Potential therapeutic strategy for non-Hodgkin lymphoma by anti-CD20scFvFc/CD28/CD3zeta gene tranfected T cells

<p>Abstract</p> <p>Background</p> <p>Anti-CD20 monoclonal antibody treatment has not only increased survival and cure rates in many non-Hodgkin lymphomas, but also has prompted an explosion in the development of novel antibodies and biologically active substances with specific cellular targets in the field of malignancies treatment. Since the robust immune responses are elicited by the gene-modified T cells, gene based T cell therapy may also provide a powerful tool for cancer immunotherapy.</p> <p>Methods</p> <p>In this study, we developed a vector construction encoding a chimeric T cell receptor that recognizes the CD20 antigen and delivers co-stimulatory signals to achieve T cell activation. One non-Hodgkin lymphoma cell line Raji cells co-cultured with peripheral blood-derived T cells were stably transfected with anti-CD20scFvFc/CD28/CD3zeta gene or anti-CD20scFvFc gene. T cells expressing anti-CD20scFvFc/CD28/CD3zeta or anti-CD20scFvFc gene co-cultured with CD20 positive Raji cells for different times. Cell lysis assay was carried by [³H]TdR release assay. The expressions of Fas, Bcl-2 and Caspase-3 of Raji cells were detected by flow cytometric. The secretion of IFN-gamma and IL-2 in co-culture medium was tested by ELISA assay. Activity of AP-1 was analyzed by EMSA.</p> <p>Results</p> <p>Following efficient transduction of peripheral blood-derived T cells with anti-CD20scFvFc/CD28/CD3zeta gene, an obvious cell lysis of Raji cells was observed in co-culture. T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene had superior secretion of IFN-gamma and IL-2 compared to T cells transduced anti-CD20scFvFc gene. Also it led to a much stronger Fas-induced apoptosis signaling transduction in target cancer cells.</p> <p>Conclusion</p> <p>So adoptively T cells transduced anti-CD20scFvFc/CD28/CD3zeta gene mediates enhanced anti-tumor activities against CD20 positive tumor cells, suggesting a potential of gene-based immunotherapy for non-Hodgkin lymphoma.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Data from: The Physiological Basis for Estimating Photosynthesis from Chlorophyll a Fluorescence

Please cite as: Jimei Han, Lianhong Gu, Yongjiang Zhang, Ying Sun. (2022) Data from: The Physiological Basis for Estimating Photosynthesis from Chlorophyll a Fluorescence. [dataset] Cornell University eCommons Repository. https://doi.org/10.7298/q3hb-zq56These files contain data supporting all results reported in Han et. al. The Physiological Basis for Estimating Photosynthesis from Chlorophyll a Fluorescence. In Han et al. we found: The availability of Solar-Induced chlorophyll Fluorescence (SIF) offers potential to curb large uncertainties in estimating photosynthesis across biomes, climates, and scales. However, it remains unclear how SIF should be used to mechanistically estimate photosynthesis. This study built a quantitative framework to estimate photosynthesis, based on a mechanistic light reaction model with chlorophyll a fluorescence from PSII (SIFPSII) as an input (MLR-SIF). Utilizing 29 C3 and C4 plant species representative of major plant biomes across the globe, we verified such a framework at the leaf level. MLR-SIF is capable of accurately reproducing photosynthesis for all C3 and C4 species under diverse light, temperature, and CO2 conditions. We further tested the robustness of MLR-SIF using Monte Carlo simulations, and found that the estimated photosynthesis is much less sensitive to parameter uncertainties relative to the conventional Farquhar, von Caemmerer, Berry (FvCB) model because of additional independent information contained in SIFPSII. SIFPSII, once inferred from direct observables of SIF, provides “parameter savings” to the MLR-SIF as compared to the mechanistically equivalent FvCB and thus shortcuts the uncertainties propagated from imperfect model parameterization. Our findings set the stage for future efforts employing SIF mechanistically to improve photosynthesis estimation across scales, functional groups, and environmental conditions.This work was supported in part through NSF Macrosystem Biology to YS, Grant #:1926488; USDA-NIFA Hatch Award to YS, Grant #: 1014740; NASA MEaSures project to YS; USDA-NIFA and Agriculture Hatch Fund to YZ, Grant #: ME022021; This research is also supported by the US Department of Energy (DOE), Office of Science, Biological and Environmental Research Program. ORNL is managed by UT-Battelle, LLC, for DOE under contract DE-AC05-00OR22725

Effect of liver abnormalities on mortality in Fontan patients: a systematic review and meta-analysis

Abstract Background Fontan-associated liver disease (FALD) is one of the most common complications following Fontan procedure, but the impact of FALD on survival outcomes remains controversial. The aim of this systematic review and meta-analysis was to examine and quantify the influence of liver disease on the survival of Fontan patients. Methods The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed, and relevant human studies published from inception up to 12 August 2022 were searched. Stata (version 17.0) was applied to perform the meta-analysis, using random effects (Mantel-Haenszel) models. The I 2 statistic was used to assess the heterogeneity. Subgroup analysis and meta-regression were employed to explore the potential sources of heterogeneity and sensitivity analysis was performed to determine the potential influence of each study on the overall pooled results. Results A total of 312 records were initially identified and 8 studies involving 2,466 patients were selected for inclusion. Results revealed a significant association between the severity of liver disease following Fontan procedure and mortality, which was confirmed by sensitivity analysis and subgroup analysis assessing post-HT mortality. Meta-regression showed that diagnostic methods for liver disease may be a source of heterogeneity. After removal of the FALD patients identified by international classification of disease codes, heterogeneity was markedly reduced, and the positive association between all-cause mortality and the severity of liver disease became significant. Conclusions This meta-analysis showed the severity of liver disease following the Fontan procedure has a significant association with mortality. Lifelong follow-up is necessary and imaging examinations are recommended for routine surveillance of liver disease. Among patients with failing Fontan and advanced liver disease, combined heart-liver transplantation may provide additional survival benefits

Right ventricular dilatation score: a new assessment to right ventricular dilatation in adult patients with repaired tetralogy of Fallot

Abstract Background Patients with repaired tetralogy of Fallot (rTOF) experience long-term chronic pulmonary valve regurgitation resulting in right ventricular (RV) dilatation. According to current guidelines, the evaluation of patients with rTOF for RV dilatation should be based on cardiac magnetic resonance (CMR). However, for many asymptomatic patients, routine CMR is not practical. Our study aims to identify screening methods for CMR based on echocardiographic data, with the goal of establishing a more practical and cheap method of screening for severity of RV dilatation in patients with asymptomatic rTOF. Methods Thirty two rTOF patients (mean age, 21(10.5) y, 21 males) with moderate to severe pulmonary regurgitation (PR) were prospectively recruited. Each patient received CMR and echocardiogram examination within 1 month prior to operation and collected clinical data, and then received echocardiogram examination at discharge and 3–6 months post-surgery. Results RV moderate-severe dilatation was defined as right ventricular end-diastolic volume index (RVEDVI) ≥ 160 ml/m2 or right ventricular end-systolic volume index (RVESVI) ≥ 80 ml/m2 in 15 of 32 patients (RVEDVI, 202.15[171.51, 252.56] ml/m2, RVESVI, 111.99 [96.28, 171.74] ml/m2). The other 17 (RVESDI, 130.19 [117.91, 139.35] ml/m2, RVESVI = 67.91 [63.35, 73.11] ml/m2) were defined as right ventricle mild dilatation, i.e., RVEDVI  2.35 were diagnosed with RV moderate-severe dilatation (AUC = 0,882; Sensitivity = 94.1%; Specificity = 77.3%). Conclusions RV moderate-severe dilatation is associated with worse preoperative cardiac function and short-term prognosis after PVR in rTOF patients with moderate to severe PR. The RV dilatation score is an effective screening method. When RV dilatation score > 2.35, the patient is indicated for further CMR examination and treatment

Granal thylakoid structure and function: Explaining an enduring mystery of higher plants

In higher plants, photosystems II and I are found in grana stacks and unstacked stroma lamellae, respectively. To connect them, electron carriers negotiate tortuous multi-media paths and are subject to macromolecular blocking. Why does evolution select an apparently unnecessary, inefficient bipartition? Here we systematically explain this perplexing phenomenon. We propose that grana stacks, acting like bellows in accordions, increase the degree of ultrastructural control on photosynthesis through thylakoid swelling/shrinking induced by osmotic water fluxes. This control coordinates with variations in stomatal conductance and the turgor of guard cells, which act like an accordion's air button. Thylakoid ultrastructural dynamics regulate macromolecular blocking/collision probability, direct diffusional pathlengths, division of function of Cytochrome  b6 f complex between linear and cyclic electron transport, luminal pH via osmotic water fluxes, and the separation of pH dynamics between granal and lamellar lumens in response to environmental variations. With the two functionally asymmetrical photosystems located distantly from each other, the ultrastructural control, nonphotochemical quenching, and carbon-reaction feedbacks maximally cooperate to balance electron transport with gas exchange, provide homeostasis in fluctuating light environments, and protect photosystems in drought. Grana stacks represent a dry/high irradiance adaptation of photosynthetic machinery to improve fitness in challenging land environments. Our theory unifies many well-known but seemingly unconnected phenomena of thylakoid structure and function in higher plants.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Ventricular Morphology and Outcomes in Fontan Circulation without Hypoplastic Left Heart Syndrome: A Single-Center's Experience

Background: The impact of dominant ventricular morphology on Fontan patient outcomes remain controversial. This study evaluates long-term results of right ventricle (RV) dominance versus left ventricle (LV) dominance in Fontan circulation without hypoplastic left heart syndrome (HLHS). Methods: We retrospectively examined 323 Fontan operations from our center. To minimize pre- and intra-Fontan heterogeneity, 42 dominant RV patients were matched with 42 dominant LV patients using propensity score matching, allowing for a comparative analysis of outcomes between groups. Results: The mean follow-up was 8.0 ± 4.6 years for matched RV dominant and 6.5 ± 4.7 years for matched LV dominant group (p > 0.05), showing no significant difference. The cumulative incidence of moderate or greater atrioventricular valve regurgitation was also comparable between the two groups (p > 0.05). Similarly, 10-year freedom from death or transplantation following the Fontan operation was 84% ± 7% in the matched dominant RV group, similar to 81% ± 7% in the matched dominant LV group (p > 0.05). The 10-year freedom from Fontan failure was 78% ± 8% in the matched dominant RV group, also similar to 75% ± 8% in the matched dominant LV group (p >0.05). Multivariate analysis did not identify RV dominance as a risk factor for Fontan failure (p > 0.05). Conclusions: In the pre- and intra-Fontan context, RV dominance demonstrated similar and comparable long-term outcomes compared to LV dominance in non-HLHS Fontan circulation

Additional file 5 of Right ventricular dilatation score: a new assessment to right ventricular dilatation in adult patients with repaired tetralogy of Fallot

Additional file 5: Table S1. Correlation analysis of echocardiography data and cardiac magnetic resonance data

Validation of transcutaneous bilirubin nomogram for identifying neonatal hyperbilirubinemia in healthy Chinese term and late-preterm infants: a multicenter study

OBJECTIVE:to prospectively validate a previously constructed transcutaneous bilirubin (TcB) nomogram for identifying severe hyperbilirubinemia in healthy Chinese term and late-preterm infants.METHODS:this was a multicenter study that included 9,174 healthy term and late-preterm infants in eight hospitals of China. TcB measurements were performed using a JM-103 bilirubinometer. TcB values were plotted on a previously developed TcB nomogram, to identify the predictive ability for subsequent significant hyperbilirubinemia.RESULTS:in the present study, 972 neonates (10.6%) developed significant hyperbilirubinemia. The 40th percentile of the nomogram could identify all neonates who were at risk of significant hyperbilirubinemia, but with a low positive predictive value (PPV) (18.9%). Of the 453 neonates above the 95th percentile, 275 subsequently developed significant hyperbilirubinemia, with a high PPV (60.7%), but with low sensitivity (28.3%). The 75th percentile was highly specific (81.9%) and moderately sensitive (79.8%). The area under the curve (AUC) for the TcB nomogram was 0.875.CONCLUSIONS:this study validated the previously developed TcB nomogram, which could be used to predict subsequent significant hyperbilirubinemia in healthy Chinese term and late-preterm infants. However, combining TcB nomogram and clinical risk factors could improve the predictive accuracy for severe hyperbilirubinemia, which was not assessed in the study. Further studies are necessary to confirm this combination