Main Fragments Research Articles

Chlorophyll and pheophytin protonated and deprotonated ions: Observation and theory.

Pheophytin a and chlorophyll a have been investigated by electrospray mass spectrometry in the positive and negative modes, in view of the importance of the knowledge of their properties in photosynthesis. Pheophytin and chlorophyll are both observed intensely in the protonated mode, and their main fragmentation route is the loss of their phytyl chain. Pheophytin is observed intact in the negative mode, while under collisions, it is primarily cleaved beyond the phytyl chain and loses the attaching propionate group. Chlorophyll is not detected in normal conditions in the negative mode, but addition of methanol solvent molecule is detected. Fragmentation of this adduct primarily forms a product (-30amu) that dissociates into dephytyllated deprotonated chlorophyll. Semi-empirical molecular dynamics calculations show that the phytyl chain is unfolded from the chlorin cycle in pheophytin a and folded in chlorophyll a. Density functional theory calculations have been conducted to locate the charges on protonated and deprotonated pheophytin a and chlorophyll a and have found the major location sites that are notably more stable in energy by more than 0.5eV than the others. The deprotonation site is found identical for pheophytin a and the chlorophyll a-methanol adduct. This is in line with experiment and calculation locating the addition of methanol on a double bond of deprotonated chlorophyll a.

Prior tuberosity screw fixation of the osteotomized tubercle can lead to favorable outcomes in retro-tubercular bi-planar opening wedge high tibial osteotomy

BackgroundExact information regarding fixing the tuberosity screw during retro-tubercular opening-wedge high tibial osteotomy (RT-OWHTO) is still lacking. The purpose of this study was to determine whether prior tuberosity screw fixation before plate fixation of main osteotomy fragment can prevent complications associated with tuberosity screw. MethodsFrom 2019 to 2021, patients who underwent RT-OWHTO were divided into two groups (group I, prior tuberosity screw fixation; group II, later tuberosity screw fixation). A total of 49 and 44 knees were included in groups I and II, respectively. Plain radiographs and computed tomography (CT) were used to analyze the parameters of tuberosity screw fixation, neurovascular (NV) safety and osteotomy configurations. Clinical outcomes and post-operative complications were assessed. ResultsThe delta (Δ) of the deformation angle of the tuberosity (P = 0.002), delta (Δ) of the posterior tibial slope (PTS) (P < 0.001), extruded screw length (P < 0.001), and retro-tuberosity tip distance (P < 0.001) of group I were significantly smaller than those of group II. All tuberosity screws were fixed medially to the NV structures. Post-operative tuberosity fracture occurred in one knee (2%) in group I and in 10 knees (23%) in group II (P = 0.003). ConclusionsRT-OWHTO with prior tuberosity screw fixation can minimize the risk of tuberosity fracture and an increase in the PTS. It can also prevent NV injuries by reducing extruded tuberosity screw length and fixing it medially from the NV structures.

Improving personalized medical implant design: An innovative and automated method leveraging implicit modeling

Advancements in manufacturing technologies have made the design and surgical applications of personalized implants increasingly popular and widespread. This study presents a fast, parametric, and automatic workflow for creating customized implants to be used in the surgical treatment of humerus bone traumas. The workflow operates on various humerus fractures, such as “Butterfly Fragment” fractures, taking into account patient-specific bone geometries and areas where screws will be applied. The workflow is carried out using implicit modelling and nTopology software. Initially, a replica of the “Butterfly Fragment” fracture is created for the study, and the damaged bone tissue is removed. Subsequently, a filler structure connecting the two main fragments is obtained using a porous structure. The workflow continues with the identification of areas where screws will be applied around the bone trauma and the selection of the surface where the implant will be created. Using selected points on the surface mesh and single-dimensional beams guided by these points, the external geometry and screw holes of the implant are shaped. The workflow is completed by offsetting certain structures created in intermediate steps and applying surface treatments to obtain the final shape and thickness of the implant, which is compatible with the bone structure. At the end of the process, the workflow is converted into a single function block, which can be shared for use by an implant designer. This enables the widespread application of personalized implant designs. The workflow accelerates the design process of the implant, providing implicit data suitable for production using additive manufacturing. This study offers a preparatory process for the rapid design and production of customized implants for patients. Future research may include comparisons of CAD design and implicit modelling methods, time studies, process modifications, optimizations, and investigations related to additive manufacturing printers. This study contributes to shortening the time until the application of surgical treatment methods by accelerating the design and production process of customized implants.

Structure analysis and in vitro evaluation of probiotic properties for polysaccharides from Phellinus baumii extracted with phosphotungstic acid assistance

Heteropolysaccharides were extracted from Phellinus baumii using hot water assisted by phosphotungstic acid, and their physicochemical properties and structures were analyzed. Two isolated components (SPB and SPC) were composed of fucose, galactose, glucose and mannose, with molecule weight of 12.6 kDa and 9.4 kDa, respectively. Structural analysis showed that →6)-Galp-(1→ and →4)-Glcp-(1→ were the main 2D structural fragments in SPB, while →6)-Galp-(1→ and →6)-Glcp-(1→ predominated in SPC. After 48 h of in vitro fermentation with human fecal inoculum, the concentration of propionic acid was extensively boosted (166.3–538.0 μg/mL) by SPB. In addition, the heteropolysaccharides could promote the abundance and diversity of gut microbiota. SPB markedly promoted proliferation of Limosilactobacillus, Megamonas and Bifidobacterium. KEGG-based functional gene prediction implied that biosynthesis of antibiotics, secondary metabolites and ribosome were promoted by SPB component, indicating a stronger probiotic proliferative ability compared to SPA. Overall, these findings emphasized the potential of these heteropolysaccharides possess to maintain the gut health as a potential prebiotic supplemented in foods and nutraceuticals.

SILVR: Guided Diffusion for Molecule Generation.

Computationally generating new synthetically accessible compounds with high affinity and low toxicity is a great challenge in drug design. Machine learning models beyond conventional pharmacophoric methods have shown promise in the generation of novel small-molecule compounds but require significant tuning for a specific protein target. Here, we introduce a method called selective iterative latent variable refinement (SILVR) for conditioning an existing diffusion-based equivariant generative model without retraining. The model allows the generation of new molecules that fit into a binding site of a protein based on fragment hits. We use the SARS-CoV-2 main protease fragments from Diamond XChem that form part of the COVID Moonshot project as a reference dataset for conditioning the molecule generation. The SILVR rate controls the extent of conditioning, and we show that moderate SILVR rates make it possible to generate new molecules of similar shape to the original fragments, meaning that the new molecules fit the binding site without knowledge of the protein. We can also merge up to 3 fragments into a new molecule without affecting the quality of molecules generated by the underlying generative model. Our method is generalizable to any protein target with known fragments and any diffusion-based model for molecule generation.

SYNTHESIS AND PROPERTIES OF NEW 1-HYDRAZINOCARBONYLMETHYL-7-BROMO-5-PHENYL-3-ARYLYDENE-1,2-DIHYDRO-3H-1,4-BENZODIAZEPIN-2-ONES

It is known that 1,4-benzodiazepines have neurotropic properties. Previously, we synthesized a series of 3-arylidene-1,2-dihydro-3H-1,4-benzdiazepin-2-ones 11-18 and showed that they exhibit significant analgesic activity. They also show significant affinity for central benzodiazepine receptors and TSPO receptors CNS. With this in mind, we have previously modified the series of 3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones by alkylation of 3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones with monobromoacetic acid methyl ester to the first position of the 1,4-diazepine ring to obtain 1-methoxycarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 19-26, which showed pronounced analgesic activity. The aim of this work is to synthesize and study the affinity for CBR and TSPO receptors 1-hydrazinocarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 27-31, which have not been previously described in the literature. Compounds 27-31 were synthesized as a result of the reaction of 1-methoxycarbonylmethyl-7-bromo-5-phenyl-3-arylidene-1,2-dihydro-3H-1,4-benzodiazepin-2-ones 19-26 with hydrazine hydrate while stirring the components in ethanol. The yields of the reaction products were 65-92%. It was shown that the hydrazinolysis technique used provides high yields of the target compounds. The structure of the synthesized compounds was confirmed by mass spectrometry and 1H NMR spectroscopy. The affinity of the synthesized compounds to the central benzodiazepine receptors CNS (CBR) and TSPO receptors CNS was studied. The affinity of compounds 27-31 was determined in vitro by radioligand analysis by their ability to displace the commercial radioligands [3H] flumazenil and [3H]PK11195 from their specific binding sites in the GABAA receptor complex and TSPO receptors of the synaptic and the mitochondrial fractions of the rat brain membranes, respectively. Compound 27 displaces the commercial [3H]flumazenil radioligand from its specific binding sites in the GABAA receptor complex by 80.1%, and simultaneously exhibits a very low affinity for TSPO receptors. Derivative 27 is the most potent CBR ligand among the investigated compounds and it is a promising compound for pharmacological research. It has been established that in the synthesized series of 3-fluorobenzylidene derivatives, varying the position of the fluorine atom in the benzylidene fragment leads to change affinity for TSPO receptors. It has been established that the para- position of the fluorine atom in the 3-benzylidene radical of the 1,4-benzodiazepin-2-one molecule is the most important descriptor that determines their affinity for the TSPO receptors. These data agree with the data available in the literature on the effect of the position of chlorine and bromine atoms in the 3-benzylidene radical of the 1,4-benzodiazepin-2-one molecule on the affinity for the TSPO receptors. It was found that the main structural fragment that determines the affinity of binding of 3-benzylidene derivatives to TSPO receptors is the presence of electronegative substituents in the para-position of the benzylidene fragment: para–Hal&gt;&gt;оrtho–Hal&gt;meta–Hal (affinity for TSPO) (Hal= Br, F) Thus, the expediency of further study of this class of compounds is shown.

Molecular pyramids - from tetrahedranes to [6]pyramidanes.

The study of 3D architectures at a molecular scale has fascinated chemists for generations. This includes molecular pyramids with all-carbon frameworks, such as trigonal, tetragonal and pentagonal pyramidal geometries. A small number of substituted tetrahedranes and all-carbon [4]-[5]pyramidanes have been experimentally generated and studied. Although the hypothetical unsubstituted parent [3]-[6]pyramidanes have only been explored computationally, the formal replacement of carbon vertices with isolobal main group element fragments has provided a number of examples of stable hetero[m]pyramidanes, which have been isolated and amply characterized. In this Review, we highlight the synthesis and chemical properties of [3]-[6]pyramidanes and summarize the progress in the development of chemistry of pyramid-shaped molecules.

Development of a 3D Computer Simulation Model Using C++ Methods

The article presents modelling of spherical elements based on the developed computer model. We recorded the main combinations of spherical particles during filling, which are formed in the hopper. It was found that the most likely combination that occurs when modelling spherical elements consists of three balls. It should be noted that in the cross-section of such a combination passing through the center of the balls, an equilateral triangle is formed. And in the cross-section of the structure, which consists of four spherical balls, a rhombus is formed, if you connect the centers of these spherical elements. It is worth noting that from this formed combination of spherical elements, it can be seen that the rhombus forms two smaller equilateral triangles that fix the process of pushing the spherical balls apart. In turn, the process of pushing spherical elements apart made it possible to fix the contact between spherical elements, as well as to state the stable position of each (individual) particle. This paper also presents the main fragments of encoding the source text of a 3D computer model for modelling spherical elements, which made it possible to optimize the model parameters. It was found that from the obtained data on the distribution of coordination numbers for different volume fillings of spherical elements, it follows that the largest filling was 72 %, which corresponds to the state when 112 lobules have an average coordination number of 3,92.

Exploring the research dynamics of futures studies: An analysis of six top journals

This paper focuses on the global literature on Futures Studies and foresight over the last thirty years by using a bibliographic dataset from the Scopus and using an integrated statistical methodological approach. Bibliometric measures, knowledge mapping tools, topic modelling, Geographical Information Systems and network analysis are used to understand the scholarly literature’s evolution, main research areas, temporal evolution, geographical differences, and fragmentation. This allows to outline a separation between research areas and understand the dynamics of the main topics. The aim of this research is to fill the gap in the literature regarding the mapping of research themes in Futures Studies and foresight, as well as their temporal evolution and geographical distribution. Results showed a notable growth in the number of published articles in the last 32 years and identified (through Latent Dirichlet Allocation) 21 topics, which summarize the most important research themes in the context of Future Studies and foresight. A dynamic topic model helped to understand the evolution of topics, while the network analysis provided quantitative measures on the interactions between the topics as well as the international collaborations. Finally, a geographical analysis of both authors and topics highlighted the global distribution of research on Futures Studies.

Chemical tracers for Wildfires–Analysis of runoff surface Water by LC/Q-TOF-MS

A quantitative methodology using high resolution mass spectrometry was developed for the identification of organic compounds derived from wildfires in surface water samples. The methodology involves the use of solid-phase extraction (SPE) followed by detection using liquid chromatography-quadrupole time of flight-mass spectrometry (LC/Q-TOF-MS) for a group of fourteen chemical compounds (pyridine, benzene, naphthalene and biphenyl polycarboxylic acids). All compounds were successfully separated chromatographically using a reversed phase column and they were identified by accurate mass using the deprotonated species and their main fragment ions. The method produced excellent accuracies (>95%) and precisions (3–10%) for all the compounds studied. This methodology was successfully applied to the identification of fourteen compounds in runoff surface waters impacted by wildfires in Colorado in 2020. Concentrations of individual compounds ranging from 0.1 to 59.5 μg/L were found in wildfire impacted waters, with totals of ∼200 μg/L, thus showing these compounds as chemical tracers of wildfire events at significantly high concentrations. In addition, non-target analysis using chromatography patterns and mass spectrometry identification by MS-MS revealed other polycarboxylic acid isomers were also present in runoff surface water samples.

A comparative evaluation on the physicochemical properties of sugarcane residues for thermal conversion processes

Sugarcane straw (SCS), sugarcane bagasse (SCB), and sugarcane bagasse pith (SBP) are three significant and widely produced by-products and wastes of sugarcane cultivation around the world. In this study, a comparative investigation on the quantitative and qualitative characteristics of sugarcane residues for the thermal conversion processes was conducted with a particular emphasis on the thermal decomposition of sugarcane residues. In this regard, the physicochemical and thermogravimetric evaluation of SCS, SCB, and SBP for thermal conversion has been thoroughly examined using a comprehensive set of experiments. The suitability of the samples, particularly as feedstock for the pyrolysis process, was investigated in detail using proximate, ultimate, and compositional analyses. In addition, the molecular structure and main fragments of the three samples were compared and discussed. Accordingly, the effect of the structural unit of functional parts of the three main biopolymeric components of sugarcane residue, including cellulose, hemicellulose, and lignin, and their interactions on the thermal stability of SCS, SCB, and SBP for the pyrolysis process has been determined. Also, a comprehensive review was carried out to compare the results of the study to the findings of the relevant literature. The outcome of the study could provide reliable information for the design and optimization of the thermal conversion processes using various sugarcane residues.

On the new mechanism of planetary long-period debris formation around white dwarfs

ABSTRACT To explain the phenomenon of metal pollution of white dwarfs (WD) photospheres, we compared three main fragmentation mechanisms of small bodies (SB): tidal force, thermal destruction, and sublimation when SB fall on to WD along star-grazing orbits. The temperatures of the WDs lie in the range of 3000–15 000 K. We consider two materials, using their internal strength: crystalline ice and chondrite. We show that inside the Roche limit, ice bodies (ISB) ranging in size from 60 m to 150 km are destroyed by tidal forces. The corresponding sizes of stony bodies (SSB) range from 90 m to 130 km. Bodies of centimetre size are subject to sublimation. The thermal destruction mechanism is effective for bodies whose size lies in the interval where tidal forces and sublimation are not so effective, destroying SSBs smaller than 50 m and ISBs smaller than 1 km near stars with ${T}_\rm{eff} \le 15\, 000$ K. Such bodies are totally destroyed by thermal tensile stresses long before they reach the Roche limit. There may be observable manifestations of SB falling in the form of short-term flashes of the order of a second from SSB with sizes ≤ 100 m and WD curtaining with dust tails from ISB, causing WD dimming for a short time of the order of an hour. We conjecture that SB, moving along elongated elliptical orbits at large distances from the star, disintegrates by thermal destruction. The fragments from debris discs have nothing to do with the Roche limit.

CALCULATION OF NUCLEAR FUEL CLADDING INTERNAL COATING THICKNESS FOR EMERGENCY RESISTANT NUCLEAR FUEL ELEMENT

CALCULATION OF NUCLEAR FUEL CLADDING INTERNAL COATING THICKNESS FOR EMERGENCY RESISTANT NUCLEAR FUEL ELEMENT

The mechanism and performance of rock breakage by undercutting disc cutter with advanced slotting

To study the mechanism and performance of rock breakage by an undercutting disc cutter with advanced slotting, a three-dimensional numerical model of rock cutting by a disc cutter with advanced slotting assistance was established based on the discrete element method. The parallel bond constitutive model was selected to describe the micromechanical properties of rock. The correctness of the established numerical model is verified through rock breakage experiments, and the rock cutting process by the disc cutter was analyzed by a combination of the force chain and crack distribution. The influencing factors, such as advanced slotting depth, cutting thickness, rock strength, and cutter rotation speed, on rock cutting performance were investigated. The results show that a compact zone is gradually formed between the rock and disc cutter at the beginning, then a large number of microscopic tensile and shear cracks in the compact zone due to micro failure of rock are formed; the subsequent main rock fragment is mainly caused by tensile failure; advanced slotting can reduce the rock bearing capacity and bending resistance, the rock above the advanced slotting fractured easily due to its lower bending resistance, and the volume compact zone is relatively small. When the advanced slotting depth is equal to 12.5 mm, the propulsive force and specific energy consumption of rock cutting by the disc cutter are reduced by 61.6% and 16.5%, respectively. The propulsive force and specific energy consumption increase as the rock strength increases, but they tend to close when the rock strength is greater than 80 MPa, which indicates that advanced slotting assistance is more suitable for hard rock. The results obtained in this paper can provide the operating parameters determination under different factors to some extent of the undercutting disc cutter in a pre-cut condition, which further improve the rock breaking performance of mechanized cutter.

Nonanatomic healing of the greater tuberosity after plating in proximal humeral fractures: a case control study

BackgroundOpen reduction and plate internal fixation (ORIF) is one of the most common treatment methods for proximal humeral fractures. Complications associated with the greater tuberosity (GT) are rarely reported, therefore, the purpose of this study was to analyze the complications associated with the GT and the risk factors after locked-plate internal fixation.MethodsWe retrospectively analyzed the medical and radiographic data of patients with proximal humeral fractures involving the GT treated with locking plates between January 2016 and July 2019. We divided all patients into two groups, the anatomic GT healing group and the nonanatomic GT healing group, depending on the radiographic outcomes of the GT. Clinical outcome was assessed by the Constant scoring system. Potential risk factors included preoperative and intraoperative factors. Preoperative factors included sex, age, body mass index, fracture type, fracture-dislocation, proximal humeral bone mineral density, humeral head extension, hinge integrity, comminuted GT, volume and surface area of the main GT fragment, and displacement of the main GT fragment. Intraoperative factors were adequate medial support, residual head-shaft displacement, head-shaft angle and residual GT displacement. Univariate logistic regression and multivariate logistic regression were used to identify risk factors.ResultsThere were 207 patients (130 women and 77 men; mean age, 55 years). GT anatomic healing was observed in 139 (67.1%) patients and nonanatomic healing in 68 (32.9%). Patients with GT nonanatomic healing had significantly inferior Constant scores than those with GT anatomic healing (75.0 ± 13.9 vs. 83.9 ± 11.8, P < 0.001). Patients with high GT malposition had worse Constant scores than patients with low GT malposition (73.3 ± 12.7 vs. 81.1 ± 11.4, P = 0.039). The multivariate logistic model showed that GT fracture characteristics were not risk factors for nonanatomic GT healing, while residual GT displacement was.ConclusionsNonanatomic healing of the GT is a high-rate complication of proximal humeral fractures, resulting in inferior clinical outcomes, especially for high GT malposition. Fracture characteristics of the GT are not risk factors for GT nonanatomic healing and GT comminution should not be regarded as a contraindication to ORIF for proximal humeral fractures.

Discovery of Chalcone-Based Hybrid Structures as High Affinity and Site-Specific Inhibitors against SARS-CoV-2: A Comprehensive Structural Analysis Based on Various Host-Based and Viral Targets.

Previous studies indicated that natural-based chalcones have significant inhibitory effects on the coronavirus enzymes 3CLpro and PLpro as well as modulation of some host-based antiviral targets (HBATs). In this study, a comprehensive computational and structural study was performed to investigate the affinity of our compound library consisting of 757 chalcone-based structures (CHA-1 to CHA-757) for inhibiting the 3CLpro and PLpro enzymes and against twelve selected host-based targets. Our results indicated that CHA-12 (VUF 4819) is the most potent and multi-target inhibitor in our chemical library over all viral and host-based targets. Correspondingly, CHA-384 and its congeners containing ureide moieties were found to be potent and selective 3CLpro inhibitors, and benzotriazole moiety in CHA-37 was found to be a main fragment for inhibiting the 3CLpro and PLpro. Surprisingly, our results indicate that the ureide and sulfonamide moieties are integral fragments for the optimum 3CLpro inhibition while occupying the S1 and S3 subsites, which is fully consistent with recent reports on the site-specific 3CLpro inhibitors. Finding the multi-target inhibitor CHA-12, previously reported as an LTD4 antagonist for the treatment of inflammatory pulmonary diseases, prompted us to suggest it as a concomitant agent for relieving respiratory symptoms and suppressing COVID-19 infection.

Locking versus nonlocking plates for the treatment of posterior malleolar ankle fractures: A retrospective cohort study and cost analysis

BackgroundWe hypothesized that, as posterior malleolar ankle fractures usually present one or two main fragments, the buttress plating principle can be successfully achieved either with conventional nonlocking or anatomic locking posterior tibia plates, and no clinical differences should be found. The aim of this study was to evaluate the outcomes of posterior malleolar ankle (PM) fractures treated with conventional nonlocking (CNP) or anatomic locking plates (ALP), and also to compare both constructs in terms of crude costs. MethodsA retrospective cohort study was designed. CNP was used in 22 patients and ALP was used in 11 patients. American Orthopedic Foot and Ankle Society (AOFAS) score was registered at four weeks, 3–6 months, 12 and 24 months to assess all patients’ functional status. The primary outcome was ankle and hindfoot AOFAS score at 12 months follow-up visit. All complications, radiographic evaluation and implant construct costs were also registered and compared. The average follow-up was 25.4 (range, 12–42) months. ResultsNo significant difference was observed between both cohorts, in terms of AOFAS score and complication rate (P > .05). We found that ALP construct is 17 times more expensive than CNP construct in our institution (P < .001). ConclusionAnatomic locking posterior tibial plates may be an interesting device when poor bone quality is present or when a true multifragmentary pilon fracture is faced. Anatomic locking posterior tibia plate should not become a regular implant for any PM fracture since equivalent clinical and radiological results were obtained in our study using CNP with a significant reduced cost.

Probing Intermediates of Ion/Molecule Reactions by their Independent Gas‐Phase Synthesis and Fragmentation – The Thiomethoxymethyl Complexes [(bipy)M(CH2SCH3)]+ (M=Pt, Pd, Ni)

AbstractIn the ion/molecule reaction (IMR) of “rollover”‐cyclometalated [(bipy−H)Pt]+ with (CH3)2S, the loss of C2H4 from the encounter complex was observed as the main process some years ago. The cationic complex [(bipy)Pt(CH2SCH3)]+ was identified as a crucial intermediate by DFT calculations. In order to prove its key role experimentally, the cation has now been generated independently and studied by collision‐induced dissociation (CID). The main process is C2H4 loss, which proves [(bipy)Pt(CH2SCH3)]+ to be an intermediate also in the IMR of [(bipy−H)Pt]+ with (CH3)2S. Based on DFT calculations, the thiomethoxymethyl complexes [(bipy)M(CH2SCH3)]+ (M=Pd and Ni) would also serve as intermediates in the IMRs of [(bipy−H)M]+. While these IMRs cannot be studied explicitly, because the parent ions cannot be generated, the potential intermediate [(bipy)M(CH2SCH3)]+ has been subjected to CID. The main fragmentation channels for both metals corresponds to C2H4 loss. The CID experiments thus provide insights into the hypothetical IMRs of [(bipy−H)M]+ with (CH3)2S. The comparison of the DFT calculations for all three metals Ni, Pd, and Pt with the experimental findings uncovers subtle aspects of the underlying reaction mechanisms. This work highlights the suitability of CID experiments of potential reaction intermediates for the elucidation of reaction mechanisms of IMRs as well as the limitations of this approach.

Integrated analysis of topoisomerase I inhibitors from flavonoids of Scutellaria baicalensis Georgi using bioaffinity ultrafiltration UPLC-TripleTOF MS/MS, molecular docking and target-based multiple complex networks

Scutellaria baicalensis Georgi (SBG) has been widely used as medical plant in East Asia with remarkable anti-cancer activity. However, the underlying mechanisms are still confused. In this study, an integrated analysis was conducted to screen topoisomerase I (topo I) inhibitors from flavonoids of SBG and investigate the anti-cancer mechanisms, containing bioaffinity ultrafiltration UPLC-ESI-TripleTOF-MS/MS, molecular docking, and multiple complex networks. The SBG extract exhibited notable cytotoxic activity on Hela cells. Five flavonoids were identified as potential topo I inhibitors, including skullcapflavone II, wogonin, chrysin, oroxylin A, and tenaxin I. Their ESI-MS/MS spectra showed that RDA reaction and neutral molecule loss were the main fragment patterns. Docking results demonstrated that π–π interaction and the formation of hydrogen bond contributed most to their binding with topo I. The selected compounds, related target proteins and pathways were integrated into target-based multiple complex networks, which consisted of three subnetworks. Statistical and topological analysis of these networks revealed a series of characteristics, including scale-free property with power-law degree distribution, Poisson degree distribution, and small-world property. Chrysin, wogonin, and oroxylin A exhibited as main active components with much higher degree values. Chemical carcinogenesis-receptor activation (hsa05207) was considered as critical pathway due to remarkable centrality indexes. Additionally, potential synergistic effect of wogonin and chrysin was observed on the conversion of supercoiled DNA to relaxed forms. These results improved current understanding of flavonoid-rich plants on the treatment of cancer. Moreover, the multi-disciplinary approach provided a new strategy for the research of natural products from medical plants.

Application of mass spectrometry fragmentation patterns for rapid screening and structure identification of fentanyl analogues in suspicious powder

Fentanyl analogues are one of the most abused categories of synthetic opioids due to their higher potency in contrast to traditional opioids. Given that fentanyl analogues are obtained by modifying the structure of fentanyl, the evolutionary rules and common fragmentation patterns of fentanyl analogues could be used for rapid screening and structural identification of these substances. Hence, the evolutionary rules and common EI-MS and ESI-MSn fragmentation patterns of fentanyl analogues are summarized based on previous literature in this study. The cleavage of the N-C4 bond is the main fragmentation pathway of fentanyl analogues in ESI-MSn mode, while the side chain cleavage at the N1 position and piperidine ring-breaking rearrangement are the featured fragmentation pathways of fentanyl analogues in EI-MS mode. ESI-MS/MS fragmentation patterns could be applied to identify the Core A (piperidine ring) and Part D (2-(thiophen-2-yl)ethyl, 2-(fluoro-2-phenyl)ethyl and benzyl, etc) of fentanyl analogues and EI-MS fragmentation patterns could be used to characterize Parts B (isobutyryl, valeryl, furan-2-formyl and benzoyl, etc) and C (substituted or unsubstituted monocyclic aromatic groups). Based on the evolutionary rules and fragmentation patterns of fentanyl analogues, five unknown fentanyl analogues in two suspected seizures are identified by LC-Q-Orbitrap/MS and GC-EI-MS. Structures of five unknown fentanyl analogues in suspicious seizures are investigated. Besides, computational results show that EI-MS fragmentation pathways are controlled by both energy barrier and spin-density difference population. Hence, more fragmentation routes are available. This method is intended to provide data for high-speed screening and structural identification of fentanyl analogues for forensic identification and regulation.