The accuracy and reliability of different midsagittal planes in the symmetry assessment using cone-beam computed tomography.

Symmetry is an essential component of esthetic assessment. Accurate assessment of facial symmetry is critical to the treatment plan of orthognathic surgery and orthodontic treatment. However, there is no internationally accepted midsagittal plane (MSP) for orthodontists and orthognathic surgeons. The purpose of this study was to explore a clinically friendly MSP, which is more accurate and reliable than what is commonly used in symmetry assessment. Forty patients with symmetric craniofacial structures were analyzed on cone-beam computed tomography (CBCT) scans. The CBCT data were exported to the Simplant Pro software to build four reference planes that were constructed by nasion (N), basion (Ba), sella (S), odontoid (Dent), or incisive foramen (IF). A total of 31 landmarks were located to determine which reference plane is the most optimal MSP by comparing the asymmetry index (AI). The mean value of AI showed a significant difference (p < 0.05) among four reference planes. Also, the mean value of AI for all landmarks showed that Plane 2 (consisting of N, Ba, and IF) and Plane 4 (consisting of N, IF, and Dent) were more accurate and stable. In conclusion, the MSP consisting of N, Dent, and IF shows more accuracy and reliability than the other planes. Further, it is more clinically friendly because of its significant advantage in landmarking.

A Critical Candidate Node-Based Attack Model of Network Controllability.

The controllability of complex networks is a core issue in network research. Assessing the controllability robustness of networks under destructive attacks holds significant practical importance. This paper studies the controllability of networks from the perspective of malicious attacks. A novel attack model is proposed to evaluate and challenge network controllability. This method disrupts network controllability with high precision by identifying and targeting critical candidate nodes. The model is compared with traditional attack methods, including degree-based, betweenness-based, closeness-based, pagerank-based, and hierarchical attacks. Results show that the model outperforms these methods in both disruption effectiveness and computational efficiency. Extensive experiments on both synthetic and real-world networks validate the superior performance of this approach. This study provides valuable insights for identifying key nodes crucial for maintaining network controllability. It also offers a solid framework for enhancing network resilience against malicious attacks.

Coupling Iron Sludge Addition and Intermittent Aeration for Achieving Simultaneous Methanogenesis, Feammox, and Denitrification in a Single Reactor Treating Fish Sludge.

An integrated anaerobic digestion system for the simultaneous removal of carbon and nitrogen from fish sludge was developed by coupling iron sludge supplementation with intermittent aeration. In terms of nitrogen removal, Fe(III) in iron sludge could trigger Feammox reactions and intermittent aeration could drive the Fe(II)/Fe(III) cycle to sustain continuous ammonia removal. Mass balance analysis suggested that nitrate was the main product of Feammox, which was subsequently removed through heterotrophic denitrification. In terms of carbon removal, the Fe(III)-induced dissimilatory iron reduction (DIR) process significantly promoted fish sludge hydrolysis and provided more simple organics for methanogens and denitrifiers, but aeration showed a negative impact on methanogenesis. To promote nitrogen removal and avoid serious methanogenesis inhibition, different aeration intensities were studied. Results showed that compared with the control without aeration or iron sludge addition, aeration for 5 min every 3 days (150 mL/min) contributed to a 29.0% lower NH4+-N concentration and a 12.1% lower total chemical oxygen demand level on day 28, and the decline in methane yield was acceptable (only 13.5% lower). Simultaneous methanogenesis, Feammox, and denitrification in a single reactor treating fish sludge were achieved, which provides a simple and low-cost strategy for the treatment of organic wastewater.

Effects of sgRNAs, Promoters, and Explants on the Gene Editing Efficiency of the CRISPR/Cas9 System in Chinese Kale.

The CRISPR/Cas9 system is extensively used for plant gene editing. This study developed an efficient CRISPR/Cas9 system for Chinese kale using multiple sgRNAs and two promoters to create various CRISPR/Cas9 vectors. These vectors targeted BoaZDS and BoaCRTISO in Chinese kale protoplasts and cotyledons. Transient transformation of Chinese kale protoplasts was assessed for editing efficiency at three BoaZDS sites. Notably, sgRNA: Z2 achieved the highest efficiency (90%). Efficiency reached 100% when two sgRNAs targeted BoaZDS with a deletion of a large fragment (576 bp) between them. However, simultaneous targeting of BoaZDS and BoaCRTISO yielded lower efficiency. Transformation of cotyledons led to Chinese kale mutants with albino phenotypes for boazds mutants and orange-mottled phenotypes for boacrtiso mutants. The mutation efficiency of 35S-CRISPR/Cas9 (92.59%) exceeded YAO-CRISPR/Cas9 (70.97%) in protoplasts, and YAO-CRISPR/Cas9 (96.49%) surpassed 35S-CRISPR/Cas9 (58%) in cotyledons. These findings introduce a strategy for enhancing CRISPR/Cas9 editing efficiency in Chinese kale.

Efficient degradation of 2,4-dichlorophenol by heterogeneous electro-Fenton using bulk carbon aerogels modified in situ with FeCo-LDH as cathodes: Operational parameters and mechanism exploration.

In this study, an in situ grown FeCo-Layered double hydroxide anchored to the surface of a bulk carbon aerogel (FeCo-LDH/CA) for contaminant degradation during the heterogeneous electro-Fenton (EF) process. The results exhibited that the FeCo-LDH/CA cathode achieved 100% of 2,4-dichlorophenol (2,4-DCP = 20 mg/L) degradation within 120 min at pH = 3, application current 20 mA, and Na2SO4 concentration 0.05 M. Moreover, the degradation efficiency was impressive in the range of pH = 2-9. The coexistence of the Fe (III)/Fe (II) and Co (III)/Co (II) as active sites on the cathode surface promoted the in-situ decomposition of H2O2 to form reactive oxygen species (ROS). •OH and O2- were confirmed to be the major degradation pollutants of ROS. Furthermore, density functional theory (DFT) was used to predict the reaction sites of 2,4-DCP, and its possible degradation pathways were proposed. The toxicity of intermediate products was evaluated and decreased after degradation. In addition, the eight cycle experiments and the degradation of other typical contaminants demonstrated the satisfactory stability and applicability of the synthetic cathode. This study presents the preparation of an efficient and stable EF cathode, further promoting the application of iron-based composites in wastewater treatment.

Investigation of CuCoFe-LDH as an efficient and stable catalyst for the degradation of acetaminophen in heterogeneous electro-Fenton system: Key operating parameters, mechanisms and pathways.

Pharmaceuticals, as anthropogenic pollutants in a wide range of water sources, generally require specific treatment methods for degradation. A trimetallic layered double hydroxide (CuCoFe-LDH) was successfully fabricated by coprecipitation and applied as a novel heterogeneous electro-Fenton (EF) catalyst for the degradation of acetaminophen (ACT) from aqueous environments. The EF experiments showed that the CuCoFe-LDH/EF process achieved 100% of ACT degradation efficiency within 60 min at pH = 5, catalyst dosage of 0.50 g/L, current density of 10 mA/cm2 and initial ACT concentration of 20 mg/L. An impressive (>80%) mineralization of ACT was obtained over a wide pH range (pH 3-9) after 180 min. Meanwhile, the role of ·OH and O2.- were certified by radical quenching experiments and electron paramagnetic resonance (EPR) analysis. Through mechanism exploration, the coexistence of Cu and Co on Fe-based LDHs can accelerate the interfacial electron transfer and promote the formation of the reactive oxygen species (ROS), thus facilitating the EF process. Furthermore, the degradation by-products and possible degradation pathways of ACT in the CuCoFe-LDH/EF process were proposed. The reusability test and the treatment of various typical organic pollutants experiments indicated that the CuCoFe-LDH/EF process has excellent stability and broad application prospects. This work provides a valuable reference for the treatment of pharmaceuticals by the heterogeneous EF process in a wide range of pH.

The role of light wavelengths in regulating algal-bacterial granules formation, protein and lipid accumulation, and microbial functions.

High value-added products recovery from algal-bacterial granular sludge (ABGS) has received great attention recently. This study aimed to explore the role of different light wavelengths in regulating granule formation, protein and lipid production, and microbial functions. Bacterial granular sludge (BGS, R0) was most conducive to forming ABGS under blue (R2) light with the highest chlorophyll a (10.2 mg/g-VSS) and diameter (1800 µm), followed by red (R1) and white (R3) lights. R0-R3 acquired high protein contents (>164.8 mg/g-VSS) with essential amino acids above 44.4%, all of which were suitable for recycling, but R2 was the best. Also, blue light significantly increased total lipid production, while red light promoted the accumulation of some unsaturated fatty acids (C18:2 and C18:3). Some unique algae and dominant bacteria (e.g., Stigeoclonium, Chlamydomonas, and Flavobacteria) enrichment and some key functions (e.g., amino acid, fatty acid, and lipid biosynthesis) up-regulation in R2 might help to improve proteins and lipids quality. Combined, this study provides valuable guidance for protein and lipid recovery from ABGS.

Variation in the Main Health-Promoting Compounds and Antioxidant Capacity of Three Leafy Vegetables in Southwest China.

Malabar spinach (Basella alba), amaranth (Amaranthus tricolor), and sweet potato (Ipomoea batatas) are leafy vegetables found in Southwest China. The variation of chlorophyll, carotenoids, ascorbic acid, total flavonoids, phenolic compounds, and antioxidant capacity was studied in the leaves and stems of the three vegetables. The content of main health-promoting compounds and the antioxidant capacity in the leaves were higher than that in the stems, indicating that the leaves of the three vegetables possess greater nutritional value. The trend of total flavonoids in all three vegetables was similar to the trend of antioxidant capacity, suggesting that the total flavonoids may be the major antioxidants wihin these vegetables. Eight individual phenolic compounds were detected in three different vegetables. The most abundant levels of individual phenolic compounds in the leaves and stems of malabar spinach, amaranth, and sweet potato were 6'-O-feruloyl-d-sucrose (9.04 and 2.03 mg g-1 DW), hydroxyferulic acid (10.14 and 0.73 mg g-1 DW), and isorhamnetin-7-O-glucoside (34.93 and 6.76 mg g-1 DW), respectively. Sweet potato exhibited a higher total and individual phenolic compound content compared to malabar spinach and amaranth. Overall, the results demonstrate that the three leafy vegetables possess high nutritional value, and could be used not only for consumption but also in various other fields, including medicine and chemistry.

Clinical finite element analysis of mandibular displacement model treated with Twin-block appliance.

INTRODUCTION: The mechanical distribution of the mandible is an important factor that affects functional orthosis during Twin-block (TB) appliance correction. Changes in the mandible before and after TB appliance correction are also key factors in maintaining the therapeutic effect. Finite element analysis, a powerful numerical, analytical tool, is widely used to predict the stress and strain distribution of the craniofacial bone that orthodontics generates. METHODS: The sample was a 14-year-old male patient with Class II malocclusion during growth. A cone-beam computed tomography scan was undertaken at pretreatment and posttreatment. In the Finite element analysis of the pretreatment model, the remote displacement model of the mandible was established with the sella point as the center. A mandibular model under TB appliance loading was established. Its mandibular displacement and von Mises stress were compared before and after loading. Three-dimensional registration was conducted on the pretreatment and posttreatment models to measure the sagittal displacement of the centrosome. RESULTS: The force on the mandible occurred mainly in the condyle neck and medial mandible after the TB appliance moved the mandible. After displacement, the posterior upper margin of the condyle was farther away from the articular fossa. Three-dimensional registration results showed that new bone had formed behind and above the condyle after TB appliance treatment. CONCLUSION: The TB appliance provides additional advantages in treating skeletal Class II malocclusions by helping to reduce the burden on the temporomandibular joint and promoting the adaptive reconstruction of the mandible.

From waste-activated sludge to algae: a self-reliant cultivation process in photoreactors using saline conditions.

In this study, microalgae-bacteria (MB) systems using saline conditions (3 and 5% salinity) were built in order to use waste-activated sludge (AS) as raw material for cultivating lipid-rich microalgae. Algae were observed to be flourishing in 60 days of operation, which totally used the N and P released from the sludge biomass. A prominent improvement of lipid content in MB consortia was obtained under algae growth and salinity stimulation, which occupied 119-136 mg/g-SS rather than a low content of 12.1 mg/g-SS in AS. Lipid enrichment also brought a 3.1-3.3 times total heat release (THR) in the MB biomass. The marine spherical algae Porphyridium, as well as filamentous Geitlerinema, Nodularia, Leptolyngbya were found to be the main lipid producers and self-flocculated to 23.0% (R1) and 33.5% (R2) volume under the effect of residue EPS. This study had a big meaning in not only waste sludge reduction but also in manufacturing useful bioenergy products.

[Chemical constituents of Helleborus thibetanus].

The chemical constituents of Helleborus thibetanus were isolated and purified by silica gel column chromatography, Sephadex LH-20 gel column chromatography, and semi-preparative RP-HPLC, and the structures of all compounds were identified by modern spectrographic technology(MS, NMR). The MTT method was used to measure the cytotoxicity of compounds 1-8. Twelve compounds were isolated from the roots and rhizomes of H. thibetanus and were identified as(25R)-22ß,25-expoxy-26-[(O-ß-D-glucopyranosyl)oxy]-1ß,3ß-dihydroxyfurosta-5-en(1), ß-sitosterol myristate(2), ß-sitosterol lactate(3), ß-sitosterol 3-O-ß-D-glucopyrannoside(4), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(5), 1,3,5-trimethoxybenzene(6), 7,8-dimethylbenzo pteridine-2,4(1H,3H)-dione(7), 1H-indole-3-carboxylic acid(8), p-hydroxy cinnamic acid(9), lauric acid(10), n-butyl α-L-arabinofuranoside(11) and methyl-α-D-fructofuranoside(12), respectively. Among them, compound 1 is a new compound and named thibetanoside L; compounds 2, 5-8, 11 are first isolated from the family Ranunculaceae; compound 12 is isolated from the genus Helleborus for the first time. The results of MTT assay showed that the IC_(50) values of compounds 1-8 against HepG2 and HCT116 cells were greater than 100 µmol·L~(-1).

Creation of an Engineered Amide Synthetase Biocatalyst by the Rational Separation of a Two-Step Nitrile Synthetase.

The synthesis of amides through acid and amine coupling is one of the most commonly used reactions in medicinal chemistry, yet still requires atom-inefficient coupling reagents. There is a current demand to develop greener, biocatalytic approaches to amide bond formation. The nitrile synthetase (NS) enzymes are a small family of ATP-dependent enzymes which catalyse the transformation of a carboxylic acid into the corresponding nitrile via an amide intermediate. The Bacillus subtilis QueC (BsQueC) is an NS involved in the synthesis of 7-cyano-7-deazaguanine (CDG) natural products. Through sequence homology and structural analysis of BsQueC we identified three highly conserved residues, which could potentially play important roles in NS substrate binding and catalysis. Rational engineering led to the creation of a NS K163A/R204A biocatalyst that converts the CDG acid into the primary amide, but does not proceed to the nitrile. This study suggests that NSs could be further developed for coupling agent-free, amide-forming biocatalysts.

Gamma-Irradiation-Induced Degradation of the Water-Soluble Polysaccharide from Auricularia polytricha and Its Anti-Hypercholesterolemic Activity.

The water-soluble polysaccharides (APPs) isolated from the edible mushroom Auricularia polytricha were irradiated by γ-ray at doses of 10, 100, and 1000 kGy. The effect of gamma irradiation on the degradation of the polysaccharide was investigated. After irradiation treatment, the viscosity and molecular weight of APPs decreased with the increase in the irradiation dose. The changes in the enthalpy of APPs after irradiation treatment were observed. Meanwhile, SEM showed that R-APPs were crushed into fragments and the surfaces became smooth and wrinkled after irradiation. In further spectrum analysis, it was found that the glycoside bonds of the polysaccharides were broken and accompanied by the formation of double bonds. This suggested that gamma irradiation could cause the depolymerization and oxidation of polysaccharides. In addition, irradiated APPs could reduce the body weight of hyperlipidemia mice. The levels of serum and liver TC, TG, and serum LDH-c significantly decreased in hyperlipidemia mice after treatment by irradiated APPs. It indicated that gamma irradiation significantly improved the anti-hypolipidemic activity of APPs. The relationship between the physicochemical properties and hypolipidemic activity of polysaccharides was interpreted, which provides a theoretical basis for the further development of APP products. Gamma irradiation is a viable technology for macromolecular modification for degradation.

Design, synthesis of Cinnamyl-paeonol derivatives with 1, 3-Dioxypropyl as link arm and screening of tyrosinase inhibition activity in vitro.

This study aimed to obtain tyrosinase inhibitors for treating hyperpigmentation. A series of cinnamyl ester analogues were designed and synthesized with cinnamic acid (CA) and peaonol compounds. The safety, melanin content and inhibitory effects of all target compounds were evaluated. In the enzymatic activity test, the inhibitory rate of compounds 8, 13 and 14 had stronger inhibitory activity with the IC50 values of 20.7 µM, 13.98 µM and 15.16 µM, respectively than the positive drug kojic acid (IC50 with 30.83 µM). The cytotoxicity evaluation showed that compounds 13 and 14 have higher safety than the other compounds to the proliferation of B16F10 cells. The result of the melanocyte test supported that compound13 has stronger cellular tyrosinase inhibitory activity than kojic acid and arbutin at 100 µM and 200 µM. The enzyme kinetics mechanism revealed that compound 13 was a non-competitive inhibitor while compounds 8 and 14 were mixed inhibitors. For the experiments of melanin content and tyrosinase activity in the B16F10 melanona cells, the inhibition rates of compounds 8, 14 and 13 were with 19.62%, 20.59% and 23.83%, respectively. In addition, compound 13 revealed the highest inhibitory activity to tyrosinase in the melanocyte with inhibition rates of 23.83%, which was better than kojic acid and arbutin (19.21% and 20.45%) at the same concentration. In the anti-melanogenesis experiment, compounds 8 and 13 had better anti-melanin effects than kojic acid from 25 µM to 100 µM. In summary, the results indicated that compounds 8, 13 and 14 had better tyrosinase inhibitory activity and anti-melanogenesis activity. Especially, the compound 13 has potentiality to develop novel tyrosinase inhibitors and whitening agents. The docking studies results revealed that the functional group of compound 13 mostly depends on the phenolic hydroxyl moiety, and its hydroxyl group did not insert into the active site of tyrosinase, which was in agreement with the results of the kinetics study.

A Comparison of Two Molecular Methods for Detecting CALR Mutations in Myeloproliferative Neoplasms.

BACKGROUND: Myeloproliferative neoplasms (MPN) are hematopoietic disorders characterized by abnormal proliferation of the myeloid lineage. Three classic subtypes are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These disorders are well known for their association with the JAK2 V617F mutation, in addition to mutations in MPL exon 10, and JAK2 exon 12. CALR mutations were detected in approximately 20% to 25% of patients with ET and PMF and not in patients with PV. Most CALR mutations were deletions and insertions in exon 9, which caused frameshift mutations. METHODS: This study included 60 Taiwanese patients with MPN. We identified CALR mutations in patients with MPN using the high-resolution melting (HRM) analysis. Additionally, the HRM analysis was compared with ipsogen CALR RGQ PCR. To confirm the results of HRM and ipsogen CALR RGQ PCR, sequencing analysis was also conducted all the samples. RESULTS: Up to 6.25% of CALR mutations were successfully detected in patients with MPN using HRM analysis. Eight out of 65 patients (12.3%) were positive for the presence of CALR mutation, including p.L367fs*46 and p.K385fs*47. The results proved 100% comparable to those obtained using ipsogen CALR RGQ PCR. CONCLUSIONS: The HRM analysis and ipsogen CALR RGQ PCR are feasible and reliable techniques for the detection of CALR mutation. Furthermore, HRM offers several benefits, for example, it is time-saving, inexpensive, and does not require many personnel.

Ultra-broadband terahertz bandpass filter with dynamically tunable attenuation based on a graphene-metal hybrid metasurface.

We propose an ultra-broadband terahertz bandpass filter with dynamically tunable attenuation based on a graphene-metal hybrid metasurface. The metasurface unit cell is composed of two metal stripes enclosed with a graphene rectangular ring. Results show that when the metasurface is normally illuminated by a terahertz wave polarized along the metal stripes, it can act as an ultra-broadband bandpass filter over the spectral range from 1.49 THz to 4.05 THz, corresponding to a fractional bandwidth of 92%. Remarkably, high transmittance above 90% covering the range from 1.98 THz to 3.95 THz can be achieved. By changing the Fermi level of graphene, we find that the attenuation within the passband can be dynamically tuned from 2% to 66%. We expect that the proposed ultra-broadband terahertz bandpass filter with tunable attenuation will find applications in terahertz communication and detection and sensing systems.

Research on polycystic ovary syndrome: a bibliometric analysis from 2009 to 2019.

Polycystic ovary syndrome (PCOS) is a common reproductive and endocrine disease. However, there have not been any bibliometric studies on the latest scientific results and research trends of PCOS. This study aimed to review the state of research in PCOS worldwide. Publications on PCOS from 2009 to 2019 were identified and evaluated from the database Web of Science. A total of 7814 articles were retrieved. Shanghai Jiao Tong University published the most articles, with 218 publications. Gynecol Endocrinol had the greatest number of publications (n = 541). J Clin Endocr Metab was cited the most, with a total of 32,207 times. An article written by March et al. in 2010 had the most global citations (737 times) and local citations (463 times). From 2009 to 2019, the number of PCOS global publications gradually increased. Gynecol Endocrinol and Endocr Metab were popular journals for PCOS research. Research trends gradually shifted from treatment and methodology to genetics and basic research. The terms 'microrna,' 'rt qpcr,' 'lncrna,' and 'histological examination' may be hotspots that should be focused on in PCOS research.

Collagen Nanofilm-Coated Partially Deproteinized Bone Combined With Bone Mesenchymal Stem Cells for Rat Femoral Defect Repair by Bone Tissue Engineering.

BACKGROUND: The advantages of good biocompatibility, low degradation and low antigenicity of collagen, and the osteogenic differentiation characteristics of bone mesenchymal stem cells (BMSCs) were used to promote the recovery of bone defects using partially deproteinized bone (PDPB) by bone tissue engineering (BTE). METHODS: The BMSCs were identified by examining their potential for osteogenic, lipogenic, and chondrogenic differentiation. The prepared pure PDPB was ground into bone blocks 4 × 2 × 2 mm in size, which were divided into the following groups: PDPB group, PDPB + collagen group, PDPB + collagen + BMSC group, PDPB with a composite collagen nanofilm, and BMSCs injected into the tail vein. At 2, 4, 6, and 8 weeks after surgery, the effects of the implants in the different groups on bone defect repair were continuously and dynamically observed through x-ray examination, gross specimen observation, histological evaluation, and microvascularization detection. RESULTS: Postoperative x-ray examination and gross specimen observation revealed that, after 4 to 8 weeks, the external contour of the graft was gradually weakened, and the transverse comparison showed that the absorption of the graft and fusion of the defect were more obvious in PDPB + collagen + BMSC group than in PDPB group and PDPB + collagen group, and the healing was better (P < 0.05). Hematoxylin and eosin staining of histological sections showed very active proliferation of trabecular hematopoietic cells in groups PDPB + collagen + BMSC and PDPB + collagen. Masson's trichrome staining for evaluation of bone defect repair showed that the mean percent area of collagen fibers was greater in PDPB + collagen + BMSC group than in the PDPB group, with degradation of the scaffold material and the completion of repair. Immunofluorescence staining showed significantly enhanced expression of the vascular marker CD31 in group C (P < 0.05). CONCLUSIONS: The proposed hybrid structure of the collagen matrix and PDPB provides an ideal 3-dimensional microenvironment for patient-specific BTE and cell therapy applications. The results showed that collagen appeared to regulate MSC-mediated osteogenesis and increase the migration and invasion of BMSCs. The combination of collagen nanofilm and biological bone transplantation with BMSC transplantation enhanced the proliferation and potential of the BMSCs for bone regeneration, successfully promoting bone repair after implantation at the defect site. This method may provide a new idea for treating clinical bone defects through BTE.

Association of the Triglyceride to High-Density Lipoprotein Ratio and the Visceral Adiposity Index with Metabolic Syndrome in Diabetic Susceptible Population.

The aim of this study was to explore the association of the triglyceride to high-density lipoprotein ratio (TG/HDL) and the visceral adiposity index (VAI) with metabolic syndrome (Mets) in high-risk populations of diabetic patients. Patients were recruited from the Endocrinology Clinic of Hebei General Hospital from April 2018 to April 2019,according to the "Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2017 Edition)". A total of 824 patients participated in the study. The association between TG/HDL or VAI and Mets in these patients was assessed using a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TG/HDL and VAI to predict Mets in the diabetic susceptible population. The prevalence of Mets gradually increased in males and females with advancing tertiles of TG/HDL or VAI. After adjusting for the relevant risk factors, TG/HDL and VAI were positively correlated with Mets in men and women. Both of them showed a better the area under the ROC curve (AUC) for Mets in females than body mass index, waist circumference, TG and homeostatic model assessment of insulin resistance. In females, the cut-off point of 1.67 for VAI showed a higher accuracy for Mets (sensitivity 0.756, specificity 0.705, Youden index 0.461), the same relationship not significant in men. TG/HDL and VAI provide a high predictive value for Mets in a diabetic susceptible population, especially in females.

Bromodomains and Extra-Terminal (BET) Inhibitor JQ1 Suppresses Proliferation of Acute Lymphocytic Leukemia by Inhibiting c-Myc-Mediated Glycolysis.

BACKGROUND Acute lymphocytic leukemia (ALL) is a common blood cancer which induces high mortality in children. Bromodomains and extra-terminal (BET) protein inhibitors, such as JQ1 and ARV-825, are promising cancer therapeutic agents that can be used by targeting c-Myc. A recent work reported that JQ1 effectively attenuates ALL in vitro by suppressing cell proliferation and accelerating apoptosis. The purpose of this research was to probe into the potential mechanism of how JQ1 inhibits ALL cell proliferation in vitro. MATERIAL AND METHODS Cell viability of ALL cells were measured by CTG after treatment by JQ1. Cell cycle analysis was done by EdU and PI staining. Cell apoptosis was assessed by Annexin V/PI staining. Glycolysis was detected using Seahorse and LC-MS kits. The expression of glycolytic rate-limiting enzymes was assessed by RNA-seq, qRT-PCR, and Western blot. RESULTS JQ1 suppressed cell proliferation by arresting the cell cycle and inducing the apoptosis of acute lymphocytic leukemia cells. JQ1 inhibited cell proliferation of B-ALL cells by restraining glycolysis. Conversely, the cell cycle block of B-ALL cells induced by JQ1 was partially abolished after pretreatment with 2-Deoxy-D-glucose (2-DG), an inhibitor of glycolysis. Furthermore, JQ1 restrained the glycolysis of B-ALL cell lines by remarkably downregulating the rate-limiting enzymes of glycolysis, such as hexokinase 2, phosphofructokinase, and lactate dehydrogenase A. Moreover, the cell cycle arrest was reversed in B-ALL cells with overexpressed c-Myc treated by JQ1, which is involved in the enhancement of glycolysis. CONCLUSIONS The BET inhibitor JQ1 suppresses the proliferation of ALL by inhibiting c-Myc-mediated glycolysis, thus providing a new strategy for the treatment of ALL.