A Zinc Finger Motif in the P1 N Terminus, Highly Conserved in a Subset of Potyviruses, Is Associated with the Host Range and Fitness of Telosma Mosaic Virus.

P1 is the first protein translated from the genomes of most viruses in the family Potyviridae, and it contains a C-terminal serine-protease domain that cis-cleaves the junction between P1 and HCPro in most cases. Intriguingly, P1 is the most divergent among all mature viral factors, and its roles during viral infection are still far from understood. In this study, we found that telosma mosaic virus (TelMV, genus Potyvirus) in passion fruit, unlike TelMV isolates present in other hosts, has two stretches at the P1 N terminus, named N1 and N2, with N1 harboring a Zn finger motif. Further analysis revealed that at least 14 different potyviruses, mostly belonging to the bean common mosaic virus subgroup, encode a domain equivalent to N1. Using the newly developed TelMV infectious cDNA clones from passion fruit, we demonstrated that N1, but not N2, is crucial for viral infection in both Nicotiana benthamiana and passion fruit. The regulatory effects of N1 domain on P1 cis cleavage, as well as the accumulation and RNA silencing suppression (RSS) activity of its cognate HCPro, were comprehensively investigated. We found that N1 deletion decreases HCPro abundance at the posttranslational level, likely by impairing P1 cis cleavage, thus reducing HCPro-mediated RSS activity. Remarkably, disruption of the Zn finger motif in N1 did not impair P1 cis cleavage and HCPro accumulation but severely debilitated TelMV fitness. Therefore, our results suggest that the Zn finger motif in P1s plays a critical role in viral infection that is independent of P1 protease activity and self-release, as well as HCPro accumulation and silencing suppression. IMPORTANCE Viruses belonging to the family Potyviridae represent the largest group of plant-infecting RNA viruses, including a variety of agriculturally and economically important viral pathogens. Like all picorna-like viruses, potyvirids employ polyprotein processing as the gene expression strategy. P1, the first protein translated from most potyvirid genomes, is the most variable viral factor and has attracted great scientific interest. Here, we defined a Zn finger motif-encompassing domain (N1) at the N terminus of P1 among diverse potyviruses phylogenetically related to bean common mosaic virus. Using TelMV as a model virus, we demonstrated that the N1 domain is key for viral infection, as it is involved both in regulating the abundance of its cognate HCPro and in an as-yet-undefined key function unrelated to protease processing and RNA silencing suppression. These results advance our knowledge of the hypervariable potyvirid P1s and highlight the importance for infection of a previously unstudied Zn finger domain at the P1 N terminus.

Marine biomaterials in biomedical nano/micro-systems.

Marine resources in unique marine environments provide abundant, cost-effective natural biomaterials with distinct structures, compositions, and biological activities compared to terrestrial species. These marine-derived raw materials, including polysaccharides, natural protein components, fatty acids, and marine minerals, etc., have shown great potential in preparing, stabilizing, or modifying multifunctional nano-/micro-systems and are widely applied in drug delivery, theragnostic, tissue engineering, etc. This review provides a comprehensive summary of the most current marine biomaterial-based nano-/micro-systems developed over the past three years, primarily focusing on therapeutic delivery studies and highlighting their potential to cure a variety of diseases. Specifically, we first provided a detailed introduction to the physicochemical characteristics and biological activities of natural marine biocomponents in their raw state. Furthermore, the assembly processes, potential functionalities of each building block, and a thorough evaluation of the pharmacokinetics and pharmacodynamics of advanced marine biomaterial-based systems and their effects on molecular pathophysiological processes were fully elucidated. Finally, a list of unresolved issues and pivotal challenges of marine-derived biomaterials applications, such as standardized distinction of raw materials, long-term biosafety in vivo, the feasibility of scale-up, etc., was presented. This review is expected to serve as a roadmap for fundamental research and facilitate the rational design of marine biomaterials for diverse emerging applications.

Highly Enantioselective Synthesis of N-Unprotected Unnatural α-Amino Acid Derivatives by Ruthenium-Catalyzed Direct Asymmetric Reductive Amination.

An unprecedented highly enantioselective Ru-catalyzed direct asymmetric reductive amination of α-keto amides with ammonium salts has been disclosed, efficiently offering valuable enantioenriched N-unprotected unnatural α-amino acid derivatives bearing a broad range of aryl or alkyl α-substituents. This protocol features easily accessible substrates, good functional-group tolerance and excellent enantiocontrol, making it a good complementary approach to the known methods. Moreover, this method is also applicable to the preparation of N-unprotected unnatural α-amino acid derivatives containing an additional stereogenic center at the ß-position through a dynamic kinetic resolution (DKR) process. Convenient transformations of the obtained products into chiral N-unprotected unnatural α-amino acids, drug intermediates, peptides, and organocatalysts/ligands further showcase the utility of this method.

Directional homing of glycosylation-modified bone marrow mesenchymal stem cells for bone defect repair.

BACKGROUND: One of the greatest challenges for tissue-engineered bone is the low survival rate of locally grafted cells. The cell homing technology can effectively increase the number of these grafted cells, therefore, enhancing the repair of bone defects. Here we explore the effect of fucosylation modification on the directional homing of bone marrow mesenchymal stem cells (BMSCs) and their ability to repair bone defects. RESULTS: Glycosylated BMSCs expressed high levels of the Sialyl Lewis-X (sLeX) antigen, which enabled the cells to efficiently bind to E- and P-selectins and to home to bone defect sites in vivo. Micro-CT and histological staining results confirmed that mice injected with FuT7-BMSCs showed an improved repair of bone defects compared to unmodified BMSCs. CONCLUSIONS: The glycosylation modification of BMSCs has significantly enhanced their directional homing ability to bone defect sites, therefore, promoting bone repair. Our results suggest that glycosylation-modified BMSCs can be used as the source of the cells for the tissue-engineered bone and provide a new approach for the treatment of bone defects.

The IMMUNE-ASSOCIATED NUCLEOTIDE-BINDING 9 Protein Is a Regulator of Basal Immunity in Arabidopsis thaliana.

A robust regulation of plant immune responses requires a multitude of positive and negative regulators that act in concert. The immune-associated nucleotide-binding (IAN) gene family members are associated with immunity in different organisms, although no characterization of their function has been carried out to date in plants. In this work, we analyzed the expression patterns of IAN genes and found that IAN9 is repressed upon pathogen infection or treatment with immune elicitors. IAN9 encodes a plasma membrane-localized protein that genetically behaves as a negative regulator of immunity. A novel ian9 mutant generated by CRISPR/Cas9 shows increased resistance to Pseudomonas syringae, while transgenic plants overexpressing IAN9 show a slight increase in susceptibility. In vivo immunoprecipitation of IAN9-green fluorescent protein followed by mass spectrometry analysis revealed that IAN9 associates with a previously uncharacterized C3HC4-type RING-finger domain-containing protein that we named IAN9-associated protein 1 (IAP1), which also acts as a negative regulator of basal immunity. Interestingly, neither ian9 or iap1 mutant plants show any obvious developmental phenotype, suggesting that they display enhanced inducible immunity rather than constitutive immune responses. Because both IAN9 and IAP1 have orthologs in important crop species, they could be suitable targets to generate plants more resistant to diseases caused by bacterial pathogens without yield penalty.

The Molecular Mechanisms Associated with the Effects of Propofol in a Rat Model of Pain Due to Inflammation Following Injection with Complete Freund's Adjuvant.

BACKGROUND This study aimed to investigate the molecular mechanisms associated with the effects of propofol in a rat model of pain due to inflammation following subcutaneous injection with complete Freund's adjuvant (CFA). MATERIAL AND METHODS Sprague-Dawley rats were injected subcutaneously in the paw with CFA. Propofol or saline was administered by tail vein injection. After CFA treatment for 0 hours, 4 hours, 1 day, 4 days, 7 days, and 14 days, the behavior of the rats was assessed. An enzyme-linked immunosorbent assay (ELISA) measured serum levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß, and IL-6. Western blot and the quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect levels of p38MAPK and NF-kappaB related mRNA and proteins, including p-p38, p38, p65, p-p65, NOD-like receptor family protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and caspase-1 in rat spinal cord tissues. RESULTS Injection of CFA significantly reduced the mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), and frequency responses to cold stimulation. Propofol treatment significantly reduced serum levels of TNF-alpha, IL-1ß, and IL-6. Protein expression levels of p-p38 and p-p65 were upregulated in the rat model, which were inhibited by propofol treatment. CFA injection increased the expression levels of NLRP3, ASC, and caspase-1 in the spinal cord tissues of rats, which were reduced by propofol treatment. CONCLUSIONS In a rat model of pain following subcutanous injection with CFA, propofol reduced CFA-induced pain and inhibited the inflammatory response through the p38MAPK-nuclear factor-kappaB (NF-kappaB) pathway and the NLRP3 inflammasome.

Medical expenses of urban Chinese patients with stomach cancer during 2002-2011: a hospital-based multicenter retrospective study.

BACKGROUND: In China, stomach cancer is the third most common cancer and the third leading cause of cancer death. Few studies have examined Chinese stomach cancer patients' medical expenses and their associated trends. The Cancer Screening Program in Urban China (CanSPUC) is a Major Public Health Project funded by the central government. Through this project, we have extracted patients' medical expenses from hospital billing data to examine the costs of the first course treatments (which refers to 2 months before and 10 months after the date of cancer diagnosis) in Chinese patients with stomach cancer and the associated trends. METHODS: The expense data of 14,692 urban Chinese patients with stomach cancer were collected from 40 hospitals in 13 provinces. We estimated the inflation-adjusted medical expenses per patient during 2002-2011. We described the time trends of medical expenses at the country-level, and those trends by subgroup, and analyzed the compositions of medical expenses. We constructed the Generalized Linear Mixed (GLM) regression model with Poisson distribution to examine the factors that were associated with medical expenses per patient. RESULTS: The average medical expenses of the first course treatments were about 43,249 CNY (6851 USD) in 2011, more than twice of that in 2002. The expenses increased by an average annual rate of 7.4%. Longer stay during hospitalization and an increased number of episodes of care are the two main contributors to the expense increase. The upward trend of medical expenses was observed in almost all patient subgroups. Drug expenses accounted for over half of the medical expenses. CONCLUSIONS: The average medical expenses of the first course (2 months before and 10 months after the date of cancer diagnosis) treatments per stomach cancer patient in urban China in 2011 were doubled during the previous 10 years, and about twice as high as the per capita disposable income of urban households in the same year. Such high expenses indicate that it makes economic sense to invest in cancer prevention and control in China.

[Acceptance and willingness-to-pay for colorectal colonoscopy screening among high-risk populations for colorectal cancer in urban China].

OBJECTIVE: To survey the acceptance and willingness-to-pay for colorectal cancer colonoscopy screening among high risk populations in urban China. METHODS: From 2012 to 2013, a Cancer Screening Program in Urban China (CanSPUC) was initiated in 9 provinces, the current survey was conducted among those participants who were evaluated as "high risk for colorectal cancer" by a risk-factor-evaluation-model (community-based) and then went through a colonoscopy screening procedure (hospital-based). All the data were obtained through a questionnaire-based interview (face-to-face or self-completed), mainly focusing on the acceptance and willingness-to-pay of the participants for colorectal colonoscopy screening. RESULTS: The current analysis included a total of 1 624 participants, with an median age of 55.0 years (P25 = 49.0, P75 = 61.0 years) and an annual income per capita of 17 thousand (range: 10-25 thousand) Chinese Yuan (CNY), 42.8% (695/1 624) of whom were males. Of all the participants, 87.0% (1 414/1 624) could totally or substantially accept the colonoscopy screening, particularly in those at higher education level (junior high school: OR = 0.34, 95% CI: 0.22-0.52; high school OR = 0.41, 95% CI: 0.26-0.66; college or over OR = 0.35, 95% CI: 0.20-0.59). Of all the participants, 13.0% (210/1 624) could not or hardly accept it, particularly in those with older age (60-69 years) (OR = 1.48, 95% CI: 1.06-2.07), not in marriage (OR = 2.15, 95% CI: 1.25-3.70) or with family member(s) to raise (OR = 1.60, 95% CI: 1.17-2.20). 1 388 (85.5%) of all the participants had willingness-to-pay for a long-term colonoscopy screening service, particularly in those working in public (OR = 0.61, 95% CI: 0.44-0.84) or enterprise sectors (OR = 0.60, 95% CI: 0.38-0.94), but 82.3% (1 141/1 386) of whom would only pay less than 100 CNY; 14.5% (236/1 624) of total had no willingness-to-pay, particularly in those living in areas with moderate (OR = 4.08, 95% CI: 2.75-6.33) or high GDP per capita (OR = 3.26, 95% CI: 2.11-4.92), or with an absence of willingness-to-pay for colonoscopy screening (OR = 3.98, 95% CI: 2.81-5.65). CONCLUSIONS: Although a larger community-based colorectal cancer screening program was warranted to examine the extrapolation of these findings, it suggested that the acceptance for colorectal cancer colonoscopy screening among the selected high-risk populations was considerable. The willing-to-pay was relatively high but the amount of payment was limited, the indicated subgroups with potentially less acceptance or willingness need to be more focused in the future to reach a higher participation rate. The data will also be informative in integrating the screening service into the local health insurance system.

CaAl-Layered Double Hydroxides-Modified Biochar Composites Mitigate the Toxic Effects of Cu and Pb in Soil on Pea Seedlings.

Compound contamination of soil with heavy metals copper (Cu) and lead (Pb) triggered by mining development has become a serious problem. To solve this problem, in this paper, corncob kernel, which is widely available and inexpensive, was used as the raw material of biochar and modified by loading CaAl-layered double hydroxides to synthesize biochar-loaded CaAl-layered double hydroxide composites (CaAl-LDH/BC). After soil remediation experiments, either BC or CaAl-LDH/BC can increase soil pH, and the available phosphorus content and available potassium content in soil. Compared with BC, CaAl-LDH/BC significantly reduced the available content of Cu and Pb in the active state (diethylenetriaminepentaacetic acid extractable state) in the soil, and the passivation rate of Cu and Pb by a 2% dosage of CaAl-LDH/BC reached 47.85% and 37.9%, respectively. CaAl-LDH/BC can significantly enhance the relative abundance of beneficial microorganisms such as Actinobacteriota, Gemmatimonadota, and Luteimonas in the soil, which can help to enhance the tolerance and reduce the enrichment ability of plants to heavy metals. In addition, it was demonstrated by pea seedling (Pisum sativum L.) growing experiments that CaAl-LDH/BC increased plant fresh weight, root length, plant height, catalase (CAT) activity, and protein content, which promoted the growth of the plant. Compared with BC, CaAl-LDH/BC significantly reduced the Cu and Pb contents in pea seedlings, in which the Cu and Pb contents in pea seedlings were reduced from 31.97 mg/kg and 74.40 mg/kg to 2.92 mg/kg and 6.67 mg/kg, respectively, after a 2% dosage of CaAl-LDH/BC, which was a reduction of 90.84% and 91.03%, respectively. In conclusion, compared with BC, CaAl-LDH/BC improved soil fertility and thus the plant growth environment, and also more effectively reduced the mobility of heavy metals Cu and Pb in the soil to reduce the enrichment of Cu and Pb by plants.

Unravelling the removal mechanisms of trivalent arsenic by sulfidated nanoscale zero-valent iron: The crucial role of reactive oxygen species and the multiple effects of citric acid.

The remediation of arsenic-contaminated groundwater by sulfidated nanoscale zero-valent iron (S-nZVI) has raised considerable attention. However, the role of trivalent arsenic (As(III)) oxidation by S-nZVI in oxic conditions (S-nZVI/O2) remains controversial, and the comprehensive effect of citric acid (CA) prevalent in groundwater on As(III) removal by S-nZVI remains unclear. Herein, the mechanisms of reactive oxygen species (ROS) generation and multiple effects of CA on As(III) removal by S-nZVI/O2 were systematically explored. Results indicated that the removal efficiency of As(III) by S-nZVI/O2 (97.81 %) was prominently higher than that by S-nZVI (66.71 %), resulting from the significant production of ROS (mainly H2O2 and OH) under oxic conditions, which played a crucial role in promoting the As(III) oxidation. Additionally, CA had multiple effects on As(III) removal by S-nZVI/O2 system: (i) CA impeded the diffusion of As(III) towards S-nZVI and increased the secondary risk of immobilized As(III) re-releasing into the environment due to the Fe dissolution from S-nZVI; (ii) CA could significantly enhance the yields of OH from 25.29 to 133.00 µM via accelerating the redox cycle of Fe(II)/Fe(III) and increasing the oriented conversion rate of H2O2 to OH; (iii) CA could also enrich the types of ROS (such as O2- and 1O2) in favor of further As(III) oxidation. This study contributed novel findings regarding the control of As(III) contaminated groundwater using S-nZVI technologies.

Acupuncture as Add-on Therapy to SSRIs Can Improve Outcomes of Treatment for Anxious Depression: Subgroup Analysis of the AcuSDep Trial.

Purpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD). Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted. Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group. Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted. Clinical Trials Registration: ChiCTR-TRC-08000297.

Ru-Catalyzed Asymmetric Reductive Amination of Aryl-Trifluoromethyl Ketones for Synthesis of Primary α-(Trifluoromethyl)arylmethylamines.

The ruthenium-catalyzed asymmetric reductive amination of aryl-trifluoromethyl ketones affording high value primary α-(trifluoromethyl)arylmethylamines using cheap NH4OAc as the nitrogen source and H2 as the reductant is reported. This user-friendly and simple catalytic method tolerates various aromatic functions with electron-withdrawing or -donating substituents at the para- or meta-positions and as well challenging heteroaromatic functions, yielding primary α-(trifluoromethyl)arylmethylamines with excellent chemoselectivities, enantioselectivities, and useful yields (80-97% ee, 51-92% isolated yields). Finally, scalable and concise synthesis of key drug intermediates using this methodology is presented.

Engineered Toll-like Receptor Nanoagonist Binding to Extracellular Matrix Elicits Safe and Robust Antitumor Immunity.

Cancer immunotherapy, such as the Toll-like receptor (TLR) agonist including CpG oligodeoxynucleotide, has shown potency in clinical settings. However, it is still confronted with multiple challenges, which include the limited efficacy and severe adverse events caused by the rapid clearance and systemic diffusion of CpG. Here we report an improved CpG-based immunotherapy approach composed of a synthetic extracellular matrix (ECM)-anchored DNA/peptide hybrid nanoagonist (EaCpG) via (1) a tailor designed DNA template that encodes tetramer CpG and additional short DNA moieties, (2) generation of elongated multimeric CpG through rolling circle amplification (RCA), (3) self-assembly of densely packaged CpG particles composed of tandem CpG building blocks and magnesium pyrophosphate, and (4) incorporation of multiple copies of ECM binding peptide through hybridization to short DNA moieties. The structurally well-defined EaCpG shows dramatically increased intratumoral retention and marginal systemic dissemination through peritumoral administration, leading to potent antitumor immune response and subsequent tumor elimination, with minimal treatment-related toxicity. Combined with conventional standard-of-care therapies, peritumor administration of EaCpG generates systemic immune responses that lead to a curative abscopal effect on distant untreated tumors in multiple cancer models, which is superior to the unmodified CpG. Taken together, EaCpG provides a facile and generalizable strategy to simultaneously potentiate the potency and safety of CpG for combinational cancer immunotherapies.

Epidemiological updates of post-traumatic related limb osteomyelitis in china: a 10 years multicentre cohort study.

BACKGROUND: Post-traumatic related limb osteomyelitis (PTRLO) is a complex bone infection. Currently, there are no available microbial data on a national scale that can guide appropriate antibiotic selection, and explore the dynamic changes in dominant pathogens over time. This study aimed to conduct a comprehensive epidemiological analysis of PTRLO in China. METHODS: The study was approved by the Institutional Research Board (IRB), and 3526 PTRLO patients were identified from 212 394 traumatic limb fracture patients at 21 hospitals between 1 January 2008 and 31 December 2017. A retrospective analysis was conducted to investigate the epidemiology of PTRLO, including changes in infection rate (IR), pathogens, infection risk factors and antibiotic resistance and sensitivity. RESULTS: The IR of PTRLO increased gradually from 0.93 to 2.16% (Z=14.392, P <0.001). Monomicrobial infection (82.6%) was significantly higher than polymicrobial infection (17.4%) ( P <0.001). The IR of Gram-positive (GP) and Gram-negative (GN) pathogens showed a significant increase from the lowest 0.41% to the highest 1.15% (GP) or 1.62% (GN), respectively. However, the longitudinal trend of GP vs. GN's composition did not show any significance (Z=±1.1918, P >0.05). The most prevalent GP strains were Methicillin-sensitive Staphylococcus aureus (MSSA) (17.03%), Methicillin-resistant Staphylococcus aureus (MRSA) (10.46%), E. faecalis (5.19%) and S. epidermidis (4.87%). In contrast, the dominant strains GN strains were Pseudomonas Aeruginosa (10.92%), E. cloacae (10.34%), E. coli (9.47%), Acinetobacter Baumannii (7.92%) and Klebsiella Pneumoniae (3.33%). In general, the high-risk factors for polymicrobial infection include opened-fracture (odds ratio, 2.223), hypoproteinemia (odds ratio, 2.328), and multiple fractures (odds ratio, 1.465). It is important to note that the antibiotics resistance and sensitivity analysis of the pathogens may be influenced by complications or comorbidities. CONCLUSIONS: This study provides the latest data of PTRLO in China and offers trustworthy guidelines for clinical practice. (China Clinical Trials.gov number, ChiCTR1800017597).

Gold Nanostar@Polyaniline Theranostic Agent with High Photothermal Conversion Efficiency for Photoacoustic Imaging-Guided Anticancer Phototherapy at a Low Dosage.

Due to the strong and tunable photothermal effect, metallic nanoparticles are of enormous interest in light-activated biomedical applications, such as photoacoustic imaging (PAI) and photothermal therapy (PTT). However, the photothermal conversion efficiency (PCE) of existing metallic photothermal agents is still unsatisfactory. Herein, we develop an efficient photothermal theranostic agent based on a gold nanostar@polyaniline core-shell nanocomposite with high PCE for PAI-guided PTT at a low dosage. After optimizing the relative composition of polyaniline (PANI) and gold nanostars (AuNSs), this nanocomposite eventually empowers an outstanding PCE of up to 78.6%, which is much better than AuNSs or PANI alone and most of the existing photothermal theranostic agents. Besides, the nanocomposite can act as a targeted probe for tumors by hyaluronic acid (HA) modification without compromising the photothermal performance. The obtained nanoprobes named AuNSPHs exhibit promising biocompatibility and great performance of PAI-guided PTT to treat triple-negative breast cancer both in vitro and in vivo. More importantly, a single injection of AuNSPHs significantly suppresses tumor growth with a low dosage of Au (0.095 mg/kg), which is attributed to the high PCE of AuNSPHs. Taking advantage of the exhilarating photothermal conversion ability, this theranostic agent can safely potentiate the antitumor therapeutic efficacy of laser-induced ablation and holds great potential for future medical applications.

Determination of the key parameters of VOCs emitted from multi-layer leather furniture using a region traversal approach.

Volatile organic compounds (VOCs) emitted from indoor materials and products are one of the main factors affecting air quality and human health. Compared with building materials and wooden furniture, leather furniture has a more complex internal structure and uneven emission surfaces. The market share of leather furniture is relatively high, while investigation on this kind of furniture is relatively rare. In this study, we develop a region traversal method to measure the three key parameters of VOC emissions from typical two-layer leather furniture, i.e., the initial emittable concentration, the diffusion coefficient, and the partition coefficient. A series of experiments examining VOC emissions from a leather sofa under different conditions, were carried out in a 1 m3 chamber. This method locks the upper and lower limits of an optimal solution through loop calculation in parameter intervals, and demonstrates high accuracy, efficiency and robustness. The good agreement (R2 > 0.95) between model predictions and experimental data confirms the reliability of this method. In addition, the influence of temperature and air exchange rate on the key parameters is explored. Results indicate that, increasing the temperature leads to an increase in Dm and a decrease in K, and that air exchange rate does not affect the key parameters, which is consistent with physical principles. The region traversal method is further applied to analyze the emission scenarios for other furniture, which is very helpful for indoor air quality pre-evaluation.

Predicting the emissions of VOCs/SVOCs in source and sink materials: Development of analytical model and determination of the key parameters.

The emissions of volatile organic compounds (VOCs) and semi-volatile organic compounds (SVOCs) from indoor materials pose an adverse effect on people's health. In this study, a new analytical model was developed to simulate the emission behaviors for both VOCs and SVOCs under ventilated conditions. Based on this model, we further introduced a hybrid optimization method to accurately determine the key parameters in the model: the initial emittable concentration, the diffusion coefficient, the material/air partition coefficient, and the chamber surface/air partition coefficient (for SVOCs). Experiments for VOC emissions from solid wood furniture were performed to determine the key parameters. We also evaluated the hybrid optimization method with the data of flame retardant emissions from polyisocyanurate rigid foam and VOC emissions from a panel furniture in the literature. The correlation coefficients are high during the fitting process (R2 = 0.92-0.99), demonstrating effectiveness of this method. In addition, we observed that chemical properties could transfer from SVOC-type to VOC-type with the increase of temperature. The transition temperatures from SVOC-type to VOC-type for the emissions of tris(2-chloroethyl) phosphate (TCEP) and tris(1-chloro-2-propyl) phosphate (TCIPP) were determined to be about 45 ℃ and 35 ℃, respectively. The present study provides a unified modelling and methodology analysis for both VOCs and SVOCs, which should be very useful for source/sink characterization and control.

QTL Detection for Rice Grain Length and Fine Mapping of a Novel Locus qGL6.1.

BACKGROUND: Grain length (GL) that is directly associated with appearance quality is a key target of selection in rice breeding. Although abundant quantitative trait locus (QTL) associated with GL have been identified, it was still relatively weak to identify QTL for GL from japonica genetic background, as the shortage of japonica germplasms with long grains. We performed QTLs analysis for GL using a recombinant inbred lines (RILs) population derived from the cross between japonica variety GY8 (short grains) and LX1 (long grains) in four environments. RESULTS: A total of 197 RILs were genotyped with 285 polymorphic SNP markers. Three QTLs qGL5.3, qGL6.1 and qGL11 were detected to control GL by individual environmental analyses and multi-environment joint analysis. Of these, a major-effect and stable QTL qGL6.1 was identified to be a novel QTL, and its LX1 allele had a positive effect on GL. For fine-mapping qGL6.1, a BC1F2 population consisting of 2,487 individuals was developed from a backcross between GY8 and R176, one line with long grain. Eight key informative recombinants were identified by nine kompetitive allele specific PCR (KASP) markers. By analyzing key recombinants, the qGL6.1 locus was narrowed down to a 40.41 kb genomic interval on chromosome 6. One candidate gene LOC_Os06g43304.1 encoding cytochrome P450 (CYP71D55) was finally selected based on the difference in the transcriptional expression and variations in its upstream and downstream region. CONCLUSIONS: Three QTLs qGL5.3, qGL6.1 and qGL11 were identified to control grain length in rice. One novel QTL qGL6.1 was fine mapped within 40.41 kb region, and LOC_Os06g43304.1 encoding cytochrome P450 (CYP71D55) may be its candidate gene. We propose that the further cloning of the qGL6.1 will facilitate improving appearance quality in japonica varieties.

Transcriptional reprogramming caused by cold acclimation in Meloidogyne incognita eggs.

BACKGROUND: Egg hatching in Meloidogyne incognita is a highly regulated developmental event and is strictly correlated with temperature. It has been demonstrated that exposure of M. incognita eggs to low temperature seriously affects their embryonic development. On the other hand, clear evidence has shown that M. incognita is able to overwinter at subzero soil temperatures in certain open fields. Therefore, subtle physiological and genetic adaptations may occur in M. incognita to minimize freezing injuries. OBJECTIVE: A growing body of evidence indicates that cold acclimation plays a large role in an individual organism's ability to cope with freezing-induced cellular damage. Given the decreasing temperatures in late autumn or early winter, we hypothesize that natural cold acclimation occurring during these periods may assist M. incognita in overwintering. METHODS: Transcriptomic analysis and functional enrichment analyses were used to identify and annotate differentially expressed genes (DEGs) in acclimated eggs. The expression of DEGs involved in signal transduction and protein assembly was subsequently validated by reverse transcription quantitative PCR (RT-qPCR). RESULTS: Relatively long-term preacclimation at 4 °C significantly accelerated the hatching of M. incognita eggs that were subjected to freezing at - 1 °C. Using a transcriptomic approach, we further identified 686 and 460 up- and downregulated transcripts, respectively, in pre-cold-acclimated eggs. Additionally, we used Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology annotations for functional enrichment analyses of the differentially expressed genes (DEGs). CONCLUSION: The phenomenon in which M. incognita safely overwinters at subzero soil temperatures in certain areas may be attributed to the natural cold acclimation occurring in late autumn. Here, the identification of DEGs between acclimated and nonacclimated eggs will provide us with promising directions for future studies on the mechanisms of M. incognita freezing tolerance.

High expression of NDRG3 in osteoarthritis patients.

BACKGROUND: Osteoarthritis (OA), as a common disease, seriously affects the quality of life of the victims, but its pathogenesis remains unclear. It has been confirmed that hypoxia-induced factor (HIF)-mediated hypoxia response plays an important role in the development and progression of OA. As a member of the N-myc downstream regulatory gene families, NDRG3 has been reported to independently regulate the hypoxic response of tumour cells, but the relationship between NDRG3 and OA development has not been reported so far. METHODS: In this study, seven OA patients were admitted to Guizhou Provincial People's Hospital from January 2017 to December 2018. The OA group included 5 patients clinically diagnosed with hip/knee OA, which required arthroplasty. The normal group included 2 patients with no previous history of OA and rheumatoid arthritis, which required amputation due to trauma or tumour. The articular cartilage samples were collected to detect the expression of HIF-1α, HIF-2α and NDRG3 using immunohistochemical (IHC), haematoxylin and eosin (HE) and toluidine blue (TB) staining. RESULTS: HE and TB staining indicated that the cartilage surface of the normal group was smooth and intact, with a columnar arrangement of hyaline chondrocytes, while the cartilage surface of the OA group was discontinuous, with cartilage missing and fibrous soft tissue growing into the defect site. HIF-1α staining was positive in both groups. Moreover, HIF-2α and NDRG3 staining was weakly positive in the normal group, but were uniformly and strongly positive in the OA group. The positively stained areas and integral optical density for NDRG3 were significantly greater in OA group than in the normal group (p < 0.05). CONCLUSIONS: NDRG3 might be closely related to the development and progression of OA. However, the relationship between NDRG3 and OA, which is independent of the HIF pathway, warrants further research.