a panel of murine BaF3 cell lines stably expressing either wild-type BCR-ABL or its mutant forms, including T315I. OGP46 exhibits potent activity against imatinib-resistant BCR-ABL mutations, including T315I. OGP46 induced cell differentiation accompanied by G0/G1 cell-cycle arrest and suppressed the colony formation capacity of cells. Treatment with OGP46 significantly decreased the mRNA and protein expression of BCR-ABL in K562 and BaF3-p210-T315I cells. Mechanistically, the anti-cancer activity of OGP46 induced by cell differentiation is likely through the BCR-ABL/JAK-STAT pathway in native BCR-ABL and mutant BCR-ABL, including T315I, of CML cells. Our findings highlight that OGP46 is active against not only native BCR-ABL but also 11 clinically relevant BCR-ABL mutations, including T315I mutation, which are resistant to imatinib. Thus, OGP46 may be a novel strategy for overcoming imatinib-resistance BCR-ABL mutations, including T315I., (© 2020 The Authors.)

The only feasible access to non-face-centered cubic (FCC) copper was by physical vapor deposition under high vacuum. Now, non-FCC copper is observed in a series of alkynyl-protected Cu 53 nanoclusters (NCs) obtained from solution-phase synthesis. Determined by single-crystal X-ray crystallography, the structures of Cu 53 (C≡CPhPh) 9 (dppp) 6 Cl 3 (NO 3 ) 9 and its two derivatives reveal an ABABC stacking sequence involving 41 Cu atoms. It can be regarded as a mixed FCC and HCP structure, which gives strong evidence that Cu can be arranged in non-FCC lattice at ambient conditions when proper ligands are provided. Characterization methods including X-ray absorption fine structure, XPS, ESI-MS, UV/Vis, Auger spectroscopy, and DFT calculations were carried out. Cu II was shown to successively coordinate with introduced ligands and changed to Cu I after bonding with phosphine. The following addition of NaBH 4 and the aging step further reduced it to the Cu 53 NC., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Through field survey and laboratory analysis, we examined the composition and fractal features of soil micro-aggregates in different types of treefall gaps and microsites (pit bottom and mound top) in broad-leaved Korean pine forest and spruce-fir-Korean pine forest. Results showed that the contents of soil microaggregates under the classes of 0.25-2 mm and 0.05-0.25 mm were higher in both forest types, ranging from 25.7% to 50.7% and from 27.0% to 42.8%, respectively, and that of <0.002 mm was the lowest, ranging from 4.4% to 8.9%. In the pit bottom and mound top of gaps, soil bulk density was higher in both forest types. Soil nutrient content in mound top was higher than that in pit bottom and was higher in broad-leaved Korean pine forest than spruce-fir-Korean pine forest. Soil microaggregates of <0.002 mm had no correlation with soil physical and chemical properties, whereas that of 0.25-2 mm and 0.002-0.02 mm had significantly positive and negative correlation with soil non-capillary porosity, total porosity, aeration porosity, organic matter, total phosphorus, total nitrogen and organic carbon, respectively. On the whole, soil fractal dimension (D) and the proportion of characteristic soil micro-aggregates (PCM) in broad-leaved Korean pine forest were larger than those in spruce-fir-Korean pine forest, and the ratio of soil microaggregates diameter (RMD) in mound top and pit bottom was increased in two forest types. Soil D and PCM had no significant correlation with soil physical and chemical properties, while RMD was negatively correlated with capillary porosity, total porosity, soil bulk density and aeration porosity. In two forest types, the formation of mound and pit microsites could decrease the larger size micro-aggregates and the stability of soil micro-aggregate, increase soil D and PCM, and signifi-cantly increase RMD. RMD could be used as a quantitative index of soil physical and chemical properties in pit and mound microsites of forest.

3,4‑Dihydroxyacetophenone (DHAP) exerts therapeutic effects on cardiovascular disease and pulmonary heart disease. However, it is not utilized as a clinical drug due to its rapid metabolism, short‑acting effect and low oral bioavailability. In the present study, three derivatives of DHAP, including 4‑acetyl‑1,2‑phenylene dipropionate (APDP), 1‑(3‑hydroxy‑4‑phenoxy‑phenyl)‑ethanone (HPPE) and a polymer derivative, PEG‑DHAP, were synthesized via the esterification or etherification of hydroxyls at C3 and C4, which are the prime metabolism sites of DHAP. The physicochemical properties, pharmacokinetic and antiplatelet aggregation activities of these derivatives were measured to determine whether they can improve the defects of DHAP. The results revealed that APDP and HPPE exhibited markedly lower water solubility and higher oil‑water partition coefficients compared to DHAP. APDP rapidly transformed into DHAP in vivo and in vitro, indicating that there were no significant differences in the values of mean residence time in vivo [MRT (0‑t)], half‑life [t1/2], oral bioavailability and antiplatelet aggregation activity in vivo and in vitro between the two agents. HPPE partially released DHAP for a period of time following oral administration. PEG‑DHAP contained 12.47% DHAP dispersed into nanoparticles with a mean particle size of 260.90 nm. This was administered in aqueous solution and was demonstrated to release DHAP slowly following oral administration. These two derivatives significantly prolonged the in vivo acting time and increased the oral bioavailability of DHAP: Following intragastric administration, their MRT (0‑t) and t1/2 values were 3.55‑11.47‑ and 6.63‑11.25‑fold higher compared with those of DHAP, respectively. Additionally, their relative bioavailability was 394.79 and 331.88%, respectively, and they exhibited longer acting times of significant antiplatelet aggregation activity. The results of the present study may thus provide a reference for the development of DHAP as an oral drug. Furthermore, the results if this study may prove to be useful to researchers addressing the issue of the poor bioavailability of phenolic drugs.

Background: Klebsiella pneumoniae is an opportunistic pathogen associated with community-acquired and nosocomial infections. Since 2010, K. pneumoniae testing has been included into an existing diarrhea-syndrome surveillance system for estimating the prevalence of K. pneumoniae in diarrhea-syndrome patients, assessing antibiotic susceptibility, and investigating molecular characteristics of K. pneumoniae . Methods: Klebsiella pneumoniae strains were isolated from stool specimens from diarrhea-syndrome outpatients in Beijing, China. Isolates were tested for antibiotic susceptibility, and phylogenetic relationships were explored though whole genome sequence analysis. Multi-locus sequence type (MLST) alleles were extracted from the whole genome sequence (WGS) data. A maximum likelihood tree was generated by MEGAX. Genomes were annotated by Prokka; core genes were produced by Roary; a maximum likelihood phylogenetic tree was generated using FastTree. Results: Forty-four K. pnuemoniae strains were isolated from 2010 to July 2019; of these 37 were K. pneumoniae and seven were K. variicola . Antibiotic susceptibility testing showed that all 44 strains were sensitive to gentamicin, imipenem, amikacin, meropenem, kanamycin; 97.73% were sensitive to cefoxitin andlavo-ofloxacin; the highest antibiotic resistance rate was 79.55%, which was to ampicillin. We found three extended-spectrum beta-lactamase (ESBL) producing strains; we identified high-virulence ST types, including ST307 and ST65; and we found that ST23 has been the epidemic clone since 2010. MLST and core genome sequence analysis showed two distinct clusters of 44 K. pnuemoniae ; 40 alleles were identified in core genome sequence analysis, while 36 alleles were identified in MLST typing. Conclusions: There is an urgent need for epidemiological and molecular studies to understand the dynamics of antibiotic resistance and virulence gene transmission to guide strategies for K. pneumoniae surveillance. WGS analysis provided high discrimination power and reliable and robust data useful for molecular epidemiology., (Copyright © 2020 Lu, Lin, Liu, Zhang, Tian, Huang, Yan, Qu, Jia and Wang.)

Background: Contamination of drugs used in minimally invasive treatment may to lead to infection outbreaks and catastrophic public health events that require prompt detection and control. Our aim was to investigate the outbreak of Burkholderia cepacia infection and its source in a tertiary care, general hospital in Beijing, China., Methods: We investigated the outbreak of B cepacia infection from January 2017 to March 2018. The investigation included a detailed review of all cases, and field investigations. Environmental and product cultures were performed at the microbiology laboratory in the hospital. Isolates were evaluated for molecular relatedness using pulsed-field gel electrophoresis performed in an independent laboratory., Results: In total, 9 patients were infected from November 2017 to March 2018, and all patients had undergone the following surgeries: transurethral resection of the prostate (n = 4), perineal prostate biopsy (n = 2), transurethral resection of bladder tumors (n = 2), and ureteroscopy (n = 1). B cepacia was isolated from the urine of 9 patients, blood of 2 patients, grilles used for puncturing, and 2 samples in 1 batch of analgesic gels. Pulsed-field gel electrophoresis confirmed that the isolates from the patients and gels were homologous., Conclusions: Our investigation revealed that the outbreak of B cepacia infection was caused by drug contamination., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Duodenal-jejunal bypass (DJB) can dramatically improve type 2 diabetes independent of weight loss and food restriction. Increasing evidence has demonstrated that brain insulin signaling plays an important role in the pathophysiology of type 2 diabetes. This study explores whether the antidiabetic effect of DJB is involved in brain insulin signaling activation and brain glucose utilization., Methods: A diabetic rat model was established by high-fat and high-glucose diet. DJB or sham surgery was performed in diabetic rats. 18F-FDG PET scanning was used to detect glucose uptake in different organs, particularly in the brain. The levels of glucose transporters, glucose utilization-related proteins (HK1 and PFK2), insulin, and insulin signaling pathway-related proteins (InsR, IRS1/2, PI3K, and p-Akt) in the brain tissues were evaluated and analyzed., Results: The results showed that DJB significantly improved basal glycemic parameters and reversed the decreasing glucose uptake in the brains of type 2 diabetic rats. DJB significantly increased not only the expression levels of brain insulin, IRS1/2, PI3K, and p-Akt but also the levels of the glucose utilization enzymes HK1 and PFK2 in the brain., Conclusion: These results indicate that enhanced brain insulin signaling transduction and brain glucose utilization play important roles in the antidiabetic effect of DJB.

Introduction: Campylobacter spp. is the most common gastrointestinal pathogen worldwide with a very low reported incidence in China. In April 2018, one 36 cases of diarrhea outbreak occurred in a high school in Beijing after a trip to another province in Southern China. The investigation for the enteric pathogen infection was conducted to identify the cause., Methodology: Eighteen stool specimens from 11 diarrheal patients and 3 close contacts were collected and tested for 16 enteric bacterial and viral pathogens using real-time PCR methods. Multilocus Sequence Typing (MLST), pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility testing were applied to C. jejuni isolates in this outbreak in order to characterize the incident., Results: Ten (90.9%) of 11 stool specimens from diarrheal patients were positive for Campylobacter jejuni, confirmed as the cause of outbreak. Eight C. jejuni strains were obtained and produced 2 sequence types (STs) and 3 PFGE patterns. Six of them had the same ST (ST2274) and PFGE pattern (SMA001). The dominant outbreak strain with an identical subtyping profile was clustered with most chicken isolates from national MLST and PulseNet Campylobacter database. The entire 8 isolates were multi-drug resistant, with the dominant resistance pattern of nalidixic acid, tetracycline and ciprofloxacin combined, except for 2 isolates resistant to florfenicol., Conclusion: Molecular typing confirmed that most of the cases belonged to a clonal cluster supporting the hypothesis of a common source; however, the source was not identified. This was the first recognized Campylobacteriosis outbreak in China among 20 years., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Mei Qu, Maojun Zhang, Xin Zhang, Lei Jia, Jun Xu, Yanhui Chu, Zhichao Liang, Bing Lv, Hao Liang, Ying Huang, Quanyi Wang.)

This work reports a fundamental study on the relationship of the electronic structure, catalytic activity and surface reconstruction process of Fe doped NiS 2 (Fe x Ni 1-x S 2 ) for the oxygen evolution reaction (OER). A combined photoemission and X-ray absorption spectroscopic study reveals that Fe doping introduces more occupied Fe 3d 6 states at the top of the valence band and thereby induces a metallic phase. Meanwhile, Fe doping also significantly increases the OER activity and results in much better stability with the optimum found for Fe 0.1 Ni 0.9 S 2 . More importantly, we performed detailed characterization to track the evolution of the structure and composition of the catalysts after different cycles of OER testing. Our results further confirmed that the catalysts gradually transform into amorphous (oxy)hydroxides which are the actual active species for the OER. However, a fast phase transformation in NiS 2 is accompanied by a decrease of OER activity, because of the formation of a thick insulating NiOOH layer limiting electron transfer. On the other hand, Fe doping retards the process of transformation, because of a shorter Fe-S bond length (2.259 Å) than Ni-S (2.400 Å), explaining the better electrochemical stability of Fe 0.1 Ni 0.9 S 2 . These results suggest that the formation of a thin surface layer of NiFe (oxy)hydroxide as an active OER catalyst and the remaining Fe 0.1 Ni 0.9 S 2 as a conductive core for fast electron transfer is the base for the high OER activity of Fe x Ni 1-x S 2 . Our work provides important insight and design principle for metal chalcogenides as highly active OER catalysts.

The non-protein amino acid γ-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to salinity. However, the physiological rationale for this elevation remains elusive. This study compared electrophysiological and whole-plant responses of salt-treated Arabidopsis mutants pop2-5 and gad1,2, which have different abilities to accumulate GABA. The pop2-5 mutant, which was able to overaccumulate GABA in its roots, showed a salt-tolerant phenotype. On the contrary, the gad1,2 mutant, lacking the ability to convert glutamate to GABA, showed oversensitivity to salinity. The greater salinity tolerance of the pop2-5 line was explained by: (i) the role of GABA in stress-induced activation of H+-ATPase, thus leading to better membrane potential maintenance and reduced stress-induced K+ leak from roots; (ii) reduced rates of net Na+ uptake; (iii) higher expression of SOS1 and NHX1 genes in the leaves, which contributed to reducing Na+ concentration in the cytoplasm by excluding Na+ to apoplast and sequestering Na+ in the vacuoles; (iv) a lower rate of H2O2 production and reduced reactive oxygen species-inducible K+ efflux from root epidermis; and (v) better K+ retention in the shoot associated with the lower expression level of GORK channels in plant leaves., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Introduction: L-glutamine is an antioxidant that plays a role in a variety of biochemical processes. Given that oxidative stress is a key component of stroke pathology, the potential of L-glutamine in the treatment of ischemic stroke is worth exploring., Aims: In this study, we investigated the effect and mechanisms of action of L-glutamine after cerebral ischemic injury., Results: L-glutamine reduced brain infarct volume and promoted neurobehavioral recovery in mice. L-glutamine administration increased the expression of heat-shock protein 70 (HSP70) in astrocytes and endothelial cells. Such effects were abolished by the coadministration of Apoptozole, an inhibitor of the ATPase activity of HSP70. L-glutamine also reduced oxidative stress and neuronal apoptosis, and increased the level of superoxide dismutase, glutathione, and brain-derived neurotrophic factor. Cotreatment with Apoptozole abolished these effects. Cell culture study further revealed that the conditioned medium from astrocytes cultured with L-glutamine reduced the apoptosis of neurons after oxygen-glucose deprivation., Conclusion: L-glutamine attenuated ischemic brain injury and promoted functional recovery via HSP70, suggesting its potential in ischemic stroke therapy., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Objective: To observe the protective role of hapatopoietin Cn (HPPcn) on acute liver injury. Methods: Six hours after 10 mmol/L CCl 4 , 150 mmol/L ethanol, or 0.6 mmol/L H 2 O 2 treatment, SMMC7721 human hepatoma cells were incubated with 10, 100, or 200 ng/ml recombinant human HPPCn protein (rhHPPCn) for an additional 24 h. The cell survival rate was analyzed using the CCK-8 assay. The CCl 4 -induced apoptosis of SMMC7721 cells was detected by flow cytometry. Then, the levels of glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), malondialdehyde (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) in SMMC7721 cell lysates and cell culture supernatant were detected. SMMC7721 cells were treated with different concentrations of rhHPPCn (0, 10, and 100 ng/ml). The cell proliferation indexes (BrdU incorporation and PCNA expression) were detected by immunohistochemistry (IHC). An acute liver injury mouse model was established by a one-time intraperitoneal injection of 20% CCl 4 at a volume of 5 ml/kg body weight. One hour after CCl 4 injection, 1.25 or 2.5 mg rhHPPCn/12 h/kg body weight was injected via the tail vein. The serum levels of GOT and GPT were detected at different time points. Pathological changes in the liver were evaluated. PCNA expression levels were observed by IHC. Results: rhHPPCn increased the survival rate of SMMC7721 cells and inhibited chemical toxicity-induced cell apoptosis. The levels of GOT, GPT, MDA, and LDH in the cell supernatant were significantly reduced, while GSH-PX and SOD were significantly increased after rhHPPCn treatment in the CCl 4 -treated SMMC7721 cells. BrdU incorporation and PCNA expression increased in a concentration-dependent manner, indicating that rhHPPCn promotes cell proliferation. The results showed that rhHPPCn significantly reduced the serum levels of GOT and GPT in CCl 4 -induced acute liver injury mice. rhHPPCn alleviated the tissue damage and increased PCNA expression, indicating the promotion of proliferation after acute injury. Conclusion: rhHPPCn protects hepatocytes from chemical toxins by promoting proliferation and inhibiting apoptosis in vivo and in vitro . Our study provides new insights for the clinical treatment of acute liver injury.

Introduction: Dl-3-N-butylphthalide (NBP), a small molecule drug used clinically in the acute phase of ischemic stroke, has been shown to improve functional recovery and promote angiogenesis and collateral vessel circulation after experimental cerebral ischemia. However, the underlying molecular mechanism is unknown., Aims: To explore the potential molecular mechanism of angiogenesis induced by NBP after cerebral ischemia., Results: NBP treatment attenuated body weight loss, reduced brain infarct volume, and improved neurobehavioral outcomes during focal ischemia compared to the control rats (P < 0.05). NBP increased the number of CD31 + microvessels, the number of CD31 + /BrdU + proliferating endothelial cells, and the functional vascular density (P < 0.05). Further study demonstrated that NBP also promoted the expression of vascular endothelial growth factor and angiopoietin-1 (P < 0.05), which was accompanied by upregulated sonic hedgehog expression in astrocytes in vivo and in vitro., Conclusion: NBP treatment promoted the expression of vascular endothelial growth factor and angiopoietin-1, induced angiogenesis, and improved neurobehavioral recovery. These effects were associated with increased sonic hedgehog expression after NBP treatment. Our results broadened the clinical application of NBP to include the later phase of ischemia., (© 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Resistance to adjuvant chemotherapy remains therapeutic challenge in nasopharyngeal carcinoma (NPC). In this work, we demonstrate that targeting eukaryotic translation initiation factor 4E (eIF4E) is a potential sensitizing strategy to overcome chemoresistance in NPC. We observe the aberrant activation of eIF4E and translational upregulation of eIF4E-regulated oncogenes in NPC cell after pro-longed exposure of cisplatin. Functional analysis demonstrates that eIF4E depletion effectively inhibits proliferation and induces apoptosis in cisplatin-resistant NPC cells. Consistently, eIF4E knockdown significantly enhances cisplatin efficacy in cisplatin-sensitive cells. We identify eIF4E as a therapeutically actionable targets by showing that ribavirin, an anti-viral drug, phenocopies the effects of eIF4E knockdown in NPC. We further demonstrate that ribavirin acts on chemoresistant NPC cells through suppressing eIF4E activity and oncogenic protein translation. Using two independent NPC xenograft mouse models, we show that ribavirin not only is effective in inhibiting chemoresistant NPC growth but also significantly augments the inhibitory effects of cisplatin efficacy in vivo without causing significant toxicity in mice. Taken together, our work shows an activation of eIF4E-mediated growth and survival mechanisms in response to chemotherapy and suggests that inhibition of eIF4E activity represents an attractive sensitizing strategy for NPC treatment. Our findings also suggest that ribavirin is a useful addition to the treatment armamentarium for NPC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Compared with their multicomponent analogues, single-component white-light-emitting diodes (WLEDs) can eliminate the disadvantages such as high cost, fluorescence self-absorption, poor machinability, and reproducibility, but how to produce white light with high quality in a single-phase host is still a big challenge. In the work, a series of Eu 3+ /Tb 3+ -doped Gd(pic) 3 and La(pic) 3 are obtained through solvothermal conditions with picolinic acid (Hpic) and lanthanide nitrate. Researchers could regularly modulate the emitting color of phosphors by adjusting the excitation wavelength as well as the relative concentration of Ln 3+ ions to obtain white light. Different luminance values [especially quantum yield (QYs)] between host materials Gd(pic) 3 and La(pic) 3 are investigated, which shows that doping of Eu 3+ into Gd(pic) 3 can improve QY to a great extent. By employing Gd 0.9512 Eu 0.0488 (pic) 3 and Gd 0.9141 Eu 0.0451 Tb 0.0408 (pic) 3 as phosphors, we successfully fabricated two excellent near-ultraviolet (365 nm) WLEDs with CIE chromaticity coordinates (0.3052, 0.3462) and (0.3007, 0.3448), relatively low color-correlated temperature (6755, 7001 K), and high color rendering index ( R a = 71.8, 72.9). This approach may open a new prospect for developing single-phase near-ultraviolet phosphors with high efficiency., Competing Interests: The authors declare no competing financial interest.

To reveal the effects of decay level of fallen trees and their formed microsite types on soil physicochemical properties, the differences in soil physicochemical properties (bulk density, capillary porosity, total porosity, capillary water holding capacity, saturated moisture capacity, soil organic carbon, total nitrogen, total phosphorous, available phosphorous, available potassium, and pH) and stoichiometry (C/N, N/P, and C/P) among different decay levels of treefalls and between different microsite types in the formed gaps by fallen trees were analyzed in a spruce-fir fore-st in a valley of Liangshui National Nature Reserve in Xiaoxing' an Mountains. The results showed that the effects of the decay levels of fallen trees on soil physical properties was not significant. In contrast, we found significant effects of the formed microsite types in soil physical properties. Except for saturated soil water holding capacity, the other soil physical properties were the best under the fallen trees and the worst in the pit bottom. Except of available phosphorus, the contents of the other soil nutrients exhibited a significant increase trend with the increasing decay levels of fallen trees. Among three microsites, the contents of soil nutrients were the lowest and pH were highest in the pit. As for the shallow soil layer, C/N, N/P and C/P of three microsites decreased with the increasing decay levels of fallen trees, while C/N in mound top and in pit bottom increased, N/P and C/P decreased, and the variation of C/P was consistent with that of available phosphorus. In conclusion, with the increasing decay levels of fallen trees, the contents of soil nutrients were signifi-cantly increased. There are significant differences of soil nutrients among different microsites, with the lowest values in the pit.