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Introduction: Inappropriate residue and nutrient management leads to soil degradation and the decline of soil quality and water storage capacity., Methods: An ongoing field experiment has been conducted since 2011 to investigate the effects of straw mulching (SM), and straw mulching combined with organic fertilizer (SM+O), on winter wheat yield, including a control treatment (CK, no straw). We studied the effects of these treatments on soil microbial biomass nitrogen and carbon, soil enzyme activity in 2019, photosynthetic parameters, evapotranspiration (ET), water use efficiency (WUE), and yields over five consecutive years (2015-2019). We also analyzed the soil organic carbon, soil structure, field capacity, and saturated hydraulic conductivity in 2015 and 2019., Results: Results indicate that compared with CK, SM and SM+O treatments increased the proportion of >0.25mm aggregates, soil organic carbon, field capacity, and saturated hydraulic conductivity, but decreased the soil bulk density. In addition, the SM and SM+O treatments also increased soil microbial biomass nitrogen and carbon, the activity of soil enzymes, and decreased the carbon-nitrogen ratio of microbial biomass. Therefore, SM and SM+O treatments both increased the leaf water use efficiency (LWUE) and photosynthetic rate (Pn), and improved the yields and water use efficiency (WUE) of winter wheat. The combination SM (4.5 t/ha)+O (0.75 t/ha) was more effective than SM alone, and both treatments were superior to the control., Conclusion: Based on the results of this study, SM+O is recommended as the most effective cultivation practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Liu, Wu, Zhang, Gao, Zhang and Tang.)

Background and Objective: Intrauterine growth restriction (IUGR) is defined as the failure of a fetus to reach its genetic growth potential in utero resulted by maternal, placental, fetal, and genetic factors. Previous studies have reported that IUGR is associated with a high incidence of neurological damage, although the precise causes of such damage remain unclear. We aimed to investigate whether cognitive impairment in rats with IUGR is related to pyroptosis of hippocampal neurons and determine the effect of early intervention with docosahexaenoic acid (DHA)., Methods: Learning and memory function was assessed using the Morris water maze test. The morphological structure and ultrastructure of the hippocampus was examined via hematoxylin and eosin staining and electron microscopy respectively. The pyroptosis of hippocampal neuron was detected by gasdermin-D (GSDMD) immunofluorescence staining, mRNA and protein expression of nuclear localization leucine-rich-repeat protein 1 (NLRP1), caspase-1, GSDMD, and quantification of inflammatory cytokines interleukin (IL)-1β and IL-18 in the hippocampus., Results: IUGR rats exhibited decreased learning and memory function, morphological structure and ultrastructural changes in hippocampus compared to controls. IUGR rats also exhibited increased hippocampal quantification of GSDMD immunofluorescence staining, increased mRNA and protein expression of NLRP1, caspase-1, and GSDMD, and increased quantification of IL-1β and IL-18 in the hippocampus. Intervention with DHA attenuated these effects., Conclusion: Cognitive impairment in rats with IUGR may be related to pyroptosis of hippocampal neurons. Early intervention with DHA may attenuate cognitive impairment and reduce hippocampal pyroptosis in rats with IUGR., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

The beef quality significantly varies between breeds. Pingliang Red Cattle resembles Wagyu in fat deposition and flavor. To screen key factors affecting beef quality, we performed meat quality trait testing, RNA-seq, and metabolomics on the longissimus dorsi of Pingliang Red Cattle, Wagyu cross F1 generation, and Simmental cattle. The gene and metabolite expression profiles were similar between Pingliang Red Cattle and Wagyu cross F1 generation. Genes such as FASN , ACACA , PLIN1 , and FABP4 were significantly upregulated in the Pingliang Red Cattle and Wagyu cross F1 generation ( P < 0.05). Similarly, numerous metabolites, such as 3-iodo-l-tyrosine, arachidonic acid, and cis -aconitate, which may improve the beef quality such as fat deposition and tenderness, were found in higher levels in the Pingliang Red Cattle and Wagyu cross F1 generation. This study revealed differences in the transcriptional and metabolic levels between Pingliang Red Cattle and premium beef breeds, suggesting that Pingliang Red Cattle harbors the genetic potential for breeding high-grade beef cattle.

Introduction: Water scarcity and seasonal drought are major constraints on agricultural development globally. Super absorbent polymer (SAP) is a good amendment that can improve soil structure, increase soil water retention, and promote crop growth even with less soil moisture. We hypothesize that long term application of SAP has a better effect on soil organic carbon, soil enzyme activity, photosynthetic characteristics, yield, and water and nitrogen use than short term application., Methods: A long term field experiment with different application rates (0 (CK), 15 (L), 30 (M), 45 (H) kg ha -1 ) of SAP was conducted at the Yuzhou water conservation agriculture base of the Henan Academy of Agricultural Sciences from 2011 to 2019., Results and Discussion: The results indicate that applying SAP increases > 0.25 mm aggregates and decreased<0.25 mm aggregates in the soil after one year (2011) and 9 years (2019) of application. In addition, soil organic carbon, soil microbial biomass carbon, soil sucrase and cellulase activities, soil water consumption, water consumption, net photosynthetic rate (Pn), leaf water use efficiency (LWUE) of wheat and yield, all increased after SAP application. SAP also boosts water use efficiency and nitrogen use efficiency. Correlation analyses show that SAP promotes the growth of wheat, and improves the utilization rate of soil water and nutrients by improving the soil structure and increasing soil organic carbon and microbial enzyme activity., Conclusion: Based on our research, SAP treatment at a dosage of 45 kg ha -1 is most effective and is thus recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Zhang, Wu, Gao, Lu and Tang.)

Polystyrene (PS) is widely used in our daily life, but it is flammable and produces a large number of toxic gases and high-temperature flue gases in the combustion process, which limit its application. Improving the flame retardancy of PS has become an urgent problem to be solved. In addition, in view of the disadvantage that small-molecule flame retardants can easily migrate from polymers during use, which leads to the gradual reduction of the flame retardant effect or even loss of flame retardant performance, and the outstanding advantages of ATRP technology in polymer structure design and function customization, we used ATRP technology to synthesize the high-molecular-weight bifunctional additive PFAA-DOPO- b -PDEAEMA, which has flame retardant properties and antistatic properties. The chemical structure and molecular weight of PFAA-DOPO- b -PDEAEMA were characterized by FTIR, 1 H NMR, GPC, and XPS. When the addition of PFAA-DOPO- b -PDEAEMA was 15 wt %, the limiting oxygen index (LOI) of polystyrene composites was 28.4%, which was 53.51% higher than that of pure polystyrene, the peak of the heat release rate (pHRR) was 37.61% lower than that of pure polystyrene, UL-94 reached V-0 grade, and the flame retardant index (FRI) was 2.98. In addition, when the PFAA-DOPO- b -PDEEMA content is 15 wt %, the surface resistivity and volume resistivity of polystyrene composites are 2 orders of magnitude lower than those of polystyrene. This research work provides a reference for the design of bifunctional and even multifunctional polymers., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Objective: General hospitals admit lower gestational age neonates than maternal and child health care centers, therefore associated with a higher morbidity and mortality. This study aimed to assess the etiology and clinical characteristics of neonatal sepsis in different medical setting models., Methods: Neonates admitted to 5 tertiary medical centers, including one national general hospital, two maternal and child health care hospitals and two regional general hospitals, in central-south China with culture-proven sepsis between January 2010 and December 2019 were included in the study. We compared maternal and neonatal characteristics, pathogen distribution, treatment and neonatal outcomes among 3 different medical setting models in this retrospective cohort., Results: We identified 757 episodes of culture-proven sepsis in 757 neonates. The predominant pathogens were coagulase-negative staphylococci, Klebsiella pneumoniae , Escherichia coli and Group B streptococci. A total of 683 neonates with detailed information were involved in further comparison; 54.6% were from the national general hospital, 35.9% were from the maternal and child health care hospital, and 9.5% were from the regional general hospital. Neonates in national and regional general hospitals had significantly lower gestational age and birthweight ( P  < 0.001). Patterns of pathogen distribution were different among these medical setting models. Early-onset sepsis was more common in maternal and child health care hospitals (61.4% vs. 42.1% vs. 46.7%, P  < 0.001), while hospital-acquired late-onset sepsis was more common in national and regional general hospitals (32.7% vs. 33.3% vs. 11.4%, P  < 0.001). The proportion of complications or comorbidities of neonates in maternal and child health care hospitals were significantly lower than neonates in national and regional general hospitals ( P  < 0.001). The case fatality rate was significantly higher in regional general hospitals (10.8% vs. 3.2% vs. 0.8%, P  = 0.001)., Conclusion: We report distinct patterns of clinical characteristics, pathogens and outcomes in patient subgroups with neonatal sepsis from national general hospital, maternal and child health care hospital and regional general hospital. It might have some implications for improvement of prevention, management and empirical antibiotic use in neonatal sepsis in different setting models, especially in resource-limited settings from middle and low-income countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Yu, Dong, Li, Qi, Tan, Ouyang, Hu, Li, Wang, Yang, Gong, He and Chen.)

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives. To estimate the prevalence rates of Alzheimer's disease and related dementias (ADRD) and their risk factors in the transgender population and compare the rates to those in cisgender adults. Methods. We identified 1784 transgender adults in the linked electronic health records and claims data between 2012 and 2020 from the OneFlorida Clinical Research Consortium. We calculated the prevalence of ADRD and ADRD risk factors for the transgender and matched cisgender control adults. Results. The prevalence of ADRD was higher in the transgender adults compared with the cisgender control adults. Overall, the prevalence of ADRD risk factors was significantly higher in the transgender adults than the cisgender controls for 11 out of the 13 risk factors, with the only exceptions being traumatic brain injury and visual impairment. Conclusions. Transgender adults are at significantly higher risk for ADRD than cisgender adults. Our study highlights the urgent need for more research on the unique ADRD risks among the aging transgender and larger sexual- and gender-minority populations. ( Am J Public Health . 2022;112(5):754-757. https://doi.org/10.2105/AJPH.2022.306720).

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 Candida albicans ( C. albicans ) 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 C. albicans in mice, as well as the underlying mechanisms. We generated MBL double-knockout (KO) mice and infected them with C. albicans 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 C. albicans 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- C. albicans infection., Competing Interests: The authors declare that they have no competing interests in this work., (© 2022 Wang et al.)

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 ( Triticum aestivum 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Li, Wu, Pan, Gao and Tang.)

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.

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., (© 2022 S. Karger AG, Basel.)

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., (© 2021. The Author(s).)

Background: 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. Methods: Metabolomics targeting amino acids and their derivatives was conducted to assess their plasma levels in ROP patients ( n =58) and premature infants without ROP ( n =25), and KEGG pathway analysis was used to identify the involved pathways. Results: 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. Conclusion: 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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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.

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 2 . Haplotype G rs1143630 A rs1143627 G rs16944 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 rs1143630 A rs1143627 G rs16944 might contribute to susceptibility to osteoporosis. The SNP-SNP interaction of polymorphisms in IL-1B revealed the accumulated effect on osteoporosis risk., (© 2020 John Wiley & Sons, Ltd.)

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.

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., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020. Published by Elsevier Ltd.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Studies have identified mutations in >50 genes that can lead to monogenic steroid-resistant nephrotic syndrome (SRNS). The NUP160 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 NUP160 impairs mouse podocytes in cell culture. Recently, siblings with SRNS and proteinuria in a nonconsanguineous family were found to carry compound-heterozygous mutations in NUP160 ., Methods: We identified NUP160 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 in vivo functional validation studies on the NUP160 mutations using a Drosophila model., Results: We identified two compound-heterozygous NUP160 mutations, NUP160 R1173× and NUP160 E803K . We showed that silencing of Drosophila NUP160 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 NUP160 gene in nephrocytes. By contrast, expression of the NUP160 mutant allele NUP160 R1173× completely failed to rescue nephrocyte phenotypes, and mutant allele NUP160 E803K rescued only nuclear pore complex and nuclear lamin localization defects., Conclusions: Mutations in NUP160 are implicated in SRNS. Our findings indicate that NUP160 should be included in the SRNS diagnostic gene panel to identify additional patients with SRNS and homozygous or compound-heterozygous NUP160 mutations and further strengthen the evidence that NUP160 mutations can cause SRNS., (Copyright © 2019 by the American Society of Nephrology.)

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 3 of virtual water (10.81 bn m 3 of blue virtual water) are used by wheat and maize production and 8.77 bn m 3 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., (Copyright © 2018. Published by Elsevier B.V.)

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.

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.

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 po ) and apparent potential evaporation (E pa ) 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 e ) was for the first time determined for various forest covers located from north to south across Japan. The values of α e 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 pa and E po /E pa , and also in depicting the asymmetry variation between E pa /E po and E/E po .

Objectives: Klebsiella pneumoniae, which exists in the intestinal and respiratory tracts of humans and animals, is an important conditional pathogen in many animals. The aim of the current study was to investigate the antimicrobial resistance profiles and genotypes of extended-spectrum β-lactamase (ESBL)- and AmpC β-lactamase-producing K. pneumoniae isolated from dogs., Methods: A total of 285 isolates, collected from faecal and urine samples of diseased dogs in a Veterinary Teaching Hospital in Beijing, were characterised by antimicrobial susceptibility testing and screened for ESBL and AmpC β-lactamase phenotypes. The relevant genes were identified by polymerase chain reaction and sequencing., Results: All K. pneumoniae isolates were susceptible to meropenem, while the rates of resistance to the remaining 27 tested antimicrobials ranged from 24% to 97%. A total of 53% and 18% of K. pneumoniae isolates were positive for ESBL and AmpC β-lactamase production, respectively. ESBL/AmpC-producing strains were significantly resistant to more antimicrobial agents compared non-ESBL/AmpC-producing strains (P<0.05). CTX-M groups 1 and 9, and DHA-1 were the predominant genotypes of the ESBL/AmpC-producing K. pneumoniae isolates., Conclusions: In conclusion, the high percentage of drug resistance among K. pneumoniae isolates suggests that routine detection of ESBL production by reliable laboratory methods is required in small animal clinical practice., (Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

MiRNAs have been focused for their wide range of biological regulatory functions. Previous studies have suggested that individual miRNAs could influence tumorigenesis through their regulation of specific proto-oncogenes and tumor suppressor genes. This study was implemented to investigate the associations between SNPs in mature microRNAs (miRNAs) and development of lung cancer in a two-stage, case-control study, followed by some functional validations. First, 11 SNPs were analyzed in a case-control study of lung cancer, and the significant results were validated in an additional population. Our results showed that rs3746444 in mir-499 (allele C vs T: OR = 1.33; 95% CI = 1.15-1.54; P = 1.2 × 10-4) and rs4919510 in mir-608 (allele G vs C: OR = 1.27; 95% CI= 1.13-1.43; P = 5.1 × 10-5) were significantly associated with increased risk of lung cancer. Rs3746444 in mir-499 was also significantly associated with poor survival of lung cancer (HR, 1.35; 95% CI, 1.15-1.58; P = 0.0002). The expression levels of mir-499 and mir-608 were significantly lower than those of adjacent normal tissues (P < 0.0005), and the carriers of minor alleles have lower expression levels of mir-499 and mir-608 than those of major alleles (P < 0.001). These findings indicated that rs3746444 in mir-499 and rs4919510 in mir-608 might play a substantial role in the susceptibility to lung cancer., Competing Interests: CONFLICT OF INTERESTS None to declare.

Wild-type p53-induced phosphatase 1 (Wip1), also termed PPM1D, is a member of the protein phosphatase 2C family, which is characterized by distinctive oncogenic properties. Overexpression of Wip1 is observed in certain types of human tumors that are associated with significantly poor prognosis. The present study aimed to detect the expression of Wip1 in non-small cell lung cancer (NSCLC) and to analyze its prognostic value in such patients. The protein expression level of Wip1 was compared between NSCLC and normal lung tissue specimens using by immunohistochemistry, and it was found that Wip1 was highly expressed in NSCLCs but was absent or weakly expressed in normal lung tissues. Detailed clinical and demographic information of patients were retrospectively collected pre- and postoperatively, and Kaplan-Meier survival and Cox's regression analyses were performed to evaluate the prognosis of patients. Survival analysis revealed that the overall survival rate for patients in the Wip1-positive expression group was significantly lower than that of the Wip1-negative group, and Cox multivariate analysis indicated that positive Wip1 expression, pN classification and pathological stage were significant prognostic predictors. The results of the current study suggest that Wip1 may be associated with pathological diagnosis and prognostic evaluation of NSCLC.

Cytokine-induced killer (CIK) cells were isolated and proliferation from human peripheral blood and cultured in appropriate growth medium. The biological characteristics of CIK cells were further determined by the characterization of surface markers by flow cytometry. CIK cells inhibited the proliferation of human lung adenocarcinoma NCL-H157 cells. Vascular endothelial growth factor (VEGF) expression was down-regulated in CIK cells co-cultured with NCL-H157 cells by western blotting analysis. Furthermore, in comparison with cells untreated by CIK, the NCL-H157 had a lower proliferation capacity. We proposed that the pharmacological mechanisms of NCL-H157 promoted by CIK can be estimated possibly with different biological significance that can be ascribed to down-regulated VEGF expression in vitro. The results suggest that the VEGF pathway guides developmental inhibiting of NCL-H157, and we speculate that the function of VEGF pathways is to guide NCL-H157 to inhibition by abundant CIK., Competing Interests: Competing financial interests: The authors declare that they have no competing financial interests.

Objective: Previous studies have demonstrated that two homozygous missense MYO1E mutations are associated with childhood autosomal recessive focal segmental glomerulosclerosis in steroid-resistant nephrotic syndrome (SRNS) families from Italy and Turkey. Non-disease-causing heterozygous MYO1E variants were also found in other SRNS patient cohorts. However, the role of MYO1E mutations in Chinese sporadic SRNS has not been established., Method: Peripheral blood samples were collected for genetic analysis from 54 children with sporadic SRNS in Chinese Han ethnic group and a normal control group of 59 healthy adult volunteers. None of the patients carried mutations in NPHS2 or WT1. Genomic DNA was extracted from peripheral blood leukocytes. Twenty-eight exons and exon-intron boundaries of the MYO1E gene were amplified by polymerase chain reaction. Mutational analysis was performed by direct DNA sequencing and restriction endonuclease digestion., Result: Fifty-one variants in the MYO1E gene were identified in 54 children with sporadic SRNS. Among them, 10 MYO1E mutations of IVS1-11T>C, IVS2-86T>A, 279T>C (D93D), IVS6-181G>A, 718C>T (L240F), 1678A>G (T560A), IVS16-35A>G, IVS18+48T>A, IVS19+38G>A and IVS25+13C>T were detected in 11 patients, whereas they were absent in the 59 normal Chinese controls. Forty-one variants in MYO1E were identified and all of them were published in single nucleotide polymorphism database from national center for biotechnology information. Furthermore, all the 10 MYO1E mutations were in heterozygous states., Conclusion: MYO1E mutations are not a major cause of Chinese children with sporadic SRNS in the study.

Activation of PI3-K-AKT and ERK pathways is a complication of mTOR inhibitor therapy. Newer mTOR inhibitors (like pp242) can overcome feedback activation of AKT in multiple myeloma (MM) cells. We, thus, studied if feedback activation of ERK is still a complication of therapy with such drugs in this tumor model. PP242 induced ERK activation in MM cell lines as well as primary cells. Surprisingly, equimolar concentrations of rapamycin were relatively ineffective at ERK activation. Activation was not correlated with P70S6kinase inhibition nor was it prevented by PI3-kinase inhibition. ERK activation was prevented by MEK inhibitors and was associated with concurrent stimulation of RAF kinase activity but not RAS activation. RAF activation correlated with decreased phosphorylation of RAF at Ser-289, Ser-296, and Ser-301 inhibitory residues. Knockdown studies confirmed TORC1 inhibition was the key proximal event that resulted in ERK activation. Furthermore, ectopic expression of eIF-4E blunted pp242-induced ERK phosphorylation. Since pp242 was more potent than rapamycin in causing sequestering of eIF-4E, a TORC1/4E-BP1/eIF-4E-mediated mechanism of ERK activation could explain the greater effectiveness of pp242. Use of MEK inhibitors confirmed ERK activation served as a mechanism of resistance to the lethal effects of pp242. Thus, although active site mTOR inhibitors overcome AKT activation often seen with rapalog therapy, feedback ERK activation is still a problem of resistance, is more severe than that seen with use of first generation rapalogs and is mediated by a TORC1- and eIF-4E-dependent mechanism ultimately signaling to RAF.

Mutations in the WT1 gene, leading to Denys-Drash syndrome and Frasier syndrome, can also cause isolated steroid-resistant nephrotic syndrome (ISRNS). Previous studies have reported six pairs of monozygotic twins with WT1 mutations, including one presenting with discordant phenotypes with identical WT1 mutations being of paternal origin and five pairs of monozygotic twins presenting the same phenotype with identical WT1 mutations. In this study, we report on female monozygotic twins showing discordant phenotypes with an identical de novo WT1 mutation, R394W, and presenting incomplete Denys-Drash syndrome and ISRNS.

Activation of NF-kappaB requires the inhibitor of kappaB (IkappaB) kinase (IKK) complex, which is made up of two functional kinases, IKKalpha and IKKbeta, and the scaffolding protein IKKgamma. We recently identified several interferon-gamma (IFN-gamma)-stimulated genes (ISGs) that are not induced in mouse embryonic fibroblast cells (MEFs) doubly null for the expression of IKKalpha and IKKbeta. We show here that the IFN-gamma-induced transcription of IKK-dependent ISGs requires IKKbeta but not IKKalpha. We also identify several additional IKKbeta-dependent ISGs that are induced by IFN-gamma both in MEFs and in RAW 264.7 macrophages. Many have a combination of kappaB and IFN-stimulated response elements (ISRE) in their promoters. Although the IFN-gamma-induced expression of the IKKbeta-dependent gene ip-10 is sensitive to the superrepressor (SR) of IkappaBalpha and requires the p65 subunit of NF-kappaB, IFN-gamma does not activate NF-kappaB. In summary, a distinct subset of IFN-gamma-dependent genes requires some components of the normal pathway of NF-kappaB activation without activation of NF-kappaB signaling by IFN-gamma.

Although satellite radar altimetry was developed and optimized for open oceans, it has been used to monitor variations in the level of inland water-bodies such as lakes and rivers. Here, for the first time, we have further used the altimetry-derived variation of water level for estimating the fluctuation of water storage as an addition to the present in situ water storage estimation systems to be used in remote areas and in emergency situation such as in the events flooding monitoring and for studying the effect of climate change. Lake Dongting, the second largest lake in China, influenced frequently by flooding, was, therefore, chosen to demonstrate the potential of the technique. By using the concept of an "assumed reference point", we converted Topex/Poseidon satellite altimetry data on water level variations in Lake Dongting to "water level" data. The "water level" time-series data and in situ water storage were used to establish a rating curve. From the rating curve, we converted data on "water level" derived from seven years (1993-1999) of Topex/Poseidon data to actual water storage in Lake Dongting. The result reveals that the seasonal and annual fluctuations of water storage occurred during the 1990s with a more frequent flooding at the late 1990s' especially the flooding in whole catchment level in 1998 and 1999. The study supports the usefulness of satellite altimetry for dense and continuous monitoring of the temporal variations in water dynamic in moderate to large lakes.

Although Puma (p53 upregulated modulator of apoptosis) was known as a principal mediator of cell death in response to diverse apoptotic signals, the molecular mechanism underlying its proapoptotic regulation remains largely uncharacterized. Here we reported that myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic member of the Bcl-2 family with a rapid turnover rate, interacts with Puma. The Puma/Mcl-1 interaction was verified by both yeast two-hybrid assay and co-immuno-precipation studies. Their binding sites were mapped to BH3 (Bcl-2 homology) domain of Puma and BH1 domain of Mcl-1, respectively. Mcl-1 and Puma was shown to colocalize at the mitochondria by immunostaining. The level of Mcl-1 was increased when coexpressed with Puma, indicating Puma is able to stabilize Mcl-1. Puma binding to Mcl-1 via its BH3 domain is the prerequisite for this effect, which is further supported by the finding that Puma mutant lacking BH3 domain no longer promotes Mcl-1 protein stability. This Puma-enhanced Mcl-1 stabilization was validated in vivo under non-overexpression conditions. We also showed that BH1 domain is essential for Mcl-1 to inhibit Puma-induced apoptosis, since Mcl-1 mutant lacking BH1 domain completely abrogates its protective function. In addition, we concluded that binding of Puma to BH1 domain of Mcl-1 is necessary, but not sufficient to prevent rapid degradation of Mcl-1. In addition to PEST (proline, glutamic acid, serine, and threonine) and BH1 domain, some additional degradation signal is expected to reside in the C-terminal region of Mcl-1. In conclusion, our results provide the first evidence that the interaction between Mcl-1 and Puma may represent a novel mechanism by which Mcl-1 prevents apoptosis by increasing its stability through binding to Puma., (Oncogene (2005) 24, 7224-7237. doi:10.1038/sj.onc.1208873; published online 27 June 2005.)

By transferring natural vegetation with soil from high elevation to low elevation, a 2 degrees C warmer condition was created. In each site, 5 different precipitation treatments were applied to test if the temperature and precipitation changes under global warming will result in a lower soil moisture condition and, therefore, feedback negatively on vegetation productivity of the Taihang Mountain. Two years' field experiment suggested that, because of the low adaptability of Arundinelia hirta under a warmer condition, its productivity decreased significantly at the end of the experiment. Productivities of grass with better adaptability such as Themeda japonica and Artemisia sacrorum did not change significantly between the two sites. Tested vegetation demonstrated a significant increase in productivity under the higher precipitation condition by showing 22% increase in productivity under 20% higher precipitation treatment. Soil moisture condition under treatments with higher precipitation was generally higher than that under treatments with lower precipitation. In the warmer site, soil moisture became higher since the beginning of the second year.

Objective: In order to search new therapeutic strategies, study the relationship between angiogenesis and vascular endothelial growth factor and its two receptors in lung carcinoma., Methods: The study consisted of 49 patients with lung carcinoma treated with curative surgery. Immunohistochemistry on paraffin sections was performed with anti-human factor VIII antibody to study the microvascular density (MVD), and with antibodies to VEGF, Flt1, and KDR to investigate the expression of these three proteins in different cellular compartments. The survival time was compared between low MVD and high MVD groups by the Kaplan-Meier method., Results: (1) Expression of VEGF and its two receptors in tumor cells, stromal fibroblasts and endothelial cells was demonstrated. (2) There was no significant difference between low MVD and high MVD groups in the clinical data, including TNM stage, clinical phase, pathologic type, and tumor cell differentiation (P > 0.05). Survival analysis showed that the high MVD group was associated with a high risk of death. (3) There was no significant difference between low MVD and high MVD groups in VEGF expression in tumor cells, but in endothelial cells both Flt1 and KDR were correlated with high microvessel count. (4) The high expression of VEGF in tumor cells was correlated with that in stromal fibroblasts. The level of expression in both cells was consistent. (5) In both tumor cells and endothelial cells, high co-expression of VEGF and KDR was consistent, but that of VEGF and Flt1 showed inconsistency., Conclusions: (1) Not or rarely affected by clinical factors, MVD is a good and independent prognostic factor for patients with lung carcinoma. (2) The angiogenesis is induced not only by VEGF itself, but via VEGF receptors too. VEGF and its receptors thus appear to be new therapeutic targets for lung carcinoma. (3) VEGF appears to be produced by both tumor cells and stromal fibroblasts. (4) The result suggests that tumor expansion and angiogenesis are mainly induced by an autocrine pathway and a paracrine loop of VEGF via KDR.