Anchoring Single-Atomic Metal Sites in Metalloporphyrin-Based Covalent Organic Frameworks for Enhanced Photocatalytic Hydrogen Evolution.

A photoactive covalent organic framework (COF) was built from metalloporphyrin and bipyridine monomers and single-atomic Pt sites were subsequently installed. Integrating photosensitizing metalloporphyrin and substrate-activating Pt(bpy) moieties in a single solid facilitates multielectron transfer and accelerates photocatalytic hydrogen evolution with a maximum production rate of 80.4 mmol h-1 gPt-1 and turnover frequency (TOF) of 15.7 h-1 observed. This work demonstrates that incorporation of single-atomic metal sites with photoactive COFs greatly enhances photocatalytic activity and provides an effective strategy for the design and construction of novel photocatalysts.

Dysregulated bidirectional epithelial-mesenchymal crosstalk: a core determinant of lung fibrosis progression.

Progressive lung fibrosis is characterised by dysregulated extracellular matrix (ECM) homeostasis. Understanding of disease pathogenesis remains limited and has prevented the development of effective treatments. While an abnormal wound healing response is strongly implicated in lung fibrosis initiation, factors that determine why fibrosis progresses rather than regular tissue repair occurs are not fully explained. Within human lung fibrosis there is evidence of altered epithelial and mesenchymal lung populations as well as cells undergoing epithelial-mesenchymal transition (EMT), a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell-cell adhesion to gain migratory properties. This review will focus upon the role of EMT and dysregulated epithelial-mesenchymal crosstalk in progressive lung fibrosis.

Onco-Circuit Addiction and Onco-Nutrient mTORC1 Signaling Vulnerability in a Model of Aggressive T Cell Malignancy.

How genetic lesions drive cell transformation and whether they can be circumvented without compromising function of non-transformed cells are enduring questions in oncology. Here we show that in mature T cells-in which physiologic clonal proliferation is a cardinal feature- constitutive MYC transcription and Tsc1 loss in mice modeled aggressive human malignancy by reinforcing each other's oncogenic programs. This cooperation was supported by MYC-induced large neutral amino acid transporter chaperone SLC3A2 and dietary leucine, which in synergy with Tsc1 deletion overstimulated mTORC1 to promote mitochondrial fitness and MYC protein overexpression in a positive feedback circuit. A low leucine diet was therapeutic even in late-stage disease but did not hinder T cell immunity to infectious challenge, nor impede T cell transformation driven by constitutive nutrient mTORC1 signaling via Depdc5 loss. Thus, mTORC1 signaling hypersensitivity to leucine as an onco-nutrient enables an onco-circuit, decoupling pathologic from physiologic utilization of nutrient acquisition pathways.

Hierarchical Self-Attention Network for Industrial Data Series Modeling With Different Sampling Rates Between the Input and Output Sequences.

For industrial processes, it is significant to carry out the dynamic modeling of data series for quality prediction. However, there are often different sampling rates between the input and output sequences. For the most traditional data series models, they have to carefully select the labeled sample sequence to build the dynamic prediction model, while the massive unlabeled input sequences between labeled samples are directly discarded. Moreover, the interactions of the variables and samples are usually not fully considered for quality prediction at each labeled step. To handle these problems, a hierarchical self-attention network (HSAN) is designed for adaptive dynamic modeling. In HSAN, a dynamic data augmentation is first designed for each labeled step to include the unlabeled input sequences. Then, a self-attention layer of variable level is proposed to learn the variable interactions and short-interval temporal dependencies. After that, a self-attention layer of sample level is further developed to model the long-interval temporal dependencies. Finally, a long short-term memory network (LSTM) network is constructed to model the new sequence that contains abundant interactions for quality prediction. The experiment on an industrial hydrocracking process shows the effectiveness of HSAN.

Multilayered Immunity by Tissue-Resident Lymphocytes in Cancer.

Lymphocytes spanning the entire innate-adaptive spectrum can stably reside in tissues and constitute an integral component of the local defense network against immunological challenges. In tight interactions with the epithelium and endothelium, tissue-resident lymphocytes sense antigens and alarmins elicited by infectious microbes and abiotic stresses at barrier sites and mount effector responses to restore tissue homeostasis. Of note, such a host cell-directed immune defense system has been recently demonstrated to surveil epithelial cell transformation and carcinoma development, as well as cancer cell metastasis, at selected distant organs and thus represents a primordial cancer immune defense module. Here we review how distinct lineages of tissue-resident innate lymphoid cells, innate-like T cells, and adaptive T cells participate in a form of multilayered cancer immunity in murine models and patients, and how their convergent effector programs may be targeted through both shared and private regulatory pathways for cancer immunotherapy. Expected final online publication date for the Annual Review of Immunology, Volume 42 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Mechanochemical synthesis of organoselenium compounds.

We disclose herein a strategy for the rapid synthesis of versatile organoselenium compounds under mild conditions. In this work, magnesium-based selenium nucleophiles are formed in situ from easily available organic halides, magnesium metal, and elemental selenium via mechanical stimulation. This process occurs under liquid-assisted grinding (LAG) conditions, requires no complicated pre-activation procedures, and operates broadly across a diverse range of aryl, heteroaryl, and alkyl substrates. In this work, symmetrical diselenides are efficiently obtained after work-up in the air, while one-pot nucleophilic addition reactions with various electrophiles allow the comprehensive synthesis of unsymmetrical monoselenides with high functional group tolerance. Notably, the method is applied to regioselective selenylation reactions of diiodoarenes and polyaromatic aryl halides that are difficult to operate via solution approaches. Besides selenium, elemental sulfur and tellurium are also competent in this process, which showcases the potential of the methodology for the facile synthesis of organochalcogen compounds.

A mitochondria-targeting dihydroartemisinin derivative as a reactive oxygen species -based immunogenic cell death inducer.

Immunogenic cell death (ICD) can activate the anticancer immune response and its occurrence requires high reliance on oxidative stress. Inducing mitochondrial reactive oxygen species (ROS) is a desirable capability for ICD inducers. However, in the category of ICD-associated drugs, numerous reported ICD inducers are a series of anthracyclines and weak in ICD induction. Herein, a mitochondria-targeting dihydroartemisinin derivative (T-D) was synthesized by conjugating triphenylphosphonium (TPP) to dihydroartemisinin (DHA). T-D can selectively accumulate in mitochondria to trigger ROS generation, leading to the loss of mitochondrial membrane potential (ΔΨm) and ER stress. Notably, T-D exhibits far more potent ICD-inducing properties than its parent compound. In vivo, T-D-treated breast cancer cell vaccine inhibits metastasis to the lungs and tumor growth. These results indicate that T-D is an excellent ROS-based ICD inducer with the specific function of trigging vigorous ROS in mitochondria and sets an example for incorporating artemisinin-based drugs into the ICD field.

Aurora B facilitates cholangiocarcinoma progression by stabilizing c-Myc.

BACKGROUND: Cholangiocarcinoma (CCA), a malignancy that arises from biliary epithelial cells, has a dismal prognosis, and few targeted therapies are available. Aurora B, a key mitotic regulator, has been reported to be involved in the progression of various tumors, yet its role in CCA is still unclarified. METHODS: Human CCA tissues and murine spontaneous CCA models were used to assess Aurora B expression in CCA. A loss-of-function model was constructed in CCA cells to determine the role of Aurora B in CCA progression. Subcutaneous and liver orthotopic xenograft models were used to assess the therapeutic potential of Aurora B inhibitors in CCA. RESULTS: In murine spontaneous CCA models, Aurora B was significantly upregulated. Elevated Aurora B expression was also observed in 62.3% of human specimens in our validation cohort (143 CCA specimens), and high Aurora B expression was positively correlated with pathological parameters of tumors and poor survival. Knockdown of Aurora B by siRNA and heteroduplex oligonucleotide (HDO) or an Aurora B kinase inhibitor (AZD1152) significantly suppressed CCA progression via G2/M arrest induction. An interaction between Aurora B and c-Myc was found in CCA cells. Targeting Aurora B significantly reduced this interaction and accelerated the proteasomal degradation of c-Myc, suggesting that Aurora B promoted the malignant properties of CCA by stabilizing c-Myc. Furthermore, sequential application of AZD1152 or Aurora B HDO drastically improved the efficacy of gemcitabine in CCA. CONCLUSIONS: Aurora B plays an essential role in CCA progression by modulating c-Myc stability and represents a new target for treatment and chemosensitization in CCA.

LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis.

The factors that determine fibrosis progression or normal tissue repair are largely unknown. We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition (EMT) in human alveolar epithelial type II (ATII) cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signalling. Here, we report that liver kinase B1 (LKB1) inactivation in ATII cells inhibits autophagy and induces EMT as a consequence. In IPF lungs, this is caused by downregulation of CAB39L, a key subunit within the LKB1 complex. 3D co-cultures of ATII cells and MRC5 lung fibroblasts coupled with RNA sequencing (RNA-seq) confirmed that paracrine signalling between LKB1-depleted ATII cells and fibroblasts augmented myofibroblast differentiation. Together these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATII cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson's disease model.

Parkinson's disease (PD) is a neurodegenerative condition that results in dyskinesia, with oxidative stress playing a pivotal role in its progression. Antioxidant peptides may thus present therapeutic potential for PD. In this study, a novel cathelicidin peptide (Cath-KP; GCSGRFCNLFNNRRPGRLTLIHRPGGDKRTSTGLIYV) was identified from the skin of the Asiatic painted frog ( Kaloula pulchra). Structural analysis using circular dichroism and homology modeling revealed a unique αßß conformation for Cath-KP. In vitro experiments, including free radical scavenging and ferric-reducing antioxidant analyses, confirmed its antioxidant properties. Using the 1-methyl-4-phenylpyridinium ion (MPP +)-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, Cath-KP was found to penetrate cells and reach deep brain tissues, resulting in improved MPP +-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1 (Sirt1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Both focal adhesion kinase (FAK) and p38 were also identified as regulatory elements. In the MPTP-induced PD mice, Cath-KP administration increased the number of tyrosine hydroxylase (TH)-positive neurons, restored TH content, and ameliorated dyskinesia. To the best of our knowledge, this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress. These findings expand the known functions of cathelicidins, and hold promise for the development of therapeutic agents for PD.

Optimum Doses and Forms of Selenium Maintaining Reproductive Health via Regulating Homeostasis of Gut Microbiota and Testicular Redox, Inflammation, Cell Proliferation, and Apoptosis in Roosters.

BACKGROUND: There is a U-shaped relationship between dietary selenium (Se) ingestion and optimal sperm quality. OBJECTIVES: This study aimed to investigate the optimal dietary dose and forms of Se for sperm quality of breeder roosters and the relevant mechanisms. METHODS: In experiment 1, 18-wk-old Jingbai laying breeder roosters were fed a Se-deficient base diet (BD, 0.06 mg Se/kg), or the BD + 0.1, 0.2, 0.3, 0.4, 0.5, or 1.0 mg Se/kg for 9 wk. In experiment 2, the roosters were fed the BD or the BD + sodium selenite (SeNa), seleno-yeast (SeY), or Se-nanoparticles (SeNPs) at 0.2 mg Se/kg for 9 wk. RESULTS: In experiment 1, added dietary 0.2 and 0.3 mg Se/kg led to higher sperm motility and lower sperm mortality than the other groups at weeks 5, 7, and/or 9. Furthermore, added dietary 0.2-0.4 mg Se/kg produced better testicular histology and/or lower testicular 8-hydroxy-deoxyguanosine than the other groups. Moreover, integrated testicular transcriptomic and cecal microbiomic analysis revealed that inflammation, cell proliferation, and apoptosis-related genes and bacteria were dysregulated by Se deficiency or excess. In experiment 2, compared with SeNa, SeNPs slightly increased sperm motility throughout the experiment, whereas SeNPs slightly reduced sperm mortality compared with SeY at week 9. Both SeY and SeNPs decreased malondialdehyde in the serum than those of SeNa, and SeNPs led to higher glutathione peroxidase (GPX) and thioredoxin reductase activities and GPX1 and B-cell lymphoma 2 protein concentrations in the testis compared with SeY and SeNa. CONCLUSIONS: The optimal dietary Se dose for reproductive health of breeder roosters is 0.25-0.35 mg Se/kg, and SeNPs displayed better effects on reproductive health than SeNa and SeY in laying breeder roosters. The optimal doses and forms of Se maintain reproductive health of roosters associated with regulation intestinal microbiota homeostasis and/or testicular redox balance, inflammation, cell proliferation, and apoptosis.

Long noncoding RNA NONHSAT160169.1 promotes resistance via hsa-let-7c-3p/SOX2 axis in gastric cancer.

In clinical trials involving patients with HER2 (ERBB2 receptor tyrosine kinase 2) positive gastric cancer, the efficacy of the HER2-targeted drug lapatinib has proven to be disappointingly poor. Under the persistent pressure exerted by targeted drug therapy, a subset of tumor cells exhibit acquired drug resistance through the activation of novel survival signaling cascades, alongside the proliferation of tumor cells that previously harbored mutations conferring resistance to the drug. This study was undertaken with the aim of elucidating in comprehensive detail the intricate mechanisms behind adaptive resistance and identifying novel therapeutic targets that hold promise in the development of effective lapatinib-based therapies for the specific subset of patients afflicted with gastric cancer. We have successfully established a gastric cancer cell line with acquired lapatinib resistance, designated as HGC-27-LR cells. Utilizing comprehensive coding and noncoding transcriptome sequencing analysis, we have identified key factors that regulate lapatinib resistance in HGC-27 cells. We have compellingly validated that among all the lncRNAs identified in HGC-27-LR cells, a novel lncRNA (long noncoding RNA) named NONHSAT160169.1 was found to be most notably upregulated following exposure to lapatinib treatment. The upregulation of NONHSAT160169.1 significantly augmented the migratory, invasive, and stemness capabilities of HGC-27-LR cells. Furthermore, we have delved into the mechanism by which NONHSAT160169.1 regulates lapatinib resistance. The findings have revealed that NONHSAT160169.1, which is induced by the p-STAT3 (signal transducer and activator of transcription 3) nuclear transport pathway, functions as a decoy that competitively interacts with hsa-let-7c-3p and thereby abrogates the inhibitory effect of hsa-let-7c-3p on SOX2 (SRY-box transcription factor 2) expression. Hence, our study has unveiled the NONHSAT160169.1/hsa-let-7c-3p/SOX2 signaling pathway as a novel and pivotal axis for comprehending and surmounting lapatinib resistance in the treatment of HER2-positive gastric cancer.

AURKA inhibitor-induced PD-L1 upregulation impairs antitumor immune responses.

Introduction: Tumor immunotherapy targeting PD-L1 has emerged as one of the powerful tools for tumor therapy. Numerous studies indicate that tumor-targeted drugs critically have an influence on the interaction between the immune system and tumors by changing the expression of PD-L1, which is beneficial for immunotherapy. Our study provided novel evidence for improving the drug regimen in tumor targeted therapy and immunotherapy. Methods: The expression of PD-L1 on SKBR3, MDA-MB-231, MCF7, 4T1, MC38 and B16 cells was evaluated by flow cytometry after treatment with six preclinical targeted drugs (ARN-509, AZD3514, Galeterone, Neratinib, MLN8237 and LGK974). AURKA was knockdowned by using the specific siRNA or CRISPR-Cas9 technology. In the 4T1-breast tumor and colorectal cancer xenograft tumor models, we determined the number of infiltrated CD3+ and CD8+ T cells in tumor tissues by IHC. Results: We found that AURKA inhibitor MLN8237 promoted the expression of PD-L1 in a time- and concentration-dependent manner while exerted its antitumor effect. Knockdown of AURKA could induce the upregulation of PD-L1 on SKBR3 cells. MLN8237-induced PD-L1 upregulation was mainly associated with the phosphorylation of STAT3. In the 4T1-breast tumor xenograft model, the infiltrated CD3+ and CD8+ T cells decreased after treatment with MLN8237. When treated with MLN8237 in combination with anti-PD-L1 antibody, the volumes of tumor were significantly reduced and accompanied by increasing the infiltration of CD3+ and CD8+ T cells in colorectal cancer xenograft tumor model. Discussion: Our data demonstrated that MLN8237 improved the effect of immunology-related therapy on tumor cells by interacting with anti-PD-L1 antibody, which contributed to producing creative sparks for exploring the possible solutions to overcoming drug resistance to tumor targeted therapy.

Initial probe function construction in ptychography based on zone-plate optics.

X-ray ptychography is a popular variant of coherent diffraction imaging that offers ultrahigh resolution for extended samples. In x-ray ptychography instruments, the Fresnel zone-plate (FZP) is the most commonly used optical probe system for both soft x-ray and hard x-ray. In FZP-based ptychography with a highly curved defocus probe wavefront, the reconstructed image quality can be significantly impacted by the initial probe function form, necessitating the construction of a suitable initial probe for successful reconstruction. To investigate the effects of initial probe forms on FZP-based ptychography reconstruction, we constructed four single-mode initial probe models (IPMs) and three multi-mode IPMs in this study, and systematically compared their corresponding simulated and experimental reconstructions. The results show that the Fresnel IPM, spherical IPM, and Fresnel-based multi-mode IPMs can result in successful reconstructions for both near-focus and defocus cases, while random IPMs and constant IPMs work only for near-focus cases. Consequently, for FZP-based ptychography, the elaborately constructed IPMs that closely resemble real probes in wavefront phase form are more advantageous than natural IPMs such as the random or constant model. Furthermore, these IPMs with high phase similarity to the high-curvature large-sized probe adopted in experiments can help greatly improve ptychography experiment efficiency and decrease radiation damage to samples.

Crosstalk between 5-Aminolevulinic Acid and Abscisic Acid Adjusted Leaf Iron Accumulation and Chlorophyll Synthesis to Enhance the Cold Tolerance in Solanum lycopersicum Seedlings.

Previous studies found that 5-aminolevulinic acid (ALA) and abscisic acid (ABA) can mitigate damage from adversity by enhancing photosynthesis. However, it is not clear whether they have positive effects on iron utilization and chlorophyll synthesis of tomato seedlings under low-temperature stress. To investigate the possible functional relationship between ABA and ALA and elucidate the possible mechanisms of action of ALA to alleviate low-temperature stress in tomato seedlings, this experiment analyzed the effects of ALA and ABA on chlorophyll synthesis in tomato seedling leaves sprayed with exogenous of ALA (25 mg·L-1) or ABA (100 µM) under low-temperature stress (8-18 °C/8-12 °C, day/night). The results show that exogenous ALA increased the Fv/Fm of tomato leaves by 5.31% and increased the accumulation of iron and chlorophyll by 101.15% and 15.18%, respectively, compared to the low-temperature treatment alone, and tomato resistance of low-temperature stress was enhanced. Meanwhile, exogenous application of ALA increased the ABA content by 39.43%, and subsequent application of exogenous ABA revealed that tomato seedlings showed similar effects to exogenous ALA under low-temperature stress, with increased accumulation of iron and chlorophyll in tomato seedlings, which eventually increased the maximum photochemical efficiency of PS II. Under low-temperature stress, application of exogenous ABA significantly reduced ALA content, but the expression of key enzyme genes (PPGD, HEMB1, HEME1, and HEMF1), precursors of chlorophyll synthesis by ALA, was significantly elevated, presumably because the increased activity of these enzymes after external application of ABA accelerated ALA consumption. In conclusion, ABA may crosstalk with ALA to improve the photochemical efficiency and low temperature resistance of tomatoes by regulating chlorophyll synthesis and iron accumulation.

Understanding the Interfacial Reactions and Band Alignment for Efficient and Stable Perovskite Solar Cells Built on Metal Substrates with Reduced Upscaling Losses.

Conventional perovskite solar cells (PSC) built on transparent conductive oxide (TCO) glass face a fundamental challenge to retain fill factor (FF) for large-area upscaling due to series resistance loss. Building a perovskite solar cell on metal has the potential to reduce this FF loss and is promising for flexible applications. However, their efficiency and stability lag far behind their TCO counterparts. Herein, findings on the complex chemical reactions and degradation-promoting processes at different perovskite/metal (Cu, Au, Ag, and Mo) interfaces, which are closely linked with the inherent stability; and the interlayer engineering for perovskite/metal interface's band alignment, which plays an essential role in achieving high efficiency, are reported. Leveraging these findings, 21% power conversion efficiency (PCE) is achieved for 1 cm2 perovskite solar cells using a p-i-n top-illumination structure on a molybdenum substrate, the highest reported for a PSC built on metal. Notably, the FF and PCE losses due to area upscaling are remarkably reduced by one order of magnitude relative to the counterparts on conventional TCO glass, highlighting an alternative pathway for PSC upscaling and module design.

High-efficiency focusing and imaging by dielectric kinoform zone plate lenses with soft X-rays.

With fast advances in enhancing the focusing/imaging resolution of Fresnel zone plate lenses toward sub-10 nm, low diffraction efficiency in connection with their rectangular zone shape still remains a big issue in both soft and hard X-ray microscopy. In hard X-ray optics, encouraging progress has recently been reported in our earlier attempts of high focusing efficiency by 3D kinoform shaped metallic zone plates, formed by greyscale electron beam lithography. This paper addresses our efforts towards high focusing/imaging efficiency by developing a novel dielectric kinoform zone plate lens for soft X-rays. The effects of the zone materials and zone shapes on the focusing/imaging quality were first theoretically investigated by a modified thin-grating-approximation method, revealing superior efficiencies of dielectric kinoform zone plates over rectangular ones in metals. Optical characterizations of replicated dielectric kinoform zone plates by greyscale electron beam lithography demonstrate a focusing efficiency of 15.5% with a resolution of 110 nm in the water window of X-rays. Apart from high efficiency, the novel kinoform zone plate lenses developed in this work exhibit significant advantages over conventional zone plates, i.e. simplified process, low cost and no need for a beamstop.

The bZIP transcription factor SlAREB1 regulates anthocyanin biosynthesis in response to low temperature in tomato.

Low temperature and abscisic acid (ABA) are the two main factors that induce anthocyanin synthesis; however, their potential relationships in governing anthocyanin biosynthesis in Solanum lycopersicum (tomato) seedlings remains unclear. Our study revealed the involvement of the transcription factor SlAREB1 in the low-temperature response of tomato seedlings via the ABA-dependent pathway, for a specific temperature range. The overexpression of SlAREB1 enhanced the expression of anthocyanin-related genes and the accumulation of anthocyanins, especially under low-temperature conditions, whereas silencing SlAREB1 dramatically reduced gene expression and anthocyanin accumulation. There is a direct interaction between SlAREB1 and the promoters of SlDFR and SlF3'5'H, which are structural genes that impact anthocyanin biosynthesis. SlAREB1 can regulate anthocyanins through controlling SlDFR and SlF3'5'H expression. Accordingly, SlAREB1 takes charge of regulating anthocyanin biosynthesis in tomato seedlings via the ABA-dependent pathway at low temperatures.

A compound Kinoform/Fresnel zone plate lens with 15 nm resolution and high efficiency in soft x-ray.

X-ray microscope as an important nanoprobing tool plays a prevailing role in nano-inspections of materials. Despite the fast advances of high resolution focusing/imaging reported, the efficiency of existing high-resolution zone plates is mostly around 5% in soft x-ray and rapidly goes down to 1%-2% when the resolution approaches 10 nm. It is well known that the rectangular zone shape, beamstop, limited height/width ratios, material absorption of light and structural defects are likely responsible for the limited efficiency. Although zone plates with Kinoform profile are supposed to be efficient, progress for achieving both high resolution (<30 nm) and high efficiency (>5%) have hardly been addressed in soft x-ray. In this work, we propose a compound Kinoform/Fresnel zone plate (CKZP) by combing a dielectric Kinoform zone plate with a 15 nm resolution zone plate. Greyscale electron beam lithography was applied to form the 3D Kinoform zone plate and atomic layer deposition was carried out to form the binary zone plate. Optical characterizations demonstrated 15 nm resolution focusing/imaging with over 7.8% efficiency in soft x-ray. The origin of the efficiency improvement behind the proposed compound lens is theoretically analyzed and discussed.

Both selenium deficiency and excess impair male reproductive system via inducing oxidative stress-activated PI3K/AKT-mediated apoptosis and cell proliferation signaling in testis of mice.

Selenium (Se) deficiency or excess impairs testicular development and spermatogenesis, while the underlying mechanisms in this regard remain unclear. This study was designed to explore the molecular biology of Se deficiency or excess in spermatogenesis in mice. Three-week-old male mice (n = 10 mice/diet) were fed with Se-deficient diet (SeD, 0.02 mg Se/kg), adequate-Se diet (SeA, 0.2 mg Se/kg), or excess-Se diet (SeE, 2.0 mg Se/kg) for 5 months. Compared with SeA, SeD reduced (P < 0.05) the body weight (10.4%) and sperm density (84.3%) but increased (P < 0.05) sperm deformity (32.8%); SeE decreased (P < 0.05) the sperm density (78.5%) and sperm motility (35.9%) of the mice. Meanwhile, both SeD and SeE increased (P < 0.05) serum FSH concentrations (10.4-25.6%) and induced testicular damage in mice in comparison with the SeA. Compared with SeA, SeD increased (P < 0.05) the 8-OHdG concentration by 25.5%; SeE increased (P < 0.05) both MDA and 8-OHdG concentrations by 118.8-180.3% in testis. Furthermore, transcriptome analysis showed that there 1325 and 858 transcripts were altered (P < 0.05) in the testis by SeD and SeE, respectively, compared with SeA. KEGG pathway analysis revealed that these differentially expressed genes were mainly enriched in the PI3K-AKT signaling pathway, which is regulated by oxidative stress. Moreover, western blotting analysis revealed that SeD and SeE dysregulated PI3K-AKT-mediated apoptosis and cell proliferation signaling, including upregulating (P < 0.05) caspase 3, cleaved-caspase 3, BCL-2 and (or) P53 and downregulating (P < 0.05) PI3K, p-AKT, p-mTOR, 4E-BP1, p-4E-BP1 and (or) p-p70S6K in the testis of mice compared with SeA. Additionally, compared with SeA, both SeD and SeE increased (P < 0.05) GPX3 and SELENOO; SeD decreased (P < 0.05) GPX1, TXRND3 and SELENOW, but SeE increased (P < 0.05) production of three selenoproteins in the testis. Conclusively, both Se deficiency and excess impairs male reproductive system in mice, potentially with the induction of oxidative stress and activation of PI3K/AKT-mediated apoptosis and cell proliferation signaling in the testis.