Publications by authors named "Yonghui Yang"

73 Publications

Irisin Protects Cerebral Neurons from Hypoxia/Reoxygenation via Suppression of Apoptosis and Expression of Pro-Inflammatory Cytokines.

Neuroimmunomodulation 2022 Jun 15:1-8. Epub 2022 Jun 15.

Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China.

Background: Ischemic stroke is a major health issue that causes high incidents of morbidity and mortality worldwide. Irisin is an excise-induced protein that has exhibited pleiotropic properties. Accumulating evidence reveals its critical roles in the regulation of various cellular functions, including nervous system functions. This study aims to disclose the effect of irisin on rat cerebral neurons suffering from hypoxia/reoxygenation (H/R) treatment and to explore the potential underlying molecular mechanisms.

Methods: The percentage of rat cerebral neuron cell death was determined by flow cytometry analysis and MTT assay. The expression levels of target genes were measured by western blotting and real-time quantitative reverse transcription PCR assay.

Results: Our results demonstrated that irisin treatment substantially reduced H/R-induced apoptosis of rat cerebral neurons. Further investigation revealed that irisin treatment markedly decreased mitogen-activated protein kinase (MAPK) signaling pathway activation and suppressed pro-informatory cytokine expression in cerebral neurons with H/R challenge. Finally, we showed that the neuroprotective effect and anti-inflammatory effect of irisin were comparable with three MAPK signaling inhibitors.

Conclusion: Irisin exerts profound neuroprotective and anti-inflammatory effects on H/R-stimulated cerebral neurons by inhibiting the MAPK signaling activation. Therefore, irisin may serve as a potential drug for the treatment of patients with ischemic stroke.
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http://dx.doi.org/10.1159/000524273DOI Listing
June 2022

Mannan-Binding Lectin Regulates the Th17/Treg Axis Through JAK/STAT and TGF-β/SMAD Signaling Against Infection.

J Inflamm Res 2022 11;15:1797-1810. Epub 2022 Mar 11.

Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan, 453003, People's Republic of China.

Background: Mannan-binding lectin (MBL) is a key molecule in innate immunity and activates the lectin complement pathway, which plays an important role in resisting () infection. However, the underlying mechanism of this resistance to infection remains unclear.

Methods: In this study, we investigated how MBL regulates the differentiation of CD4 T cells into T helper type 17 (Th17) and T regulatory (Treg) cells against in mice, as well as the underlying mechanisms. We generated MBL double-knockout (KO) mice and infected them with by intraperitoneal injection.

Results: Compared with that in wild-type (WT) mice, the percentage of Th17 cells increased in MBL-null mice, whereas Treg cells decreased, indicating that MBL might regulate the Th17/Treg balance. In addition, in MBL-null mice, the expression levels of interleukin (IL)-17A, IL-21, and the master transcription factor of Th17 cells, RORγt, significantly increased. Conversely, IL-10, IL-2, and the Treg-specific transcription factor, Foxp3, decreased. Moreover, we found that the levels of TGF-β and IL-6 upregulated in MBL-null mice. Mechanistically, we found that MBL regulated the TGF-β/SMAD pathway through the inhibition of p-SMAD2 and promotion of p-SMAD3, and mediated the JAK/STAT pathway through the inhibition of p-JAK2 and p-STAT3 and promotion of p-JAK3 and p-STAT5. MBL double-KO mice showed a more severe inflammatory response and significantly lower survival rates with infection.

Conclusion: These results suggest that MBL regulates the Th17/Treg cell balance to inhibit inflammatory responses, possibly via IL-6- and TGF-β-mediated JAK/STAT and TGF-β/SMAD signaling, and play an important role in anti- infection.
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http://dx.doi.org/10.2147/JIR.S344489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923702PMC
March 2022

Impact of Combining Long-Term Subsoiling and Organic Fertilizer on Soil Microbial Biomass Carbon and Nitrogen, Soil Enzyme Activity, and Water Use of Winter Wheat.

Front Plant Sci 2021 8;12:788651. Epub 2022 Feb 8.

Soil Physics and Land Management Group, Wageningen University and Research, Wageningen, Netherlands.

Reductions in soil productivity and soil water retention capacity, and water scarcity during crop growth, may occur due to long-term suboptimal tillage and fertilization practices. Therefore, the application of appropriate tillage (subsoiling) and fertilization (organic fertilizer) practices is important for improving soil structure, water conservation and soil productivity. We hypothesize that subsoiling tillage combined with organic fertilizer has a better effect than subsoiling or organic fertilizer alone. A field experiment in Henan, China, has been conducted since 2011 to explore the effects of subsoiling and organic fertilizer, in combination, on winter wheat ( L.) farming. We studied the effects of conventional tillage (CT), subsoiling (S), organic fertilizer (OF), and organic fertilizer combined with subsoiling (S+OF) treatments on dry matter accumulation (DM), water consumption (ET), water use efficiency (WUE) at different growth stages, yield, and water production efficiency (WPE) of winter wheat over 3 years (2016-2017, 2017-2018, 2018-2019). We also analyzed the soil structure, soil organic carbon, soil microbial biomass carbon and nitrogen, and soil enzymes in 2019. The results indicate that compared with CT, the S, OF and S+OF treatments increased the proportion of >0.25 mm aggregates, and S+OF especially led to increased soil organic carbon, soil microbial biomass carbon and nitrogen, soil enzyme activity (sucrase, cellulose, and urease). S+OF treatment was most effective in reducing ET, and increasing DM and WUE during the entire growth period of wheat. S+OF treatment also increased the total dry matter accumulation (Total DM) and total water use efficiency (total WUE) by 18.6-32.0% and 36.6-42.7%, respectively, during these 3 years. Wheat yield and WPE under S+OF treatment increased by 11.6-28.6% and 26.8-43.6%, respectively, in these 3 years. Therefore, S+OF in combination was found to be superior to S or OF alone, which in turn yielded better results than the CT.
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http://dx.doi.org/10.3389/fpls.2021.788651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861283PMC
February 2022

[Mechanical Design and Research of Wearable Exoskeleton Assisted Robot for Upper Limb Rehabilitation].

Zhongguo Yi Liao Qi Xie Za Zhi 2022 Jan;46(1):42-46

The Third Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031.

Based on the biomechanical mechanism of human upper limb, the disadvantages of traditional rehabilitation training and the current status of upper limb rehabilitation robot, a six degree of freedom, flexible adjustment, wearable upper limb rehabilitation exoskeleton design scheme is proposed. Firstly, the mechanics of each joint of the upper limb is analyzed, and the virtual prototype design of the whole mechanical structure of the upper limb rehabilitation wearable exoskeleton is carried out by using CATIA three-dimensional software. The tooth transmission of the forearm and the upper arm single row four point contact ball bearing with internal/external rotation and the shoulder flexible passive adjustment mechanism (viscoelastic damper) are innovatively designed. Then, the joints of the upper limb rehabilitation exoskeleton are analyzed, theoretical analysis and calculation of the driving torque, the selection of the motor and gearbox of each driving joint are carried out. Finally, the whole finite element analysis of the upper limb exoskeleton is carried out. The research and experimental results showed that the design scheme of the upper limb exoskeleton assist structure is highly feasible, which can help the patients with upper limb paralysis and motor dysfunction self-rehabilitation.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2022.01.009DOI Listing
January 2022

The Demand Supply Steady-State Process-Based Multi-Level Spare Parts Optimization.

Sensors (Basel) 2021 Dec 13;21(24). Epub 2021 Dec 13.

Institute of Computer Application, China Academy of Engineering Physics, Mianyang 621900, China.

Spare parts are one of the important components of the equipment comprehensive support system. Spare parts management plays a decisive role in achieving the desired availability with the minimum cost. With the equipment complexity increasing, the price of spare parts has risen sharply. The traditional spare parts management makes the contradiction between fund shortage and spare parts shortage increasingly prominent. Based on the analysis of the multi-echelon and multi-indenture spare parts support model VARI-METRIC (vary multi-echelon technology for recoverable item control, VARI-METRIC), which is widely used by troops and enterprises in various countries, the model is mainly used in high system availability scenarios. However, in the case of low equipment system availability, the accuracy and cost of model inventory prediction are not ideal. This paper proposed the multi-level spare parts optimization model, which is based on the demand-supply steady-state process. It is an analytical model, which is used to solve the low accuracy problem of the VARI-METRIC model in the low equipment system availability. The analytical model is based on the multi-level spare parts support process. The article deduces methods for solving demand rate, demand-supply rate, equipment system availability, and support system availability. The marginal analysis method is used in the model to analyze the spare parts inventory allocation strategy's current based cost and availability optimal value. Finally, a simulation model is established to evaluate and verify the model. Then, the simulation results show that, when the low availability of equipment systems are 0.4, 0.6, the relative errors of the analytical model are 3.54%, 3.86%, and its costs are 0.52, 1.795 million ¥ RMB. The experiment proves that the inventory prediction accuracy of the analytical model is significantly higher than that of the VARI-METRIC model in low equipment system availability. Finally, the conclusion and future research directions are discussed.
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http://dx.doi.org/10.3390/s21248324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707947PMC
December 2021

Fc receptor-like 1, 3, and 6 variants are associated with rheumatoid arthritis risk in the Chinese Han population.

Genes Environ 2021 Oct 7;43(1):42. Epub 2021 Oct 7.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6 East Wenhui Road, Xianyang, 712082, Shaanxi, China.

Background: Rheumatoid arthritis (RA) is the most common autoimmune system diseases in our world. More studies in recent years have shown that FCRL gene polymorphisms is closely related to autoimmune diseases. It is suggested that genetic factors play a crucial role in the pathogenesis of this disease. In this study, we aimed to investigate the relationship between FCRL1 rs2050568, FCRL3 rs2317230 and FCRL6 rs58240276 polymorphisms and RA risk in the Chinese Han population. 506 with RA patients and 509 healthy controls were recruited in this study, and the single nucleotide polymorphisms (SNPs) was successfully genotyped using the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for age and gender were conducted to assess these SNPs polymorphisms and RA risk. The multifactor dimensionality reduction (MDR) method was conducted to analyze SNP-SNP interaction.

Results: Our results revealed that there no significant association was observed between the allele and genotype frequencies among these SNPs and RA risk (all p > 0.05). Straified analysis by age and gender, the results confirmed that FCRL1 rs2050568 T/T genotype enhanced the risk of RA in females (p = 0.014). The G/T - T/T genotype of FCRL3 rs2317230 was correlated with a decreased RA risk in males (p = 0.021). We also observed that the C/T-T/T genotype of FCRL6 rs58240276 was increased the risk of RA in the group at age >  54 years (p = 0.016). In addition, FCRL1 rs2050568-TT, FCRL6 rs58240276-TT and FCRL1 rs2050568-TT, FCRL3 rs2317230-TT, FCRL6 rs58240276-TT are the best models for multi-site MDR analysis (p < 0.05), and the two best models mentioned above and classes RA have the most significant correlation.

Conclusions: Our study demonstrated that FCRL1 rs2050568, FCRL3 rs2317230, and FCRL6 rs58240276 polymorphisms were correlated with RA susceptibility in the Chinese Han population.
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http://dx.doi.org/10.1186/s41021-021-00213-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499487PMC
October 2021

Plasma levels of amino acids and derivatives in retinopathy of prematurity.

Int J Med Sci 2021 27;18(15):3581-3587. Epub 2021 Aug 27.

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Retinopathy of prematurity (ROP) is a retinal disease that causes blindness in premature infants. This study aimed to reveal the changes in amino acids and derivatives in the plasma of ROP patients compared with premature infants without ROP. Metabolomics targeting amino acids and their derivatives was conducted to assess their plasma levels in ROP patients (=58) and premature infants without ROP (=25), and KEGG pathway analysis was used to identify the involved pathways. Among the 31 assessed metabolites, the levels of 4 amino acids were significantly altered in the ROP group. Creatinine was downregulated in the plasma of the ROP patients, while the levels of citrulline, arginine, and aminoadipic acid were upregulated in the ROP group. Significant correlations were identified between the ROP stage and plasma levels of citrulline, creatinine, and aminoadipic acid. The involved pathways included biosynthesis of amino acids, arginine and proline metabolism, and arginine biosynthesis. The plasma levels of citrulline, creatinine, arginine, and aminoadipic acid were significantly changed in ROP patients. These metabolites could be considered potential biomarkers of ROP, and their related metabolic pathways might be involved in ROP pathogenesis.
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http://dx.doi.org/10.7150/ijms.63603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436098PMC
March 2022

The Influence of NDRG1 Single Nucleotide Polymorphisms on Glioma Risk and Prognosis in Chinese Han Population.

Cell Mol Neurobiol 2022 Aug 12;42(6):1949-1964. Epub 2021 Mar 12.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, China.

Glioma is a highly fatal malignant tumor with a high recurrence rate, poor clinical treatment effect, and prognosis. We aimed to determine the association between single nucleotide polymorphisms (SNPs) of NDRG1 and glioma risk and prognosis in the Chinese Han population. 5 candidate SNPs were genotyped by Agena MassARRAY in 558 cases and 503 controls; logistic regression was used to analyze the relationship between SNPs and glioma risk. We used multi-factor dimensionality reduction to analyze the interaction of 'SNP-SNP'; the prognosis analysis was performed by log-rank test, Kaplan-Meier analysis, and Cox regression model. Our results showed that the polymorphisms of rs3808599 was associated with the reduction of glioma risk in all participants (OR 0.41, p = 0.024) and the participants ≤ 40 years old (OR 0.30, p = 0.020). rs3802251 may reduce glioma risk in all participants (OR 0.79, p = 0.008), the male participants (OR 0.68, p = 0.033), and astrocytoma patients (OR 0.81, p = 0.023). rs3779941 was associated with poor glioma prognosis in all participants (HR = 2.59, p = 0.039) or astrocytoma patients (HR = 2.63, p = 0.038). We also found that the key factors for glioma prognosis may include surgical operation, radiotherapy, and chemotherapy. This study is the first to find that NDRG1 gene polymorphisms may have a certain association with glioma risk or prognosis in the Chinese Han population.
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http://dx.doi.org/10.1007/s10571-021-01075-6DOI Listing
August 2022

4-Hydroxyisoleucine Alleviates Macrophage-Related Chronic Inflammation and Metabolic Syndrome in Mice Fed a High-Fat Diet.

Front Pharmacol 2020 21;11:606514. Epub 2021 Jan 21.

School of Life Sciences, Zhengzhou University, Zhengzhou, China.

In obesity, macrophages and other immune cells accumulate in organs affected by insulin, leading to chronic inflammation and insulin resistance. 4-Hydroxyisoleucine (4-HIL) is a non-protein amino acid found in fenugreek seeds. 4-HIL enhances insulin sensitivity, but its mechanism is still unclear. In this study, 4-HIL intervention reduced weight gain, liver steatosis, and dyslipidemia; moreover, it increased systemic insulin sensitivity and improved insulin resistance in mice. Importantly, after administration, the accumulation of M1 like CD11c macrophages and inflammation in the liver and adipose tissue were reduced in the mice. 4-HIL also reduced the proportion of CD11c macrophages among bone marrow-derived macrophages, which were induced . These observations demonstrate a new role of 4-HIL in insulin resistance in hepatocytes and adipocytes. 4-HIL inhibits obesity-related insulin resistance by reducing inflammation and regulating the state of M1/M2 macrophages.
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http://dx.doi.org/10.3389/fphar.2020.606514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858251PMC
January 2021

Fracture Models and Effect of Fibers on Fracture Properties of Cementitious Composites-A Review.

Materials (Basel) 2020 Dec 2;13(23). Epub 2020 Dec 2.

Department of Civil, Construction and Environmental Engineering, Iowa State University, Ames, IA 50011, USA.

Cementitious composites have good ductility and pseudo-crack control. However, in practical applications of these composites, the external load and environmental erosion eventually form a large crack in the matrix, resulting in matrix fracture. The fracture of cementitious composite materials causes not only structural insufficiency, but also economic losses associated with the maintenance and reinforcement of cementitious composite components. Therefore, it is necessary to study the fracture properties of cementitious composites for preventing the fracture of the matrix. In this paper, a multi-crack cracking model, fictitious crack model, crack band model, pseudo-strain hardening model, and double-K fracture model for cementitious composites are presented, and their advantages and disadvantages are analyzed. The multi-crack cracking model can determine the optimal mixing amount of fibers in the matrix. The fictitious crack model and crack band model are stress softening models describing the cohesion in the fracture process area. The pseudo-strain hardening model is mainly applied to ductile materials. The double-K fracture model mainly describes the fracture process of concrete. Additionally, the effects of polyvinyl alcohol (PVA) fibers and steel fibers (SFs) on the fracture properties of the matrix are analyzed. The fracture properties of cementitious composite can be greatly improved by adding 1.5-2% PVA fiber or 4% steel fiber (SF). The fracture property of cementitious composite can also be improved by adding 1.5% steel fiber and 1% PVA fiber. However, there are many problems to be solved for the application of cementitious composites in actual engineering. Therefore, further research is needed to solve the fracture problems frequently encountered in engineering.
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http://dx.doi.org/10.3390/ma13235495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730242PMC
December 2020

Supramolecular ensembles modified by near-infrared dyes and their biological applications.

J Mater Chem B 2020 12 6;8(47):10686-10699. Epub 2020 Nov 6.

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

Near-infrared dyes possess the qualities of lower interference with biological autofluorescence, low photon scattering, and deep tissue penetration, and are being increasingly involved in the development of biomaterials for sensing and precision medicine. However, dyes usually suffer from the disadvantages of poor water solubility and photobleaching, factors that limit their application in vivo. The introduction of supramolecular ensembles can provide an ideal solution. This review presents recently developed supramolecular ensembles modified by near-infrared dyes. Compared with small-molecule fluorophores, the specific size of a supramolecular-based fluorophore endows it with longer circulation time in the bloodstream, increasing its chances of reaching a specific target. In addition, the construction of supramolecule-based fluorophores with versatile functions can be achieved by simple encapsulation or doping, instead of by complicated chemical synthesis. Thus, supramolecular-complex-based fluorophores offer high potential in diagnosis and therapy. This review outlines four different species of near-infrared dye based ensembles in terms of their method of formation, including simple encapsulation or doping and copolymerisation. Recently, a new technology has employed modified fluorophores for in situ self-assembly that form supramolecular ensembles at a specific position, thus solving the problem of poor uptake of nanoparticles by cells, and is included in this review. Finally, the future of this field is considered.
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http://dx.doi.org/10.1039/d0tb01829eDOI Listing
December 2020

Assessment of interleukin 6 gene polymorphisms with rheumatoid arthritis.

Gene 2021 Jan 6;765:145070. Epub 2020 Sep 6.

Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China. Electronic address:

Background: Rheumatoid arthritis (RA) is complex autoimmune system disease and significant impact on the health of population in our world. Numerous studies confirmed that genetic factors play a crucial role in the pathogenesis of RA. In this current study, we aimed to investigate IL-6 polymorphisms and RA risk in Chinese Han population.

Methods: 508 RA patients and 494 age- and gender- matched healthy controls were recruited, all subjects were genotyped with an Agena MassARRAY platform. Subsequently, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjusting for age and gender.

Results: Our results suggested that IL-6 rs2243289 allele and genotype frequencies were associated with reduced RA risk under all genetic models (all p < 0.05). Stratification analysis revealed that IL-6 rs2243289 polymorphism was significant associated with decreased the risk of RA in the old groups (age > 54) (all p < 0.05). However, IL-6 rs2069837 and rs1800796 polymorphisms were associated with increased risk of RA among the young groups (age ≤ 54) (all p < 0.05). In addition, subgroup analysis by gender suggested that IL-6 rs2069837 and rs1800796 polymorphism were interacted with increased the risk of RA in males (all p < 0.05). Besides, IL-6 rs2243289 was associated with reduced RA risk in females.

Conclusions: In conclusion, our results demonstrated the correlation between IL and 6 polymorphisms and RA susceptibility and confirmed for the first time that the relationship was restricted to age and gender in Chinese Han population.
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http://dx.doi.org/10.1016/j.gene.2020.145070DOI Listing
January 2021

Irisin Protects Brain against Ischemia/Reperfusion Injury through Suppressing TLR4/MyD88 Pathway.

Cerebrovasc Dis 2020 5;49(4):346-354. Epub 2020 Aug 5.

Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China,

Background: Inflammatory response exerts an important role in ischemia/reperfusion (I/R) injury. TLR4 and myeloid differentiation factor 88 (MyD88) are key components in inflammation and are involved in the cerebral I/R injury. Irisin is a skeletal muscle-derived myokine produced after exercise, which was found to suppress inflammation. In this study, we investigated whether irisin could protect the brain from I/R injury through the TLR4/MyD88 pathway.

Methods: Male Sprague Dawley rats (20 months, 190 ∼ 240 g) were pretreated with irisin at 10, 50, or 100 mg/kg for consecutive 3 days and then subjected to surgery of middle cerebral artery occlusion or sham operation. Infarct size and neuron loss were measured to evaluate brain damage. The mRNA and protein levels of TLR4 and MyD88 were measured by in situ hybridization and immunohistochemistry, respectively. NF-κB activation was assessed by electrophoretic mobility shift assay. Neurological function was evaluated by neurobehavior score test and passive avoidance test.

Results: Irisin could reduce neuronal damage and neurofunctional impairment after I/R injury. This effect was mediated by downregulating the TLR4/MyD88 and inhibiting NF-κB activation.

Conclusion: Irisin plays a beneficial effect in I/R injury through regulating the TLR4/MyD88 pathway.
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http://dx.doi.org/10.1159/000505961DOI Listing
November 2020

Continuous exposure of PM2.5 exacerbates ovalbumin-induced asthma in mouse lung via a JAK-STAT6 signaling pathway.

Adv Clin Exp Med 2020 07;29(7):825-832

Department of Pathology, Hebei Province Chest Hospital, Lung Cancer Prevention and Control Center of Hebei Province, Shijiazhuang, China.

Background: Epidemiological studies and mice models have demonstrated that air pollution containing particulate matter smaller than 2.5 μm (PM2.5) exacerbates acute episodes of asthma in both children and adults.

Objectives: To investigate the effect of continuous PM2.5 treatment on asthma regulation mechanism behind this effect.

Material And Methods: In this study, the effects of continuous exposure to PM2.5 on asthma and eosinophil recruitment was compared to the effect of a single pre-ovalbumin (OVA)-sensitization exposure to PM2.5. Wild-type mice were either challenged once with PM2.5 + OVA before sensitization and asthma induction over a 27-day period, or with 5 times of PM2.5 + OVA treatment and sensitization/asthma induction over the same period.

Results: Continuous exposure to PM2.5 significantly increased total plasma immunoglobulin E (IgE), bronchial alveolar lavage fluid (BALF) cell numbers, eosinophils, and macrophages, leading to increased lung injury. This effect was regulated through increased production of chemokines and cytokines, such as interleukin (IL)-1β, monocyte chemoattractant protein 1 (MCP-1), IL-12, IL-5, IL-13, and prostaglandin D2 (PGD2). Eosinophil recruitment during continuous PM2.5 treatment was regulated through phosphorylation of the JAK/STAT6 pathway. As this study shows, continuous PM2.5 treatment significantly worsens asthma as compared to single exposure to PM2.5 or OVA exposure alone.

Conclusions: Our findings reveal that continuous exposure of PM2.5 exacerbates OVA-induced asthma in mouse lung through JAK-STAT6 signaling pathway.
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http://dx.doi.org/10.17219/acem/121009DOI Listing
July 2020

Evaluation of genetic variants in IL-1B and its interaction with the predisposition of osteoporosis in the northwestern Chinese Han population.

J Gene Med 2020 10 7;22(10):e3214. Epub 2020 Jun 7.

Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China.

Background: Interleukin (IL)-1β stimulates the proliferation and differentiation of osteoclast precursors into mature osteoclasts. IL-1B polymorphisms may influence the gene and protein expression of IL-1β. The present study aimed to investigate the association of IL-1B variants (rs2853550, rs1143643, rs3136558, rs1143630, rs1143627, rs16944 and rs1143623) and their interaction with osteoporosis risk among the northwestern Chinese Han population.

Methods: AN Agena MassARRAY system (Agena, San Diego, CA, USA) was employed for genotyping in 594 osteoporosis patients and 599 healthy controls. The possible association between IL-1B polymorphisms and risks of osteoporosis development was identified with odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Haplotype analysis and multifactor dimension reduction analysis were used to explore the potential association between combined single nucleotide polymorphisms (SNPs) and osteoporosis risk.

Results: The AA genotype of rs2853550 was a protective factor for osteoporosis occurrence (OR = 0.11, p = 0.038), whereas rs16944 (OR = 1.19, p = 0.037) and rs1143623 (OR = 1.21, p = 0.025) conferred an increased risk of osteoporosis. Moreover, rs1143627, rs16944 and rs1143623 were associated with an elevated susceptibility to osteoporosis, especially in females and individuals aged > 60 years or with a body mass index > 24 kg/m . Haplotype G A G was a risk factor of osteoporosis occurrence (OR = 1.20, p = 0.032). The best model of SNP-SNP analysis was a four-locus combination of rs1143643, rs3136558, rs1143630 and rs1143623 (testing accuracy = 0.5623).

Conclusions: IL-1B polymorphisms and haplotype G A G might contribute to susceptibility to osteoporosis. The SNP-SNP interaction of polymorphisms in IL-1B revealed the accumulated effect on osteoporosis risk.
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http://dx.doi.org/10.1002/jgm.3214DOI Listing
October 2020

The responses of the gut microbiota to MBL deficiency.

Mol Immunol 2020 Apr 21;122:99-108. Epub 2020 Apr 21.

School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China; Xinxiang Key Laboratory of Immunoregulation and Molecular Diagnostics, Xinxiang 453003, China. Electronic address:

Mannose-binding lectin (MBL) deficiency is a common innate immune system deficiency, and is associated with exacerbations and increased colonization of some pathogens. However, the response of the gut microbiota, a pivotal factor in host health, to MBL deficiency is not clear. In this study, MBL and wild-type (WT) mice were generated by backcrossing from MBL-A and MBL-C knockout (KO) mice, and fecal samples were collected at different ages (4th, 8th, 12th, 19th and 27th weeks). The gut microbiota was analyzed by high-throughput sequencing with universal 16S rDNA primers (V3-V5 region). The results showed that structural segregation of the gut microbiota occurred at the 8th, 12th, 19th and 27th weeks of age, although there were no significant differences in alpha diversities between MBL and WT mice at different ages. Impressively, in MBL mice, Akkermansia (from the family Verrucomicrobiaceae) were decreased significantly, Lactobacillus (from the family Lactobacillaceae) abundances, Alistipes and Rikenella (both from the family of Rikenellaceae) were always enriched. Network analysis showed that more interactions existed in the gut microbiota from WT mice (33 nodes and 70 edges) than in the gut microbiota from MBL mice (23 nodes and 40 edges). The 16S rDNA function prediction results indicated that the abundances of predicted genes in the "immune system disease", "metabolic disease" and "nucleotide metabolism" pathways were significantly increased in the MBL mice. In conclusion, this study revealed that the gut microbiota changed in MBL deficient mice, especially at ages older than 4 weeks.
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http://dx.doi.org/10.1016/j.molimm.2020.03.008DOI Listing
April 2020

Bone Turnover Markers and Bone Histomorphometry in Pubertal Rats with Intrauterine Growth Restriction.

Fetal Pediatr Pathol 2021 Oct 28;40(5):359-368. Epub 2020 Jan 28.

Division of Neonatology, Children's Medical Center, the Second Xiangya Hospital of Central South University, Changsha, China.

Objective: To investigate the effect of malnutrition during pregnancy on bone development in rat pups with intrauterine growth restriction (IUGR). IUGR offspring were induced with a 10% low protein diet, while the control group was given a 21% protein diet during pregnancy. Serum biomarkers including bone glutamyl protein (BGP), amino-terminal propeptide of type 1 procollagen (P1NP), cross linked N-telopeptide of type I collagen (NTX), and insulin like growth factor 1 (IGF-1) levels were measured at 7, 21 and 56 d. Left femurs taken at 56 d were used for bone histomorphometry analysis by micro-computed tomography (micro-CT). Compared with the control group, the IUGR group had lower IGF-1 and BGP levels at 7 and 21 d, and higher P1NP and NTX levels at 7 d. The IUGR group had thinner trabecular thickness (Tb.Th), lower trabecular number (Tb.N), and increased trabecular separation (Tb.Sp) at 56 d. The effect of IUGR on bone development may persist after birth.
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http://dx.doi.org/10.1080/15513815.2019.1710791DOI Listing
October 2021

Application of a modified electrocardiogram-guided technique for umbilical venous catheterisation in neonates: A retrospective trial.

J Paediatr Child Health 2020 05 17;56(5):716-720. Epub 2019 Dec 17.

Division of Neonatology, Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, China.

Aim: To investigate the effectiveness and safety of modified electrocardiogram (ECG)-guided technique in umbilical venous catheterisation in neonates.

Methods: Sixty-six critically ill neonates underwent umbilical venous catheterisation with (ECG group) or without (control group) ECG guidance from January 2017 to March 2019. We retrospectively analysed and compared the rate of correct tip placement on first try, unplanned extubation rate and incidence of catheter-related complications between the two groups.

Results: There were 33 patients in each group. The ECG group showed significantly higher rate of correct tip placement on first try (P < 0.001), lower unplanned extubation rate (P < 0.001), but identical incidence of catheter-related complications (P = 0.492) comparing with the control group.

Conclusion: The ECG-guided technique is an effective and safe method for umbilical venous catheterisation. The connecting method we modified made this technique more practical and can be promoted to areas without access to specific ECG adaptors.
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http://dx.doi.org/10.1111/jpc.14710DOI Listing
May 2020

Polymorphisms are Associated with Increased Risk of Esophageal Cancer.

Curr Mol Med 2020 ;20(5):379-387

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, Shaanxi, China.

Background: Esophageal cancer (EC) is the sixth leading cause of cancer death worldwide, and the overall incidence is increasing.

Objective: The aim of this study was to evaluate the association between single nucleotide polymorphisms in IL1R2 and EC risk in the Chinese population.

Methods: Genotyping of six SNPs of IL1R2 was performed with the Agena MassARRAY platform from 384 EC and 499 controls. The association between polymorphisms and EC risk was assessed by performing genetics models and haplotype analyses.

Results: Overall analysis results showed that the allele C of rs11674595 (odds ratio [OR] = 1.42, 95% confidence interval [CI]: 1.14-1.77, p = 0.002) and allele G of rs2072472 (allele: OR = 1.35, 95% CI: 1.08-1.69, p = 0.008) were associated with an increased EC risk. The rs11674595 and rs2072472 were found to be correlated with EC risk under the codominant, dominant, and additive models. Stratification analysis found that rs11674595 and rs2072472 were associated with increased EC risk in male and in age > 55 years old subgroup. In addition, Crs11674595Grs4851527 haplotype was significantly associated with 1.44-fold increased risk of EC (95% CI: 1.12-1.84, p = 0.004).

Conclusion: Our results reveal the significant association between SNPs (rs11674595 and rs2072472) in the IL1R2 and EC risk in the Chinese Han population. The findings may provide meaningful reference for the prevention and treatment of EC.
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http://dx.doi.org/10.2174/1566524019666191025091204DOI Listing
June 2021

A nationwide survey on neonatal medical resources in mainland China: current status and future challenges.

BMC Pediatr 2019 11 13;19(1):436. Epub 2019 Nov 13.

Neonatal Intensive Care Unit, Affiliated BaYi Children's Hospital of the Seventh Medical Center of PLA General Hospital, Beijing, China.

Background: With the rapid development of economy in recent two decades, neonatology has been progressing quickly in China. However, there is little knowledge about the exact developmental status of neonatal departments in China. The aim of this study was to assess resources available for care of sick newborns in mainland China.

Methods: Questionnaires were sent to the membership of the Chinese Neonatologist Association (CNA) and used to survey the scale, facilities, staff, technologies, transport systems and preterm infants' outcomes of neonatal departments (NDs) in different areas of China from June 2012 to December 2012.

Results: The result of this survey including a total of 117 questionnaires showed that investigated ND had a mean of 65 (median 47; range 5-450) beds, including 19.59 (median 15, range 0-100) NICU beds. The overall doctor/bed and nurse/bed ratio was 1:3.84 and 1:1.43, respectively. Lack of medical equipment was one of the main problems in most NDs surveyed, and only 26 NDs (22.2%) had more than one neonatal incubator per bed. Only 70.1, 30.6, 30.8 and 4.3% NDs carried out high-frequency ventilation, hypothermia, nitric oxide inhalation, and ECMO respectively. The capacity to provide advanced therapies increased with the size of the NDs (P < .01). A total of 81 NDs (69.2%) carried out neonatal transport, but only 70 NDs (86.4%) were equipped with transport incubators, 36 NDs (44.4%) had the ability of performing intrauterine transport of the preterm infants, and 3 NDs (3.7%) had the ability of performing air transport. The survival rate of extremely preterm infants (Gestational age less than 28w) to discharge home was 47.8% in 2011.

Conclusion: NDs in mainland China are not well distributed and still face many problems, such as staff shortage, inadequate facilities, and imperfect transport. It is urgent to set up a classification of neonatal care to enhance the utilization rate of medical resources and improve the prognosis of critically ill infants.
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http://dx.doi.org/10.1186/s12887-019-1780-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852994PMC
November 2019

Preconditioning with hydrogen sulfide ameliorates cerebral ischemia/reperfusion injury in a mouse model of transient middle cerebral artery occlusion.

Chem Biol Interact 2019 Sep 5;310:108738. Epub 2019 Jul 5.

Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, Shaanxi, China. Electronic address:

Ischemic stroke and reperfusion injury are a common and serve medical situation in the elderly population. HS is a gas neuromodulator which also possesses anti-oxidant and anti-inflammatory properties, and is found to play neuroprotective effect in neurodegenerative diseases. This study investigated the effect of endogenous and exogenous HS in a mouse model of ischemic stroke. 129P2-Cbs/J mice with heterozygous mutants in HS generating enzyme cystathionine β-synthase were used to study the effect of endogenous HS. HS donor NaHS was used as exogenous HS. Animals were pretreated with HS and then subjected to middle cerebral artery occlusion surgery. Behavioral outcome was evaluated by novel object recognition test. Inflammatory cytokines were measured using ELISA. Western blot was used to detect the activation of NF-κB. Aged 129P2-Cbs/J mice showed exaggerated inflammation and more severe cognitive impairment after ischemia, while exogenous HS treatment inhibited inflammation and attenuated behavioral impairment. The anti-inflammatory effect of HS was mediated by inhibiting NF-κB. Our findings suggest that both endogenous and exogenous HS are involved in the neuroprotection against ischemia/reperfusion-induced cerebral injury.
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http://dx.doi.org/10.1016/j.cbi.2019.108738DOI Listing
September 2019

Genetic analysis of the relation between IL2RA/IL2RB and rheumatoid arthritis risk.

Mol Genet Genomic Med 2019 07 27;7(7):e00754. Epub 2019 May 27.

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China.

Background: The biological mechanisms driving disease chronicity in rheumatoid arthritis (RA) are largely unidentified. Therefore, we aimed to determine genetic risk factors for RA.

Methods: In this case-control study, which includes samples from 499 patients and 507 healthy controls, six single-nucleotide polymorphisms (SNPs) in interleukin-2 receptor subunit alpha (IL2RA) and IL2RB were selected. Genotyping was performed using the Agena MassARRAY platform, and the statistical analyses were performed using the chi-squared and Fisher's exact tests, genetic model analysis, and haplotype analysis.

Result: In the allele model, using the chi-squared test, the result showed that rs791588 in IL2RA was associated with a decreased RA risk (odds ratios [OR] = 0.74, 95% confidence intervals [CI] = 0.62-0.89, p = 0.0014) after adjusting for age and gender. In the genetic model, logistic regression analyses revealed that rs791588 was associated with a decreased risk of RA under the codominant model, dominant model, recessive model, and log-additive model. Stratification analysis revealed that two SNPs (rs791588 and rs2281089) were significantly associated with a reduced RA risk in an allele and genetic model after stratification by gender or age (p < 0.05). In addition, the haplotypes "C G " and "C T " of IL2RA was associated with an increased risk of RA adjusted by age and gender (OR = 1.35, 95% CI: 1.12-1.64, p = 0.0016; OR = 1.24, 95% CI: 1.03-1.48, p = 0.021).

Conclusion: This finding indicates that the inherited altered genetic constitution at IL2RA may predispose to a less destructive course of RA.
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http://dx.doi.org/10.1002/mgg3.754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625105PMC
July 2019

Mutations in Are Implicated in Steroid-Resistant Nephrotic Syndrome.

J Am Soc Nephrol 2019 05 25;30(5):840-853. Epub 2019 Mar 25.

Center for Genetic Medicine Research, Children's National Health System, Washington, DC;

Background: Studies have identified mutations in >50 genes that can lead to monogenic steroid-resistant nephrotic syndrome (SRNS). The gene, which encodes one of the protein components of the nuclear pore complex nucleoporin 160 kD (Nup160), is expressed in both human and mouse kidney cells. Knockdown of impairs mouse podocytes in cell culture. Recently, siblings with SRNS and proteinuria in a nonconsanguineous family were found to carry compound-heterozygous mutations in .

Methods: We identified mutations by whole-exome and Sanger sequencing of genomic DNA from a young girl with familial SRNS and FSGS who did not carry mutations in other genes known to be associated with SRNS. We performed functional validation studies on the mutations using a model.

Results: We identified two compound-heterozygous mutations, and . We showed that silencing of specifically in nephrocytes (fly renal cells) led to functional abnormalities, reduced cell size and nuclear volume, and disorganized nuclear membrane structure. These defects were completely rescued by expression of the wild-type human gene in nephrocytes. By contrast, expression of the mutant allele completely failed to rescue nephrocyte phenotypes, and mutant allele rescued only nuclear pore complex and nuclear lamin localization defects.

Conclusions: Mutations in are implicated in SRNS. Our findings indicate that should be included in the SRNS diagnostic gene panel to identify additional patients with SRNS and homozygous or compound-heterozygous mutations and further strengthen the evidence that mutations can cause SRNS.
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http://dx.doi.org/10.1681/ASN.2018080786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493979PMC
May 2019

Cystathionine -Synthase-Derived Hydrogen Sulfide Correlates with Successful Aging in Mice.

Rejuvenation Res 2019 Dec 29;22(6):513-520. Epub 2019 Mar 29.

Department of Anesthesiology, the Second Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi, China.

Although learning and memory decline are associated with aging, some older individuals show high cognitive function. The mechanism underlying successful aging is not clear, although augmented N-methyl-D-aspartate receptor-independent long-term depression (LTD) has been found in successfully aged rats. We hypothesized that metabotropic glutamate receptor dependent LTD (mGluR-LTD) is associated with successful aging in mice and explored its molecular mechanisms. We divided aged mice into impaired and unimpaired groups and examined mGluR-LTD in the hippocampus. We examined the role of hydrogen sulfide (HS) in mGluR-LTD establishment in aged mice and investigated the requirement of protein synthesis and intracellular calcium levels. We assessed learning and memory of mice treated with sodium hydrogen sulfide (NaHS) using behavior tests. We found that unimpaired mice elicited larger mGluR-LTD that correlated with HS production which was blocked by inhibiting cystathionine synthase. Enhanced HS production of NaHS treatment augmented mGluR-LTD in impaired group. mGluR-LTD establishment required protein synthesis, as well as intracellular calcium, although NaHS treatment leads to reduced sensitivity to calcium chelator 1,2-bis(o-amino phenoxy)ethane-N,N,N',N'-tetraacetic acid treatment. Finally, we found that NaHS treatment enhanced learning and memory of aged mice as indicated by behavioral assessments. Our results indicate that successful aging mice are associated with the function of HS.
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http://dx.doi.org/10.1089/rej.2018.2166DOI Listing
December 2019

Mannan-Binding Lectin Suppresses Peptidoglycan-Induced TLR2 Activation and Inflammatory Responses.

Mediators Inflamm 2019 9;2019:1349784. Epub 2019 Jan 9.

School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.

Peptidoglycan (PGN), as the major components of the bacterial cell wall, is known to cause excessive proinflammatory cytokine production. Toll-like receptor 2 (TLR2) is abundantly expressed on immune cells and has been shown to be involved in PGN-induced signaling. Although more and more evidences have indicated that PGN is recognized by TLR2, the role of TLR2 PGN recognition is controversial. Mannan-binding lectin (MBL), a plasma C-type lectin, plays a key role in innate immunity. More and more evidences show that MBL could suppress the amplification of inflammatory signals. Whether MBL can alter PGN-elicited cellular responses through TLR2 in macrophages is still unknown, and possible mechanism underlying it should be investigated. In this study, we found that MBL significantly attenuated PGN-induced inflammatory cytokine production, including TNF- and IL-6, in PMA-stimulated THP-1 cells at both mRNA and protein levels. The expression of TLR2 was strongly induced by PGN stimulation. Furthermore, the administration of TLR2-neutralized antibody effectively suppressed PGN-induced TNF- and IL-6 expression. These results supplied the evidence that PGN from could be recognized by TLR2. In addition, we also found that MBL decreased PGN-induced TLR2 expression and suppressed TLR2-mediated downstream signaling, including the phosphorylation of IB, nuclear translocation of NF-Bp65, and phosphorylation of MAPK p38 and ERK1/2. Administration of MBL alone did not have an effect on the expression of TLR2. Finally, our data showed that PGN-mediated immune responses were more severely suppressed by preincubation with MBL and indicated that MBL can combine with both TLR2 and PGN to block the inflammation cytokine expression induced by PGN. All these data suggest that MBL could downregulate inflammation by modulating PGN/TLR2 signaling pathways. This study supports an important role for MBL in immune regulation and signaling pathways involved in inflammatory responses.
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http://dx.doi.org/10.1155/2019/1349784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343158PMC
August 2019

Construction of High Sensitive CD133 Immune PLGA Magnetic Spheres Platform for Lung Cancer Stem Cells Isolation and Its Property Evaluation.

J Biomed Nanotechnol 2018 Jun;14(6):1066-1074

High sensitive immune CD133 PLGA magnetic spheres platform is constructed to isolate and enrich lung cancer stem cells in order to study their biological characteristics, such as their proliferation, self-renewal and invasion and metastasis in vitro. The expression of the specific transcription factors Oct 4 and Nanog genes of stem cells were detected by immunofluorescence and RT-PCR. The tumorigenic capacity of lung cancer cells were studied using the tumorigenesis experiment in nude mice in vivo. The results indicated that the CD133 immune PLGA magnetic beads (with diameter 356.25 ± 0.64 nm) can effectively separate more lung cancer stem cells under the serum-free suspension culture compared with MACS CD133 MicroBead Kit. Some A549 cells sorted magnetically could form stable tumor suspended spheres that were able to undergo passage stably after 3 to 6 days. The self-renewal, clonal formation and invasion and metastasis capacities of the suspended spheres were higher than those of the parent cells (P < 0.05). The expressions of Oct 4 and Nanog mRNA in stem cells were significantly elevated (P < 0.05), and the A549 suspended spheres could significantly improve the in vivo tumorigenic capacity of nude mice. Among the peripheral blood of 20 patients with lung adenocarcinoma, CD133+ cells were isolated from the peripheral blood of 14 (70%), and CD133+ cells sorted from 11 (55%) patients were cultured into spheres.
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http://dx.doi.org/10.1166/jbn.2018.2562DOI Listing
June 2018

Land-Water-Food Nexus and indications of crop adjustment for water shortage solution.

Sci Total Environ 2018 Jun 12;626:11-21. Epub 2018 Jan 12.

Key Laboratory of Agricultural Water Resources, Hebei Laboratory of Agricultural Water-saving, Center for Agricultural Resources Research, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 286 Huaizhong Road, Shijiazhuang 050021, China.

While agriculture places the greatest demand on water resources, increasing agricultural production is worsening a global water shortage. Reducing the cultivation of water-consuming crops may be the most effective way to reduce agricultural water use. However, when also taking food demand into consideration, sustaining the balance between regional water and food securities is a growing challenge. This paper addresses this task for regions where water is unsustainable for food production (Beijing-Tianjin-Hebei Region for example) by: (i) assessing the different effects of wheat and maize on water use; (ii) analyzing virtual water and virtual land flows associated with food imports and exports between Beijing-Tianjin-Hebei and elsewhere in China; (iii) identifying sub-regions where grain is produced using scarce water resources but exported to other regions; and (iv) analyzing the potentiality for mitigating water shortage via Land-Water-Food Nexus. In the Beijing-Tianjin-Hebei Region, the study reveals that 29.76 bn m of virtual water (10.81 bn m of blue virtual water) are used by wheat and maize production and 8.77 bn m of virtual water used in nearly 2 million ha of cropland to overproduce 12 million ton of maize for external food consumption. As an importing-based sub-region with high population density, Beijing & Tianjin imported mostly grain (wheat and maize) from Shandong Province. Then, Hebei Province, as an exporting-based sub-region with severe water shortage, overproduced too much grain for other regions, which aggravated the water crisis. To achieve an integrated and sustainable development of the Beijing-Tianjin-Hebei Region, Hebei Province should stop undertaking the breadbasket role for Beijing & Tianjin and pay more attention to groundwater depletion. The analysis of the Land-Water-Food Nexus indicates how shifts in cultivated crops can potentially solve the overuse of water resources without adverse effects on food supply. It also provides meaningful information to support policy decisions about regional cropping strategies.
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http://dx.doi.org/10.1016/j.scitotenv.2018.01.071DOI Listing
June 2018

Assessment of the responses of soil pore properties to combined soil structure amendments using X-ray computed tomography.

Sci Rep 2018 01 12;8(1):695. Epub 2018 Jan 12.

State Key Laboratory of Crop Stress Biology in Arid Areas, College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, 712100, China.

Soil amendments, such as straw mulch, organic fertilizers and superabsorbent polymer (SAP), are extensively applied to improve soil structure and porosity, and we reported the functional consequences of the individual application of these amendments in our previous study. However, whether combined amendments are more effective than their individual applications for improving soil pore structure is unknown. Here, we conducted X-ray computed tomography (CT) scanning on undisturbed soil columns to investigate the efficiency of two-amendment application, including straw mulch and organic manure, SAP and organic manure, or SAP and straw mulch, for improving soil pore properties and pore distribution. The X-ray CT technique allows us to accurately determine the number, morphology, and location of macropores (>1 mm in diameter) and smaller pores (0.13-1.0 mm). Compared to the control treatment, which showed the lowest increase in soil porosity, all the combined treatments led to an increase in the numbers of both macropores and smaller soil pores, causing a significant improvement in soil structure and porosity. Among these treatments, the application of both straw mulch and organic manure was the most effective for improving soil porosity and soil physical structure.
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http://dx.doi.org/10.1038/s41598-017-18997-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766547PMC
January 2018

Estimation of land-surface evaporation at four forest sites across Japan with the new nonlinear complementary method.

Sci Rep 2017 12 19;7(1):17793. Epub 2017 Dec 19.

Center for Regional Environmental Research, National Institute for Environmental Studies, Tsukuba, 305-8506, Japan.

Evaporation from land surfaces is a critical component of the Earth water cycle and of water management strategies. The complementary method originally proposed by Bouchet, which describes a linear relation between actual evaporation (E), potential evaporation (E) and apparent potential evaporation (E) based on routinely measured weather data, is one of the various methods for evaporation calculation. This study evaluated the reformulated version of the original method, as proposed by Brutsaert, for forest land cover in Japan. The new complementary method is nonlinear and based on boundary conditions with strictly physical considerations. The only unknown parameter (α ) was for the first time determined for various forest covers located from north to south across Japan. The values of α ranged from 0.94 to 1.10, with a mean value of 1.01. Furthermore, the calculated evaporation with the new method showed a good fit with the eddy-covariance measured values, with a determination coefficient of 0.78 and a mean bias of 4%. Evaluation results revealed that the new nonlinear complementary relation performs better than the original linear relation in describing the relationship between E/E and E/E, and also in depicting the asymmetry variation between E/E and E/E.
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http://dx.doi.org/10.1038/s41598-017-17473-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5736731PMC
December 2017

Structure-activity relationship study of small molecule inhibitors of the DEPTOR-mTOR interaction.

Bioorg Med Chem Lett 2017 10 6;27(20):4714-4724. Epub 2017 Sep 6.

Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Jonnson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Research and Development, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA 91343, USA. Electronic address:

DEPTOR is a 48kDa protein that binds to mTOR and inhibits this kinase within mTORC1 and mTORC2 complexes. Over-expression of DEPTOR specifically occurs in the multiple myeloma (MM) tumor model and DEPTOR knockdown is cytotoxic to MM cells, suggesting it is a potential therapeutic target. Since mTORC1 paralysis protects MM cells against DEPTOR knockdown, it indicates that the protein-protein interaction between DEPTOR and mTOR is key to MM viability vs death. In a previous study, we used a yeast two-hybrid screen of a small inhibitor library to identify a compound that inhibited DEPTOR/mTOR binding in yeast. This therapeutic (compound B) also prevented DEPTOR/mTOR binding in MM cells and was selectively cytotoxic to MM cells. We now present a structure-activity relationship (SAR) study around this compound as a follow-up report of this previous work. This study has led to the discovery of five new leads - namely compounds 3g, 3k, 4d, 4e and 4g - all of which have anti-myeloma cytotoxic properties superior to compound B. Due to their targeting of DEPTOR, these compounds activate mTORC1 and selectively induce MM cell apoptosis and cell cycle arrest.
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http://dx.doi.org/10.1016/j.bmcl.2017.09.002DOI Listing
October 2017
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