Carbon reduction and water saving potentials for growing corrugated boxes for express delivery services in China.

Corrugated packaging for express grew by 90 times to 16.5 Mt y-1 in China, where 81% of recent global express delivery growth occurred. However, the environmental impacts of production, usage, disposal, and recycling of corrugated boxes under the entire supply chain remain unclear. Here, we estimate the magnitudes, drivers, and mitigation potentials of cradle-to-grave life-cycle carbon footprint (CF) and three colors of water footprints (WFs) for corrugated cardboard packaging in China. Over 2007 to 2021, CF, blue and gray WFs per unit package decreased by 45%, 60%, and 84%, respectively, while green WF increased by 23% with growing imports of virgin pulp and China's waste ban. National total CF and WFs were 21 to 102 folded with the scale effects. Only a combination of the supply chain reconstruction, lighter single-piece packaging, and increased recycling rate can possibly reduce the environmental footprints by 24 to 44% by 2035.

A genome-wide in vivo CRISPR screen identifies essential regulators of T cell migration to the CNS in a multiple sclerosis model.

Multiple sclerosis (MS) involves the infiltration of autoreactive T cells into the CNS, yet we lack a comprehensive understanding of the signaling pathways that regulate this process. Here, we conducted a genome-wide in vivo CRISPR screen in a rat MS model and identified 5 essential brakes and 18 essential facilitators of T cell migration to the CNS. While the transcription factor ETS1 limits entry to the CNS by controlling T cell responsiveness, three functional modules, centered around the adhesion molecule α4-integrin, the chemokine receptor CXCR3 and the GRK2 kinase, are required for CNS migration of autoreactive CD4+ T cells. Single-cell analysis of T cells from individuals with MS confirmed that the expression of these essential regulators correlates with the propensity of CD4+ T cells to reach the CNS. Our data thus reveal key regulators of the fundamental step in the induction of MS lesions.

Tracking indirect water footprints, virtual water flows, and burden shifts related to inputs and supply chains for croplands: A case for maize in China.

Increasing crop yields to ensure an adequate food supply under water and land scarcity is dependent on intensive agricultural inputs (such as fertilizers, pesticides, agri-films, or energy) which consume water resources and generate water pollution. However, the burden shifting of water quantity and quality stress from producers to importer and consumers through agricultural input production, trade, and consumption have been largely overlooked. Here, taking maize in China as the study case, we mapped step-by-step indirect water footprint (IWF) of maize production, virtual water (VW) flows related to inputs driven by maize consumption, and the resulting burden shifting of water quantity and quality. Bottom-up WF accounting approach was applied. The maize consumption was intercepted into two stages: the crop production stage (CPS) from raw materials to the farm, and the crop trade stage (CTS) from farm to fork. Results show that the national average blue and grey IWF of maize production was 3.91 and 26.86 m3/t, respectively. In the CPS, the input-related VW flowed from the west and east coast to the north. In the CTS, the VW flows from the north to the south. Blue and grey VW flows in CTS caused by secondary flows of VW in CPS accounted for 48% and 18% of the total flows, respectively. In total VW flows along the maize supply chain, 63% of blue VW and 71% of grey VW net exports occurred in the north of severe water scarcity and water pollution levels. The analysis highlights the impact of the crop supply chain on water quantity and water quality in the consumption of agricultural inputs, the importance of step-by-step supply chain analysis for regional crop water conservation management, and the urgent need for integrated management of agricultural and industrial water resources.

Effects of new antiseizure medication on bone metabolism and bone mineral density in children: A meta-analysis.

Objective: To explore the effect of new antiseizure medication on bone metabolism and bone mineral density in children. Methods: The Chinese and English databases (PubMed, EMBASE, Cochrane Library, CNKI, Wanfang and VIP) were systematically searched for observational studies evaluating the effects of new antiseizure medication on bone metabolism and bone mineral density in children with epilepsy. The effects of new antiseizure medication on serum calcium, phosphorus, alkaline phosphatase, bone alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone mineral density in children were systematically evaluated. Results: After systematic retrieval and screening, 12 studies with high literature quality (including 629 epileptic children and 627 control subjects) were included in the systematic evaluation. Meta-analysis showed that new antiseizure medication decreased bone mineral density (MD: -0.05, 95%CI, -0.09, -0.02; P = 0.004). From different kinds of antiseizure medication, levetiracetam can reduce blood phosphorus concentration in children (MD: -0.04; 95%CI, -0.07, -0.01). Oxcarbazepine increased serum alkaline phosphatase in children (MD:17.98; 95%CI, 10.43,25.53; P < 0.00001), and the increase intensity was significantly higher than that of levetiracetam (MD: 7.66; 95%CI, 0.29, 15.02; P = 0.04). In addition, oxcarbazepine can cause a significant increase in parathyroid hormone in children (MD: 7.52; 95%CI, 3.37,11.66; P = 0.0004), and 25 - hydroxyvitamin D was reduced, and the difference was statistically significant (MD:-2.18; 95%CI, -3.23, -1.13; P = 0.00006). However, the effects of new antiseizure medication on serum calcium and bone alkaline phosphatase in children were not statistically significant. Conclusion: New antiseizure medication have different effects on bone metabolism and bone mineral density in children with epilepsy, and the effects of different types of new antiseizure medication are different.

Large-area transfer of two-dimensional materials free of cracks, contamination and wrinkles via controllable conformal contact.

The availability of graphene and other two-dimensional (2D) materials on a wide range of substrates forms the basis for large-area applications, such as graphene integration with silicon-based technologies, which requires graphene on silicon with outperforming carrier mobilities. However, 2D materials were only produced on limited archetypal substrates by chemical vapor deposition approaches. Reliable after-growth transfer techniques, that do not produce cracks, contamination, and wrinkles, are critical for layering 2D materials onto arbitrary substrates. Here we show that, by incorporating oxhydryl groups-containing volatile molecules, the supporting films can be deformed under heat to achieve a controllable conformal contact, enabling the large-area transfer of 2D films without cracks, contamination, and wrinkles. The resulting conformity with enhanced adhesion facilitates the direct delamination of supporting films from graphene, providing ultraclean surfaces and carrier mobilities up to 1,420,000 cm2 V-1 s-1 at 4 K.

Inputs for staple crop production in China drive burden shifting of water and carbon footprints transgressing part of provincial planetary boundaries.

Crop production is the biggest water user and key contributor to anthropogenic greenhouse gas emissions. Increasing crop yields to ensure adequate food supply under water and land scarcity is excessively dependents on intensive agricultural inputs (such as fertilizers, pesticides, agri-films, or energy), resulting in unintended environmental consequences. Supply chains bringing environmental-intensive inputs from their place of production to the croplands. However, most food-related environmental assessments ignore the environmental burden of agricultural input production, trade, and consumption. Here, we estimate spatially-detailed water (WF) and carbon footprints (CF) of wheat, maize, and rice production in China with extended system boundary from upstream raw material mining to the field. The agricultural inputs account for up to 24% and 89% of a crop's WF and CF, respectively, at the provincial level. The total local generated WF in Chinese northern provinces and CF in Shanxi and Inner Mongolia provinces for producing crops and agricultural inputs transgresses the corresponding downscaled blue water and carbon planetary boundaries. The study broadens the scope of traditional environmental impact assessments in agricultural production and sheds light on the significances to manage the linkages between the crop production and the agricultural inputs' upstream supply chains towards more efficient water use and less greenhouse gas emissions in food system.

Limited water scarcity mitigation by expanded interbasin physical and virtual water diversions with uneven economic value added in China.

Interbasin water diversion projects and virtual water transfers embedded in exchanged goods and services are two effective solutions to water deficits. However, the associated real responses in water quantity and quality scarcities and the economic efficiencies remain unclear. Here, we tracked the blue water scarcities, water pollution levels, and economic value added through interbasin physical and virtual water diversions across nine river basins by sector in China from 2007 to 2015. The total national blue and grey water footprints were 365 Gm3yr-1 and 592 Gm3 yr-1, in which the Yangtze River basin accounts the most for 32 % and 37 %, respectively, by 2015. The physical water diversions increased by 52 % to 16.9 Gm3yr-1. The blue virtual water transfers increased by 24 % to 176 Gm3yr-1, whereas the grey virtual water transfers decreased by 10 % to 266 Gm3yr-1. Agriculture related interbasin virtual water flows showed opposite directions to those driven by the industry sector. Although with uneven value added while growing, limited effects mitigated water quantity and quality stresses, especially in the drier Yellow, Northwest, and Hai River basins where the capital is located. Half of the basins had low and declining synergy scores, suggesting an urgent need to achieve synergies between resources, the environment, and the economy across basins.

Subacute combined degeneration of the spinal cord concurrent with acute pulmonary embolism: a case report.

A 58-year-old male vegetarian presented with progressive numbness and weakness in the lower extremities. Laboratory examinations showed reduced vitamin B12 level with megaloblastic anaemia. Spinal magnetic resonance imaging (MRI) revealed hyperintensity within the posterior and lateral columns on T2-weighted imaging. The diagnosis of subacute combined degeneration (SCD) of the spinal cord was established. Unexpectedly, the patient developed transitory syncope on the second day after hospitalization. The diagnostic computed tomography pulmonary angiography (CTPA) confirmed multiple small pulmonary emboli. An isolated significantly elevated level of homocysteine (117.1 µmol/l) was documented when screening for hypercoagulable markers. Except for a long-term vegetarian diet, no other risk factors for hyperhomocysteinaemia (such as a family history of homocysteinuria) was found. The severity of the hyperhomocysteinaemia found in this current patient was unusual for patients with an insufficient intake of vitamin B12. In SCD patients, elevated homocysteine may increase the risk of thrombosis, which may exacerbate existing problems. Knowing the risk factors should help physicians choose appropriate diagnostic and therapeutic strategies.

The first report of human primary pyogenic ventriculitis caused by Streptococcus suis: a case report.

Streptococcus suis (S. suis), a gram-positive facultative anaerobe, has emerged as a zoonotic pathogen of suppurative infections in various human organs. Never reported is human primary ventriculitis caused by S. suis. A 70-year-old Chinese woman with a history of eating undercooked pork tongue was admitted to our hospital due to vomiting, headache and high fever. Brain magnetic resonance imaging (MRI) revealed intraventricular empyema and hydrocephalus, while cerebrospinal fluid (CSF) analysis showed purulent changes. S. suis was cultured in the CSF and blood samples of the patient, and confirmed as serotype 2 by real-time polymerase chain reaction (PCR). Therefore, the diagnosis of primary ventriculitis caused by S. suis was established. She was treated with intravenous (IV) meropenem for six weeks. To solve hydrocephalus, external ventricular drain (EVD) was performed, followed by ventriculoperitoneal shunt. Finally, the patient achieved a good outcome after a 6-month follow-up. S. suis is a rare pathogen in northern China but can cause severe infection and complications. S. suis infection should be considered when a patient with bacterial infection has a history of eating undercooked pork. MRI can help detect ventriculitis. It is worth noting that rapid and prolongated administration of IV antibiotics and timely neurosurgical intervention can achieve desirable outcomes.

Enhancing water and land efficiency in agricultural production and trade between Central Asia and China.

Besides posing soaring pressure on water and land resources, the ever-intensifying agricultural production redistributes these pressures trough increasingly intensive trade. Environmental consequences are complicated and unprecedented, and postulate thorough scrutiny. Little attention is paid to developing regions which are small nodes in terms of trade volume in global trade however of visible gaps in water and land productivities. Five Central Asian nations (CANs) have close trade activities with their neighbour China, but their agricultural production efficiency is strikingly low and the ecological environment is severely degraded. Here we evaluate, among CANs and China, the water and land footprints, virtual water and land trades, as well as potentials in enhancing water and land efficiency related to sixteen primary crop products, four primary animal products, and twelve derivative products production and trade over the period 2000-2014. We find that the blue water footprint and land footprint per unit product in CANs were up to 61- and 17-times higher than in China. Through enhancing water and land efficiency without further intervention in water and land endowments, the scenario for CANs shows an additional food supply for feeding 387 million people or half the starving population in the world.

Progress and Promise of Nur77-based Therapeutics for Central Nervous System Disorders.

Nur77 belongs to the NR4A subgroup of the nuclear receptor superfamily. Unlike other nuclear receptors, a natural ligand for Nur77 has not been identified yet. However, a few small molecules can interact with this receptor and induce a conformational change to mediate its activity. The expression and activation of Nur77 can be rapidly increased using various physiological and pathological stimuli. In vivo and in vitro studies have demonstrated its regulatory role in tissues and cells of multiple systems by means of participation in cell differentiation, apoptosis, metabolism, mitochondrial homeostasis, and other processes. Although research on Nur77 in the pathophysiology of the central nervous system (CNS) is currently limited, the present data support the fact that Nur77 is involved in many neurological disorders such as stroke, multiple sclerosis, Parkinson's disease. This indicates that activation of Nur77 has considerable potential in treating these diseases. This review summarizes the regulatory mechanisms of Nur77 in CNS diseases and presents available evidence for its potential as targeted therapy, especially for cerebrovascular and inflammationrelated CNS diseases.

Water for maize for pigs for pork: An analysis of inter-provincial trade in China.

Trade in commodities implies trade in virtual water (VW), which refers to the water that was used to produce the traded goods. Various studies have quantified international or inter-provincial virtual water (VW) flows related to the trade in crops and animal products. Until date, however, no effort has been undertaken to understand how the water embodied in traded feed crops (trade stage TS1) will be transferred further because of trade in animal products (trade stage TS2). This is the first study showing this mechanism, in a case study in China for maize (the major pig feed) and pork (the dominant meat), considering the period 2000-2013. We estimate the annual green and blue water footprints in maize production and then quantify the inter-provincial VW flows related to trade in maize (TS1) and trade in maize embodied in pork (TS2). Results show that in TS1, maize-related VW flowed from the water-scarce North to the water-rich South, with an increase of 40% over the study period (from 43 to 61 billion m3 y-1). In TS2, about 10% of the water embodied in maize exports from North to South China returns in the form of pork, with an increase in the absolute amount of 25% (from 4.8 to 6.1 billion m3 y-1). Considering blue VW flows specifically, we find that North-to-South blue VW flows decreased by 5% in TS1, while South-to-North blue VW flows increased by 23% in TS2.

Monthly blue water footprint caps in a river basin to achieve sustainable water consumption: The role of reservoirs.

The blue water footprint (WF) measures the consumption of runoff in a river basin. In order to ensure sustainable water consumption, setting a monthly blue WF cap, that is an upper-limit to the blue WF in a river basin each month, can be a suitable policy instrument. The blue WF cap in a river basin depends on the precipitation that becomes runoff and the need to maintain a minimum flow for sustaining ecosystems and livelihoods. Reservoirs along the river generally smooth runoff variability and thus raise the WF cap and reduce blue water scarcity during the dry season. Previous water scarcity studies, considering the ratio of actual blue WF to the blue WF cap under natural background conditions, have not studied this effect of reservoir storages. Here we assess how water reservoirs influence blue WF caps over time and how they affect the variability of blue water scarcity in a river basin. We take the Yellow River Basin over the period January 2002-July 2006 as case study and consider data on observed storage changes in five large reservoirs along the main stream. Results indicate that reservoirs redistribute the blue WF cap and blue water scarcity levels over time. Monthly blue WF caps were generally lowered by reservoir storage during the flood season (July-October) and raised by reservoir releases over the period of highest crop demand (March-June). However, with water storage exceeding 20% of natural runoff in most rainy months, reservoirs contribute to "scarcity in the wet months", which is to be understood as a situation in which environmental flow requirements related to the occurrence of natural peak flows are no longer met.

Optimal allocation of physical water resources integrated with virtual water trade in water scarce regions: A case study for Beijing, China.

This study provides an innovative application of virtual water trade in the traditional allocation of physical water resources in water scarce regions. A multi-objective optimization model was developed to optimize the allocation of physical water and virtual water resources to different water users in Beijing, China, considering the trade-offs between economic benefit and environmental impacts of water consumption. Surface water, groundwater, transferred water and reclaimed water constituted the physical resource of water supply side, while virtual water flow associated with the trade of five major crops (barley, corn, rice, soy and wheat) and three livestock products (beef, pork and poultry) in agricultural sector (calculated by the trade quantities of products and their virtual water contents). Urban (daily activities and public facilities), industry, environment and agriculture (products growing) were considered in water demand side. As for the traditional allocation of physical water resources, the results showed that agriculture and urban were the two predominant water users (accounting 54% and 28%, respectively), while groundwater and surface water satisfied around 70% water demands of different users (accounting 36% and 34%, respectively). When considered the virtual water trade of eight agricultural products in water allocation procedure, the proportion of agricultural consumption decreased to 45% in total water demand, while the groundwater consumption decreased to 24% in total water supply. Virtual water trade overturned the traditional components of water supplied from different sources for agricultural consumption, and became the largest water source in Beijing. Additionally, it was also found that environmental demand took a similar percentage of water consumption in each water source. Reclaimed water was the main water source for industrial and environmental users. The results suggest that physical water resources would mainly satisfy the consumption of urban and environment, and the unbalance between water supply and demand could be filled by virtual water import in water scarce regions.

Consumptive water footprint and virtual water trade scenarios for China - With a focus on crop production, consumption and trade.

The study assesses green and blue water footprints (WFs) and virtual water (VW) trade in China under alternative scenarios for 2030 and 2050, with a focus on crop production, consumption and trade. We consider five driving factors of change: climate, harvested crop area, technology, diet, and population. Four scenarios (S1-S4) are constructed by making use of three of IPCC's shared socio-economic pathways (SSP1-SSP3) and two of IPCC's representative concentration pathways (RCP 2.6 and RCP 8.5) and taking 2005 as the baseline year. Results show that, across the four scenarios and for most crops, the green and blue WFs per tonne will decrease compared to the baseline year, due to the projected crop yield increase, which is driven by the higher precipitation and CO2 concentration under the two RCPs and the foreseen uptake of better technology. The WF per capita related to food consumption decreases in all scenarios. Changing to the less-meat diet can generate a reduction in the WF of food consumption of 44% by 2050. In all scenarios, as a result of the projected increase in crop yields and thus overall growth in crop production, China will reverse its role from net VW importer to net VW exporter. However, China will remain a big net VW importer related to soybean, which accounts for 5% of the WF of Chinese food consumption (in S1) by 2050. All scenarios show that China could attain a high degree of food self-sufficiency while simultaneously reducing water consumption in agriculture. However, the premise of realizing the presented scenarios is smart water and cropland management, effective and coherent policies on water, agriculture and infrastructure, and, as in scenario S1, a shift to a diet containing less meat.

The effect of inter-annual variability of consumption, production, trade and climate on crop-related green and blue water footprints and inter-regional virtual water trade: A study for China (1978-2008).

Previous studies into the relation between human consumption and indirect water resources use have unveiled the remote connections in virtual water (VW) trade networks, which show how communities externalize their water footprint (WF) to places far beyond their own region, but little has been done to understand variability in time. This study quantifies the effect of inter-annual variability of consumption, production, trade and climate on WF and VW trade, using China over the period 1978-2008 as a case study. Evapotranspiration, crop yields and green and blue WFs of crops are estimated at a 5 × 5 arc-minute resolution for 22 crops, for each year in the study period, thus accounting for climate variability. The results show that crop yield improvements during the study period helped to reduce the national average WF of crop consumption per capita by 23%, with a decreasing contribution to the total from cereals and increasing contribution from oil crops. The total consumptive WFs of national crop consumption and crop production, however, grew by 6% and 7%, respectively. By 2008, 28% of total water consumption in crop fields in China served the production of crops for export to other regions and, on average, 35% of the crop-related WF of a Chinese consumer was outside its own province. Historically, the net VW within China was from the water-rich South to the water-scarce North, but intensifying North-to-South crop trade reversed the net VW flow since 2000, which amounted 6% of North's WF of crop production in 2008. South China thus gradually became dependent on food supply from the water-scarce North. Besides, during the whole study period, China's domestic inter-regional VW flows went dominantly from areas with a relatively large to areas with a relatively small blue WF per unit of crop, which in 2008 resulted in a trade-related blue water loss of 7% of the national total blue WF of crop production. The case of China shows that domestic trade, as governed by economics and governmental policies rather than by regional differences in water endowments, determines inter-regional water dependencies and may worsen rather than relieve the water scarcity in a country.

Baicalin inhibits PDGF-induced proliferation and migration of airway smooth muscle cells.

Airway smooth muscle (ASM) cell proliferation and migration play important roles in airway remodeling in asthma. In vitro platelet-derived growth factor (PDGF) induced ASM cell proliferation and migration. Baicalin is one of flavonoid extracts from Scutellaria baicalensis, which has an anti-asthma effect. However, little is known about its role in PDGF-induced proliferation and migration in rat ASM (RASM) cells. In this study, we aimed to investigate the effects of baicalin on PDGF-induced RASM cell proliferation and migration. We also identified the signaling pathway by which baicalin influences RASM cell proliferation and migration. In the current study, we demonstrated that baicalin suppressed PDGF-induced RASM cell proliferation, arrested PDGF-induced cell-cycle progression. It also suppressed PDGF-induced RASM cell migration. Furthermore, baicalin suppressed PDGF-induced expression of phosphorylated p38, ERK1/2 and JNK in RASM cells. In summary, our study is the first to show that baicalin pretreatment can significantly inhibit PDGF-induced RASM cell proliferation and migration by suppressing the MAPK signaling pathway, and baicalin may be a useful chemotherapeutic agent for asthma.

[Changes of ophthalmic blood flow in obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To observe the ophthalmic artery (OA), central retinal artery (CRA) and posterior ciliary artery (PCA) blood flow and the changes of eye vascular auto-regulation in patients with obstructive sleep apnea-hypopnea syndrome (OSAS). METHODS: It was a case-control study. Fifteen health overweight male adult (as normal control) and 42 patients with OSAS were randomly selected from examination center and sleep detection center, respectively. The OSAS patients were divided into mild (14 patients) and moderate and severe (28 patients) groups based on the apnea-hypopnea index (AHI). All subjects filled the sleep questionnaire and carried out polysomnogram monitoring all night for at least 7 hours. Fasting peripheral venous blood was collected at 7 AM on next day. The end-tidal CO(2) (ETCO(2)), intraocular pressure and color doppler sonography were examined next day to record the data in the inspection process before and after Mueller maneuver. Doppler ultrasound measurement of ocular blood flow diameter and blood flow velocity values were described in the median (max, min) and compared with Kruskal-Wallis test. And then two groups were compared with Bonferroni t test. Ocular blood flow velocity of patients with OSAS and PSG monitoring indicators were analyzed using partial correlation analysis. RESULTS: OA inner diameter in moderate and severe OSAS group [0.08 (0.15, 0.06) cm] was lower than that in healthy control [0.15 (0.26, 0.11) cm] and the difference was statistically significant (P = 0.000). PCA inner diameter in moderate and severe OSAS group [0.10 (0.13, 0.07) cm] were higher than that in healthy controls [0.05 (0.09, 0.04) cm]. CRA peak systolic velocity (PSV) in moderate and severe OSAS group [16.50 (19.40, 13.10) cm/s] was greater than that in healthy controls [11.30 (16.70, 8.20) cm/s]. The differences between these two groups were statistically significant (PCA inner diameter: P = 0.000, CRA-PSV: P = 0.001). The difference of CRA end diastolic velocity (EDV) between the moderate and severe group [8.90 (9.90, 5.10) cm/s], mild group [7.00 (8.30, 4.50) cm/s] and healthy control group [5.50 (7.40, 3.40) cm/s] was statistically significant (χ(2) = 14.45, P < 0.05). PCA-PSV [32.50 (43.10, 19.10) cm/s] and PCA-EDV [12.80 (15.20, 5.70) cm/s] in the moderate and severe group were higher than those in healthy control group [22.60 (32.20, 12.40) cm/s] and [7.20 (11.20, 3.90) cm/s], as well as those in the mild group [24.00 (30.70, 13.30) cm/s] and [8.00 (9.90, 3.90) cm/s]. These differences were statistically significant (PCA-PSV: P = 0.000, 0.002; PCA-EDV: P = 0.000, 0.001). The diameter of OA and PCA correlated negatively with ETCO(2) (r = -0.41, -0.34; P < 0.05); CRA-PSV was correlated with SaO2 min (r = -0.37, P < 0.05). CRA-EDV was correlated with ETCO(2) and SaO2 mean (r = 0.57, -0.39; P < 0.05). PCA-PSV was correlated with SaO2 min and MAI (r = -0.34, 0.56; P < 0.05). PCA-EDV was correlated SaO2 min and MAI (r = -0.29, 0.61; P < 0.05). CONCLUSIONS: The diameter and blood flow of OA, PCA and CRA change in OSAS patients. Compared with non-OSAS patients, the autoregulation function of PCA and CRA is weakened in OSAS patients.

Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression.

BACKGROUND: The signal transducer and activator of transcription 6 (STAT6) expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 (Th2) cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore, antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation. METHODS: In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide (ASODN) overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA (pANTI-STAT6), then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma. RESULTS: In vitro, we showed suppression of STAT6 expression and interleukin (IL)-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate (FITC)-labeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production. CONCLUSION: These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.

Inhibition of allergic airway inflammation by antisense-induced blockade of STAT6 expression / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The signal transducer and activator of transcription 6 (STAT6) expression in lung epithelial cells plays a pivotal role in asthma pathogenesis. Activation of STAT6 expression results in T helper cell type 2 (Th2) cell differentiation leading to Th2-mediated IgE production, development of allergic airway inflammation and hyperreactivity. Therefore, antagonizing the expression and/or the function of STAT6 could be used as a mode of therapy for allergic airway inflammation.</p><p><b>METHODS</b>In this study, we synthesized a 20-mer phosphorothioate antisense oligonucleotide (ASODN) overlapping the translation starting site of STAT6 and constructed STAT6 antisense RNA (pANTI-STAT6), then transfected them into murine spleen lymphocytes and analyzed the effects of antagonizing STAT6 function in vitro and in a murine model of asthma.</p><p><b>RESULTS</b>In vitro, we showed suppression of STAT6 expression and interleukin (IL)-4 production of lymphocytes by STAT6 ASODN. This effect was more prominent when cells were cultured with pANTI-STAT6. In a murine model of asthma associated with allergic pulmonary inflammation in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate (FITC)-labeled STAT6 ASODN to DNA uptake in lung cells was accompanied by a reduction of intracellular STAT6 expression. Such intrapulmonary blockade of STAT6 expression abrogated signs of lung inflammation, infiltration of eosinophils and Th2 cytokine production.</p><p><b>CONCLUSION</b>These data suggest a critical role of STAT6 in the pathogenesis of asthma and the use of local delivery of STAT6 ASODN as a novel approach for the treatment of allergic airway inflammation such as in asthma.</p>