Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19.

BACKGROUND: The objective of this study was to identify potential biomarkers for predicting response to MSC therapy by pre-MSC treatment plasma proteomic profile in severe COVID-19 in order to optimize treatment choice. METHODS: A total of 58 patients selected from our previous RCT cohort were enrolled in this study. MSC responders (n = 35) were defined as whose resolution of lung consolidation ≥ 51.99% (the median value for resolution of lung consolidation) from pre-MSC to 28 days post-MSC treatment, while non-responders (n = 23) were defined as whose resolution of lung consolidation < 51.99%. Plasma before MSC treatment was detected using data-independent acquisition (DIA) proteomics. Multivariate logistic regression analysis was used to identify pre-MSC treatment plasma proteomic biomarkers that might distinguish between responders and non-responders to MSC therapy. RESULTS: In total, 1101 proteins were identified in plasma. Compared with the non-responders, the responders had three upregulated proteins (CSPG2, CTRB1, and OSCAR) and 10 downregulated proteins (ANXA1, AGRG6, CAPG, DDX55, KV133, LEG10, OXSR1, PICAL, PTGDS, and S100A8) in plasma before MSC treatment. Using logistic regression model, lower levels of DDX55, AGRG6, PICAL, and ANXA1 and higher levels of CTRB1 pre-MSC treatment were predictors of responders to MSC therapy, with AUC of the ROC at 0.910 (95% CI 0.818-1.000) in the training set. In the validation set, AUC of the ROC was 0.767 (95% CI 0.459-1.000). CONCLUSIONS: The responsiveness to MSC therapy appears to depend on baseline level of DDX55, AGRG6, PICAL, CTRB1, and ANXA1. Clinicians should take these factors into consideration when making decision to initiate MSC therapy in patients with severe COVID-19.

Additional cytogenetic abnormalities in patients with newly diagnosed acute promyelocytic leukemia predict inferior event-free survival.

BACKGROUND: The innovative combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated. METHODS: In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA-ATO-containing regimens. RESULTS: Patients with ACA had markedly decreased hemoglobin levels than that without ACA (p = 0.021). Risk stratification in the ACA group was significantly worse than that in the non-ACA group (p = 0.032). With a median follow-up period of 62.0 months, worse event-free survival (EFS) was demonstrated in patients harboring ACA. Multivariate analysis showed that ACA was an independent adverse factor for EFS (p = 0.033). By further subgroup analysis, in CD34 and CD56 negative APL, patients harboring ACA had inferior EFS (p = 0.017; p = 0.037). CONCLUSIONS: To sum up, ACA remains the independent prognostic value for EFS, we should build risk-adapted therapeutic strategies in the long-term management of APL when such abnormalities are detected.

Effects of glucose metabolism pathways on sperm motility and oxidative status during long-term liquid storage of goat semen.

Although great efforts were made to prolong the fertility of liquid-stored semen, limited improvements have been achieved in different species. Although it is expected that energy supply and the redox potential will play an essential role in sperm function, there are few reports on the impact of specific energy substrates on spermatozoa during liquid semen storage. Furthermore, although it is accepted that glucose metabolism through glycolysis provides energy, roles of pentose phosphate pathway (PPP) and tricarboxylic acid cycle remain to be unequivocally found in spermatozoa. We have studied the pathways by which spermatozoa metabolize glucose during long-term liquid storage of goat semen. The results indicated that among the substrates tested, glucose and pyruvate were better than lactate in maintaining goat sperm motility. Although both glycolysis and PPP were essential, PPP was more important than glycolysis to maintain sperm motility. Pentose phosphate pathway reduced oxidative stress and provided glycolysis with more intermediate products such as fructose-6-phosphate. Pyruvate entered goat spermatozoa through monocarboxylate transporters and was oxidized by the tricarboxylic acid cycle and electron transfer to sustain sperm motility. Long-term liquid semen storage can be used as a good model to study sperm glucose metabolism. The data are important for an optimal control of sperm survival during semen handling and preservation not only in the goat but also in other species.

Effects of pH during liquid storage of goat semen on sperm viability and fertilizing potential.

A specific problem in goat semen preservation is the detrimental effect of seminal plasma on sperm viability in extenders containing yolk or milk. Thus, the use of chemically defined extenders will have obvious advantages. Although previous studies indicate that the initial pH of an extender is crucial to sustain high sperm motility, changes in extender pH during long-term semen storage have not been observed. Monitoring extender pH at different times of semen storage and modeling its variation according to nonlinear models is thus important for protocol optimization for long-term liquid semen preservation. The present results showed that during long-term liquid storage of goat semen, both sperm motility and semen pH decreased gradually, and a strong correlation was observed between the two. Whereas increasing the initial extender pH from 6.04 to 6.25 or storage with stabilized pH improved, storage with artificially lowered pH impaired sperm motility. Extender renewal improved sperm motility by maintaining a stable pH. Sperm coating with chicken (Gallus gallus) egg yolk improved motility by increasing tolerance to pH decline. A new extender (n-mZAP) with a higher buffering capacity was formulated, and n-mZAP maintained higher sperm motility, membrane integrity and acrosome intactness than the currently used mZAP extender did. Goat semen liquid-stored for 12 d in n-mZAP produced pregnancy and kidding rates similar to those obtained with freshly collected semen following artificial insemination. In conclusion, maintenance of a stable pH during liquid semen storage dramatically improved sperm viability and fertilizing potential.

Electrophysiological responses of the rice leaffolder, Cnaphalocrocis medinalis, to rice plant volatiles.

The rice leaffolder, Cnaphalocrocis medinalis Guenée (Lepidoptera: Pyralidae), is one of the most destructive pests of rice. Electrophysiological responses of this species to 38 synthetic volatiles known to be released from rice plants (Poaceae: Oryza spp.) were studied using the electroantennogram (EAG) method. Compounds that elicited the strongest EAG responses for each physiological condition were selected for EAG dose-response tests at five concentrations. These compounds included: methyl salicylate, heptanol, linalool, cyclohexanol, and 2-heptanone for one-day-old male moths; heptanol, hexanal, (Z)-2-hexen-1-ol, and nonadecane for one-day- old females; methyl salicylate, heptanol, (E)-2-hexen-1-ol, and (Z)-2-hexen-1-ol for three-day- old males; linalool, heptanol, (E)-2-hexen-1-ol, 2-heptanone, and hexanal for three-day-old females; 2-heptanone, cyclohexanol, linalool, heptanol, and methyl salicylate for five-day-old virgin females; and methyl benzoate, (Z)-2-hexen-1-ol, heptanol, linalool, and hexanal for five- day-old mated females. Female and male C. medinalis exhibited broad overlap in their EAG responses, and there was no clear difference between male and female EAG responses to different compounds. Statistical analyses revealed that both volatile compound chemical structure and C. medinalis physiological condition (age, sex, and mating condition) had an effect on EAG response.

Discriminative analysis of mild Alzheimer's disease and normal aging using volume of hippocampal subfields and hippocampal mean diffusivity: an in vivo magnetic resonance imaging study.

BACKGROUND: Studies discovered that the hippocampal subfields are differentially affected by pathological damage, and magnetic resonance (MR) diffusion tensor imaging parameters might be more sensitive measures of early degeneration in Alzheimer's disease (AD) than conventional MR imaging techniques. The purpose of this study was to evaluate the significance of the volume of hippocampal subfields and the mean diffusivity (MD) value of hippocampus in discrimination between mild AD and normal aging. METHODS: A total of 29 patients with mild AD and 30 normal aging were scanned. Binary logistic regression analysis was applied to assess the diagnostic significance of the volumes of hippocampal subfields and the MD value of hippocampus. RESULTS: All hippocampal subfields except right tail atrophied significantly in the mild AD group (P < .05). The relative volumes of right CA1 and subiculum subfields entered the binary logistic regression model. The accuracy was 91.8%, which was improved to 93.9% as the MD value of right hippocampus entered the model. CONCLUSION: Atrophy was present in almost all hippocampal subfields at mild AD stage. The volumes of CA1 and subiculum were of the most diagnostic significance in discrimination of mild AD, which can be improved by the combination of volume and diffusivity analysis.

Discriminative analysis of early-stage Alzheimer's disease and normal aging with automatic segmentation technique in subcortical gray matter structures: a multicenter in vivo MRI volumetric and DTI study.

BACKGROUND: Previous studies have revealed that amyloid depositions exist in not only the hippocampus but in other subcortical gray matter structures as well. Diffusion-tensor imaging (DTI) parameters might be more sensitive measures of early degeneration in Alzheimer's disease (AD) than conventional magnetic resonance imaging (MRI) techniques. PURPOSE: To evaluate the significance of the volumes and the mean diffusivity (MD) values of subcortical gray matter structures in discrimination between early-stage AD and normal subjects using the Integrated Registration and Segmentation Tool in FMRIB's Software Library. MATERIAL AND METHODS: Fifty-three cases of early-stage AD and 30 normal aging volunteers from two hospitals were scanned with 3D-FSPGRIR and SSSE-EPI sequences using two similar 1.5T MR systems. The mean relative volumes and mean MD values of subcortical gray matter structures were compared between early-stage AD and control groups. Binary logistic regression analysis and receiver-operating characteristic (ROC) curves were applied to assess the diagnostic significance of every structure's relative volume, MD value, and combination of both. RESULTS: The relative volumes of the left hippocampus, right amygdala, bilateral thalamus, right caudate, left putamen, and bilateral pallidum were significantly lower in the early-stage AD group than in the control group (P < 0.05). The MD values of the bilateral hippocampus and pallidum, and of the right thalamus and caudate were significantly elevated in the early-stage AD group (P < 0.05). In binary logistic regression analysis, the relative volume of left hippocampus and age entered the final model of volumetric analysis. The MD values of bilateral hippocampi and pallidums entered the final model of MD analysis. The MD values of bilateral hippocampi and pallidums, and the relative volume of left pallidum, entered the final model of combination analysis. The accuracy of three models was 84.7%, 88.9%, and 93.1%, respectively. CONCLUSION: Pathological changes takes place in the hippocampus and other subcortical gray matter structures in early-stage AD. Diffusive imaging has great diagnostic significance in early-stage AD. The combination of both imaging modalities can lead to better discrimination between early-stage AD and normal aging.

Analysis of a cDNA library from the antenna of Cnaphalocrocis medinalis and the expression pattern of olfactory genes.

Chemoreception is a key feature in selection of host plants by insects. In this study, preliminary characterization and isolation of cDNA clones from Cnaphalocrocis medinalis antennal libraries identified eight olfactory genes, including two putative general odorant-binding proteins (GOBPs), three pheromone binding proteins (PBPs) and three chemosensory proteins (CSPs). The expression profiles of these eight genes in different tissues (antenna, head (without antennae), thorax, abdomen, leg and wing) were measured by real time qPCR. The results showed that GOBP and PBP genes in C. medinalis seemed to be antenna-specific, but differentially expressed in male and female antennae; while CSP genes were expressed ubiquitously during different developmental stages, but with an extremely elevated transcript level in antennae, legs and wings compared to head, thorax and abdomen. And also, the transcription levels of olfactory genes depended on the age, sex, and mating status of the adults. These findings support the hypothesis that OBPs and CSPs play dynamic roles during development of C. medinalis and are likely to be involved in broader physiological functions.