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The issue of urban resilience plays great significance and value for the sustainable development of cities, which has attracted increasing attention from scholars and governments, especially in the western region of China. Based on the Production-Living-Ecological (PLE) system, this study attempts to describe urban resilience by the combination system that contains with P,L,E subsystem. The integrated approach including FAHP-EM,GRA-TOPSIS, CCDM, and ODM is proposed to reveal the urban resilience level and seek out the key constraints' indicators. Then, an empirical analysis of panel data of 18 cities in Sichuan Province from 2011 to 2021 was conducted to analyze the development process. The valuation results suggested that:(1)for urban resilience level, most cities at the moderate imbalance level and basically maintained at this level, only Chengdu is reaching the basic coordination level since in 2013.(2)The insufficient development of P,L,E subsystem is the reason for the moderate imbalance development, especially the key limiting factor is the P subsystem's low development level.(3)the most prominent obstacle indicators are x1(per capita local financial expenditure on science and technology), x2(per capita of R&D spending), x8(total export-import per capita), x14(number of people with basic medical insurance), x22(length of urban drainage pipeline), x23(number of public toilets per person) and the contribution values reach 7.56%,7.49%,11.02%, 9.14%,12.53%, 12.60% respectively. The detailed reference suggestions and effective measures put forwarded for policy makers and planners to promote urban resilience in Western China. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a zoonotic parasitic disease. Schistosoma japonicum eggs deposited in the liver tissue induce egg granuloma formation and liver fibrosis, seriously threatening human health. Natural killer (NK) cells kill activated hepatic stellate cells (HSCs) or induce HSC apoptosis and inhibit the progression of liver fibrosis. However, the function of NK cells in liver fibrosis caused by S. japonicum infection is significantly inhibited. The mechanism of this inhibition remains unclear. Twenty mice were percutaneously infected with S. japonicum cercariae. Before infection and 2, 4, 6, and 8 weeks after infection, five mice were euthanized and dissected at each time point. Hepatic NK cells were isolated and transcriptome sequenced. The sequencing results showed that Tigit expression was high at 4–6 weeks post infection. This phenomenon was verified by reverse transcription quantitative PCR (RT-qPCR) and flow cytometry. NK cells derived from Tigit-/- and wild-type (WT) mice were co-cultured with HSCs. It was found that Tigit-/- NK cells induced apoptosis in a higher proportion of HSCs than WT NK cells. Schistosomiasis infection models of Tigit-/- and WT mice were established. The proportion and killing activity of hepatic NK cells were significantly higher in Tigit-/- mice than in WT mice. The degree of liver fibrosis in Tigit-/- mice was significantly lower than that in WT mice. NK cells were isolated from Tigit-/- and WT mice and injected via the tail vein into WT mice infected with S. japonicum. The degree of liver fibrosis in mice that received NK cell infusion reduced significantly, but there was no significant difference between mice that received NK cells from Tigit-/- and WT mice, respectively. Our findings indicate that Tigit knockout enhanced the function of NK cells and reduced the degree of liver fibrosis in schistosomiasis, thus providing a novel strategy for treating hepatic fibrosis induced by schistosomiasis. Author summary: Schistosomiasis is a serious zoonotic parasitic disease. Schistosoma japonicum egg deposition in the liver induces granuloma formation and liver fibrosis, which are the main causes of death in patients with chronic and advanced schistosomiasis. Identifying the regulatory mechanism of liver fibrosis in schistosomiasis is crucial to inhibiting its progression. Natural killer (NK) cells kill activated hepatic stellate cells or induce their apoptosis and stop the progression of liver fibrosis. We found that TIGIT, an inhibitory receptor, was significantly highly expressed on NK cells at 4 and 6 weeks post infection, which may be associated with NK cell inhibition in schistosomiasis. We further explored the role of the TIGIT receptor in regulating NK cell-killing activity and liver fibrosis in schistosomiasis. Results indicate that blocking TIGIT receptors activated NK cells and decreased the extent of liver fibrosis, providing a novel target for treating liver fibrosis in schistosomiasis. [ABSTRACT FROM AUTHOR]

Interdisciplinary scientific collaboration promotes the innovative development of scientific research. Photocatalytic hydrogen evolution (PHE) is a typical interdisciplinary subject. This study aims to explore the characteristics of discipline interaction and the temporal evolution in the field. Bibliometric analysis could be used to understand the stage of research in a particular subject. In this work, the publications on the topic in Web of Science (WoS) platform from 1999 to 2020 were selected. On the basis of social network theory, the characteristics of interdisciplinary were revealed from three perspectives. First, the disciplinary interaction network is constructed through disciplinary co-occurrence to detect the characteristics of interaction structure among different disciplines. Then the node centrality index is employed to explore the influence of disciplines in the interactive network by using network centrality analysis. Moreover, the dynamic of discipline interaction evolution is studied using blockmodeling analysis. In the field of PHE, the number of disciplines and the intensity of interaction among different subjects gradually increased in the past 20 years. Chemistry and Material Sciences are the core discipline, and they play an important role in the network. The whole network is divided into different discipline groups. The scale of the discipline group is becoming large, and the disciplinary interaction is becoming more complex. The obtained results are helpful for guiding scholars to carry out interdisciplinary interaction. The methods of detecting interdisciplinary interactive relationship could provide paths for interdisciplinary research in other fields. [ABSTRACT FROM AUTHOR]

During the seed aging process, reactive oxygen species (ROS) can induce the carbonylation of proteins, which changes their functional properties and affects seed vigor. However, the impact and regulatory mechanisms of protein carbonylation on wheat seed vigor are still unclear. In this study, we investigated the changes in wheat seed vigor, carbonyl protein content, ROS content and embryo cell structure during an artificial aging process, and we analyzed the correlation between protein carbonylation and seed vigor. During the artificial wheat-seed aging process, the activity levels of antioxidant enzymes and the contents of non-enzyme antioxidants decreased, leading to the accumulation of ROS and an increase in the carbonyl protein content, which ultimately led to a decrease in seed vigor, and there was a significant negative correlation between seed vigor and carbonyl protein content. Moreover, transmission electron microscopy showed that the contents of protein bodies in the embryo cells decreased remarkably. We postulate that during the wheat seed aging process, an imbalance in ROS production and elimination in embryo cells leads to the carbonylation of proteins, which plays a negative role in wheat seed vigor. [ABSTRACT FROM AUTHOR]

Schistosomiasis, which is caused by infection with Schistosoma spp., is characterized by granuloma and fibrosis in response to egg deposition. Pattern recognition receptors are important to sense invading Schistosoma, triggering an innate immune response, and subsequently shaping adaptive immunity. Cyclic GMP-AMP synthase (cGAS) was identified as a major cytosolic DNA sensor, which catalyzes the formation of cyclic GMP-AMP (cGAMP), a critical second messenger for the activation of the adaptor protein stimulator of interferon genes (STING). The engagement of STING by cGAMP leads to the activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and the subsequent type I interferon (IFN) response. cGAS is suggested to regulate infectious diseases, autoimmune diseases, and cancer. However, the function of cGAS in helminth infection is unclear. In this study, we found that Cgas deficiency enhanced the survival of mice infected with S. japonicum markedly, without affecting the egg load in the liver. Consistently, Cgas deletion alleviated liver pathological impairment, reduced egg granuloma formation, and decreased fibrosis severity. In contrast, Sting deletion reduced the formation of egg granulomas markedly, but not liver fibrosis. Notably, Cgas or Sting deficiency reduced the production of IFNβ drastically in mice infected with S. japonicum. Intriguingly, intravenous administration of recombinant IFNβ exacerbated liver damage and promoted egg granuloma formation, without affecting liver fibrosis. Clodronate liposome-mediated depletion of macrophages indicated that macrophages are the major type of cells contributing to the induction of the type I IFN response during schistosome infection. Moreover, cGAS is important for type I IFN production and phosphorylation of TBK1 and IRF3 in response to stimulation with S. japonicum egg- or adult worm-derived DNA in macrophages. Our results clarified the immunomodulatory effect of cGAS in the regulation of liver granuloma formation during S. japonicum infection, involving sensing schistosome-derived DNA and producing type I IFN. Additionally, we showed that cGAS regulates liver fibrosis in a STING-type I–IFN-independent manner. Author summary: The sensing of invading pathogens by pattern recognition receptors (PRRs) is important for the host to mount an immune response. Cytosolic DNA receptor cGAS has been documented as critical for the induction of innate immunity, manifesting as a type I IFN response. However, little is known about the role of cGAS or type I IFN in the process of helminth infection. In this study, we identified an important role of the cGAS-STING-type I IFN signaling axis in driving schistosome infection-induced liver inflammation. Moreover, we revealed a hitherto unknown role of cGAS in the regulation of liver fibrosis during Schistosoma infection, a process that is independent of STING. Our study revealed cGAS as a novel functional receptor for the recognition of invading Schistosoma, paving the way for the development of novel strategies to treat schistosomiasis. [ABSTRACT FROM AUTHOR]

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It's suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS. Author summary: Thrombocytopenia in SFTSV is a multifactor-process involving a combination of platelet size or morphology alterations, fibrinolysis activation and coagulation abnormalities, increased inflammatory response and endothelial injury. Platelet supplementation alone shows minor role in improving disease, therefore new therapeutic intervention to regulate host response should be proposed. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus in the Bunyaviridae family, causing SFTS with high mortality rate. Haemaphysalis longicornis ticks has been demonstrated as a competent vector of SFTSV by experimental transmission study and field study. However, there has been query whether other tick species that infest human beings in the SFTS endemic regions are capable of transmitting the pathogen. Here by performing experimental transmission study, we compared the capable of transmitting SFTSV among Ixodes sinensis, Ixodes persulcatus and Dermacentor silvarum ticks. The transovarial transmission was seen in the I. sinensis ticks with a rate of 40%, but neither in I. persulcatus nor in D. silvarum ticks. I. sinensis ticks also have the ability to transmit SFTSV horizontally to uninfected mice at 7 days after feeding, but not for I. persalcatus or D. silvarum ticks. In the transstadial transmission of I. persulcatus and D. silvarum ticks, I. persulcatus ticks were tested negative from larvae to adults. But the D. silvarum ticks were tested positive from larvae to nymphs, with the positive rate of 100% (10/10) for engorged larval ticks and 81.25% (13/16) for molted nymphs. However, the mice bitten by SFTSV-infected D. silvarum nymphs were negative for SFTSV detection. Therefore, there is not enough evidence to prove the transstadial transmission of SFTSV in I. persalcatus and D. silvarum ticks. Author summary: Due to its wide distribution and high fatality rate (16%-30%), severe fever with thrombocytopenia syndrome (SFTS) has been listed in the top 10 priority diseases blueprint by the world health organization (WHO) in 2017. SFTSV is a novel phlebovirus in the Bunyaviridae family, and Haemaphysalis longicornis tick has been demonstrated as a competent vector of SFTSV by experimental transmission study and field study. However, there are many other tick species that infest human beings in the SFTS endemic regions. Therefore, it's neccessary to query whether these tick species are capable of transmitting SFTSV. The authors found that in addition to H. longicornis ticks, Ixodes sinensis ticks also served as an efficient vector capable of transovarial transmitting SFTSV, therefore posing as a potential threat in causing the circulation of SFTSV. In contrast, Dermacentor silvarum and Ixodes persulcatus ticks might not serve as an efficient vector of transmitting SFTSV. This research will provide important reference for the surveillance of SFTSV and the disease prevention and control. [ABSTRACT FROM AUTHOR]

To investigate the emotional conflict processing during the processing of emotional stimuli in individuals with different levels of social adjustment through developing an event-related potential (ERP) method, the study used positive words (happy), negative words (disgusted), positive faces and negative faces as experimental materials for a face-word Stroop emotional conflict task, which was completed by 34 participants. For the N2 component, there was a significant difference between the high and low social adjustment groups for the congruent condition; the low social adjustment group evoked more negative amplitude under the congruent condition. Under the incongruent condition, there was a marginally significant difference between the high and low social adjustment groups; the low social adjustment group evoked more negative amplitude under the incongruent condition. For the SP component, there were no significant differences for both the high and low social adjustment group between the congruent and incongruent conditions of emotional conflict. However, within the low social adjustment group, the incongruent evoked more positive amplitude. Our findings indicate that the difference in the emotional conflict process between individuals with high and low social adjustment mainly lies in the early processing stages of emotional information. That is, for both congruent and incongruent emotional stimuli, individuals with high social adjustment showed better emotional conflict monitoring, used less cognitive resources, and had a higher degree of automated processing than those with low social adjustment. During the later stages of emotional conflict processing, individuals with low social adjustment showed poorer conflict processing. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus SFTSV. Currently our knowledge of the host-related factors that influence the pathogenesis of disease is inadequate to allow prediction of fatal outcome. Here we conducted a prospective study of the largest database on the SFTS patients, to identify the presence of comorbidities in SFTS, and estimate their effect on the fatal outcome. Among 2096 patients eligible for inclusion, we identified nine kinds of comorbidities, from which hyperlipidemia (12.2%; 95% CI: 10.8%–13.6%), hypertension (11.0%; 95% CI: 9.6%–12.3%), chronic viral hepatitis (CVH) (9.3%; 95% CI: 8.1%–10.5%), and diabetes mellitus (DM) (6.8%; 95% CI: 5.7%–7.9%) were prevalent. Higher risk of death was found in patients with DM (adjusted OR = 2.304; 95% CI: 1.520–3.492; P<0.001), CVH (adjusted OR = 1.551; 95% CI: 1.053–2.285; P = 0.026) and chronic obstructive pulmonary diseases (COPD) (adjusted OR = 2.170; 95% CI: 1.215–3.872; P = 0.009) after adjusting for age, sex, delay from disease onset to admission and treatment regimens. When analyzing the comorbidities separately, we found that the high serum glucose could augment diseases severity. Compared to the group with max glucose < 7.0 mmol/L, patients with glucose between 7.0–11.1 mmol/L and glucose ≥11.1 mmol/L conferred higher death risk, with the adjusted OR to be 1.467 (95% CI: 1.081–1.989; P = 0.014) and 3.443 (95% CI: 2.427–4.884; P<0.001). Insulin therapy could effectively reduce the risk of severe outcome in DM patients with the adjusted OR 0.146 (95% CI: 0.058–0.365; P<0.001). For CVH patients, severe damage of liver and prolongation of blood coagulation time, as well as high prevalence of bleeding phenotype were observed. These data supported the provocative hypothesis that treating SFTS related complications can attain potentially beneficial effects on SFTS. [ABSTRACT FROM AUTHOR]

Osteoporosis is characterized by increased bone loss and deterioration of bone microarchitecture, which will lead to reduced bone strength and increased risk of fragility fractures. Previous studies have identified many genetic loci associated with osteoporosis, but functional mechanisms underlying the associations have rarely been explored. In order to explore the potential molecular functional mechanisms underlying the associations for osteoporosis, we performed integrative analyses by using the publically available datasets and resources. We searched 128 identified osteoporosis associated SNPs (P<10−6), and 8 SNPs exert cis-regulation effects on 11 eQTL target genes. Among the 8 SNPs, 2 SNPs (RPL31 rs2278729 and LRP5 rs3736228) were confirmed to impact the expression of 3 genes (RPL31, CPT1A and MTL5) that were differentially expressed between human subjects of high BMD group and low BMD group. All of the functional evidence suggested the important functional mechanisms underlying the associations of the 2 SNPs (rs2278729 and rs3736228) and 3 genes (RPL31, CPT1A and MTL5) with osteoporosis. This study may provide novel insights into the functional mechanisms underlying the osteoporosis associated genetic variants, which will help us to comprehend the potential mechanisms underlying the genetic association for osteoporosis. [ABSTRACT FROM AUTHOR]

Objective: To assess stereoacuity in a population-based sample of children and to examine ocular and systemic parameters related to stereoacuity. Methods: Using a random cluster sampling method, four- to 18-year-old children from kindergartens, elementary schools, junior high schools and senior high schools from a rural area and an urban area in the East Chinese province of Shandong were included in the school-based cross-sectional study. All participants underwent a comprehensive eye examination including assessment of cycloplegic refraction and measurement of stereoacuity using the Titmus Stereo test. Results: Out of 6364 eligible children, 5780 (90.8%) children with a mean age of 10.1 ± 3.2 years (range: 4 to 18 years) participated. Mean (± standard deviation) stereoacuity was 50.2 ± 50.6 arc seconds. Stereoacuity improved significantly (P<0.01) from the age group of 4 years to the age group of 6 to 7 years, then showed a plateau, deteriorated (P = 0.001) for both sexes from the age group of 9 years to the age group of 12 years (P<0.001), after which it improved (P = 0.001) again in the age group of 16 years or older to the pre-puberty values. In multivariate analysis, larger angle of binocular disparity (i.e., lower stereoacuity) was significantly associated with lower best corrected visual acuity (logMAR; P<0.001), higher intereye difference in refractive error (spherical equivalent) (P<0.001), higher cylindrical refractive error (P<0.001), higher refractive error (spherical value; P<0.001), higher intereye difference in best corrected visual acuity (logMAR) (P = 0.001), higher intereye difference in axial length (P = 0.001), and rural region of habitation (P = 0.006). Conclusions: Stereoacuity as tested with the Titmus Stereo test improved significantly from an age of 4 years to an age of 6 and 7 years, then remained constant, temporarily deteriorated for both sexes in pre-puberty and puberty, after which it improved again to pre-puberty or better values at the age of 16 years or older. Lower stereoacuity was associated with lower best corrected visual acuity and higher intereye difference in best corrected visual acuity, higher cylindrical and spherical refractive errors, higher inter-eye difference in refractive error, higher intereye difference in axial length, and rural region of habitation. [ABSTRACT FROM AUTHOR]

Chronic Hepatitis B Virus (HBV) infections can progresses to liver cirrhosis and hepatocellular carcinoma (HCC). The HBV covalently-closed circular DNA cccDNA is a key to HBV persistence, and its degradation can be induced by the cellular deaminase APOBEC3. This study aimed to measure the distribution of intrahepatic cccDNA levels and evaluate the association between levels of cccDNA and APOBEC3 in HCC patients. Among 49 HCC patients, 35 matched cancerous and contiguous noncancerous liver tissues had detectable cccDNA, and the median intrahepatic cccDNA in the cancerous tissues (CT) was significantly lower than in the contiguous noncancerous tissues (CNCT) (p = 0.0033). RCA (rolling circle amplification), followed by 3D-PCR identified positive amplification in 27 matched HCC patients. Sequence analysis indicated G to A mutations accumulated to higher levels in CT samples compared to CNCT samples, and the dinucleotide context showed preferred editing in the GpA context. Among 7 APOBEC3 genes, APOBEC3B was the only one up-regulated in cancerous tissues both at the transcriptional and protein levels (p < 0.05). This implies APOBEC3B may contribute to cccDNA editing and subsequent degradation in cancerous tissues. [ABSTRACT FROM AUTHOR]

Huang-Lian-Jie-Du Decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) formula with heat-dissipating and detoxifying effects. It is used to treat inflammation-associated diseases. However, no systematic pharmacokinetic (PK) and pharmacodynamic (PD) data concerning the activity of HLJDD under inflammatory conditions is available to date. In the present study, the concentration-time profiles and the hepatic clearance rates (HCR) of 41 major components in rat plasma in response to the oral administration of a clinical dose of HLJDD were investigated by LC-QqQ-MS using a dynamic multiple reaction monitoring (DMRM) method. Additionally, the levels of 7 cytokines (CKs) in the plasma and the body temperature of rats were analyzed. Furthermore, a PK-PD model was established to describe the time course of the hemodynamic and anti-inflammatory effects of HLJDD. As one of the three major active constituents in HLJDD, iridoids were absorbed and eliminated more easily and quickly than alkaloids and flavonoids. Compared with the normal controls, the flavonoids, alkaloids and iridoids in inflamed rats exhibited consistently changing trends of PK behaviors, such as higher bioavailability, slower elimination, delays in reaching the maximum concentration (Tmax) and longer substantivity. The HCR of iridoids was different from that of alkaloids and flavonoids in inflamed rats. Furthermore, excellent pharmacodynamic effects of HLJDD were observed in inflamed rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, IL-10, and macrophage inflammatory protein-2 (MIP-2) and body temperature significantly decreased after the administration of HLJDD. Based on PK-PD modeling with the three-phase synchronous characterization of time-concentration-effect, flavonoids exhibited one mechanism of action in the anti-inflammatory process, while iridoids and alkaloids showed another mechanism of action. Taken together, the results demonstrated that HLJDD may restrain inflammation synergistically via its major constituents (alkaloids, flavonoids and iridoids). A correlation between the exposure concentration of different types of compounds and their anti-inflammatory effects in the body was shown. This study provides a comprehensive understanding of the anti-inflammatory activity of HLJDD. [ABSTRACT FROM AUTHOR]

Background: 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) interconverts active 11β-hydroxyl glucocorticoids and inactive 11keto forms. However, its directionality is determined by availability of NADP+/NADPH. In liver cells, 11β-HSD1 behaves as a primary reductase, while in Leydig cells it acts as a primary oxidase. However, the exact mechanism is not clear. The direction of 11β-HSD1 has been proposed to be regulated by hexose-6-phosphate dehydrogenase (H6PDH), which catalyzes glucose-6-phosphate (G6P) to generate NADPH that drives 11β-HSD1 towards reduction. Methodology: To examine the coupling between 11β-HSD1 and H6PDH, we added G6P to rat and human liver and testis or Leydig cell microsomes, and 11β-HSD1 activity was measured by radiometry. Results and Conclusions: G6P stimulated 11β-HSD1 reductase activity in rat (3 fold) or human liver (1.5 fold), but not at all in testis. S3483, a G6P transporter inhibitor, reversed the G6P-mediated increases of 11β-HSD1 reductase activity. We compared the extent to which 11β-HSD1 in rat Leydig and liver cells might be coupled to H6PDH. In order to clarify the location of H6PDH within the testis, we used the Leydig cell toxicant ethane dimethanesulfonate (EDS) to selectively deplete Leydig cells. The depletion of Leydig cells eliminated Hsd11b1 (encoding 11β-HSD1) expression but did not affect the expression of H6pd (encoding H6PDH) and Slc37a4 (encoding G6P transporter). H6pd mRNA level and H6PDH activity were barely detectable in purified rat Leydig cells. In conclusion, the availability of H6PDH determines the different direction of 11β-HSD1 in liver and Leydig cells. [ABSTRACT FROM AUTHOR]

Hyperthermia as an anticancer method has been paid increasing attention in recent years. Several studies have shown that hyperthermia can kill tumor cells by inducing apoptosis. However, the underlying molecular mechanisms of hyperthermia-induced apoptosis are largely unknown. To investigate the effects and molecular mechanism of hyperthermia on the apoptosis in renal carcinoma 786-O cells, we firstly examined apoptosis and Ku expression in 786-O cell line treated with heat exposure (42°C for 0-4 h). The results showed that hyperthermia induced apoptosis of 786-O cells, and suppressed significantly Ku80 expression, but not Ku70 expression. Next, we knock-down Ku80 in 786-O cells, generating stable cell line 786-O-shKu80, and detected apoptosis, cell survival and cell cycle distribution. Our data showed higher apoptotic rate and lower surviving fraction in the stable cell line 786-O-shKu80 compared with those in control cells, exposed to the same heat stress (42°C for 0-4 h). Moreover, the results also showed suppression of Ku80 led to G2/M phase arrest in the stable cell line 786-O-shKu80 following heat treatment. Together, these findings indicate that Ku80 may play an important role in hyperthermia-induced apoptosis and heat-sensitivity of renal carcinoma cells through influencing the cell cycle distribution. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of 1% cyclopentolate on the refractive status of children aged 4 to 18 years. Methods: Using a random cluster sampling in a cross-sectional school-based study design, children with an age of 4–18 years were selected from kindergardens, primary schools, junior and senior high schools in a rural county and a city. Auto-refractometry was performed before and after inducing cycloplegia which was achieved by 1% cyclopentolate eye drops. Results: Out of 6364 eligible children, data of 5999 (94.3%) children were included in the statistical analysis. Mean age was 10.0±3.3 years (range: 4–18 years). Mean difference between cycloplegic and non-cycloplegic refractive error (DIFF) was 0.78±0.79D (median: 0.50D; range: -1.00D to +10.75D). In univariate analysis, DIFF decreased significantly with older age (P<0.001;correlation coefficient r:-0.24), more hyperopic non-cycloplegic refractive error (P<0.001;r = 0.13) and more hyperopic cycloplegic refractive error (P<0.001;r = 0.49). In multivariate analysis, higher DIFF was associated with higher cycloplegic refractive error (P<0.001; standardized regression coefficient beta:0.50; regression coefficient B: 0.19; 95% confidence interval (CI): 0.18, 0.20), followed by lower intraocular pressure (P<0.001; beta: -0.06; B: -0.02; 95%CI: -0.03, -0.01), rural region of habitation (P = 0.001; beta: -0.04; B: -0.07; 95%CI: -0.11, -0.03), and, to a minor degree, with age (P = 0.006; beta: 0.04; B: 0.009; 95%CI: 0.003, 0.016). 66.4% of all eyes with non-cycloplegic myopia (≤-0.50D) remained myopic after cycloplegia while the remaining 33.6% of eyes became emmetropic (18.0%) or hyperopic (15.7%) under cycloplegia. Prevalence of emmetropia decreased from 37.5% before cycloplegia to 19.8% after cycloplegia while the remaining eyes became hyperopic under cycloplegia. Conclusions: The error committed by using non-cycloplegic versus cycloplegic refractometry in children with mid to dark-brown iris color decreased with older age, and in parallel manner, with more myopic cycloplegic refractive error. Non-cycloplegic refractometric measures lead to a misclassification of refractive error in a significant proportion of children. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the distribution of the (CCR) and its associated factors in children. Methods: Using a random cluster sampling method, the school-based, cross-sectional Shandong Children Eye Study included children aged 4 to 18 years from the rural county of Guanxian and the city of Weihai in the province of Shandong in East China. CCR was measured by ocular biometry. Results: CCR measurements were available for 5913 (92.9%) out of 6364 eligible children. Mean age was 10.0±3.3 years, and mean CCR was 7.84±0.27 mm (range: 6.98 to 9.35 mm). In multivariate linear regression analysis, longer CCR (i.e. flatter cornea) was significantly associated with the systemic parameters of male sex (P<0001;standardized regression coefficient beta: -0.08;regression coefficient B:-0.04; 95% Confidence Interval (CI):-0.05,-0.03), younger age (P<0.001;beta:-0.37;B:-0.03;95%CI:-0.04,-0.03), taller body height (P = 0.002;beta:0.06;B:0.001;95%CI:0.000,0.001), lower level of education of the father (P = 0.001;beta:-0.04;B:-0.01;95%CI:-0.02,-0.01) and maternal myopia (P<0.001;beta:-0.07;B:-0.04;95%CI:-0.06,-0.03), and with the ocular parameters of longer ocular axial length (P<0.001;beta:0.59;B:0.13;95%CI:0.12,0.14), larger horizontal corneal diameter (P<0.001;beta:0.19;B:0.13;95%CI:0.11,0.14), and smaller amount of cylindrical refractive error (P = 0.001;beta:-0.09;B:-0.05;95%CI:-0.06,-0.04). Conclusions: Longer CCR (i.e., flatter corneas) (mean:7.84±0.27mm) was correlated with male sex, younger age, taller body height, lower paternal educational level, maternal myopia, longer axial length, larger corneas (i.e., longer horizontal corneal diameter), and smaller amount of cylindrical refractive error. These findings may be of interest for elucidation of the process of emmetropization and myopization and for corneal refractive surgery. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an emerging technique for the rapid and high-throughput identification of microorganisms. There remains a dearth of studies in which a large number of pathogenic microorganisms from a particular country or region are utilized for systematic analyses. In this study, peptide mass reference spectra (PMRS) were constructed and evaluated from numerous human pathogens (a total of 1019 strains from 94 species), including enteric (46 species), respiratory (21 species), zoonotic (17 species), and nosocomial pathogens (10 species), using a MALDI-TOF MS Biotyper system (MBS). The PMRS for 380 strains of 52 species were new contributions to the original reference database (ORD). Compared with the ORD, the new reference database (NRD) allowed for 28.2% (from 71.5% to 99.7%) and 42.3% (from 51.3% to 93.6%) improvements in identification at the genus and species levels, respectively. Misidentification rates were 91.7% and 57.1% lower with the NRD than with the ORD for genus and species identification, respectively. Eight genera and 25 species were misidentified. For genera and species that are challenging to accurately identify, identification results must be manually determined and adjusted in accordance with the database parameters. Through augmentation, the MBS demonstrated a high identification accuracy and specificity for human pathogenic microorganisms. This study sought to provide theoretical guidance for using PMRS databases in various fields, such as clinical diagnosis and treatment, disease control, quality assurance, and food safety inspection. [ABSTRACT FROM AUTHOR]

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3, ATO) has been effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but the long-term efficacy and safety among newly diagnosed APL patients are unclear. In this retrospective study, total 45 newly diagnosed APL patients received ATRA/chemotherapy combination regimen to induce remission. Among them, 43 patients (95.6%) achieved complete remission (CR) after induction therapy, followed by ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment with a median follow-up of 55 months. In these patients, the estimated overall survival (OS) and the relapse-free survival (RFS) were 94.4%±3.9% and 94.6±3.7%, respectively. The toxicity profile was mild and reversible. No secondary carcinoma was observed. These results demonstrated the high efficacy and minimal toxicity of ATO/ATRA/anthracycline-based chemotherapy sequential consolidation treatment for newly diagnosed APL in long-term follow-up, suggesting a potential frontline therapy for APL. [ABSTRACT FROM AUTHOR]