Search

Frozen pears, obtained by repeated freezing and thawing under cold outdoor conditions in winter, are very popular in northeast China. The effects of three freeze-thaw cycles (FT1–FT3) on Nanguo pear flavor were studied under fast (−80°C) and slow (−20°C) freezing conditions. Significant differences were found in the flavor of Nanguo pear after subsequent freeze-thaw cycles. The total soluble solid (TSS) content of fresh pear was 14.17 g/100 g and increased significantly after the first freeze-thaw cycle to 17.57–18.17 g/100 g. Lower TSS content was found in pears after the repeated freeze-thawing process. Citric acid was determined as the main organic acid of Nanguo pear. Its content and the overall content of organic acids decreased successively after each freezing and thawing cycle. The electronic tongue analysis results showed that the sourness of fresh pears generally decreased after their repeated freezing and thawing, that the odor of Nanguo pear changed significantly after freeze-thaw cycles, and that nitrogen oxides and hydrocarbons were the most differentiating odor compounds. The content of ethyl caproate was the highest in the volatile compound profile of the Nanguo pear and ranged from 377.26 to 526.77 μg/kg. In short, after repeated freezing and thawing, the changes in the chemical composition impart the frozen pear a unique flavor.

Changes in physio-biochemical metabolism, phenolics and antioxidant capacity during germination were studied in eight different wheat varieties. Results showed that germination enhanced sprout growth, and caused oxidative damage, but enhanced phenolics accumulation. Ferulic acid and p-coumaric acid were the main phenolic acids in wheat sprouts, and dihydroquercetin, quercetin and vitexin were the main flavonoids. The phenolic acid content of Jimai 44 was the highest on the 2th and 4th day of germination, and that of Bainong 307 was the highest on the 6th day. The flavonoid content of Hei jingang was the highest during whole germination. The enzymes activities of phenylalanine ammonia lyase (PAL), cinnamic acid 4-hydroxylase (C4H) and 4-coumarate coenzyme A ligase (4CL) were up-regulated. The activities of catalase, polyphenol oxidase and peroxidase were also activated. Antioxidant capacity of wheat sprouts was enhanced. The results provided new ideas for the production of naturally sourced phenolic rich foods.

Abstract Background Long noncoding RNAs (lncRNAs) have been shown to play important roles in the response of plants to various abiotic stresses, including drought, heat and salt stress. However, the identification and characterization of genome-wide salt-responsive lncRNAs in tobacco (Nicotiana tabacum L.) have been limited. Therefore, this study aimed to identify tobacco lncRNAs in roots and leaves in response to different durations of salt stress treatment. Results A total of 5,831 lncRNAs were discovered, with 2,428 classified as differentially expressed lncRNAs (DElncRNAs) in response to salt stress. Among these, only 214 DElncRNAs were shared between the 2,147 DElncRNAs in roots and the 495 DElncRNAs in leaves. KEGG pathway enrichment analysis revealed that these DElncRNAs were primarily associated with pathways involved in starch and sucrose metabolism in roots and cysteine and methionine metabolism pathway in leaves. Furthermore, weighted gene co-expression network analysis (WGCNA) identified 15 co-expression modules, with four modules strongly linked to salt stress across different treatment durations (MEsalmon, MElightgreen, MEgreenyellow and MEdarkred). Additionally, an lncRNA-miRNA-mRNA network was constructed, incorporating several known salt-associated miRNAs such as miR156, miR169 and miR396. Conclusions This study enhances our understanding of the role of lncRNAs in the response of tobacco to salt stress. It provides valuable information on co-expression networks of lncRNA and mRNAs, as well as networks of lncRNAs-miRNAs-mRNAs. These findings identify important candidate lncRNAs that warrant further investigation in the study of plant-environment interactions.

This study identified phenolic compounds in five flaxseed varieties and evaluated their antioxidant activities. Results showed significant variations in phenolic acids and flavonoids among the varieties. Longya 16 had the lowest flavonoid content, Longya 13 had the lowest phenolic acid content, while Longya 10 exhibited the highest content and diversity of polyphenols, including six flavonoids (vitexin, quercitrin, quercetin, apigenin, kaempfero1, (+)-dihydroquercetin) and five phenolic acids (gallic acid, vanillic acid, ferulic acid, sinapic acid, and 4-hydroxybenzoic acid). Antioxidant activity was assessed using DPPH and ABTS radical scavenging assays, and cell-based assays under tBHP-induced oxidative stress. Flaxseed polyphenol extracts significantly reduced ROS, MDA, and GSSG levels and increased SOD and CAT activities, preserving cell vitality and morphology. These findings confirmed the significant antioxidant activity of flaxseed polyphenols, providing a theoretical basis for their application in antioxidative functional areas.

Under the long-term effect of mineral resource exploitation, especially open-pit mining, ecosystems are severely disturbed. Constructing and optimizing urban ecological networks influenced by open-pit mines based on mine-city coordination helps integrate ecological restoration and the construction of urban ecological environments. We applied an InVEST model to Fushun City to evaluate urban ecosystem services under the influence of large open-pit mines. Twenty-one key patches important for maintaining landscape connectivity were screened as the ecological sources in the network, from which ecological resistance surfaces were constructed by combining the impacts of mines on the environment. Minimum cumulative resistance (MCR) and gravity models were then used to extract and classify ecological corridors favorable to species migration and diffusion. Fushun City had large spatial differences in ecosystem service functions, with high-value areas concentrated in the forest-rich Dongzhou District and the northern Shuncheng District. Under the influence of open-pit mining, the ecosystem service capacity of the region south of the Hunhe River was poor and lacked ecological sources. Urban ecological resistance surfaces reached a maximum in the open-pit mining area, and 210 ecological corridors were estimated using the MCR model, of which 46 were important. Only two corridors crossed the West and East open pit, forming two "ecological fracture surfaces." The Dongzhou and eastern Shuncheng districts had complex network structures and stable ecological environments. In contrast, the central and southern parts of Fushun City lacked ecological corridors owing to the influence of mining pits and gangue mountains, had simple network structures, and low connectivities with other sources. Combined with Fushun City's development plan, we propose that ecological network optimization should add new ecological source sites, reconstruct and repair ecological corridors, and upgrade ecological breakpoints. This study provides reference and basis for ecological network research in mining cities influenced by open-pit mines.

[This corrects the article DOI: 10.1371/journal.pone.0049468.].

Abstract Toxic protein aggregates can spread among neurons to promote human neurodegenerative disease pathology. We found that in C. elegans touch neurons intermediate filament proteins IFD-1 and IFD-2 associate with aggresome-like organelles and are required cell-autonomously for efficient production of neuronal exophers, giant vesicles that can carry aggregates away from the neuron of origin. The C. elegans aggresome-like organelles we identified are juxtanuclear, HttPolyQ aggregate-enriched, and dependent upon orthologs of mammalian aggresome adaptor proteins, dynein motors, and microtubule integrity for localized aggregate collection. These key hallmarks indicate that conserved mechanisms drive aggresome formation. Furthermore, we found that human neurofilament light chain (NFL) can substitute for C. elegans IFD-2 in promoting exopher extrusion. Taken together, our results suggest a conserved influence of intermediate filament association with aggresomes and neuronal extrusions that eject potentially toxic material. Our findings expand understanding of neuronal proteostasis and suggest implications for neurodegenerative disease progression.

Most traditional multi-aircraft flight path optimization methods are oriented toward area coverage, use static optimization models, and face the challenge of model mismatch under complex dynamic environments. Therefore, this study proposes a flight path optimization method for dynamic area coverage based on multi-aircraft radars. First, we introduce an attenuation factor to this method to characterize the actual coverage effect of airborne radar on a dynamic environment, and we take the area coverage rate under the dynamic area coverage background as the optimization function. After integrating the constraints of multi-dimensional flight path control parameters to be optimized, we built a mathematical model for dynamic area coverage flight path optimization based on multi-aircraft radars. Then, the stochastic optimization method is used to solve the flight path optimization problem of dynamic area coverage. Finally, the simulation results show that the proposed flight path optimization method can significantly improve the dynamic coverage performance in dynamic areas compared with the search mode using preset flight paths based on multi-aircraft radars. Compared with the traditional flight path optimization method oriented to static environments, the dynamic coverage performance of our proposed method is improved by approximately 6% on average.

Abstract Processing can affect milk properties and alter the composition of milk metabolites, which has corresponding effects on milk flavor and quality. It is quite important to study the safe quality control of milk processing. Therefore, the purpose of this study was to identify metabolites at different steps of ultra‐high‐temperature‐sterilized (UHT) milk processing using gas chromatography–mass spectrometry (GC–MS). These steps included raw milk, pasteurized milk (80°C for 15 s), semi‐finished milk (after pasteurizing, it was homogenized at 75°C with pressure of 250 bar), UHT milk (at 140°C for 10 s), and finished milk (homogenized UHT milk). A total of 66 metabolites were identified across all samples, including 30 metabolites in the chloroform layers of the milk samples and 41 metabolites in the water layers; 5 metabolites were found in both layers. The metabolites were primarily fatty acids, amino acids, sugars, and organic acids. For example, pasteurized and ultra‐high‐temperature‐sterilized kinds of milk had lactose contents similar to those of raw milk, with increases in saturated fatty acids such as hexadecanoic acid and octadecanoic acid. Additionally, these findings indicated that these methods of processing can affect the contents of some components of milk. Therefore, from the perspective of milk's nutritional value and consumer health, the excessive heating of dairy products should be avoided and the milk heat treatment process should be standardized from the source.

Reducing greenhouse gas emissions while improving productivity is the core of sustainable agriculture development. In recent years, rice ratooning has developed rapidly in China and other Asian countries, becoming an effective measure to increase rice production and reduce greenhouse gas emissions in these regions. However, the lower yield of ratooning rice caused by the application of a single nitrogen fertilizer in the ratooning season has become one of the main reasons limiting the further development of rice ratooning. The combined application of nitrogen and phosphorus plays a crucial role in increasing crop yield and reducing greenhouse gas emissions. The effects of combined nitrogen and phosphorus application on ratooning rice remain unclear. Therefore, this paper aimed to investigate the effect of combined nitrogen and phosphorus application on ratooning rice. Two hybrid rice varieties, ‘Luyou 1831’ and ‘Yongyou 1540’, were used as experimental materials. A control treatment of nitrogen-only fertilization (187.50 kg·ha−1 N) was set, and six treatments were established by reducing nitrogen fertilizer by 10% (N1) and 20% (N2), and applying three levels of phosphorus fertilizer: N1P1 (168.75 kg·ha−1 N; 13.50 kg·ha−1 P), N1P2 (168.75 kg·ha−1 N; 27.00 kg·ha−1 P), N1P3 (168.75 kg·ha−1 N; 40.50 kg·ha−1 P), N2P1 (150.00 kg·ha−1 N; 13.50 kg·ha−1 P), N2P2 (150.00 kg·ha−1 N; 27.00 kg·ha−1 P), and N2P3 (150.00 kg·ha−1 N; 40.50 kg·ha−1 P). The effects of reduced nitrogen and increased phosphorus treatments in ratooning rice on the yield, the greenhouse gas emissions, and the community structure of rhizosphere soil microbes were examined. The results showed that the yield of ratooning rice in different treatments followed the sequence N1P2 > N1P1 > N1P3 > N2P3 > N2P2 > N2P1 > N. Specifically, under the N1P2 treatment, the average two-year yields of ‘Luyou 1831’ and ‘Yongyou 1540’ reached 8520.55 kg·ha−1 and 9184.90 kg·ha−1, respectively, representing increases of 74.30% and 25.79% compared to the N treatment. Different nitrogen and phosphorus application combinations also reduced methane emissions during the ratooning season. Appropriately combined nitrogen and phosphorus application reduced the relative contribution of stochastic processes in microbial community assembly, broadened the niche breadth of microbial communities, enhanced the abundance of functional genes related to methane-oxidizing bacteria and soil ammonia-oxidizing bacteria in the rhizosphere, and decreased the abundance of functional genes related to methanogenic and denitrifying bacteria, thereby reducing greenhouse gas emissions in the ratooning season. The carbon footprint of ratooning rice for ‘Luyou 1831’ and ‘Yongyou 1540’ decreased by 25.82% and 38.99%, respectively, under the N1P2 treatment compared to the N treatment. This study offered a new fertilization pattern for the green sustainable development of rice ratooning.

Bacterial wilt, caused by the Ralstonia solanacearum species complex, is one of the most damaging bacterial diseases in tobacco and other Solanaceae crops. In this study, we conducted an analysis and comparison of transcriptome landscape changes in seedling roots of three tobacco BC4F5 lines, C244, C010, and C035, with different resistance to bacterial wilt at 3, 9, 24, and 48 h after R. solanacearum infection. A number of biological processes were highlighted for their differential enrichment between C244, C010, and C035, especially those associated with cell wall development, protein quality control, and stress response. Hence, we performed a genome-wide identification of seven cell wall development-related gene families and six heat shock protein (Hsp) families and proposed that genes induced by R. solanacearum and showing distinct expression patterns in C244, C010, and C035 could serve as a potential gene resource for enhancing bacterial wilt resistance. Additionally, a comparative transcriptome analysis of R. solanacearum-inoculated root samples from C244 and C035, as well as C010 and C035, resulted in the identification of a further 33 candidate genes, of which Nitab4.5_0007488g0040, a member of the pathogenesis-related protein 1 (PR-1) family, was found to positively regulate bacterial wilt resistance, supported by real-time quantitative PCR (qRT-PCR) and virus-induced gene silencing (VIGS) assays. Our results contribute to a better understanding of molecular mechanisms underlying bacterial wilt resistance and provide novel alternative genes for resistance improvement.

Strategically upcycling industrial wastes such as petroleum coke and dye wastewater into value-added materials through scalable and economic processes is an effective way to simultaneously tackle energy and environmental issues. Doping carbon electrodes with heteroatoms proves effective in significantly enhancing electrochemical performance through alterations in electrode wettability and electrical conductivity. This work reports the use of dye wastewater as the sole dopant source to synthesize N and S co-doped petroleum coke-based activated carbon (NS-AC) by the one-step pyrolysis method. More importantly, our wastewater and petroleum coke-derived activated carbon produced on a large scale (20 kg/batch) shows a specific surface area of 2582 m2 g−1 and an energy density of about 95 Wh kg−1 in a soft-packaged full cell with 1 M TEATFB/PC as the electrolyte. The scalable production method, together with the green and sustainable process, can be easily adopted and scaled by industry without the need for complex processes and/or units, which offers a convenient and green route to produce functionalized carbons from wastes at a low cost.

Aim: 20 mg of vonoprazan (VPZ20) is recommended in most countries to treat erosive esophagitis (EE). Whether other doses of vonoprazan, such as 5 mg (VPZ5), 10 mg (VPZ10), 20 mg (VPZ20), and 40 mg (VPZ40) are more effective is unknown. Materials & methods: Three databases were electronically searched to identify studies published before November 2021. Network meta-analysis was performed using STATA 14.0. Results: VPZ20 and VPZ40 were comparable to PPI, VPZ5 and VPZ10 in 4- and 8-week healing rates, and this was also detected in patients with refractory EE. All regimens resulted in similar treatment-emergent adverse events (TEAEs). However, VPZ40 ranked first for healing rate and TEAEs; however, VPZ20 ranked worst for TEAEs. Conclusion: Different doses of VPZ are comparable in efficacy and safety, but VPZ40 may be best in both effectiveness and safety.

Abstract Background Chronic obstructive pulmonary disease (COPD) is one of the diseases with high mortality and morbidity with complex pathogenesis. Airway remodeling is an unavoidable pathological characteristic. However, the molecular mechanisms of airway remodeling are incompletely defined. Methods lncRNAs highly correlated with transforming growth factor beta 1(TGF–β1) expression were chosen, the lncRNA ENST00000440406 (named HSP90AB1 Assoicated LncRNA 1, HSALR1) was chosen for further functional experiments. Dual luciferase and ChIP assay were used to detect the upstream of HSALR1, transcriptome sequencing, Cck–8, Edu, cell proliferation, cell cycle assay, and WB detection of pathway levels confirmed the effect of HSALR1 on fibroblast proliferation and phosphorylation levels of related pathways. Mice was infected with adeno–associated virus (AAV) to express HSALR1 by intratracheal instillation under anesthesia and was exposure to cigarette smoke, then mouse lung function was performed and the pathological sections of lung tissues were analyzed. Results Herein, lncRNA HSALR1 was identified as highly correlated with the TGF–β1 and mainly expressed in human lung fibroblasts. HSALR1 was induced by Smad3 and promoted fibroblasts proliferation. Mechanistically, it could directly bind to HSP90AB1 protein, and acted as a scaffold to stabilize the binding between Akt and HSP90AB1 to promote Akt phosphorylation. In vivo, mice expressed HSALR1 by AAV was exposure to cigarette smoke (CS) for COPD modeling. We found that lung function was worse and airway remodeling was more pronounced in HSLAR1 mice compare to wild type (WT) mice. Conclusion Our results suggest that lncRNA HSALR1 binds to HSP90AB1 and Akt complex component, and enhances activity of the TGF–β1 smad3–independent pathway. This finding described here suggest that lncRNA can participate in COPD development, and HSLAR1 is a promising molecular target of COPD therapy.

BackgroundThe global outbreak of COVID-19, and the limited availability of clinical treatments, forced researchers around the world to search for the pathogenesis and potential treatments. Understanding the pathogenesis of SARS-CoV-2 is crucial to respond better to the current coronavirus disease 2019 (COVID-19) pandemic.MethodsWe collected sputum samples from 20 COVID-19 patients and healthy controls. Transmission electron microscopy was used to observe the morphology of SARS-CoV-2. Extracellular vesicles (EVs) were isolated from sputum and the supernatant of VeroE6 cells, and were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western-Blotting. Furthermore, a proximity barcoding assay was used to investigate immune-related proteins in single EV, and the relationship between EVs and SARS-CoV-2.ResultTransmission electron microscopy images of SARS-COV-2 virus reveal EV-like vesicles around the virion, and western blot analysis of EVs extracted from the supernatant of SARS-COV-2-infected VeroE6 cells showed that they expressed SARS-COV-2 protein. These EVs have the infectivity of SARS-COV-2, and the addition can cause the infection and damage of normal VeroE6 cells. In addition, EVs derived from the sputum of patients infected with SARS-COV-2 expressed high levels of IL6 and TGF-β, which correlated strongly with expression of the SARS-CoV-2 N protein. Among 40 EV subpopulations identified, 18 differed significantly between patients and controls. The EV subpopulation regulated by CD81 was the most likely to correlate with changes in the pulmonary microenvironment after SARS-CoV-2 infection. Single extracellular vesicles in the sputum of COVID-19 patients harbor infection-mediated alterations in host and virus-derived proteins.ConclusionsThese results demonstrate that EVs derived from the sputum of patients participate in virus infection and immune responses. This study provides evidence of an association between EVs and SARS-CoV-2, providing insight into the possible pathogenesis of SARS-CoV-2 infection and the possibility of developing nanoparticle-based antiviral drugs.

The use of machine learning to characterise quantum states has been demonstrated, but usually training the algorithm using data from the same state one wants to characterise. Here, the authors show an algorithm that can learn all states that share structural similarities with the ones used for the training.

DNA methyltransferase 3A, a mutated gene associated with hematologic malignancies in age-related clonal haematopoiesis lacks targeted therapies. Here, the authors screen carbon nanomaterials and find graphdiyne oxide binds to mutant cells and disrupts cellular processes with a therapeutic effect in vitro and in vivo.

Phytosterols have received extensive attention owing to their excellent cholesterol-lowering activity and the role in cardiovascular diseases prevention. However, poor solubility in both oil and water limited the application of free phytosterols in the food industry. Chemical or enzymatic modifications were effective to improve the physicochemical properties as well as the bioavailability and cholesterol-lowering activity of phytosterols. Higher oil solubility and lower melting point of phytosterols have been achieved by esterification and transesterification with fatty acids and triacylglycerols so as to enhance the bioavailability, reduce formation of precipitates, and improve the sensory quality of products. While the researches on the improvement on its water solubility is a hot topic. Hydrophilic phytosterol derivatives have promising applications in the food industry because most of foods belong to aqueous matrix. Hydrophilic modification is useful and meaningful for phytosterols in both industrial and commercial applications. This review mainly highlights the hydrophilic phytosterol derivatives in the following aspects: (i) hydrophilic modifications of phytosterols by coupling with various polar components; (ii) cholesterol-lowering activity and possible molecular mechanisms of hydrophilic phytosterol derivatives on reducing serum cholesterol level; and (iii) safety evaluation of hydrophilic phytosterol derivatives in cell-culture studies, animal models and clinical trials.

Abstract Background Zinc finger protein 143(ZNF143), a member of the Krüppel C2H2-type zinc finger protein family, is strongly associated with cell cycle regulation and cancer development. A recent study suggested that ZNF143 plays as a transcriptional activator that promotes hepatocellular cancer (HCC) cell proliferation and cell cycle transition. However, the exact biological role of ZNF143 in liver regeneration and normal liver cell proliferation has not yet been investigated. Methods In our study, we constructed a stable rat liver cell line (BRL-3A) overexpressing ZNF143 and then integrated RNA-seq and Cleavage Under Targets and Tagmentation (CUT&Tag) data to identify the mechanism underlying differential gene expression. Results Our results show that ZNF143 expression is upregulated during the proliferation phase of liver regeneration after 2/3 partial hepatectomy (PH). The cell counting kit-8 (CCK-8) assay, EdU staining and RNA-seq data analyses revealed that ZNF143 overexpression (OE) significantly inhibited BRL-3A cell proliferation and cell cycle progression. We then performed CUT&Tag assays and found that approximately 10% of ZNF143-binding sites (BSs) were significantly changed genome-wide by ZNF143 OE. However, CCCTC-binding factor (CTCF) binding to chromatin was not affected. Interestingly, the integration analysis of RNA-seq and CUT&Tag data showed that some of genes affected by ZNF143 differential BSs are in the center of each gene regulation module. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these genes are critical in the maintenance of cell identity. Conclusion These results indicated that the expression level of ZNF143 in the liver is important for the maintenance of cell identity. ZNF143 plays different roles in HCC and normal liver cells and may be considered as a potential therapeutic target in liver disease.

Abstract Complex processes often arise from sequences of simpler interactions involving a few particles at a time. These interactions, however, may not be directly accessible to experiments. Here we develop the first efficient method for unravelling the causal structure of the interactions in a multipartite quantum process, under the assumption that the process has bounded information loss and induces causal dependencies whose strength is above a fixed (but otherwise arbitrary) threshold. Our method is based on a quantum algorithm whose complexity scales polynomially in the total number of input/output systems, in the dimension of the systems involved in each interaction, and in the inverse of the chosen threshold for the strength of the causal dependencies. Under additional assumptions, we also provide a second algorithm that has lower complexity and requires only local state preparation and local measurements. Our algorithms can be used to identify processes that can be characterized efficiently with the technique of quantum process tomography. Similarly, they can be used to identify useful communication channels in quantum networks, and to test the internal structure of uncharacterized quantum circuits.

Human NIMA-related kinases have primarily been studied for their roles in cell cycle progression (NEK1/2/6/7/9), checkpoint-DNA-damage control (NEK1/2/4/5/10/11), and ciliogenesis (NEK1/4/8). We previously showed that Caenorhabditis elegans NEKL-2 (NEK8/9 homolog) and NEKL-3 (NEK6/7 homolog) regulate apical clathrin-mediated endocytosis (CME) in the worm epidermis and are essential for molting. Here we show that NEKL-2 and NEKL-3 also have distinct roles in controlling endosome function and morphology. Specifically, loss of NEKL-2 led to enlarged early endosomes with long tubular extensions but showed minimal effects on other compartments. In contrast, NEKL-3 depletion caused pronounced defects in early, late, and recycling endosomes. Consistently, NEKL-2 was strongly localized to early endosomes, whereas NEKL-3 was localized to multiple endosomal compartments. Loss of NEKLs also led to variable defects in the recycling of two resident cargoes of the trans-Golgi network (TGN), MIG-14/Wntless and TGN-38/TGN38, which were missorted to lysosomes after NEKL depletion. In addition, defects were observed in the uptake of clathrin-dependent (SMA-6/Type I BMP receptor) and independent cargoes (DAF-4/Type II BMP receptor) from the basolateral surface of epidermal cells after NEKL-2 or NEKL-3 depletion. Complementary studies in human cell lines further showed that siRNA knockdown of the NEKL-3 orthologs NEK6 and NEK7 led to missorting of the mannose 6-phosphate receptor from endosomes. Moreover, in multiple human cell types, depletion of NEK6 or NEK7 disrupted both early and recycling endosomal compartments, including the presence of excess tubulation within recycling endosomes, a defect also observed after NEKL-3 depletion in worms. Thus, NIMA family kinases carry out multiple functions during endocytosis in both worms and humans, consistent with our previous observation that human NEKL-3 orthologs can rescue molting and trafficking defects in C. elegans nekl-3 mutants. Our findings suggest that trafficking defects could underlie some of the proposed roles for NEK kinases in human disease.

Caenorhabditis elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons in C. elegans are engulfed by surrounding hypodermal skin cells and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that exopher removal requires hypodermal actin and Arp2/3, and the hypodermal plasma membrane adjacent to newly formed exophers accumulates dynamic F-actin during budding. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents requires phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor-associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease.

Unextendible product bases (UPBs) play a key role in the study of quantum entanglement and nonlocality. Here we provide an equivalent characterization of UPBs in graph-theoretic terms. Different from previous graph-theoretic investigations of UPBs, which focused mostly on the orthogonality relations between different product states, our characterization includes a graph-theoretic reformulation of the unextendibility condition. Building on this characterization, we develop a constructive method for building UPBs in low dimensions and shed light on the open question of whether there exist genuinely unextendible product bases (GUPBs), that is, multipartite product bases that are unextendible with respect to every possible bipartition. We derive a lower bound on the size of any candidate GUPB, significantly improving over the state of the art. Moreover, we show that every minimal GUPB saturating our bound must be associated to regular graphs and discuss a possible path towards the construction of a minimal GUPB in a tripartite system of minimal local dimension. Finally, we apply our characterization to the problem of distinguishing UPB states under local operations and classical communication, deriving a necessary condition for reliable discrimination in the asymptotic limit.

The bHLH transcription factors play pivotal roles in plant growth and development, production of secondary metabolites and responses to various environmental stresses. Although the bHLH genes have been well studied in model plant species, a comprehensive investigation of the bHLH genes is required for tobacco with newly obtained high-quality genome. In the present study, a total of 309 NtbHLH genes were identified and can be divided into 23 subfamilies. The conserved amino acids which are essential for their function were predicted for the NtbHLH proteins. Moreover, the NtbHLH genes were conserved during evolution through analyzing the gene structures and conserved motifs. A total of 265 NtbHLH genes were localized in the 24 tobacco chromosomes while the remained 44 NtbHLH genes were mapped to the scaffolds due to the complexity of tobacco genome. Moreover, transcripts of NtbHLH genes were obviously tissue-specific expressed from the gene-chip data from 23 tobacco tissues, and expressions of 20 random selected NtbHLH genes were further confirmed by quantitative real-time PCR, indicating their potential functions in the plant growth and development. Importantly, overexpressed NtbHLH86 gene confers improve drought tolerance in tobacco indicating that it might be involved in the regulation of drought stress. Therefore, our findings here provide a valuable information on the characterization of NtbHLH genes and further investigation of their functions in tobacco.

Abstract Background Frailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association. Methods The Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41–97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment. Results A total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age. Conclusions A higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.

Black shank disease caused by Phytophthora nicotianae is one of the most important diseases in tobacco worldwide and can result in a devastating loss in tobacco cultivation. Many efforts have been carried out to identify the chromosome segment from Nicotiana plumbaginifolia containing a resistance locus carrying a gene named Php; however, the Php gene has not been cloned, and knowledge of the potential mechanism of the Php gene in the resistant lines is limited. To further characterize the resistance mechanism of the Php gene, we first used the resistant line “RBST” and the susceptible cultivar “Honghuadajinyuan” (HD) to obtain the near-isogenic line RBS89 containing the Php gene from RBST. RBS89 showed high resistance to black shank disease. Transcriptomic and iTRAQ analyses were applied to explore the potential defense mechanisms in RBS89 plants in comparison with HD plants with or without inoculation. Many differentially expressed genes (DEGs) and proteins were identified, and some pathogenesis-related (PR) proteins were extensively abundant in the RBS89 plants when compared with the HD plants in response to black shank disease. Importantly, overexpression of the PR gene NtPR-1B in HD plants improved the resistance of tobacco plants to black shank disease, indicating that NtPR-1B and Php genes might have similar roles in protecting tobacco from black shank disease. However, the relationship between NtPR-1B and Php genes requires further analysis. Therefore, our study provides valuable information for breeding tobacco cultivars with black shank disease resistance and sheds light on the defense mechanism of black shank disease in tobacco for enhancing Phytophthora resistance in other Solanaceae crops.

Proteins of the Nitrate Transporter 1/Peptide Transporter (NPF) family transport a diverse variety of substrates, such as nitrate, peptides, hormones and chloride. In this study, a systematic analysis of the tobacco (Nicotiana tabacum) NPF family was performed in the cultivated ‘K326’. In total, 143 NtNPF genes were identified and phylogenetically classified into eight subfamilies, NPF1 to NPF8, based on the classification of NPF families in other plant species. The chromosomal locations and structures of the NtNPF genes were analyzed. The expression profiles of NtNPF genes under NaCl stress were analyzed to screen the possible NPF genes involving in chloride regulation in tobacco. Most NtNPF6 genes responded to salt stress in the roots and leaves. The expression of NtNPF6.13 was significantly down-regulated after salt stress for 12h. The chloride content was reduced in the roots of ntnpf6.13 mutant. These findings support the participation of NtNPF6.13 in chloride uptake. Several other NtNPF genes that play potential roles in chloride metabolism of tobacco require further study.

When temperature and refractive index are measured in same spectrum, the measurement range of parameters is generally narrow due to bandwidth limitation. We proposed a sensor for simultaneous measurement of them in a wide wavelength range for this problem. The proposed sensor is a dual-channel structure based on the photonic crystal fiber (PCF) with three air holes and a polished plane. The silver film deposited on the polished plane is responsible for refractive index measurement, and the sodium film and polydimethylsiloxane (PDMS) filled in an air hole for temperature measurement. According to research findings, the two kinds of metal films work in different wavebands, which increases the sensing bandwidth and the measurement range of the parameters to be measured. Numerical results show that when the refractive index of analyte is 1.35 ∼ 1.41 and the temperature is 10 ∼ 60℃, the maximum spectral sensitivity of the sensor is 8400 nm/RIU and 10.2 nm/℃, respectively. The results show that the performance of the sensor is not sensitive to structural parameters. It makes the sensor easy to manufacture. The excellent performances and wide detection range make the proposed sensor have a good application prospect in biochemical detection, environmental monitoring, medical sensing, and other fields.

Objective This study aims to characterise and evaluate the largest 100 hospitals in the USA that have adopted aggressive collection tactics to pursue patients with unpaid medical bills, such as lawsuits, wage garnishments and liens.Design Cross-sectional study.Setting We examined state and county court record systems to measure the magnitude and prevalence of these practices at the largest 100 hospitals in the UA between 1 January 2018 and 31 July 2020.Main outcomes measures The main outcome of this study was the number of lawsuits, wage garnishments and liens. A secondary outcome was the characterisation of a hospital’s safety, charitability, size and financial practices.Results Between 1 January 2018 and 31 July 2020, 26 hospitals filed 38 965 court actions (lawsuits, wage garnishments and liens) against patients for unpaid medical debt. For 16 of 26 hospitals, the dollar amount pursued in the court claim was available for 100% of cases, totalling US$71.8 million. The average aggregate amount sought by hospital lawsuits during the study period was US$4.5 million. Three hospitals filed US$56.2 million in amounts pursued in court, or 78.3% of the total amount pursued by all hospitals in the sample. In the remaining 74 hospitals, the study team did not identify extraordinary collection actions through the court system.Conclusions Standardised medical debt collections best practices and metrics of medical debt collections quality are needed to increase public accountability for hospitals, particularly non-profit hospitals. There is a need to re-evaluate Internal Revenue Service rules pertaining to non-profit hospitals’ tax-exempt status to ensure tax-exempt hospitals provide community benefits commensurate with the value of tax exemption.

Our previous work have shown that certain subpopulations of Klebsiella pneumoniae exhibit significant phenotypic changes under simulated microgravity (SMG), including enhanced biofilm formation and cellulose synthesis, which may be evoked by changes in gene expression patterns. It is well known that prokaryotic cells genomic DNA can be hierarchically organized into different higher-order three-dimensional structures, which can highly influence gene expression. It is remain elusive whether phenotypic changes induced by SMG in the subpopulations of K. pneumoniae are driven by genome higher-order structural changes. Here, we investigated the above-mentioned issue using the wild-type (WT) K. pneumoniae (WT was used as a control strain and continuously cultivated for 2 weeks under standard culture conditions of normal gravity) and two previous identified subpopulations (M1 and M2) obtained after 2 weeks of continuous incubation in a SMG device. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, we found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that most differentially expressed genes (DEGs) were upregulated, whereas a few DEGs were downregulated in M1 and M2. The functions of both types DEGs were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Using combined analysis of multi-omics data, we discovered that most upregulated DEGs were significantly enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that K. pneumoniae may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.

Phytosterols, which are naturally occurring in plants, have excellent nutritional and health values on lowering both the blood cholesterol level and the risk of cardiovascular diseases. Edible oils are the main source of daily intake of phytosterols, whereas the properties of phytosterols may vary a lot depending on their sources. During the processing of edible oil including refining and frying, phytosterol's content fluctuates, which influences the properties of the final product. Phytosterols and their derivatives undergo physical migration between different phases and chemical conversion during the processing, which reduces the quality and the commercial value of edible oils. Therein, the loss of phytosterols is the major concern in the process of neutralization and deodorization. In addition, oxidation and thermal degradation of phytosterols occur simultaneously during frying, which also reduces the content of phytosterols. Nevertheless, the oil matrix has a promoting or an inhibitory effect on the thermal oxidation of phytosterols. Therefore, various efforts have been devoted to analyzing and improving the remaining contents of phytosterols in edible oil. Regardless of the processing method, temperature plays an important role in the loss of phytosterols. At present, the main analysis methods of phytosterols include gas chromatography and liquid chromatography, in which the pretreatment of different types of phytosterols is also a crucial step. This review focused on the following topics comprehensively: (i) the distribution of phytosterols in the oil-containing plants and edible oils during the refining processing; (ii) the pretreatment and analysis methods of various phytosterols (free phytosterols, phytosteryl fatty acid esters, phytosteryl glycosides and acylated phytosteryl glycosides); (iii) the variation of phytosterols in process of esterification and oxidation, storage and so on. The study also proposed that the investigation in the loss and safety of phytosterols during processing of the vegetable oils should be proceeded further in combination with efficient and accurate chromatography methods.

Hospitals acquire and maintain long-term operating assets such as land, buildings, and equipment. In this study, we analyzed hospitals’ long-term assets acquisitions data extracted from the Medicare Cost Report, a mandatory annual filing for all Medicare-certified hospitals. The first objective of this study is to examine the time trend of land, buildings, and equipment acquisitions of all general acute care hospitals in the U.S. from 2005 to 2019 to understand the relative magnitude and temporal changes for the operating assets. The second objective is to examine the 15-year accumulated acquisitions of land, buildings, and equipment per capita in each state to understand the variations of potential access to hospital operating resources across states. To understand the longitudinal changes in acquisitions of operating assets for each year from 2005 to 2019, we calculated the total acquisition amounts across all hospitals for land, buildings, and equipment, respectively, and adjusted the amounts to 2019 dollars based on the consumer price index (CPI). For each state (including Washington D.C.) and the whole nation, the 15-year accumulated CPI-adjusted acquisition amounts per capita for land, buildings, and equipment were also calculated, respectively. The nationwide acquisitions of those operating assets grew rapidly from 2005 to 2008 followed by a negative overall growth from 2008 to 2014 and since 2015, started increasing steadily again. In 2019, U.S. general acute care hospitals acquired $3.0 billion of land, $44.6 billion of buildings, and $33.9 billion of equipment. Huge geographical variation in per capita cumulative total asset investment were also found with the first place North Dakota having a per capita investment that is almost four times higher than that in the lowest ranked state of Alabama.

Background: Since the novel coronavirus disease (COVID-19) has been a worldwide pandemic, the early surveillance and public health emergency disposal are considered crucial to curb this emerging infectious disease. However, studies of COVID-19 on this topic in China are relatively few.Methods: A case-comparison study was conducted using a set of six key time nodes to form a reference framework for evaluating early surveillance and public health emergency disposal between H7N9 avian influenza (2013) in Shanghai and COVID-19 in Wuhan, China.Findings: A report to the local Center for Disease Control and Prevention, China, for the first hospitalized patient was sent after 6 and 20 days for H7N9 avian influenza and COVID-19, respectively. In contrast, the pathogen was identified faster in the case of COVID-19 than in the case of H7N9 avian influenza (12 vs. 31 days). The government response to COVID-19 was 10 days later than that to avian influenza. The entire process of early surveillance and public health emergency disposal lasted 5 days longer in COVID-19 than in H7N9 avian influenza (46 vs. 41 days).Conclusions: The identification of the unknown pathogen improved in China between the outbreaks of avian influenza and COVID-19. The longer emergency disposal period in the case of COVID-19 could be attributed to the government's slower response to the epidemic. Improving public health emergency management could lessen the adverse social effects of emerging infectious diseases and public health crisis in the future.

The objective of the study was to elucidate the stearoyl-coenzyme A desaturase (SCD1)-dependent gene network of c9, t11-CLA biosynthesis in MAC-T cells from an energy metabolism perspective. The cells were divided into the CAY group (firstly incubated with CAY10566, a chemical inhibitor of SCD1, then incubated with trans-11-octadecenoic acid, (TVA)), the TVA group (only TVA), and the control group (without CAY, TVA). The c9, t11-CLA, and TVA contents were determined by gas chromatography. The mRNA levels of SCD1 and candidate genes were analyzed via real-time PCR. Tandem mass tag (TMT)-based quantitative proteomics, bioinformatic analysis, parallel reaction monitoring (PRM), and small RNA interference were used to explore genes involved in the SCD1-dependent c9, t11-CLA biosynthesis. The results showed that the SCD1 deficiency led by CAY10566 blocked the biosynthesis of c9, t11-CLA. In total, 60 SCD1-related proteins mainly involved in energy metabolism pathways were primarily screened by TMT-based quantitative proteomics analysis. Moreover, 17 proteins were validated using PRM analysis. Then, 11 genes were verified to have negative relationships with SCD1 after the small RNA interference analysis. Based on the above results, we concluded that genes involved in energy metabolism pathways have an impact on the SCD1-dependent molecular mechanism of c9, t11-CLA biosynthesis.

The traditional optical fiber-based twist sensing has the disadvantage of low sensitivity and difficulty of distinguishing the twist direction. Moreover, chiral isomerism may lead to sensing errors. In this paper, a six-hole helical microstructured optical fiber (HMSF) with a thin-gold-film-coat based on the surface plasmon resonance (SPR) effect was designed. The twist sensing characteristics of this fiber were further analyzed. Numerical calculation and analysis show that the combination of helical effect and SPR effect can design an HMSF-based sensor that is very sensitive to distortion. In the torsion range of ±300°, the distortion sensitivity can reach 2470.7 pm/(rad/m), and the linear correlation coefficient is 0.99996. Based on the special sensing mechanism, it has a good linear coefficient over a large range. Additionally, the direction of the twist can be easily discerned. The HMSF in this work not only has high sensitivity, high linearity, high fault tolerance rate, and a wide range of measurement, but is also easy to manufacture. Therefore, it is promising in the field of twist sensing and has a good application prospect.

Abstract Background Abscisic acid (ABA) is an important phytohormone for plant growth, development and responding to stresses such as drought, salinity, and pathogen infection. Pyrabactin Resistance 1 (PYR1)/PYR1-Like (PYL)/Regulatory Component of ABA Receptor (RCAR) (hereafter referred to as PYLs) has been identified as the ABA receptors. The PYL family members have been well studied in many plants. However, the members of PYL family have not been systematically identified at genome level in cultivated tobacco (Nicotiana tabacum) and its two ancestors. In this study, the phylogenic relationships, chromosomal distribution, gene structures, conserved motifs/regions, and expression profiles of NtPYLs were analyzed. Results We identified 29, 11, 16 PYLs in the genomes of allotetraploid N. tabacum, and its two diploid ancestors N. tomentosiformis and N. sylvestris, respectively. The phylogenetic analysis revealed that NtPYLs can be divided into three subfamilies, and each NtPYL has one counterpart in N. sylvestris or N. tomentosiformis. Based on microarray analysis of NtPYL transcripts, four NtPYLs (from subfamily II, III), and five NtPYLs (from subfamily I) are highlighted as potential candidates for further functional characterization in N. tabacum seed development, response to ABA, and germination, and resistance to abiotic stresses, respectively. Interestingly, the expression profiles of members in the same NtPYL subfamily showed somehow similar patterns in tissues at different developmental stages and in leaves of seedlings under drought stress, suggesting particular NtPYLs might have multiple functions in both plant development and drought stress response. Conclusions NtPYLs are highlighted for important functions in seed development, germination and response to ABA, and particular in drought tolerance. This work will not only shed light on the PYL family in tobacco, but also provides some valuable information for functional characterization of ABA receptors in N. tabacum.

Mutations in glycyl-tRNA synthetase (GlyRS) cause Charcot-Marie-Tooth disease, a neuromuscular disorder characterized by axonal degeneration. Here the authors show that mutant GlyRS interacts with histone deacetylase 6, resulting in increased deacetylation of α-tubulin and axonal transport deficits.

Abstract Background As the most populous nation in the world, China has now becoming an emerging ageing society. Shanghai is the first city facing the challenge of ageing demographics. Against this background, a study that employs self-rated health (SRH) assessment system was designed to explore the health status of Shanghai elders, and learn their attitudes toward health issues; as well as to investigate the determinants of SRH among Shanghai elders. Understanding SRH is crucial for finding appropriate solutions that could effectively tackle the increasing eldercare demand. Methods This study adopted a quantitative research strategy. Using a multistage stratified cluster sampling method, we conducted a questionnaire survey in August 2011 in Shanghai, which collected 2001 valid survey responses. SRH assessments were categorized by five levels: very good, fairly good, average, fairly poor, or poor. The respondents’ functional status was evaluated using the Barthel index of activities for daily living. In the data analysis, we used chi-squared test to determine differences in socio-demographic characteristics among various groups. Along with statistics, several logistic regression models were designed to determine the associations between internal influence factors and SRH. Results Younger age (χ2 = 27.5, p

Abstract The mechanism by which dominantly inherited mutations in the housekeeping gene GARS, which encodes glycyl-tRNA synthetase (GlyRS), mediate selective peripheral nerve toxicity resulting in Charcot-Marie-Tooth disease type 2D (CMT2D) is still largely unresolved. The transmembrane receptor protein neuropilin 1 (Nrp1) was recently identified as an aberrant extracellular binding partner of mutant GlyRS. Formation of the Nrp1/mutant GlyRS complex antagonises Nrp1 interaction with one of its main natural ligands, vascular endothelial growth factor-A (VEGF-A), contributing to neurodegeneration. However, reduced extracellular binding of VEGF-A to Nrp1 is known to disrupt post-natal blood vessel development and growth. We therefore analysed the vascular system at early and late symptomatic time points in CMT2D mouse muscles, retina, and sciatic nerve, as well as in embryonic hindbrain. Mutant tissues show no difference in blood vessel diameter, density/growth, and branching from embryonic development to three months, spanning the duration over which numerous sensory and neuromuscular phenotypes manifest. Our findings indicate that mutant GlyRS-mediated disruption of Nrp1/VEGF-A signalling is permissive to maturation and maintenance of the vasculature in CMT2D mice.

Ornithine decarboxylase (ODC) catalyzes ornithine decarboxylation to yield putrescine, a key precursor of polyamines, and tropane alkaloids (TAs). Here, to investigate in depth the role of ODC in polyamine/TA biosynthesis and to provide a candidate gene for engineering polyamine/TA production, the ODC gene (HnODC) was characterized from Hyoscyamus niger, a TA-producing plant. Our phylogenetic analysis revealed that HnODC was clustered with ODC enzymes of plants. Experimental work showed HnODC highly expressed in H. niger roots and induced by methyl jasmonate (MeJA). In the MeJA treatment, the production of both putrescine and N-methylputrescine were markedly promoted in roots, while contents of putrescine, spermidine, and spermine were all significantly increased in leaves. By contrast, MeJA did not significantly change the production of either hyoscyamine or scopolamine in H. niger plants. Building on these results, the 50-kDa His-tagged HnODC proteins were purified for enzymatic assays. When ornithine was fed to HnODC, the putrescine product was detected by HPLC, indicating HnODC catalyzed ornithine to form putrescine. Finally, we also investigated the enzymatic kinetics of HnODC. Its Km, Vmax, and Kcat values for ornithine were respectively 2.62 ± 0.11 mM, 1.87 ± 0.023 nmol min-1 μg-1 and 1.57 ± 0.015 s-1, at pH 8.0 and at 30°C. The HnODC enzyme displays a much higher catalytic efficiency than most reported plant ODCs, suggesting it may be an ideal candidate gene for engineering polyamine/TA biosynthesis.

Community health centres (CHCs) are the health gatekeepers of the local population. Location and numbers of the CHCs affect fairness and effectiveness with regard to access to primary health care. In the past, the distribution of the CHCs was solely empiric-based. The goal of this study was to devise a method for CHC distribution based on the principle of improving equity as well as ensuring efficiency. We tested the effectiveness and operability of the method through a process of revision and simulation using Guangdong Province, China as sample district. A methodology based on literature review and expert consultation was repeatedly applied until an ideal result had been reached. A hexagonal, mesh-based method was developed and used to find a solution where the CHCs could be distributed where their location would be the most needed and total number suitable. Testing the effectiveness of the proposed plan, we found the proportion of area covered to be 52.8% and the proportion of the population covered 80.7%, which is 15.4% and 14.7%, respectively, better than before. It was concluded that the hexagonal mesh-based, distribution method can effectively define the location as well as the number or required CHCs, not only improving the accessibility for residents to primary health care services but also maximizing cost-effectiveness. Management of the city by grid is a new idea in urban management, which improves rationality of planning and also may be applied for many different purposes in addition to CHC localization.

Ciprofloxacin, a third-generation fluoroquinolones (FQs) antibiotic, is observed to increasingly pollute the environment. In this study, a three-dimensional reduced graphene oxide-attapulgite-based catalyst Fe2O3/RGO-ATP was prepared and used to analyze the degradation of ciprofloxacin in a heterogeneous Fenton reaction. The heterogeneous catalyst Fe2O3/RGO-ATP was prepared by a one-step hydrothermal method, and the samples were characterized using BET(Brunauer-Emmett-Teller) surface area, Raman spectroscopy, X-ray diffraction (XRD), Fourier infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The effect of reaction time, temperature, pH, initial concentration, H2O2 dosage and reuse time on the degradation of ciprofloxacin by the catalyst Fe2O3/RGO-ATP was investigated. The optimum conditions of degradation of ciprofloxacin are observed to be 60 °C, pH 5, H2O2 concentration of 2.9724 mmol/L, and initial ciprofloxacin concentration of 50 mg/L. The catalyst could be reused several times with a decline in catalytic capacity. Fourier-transform ion cyclotron resonance mass spectrometer (FT) was also employed to study the degradation products of ciprofloxacin in the aqueous solution. The results show that the heterogeneous catalyst Fe2O3/RGO-ATP possessed an excellent ability for the catalytic degradation of ciprofloxacin. Direct hydroxyl oxidation is noted to be the main pathway of degradation of ciprofloxacin, and no defluorination reaction is observed during the degradation process.

We design quantum compression algorithms for parametric families of tensor network states. We first establish an upper bound on the amount of memory needed to store an arbitrary state from a given state family. The bound is determined by the minimum cut of a suitable flow network, and is related to the flow of information from the manifold of parameters that specify the states to the physical systems in which the states are embodied. For given network topology and given edge dimensions, our upper bound is tight when all edge dimensions are powers of the same integer. When this condition is not met, the bound is optimal up to a multiplicative factor smaller than 1.585. We then provide a compression algorithm for general state families, and show that the algorithm runs in polynomial time for matrix product states.

Background and study aims Endoscopic ultrasound-guided drainage is an effective and accepted primary modality for management of pancreatic pseudocyst (PP). A lumen-apposing metal stent (LAMS) has recently been developed specifically for drainage of pancreatic fluid collections which may be superior to using traditional plastic stents (PS) but is more expensive. Because use of a stent involves a risk of unplanned endoscopy, percutaneous drainage (PCD) and surgery, their costs should also be included in the comparison and a cost-effectiveness analysis of LAMS and PS should therefore be performed Patients and methods A decision tree was developed assessing both endoscopic drainage strategies for patients with PP: LAMS and PS over a 6-month time horizon. For each strategy, inpatients received a stent and were followed for subsequent need for direct further interventions or adverse events leading to unplanned endoscopy, PCD, surgery, or successful endoscopic drainage using probabilities obtained from the literature. The unit of effectiveness was successful endoscopic drainage without need for PCD or surgery. Sensitivity analyses were performed. Results Success rates were 93.9 % for LAMS and 96.96 % for PS. Respective costs per successful drainage were US $ 18,129 (LAMS) and US $ 10,403 (PS). The LAMS strategy was thus characterized as dominated by the PS approach because it was costlier and less effective than PS. Both deterministic and probabilistic sensitivity analyses confirmed the robustness of these findings. Conclusion Use of LAMS is not less effective and more costly than PS in management of patients with PP. As such, PS should be preferred over LAMS as initial management of these patients.

MADS-box genes play a pivotal role in various processes, including floral and seed development, controlling flowering time, regulation of fruits ripening, and respond to abiotic and biotic stressors in planta. Tobacco (Nicotiana tabacum) has been widely used as a model plant for analyzing the gene function, however, there has been less information on the regulation of flowering, and the associated genes. In the present study, a total of 168 NtMADS-box genes were identified from tobacco, and their phylogenetic relationship, chromosome locations, and gene structures were further analyzed. NtMADS-box genes can be clustered into four sub-families of Mα, Mγ, MIKC*, and MIKCC. A total of 111 NtMADS-box genes were distributed on 20 chromosomes, and 57 NtMADS-box genes were located on the unanchored scaffolds due to the complex and incomplete assembly of the tobacco genome. Expression profiles of NtMADS-box genes by microarray from 23 different tissues indicated that members in different NtMADS-box gene subfamilies might play specific roles in the growth and flower development, and the transcript levels of 24 NtMADS-box genes were confirmed by quantitative real-time PCR. Importantly, overexpressed NtSOC1/NtMADS133 could promote early flowering and dwarfism in transgenic tobacco plants. Therefore, our findings provide insights on the characterization of NtMADS-box genes to further study their functions in plant development.

Aims. Protein kinase-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 alpha (eIF2α) pathway mutations lead to failure of β-cell function. The aim of this article was to assess the association between eIF2α and the risk of glucose metabolism abnormalities. Methods. Two eIF2α SNPs (rs9840992 T>C and rs13072593 A>G) were selected based on CHB data from HapMap, and 1466 unrelated nondiabetes individuals were genotyped. All subjects were examined by the 75 g oral glucose tolerance test, and 733 participated in a subsequent insulin release test. Various indicators of insulin resistance and islet β-cell function were examined. Results. There were no significant differences in genotype distribution and allele frequency between the prediabetes and controls. CC genotype carriers at rs9840992 showed higher insulin levels at 120 min after a 75 g glucose load than noncarriers. Also, CC homozygotes had higher ΔI30/ΔG30 and ΔI120/ΔG120 than noncarriers, even after adjusting for insulin resistance. CC homozygotes had greater AUCi values than noncarriers. Subjects aged ≥ 65 yrs, those with a BMI ≥ 24 kg/m2 and those carrying the rs9840992 risk allele, had a 2.5-fold higher risk of glucose abnormalities than subjects who had none of these risk factors. Conclusion. The eIF2α polymorphism is associated with islet β-cell function in a Chinese population.

Background. Glucagon-like peptide 1 (GLP-1) bestows protective effects upon the cardiovascular system through direct cardiovascular interactions or by improvements to metabolic function. Both these effects are thought to be at least partly mediated by the GLP-1 receptor (GLP-1R). This case-controlled study investigated whether polymorphisms in the GLP-1R gene affect the risk of cardiovascular disease in type 2 diabetic patients in the Chinese Han population. Methods. Eleven haplotype-tagging single nucleotide polymorphisms (SNPs), distributed across 22 kb of the 39 kb GLP-1R gene, were selected and genotyped in diabetic patients from a Chinese Han population. Patients were classified based on the severity of coronary artery stenosis. Coronary artery stenosis was ≥50% in 394 patients (coronary artery disease- (CAD-) positive group), and coronary artery stenosis was

OBJECTIVE:To develop a set of structure and process indicators to evaluate tertiary hospitals' performance in the Healthcare Improvement Initiative, a national program with a goal to improve quality of patient-centered care. METHODS:A modified Delphi technique, including literature review, multidisciplinary panel meeting and anonymous rating, was used to generate a set of indicators. A practice test involving both general and special hospitals was conducted to ensure the feasibility of data collection for these indicators. RESULTS:62 indicators were generated by literature review. The panel review procedure involving 39 panelists with diverse backgrounds resulted in a total of 59 indicators, which included 40 qualitative indicators and 19 quantitative indicators. In the practice test, six quantitative indicators were found unfeasible. According to the suggestion of the experts in the hospital evaluation committee, three of those indicators were kept by adjusting their data collection methods, while other three ones were discarded. DISCUSSION:A set of 56 structure and process indicators was developed to evaluate hospitals' performance in the implementation of the Healthcare Improvement Initiative, which could be used in both general and special tertiary hospitals. Results of the indicator measurement could present a panorama of the quality of patient-centered care in tertiary hospitals nation-wide, and inform health administrators of the ways to attain the goal of the Initiative.