Protein prenylation and human diseases: a balance of protein farnesylation and geranylgeranylation.

The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate (FPP) or geranylgeranyl pyrophosphate (GGPP) as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess CaaX motif, such as Ras small GTPase family.

GGPPS deficiency aggravates CCl4-induced liver injury by inducing hepatocyte apoptosis.

GGPPS catalyses the expression of GGPP, a key protein in the mevalonate metabolic pathway. HMG-CoA reductase inhibitor statins can induce liver injury by inhibiting GGPP. However, the function of GGPPS in liver injury has not yet been revealed.

Rhodium(I)-catalyzed regiospecific dimerization of aromatic acids: two direct C-H bond activations in water.

2,2'-Diaryl acids are key building blocks for some of the most important and high-performance polymers such as polyesters and polyamides (imides), as well as structural motifs of MOFs (metal-organic frameworks) and biological compounds. In this study, a direct, regiospecific and practical dimerization of simple aromatic acids to generate 2,2'-diaryl acids has been discovered, which proceeds through two rhodium-catalyzed C-H activations in water. This reaction can be easily scaled up to gram level by using only 0.

Empowering a transition-metal-free coupling between alkyne and alkyl iodide with light in water.

Methods to assemble alkynes are essential for synthesizing fine chemicals, pharmaceuticals and polymeric photo-/electronic materials. Using light as a clean energy form and water as a green solvent has the potential to make synthetic chemistry more environmentally friendly. Here we present a transition-metal-free coupling protocol between aryl alkyne and alkyl iodide enabled by photoenergy in water.

MILI, a PIWI family protein, inhibits melanoma cell migration through methylation of LINE1.

MILI, a member of the PIWI/AGO gene family, has been well documented to maintain genome integrity by transposon silencing in animal germ cells. It has been reported to be selectively expressed in precancerous stem cells (pCSCs), tumor cell lines and various malignancies. However, the underlying mechanism remains largely unclear.

A convenient synthesis of N-aryl benzamides by rhodium-catalyzed ortho-amidation and decarboxylation of benzoic acids.

The rhodium-catalyzed amidation of substituted benzoic acids with isocyanates by directed CH functionalization followed by decarboxylation to afford the corresponding N-aryl benzamides is demonstrated, in which the carboxylate serves as a unique, removable directing group. Notably, less common meta-substituted N-aryl benzamides are generated readily from more accessible para- or ortho-substituted groups by employing this strategy.

Switching the Z/E selectivity in the palladium(II)-catalyzed decarboxylative Heck arylations of trans-cinnamaldehydes by solvent.

The Z/E selectivity of Pd(II)-catalyzed decarboxylative Heck-type arylations of trans-cinnamaldehydes can be controlled readily by switching the reaction solvent. Depending on the type of solvent used, each of the two isomeric products can be obtained with good to excellent Z/E ratio. In THF, Z-isomers were formed preferentially, whereas DMF provided the E-isomers predominantly.

Palladium-catalyzed benzothieno[2,3-b]indole formation via dehydrative-dehydrogenative double C-H sulfuration using sulfur powder, indoles and cyclohexanones.

Palladium-catalyzed C-S bond formation via dehydrative-dehydrogenative double C-H sulfuration using sulfur powder is described. The dehydrogenated intermediates of cyclohexanones can be trapped to act as efficient aryl sources under an oxygen atmosphere. This procedure provides a novel approach for the preparation of benzothieno[2,3-b]indoles.

The constitutive activation of Egr-1/C/EBPa mediates the development of type 2 diabetes mellitus by enhancing hepatic gluconeogenesis.

The sequential secretion of insulin and glucagon delicately maintains glucose homeostasis by inhibiting or enhancing hepatic gluconeogenesis during postprandial or fasting states, respectively. Increased glucagon/insulin ratio is believed to be a major cause of the hyperglycemia seen in type 2 diabetes. Herein, we reveal that the early growth response gene-1 (Egr-1) can be transiently activated by glucagon in hepatocytes, which mediates glucagon-regulated gluconeogenesis by increasing the expression of gluconeogenesis genes.

Efficient merging of copper and photoredox catalysis for the asymmetric cross-dehydrogenative-coupling of alkynes and tetrahydroisoquinolines.

A highly efficient catalytic asymmetric alkynylation of prochiral CH2 groups in tetrahydroisoquinoline was developed using copper catalyzed cross-dehydrogenative-coupling of sp(3) and sp C-H bonds with the assistance of a photocatalyst and visible light.

Thermal non-oxidative aromatization of light alkanes catalyzed by gallium nitride.

The thermal catalytic activity of GaN in non-oxidative alkane dehydroaromatization has been discovered for the first time. The origin of the catalytic activity was studied experimentally and theoretically. Commercially available GaN powders with a wurtzite crystal structure showed superior stability and reactivity for converting light alkanes, including methane, propane, n-butane, n-hexane and cyclohexane into benzene at an elevated temperature with high selectivity.

Combined A Coupling and Click Chemistry Approach for the Synthesis of Dendrimer-Based Biological Tools.

We report a versatile approach in which two highly efficient chemical reactions, multicomponent A coupling and alkyne-azide click chemistry, are combined to construct dendrimer-based tools for applications in biology. Using a convergent approach, dendrons with desired architecture and an alkyne at the focal point are first assembled and then stitched together via multicomponent A coupling reaction. The desired functional groups, including a stealth agent, imaging dye, and drug molecules, could be easily covalently linked to the surfaces of these hyperbranched macromolecules using alkyne-azide click chemistry.

A complete switch of the directional selectivity in the annulation of 2-hydroxybenzaldehydes with alkynes.

Controlling reaction selectivity is an eternal pursuit for chemists working in chemical synthesis. As part of this endeavor, our group has been exploring the possibility of constructing different natural product skeletons from the same simple starting materials by using different catalytic systems. In our previous work, an isoflavanone skeleton was obtained from the annulation of a salicylaldehyde and an alkyne when a gold catalyst was employed.

Prognostic value of residual node involvement after induction chemotherapy in operable oral squamous cell carcinoma.

Objective: The aim of this study was to assess the prognostic value of residual node involvement after induction chemotherapy (ICT) for head and neck squamous cell carcinoma and to investigate post-ICT node status associated with tumor characteristics.

Study Design: We retrospectively analyzed a cohort of 109 patients with operable oral squamous cell carcinoma who underwent ICT followed by surgery with neck dissection. The median follow-up was 45 months.

Aniline carbamates: a versatile and removable motif for palladium-catalyzed directed C-H activation.

The aniline carbamate is introduced as a new removable directing group for C-H activation. Its versatility and ability as a directing group are demonstrated by its use in the ortho-arylation of a wide variety of aniline derivatives under palladium(II) catalysis, with symmetric diaryliodonium salts as aryl donors. The reaction differs from previously reported arylations in its selectivity and its mechanism, as elucidated by kinetic and isotopic experiments.

GRP78 inhibits macrophage adhesion via SR-A.

Class A scavenger receptor (SR-A) plays an important role in macrophage adhesion. However, the underlying mechanism remains unclear. We previously found that 78 kDa glucose-regulated protein (GRP78) inhibited SR-A-mediated ligand internalization into macrophage by binding to SR-A.

The Barbier-Grignard-type arylation of aldehydes using unactivated aryl iodides in water.

Carbon-carbon bond formation is the essence of organic synthesis. One of the most important methods for forming carbon-carbon bonds is the Barbier-Grignard-type reaction, which was discovered over a century ago. However, it is still highly desirable to further improve this process.

Photoinduced conversion of methane into benzene over GaN nanowires.

As a class of key building blocks in the chemical industry, aromatic compounds are mainly derived from the catalytic reforming of petroleum-based long chain hydrocarbons. The dehydroaromatization of methane can also be achieved by using zeolitic catalysts under relatively high temperature. Herein we demonstrate that Si-doped GaN nanowires (NWs) with a 97% rationally constructed m-plane can directly convert methane into benzene and molecular hydrogen under ultraviolet (UV) illumination at rt.

Head and neck rhabdomyosarcoma in adults.

Aim: The purpose of this study was to explore the treatment and prognosis of head and neck rhabdomyosarcoma (RMS) in adults.

Methods: Fifty-nine patients with head and neck RMS in adults (AHNRMS) treated in one institution were selected. Multivariate analysis was used to evaluate the various variables related to overall survival (OS).

GARNL1, a major RalGAP α subunit in skeletal muscle, regulates insulin-stimulated RalA activation and GLUT4 trafficking via interaction with 14-3-3 proteins.

Insulin and muscle contraction each stimulate translocation of the glucose transporter GLUT4 to the plasma membrane in skeletal muscle, an important process regulating whole-body glucose homeostasis. RalA mediates insulin-stimulated GLUT4 translocation; however, it is unclear how this small GTPase is regulated in skeletal muscle in response to insulin. Here, we identified GARNL1/RalGAPα1, a major α subunit of the Ral-GTPase activating protein in skeletal muscle, as a protein whose phosphorylation and binding to the regulatory 14-3-3 proteins is stimulated by insulin and also by muscle contraction.

GGPPS1 predicts the biological character of hepatocellular carcinoma in patients with cirrhosis.

Background: Hepatocellular carcinoma (HCC) has been associated with diabetes and obesity, but a possible connection with the metabolic syndrome (MetS) and its potential interaction with hepatitis and cirrhosis are open to discussion. Our previous investigations have shown that GGPPS1 plays a critical role during hyperinsulinism. In this report, the expression and distribution of GGPPS1 in liver cancer, and its clinical significance were investigated.

Direct sp3 C-H bond arylation, alkylation, and amidation of tetrahydroisoquinolines mediated by hypervalent iodine(III) under mild conditions.

We have developed a method for the sp(3) C-H bond functionalization of tetrahydroisoquinolines (THIQs) mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA). The treatment of the THIQs with various nucleophiles in the presence of PIFA in a green solvent alternative gave the coupled products, with a C-C, C-N, or quaternary carbon center in high yields.

Neck dissection for oral mucosal melanoma: caution of nodular lesion.

Background: Oral mucosal melanoma (OMM) often metastasizes to cervical nodes. A great number of studies have been conducted to evaluate the efficacy of neck dissection in the treatment of OMM, but considerable controversy remains in this field.

Patients And Methods: The clinical features, treatments, and outcomes of 254 OMM patients were retrospectively analyzed from Jan.

Sequential therapy of advanced buccal mucosa squamous cell carcinoma: three-year outcome.

Purpose: Squamous cell carcinoma (SCC) of the buccal mucosa is aggressive and requires multimodal treatment. The objective of this study was to evaluate the outcome of sequential therapy (neoadjuvant therapy plus surgery plus radiotherapy) in advanced buccal SCC and explore the prognostic factors.

Patients And Methods: In this retrospective cohort study, patients with advanced buccal cancer who received neoadjuvant chemotherapy (cisplatin, docetaxel, and 5-fluorouracil) followed by surgery and radiotherapy in the authors' department were reviewed.