Phonon energy dissipation in friction between black phosphorus layers.

Herein, we employ molecular dynamics simulations to decode the friction properties and phonon energy dissipation between black phosphorus layers. The observations reveal the influence of three factors, temperature, velocity, and normal load, on the friction force of monolayer/bilayer black phosphorus. Specifically, friction is negatively correlated with layer thickness and temperature, and positively correlated with velocity and normal load. The change in friction force is further explained in terms of frictional energy dissipation, and supplemented by the height of potential barriers as well as the number of excited phonons. From the phonon spectrum analysis, the phonon number at the contact interface is found to be higher than that at the non-contact interface. This is due to the larger distance of the contact interface atoms deviate from their equilibrium positions, resulting in higher total energy generated by more intense oscillations, and therefore contributes greater to friction.

Kisspeptin regulates the proliferation and apoptosis of ovary granulosa cells in polycystic ovary syndrome by modulating the PI3K/AKT/ERK signalling pathway.

BACKGROUND: The development of polycystic ovary syndrome (PCOS) is closely correlated with apoptosis and oxidative stress in ovarian granulosa cells. Kisspeptin plays an important role in reproductive organ function. This study aimed to explore the role of kisspeptin in PCOS and oxidative stress-triggered apoptosis of ovarian granular cells. METHODS: A PCOS rat model was established by injecting dehydroepiandrosterone (DHEA) and feeding the rats a high-fat diet. The RNA and protein levels of kisspeptin were analysed by quantitative PCR, western blotting, and histological staining. Tissue damage was evaluated using haematoxylin and eosin (H&E) staining. The viability and proliferation of human granulosa cell KGN were measured using the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell cycle and apoptosis were analysed by flow cytometry. Oxidative stress was analysed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels. RESULTS: Kisspeptin was downregulated in the ovarian granulosa cells of PCOS rats compared to those of control rats. Kisspeptin overexpression enhanced KGN cell proliferation and inhibited apoptosis. ROS generation was suppressed by kisspeptin, along with decreased levels of MDA and increased levels of the antioxidants GSH, SOD, and CAT. Kisspeptin activates PI3K/AKT and ERK signalling, and inactivation of ERK1/2 suppresses the protective role of kisspeptin in ovarian granulosa cells. CONCLUSION: Kisspeptin improves proliferation and alleviates apoptosis and oxidative stress in ovarian granulosa cells by activating PI3K/AKT and ERK signalling.

[Analysis of ARX gene variant in a child with X-linked lissencephaly with abnormal genitalia].

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child with X-linked lissencephaly with abnormal genitalia (XLAG). METHODS: A child with XLAG who had presented at the Third Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to high-throughput sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the result was analyzed by using bioinformatic software. RESULTS: The child was found to have harbored a hemizygous c.945_948del variant in exon 2 of the ARX gene, which as a frameshifting variant has resulted in a truncated protein. His mother was found to be heterozygous for the variant, whilst his father was of wild type. The variant was unreported previously. CONCLUSION: The hemizygous c.945_948del variant of the ARX gene probably underlay the XLAG in this patient. Above finding has provided a basis for the diagnosis and genetic counseling for this family.

Neural Network-Based Prediction for Secret Key Rate of Underwater Continuous-Variable Quantum Key Distribution through a Seawater Channel.

Continuous-variable quantum key distribution (CVQKD) plays an important role in quantum communications, because of its compatible setup for optical implementation with low cost. For this paper, we considered a neural network approach to predicting the secret key rate of CVQKD with discrete modulation (DM) through an underwater channel. A long-short-term-memory-(LSTM)-based neural network (NN) model was employed, in order to demonstrate performance improvement when taking into account the secret key rate. The numerical simulations showed that the lower bound of the secret key rate could be achieved for a finite-size analysis, where the LSTM-based neural network (NN) was much better than that of the backward-propagation-(BP)-based neural network (NN). This approach helped to realize the fast derivation of the secret key rate of CVQKD through an underwater channel, indicating that it can be used for improving performance in practical quantum communications.

Maize Dek15 Encodes the Cohesin-Loading Complex Subunit SCC4 and Is Essential for Chromosome Segregation and Kernel Development.

Cohesin complexes maintain sister chromatid cohesion to ensure proper chromosome segregation during mitosis and meiosis. In plants, the exact components and functions of the cohesin complex remain poorly understood. Here, we positionally cloned the classic maize (Zea mays) mutant defective kernel 15 (dek15), revealing that it encodes a homolog of SISTER CHROMATID COHESION PROTEIN 4 (SCC4), a loader subunit of the cohesin ring. Developing dek15 kernels contained fewer cells than the wild type, but had a highly variable cell size. The dek15 mutation was found to disrupt the mitotic cell cycle and endoreduplication, resulting in a reduced endosperm and embryo lethality. The cells in the dek15 endosperm and embryo exhibited precocious sister chromatid separation and other chromosome segregation errors, including misaligned chromosomes, lagging chromosomes, and micronuclei, resulting in a high percentage of aneuploid cells. The loss of Dek15/Scc4 function upregulated the expression of genes involved in cell cycle progression and stress responses, and downregulated key genes involved in organic synthesis during maize endosperm development. Our yeast two-hybrid screen identified the chromatin remodeling proteins chromatin remodeling factor 4, chromatin remodeling complex subunit B (CHB)102, CHB105, and CHB106 as SCC4-interacting proteins, suggesting a possible mechanism by which the cohesin ring is loaded onto chromatin in plant cells. This study revealed biological functions for DEK15/SCC4 in mitotic chromosome segregation and kernel development in maize.

Femtosecond Pumping of Nuclear Isomeric States by the Coulomb Collision of Ions with Quivering Electrons.

Efficient production of nuclear isomers is critical for pioneering applications, like nuclear clocks, nuclear batteries, clean nuclear energy, and nuclear γ-ray lasers. However, due to small production cross sections and quick decays, it is extremely difficult to acquire a significant amount of isomers with short lifetimes via traditional accelerators or reactors because of low beam intensity. Here, for the first time, we experimentally present femtosecond pumping of nuclear isomeric states by the Coulomb excitation of ions with the quivering electrons induced by laser fields. Nuclei populated on the third excited state of ^{83}Kr are generated with a peak efficiency of 2.34×10^{15} particles/s from a tabletop hundred-TW laser system. It can be explained by the Coulomb excitation of ions with the quivering electrons during the interaction between laser pulses and clusters at nearly solid densities. This efficient and universal production method can be widely used for pumping isotopes with excited state lifetimes down to picoseconds, and could be a benefit for fields like nuclear transition mechanisms and nuclear γ-ray lasers.

Robust Trajectory Tracking Control for Continuous-Time Nonlinear Systems with State Constraints and Uncertain Disturbances.

In this paper, a robust trajectory tracking control method with state constraints and uncertain disturbances on the ground of adaptive dynamic programming (ADP) is proposed for nonlinear systems. Firstly, the augmented system consists of the tracking error and the reference trajectory, and the tracking control problems with uncertain disturbances is described as the problem of robust control adjustment. In addition, considering the nominal system of the augmented system, the guaranteed cost tracking control problem is transformed into the optimal control problem by using the discount coefficient in the nominal system. A new safe Hamilton-Jacobi-Bellman (HJB) equation is proposed by combining the cost function with the control barrier function (CBF), so that the behavior of violating the safety regulations for the system states will be punished. In order to solve the new safe HJB equation, a critic neural network (NN) is used to approximate the solution of the safe HJB equation. According to the Lyapunov stability theory, in the case of state constraints and uncertain disturbances, the system states and the parameters of the critic neural network are guaranteed to be uniformly ultimately bounded (UUB). At the end of this paper, the feasibility of the proposed method is verified by a simulation example.

Optical steering of electron beam in laser plasma accelerators.

Using a Dazzler system and tilting a compressor grating, we provide an effective way of using the laser group delay dispersion to continuously steer the electron beam accelerated by an asymmetric laser wakefield. The deviation angle of the electron beam was the same as that of the angularly chirped laser pulse from its initial optical axis, which is determined by the laser pulse-front-tilt (PFT). This method can be utilized to continuously control over the pointing direction of electron bunches to the requisite trajectories, especially for practical applications in highly sensitive alignment devices such as electron-positron colliders or undulators. Additionally, we investigate the effect of PFT on the properties of the electron beam.

Clinical outcomes of EGFR kinase domain duplication to targeted therapies in NSCLC.

Kinase domain duplications of the epidermal growth factor receptor (EGFR-KDD) have been identified and implicated to be oncogenic in nonsmall cell lung cancers (NSCLCs). However, its prevalence and clinical contributions in lung cancer are largely unknown. Here, we conducted a multicenter record review of 10,759 NSCLC patients who underwent genetic testing using next-generation sequencing (NGS) targeting EGFR exons and the introns involved in EGFR-KDD rearrangements. EGFR-KDDs were identified in a total of 13 patients, which is approximately 0.12% of the total population reviewed, and also consisted of 0.24% (13/5394) of EGFR mutation-positive patients. A total of 85% of patients (11/13) were identified with the canonical EGFR-KDD duplication of exons 18-25, while the remaining two cases harbored duplications of EGFR exons 14-26 and exons 17-25, which have not been previously described. Importantly, none of the 13 patients had other coexisting driver mutations, highlighting the potential oncogenic role of this type of alteration. Three out of five patients who had exon 18-25 duplications showed partial antitumor responses to targeted therapies, while the other two patients demonstrated no clinical improvement. Furthermore, our data suggested that the EGFR T790 M mutation and EGFR amplification may represent the major resistance mechanisms against targeted therapies in tumors bearing EGFR-KDD. In summary, our findings provide valuable insight into the prevalence of EGFR-KDDs in NSCLCs and their clinical outcomes to targeted therapies.

Short-period high-strength helical undulator by laser-driven bifilar capacitor coil.

Laser wakefield accelerators have emerged as a promising candidate for compact synchrotron radiation and even x-ray free electron lasers. Today, to make the electrons emit electromagnetic radiation, the trajectories of laser wakefield accelerated electrons are deflected by transverse wakefield, counter-propagating laser field or external permanent magnet insertion device. Here, we propose a novel type of undulator that has a period of a few hundred microns and a magnetic field of tens of Tesla. The undulator consists of a bifilar capacitor-coil target that sustains a strong discharge current that generates a helical magnetic field around the coil axis when irradiated by a high-energy laser. Coupling this undulator with state-of-the-art laser wakefield accelerators can, simultaneously, produce ultra-bright quasi-monochromatic x-rays with tunable energy ranging 5-250 keV and optimize the free electron laser parameter and gain length compared with a permanent magnet-based undulator. This concept may pave a path toward ultra-compact synchrotron radiation and even x-ray free electron lasers.

Host Cellular Protein TRAPPC6AΔ Interacts with Influenza A Virus M2 Protein and Regulates Viral Propagation by Modulating M2 Trafficking.

Influenza A virus (IAV) matrix protein 2 (M2) plays multiple roles in the early and late phases of viral infection. Once synthesized, M2 is translocated to the endoplasmic reticulum (ER), travels to the Golgi apparatus, and is sorted at the trans-Golgi network (TGN) for transport to the apical plasma membrane, where it functions in virus budding. We hypothesized that M2 trafficking along with its secretory pathway must be finely regulated, and host factors could be involved in this process. However, no studies examining the role of host factors in M2 posttranslational transport have been reported. Here, we used a yeast two-hybrid (Y2H) system to screen for host proteins that interact with the M2 protein and identified transport protein particle complex 6A (TRAPPC6A) as a potential binding partner. We found that both TRAPPC6A and its N-terminal internal-deletion isoform, TRAPPC6A delta (TRAPPC6AΔ), interact with M2. Truncation and mutation analyses showed that the highly conserved leucine residue at position 96 of M2 is critical for mediating this interaction. The role of TRAPPC6AΔ in the viral life cycle was investigated by the knockdown of endogenous TRAPPC6AΔ with small interfering RNA (siRNA) and by generating a recombinant virus that was unable to interact with TRAPPC6A/TRAPPC6AΔ. The results indicated that TRAPPC6AΔ, through its interaction with M2, slows M2 trafficking to the apical plasma membrane, favors viral replication in vitro, and positively modulates virus virulence in mice. IMPORTANCE: The influenza A virus M2 protein regulates the trafficking of not only other proteins but also itself along the secretory pathway. However, the host factors involved in the regulation of the posttranslational transport of M2 are largely unknown. In this study, we identified TRAPPC6A and its N-terminal internal-deletion isoform, TRAPPC6AΔ, as interacting partners of M2. We found that the leucine (L) residue at position 96 of M2 is critical for mediating this interaction, which leads us to propose that the high level of conservation of 96L is a consequence of M2 adaptation to its interacting host factor TRAPPC6A/TRAPPC6AΔ. Importantly, we discovered that TRAPPC6AΔ can positively regulate viral replication in vitro by modulating M2 trafficking to the plasma membrane.

Highly efficient generation of 0.2 mJ terahertz pulses in lithium niobate at room temperature with sub-50 fs chirped Ti:sapphire laser pulses.

We demonstrate generation of 0.2 mJ terahertz (THz) pulses in lithium niobate driven by Ti:sapphire laser pulses at room temperature. Employing tilted pulse front technique, the 800 nm-to-THz energy conversion efficiency has been optimized to 0.3% through chirping the sub-50 fs pump laser pulses to overcome multi-photon absorption and to extend effective interaction length for phase matching. Our approach paves the way for mJ-level THz generation via optical rectification using existing Ti:sapphire laser systems which can deliver Joule-level pulse energy with sub-50 fs pulse duration.

[L-carnitine improves sperm acrosin activity in male infertility patients].

OBJECTIVE: To evaluate the effect of L-carnitine (LC) on low sperm acrosin activity in infertile man. METHODS: A total of 240 male infertility patients with low sperm acrosin activity were randomly assigned to an LC group (n = 180) and a control group (n = 60) to be treated with LC (1g, tid) and vitamin E (VE) capsules (100 mg, tid) respectively, both for 3 months. Based on the results of routine semen analysis, the patients in the experimental group were further divided into oligozoospermia, asthenozoospermia and normozoospermia subgroups. Semen parameters and sperm acrosin activity were examined before and after treatment. RESULTS: Totally, 220 of the patients completed the treatment and follow-up, 163 in the LC medication and 57 in the VE control group. Compared with the baseline, the percentage of progressively motile sperm (PMS) was significantly increased in the LC group after 3 months of treatment (ï¼»32.58 ± 1.13ï¼½% vs ï¼»36.35 ± 1.26ï¼½%, P < 0.05), and so was sperm acrosin activity (ï¼»37.05±0.66ï¼½ vs ï¼»58.61±1.93ï¼½ µIU/106 sperm, P < 0.01). Sperm concentration, PMS and sperm acrosin activity were also improved in the VE control group after treatment, but with no statistically significant difference (P > 0.05). In comparison with pretreatment, remarkable increases were observed after LC medication in sperm concentration in the oligozoospermia subgroup (ï¼»11.27 ± 0.73ï¼½ vs ï¼»21.82 ± 4.21ï¼½ ×106/ml, P < 0.01) and PMS in the asthenozoospermia patients (ï¼»20.61 ± 0.85ï¼½% vs ï¼»29.81 ± 1.88ï¼½%, P < 0.01). And sperm acrosin activity was even higher after treatment in the asthenozoospermia than in the oligozoospermia and normozoospermia subgroups (ï¼»60.85 ± 3.04ï¼½ vs ï¼»56.32 ± 2.86ï¼½ and ï¼»57.09 ± 6.31ï¼½ µIU/106 sperm, P < 0.05). CONCLUSIONS: L-carnitine can effectively elevate sperm acrosin activity in male infertility patients, particularly in those with asthenozoospermia.

Binding modes and interaction mechanism between different base pairs and methylene blue trihydrate: a quantum mechanics study.

Different quantum mechanic methods have been evaluated for the calculation of binding modes and interactions between intercalators with different DNA base pairs by comparing with the results of MP2, which is very expensive, indicating that WB97XD method under 6-311+G* basis set is able to efficiently reproduce MP2 results. We discovered that the methylene blue trihydrate intercalated into the DNA base pairs, and DNA intercalation increased the distance between DNA base pairs, depending on the types of DNA bases. According to the binding energy results, it was found that the intercalation of methylene blue trihydrate into AA-TT base pair was more favorable in the orientation of nitrogen than other directions and intercalation, and the electric charge was transferred from methylene blue trihydrate to the AA-TT base pair. The analysis of change in the charge density shows that changes often take place in the heavy atom in the middle of the system which the charge density changes most remarkable.

Advancement of polarizable force field and its use for molecular modeling and design.

The most important requirement of biomolecular modeling is to deal with electrostatic energies. The electrostatic polarizability is an important part of electrostatic interaction for simulation systems. However, AMBER, CHARMM, OPLS, GROMOS, MMFF force fields etc. used in the past mostly apply fixed atomic center point charge to describe electrostatic energies, and are not sufficient for considering the influence of the electrostatic polarization. The emergence of polarizable force fields has solved this problem. In recent years, quickly developed polarizable force fields have involved a lot of fields. The chapter relating to polarizable force fields spread over several aspects. Firstly, we reviewed the history of the classical force fields and compared with polarizable force fields to elucidate the advancements of polarizable force fields. Secondly, it is introduced that the application of polarizable force fields to small molecules and biological macromolecules simulation, including molecular design. Finally, a brief development trend and perspective is given on rapidly growing polarizable force fields.

Folding mechanisms of Trefoil Knot proteins studied by molecular dynamics simulations and Go-model.

Most proteins need to avoid the complex topologies when folding into the native structures, but some proteins with nontrivial topologies have been found in nature. Here we used protein unfolding simulations under high temperature and all-atom Go-model to investigate the folding mechanisms for two trefoil knot proteins. Results show that, the contacts in ß-sheet are important to the formation of knot protein, and if these contacts disappeared, the knot protein would be easy to untie. In the Go-model simulations, the folding processes of the two knot proteins are similar. The compact structures of the two knot proteins with the native contacts in ß-sheet are formed in transition state, and the intermediate state has loose C-terminal. This model also reveals the detailed folding mechanisms for the two proteins.

Theoretical studies on the folding mechanisms for different DNA G-quadruplexes.

The G-quadruplex DNA formed by the stack of guanines in human telomere sequence is a promising anticancer target. In this study we used the energy landscape theory to elucidate the folding mechanisms for the thrombin aptamer, Form 1 and Form 3 G-quadruplexes. The three G-quadruplexes were simulated with all-atom Go-model. Results show that, the three G-quadruplexes fold through a two-state mechanism. In the initial stage of the folding process, the compact structures are formed. The G-quadruplexes need to form G-triplex structures on the basis of the compact structures before folding to the native states. The folding free energy barrier of Form 3 G-quadruplex is higher than thrombin aptamer and Form 1, which shows that the structure of Form 3 G-quadruplex has more stability than the other two G-quadruplexes.

Advances in understanding the reproductive toxicity of endocrine-disrupting chemicals in women.

Recently, there has been a noticeable increase in disorders of the female reproductive system, accompanied by a rise in adverse pregnancy outcomes. This trend is increasingly being linked to environmental pollution, particularly through the lens of Endocrine Disrupting Chemicals (EDCs). These external agents disrupt natural processes of hormones, including synthesis, metabolism, secretion, transport, binding, as well as elimination. These disruptions can significantly impair human reproductive functions. A wealth of animal studies and epidemiological research indicates that exposure to toxic environmental factors can interfere with the endocrine system's normal functioning, resulting in negative reproductive outcomes. However, the mechanisms of these adverse effects are largely unknown. This work reviews the reproductive toxicity of five major environmental EDCs-Bisphenol A (BPA), Phthalates (PAEs), Triclocarban Triclosan and Disinfection Byproducts (DBPs)-to lay a foundational theoretical basis for further toxicological study of EDCs. Additionally, it aims to spark advancements in the prevention and treatment of female reproductive toxicity caused by these chemicals.

Coupling Effect of Structural Lubrication and Thermal Excitation on Phononic Friction.

This work investigates the coupling effect of structural lubrication and thermal excitation on phononic friction between black phosphorus (BP) layers. As the rotation angle increases from commensurate to incommensurate states, the friction gradually decreases at any temperature. However, the role of temperature in friction depends on commensurability. For a rotation angle less than 10°, increasing temperature leads to a decrease in friction due to thermal excitation. Conversely, when the rotation angle exceeds 10°, elevated temperature results in an increase in friction due to the effect of thermal collision. At a critical rotation angle of 10°, higher temperatures lead to reduced friction through thermal lubrication at low speeds, and at large speeds, the thermal excitation duration becomes so short that the role of thermal lubrication is weakened, and instead thermal collision dominates. Further research reveals that BP's ability to withstand different maximum speeds is also determined by commensurability. Finally, a method to measure the sliding period length of a rotated tip through an unrotated substrate potential energy topography is proposed and simply verified by using the phonon spectrum.

[Mechanism of Shikonin on spinal cord injury in rats based on TNFR/RIPK1 pathway].

OBJECTIVE: To explore the effect of shikonin on the recovery of nerve function after acute spinal cord injury(SCI) in rats. METHODS: 96 male Sprague-Dawley(SD)rats were divided into 4 groups randomly:sham operation group (Group A), sham operation+shikonin group (Group B), SCI+ DMSO(Group C), SCI+shikonin group (Group D).The acute SCI model of rats was made by clamp method in groups C and D . After subdural catheterization, no drug was given in group A. rats in groups B and D were injected with 100 mg·kg-1 of shikonin through catheter 30 min after modeling, and rats in group C were given with the same amount of DMSO, once a day until the time point of collection tissue. Basso-Beattie-Bresnahan(BBB) scores were performed on 8 rats in each group at 6, 12, and 3 d after moneling, and oblique plate tests were performed on 1, 3, 7 and 14 d after modeling, and then spinal cord tissues were collected. Eight rats were intraperitoneally injected with propidine iodide(PI) 1 h before sacrificed to detection PI positive cells at 24 h in each group. Eight rats were sacrificed in each group at 24 h after modeling, the spinal cord injury was observed by HE staining.The Nissl staining was used to observe survivor number of nerve cells. Western-blot technique was used to detect the expression levels of Bcl-2 protein and apoptosis related protein RIPK1. RESULTS: After modeling, BBB scores were normal in group A and B, but in group C and D were significantly higher than those in group A and B. And the scores in group D were higher than those in group C in each time point (P<0.05). At 12 h after modeling, the PI red stained cells in group D were significantly reduced compared with that in group C, and the disintegration of neurons was alleviated(P<0.05). HE and Nissl staining showed nerve cells with normal morphology in group A and B at 24h after operation. The degree of SCI and the number of neuronal survival in group D were better than those in group C, the difference was statistically significant at 24h (P<0.05). The expression of Bcl-2 and RIPK1 proteins was very low in group A and B;The expression of RIPK1 was significantly increased in Group C and decreased in Group D, with a statistically significant difference (P<0.05);The expression of Bcl-2 protein in group D was significantly higher than that in group C (P<0.05). CONCLUSION: Shikonin can alleviate the pathological changes after acute SCI in rats, improve the behavioral score, and promote the recovery of spinal nerve function. The specific mechanism may be related to the inhibition of TNFR/RIPK1 signaling pathway mediated necrotic apoptosis.