Unveiling the role of HP1α-HDAC1-STAT1 axis as a therapeutic target for HP1α-positive intrahepatic cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear.

Effects of driving pressure-guided ventilation on postoperative pulmonary complications in patients with COVID-19 undergoing abdominal surgery: A post-hoc propensity score-matched analysis.

Background: Application of individualized positive end-expiratory pressure (PEEP) based on minimum driving pressure facilitates to prevent from postoperative pulmonary complications (PPCs). Whether lung protective ventilation strategy can reduce the risk of PPCs in COVID-19 patients remains unclear. In this study, we compared the effects of driving pressure-guided ventilation with conventional mechanical ventilation on PPCs in patients with COVID-19.

Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.

Decades of research have demonstrated an incontrovertible role of amyloid-β (Aβ) in the etiology of Alzheimer's disease (AD). However, the overemphasis on the pathological impacts of Aβ may obscure the role of its metabolic precursor, amyloid precursor protein (APP), as a significant hub in the occurrence and progression of AD. The complicated enzymatic processing, ubiquitous receptor-like properties, and abundant expression of APP in the brain, as well as its close links with systemic metabolism, mitochondrial function and neuroinflammation, imply that APP plays multifaceted roles in AD.

APP mediates tau uptake and its overexpression leads to the exacerbated tau pathology.

Alzheimer's disease (AD), as the most common type of dementia, has two pathological hallmarks, extracellular senile plaques composed of β-amyloid peptides and intracellular neurofibrillary tangles containing phosphorylated-tau protein. Amyloid precursor protein (APP) and tau each play central roles in AD, although how APP and tau interact and synergize in the disease process is largely unknown. Here, we showed that soluble tau interacts with the N-terminal of APP in vitro in cell-free and cell culture systems, which can be further confirmed in vivo in the brain of 3XTg-AD mouse.

Xishacorenes A-C, Diterpenes with Bicyclo[3.3.1]nonane Nucleus from the Xisha Soft Coral Sinularia polydactyla.

Three new diterpenes, xishacorenes A-C, featuring an undescribed bicyclo[3.3.1]nonane nucleus bearing 1-vinyl and 13-[(E)-4-methylpenta-1,3-dien-1-yl] alkyl chains, and a related monocyclic known compound, were isolated from the Xisha soft coral Sinularia polydactyla.

Investigation of halogenation during the biosynthesis of ramoplanin in Actinoplanes sp. ATCC33076.

Ramoplanin and enduracidin are lipopeptide antibiotics effective against Gram-positive pathogens, which share close similarity in structure and biosynthetic pathway. Both compounds have chlorine atoms attached to 4-hydroxyphenylglycine (Hpg) but with different chlorinating sites and levels. Here, to probe the factor affecting the site and level of halogenation, gene inactivation and heterologous expression were carried out in Actinoplanes sp.

Photophysical Properties of a Post-Self-Assembly Host/Guest Coordination Cage: Visible Light Driven Core-to-Cage Charge Transfer.

Supramolecular systems are capable of unique photophysical properties due to possible interactions between subcomponents, such as between an encapsulated molecule and its cage in a host/guest environment. Here, we report that the encapsulation of a chromophore by a metallacage dramatically enhances its photophysical properties. In the visible region, the encapsulated photosensitizer achieves a 6.

Influence of seismic loading on segment opening of a shield tunnel.

The influence of seismic loading on segment opening of a shield tunnel was explored using the dynamic finite element method to analyze the distribution of segment opening under multidirectional seismic loading, combined with a typical engineering installation. The calculation of segment opening was deduced from equivalent continuous theory and segment opening was obtained through calculations. The results show that the scope of influence of the foundation excavation on segment opening is mainly resigned to within 5 segment rings next to the diaphragm wall and 4 joints nearest the working well when the tunnel is first excavated followed by the working well in the excavation order.

Sensing mechanism for biothiols chemosensor DCO: roles of excited-state hydrogen-bonding and intramolecular charge transfer.

The biothiols sensing mechanism of (E)-7-(diethylamino)-3-(2-nitrovinyl)-2H-chromen-2-one (DCO) has been investigated using the density functional theory (DFT) and time-dependent DFT methods. The theoretical results indicate that the excited-state intermolecular hydrogen bonding (H-B) plays an important role for the biothiols sensing mechanism of the fluorescence sensor DCO. Multiple H-B interaction sites exist in DCO and in its Michael addition product DCOT, which then induce the formation of the H-B complexes with water molecules, DCOH2 and DCOTH4.

Steady-state and time-resolved spectroscopic investigations on the existence of stable methanol/AOT/n-heptane reverse micelles.

In this work, we have reported our study on the controversial issue whether methanol molecules can be effectively encapsulated by surfactant AOT to form true reverse micelles. We compared the different photophysical properties of coumarin 153 (C153) in methanol/AOT/n-heptane reverse micelles and methanol/n-heptane binary mixture by means of steady-state absorption, fluorescence and time-resolved fluorescence spectroscopies. In the reverse micelles, the fluorescence emission spectra of C153 were dependent on the excitation wavelength, while in binary mixtures, the excitation wavelength dependence was not observed.

Sensing mechanism for a fluoride chemosensor: invalidity of excited-state proton transfer mechanism.

Our density functional theory (DFT)/time-dependent DFT calculations for the fluoride anion sensor, 5,7-dibromo-8-tert-butyldimethylsilyloxy-2-methylquinoline (DBM), suggested a different sensing mechanism from the experimentally proposed one (Chem. Commun., 2011, 47, 7098).

Functional identification of the gene encoding the enzyme involved in mannosylation in ramoplanin biosynthesis in Actinoplanes sp.

Ramoplanin is a lipopeptide antibiotic active against multi-drug-resistant, Gram-positive pathogens. Structurally, it contains a di-mannose moiety attached to the peptide core at Hpg(11). The biosynthetic gene cluster of ramoplanin has already been reported and the assembly of the depsipeptide has been elucidated but the mechanism of transferring sugar moiety to the peptide core remains unclear.

Production of ramoplanin analogues by genetic engineering of Actinoplanes sp.

Ramoplanins are lipopeptides effective against a wide range of Gram-positive pathogens. Ramoplanin A2 is in Phase III clinical trials. The structure-activity relationship of the unique 2Z,4E-fatty acid side-chain of ramoplanins indicates a significant contribution to the antimicrobial activities but ramoplanin derivatives with longer 2Z,4E-fatty acid side-chains are not easy to obtain by semi-synthetic approaches.

Fluoride anion sensing mechanism of 2-ureido-4[1H]-pyrimidinone quadruple hydrogen-bonded supramolecular assembly: photoinduced electron transfer and partial configuration change.

The fluoride anion sensing mechanism of 6-methyl-5-(9-methylene-anthracene)-(2-butylureido-4[1H]-pyrimidinone) (AnUP) has been investigated using the DFT/TDDFT method. The theoretical results indicate that the proton of the N3-H3 group in pyrimidine moiety is captured by the added fluoride anion and then deprotonated. The calculated vertical excitation energies of AnUP-dimer and its deprotonated form agree well with the experimental results.

Photophysical properties of self-assembled multinuclear platinum metallacycles with different conformational geometries.

In this work, spectroscopic techniques and quantum chemistry calculations were used to investigate the photophysical properties of various multinuclear platinum complexes with different conformational geometries. This suite of complexes includes a Pt-pyridyl square, a Pt-carboxylate triangle, and a mixed Pt-pyridyl-carboxylate rectangle, as well as two mononuclear Pt model complexes. Studying the individual molecular precursors in the context of larger assemblies is important to provide a complete understanding of the factors governing the observed photophysical properties of a given system.

Genetic manipulation revealing an unusual N-terminal region in a stand-alone non-ribosomal peptide synthetase involved in the biosynthesis of ramoplanins.

Ramoplanins produced by Actinoplanes are new structural class of lipopeptide and are currently in phase III clinical trials for the prevention of vancomycin-resistant enterococcal infections. The depsipeptide structures of ramoplanins are synthesized by non-ribosomal peptide synthetases (NRPS). Romo-orf17, a stand-alone NRPS, is responsible for the recruitment of Thr into the linear NRPS pathways for which the corresponding adenylation domain is absent.

Experimental and theoretical study on the photophysical properties of 90° and 60° bimetallic platinum complexes.

The 90° and 60° bimetallic platinum complexes with special structures are widely used in coordination-driven self-assembled metallosupramolecular architectures, and these complexes are the key components of triangular, rectangular, and polygonal metallacycle and metallocage supramolecules. Therefore, spectroscopic techniques and quantum chemistry calculations were employed in this article to investigate the photophysical properties of these bimetallic platinum complexes. Compared with spectra for the ligands, the absorption spectra of these Pt complexes are red-shifted, and the fluorescence spectra become wider and are also red-shifted.

[Reconstruction and analysis of three-dimensional finite element model of human middle ear].

Objective: To reconstruct a finite element model of human middle ear and measure characteristic dimensions of this model and calculate the mass properties of the ossicles.

Methods: The proposed method starts with the histologic section preparation of human temporal bone. Through tracing outlines of the middle ear components on the sections in AutoCAD2005, a set of exterior contours of the components is obtained.