[Effect of HCMV infection on immune reconstitution of CD8+T cells in children with allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the risk factors for human cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation in children and the impact of human cytomegalovirus infection on post-transplant immune reconstitution. Methods: A Retrospective Co-Hort study design was used to include 81 children treated with allo-HSCT from January 2020 to March 2022 at the Department of Hematology, Capital Institute of Pediatrics, Beijing, China, and followed up for 1 year. Real-time quantitative PCR was used to detect positive detection of HCMV in children after allo-HSCT, multifactorial logistic regression modeling was used to analyze the risk factors leading to HCMV infection, and generalized estimating equation modeling was used to analyze the effect of HCMV infection on the T-cells of the children who received allo-HSCT. Results: The age M(Q1, Q3) of 81 children was 5.1 years (10 months, 13.8 years), and 50 (61.7%) were male. By the endpoint of follow-up, a total of 50 HCMV-positive cases were detected, with an HCMV detection rate of 61.7%; The results of multifactorial logistic regression modeling showed that children with grade 2-4 aGVHD had a higher risk of HCMV infection compared with grade 0-1 after transplantation [OR (95%CI) value: 2.735 (1.027-7.286)]. The results of generalized estimating equation modeling analysis showed that the number of CD3+T cells in HCMV-positive children after transplantation was higher than that in the HCMV-negative group [RR (95%CI) value: 1.34 (1.008-1.795)]; the ratio of CD4+T/CD8+T cells was smaller than that in the HCMV-negative group [RR (95%CI) value: 0.377 (0.202-0.704)]; the number of CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.435 (1.025-2.061)]; the number of effector memory CD8+T cells was higher than that in the HCMV-negative group [RR (95%CI) value: 1.877 (1.089-3.236)]. Conclusion: Acute graft-versus-host disease may be a risk factor for HCMV infection in children after allo-HSCT; post-transplant HCMV infection promotes proliferation of memory CD8+T-cell populations and affects immune cell reconstitution.

Genistein for glycolipid metabolism in postmenopausal women: a meta-analysis.

OBJECTIVE: This study aimed to evaluate the effects of genistein on glycolipid metabolism in postmenopausal women. METHODS: Electronic databases were searched and relevant reports were hand-screened. We included only randomized controlled trials of isolated genistein for glycolipid metabolism. The primary outcome for lipid metabolism included a changed value of low-density lipoprotein cholesterol (LDL-C), and for glucose metabolism was a changed value of homeostasis model assessment for insulin resistance (HOMA-IR). Secondary outcomes included a changed value of total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), fasting blood insulin (INS), and body mass index (BMI). RESULTS: Ten trials with 11 articles were included. The level of LDL-C was not decreased in the genistein group compared with the placebo group (standardized mean difference [SMD] = -0.58; 95% confidence interval [CI] - 1.19, 0.02; p = 0.06). No statistical significance was found in subgroup analyses. HOMA-IR was obviously improved in the genistein group with SMD of -0.51 (95% CI -0.88, -0.14; p = 0.006). In subgroup analyses, HOMA-IR was improved more in women with BMI <30 kg/m2 and without metabolic disorders (p < 0.0001). For secondary outcomes, there were significant differences in total cholesterol, HDL-C, FBG, and INS, but not triglyceride or BMI. CONCLUSIONS: Genistein was effective in ameliorating glycolipid metabolism by increasing HDL-C levels and decreasing total cholesterol levels and improving insulin sensitivity.

Very high external quantum efficiency and wall-plug efficiency 527 nm InGaN green LEDs by MOCVD.

We demonstrate very high luminous efficacy InGaN-based green light-emitting diodes (LEDs) grown on c-plane patterned sapphire substrates (PSS) using metal organic chemical vapor deposition (MOCVD). The 527 nm green LEDs show a peak external quantum efficiency (EQE) of 53.3%, a peak wall-plug efficiency (WPE) of 54.1% and a peak luminous efficacy of 329 lm/W, respectively. A high EQE of 38.4%, a WPE of 32.1% and a very low forward voltage of 2.86 V were obtained at a typical working current density of 20 A/cm2. By operating low cost green LEDs at a low current density, our devices (0.5 mm2) demonstrating an EQE and a WPE higher than 50% and an efficacy of 259 lm/W at 4 A/cm2 with an output power of 24 mW. High crystal quality of the InGaN/GaN MQWs was characterized by X-ray diffraction (XRD) and the advantage of the epitaxy design was investigated by APSYS software simulation. These results provide a simple way to achieve very high efficiency InGaN green LEDs.

Optically pumped lasing with a Q-factor exceeding 6000 from wet-etched GaN micro-pyramids.

We report the observation of room-temperature optically pumped lasing modes from a single GaN pyramid microcavity on a metallic mirror. The mode at 367.2 nm exhibits a low threshold (0.4-0.5 MW/cm2) and a narrow linewidth (0.054 nm), by which the quality factor can be estimated to be >6000. These lasing behaviors can be attributed to the specific wet-etching approach by selectively etching away defects and pyramid geometry with bottom Ag reflectors for better light confinement. Optical resonances in these pyramids are further investigated in combination with three-dimensional finite-difference time-domain simulations.

Diagnostic performance of microRNA-29a for colorectal cancer: a meta-analysis.

Previous studies have revealed that the expression level of microRNA-29a (miR-29a) was remarkably different in colorectal cancer (CRC) patients and healthy controls, indicating that miR-29a can be used as a diagnostic marker of CRC, but the results have been inconsistent. We conducted this meta-analysis to assess the diagnostic performance of blood-based miR-29a for CRC. We performed a systematic review of studies published over the past two decades to investigate the diagnostic performance of serum miR-29a for the diagnosis of CRC. QUADAS-2 was used to evaluate the quality of the studies. Performance characteristics (diagnostic sensitivity, specificity, and other measures of accuracy) were pooled and examined using random-effect models. Five studies, which included 281 CRC patients and 299 healthy controls, met the inclusion criteria. The summary estimates for miR-29a in CRC diagnoses showed a diagnostic sensitivity of 0.59 (95%CI = 0.53-0.65), a specificity of 0.89 (95%CI = 0.85-0.93), and a diagnostic odds ratio of 12.22 (95%CI = 5.07-29.44). The area under curve and Q value for the summary receiver operating characteristic curves were 0.9128 and 0.8453, respectively. In conclusion, miR-29a may be a novel potential biomarker for CRC diagnosis.

Interaction between ALOX5AP-SG13S114A/T and COX-2-765G/C increases susceptibility to cerebral infarction in a Chinese population.

We made a case-control study to investigate a possible association between ALOX5AP-SG13S114A/T, COX-2-765G/C, and COX-1-50C/T polymorphisms with cerebral infarction in a Chinese population. A total of 411 cases with cerebral infarction were included; 411 controls matched for age, gender, and risk factors were also selected. The ALOX5AP-SG13S114A/T (rs10507391), COX-2-765G/C (rs20417), and COX-1-50C/T (rs3842787) polymorphisms were determined using PCR-RFLP. The generalized multifactor dimensionality reduction method was employed to detect gene-gene interactions. Based on single-gene analysis, there were no significant differences in the genotype and allele frequency distributions of ALOX5AP-SG13S114A/T, COX-2-765G/C, and COX-1-50C/T between the cerebral infarction group and controls. However, in those cases carrying ALOX5AP-SG13S114AA as well as COX-2-765CC, the risk of cerebral infarction increased significantly by 2.84 times (95%CI = 1.324-6.543). The single-gene ALOX5AP-SG13S114A/T, COX-2-765G/C, and COX-1-50C/T polymorphisms appear not to be associated with the development of cerebral infarction in Chinese populations. However, the interaction between ALOX5AP-SG13S114AA and COX-2-765CC apparently increases susceptibility to cerebral infarction.

Predictive role of admission serum glucose, baseline NIHSS score, and fibrinogen on hemorrhagic transformation after intravenous thrombolysis with alteplase in acute ischemic stroke.

OBJECTIVE: This study aimed to investigate the predictive role of admission serum glucose, baseline NIHSS score, and fibrinogen on hemorrhagic transformation after intravenous thrombolysis with alteplase in acute ischemic stroke. PATIENTS AND METHODS: A total of 254 patients admitted with acute ischemic stroke who received intravenous thrombolysis with alteplase from January 2016 to December 2017 were selected to collect clinical data. Patients were divided into a hemorrhagic transformation group (n=70) and a no-hemorrhagic transformation group (n=184) based on repeat CT/magnetic resonance imaging (MRI) findings during the acute period. The demographic data, past medical history and laboratory examination indexes of the two groups were compared. Multivariate Logistic regression analysis was used to explore the influencing factors of hemorrhage transformation after intravenous thrombolysis in patients with acute ischemic stroke. ROC curve was used to plot the ability of blood glucose at admission, baseline NIHSS score and fibrinogen alone to predict bleeding transformation after intravenous thrombolysis of alteplase, and then the combined model of the three was constructed and the predictive ability of this model to bleeding transformation was evaluated. RESULTS: Among 254 patients, 70% (27.55%) had hemorrhage transformation. Except for DNT, red blood cell count, platelet count, fibrinogen, smoking, atrial fibrillation, baseline NIHSS score and admission serum glucose, there were statistically significant differences between the hemorrhagic transformation group and the non-hemorrhagic transformation group (p<0.05), and there were no statistically significant differences in other indicators between the two groups (p>0.05). The combined model was better than the three models alone in predicting the risk of bleeding conversion (p<0.05). Compared with the group without hemorrhagic transformation, the 90d prognosis was worse in the hemorrhage transformation group (p<0.05). CONCLUSIONS: Admission blood glucose, NIHSS score, and fibrinogen are independent risk factors for hemorrhage transformation after intravenous thrombolysis of alteplase in patients with acute ischemic stroke, and the combined model established by them has high predictive efficacy for hemorrhage transformation risk after intravenous thrombolysis of alteplase.

RGD-independent cell adhesion to the carboxy-terminal heparin-binding fragment of fibronectin involves heparin-dependent and -independent activities.

Cell adhesion to extracellular matrix components such as fibronectin has a complex basis, involving multiple determinants on the molecule that react with discrete cell surface macromolecules. Our previous results have demonstrated that normal and transformed cells adhere and spread on a 33-kD heparin binding fragment that originates from the carboxy-terminal end of particular isoforms (A-chains) of human fibronectin. This fragment promotes melanoma adhesion and spreading in an arginyl-glycyl-aspartyl-serine (RGDS) independent manner, suggesting that cell adhesion to this region of fibronectin is independent of the typical RGD/integrin-mediated binding. Two synthetic peptides from this region of fibronectin were recently identified that bound [3H]heparin in a solid-phase assay and promoted the adhesion and spreading of melanoma cells (McCarthy, J. B., M. K. Chelberg, D. J. Mickelson, and L. T. Furcht. 1988. Biochemistry. 27:1380-1388). The current studies further define the cell adhesion and heparin binding properties of one of these synthetic peptides. This peptide, termed peptide I, has the sequence YEKPGSP-PREVVPRPRPGV and represents residues 1906-1924 of human plasma fibronectin. In addition to promoting RGD-independent melanoma adhesion and spreading in a concentration-dependent manner, this peptide significantly inhibited cell adhesion to the 33-kD fragment or intact fibronectin. Polyclonal antibodies generated against peptide I also significantly inhibited cell adhesion to the peptide, to the 33-kD fragment, but had minimal effect on melanoma adhesion to fibronectin. Anti-peptide I antibodies also partially inhibited [3H]heparin binding to fibronectin, suggesting that peptide I represents a major heparin binding domain on the intact molecule. The cell adhesion activity of another peptide from the 33-kD fragment, termed CS1 (Humphries, M. J., A. Komoriya, S. K. Akiyama, K. Olden, and K. M. Yamada. 1987. J. Biol. Chem., 262:6886-6892) was contrasted with peptide I. Whereas both peptides promoted RGD-independent cell adhesion, peptide CS1 failed to bind heparin, and exogenous peptide CS1 failed to inhibit peptide I-mediated cell adhesion. The results demonstrate a role for distinct heparin-dependent and -independent cell adhesion determinants on the 33-kD fragment, neither of which are related to the RGD-dependent integrin interaction with fibronectin.

Definition of a sequence, RYVVLPR, within laminin peptide F-9 that mediates metastatic fibrosarcoma cell adhesion and spreading.

A synthetic peptide from the inner globule of the B1 chain of laminin, termed peptide F-9 (RYVVLPRPVCFEKGMNYTVR; residues 641-660), has been shown to have heparin-binding and cell adhesion-promoting activities for diverse cell types (Charonis et al., J. Cell. Biol., 107: 1253-1260, 1988). In this study, the metastatic murine fibrosarcoma cell line, UV-2237-MM, adhered and spread on surfaces coated with laminin and peptide F-9 in a concentration- and time-dependent fashion. Cells migrated toward laminin in Boyden microchemotaxis chambers but not toward peptide F-9. However, exogenous soluble peptide F-9 inhibited both the adhesion and migration of cells toward laminin. Polyclonal antibodies raised against peptide F-9 were capable of inhibiting laminin-mediated cell adhesion and migration. Peptide F-9 is located 265 residues from CDPGYIGSR, another sequence on the B1 chain of laminin which has been reported by others to promote cell adhesion (Graft et al., Cell, 48: 989-996, 1987). In contrast to peptide F-9, various control peptides including CDPGYIGSR did not promote the adhesion, spreading, or migration of the UV-2237-MM fibrosarcoma cells. In addition, neither exogenous peptide CDPGYIGSR nor antibodies raised against peptide CDPGYIGSR were capable of inhibiting laminin-mediated cell adhesion or migration. These results indicate that peptide F-9, but not peptide CDPGYIGSR, represents a major fibrosarcoma cell adhesion-promoting domain on intact laminin. A series of overlapping peptides were synthesized which contained various portions of the parent peptide F-9. The use of these peptides in cell adhesion assays demonstrated that the sequence RYVVLPR from the amino terminus of peptide F-9 was essential for cell adhesion-promoting activity.

Dissociation of antibody responses during human schistosomiasis and evidence for enhancement of granuloma size by anti-carbohydrate IgM.

Immunoglobulin (Ig) G and IgM antibody levels to soluble egg antigens (SEA), adult worm glycoproteins (AWGP), carbohydrate antigens (CHO) and cationic exchange fraction 6 (CEF6) were measured in serum specimens taken from Brazilian patients with acute, intestinal, hepato-intestinal and hepatosplenic schistosomiasis mansoni. The antibody levels varied among the groups, with the highest anti-egg antigen responses in the acute patients and the highest anti-adult worm responses in patients with chronic disease. The responses to the component parts of the egg antigens were dissociated, with anti-carbohydrate IgG and IgM responses being highest in the acute infection group and anti-CEF6 IgG responses being uniform among the clinical groups. The possibility of a direct role for anti-CHO antibody responses in egg-induced pathology was investigated using the mouse lung model. The anti-carbohydrate monoclonal antibody NIMP/M45 significantly enhanced granuloma formation. Mice given NIMP/M45 produced granulomas larger than those of naive mice or mice given an unrelated monoclonal antibody, and as large as those produced by mice which had been presensitized to egg antigens. The independent regulation of responses to egg antigens may indicate that such responses are minimized to reduce the pathological consequences of infection whilst allowing the development of protective anti-worm responses.

[Differentiation of schistosome species and strains by DNA hybridization].

Genomic DNA from Schistosoma mansoni and S. japonicum adult worms was hybridized to a 32p-labelled pSM 889 probe after cleavage by restriction endonuclease BglII, BamHI, XbaI and EcoRI, or to a 32p-labelled pSM 389 probe after cleavage by EcoRI. The resulting hybridization banding patterns were significantly different between the two species. Genomic DNA from S. japonicum adult worms of Hunan, Hubei, Jiangxi, Zhejiang and Yunnan isolates was hybridized to a 32p-labelled pSM 389 probe after cleavage by EcoRI. The major hybridization bands were identical while the minor bands were more or less different among the isolates. Of them, isolates Hunan, Hubei and Zhejiang have similar minor bands while isolates Jiangxi and Yunnan have minor bands significantly different from those of the above three isolates and also markedly distinct from those of each other. These results indicate that the major hybridization banding patterns are unique to schistosome species while the minor banding patterns may serve as the basis for strain differentiation.

[Immunity against Schistosoma japonicum induced by phage display peptides mimicking antigenic epitopes of Trichinella spiralis].

OBJECTIVE: To obtain the short peptides mimicking antigenic epitopes of Trichinella spiralis (T. s.), and explore their cross protective immunity against Schistosoma japonicum (S.j.) in mice. METHODS: IgG antibodies were purified from sera of mice infected with T.s.. The purified IgG was used to immunoscreen a phage random peptide library of 7 amino-acid residues displayed as a fusion to protein of filamentous phage. Positive clones were obtained by affinity selection, the reactivity of each clone binding to specific IgG was detected by ELISA. Kunming mice were immunized subcutaneously three times with mixed phage clones. The mice were sacrificed 45 days after challenge. The worms and the liver eggs were counted. RESULTS: After three rounds of panning, the relevant phages had been enriched approximately 150 times in production as compared to those from the first round. Of 24 phage clones randomly selected from the third round biopanning, 21 clones were shown to actually bind to the specific IgG. As compared with the control group, the worm and the liver egg reduction rates in vaccination group were 42.8% and 66.3% (P < 0.001), respectively. CONCLUSION: The above results demonstrate that antigenic epitopes of T. s. can be prepared by immunoscreening phage random peptide library and a significant protective immunity against S. j. can be induced by these epitopes in mice.

[Evaluation of Schistosoma japonicum tegumental membrane antigen (SjMAg) in immunodiagnosis and efficacy assessment].

OBJECTIVE: To evaluate the specificity and sensitivity of SjMAg in detecting specific antibodies in sera of patients with schistosomiasis japonica and in assessing therapeutic efficacy. METHODS: SjMAg-ELISA was used to determine the specific IgG and IgG4 in sera of patients with schistosomiasis japonica at different time points after chemotherapy. RESULTS: SjMAg-ELISA was as sensitive and specific as SEA-ELISA. The negative conversion rate of IgG detected by SjMAg-ELISA 12 months after treatment was 80.0%, being significantly higher than 43.3% by SEA-ELISA. The negative conversion rate of IgG4 detected by SjMAg-ELISA 12 months after treatment was 93.3%, being significantly higher than 60.0% by SEA-ELISA. The negative conversion rates of IgG and IgG4 2 yr after treatment were 92.9% and 97.6% respectively. CONCLUSION: SjMAg-ELISA is comparable to SEA-ELISA in diagnosing schistosomiasis japonica and is more effective in assessing therapeutic efficacy.

[Cloning and characterization of three novel genes encoding transmembrane proteins of Schistosoma japonicum].

OBJECTIVE: To clone and analyze novel antigen molecules of Schistosoma japonicum (Sj), and to provide effective vaccine candidate antigens against schistosomiasis japonica. METHODS: Sj adult cDNA library was screened using sera of mice infected with Trichinella spiralis (Ts) and the inserts of positive clones were specifically amplified by PCR. The positive clones were sequenced and the sequence data were analyzed using Nucleotide BLAST software of NCBI and Expert Protein Analysis System of Swiss Institute of Bioinformatics. RESULTS: Nine positive clones were obtained after three rounds of immunoscreening. The size of these inserts ranged from 0.6 kb to 2.1 kb. Among five novel genes, Sj-Ts1, Sj-Ts3 and Sj-Ts5 (GenBank accession number: AY005816, AF299080 and AY024352, respectively) encode trans-membrane proteins with 83, 83 and 233 amino acids, respectively. Sj-Ts1 protein predicted contains one possible trans-membrance helix, one N-myristoylation site, two phosphorylation sites for protein kinase C and one for tyrosine kinase, Sj-Ts3 protein contains two possible transmembrance helices and one casein kinase II phosphorylation site, whereas Sj-Ts5 protein has five possible transmembrance helices, one N-glycosylation site, one N-myristoylation site, two phosphorylation sites for cAMP- and cGMP-dependent protein kinase and four for protein kinase C and one for casein kinase II. CONCLUSION: Three novel genes encoding three transmembrane proteins might be developed as new vaccine candidates against Sj infection.

[Effect of acryl thiourea on liver pathologic changes in mice infected with Schistosoma japonicum].

OBJECTIVE: To observe the effect of acryl thiourea, an inhibitor of phenol oxidase, on pathological changes in the liver of mice infected with Schistosoma japonicum. METHODS: From day 22 to day 42 postinfection with cercariae, the mice of the acryl thiourea group were each injected i.p. with acryl thiourea at a dose of 300 mg/kg every other day. The mice were killed on the 42nd day postinfection to observe the pathological changes in the liver. RESULTS: Compared to the infected control group, the liver tissue of the acryl thiourea group showed scattered foci of inflammatory cell infiltration, the mean diameter and area of the foci were significantly reduced (P < 0.01), and there were no eggs in the center of the foci except for some granules. CONCLUSION: After i.p. injections of acryl thiourea, no typical egg granuloma was found in the liver of infected mice. This was possibly due to the inhibition of schistosome phenol oxidase activity and so the female adult schistosomes could not produce normal eggs.

Construction of an artificial microalgal-bacterial consortium that efficiently degrades crude oil.

Four oil component-degrading bacteria and one oil-tolerant microalgae, Scenedesmus obliquus GH2, were used to construct an artificial microalgal-bacterial consortium for crude-oil degradation. The bacterial strains included Sphingomonas GY2B and Burkholderia cepacia GS3C, along with a mixed culture, named GP3, containing Pseudomonas GP3A and Pandoraea pnomenusa GP3B. GY2B could only degrade polycyclic aromatic hydrocarbons, GS3C was able to degrade aliphatic chain hydrocarbons, and GP3 could utilize both saturated and aromatic hydrocarbons. In combination with unialgal or axenic algae, the bacteria showed different effects on oil degradation. Unialgal GH2 was not suitable for the consortium construction, as it could not cooperate well with GS3C and GP3. The axenic GH2 exhibited no oil-degrading ability; however, it significantly promoted the degradation ability of the oil component-degrading bacteria, especially for degrading biorefractory polycyclic aromatic hydrocarbons. Axenic S. obliquus GH2, combined with the four bacteria mentioned above, formed an optimal algal-bacterial consortium. The artificial consortium demonstrated an elevated efficiency in degrading both aliphatic and aromatic hydrocarbons of crude oil.

[Study of depyrogen deactivation of syringes by using 3 efficacious pyrogen deactivator methods].

2% three-efficacious pyrogen deactivator (TEPD) was put into ultrasound washer for syringe washing. A total of 370 syringes were divided into three groups. Each group was washed by using a different program of sterilization, decontamination, and depyrogen. The results showed that the following program was not only effective for depyrogen but also convenient and inexpensive: (1)5 minutes' ultra-washing by using ultrasound washer with TEPD; (2)suspension over 1 hours; (3) another 5 minutes' ultra-washing; (4)ordinary washing and sterilization.

[Experimental study on immunization of mice with nucleic acid vaccine Sj31BIN combining IL-12 against Schistosoma japonicum].

Based on the anti-fecundity effect of Schistosoma japonicum nucleic acid vaccine Sj31BIN, we combined Sj31BIN with IL-12 in vaccination of mice to explore the role of IL-12 as an adjuvant. The result showed that immunization of the mice with Sj31BIN + IL-12 led to a significant decrease in adult worm recovery, a liver egg count reduction of 59.74%, an intestine egg count reduction of 59.60% and a liver surface egg granuloma reduction of 71.3%. In addition, vaccination of the mice with IL-12 alone also led to some but not significant decrease in adult worm recovery and the egg counts. It is concluded that Sj31BIN plus IL-12 induces significant anti-fecundity immunity.