Sociodemographic factors impacting the spatial distribution of private dental clinics in major cities of Peoples Republic of China.

OBJECTIVES: Investigate the geographical distribution of private dental practices in major Chinese cities and analyze the variables influencing this distribution. METHODS: This study used Python to extract various types of Point of Interest (POI) data spanning from 2016 to 2022 from the AutoNavi map. A 1km*1km grid was constructed to establish the study sample. Additional spatial pattern data, including nighttime lighting, population, and air quality data, were integrated into this grid. Global Moran's I index was used to analyze the spatial autocorrelation. The spatial lag model was used to explore the influencing factors of private dental practice distribution. RESULTS: This study reveals a specific clustering pattern for private dental practices in major Chinese cities. The primary influencing factors include nighttime lights, population density, and housing prices, suggesting that dental practices are typically concentrated in highly developed regions with dense populations and high housing costs. Additionally, we discovered that patterns vary across different metropolises, with the most pronounced clustering patterns and substantial inequalities found in the most developed areas. CONCLUSIONS: This study establishes that factors such as regional development and population density positively correlate with private dental practice. Additionally, it reveals a strong mutual correlation in the clustering of dental practices, which does not show a substantial correlation with public resources. Finally, it suggests that the spatial heterogeneity pattern implies a rising necessity to tackle inequality issues within urban areas as economic development progresses.

Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

Enterovirus 71 Activates Plasmacytoid Dendritic Cell-Dependent PSGL-1 Binding Independent of Productive Infection.

Enterovirus 71 (EV71) is a significant causative agent of hand, foot, and mouth disease, with potential serious neurologic complications or fatal outcomes. The lack of effective treatments for EV71 infection is attributed to its elusive pathogenicity. Our study reveals that human plasmacytoid dendritic cells (pDCs), the main type I IFN-producing cells, selectively express scavenger receptor class B, member 2 (SCARB2) and P-selectin glycoprotein ligand 1 (PSGL-1), crucial cellular receptors for EV71. Some strains of EV71 can replicate within pDCs and stimulate IFN-α production. The activation of pDCs by EV71 is hindered by Abs to PSGL-1 and soluble PSGL-1, whereas Abs to SCARB2 and soluble SCARB2 have a less pronounced effect. Our data suggest that only strains binding to PSGL-1, more commonly found in severe cases, can replicate in pDCs and induce IFN-α secretion, highlighting the importance of PSGL-1 in these processes. Furthermore, IFN-α secretion by pDCs can be triggered by EV71 or UV-inactivated EV71 virions, indicating that productive infection is not necessary for pDC activation. These findings provide new insights into the interaction between EV71 and pDCs, suggesting that pDC activation could potentially mitigate the severity of EV71-related diseases.

Particle Size Determines the Phytotoxicity of ZnO Nanoparticles in Rice (Oryza sativa L.) Revealed by Spatial Imaging Techniques.

To understand the nanotoxicity effects on plants, it is necessary to systematically study the distribution of NPs in vivo. Herein, elemental and particle-imaging techniques were used to unravel the size effects of ZnO NPs on phytotoxicity. Small-sized ZnO NPs (5, 20, and 50 nm) showed an inhibitory effect on the length and biomass of rice (Oryza sativa L.) used as a model plant. ZnO NP nanotoxicity caused rice root cell membrane damage, increased the malondialdehyde content, and activated antioxidant enzymes. As a control, the same dose of Zn2+ salt did not affect the physiological and biochemical indices of rice, suggesting that the toxicity is caused by the entry of the ZnO NPs and not the dissolved Zn2+. Laser ablation inductively coupled plasma optical emission spectroscopy analysis revealed that ZnO NPs accumulated in the rice root vascular tissues of the rhizodermis and procambium. Furthermore, transmission electron microscopy confirmed that the NPs were internalized to the root tissues. These results suggest that ZnO NPs may exist in the rice root system and that their particle size could be a crucial factor in determining toxicity. This study provides evidence of the size-dependent phytotoxicity of ZnO NPs.

Urban Microplastic Pollution Revealed by a Large-Scale Wetland Soil Survey.

Microplastics (MPs), as a new persistent pollutant, can be emitted and accumulated in urban environments, but there is no detailed information on the driving factors of MP pollution. In this study, through a large-scale wetland soil survey, the features of MPs were characterized in each urban area. The results showed an average abundance to be 379 n/kg in wetland soil. Polypropylene, fiber or fragment, and black color were common composition, shape, and color, respectively. The spatial distribution information showed that MP abundance was significantly relevant to the distance from the urban economic center. Furthermore, the correlation and regression analysis revealed that MP abundance was related to soil heavy metal and atmospheric particle (PM10 and PM2.5) concentrations (P < 0.05), while the promotion of socioeconomic activities (urbanization level, population density, etc.) may aggravate the pollution degree. Additionally, by using structural equation modeling, it was found that the urbanization level was the dominant factor driving the MP pollution degree, with a total effect coefficient of 0.49. Overall, this work provides multi-sided environmental information regarding MP pollution in urban ecosystems, which is significant for follow-up studies of MP pollution control and restoration.

An Integrated Single-Beam Three-Axis High-Sensitivity Magnetometer.

Three-axis atomic magnetometers have great advantages for interpreting information conveyed by magnetic fields. Here, we demonstrate a compact construction of a three-axis vector atomic magnetometer. The magnetometer is operated with a single laser beam and with a specially designed triangular 87Rb vapor cell (side length is 5 mm). The ability of three-axis measurement is realized by reflecting the light beam in the cell chamber under high pressure, so that the atoms before and after reflection are polarized along two different directions. It achieves a sensitivity of 40 fT/Hz in x-axis, 20 fT/Hz in y-axis, and 30 fT/Hz in z-axis under spin-exchange relaxation-free regime. The crosstalk effect between different axes is proven to be little in this configuration. The sensor configuration here is expected to form further values, especially for vector biomagnetism measurement, clinical diagnosis, and field source reconstruction.

RNF213 modulates γ-herpesvirus infection and reactivation via targeting the viral Replication and Transcription Activator.

Interferons (IFNs) and the products of interferon-stimulated genes (ISGs) play crucial roles in host defense against virus infections. Although many ISGs have been characterized with respect to their antiviral activity, their target specificities and mechanisms of action remain largely unknown. Kaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus that is linked to several human malignancies. Here, we used the genetically and biologically related virus, murine gammaherpesvirus 68 (MHV-68) and screened for ISGs with anti-gammaherpesvirus activities. We found that overexpression of RNF213 dramatically inhibited MHV-68 infection, whereas knockdown of endogenous RNF213 significantly promoted MHV-68 proliferation. Importantly, RNF213 also inhibited KSHV de novo infection, and depletion of RNF213 in the latently KSHV-infected iSLK-219 cell line significantly enhanced lytic reactivation. Mechanistically, we demonstrated that RNF213 targeted the Replication and Transcription Activator (RTA) of both KSHV and MHV-68, and promoted the degradation of RTA protein through the proteasome-dependent pathway. RNF213 directly interacted with RTA and functioned as an E3 ligase to ubiquitinate RTA via K48 linkage. Taken together, we conclude that RNF213 serves as an E3 ligase and inhibits the de novo infection and lytic reactivation of gammaherpesviruses by degrading RTA through the ubiquitin-proteasome pathway.

Individual variation in and lateral asymmetry of mouse epididymal draining lymph nodes.

PROBLEM: Draining lymph nodes (LNs) are pivotal sites for maintaining tolerance to self-antigens as well as eliciting immune responses to exogenous antigens. The epididymis is a male reproductive organ with a unique local immune environment. Although mice are the most commonly used laboratory animals for immunology research, there are no detailed descriptions of the anatomical location and function of LNs that drain the epididymis. METHOD OF STUDY: Evans blue labeling was utilized to explore lymphatic drainage of the epididymis in eight- to ten-week-old male C57BL/6 mice. We confirmed the lymphatic drainage of the epididymis in mice using the objective technique of carboxyfluorescein succinimidyl ester (CFSE)-labeled cells. RESULTS: By combined Evans blue labeling and fluorescent labeling, we found that 1) the patterns of epididymal LN drainage are highly heterogeneous between individual mice; 2) the leftside LNs participate in drainage more frequently than the right-side LNs; and 3) epididymal lymphatic drainage bypasses both the paraaortic and renal LNs in some mice. CONCLUSIONS: These data highlighted the need to consider the individual variation in and lateral asymmetry of draining LNs when characterizing the regional immunology of the mouse epididymis.

Time-dependent effects of microplastics on soil bacteriome.

Microplastic threats to biodiversity, health and ecological safety are adding to concern worldwide, but the real impacts on the functioning of organisms and ecosystems are obscure owing to their inert characteristics. Here we investigated the long-lasting ecological effects of six prevalent microplastic types: polyethylene (PE), polypropylene (PP), polyamide (PA), polystyrene (PS), polyethylene terephthalate (PET), and polyvinyl chloride (PVC) on soil bacteria at a 2 % (w/w) level. Due to the inertia and lack of available nitrogen of these microplastics, their effects on bacteriome tended to converge after one year and were strongly different from their short-term effects. The soil volumes around microplastics were very specific, in which the microplastic-adapted bacteria (e.g., some genera in Actinobacteria) were enriched but the phyla Bacteroidetes and Gemmatimonadetes declined, resulting in higher microbial nitrogen requirements and reduced organic carbon mineralization. The reshaped bacteriome was specialized in the genetic potential of xenobiotic and lipid metabolism as well as related oxidation, esterification, and hydrolysis processes, but excessive oxidative damage resulted in severe weakness in community genetic information processing. According to model predictions, microplastic effects are indirectly derived from nutrients and oxidative stress, and the effects on bacterial functions are stronger than on structure, posing a heavy risk to soil ecosystems.

Factors influencing perceived function in the upper limb prosthesis user population.

BACKGROUND: Patient-reported outcomes (PROs) can be used to evaluate perceived capacity of an individual in executing tasks in a natural environment with their prosthetic device. According to the World Health Organization International Classification of Health, Functioning, and Disability (ICF) models, there may be specific factors of a person, factors of assistive prosthetic technology, or factors related to the health condition or body function that affect their functioning and disability. However, an understanding of factors affecting an upper limb prosthesis user's perception of their ability to execute tasks in a natural environment is not well established. OBJECTIVE: To use the ICF model to identify which health condition-related, body function, environmental, and personal factors influence activity as measured by perceived function in the upper limb prosthesis user population. DESIGN: Quantitative clinical descriptive study. SETTING: Clinical offices within outpatient private practice (removed for blinding). PARTICIPANTS: A sample of 101 participants with upper limb amputation who use a prosthetic device and were undergoing a prosthesis fitting process. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: PROs on pain with/without a prosthesis, satisfaction, and perceived function derived from the Comprehensive Arm Prosthesis and Rehabilitation Outcomes Questionnaire. RESULTS: Model coefficients indicate that with a unit increase in satisfaction (p < .001) and pain (p = .031) scores (with higher pain scores signifying less pain), the mean of perceived function increases by 0.66 and 0.47 units, respectively. Conversely, for individuals with elbow disarticulation, transhumeral, shoulder disarticulation, and interscapulothoracic amputations, the mean of perceived function decreases by 22.02 units (p = .006). CONCLUSIONS: Based on our sample, perceived function is significantly associated with satisfaction, pain, and amputation level. These findings could potentially help to inform initial clinical approach and targeted outcomes for patients based on these factors.

Integrating electronic structure regulation and dynamic active sites construction on NixCd1-xS-Ni0 photocatalyst for efficient hydrogen evolution.

Regulating electronic structure and enriching active sites of photocatalysts are effective strategies to promote hydrogen evolution. Herein, a unique NixCd1-xS-Ni0 photocatalyst, including the surface nickel (Ni) doping and atomic Ni0 anchoring sites, is successfully prepared by Ni2+ ions exchange reaction (Ni2++ CdS â†’ NixCd1-xS) and in-situ photo-induction of Ni0(Ni2++NixCd1-xS→hνNixCd1-xS-Ni0), respectively. As to Ni doping, the Ni replaced cadmium (Cd) atoms introduce hybridized states around the Fermi level, modulating the electronic structure of adjacent S atoms and optimizing the photocatalytic activity of sulfur (S) atoms. Besides, photogenerated Ni0 atoms, anchored on unsaturated S atoms, act as charge transfer bridges to reduce Ni2+ ions in the solution to Ni clusters (NixCd1-xS-Ni0→ne-NixCd1-xS-Ni). Subsequently, the displacement reaction of Ni clusters with protons (H+) spontaneously proceeds to produce hydrogen (H2) in an acidic solution (NixCd1-xS-Ni→2H+H2↑+Ni2++NixCd1-xS-Ni0). The equilibrium of photo-deposition/dissolution of Ni clusters realizes the construction of dynamic active sites, providing sustainable reaction centers and enhancing surface redox kinetics. The NixCd1-xS-Ni0 exhibits a high hydrogen evolution rate of 428 mmol·h-1·g-1 with a quantum efficiency of 75.6 % at 420 nm. This work provides the optimal S electronic structure for photocatalytic H2 evolution and constructs dynamic Ni clusters for chemical replacement reaction. This work provides the optimal S electronic structure for photocatalytic H2 evolution and constructs dynamic Ni clusters for displacement reaction, opening a dual pathway for efficient water reduction.

Recognition of cyclic dinucleotides and folates by human SLC19A1.

Cyclic dinucleotides (CDNs) are ubiquitous signalling molecules in all domains of life1,2. Mammalian cells produce one CDN, 2'3'-cGAMP, through cyclic GMP-AMP synthase after detecting cytosolic DNA signals3-7. 2'3'-cGAMP, as well as bacterial and synthetic CDN analogues, can act as second messengers to activate stimulator of interferon genes (STING) and elicit broad downstream responses8-21. Extracellular CDNs must traverse the cell membrane to activate STING, a process that is dependent on the solute carrier SLC19A122,23. Moreover, SLC19A1 represents the major transporter for folate nutrients and antifolate therapeutics24,25, thereby placing SLC19A1 as a key factor in multiple physiological and pathological processes. How SLC19A1 recognizes and transports CDNs, folate and antifolate is unclear. Here we report cryo-electron microscopy structures of human SLC19A1 (hSLC19A1) in a substrate-free state and in complexes with multiple CDNs from different sources, a predominant natural folate and a new-generation antifolate drug. The structural and mutagenesis results demonstrate that hSLC19A1 uses unique yet divergent mechanisms to recognize CDN- and folate-type substrates. Two CDN molecules bind within the hSLC19A1 cavity as a compact dual-molecule unit, whereas folate and antifolate bind as a monomer and occupy a distinct pocket of the cavity. Moreover, the structures enable accurate mapping and potential mechanistic interpretation of hSLC19A1 with loss-of-activity and disease-related mutations. Our research provides a framework for understanding the mechanism of SLC19-family transporters and is a foundation for the development of potential therapeutics.

Intestinal flora variation reflects the short-term damage of microplastic to the intestinal tract in mice.

The potential toxicity of microplastic (MPs) to organisms has attracted extensive attention. However, due to the subacute toxicity of MPs, the biological effect is hard to verify in short-term exposure experiment. Here, by tracking the dynamics of gut microbes, mice model was utilized to evaluate the toxicity of compositional MPs (PE, PET, PP, PS and PVC). After 7 days digestive exposure, the physiological indicators were normal as the control group that the body weight and serum cholesterol levels were insignificant change. Whereas, through histopathological examination, all the treatment groups suffered colon tissue damage, among which PS had the most inflammatory cells. Moreover, the high-throughput sequencing results revealed great variation of intestinal flora in treated mice. The ratio of Bacteroidetes and Firmicutes in PE, PET and PP treatment groups heighten, and the relative abundance of Ruminococcaceae and Lachnospiraceae increased significantly at family levels. At the genus level, Alistipes bacteria in PS treatment group significantly decreased that is associated with obesity risk. It indicated that MPs induced inflammatory response would further interfere the dynamics of intestinal flora causing health effect in living organisms. This work shed light on MPs toxicity in short-term exposure and supplied research paradigm of MPs health risk assessment.

The Deficiency of SCARB2/LIMP-2 Impairs Metabolism via Disrupted mTORC1-Dependent Mitochondrial OXPHOS.

Deficiency in scavenger receptor class B, member 2 (SCARB2) is related to both Gaucher disease (GD) and Parkinson's disease (PD), which are both neurodegenerative-related diseases without cure. Although both diseases lead to weight loss, which affects the quality of life and the progress of diseases, the underlying molecular mechanism is still unclear. In this study, we found that Scarb2-/- mice showed significantly reduced lipid storage in white fat tissues (WAT) compared to WT mice on a regular chow diet. However, the phenotype is independent of heat production, activity, food intake or energy absorption. Furthermore, adipocyte differentiation and cholesterol homeostasis were unaffected. We found that the impaired lipid accumulation of Adiponectin-cre; Scarb2fl/fl mice was due to the imbalance between glycolysis and oxidative phosphorylation (OXPHOS). Mechanistically, the mechanistic target of rapamycin complex 1 (mTORC1)/ eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) pathway was down-regulated in Scarb2 deficient adipocytes, leading to impaired mitochondrial respiration and enhanced glycolysis. Altogether, we reveal the role of SCARB2 in metabolism regulation besides the nervous system, which provides a theoretical basis for weight loss treatment of patients with neurodegenerative diseases.

Combined toxicity of zinc oxide nanoparticles and cadmium inducing root damage in Phytolacca americana L.

In recent years, nano-contamination in the soil environment has aroused concern. But it is still uncertain whether the interactions of nano- and metal-pollutants would have a combined toxic effect on plants. In this study, we investigated the effects of joint exposure to zinc oxide nanoparticles (ZnO NPs) and Cd on the root tissue of Phytolacca americana L. Spin-polarized density functional theory simulations assumed that the plant may undergo metal toxicity or acidosis upon joint exposure to ZnO NPs/Cd. Subsequently, experimental exposure of P. americana verified the combined toxic effects. The plant grew normally with a single treatment of ZnO NPs (500 mg/kg) or low doses of Cd (10 mg/kg). However, root growth was significantly inhibited with the combined treatments (up to 43% reduction); additionally, Cd ions were transported to the shoot, leading to shoot growth inhibition (translocation factor > 1). The antioxidant enzymes in the root (superoxide dismutase, peroxidase, and catalase) were highly activated to resist stress, accompanied by a greater than two-fold increase in thiobarbituric acid reactive substances. Corresponding to physiological indicators, biological transmission electron microscopy revealed severe damage to the root cells. Moreover, ZnO NPs/Cd accumulation was observed in the root cytoderm, which confirmed the toxicity of the combined effects. Our study provides insight into the potential combined toxicity of ZnO NPs and heavy metals in polluted environments, such as mining areas and electronic waste sites, and agricultural soils.

Understanding the Relationship Between Patient-Reported Function and Actual Function in the Upper Limb Prosthesis User Population: A Preliminary Study.

OBJECTIVE: To understand how perceived function relates to actual function at a specific stage in the rehabilitation process for the population using upper limb prostheses. DESIGN: Quantitative clinical descriptive study. SETTING: Clinical offices. PARTICIPANTS: A sample of 61 participants (N=61; mean age, 43.0±12.8y; 51 male/10 female) with upper limb amputation who use a prosthetic device and were in the definitive stage of a prosthesis fitting process. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A patient-reported outcome measure, the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH), and 2 performance-based outcome measures, Box and Blocks Test (BBT) and Capacity Assessment of Prosthesis Performance for the Upper Limb (CAPPFUL), were used as variables in multiple linear regression models. RESULTS: The multiple linear regression models, which controlled for prosthesis type and amputation level, did not show evidence that changes in the independent variable (DASH) are significantly associated with changes in the dependent variables (log(BBT) (B=-0.007; 95% confidence interval [CI], -0.015 to 0.001; P=.0937) and CAPPFUL (B=-0.083, 95% CI, -0.374 to 0.208; P=.5623)). In both models, individuals with elbow, transhumeral (above elbow), and shoulder disarticulation showed a significant negative association with the dependent variable (CAPPFUL or logBBT). In the CAPPFUL model, there was a significant negative association with individuals using a hybrid prosthesis (B=-20.252; 95% CI, -36.562 to -3.942; P=.0170). In the logBBT model, there was a significant positive association with individuals using body-powered prostheses (B=0.430; 95% CI, 0.089-0.771; P=.0157). CONCLUSIONS: Although additional data and analyses are needed to more completely assess the association between self-reported measures and performance-based measures of functional abilities, these preliminary results indicate that patient-reported outcomes alone may not provide a complete assessment of an upper limb prosthesis users' functional ability and should be accompanied by population-specific performance-based measures.

Systematical review of interactions between microplastics and microorganisms in the soil environment.

Terrestrial ecosystems are widely contaminated by microplastics due to extensive usage and poor handling of plastic materials, but the subsequent fate and remediate strategy of these pollutants are far from fully understood. In soil environments, microplastics pose a potential threat to the survival, growth, and reproduction of soil microbiota that in turn threaten the biodiversity, function, and services of terrestrial ecosystems. Meanwhile, microorganisms are sensitive to microplastics due to the adaptability to changes in substrates and soil properties. Through the metabolic and mineralization processes, microorganisms are also crucial participator to the plastic biodegradation. In this review, we present current knowledges and research results of interactions between microplastics and microorganisms (both fungi and bacteria) in soil environments and mainly discuss the following: (1) effects of microplastics on microbial habitats via changes in soil physical, chemical, and biological properties; (2) effects of microplastics on soil microbial communities and functions; and (3) soil microbial-mediated plastic degradation with the likely mechanisms and potential remediation strategies. We aim to analyze the mechanisms driving these interactions and subsequent ecological effects, propose future directives for the study of microplastic in soils, and provide valuable information on the plastic bioremediation in contaminated soils.

Microorganism structure variation in urban soil microenvironment upon ZnO nanoparticles contamination.

Nanoparticles (NPs) sink into the soil via agricultural spreading, surface water, atmospheric deposition, and industrial emission, which affects plant growth and soil microenvironment. To understand how NPs influence urban soil microenvironment, the effect of typical nano-pollutants zinc oxide nanoparticles (ZnONPs) was investigated in urban solid-waste land. Pokeweed (Phytolacca Americana L.) soil samples from solid-waste land were collected and exposed to 200, 500, and 1000 mg kg-1 ZnONPs. The physiological characteristics of pokeweed, soil bacterial community composition, and soil physiochemical properties and enzymatic activities were determined. Our results show that pokeweed growth was slightly inhibited, and soil acid-base homeostasis was affected in ZnONPs-contaminated samples. Meanwhile, enzymatic activities related to soil C cycle were enhanced, and bacterial community structure at the phylum and genus levels was altered. Specifically, the abundance of hydrocarbon-degrading taxa reduced substantially upon ZnONPs exposure. The phenoloxidase (PPO) activity and the refractory hydrocarbon-degrading bacteria Bacteroidetes was adversely affected by ZnONPs exposure. In addition, Subgroup_10 of Acidobacteria was identified as an indicator of soil ZnONPs contamination. Our study detected changes in plant growth, soil environmental factors, and soil microbe community composition in urban solid-waste land treated by ZnONPs. The results of this research provide evidence for ZnONPs toxicology on urban soil microenvironment.

Comparative transcriptomic and proteomic analyses provide insights into functional genes for hypoxic adaptation in embryos of Tibetan chickens.

The Tibetan chicken is a unique breed that has adapted to the high-altitude hypoxic conditions of the Tibetan plateau. A number of positively selected genes have been reported in these chickens; however, the mechanisms of gene expression for hypoxia adaptation are not fully understood. In the present study, eggs from Tibetan and Chahua chickens were incubated under hypoxic and normoxic conditions, and vascularization in the chorioallantoic membrane (CAM) of embryos was observed. We found that the vessel density index in the CAM of Tibetan chickens was lower than in Chahua chickens under hypoxia conditions. Transcriptomic and proteomic analyses of CAM tissues were performed in Tibetan and Chahua chicken embryos under hypoxic incubation using RNA-Seq and iTRAQ. We obtained 160 differentially expressed genes and 387 differentially expressed proteins that were mainly enriched in angiogenesis, vasculature development, blood vessel morphogenesis, blood circulation, renin-angiotensin system, and HIF-1 and VEGF signaling pathways. Twenty-six genes involved in angiogenesis and blood circulation, two genes involved in ion transport, and six genes that regulated energy metabolism were identified as candidate functional genes in regulating hypoxic adaptation of chicken embryos. This research provided insights into the molecular mechanism of hypoxia adaptation in Tibetan chickens.

Identification of new type I interferon-stimulated genes and investigation of their involvement in IFN-ß activation.

Virus infection induces the production of type I interferons (IFNs). IFNs bind to their heterodimeric receptors to initiate downstream cascade of signaling, leading to the up-regulation of interferon-stimulated genes (ISGs). ISGs play very important roles in innate immunity through a variety of mechanisms. Although hundreds of ISGs have been identified, it is commonly recognized that more ISGs await to be discovered. The aim of this study was to identify new ISGs and to probe their roles in regulating virus-induced type I IFN production. We used consensus interferon (Con-IFN), an artificial alpha IFN that was shown to be more potent than naturally existing type I IFN, to treat three human immune cell lines, CEM, U937 and Daudi cells. Microarray analysis was employed to identify those genes whose expressions were up-regulated. Six hundred and seventeen genes were up-regulated more than 3-fold. Out of these 617 genes, 138 were not previously reported as ISGs and thus were further pursued. Validation of these 138 genes using quantitative reverse transcription PCR (qRT-PCR) confirmed 91 genes. We screened 89 genes for those involved in Sendai virus (SeV)-induced IFN-ß promoter activation, and PIM1 was identified as one whose expression inhibited SeV-mediated IFN-ß activation. We provide evidence indicating that PIM1 specifically inhibits RIG-I- and MDA5-mediated IFN-ß signaling. Our results expand the ISG library and identify PIM1 as an ISG that participates in the regulation of virus-induced type I interferon production.