Formation Mechanism Research Articles

Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.

Human mitochondria possess a multi-copy circular genome, mitochondrial DNA (mtDNA), that is essential for cellular energy metabolism. The number of copies of mtDNA per cell, and their integrity, are maintained by nuclear-encoded mtDNA replication and repair machineries. Aberrant mtDNA replication and mtDNA breakage are believed to cause deletions within mtDNA. The genomic location and breakpoint sequences of these deletions show similar patterns across various inherited and acquired diseases, and are also observed during normal ageing, suggesting a common mechanism of deletion formation. However, an ongoing debate over the mechanism by which mtDNA replicates has made it difficult to develop clear and testable models for how mtDNA rearrangements arise and propagate at a molecular and cellular level. These deletions may impair energy metabolism if present in a high proportion of the mtDNA copies within the cell, and can be seen in primary mitochondrial diseases, either in sporadic cases or caused by autosomal variants in nuclear-encoded mtDNA maintenance genes. These mitochondrial diseases have diverse genetic causes and multiple modes of inheritance, and show notoriously broad clinical heterogeneity with complex tissue specificities, which further makes establishing genotype-phenotype relationships challenging. In this review, we aim to cover our current understanding of how the human mitochondrial genome is replicated, the mechanisms by which mtDNA replication and repair can lead to mtDNA instability in the form of large-scale rearrangements, how rearranged mtDNAs subsequently accumulate within cells, and the pathological consequences when this occurs.

Fabrication and characterization of glycosylated-zein as an effective delivery system for rutin: Formation mechanism, physicochemical properties, and bioaccessibility in vitro

Fabrication and characterization of glycosylated-zein as an effective delivery system for rutin: Formation mechanism, physicochemical properties, and bioaccessibility in vitro

Formation mechanisms and mechanical properties in aluminum cables and copper terminals ultrasonic welded joint

Formation mechanisms and mechanical properties in aluminum cables and copper terminals ultrasonic welded joint

Exploring the Interplay between Calcium Oxalate Crystals and Renal Tubular Epithelial Cell Injury: Implications for the Formation and Prevention of Kidney Stones

Kidney stones are a prevalent and clinically significant disease that affects millions of individuals worldwide, which have emerged as a significant global public health concern. The majority of kidney stones are composed of calcium oxalate (CaOx). The mechanisms of stone formation and development are unclear, involving a complex interplay of physical and biochemical processes. The injury of tubular epithelial cells (TECs) represents a pivotal event in the pathogenesis of this condition, as it initiates oxidative stress and immune-inflammatory reactions. Macrophages play a pivotal role in the inflammatory process, interacting with a multitude of molecules and pathways, thereby influencing the stone formation. Furthermore, apoptosis and autophagy induce TECs injury and contribute to the pathogenesis of CaOx stones. The current treatment strategies mainly focus on the management of crystal-cell interactions and the protection of TECs, in conjunction with the application of antioxidants, anti-inflammatory agents, and inhibitors of apoptosis and autophagy. These strategies have demonstrated promising results. Future research will aim to modulate the immune-inflammatory response, offering hope for the effective prevention of stone recurrence.

A Comprehensive Review of the Benzimidazole Scaffold as a Potential Nucleus for Anti-Ulcer Activity

Abstract: The benzimidazole scaffold is a promising nucleus for developing novel therapeutic agents for ulcer treatment. Its unique chemical structure provides desirable pharmacological properties, such as excellent bioavailability, metabolic stability, and low toxicity, making it an attractive candidate for ulcer treatment. Several benzimidazole derivatives have shown significant anti-ulcer activity in preclinical and clinical studies, acting through multiple pathways, including inhibition of gastric acid secretion, suppression of gastric inflammation, and promotion of mucosal protection. Some benzimidazole derivatives have also demonstrated anti-Helicobacter pylori activity, suggesting their potential for eradicating bacteria associated with ulcer formation. However, challenges such as poor solubility and limited selectivity remain. Various approaches, such as prodrug design and formulation optimization, have been explored to overcome these issues and improve the therapeutic profile of benzimidazole derivatives. Overall, the benzimidazole scaffold holds great promise as a nucleus for developing novel anti-ulcer agents. Further research and optimization efforts are needed to harness its full potential and translate it into effective treatments for ulcers. With continued advancements in medicinal chemistry and drug design, benzimidazole-based compounds may offer new therapeutic options for patients suffering from ulcers and related gastrointestinal disorders. Hence, this review highlights the knowledge about benzimidazole scaffold, the mechanism of ulcer formation, and various benzimidazole derivatives with anti-ulcer activity, which can be further studied in pre-clinical and clinical trials.

Formation Mechanism and Morphology Evolution of β-NaYF4 Single Microcrystals in Hydrothermal Process

Lanthanide-doped upconversion (Ln-doped UC) materials with predicable phase and geometry are attractive for their promising application in optics and biological. Herein, we report a facile strategy for deterministic synthesis of β-NaYF4 microcrystals by an ethylenediaminetetraacetic acid (EDTA) assisted hydrothermal process. The nucleation and growth process of the β-NaYF4 microcrystals have been experimentally revealed with different hydrothermal times. The phase and geometry of as-obtained crystals can be well manipulated by the experimental parameters such as pH values, precursors’ ratio, and reactant concentrations. The formation and morphology evolution mechanism of β-NaYF4 single microcrystals can be qualitatively analyzed using energy minimization principles under the thermodynamic and kinetic control. In addition, we presented the colour-changing up-conversion of Tm3+ and Yb3+ doped single β-NaYF4 microrod. Our work could help the understanding on crystal growth and design of rare earth fluoride mateirals at micro and nanoscale.

Four-band terahertz perfect-absorption and high-sensitivity sensor based on tunable Dirac semimetal

In this paper, we designed a dynamically tunable four-band perfect sensor based on bulk Dirac semimetal (BDS). The sensor comprises a top BDS layer, a bottom Au layer, and an intermediate dielectric layer. Four resonant modes with >98 % absorption are achieved in the range of 9–11.8 THz. Due to the rotationally symmetric design, the sensor is polarization insensitive. The formation mechanism of perfect absorption is explained using the principles of impedance matching. We also determined the effects of structural parameters and Fermi energy of the BDS on the absorption spectra. We explain the blue-shift and red-shift phenomena of the resonant frequency based on equivalent circuits. Additionally, we define the refractive index sensitivity (S) and find that the maximum sensitivity is 516 GHz/RIU. Due to these excellent properties, our design provides a way of thinking about actively tunable terahertz sensors and expands their application scope.

The property and function of proteins undergoing liquid-liquid phase separation in plants.

A wide variety of membrane-less organelles in cells play an essential role in regulating gene expression, RNA processing, plant growth and development, and helping organisms cope with changing external environments. In biology, liquid-liquid phase separation (LLPS) usually refers to a reversible process in which one or more specific molecular components are spontaneously separated from the bulk environment, producing two distinct liquid phases: concentrated and dilute. LLPSmay be a powerful cellular compartmentalisation mechanism whereby biocondensates formed via LLPS when biomolecules exceed critical or saturating concentrations in the environment where they are found will be generated. It has been widely used to explain the formation of membrane-less organelles in organisms. LLPS studies in the context of plant physiology are now widespread, but most of the research is still focused on non-plant systems; the study of phase separation in plants needs to be more thorough. Proteins and nucleic acids are the main components involved in LLPS. This review summarises the specific features and properties of biomolecules undergoing LLPS in plants. We describe in detail these biomolecules' structural characteristics, the mechanism of formation of condensates, and the functions of these condensates. Finally, We summarised the phase separation mechanisms in plant growth, development, and stress adaptation.

Predictive Synthesis of Transition Metal Carbide via Thermochemical Oxocarbon Equilibrium.

Fabricating nanoscale metal carbides is a great challenge due to them having higher Gibbs free energy of formation (ΔG°) values than other metal compounds; additionally, these carbides have harsh calcination conditions, in which metal oxidation is preferred in the atmosphere. Herein, we report oxocarbon-mediated calcination for the predictive synthesis of nanoscale metal carbides. The thermochemical oxocarbon equilibrium of CO-CO2 reactions was utilized to control the selective redox reactions in multiatomic systems of Mo-C-O, contributing to the phase-forming and structuring of Mo compounds. By harnessing the thermodynamically predicted processing window, we controlled a wide range of Mo phases (MoO2, α-MoC1-x, and β-Mo2C) and nanostructures (nanoparticle, spike, stain, and core/shell) in the Mo compounds/C nanofibers. By inducing simultaneous reactions of C-O (selective C combustion) and Mo-C (Mo carbide formation) in the nanofibers, Mo diffusion was controlled in C nanofibers, acting as a template for the nucleation and growth of Mo carbides and resulting in precise control of the phases and structures of Mo compounds. The formation mechanism of nanostructured Mo carbides was elucidated according to the CO fractions of CO-CO2 calcination. Moreover, tungsten (W) and niobium (Nb) carbides/C nanofibers have been successfully synthesized by CO-CO2 calcination. We constructed the thermodynamic map for the predictive synthesis of transition metal carbides to provide universal guideline via thermochemical oxocarbon equilibrium. We revealed that our thermochemical oxocarbon-mediated gas-solid reaction enabled the structure and phase control of nanoscale transition metal compounds to optimize the material-property relationship accordingly.

Coordination-induced amidated modified polyacrylonitrile loaded ultrafine palladium nanoparticles for thermocatalytic hydrogen evolution

A promising approach for powering hydrogen fuel cells (HFCs) involves the in-situ production of hydrogen from formic acid decomposition, with Pd-based catalysts recognized as effective for formic acid dehydrogenation. However, the immobilization of ultrafine palladium nanoparticles (Pd NPs) on catalytic supports presents a challenge and necessitates further investigation into their formation mechanism. We propose a coordination-induced strategy to understand the behavior of ultrafine Pd NPs formation based on multi-functional groups. To establish the structure–activity relationship for tunable Pd microenvironment and catalytic performance, we synthesized various polyacrylonitrile (PAN) carriers through hydrolysis and amidation modification. Molecular dynamics simulations confirmed that a stronger coordination-induced microenvironment facilitates the dispersion of Pd2+, suppressing aggregation and enhancing Pd loading. Our experimental results and density functional theory (DFT) calculations demonstrated that the catalytic activity of Pd@APAN(15_1%) with ultrafine Pd NPs (1.5 nm) exhibits over 10 times higher than that of Pd@PAN NPs with the turnover of frequency climbing from 112.6 h−1 to 1309.4 h−1 at 323 K. And Pd-imine and Pd-secondary amine moieties were verified to contribute to the creation of a favorable catalysis microenvironment. This study provides new insights into the design of modified supports with various groups to load well-dispersed and ultrafine Pd for highly efficient catalysts based on a coordination-induced strategy.

Uncovering the crystallography and formation mechanism of nanoscale clusters in Sb-rich SPPs of a p-type (Bi, Sb)2Te3 alloy.

Considering that the crystallographic characteristics of the Sb-rich secondary phase particles (SPPs) greatly affect the thermoelectric properties of Bi2Te3 based materials, it is of great significance to explore the mechanism behind the Sb-rich SPPs in the p-type (Bi, Sb)2Te3 material. Here a conventional TEM technique was used to characterize the composition, size and distribution of Sb-rich SPPs in a spark plasma sintered p-type (Bi, Sb)2Te3 alloy. The results indicated that two different morphologies of Sb-rich SPPs including elongated and circular Sb-rich SPPs were frequently observed. Combined with high-resolution transmission electron microscopy, this work provides atomic-scale evidence for the formation mechanism behind the Sb-rich SPPs in the (Bi, Sb)2Te3 material.

Spatial distribution of toponyms and formation mechanism in traditional villages in Western Hunan, China

Spatial distribution of toponyms and formation mechanism in traditional villages in Western Hunan, China

Dengue virus exploits autophagy vesicles and secretory pathways to promote transmission by human dendritic cells

Dengue virus (DENV), transmitted by infected mosquitoes, is a major public health concern, with approximately half the world’s population at risk for infection. Recent decades have increasing incidence of dengue-associated disease alongside growing frequency of outbreaks. Although promising progress has been made in anti-DENV immunizations, post-infection treatment remains limited to non-specific supportive treatments. Development of antiviral therapeutics is thus required to limit DENV dissemination in humans and to help control the severity of outbreaks. Dendritic cells (DCs) are amongst the first cells to encounter DENV upon injection into the human skin mucosa, and thereafter promote systemic viral dissemination to additional human target cells. Autophagy is a vesicle trafficking pathway involving the formation of cytosolic autophagosomes, and recent reports have highlighted the extensive manipulation of autophagy by flaviviruses, including DENV, for viral replication. However, the temporal profiling and function of autophagy activity in DENV infection and transmission by human primary DCs remains poorly understood. Herein, we demonstrate that mechanisms of autophagosome formation and extracellular vesicle (EV) release have a pro-viral role in DC-mediated DENV transmission. We show that DENV exploits early-stage canonical autophagy to establish infection in primary human DCs. DENV replication enhanced autophagosome formation in primary human DCs, and intrinsically-heightened autophagosome biogenesis correlated with relatively higher rates of DC susceptibility to DENV. Furthermore, our data suggest that viral replication intermediates co-localize with autophagosomes, while productive DENV infection introduces a block at the late degradative stages of autophagy in infected DCs but not in uninfected bystander cells. Notably, we identify for the first time that approximately one-fourth of DC-derived CD9/CD81/CD63+ EVs co-express canonical autophagy marker LC3, and demonstrate that DC-derived EV populations are an alternative, cell-free mechanism by which DCs promote DENV transmission to additional target sites. Taken together, our study highlights intersections between autophagy and secretory pathways during viral infection, and puts forward autophagosome accumulation and viral RNA-laden EVs as host determinants of DC-mediated DENV infection in humans. Host-directed therapeutics targeting autophagy and exocytosis pathways thus have potential to enhance DC-driven resistance to DENV acquisition and thereby limit viral dissemination by initial human target cells following mosquito-to-human transmission of DENV.

Unveiling the Molecular Dynamics, Anticancer Activity, and Stability of Spearmint Oil Nanoemulsions with Triglycerides.

Although spearmint oil (SMO) has various pharmacological properties, especially for cancer treatment, its low water solubility results in poor bioavailability. This limits its application as a medicine. One possible solution is to the use of SMO in the form of nanoemulsion, which has already been shown to have anticancer effects. However, the mechanism of SMO nanoemulsion formation remains unclear. The objective of this study was to use molecular dynamics (MD) for clarifying the formation of SMO nanoemulsion with triglycerides (trilaurin, tripalmitin, and triolein) and Cremophor RH40 (PCO40). Nanoemulsions with different SMO:triglyceride ratios and triglyceride types were prepared and analyzed for anticancer activity, droplet size, droplet morphology, and stability. Despite switching the type of carrier oil, SMO nanoemulsions retained strong anticancer effects. A ratio of 80SMO:20triglycerides produced the smallest droplets (<100 nm) and exhibited excellent physical stability after a temperature cycling test. MD simulations showed that polyoxyethylenes of PCO40 are located at the water interface, stabilizing the emulsion structure in an egglike layer. Droplet size correlated with triglyceride concentration, which was consistent with the experimental findings. Decreasing triglyceride content, except for the 90SMO:10triglyceride ratio, led to a decrease in droplet sizes. Hydrogen bond analysis identified interactions between triglyceride-PCO40 and carvone-PCO40. Geometry analysis showed PCO40 had an "L-like" shape, which maximizes the hydrophilic interfaces. These findings highlight the value of MD simulations in understanding the formation mechanism of SMO and triglyceride nanoemulsions. In addition, it might also be beneficial to use MD simulations before the experiment to select the potential composition for nanoemulsions, especially essential oil nanoemulsions.

Effect of Al Content on Formation Mechanism of AlN and MnS Inclusions in Fe-5Mn-xAl-0.15C-0.23Si Medium Mn Steel

Effect of Al Content on Formation Mechanism of AlN and MnS Inclusions in Fe-5Mn-xAl-0.15C-0.23Si Medium Mn Steel

Ultrathin 2D Alloyed Cu−Ga−Zn−S Curved Nanobelts for Boosting Visible‐Light Photocatalytic Hydrogen Evolution

Abstract2D semiconductor nanomaterials have received significant attention as photocatalysts for solar‐to‐hydrogen conversion due to their robust light absorption capacity, large specific surface area, and superior electron transport characteristics. Nevertheless, it is challenging to develop 2D quaternary copper‐based sulfides (QCSs) with functional integration of conducive structural features for photocatalysis from multiple elements and intricate control conditions. Herein, ultrathin 2D alloyed Cu−Ga−Zn−S (CGZS) curved nanobelts (NBs) are fabricated by using a facile one‐pot colloidal method. Subsequently, the derived Cu31S16‐CGZS Janus heterostructures are designed by increasing Cu concentrations. The formation mechanism of 2D curved alloys and Janus heterostructures is systematically investigated. Without cocatalysts, curved alloyed CGZS NBs demonstrated superior photocatalytic activities of 1264.2 µmol g−1 h−1 compared to Janus heterostructured Cu31S16−CGZS (463.1 µmol g−1 h−1) under visible light (&gt; 400 nm). Experimental and theoretical results unveiled that the improved photocatalytic activities of curved CGZS NBs can be attributed to enhanced charge–carrier separation efficiency resulting from high crystallinity and ultrathin 2D structure, abundant active sites from curved structure, high‐active (0001) crystal facet with the lowest reaction Gibbs energy, work function, and metal‐like properties. This work offers new insights into functional integration into ultrathin 2D QCSs with enhanced visible‐light photocatalytic performance.

Analysis of Bottom Reverberation Intensity Under Beam-Controlled Emission Conditions in Deep Water

A comprehensive understanding of the characteristics and the formation mechanism of reverberation is the key to improving the performance of the active target detection. In response to the challenge of analyzing the intensity of bottom reverberation in typical deep-sea environments, this study proposes a prediction method for the bottom reverberation intensity under beam-controlled emission conditions. It explains the variation law of bottom reverberation intensity under beam-controlled emission conditions in typical deep-sea environments of the South China Sea through theoretical and simulation analyses. Reverberation intensity of the deep-sea bottom under beam-controlled emission conditions exhibits significant fluctuations during the duration of reverberations in the direct sound zone of the seabed. This phenomenon is closely related to the directionality of the source emission, leading to intermittent reverberation masking and detectable areas in the active sonar detection. In addition, the duration of the high-reverberation zone near the cutoff distance of the direct sound from the seabed is longer under the beam-controlled emission conditions of the emission array located within the surface waveguide layer of the deep sea during winter.

Counter-intuitive discovery in the formulation of poorly water-soluble drugs: Amorphous small-molecule gels.

Amorphous strategies have been extensively used in improving the dissolution of insoluble drugs for decades due to their high free energy. However, the formation of amorphous small-molecule gels (ASMGs) presents a counter-intuitive discovery that significantly limits their practical application. Recently, ASMGs have garnered attention because of their noncovalent structures, excellent biodegradability, and significant potential in various drug delivery systems in the pharmaceutical field. Hence, a comprehensive review is necessary to contribute to a better understanding of recent advances in ASMGs. This review aimed to introduce the main formation mechanisms, summarize possible influencing factors, generalize unique properties, outline elimination strategies, and discuss clinical application potential with preclinical cases of ASMGs. Moreover, few ASMGs are advanced to clinical stages. Intensive clinical research is needed for further development. We hope that this review can provide more efficient and rational guidance for exploring further clinical applications of ASMGs.

Penetration Characteristics of Mono-Column Composite Bucket Foundation for Offshore Wind Turbines

To address the issue of seepage and soil plugging during the sinking of mono-column composite bucket foundations (MCCBFs), experiments were conducted on the installation of foundations under a variety of complex geological conditions. The effect of negative pressure sinking mode on the foundation’s seepage field was analyzed, the formation mechanism of soil plugging in sand was explained, and an efficient method for calculating the height of soil plugging was proposed in conjunction with these investigations. The findings demonstrate that the finite element method simulation of the soil’s seepage field is the most accurate, that the pumping volume of the foundation during sinking through is high, that the formation of the soil plug height is high, and that clear depressions can be seen on the foundation manifold’s exterior. The equation presented in this study makes it easier to forecast the height of a foundation plug and can offer direction for engineering design.

Dynamics of transformed nonlinear waves for the (2+1)-dimensional pKP-BKP equation: interactions and molecular waves

Abstract In this paper, the dynamical behaviors of transformed nonlinear waves for the (2+1)-dimensional combined potential Kadomtsev-Petviashvili and B-type Kadomtsev-Petviashvili (pKP-BKP) equation are investigated, which can be used to reveal the nonlinear wave phenomena in nonlinear optics, plasma physics and hydrodynamics. The breath-wave and the lump solutions are constructed by means of the soliton solutions. The conversion mechanism for the breath-waves is systematically analyzed, which leads to several new kink-shaped nonlinear waves. The gradient relationships of these transformed waves are revealed by a Riemannian circle. Through the analysis of the nonlinear superposition between the periodic wave component and the kink solitary wave component, the dynamical characteristics including the formation mechanism, oscillation and locality for the nonlinear waves are investigated. The time-varying properties of transformed waves are showed by the study of time variables. By virtue of the two breath-wave solution, several interactions including elastic and inelastic collisions between two nonlinear waves are studied. In particular, some transformed molecular waves encompassing the non-, semi- and full-transition modes are presented with the aid of velocity resonance. The results can help us further understand the complex nonlinear waves existing in the integrable systems.