Search Results (128)

Ferrocenium-catalyzed transformations provide a practical and sustainable approach to propargylic substitution reactions. Herein, we investigate the ring-opening of cyclopropyl-substituted propargylic alcohols with alcohol nucleophiles, catalyzed by ferrocenium tetrafluoroborate ([FeCp₂][BF₄]) to afford synthetically valuable enyne ethers. Mechanistic studies using GC and NMR spectroscopy reveal that the reaction proceeds via initial formation of a ring-closed propargylic ether intermediate, which subsequently undergoes ring opening to the enyne ether. Experimental evidence supports a carbocationic pathway in which the ferrocenium cation promotes ionization to a stabilized cyclopropyl ether intermediate, followed by intramolecular, ferrocenium-assisted cyclopropyl ring opening to the enyne product. Reaction rates and product distributions are strongly influenced by temperature and solvent polarity, with polar solvents and elevated temperatures favoring ring opening. At room temperature, the ring-closed substitution product predominates, whereas efficient formation of enynes occurs at 65 °C. The reaction progresses faster in a polar solvent, indicating an ionic mechanism. Studies employing substrates containing substituted cyclopropyl rings demonstrated pronounced regioselectivity during nucleophilic ring opening with alcohols, with preferential cleavage of the bond between the two substituted carbon atoms. This selectivity is consistent with partial positive-charge stabilization in the transition state. The corresponding enyne ether products were isolated in 98–31% isolated yields, in most cases as a single regio- and E/Z stereoisomer (5 h at 45 °C, 5 mol% [FeCp₂][BF₄] catalyst load, six equivalents alcohol nucleophile). The ferrocenium-catalyzed cyclopropyl ring opening establishes a convenient method for accessing enyne motifs, which are important structural units in organic synthesis and medicinal chemistry. Full article

To address the critical challenges of edge chipping and poor processing quality in sapphire precision dicing, this paper proposes a femtosecond laser filamentation-guided dicing technology. By systematically investigating the influence of pulse overlap rate, energy, and scan counts on damage evolution, the physical differences between 343 nm UV and 515 nm visible lasers in suppressing plasma shielding and breaking through processing saturation limits are revealed. The results indicate that an extremely high pulse overlap rate (>98%) significantly inhibits lateral energy dissipation and drives the efficient propagation of the filament deep along the optical axis; furthermore, the 343 nm laser demonstrates superior removal rates and localisation compared to the 515 nm laser. Using super-resolution imaging, the precision cleavage cross-section is clearly categorised into four evolutionary stages: general ablation, filament ablation, transition, and mechanical cleavage. To mitigate morphological degradation induced by multiple scans, a sacrificial-layer-assisted strategy is innovatively proposed to achieve spatial damage transfer and in situ self-polishing, effectively eliminating longitudinal damage striations and residual stress-induced hackles. Finally, taper-free, high-precision separation of 1 mm × 450 μm micro-units is successfully achieved on a 220-μm-thick sapphire wafer. This technology not only achieves ultra-low-loss dicing but also establishes a highly efficient, contamination-free in situ characterisation paradigm for buried structures in hard and brittle materials. Full article

As space exploration activities and strategic deployments in polar regions continue to advance, higher demands have been placed on the low-temperature resistance of propellant binders. Here, high cis-1,4 content hydroxyl-terminated polybutadiene (HTPB) was successfully synthesized via an oxidative cleavage method using commercial cis-polybutadiene (BR). The microstructure, molecular weight, hydroxyl value, rheological behavior, thermal properties, and mechanical performance of the resulting cis-HTPB were systematically characterized. By adjusting the molar ratio of mCPBA to butadiene units, three cis-HTPB samples with varying molecular weights were obtained. The high cis-1,4 structure (93%) was preserved after modification. The synthesized cis-HTPB exhibited an ultra-low glass transition temperature (Tg) of approximately −100 °C and lower viscosity compared to commercial HTPB, indicating excellent low-temperature flexibility and processability. In addition, the cis-HTPB was further modified with acrylate groups to produce a UV-curable derivative (AcTPB). The cured AcTPB also retained a Tg near −100 °C, demonstrating its suitability for ultra-low-temperature applications and its promise as a photocurable binder for 3D printing propellant. Full article

UVA exposure elicits immediate and persistent pigment darkening of the skin, which is thought to result from the oxidation and polymerization of existing melanin and/or precursors. Melanocytes produce eumelanin and pheomelanin. Eumelanin consists of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), while pheomelanin consists of benzothiazine and benzothiazole units. Melanins can be analyzed by quantifying specific degradation products using HPLC. Specifically, eumelanin can be analyzed as pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA), specific degradation products of DHICA and DHI, respectively. Benzothiazole pheomelanin can be analyzed as thiazole-2,4,5-tricarboxylic acid (TTCA), whereas benzothiazine pheomelanin is analyzed as 4-amino-3-hydroxyphenylalanine (4-AHP) and 3-amino-4-hydroxyphenylalanine (3-AHP). Upon UVA exposure, melanins undergo structural modifications. Eumelanin undergoes oxidative cleavage to free pyrrole-2,3,5-tricarboxylic acid (Free PTCA) and undergoes cross-linking to form pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA). UVA exposure of pheomelanin induces oxidative conversion from the benzothiazine to the benzothiazole. Nevertheless, these structural modifications have never been previously characterized in human skin. In this study, we exposed ex vivo skin to increasing UVA1 doses (60, 90 and 120 J/cm²; n = 6 in triplicate) and characterized the induced pigment darkening before, immediately, and 2 h after exposure through colorimetry, HPLC and spectrophotometry. The results showed changes in the CIELAB colorimetric parameters, namely a decrease in Luminance L*, the yellow-blue component b* and the Individual Typology Angle (ITA) in UVA1-exposed samples, indicative of skin darkening. In parallel, UVA1 exposure induced significant modifications of the levels of absorbance at 500 nm (A500) and melanin markers PTCA, PTeCA, PDCA, TTCA, and 4-AHP, as well as in the ratios of various markers, such as PTeCA/PTCA, Free/Total PTCA, and TTCA/4-AHP, indicative of photooxidation/degradation of melanins. Our study provides the first evidence of UVA1-induced modifications of melanins associated with pigment darkening occurring in human skin. Full article

Against the backdrop of self-financing difficulties, an effect of the transition from a centralized to a market economy, Romanian cities are marked by significant differences in the way local public finances are used. The difficulties generated by insufficient income, complemented by subsidies from the centralized budget, create strong disparities that manifest themselves both vertically within the urban hierarchy (small towns are the most affected) and spatially along development axes. The influence of social, economic, and cultural factors can explain these cleavages, but also expresses the excessive centralization of governance in Romania. The statistical processing of information on budget execution for the years 2019–2023, at the level of the 319 official urban centers in Romania, provides an image of the structure of local budgets through the prism of their self-financing capacity and their supplementation with community funds or government subsidies. The descriptive analysis, which highlights specific structural patterns, is complemented by a multivariate analysis aimed at examining the relationships between self-financing capacity and a set of explanatory variables. The study’s results demonstrate the need to implement programs to reduce urban administrative units’ dependence on the centralized budget and to streamline their own revenue collection. Full article

Elastane is ubiquitous in polyester-based textiles and complicates depolymerization-based recycling because it can undergo thermal degradation and chemical bond cleavage, consuming reagents and forming low-molecular by-products that may compromise monomer quality. Here, we investigate alkaline PET depolymerization of PET/elastane blends under an intentional base-competition scenario in a laboratory kneader. Pure PET (100/0) and PET/EL blends (95/5 and 85/15, wt/wt) were processed under quasi-solid-state conditions at 140 °C for 5 min using solid NaOH dosed at 2.1 mol per mol PET repeat unit and pelletized feedstocks to ensure scale-relevant mixing and reproducible chamber filling. Torque and bulk-temperature profiles were similar across compositions, and isolated terephthalic acid yields remained in a narrow corridor (68–71%), indicating that PET depolymerization is not measurably impaired by 5–15 wt% elastane within this reaction window. Differential scanning calorimetry of water-insoluble residues revealed pronounced changes in elastane-related thermal transitions, evidencing elastane modification during treatment. Targeted ¹H NMR screening of recovered TA against a 4,4′-methylenedianiline spiked reference showed no detectable co-isolated aromatic diamines. Overall, the study demonstrates robust monomer recovery from mixed PET/EL textiles under solid-NaOH, short-residence, solvent-lean processing, while identifying residue analytics as the key bottleneck for quantifying elastane fate and closing component balances. Full article

The fate of a selection of linear and cyclic silicone oil formulations in heavy-duty fluid dampers is studied from molecular dynamics simulations. Mimicking cyclic agitation to all-atom simulation models, we elaborate oscillatory compression/decompression runs that feature degradation reactions within only hundreds of loading cycles. This enables the assessment of chain scission, reassembly and cyclization mechanisms from ns-scale molecular dynamics simulations. Using analogous testing scenarios, we compare the degradation reactions of linear and cyclic silicone chains and demonstrate the importance of silicone ring formation. In turn, cyclic silicone moieties show relative persistence in our compression/decompression runs. We conclude that long-term degradation finally leads to a manifold of cyclic silicone molecules, featuring rings of up to tens of monomeric units. The underlying molecules are not inert to Si-O bond cleavage and reformation, but feature reactivity in terms of the fusion of small to large rings and vice versa. Full article

Sb-rich avicennite (first discovery in Russia) was found at the Khokhoy gold deposit, 120 km west of Aldan, Aldan district, Republic of Sakha (Yakutia), Eastern Siberia, Russia. The mineral of critical metal thallium forms irregularly shaped grains up to 0.25 mm in size, in association with amgaite, weissbergite, goethite, gold, and unidentified Tl-bearing phases. Aggregates of colloform structure prevail, represented by rhythmic-, concentric-zonal, kidney-shaped, and spherulitic varieties. Avicennite is black in color, with metallic luster, and it fractures unevenly. No cleavage is observed. The density value of avicennite, obtained using its empirical formula and the unit cell parameters calculated from the powder X-ray diffraction data, is 8.548 g/cm³. In reflected light, avicennite is light gray and isotropic. Internal reflections are absent. Reflection is very low; the reflectivity curve is of mixed type with a small maximum in the blue part. Its chemical composition (average value on 10 analyses, wt.%): Tl₂O₃—85.36, V₂O₅—0.73, As₂O₅—0.85, Sb₂O₅—12.98, Total—99.92; It corresponds to the following empirical formula (calculation for three atoms of O): Tl_1.40Sb⁵⁺_0.30V⁵⁺_0.03As⁵⁺_0.03O₃. The unit cell parameters calculated from the powder X-ray diffraction data are as follows: the mineral is cubic, a = 10.496(6) Å, V = 1156(2) Å3. Full article

The genome of the herpesvirus is a linear double-stranded DNA. The viral genome replicates in the host cell to form a concatemeric DNA, which is then cleaved to produce a unit-length genome. This unit-length genome is packaged into procapsid to produce mature virus particles. The terminase large subunit, pUL15, mediates the cleavage and packaging of viral concatemeric genomes. Duck plague virus (DPV) is a member of the α herpesvirus subfamily. Previous studies have demonstrated that the C-terminal region of DPV pUL15 exhibits non-sequence-specific DNA cleavage activity in vitro, but the characteristics of DPV full-length pUL15 remain unclear. In this study, it was determined that the full-length pUL15 exerted non-sequence-specific nuclease activity. Additionally, full-length pUL15 was capable of binding to DNA and hydrolyzing ATP. To analyze the functional domain of DPV pUL15, pUL15 mutants were constructed, expressed, and purified. The results revealed that DNA-binding and ATPase functions of pUL15 were primarily mediated by its N-terminal region, and the nuclease activity was conducted by its C-terminus. The loss of the nuclease activity did not effect on the DNA-binding and ATPase activity. Taken together, this study’s findings demonstrated that DPV pUL15 is a multifunctional enzyme with ATPase, nuclease, and DNA-binding activities. These results will provide important clues for subsequent studies on the function of terminase and the process of viral genome packaging, and provide a foundational basis for the development of broad-spectrum anti-herpesviral drugs targeting the conserved terminase complex, with direct relevance to veterinary medicine. Full article

Most botulinum toxin A (BoNT-A) products for esthetic use require reconstitution before administration. Ready-to-use relabotulinumtoxinA is a liquid manufactured using Precipitation-free Extraction and Activity-preserving, Refined Liquid (PEARL™) Technology from a proprietary C. botulinum type A1 strain. We examined the in vitro characteristics of relabotulinumtoxinA. The specific BoNT-A1 potency remained consistent throughout drug substance manufacturing (1.9 × 10⁸–2.2 × 10⁸ LD₅₀ mouse potency units/mg of BoNT-A1, four fractions sampled). Using glabellar line (GL) on-label doses, relabotulinumtoxinA liquid product was compared with powder onabotulinumtoxinA using the following: BoNT-A1 amount based on ELISA; specific enzyme activity based on SNAP-25 cleavage by a fluorescence resonance energy transfer-based assay (BoTest^®); biological activity (binding, internalization, and SNAP-25 cleavage over time) using a cell-based assay. RelabotulinumtoxinA contained more BoNT-A1 per on-label GL dose (0.27 ng) than onabotulinumtoxinA (0.18 ng), had higher enzyme activity (53 vs. 29 BoTest^® units) per GL dose, and had higher specific activity per pg BoNT-A, with onabotulinumtoxinA displaying 81% of the specific activity of relabotulinumtoxinA. In vitro, relabotulinumtoxinA demonstrated higher biological activity and earlier onset of SNAP-25-cleavage than onabotulinumtoxinA. PEARL^TM Technology thus produces high-quality BoNT-A1 with high specific enzyme and biological activities, which may explain the clinical performance of relabotulinumtoxinA in Phase 3 clinical trials examining treatment of GLs and/or LCLs. Full article

Modification of synthetic oligonucleotides and DNA is widely used in many applications in the life sciences. However, in most cases, modified DNA cannot be restored to its native state. Here, we report the preparation of a thymidine-inosine dimer building block (TID) for oligonucleotide synthesis. The TID modification supports the functionalization of synthetic oligonucleotides, which can later be removed to restore the DNA strand to its native state. The TID unit allows for a wide spectrum of postsynthetic modifications of oligonucleotides through click chemistry, including conjugation with fluorescent tags and small molecules, preparation of branched oligonucleotide scaffolds, and anchoring to a solid support. Due to the modification of the thymine base, the TID unit reduces the stability of the DNA duplex. We found that the negative effect of internal TID modification on duplex stability does not exceed the same for a single base mismatch. As long as the TID modification is present in the DNA strand, it disrupts its natural functionality. The “caging” effect of TID in the template strand with respect to DNA polymerase was demonstrated in primer extension experiments. Traceless removal of the temporary functional group occurs through oxidative cleavage of the inosine subunit, resulting in the formation of a native DNA strand with the thymine base left at the cleavage site. An anthracene-modified dodecamer oligonucleotide and a branched oligonucleotide scaffold were used to study the cleavage of the reporter group or the oligonucleotide side strand, respectively. It was shown that aqueous tetramethylguanidine efficiently cleaves the oxidized inosine subunit of TID at 37 °C, forming the native DNA strand. Full article

Although the pancreas is the organ that produces the most critical digestive enzymes, there are other important contributors to the cleavage of food into absorbable units. Pre-pancreatic digestion of carbohydrates occurs through the action of salivary amylase. Pre-pancreatic digestion of fats is mediated by lingual and gastric lipases, and their action may be important as a signal for coordinated digestion. Pepsin, which is present in the stomach, initiates the digestion of dietary proteins into peptides and amplifies distal proteolysis. The major post-pancreatic intestinal carbohydrate-digesting enzymes are sucrase-isomaltase, maltase-glucoamylase and lactase-phlorizin hydrolase. There are no post-pancreatic mucosal enzymes that act on dietary triglycerides; however, the complete digestion of phospholipids depends on several brush border phospholipases. Intestinal processing is an important contributor to digestion of proteins, although mucosal proteases may serve as signaling proteins rather than as primary adjuncts to dietary protein digestion and absorption. This review describes the role of these non-pancreatic digestive enzymes in supporting nutritional health. Full article

Herpesviruses are prevalent infectious agents in humans, with complex structures and life cycles. The viability and detail of a model of capsid assembly and maturation can now be examined against the recently available mature herpesvirus capsids structures. The first large assembly product is the icosahedral procapsid with an outer shell composed of major capsid proteins (MCPs) connected by triplexes (heterotrimers composed of one Tri1 protein and two Tri2 proteins), and an inner shell of scaffold proteins. The asymmetric triplexes have specific and conserved orientations, suggesting a key role in assembly. In the mature capsid structures, triplexes bound to three MCPs may represent an assembly unit where, in most cases, the N-terminus of one MCP wraps around the E-loop of another MCP. The model accommodates the incorporation of a portal into capsid, required for genome encapsidation and viral viability. Cleavage of the scaffold triggers maturation of procapsid. Each of the MCPs rotates mostly as a rigid body, except for the flexible peripheral parts that remodel to close the capsid inner surface. Angularization of the capsid shifts the portal outward to a better contact with the capsid shell. Understanding these events in the herpesvirus life cycle to atomic detail could facilitate the development of drugs that uniquely target assembly and maturation. Full article

The Southern Lhasa Terrane, as the southernmost tectonic unit of the Eurasian continent, has long been a focal area in global geoscientific research due to its complex evolutionary history. The Yeba Formation exposed in this terrane comprises an Early–Middle Jurassic volcanic–sedimentary sequence that records multiphase tectonic deformation. This study applies structural analysis to identify three distinct phases of tectonic deformation in the Yeba Formation of the Southern Lhasa Terrane. The D₁ deformation is characterized by brittle–ductile shearing, as evidenced by the development of E-W-trending regional shear foliation (S₁). S₁ planes dip northward at angles of 27–87°, accompanied by steeply plunging stretching lineations (85–105°). Both south- and north-directed shear-rotated porphyroclasts are observed in the hanging wall. ⁴⁰Ar-³⁹Ar dating results suggest that the D₁ deformation occurred at ~79 Ma and may represent an extrusion-related structure formed under a back-arc compressional regime induced by the low-angle subduction of the Neo-Tethys Ocean plate. The D₂ deformation is marked by the folding of the pre-existing shear foliation (S₁), generating an axial planar cleavage (S₂). S₂ planes dip north or south with angles of 40–70° and fold hinges plunge westward or NWW. Based on regional tectonic evolution, it is inferred that the deformation may have resulted from sustained north–south compressional stress during the Late Cretaceous (79–70 Ma), which caused the overall upward extrusion of the southern Gangdese back-arc basin, leading to upper crustal shortening and thickening and subsequently initiating folding. The D₃ deformation is dominated by E-W-striking ductile shear zones. The regional shear foliation (S₃) exhibits a preferred orientation of 347°∠75°. Outcrop-scale ductile deformation indicators reveal a top-to-the-NW shear sense. Combined with regional tectonic evolution, the third-phase (D3) deformation is interpreted as a combined product of the transition from compression to lateral extension within the Lhasa terrane, associated with the activation of the Gangdese Central Thrust (GCT) and the uplift of the Gangdese batholith since ~25 Ma. Full article

Peptidoglycan (PGN) is a component of bacterial cell walls; its fragments are recognized by the cytoplasmic receptors Nod1 and Nod2, thereby promoting the production of inflammatory cytokines and antibodies. To further elucidate these biological defense mechanisms, a large and stable supply of the PGN fragments via chemical synthesis is essential. However, the synthesis and purification of long PGN fragments are quite challenging due to their low solubility. In this study, we efficiently synthesized PGN fragments via solid-phase oligosaccharide synthesis (SPOS). Using the JandaJel™ Wang resin (JJ-Wang), an octasaccharide glycan chain of PGN was constructed by repeating glycosylation reactions to elongate β-1,4-linked disaccharide units composed of MurNAc and GlcNAc. To enhance reactivity, glycosylation was performed in a mixed solvent comprising C₄F₉OEt/CH₂Cl₂/THF with the intention of promoting substrate concentration onto the solid support through the fluorophobic effect, affording the PGN octasaccharide in a 19% overall yield (10 steps). Subsequently, after deprotection of the O-Fmoc, N-Troc, and ethyl ester groups, N- and O-acetylation proceeded smoothly, owing to the high swelling property of JJ-Wang. Peptide condensation with L-Ala-D-isoGln(OBn) and carboxylic acids was also achieved. Finally, cleavage of the PGN fragment from the resin with TFA afforded the desired octasaccharide with dipeptides in a 2.3% overall yield (15 steps). Full article