The current challenge in fluorescence guided surgery (FGS) for prostate cancer (PCa) is in the design of imaging probes with high selectivity, clear visualization of tumour margins, and minimal toxicity. This report aims to design and develop a novel NIR-nanoprobe, and evaluate its potential in the penetration of PCa tumour tissues. The PSMA receptor-targeted quantum dot (PSMA-QD655) is a NIR, deep-tissue imaging agent, which has the potential for intraoperative navigation during surgery and improved detection specificity for PCa.  https://www.selleckchem.com/  The probe was designed and synthesized by conjugating functionalized amino-PEG quantum dots (QDs) through a heterobifunctional linker to a DUPA targeted polypeptide construct. The nanoprobe was evaluated in vitro in PSMA+ PCa cell lines for specificity and its binding affinity was determined by flow cytometric analysis. The penetration efficacy was tested further on large PCa 3D tumour spheroids (dia ∼1200 μm, thickness ∼450 μm) by deep tissue multiphoton imaging. PSMA-QD655 was found to be an efficient deep tissue intra-operative guided surgical tool with a high affinity (KD = 15.3 nM) and penetrative capacity. The results have been demonstrated in vitro in 2D and 3D tissue models, mimicking cancer lesions in vivo. In summary, we have developed a deep-tissue imaging NIR nanoprobe targeting prostatic lesions that (i) binds to PSMA+ tumour with sub-nanomolar affinity and high specificity, (ii) shows an excellent safety profile in primary cell lines in vitro and (iii) shows high penetrative capacity in a 3D prostate tumour model (∼450 μm tissue depth).The ultrafast excited-state dynamics of 2,4,6-triaminopyrimidine - thought to be a promising candidate for a proto-RNA nucleobase - have been investigated via static multireference quantum-chemical calculations and mixed-quantum-classical/trajectory surface-hopping dynamics with a focus on the lowest-lying electronic states of the singlet manifold and with a view towards understanding the UV(C)/UV(B) photostability of the molecule. Ultrafast internal conversion channels have been identified that connect the lowest-lying ππ* electronically-excited state of 2,4,6-triaminopyrimidine with the ground electronic state, and non-radiative decay has been observed to take place on the picosecond timescale via a ππ* out-of-plane NH2 ("oop-NH2") minimum-energy crossing point. The short excited-state lifetime is competitive with the excited-state lifetimes of the canonical pyrimidine nucleobases, affirming the promise of 2,4,6-triaminopyrimidine as an ancestor. Evidence for energy-dependent excited-state dynamics is presented, and the open question of intersystem crossing is discussed speculatively.The activation of GABAA receptors by the neurotransmitter gamma-aminobutyric acid mediates the rapid inhibition response in the central nervous system of mammals. Many neurological and mental health disorders arise from alterations in the structure or function of these pentameric ion channels. GABAA receptors are targets for numerous drugs, including benzodiazepines, which bind to α1β2γ2 GABAA receptors with high affinity to a site in the extracellular domain, between subunits α1 and γ2. It has been established experimentally that the binding of these drugs depends on the presence of one particular amino acid in the α1 subunit histidine 102. However, the specific role it plays in the intermolecular interaction has not been elucidated. In this work, we applied in silico methods to understand whether certain protonation and rotamer states of α1His102 facilitate the binding of modulators. We analysed diazepam binding, a benzodiazepine, and the antagonist flumazenil to the GABAA receptor using molecular dynamics simulations and adaptive biasing force simulations. The binding free energy follows changes in the protonation state for both ligands, and rotameric states of α1His102 were specific for the different compounds, suggesting distinct preferences for positive allosteric modulators and antagonists. Moreover, in the presence of diazepam and favoured by a neutral tautomer, we identified a water molecule that links loops A, B, and C and may be relevant to the modulation mechanism.Needle insertion, a standard process for various minimally invasive surgeries, results in tissue damage which sometimes leads to catastrophic outcomes. Opaqueness and inhomogeneity of the tissues make it difficult to observe the underlying damage mechanisms. In this paper, we use transparent and homogeneous polyacrylamide hydrogel as a tissue mimic to investigate the damages caused during needle insertion. The insertion force shows multiple events, characterised by a gradual increase in the force followed by a sharp fall. Synchronised recording of the needle displacement into the gel shows that each event corresponds to propagation of stable cone crack. Though sporadic uncontrolled cracking has been discussed earlier, this is the first report of nearly periodic, stable and well-controlled 3-D cone cracks inside the hydrogel during deep penetration. We show that the stress field around the needle tip is responsible for the symmetry and periodicity of the cone cracks. These results provide a better understanding of the fracture processes in soft and brittle materials and open a promising perspective in needle designs and the control of tissue damages during surgical operations.Using first principles calculations, we have designed a new polymorph for two-dimensional (2D) III-V group materials with an orthorhombic phase, including BN, BP, BAs, AlN, AlP, and GaN, and investigated their structural, electronic, and optical properties. The phonon dispersion calculations have shown that BN, BP, AlN, and GaN possess excellent dynamic stabilities. The 2D BN is a direct semiconductor, and its bandgap predicted by PBE and HSE calculations is 0.76 and 1.73 eV, respectively. The calculated mobilities of the BN, AlN, and GaN monolayers have shown their high conductivities, and the monolayered AlN and GaN possess strong anisotropic carrier transport characters. The 2D AlN and AlP and GaN monolayers are found to be indirect semiconductors with bandgaps in the range of 0.66-1.65 eV. The 2D BN and BP monolayers exhibit extremely high and anisotropic absorbance, and their absorption energy range covers the whole solar spectrum, rendering them potential candidates for applications in solar cells. More importantly, their optical properties are shown to have highly anisotropic optical absorbance, making them promising candidates for manufacturing anisotropic optoelectronic devices.