Hepatitis B surface antigen positivity is associated with poor short- and long-term outcomes in patients with diffuse large B-cell lymphoma who received CHOP or R-CHOP

ObjectiveThe development of diffuse large B-cell lymphoma (DLBCL) is closely related to the host infection status. China is a highly endemic area for hepatitis B virus (HBV) infection. It is not clear whether HBV infection has a consistent effect on the prognostic implications of patients with DLBCL in different treatment settings.Materials and methodsWe conducted a cohort study of 692 patients with DLBCL receiving three or more cycles of treatment with a CHOP or R-CHOP regimen from the First Hospital of Jilin University between July 2011 and July 2022. The patients were divided into two groups based on their hepatitis B surface antigen (HBsAg) status: HBsAg-positive (n = 84, 12.1%) and HBsAg-negative (n = 608, 87.9%) groups. Tumor specimens from 180 patients with primary DLBCL were collected for next-generation sequencing (NGS).ResultsThe HBsAg-positive group had more frequent abnormal liver function (P = 0.003), hypoalbuminemia (P < 0.001), incidence of > 2 extranodal organs (P = 0.011), and spleen involvement (P < 0.001) than the HBsAg-negative group. HBsAg-positive patients had lower complete response (CR) and overall response rates (ORR) rates (all the p values < 0.05), in either the CHOP group or R-CHOP group. Among patients receiving R-CHOP, the rates of disease progression within 12 and 24 months were higher in the HBsAg-positive group than in the HBsAg-negative group (P=0.018, P=0.029). However, no significant difference in disease progression was observed between HBsAg-positive and HBsAg-negative patients in the CHOP group(P > 0.05). HBsAg positivity (OS: HR [95% CI] = 2.511 [1.214-5.192], P = 0.013) was only associated with poorer OS in the CHOP group. Whereas in the R-CHOP group, HBsAg positivity was associated with both poorer OS and PFS (OS: HR [95% CI] = 1.672 [1.050-2.665], P = 0.030; PFS: HR [95% CI] = 1.536 [1.013-2.331], P = 0.043). Additionally, HBsAg-positive patients with DLBCL also had a higher prevalence of mutations in MYC, ATM, PTPN6, and epigenetically regulated genes.ConclusionThese findings suggest that HBsAg-positive DLBCL patients may represent a distinct subgroup with a poorer prognosis. The standard therapies may be insufficient and new therapeutic strategies should be developed based on a better understanding of the underlying mechanisms of chemoresistance

Benzoate Catabolite Repression of the Phenol Degradation in Acinetobacter calcoaceticus PHEA-2

Acinetobacter calcoaceticus PHEA-2 exhibited a delayed utilization of phenol in the presence of benzoate. Benzoate supplementation completely inhibited phenol degradation in a benzoate 1,2-dioxygenase knockout mutant. The mphR encoding the transcriptional activator and mphN encoding the largest subunit of multi-component phenol hydroxylase in the benA mutant were significantly downregulated (about 7- and 70-fold) on the basis of mRNA levels when benzoate was added to the medium. The co-transformant assay of E. coli JM109 with mphK::lacZ fusion and the plasmid pETR carrying mphR gene showed that MphR did not activate the mph promoter in the presence of benzoate. These results suggest that catabolite repression of phenol degradation by benzoate in A. calcoaceticus PHEA-2 is mediated by the inhibition of the activator protein MphR

Disrupted Asymmetry of Inter- and Intra-Hemispheric Functional Connectivity at Rest in Medication-Free Obsessive-Compulsive Disorder

Disrupted functional asymmetry of cerebral hemispheres may be altered in patients with obsessive-compulsive disorder (OCD). However, little is known about whether anomalous brain asymmetries originate from inter- and/or intra-hemispheric functional connectivity (FC) at rest in OCD. In this study, resting-state functional magnetic resonance imaging was applied to 40 medication-free patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs). Data were analyzed using the parameter of asymmetry (PAS) and support vector machine methods. Patients with OCD showed significantly increased PAS in the left posterior cingulate cortex, left precentral gyrus/postcentral gyrus, and right inferior occipital gyrus and decreased PAS in the left dorsolateral prefrontal cortex (DLPFC), bilateral middle cingulate cortex (MCC), left inferior parietal lobule, and left cerebellum Crus I. A negative correlation was found between decreased PAS in the left DLPFC and Yale–Brown Obsessive-compulsive Scale compulsive behavior scores in the patients. Furthermore, decreased PAS in the bilateral MCC could be used to distinguish OCD from HCs with a sensitivity of 87.50%, an accuracy of 88.46%, and a specificity of 89.47%. These results highlighted the contribution of disrupted asymmetry of intra-hemispheric FC within and outside the cortico-striato-thalamocortical circuits at rest in the pathophysiology of OCD, and reduced intra-hemispheric FC in the bilateral MCC may serve as a potential biomarker to classify individuals with OCD from HCs

Quantitative analysis and comparison of 3D morphology between viable and apoptotic MCF-7 breast cancer cells and characterization of nuclear fragmentation

Morphological changes in apoptotic cells provide essential markers for defining and detection of apoptosis as a fundamental mechanism of cell death. Among these changes, the nuclear fragmentation and condensation have been regarded as the important markers but quantitative characterization of these changes is yet to be achieved. We have acquired confocal image stacks of 206 viable and apoptotic MCF-7 cells stained by three fluorescent dyes. Three-dimensional (3D) parameters were extracted to quantify and compare their differences in morphology. To analyze nuclear fragmentation, a new method has been developed to determine clustering of nuclear voxels in the reconstructed cells due to fluorescence intensity changes in nuclei of apoptotic cells. The results of these studies reveal that the 3D morphological changes in cytoplasm and nuclear membranes in apoptotic cells provide sensitive targets for label-free detection and staging of apoptosis. Furthermore, the clustering analysis and morphological data on nuclear fragmentation are highly useful for derivation of optical cell models and simulation of diffraction images to investigate light scattering by early apoptotic cells, which can lead to future development of label-free and rapid methods of apoptosis assay based on cell morphology.Open Access Fundin

Genome Sequence and Transcriptome Analysis of the Radioresistant Bacterium Deinococcus gobiensis: Insights into the Extreme Environmental Adaptations

The desert is an excellent model for studying evolution under extreme environments. We present here the complete genome and ultraviolet (UV) radiation-induced transcriptome of Deinococcus gobiensis I-0, which was isolated from the cold Gobi desert and shows higher tolerance to gamma radiation and UV light than all other known microorganisms. Nearly half of the genes in the genome encode proteins of unknown function, suggesting that the extreme resistance phenotype may be attributed to unknown genes and pathways. D. gobiensis also contains a surprisingly large number of horizontally acquired genes and predicted mobile elements of different classes, which is indicative of adaptation to extreme environments through genomic plasticity. High-resolution RNA-Seq transcriptome analyses indicated that 30 regulatory proteins, including several well-known regulators and uncharacterized protein kinases, and 13 noncoding RNAs were induced immediately after UV irradiation. Particularly interesting is the UV irradiation induction of the phrB and recB genes involved in photoreactivation and recombinational repair, respectively. These proteins likely include key players in the immediate global transcriptional response to UV irradiation. Our results help to explain the exceptional ability of D. gobiensis to withstand environmental extremes of the Gobi desert, and highlight the metabolic features of this organism that have biotechnological potential

Mechanistic study of the ligand controlled regioselectivity in iridium catalyzed C- H borylation of aromatic imines

As a major challenge in C-H borylation, how to control the selectivity has attracted lots of attention, however, the related mechanistic information still needs to be uncovered. Herein, density functional theory (DFT) has been used to study the mechanism for the ligand controlled regioselectivity in the iridium-catalyzed C-H borylation of aromatic imines, which is inspired by experimental observations (R. Bisht, B. Chattopadhyay, J. Am. Chem. Soc., 2016, 138, 84-87). The proposed Ir(i)-Ir(iii) catalytic cycle includes (i) the oxidative addition of the C-H bond to iridium(i); (ii) the reductive elimination of a C-B bond; (iii) the oxidative addition of B(2)pin(2) to an iridium(i) hydride complex; and (iv) the reductive elimination of a B-H bond. The oxidative addition of a C-H bond to the iridium center is the determining step. For the ligand AQ, ortho-selectivity is proposed to be attributed to the decreased steric hindrance and increased electron donating effect of AQ (8-aminoquinoline) which promotes proton-transfer in the ortho-transition state of C-H activation. While, for the TMP ligand, the steric repulsion between the TMP (4,5,7,8-tetramethyl-1, 10-phenanthroline) ligand and the ortho-substituted imine hinders the ortho C-H activation and favors meta borylation. Our calculations provide insights into further ligand design to achieve different regioselective borylation of aromatics. Guided by the results, the regioselectivity in the borylation of aromatics may be achieved by accordingly modifying the electronic and steric substituents of the ligand

Genome-Wide Analysis of Sugar Transporters Identifies the gtsA Gene for Glucose Transportation in Pseudomonas stutzeri A1501

Pseudomonas stutzeri A1501 possesses an extraordinary number of transporters which confer this rhizosphere bacterium with the sophisticated ability to metabolize various carbon sources. However, sugars are not a preferred carbon source for P. stutzeri A1501. The P. stutzeri A1501 genome has been sequenced, allowing for the homology-based in silico identification of genes potentially encoding sugar-transport systems by using established microbial sugar transporters as a template sequence. Genomic analysis revealed that there were 10 sugar transporters in P. stutzeri A1501, most of which belong to the ATP-binding cassette (ABC) family (5/10); the others belong to the phosphotransferase system (PTS), major intrinsic protein (MIP) family, major facilitator superfamily (MFS) and the sodium solute superfamily (SSS). These systems might serve for the import of glucose, galactose, fructose and other types of sugar. Growth analysis showed that the only effective medium was glucose and its corresponding metabolic system was relatively complete. Notably, the loci of glucose metabolism regulatory systems HexR, GltR/GtrS, and GntR were adjacent to the transporters ABCMalEFGK, ABCGtsABCD, and ABCMtlEFGK, respectively. Only the ABCGtsABCD expression was significantly upregulated under both glucose-sufficient and -limited conditions. The predicted structure and mutant phenotype data of the key protein GtsA provided biochemical evidence that P. stutzeri A1501 predominantly utilized the ABCGtsABCD transporter for glucose uptake. We speculate that gene absence and gene diversity in P. stutzeri A1501 was caused by sugar-deficient environmental factors and hope that this report can provide guidance for further analysis of similar bacterial lifestyles

Interspecific hybridizations of Fraxinus L. (F. mandshurica × F. americana and F. mandshurica × F. velutina) and heterosis analysis and selection of F1 progenies

The interspecific hybridizations of Fraxinus mandshurica Rupr. × Fraxinus americana L. (MA) and Fraxinus mandshurica × Fraxinus velutina Torr. (MV) were conducted to solve the problems of poor cold adaption associated with the introduction of Fraxinus in Heilongjiang province. High-voltage electrostatic field (HVEF) treatment to pollen was performed to overcome the prefertilization barriers. The hybrids adapted more strongly and grew better than the pure species (heterosis over higher parent (HHP) of the 9-year volume index was 5.5% for MA and 23.1% for MV) in Heilongjiang province. HVEF treatment greatly improved the number of seeds (0.25- to 5.52-fold) and seedlings (1.63- to 8.71-fold) of the hybrids. Additionally, three excellent female parents (nos. 15, 16, and 17) and seven hybrid combinations of MA (D94, D70, and D100) and MV (D103, D116, D105, and D104) with excellent growth traits were selected. The HHPs of volume index were 39.1%–112.5% for selected hybrids. Additionally, predicted growth trends of the hybrids showed that the hybrids will maintain a 7.7% to 9.3% height advantage over F. mandshurica through ages 10 to 15 years in Mao Ershan. These findings will accelerate the genetic breeding process of Fraxinus species.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author