Camellia japonica
petals are colorful, rich in anthocyanins, and possess important ornamental, edible, and medicinal value. However, the regulatory mechanism of anthocyanin accumulation in
C. ...japonica
is still unclear. In this study, an integrative analysis of the metabolome and transcriptome was conducted in five
C. japonica
cultivars with different petal colors. Overall, a total of 187 flavonoids were identified (including 25 anthocyanins), and 11 anthocyanins were markedly differentially accumulated among these petals, contributing to the different petal colors in
C. japonica
. Moreover, cyanidin-3-
O-
(6
″
-
O-
malonyl) glucoside was confirmed as the main contributor to the red petal phenotype, while cyanidin-3-
O-
rutinoside, peonidin-3-
O-
glucoside, cyanidin-3-
O-
glucoside, and pelargonidin-3-
O-
glucoside were responsible for the deep coloration of the
C. japonica
petals. Furthermore, a total of 12,531 differentially expressed genes (DEGs) and overlapping DEGs (634 DEGs) were identified by RNA sequencing, and the correlation between the expression level of the DEGs and the anthocyanin content was explored. The candidate genes regulating anthocyanin accumulation in the
C. japonica
petals were identified and included 37 structural genes (especially
CjANS
and
Cj4CL
), 18 keys differentially expressed transcription factors (such as
GATA
,
MYB
,
bHLH
,
WRKY
, and
NAC
), and 16 other regulators (mainly including transporter proteins, zinc-finger proteins, and others). Our results provide new insights for elucidating the function of anthocyanins in
C. japonica
petal color expression.
Minimal residual disease that persists after chemotherapy is the most valuable prognostic marker for haematological malignancies and solid cancers. Unfortunately, our understanding of the resistance ...elicited in minimal residual disease is limited due to the rarity and heterogeneity of the residual cells. Here we generated 161,986 single-cell transcriptomes to analyse the dynamic changes of B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis, residual and relapse by combining single-cell RNA sequencing and B-cell-receptor sequencing. In contrast to those at diagnosis, the leukaemic cells at relapse tended to shift to poorly differentiated states, whereas the changes in the residual cells were more complicated. Differential analyses highlighted the activation of the hypoxia pathway in residual cells, resistant clones and B-ALL with MLL rearrangement. Both in vitro and in vivo models demonstrated that inhibition of the hypoxia pathway sensitized leukaemic cells to chemotherapy. This single-cell analysis of minimal residual disease opens up an avenue for the identification of potent treatment opportunities for B-ALL.
•Rats with MHE showed impaired spatial memory and decreased exploratory behavior.•Dysregulated peripheral iron homeostasis resulting from MHE led to increased iron deposition in the brain.•Iron ...overload disrupted normal neuronal function, leading to hippocampal neuroinflammation.•Neuroinflammation is associated with MHE, and dysregulated iron homeostasis is the main cause of neuroinflammation.
Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated.
Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA.
MHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats.
MHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.
MAVS is a critical adaptor required for activating an innate antiviral immune response against viral infection. The activation of MAVS requires modification of the Lys63-linked ubiquitination and ...formation of prion-like aggregates. However, the molecular mechanisms regulating MAVS activity remain largely obscured. In this study, we identified a deubiquitinase YOD1, also known as a member of the ovarian tumor family, as a negative regulator of MAVS activation in both human and murine cells. YOD1 was recruited to mitochondria to interact with MAVS through its UBX and Znf domains after viral infection. Subsequently, YOD1 cleaved the K63-linked ubiquitination and abrogated the formation of prion-like aggregates of MAVS, which led to attenuation of IRF3, P65 activation, and IFN-β production. Knockdown of YOD1 potentiated IRF3 and P65 activation, IFN-β production, and antiviral innate immune response to RNA virus. Our findings thus provided, to our knowledge, novel insights into the regulatory cascade of the cellular antiviral response through YOD1-mediated K63-linked deubiquitination and aggregation of MAVS.
Although Option B+ may be more costly than Options B, it may provide additional health benefits that are currently unclear in Yunnan province. We created deterministic models to estimate the ...cost-effectiveness of Option B+.
Data were used in two deterministic models simulating a cohort of 2000 HIV+ pregnant women. A decision tree model simulated the number of averted infants infections and QALY acquired for infants in the PMTCT period for Options B and B+. The minimum cost was calculated. A Markov decision model simulated the number of maternal life year gained and serodiscordant partner infections averted in the ten years after PMTCT for Option B or B+. ICER per life year gained was calculated. Deterministic sensitivity analyses were conducted.
If fully implemented, Option B and Option B+ averted 1016.85 infections and acquired 588,01.02 QALYs.The cost of Option B was US$1,229,338.47, the cost of Option B+ was 1,176,128.63. However, when Options B and B+ were compared over ten years, Option B+ not only improved mothers'ten-year survival from 69.7 to 89.2%, saving more than 3890 life-years, but also averted 3068 HIV infections between serodiscordant partners. Option B+ yielded a favourable ICER of $32.99per QALY acquired in infants and $5149per life year gained in mothers. A 1% MTCT rate, a 90% coverage rate and a 20-year horizon could decrease the ICER per QALY acquired in children and LY gained in mothers.
Option B+ is a cost-effective treatment for comprehensive HIV prevention for infants and serodiscordant partners and life-long treatment for mothers in Yunnan province, China. Option B+ could be implemented in Yunnan province, especially as the goals of elimination mother-to-child transmission of HIV and "90-90-90" achieved, Option B+ would be more attractive.
Pregnant women living with HIV represent one of the most high-priority groups for HIV treatment and health assessment. Although social support has been shown to be a protective factor for improved ...health-related quality of life (HRQoL), and depression and anxiety have been identified as two major causes of psychological distress among people living with HIV, it is still unclear how social support, anxiety, and depression interact to influence HRQoL. The objective of our study was to demonstrate the nature of predictors, direct effects and mediator effects among social support, anxiety, depression symptoms and HRQoL in pregnant women living with HIV. We investigated a total of 101 pregnant women living with HIV in Yunnan province in China from April 2016 to June 2016. All participants completed the Social Support Rating Scale (SSRS), the Chinese version of the Hospital Anxiety and Depression Scales (HADS) and Quality of Life instruments (EuroQoL Five Dimensions Questionnaire, EQ-5D). The relationships between the variables were examined by Pearson's or Spearman's correlation analysis. Predictor effects were tested using separate multiple regressions, controlling for demographic variables and HIV diagnosis variables. Direct and mediation effects of social support on HRQoL were tested using a structural equation model (SEM). Anxiety and depression symptoms were negatively correlated with subjective social support, support utilization, social support and HRQoL. Social support significantly predicted better HRQoL, and anxiety and depression symptoms significantly predicted poorer HRQoL. Anxiety and depression symptoms partially mediated the associations between social support and HRQoL. Anxiety and depression symptoms completely mediated the associations of objective support and support utilization with HRQoL. Interventions to improve HRQoL in pregnant women living with HIV must consider the mediation effect of anxiety and depression symptoms on the association between social support and HRQoL. Social support interventions are valid only when anxiety and depression symptoms are managed effectively.
Prevention of mother-to-child transmission (PMTCT) of HIV programmes have substantially reduced HIV infections among infants in Yunnan Province, China. We conducted a macro-level economic evaluation ...of Yunnan's PMTCT programmes over the 10 years from 2006 to 2015 from a policymaker perspective.
The study methodology was in accordance with the guidelines from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. We quantified the output from the Yunnan's PMTCT programmes by estimating the number of paediatric HIV infections averted and the relative savings to both the health care system and society. The return-on-investment ratio (ROI) was calculated as the output (numerator) divided by the input (denominator).
We have found that the US$ 49 million investment in Yunnan's PMTCT programmes over the period from 2006 to 2015 averted an estimated 2725 new paediatric HIV infections and resulted in an estimated 134,008 QALY acquired. It saved an estimated US$ 0.5 billion in treatment expenditures for Yunnan's healthcare system and nearly US$ 3.9 billion in productivity. The ROI was 88.4, meaning every US$ 1 invested brought about US$ 88.4 in benefits.
Our results support the ongoing investment in PMTCT programmes in Yunnan Province. The PMTCT strategy is a cost effective and cost-benefit strategy in the periods from 2006 to 2015. Despite higher investments in the future, the overall investment in the PMTCT programmes in Yunnan province could be offset by averting more paediatric infections.
Plant-specific TCP transcription factors play an essential role in plant growth and development. They can regulate leaf curvature, flower symmetry and the synthesis of secondary metabolites. The ...flavonoids in Ginkgo biloba leaf are one of the main medicinally bioactivate compounds, which have pharmacological and beneficial health effects for humans. In this study, a total of 13 TCP genes were identified in G. biloba, and 5 of them belonged to PCF subclades (GbTCP03, GbTCP07, GbTCP05, GbTCP13, GbTCP02) while others belonged to CIN (GbTCP01, GbTCP04, GbTCP06, GbTCP08, GbTCP09, GbTCP10, GbTCP11, GbTCP12) subclades according to phylogenetic analysis. Numerous cis-acting elements related to various biotic and abiotic signals were predicted on the promoters by cis-element analysis, suggesting that the expression of GbTCPs might be co-regulated by multiple signals. Transcript abundance analysis exhibited that most of GbTCPs responded to multiple phytohormones. Among them, the relative expression levels of GbTCP06, GbTCP11, and GbTCP13 were found to be significantly influenced by exogenous ABA, SA and MeJA application. In addition, a total of 126 miRNAs were predicted to target 9 TCPs (including GbTCP01, GbTCP02, GbTCP04, GbTCP05, GbTCP06, GbTCP08, GbTCP11, GbTCP12, GbTCP13). The correlation analysis between the expression level of GbTCPs and the flavonoid contents showed that GbTCP03, GbTCP04, GbTCP07 might involve in flavonoid biosynthesis in G. biloba. In short, this study mainly provided a theoretical foundation for better understanding the potential function of TCPs in G. biloba.
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through ...modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models.
PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining.
Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P<0.05). The pathology showed lymphocyte infiltration in the portal area, damage, and reactive proliferation of the small bile duct (P<0.05). The flow cytometric showed the imbalance of Th17/Treg cells in the liver of PBC mouse models, with decreased Treg cells, increased Th17 cells, and Th17/Treg ratio (P < 0.05). After the low-dose IL-2 intervention, biochemical index and liver pathologies showed improvement at 12 weeks. Besides, the imbalance of Th17 and Treg cells recovered. Public database mining showed that Th17 cell differentiation may contribute to poor response in PBC patients.
Low-dose IL-2 can significantly improve liver biochemistry and pathology by reversing the imbalance of Th17 and Treg cells, suggesting that it may be a potential therapeutic target for PBC.
As unique secondary metabolites of
Ginkgo biloba
L. and relics of Ginkgoaceae, terpene trilactones (TTLs) possess great medicinal value. In this study, we investigated the effects of ultraviolet (UV) ...irradiation, cold stress (4 °C), and exogenous hormone treatment on TTLs and key genes expression in ginkgo leaves in annual potted ginkgo seedlings subjected to different stress treatments. The processing conditions were as follows: UV treatment (1500 μJ/m
2
) for 0, 8, 16, 24, and 48 h; cold stress at 4 °C, 400 µmol photons m
−2
s
−1
; 100 μM abscisic acid (ABA); 100 μM methyl jasmonate (MeJA); 10 mM salicylic acid (SA); and 10 mM ethephon (ETH) treatments for 0, 2, 4, 6, and 8 days. Results of evaporative light-scattering detector–high-performance liquid chromatography showed that UV, cold stress, ABA, SA, MeJA, and ETH treatments increased the TTL content at various levels and up to 21.9%. The relationships among the expression levels of the key enzyme genes
GbDXS
,
GbGGPPS
,
GbLPS
, and
GbMVD
in the TTL biosynthesis pathway were also analyzed. Changes in the TTL content and expression levels of the key genes were significantly and positively correlated with TTL content. UV, cold stress, ABA, SA, MeJA, and ETH were found to increase the TTL content by upregulating the expression of the key genes. This study aimed to reveal the molecular mechanism through which TTLs are synthesized. The results can also provide theoretical guidance for the application of treatment methods to increase TTL content.
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