Flow-driven translocation of comb-like copolymer micelles through a nanochannel.

Using hybrid lattice-Boltzmann molecular dynamics simulations, we investigate the flow-driven translocation of comb-like copolymer micelles through a nanochannel, in particular, making a detailed comparison with micelles formed by the corresponding diblock copolymers. Our results demonstrate that the critical flow flux of micelles formed by the comb-like copolymers is higher than that of micelles formed by the corresponding diblock copolymers, which is more pronounced with increasing side chain lengths or grafting densities, as evidenced by the free energy computed by self-consistent field theory. Our work indicates that the impact of chain topology on the stability of micelles, especially with the same size, can be well characterized using the critical flow fluxes, which provides a theoretical basis for designing self-assembling micelles for various applications.

Nickel-Catalyzed C-I-Selective C(sp2 )-C(sp3 ) Cross-Electrophile Coupling of Bromo(iodo)arenes with Alkyl Bromides.

Despite several methodologies established for C(sp2 )-I selective C(sp2 )-C(sp3 ) bond formations, achieving arene-flanked quaternary carbons by cross-coupling of tertiary alkyl precursors with bromo(iodo)arenes in a C(sp2 )-I selective manner is rare. Here we report a general Ni-catalyzed C(sp2 )-I selective cross-electrophile coupling (XEC) reaction, in which, beyond 3° alkyl bromides (for constructing arene-flanked quaternary carbons), 2° and 1° alkyl bromides are also demonstrated to be viable coupling partners. Moreover, this mild XEC displays excellent C(sp2 )-I selectivity and functional group compatibility. The practicality of this XEC is demonstrated in simplifying the routes to several medicinally relevant and synthetically challenging compounds. Extensive experiments show that the terpyridine-ligated NiI halide can exclusively activate alkyl bromides, forming a NiI -alkyl complex through a Zn reduction. Attendant density functional theory (DFT) calculations reveal two different pathways for the oxidative addition of the NiI -alkyl complex to the C(sp2 )-I bond of bromo(iodo)arenes, explaining both the high C(sp2 )-I selectivity and generality of our XEC.

Diagnosis, treatment and genetic analysis of a case of hypoglycemia caused by glucokinase gene mutation.

Congenital hyperinsulinemia (CHI) is a disease phenotype characterized by persistent or recurrent hypoglycemia due to abnormal secretion of insulin by ß cells of the pancreas. CHI induced by activation mutation of a single allele of glucokinase (GCK) is the rarest type. In this paper, the clinical data of a patient with hypoglycemia of unknown cause were collected without obvious clinical symptoms. And a heterozygous missense mutation (c.295T> C:p.W99R) was detected in exon 3 of the GCK gene. The mutation was found in both the son and daughter of the proband, and the blood glucose level was low, while the others were normal. By summarizing and analyzing the characteristics of this case and the genetic pedigree of the family, the possibility of congenital hyperinsulinemia caused by a single gene mutation should be considered for hypoglycemia whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.

Chemoselective and Diastereoselective Synthesis of C-Aryl Nucleoside Analogues by Nickel-Catalyzed Cross-Coupling of Furanosyl Acetates with Aryl Iodides.

Canonical nucleosides are vulnerable to enzymatic and chemical degradation, yet their stable mimics-C-aryl nucleosides-have demonstrated potential utility in medicinal chemistry, chemical biology, and synthetic biology, although current synthetic methods remain limited in terms of scope and selectivity. Herein, we report a cross-electrophile coupling to prepare C-aryl nucleoside analogues from readily available furanosyl acetates and aryl iodides. This nickel-catalyzed modular approach is characterized by mild reaction conditions, broad substrate scope, excellent ß-selectivity, and high functional-group compatibility. The exclusive chemoselectivity with respect to the aryl iodide enables efficient preparation of a variety of C-aryl halide furanosides suitable for various downstream transformations. The practicality of this transformation is demonstrated through the synthesis of a potent analogue of a naturally occurring NF-κB activator.

Electrochemically Enabled, Nickel-Catalyzed Dehydroxylative Cross-Coupling of Alcohols with Aryl Halides.

As alcohols are ubiquitous throughout chemical science, this functional group represents a highly attractive starting material for forging new C-C bonds. Here, we demonstrate that the combination of anodic preparation of the alkoxy triphenylphosphonium ion and nickel-catalyzed cathodic reductive cross-coupling provides an efficient method to construct C(sp2)-C(sp3) bonds, in which free alcohols and aryl bromides-both readily available chemicals-can be directly used as coupling partners. This nickel-catalyzed paired electrolysis reaction features a broad substrate scope bearing a wide gamut of functionalities, which was illustrated by the late-stage arylation of several structurally complex natural products and pharmaceuticals.

Total Synthesis of (-)-Daphnezomines A and B.

Daphnezomines A and B are structurally unusual Daphniphyllum alkaloids that contain a unique aza-adamantane core skeleton. Herein, a modular approach to these alkaloids is presented that exploits a diverse array of reaction strategies. Commencing from a chiral pool terpene-(S)-carvone, the azabicyclo[3.3.1]nonane backbone, which occurs widely in Daphniphyllum alkaloids, was easily accessed through a Sharpless allylic amination and a palladium-catalyzed oxidative cyclization. A protecting group enabled a stereoselective B-alkyl Suzuki-Miyaura coupling sequence and an Fe-mediated hydrogen atom transfer (HAT)-based radical cyclization were then applied to construct C6 and C8 stereocenters. A final epimer locking strategy enabled the assembly of the highly congested aza-adamantane core, thereby achieving the first total synthesis of (-)-daphnezomines A and B in 14 steps.

Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/ß-catenin pathway in mice.

Liver regeneration is a complicated pathophysiologic process that is regulated by a myriad of signaling pathways and transcription factors. The interaction among these pathways and factors, either cooperatively or antagonistically, may ultimately lead to recovery and restoration of liver function or permanent loss of liver function and liver failure. In the present study, we investigated the mechanism whereby the chromatin remodeling protein brahma related gene 1 (Brg1) regulates liver regeneration in mice. The Smarca4-Flox strain of mice was crossbred with the Alb-Cre strain to generate hepatocyte-specific Brg1 knockout mice. Liver injury was induced by partial hepatectomy (PHx). We report that Brg1 deletion in hepatocyte compromised liver regeneration and dampened survival after PHx in mice. Brg1 interacted with ß-catenin to potentiate Wnt signaling and promote hepatocyte proliferation. Mechanistically, Brg1 recruited lysine demethylase 4 (KDM4) to activate ß-catenin target genes. Our data suggest that Brg1 might play an essential role maintaining hepatic homeostasis and contributing to liver repair.-Li, N., Kong, M., Zeng, S., Hao, C., Li, M., Li, L., Xu, Z., Zhu, M., Xu, Y. Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/ß-catenin pathway in mice.

Megakaryocytic leukemia 1 (MKL1) mediates high glucose induced epithelial-mesenchymal transition by activating LOX transcription.

Diabetic retinopathy (DR) is one of the most devastating complications of diabetes mellitus. When exposed to high glucose (HG), retinal epithelial cells undergo profound alterations both morphologically and functionally in a well-conserved process known as epithelial-to-mesenchymal transition (EMT). The mechanism governing HG-induced EMT in retinal epithelial cells is not completely understood. Here we report that treatment with 25 mM glucose led to EMT in retinal pigmented epithelial cells (RPE) characterized by a simultaneous down-regulation of E-Cadherin (encoded by CDH1) and up-regulation of alpha smooth muscle actin (encoded by ACTA2). HG-induced EMT in RPEs was accompanied by augmented expression and enhanced nuclear enrichment of MKL1, a transcriptional modulator. In contrast, MKL1 knockdown by siRNA or inhibition by CCG-1423 abrogated HG-induced EMT in RPEs. Of interest, MKL1 mediated the transcriptional activation of LOX, a mesenchymal marker, in RPEs in response to HG stimulation. Mechanistically, MKL1 interacted with and was recruited by AP-1 to the proximal LOX promoter to promote LOX trans-activation likely through altering the chromatin structure. Finally, LOX depletion by siRNA or inhibition by aminopropionitrile in RPEs abolished HG-induced EMT. In conclusion, our data support a role for MKL1 in mediating HG-induced EMT in retinal epithelial cells via epigenetic activation of LOX transcription.

SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice.

Hepatic stellate cells (HSCs) are a major source of fibrogenesis in the liver, contributing to cirrhosis. When activated, HSCs transdifferentiate into myofibroblasts and undergo profound functional alterations paralleling an overhaul of the transcriptome, the mechanism of which remains largely undefined. We investigated the involvement of the class III deacetylase sirtuin [silent information regulator 1 (SIRT1)] in HSC activation and liver fibrosis. SIRT1 levels were down-regulated in the livers in mouse models of liver fibrosis, in patients with cirrhosis, and in activated HSCs as opposed to quiescent HSCs. SIRT1 activation halted, whereas SIRT1 inhibition promoted, HSC transdifferentiation into myofibroblasts. Liver fibrosis was exacerbated in mice with HSC-specific deletion of SIRT1 [conditional knockout (cKO)], receiving CCl4 (1 mg/kg) injection or subjected to bile duct ligation, compared to wild-type littermates. SIRT1 regulated peroxisome proliferator activated receptor γ (PPARγ) transcription by deacetylating enhancer of zeste homolog 2 (EZH2) in quiescent HSCs. Finally, EZH2 inhibition or PPARγ activation ameliorated fibrogenesis in cKO mice. In summary, our data suggest that SIRT1 plays an essential role guiding the transition of HSC phenotypes.-Li, M., Hong, W., Hao, C., Li, L., Wu, D., Shen, A., Lu, J., Zheng, Y., Li, P., Xu, Y. SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice.

The histone methyltransferase Suv39h2 contributes to nonalcoholic steatohepatitis in mice.

Uncontrolled inflammatory response highlights the central theme of nonalcoholic steatohepatitis (NASH), a growing global pandemic. Hepatocytes and macrophages represent two major sources of hepatic inflammation during NASH pathogenesis, contributing to excessive synthesis of proinflammatory mediators. The epigenetic mechanism that accounts for the activation of hepatocytes and macrophages in this process remains obscure. Here, we report that compared to wild-type littermates, mice with a deficiency in the histone H3K9 methyltransferase suppressor of variegation 39 homolog 2 (Suv39h2, knockout) exhibited a less severe form of NASH induced by feeding with a high-fat, high-carbohydrate diet. Pro-NASH stimuli increased Suv39h2 expression in cell culture, in mice, and in human livers. In hepatocytes, Suv39h2 bound to the Sirt1 gene promoter and repressed Sirt1 transcription. Suv39h2 deficiency normalized Sirt1 expression, allowing nuclear factor kappa B/p65 to become hypoacetylated and thus dampening nuclear factor kappa B-dependent transcription of proinflammatory mediators. In macrophages, Suv39h2-mediated repression of peroxisome proliferator-activated receptor gamma transcription favored a proinflammatory M1 phenotype over an anti-inflammatory M2 phenotype, thereby elevating hepatic inflammation. CONCLUSION: Suv39h2 plays a pivotal role in the regulation of inflammatory response in hepatocytes and macrophages, contributing to NASH pathogenesis. (Hepatology 2017;65:1904-1919).

Suv39h2 deficiency ameliorates diet-induced steatosis in mice.

Steatosis is a prototypical metabolic disorder characterized by accumulation of lipid droplets in the liver, extensive hepatic inflammation, and, in advanced stages, accelerated liver fibrogenesis. The molecular mechanism underlying steatosis is not completely understood. In the present study we investigated the involvement of the histone methyltransferase Suv39h2 in the pathogenesis of steatosis. Expression of Suv39h2 was up-regulated in the liver in two different mouse models of steatosis. Suv39h2 knockout (KO) mice developed a less severe form of steatosis fed on a methione-and-choline deficient (MCD) diet, compared to wild type (WT) littermates, as evidenced by reduced levels of plasma ALT, down-regulated expression of pro-inflammatory mediators, and decreased infiltration of macrophages. In addition, Masson's trichrome staining as well as qPCR measurements of fibrogenic genes suggested that liver fibrosis was attenuated in MCD diet-fed KO mice compared to WT mice. Further analysis found that Suv39h2 repressed SIRT1 expression in the liver by stimulating histone H3K9 trimethylation surrounding the SIRT1 promoter and that Suv39h2 deficiency alleviated SIRT1 expression in MCD diet-fed mice. Therefore, our data support a role of Suv39h2 in promoting steatosis in mice likely through contributing to SIRT1 trans-reperssion.

Hepatic stellate cell-specific deletion of SIRT1 exacerbates liver fibrosis in mice.

Liver fibrosis is widely perceived as a host defense mechanism that aids tissue repair following liver injury. Excessive fibrogenesis, however, serves to disrupt normal liver structure and precedes such irrevocable human pathologies as cirrhosis and hepatocellular carcinoma. Activation of hepatic stellate cells (HSCs) is a hallmark event during liver fibrosis. In the present study we investigated the mechanism by which the lysine deacetylase SIRT1 regulates HSC activation. We report here that SIRT1 levels were decreased in the liver in different mouse models and in cultured HSCs undergoing activation. SIRT1 down-regulation paralleled HDAC4 up-regulation. HDAC4 was recruited to the SIRT1 promoter during HSC activation and removed acetylated histones H3 and H4 from the SIRT1 promoter leading to SIRT1 trans-repression. HDAC4 silencing restored SIRT1 expression and attenuated HSC activation in SIRT1-dependent manner. More important, selective deletion of SIRT1 in HSCs exacerbated CCl4-induced liver fibrosis in mice. Mechanistically, SIRT1 deacetylated PPARγ to block HSC activation. Together, our data reveal an HDAC4-SIRT1-PPARγ axis that contributes to the regulation of HSC activation and liver fibrosis.

Histone Methyltransferase SET1 Mediates Angiotensin II-Induced Endothelin-1 Transcription and Cardiac Hypertrophy in Mice.

OBJECTIVE: Endothelin-1 is a potent vasoconstrictor derived from vascular endothelium. Elevated endothelin-1 levels are observed in a host of cardiovascular pathologies including cardiomyopathy. The epigenetic mechanism responsible for endothelin-1 induction in these pathological processes remains elusive. APPROACH AND RESULTS: We report here that induction of endothelin-1 expression in endothelial cells by angiotensin II (Ang II) was accompanied by the accumulation of histone H3K4 trimethylation, a preeminent histone modification for transcriptional activation, on the endothelin-1 promoter. In the meantime, Ang II stimulated the expression and the occupancy of Suv, Ez, and Trithorax domain 1 (SET1), a mammalian histone H3K4 trimethyltransferase, on the endothelin-1 promoter, both in vitro and in vivo. SET1 was recruited to the endothelin-1 promoter by activating protein 1 (c-Jun/c-Fos) and synergized with activating protein 1 to activate endothelin-1 transcription in response to Ang II treatment. Knockdown of SET1 in endothelial cells blocked Ang II-induced endothelin-1 synthesis and abrogated hypertrophy of cultured cardiomyocyte. Finally, endothelial-specific depletion of SET1 in mice attenuated Ang II-induced pathological hypertrophy and cardiac fibrosis. CONCLUSIONS: Our data suggest that SET1 epigenetically activates endothelin-1 transcription in endothelial cells, thereby contributing to Ang II-induced cardiac hypertrophy. As such, screening of small-molecule compound that inhibits SET1 activity will likely offer a new therapeutic solution to the treatment of cardiomyopathy.

A crosstalk between chromatin remodeling and histone H3K4 methyltransferase complexes in endothelial cells regulates angiotensin II-induced cardiac hypertrophy.

Angiotensin II (Ang II) induces cardiac hypertrophy and fibrosis in part by stimulating endothelin (ET-1) transcription. The involvement of the epigenetic machinery in this process is largely undefined. In the present study, we examined the epigenetic maneuvering underlying cardiac hypertrophy and fibrosis following ET-1 transactivation by Ang II. In response to Ang II stimulation, core components of the mammalian chromatin remodeling complex (Brahma-related gene 1, or Brg1, and Brahma or Brm) and histone H3K4 methylation complex (Ash2, absent, small, or homeotic discs 2, or Ash2 and WD domain repeat 5, or Wdr5) were recruited to the ET-1 promoter region in endothelial cells. Over-expression of Brg1/Brm or Ash2/Wdr5 enhanced while depletion of Brg1/Brm or Ash2/Wdr5 attenuated Ang II-induced ET-1 transactivation. Endothelial-specific knockdown of Brg1/Brm or Ash2/Wdr5 ameliorated cardiac hypertrophy both in vitro and in vivo. More important, Brg1/Brm interacted with Ash2/Wdr5 on the ET-1 promoter to catalyze H3K4 methylation. The crosstalk between Brg11/Brm and Ash2/Wdr5 was mediated by myocardin-related transcription factor A (MRTF-A). In conclusion, our data have unveiled an epigenetic complex that links ET-1 transactivation in endothelial cells to Ang II-induced cardiac hypertrophy and fibrosis.

Endothelial MRTF-A mediates angiotensin II induced cardiac hypertrophy.

Angiotensin II (Ang II) stimulates endothelin (ET-1) transcription, which contributes to cardiac hypertrophy and fibrosis. We have previously reported that myocardin related transcription factor A (MRTF-A) is indispensable for ET-1 transcription in vascular endothelial cells under hypoxic conditions, indicating that MRTF-A might mediate Ang II-induced pathological hypertrophy. Here we report that Ang II augmented the expression of MRTF-A in cultured endothelial cells and in the lungs of mice with cardiac hypertrophy. Over-expression of MRTF-A enhanced, whereas depletion of MRTF-A attenuated, transcriptional activation of ET-1 gene by Ang II. MRTF-A deficiency ameliorated Ang II induced cardiac hypertrophy and fibrosis in mice paralleling diminished synthesis and release of ET-1. Mechanistically, MRTF-A was recruited to the ET-1 promoter by c-Jun/c-Fos (AP-1) in response to Ang II treatment. Once bound, MRTF-A altered the chromatin structure by modulating histone acetylation and H3K4 methylation on the ET-1 promoter. More importantly, mice with endothelial-specific MRTF-A silencing by lentiviral particles phenocopied mice with systemic MRTF-A deletion in terms of Ang II-induced pathological hypertrophy. In conclusion, we data have unveiled a MRTF-A-containing complex that links ET-1 transactivation in endothelial cells to cardiac hypertrophy and fibrosis by Ang II.

[Study on Identification of Three Medicinal Plant Leaves from Elaeagnus Genus by Infrared Spectroscopy].

OBJECTIVE: To study and identify the three species of dry medicinal plant leaves trom Elaeagnus genus (E. pungens, E. lanceolata and E. henryi) by Infrared Spectroscopy(IR). METHODS: Fourier transform infrared spectroscopy and second derivative infrared spectroscopy were used to study and compare the characteristics of leaves of three Elaeagnus medicinal plants. RESULTS: The IR spectra and second derivative infrared spectra of the three Elaeagnus plants leaves were similar on the whole, the intensity or ratio of intensity of some absorption peaks still had certain distinctions, and the differences of the second derivative infrared spectra were more obvious. There were only slight differences between large and small leaf type of samples of Elaeagnus lanceolata; the differences of the plant leaves of one species collected in different harvest periods were far smaller than those of others belonging to the same genus. CONCLUSION: IR can be relatively reliably used for identification of the three Elaeagnus leaves.

Autotrophic denitrification based on sulfur-iron minerals: advanced wastewater treatment technology with simultaneous nitrogen and phosphorus removal.

Autotrophic denitrification technology has many advantages, including no external carbon source addition, low sludge production, high operating cost efficiency, prevention of secondary sewage pollution, and stable treatment efficiency. At present, the main research on autotrophic denitrification electron donors mainly includes sulfur, iron, and hydrogen. In these autotrophic denitrification systems, pyrite has received attention due to its advantages of easy availability of raw materials, low cost, and pH stability. When pyrite is used as a substrate for autotropic denitrification, sulfide (S2-) and ferrous ion (Fe2+) in the substrate will provide electrons to convert nitrate (NO3-) in sewage first to nitrite (NO2-), then to nitrogen (N2), and finally to discharge the system. At the same time, sulfide (S2-) loses electrons to sulfate (SO42-) and ferrous ion (Fe2+) loses electrons to ferric iron (Fe3+). Phosphates (PO43-) in wastewater are chemically combined with ferric iron (Fe3+) to form ferric phosphate (FePO4) precipitate. This paper aims to provide a detailed and comprehensive overview of the dynamic changes of nitrogen (N), phosphorus (P), and other substances in the process of sulfur autotrophic denitrification using iron sulfide, and to summarize the factors that affect wastewater treatment in the system. This work will provide a relevant research direction and theoretical basis for the field of sulfur autotrophic denitrification, especially for the related experiments of the reaction conversion of various substances in the system.

High-Density Packing of Spherical Microdomains from A(AB3)3 Dendron-like Miktoarm Star Copolymer.

An A(AB3)3 dendron-like miktoarm star copolymer consisting of polystyrene (PS, A) and poly(2-vinylpyridine) (P2VP, B) was synthesized using a series of anionic polymerization, atom-transfer radical polymerization (ATRP), and click reaction. The morphology of A(AB3)3 changed greatly depending on the volume fraction of A and the chain asymmetry. Interestingly, a body-centered cubic spherical phase was found even at fA = 0.51 because the chain architecture of A(AB3)3 stabilizes the large interfacial curvature toward A domains. On the other hand, when the length difference between the end and middle A blocks decreased, a hexagonally packed cylindrical phase was formed at fA = 0.50. This is attributed to the fact that the middle A chains are arranged in a more relaxed way, resulting in a milder interfacial curvature toward A domains. The experimental observations are well-consistent with the predictions based on self-consistent-field theory.

Influence of a Mixture of Protein Hydrolysate from Black Soldier Fly Larvae and Schizochytrium on Palatability, Plasma Biochemistry, and Antioxidative and Anti-Inflammatory Capacity in Cat Diets.

The objective of this research was to evaluate palatability, plasma biochemistry, antioxidative and anti-inflammatory capacity, and immune levels in cats by feeding supplementing inclusion of different levels of a mixture of protein hydrolysate from black soldier fly larvae and schizochytrium (BSFPs) in diets. In the feed experiment, a total of 24 adult cats (12 females and 12 males; BW: 3.02 ± 0.06 kg) were randomly divided into four groups: (1) diet with chicken and fish meal as primary protein resource (CON); (2) diet with 5% BSFPs replacing chicken meal, fish meal, chicken oil, and fish oil (5% BSFPs); (3) 10% BSFPs; and (4) 15% BSFPs. The body weight and feed intake were recorded, and a blood sample was collected for analysis. In the palatability experiment, three diets containing 5%, 10%, and 15% BSFPs were evaluated by comparing with CON. These results suggested that different levels of BSFPs could improve palatability in cat diets by enhancing the first sniff, the first bite, and feed intake (p < 0.05). However, no significant influence existed in body weight and average daily feed intake (p > 0.05). In comparison to the CON group, 5% and 15% BSFPs significantly increased the total protein content, and all treatment groups decreased the triglyceride content and enhanced the calcium concentration in plasma; in addition, the activity of aspartate aminotransferase and alanine aminotransferase and the content of creatinine and urea nitrogen were significantly reduced by the supplementation inclusion of BSFPs in the diets (p < 0.05). The enzyme activity of glutathione peroxidase was dramatically enhanced by the supplementation of 10% and 15% BSFPs in diets compared with the CON diet, and the activity of superoxide dismutase was increased and the malondialdehyde concentration was remarkably reduced in all three treatments (p < 0.05). Compared with the CON group, different levels of BSFPs in the diets significantly increased the immunoglobulin A content in plasma; similarly, the immunoglobulin G concentration was significantly enhanced by the supplementation of 10% and 15% BSFPs in the diets (p < 0.05). Furthermore, the interleukin-1ß content was significantly reduced in the inclusion of 10% and 15% BSFPs in the diets, and 15% BSFPs remarkably decreased the content of interleukin-8 in plasma compared with the CON diet (p < 0.05). To sum up, the supplementation of different levels of BSFPs exhibited a positive effect on palatability and enhanced the antioxidant, anti-inflammatory, and immune capacity. Particularly, the addition levels of 10% and 15% BSFPs were more effective in antioxidation, anti-inflammation, and immunity.

GINv2.0: a comprehensive topological network integrating molecular interactions from multiple knowledge bases.

Knowledge bases have been instrumental in advancing biological research, facilitating pathway analysis and data visualization, which are now widely employed in the scientific community. Despite the establishment of several prominent knowledge bases focusing on signaling, metabolic networks, or both, integrating these networks into a unified topological network has proven to be challenging. The intricacy of molecular interactions and the diverse formats employed to store and display them contribute to the complexity of this task. In a prior study, we addressed this challenge by introducing a "meta-pathway" structure that integrated the advantages of the Simple Interaction Format (SIF) while accommodating reaction information. Nevertheless, the earlier Global Integrative Network (GIN) was limited to reliance on KEGG alone. Here, we present GIN version 2.0, which incorporates human molecular interaction data from ten distinct knowledge bases, including KEGG, Reactome, and HumanCyc, among others. We standardized the data structure, gene IDs, and chemical IDs, and conducted a comprehensive analysis of the consistency among the ten knowledge bases before combining all unified interactions into GINv2.0. Utilizing GINv2.0, we investigated the glycolysis process and its regulatory proteins, revealing coordinated regulations on glycolysis and autophagy, particularly under glucose starvation. The expanded scope and enhanced capabilities of GINv2.0 provide a valuable resource for comprehensive systems-level analyses in the field of biological research. GINv2.0 can be accessed at: https://github.com/BIGchix/GINv2.0 .