Evaluation of iron-modified biochar on arsenic accumulation by rice: a pathway to assess human health risk from cooked rice.

Arsenic (As) contamination of rice grain poses a serious threat to human health. Therefore, it is crucial to reduce the bioavailability of As in the soil and its accumulation in rice grains to ensure the safety of food and human health. In this study, mango (Mangifera indica) leaf-derived biochars (MBC) were synthesized and modified with iron (Fe) to produce FeMBC. In this study, 0.5 and 1% (w/w) doses of MBC and FeMBC were used. The results showed that 1% FeMBC enhanced the percentage of filled grains/panicle and biomass yield by 17 and 27%, respectively, compared to the control. The application of 0.5 and 1% FeMBC significantly (p < 0.05) reduced bioavailable soil As concentration by 33 and 48%, respectively, in comparison to the control. The even higher As flux in the control group as compared to the biochar-treated groups indicates the lower As availability to biochar-treated rice plant. The concentration of As in rice grains was reduced by 6 and 31% in 1% MBC and 1% FeMBC, respectively, compared to the control. The reduction in As concentration in rice grain under 1% FeMBC was more pronounced due to reduced bioavailability of As and enhanced formation of Fe-plaque. This may restrict the entry of As through the rice plant. The concentrations of micronutrients (such as Fe, Zn, Se, and Mn) in brown rice were also improved after the application of both MBC and FeMBC in comparison to the control. This study indicates that the consumption of parboiled rice reduces the health risk associated with As compared to cooked sunned rice. It emphasizes that 1% MBC and 1% FeMBC have great potential to decrease the uptake of As in rice grains.

Innovative utilization of harvested mushroom substrate for green synthesis of silver nanoparticles: A multi-response optimization approach.

In this work, harvested mushroom substrate (HMS) has been explored for the first time through a comprehensive optimization study for the green synthesis of silver nanoparticles (AgNPs). A multiple response central composite design with three parameters: pH of the reaction mixture, temperature, and incubation period at three distinct levels was employed in the optimization study. The particle size of AgNPs, UV absorbance, and the percentage of Ag/Cl elemental ratio were considered as the response parameters. For each response variable examined the model used was found to be significant (P < 0.05). The ideal conditions were: pH 8.9, a temperature of 59.4 °C, and an incubation period of 48.5 h. The UV-visible spectra of AgNPs indicated that the absorption maxima for AgNP-3 were 414 nm, 420 for AgNPs-2, and 457 for AgNPs-1. The XRD analysis of AgNPs-3 and AgNPs-2 show a large diffraction peak at ∼38.2°, ∼44.2°, ∼64.4°, and ∼77.4°, respectively, which relate to the planes of polycrystalline face-centered cubic (fcc) silver. Additionally, the XRD result of AgNPs-1, reveals diffraction characteristics of AgCl planes (111, 200, 220, 311, 222, and 400). The TEM investigations indicated that the smallest particles were synthesized at pH 9 with average diameters of 35 ± 6 nm (AgNPs-3). The zeta potentials of the AgNPs are -36 (AgNPs-3), -28 (AgNPs-2), and -19 (AgNPs-1) mV, respectively. The distinct IR peak at 3400, 1634, and 1383 cm-1 indicated the typical vibration of phenols, proteins, and alkaloids, respectively. The AgNPs were further evaluated against gram (+) strain Bacillus subtilis (MTCC 736) and gram (-) strain Escherichia coli (MTCC 68). All of the NPs tested positive for antibacterial activity against both bacterial strains. The study makes a sustainable alternative to disposing of HMS to achieve the Sustainable Development Goals (SDGs).

Coherent light control of a metastable hidden state.

Metastable phases present a promising route to expand the functionality of complex materials. Of particular interest are light-induced metastable phases that are inaccessible under equilibrium conditions, as they often host new, emergent properties switchable on ultrafast timescales. However, the processes governing the trajectories to such hidden phases remain largely unexplored. Here, using time- and angle-resolved photoemission spectroscopy, we investigate the ultrafast dynamics of the formation of a hidden quantum state in the layered dichalcogenide 1T-TaS2 upon photoexcitation. Our results reveal the nonthermal character of the transition governed by a collective charge-density-wave excitation. Using a double-pulse excitation of the structural mode, we show vibrational coherent control of the phase-transition efficiency. Our demonstration of exceptional control, switching speed, and stability of the hidden state are key for device applications at the nexus of electronics and photonics.

Hyaluronic acid-graphene oxide quantum dots nanoconjugate as dual purpose drug delivery and therapeutic agent in meta-inflammation.

Type 2 diabetes mellitus (T2DM) predominantly considered a metabolic disease is now being considered an inflammatory disease as well due to the involvement of meta-inflammation. Obesity-induced adipose tissue inflammation (ATI) is one of the earliest phenomena in the case of meta-inflammation, leading to the advent of insulin resistance (IR) and T2DM. The key events of ATI are orchestrated by macrophages, which aggravate the inflammatory state in the tissue upon activation, ultimately leading to systemic chronic low-grade inflammation and Non-Alcoholic Steatohepatitis (NASH) through the involvement of proinflammatory cytokines. The CD44 receptor on macrophages is overexpressed in ATI, NASH, and IR. Therefore, we developed a CD44 targeted Hyaluronic Acid functionalized Graphene Oxide Quantum Dots (GOQD-HA) nanocomposite for tissue-specific delivery of metformin. Metformin-loaded GOQD-HA (GOQD-HA-Met) successfully downregulated the expression of proinflammatory cytokines and restored antioxidant status at lower doses than free metformin in both palmitic acid-induced RAW264.7 cells and diet induced obese mice. Our study revealed that the GOQD-HA nanocarrier enhanced the efficacy of Metformin primarily by acting as a therapeutic agent apart from being a drug delivery platform. The therapeutic properties of GOQD-HA stem from both HA and GOQD having anti-inflammatory and antioxidant properties respectively. This study unravels the function of GOQD-HA as a targeted drug delivery option for metformin in meta-inflammation where the nanocarrier itself acts as a therapeutic agent.

Mitochondrial sourcing of interferogenic ligands and an autoantigen in human obesity-associated metaflammation.

OBJECTIVE: Visceral adipose tissue (VAT) inflammation contributes to metabolic dysregulation in obesity. VAT recruitment and activation of plasmacytoid dendritic cells (pDCs) through toll-like receptor 9 (TLR9) recognition of self-DNA, leading to induction of type I interferons, are crucial innate triggers for this VAT inflammation. It was hypothesized that mitochondrial DNA (mtDNA) can contribute to TLR9 activation in VAT-recruited pDCs in obesity, and this study aimed to identify the carrier protein for ligand access to TLR9 and to explore whether this also provides for a source of autoantigens in this context. METHODS: VAT samples, used for gene expression studies as well as adipose explant cultures, were collected from patients with obesity (n = 54) and lean patients (n = 10). Supernatants from human pDC cultures, treated with adipose explant culture supernatants, were used for interferon α ELISA. Venous plasma, from patients with (n = 114) and without (n = 45) obesity, was used for an ELISA for autoantibodies. RESULTS: MtDNA from VAT in obesity, in complex with mitochondrial transcription factor A protein (TFAM), acts as interferogenic ligands for pDCs. Humoral autoreactivity against TFAM is also induced in obesity. CONCLUSIONS: Interferogenic ligands and an autoantigen can be sourced from dysfunctional mitochondria in VAT of humans with obesity. Further therapeutic and prognostic potential for this immune mechanism in obesity warrants exploration.

Butyrate limits inflammatory macrophage niche in NASH.

Immune cell infiltrations with lobular inflammation in the background of steatosis and deregulated gut-liver axis are the cardinal features of non-alcoholic steatohepatitis (NASH). An array of gut microbiota-derived metabolites including short-chain fatty acids (SCFA) multifariously modulates NASH pathogenesis. However, the molecular basis for the favorable impact of sodium butyrate (NaBu), a gut microbiota-derived SCFA, on the immunometabolic homeostasis in NASH remains elusive. We show that NaBu imparts a robust anti-inflammatory effect in lipopolysaccharide (LPS) stimulated or classically activated M1 polarized macrophages and in the diet-induced murine NASH model. Moreover, it impedes monocyte-derived inflammatory macrophage recruitment in liver parenchyma and induces apoptosis of proinflammatory liver macrophages (LM) in NASH livers. Mechanistically, by histone deactylase (HDAC) inhibition NaBu enhanced acetylation of canonical NF-κB subunit p65 along with its differential recruitment to the proinflammatory gene promoters independent of its nuclear translocation. NaBu-treated macrophages thus exhibit transcriptomic signatures that corroborate with a M2-like prohealing phenotype. NaBu quelled LPS-mediated catabolism and phagocytosis of macrophages, exhibited a differential secretome which consequently resulted in skewing toward prohealing phenotype and induced death of proinflammatory macrophages to abrogate metaflammation in vitro and in vivo. Thus NaBu could be a potential therapeutic as well as preventive agent in mitigating NASH.

Nanotherapeutic potential of antibacterial folic acid-functionalized nanoceria for wound-healing applications.

Aim: The functionalization and characterization of antibacterial nanoceria with folic acid (FA) and elucidation of their in vivo wound-healing application. Materials & methods: Functionalization of nanoceria were done with FA using a chemical method and their antibacterial activity, cellular biocompatibility and in vivo wound-healing application were evaluated. Results: The functionalization of nanoceria with FA was done with 10-20 nm size and -20.1 mV zeta potential. The nanoformulation showed a bacteriostatic effect along with biocompatibility to different cell lines; 0.1% w/v spray of FA-nanoceria demonstrated excellent wound-healing capacity within 14 days in a Wister rat model. Conclusion: The antioxidant and reactive oxygen species scavenging activity of the FA-nanoceria make it a promising therapeutic agent as a unique spray formulation in wound-healing applications.

The emergence of chronic wounds is a main reason for mortality in patients with diabetes and other severe pathological complications. Advances in the use of nanotechnology have resulted in beneficial technology for tailoring of pharmacokinetic properties of different drug-delivery vehicles for different biomedical applications. In this study, folic acid (FA) functionalized nanoceria (FA-nanoceria) were formulated and their potential efficacy in the wound-healing process was explored. The nanoformulation showed a remarkable bacteriostatic effect on both Gram-negative and Gram-positive bacteria. In vitro cell line studies showed satisfactory biocompatibility in three different types of cell lines. In addition, a 0.1% w/v spray of FA-nanoceria was applied to full-thickness wounds in an in vivo mice model where it demonstrated excellent wound-healing capacity within 14 days. The combined antioxidant and reactive oxygen species scavenging activity of both the FA and nanoceria makes FA-nanoceria a promising therapeutic agent as a unique spray formulation in wound-healing applications.

A State-of-the-Art Systemic Review on Selenium Nanoparticles: Mechanisms and Factors Influencing Biogenesis and Its Potential Applications.

Selenium is a trace element required for the active function of numerous enzymes and various physiological processes. In recent years, selenium nanoparticles draw the attention of scientists and researchers because of its multifaceted uses. The process involved in chemically synthesized SeNPs has been found to be hazardous in nature, which has paved the way for safe and ecofriendly SeNPs to be developed in order to achieve sustainability. In comparison to chemical synthesis, SeNPs can be synthesized more safely and with greater flexibility utilizing bacteria, fungi, and plants. This review focused on the synthesis of SeNPs utilizing bacteria, fungi, and plants; the mechanisms involved in SeNP synthesis; and the effect of various abiotic factors on SeNP synthesis and morphological characteristics. This article discusses the synergies of SeNP synthesis via biological routes, which can help future researchers to synthesize SeNPs with more precision and employ them in desired fields.

Application of potassium humate to reduce arsenic bioavailability and toxicity in rice plants (Oryza sativa L.) during its course of germination and seedling growth.

Arsenic (As), a metalloid is a class I carcinogen and is a major problem in various parts of the world. Food crops are severely affected due to As poisoning and suffer from low germination, yield and disfiguration of morphological and anatomical traits. To attenuate such adverse effects and tone down As uptake by plants, the present study attempts to explore the role of K-humate (KH) in alleviation of As toxicity in rice. KH was administered in the growth media containing 800 ppb As (III) at varying doses to observe the stress alleviating capacity of the amendment. Five treatments were investigated, viz: (a) 800 ppb As (control), (b) 800 ppb As + 25 ppm KH, (c) 800 ppb As + 50 ppm KH, (d) 800 ppb As + 75 ppm KH and (e) 800 ppb As + 100 ppm KH. The results of the amendment administration were noted at 14 days after seeding (DAS). Application of KH significantly improved germination percentage, vigour indices and chlorophyll content by reducing the oxidative stress, antioxidant and antioxidant enzyme activities under As stress. In vivo detection of reactive oxygen species (ROS) using DCF-2DA fluorescent dye and scanning electron microscope (SEM) study of root further depicted that KH application effectively reduced ROS formation and improved root anatomical structure under As stress, respectively. Gradually increasing concentrations of KH was capable of decreasing the bioavailability of As to the rice plants, thus minimizing toxic effect of the metalloid.

Inferring the characteristics of marine sediments from the acoustic response of a known, partially buried object.

We investigate the feasibility of using a known elastic target located near the seabed for the purpose of inferring characteristics of marine sediment. In the problem considered the object position and its burial depth are not known with precision. First, the admittance matrix of the elastic object is determined (numerically or experimentally) over a wide frequency range in the structural acoustic regime. Then, the equivalent source method (ESM) coupled with a spectral representation of the Green's functions in stratified domains is used to predict the object acoustic signature in various environments and experimental configurations. The resulting solver takes into account all multiple scattering between target (buried or not), sea floor, and sea surface and is not limited to short distances. After presenting the solution to the forward problem several synthetic inversions for sediment characteristics are shown. They are based upon a resonance-based misfit function we describe. The Bayesian procedure also infers object burial and source-object range, broadening its range of application.

Reversible Complexation Mediated Living Radical Polymerization Using Tetraalkylammonium Chloride Catalysts.

This work reports the first use of organic chloride salts as catalysts for reversible complexation mediated living radical polymerization. Owing to the strong halogen-bond forming ability of Cl- , the studied four tetraalkylammonium chloride catalysts (R4 N+ Cl- ) successfully control the polymerizations of methyl methacrylate, yielding polymers with low dispersities up to high monomer conversion (>90%). Benzyldodecyldimethylammonium chloride is further exploited to other methacrylates and yields low-dispersity block copolymers. The advantages of the chloride salt catalysts are wide monomer scope, good livingness, accessibility to block copolymers, and good solubility in organic media. Because of the good solubility, the use of the chloride salt catalysts can prevent agglomeration of catalysts on reactor walls in organic media, which is an industrially attractive feature. Among halide anions, chloride anion is the most abundant and least expensive halide anion, and therefore, the use of the chloride salt catalysts may lower the cost of the polymerization.

Identification and epidemiological characterization of Type-2 diabetes sub-population using an unsupervised machine learning approach.

BACKGROUND: Studies on Type-2 Diabetes Mellitus (T2DM) have revealed heterogeneous sub-populations in terms of underlying pathologies. However, the identification of sub-populations in epidemiological datasets remains unexplored. We here focus on the detection of T2DM clusters in epidemiological data, specifically analysing the National Family Health Survey-4 (NFHS-4) dataset from India containing a wide spectrum of features, including medical history, dietary and addiction habits, socio-economic and lifestyle patterns of 10,125 T2DM patients. METHODS: Epidemiological data provide challenges for analysis due to the diverse types of features in it. In this case, applying the state-of-the-art dimension reduction tool UMAP conventionally was found to be ineffective for the NFHS-4 dataset, which contains diverse feature types. We implemented a distributed clustering workflow combining different similarity measure settings of UMAP, for clustering continuous, ordinal and nominal features separately. We integrated the reduced dimensions from each feature-type-distributed clustering to obtain interpretable and unbiased clustering of the data. RESULTS: Our analysis reveals four significant clusters, with two of them comprising mainly of non-obese T2DM patients. These non-obese clusters have lower mean age and majorly comprises of rural residents. Surprisingly, one of the obese clusters had 90% of the T2DM patients practising a non-vegetarian diet though they did not show an increased intake of plant-based protein-rich foods. CONCLUSIONS: From a methodological perspective, we show that for diverse data types, frequent in epidemiological datasets, feature-type-distributed clustering using UMAP is effective as opposed to the conventional use of the UMAP algorithm. The application of UMAP-based clustering workflow for this type of dataset is novel in itself. Our findings demonstrate the presence of heterogeneity among Indian T2DM patients with regard to socio-demography and dietary patterns. From our analysis, we conclude that the existence of significant non-obese T2DM sub-populations characterized by younger age groups and economic disadvantage raises the need for different screening criteria for T2DM among rural Indian residents.

Air-Tolerant Reversible Complexation Mediated Polymerization (RCMP) Using Aldehyde.

An air-tolerant reversible complexation mediated polymerization (RCMP) technique, which can be carried out without prior deoxygenation, is developed. The system contains a monomer, an alkyl iodide initiating dormant species, air (oxygen), an aldehyde, N-hydroxyphthalimide (NHPI), and a base. Oxygen is consumed via the NHPI-catalyzed conversion of the aldehyde (RCHO) to a carboxylic acid (RCOOH). The generated RCOOH is further converted to a carboxylate anion (RCOO- ) by the base. The RCOO- generated in situ works as an RCMP catalyst; the polymerization proceeds with the monomer, alkyl iodide dormant species, and RCOO- catalyst. Thus, the system is not only air-tolerant but also does not require additional RCMP catalysts, which is a notable feature of this system. (NHPI is used as an oxidation catalyst for converting RCHO to RCOOH.) This technique is amenable to methyl methacrylate, butyl methacrylate, benzyl methacrylate, 2-hydroxyethyl methacrylate, and styrene, yielding polymers with relatively low-dispersity (Mw /Mn  = 1.20-1.49), where Mw and Mn are the weight- and number-average molecular weights, respectively.

Moving source ocean acoustic tomography with uncertainty quantification using controlled source-tow observations.

Ocean sound speed and its uncertainty are estimated using travel-time tomography at ranges up to 2 km using a moving source in ∼600 m water depth. The experiment included two 32-element vertical line arrays deployed about 1 km apart and a towed source at ∼10 m depth transmitting a linear frequency modulated waveform. The inversion accounts for uncertainties in the positions and velocities of the source and receivers in addition to the background sound speed state. At these short ranges, the sound speed effects are small and the representational error of the candidate forward models must be carefully evaluated and minimized. This is tested stringently by a separate position parameter inversion and by cross-validating the estimates of sound speed and arrival time, including uncertainties. In addition, simulations are used to explore the effects of adding additional constraints to the inversion and to compare the performance of moving to fixed source tomography. The results suggest that the ray diversity available from the moving source reduces the posterior sound speed uncertainty compared to the fixed source case.

Distinct pathoclinical clusters among patients with uncontrolled type 2 diabetes: results from a prospective study in rural India.

INTRODUCTION: Inadequate glycemic control among patients with type 2 diabetes mellitus (T2DM) poses an enormous challenge. Whether this uncontrolled T2DM population is a heterogenous mix of disease subtypes remains unknown. Identification of these subtypes would result in a customized T2DM management protocol thereby paving the way toward personalized therapy. RESEARCH DESIGN AND METHODS: Electronic health records of 339 patients with uncontrolled T2DM patients followed up for a median period of 14 months were analyzed using Uniform Manifold Approximation and Projection followed by density-based spatial clustering of applications with noise. Baseline clinical features and final diagnoses with drug combinations were selected in the analysis. A 30 min oral glucose tolerance test was next performed for assessing the underlying insulin resistance and ß cell dysfunction. RESULTS: Three major clusters were identified. The first cluster characterized by recent onset T2DM had moderately preserved ß cell function. The second cluster with a longer duration of T2DM and associated hypertension showed the best glycemic control with dual antidiabetic therapy. The third cluster with the longest history of T2DM and no history of hypertension had the worst glycemic control in spite of the highest percentage of patients on triple therapy (34.58%) and quadruple therapy (8.41%). CONCLUSIONS: Uncontrolled T2DM comprises a heterogeneous population with respect to disease duration, presence of co-morbidities and ß cell function without significant difference in insulin resistance. Stratifying them on the basis of pathoclinical features is the first step toward a personalized management in T2DM.

Effect of sulfate application on inhibition of arsenic bioaccumulation in rice (Oryza sativa L.) with consequent health risk assessment of cooked rice arsenic on human: A pot to plate study.

Arsenic (As) in rice is posing a serious threat worldwide and consumption of As contaminated rice by human is causing health risks. A pot experiment with different levels of sulfate dosage (0, 20, 40, 60 and 80 mg/kg) was set up in this study to explore the influence of sulfate fertilizer on rice plant growth, yield, and As accumulation in rice grain. Apart from As bioaccumulation in rice grains, the As fraction of cooked rice was quantified, and the health risks associated with cooked rice consumption were also investigated. The sulfate application significantly (p ≤ 0.05) enhanced the chlorophyll, tiller number, grains per panicle, grain and biomass yield under As stressed condition. The sulfate application also reduced the oxidative stress and antioxidant activity in rice plants. Sulfate fertigation improved the accumulation of total sulfur (S) and reduced the uptake and translocation of As in rice plants. Arsenic concentration in rice grain was reduced by 50.1% in S80 treatment (80 mg of sulfate/kg of soil) as compared to S0 set. The reduction percentage of As in cooked parboiled and sunned rice with correspond to raw rice ranged from 55.9 to 74% and 40.3-60.7%, respectively. However, the sulfate application and cooking of parboiled rice reduced the potential non-cancer and cancer risk as compared to sunned rice. The S80 treatment and cooking of parboiled rice reduce the As exposure for both children and adults by 51% as compared to cooked sunned rice under S80 treatment and this trend was similar for all treatments. Therefore, sulfate application in soil can be recommended to produce safer rice grains and subsequent cooking of parboiled rice grain with low-As contaminated water need to be done to avoid any potential health risk in As endemic areas.

Prion-derived tetrapeptide stabilizes thermolabile insulin via conformational trapping.

Unfolding followed by fibrillation of insulin even in the presence of various excipients grappled with restricted clinical application. Thus, there is an unmet need for better thermostable, nontoxic molecules to preserve bioactive insulin under varying physiochemical perturbations. In search of cross-amyloid inhibitors, prion-derived tetrapeptide library screening reveals a consensus V(X)YR motif for potential inhibition of insulin fibrillation. A tetrapeptide VYYR, isosequential to the ß2-strand of prion, effectively suppresses heat- and storage-induced insulin fibrillation and maintains insulin in a thermostable bioactive form conferring adequate glycemic control in mouse models of diabetes and impedes insulin amyloidoma formation. Besides elucidating the critical insulin-IS1 interaction (R4 of IS1 to the N24 insulin B-chain) by nuclear magnetic resonance spectroscopy, we further demonstrated non-canonical dimer-mediated conformational trapping mechanism for insulin stabilization. In this study, structural characterization and preclinical validation introduce a class of tetrapeptide toward developing thermostable therapeutically relevant insulin formulations.

Bistatic scattering of an elastic object using the structural admittance and noise-based holographic measurements.

This paper presents a method to calculate the bistatic response of an elastic object immersed in a fluid using its structural Green's function (in vacuo structural admittance matrix), calculated by placing the object in a spatially random noise field in air. The field separation technique and equivalent source method are used to reconstruct pressure and velocity fields at the object's surface from pressure measurements recorded on two conformal holographic surfaces surrounding the object. Accurate reconstruction of the surface velocity requires subtraction of the rigid body response computed using a finite element approach. The velocity and pressure fields on the surface lead to the extraction of the in vacuo structural admittance matrix of the elastic object, which is manipulated to yield the farfield bistatic response for a fluid-loaded target for several angles of incidence. This method allows the computation of the scattering properties of an elastic object using exclusive information calculated on its surface (no knowledge of the internal structure required). A numerical experiment involving a cylindrical shell with hemispherical caps is presented, and its bistatic response in water shows excellent agreement with a finite element solution.

Organocatalyzed Living Radical Polymerization of Itaconates and Self-Assemblies of Rod-Coil Block Copolymers.

Organocatalyzed living radical polymerizations of itaconates are studied, yielding low-dispersity linear and star polymers (D = Mw /Mn = 1.28-1.46) up to Mn = 20 000 and monomer conversion = 62%, where Mn and Mw are the number- and weight-average molar masses, respectively. The block polymerization with functional methacrylates, an acrylate, and styrene yields various rod-coil block copolymers. Linear A-B diblock, linear B-A-B triblock, and 3-arm star A-B diblock copolymers generate spherical micelles (nanoparticles) and vesicles (nanocapsules), depending on the polymer structures. Itaconates can be derived from bioresources, and thus the obtained polymers may serve as green polymers. Because of the biocompatibility of polyitaconates, the assemblies may serve as biocompatible nanocarriers.

DBC1, p300, HDAC3, and Siah1 coordinately regulate ELL stability and function for expression of its target genes.

Among all of the Super Elongation Complex (SEC) components, ELL1 (also known as ELL) is the only bona fide elongation factor that directly stimulates transcription elongation by RNA polymerase II. However, the mechanism(s) of functional regulation of ELL1 (referred to as ELL hereafter), through its stabilization, is completely unknown. Here, we report a function of human DBC1 in regulating ELL stability involving HDAC3, p300, and Siah1. Mechanistically, we show that p300-mediated site-specific acetylation increases, whereas HDAC3-mediated deacetylation decreases, ELL stability through polyubiquitylation by the E3 ubiquitin ligase Siah1. DBC1 competes with HDAC3 for the same binding sites on ELL and thus increases its acetylation and stability. Knockdown of DBC1 reduces ELL levels and expression of a significant number of genes, including those involved in glucose metabolism. Consistently, Type 2 diabetes patient-derived peripheral blood mononuclear cells show reduced expression of DBC1 and ELL and associated key target genes required for glucose homeostasis. Thus, we describe a pathway of regulating stability and functions of key elongation factor ELL for expression of diverse sets of genes, including ones that are linked to Type 2 diabetes pathogenesis.