IgG antibody response to SARS-CoV-2 infection and its influencing factors in lymphoma patients.

BACKGROUND: The ability of generating effective humoral immune responses to SARS-CoV-2 infection has not been clarified in lymphoma patients. The study aimed to investigate the antibody (Ab) production after SARS-Cov-2 infection and clarify the factors affecting the Ab generation in these patients. PATIENTS & METHODS: 80 lymphoma patients and 51 healthy controls were included in this prospective observational study. Clinical factors and treatment regimens affecting Ab positive rate (APR) and Ab levels were analyzed by univariate and multivariate methods. RESULTS: The anti-SARS-CoV-2 IgG APR and Ab levels in lymphoma patients were significantly lower than those in healthy controls. Lymphoma patients with COVID-19 vaccination had significantly higher APR and Ab levels compared with those without vaccination. Additionally, the use of dexamethasone for COVID-19 treatment had a negative impact on Ab levels. For the impact of treatment regimens on the APR and Ab levels, the results showed that patients treated with ≥ 6 times CD20 monoclonal Ab (mAb) and patients treated with autologous hematopoietic stem cell transplantation (ASCT) prior to infection produced a statistically lower APR and Ab levels compared with those treated with 1-5 times CD20 mAb and those treated without ASCT, respectively. Furthermore, multiple regression analysis indicated that the number of anti-CD20 treatment was an independent predictor for both APR and Ab levels. CONCLUSIONS: Humoral immune response to SARS-CoV-2 infection was impaired in lymphoma patients partly due to anti-CD20 and ASCT treatment. COVID-19 vaccination may be more needed for these patients.

Long noncoding RNA SENCR facilitates the progression of acute myeloid leukemia through the miR-4731-5p/IRF2 pathway.

BACKGROUND: Acute myeloid leukemia (AML) is a type of hematological tumor caused by malignant clone hematopoietic stem cells. The relationship between lncRNAs and tumor occurrence and progression has been gaining attention. Research has shown that Smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) is abnormally expressed in various diseases, whereas its role in AML is still poorly understood. METHODS: The expression of SENCR, microRNA-4731-5p (miR-4731-5p) and Interferon regulatory factor 2 (IRF2) were measured using qRT-PCR. The proliferation, cycle and apoptosis of AML cells with or without knockdown of SENCR were detected by CCK-8 assay, EdU assay, flow cytometry, western blotting and TUNEL assay, respectively. Consistently, SENCR knockdown was impaired the AML progression in immunodeficient mice. In addition, the binding of miR-4731-5p to SENCR or IRF2 was confirmed by luciferase reporter genes assay. Finally, rescue experiments were conducted to confirm the role of SENCR/miR-4731-5p/IRF2 axis in AML. RESULTS: SENCR is highly expressed in AML patients and cell lines. The patients with high SENCR expression had poorer prognosis compared with those with low SENCR expression. Interestingly, knockdown of SENCR inhibits the growth of AML cells. Further results demonstrated that the reduction of SENCR slows the progression of AML in vivo. SENCR could function as a competing endogenous RNA (ceRNA) to negatively regulate miR-4731-5p in AML cells. Furthermore, IRF2 was validated as a direct target gene of miR-4731-5p in AML cells. CONCLUSIONS: Our findings underscore the important role of SENCR in regulating the malignant phenotype of AML cells by targeting the miR-4731-5p/IRF2 axis.

The reference genome and full-length transcriptome of pakchoi provide insights into cuticle formation and heat adaption.

Brassica rapa includes various vegetables with high economic value. Among them, green petiole type pakchoi (B. rapa ssp. chinensis) is one of the major vegetables grown in southern China. Compared with other B. rapa varieties, green petiole type pakchoi shows a higher level of heat resistance, which is partially derived from the rich epicuticular wax. Here we sequence a high-quality genome of green petiole type pakchoi, which has been widely used as the parent in breeding. Our results reveal that long terminal repeat retrotransposon insertion plays critical roles in promoting the genome expansion and transcriptional diversity of pakchoi genes through preferential insertions, particularly in cuticle biosynthetic genes. After whole-genome triplication, over-retained pakchoi genes escape stringent selection pressure, and among them a set of cuticle-related genes are retained. Using bulked-segregant analysis of a heat-resistant pakchoi cultivar, we identify a frame-shift deletion across the third exon and the subsequent intron of BrcCER1 in candidate regions. Using Nanopore long-read sequencing, we analyze the full-length transcriptome of two pakchoi cultivars with opposite sensitivity to high temperature. We find that the heat-resistant pakchoi cultivar can mitigate heat-caused leaf damage by activating an unfolded protein response, as well as by inhibiting chloroplast development and energy metabolism, which are presumably mediated by both transcriptional regulation and splicing factors. Our study provides valuable resources for Brassica functional genomics and breeding research, and deepens our understanding of plant stress resistance.

Arcuate NPY is involved in salt-induced hypertension via modulation of paraventricular vasopressin and brain-derived neurotrophic factor.

Chronic high salt intake is one of the leading causes of hypertension. Salt activates the release of the key neurotransmitters in the hypothalamus such as vasopressin to increase blood pressure, and neuropepetide Y (NPY) has been implicated in the modulation of vasopressin levels. NPY in the hypothalamic arcuate nucleus (Arc) is best known for its control in appetite and energy homeostasis, but it is unclear whether it is also involved in the development of salt-induced hypertension. Here, we demonstrate that wild-type mice given 2% NaCl salt water for 8 weeks developed hypertension which was associated with marked downregulation of NPY expression in the hypothalamic Arc as demonstrated in NPY-GFP reporter mice as well as by in situ hybridization analysis. Furthermore, salt intake activates neurons in the hypothalamic paraventricular nucleus (PVN) where mRNA expression of brain-derived neurotrophic factor (BDNF) and vasopressin was found to be upregulated, leading to elevated serum vasopressin levels. This finding suggests an inverse correlation between the Arc NPY level and expression of vasopressin and BDNF in the PVN. Specific restoration of NPY by injecting AAV-Cre recombinase into the Arc only of the NPY-targeted mutant mice carrying a loxP-flanked STOP cassette reversed effects of salt intake on vasopressin and BDNF expression, leading to a normalization of salt-dependent blood pressure. In summary, our study uncovers an important Arc NPY-originated neuronal circuitry that could sense and respond to peripheral electrolyte signals and thereby regulate hypertension via vasopressin and BDNF in the PVN.

Ethylene and Benzaldehyde Emitted from Postharvest Tomatoes Inhibit Botrytis cinerea via Binding to G-Protein Coupled Receptors and Transmitting with cAMP-Signal Pathway of the Fungus.

Tomato storage conditions are difficult largely due to Botrytis cinerea infection which causes gray mold disease. However, the effects of the volatile organic compounds (VOCs) emitted by postharvest tomatoes on this fungus remain unclear. We analyzed the effects of tomato-emitted VOCs on B. cinerea pathogenicity, germination, and hyphal growth with bioassay, predicted the causative active compounds by principle component analysis, identified G-protein-coupled receptors (GPCRs) which captured chemical signals in the B. cinerea genome by stimulating molecular docking, tested the binding affinities of these receptors for the active compounds by fluorescence binding competition assay, and identified an associated signaling pathway by RNA interfere. The VOCs emitted by postharvest tomatoes inhibited B. cinerea; ethylene and benzaldehyde were the active compounds causing this effect. One of the identified GPCRs in B. cinerea, BcGPR3, bound tightly to both active compounds. Two genes associated with the cAMP signaling pathway (BcRcn1 and BcCnA) were downregulated in wild-type B. cinerea exposed to the active compounds, as well as in the ΔBcgpr3 B. cinerea mutant. Exposure to postharvest tomato VOCs reduces B. cinerea pathogenicity due to ethylene and benzaldehyde volatiles. The BcGPR3 protein is inactivated by the active compounds, and thus fails to transmit signals to the cAMP pathway, thereby inhibiting B. cinerea.

Transcription factor Tbx18 induces the differentiation of c-kit+ canine mesenchymal stem cells (cMSCs) into SAN-like pacemaker cells in a co-culture model in vitro.

Bone mesenchymal stem cells (MSCs), as well as cardiomyocytes, are derived from early mesoderm, becoming committed to their fate under the influence of different differentiation factors. We examined whether the overexpression of Tbx18 can induce the differentiation of c-kit+ cMSCs into a phenotype similar to that of native pacemaker cells and whether these transfected cells can couple to adjacent atrial cells with functional consequences. The c-kit+ cMSCs were first sorted, then transfected with different lentiviral vectors. Tbx18-c-kit+ cMSCs represented the experimental group, while EYFP-c-kit+ cMSCs and canine sinoatrial node (SAN) cells were used as controls. Within days of transfection, the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel HCN4 protein and gap junction protein Connexin 45 (Cx45) expression in Tbx18-c-kit+ cMSCs were 12-fold and 5.6-fold higher, respectively, than that in EYFP-c-kit+ cMSCs. After co-culture with canine atrial cells in vitro for three days, the funny currents (If) were recorded in the Tbx18-c-kit+ cMSCs, but not in EYFP-c-kit+ cMSCs. The trend of these If currents was highly similar to that of SAN cells, although the current density was smaller. The Tbx18-EYFP-c-kit+ cMSCs showed responsiveness to ß-adrenergic stimulation, and the intracellular cyclic adenosine monophosphate (cAMP) level was higher than that in EYFP-c-kit+ cMSCs. The Tbx18-EYFP-c-kit+ cMSCs delivered fluorescent dye to neighboring atrial cells via gap junctions, thus these cell pairs could communicate as a pacemaker unit. We propose that the overexpression of Tbx18 in c-kit+ cMSCs induces their differentiation to SAN-like pacemaker cells.

Comprehensive Analysis of Photosynthetic Characteristics and Quality Improvement of Purple Cabbage under Different Combinations of Monochromatic Light.

Light is essential for plant growth. Light intensity, photoperiod, and light quality all affect plant morphology and physiology. Compared to light intensity, photoperiod, little is known about the effects of different monochromatic lights on crop species. To investigate how different lighting conditions influence crops with heterogeneous colors in leaves, we examined photosynthetic characteristics and quality (regarding edibility and nutrition) of purple cabbage under different combinations of lights. Eight different treatments were applied including monochromic red (R), monochromic blue (B), monochromic yellow (Y), monochromic green (G), and the combination of red and blue (3/1, RB), red/blue/yellow (3/1/1, RBY), red/blue/green (3/1/1,RBG), and white light as the control. Our results indicate that RBY (3/1/1) treatment promotes the PSII activity of purple cabbage, resulting in improved light energy utilization. By contrast, both G and Y lights alone have inhibitory effect on the PSII activity of purple cabbage. In addition, RBY (3/1/1) significantly boosts the anthocyanin and flavonoids content compared with other treatments. Although we detected highest soluble protein and vitamin C content under B treatment (increased by 30.0 and 14.3% compared with the control, respectively), RBY (3/1/1) appeared to be the second-best lighting condition (with soluble protein and vitamin C content increased by 8.6 and 4.1%, respectively compared with the control). Thus we prove that the addition of yellow light to the traditional combination of red/blue lighting conditions is beneficial to synthesizing photosynthetic pigments and enables superior outcome of purple cabbage growth. Our results indicate that the growth and nutritional quality of purple cabbage are greatly enhanced under RBY (3/1/1) light, and suggest that strategical management of lighting conditions holds promise in maximizing the economic efficiency of plant production and food quality of vegetables grown in controlled environments.

Elevated Type II Secretory Phospholipase A2 Increases the Risk of Early Atherosclerosis in Patients with Newly Diagnosed Metabolic Syndrome.

A critical association between type II secretory phospholipase A2 (sPLA2-IIa) and established atherosclerotic cardiovascular disease has been demonstrated. However, the contribution of sPLA2-IIa to early atherosclerosis remains unknown. This study investigated the association between early-stage atherosclerosis and sPLA2-IIa in metabolic syndrome (MetS) patients. One hundred and thirty-six MetS patients and 120 age- and gender-matched subjects without MetS were included. Serum sPLA2-IIa protein levels and activity were measured using commercial kits. Circulating endothelial activation molecules (vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and P-selectin), and carotid intima-media thickness (cIMT), were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. MetS patients exhibited significantly higher sPLA2-IIa protein and activity levels than the controls. Both correlated positively with fasting blood glucose and waist circumference in MetS patients. Additionally, MetS patients exhibited strikingly higher levels of endothelial activation molecules and increased cIMT than controls. These levels correlated positively with serum sPLA2-IIa protein levels and activity. Moreover, multivariate analysis showed that high sPLA2-IIa protein and activity levels were independent risk factors of early atherosclerosis in MetS patients. This study demonstrates an independent association between early-stage atherosclerosis and increased levels of sPLA2-IIa, implying that increased sPLA2-IIa may predict early-stage atherosclerosis in MetS patients.