The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic ...high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including
(G1),
(G2),
(G3), biallelic
mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of
(p.N159S) (n = 7). In contrast, most
mutations and
and
fusions clustered into G6-G8, showing high expression of
/
genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely
-primitive (G7),
-mixed (G8), and
-committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.
We examine two inconclusive issues in the IPO (initial public offering) underpricing literature. It is unclear whether private firms or state-owned enterprises (SOEs) underprice their IPOs more and ...how the institutional environment affects IPO underpricing. Using a much larger China IPO sample of SOEs, we conclude that SOEs underprice their IPOs more than private firms. Specifically, SOEs controlled by the central government (CSOEs) underprice their IPOs 27 percentage points more than private firms, whereas SOEs controlled by local governments (LSOEs) underprice theirs 7 percentage points more than those of private firms. Using the National Economic Research Institute Index of Marketization (NERIIM) to measure the institutional environment, we find that one index score improvement in institutional environment is associated with a two percentage-point reduction in IPO underpricing. Importantly, a better institutional environment reduces IPO underpricing most effectively for private firms, followed by LSOEs, and the least for CSOEs.
•Using China data, we study how the institutional environment affects IPO underpricing.•We also study whether private firms or state-owned enterprises (SOEs) underprice their IPOs more.•We find central-government controlled SOEs (CSOEs) underprice the most.•Local-government controlled SOEs (LSOEs) underprice less, private firms underprice the least.•Institutional environment affects underpricing differently on private firms, LSOEs and CSOEs.
The role of inflammation in silicosis Liu, Tong-Tong; Sun, Hai-Fei; Han, Yan-Xing ...
Frontiers in pharmacology,
03/2024, Letnik:
15
Journal Article
Recenzirano
Odprti dostop
Silicosis is a chronic illness marked by diffuse fibrosis in lung tissue resulting from continuous exposure to SiO
-rich dust in the workplace. The onset and progression of silicosis is a complicated ...and poorly understood pathological process involving numerous cells and molecules. However, silicosis poses a severe threat to public health in developing countries, where it is the most prevalent occupational disease. There is convincing evidence supporting that innate and adaptive immune cells, as well as their cytokines, play a significant role in the development of silicosis. In this review, we describe the roles of immune cells and cytokines in silicosis, and summarize current knowledge on several important inflammatory signaling pathways associated with the disease, aiming to provide novel targets and strategies for the treatment of silicosis-related inflammation.
Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic guanosine ...monophosphate—adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-β induction by the virus, suggesting that the reverse-transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus, and simian immunodeficiency virus. These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses.
There were several reports describing the biomechanics and microstructure of multifidus muscles in patients with lumbar disc herniation. However, correlations between lumbar multifidus muscle atrophy ...(LMA), spinopelvic parameters, and severity of adult degenerative scoliosis (ADS) have not been investigated. The study evaluated the impact of LMA and spinopelvic parameters on the severity of ADS.
One hundred and thirty-two patients with ADS were retrospectively reviewed. Standing whole-spine X-ray was used to evaluate the coronal (coronal Cobb angle, CA; coronal vertical axis, CVA) and sagittal (sagittal vertical axis, SVA; thoracic kyphosis, TK; lumbar lordosis, LL; pelvic incidence, PI; pelvic tilt, PT; sacral slope, SS) parameters. LMA was evaluated on axial T2-weighted magnetic resonance imaging (MRI) at intervertebral levels above and below the vertebra at the apex of the scoliotic curve. Clinical symptoms were evaluated by the Oswestry Disability Index (ODI) and the Japanese Orthopaedic Association (JOA) score. Multiple linear regression was used to assess correlations between LMA, spinopelvic parameters, and severity of scoliosis.
LL and PT were negatively correlated with CA (P < 0.001); LL was positively correlated with SVA (P < 0.001). PI was positively correlated with CA (P < 0.001) and CVA (P < 0.001). PT (P < 0.001) and SS (P < 0.001) were negatively correlated with CVA. SS was negatively correlated with SVA (P < 0.001). Concave LMA at the upper or lower intervertebral level of the apical vertebra was positively correlated with CA (P ≤ 0.001); convex LMA at the upper or lower intervertebral level was negatively correlated with CA (P < 0.001). Convex LMA at the upper intervertebral level and concave LMA at the lower intervertebral level of the apical vertebra were negatively correlated with the SVA (P ≤ 0.001). At the upper intervertebral level, LMA on the concave side was positively correlated with CVA (P = 0.028); LMA on the convex side was negatively correlated with CVA (P = 0.012). PI was positively correlated with ODI (P < 0.001); PT (P < 0.001) and SS (P < 0.001) were negatively correlated with ODI. At the lower intervertebral level, LMA on the concave side was positively correlated with ODI (P = 0.038); LMA on the convex side was negatively correlated with ODI (P = 0.011). PI was positively correlated with JOA (P < 0.001); PT (P < 0.001) and SS (P < 0.001) were negatively correlated with JOA.
Spinopelvic parameters are correlated with the severity of ADS. Asymmetric LMA at both upper and lower intervertebral levels of the apical vertebra is positively correlated with CA. LMA on the diagonal through the apical vertebra is very important to maintain sagittal imbalance via parallelogram effect. LMA at lower intervertebral levels of the apical vertebra may have a predictive effect on ODI. JOA score seems to be more correlated with spinopelvic parameters than LMA.
High quality CdS/ZnS:Cu quantum dots (QDs) were first synthesized via a green microwave irradiation route. As-prepared core/shell doped QDs presented a strong absorption in the blue light region and ...highly efficient red to deep red emission with a maximum quantum yield of 40%. The composite formed by dispersing CdS/ZnS:Cu QDs into silicone resin showed an excellent photostability under blue illumination. Finally, high color rendition white light was generated from the CdS/ZnS:Cu QDs-assisted phosphor-converted white light-emitting diode (WLED) in which there was no reabsorption between quantum dots and phosphors. Under operation of 40 mA forward bias current, the fabricated WLED emitted bright natural white light with a high color rendering index of 90, a luminous efficiency of 46.5 lm/W, and the correlated color temperature of 6591 K. Simultaneously, the good color stability was accompanied by the CIE color coordinates of (0.3155, 0.3041) under different forward bias currents.
Lithium–sulfur (Li–S) batteries are highly regarded as the next‐generation energy‐storage devices because of their ultrahigh theoretical energy density of 2600 Wh kg−1. Sulfurized polyacrylonitrile ...(SPAN) is considered a promising sulfur cathode to substitute carbon/sulfur (C/S) composites to afford higher Coulombic efficiency, improved cycling stability, and potential high‐energy‐density Li–SPAN batteries. However, the instability of the Li‐metal anode threatens the performances of Li–SPAN batteries bringing limited lifespan and safety hazards. Li‐metal can react with most kinds of electrolyte to generate a protective solid electrolyte interphase (SEI), electrolyte regulation is a widely accepted strategy to protect Li‐metal anodes in rechargeable batteries. Herein, the basic principles and current challenges of Li–SPAN batteries are addressed. Recent advances on electrolyte regulation towards stable Li‐metal anodes in Li–SPAN batteries are summarized to suggest design strategies of solvents, lithium salts, additives, and gel electrolyte. Finally, prospects for future electrolyte design and Li anode protection in Li–SPAN batteries are discussed.
Increased attention SPAN: Recent advances in electrolyte regulation towards stable lithium‐metal anodes for Li‐sulfurized polyacrylonitrile (SPAN) batteries are summarized to afford design strategies of solvents, lithium salts, additives, and gel electrolyte.
This study aims to evaluate specific risk factors influencing prognosis of HIV-infected patients with toxoplasma encephalitis (TE) in order to develop a prognostic risk scoring system for them.
This ...is a six-center retrospective study of hospitalized HIV/TE patients. Data including six-week mortality after diagnosis, baseline characteristics, clinical features, laboratory tests and radiological characteristics of eligible patients were assimilated for risk model establishing.
In this study, the six-week mortality among 94 retrospective cases was 11.7% (11/94). Seven specific risk factors, viz. time from symptom onset to presentation, fever, dizziness, CD4+ T-cell counts, memory deficits, patchy brain lesions, and disorders of consciousness were calculated to be statistically associated with mortality. A criterion value of '9' was selected as the optimal cut-off value of the established model. The AUC of the ROC curve of this scoring model was 0.976 (p < 0.001). The sensitivity and specificity of the risk scoring model was 100.0 and 86.9%, respectively, which were 81.8 and 94.1% of this scoring model in the verification cohort, respectively.
The developed scoring system was established with simple risk factors, which also allows expeditious implementation of accurate prognostication, and appropriate therapeutic interventions in HIV-infected patients with TE.
Ether based electrolytes have surfaced as alternatives to conventional carbonates allowing for enhanced electrochemical performance of sodium-ion batteries; however, the primary source of the ...improvement remains poorly understood. Here we show that coupling titanium dioxide and other anode materials with diglyme does enable higher efficiency and reversible capacity than those for the combination involving ester electrolytes. Importantly, the electrolyte dependent performance is revealed to be the result of the different structural evolution induced by a varied sodiation depth. A suit of characterizations show that the energy barrier to charge transfer at the interface between electrolyte and electrode is the factor that dominates the interfacial electrochemical characteristics and therefore the energy storage properties. Our study proposes a reliable parameter to assess the intricate sodiation dynamics in sodium-ion batteries and could guide the design of aprotic electrolytes for next generation rechargeable batteries.
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