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Abstract Background Chromosomal 16p11.2 deletions and duplications are genomic disorders which are characterized by neurobehavioral abnormalities, obesity, congenital abnormalities. However, the prenatal phenotypes associated with 16p11.2 copy number variations (CNVs) have not been well characterized. This study aimed to provide an elaborate summary of intrauterine phenotypic features for these genomic disorders. Methods Twenty prenatal amniotic fluid samples diagnosed with 16p11.2 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed in parallel. The pregnancy outcomes and health conditions of all cases after birth were followed up. Meanwhile, we made a pooled analysis of the prenatal phenotypes in the published cases carrying 16p11.2 CNVs. Results 20 fetuses (20/20,884, 0.10%) with 16p11.2 CNVs were identified: five had 16p11.2 BP2-BP3 deletions, 10 had 16p11.2 BP4-BP5 deletions and five had 16p11.2 BP4-BP5 duplications. Abnormal ultrasound findings were recorded in ten fetuses with 16p11.2 deletions, with various degrees of intrauterine phenotypic features observed. No ultrasound abnormalities were observed in any of the 16p11.2 duplications cases during the pregnancy period. Eleven cases with 16p11.2 deletions terminated their pregnancies. For 16p11.2 duplications, four cases gave birth to healthy neonates except for one case that was lost to follow-up. Conclusions Diverse prenatal phenotypes, ranging from normal to abnormal, were observed in cases with 16p11.2 CNVs. For 16p11.2 BP4-BP5 deletions, abnormalities of the vertebral column or ribs and thickened nuchal translucency were the most common structural and non-structural abnormalities, respectively. 16p11.2 BP2-BP3 deletions might be closely associated with fetal growth restriction and single umbilical artery. No characteristic ultrasound findings for 16p11.2 duplications have been observed to date. Given the variable expressivity and incomplete penetrance of 16p11.2 CNVs, long-term follow-up after birth should be conducted for these cases.

AbstractWe conducted an analysis of the complete mitochondrial genome of Rhipicephalus haemaphysaloides, a tick species known for transmitting various bacteria and viruses. The mitochondrial genome of R. haemaphysaloides has a length of 14,739 bp and consists of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and 2 control regions. By utilizing the maximum likelihood method, we established the phylogenetic relationship among R. haemaphysaloides and other species within the Rhipicephalus genus of the Ixodidae family. This analysis revealed that R. haemaphysaloides and other Rhipicephalus species belong to the same clade, further affirming the taxonomic placement of R. haemaphysaloides within the Rhipicephalus genus. Furthermore, we compared the mitochondrial genomes of R. haemaphysaloides isolates from Changning, Yunnan Province, China, with isolates from Yangxin, Ganzhou, and Yingtan, Hubei Province, China. In summary, our investigation offers genetic proof endorsing the taxonomic categorization and phylogenetic placement of Ixodidae by assessing the entire mitochondrial genome of R. haemaphysaloides.

In this paper, using the data collected from phasor measurement units (PMUs), two methods based on Fisher random matrix are proposed to detect faults in power grids. Firstly, the fault detection matrix is constructed and the event detection problem is reformatted as a testing problem for two-sample covariance matrices, which is related with the so-called Fisher matrix. To save computing resources, the screening step of fault interval based on the test statistic is designed to check the existence of faults. Then two point-by-point methods are proposed to determine the time of the fault in the selected interval. One method detects faults by the limiting spectral distribution of the standard Fisher matrix, which can detect the faults with higher accuracy. The other method tests the faults based on the proposed test statistic , which has a faster detection speed. Compared with existing works, the simulation results illustrate that two methods proposed in this paper cost less computational time and provide a higher degree of accuracy and sensitivity.

Abstract Tumor immune escape caused by low levels of tumor immunogenicity and immune checkpoint‐dependent suppression limits the immunotherapeutic effect. Herein, a “two‐way regulation” epigenetic therapeutic strategy is proposed using a novel nano‐regulator that inhibits tumor immune escape by upregulating expression of tumor‐associated antigens (TAAs) to improve immunogenicity and downregulating programmed cell death 1 ligand 1 (PD‐L1) expression to block programmed death‐1 (PD‐1)/PD‐L1. To engineer the nano‐regulator, the DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) and the bromodomain‐containing protein 4 (BRD4) inhibitor JQ1 are co‐loaded into the cationic liposomes with condensing the toll‐like receptor 9 (TLR9) agonist cytosine‐phosphate‐guanine (CpG) via electrostatic interactions to obtain G‐J/ZL. Then, asparagine–glycine–arginine (NGR) modified material carboxymethyl‐chitosan (CMCS) is coated on the surface of G‐J/ZL to construct CG‐J/ZL. CG‐J/ZL is shown to target tumor tissue and disassemble under the acidic tumor microenvironment (TME). Zeb upregulated TAAs expression to improve the immunogenicity; JQ1 inhibited PD‐L1 expression to block immune checkpoint; CpG promote dendritic cell (DC) maturation and reactivated the ability of tumour‐associated macrophages (TAM) to kill tumor cells. Taken together, these results demonstrate that the nano‐regulator CG‐J/ZL can upregulate TAAs expression to enhance T‐cell infiltration and downregulate PD‐L1 expression to improve the recognition of tumor cells by T‐cells, representing a promising strategy to improve antitumor immune response.

Exhaled ammonia (NH3) is an essential noninvasive biomarker for disease diagnosis. In this study, an acetone-modifier positive photoionization ion mobility spectrometry (AM-PIMS) method was developed for accurate qualitative and quantitative analysis of exhaled NH3 with high selectivity and sensitivity. Acetone was introduced into the drift tube along with the drift gas as a modifier, and the characteristic NH3 product ion peak of (C3H6O)4NH4+ (K0 = 1.45 cm2/V·s) was obtained through the ion-molecule reaction with acetone reactant ions (C3H6O)2H+ (K0 = 1.87 cm2/V·s), which significantly increased the peak-to-peak resolution and improved the accuracy of exhaled NH3 qualitative identification. Moreover, the interference of high humidity and the memory effect of NH3 molecules were significantly reduced via online dilution and purging sampling, thus realizing breath-by-breath measurement. As a result, a wide quantitative range of 5.87–140.92 μmol/L with a response time of 40 ms was achieved, and the exhaled NH3 profile could be synchronized with the concentration curve of exhaled CO2. Finally, the analytical capacity of AM-PIMS was demonstrated by measuring the exhaled NH3 of healthy subjects, demonstrating its great potential for clinical disease diagnosis.

Abstract Aims To explore the effects of training programs for ophthalmic specialist nurses in Zhejiang Province of China. Methods The training program included one month of theoretical training and three months of practical clinical training. The Two-Tutor system was used in training. The training contents were mainly set up around four modules: specialty knowledge and clinical skills, management, clinical teaching, and nursing research. We used theoretical examination, clinical practice assessment and trainee evaluation to assess the effectiveness of the training program. Before and after the training, the trainees’ core competence was assessed by a homemade questionnaire. Results In total, 48 trainees from 7 provinces (municipalities) in China participated in the training program. All trainees passed theoretical and clinical practice examinations and trainee evaluations. Their core competencies were significantly improved after training (p

Purpose This retrospective analysis aimed to evaluate the clinical outcomes and cost-effectiveness of long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia caused by chemotherapy for breast cancer. Methods Patients with breast cancer who received long- or short-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia were enrolled in this study, and incidences of neutropenia were compared between two groups. A decision-analytic and a Markov model were used to compare the health benefits and costs of utilizing long- vs short-acting granulocyte-colony stimulating factor as the primary prophylaxis from the perspective of the Chinese health service system. Subsequently, one-way deterministic and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratios were calculated in baseline and sensitivity analyses. Results Patients receiving long-acting granulocyte-colony stimulating factor as the primary prophylaxis of chemotherapy-induced neutropenia experienced a significant lower incidence of this adverse event, compared with the short-acting one for 2 to 7 days. The outcomes of baseline analysis indicated that long-acting granulocyte-colony stimulating factor had a gain of 0.08 quality-adjusted life years and costed $149 more than the short-acting one, yielding an incremental cost-effectiveness ratio of $1792 per quality-adjusted life year. The sensitivity analysis proved the stability of our models and economic efficiency of long-acting granulocyte-colony stimulating factor. Conclusions Patients receiving long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia experienced lower risk of this event compared with those underusing short-acting one. The long-acting granulocyte-colony stimulating factor may be a more cost-effective strategy for primary prophylaxis of neutropenia than short-acting one, considering the Chinese willingness-to-pay threshold of $12158.6 per quality-adjusted life year.

Tree species composition in forest ecosystems is an important biological factor affecting the diversity of ectomycorrhizal fungi (EMF). However, little is known about the composition and diversity of EMF communities associated with Pinus massoniana in different P. massoniana association habitats (MpAHs) in subtropical mountains. This study investigated the EMF community characteristics of P. massoniana in different MpAHs using plant community surveys, soil property analyses, and mycorrhizal identification. A total of 56 operational taxonomic units (OTUs), belonging to 20 families and 22 genera, were identified. OTU richness of Basidiomycota (58.93%) was higher than that of Ascomycota (41.07%). Unclassified Helotiales, Russula, Lactarius, and Tomentella were the dominant groups. Different stand types significantly altered the EMF communities of P. massoniana (p < 0.05, for Shannon index) and the associations of P. massoniana + Populus adenopoda (Mp_Pa) had the highest diversity of EMF, while P. massoniana + Cunninghamia lanceolata (Mp_Cl) had the lowest diversity. The number of specific OTUs was higher than shared OTUs. Similarity index and principal coordinate analysis indicated that the EMF communities of P. massoniana varied significantly in different MpAHs (R2 = 0.21, p = 0.001). The linear regression model showed that the EMF diversity of P. massoniana was positively related to tree species diversity, indicating that the EMF diversity of P. massoniana is influenced by tree species diversity. The findings provide a reasonable reference for tree species configuration in the process of mixed transformation or near-natural management of plantations.

Fleas represent a group of paramount medical significance, subsisting on blood and acting as vectors for an array of naturally occurring diseases. These pathogens constitute essential elements within the plague biome, exerting deleterious effects on both human and livestock health. In this study, we successfully assembled and sequenced the whole mitochondrial genome of Frontopsylla spadix and Neopsylla specialis using long-range PCR and next-generation sequencing technologies. The mitogenomes of F. spadix and N. specialis both have 37 genes with full lengths of 15,085 bp and 16,820 bp, respectively. The topology of the phylogenetic tree elucidates that species F. spadix is clustered in a branch alongside other members of the family Leptopsyllidae, whereas species N. specialis is a sister taxon to Dorcadia ioffi and Hystrichopsylla weida qinlingensis. It also suggests that Pulicidae form a monophyletic clade, Ctenopthalmidae, Hystrichopsyllidae, Vermipsyllidae form a sister group to Ceratophyllidae/Leptopsyllidae group. The mitochondrial genomes of F. spadix and N. specialis were sequenced for the first time, which will contribute to a more comprehensive phylogenetic analysis of the Siphonaptera order. The foundation for subsequent systematic studies, and molecular biology of fleas was established.

Immunotherapy represents one of the most effective strategies for cancer treatment. Recently, progress has been made in using natural killer (NK) cells for cancer therapy. NK cells can directly kill tumor cells without pre-sensitization and thus show promise in clinical applications, distinct from the use of T cells. Whereas, research and development on NK cell-based immunotherapy is still in its infancy, and enhancing the therapeutic effects of NK cells remains a key problem to be solved. An incompletely understanding of the mechanisms of action of NK cells, immune resistance in the tumor microenvironment, and obstacles associated with the delivery of therapeutic agents in vivo, represent three mountains that need to be scaled. Here, we firstly describe the mechanisms underlying the development, activity, and maturation of NK cells, and the formation of NK‑cell immunological synapses. Secondly, we discuss strategies for NK cell-based immunotherapy strategies, including adoptive transfer of NK cell therapy and treatment with cytokines, monoclonal antibodies, and immune checkpoint inhibitors targeting NK cells. Finally, we review the use of nanotechnology to overcome immune resistance, including enhancing the anti-tumor efficiency of chimeric antigen receptor-NK, cytokines and immunosuppressive-pathways inhibitors, promoting NK cell homing and developing NK cell-based nano-engagers.

Background Venous thromboembolism (VTE) is a severe preventable complication among ophthalmic surgical patients. The knowledge, attitude, and practice (KAP) of nurses play a key role in effective VTE prevention. However, little is known about the KAP of ophthalmic nurses’ VTE prevention. This study aimed to examine the level of KAP toward VTE prevention among Chinese ophthalmic nurses and to investigate the influencing factors of their VTE practice. Methods A total of 610 ophthalmic nurses from 17 cities in Hunan and Zhejiang Provinces, China, participated in this study. Data was collected via the Sojump online platform from March to April 2021. A self-administered VTE questionnaire was developed to assess nurses’ KAP toward VTE prevention. Multiple linear regression analysis was used to analyze the influencing factors of ophthalmic nurses’ VTE prevention practice. Results The scores (correct rates) of ophthalmic nurses’ knowledge, attitude, and practice were 103.87 ± 20.50 (76.4%), 21.96 ± 2.72, and 48.96 ± 11.23 (81.6%), respectively. The three lowest-scored knowledge items were related to VTE complications, physical prevention, and risk assessment. The three lowest-scored attitude items were related to nurses’ training, VTE risk, and patient education. The three lowest-scored practice items were related to the assessment scale, VTE assessment, and patient education. Nurses’ knowledge, attitude, and practice were significantly correlated with each other. Multiple linear regression analysis showed that Hunan Province (B = 2.77, p = 0.006), general hospital (B = 2.97, p = 0.009), outpatient department (B = 3.93, p = 0.021), inpatient department (B = 2.50, p = 0.001), previous VTE prevention training (B = 3.46, p < 0.001), VTE prevention management in hospital (B = 4.93, p < 0.001), better knowledge (B = 0.04, p = 0.038), and positive attitude towards VTE prevention (B = 1.35, p < 0.001) were all significantly and positively associated with higher practice scores in VTE prevention. Conclusions Our study provided a comprehensive understanding of the ophthalmic nurses’ knowledge, attitude, and practice in VTE prevention, as well as identified specific items in each dimension for improvement. In addition, our study showed multiple factors were associated with ophthalmic nurses’ practice in VTE prevention, including environmental factors, training and management, knowledge and attitudes toward VTE prevention. Our findings provide important implications and guidance for future intervention programs to improve the ophthalmic nurses’ knowledge, attitude, and practice in VTE prevention.

Glycerol 3-phosphate dehydrogenase 1 (GPD1) acts as a tumor suppressor in various types of cancer. However, the mechanisms of GPD1 anti-tumor remain unclear in breast cancer. This study aims to explore the function and clinical relevance of GPD1 in breast cancer. We confirmed that GPD1 inhibited the ability of proliferation, migration, and invasion in GPD1 overexpression breast cancer cells by CCK-8, wound healing, and Transwell assays, respectively. We found that GPD1 overexpression activated the lipid synthesis pathway and PI3K/AKT signaling pathway. The inhibitory effect of GPD1 on breast cancer cells was also weakened after treatment with LY294002, a PI3K/AKT pathway inhibitor. These results indicated that GPD1 suppressed the carcinogenesis of breast cancer through increasing PI3K/AKT-mediated lipid signaling pathways. Meanwhile, we detected that the relationship between GPD1 level and survival rate presents a positive correlation in breast cancer patients from the Cancer Genome Atlas (TCGA) database. Therefore, GPD1 can be a prognostic biomarker and target in developing therapeutic strategies for breast cancer patients.

With the vigorous development of e-commerce, efficient order picking in e-commerce warehouses has attracted the attention of many scholars. To analyze the issues about order-picking efficiency currently being studied by relevant scholars in e-commerce warehouses, this paper reviews the literature on the application of order-picking strategy and efficiency optimization direction from 2020 to 2022. That mainly falls into two categories of picking systems: “picker-to-parts” and “parts-to-picker”. In the “picker-to-parts” picking system, more attention is paid to the picking strategies of storage assignment and order batching and the integration of multiple picking strategies. In contrast, in the “parts-to-picker” picking system, the main attention is on the man-machine cooperation in the Mobile Robot Fulfillment System (RMFS) and the Automated Storage and Retrieval System (AS/RS), as well as the coordination of the picking station. Further, this paper proposes future research directions for two categories of picking systems: further studying the order splitting strategy and order delivery issues; considering the dynamic uncertainties; combining the automated picking system with different picking strategies, and so on.

Marine hydrates mainly occur in clayey silt sediments, and their occurrence environment has the characteristics of a high clay content and low permeability, which seriously inhibit an increase in the gas production rate. This study presents a new method, the high-pressure jet breaking and sand filling method, to transform the natural gas hydrate (NGH) reservoir near the production well, whereby a water jet is used to form an area of sediment with large particle diameters and high permeability. Based on indoor experiments, we report the characteristics of hydrate formation, decomposition, and phase equilibrium in the transition area formed by this method under different sand particle sizes and mass fractions. The addition of sand at a high mass fraction with a large particle diameter significantly shortened the time required for rapid hydrate formation, prolonged slow hydrate formation, and reduced the increase in temperature. With an increase in the mass fraction of large-diameter sand, the free water content of pores increased, which made it easier to form hydrates with large particles, thus delaying the hydrate decomposition rate. The phase equilibrium curves of hydrates in clayey silt sediments with sand added at mass fractions of 30% and 50% were close to that of bulk hydrate in pure water at lower temperatures. As the temperature increased, the phase equilibrium curves gradually approached those of hydrates in clayey silt sediments.

Abstract Objective To analyze the changes in the prevalence of myopia and its relation to ocular biological parameters, and behaviors among primary school students in China, and understand the prevention and control of myopia. Methods Cross-sectional surveys were performed on 7–9-year-old children in the yrs. 2012 and 2019. In addition, spherical equivalent refraction (SER), axial length (AL), and AL/corneal radius ratio (AL/CR ratio) were collected without cycloplegia. Participants completed detailed questionnaires on behavior related to myopia. Results Data was collected on 623 children (8.02 ± 0.57 years old) in 2012 and 536 students in 2019 (8.09 ± 0.65 years old). The prevalence of myopia was 37.7% in 2012 and 39.9% in 2019. The SER was -0.25 (0.92) D in 2012 and -0.25 (1.25) in 2019. There was no statistical difference in the prevalence of myopia and SER over the 7 years (all P > 0.05). In 2019, the prevalence of myopia among girls demonstrated an increasing trend (33.8% vs. 37.8%), but there was no statistical difference (P > 0.05). The mean AL and AL/CR ratio of boys were decreasing (all P

Abstract Background This study aimed to investigate the differences in optical axial length and close-work activities between only children and children with siblings in Wenzhou. Methods This was a cross-sectional population-based study. In total, 2913 school-aged children and their parents in Wenzhou were included as study subjects from April to May 2021. Data regarding the optical axial length, spherical equivalent refraction, number of children in a family, parental myopia, and close-work activities were collected through eye examinations and questionnaires. A multivariable logistic regression was used to analyze the association between the number of children in a family and optical axial length. Results The children were aged 9.80 ± 3.41 years. The overall percentage of children with an axial length > 24 mm was 38.9%, 44.5% in only children and 35.6% in multiples. The multivariable logistic regression analysis showed that the odds of having an AL > 24 mm were 1.24 times higher in only children than in multiples (OR: 1.24, 95% CI: 1.025–1.480, P = 0.028). Only children were 1.331 times more likely to perform homework > 1 h on weekends than multiples (OR: 1.331, 95% CI: 1.049–1.688, P = 0.019). Only children in upper grades were 1.543 times more likely to perform homework > 1 h on weekends than multiples (OR: 1.543, 95% CI: 1.065–2.235, P = 0.025). Boys who were only children were more likely to attend three or more extracurricular classes for academic subjects than multiples (OR: 1.224, 95% CI: 1.011–1.562, P = 0.004). Conclusions Being an only child may be associated with a higher risk of myopia and higher odds of close-work behaviors. Only children, especially those in upper grades, are more likely to spend more time on homework than their peers who are multiples. Only children, especially boys, are more likely to attend extracurricular classes in academic subjects. Trial registration This trial is registered as ChiCTR1900020584 at www.Chictr.org.cn .

Fleas are one of the most common ectoparasites in warm-blooded mammals and an important vector of zoonotic diseases with serious medical implications. We sequenced the complete mitochondrial genomes of Ceratophyllus anisus and Leptopsylla segnis for the first time using high-throughput sequencing and constructed phylogenetic relationships. We obtained double-stranded circular molecules of lengths 15,875 and 15,785 bp, respectively, consisting of 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and two control regions. AT-skew was negative in both C. anisus (−0.022) and L. segnis (−0.231), while GC-skew was positive in both (0.024/0.248), which produced significant differences in codon usage and amino acid composition. Thirteen PCGs encoding 3,617 and 3,711 codons, respectively, isoleucine and phenylalanine were used most frequently. The tRNA genes all form a typical secondary structure. Construction of phylogenetic trees based on Bayesian inference (BI) and maximum likelihood (ML) methods for PCGs. The results of this study provide new information for the mitochondrial genome database of fleas and support further taxonomic studies and population genetics of fleas.

Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that contains two catalytic domains and a zinc-finger ubiquitin binding domain (ZnF-UBP) domain. The deacetylation function of HDAC6 has been extensively studied with common substrates such as α-tubulin, cortactin, and Hsp90. Apart from its deacetylase activity, HDAC6 ZnF-UBP binds to unanchored ubiquitin of specific sequences and serves as a carrier for transporting aggregated proteins. As a result, aggresomes are formed and protein degradation is facilitated by the autophagy-lysosome pathway. This HDAC6-dependent microtubule transport can be used by cells to assemble and activate inflammasomes, which play a critical role in immune regulation. Even viruses can benefit from the carrier of HDAC6 to assist in uncoating their surfaces during their infection cycle. However, HDAC6 is also capable of blocking virus invasion and replication in a non-enzymatic manner. Given these non-enzymatic functions, HDAC6 is closely associated with various diseases, including neurodegeneration, inflammasome-associated diseases, cancer, and viral infections. Small molecule inhibitors targeting the ubiquitin binding pocket of HDAC6 have been investigated. In this review, we focus on mechanisms in non-enzymatic functions of HDAC6 and discuss the rationality and prospects of therapeutic strategies by intervening the activation of HDAC6 ZnF-UBP in concrete diseases.

Ixodes ovatus is referred to as an obligatory blood-sucking ectoparasite that is capable to infest both humans and animals. In the present study, the complete mitochondrial genome of I. ovatus was sequenced and analyzed using next-generation sequencing (NGS) technology. With a size of 14,520 bp, the entire mitogenome contains 37 genes including 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNAs (rRNAs), and 3 control regions (D-loops). Based on the 13 PCGs nucleotide sequences, the phylogenetic relationship of I. ovatus was analyzed using Maximum-likelihood. As suggested by the results of the obtained phylogenety, I. ovatus is most closely associated with Ixodes hexagonus. This study is expected to promote further studies on the evolution of Ixodidae.

Cyclic GMP-AMP Synthase (cGAS) is a pivotal adaptor of the signaling pathways involving the pattern recognition receptors and plays an important role in apoptosis and immune regulation. The cGAS function in mammals has been investigated extensively; however, the function of duck cGAS (du-cGAS) in response to viral infections is still unclear. This study aimed to clone the mallard (Anas platyrhynchos) cGAS homolog to investigate the function of duck cGAS (du-cGAS) in host antiviral innate immunity. The results showed that the open reading frame (ORF) region of the du-cGAS gene was 1296 bp, encoding 432 amino acids (aa) and exhibiting similar functional domains with its chicken counterpart. Knockdown of the endogenous du-cGAS by specific sgRNA strongly increased the replication of DNA viruses, including duck adenovirus B2 (DAdV B2) and duck short beak and dwarfism syndrome virus (SBDSV). However, the knockout did not impair the replication of novel duck reovirus (NDRV), an RNA virus. Furthermore, the mRNA expressions of type I interferon (IFNs) and vital interferon-stimulated genes (ISGs) were remarkably reduced in the du-cGAS knockout DEF cell line. Inversely, du-cGAS overexpression greatly activated the transcription of IFN-α, IFN-β, and vital ISGs, and impaired the replication of DAdV B2, SBDSV, and NDRV in the DEF cell line. Importantly, we found that a deletion of 68 aa in the N terminus didn’t impair the antiviral function of du-cGAS. Overexpressing NTase Core, C-Domain (Mab21), or Zinc-Ribbon domain independently had no antiviral effects. Generally, these results reveal that du-cGAS is a vital component of the innate immune system of ducks, with a universal antiviral activity, and provides a useful strategy for the control of waterfowl viral diseases.

A fluorescent and colorimetric poly (acrylamide)-based copolymer probe P(AAm-co-RBNCH) has been designed via free radical polymerization of a commercial acrylamide monomer with a rhodamine-functionalized monomer RBNCH. Metal ion selectivity of RBNCH was investigated by fluorescence and colorimetric spectrophotometry. Upon addition of Fe3+, a visual color change from colorless to red and a large fluorescence enhancement were observed for the ring-opening of the rhodamine spirolactam mechanism. The monomer gives a sensitive method for quantitatively detecting Fe3+ in the linear range of 100–200 μM, with a limit of detection as low as 27 nM and exhibiting high selectivity for Fe3+ over 12 other metal ions. The hydrogel sensor was characterized by FTIR, and the effects of RBNCH amount on gel content and swelling properties were explored. According to the recipe of 1.0 mol% RBNCH to the total monomers, the fabricated hydrogel sensor displayed a good swelling property and reversibility performance and has potential for application in the imaging of Fe3+ level in industrial wastewater.

Despite surpassing lung cancer as the most frequently diagnosed cancer, female breast cancer (BC) still lacks rapid detection methods for screening that can be implemented on a large scale in practical clinical settings. However, urine is a readily available biofluid obtained non-invasively and contains numerous volatile organic metabolites (VOMs) that offer valuable metabolic information concerning the onset and progression of diseases. In this work, a rapid method for analysis of VOMs in urine by using high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) coupled with dynamic purge injection. A simple pretreatment process of urine samples by adding acid and salt was employed for efficient VOM sampling, and the numbers of metabolites increased and the detection sensitivity was improved after the acid (HCl) and salt (NaCl) addition. The established mass spectrometry detection method was applied to analyze a set of training samples collected from a local hospital, including 24 breast cancer patients and 27 healthy controls. Statistical analysis techniques such as principal component analysis, partial least squares discriminant analysis, and the Mann–Whitney U test were used, and nine VOMs were identified as differential metabolites. Finally, acrolein, 2-pentanone, and methyl allyl sulfide were selected to build a metabolite combination model for distinguishing breast cancer patients from the healthy group, and the achieved sensitivity and specificity were 92.6% and 91.7%, respectively, according to the receiver operating characteristic curve analysis. The results demonstrate that this technology has potential to become a rapid screening tool for breast cancer, with significant room for further development.

Gastric cancer is a common gastrointestinal cancer. Survival outcome for patients with the recurrence or metastasis remains poor due to the lack of effective targeting drugs. The mechanisms of non-histone acetylation modifications are key epigenetic regulations that participate in various biological processes. HDAC6 is mostly located in the cytoplasm to deacetylate non-histone substrates, which has been identified as a critical promoter of many oncogenic pathways in cancers, including gastric cancer. Nevertheless, its inhibitor has not been applied in gastric cancer clinically. In this study, we identified canagliflozin as an active HDAC6-targeted inhibitor from FDA-approved Drug Library by enzymatic assay. The strong affinity of the compounds with HDAC6 was further verified by surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA). In addition, molecular docking showed that canagliflozin could bind to the active pocket of HDAC6 and form interactions with key residues. Further experiments revealed that canagliflozin could effectively inhibit the migration and epithelial-mesenchymal-transition (EMT) of gastric cancer cells in vitro and in vivo. These results reveal a novel finding that canagliflozin has the potential to be an effective agent in inhibiting gastric cancer metastasis.

ObjectivesInvestigating whether dipeptidyl peptidase-4 inhibitors (DPP4i) could influence the progression of type B intramural hematoma (IMHB) in patients with diabetes mellitus (DM).Materials and methodsUncomplicated IMHB patients were matched by age, sex, and body mass index. Cox proportional hazard models were constructed to identify risk factors. A Kaplan–Meier survival analysis was used to estimate all-cause and aorta-related mortality.ResultsNinety-six matched IMHB patients were divided into Group A (n = 32, IMHB patients without DM), Group B (n = 32, IMHB patients with DMreceiving oral antidiabetic drugs [without DPP4i]) and Group C (n = 32, IMHB patients with DM receiving oral antidiabetic drugs [with DPP4i]). Group C had the lowest rate of aorta-related adverse events (3.1%), aorta-related mortality (0.0%) and reintervention (3.1%). Cox proportional hazard models revealed that a lower eosinophil count (per 0.1, HR, 0.48; 95% CI, 0.29–0.79, P = 0.004) and a higher neutrophil to lymphocyte ratio (NLR) (HR, 1.13; 95% CI, 1.05–1.21, P = 0.001) were associated with higher occurrences of aorta-related adverse events. A lower eosinophil count (per 0.1, HR, 0.40; 95% CI, 0.18–0.89, P = 0.025) and a higher NLR (HR, 1.19; 95% CI, 1.08–1.32, P = 0.001) were also associated with increased aorta-related mortality.ConclusionDPP4i administration in DM patients with IMHB was associated with lower aorta-related mortality and more benign progression than in those who did not receive DPP4i or those without DM. Furthermore, a higher eosinophil count and a lower NLR ratio are potential protective factors that may explain the potential therapeutic benefit of DPP4i.

Ixodes acutitarsus is regarded as the largest Ixodes tick around the world. I. acutitarsus is capable to transmit a wide range of animal and human pathogens. This research pioneered sequencing of the complete mitochondrial genome of I. acutitarsus. With a length of 14,475 bp, the complete mitochondrial genome encodes 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and one replication-initiating region. The phylogenetic relationship was established using the Maximum-likelihood method to indicate that I. acutitarsus and the others of the genus Ixodes fit into the same branch, which confirms the inclusion of I. acutitarsus in the genus Ixodes. The complete mitogenome of sequenced I. acutitarsus provides molecular evidence for the taxonomic status and phylogenetic position of several Ixodes species.

Ixodes vespertilionis is a tick parasitizing on the bodies of bats. In our study, the complete mitogenome of I. vespertilionis was determined by using Illumina sequencing technology. The mitogenome was 14,559 bp in size and was predicted to encode 37 genes including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and one control region. The gene order of the mitogenome is identical to Argasidae and non-Australasian Prostriata. The phylogenetic analysis by the Maximum-likelihood method reveals that I. vespertilionis is phylogenetically closest to Ixodes simplex. These data provide novel reference for further studies on the population genetics and phylogenetics of ticks.

To improve therapeutic effect and reduce severely side effects of carboplatin (CBP), the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus delivery. CBP/SB-NC was prepared by co-loading CBP and NaHCO3 (SB) in nanocapsules using w/o/w emulsification solvent evaporation. They exhibited vesicle-like spherical morphology, uniform particle size and negative zeta potential. Reaching the tumor site with a relatively high concentration is the first step for CBP delivery and the results showed that CBP/SB-NC could effectively increase drug accumulation at tumor site. After that, the drug delivery carriers need to be internalized into tumor cells and the in vitro cellular uptake ability results showed CBP/SB-NC could be internalized into RM-1 cells more efficient than CBP solution. After internalized by RM-1 cells, the gas-blasting release process was tested in acid environment. It was demonstrated that 5 mg/ml NaHCO3 was optimal to achieve pH-responsive gas-blasting release. In vitro release results showed that CBP significantly rapid release in acid environment (pH 5.0) compared to neutral pH (pH 7.4) (P

H146-like goose-origin calicivirus (H146-like GCV) is a novel Caliciviridae family member in the Sanovirus genus that was recently discovered and proposed to cause runting-stunting syndrome and urate deposition in geese. At present, however, there is a lack of epidemiological information pertaining to the dynamics and distribution of H146-like GCV. The development of novel molecular diagnostic approaches capable of rapidly and accurately detecting this virus would support the strengthening, the prevention, and control of H146-like GCV infection. In the present study, we therefore used a TaqMan probe and primers specific for the viral nonstructural (NS) gene to develop a highly sensitive and specific PCR assay capable of detecting this H146-like GCV. The assay reproducibly detected 5.07 × 102 copies of a recombinant DNA plasmid containing the NS gene, with a dynamic range of 8 orders of magnitude (102–109 copies). Importantly, no cross-reactivity was observed with common viruses that affected waterfowl, and when we used this assay to evaluate clinical samples, we found it to be more sensitive and faster than traditional PCR. In summary, herein, we developed a novel TaqMan-based real-time PCR approach that could reliably detect and diagnose H146-like GCV. This tool will allow for the real-time diagnosis of H146-like GCV infections, enabling researchers to better understand the epidemiology and clinical presentation of this disease.

Abstract Background To evaluate the impact of parental myopia and outdoor time on myopia among students in Wenzhou. Methods We examined 1388 primary students from first grade to third grade in Wenzhou from September 2012 to March 2015. We performed noncycloplegic refractometry on each student every six months and axial length (AL) measurements every year. At the commencement of our study, children were asked to complete a questionnaire regarding near work activity and outdoor activity, whereas parents were asked to complete a self-administered questionnaire regarding their background circumstances and their history of myopia. Results A total of 1294 students (93.2%) returned for follow-up examinations. Children with initial and final no myopia spent more time on outdoor activities than those with new onset myopia (1.92 vs. 1.81 h/d, p = 0.022), and elongation of AL in children with a high level (> 2.5 h/day) of outdoor time (0.22 ± 0.13 mm/Y) was less than those with a low level (≤ 1.5 h/day) of outdoor time (0.24 ± 0.14 mm/Y, p = 0.045). The proportion of rapid myopia progression (≤-0.5D/Y) was 16.7%, 20.2% and 31.5% among the children with no myopic parent, one myopic parent and two myopic parents, respectively (X2 = 28.076, p

The solvent-producing bacterium Clostridium acetobutylicum is able to grow on a variety of carbohydrates. The main hexose transport system is the phosphoenolpyruvate-dependent phosphotransferase system (PTS). When the gene glcG that encodes the glucose transporter was inactivated, the resulting mutant glcG::int(1224) grew as well as the wild type, yet its glucose consumption was reduced by 17% in a batch fermentation. Transcriptomics analysis of the phosphate-limited continuous cultures showed that the cellobiose transporter GlcCE was highly up-regulated in the mutant glcG::int(1224). The glcCE mutation did not affect growth and even consumed slightly more glucose during solventogenesis growth compared to wild type, indicating that GlcG is the primary glucose-specific PTS. Poor growth of the double mutant glcG::int(1224)-glcCE::int(193) further revealed that GlcCE was the secondary glucose PTS and that there must be other PTSs capable of glucose uptake. The observations obtained in this study provided a promising foundation to understand glucose transport in C. acetobutylicum.

Abstract Background The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains in southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals. Results The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations between metabolite types and bacterial genus were detected. Conclusions There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.

Objective. We analyzed the etiological classification and clinical characteristics of patients with abnormal liver function indices and elevated serum IgG4 levels and investigated the effects of intrahepatic follicular helper T cell (Tfh) infiltration and serum IL-21. Methods. Clinical data (age, sex, past history, clinical manifestations, laboratory tests, imaging, diagnosis, and treatment) and etiology of liver injury from 136 patients were analyzed. We compared the general condition, clinical characteristics, and laboratory tests of 19 AIH (autoimmune hepatitis) patients with elevated serum IgG4 levels with those of 20 AIH patients with normal serum IgG4 levels admitted at the same time. Five patients with AIH and elevated serum IgG4 levels and five AIH patients with normal IgG4 levels were matched by sex, age, and liver function, and Tfh infiltration in liver biopsy tissues of patients in both groups was determined by immunofluorescence staining. Five AIH patients with elevated serum IgG4 levels were selected for measurement of serum interleukin-21 (IL-21) levels by enzyme-linked immunosorbent assay (ELISA), seventeen AIH patients with normal serum IgG4 were matched by sex, age, and liver function indices, and 29 physically healthy individuals matched by sex and age were selected as the control group. The changes in patients with IgG4-RD and abnormal liver function before and after glucocorticoid treatment were measured. Results. Patients (136) with abnormal liver function indices and elevated serum IgG4 levels were diagnosed with liver disease of different etiologies. IgG4-related disease was the most frequent, followed by AIH and malignancy. Abnormal liver function indices with high serum IgG4 were most commonly seen as elevated gamma glutamyl transferase (GGT). The AIH group with elevated serum IgG4 had increased intrahepatic levels of Tfh. IL-21 in AIH patients with elevated IgG4 was higher than in patients with normal IgG4 and healthy controls. Patients (n = 28) with abnormal liver function indices and IgG4-related disease received glucocorticoid therapy for six months, and ALT, AST, ALKP, GGT, TBil, DBil, IgG, IgG4, and IgE were significantly lower after treatment. Conclusions. Elevated serum IgG4 was seen in patients with abnormal liver function indices with diverse causes. Tfh infiltration and increased IL-21 production may be related to the pathogenesis of AIH with elevated serum IgG4. Glucocorticoid therapy is effective in patients with abnormal liver function indices and IgG4-related disease. Assessing immune function in patients with abnormal liver function indices and elevated serum IgG4 levels should facilitate diagnosis and treatment of the disease.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most deadly cancer worldwide. Multiple long noncoding RNAs (lncRNAs) are recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the functon and mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in the progression of HCC. Methods Expression levels of DUXAP8 in HCC tissue samples were measured using qRT‐PCR. The association between pathological indexes and the expression of DUXAP8 was also analyzed. Human HCC cell lines SMMC‐7721 and QSG‐7701 were used in in vitro studies. CCK‐8 assay was used to assess the effect of DUXAP8 on HCC cell line proliferation. Scratch healing assay and Transwell assay were conducted to detect the effect of DUXAP8 on migration and invasion. Furthermore, dual‐luciferase reporter assay was used to confirm targeting relationship between miR‐422a and DUXAP8. Additionally, Western blot was used to detect the regulatory function of DUXAP8 on pyruvate dehydrogenase kinase 2 (PDK2). Results DUXAP8 expression HCC clinical samples was significantly increased and this was correlated with unfavorable pathological indexes. High expression of DUXAP8 was associated with shorter overall survival time of patients. Its overexpression remarkably facilitated the proliferation, metastasis, and epithelial‐mesenchymal transition of HCC cells. Accordingly, knockdown of it suppressed the malignant phenotypes of HCC cells. Overexpression of DUXAP8 significantly reduced the expression of miR‐422a by sponging it, but enhanced the expression of PDK2. Conclusions DUXAP8 was a sponge of tumor suppressor miR‐422a in HCC, enhanced the expression of PDK2 indirectly, and functioned as an oncogenic lncRNA.

The giant panda (Ailuropoda melanoleuca) is one of the world’s most endangered mammals and remains threatened as a result of intense environmental and anthropogenic pressure. The transformation and specialization of the giant panda’s diet into a herbivorous diet have resulted in unique adaptabilities in many aspects of their biology, physiology and behavior. However, little is known about their adaptability at the molecular level. Through comparative analysis of the giant panda’s genome with those of nine other mammalian species, we found some genetic characteristics of the giant panda that can be associated with adaptive changes for effective digestion of plant material. We also found that giant pandas have similar genetic characteristics to carnivores in terms of olfactory perception but have similar genetic characteristics to herbivores in terms of immunity and hydrolytic enzyme activity. Through the analysis of gene family expansion, 3752 gene families were found, which were enriched in functions such as digestion. A total of 93 genes under positive selection were screened out and gene enrichment identified these genes for the following processes: negative regulation of cellular metabolic process, negative regulation of nitrogen compound metabolic process, negative regulation of macromolecule metabolic process and negative regulation of metabolic process. Combined with the KEGG pathway, it was found that genes such as CREB3L1, CYP450 2S1, HSD11B2, LRPAP1 play a key role in digestion. These genes may have played a key role in the pandas’ adaptation to its bamboo diet.

An unmanned aerial vehicle (UAV) aeromagnetic measurement system can precisely obtain large-scale data with high efficiency and low cost in regions with complex exploration conditions, which has aroused interest in the field of aerial survey. In this article, based on the unmanned helicopter platform, an aeronautical magnetic field measurement system is integrated to complete the integration of a rotor UAV, magnetometers, and data recorders. Equipped with a three-axis fluxgate magnetometer for real-time flight compensation, the compensation deviation is ±0.052 nT, which meets the aeromagnetic survey specifications. The UAV can fly autonomously with a maximum load of 45 kg at a speed of 60 km/h for 2 h, and the wind resistance level is level 7. The system has completed a field test of 111.9 km in the Ma'anshan crisis mine region of China and collected 145,495 data points. Then, the adaptive down-sampling method is used to compress the data (to 1.7% of the original data), and it is applied to the three-dimensional magnetic inversion, which successfully obtains the spatial distribution characteristics of the underground orebody, improving the inversion efficiency while ensuring the target area resolution. Six favorable magnetite prospecting sites are delineated in the survey area through inversion results, which demonstrates the potential of the developed UAV aeromagnetic system in the exploration over the areas with complex terrain.

Adipose tissue inflammation plays an important role in the regulation of glucose and lipids metabolism. It is unknown whether Ursolic acid (UA) could regulate adipose tissue inflammation, though it can regulate inflammation in many other tissues. In this study, 3T3-L1 adipocytes, DIO mice and lean mice were treated with UA or vehicle. Gene expression of inflammatory factors, chemokines and immune markers in adipocytes and adipose tissue, cytokines in cell culture medium and serum, and inflammation regulatory pathways in adipocytes were detected. Results showed that UA increased the expression of interleukins and chemokines, but not TNFα, in both adipocytes and adipose tissue. IL6 and MCP1 levels in the cell culture medium and mouse serum were induced by UA treatment. Cd14 expression level and number of CD14+ monocytes were higher in UA treated adipose tissue than those in the control group. Glucose tolerance test was impaired by UA treatment in DIO mice. Mechanistically, UA induced the expression of Tlr4 and the phosphorylation levels of ERK and NFκB in adipocytes. In conclusion, our study indicated that short-term UA administration could induce CD14+ monocytes infiltration by increasing the production of interleukins and chemokines in mouse adipose tissue, which might further impair glucose tolerance test.

A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring’s liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7α hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD.

ObjectiveThe present study was designed to investigate whether the extracellular signal-regulated kinase (ERK) signaling pathway, a downstream component of dopamine signaling, is involved in myopia among Chinese children.MethodsDuring a 3.5-year follow-up, 488 primary school students were enrolled in this study. Non-cycloplegic spherical equivalent refraction (SE) and other ocular parameters were assessed. Four variants of four genes in the ERK signaling pathway were selected: RASGRF1 rs6495367, PTPN5 rs1550870, PTPRR rs11178469, and PDGFRA rs6554163. SNPscan was used to genotype single-nucleotide polymorphisms (SNPs). PLINK software was used to assess the associations of the genetic variants with the occurrence or development of myopia, SE, and other ocular parameters. We created a protein-protein interaction (PPI) network and microRNA (miRNA)-gene network using String and Cytoscape and conducted enrichment analyses on the genes in these networks.ResultsIn total, 426 children (baseline age: 7.28 ± 0.26 years; 236 (55.4%) boys and 190 girls) wereenrolled. After adjusting for confounding factors with 10,000 permutations, children with the CT or TT genotype of PTPN5 rs1550870 were more susceptible to myopia than those with the CC genotype (adjusted p = 0.011). Additionally, PTPN5 rs1550870 was correlated with significant myopic shift and increasing axial length (AL) and lens thickness (LT) but had a negative effect on central corneal thickness (CCT). RASGRF1 rs6495367 was negatively associated with myopic shift (additive: adjusted p = 0.034; dominant: adjusted p = 0.020), myopic SE and AL. PDGFRA rs6554163 TA or AA was negatively associated with increasing LT (adjusted p = 0.033). Evaluation of the effects of SNP-SNP combinations on incident myopia revealed a statistically significant one-locus model: PTPN5 rs1550870 [cross-validation consistency (CVC) = 10/10, adjusted p = 0.0107]. The genes in the PPI and miRNA-gene interaction networks were subjected to enrichment analyses, which suggested that these genes are involved mainly in eye development and dopaminergic synapse-related processes.ConclusionWe identified genetic variants of crucial ERK signaling pathway genes that were significantly correlated with myopia and ocular parameter alterations in Chinese children. A combination of gene and miRNA functional analyses with enrichment analyses highlights the regulatory effects associated with ocular development and dopamine biological functions. This study offers novel clues to understand the role of dopamine in the molecular mechanisms of myopia.

BackgroundMyopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-β signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children.MethodsA total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the TGFBR1 rs10760673 and TGFB2-AS1 rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase.ResultsA total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to TGFB2-AS1 were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: P’ = 0.022; dominant: P’ = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of TGFBR1 were associated with a significant myopic shift (additive: P’ = 0.008; dominant: P’ = 0.028; recessive: P’ = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (P’ = 0.013, β = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (P’ = 0.031, β = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak.ConclusionThe present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the TGFBR1 and TGFB2-AS1 genes with myopia may be mediated by the TGF-β signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr.org.cn.

Background: Global consumption of protein per capita is rising, while rates of infertility are increasing. However, a clear relationship between protein intake and reproductive health has not been demonstrated. The activation of the quiescent primordial follicles is the first step of folliculogenesis, and their activation must be tightly controlled to prevent premature exhaustion of the ovarian follicular reserve. Methods: The primordial follicle reserve of wild-type or liver-specific ablation of fibroblast growth factor 21 (FGF21) in mice, subjected to limited or excessive protein diets or oral gavage test, were detected in vivo. Mouse ovary organ cultures were used to examine the direct role of metabolites or metabolic hormones on primordial follicle activation. Findings: Mouse primordial follicle activation, was reduced by restricted protein intake and was accelerated by excessive protein intake, in an ovarian mTORC1 signaling-dependent manner. Furthermore, restricted or excessive protein intake resulted in an augmentation or decline of oocyte number and fertility at older age, respectively. Liver-specific ablation of FGF21, which resulted in a reduction of 87% in circulating FGF21, abrogated the preserving effect of low-protein intake on primordial follicle pool. Interestingly, FGF21 had no direct effect on the activation of primordial follicles, but instead required an adipokine adiponectin. Moreover, AdipoRon, an oral adiponectin receptor agonist, prevented the over-activation effect of excessive protein intake on primordial follicle activation. Interpretation: Dietary protein consumption controlled ovarian primordial follicle reserve and fertility, which required coordination between FGF21 and adiponectin. Fund: Natural Science Foundation of China (Grant 31772616). Keywords: Adiponectin, FGF21, Primordial follicle, Protein intake

To reduce the delay caused by the interweaving and parallel driving of multiple left-turn vehicles and through vehicles upstream of the intersection entrance, the influencing factors and determination methods of unconventional left-turn lanes are studied in right-hand traffic (RHT) countries. For countries driving right, left-turn lanes are usually on the inside of roads. However, when there are a large number of vehicles turning left in the outer lane of the upstream section of the intersection, these vehicles will be forced to pass many consecutive parallel lanes and then enter the left-turn lane. During this process, many traffic conflicts will occur between left-turning vehicles and going-straight vehicles, which will lead to longer traffic delays. To reduce traffic conflicts and delays caused by problems mentioned before, a scheme of setting left-turn lanes abroad is proposed, and major influencing factors and judgment methods of such a scheme are also studied. With the help of traffic simulation software VISSIM, the simulation model of intersection entrance with a different number of through lanes, length of weaving section and left turn inner and outer lanes is established. By inputting different numbers of entry through vehicles and left-turning vehicles in the outer lane, the delay data under different geometric and traffic conditions are obtained for simulation analysis. With the help of MATLAB software, this paper analyzes the influence of the length of the weaving area and the number of left-turning vehicles on the delay of inside and outside left-turning lanes under the condition of a different number of straight vehicles, as well as the variation law between them. By inputting parameters such as the length of the weaving area and the number of lanes, go-straight vehicles and left-turning vehicles into the system of VISSIM, a BP neural network model is constructed and trained. When investigating the entrances of four intersections, the BP neural network model is used to analyze and calculate the traffic delay and determine the setting scheme of the inside or outside of the left-turn lane. Through experiments and further studies, a phenomenon was found: When more vehicles chose to turn left or go straight in the outside lane, the length of the weaving area will become shorter, and the delay reduction effect of the unconventional left-turn lane will more obvious. The specific location of the left-turn lane should be determined by the constructed BP neural network model through the comparative analysis of delay, and the judgment results are in good agreement with the realistic scheme.

Objective. To investigate the association between myopia progression and school entrance age among Chinese schoolchildren and to suggest a more appropriate school age. Methods. 1,463 children aged six to nine years from Wenzhou, China, were examined and followed up for two and a half consecutive years. Their noncycloplegic refraction was measured twice each year by using an automatic refractometer; axial length (AL) and corneal radius of curvature (CRC) were tested annually by using the IOLMaster for 2.5 years. The questionnaires were completed by the children to collect detailed information regarding risk factors. Here, myopia is defined as a spherical equivalent less than −1.0D. Results. The changes in spherical equivalent (SE) of 7-year-old children in grade 1 and grade 2 were −0.45D and -0.56D, while changes in AL were 0.59 mm and 0.62 mm, respectively. The SE changes of 8-year-old children in grade 2 and grade 3 were −0.54D and −0.75D; meanwhile, the AL changes were 0.57 mm and 0.61 mm, respectively. Significant statistical differences were observed in ocular biological structure parameters, except for corneal radius of curvature (CRC) or anterior chamber depth (ACD), among children with the same age in different grades during this study. The prevalence of myopia was also significantly higher in higher grades for children with same age. Conclusions. Myopia is related to children’s school entrance age. Children who start school in an earlier age are more likely to suffer from myopia, and the progression of myopia can be considerably faster. Therefore, it is recommended to enter school after the age of 7.

Purpose. To determine whether the neutrophil-to-lymphocyte ratio (NLR) aids in the detection of obstructive sleep apnea (OSA) in patients with type B aortic dissection (TBAD). Methods. 324 patients with TBAD or type B aortic intramural hematoma (TB-AIMH) underwent an overnight sleep study. We divided the eligible 256 studied subjects into three groups: group A (n = 109, TBAD patients with OSA), group B (n = 68, TB-AIMH patients with OSA), and group C (n = 79, TBAD patients without OSA). Baseline characteristics, biochemical and sleep parameters, and STOP-Bang questionnaire scores were collected. To assess the predictive efficacy of potential variables, multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used. Results. The study found that about 58% of TBAD patients and 54% of TB-AIMH patients had OSA, a majority of whom had moderate to severe OSA (95.41% and 89.71%, respectively). In the comparison of sleep parameters between patients with TBAD and TB-AIMH, no other than apnea and hypopnea index (AHI) made a significant difference. The multivariate logistic regression analysis showed that neutrophil-to-lymphocyte ratio (NLR) (odds ratio (OR): 3.614, 95% confidence interval (CI): 2.273–5.748, and P

The complete mitogenome of Haemaphysalis montgomeryi is reported for the first time in this study. The mitochondrial genome is 14,681 bp in length and includes 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1 control region. The phylogenetic relations base on the maximum-likelihood (ML) method show that H. montgomeryi and the other members of the genus Haemaphysalis constitute a monophyletic group, confirming that H. montgomeryi belongs to the genus Haemaphysalis.

BackgroundMyopia is a common eye disorder that is approaching epidemic proportions worldwide. A genome-wide association study identified AREG (rs12511037), GABRR1 (rs13215566), and PDE10A (rs12206610) as being associated with refractive error in Asian populations. The present study investigated the associations between these three genetic variants and the occurrence and development of myopia, spherical equivalent refraction (SER), axial length (AL), and corneal curvature (CC) in a cohort of southeastern Chinese schoolchildren.MethodsWe examined and followed 550 children in grade 1 enrolled in the Wenzhou Epidemiology of Refractive Error (WERE) project. During the 4-year follow-up, non-cycloplegic refraction was evaluated twice each year, and the AL and CC were measured once every year. Age, sex, and the amounts of time spent on near work and outdoors were documented with a questionnaire. Sanger DNA sequencing was used to genotype single nucleotide polymorphisms (SNPs). SNPtest software was used to identify potential genetic variants associated with myopia, SER, AL, and CC. Ten thousand permutations were used to correct for multiple testing.ResultsIn total, 469 children, including 249 (53.1%) boys and 220 (46.9%) girls, were included in analyses. The mean age of all the children was 6.33 ± 0.48 years. After adjusting for age, sex, time spent on near work and time spent outdoors, neither the genotypes nor the allele frequencies of the three SNPs were significantly associated with myopic shift, incident myopia or the change in SER. After adjusting for age, sex, near-work time and outdoor time with 10,000 permutations, the genotype AREG (rs12511037) was associated with an increase in AL (P′-values for the dominant, recessive, additive and general models were 0.0032, 0.0275, 0.0045, and 0.0099, respectively); the genotype PDE10A (rs12206610) was associated with a change in CC in the additive (P′ = 0.0096), dominant (P′ = 0.0096), and heterozygous models (P′ = 0.0096).ConclusionThese findings preliminarily indicate that AREG SNP rs12511037 and PDE10A SNP rs12206610 are etiologically relevant for ocular traits, providing a basis for further exploration of the development of myopia and its molecular mechanism. However, elucidating the role of AREG and PDE10A in the pathogenesis of myopia requires further animal model and human genetic epidemiology studies. This trial is registered as ChiCTR1900020584 at www.Chictr.org.cn.

The explosive increasing of the social media data on the Web has created and promoted the development of the social media big data mining area welcomed by researchers from both academia and industry. The sentiment computing of news event is a significant component of the social media big data. It has also attracted a lot of researches, which could support many real-world applications, such as public opinion monitoring for governments and news recommendation for Websites. However, existing sentiment computing methods are mainly based on the standard emotion thesaurus or supervised methods, which are not scalable to the social media big data. Therefore, we propose an innovative method to do the sentiment computing for news events. More specially, based on the social media data (i.e., words and emoticons) of a news event, a word emotion association network (WEAN) is built to jointly express its semantic and emotion, which lays the foundation for the news event sentiment computation. Based on WEAN, a word emotion computation algorithm is proposed to obtain the initial words emotion, which are further refined through the standard emotion thesaurus. With the words emotion in hand, we can compute every sentence's sentiment. Experimental results on real-world data sets demonstrate the excellent performance of the proposed method on the emotion computing for news events.

Objective Application of rapid on-site evaluation (ROSE) for thyroid fine needle aspiration (FNA) is controversial. Therefore, ROSE has not been universally applied. This study aimed to evaluate the value of ROSE for ultrasound-guided thyroid FNA. Methods A total of 997 patients with 1103 suspicious thyroid nodules had ultrasound-guided FNA performed from January 2016 to February 2018. There were 513 nodules with ROSE and 590 nodules without ROSE. The cytological nondiagnostic rate, needle passes, and procedural times of thyroid FNA with or without ROSE were compared. The nondiagnostic rates of subsets of suspicious thyroid nodules were further compared. Results There was no significant effect of ROSE on the nondiagnostic rate of FNA. However, FNA with ROSE significantly reduced the numbers of sub-centimeter, mixed solid-cystic, macrocalcified, and hypervascular nodules. There was a significantly smaller number of needle passes and less procedural times with ROSE than without ROSE. There was no significant difference in the complication rate of FNA with and without ROSE. Conclusion ROSE for thyroid FNA reduces the number of needle passes and procedural times. ROSE has a higher clinical application value in subsets of thyroid nodules, which tend to be difficult to diagnose with FNA.

Purpose. To assess the changing profile of astigmatism in Chinese schoolchildren and the association between astigmatism changes and ocular biometry. Methods. We examined and followed up 1,463 children aged 6–9 years from Wenzhou, China. We measured noncycloplegic refraction twice each year and tested axial length (AL) and corneal radius of curvature (CRC) annually for two years. We defined clinically significant astigmatism (CSA) as ≤−0.75 diopter (D) and non-CSA astigmatism as ≤0 to >−0.75 D. Results. Prevalence of CSA at baseline was 22.4% (n = 327) and decreased to 20.3% (n = 297) at the two-year follow-up (P=0.046). Ninety-two (8.1%) non-CSA children developed CSA. In multiple regression, after adjusting for age, gender, baseline cylinder refraction, and axis, children who had longer baseline ALs (>23.58 mm; odds ratio (OR) = 5.19, 95% confidence interval (CI): 2.72–9.90) and longer baseline AL/CRC ratio (>2.99, OR = 4.99, 95% CI: 2.37–10.51) were more likely to develop CSA after two years. Four-hundred and two (27.5%) children had increased astigmatism, 783 (53.5%) had decreased, and 278 (19.0%) had no change during the two-year follow-up. Children with increased astigmatism had longer baseline ALs (23.33 mm, P

Three-dimensional magnetic inversion allows the distribution of magnetic parameters to be obtained, and it is an important tool for geological exploration and interpretation. However, because of the redundancy of the data obtained from large-scale investigations or high-density sampling, it is very computationally intensive to use these data for iterative inversion calculations. In this paper, we propose a method for compressing magnetic data by using an adaptive quadtree decomposition method, which divides the two-dimensional data region into four quadrants and progressively subdivides them by recursion until the data in each quadrant meets the regional consistency criterion. The method allows for dense sampling at the abnormal boundaries with large amplitude changes and sparse sampling at regions with small amplitude changes, and achieves the best approximation to the original data with the least amount of data, thus retaining more anomalous information while achieving the purpose of data compression. In addition, assigning values to the data in the quadrants using the averaging method is essentially equivalent to average filtering, which reduces the noise of the magnetic data. Testing the synthetic model and applying the method to mineral exploration a prove that it can effectively compress the magnetic data and greatly improve the computational efficiency.