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33 heat shock protein 20 (Hsp20) genes were identified from the carnation genome whose expression were altered by abiotic stresses. DcHsp17.8 may function to improve the heat resistance of Arabidopsis. Heat shock proteins 20 (Hsp20s) mainly function as molecular chaperones that play crucial roles in relieving abiotic stresses such as heat stress. In this study, we identified and characterized 33 DcHsp20 genes from the carnation genome that were classified into 9 subfamilies. Gene structure analysis showed that 25 DcHsp20 genes contained 1 intron whilst the remaining 8 DcHsp20 genes did not contain introns. Motif analysis found that DcHsp20 proteins were relatively conserved. Cis-regulatory elements analysis of the Hsp20 promoters revealed a number of cis-regulatory elements that regulate growth and development, hormone and stress responses. Gene expression analysis revealed that DcHsp20 genes had multiple response patterns to heat stress. The largest range of induction occurred in DcHsp17.8 after 1 h of heat stress. Under cold stress, or treatment with saline or abscisic acid, the expression of most DcHsp20 genes was inhibited. To further understand the function of DcHsp20 genes in response to heat stress, we overexpressed DcHsp17.8 in Arabidopis and the plants showed improved heat tolerance, O

Low temperature can affect the growth and development of plants through changes in DNA demethylation patterns. Another known effect of low temperature is the accumulation of anthocyanin pigments. However, it is not known whether the two phenomena are linked, specifically whether DNA demethylation participates in anthocyanin accumulation in response to low-temperature stress. The ROS1 gene is involved in plant DNA demethylation and influences methylation levels in response to low-temperature stress. In this study, using RNA sequencing, we detected the transcription levels of MdROS1, as well as those of anthocyanin biosynthesis-related genes, correlate with the anthocyanin content in apple (Malus domestica), at low temperature. Genomic bisulfite sequencing showed that the methylation levels of the promoters of the anthocyanin-related genes MdCHS, MdCHI, MdF3′H, MdANS, MdUFGT, and MdMYB10 decreased in apple leaves after low-temperature treatment. Similar expression and methylation results were found in apple fruit. Transiently silencing MdROS1 in the leaves and fruit of apple cultivars inhibited the accumulation of anthocyanins and led to decreased expression of anthocyanin biosynthetic genes, and the opposite results were detected in MdROS1-overexpressing leaves and fruit. A promoter binding assay showed that the conserved RRD-DME domains of MdROS1 bind directly to the promoters of MdF3′H and MdUFGT. Taken together, these results suggest that ROS1 affects the anthocyanin biosynthetic pathway by decreasing the methylation level of anthocyanin-related gene promoters, thereby increasing their expression and increasing anthocyanin accumulation.

Prostaglandins (PGs) play many essential roles in the development, immunity, metabolism, and reproduction of animals. In vertebrates, arachidonic acid (ARA) is generally converted to prostaglandin G2 (PGG2) and H2 (PGH2) by cyclooxygenase (COX); then, various biologically active PGs are produced through different downstream prostaglandin synthases (PGSs), while PGs are inactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH). However, there is very limited knowledge of the PG biochemical pathways in invertebrates, particularly for crustaceans. In this study, nine genes involved in the prostaglandin pathway, including a COX, seven PGSs (PGES, PGES2, PGDS1/2, PGFS, AKR1C3, and TXA2S), and a PGDH were identified based on the Pacific white shrimp (Litopenaeus vannamei) genome, indicating a more complete PG pathway from synthesis to inactivation in crustaceans than in insects and mollusks. The homologous genes are conserved in amino acid sequences and structural domains, similar to those of related species. The expression patterns of these genes were further analyzed in a variety of tissues and developmental processes by RNA sequencing and quantitative real-time PCR. The mRNA expression of PGES was relatively stable in various tissues, while other genes were specifically expressed in distant tissues. During embryo development to post-larvae, COX, PGDS1, GDS2, and AKR1C3 expressions increased significantly, and increasing trends were also observed on PGES, PGDS2, and AKR1C3 at the post-molting stage. During the ovarian maturation, decreasing trends were found on PGES1, PGDS2, and PGDH in the hepatopancreas, but all gene expressions remained relatively stable in ovaries. In conclusion, this study provides basic knowledge for the synthesis and inactivation pathway of PG in crustaceans, which may contribute to the understanding of their regulatory mechanism in ontogenetic development and reproduction.

Tolerizing DNA vaccines encoding key autoantigens are one of emerging strategies for the treatment of rheumatoid arthritis (RA). Among these vaccines, the most representative is pcDNA-CCOL2A1, an antigen-specific DNA vaccine encoding chicken type Ⅱ collagen (CCⅡ) with significant therapeutic and prophylactic efficacy in collagen-induced arthritis (CIA) rat models. We compared the in situ expression levels of CCOL2A1-mRNA and CCⅡ protein and the protective efficacies against CIA after a single dose (300 μg/kg) of this vaccine via intramuscular (IM), subcutaneous (SC) and intravenous (IV) vaccinations. The IM vaccination routes resulted in good protective efficacies in terms of decreasing CIA incidence and severity and significantly improved radiographic and histopathologic findings and scores of joints. Furthermore, IM, SC, and IV vaccinations markedly decreased serum levels of anti-type Ⅱ collagen (CⅡ) IgG antibodies, but only IM vaccination significantly reduced serum levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody. The vaccine exhibited a continuous CCOL2A1-mRNA expression in the tail and abdominal subcutaneous tissue injection sites, but no CCOL2A1-mRNA signal was observed in muscle. Strikingly, CCⅡ protein expression levels at the three injection sites were comparable with minimal variation. IM administration may be considered the preferred route for RA treatment in clinical practice.

BackgroundIndependent studies on exhaled carbon monoxide (CO) and saliva cotinine levels in regular heated tobacco product (HTP) users, and how they compare with conventional cigarette (CC) smokers, are lacking.MethodsA total of 3294 current users of CCs, HTPs or electronic cigarettes (ECs) from a household survey and a smoking hotspot survey were classified into seven groups: exclusive users of CCs, HTPs, ECs; dual users of CCs and HTPs, CCs and ECs, HTPs and ECs; and triple users. We measured exhaled CO level using the piCo Smokerlyzer (n=780) and saliva cotinine using NicAlert cotinine test strips (n=620). Among the seven groups, the differences in (1) CO and cotinine levels were examined using Kruskal-Wallis test, and (2) the average daily tobacco consumption in the past 30 days was examined using multivariable linear regression.ResultsBoth exclusive and dual users of CCs had a higher CO level than exclusive HTP or EC users (pConclusionsHTP or EC use showed lower exhaled CO but similar saliva cotinine levels compared with CC use. Dual users of CCs and HTPs/ECs smoked fewer CCs than exclusive CC users, but consumed more tobacco in total.

Methyl farnesoate (MF) is an essential endocrine hormone in crustaceans, which can promote the occurrence of crustaceans molting, control morphogenesis, affect gonad development, and regulate the stress stimulation to the external environment. The farnesoic acid O-methyltransferase (FAMeT) is a key rate-limiting enzyme in MF synthesis, catalyzing the conversion of farnesoic acid (FA) into MF. Neocaridina denticulata sinensis [Decapoda] is a suitable animal model for studying crustaceans because it can reproduce many times under artificial control and has a short reproductive cycle. According to its transcriptomic and genomic information, the full-length cDNA sequence of FAMeT from N. denticulata sinensis (NdFAMeT) was cloned and the characterization of its deduced amino acid sequence was also analyzed. The relative expression of NdFAMeT in different tissues was determined. The NdFAMeT protein was recombinantly expressed in E. coli and its enzyme activity was determined. After gene knockdown by RNAi technology, the protein activity of shrimp was decreased and the individual phenotype was also observed.

Changes in tobacco use and related personal and environmental factors amid the COVID-19 pandemic can be captured by qualitative studies, but they are few in non-Western populations. We assessed the perceived links between tobacco use and COVID-19, and changes in the use of cigarettes, electronic cigarettes (ECs) and heated tobacco products (HTPs) in the early phase of the pandemic in Hong Kong, where lockdown was not implemented.Semi-structured telephone interviews were conducted from January to June 2021 in 95 participants (36 EC users, 28 HTP users, 32 exclusive cigarette users). Transcriptions were coded using deductive and inductive approaches, and factors for changes were nested in the social-ecological model.Two-thirds of participants perceived their infection susceptibility was the same as never tobacco users, and 44.2% perceived more severe COVID-19 disease if infected. Amid the pandemic, tobacco use decreased overall but increased indoors for all three products. Increased tobacco use was mostly attributed to increased emotional distress, while decreases were attributed to various personal (health concerns) and environmental factors (e.g. COVID-19 regulations). Perceived convenience and lower costs were reasons for increased EC use. Limited access to HTPs was compensated by cigarette use.Many participants were unaware of the potential harm of tobacco use on COVID-19. Overall tobacco use decreased due to COVID-19 regulations, which may not be sustainable post-pandemic. Indoor consumption increased, supporting a comprehensive smoke-free policy that covers private indoor areas. Better cessation services targeting EC, HTP and cigarette use are needed.Smokers need better awareness of the risk of tobacco use on COVID-19. Smoking cessation services can be improved by offering brief advice, strengthening advocacy against secondhand smoke, and covering EC and HTP use, highlighting their potential harms to users and others, and their risk of addiction and relapse to cigarette use.

The major histocompatibility complex (MHC) is closely associated with numerous diseases, but its high degree of polymorphism complicates the discovery of disease-associated variants. In principle, recombination and de novo mutations are two critical factors responsible for MHC polymorphisms. However, direct evidence for this hypothesis is lacking. Here, we report the generation of fine-scale MHC recombination and de novo mutation maps of ∼5 Mb by deep sequencing (100×) of the MHC genome for 17 MHC recombination and 30 non-recombination Han Chinese families (a total of 190 individuals). Recombination hotspots and Han-specific breakpoints are located in close proximity at haplotype block boundaries. The average MHC de novo mutation rate is higher than the genome-wide de novo mutation rate, particularly in MHC recombinant individuals. Notably, mutation and recombination generated polymorphisms are located within and outside linkage disequilibrium regions of the MHC, respectively, and evolution of the MHC locus was mainly controlled by positive selection. These findings provide insights on the evolutionary causes of the MHC diversity and may facilitate the identification of disease-associated genetic variants.

Changes in tobacco use since the COVID-19 outbreak differed by countries and little is known about changes in the use of specific tobacco products.We analyzed data from four cross-sectional telephone/online surveys from April to June 2020 to investigate such changes since the 1st and 2nd wave outbreaks (February to April 2020) in Hong Kong. The respondents were 1595 adults (83.2% male) who used tobacco before the COVID-19 outbreak from our previous intervention study and surveys. We investigated the changes in tobacco use, intention to quit and quit attempts during the outbreak.About two-thirds (65.3%) of respondents reported no change in overall tobacco use, while 23.1% used less (including cessation) and 11.6% used more, resulting in a net decrease of 11.5 percentage points. A greater net decrease was observed for cigarettes (14.3% points) than heated tobacco products (HTPs, 3.3% points) and electronic cigarettes (e-cigarettes, 2.5% points). Decreased use was mainly due to the more extended stay at home (63.2%), health considerations (52.6%) and mask-wearing (47.4%), while increased use was for passing time (75.0%) and releasing stress (46.4%). Eight percent of cigarette, HTP and e-cigarette users reported a higher intention to quit since the pandemic outbreak. Nineteen percent of tobacco users (176/948) attempted to quit during the pandemic. Only 2.9% (46/1569) were abstinent at the time of the survey.Overall tobacco use decreased after the first two waves of the COVID-19 outbreak in Hong Kong. A greater proportion of cigarette users decreased use than HTP and e-cigarette users. Given the different methods used in the four surveys, future studies should aim for a large and representative sample.

The burden of lung cancer in Hong Kong continues to rise. We analyzed trends in lung cancer incidence and associations with age, period, and cohort from 1985 to 2019, made projections up to 2030 and examined the drivers of lung cancer incidence. We used age-period-cohort modeling to estimate age, period, and cohort effects on lung cancer incidence rates in Hong Kong between 1985 and 2019. We projected lung cancer incidence in Hong Kong from 2020 to 2030 using Bayesian age-period-cohort analysis with an integrated nested Laplace approximation. We decomposed changes in the number of lung cancer cases into population growth, population aging, and epidemiologic changes. From 1985 to 2019, the number of lung cancer incident cases in Hong Kong continued to rise, yet the age-standardized incidence rates have declined for both sexes while have fluctuated for females over the past two decades. The overall annual percentage change from 1985 to 2019 was -2.29 (95% CI, -2.53 to -2.05) for males and -0.86 (95% CI, -1.06 to -0.65) for females. Age-specific annual percentages for both sexes showed a decreasing trend in all age groups and were more pronounced for females older than 65 years and males younger than 65 years. Period effects for both sexes showed a similar monotonic downward pattern, with the downward trend slowing for females after 2000. The cohort effect declined monotonically for males and started to plateau for females after the 1945 birth cohort. It was projected that the incident cases of lung cancer in Hong Kong would continue to increase, with 4,435 male cases and 3,561 female cases in 2030. Demographic decomposition suggested that population growth and population aging play an important role in the change of lung cancer cases. Much progress has been made in reducing the incidence of lung cancer in Hong Kong, but this has been offset by demographic changes that will continue to increase the incident cases of lung cancer in Hong Kong, especially among females. There is an urgent need for continued public health policies and clinical programs for risk factor control and necessary screening.

Air source heat pumps (ASHPs) have been widely used for space cooling in recent years. When a space cooling ASHP unit is operated in an ambience with poor air quality, fouling of its outdoor coil can be easily built up, leading to a significant drop in the operating efficiency and output cooling capacity of the ASHP unit. Therefore, as a follow-up to a previous related study, a study to develop a novel defouling initiation method for the fouled outdoor coil in a space cooling ASHP unit based on its measurable characteristic ambient and operating temperatures has been carried out and the study results are reported in this paper. Firstly, a characteristic parameter of TTT, which can be evaluated based on ambient air Temperature, outdoor coil metal surface Temperature and outdoor coil outlet air Temperature, is defined. Secondly, the development of the novel defouling initiation method is detailed. Finally, further field comparative studies using the developed novel defouling initiation method have been carried out, and the study results demonstrated that the novel defouling initiation method can provide an accurate and convenient way to initiate defouling of the fouled outdoor coil in an ASHP unit at a reasonable defouling frequency to ensure its best possible operating performances.

Communicated by Ramaswamy H. Sarma.

The assumption that market efficiency informs the pricing of oil stocks is critical to understanding the co-movement between stock markets and oil markets. To test this assumption in relation to various types of real oil price changes, this article proposes a two-stage analysis method that starts with a quantile regression to identify oil shocks and develop interval-valued factor pricing models. These interval-based methods, relative to traditional point-based methods, can produce more efficient parameter estimations by providing more information. The results show that oil stocks tend to be overpriced following negative oil price shocks, which partially violates the efficient market hypothesis. Yet oil stocks are efficiently priced in response to moderate changes or positive oil price shocks, such that in most cases, the market remains efficient in pricing oil stocks. (C) 2019 Elsevier B.V. All rights reserved.

Methyl farnesoate (MF) is considered the equivalent of JH in crustaceans and plays an essential role in many crucial physiological processes. It is believed that farnesyl pyrophosphate synthase (FPPS) plays an essential role in the biosynthesis of mevalonate, which is a branch of the JH/MF pathway. The full-length cDNA of FPPS (NdFPPS) from Neocaridina denticulata sinensis was isolated and characterized, and the deduced amino acid of NdFPPS contained a polyprenyl_synt domain. In addition to its ubiquitous tissue expression, NdFPPS was significantly expressed in the ovary. In vivo gene silencing with dsRNA interference was performed to further investigate the function of NdFPPS. An ovarian transcriptomic analysis of dsNdFPPS experimental and control groups was used to compare, annotate, and classify differentially expressed genes (DEGs). A total of 9230 DEGs were identified in the experimental and control groups based on FPKM values, of which 5082 were up-regulated genes and 4148 were down-regulated genes. 761 GO terms and 102 KEGG pathways were enriched for the DEGs. Our results suggest that NdFPPS might play an important role in ovarian development, however, further functional study is needed to elucidate physiological role of NdFPPS in reproduction.

Neocaridina denticulate sinensis is a promising crustacean model species due to its merits in raising and breeding. However, its molecular responses to copper remains largely unknown. In the present research, RNA-seq was used to mine the alteration in transcriptome of N. denticulate sinensis hepatopancreas under copper exposure. A total of 16,423 DEGs was identified between control and Cu2+ treatment groups. GO enrichment analysis of all DEGs suggested down-regulated genes exceeded up-regulated genes in all the significantly enriched terms, except for RNA polymerase III complex (GO:0005666). KEGG analysis showed Cu exposure only induced two significantly enriched pathways, including Phagosome (ko04145) and Pathogenic Escherichia coli infection (ko05130). Besides, pattern recognition receptors as Toll, lectin B, CTL1 and SRB, AMPs as crustin type I, lysozyme, and NOS were down-regulated after Cu2+ exposure, while hemocyanin, MT, HSP70 and HSP90 were significantly up-regulated, implying these molecules may play vital role in Cu2+ detoxification of N. denticulate sinensis. Our results here provide research direction of heavy metal detoxification of N. denticulate sinensis, simultaneously enriched its genomic information.

We conducted a cluster randomised controlled trial of parents in 56 primary schools and community service centres (clusters) to evaluate the effectiveness of a single-session workshop on promoting more fruit and vegetable (FV) intake. A total of 803 parents were randomised to the FV intervention arm (16 clusters, n = 197), the more appreciation control arm (19 clusters, n = 270), or the less criticism control arm (21 clusters, n = 336). The FV intake of the FV arm was compared with that of the combined more appreciation or less criticism (MALC) arm. Both arms received a 2 h workshop: (i) the FV arm on increasing FV consumption and related food literacy, (ii) the MALC arm on increasing appreciation or reducing criticism of children. Primary outcomes were FV consumption per day in the past week assessed at baseline, 2-weeks, and 6-weeks. Secondary outcomes were behavioural determinants proposed by the Health Action Process Approach (HAPA), including outcome expectancies, self-efficacy, intention, and planning behaviour. The FV arm had a greater increase in FV consumption than the MALC arm, with large effect sizes (d: 0.97–1.08) and improvements in behavioural determinants with small effect sizes at all time points (d: 0.19–0.43). Our study was the first population-based randomised controlled trial to show that a brief, single 2 h HAPA-based workshop was effective in promoting fruit and vegetable intake in parents.

e17535 Background: Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death among women. Most of patients often have refractory or relapse. We have developed a CAR T cell secreting PD-1 nanoantibodies and targeting mesothelin (αPD-1-mesoCAR-T) and conducted a phase I clinical trial for evaluation of safety and efficacy of the αPD-1-mesoCAR-T cells in gynecologic tumors. Methods: This study is a single-arm, open, dose-increasing clinical study and two infusions (interval 14-35 days). Patients with advanced gynecological cancer were enrolled when immunohistochemical analysis for positive mesothelin over 70% and failed second-line treatment in Mengchao Cancer Hospital affiliated to Shanghai University and Shanghai Tenth People's Hospital affiliated to Tongji University. All patients underwent lymphodepletion before infusion at a dose of 1 to 15x106/kg. CAR copies, nanobody levels, cytokines, T lymphocyte subtypes were determined before and after infusion. Results: a total of 7 patients were enrolled so far and completed the first evaluation. After treatment, most symptoms of the patients were alleviated, two patients (#2, #3) had their lesions decreased. By RECIST 1.1, all 7 patients’ diseases became stable, and the disease control rate was 100%. The PFS of #3 patient with stable disease (SD) was 5.3 months, the patient #2 was 4.1 months. The frequent adverse events were fever, fatigue, nausea and pruritus. No sever adverse events above grade 3 occurred. The number of CAR-T cells in the peripheral blood increased significantly during day 4-14 after the infusion, and the PD-1 nanoantibody levels and the contents of INF-γ、IL-6、IL-2 and MCP-1 also increased at day 1-4. Conclusions: The preliminary clinical study showed that the aPD-1-mesoCAR-T cells are safe for the treatment of gynecologic cancer and stabilized the diseases. More data of the treatment is warrantied to continually follow up these patients.

Metallothioneins (MTs) belong to a conserved low-molecular-weight protein family that participates in heavy metal binding and detoxification. EcMT-1 was amplified by PCR from genomic DNA of Exopalaenon carinicauda. It contained a 180 bp open reading frame and encoded 59 amino acids. A total of 18 cysteine (Cys) residues were found in the deduced amino acid sequence, which was consistent with the Cys-rich characteristics of MTs. EcMT-1 was mainly expressed in hepatopancreas, followed by stomach and gill. The expression profiles of EcMT-1 indicated that EcMT-1 was significantly increased at 24, 48 h and 12, 24, and 48 h under the treatment of 2.5 μmol/L CdCl

This article considers model averaging in the class of the integer-valued autoregressive (INAR) processes. The INAR process is a class of structural models that can be used to model dependent count data in fields such as medicine, economics, finance and marketing. It specifies the data generating process (DGP) via the distributions of certain thinning and arrival processes instead of an approximate multiplicative and additive relationship, which means that maximum likelihood (ML) is a natural candidate for estimation. Forecasts can not only be evaluated in terms of points and intervals but also through the entire forecast distribution. Here, we propose a K-fold cross-validation model averaging (KCVMA) estimator based on ML and prove that the KCVMA estimator is asymptotically optimal in a metric equivalent to a squared loss criterion. The KCVMA estimators are consistent, provided at least one candidate model is not underfitted. The probabilistic nature of the INAR process also enables us to conduct probabilistic forecasts based on the KCVMA estimator. Monte Carlo simulations and empirical analysis show that the KCVMA estimator can improve forecast accuracy over existing model averaging and model selection methods.

Background: Minimal residual disease (MRD) refers to the remaining leukemic clones in post-therapeutic patients, which may lead to relapse of acute lymphoblastic leukemia (ALL). ALL-discordant co-twin design provides an efficient way to develop more clinically applicable molecular markers for MRD monitoring of ALL. Methods: Whole-genome and whole-methylome sequencing were performed on peripheral blood samples. DNA methylation gene panel was analyzed by an amplicon sequencing strategy. XGBoost and random forest model was applied to train and evaluate the candidate gene panel in 133 ALL-discordant sibling pairs and 1670 extra public methylation datasets. Findings: No evidence showed that any leukemia-associated genomic mutations were detected in the blood of B-ALL-discordant twins at complete remission (CR). 26 recurrent differential methylated regions (DMRs) were commonly identified. A 10-gene diagnosis panel were identified from 133 ALL-discordant siblings, which showed 80·8% specificity and 86·1% sensitivity. RT-PCR revealed that aberrant DNA methylation in introns of PRDM16 and LCP2 correlates with their differential transcript usage, implying their potential roles in ALL pathogenesis. Finally, we obtained a clinically applicable 4-probe panel that displayed highly promising predictive value both in blood and bone marrow samples: 98·89% sensitivity and 94·12% specificity to diagnose ALL and 100% sensitivity and 100% specificity to differentiate relapse from remission patients. Interpretation: We proved DNA methylation aberrations exist in blood samples of B-ALL patients at CR and established a 4-probe DNA methylation marker that can be potentially used in clinics for more sensitive, fast and standardized MRD monitoring in ALL. Funding Statement: Scientific Research Innovation Key Program (No. 2012213-5), Research-based Disciplines Program (No.201314-3), Research-based Talents Program (No.201314-6) of Beijing 307 Hospital Affiliated, the State Key Development Program for Basic Research of China (No. 2003CB515509 and 2009CB522401), the National High Technology Research and Developmental Program of China (2012AA02A201), and the innovative R&D team program of Guangdong Province (2009010016). Declaration of Interests: None to declare Ethics Approval Statement: Ethics permission approved by the human ethics committee of Beijing 307 Hospital.

Purpose To evaluate the role of Toll-like receptor 2 (TLR2) signaling in retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Materials and methods The OIR model was established in C57BL/6J wild type (WT) mice and TLR2−/− mice. Retinal neovascularization in the OIR model was measured by counting new vascular cell nuclei above the internal limiting membrane and analyzing flat-mounted retinas perfused with fluorescein dextran and immunostained with Griffonia Simplicifolia (GS) isolectin. The expression of TLR2 and VEGF in the retina was detected by immunofluorescence. Expression of TGF- β1, b-FGF, and IL-6 mRNA in the retina was measured by quantitative real-time PCR. Results Compared to WT OIR mice, retinal neovascularization was attenuated in TLR2−/− OIR mice. The co-expressions of TLR2 and VEGF were remarkably and consistently increased in WT OIR mice; however, there was no expression of TLR2 and a significant decrease in VEGF expression in TLR2−/− OIR mice. These results suggest that TLR2 plays a central role in OIR model angiogenesis. Expression of TGF- β1, b-FGF, and IL-6 mRNA were reduced in the TLR2−/− OIR mice, suggesting that the inflammatory response induced by TLR2 relates to angiogenesis. Conclusion TLR2 signaling in the retina is associated with neovascularization in mice. Inflammation contributes to the activation of angiogenesis and is partially mediated through the TLR2-VEGF retinal signaling pathway.

Objective Effective and brief positive parenting interventions could be adopted widely, but evidence is limited. We aimed to evaluate the effectiveness of a positive parenting programme in Hong Kong Chinese parents. Methods We conducted a pilot cluster randomised controlled trial in 2017 in 144 Hong Kong Chinese parents (84.7% women, mean age 42.5 [SD 5.87] years) of school-age children (mean age 10.9 [2.8] years) in 4 family service centres (clusters). The intervention included two 2-hour interactive talks (4 hours in total). The contents covered skills of giving praise, showing appreciation and playing enjoyable family games. The control group was offered the intervention after all the data were collected. Praise, appreciation and enjoyment related behaviours were measured as primary outcomes at baseline, 1 month and 3 months. The secondary outcomes were subjective happiness, wellbeing, personal health and happiness, family health, family happiness and harmony, and family relationship. After the completion of all assessments, five focus group discussions with the parents and four individual in-depth interviews with community service providers were conducted to explore their experiences. Results Compared with the control group (n = 69), the intervention group (n = 75) showed greater positive changes in appreciation and enjoyment at 3 months with small effect sizes (d = 0.42 and 0.32, respectively), and greater improvements in the secondary outcomes at 3 months with small effect sizes (d: 0.29–0.48). In the focus groups, the parents reported more praise to their children, better temper control, more focus on their children’s strengths and better family relationships. According to the service providers, most of the parents enjoyed the activities. Conclusions The brief intervention in community settings with the engagement of community service providers has shown preliminary effectiveness in promoting positive parenting and mental wellbeing of Hong Kong Chinese parents. Trial registration The authors confirm that all ongoing and related trials for this intervention are registered. The study reported in this manuscript is registered as clinical trial at clinicaltrials.gov: NCT03282071. https://clinicaltrials.gov/ct2/show/NCT03282071.

This study was to observe smoking behaviours and infection control behaviours in smokers at outdoor smoking hotspots during the COVID-19 pandemic in Hong Kong. We conducted unobtrusive observations at nine hotspots during 1 July 2019&ndash, 31 January 2020 (pre-outbreak, 39 observations), 1 February&ndash, 30 April 2020 (outbreak, eight observations), and 1 May&ndash, 11 June 2020 (since-outbreak, 20 observations). Sex, age group, type of tobacco products used, duration of stay, group smoking behaviours, face mask wearing and infection control behaviours of smokers, and mask wearing of non-smoking pedestrians were observed. Compared with pre-outbreak, lower volumes of smokers were observed during outbreak and since-outbreak. Smokers gathered more in a group (24.5% and 25.8% vs. 13.4%, respectively) and stayed longer (91.5% and 83.6% vs. 80.6% stayed &ge, 1 min) during outbreak and since-outbreak than pre-outbreak. Ninety-six percent smokers possessed a face mask. While smoking, 81.6% of smokers put the mask under the chin and 13.8% carried it in the hand, 32.4% did not wear a mask immediately after smoking, 98.0% did not sanitize hands, and 74.3% did not keep a distance of at least one metre. During the COVID-19 pandemic, smokers gathered closely and stayed longer at the hotspots, and few practised hand hygiene, all of which may increase the risk of infection.

BACKGROUND Mental health problems in adolescents are prevalent while population-based interventions for improving mental wellbeing of adolescents are limited. OBJECTIVE To design a smartphone app and evaluate its effect on promoting mental wellbeing of adolescents and awareness of anxiety disorders. METHODS A pilot cluster randomised controlled trial was conducted with 2 secondary schools (390 students, mean age 13.1 years) randomised to the intervention and control groups. A smartphone app was designed for one month’s use to promote mental wellbeing through “Sharing, Mind and Enjoyment (SME)” related interactions between students and their parents (e.g., express gratitude to family in words or actions), with assistance of App designers in releasing SME tasks daily. The waitlist control group was offered the app after completing all assessments. The primary outcomes were SME behaviours measured at 3-month after baseline. Secondary outcomes included subjective happiness, wellbeing, personal health and happiness, family health, happiness and harmony, self-perceived knowledge and understanding of anxiety disorders. Two focus groups of students and three individual in-depth interviews of service providers were conducted. RESULTS In the intervention students, 11.2% used the app together with parents and 45.4% used it without involving parents. The intervention group did not show significant difference in the change of SME behaviours at 1-month or 3-month compared with the control group. The intervention group showed greater increase in the awareness of anxiety disorders at follow-ups than the control group (Cohen’s d=0.52 at 1-month and 0.43 at 3-month, both P CONCLUSIONS The app did not show effectiveness in increasing SME behaviours of students but was effective in increasing awareness of anxiety disorders. Further improvements and tests among younger children and their parents are warranted. CLINICALTRIAL ClinicalTrials.gov NCT03361475

This paper proposes a satellite laser communication system based on M-QAM OFDM and analyzes the system performance. The relationship between the link bit error rate and the transmission power under different conditions of atmospheric turbulence intensity and QAM modulation order is simulated. The results show that as the turbulence intensity increases, the QAM modulation order M increases, and the performance of OFDM optical links continues to deteriorate. This provides a reference for parameter optimization and performance evaluation of OFDM optical links in satellite laser communications.

Air source heat pump (ASHP) units have been widely used for space heating in recent years. While a space heating ASHP unit is normally rated at its nominal operating condition, however, during its actual space heating operation, it rarely works at the nominal condition. The actual output heating capacity can remarkably deviate from that at the nominal condition, due to the influences of ambient air temperature and frosting-defrosting operation. Therefore, to enable a comprehensive and convenient evaluation of the operating performance of ASHP units with frosting-defrosting operation and to provide designers with appropriate design guidelines to size a space heating ASHP unit, a new performance index has been proposed. The new performance index, ɛNL, or the loss coefficient in the nominal output heating energy, was actually based on the nominal output heating capacity of ASHP units, which was readily available and stayed unchanged irrespective when and where ASHP units were operated. In this paper, the definition of ɛNL was firstly given, following a detailed explanation of the frosting-defrosting operation of an ASHP unit. Secondly, a GRNN model for predicting the ɛNL of a field ASHP unit was established following a correlation analysis using a total of 473 groups of field measured data from the field ASHP unit. Finally, a modeling study using the developed GRNN model was carried out, and the study results suggested that when an ASHP unit was operated at a fixed ambient condition, defrosting initiating time would affect the ɛNL, and there may exist an optimal defrosting initiating time at which ɛNL was at its minimum. The model results also demonstrated that an increase in ambient air relative humidity or a decrease in ambient air temperature would result in an increase in ɛNL, when an ASHP unit was operated with a fixed defrosting initiating time.

Modelling and analyzing the pass-through of crude oil prices to retail gasoline prices has received an increasing attention in existing literature. However, most of the ongoing efforts focus on point-valued data, which may suffer from the informational loss. This paper first employs the threshold autoregressive interval-valued (TARI) models developed recently by Sun et al. (2018a) to investigate this transmission, and proposes a novel consistent interval-based test to detect threshold effects, and derives its asymptotic properties. These interval-based TARI model and test, superior to traditional point-based methods, can produce more efficient parameter estimation and more powerful inference due to the informational gain of interval data. That is, interval data simultaneously contain more information (e.g., trend and volatility) than point-valued data during the same period. Empirical results suggest that retail gasoline prices are adjusted upwards faster than downwards, and this short-run asymmetry is statistically significant during the whole sample. Our findings reveal that both the level and volatility of oil prices have a positive impact on the price of gasoline, which contributes to the asymmetries in the transmission of oil price shocks. These results are robust before and after financial crisis. Furthermore, it is interesting to find that after financial crisis, both the error correction adjustment speeds and the asymmetries decrease.

Air source heat pumps (ASHPs) have been widely used for providing buildings with heating in winter and cooling in summer. In certain locations, with an increased level of air pollutions, fouling of the outdoor coil in a space cooling ASHP unit may appear, which affects the operating performances of the ASHP unit. Furthermore, the operating performances of an ASHP unit can also be affected by ambient air temperature (Ta). In this paper, a field study on the effects of outdoor coil fouling at different Ta on the operating performances of a field space cooling ASHP unit is presented. The study results demonstrated that the operating performances of the field ASHP unit were significantly affected by the changes in both Ta and percentage of fouled outdoor coil surface (PFOCS). For example, at Ta = 30 °C, the variation in PFOCS from 0 to 100% led to a reduction in COP for the field ASHP unit from 2.7 to 2.0. At a fixed PFOCS of 60%, the changes in Ta from 26 to 33 °C resulted in a reduction in COP from 2.6 to 2.1. In order to more conveniently investigate the combined impacts of fouling on the operating performances of an ASHP unit at different Ta, an equivalent ambient air temperature rise (ETR) was proposed. Based on the measured and evaluated operating parameters of the field ASHP unit at different Ta and PFOCS values, ETR values at 0 - 40%, 40 - 60%, 60 - 100% and 0 - 100% PFOCS ranges were evaluated. These ETR values implied that defouling of a fouled outdoor coil may be initiated when PFOCS was at 40 - 60%. With the ETR values for the full PFOCS range of 0 - 100%, the impact of full fouling on the operating performances of an ASHP unit may be evaluated as if it was operated with a clean outdoor coil but at an equivalent ambient air temperature of Ta + ETR.

To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy (NYTYST) in combination with the Western Medicine Climen in treating diminished ovarian reserve (DOR).From September 2014 to September 2016, 46 patients with DOR who received NYTYST and Climen (treatment group) and 51 patients who received Climen only (control group) at the Jiangsu Provincial Traditional Chinese Medicine Hospital (Nanjing, China) were retrospectively reviewed. Before and at 3 months after treatment, serum levels of follicle-stimulating hormone (FSH), FSH/luteinizing hormone (LH), estradiol (E2), and anti-Mullerian hormone (AMH), the antral follicle count (AFC), stromal peak systolic velocity (PSV), symptom scores, and the clinical effectiveness rate were measured and compared between the two groups.After treatment, serum levels of FSH, FSH/LH and E2, and symptom scores were significantly decreased compared with before treatment (all P0.05) in the two groups. AMH levels, AFC, and PSV were significantly increased after treatment compared with before treatment in both groups (all P0.05). Serum levels of FSH, FSH/LH, and E2 after treatment were significantly lower in the treatment group than in the control group (all P0.05). However, AMH levels and the AFC were significantly higher after treatment in the treatment group than in the control group (both P0.05). The clinical effectiveness rate was significantly higher in the treatment group than in the control group (87% vs 68.6%, P0.05).NYTYST combined with Climen may be more effective in treating DOR than Climen alone.

This study aims to reveal the visible–light photocatalytic performance of Pt supported and carbon coated Bi2MoO6 (Pt/C@Bi2MoO6) composite on the degradation of aquatic 2,4–dibromophenol (DBP) pollutant. The surface structure analysis shows that Pt and carbon layer can tightly bind to the surface of Bi2MoO6 with the chemical bonds, and hybrid the original band gap to generate new impurity levels to enhance the visible–light utilization efficiency. The carbon layer has excellent conductivity to transformation electrons from valence band (VB) site, and the supported Pt atoms on carbon layer generate a plasma electron field to enhance the reductive activity on conduction band (CB) site. The Pt/C@Bi2MoO6 composite shows more efficient and reliable abilities in DBP photocatalytic degradation, and the debromination and oxidization processes are performed separately on CB and VB site, respectively. The DBP debromination proceeds by electrons in the CB site in priority to generate non–brominated intermediate products, and then the oxidization and mineralization procedures start by hydroxide radicals in the VB site to finish the complete degradation of DBP. This research reveals the important roles of Pt and carbon layer in band gap structure modification and photocatalytic activity improvement, exhibiting a new insight to design an efficient and stable photocatalyst for persistent organic pollutant degradation under visible–light irradiation.

The gC1qR is a ubiquitously expressed cell protein that interacts with the globular heads of C1q (gC1q) and many other ligands. In this study, one gC1qR homolog gene was obtained from Exopalaemon carinicauda and named EcgC1qR. The complete nucleotide sequence of EcgC1qR contained a 774 bp open reading frame (ORF) encoding EcgC1qR precursor of 257 amino acids. The deduced amino acid sequence of EcgC1qR revealed a 55-amino-acid-long mitochondrial targeting sequence at the N-terminal and a mitochondrial acidic matrix protein of 33 kDa (MAM33) domain. The genomic organization of EcgC1qR gene showed that EcgC1qR gene contained five exons and four introns. EcgC1qR could express in all of the detected tissues and its expression was much higher in hepatopancreas and hemocytes. The expression of EcgC1qR in the hepatopancreas of prawns challenged with Vibrio parahaemolyticus and Aeromonas hydrophila changed in a time-dependent manner. The expression of EcgC1qR in prawns challenged with V. parahaemolyticus was up-regulated at 6 h (p 0.05), and significantly up-regulated at 12 h and 24 h (p 0.01), and then returned to the control levels at 48 h post-challenge (p 0.05). At the same time, the expression in Aeromonas-challenged group was significantly up-regulated at 6, 12 and 24 h. The recombinant EcgC1qR could inhibit the growth of two tested bacteria. In addition, we successfully deleted EcgC1qR gene through CRISPR/Cas9 technology and it was the first time to obtain the mutant of gC1qR homolog gene in crustacean. It's a great progress to study the biological function of gC1qR in crustacean in future.

Crude oil is one of the most important energy sources in the world, and it is very important for policymakers, enterprises and investors to forecast the price of crude oil accurately. This paper proposes an interval decomposition ensemble (IDE) learning approach to forecast interval-valued crude oil price by integrating bivariate empirical mode decomposition (BEMD), interval MLP (MLPI) and interval exponential smoothing method (HoltI). Firstly, the original interval-valued crude oil price is transformed into a complex-valued signal. Secondly, BEMD is used to decompose the constructed complex-valued signal into a finite number of complex-valued intrinsic mode functions (IMFs) components and one complex-valued residual component. Thirdly, MLPI is used to simultaneously forecast the lower and the upper bounds of each IMF (non-linear patterns), and HoltI is used for modeling the residual component (linear pattern). Finally, the forecasting results of the lower and upper bounds of all the components are combined to generate the aggregated interval-valued output by employing another MLPI as the ensemble tool. The empirical results show that our proposed IDE learning approach with different forecasting horizons and different data frequencies significantly outperforms some other benchmark models by means of forecasting accuracy and hypothesis tests.

A defrosting initiation strategy based on tube-encircled photoelectric sensors (TEPS) was previously proven effective for enhancing the frosting-defrosting performances of air source heat pumps (ASHPs) in cold and dry regions. To verify its applicability to, and evaluate the energy-saving potential when using the TEPS-based strategy in mild and humid regions, field tests were conducted in Guiyang City, China, where the outdoor averaged air temperature and relative humidity were 4.5 °C and 80% in winter, respectively. Two ASHPs of the same-make, one with the TEPS-based strategy and the other with the commonly used temperature-time (TT) strategy, were tested. Totally, seven test cases were organised. Cases 1–5 were for short-term tests to verify the technical feasibility of TEPS-based strategy by comparing the defrosting accuracy of the two strategies. Cases 6–7 were for long-term tests to validate the reliability and effectiveness of the TEPS-based strategy by comparing two ASHPs’ operating performances. The test results demonstrated that the use of TEPS-based strategy in mild and humid regions can initiate defrosting more accurately, reliably and efficiently, and thus improve the COP and heating capacity by 11.3% and 12.1%, respectively, compared to the use of the TT strategy. Therefore, it was proven that the TEPS-based strategy was more effective for the ASHPs used in mild and humid regions, for a more accurate defrosting initiation and higher energy efficiency.

Modeling and forecasting symbolic data, especially interval-valued time series (ITS) data, has received considerable attention in statistics and related fields. The core of available methods on ITS analysis is based on various applications of conventional linear modeling. However, few works have considered possible nonlinearities in ITS data. In this paper, we propose a new class of threshold autoregressive interval (TARI) models for ITS data. By matching the interval model with interval observations, we develop a minimum-distance estimation method for TARI models, and establish the asymptotic theory for the proposed estimators. We show that the threshold parameter estimator is T-consistent and follows an asymptotic compound Poisson process as the sample size T → ∞ . And the estimators for other TARI model parameters are root-T consistent and asymptotically normal. Simulation studies show that the proposed TARI model provides more accurate out-of-sample forecasts than the existing center–radius self-exciting threshold (CR-SETAR) model for ITS data in the literature. Empirical applications to the S&P 500 Price Index document significant asymmetric reactions of the stock markets in Japan, U.K. and France to shocks from the U.S. stock market and that incorporating this asymmetric effect yield better out-of-sample forecasts than a variety of popular models available in the literature.