Structural and functional changes of anterior cingulate cortex subregions in migraine without aura: relationships with pain sensation and pain emotion.

Migraine without aura is a multidimensional neurological disorder characterized by sensory, emotional, and cognitive symptoms linked to structural and functional abnormalities in the anterior cingulate cortex. Anterior cingulate cortex subregions play differential roles in the clinical symptoms of migraine without aura; however, the specific patterns and mechanisms remain unclear. In this study, voxel-based morphometry and seed-based functional connectivity were used to investigate structural and functional alterations in the anterior cingulate cortex subdivisions in 50 patients with migraine without aura and 50 matched healthy controls. Compared with healthy controls, patients exhibited (1) decreased gray matter volume in the subgenual anterior cingulate cortex, (2) increased functional connectivity between the bilateral subgenual anterior cingulate cortex and right middle frontal gyrus, and between the posterior part of anterior cingulate cortex and right middle frontal gyrus, orbital part, and (3) decreased functional connectivity between the anterior cingulate cortex and left anterior cingulate and paracingulate gyri. Notably, left subgenual anterior cingulate cortex was correlated with the duration of each attack, whereas the right subgenual anterior cingulate cortex was associated with migraine-specific quality-of-life questionnaire (emotion) and self-rating anxiety scale scores. Our findings provide new evidence supporting the hypothesis of abnormal anterior cingulate cortex subcircuitry, revealing structural and functional abnormalities in its subregions and emphasizing the potential involvement of the left subgenual anterior cingulate cortex-related pain sensation subcircuit and right subgenual anterior cingulate cortex -related pain emotion subcircuit in migraine.

Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Dendrobium officinale Kinura et Migo glycoprotein promotes skin wound healing by regulating extracellular matrix secretion and fibroblast proliferation on the proliferation phase.

Dendrobium officinale Kinura et Migo (DOKM) has a variety of medicinal applications; however, its ability to promote wound healing has not been previously reported. The purpose of this study is to investigate the proliferative phase of the wound-healing effect of DOKM glycoprotein (DOKMG) in rats and to elucidate its mechanism of action in vitro. In the present study, the ointment mixture containing DOKMG was applied to the dorsal skin wounds of the full-thickness skin excision rat model, and the results showed that the wound healing speed was faster in the proliferative phase than vaseline. Histological analysis demonstrates that DOKMG promoted the re-epithelialization of wound skin. Immunofluorescence staining and quantitative polymerase chain reaction assays revealed that DOKMG promotes the secretion of Fibronectin and inhibits the secretion of Collagen IV during the granulation tissue formation period, indicating that DOKMG could accelerate the formation of granulation tissue by precisely regulating extracellular matrix (ECM) secretion. In addition, we demonstrated that DOKMG enhanced the migration and proliferation of fibroblast (3T6 cell) in two-dimensional trauma by regulating the secretion of ECM, via a mechanism that may implicate the AKT and JAK/STAT pathways under the control of epidermal growth factor receptor (EGFR) signalling. In summary, we have demonstrated that DOKMG promotes wound healing during the proliferative phase. Therefore, we suggest that DOKMG may have a potential therapeutic application for the treatment and management of cutaneous wounds.

Site-Specific Modification of Virus-Like Particles for Exogenous Tumor Antigen Display and Minimizing Preexisting Immunity.

The widespread preexisting immunity against virus-like particles (VLPs) seriously limits the applications of VLPs as vaccine vectors. Enabling technology for exogenous antigen display should not only ensure the assembly ability of VLPs and site-specific modification, but also consider the effect of preexisting immunity on the behavior of VLPs in vivo. Here, combining genetic code expansion technique and synthetic biology strategy, a site-specific modification method for hepatitis B core (HBc) VLPs via incorporating azido-phenylalanine into the desired positions is described. Through modification position screening, it is found that HBc VLPs incorporated with azido-phenylalanine at the main immune region can effectively assemble and rapidly conjugate with the dibenzocycolctyne-modified tumor-associated antigens, mucin-1 (MUC1). The site-specific modification of HBc VLPs not only improves the immunogenicity of MUC1 antigens but also shields the immunogenicity of HBc VLPs themselves, thereby activating a strong and persistent anti-MUC1 immune response even in the presence of preexisting anti-HBc immunity, which results in the efficient tumor elimination in a lung metastatic mouse model. Together, these results demonstrate the site-specific modification strategy enabled HBc VLPs behave as a potent antitumor vaccine and this strategy to manipulate immunogenicity of VLPs may be suitable for other VLP-based vaccine vectors.

Pirh2 restricts influenza A virus replication by modulating short-chain ubiquitination of its nucleoprotein.

Influenza A viruses (IAVs) rely on viral ribonucleoprotein (vRNP) complexes to control transcription and replication. Each vRNP consists of one viral genomic RNA segment associated with multiple nucleoproteins (NP) and a trimeric IAV RNA polymerase complex. Previous studies showed that post-translational modifications of vRNP components, such as NP, by host factors would in turn affect the IAV life cycle or modulate host anti-viral response. In this study, we found host E3 ubiquitin ligase Pirh2 interacted with NP and mediated short-chain ubiquitination of NP at lysine 351, which suppressed NP-PB2 interaction and vRNP formation. In addition, we showed that knockdown of Pirh2 promoted IAV replication, whereas overexpression of Pirh2 inhibited IAV replication. However, Pirh2-ΔRING lacking E3 ligase activity failed to inhibit IAV infection. Moreover, we showed that Pirh2 had no effect on the replication of a rescued virus, WSN-K351R, carrying lysine-to-arginine substitution at residue 351. Interestingly, by analyzing human and avian IAVs from 2011 to 2020 in influenza research databases, we found that 99.18% of 26 977 human IAVs encode lysine, but 95.3% of 9956 avian IAVs encode arginine at residue 351 of NP protein. Consistently, knockdown of Pirh2 failed to promote propagation of two avian-like influenza viruses, H9N2-W1 and H9N2-C1, which naturally encode arginine at residue 351 of NP. Taken together, we demonstrated that Pirh2 is a host factor restricting IAV infection by modulating short-chain ubiquitination of NP. Meanwhile, it is noteworthy that residue 351 of NP targeted by Pirh2 may associate with the evasion of human anti-viral response against avian-like influenza viruses.

Application of ZnO Nanoparticles Encapsulated in Mesoporous Silica on the Abaxial Side of a Solanum lycopersicum Leaf Enhances Zn Uptake and Translocation via the Phloem.

Foliar application of nutrient nanoparticles (NPs) is a promising strategy for improving fertilization efficiency in agriculture. Phloem translocation of NPs from leaves is required for efficient fertilization but is currently considered to be feasible only for NPs smaller than a cell wall pore size exclusion limit of <20 nm. Using mass spectrometry imaging, we provide here the first direct evidence for phloem localization and translocation of a larger (∼70 nm) fertilizer NP comprised of ZnO encapsulated in mesoporous SiO2 (ZnO@MSN) following foliar deposition. The Si content in the phloem tissue of the petiole connected to the dosed leaf was ∼10 times higher than in the xylem tissue, and ∼100 times higher than the phloem tissue of an untreated tomato plant petiole. Direct evidence of NPs in individual phloem cells has only previously been shown for smaller NPs introduced invasively in the plant. Furthermore, we show that uptake and translocation of the NPs can be enhanced by their application on the abaxial (lower) side of the leaf. Applying ZnO@MSN to the abaxial side of a single leaf resulted in a 56% higher uptake of Zn as well as higher translocation to the younger (upper) leaves and to the roots, than dosing the adaxial (top) side of a leaf. The higher abaxial uptake of NPs is in alignment with the higher stomatal density and lower density of mesophyll tissues on that side and has not been demonstrated before.

Flavonoids in Amomum tsaoko Crevost et Lemarie Ameliorate Loperamide-Induced Constipation in Mice by Regulating Gut Microbiota and Related Metabolites.

Amomum tsaoko (AT) is a dietary botanical with laxative properties; however, the active ingredients and mechanisms are still unclear. The active fraction of AT aqueous extract (ATAE) for promoting defecation in slow transit constipation mice is the ethanol-soluble part (ATES). The total flavonoids of ATES (ATTF) were the main active component. ATTF significantly increased the abundance of Lactobacillus and Bacillus and reduced the dominant commensals, such as Lachnospiraceae, thereby changing the gut microbiota structure and composition. Meanwhile, ATTF changed the gut metabolites mainly enriched in pathways such as the serotonergic synapse. In addition, ATTF increased the serum serotonin (5-HT) content and mRNA expression of 5-hydroxytryptamine receptor 2A (5-HT2A), Phospholipase A2 (PLA2), and Cyclooxygenase-2 (COX2), which are involved in the serotonergic synaptic pathway. ATTF increased Transient receptor potential A1 (TRPA1), which promotes the release of 5-HT, and Myosin light chain 3(MLC3), which promotes smooth muscle motility. Notably, we established a network between gut microbiota, gut metabolites, and host parameters. The dominant gut microbiota Lactobacillus and Bacillus, prostaglandin J2 (PGJ2) and laxative phenotypes showed the most significant associations. The above results suggest that ATTF may relieve constipation by regulating the gut microbiota and serotonergic synaptic pathway and has great potential for laxative drug development in the future.

Environmental risks of antibiotic resistance genes released from biological laboratories and its control measure.

Antibiotic resistance genes (ARGs) are a growing global threat to public health. Biological laboratory wastewater contains large amounts of free ARGs. It is important to assess the risk of free ARGs from biological laboratories and to find appropriate treatments to control their spread. The fate of plasmids in the environment and the effect of different thermal treatments on their persistence activity were tested. The results showed that untreated resistance plasmids could exist in water for more than 24 h (the special 245 bp fragment). Gel electrophoresis and transformation assays showed that the plasmids boiled for 20 min retained 3.65% ± 0.31% transformation activity of the intact plasmids, while autoclaving for 20 min at 121 °C could effectively degrade the plasmids and that NaCl, bovine serum albumin, and EDTA-2Na affected the degradation efficiency of the plasmids during boiling. In the simulated aquatic system, using 106 copy/µL of plasmids after autoclaving, only 102 copies/µL of the fragment after only 1-2 h could be detected. By contrast, boiled plasmids for 20 min were still detectable after plunging them into water for 24 h. These findings suggest that untreated and boiled plasmids can remain in the aquatic environment for a certain time resulting in the risk of disseminating ARGs. However, autoclaving is an effective way of degrading waste free resistance plasmids.

Research on high-temperature characteristics of a miniature Fabry-Pérot cavity acoustic sensor.

The applications of fiber-optic acoustic sensors are expanded to the high-temperature field, but it still faces challenges to realize the wide-band and high-sensitivity acoustic signal detection in high-temperature environments. Here, we propose a miniature membrane-free fiber-optic acoustic sensor based on a rigid Fabry-Pérot (F-P) cavity and construct an acoustic signal detection system. The system can achieve high-sensitivity acoustic detection while maintaining a wide frequency band in temperatures ranging from 20 °C to 200 °C. The prepared F-P cavity based on optical contact technology is the sensitive unit of the sensor, and has a high-quality factor of 8.8×105. Specifically, with the increasing of temperature, the sensitivity gradually increases, and the frequency response range does not change. A maximum sensitivity of 491.2 mV/Pa and a high signal-to-noise ratio of 60.9 dB are achieved at 200 °C. The sensor has an excellent acoustic signal response in the frequency range of 10 Hz-50 kHz with a flatness of ±2 dB. This study is important for the application of the fiber-optic acoustic sensor in high-temperature environments.

ASFV pD345L protein negatively regulates NF-κB signalling by inhibiting IKK kinase activity.

The NF-κB pathway is an essential signalling cascade in the defence against viral infections, including African swine fever virus (ASFV) infection. ASFV encodes more than 151 proteins via its own transcription machinery and possesses a great capacity to evade or subvert antiviral innate immune responses. Although some of these viral proteins have been reported, many remain unknown. Here, we show that pD345L, an ASFV-encoded lambda-like exonuclease, acts as an inhibitor of cGAS/STING-mediated NF-κB signalling by blocking the IkappaB kinase (IKKα/ß) activity. Specifically, we showed that overexpression of pD345L suppresses cGAS/STING-induced IFNß and NF-κB activation, resulting in decreased transcription of IFNß and several proinflammatory cytokines, including IL-1α, IL-6, IL-8, and TNFα. In addition, we showed that pD345L acts at or downstream of IKK and upstream of p65. Importantly, we found that pD345L associates with the KD and HLH domains of IKKα and the LZ domain of IKKß and thus interrupts their kinase activity towards the downstream substrate IκBα. Finally, we showed that pD345L-mediated inhibition of NF-κB signalling was independent of its exonuclease activity. Considering these results collectively, we concluded that pD345L blocks IKKα/ß kinase activity via protein-protein interactions and thus disrupts cGAS/STING-mediated NF-κB signalling.

Uptake and Translocation of a Silica Nanocarrier and an Encapsulated Organic Pesticide Following Foliar Application in Tomato Plants.

Pesticide nanoencapsulation and its foliar application are promising approaches for improving the efficiency of current pesticide application practices, whose losses can reach 99%. Here, we investigated the uptake and translocation of azoxystrobin, a systemic pesticide, encapsulated within porous hollow silica nanoparticles (PHSNs) of a mean diameter of 253 ± 73 nm, following foliar application on tomato plants. The PHSNs had 67% loading efficiency for azoxystrobin and enabled its controlled release over several days. Thus, the nanoencapsulated pesticide was taken up and distributed more slowly than the nonencapsulated pesticide. A total of 8.7 ± 1.3 µg of the azoxystrobin was quantified in different plant parts, 4 days after 20 µg of nanoencapsulated pesticide application on a single leaf of each plant. In parallel, the uptake and translocation of the PHSNs (as total Si and particulate SiO2) in the plant were characterized. The total Si translocated after 4 days was 15.5 ± 1.6 µg, and the uptake rate and translocation patterns for PHSNs were different from their pesticide load. Notably, PHSNs were translocated throughout the plant, although they were much larger than known size-exclusion limits (reportedly below 50 nm) in plant tissues, which points to knowledge gaps in the translocation mechanisms of nanoparticles in plants. The translocation patterns of azoxystrobin vary significantly following foliar uptake of the nanosilica-encapsulated and nonencapsulated pesticide formulations.

Compact fiber-optic Fabry-Perot cavity based on sandwich structure adopting direct bonding of quartz glass.

A compact fiber-optic Fabry-Perot (F-P) cavity for a sensor is designed based on a sandwich structure, adopting direct bonding of quartz glass. The reflective F-P cavity is manufactured by a fiber optic with a quartz glass ferrule and the sandwich structure with an air cavity, which is achieved by direct bonding of quartz glass. This fabrication process includes plasma surface activation, hydrophilic pre-bonding, high-temperature annealing, and dicing. The cross section of the bonding interface tested by a scanning electron microscope indicates that the sandwich structure is well bonded, and the air cavity is not deformed. Experiments show that the quality factor of the F-P cavity is 2711. Tensile strength testing shows that the bond strength exceeds 35 MPa. The advantage of direct bonding of quartz glass is that high consistency and mass production of the cavity can be realized. Moreover, the cavity is free of problems caused by the mismatch of thermal expansion coefficients between different materials. Therefore, the F-P cavity can be made into a sensor, which is promising in detecting air pressure, acoustic and high temperature.

A novel electrochemical immunosensor based on Fe3O4@graphene nanocomposite modified glassy carbon electrode for rapid detection of Salmonella in milk.

Foods contaminated by foodborne pathogens have always been a great threat to human life. Herein, we constructed an electrochemical immunosensor for Salmonella detection by using a Fe3O4@graphene modified electrode. Because of the excellent electrical conductivity and mechanical stability of graphene and the large specific surface area of Fe3O4, the Fe3O4@graphene nanocomposite exhibits an excellent electrical signal, which greatly increased the sensitivity of the immunosensor. Gold nanoparticles were deposited on Fe3O4@graphene nanocomposite by electrochemical technology for the immobilization of the antibody. Cyclic voltammetry was selected to electrochemically characterize the construction process of immunosensors. The microstructure and morphology of related nanocomposites were analyzed by scanning electron microscopy. Under optimized experimental conditions, a good linear relationship was achieved in the Salmonella concentration range of 2.4 × 102 to 2.4 × 107 cfu/mL, and the limit of detection of the immunosensor was 2.4 × 102 cfu/mL. Additionally, the constructed immunosensor exhibited acceptable selectivity, reproducibility, and stability and provides a new reference for detecting pathogenic bacteria in milk.

A fluorescent biosensor based on quantum dot-labeled streptavidin and poly-l-lysine for the rapid detection of Salmonella in milk.

Salmonella, as a common foodborne pathogen in dairy products, poses a great threat to human health. We studied a new detection method based on quantum dots (QD). A fluorescent biosensor with multiple fluorescent signal amplification based on a streptavidin (SA) biotin system and the polyamino linear polymer poly-l-lysine (PLL) were established to detect Salmonella in milk. First, Salmonella was captured on a black 96-well plate with paired Salmonella mAb to form a double-antibody sandwich. Second, SA was immobilized on biotin-modified mAb by SA-biotin specific bond. Then, the biotin-modified polylysine (BT-PLL) was bound on SA and specifically bonded again through the SA-biotin system. Finally, water-soluble CdSe/ZnS QD-labeled SA was added to a black 96-well plate for covalent coupling with BT-PLL. The fluorescent signal was amplified in a dendritic manner by the layer-by-layer overlap of SA and biotin and the covalent coupling of biotinylated PLL. Under optimal conditions, the detection limit was 4.9 × 103 cfu/mL in PBS. The detection limit was 10 times better than that of the conventional sandwich ELISA. In addition, the proposed biosensor was well specific and could be used for detecting Salmonella in milk samples.

The Associations between Evacuation Movements and Children's Physiological Demands Analyzed via Wearable-Based Sensors.

During fire evacuations, crawling is recommended to prevent harm from toxic smoke and to access more breathable air. Few studies have evaluated the physiological burden of crawling, especially for children. The method of using wearable sensors to collect data (e.g., electrodermal activity, EDA; skin temperature, SKT) was used to evaluate the effects of different locomotive postures on children's velocity and physiological demands. Twenty-eight (28) children (13 boys and 15 girls), aged 4 to 6 years old, traveled up to 22.0 m in different postures: Upright walking (UW), stoop walking (SW), knee and hand crawling (KHC). The results showed that: (1) Gender and age had significant impacts on children's velocity (p < 0.05): Boys were always faster than girls in any of the three postures and the older the child, the faster the velocity for KHC. (2) Physiological results demonstrated that KHC was more physically demanding than bipedal walking, represented by higher scores of the EDA and SKT indicators, similar to the findings of adults. (3) Gender and age had significant impacts on children's physiological demands (p < 0.05). The physiological demands were greater for boys than girls. In addition, the higher the age, the less physiological demands he/she needs. Overall, the findings suggest that children are unnecessarily required to choose crawling precisely as adults as the best posture to respond to emergency scenarios. In a severe fire, stoop walking is suggested, as there is more respired air and children could move quickly and avoid overworking physiological burdens. The results of this study are expected to be considered in the evaluation of current evacuation recommendations and for the safety guide of preparedness to improve the effectiveness of risk reduction for children.

Pre-attack and pre-episode symptoms in cluster headache: a multicenter cross-sectional study of 327 Chinese patients.

BACKGROUND: There have been a few studies regarding the pre-attack symptoms (PAS) and pre-episode symptoms (PES) of cluster headache (CH), but none have been conducted in the Chinese population. The purpose of this study was to identify the prevalence and features of PAS and PES in Chinese patients, as well as to investigate their relationships with pertinent factors. METHODS: The study included patients who visited a tertiary headache center and nine other headache clinics between January 2019 and September 2021. A questionnaire was used to collect general data and information about PAS and PES. RESULTS: Among the 327 patients who met the CH criteria (International Classification of Headache Disorders, 3rd edition), 269 (82.3%) patients experienced at least one PAS. The most common PAS were head and facial discomfort (74.4%). Multivariable logistic regression analysis depicted that the number of triggers (OR = 1.798, p = 0.001), and smoking history (OR = 2.067, p = 0.026) were correlated with increased odds of PAS. In total, 68 (20.8%) patients had PES. The most common symptoms were head and facial discomfort (23, 33.8%). Multivariable logistic regression analysis showed that the number of triggers were associated with increased odds of PES (OR = 1.372, p = 0.005). CONCLUSIONS: PAS are quite common in CH patients, demonstrating that CH attacks are not comprised of a pain phase alone; investigations of PAS and PES could help researchers better understand the pathophysiology of CH.

Refractive Error and Retinopathy Outcomes in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study.

PURPOSE: To determine the relationship between refractive error and diabetic retinopathy (DR). DESIGN: Clinical trial. PARTICIPANTS: Type I diabetes individuals with serial refractive error and DR stage measurements over 30 years in the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study. METHODS: Stage of DR was measured every 6 months from standard fundus photographs, and refractive error was measured annually during the 6.5 years of DCCT; then, both were staggered every fourth year during EDIC with the full cohort measured at EDIC years 4 and 10. Outcomes of DR were 2- or 3-step progression, presence of proliferative DR (PDR), clinically significant macular edema (CSME), diabetic macular edema (DME), or ocular surgery. Myopia, emmetropia, and hyperopia were defined as a spherical equivalent of ≤-0.5, >-0.5 and <0.5, and ≥0.5, respectively. MAIN OUTCOME MEASURES: For each outcome separately, Cox proportional hazard (PH) models assessed the association between the refractive error status and the subsequent risk of that outcome, both without and with adjustment for potential risk factors. RESULTS: Hyperopia was associated with a higher risk of 2-step progression (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.05-1.59), 3-step progression (HR, 1.35; 95% CI, 1.05-1.73), and PDR (HR, 1.40; 95% CI, 1.02-1.92) compared with emmetropia in unadjusted models. These associations remained significant after adjustment for DCCT treatment group, cohort, age, sex, smoking, duration of diabetes, systolic and diastolic blood pressures, pulse, low-density lipoprotein, high-density lipoprotein, triglycerides, albumin excretion rate, and DCCT/EDIC mean updated hemoglobin A1c (HbA1c) (2-step progression: HR, 1.28; 95% CI, 1.03-1.58; 3-step progression: HR, 1.30; 95% CI, 1.00-1.68; PDR: HR, 1.38; 95% CI, 1.00-1.90). Myopia was not associated with any of the 5 DR outcomes in the unadjusted models and only marginally associated with 2-step progression (HR, 1.11; 95% CI, 1.00-1.24) in the adjusted models. CONCLUSIONS: Myopia is not associated with DR progression risk. Hyperopia is an independent risk factor for 2-step and 3-step DR progression and PDR.

Association of VEGFA polymorphisms with chronic obstructive pulmonary disease in Chinese Han and Mongolian populations.

NEW FINDINGS: What is the central question of this study? Vascular endothelial growth factor A (VEGFA) is an important growth factor involved in changes in the bronchial microvascular and airway inflammation in chronic obstructive pulmonary disease (COPD) progression. What is the association of single nucleotide polymorphisms (SNPs) in VEGFA with the risk of COPD in the Chinese Han and Mongolian populations? What is the main finding and its importance? The effect of five SNPs in the VEGFA gene was analysed and compared between the Chinese Han and Mongolian populations. A contribution of risk alleles rs833068, rs833070 and rs3024997 to COPD was detected in the Chinese Mongolian population only. The study provided data from different populations to validate the role of VEGFA polymorphisms in COPD and provided reliable SNPs to predict the risk of COPD. ABSTRACT: We attempted to define the associations between single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGFA) gene and chronic obstructive pulmonary disease (COPD) in Chinese Han and Mongolian cohorts. Five SNPs were genotyped in cohorts of 684 COPD patients (350 Mongolian and 334 Han) and 784 healthy controls (350 Mongolian and 434 Han) using SNPscan multiplex PCR. SNP frequencies, genetic models and haplotypes were analysed using the chi-square test. The associations of SNPs with COPD and linkage disequilibrium were analysed using logistic regression and HaploView, respectively. We found that only rs833068G>A, rs833070T>C and rs3024997G>A were significantly associated with the risk of COPD in the Mongolian population (rs833068: P < 0.001, rs833070: P < 0.001, rs3024997: P = 0.002). In the analysis of genotype distributions, the A/A and G/A genotypes in rs833068 (A/A: odds ratio (OR) = 0.313, P < 0.001; G/A: OR = 0.724, P < 0.001) and rs3024997 (A/A: OR = 0.513, P = 0.008; G/A: OR = 0.671, P = 0.008) and the C/C and T/C genotypes in rs833070 (C/C: OR = 0.435, P = 0.007; T/C: OR = 0.593, P = 0.007) were associated with protection against COPD in the Mongolian population. The haplotype frequencies of GCCAT and GTCGC were significantly different between the patients and controls (GCCAT: P = 0.001; GTCGC: P < 0.001) in the Mongolian population. Our findings indicate that five SNPs in the VEGFA gene play divergent roles in the Han and Mongolian populations. rs833068A, rs833070C and rs3024997A were observed to be associated with the risk of COPD in the Mongolian population.

Pulmonary surfactant-associated protein B regulates prostaglandin-endoperoxide synthase-2 and inflammation in chronic obstructive pulmonary disease.

NEW FINDINGS: What is the central question of this study? It is reported that polymorphism of the gene for pulmonary surfactant-associated protein B (SFTPB) is associated with chronic obstructive pulmonary disease (COPD): what are the function and mechanism of action of SFTPB in COPD? What is the main finding and its importance? Under stimulation of the risk factors of COPD, SFTPB expression is decreased, which may be involved in the formation of COPD. The progress of COPD induces an inflammatory response and reduces SFTPB expression. Levels of prostaglandin-endoperoxide synthase-2 (PTGS2) and inflammatory responses are changed by SFTPB, which indicates that SFTPB promotes the progression of COPD by PTGS2 and inflammation. ABSTRACT: Pulmonary surfactant-associated protein B (SFTPB) is a critical protein for lung homeostasis, and polymorphism of its gene is associated with chronic obstructive pulmonary disease (COPD). However, few studies have so far confirmed the functional involvement of SFTPB in COPD. Serum SFTPB and inflammatory cytokine levels were measured in 54 patients with acute exacerbation of COPD and 29 healthy controls. A549 cells were induced using 10% cigarette smoke extract (CSE) and treated with dexamethasone to investigate the effect of inflammation on SFTPB expression, and the effect of SFTPB overexpression and silencing on inflammatory cytokines was measured using real-time PCR and enzyme-linked immunosorbent assay. SFTPB expression was assessed in mouse lung tissues using immunofluorescence. Serum levels of SFTPB were significantly lower in COPD patients than in controls (P = 0.009). Conversely, levels of interleukin (IL)-6 and prostaglandin-endoperoxide synthase-2 (PTGS2) were increased in COPD patients (IL-6: P = 0.006; PTGS2: P = 0.043). After CSE treatment, SFTPB mRNA and protein levels were significantly decreased compared to controls (mRNA: P = 0.002; protein: P = 0.011), while IL-6, IL-8 and PTGS2 were elevated. Dexamethasone treatment increased SFTPB levels. Following overexpression of SFTPB in A549 cells, mRNA and protein levels of IL-6, IL-8 and PTGS2 were significantly reduced, while gene silencing induced the opposite effect. SFTPB levels were significantly reduced in the lung tissue of a mouse model of COPD compared to controls. Reduced SFTPB levels may induce PTGS2 and inflammatory responses in COPD and SFTPB could be a key protein for evaluation of COPD progression.

Uptake and Translocation of Mesoporous SiO2-Coated ZnO Nanoparticles to Solanum lycopersicum Following Foliar Application.

Nanoparticles composed of ZnO encapsulated in a mesoporous SiO2 shell (nZnO@SiO2) with a primary particle diameter of ∼70 nm were synthesized for delivery of Zn, a micronutrient, by foliar uptake. Compared to the rapid dissolution of bare nZnO (90% Zn dissolution after 4 h) in a model plant media (pH = 5), nZnO@SiO2 released Zn more slowly (40% Zn dissolution after 3 weeks), thus enabling sustained Zn delivery over a longer period. nZnO@SiO2, nZnO, and ZnCl2 were exposed to Solanum lycopersicum by dosing 40 µg of Zn micronutrient (in a 20 µL suspension) on a single leaf. No Zn uptake was observed for the nZnO treatment after 2 days. Comparable amounts of Zn uptake were observed 2 days after ZnCl2 (15.5 ± 2.4 µg Zn) and nZnO@SiO2 (11.4 ± 2.2 µg Zn) dosing. Single particle inductively coupled plasma mass spectrometry revealed that for foliar applied nZnO@SiO2, almost all of the Zn translocated to upper leaves and the stem were in nanoparticulate form. Our results suggest that the SiO2 shell enhances the uptake of ZnO nanoparticles in Solanum lycopersicum. Sustained and controlled micronutrient delivery in plants through foliar application will reduce fertilizer, energy, and water use.