Cresyl Diphenyl Phosphate exposure induces reproductive functional defects in men and male mice.

Cresyl Diphenyl Phosphate (CDP), as a novel organophosphate esters (OPEs), achieves widely used and exposed in multiple industries. However, its male reproductive toxicity and underlying mechanism remains unclear. In vivo, male mice were gavaged with CDP (0, 4, 20, or 100 mg/kg/d) for 8 weeks. And we treated TM3, TM4 and GC-2 cells with 0, 10, 25, and 50 µM CDP for 24 h to detect its reproductive toxicity effect in vitro. In our study, we revealed that CDP inhibited proliferation and induced apoptosis in mice testis and GC-2 cells, thereby leading to the decreased sperm quality. In mechanism, CDP trigger the oxidative stress and ROS production, thus partially causing DNA damage and cell apoptosis. Moreover, CDP exposure causes injury to Ledyig cells and Sertoli cells, thus disturbing the testicular microenvironment and inhibiting spermatogonia proliferation. In conclusion, this research reveals multiple adverse impacts of CDP on the male reproductive system and calls for further study of the toxicological effects of CDP on human health.

Terahertz-driven positron acceleration assisted by ultra-intense lasers.

Generation and acceleration of energetic positrons based on laser plasma have attracted intense attention due to their potential applications in medical physics, high energy physics, astrophysics and nuclear physics. However, such compact positron sources face a series of challenges including the beam dispersion, dephasing and unstability. Here, we propose a scheme that couples the all-optical generation of electron-positron pairs and rapid acceleration of copious positrons in the terahertz (THz) field. In the scheme, nanocoulomb-scale electrons are first captured in the wakefield and accelerated to 2.5 GeV. Then these energetic electrons emit strong THz radiation when they go through an aluminum foil. Subsequently, abundant γ photons and positrons are generated during the collision of GeV electron beam and the scattering laser. Due to the strong longitudinal acceleration field and the transvers confining field of the emitted THz wave, the positrons can be efficiently accelerated to 800 MeV, with the peak beam brilliance of 2.26 × 1012s-1mm-2mrad-2eV-1. This can arouse potential research interests from PW-class laser facilities together with a GeV electron beamline.

Tuning the water-splitting mechanism on titanium dioxide surfaces through hydroxylation.

Experimental research demonstrates that surface hydroxyl groups can boost TiO2's ability to split water but the water splitting mechanism and roles of hydroxyl groups are still not clear. The hydroxyl groups formed by H2O or H2 cracking on pure TiO2 surfaces are represented by types I (OH1) and II (OH2), respectively. Six types of hydroxylated TiO2 surfaces of anatase (101), rutile (110), and brookite (210) with OH1 and OH2 hydroxyl groups were constructed. The mechanism of the water oxidation process on the hydroxylated TiO2 surfaces was systematically investigated through density functional theory calculations. The variation and significant roles of hydroxyl groups in the mechanism of the oxygen evolution reaction (OER) and product selectivity were discussed. All hydroxylated TiO2 surfaces eventually tend to produce oxygen through a four-electron/proton process, which is fundamentally different from the OER process on pure Ti2O surfaces from a thermodynamic standpoint. The lowest surface overpotential of R-110-OH1 is 0.53 V, the highest surface overpotential of B-210-OH2 is 1.49 V, and the surface overpotentials of other hydroxylated TiO2 are between 0.5 and 1.5 V. Rutile (110) and brookite (210) have hydroxyl groups of the OH1-type that are more conducive to the OER process. This study investigates the mechanism of water splitting on the surface of hydroxylated TiO2, allowing for a deeper understanding of the function of surface hydroxyl groups in the OER process as well as providing instructions for future research into the development of effective water-splitting catalysts based on hydroxylated TiO2 surfaces.

Efficient high-order harmonics generation from overdense plasma irradiated by a two-color co-rotating circularly polarized laser pulse.

High-order harmonics generated from the interaction between a two-color circularly polarized laser and overdense plasma is proposed analytically and investigated numerically. By mixing two circularly polarized lasers rotating in the same direction with different frequencies (ω0, 2ω0), the laser envelope is modulated to oscillate at the laser fundamental frequency while the peak intensity of each cycle becomes greater than that of the monochromatic light. This feature makes the plasma oscillate more violently and frequently under the striking of the two-color laser than the monochromatic one, thereby generating stronger harmonics and attosecond pulses. In addition, the incorporation of the 2ω0 light greatly expands the spectral width of harmonics, which facilitates the production of shorter attosecond pulses. Particle-in-cell simulations prove that under the same condition, the harmonic radiation efficiency in the two-color laser case can be improved by orders of magnitude, and isolated attosecond pulses can be even generated as a bonus in some cases.

Generation of single circularly polarized attosecond pulses from near-critical density plasma irradiated by a two-color co-rotating circularly polarized laser.

In this paper, a new method is proposed to efficiently generate a single intense attosecond pulse with circular polarization (CP) through the interaction of an intense driving laser with a near-critical density plasma target. The driving laser is composed of two co-rotating CP lasers with similar frequencies but different pulse widths. When the matching condition is satisfied, the combined field is modulated to a short intense pulse followed by a weak tail. The resulting laser falling edge becomes steeper than the initial sub-pulses, which induces a quick one-time oscillation of the target surface. Meanwhile, the tail guarantees the energy to be compressed simultaneously in both polarization directions to the same extent, so that a single CP attosecond pulse can be produced efficiently and robustly via our method, which has been confirmed through extensive numerical simulations. In addition, our method makes it possible to generate a single CP attosecond pulse even for multi-cycle pulses that are already available for existing laser systems. This provides a novel way to advance the investigation of chiral-sensitive light-matter interactions in attosecond scales.

Ultra-intense vortex laser generation from a seed laser illuminated axial line-focused spiral zone plate.

Relativistic vortex laser has drawn increasing attention in the laser-plasma community owing to its potential applications in various domains, e.g., generation of energetic charged particles with orbital angular momentum (OAM), high OAM X/γ-ray emission, high harmonics generation, and strong axial magnetic-field production. However, the generation of such relativistic vortex laser is still a challenge to the current laser technology. Using micro-structure targets named axial line-focused spiral zone plate (ALFSZP), we propose a novel scheme for ultra-intense vortex laser generation. In the scheme, a relativistic Gaussian laser pulse irradiates an ALFSZP, and diffracts as it passes through the ALFSZP. Due to the focusing and radial Hilbert transform capabilities of the ALFSZP, the seed laser is converted efficiently to a vortex one which is then well focused in a tunable focal volume. Three-dimensional particle-in-cell simulations indicate that using a seed laser pulse with intensity of 1.3 × 1020 W/cm2, the vortex laser intensity achieved is as high as 1.3 × 1021 W/cm2 with the averaged angular momentum per photon up to 0.73ℏ, promising diverse applications in various fields aforementioned.

Electronic structures of hydroxylated low index surfaces of rutile and anatase-type titanium dioxide.

Different surface planes of various types of titanium dioxide (TiO2) crystals have diverse catalysis effects on the splitting of H2O and H2 and the electronic structures of the formed hydroxylated TiO2 vary significantly. A series of sixteen types of hydroxylated TiO2 surfaces containing two types of hydroxyls (OH1 and OH2) on four kinds of low index surfaces [(001), (100), (101), and (110)] of two types of crystals [anatase (A) and rutile (R)] are studied using first-principles density functional theory calculations. The catalyzed splitting of H2O and H2 on the eight low index surfaces is compared using Gibbs free energy. The geometries and electronic structures including the total and partial density of states and the charge density distribution of the sixteen hydroxylated surfaces are systematically described. The electronic structures of R-101, R-001, A-110, A-100, and A-001 surfaces are more significantly influenced by hydroxylation than other surfaces and the effects of OH2 are larger than those of OH1. In particular, the band gap values decrease and a new electronic energy state appears in R-001-OH2 and A-100-OH2. A new electronic state appears in the middle of the bands of R-101 and A-110 surfaces upon hydroxylation. The electron spin balance at the edge of the conduction band minimum of A-001-OH2 is disturbed. This research can provide theoretical guidance for experimental researchers to design surface hydroxylated TiO2 materials with tunable electronic structures and high catalytic performance.

Ultra-brilliant GeV betatronlike radiation from energetic electrons oscillating in frequency-downshifted laser pulses.

Electrons can be accelerated to GeV energies with high collimation via laser wakefield acceleration in the bubble regime and emit bright betatron radiation in a table-top size. However, the radiation brightness is usually limited to the third-generation synchrotron radiation facilities operating at similar photon energies. Using a two-stage plasma configuration, we propose a novel scheme for generating betatronlike radiation with an extremely high brilliance. In this scheme, the relativistic electrons inside the bubble injected from the first stage can catch up with the frequency-downshifted laser pulse formed in the second stage. The laser red shift originates from the phase modulation, together with the group velocity dispersion, which enables more energy to be transfered from the laser pulse to γ-photons, giving rise to ultra-brilliant betatronlike radiation. Multi-dimensional particle-in-cell simulations indicate that the radiated γ-photons have the cut-off energy of GeV and a peak brilliance of 1026 photons s-1 mm-2 mrad-2 per 0.1%BW at 1 MeV, which may have diverse applications in various fields.

Titanium Vacancies in TiO2 Nanofibers Enable Highly Efficient Photodriven Seawater Splitting.

Photodriven seawater splitting is considered to be one of the most promising techniques for sustainable hydrogen production. However, the high salinity of seawater would deactivate catalysts and consume the photogenerated carriers. Metal vacancies in metal oxide semiconductors are critical to directed electron transfer and high salinity resistance; they are thus desirable but remain a challenge. We demonstrate a facile controllable calcination approach to synthesize TiO2 nanofibers with rich Ti vacancies with excellent photo/electro performances and long-time stability in photodriven seawater splitting, including photocatalysis and photo-electrocatalysis. Experimental measurements and theoretical calculations reveal the formation of titanium vacancies, as well as unidirectional electron trap and superior H+ adsorption ability for efficient charge transfer and resistance to corrosion by seawater. Therefore, atomic-/nanoscale characteristics and mechanism have been proposed to clarify the generation of titanium vacancies and the corresponding interfacial electron transfer.

Titanium Vacancies in TiO2 Nanofibers Enable Highly Efficient Photodriven Seawater Splitting.

Invited for the cover of this issue are Xiao-Yu Yang and co-workers at Wuhan University of Technology, Heinrich-Heine-Universität Düsseldorf, University of the Witwatersrand, and Ben-Gurion University of the Negev. The image depicts Ti vacancies in TiO2 as powerful drivers of photo- and photo-electrocatalytic seawater splitting for hydrogen production. Read the full text of the article at 10.1002/chem.202101817.

Identification and validation of senescence-related genes in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an exceedingly intractable issue affecting female endocrine and reproductive health. However, the etiology and intricate pathological mechanisms of PCOS remain unclear. Nowadays, aging was found to share multiple common pathological mechanisms with PCOS, which causes probing into the pathogenesis of PCOS from senescence. However, no bioinformatics analyses have specifically focused on connection between PCOS and ovarian aging. METHODS: Differentially expressed aging-related genes in PCOS were identified and then analyzed using function enrichment method. Hub genes were determined based on multiple algorithms, and expression validation of hub genes was performed in both datasets and experiments (human granulosa-like tumor cell line, KGN; human Granulosa Cell, hGCs). Finally, a transcription factor-miRNA-gene network of hub genes was constructed. RESULTS: Here, we identified 73 aging-related differential expression genes (ARDEGs) by intersecting DEGs in PCOS and senescence-related gene set. Furthermore, we performed biological functions and potential pathways of ARDEGs and potential hub genes were also screened by multiple algorithms. From the perspective of immune dysfunction, we analyzed the correlation between PCOS and immune cells. Finally, TF-miRNA-gene networks were constructed. Finally, TF-miRNA-gene networks were constructed. CONCLUSIONS: Our work aimed to elucidate the relation between PCOS and cellular senescence based on bioinformatics strategy, deepening the understanding of mechanisms and to seek for novel therapy strategies for improving reproductive lifespan and female health. Exploring the potential molecular mechanism of cell aging in PCOS is expected to bring a new breakthrough for PCOS diagnosis and therapy strategies. And this, might deepen our understanding about intricate mechanisms of ovarian aging.

KRAS mutation predict response and outcome in advanced non-small cell lung carcinoma without driver alterations receiving PD-1 blockade immunotherapy combined with platinum-based chemotherapy: a retrospective cohort study from China.

Background: The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Kirsten rat sarcoma (KRAS) mutation is the most frequent molecular alteration found in advanced non-small cell lung carcinoma (NSCLC). We explored whether KRAS mutation status predicted the effects of first-line immune checkpoint inhibitor (ICI) treatment and platinum-based chemotherapy in Chinese patients with advanced NSCLC. Methods: Clinical data were extracted from medical records of patients with advanced NSCLC at the First Affiliated Hospital of Guangzhou Medical University in China between January 2019 and March 2020. Overall survival (OS) and progression-free survival (PFS) rates were compared via log-rank tests, and independent prognostic factors were identified via Cox regression. Results: Patients with advanced NSCLC without driver alterations who were treated with ICI and platinum-based chemotherapy (N=80) were identified, including 28.7% with KRAS mutations and 71.3% with non-KRAS mutations. Tumor programmed death-ligand 1 (PD-L1) expression was analyzed using a 1% cutoff, and 32.5% of patients were negative and 67.5% were positive. The median tumor mutational burden (TMB) was 7.29 mutations per megabase (muts/Mb) (range, 0.08-44.8 muts/Mb), with 32.5% of cases <5 muts/Mb and 67.5% ≥5 muts/Mb. The median PFS and OS for the entire cohort were 9.8 (95% CI: 9.1-10.5) and 17.6 (95% CI: 14.4-20.8) months, respectively. The 6-month PFS rate was 67.5% and the 1-year OS rate was 72.5%. Thirty-five patients survived until the last follow-up. The OS and PFS of patients with KRAS mutations were significantly higher than those in the non-KRAS mutant group (P<0.05). The Cox multivariate analyses showed that brain metastasis [hazard ratio (HR) =0.232, 95% CI: 0.102-0.530; P=0.001], TMB (HR =5.675, 95% CI: 1.948-16.535; P=0.001), KRAS mutation (HR =2.552, 95% CI: 1.141-5.708; P=0.023) were independent predictors of OS in patients treated with ICIs and platinum-based chemotherapy. Liver metastasis (HR =0.344, 95% CI: 0.191-0.619; P<0.001) and KRAS/tumor protein p53 (TP53) co-mutation (HR =0.220, 95% CI: 0.067-0.725; P=0.013) were the prognostic factor for PFS of qualified patients. Conclusions: This work provides evidence that KRAS mutation in advanced NSCLC may be served as a potential predictive biomarker for immunotherapeutic efficacy.

KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway.

Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target.