Research has established that the incorporation of 3D-printed lattice structures in cement substrates enhances the mechanical properties of cementitious materials. However, given that 3D-printing materials, notably polymers, exhibit varying degrees of mechanical performance under high-temperature conditions, their efficacy is compromised. Notably, at temperatures reaching 150 °C, these materials soften and lose their load-bearing capacity, necessitating further investigation into their compressive mechanical behavior in such environments. This study evaluates the compressibility of cement materials reinforced with lattice structures made from polyamide 6 (PA6) across different structural configurations and ambient temperatures, employing ABAQUS for simulation. Six distinct 3D-printed lattice designs with equivalent volume but varying configurations were tested under ambient temperatures of 20 °C, 50 °C, and 100 °C to assess their impact on compressive properties. The findings indicate that heightened ambient temperatures significantly diminish the reinforcing effect of 3D-printed materials on the properties of cement-based composites.
INTRODUCTION: This study aimed to evaluate the accuracy of our own artificial intelligence (AI)-generated model to assess automated segmentation and quantification of body composition-derived computed tomography (CT) slices from the lumber (L3) region in colorectal cancer (CRC) patients. METHODS: A total of 541 axial CT slices at the L3 vertebra were retrospectively collected from 319 patients with CRC diagnosed during 2012-2019 at a single Australian tertiary institution, Western Health in Melbourne. A two-dimensional U-Net convolutional network was trained on 338 slices to segment muscle, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Manual reading of these same slices of muscle, VAT and SAT was created to serve as ground truth data. The Dice similarity coefficient was used to assess the U-Net-based segmentation performance on both a validation dataset (68 slices) and a test dataset (203 slices). The measurement of cross-sectional area and Hounsfield unit (HU) density of muscle, VAT and SAT were compared between two methods. RESULTS: The segmentation for muscle, VAT and SAT demonstrated excellent performance for both the validation (Dice similarity coefficients >0.98, respectively) and test (Dice similarity coefficients >0.97, respectively) datasets. There was a strong positive correlation between manual and AI segmentation measurements of body composition for both datasets (Spearman's correlation coefficients: 0.944-0.999, P < 0.001). CONCLUSIONS: Compared to the gold standard, this fully automated segmentation system exhibited a high accuracy for assessing segmentation and quantification of abdominal muscle and adipose tissues of CT slices at the L3 in CRC patients.
Microcantilever structures such as microgears play an important role in precision mechanisms, where highly accurate cantilever characteristics guarantee the reliable function of these structures. Projection-based stereolithography (PSL) technology is widely used to fabricate sophisticated microstructures owing to its high precision and remarkable efficiency, and plenty of works have been done to improve the precision of structures with macroscale. However, the shape accuracy of microcantilever structures fabricated through PSL process is always neglected, which severely hinders its application in precision mechanisms. In this work, we investigated the influence of major factors on the shape accuracy of microcantilever structures in PSL process through orthogonal tests. Different resin materials were tested to investigate the influence of material properties. Printing experiments showed that for a given PSL system, microcantilever structures with confined size could be directly and accurately manufactured using a set of optimized processing parameters, which dramatically speed up the production process and effectively improved the reliability of microcantilevers. This work provides a comprehensive understanding of the capability of PSL to fabricate microcantilever structures and guides the manufacturing processes of micromechanisms with cantilever features, which effectually promotes the industrial application of PSL technology.
BACKGROUND: Formolase (FLS) is a computationally designed enzyme that catalyzes the carboligation of two or three C1 formaldehyde molecules into C2 glycolaldehyde or C3 dihydroxyacetone (DHA). FLS lays the foundation for several artificial carbon fixation and valorization pathways, such as the artificial starch anabolic pathway. However, the application of FLS is limited by its low catalytic activity and product promiscuity. FINDINGS: FLS, designed and engineered based on benzoylformate decarboxylase from Pseudomonas putida, was selected as a candidate for modification. To evaluate its catalytic activity, 25 residues located within an 8 Å distance from the active center were screened using single-point saturation mutagenesis. A screening approach based on the color reaction of the DHA product was applied to identify the desired FLS variants. After screening approximately 5,000 variants (approximately 200 transformants per site), several amino acid sites that were not identified by directed evolution were found to improve DHA formation. The serine-to-phenylalanine substitution at position 236 improved the activity towards DHA formation by 7.6-fold. Molecular dynamics simulations suggested that the mutation increased local hydrophobicity at the active site, predisposing the cofactor-C2 intermediate to nucleophilic attack by the third formaldehyde molecule for subsequent DHA generation. CONCLUSIONS: This study provides improved FLS variants and valuable information into the influence of residues adjacent to the active center affecting catalytic efficiency, which can guide the rational engineering or directed evolution of FLS to optimize its performance in artificial carbon fixation and valorization.
Environmental factors such as diet and lifestyle can influence the health of both mothers and offspring. However, its transgenerational transmission and underlying mechanisms remain largely unknown. Here, using a maternal lactation-period low-protein diet (LPD) mouse model, we show that maternal LPD during lactation causes decreased survival and stunted growth, significantly reduces ovulation and litter size, and alters the gut microbiome in the female LPD-F1 offspring. The transcriptome of LPD-F1 metaphase II (MII) oocytes shows that differentially expressed genes are enriched in female pregnancy and multiple metabolic processes. Moreover, maternal LPD causes early stunted growth and impairs metabolic health, which is transmitted over two generations. The methylome alteration of LPD-F1 oocytes can be partly transmitted to the F2 oocytes. Together, our results reveal that LPD during lactation transgenerationally affects offspring health, probably via oocyte epigenetic changes.
BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. CONCLUSION: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.
Designing a functional, conductive metal-organic framework (cMOF) is highly desired. Substantial efforts have been dedicated to increasing the intralayer conjugation of the cMOFs, while less dedication has been made to tuning the interlayer charge transport of the metal-organic nanosheets for the controllable dielectric property. Here, we construct a series of conductive bimetallic organic frameworks of (ZnxCu3-x) (hexahydroxytriphenylene)2 (ZnCu-HHTP) to allow for fine-tuned interlayer spacing of two-dimensional frameworks, by adjusting the ratios of Zn and Cu metal ions. This approach for atomistic interlayer design allows for the finely control of the charge transport, band structure, and dielectric properties of the cMOF. As a result, Zn3Cu1-HHTP, with an optimal dielectric property, exhibits high-efficiency absorption in the gigahertz microwave range, achieving an ultra-strong reflection loss of -81.62 decibels. This study not only advances the understanding of the microstructure-function relationships in cMOFs but also offers a generic nanotechnology-based approach to achieving controllable interlayer spacing in MOFs for the targeted applications.
Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children, and botryoid rhabdomyosarcoma (BRMS) represents a subtype of RMS. BRMS primarily occurs in infants, young children, and adolescent females, with a predilection for mucosa-lined hollow organs such as the bladder, vagina, bile duct, and so on. Its occurrence in the biliary tract is extremely rare. Due to the high malignancy and rapid metastasis of biliary botryoid rhabdomyosarcoma, early diagnosis and treatment are crucial for improving prognosis.
Improving interface connectivity of magnetic nanoparticles in carbon aerogels is crucial, yet challenging for assembling lightweight, elastic, high-performance, and multifunctional carbon architectures. Here, an in situ growth strategy to achieve high dispersion of metal-organic frameworks (MOFs)-anchored cellulose nanofibrils to enhance the interface connection quality is proposed. Followed by a facile freeze-casting and carbonization treatment, sustainable biomimetic porous carbon aerogels with highly dispersed and closely connected MOF-derived magnetic nano-capsules are fabricated. Thanks to the tight interface bonding of nano-capsule microstructure, these aerogels showcase remarkable mechanical robustness and flexibility, tunable electrical conductivity and magnetization intensity, and excellent electromagnetic wave absorption performance. Achieving a reflection loss of -70.8 dB and a broadened effective absorption bandwidth of 6.0 GHz at a filling fraction of merely 2.2 wt.%, leading to a specific reflection loss of -1450 dB mm-1, surpassing all carbon-based aerogel absorbers so far reported. Meanwhile, the aerogel manifests high magnetic sensing sensibility and excellent thermal insulation. This work provides an extendable in situ growth strategy for synthesizing MOF-modified cellulose nanofibril structures, thereby promoting the development of high-value-added multifunctional magnetic carbon aerogels for applications in electromagnetic compatibility and protection, thermal management, diversified sensing, Internet of Things devices, and aerospace.
A green and practical protocol of defluoroborylation of polyfluoroarenes with stable and readily accessible NHC-borane was developed, using 1,2-diphenyldisulfane as a hydrogen atom transfer (HAT) and single electron transfer (SET) reagent precursor under visible-light irradiation, leading to the concise formation of value-added fluorinated organoboron scaffolds. Mechanism studies revealed the method underwent a boryl radical addition reaction with polyfluoroarene, followed by successive single electron transfer pathways and defluorination of the C-F bond to offer the targeted product. This unprecedented platform relies on 1,2-diphenyldisulfane and base without using expensive photocatalysts, highlighting the methodology has promising application value to prepare borylated polyfluoroarene compounds.
PURPOSE: Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease. However, limited studies have investigated the actual efficacy of selenium in GO therapy. This longitudinal study explored the effect of selenium on QOL and prognosis of patients with mild-to-moderate GO. METHODS: We conducted a 5-year prospective controlled cohort clinical trial to determine the effect of selenium on 74 patients with mild-to-moderate GO. Patients received selenium yeast or placebo orally for 6 months and were followed up at 6 months and at 5 years by biochemical examination, ophthalmologist evaluation and QOL questionnaire to assess oculopathy and QOL. RESULTS: (1) During a follow-up period of 3-6 months, in the selenium group, the symptoms of tearing, grittiness and conjunctival congestion improved (P < 0.01); clinical activity scores and total GO-QOL scores increased relative to baseline (P < 0.01); TRAb was decreased at the 6-month evaluation (P = 0.003); and patients treated with selenium had a higher rate of improvement and a lower rate of worsening than patients treated with placebo (P < 0.05). (2) Exploratory evaluations at 6 months after drug withdrawal confirmed the earlier results; further changes included alleviation of blurred vision and double vision symptoms in the selenium group (P < 0.01). (3) At the 5-year follow-up, compared with baseline, proptosis, clinical activity scores, TRAb level and total GO-QOL scores in both the selenium and placebo groups were significantly improved (P < 0.01). CONCLUSION: Six months of selenium supplementation may effectively change the early course of mild-to-moderate GO, but this regimen makes no difference in long-term outcomes.
RATIONALE AND OBJECTIVES: This study aimed to determine the feasibility of using the deep learning (DL) method to determine the degree (whether myometrial invasion [MI] >50%) of MI in patients with endometrial cancer (EC) based on ultrasound (US) images. MATERIALS AND METHODS: From September 2017 to April 2023, 1289 US images of 604 patients with EC who underwent surgical resection at center 1, center 2 or center 3 were obtained and divided into a training set and an internal validation set. Ninety-five patients from center 4 and center 5 were randomly selected as the external testing set according to the same criteria as those for the primary cohort. This study evaluated three DL models trained on the training set and tested them on the validation and testing sets. The models' performance was analyzed based on accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), and the performance of the models was subsequently compared with that of 15 radiologists. RESULTS: In the final clinical diagnosis of MI in patients with EC, EfficientNet-B6 showed the best performance in the testing set in terms of area under the curve (AUC) [0.814, 95% CI (0.746-0.882]; accuracy [0.802, 95% CI (0.733-0.855]; sensitivity [0.623]; specificity [0.879]; positive likelihood ratio (PLR) [6.750]; and negative likelihood ratio (NLR) [0.389]. The diagnostic efficacy of EfficientNet-B6 was significantly better than that of the 15 radiologists, with an average diagnostic accuracy of 0.681, average AUC of 0.678, AUC of the best performance of 0.739, accuracy of 0.716, sensitivity of 0.806, specificity 0.672, PLR2.457, and NLR 0.289. CONCLUSION: Based on the preoperative US images of patients with EC, the DL model can accurately determine the degree of endometrial MI; the performance of this model is significantly better than that of radiologists, and it can effectively assist in clinical treatment decisions.
OBJECTIVES: The MED12 gene encodes mediator complex subunit 12, which is a component of the mediator complex involved in the transcriptional regulation of nearly all RNA polymerase II-dependent genes. MED12 variants have previously been associated with developmental disorders with or without nonspecific intellectual disability. This study aims to explore the association between MED12 variants and epilepsy. MATERIALS AND METHODS: Trios-based whole-exome sequencing was performed in a cohort of 349 unrelated cases with partial (focal) epilepsy without acquired causes. The genotype-phenotype correlations of MED12 variants were analyzed. RESULTS: Five hemizygous missense MED12 variants, including c.958A>G/p.Ile320Val, c.1757G>A/p.Ser586Asn, c.2138C>T/p.Pro713Leu, c.3379T>C/p.Ser1127Pro, and c.4219A>C/p.Met1407Leu were identified in five unrelated males with partial epilepsy. All patients showed infrequent focal seizures and achieved seizure free without developmental abnormalities or intellectual disability. All the hemizygous variants were inherited from asymptomatic mothers (consistent with the X-linked recessive inheritance pattern) and were absent in the general population. The two variants with damaging hydrogen bonds were associated with early-onset seizures. Further genotype-phenotype analysis revealed that congenital anomaly disorder (Hardikar syndrome) was associated with (de novo) destructive variants in an X-linked dominant inheritance pattern, whereas epilepsy was associated with missense variants in an X-linked recessive inheritance pattern. Phenotypic features of intellectual disability appeared as the intermediate phenotype in terms of both genotype and inheritance. Epilepsy-related variants were located at the MED12-LCEWAV domain and the regions between MED12-LCEWAV and MED12-POL. CONCLUSION: MED12 is a potentially causative gene for X-linked recessive partial epilepsy without developmental or intellectual abnormalities. The genotype-phenotype correlation of MED12 variants explains the phenotypic variations and can help the genetic diagnosis.
Epilepsies, Partial , Epilepsy , Intellectual Disability , Male , Humans , Intellectual Disability/genetics , Genes, X-Linked/genetics , Phenotype , Mediator Complex/genetics , Mediator Complex/chemistry , Mediator Complex/metabolism , Epilepsies, Partial/genetics , Epilepsy/genetics , Transcription Factors/genetics
INTRODUCTION: The discovery of longevity molecules that delay aging and prolong lifespan has always been a dream of humanity. Sitagliptin phosphate (SIT), an oral dipeptidyl peptidase-4 (DPP-4) inhibitor, is an oral drug commonly used in the treatment of type 2 diabetes (T2D). In addition to being antidiabetic, previous studies have reported that SIT has shown potential to improve health. However, whether SIT plays a role in the amelioration of aging and the underlying molecular mechanism remain undetermined. METHODS: Caenorhabditis elegans (C. elegans) was used as a model of aging. Lifespan assays were performed with adult-stage worms on nematode growth medium plates containing FUdR with or without the specific concentration of SIT. The period of fast body movement, body bending rates, and pharyngeal pumping rates were recorded to assess the healthspan of C. elegans. Gene expression was confirmed by GFP fluorescence signal of transgenic worms and qPCR. In addition, the intracellular reactive oxygen species levels were measured using a free radical sensor H2DCF-DA. RESULTS: We found that SIT significantly extended lifespan and healthspan of C. elegans. Mechanistically, we found that several age-related pathways and genes were involved in SIT-induced lifespan extension. The transcription factors DAF-16/FOXO, SKN-1/NRF2, and HSF-1 played important roles in SIT-induced longevity. Moreover, our findings illustrated that SIT-induced survival benefits by inhibiting the insulin/insulin-like signaling pathway and activating the dietary restriction-related and mitochondrial function-related signaling pathways. CONCLUSION: Our work may provide a theoretical basis for the development of anti-T2D drugs as antiaging drugs, especially for the treatment of age-related disease in diabetic patients.
Caenorhabditis elegans Proteins , Diabetes Mellitus, Type 2 , Animals , Humans , Caenorhabditis elegans/genetics , Longevity , Insulin , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Sitagliptin Phosphate/pharmacology , Sitagliptin Phosphate/metabolism , Signal Transduction , Forkhead Transcription Factors/genetics , Oxidative Stress
Motor endplates of the interossei muscles become destabilized, whereas those of the biceps muscles remain stable in a rat model of obstetric brachial plexus palsy. However, it is unclear whether the morphology of the motor endplates of the interossei muscles is different from that of the biceps muscles in normal rat. We hypothesized that the motor endplates in the interossei muscles have specific characteristics different from those in the biceps muscles. The motor endplates were labeled with α-bungarotoxin and synaptophysin. The cross-sectional areas of the muscle fibers, the morphologies of the motor endplates, and the absolute and normalized areas (corrected by muscle fiber diameter) of the motor endplates of the interossei muscles and the biceps muscles were compared in rats at 1, 3, and 5 weeks after birth. The cross-sectional area of the interossei muscles and biceps muscle fibers were found to have increased gradually at 1, 3, and 5 weeks, but that of the biceps muscles was larger than that of the interossei muscles. The motor endplates of the interossei muscles and the biceps muscles gradually develop from crescent to pretzel shape after birth, and those of the interossei muscles have a smaller area. At 1, 3, and 5 weeks postnatally, the area of postnatal normalized motor endplates of the interossei muscles was much smaller than that of the biceps muscles. A better understanding of the morphological differences of the motor endplates between the interossei muscles and the biceps muscles may help to understand their physiological and pathological changes.
Muscle, Skeletal , Neuromuscular Junction , Rats , Animals , Motor Endplate , Muscle Fibers, Skeletal
The exploitation of advanced electromagnetic functional devices is perceived as the effective prescription to deal with environmental contamination and energy deficiency. From the perspective of observing and imitating nature, pine branch-like zirconium dioxide/cobalt nanotubes@nitrogen-doped carbon nanotubes are synthesized victoriously through maneuverable electrospinning process and follow-up thermal treatments. In particular, introducing carbon nanotubes on the surface of hollow nanofibers to construct hierarchical architecture vastly promoted the material's dielectric properties by significantly augmenting specific surface area, generating abundant heterogeneous interfaces, and inducing the formation of defects. Supplemented by the synergistic effect between each constituent, ultra-strong attenuation capacity and perfect impedance matching characteristics are implemented simultaneously, and jointly made contributions to the splendid microwave absorption performance with a minimum reflection loss of -67.9 dB at 1.5 mm. Moreover, this fibrous absorber also exhibited promising potential to be utilized as a green and efficient electromagnetic interference shielding material when the filler loading is enhanced. Therefore, this design philosophy is destined to inspire the future development of energy conversion and storage devices, and provide theoretical direction for the creation of sophisticated electromagnetic functional materials.
The p38 mitogen-activated protein kinase (p38 MAPK) is a multifunctional molecule that is involved in cellular response to various stressful stimuli. In the present study, the full-length cDNA sequence of p38 MAPK (Lcp38 MAPK) was identified from the large yellow croaker Larimichthys crocea, which encoded a polypeptide of 361 amino acid residues. The predicted Lcp38 MAPK protein contained a highly conserved Thr-Gly-Tyr (TGY) motif, a glutamate and aspartate (ED) site, a substrate binding site (Ala-Thr-Arg-Trp < ATRW>), and a serine/threonine kinase catalytic (S_TKc) domain characteristic of the MAPK family. The constitutive expression of Lcp38 MAPK was detected in most of the tissues examined with the strongest expression in intestine. Subcellular localization in LCK cells (kidney cell line from a L. crocea) revealed that Lcp38 MAPK existed in both the cytoplasm and cell nucleus. The expression of Lcp38 MAPK after temperature stress was tested in LCK cells. The results indicated that Lcp38 MAPK transcripts were significantly upregulated under both cold (10 °C) and heat stress (35 °C) (P < 0.05). Furthermore, the phosphorylation levels of p38 MAPK as well the transcriptional levels of heat shock protein 27 (HSP27) and caspase3 in LCK cells were significantly induced under thermal exposure (P < 0.05). However, the cold- and heat induced HSP27 and caspase3 expression was significantly suppressed by SB203580, a specific inhibitor of p38-MAPK (P < 0.05). These findings indicated that Lcp38 MAPK might be involved in the cellular stress response via HSP27 and caspase3 in large yellow croaker.
Perciformes , p38 Mitogen-Activated Protein Kinases , Animals , p38 Mitogen-Activated Protein Kinases/genetics , HSP27 Heat-Shock Proteins/metabolism , Phosphorylation , Temperature , Perciformes/genetics , Perciformes/metabolism
Phenols, dyes, and metal ions present in industrial wastewater can adversely affect the environment and leach biological carcinogens. Given that the current research focuses only on the removal of one or two of those categories. Herein, this work reports a novel ZIF-8@IL-MXene/Poly(N-isopropylacrylamide) (NIPAM) nanocomposite hydrogel that can efficiently and conveniently absorb and separate multiple pollutants from industrial wastewater. Ionic liquid (IL) was grafted onto MXene surfaces using a one-step method, and then incorporated into NIPAM monomer solutions to obtain the IL-MXene/PNIPAM composite hydrogel via in-situ polymerization. ZIF-8@IL-MXene/PNIPAM nanocomposite hydrogels were obtained by in-situ growth of ZIF-8 on the pore walls of composite hydrogels. As-prepared nanocomposite hydrogel showed excellent mechanical properties and can withstand ten repeated compressions without any damage, the specific surface area increased by 100 times, and the maximum adsorption capacities for p-nitrophenol (4-NP), crystal violet (CV), and copper ion (Cu2+) were 198.40, 325.03, and 285.65 mg g-1, respectively, at room temperature. The VPTTs of all hydrogels ranged from 33 to 35 °C, so the desorption process can be achieved in deionized water at 35-40 °C, and its adsorption capacities after five adsorption-desorption cycles decreased to 79%, 91%, and 29% for 4-NP, CV, and Cu2+, respectively. The adsorption data fitting results follow pseudo-second-order kinetics and Freundlich models, which is based on multiple interactions between the functional groups contained in hydrogels and adsorbent molecules. The hydrogel is the first to realize the high-efficiency adsorption of phenols, dyes and metal ions in industrial wastewater simultaneously, and the preparation process of hydrogels is environmentally friendly. Also, giving hydrogel multifunctional adsorption is beneficial to promote the development of multifunctional adsorption materials.
Acrylamides , Ionic Liquids , Nitrites , Transition Elements , Water Pollutants, Chemical , Copper , Nanogels , Wastewater , Adsorption , Coloring Agents , Hydrogels/chemistry , Ions , Phenols , Water Pollutants, Chemical/chemistry , Kinetics , Hydrogen-Ion Concentration
The treatment of PML/RARA+ acute promyelocytic leukemia (APL) with all-trans-retinoic acid and arsenic trioxide (ATRA/ATO) has been recognized as a model for translational medicine research. Though an altered microenvironment is a general cancer hallmark, how APL blasts shape their plasma composition is poorly understood. Here, we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters, proteomes, and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy. Our study revealed the two prominent features of the APL plasma, suggesting a possible involvement of APL blasts in modulating plasma composition. One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts, and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA. Furthermore, results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage, which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins. Overall, our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.
Arsenic Trioxide , Blood Proteins , Leukemia, Promyelocytic, Acute , Tretinoin , Humans , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/blood , Tretinoin/therapeutic use , Arsenic Trioxide/therapeutic use , Cross-Sectional Studies , Blood Proteins/metabolism , Male , Female , Metabolome , Adult , Antineoplastic Agents/therapeutic use , Middle Aged
BACKGROUND: Bilirubin's ability to lower lipid levels was confirmed by several studies, but those studies mainly focused on total bilirubin (TBil). The present study aimed to elucidate the correlations of the two subtypes of bilirubin with lipid levels. METHODS: A total of 1732 male patients undergoing health checkups were categorized into three groups according to the levels of direct bilirubin (DBil) and indirect bilirubin (IBil). The differences in medical characteristics among the three groups were analysed. RESULTS: Subjects in the elevated DBil group had the lowest serum alanine aminotransferase (ALT), total cholesterol (TC), blood urea nitrogen (BUN), γ-glutamyl transpeptidase (γ-GT), fasting blood glucose (FBG), haemoglobin (HGB), and triglyceride (TG) levels in contrast to the other groups (P < 0.01), while subjects in the elevated IBil group had the highest ALT, γ-GT, BUN, serum creatinine (SCR), HGB, TC, and TG levels among the three groups (P < 0.01). DBil levels exhibited a significant negative correlation with TC (r = -0.777, P < 0.01) and TG (r = -0.397, P < 0.01) levels, while IBil levels exhibited a significant positive correlation with TC (r = 0.790, P < 0.01) and TG (r = 0.302, P < 0.01) levels. The frequencies of abnormal TC, TG, HGB and BUN levels were the lowest in the elevated DBil group, while the levels of these four variables were the highest in the elevated IBil group. Mildly elevated DBil levels were related to lower TG (OR = 0.112, 95% CI = 0.027-0.458) and TC (OR = 0.097, 95% CI = 0.013-0.700), and mildly elevated IBil levels were connected with increased TC (OR = 3.436, 95% CI = 2.398-4.924) and TG (OR = 1.636, 95% CI = 1.163-2.303). DBil was an independent protective factor against increased TC (OR = 0.702, 95% CI = 0.602-0.817, P < 0.01) and TG (OR = 0.632, 95% CI = 0.541-0.739, P < 0.01) levels, and IBil was an independent risk factors for increased TC (OR = 1.251, 95% CI = 1.176-1.331, P < 0.01). CONCLUSIONS: DBil was an independent protective factor against high TC and TG levels. IBil was an independent risk factors for elevated TC levels. The prognostic value of IBil levels warrants further attention.
Bilirubin , gamma-Glutamyltransferase , Humans , Male , Liver Function Tests , Prognosis , Lipids
