[Pathogenic agents causing acute respiratory tract infections in pediatric patients in Spring, 2023, in Beijing].

Objective: To explore the pathogenic agents of acute respiratory infection (ARI) in children in Beijing. Methods: In the cross-sectional study, 3 groups of children from different departments were enrolled from Feb 6th, 2023 (6th week) to May 28th (21th week), 2023, including influenza-like case group from emergency department for nucleic acid testing of influenza virus (Flu) and human metapneumovirus (HMPV), the outpatient ARI group under nucleic acid testing for Flu, respiratory syncytial virus (RSV), adenovirus (ADV), and parainfluenza virus (PIV), and the inpatient ARI group under nucleic acid testing for Flu, RSV, HMPV, ADV, human bocavirus (HBoV), Rhinovirus (Rh), PIV, coronavirus (HCoV), Mycoplasma pneumoniae (Mp) and Chlamydia pneumonia (Cp). Results: There were 320 influenza-like cases enrolled, including 192 males and 128 females, aged 4.7 (3.6, 6.9) years, and 117 cases (36.6%) positive for Flu A, which contained similar proportion of pandemic H1N1 (H1N1) 47.0% (55/117) and H3N2 53.0% (62/117), and 13 cases for HMPV 4.1% (13/320). The rate of Flu reached its peak at the 10th week, with H1N1 as the predominant one from the 6th to 9th week (10.0%-50.0%) and then H3N2 from the 10th to 16th week (15.0%-90.0%). HMPV was detected from the 15th week 5.0% (1/20), and then reached to 30.0% (6/20) at the 20th week. In the outpatient ARI group, 7 573 were enrolled, including 4 131 males and 3 442 females, aged 4.0 (2.1, 5.3) years, and the highest positive rate for RSV 32.9% (2 491/7 573), followed by Flu A 12.1% (915/7 573). The dominant one was Flu A in weeks 6-14 (23.2%-74.7%), then RSV in the 15th week 24.8% (36/145). In the inpatient ARI group, 1 391 patients were enrolled, including 804 males and 587 females, aged 3.3 (0.4, 5.8) years, and the highest positive rate for Rh 18.7% (260/1 391), followed by RSV 12.4% (173/1 391), Flu A 10.2% (142/1 391, of which 116 cases (81.7%) were H1N1, and 26 cases (18.3%) were H3N2) and HMPV 3.1% (43/1 391). H1N1 was detected from the 7th week 10% (6/60), to peak in the 11th week 31.8% (21/66). H3N2 was detected from the 8th week 1.5% (1/68), and then kept in low level. The proportion of H1N1 among Flu was 81.7% (116/142) in the inpatient ARI group. RSV was detected from 12th week 1.3% (1/80), reaching 30.4% (35/115) at 19th week. The positive rate of HMPV reached 12.1% (14/116) at 21th week. Conclusions: In the spring of 2023, the first one in Beijing is the Flu epidemic, with H1N1 being the predominant one in the early stage and H3N2 in the later stage. Then, there is a postponed RSV epidemic and an increased HMPV detection. In addition, nucleic acid testing for outpatient children should be strengthened to provide early warning of epidemics.

[The role and mechanism of tumor metastasis-associated gene 1 in radiosensitivity of HeLa cells].

Objective: To determine the effect of tumor metastasis-associated gene 1 (MTA1) on the sensitivity of HeLa cells to radiotherapy, and to clarify its molecular mechanism. Methods: The transcriptome differences between MTA1 knocked down Hela cells and control cells were analyzed, and the differentially expressed genes (DEGs) was used to perform Gene-Set Enrichment Analysis (GSEA) and Gene Ontology (GO) cluster analysis. Flow cytometry was used to detect apoptosis in MTA1-overexpressed HeLa cells and control cells before and after 10 Gy X-ray irradiation. Cloning formation assay and real-time cellular analysis (RTCA) were used to monitor the cell proliferation before and after 2 Gy X-ray irradiation. To dissect the underlying molecular mechanisms of MTA1 affecting the sensitivity of radiotherapy, the proteins encoded by the DEGs were selected to construct a protein-protein interaction network, the expression of γ-H2AX was detected by immunofluorescence assay, and the expression levels of γ-H2AX, ß-CHK2, PARP and cleaved caspase 3 were measured by western blot. Results: By transcriptome sequencing analysis, we obtained 649 DEGs, of which 402 genes were up-regulated in MTA1 knockdown HeLa cells and 247 genes were down-regulated. GSEA results showed that DEGs associated with MTA1 were significantly enriched in cellular responses to DNA damage repair processes. The results of flow cytometry showed that the apoptosis rate of MTA1 over-expression group (15.67±0.81)% after 10 Gy X-ray irradiation was significantly lower than that of the control group [(40.27±2.73)%, P<0.001]. After 2 Gy X-ray irradiation, the proliferation capacity of HeLa cells overexpressing MTA1 was higher than that of control cells (P=0.024). The numbers of colon in MTA1 over-expression group before and after 2 Gy X-ray irradiation were (176±7) and (137±7) respectively, higher than (134±4) and (75±4) in control HeLa cells (P<0.05). The results of immunofluorescence assay showed that there was no significant expression of γ-H2AX in MTA1 overexpressed and control HeLa cells without X-ray irradiation. Western blot results showed that the expression level of ß-CHK2 in MTA1-overexpressing HeLa cells (1.04±0.06) was higher than that in control HeLa cells (0.58±0.25, P=0.036) after 10 Gy X-ray irradiation. The expression levels of γ-H2AX, PARP, and cleaved caspase 3 were 0.52±0.13, 0.52±0.22, and 0.63±0.18, respectively, in HeLa cells overexpressing MTA1, which were lower than 0.87±0.06, 0.78±0.12 and 0.90±0.12 in control cells (P>0.05). Conclusions: This study showed that MTA1 is significantly associated with radiosensitivity in cervical cancer HeLa cells. MTA1 over-expression obviously reduces the sensitivity of cervical cancer cells to X-ray irradiation. Mechanism studies initially indicate that MTA1 reduces the radiosensitivity of cervical cancer cells by inhibiting cleaved caspase 3 to suppress apoptosis and increasing ß-CHK2 to promote DNA repair.

[Value of tumor growth rate in evaluating the early therapeutic efficacy of neuroendocrine neoplasm].

Objective: To determinate the value of tumor growth rate (TGR) in evaluating the efficacy of early drug treatment for neuroendocrine neoplasm (NEN). Methods: Patients with NEN who treated at Chinese Academy of Medical Sciences Cancer Hospital from January 2010 to December 2018 were retrospectively enrolled. A total of 30 patients (16 males and 14 females, aged from 26 to 73 (53±11) years) were enrolled. The sum of largest diameter of target lesions and the interval time were measured, TGR of 3 months after the first treatment was calculated using a formula. Intraclass correlation coefficient (ICC) were used to test the repeatability of TGR. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal cut-off values of TGR for predicting progression-free survival (PFS). Overall patients and SD patients assessed by RECIST were grouped by the optimal cut-off values of TGR. Kaplan-Meier method was used to estimate PFS rates and plot patient survival curves of patients at different group of TGR. Cox risk proportional hazard model was used to assess the effect of TGR on the prognosis. Results: The optimal cut-off value of TGR was -5.8(%/m), the area under the curve was 0.921 (95%CI: 0.824-0.999, P<0.001). Interobserver ICC was 0.955 (95%CI: 0.907-0.978,P<0.001). Multivariate Cox analysis showed that compared with the patients with TGR<-5.8, the patients with TGR ≥-5.8 had a higher risk of progression in either overall population (HR: 10.906, 95%CI: 1.953-60.898, P=0.006) or the SD population (HR: 14.354, 95%CI: 1.602-128.627, P=0.017); TGR ≥-5.8 was an independent risk factor affecting the prognosis of NEN. Conclusions: TGR can evaluate the efficacy of NEN's early anti-tumor drug treatment, and associate with prognosis.

[Clinical characteristics of human adenovirus infection in hospitalized children with acute respiratory infection in Beijing].

Objective: To compare the clinical characteristics of different types of human adenovirus (HAdV) infection in hospitalized children with acute respiratory infection in Beijing, and to clarify the clinical necessity of adenovirus typing. Methods: In a cross-sectional study, 9 022 respiratory tract specimens collected from hospitalized children with acute respiratory infection from November 2017 to October 2019 in Affiliated Children's Hospital, Capital Institute of Pediatrics were screened for HAdV by direct immunofluorescence (DFA) and (or) nucleic acid detection. Then the Penton base, Hexon and Fiber gene of HAdV were amplified from HAdV positive specimens to confirm their HAdV types by phylogenetic tree construction. Clinical data such as laboratory results and imaging data were analyzed for children with predominate type HAdV infection using t, U, or χ2 test. Results: There were 392 cases (4.34%) positive for HAdV among 9 022 specimens from hospitalized children with acute respiratory infection. Among those 205 cases who were successfully typed, 131 were male and 74 were female, age of 22.6 (6.7, 52.5) months,102 cases (49.76%) were positive for HAdV-3 and 86 cases (41.95%), HAdV-7, respectively, while 17 cases were confirmed as HAdV-1, 2, 4, 6, 14 or 21. In comparison of clinical characteristics between the predominate HAdV type 7 and 3 infection, significant differences were shown in proportions of children with wheezing (10 cases (11.63%) vs. 25 cases (24.51%)), white blood cell count >15 ×109/L (4 cases (4.65%) vs.14 cases (13.73%)), white blood cell count <5×109/L (26 cases (30.23%) vs.11 cases (10.78%)), procalcitonin level>0.5 mg/L (43 cases (50.00%) vs. 29 cases (28.43%)), multilobar infiltration (45 cases (52.33%) vs.38 cases (37.25%)), pleural effusion (23 cases (26.74%) vs. 10 cases (9.80%)), and severe adenovirus pneumonia (7 cases (8.14%) vs. 2 cases (1.96%)) with χ²=5.11, 4.44, 11.16, 9.19, 4.30, 9.25, 3.91 and P=0.024, 0.035, 0.001, 0.002, 0.038, 0.002, 0.048, respectively, and also in length of hospital stay (11 (8, 15) vs. 7 (5, 13) d, Z=3.73, P<0.001). Conclusions: HAdV-3 and 7 were the predominate types of HAdV infection in hospitalized children with acute respiratory tract infection in Beijing. Compared with HAdV-3 infection, HAdV-7 infection caused more obvious inflammatory reaction, more severe pulmonary symptoms, longer length of hospital stay, suggesting the clinical necessity of further typing of HAdVs.

[Clinical characteristics of children infected with different subtypes/genotypes of human respiratory syncytial virus in Beijing from 2009 to 2017].

Objective: To explore the different clinical characteristics of children infected with different subtype/genotype of human respiratory syncytial virus (HRSV) in Beijing. Methods: Respiratory specimens for positive HRSV were randomly collected from children with acute respiratory tract infection (ARTI) in the epidemic season of HRSV from November of each year to January of the next year during 2009 and 2017. G genes of HRSV were amplified and sequenced for subtyping and genotyping by bioinformatics analysis. Clinical data were collected and analyzed. Results: Out of 590 children, 376 (63.7%) with subtype A, and 214 (36.3) with subtype B. The annual dominant subtypes of HRSV from 2009 to 2017 were B-A-A-B-AB-A-A-B-A, respectively, whilst a total of 10 genotypes were detected with 95.8% assigned to genotype ON1 and NA1 of subtype A, and genotype BA9 of subtype B. Children infected with subtype B (96 cases, 44.9%) were more likely aged 0-3 month old than those with subtype A (118 cases, 31.4%) (P=0.001), and more likely to be admitted to Intensive Care Unit(ICU) ((124 cases, 57.9%) than those with subtype A (172 cases, 45.7%)) (P=0.005). Statistical significance were shown among children infected with genotype ON1, NA1 or BA9, in the possibility of infection in children aged 0-3 month (P=0.003), proportion of admission into ICU (P=0.007), length of stay in hospital (P=0.001), and clinical outcome (P=0.001), respectively. Conclusion: Children infected with different subtype or genotype of HRSV have different clinical characteristics, which stresses the important role of the monitoring HRSV subtypes and genotypes among children.

LncRNA ZEB2-AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR-574-3p/HMGA2 axis.

The article "LncRNA ZEB2-AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR-574-3p/HMGA2 axis, by J.-H. Xu, R.-Z. Chen, L.-Y. Liu, X.-M. Li, C.-P. Wu, Y.-T. Zhou, J.-D. Yan, Z.-Y. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (10): 5391-5403-DOI: 10.26355/eurrev_202005_21323-PMID: 32495874" has been withdrawn from the authors due to some technical reasons. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21323.

[Investigation of pathogenic agents causing acute respiratory tract infections in pediatric patients in a children's hospital assigned for case screening in Beijing during the outbreak of COVID-19].

Objective: To investigate the spectrum of pathogenic agents in pediatric patients with acute respiratory infections (ARI) during the outbreak of coronavirus infectious diseases 2019 (COVID-19). Methods: Three groups of children were enrolled into the prospective study during January 20 to February 20, 2020 from Capital Institute of Pediatrics, including children in the exposed group with ARI and epidemiological history associated with COVID-19 from whom both pharyngeal and nasopharyngeal swabs were collected, children in the ARI group without COVID-19 associated epidemiological history and children in the screening group for hospital admission, with neither COVID-19 associated epidemiological history nor ARI. Only nasopharyngeal swabs were collected in the ARI group and screening group. Each group is expected to include at least 30 cases. All specimens were tested for 2019-nCoV nucleic acid by two diagnostic kits from different manufacturers. All nasopharyngeal swabs were tested for multiple respiratory pathogens, whilst the results from the ARI group were compared with that in the correspondence periods of 2019 and 2018 used by t or χ(2) test. Results: A total of 244 children were enrolled into three groups, including 139 males and 105 females, the age was (5±4) years. The test of 2019-nCoV nucleic acid were negative in all children, and high positive rates of pathogens were detected in exposed (69.4%, 25/36) and ARI (55.3%, 73/132) groups, with the highest positive rate for mycoplasma pneumoniae (MP) (19.4%, 7/36 and 17.4%, 23/132, respectively), followed by human metapneumovirus (hMPV) (16.7%, 6/36 and 9.8%, 13/132, respectively). The positive rate (11.8%, 9/76) of pathogens in the screening group was low. In the same period of 2019, the positive rate of pathogens was 83.7% (77/92), with the highest rates for respiratory syncytial virus (RSV) A (29.3%, 27/92), followed by influenza virus (Flu) A (H1N1) (19.6%, 18/92) and adenovirus (ADV) (14.1%, 13/92), which showed significant difference with the positive rates of the three viruses in 2020 (RSV A: χ(2)=27.346, P<0.01; FluA (H1N1): χ(2)=28.083, P<0.01; ADV: χ(2)=7.848, P=0.005) . In 2018, the positive rate of pathogens was 61.0% (50/82), with the highest rate for human bocavirus (HBoV) (13.4%, 11/82) and followed by ADV (11.0%, 9/82), and significant difference was shown in the positive rate of HBoV with that in 2020 (χ(2)=6.776, P=0.009). Conclusions: The infection rate of 2019-nCoV is low among children in Beijing with no family clustering or no close contact, even with epidemiological history. The spectrum of pathogens of ARI in children during the research period is quite different from that in the previous years when the viral infections were dominant. MP is the highest positively detected one among the main pathogens during the outbreak of COVID-19 in Beijing where there is no main outbreak area.

LncRNA ZEB2-AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR-574-3p/HMGA2 axis.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a common malignant epithelial tumor in the elderly, and the cause is very complicated. Therefore, the study of the pathogenesis of ESCC is conducive to the effective treatment of ESCC. Many studies indicated that lncRNAs were important regulatory factors in tumor formation and disease development. However, the regulatory network of lncRNA in ESCC has not been fully explored. MATERIALS AND METHODS: The expression of miR-574-3p, ZEB2-AS1, and HMGA2 was measured using qRT-PCR. The protein expression of PCNA, Cleaved-caspase3, MMP9, and HMGA2 was detected through Western blot. Cell proliferation or apoptosis of transfected cells was calculated via CKK-8 assay or flow cytometry. Transwell assay was applied to detect cell migration and invasion of ESCC cells. Luciferase reporter assay and RNA pull-down were used to determine the relationship among miR-574-3p, ZEB2-AS1, and HMGA2 in ESCC. Moreover, the regulatory network of ZEB2-AS1 has been verified in vivo in this study. RESULTS: We found that ZEB2-AS1 was upregulated in ESCC tissues and cells. The knockdown of ZEB2-AS1 could inhibit cell proliferation, invasion, and migration, as well as promoted cell apoptosis in ESCC. Interestingly, miR-574-3p deficiency or HMGA2 promotion could reverse the effects of si-ZEB2-AS1 on ESCC cell progression. Luciferase reporter assay indicated that miR-574-3p was a target miRNA of ZEB2-AS1 and HMGA2 was a target gene of miR-574-3p in ESCC. CONCLUSIONS: In this paper, we first verified the novel regulatory mechanism of lncRNA ZEB2-AS1 in ESCC cellular process. LncRNA ZEB2-AS1 promoted the proliferation, migration, and invasion of ESCC by modulating miR-574-3p/HMGA2 axis, indicating that ZEB2-AS1 played essential roles in cell progression in ESCC and providing a new therapeutic target of ESCC.

Quantitative analysis of multiple elements in healthy and remodeled epithelium from human upper airway mucosa using nuclear microscopy.

Elements are vital in airway mucosal physiology and pathology, but their distribution and levels in the mucosa remain unclear. This study uses the state-of-the-art nuclear microscopy facility to map and quantify multiple elements in the histology sections of nasal mucosa from patients with nasal polyps or inverted papilloma. Our results demonstrate that P and Ca are the most abundant elements in mucosa and their distinct difference between epithelial and subepithelial regions; more importantly, our results reveal decreased amounts of Cu and Zn in the remodeled epithelium as compared to the normal epithelium. These findings suggest that Cu and Zn may be beneficial targets to regulate aberrant epithelial remodeling in airway inflammation.

The polymorphism of XRCC1 and coronary artery disease risk: a meta-analysis.

OBJECTIVE: Coronary artery disease (CAD) is a life-threatening disease and is caused by various factors, with genetic variation being an important risk factor. The association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and CAD has been extensively studied with conflicting results. We performed a meta-analysis to investigate the overall association between XRCC1 polymorphisms and CAD risk. MATERIALS AND METHODS: We searched PubMed and Embase databases until October 19, 2016. The total number and distribution of genotypes, genotyping methods, and ethnicity were extracted. Overall and subgroup analyses were performed. RESULTS: A total of seven publications involving 1.862 subjects and 1.568 controls were included in this meta-analysis. The Arg399Gln and Arg194Trp polymorphisms of XRCC1 were analyzed. The results indicated that the XRCC1 Arg399Gln homozygous GG genotype showed no association with CAD risk [GG vs. GA+AA: odd's ratio (OR) = 0.95, 95% confidence interval (CI) = 0.82-1.11, p = 0.53] both in the overall and subgroups evaluation. However, the XRCC1 Arg194Trp homozygous TT genotype was associated with an increased CAD risk [(TT vs. TC+CC: OR =1.52, 95%CI = 1.16-2.00, p=0.003)]. Subgroup analysis based on ethnicity showed a significant increase in the association of CAD risk and the Arg194Trp gene polymorphism among the Asian population. CONCLUSIONS: This meta-analysis suggested that TT genotype in the Arg194Trp polymorphism contributes to the CAD susceptibility, particularly in the Asian population.

Identification of odorant-binding protein genes in Galeruca daurica (Coleoptera: Chrysomelidae) and analysis of their expression profiles.

Odorant-binding proteins (OBPs) play a fundamental role in insect olfaction. In recent years, Galeruca daurica (Joannis) (Coleoptera: Chrysomelidae) has become one of the most important insect pests in the Inner Mongolian grasslands of China. This pest only feeds on the species of Allium plants, implying the central role of olfaction in its search for specific host plants. However, the olfaction-related proteins have not been investigated in this beetle. In this study, we identified 29 putative OBP genes, namely GdauOBP1-29, from the transcriptome database of G. daurica assembled in our laboratory by using RNA-Seq. All 29 genes had the full-length open reading frames except GdauOBP29, encoding proteins in length from 119 to 202 amino acids with their predicted molecular weights from 12 to 22 kDa with isoelectric points from 3.88 to 8.84. Predicted signal peptides consisting of 15-22 amino acid residues were found in all except GdauOBP6, GdauOBP13 and GdauOBP29. The amino acid sequence identity between the 29 OBPs ranged 8.33-71.83%. GdauOBP1-12 belongs to the Classic OBPs, while the others belong with the Minus-C OBPs. Phylogenetic analysis indicated that GdauOBPs are the closest to CbowOBPs from Colaphellus bowringi. RT-PCR and qRT-PCR analyses showed that all GdauOBPs were expressed in adult antennae, 11 of which with significant differences in their expression levels between males and females. Most GdauOBPs were also expressed in adult heads (without antennae), thoraxes, abdomens, legs and wings. Moreover, the expression levels of the GdauOBPs varied during the different development stages of G. daurica with most GdauOBPs expressed highly in the adult antennae but scarcely in eggs and pupae. These results provide insights for further research on the molecular mechanisms of chemical communications in G. daurica.

Effects of Candidatus Liberibacter asiaticus on the fitness of the vector Diaphorina citri.

AIMS: The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama transmits the bacterium 'Candidatus Liberibacter asiaticus' (Las), which causes citrus huanglongbing (HLB) disease. Although many studies have been conducted on the biology of ACP on different host plants, few have taken the plant, Las bacteria and the vector insect within one context to evaluate the effects of Las on the fitness of ACP under field conditions. Understanding the relationship between Las and ACP is critical for both ACP and HLB disease management. METHODS AND RESULTS: We estimated the development and survival of ACP immatures, the longevity and fecundity of ACP female adults in four treatments (Las-positive or -negative ACP on Las-infected and -free citrus plants). Las-positive ACP immatures developed significantly faster on Las-infected citrus than those on Las-free plants. The fecundity and longevity of Las-positive female adults were also greater, or longer on Las-infected citrus shoots, whereas the survival of Las-positive immatures was significantly lower on Las-infected citrus shoots, compared to those that developed on Las-free plants. Similarly, the intrinsic rate of population increase (rm ) was highest (0·1404) when Las-positive ACP fed on Las-infected citrus shoots and the lowest (0·1328) when the Las-negative ACP fed on Las-free citrus shoots. CONCLUSIONS: Both the Las infection in ACP and citrus plants had obvious effects on the biology of ACP. When compared to the Las infection in ACP insects, the Las infection in citrus shoots had a more significant effect on the fitness of ACP. SIGNIFICANCE AND IMPACT OF THE STUDY: To efficiently prevent the occurrence and spread of HLB disease, it is critical to understand the ecological basis of vector outbreaks and disease incidence, especially under field conditions. Thus, this study has increased our understanding of the epidemiology of HLB transmitted by psyllids in nature.

Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1? expression

Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T0), 1 h (T1), 3 h (T3), 6 h (T6), 12 h (T12), and 24 h (T24). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T0-T24), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.

Putative role of ischemic postconditioning in a rat model of limb ischemia and reperfusion: involvement of hypoxia-inducible factor-1α expression.

Hypoxia-inducible factor-1α (HIF-1α) is one of the most potent angiogenic growth factors. It improves angiogenesis and tissue perfusion in ischemic skeletal muscle. In the present study, we tested the hypothesis that ischemic postconditioning is effective for salvaging ischemic skeletal muscle resulting from limb ischemia-reperfusion injury, and that the mechanism involves expression of HIF-1α. Wistar rats were randomly divided into three groups (n=36 each): sham-operated (group S), hindlimb ischemia-reperfusion (group IR), and ischemic postconditioning (group IPO). Each group was divided into subgroups (n=6) according to reperfusion time: immediate (0 h, T0), 1 h (T1), 3 h (T3), 6 h (T6), 12 h (T12), and 24 h (T24). In the IPO group, three cycles of 30-s reperfusion and 30-s femoral aortic reocclusion were carried out before reperfusion. At all reperfusion times (T0-T24), serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, as well as interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α) concentrations, were measured in rats after they were killed. Histological and immunohistochemical methods were used to assess the skeletal muscle damage and HIF-1α expression in skeletal muscle ischemia. In groups IR and IPO, serum LDH and CK activities and TNF-α, IL-6, and IL-10 concentrations were all significantly increased compared to group S, and HIF-1α expression was up-regulated (P<0.05 or P<0.01). In group IPO, serum LDH and CK activities and TNF-α and IL-6 concentrations were significantly decreased, IL-10 concentration was increased, HlF-1α expression was down-regulated (P<0.05 or P<0.01), and the pathological changes were reduced compared to group IR. The present study suggests that ischemic postconditioning can reduce skeletal muscle damage caused by limb ischemia-reperfusion and that its mechanisms may be related to the involvement of HlF-1α in the limb ischemia-reperfusion injury-triggered inflammatory response.

Atomic-scale configurations of synchroshear-induced deformation twins in the ionic MnS crystal.

Deformation twinning was thought as impossible in ionic compounds with rock-salt structure due to the charge effect on {111} planes. Here we report the presence and formation mechanism of deformation {111} twins in the rock-salt manganese sulphide (MnS) inclusions embedded in a hot-rolled stainless steel. Based on the atomic-scale mapping under aberration-corrected scanning transmission electron microscopy, a dislocation-based mechanism involved two synchronized shear on adjacent atomic layers is proposed to describe the dislocation glide and consequently twinning formation. First-principles calculations of the energy barriers for twinning formation in MnS and comparing with that of PbS and MgO indicate the distinct dislocation glide scheme and deformation behaviors for the rock-salt compounds with different ionicities. This study may improve our understanding of the deformation mechanisms of rock-salt crystals and other ionic compounds.

Atomic-scale decoration for improving the pitting corrosion resistance of austenitic stainless steels.

Stainless steels are susceptible to the localized pitting corrosion that leads to a huge loss to our society. Studies in the past decades confirmed that the pitting events generally originate from the local dissolution in MnS inclusions which are more or less ubiquitous in stainless steels. Although a recent study indicated that endogenous MnCr2O4 nano-octahedra within the MnS medium give rise to local nano-galvanic cells which are responsible for the preferential dissolution of MnS, effective solutions of restraining the cells from viewpoint of electrochemistry are being tantalizingly searched. Here we report such a galvanic corrosion can be greatly resisted via bathing the steels in Cu(2+)-containing solutions. This chemical bath generates Cu(2-δ)S layers on the surfaces of MnS inclusions, invalidating the nano-galvanic cells. Our study provides a low-cost approach via an atomic scale decoration to improve the pitting corrosion resistance of stainless steels in a volume-treated manner.

Sulforaphane enhances the activity of the Nrf2-ARE pathway and attenuates inflammation in OxyHb-induced rat vascular smooth muscle cells.

AIM: A growing body of evidence indicates that the nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) pathway plays a protective role in many physiological stress processes such as inflammatory damage, oxidative stress, and the accumulation of toxic metabolites, which are all involved in the cerebral vasospasm following subarachnoid hemorrhage (SAH). We hypothesized that the Nrf2-ARE pathway might have a protective role in cerebral vasospasm following SAH. MATERIALS AND METHODS: In our study, we investigate whether the oxyhemoglobin (OxyHb) can induce the activation of the Nrf2-ARE pathway in vascular smooth muscle cells (VSMCs), and evaluate the modulatory effects of sulforaphane (SUL) on OxyHb-induced inflammation in VSMCs. RESULTS: As a result, both the protein level and the mRNA level of the nuclear Nrf2 were significantly increased, while the mRNA levels of two Nrf2-regulated gene products, both heme oxygenase-1 and NAD(P)H: quinone oxidoreductase-1, were also up-regulated in VSMCs induced with OxyHb. A marked increase of inflammatory cytokines such as IL-1ß, IL-6 and TNF-α release was observed at 48 h after cells were treated with OxyHb. SUL enhanced the activity of the Nrf2-ARE pathway and suppressed cytokine release. CONCLUSIONS: Our results indicate that the Nrf2-ARE pathway was activated in OxyHb-induced VSMCs. SUL suppressed cytokine release via the activation of the Nrf2-ARE pathway in OxyHb-induced VSMCs.

Local decomposition induced by dislocation motions inside precipitates in an Al-alloy.

Dislocations in crystals are linear crystallographic defects, which move in lattice when crystals are plastically deformed. Motion of a partial dislocation may remove or create stacking fault characterized with a partial of a lattice translation vector. Here we report that motion of partial dislocations inside an intermetallic compound result in a local composition deviation from its stoichiometric ratio, which cannot be depicted with any vectors of the primary crystal. Along dislocation slip bands inside the deformed Al(2)Cu particles, redistribution of Cu and Al atoms leads to a local decomposition and collapse of the original crystal structure. This finding demonstrates that dislocation slip may induce destabilization in complex compounds, which is fundamentally different from that in monometallic crystals. This phenomenon of chemical unmixing of initially homogeneous multicomponent solids induced by dislocation motion might also have important implications for understanding the geologic evolvement of deep-focus peridotites in the Earth.

Analyses of the floral organ morphogenesis and the differentially expressed genes of an apetalous flower mutant in Brassica napus.

The floral organ morphogenesis of the apetalous flower mutant Apet33-10 in Brassica napus was investigated and the result showed that all the floral organ morphogenesis was normal except that petal primordium was not observed during flower development. Eighteen genes were found to be down regulated in early floral buds (less than 200 mum in length) of Apet33-10 at the stage of floral organ initiation by means of suppressive subtraction hybridization (SSH) and RT-PCR. These genes were involved in petal identity, calcium iron signal transduction, mRNA processing, protein synthesis and degradation, construction of cytoskeleton, hydrogen transportation, nucleic acid binding, alkaloid biosynthesis and unknown function. Three overall coding region cDNAs of APETALA3 (AP3) gene, BnAP3-2, BnAP3-3 and BnAP3-4 were obtained by RT-PCR, respectively. Real-time quantitative PCR analysis showed that the expression ratio among BnAP3-2, BnAP3-3 and BnAP3-4 was 3.67:3.68:1 in early floral buds of wild type Pet33-10. The expression level of BnAP3-2, BnAP3-3 and BnAP3-4 in early floral buds of Apet33-10 was down-regulated to 36.6, 28.3 and 66.8% with the comparison of that of wild type, respectively, and the overall expression level of AP3 genes in apetalous mutant amounted to 45.0% of that in wild type. The difference in the expression level of each AP3 gene in stamen between apetalous and wild type lines was not significant. It is suggested that lower abundant expression of AP3 genes during the early flower development might be enough for stamen primordium initiation, but not enough for petal primordium initiation in the apetalous line Apet33-10.

BNIP-Salpha induces cell rounding and apoptosis by displacing p50RhoGAP and facilitating RhoA activation via its unique motifs in the BNIP-2 and Cdc42GAP homology domain.

Changes in cell morphology are linked to many cellular events including cytokinesis, differentiation, migration and apoptosis. We recently showed that BNIP-Salpha induced cell rounding that leads to apoptosis via its BNIP-2 and Cdc42GAP Homology (BCH) domain, but the underlying mechanism has not been determined. Here, we have identified a unique region (amino acid 133-177) of the BNIP-Salpha BCH domain that targets RhoA, but not Cdc42 or Rac1 and only the dominant-negative form of RhoA could prevent the resultant cell rounding and apoptotic effect. The RhoA-binding region consists of two parts; one region (residues 133-147) that shows some homology to part of the RhoA switch I region and an adjacent sequence (residues 148-177) that resembles the REM class I RhoA-binding motif. The sequence 133-147 is also necessary for its heterophilic interaction with the BCH domain of the Rho GTPase-activating protein, p50RhoGAP/Cdc42GAP. These overlapping motifs allow tripartite competition such that overexpression of BNIP-Salpha could reduce p50RhoGAP binding to RhoA and restore RhoA activation. Furthermore, BNIP-Salpha mutants lacking the RhoA-binding motif completely failed to induce cell rounding and apoptosis. Therefore, via unique binding motifs within its BCH domain, BNIP-Salpha could interact and activate RhoA while preventing its inhibition by p50RhoGAP. This concerted mechanism could allow effective propagation of the RhoA pathway for cell rounding and apoptosis.