Monitoring Blood Glucose in Mouse Offspring after Intracytoplasmic sperm injection - Embryo Transfer.

Human lifespan is considerably long, while mouse models can simulate the entire human lifespan in a relatively short period, with one year of mouse life roughly equivalent to 40 human years. Intracytoplasmic sperm injection (ICSI) is a commonly used assisted reproductive technology in clinical practice. However, given its relatively recent emergence about 30 years ago, the long-term effects of this technique on human development remain unclear. In this study, we established the ICSI combined with embryo transfer (ET) method using a mouse model. The results demonstrated that normal mouse sperm, after undergoing in vitro culture and subsequent ICSI, exhibited a fertilization rate of 89.57% and a two-cell rate of 87.38%. Following ET, the birth rate of offspring was approximately 42.50%. Furthermore, as the mice aged, fluctuations in glucose metabolism levels were observed, which may be associated with the application of the ICSI technique. These findings signify that the mouse ICSI-ET technique provides a valuable platform for evaluating the impact of sperm abnormalities on embryo development and their long-term effects on offspring health, particularly concerning glucose metabolism. This study provides important insights for further research on the potential effects of the ICSI technique on human development, emphasizing the necessity for in-depth investigation into the long-term implications of this technology.

The relationship between physical activity and Internet addiction among adolescents in western China: a chain mediating model of anxiety and inhibitory control.

This study aims to investigate the mediating effect of anxiety and inhibitory control in the relationship between physical activity and Internet addiction (IA) among adolescents. A total of 951 adolescents from western China completed a self-report survey assessing physical activity, anxiety, inhibitory control, and IA. Descriptive analysis, correlation analysis, and mediation analysis were conducted using SPSS software and the Process plug-in. Controlling for age, gender, and only child status, the findings revealed a negative association between physical activity and anxiety, inhibitory control, and IA. Moreover, anxiety were positively correlated with inhibitory control and IA. Additionally, anxiety exhibited a positive association with inhibitory control. Notably, physical activity directly and negatively predicted IA in adolescents, while also indirectly predicting it through anxiety and inhibitory control. This study contributes to a deeper understanding of the mechanisms that underlie the complex effects of physical activity on IA among adolescents.

The relationship between childhood psychological abuse and depression in college students: a moderated mediation model.

BACKGROUND: Childhood psychological abuse (CPA) are highly correlated with depression among college students, but the underlying mechanisms between variables need further exploration. This study aims to investigate internet addiction as a mediating factor and alexithymia as a moderating factor, in order to further elucidate the potential risk factors between CPA and depression among college students. METHODS: A self-report survey was conducted among 1196 college students from four universities in three provinces in China. The survey included measures of CPA, internet addiction, alexithymia, and depression. Descriptive and correlational analyses were performed on these variables, and a moderated mediation model was constructed. RESULTS: CPA was positively correlated with depression among college students, as well as internet addiction with alexithymia. Internet addiction partially mediated the relationship between CPA and depression among college students, while alexithymia strengthened the relationships among the paths in the moderated mediation model. CONCLUSION: This study provides further insights into the psychological mechanisms underlying the relationship between CPA and depression among college students. Internet addiction serves as a mediating factor in this relationship, while alexithymia may enhance the strength of the relationships among the three variables.

A blueprint for tumor-infiltrating B cells across human cancers.

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.

The mediating effect of internet addiction and the moderating effect of physical activity on the relationship between alexithymia and depression.

There is a certain relationship between alexithymia and depression, but further investigation is needed to explore their underlying mechanisms. The aims of this study was to explore the mediating role of internet addiction between alexithymia and depression and the moderating role of physical activity. A total of 594 valid responses were included in the analysis, with a mean age of 18.72 years (SD = 1.09). The sample comprised 250 males (42.09%) and 344 females (57.91%). These responses were utilized for descriptive analysis, correlation analysis, regression analysis, and the development of mediation and moderation models. Alexithymia showed positive correlations with depression and internet addiction, and physical activity was negatively correlated with internet addiction and depression. Internet addiction partially mediated the relationship between alexithymia and depression, while physical activity weakened the association between internet addiction and depression, acting as a moderator. Our findings suggest that excessive Internet engagement may mediate the relationship between alexithymia and depression as an emotional regulatory coping strategy, and that physical activity attenuates the predictive effect of Internet addiction on depression.

Neutrophil profiling illuminates anti-tumor antigen-presenting potency.

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.

Environmental Evaluation on Toxicity, Toxic Mechanism, and Hydrolysis Behavior of Potential Acethydrazide Fungicide Candidates.

The evaluation of toxicity and environmental behavior of bioactive lead molecules is helpful in providing theoretical support for the development of agrochemicals, in line with the sustainable development of the ecological environment. In previous work, some acethydrazide structures have been demonstrated to exhibit excellent and broad-spectrum fungicidal activity; however, its environmental compatibility needs to be further elucidated if it is to be identified as a potential fungicide. In this project, the toxicity of fungicidal acethydrazide lead compounds F51, F58, F72, and F75 to zebrafish was determined at 10 µg mL-1 and 1 µg mL-1. Subsequently, the toxic mechanism of compound F58 was preliminarily explored by histologic section and TEM observations, which revealed that the gallbladder volume of common carp treated with compound F58 increased, accompanied by a deepened bile color, damaged plasma membrane, and atrophied mitochondria in gallbladder cells. Approximately, F58-treated hepatocytes exhibited cytoplasmic heterogeneity, with partial cellular vacuolation and mitochondrial membrane rupture. Metabolomics analysis further indicated that differential metabolites were enriched in the bile formation-associated steroid biosynthesis, primary bile acid biosynthesis, and taurine and hypotaurine metabolism pathways, as well as in the membrane function-related glycerophospholipid metabolism, linolenic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism pathways, suggesting that the acethydrazide F58 may have acute liver toxicity to common carp. Finally, the hydrolysis dynamics of F58 was investigated, with the obtained half-life of 5.82 days. The above results provide important guiding significance for the development of new green fungicides.

Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice.

Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics; however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice. Moreover, several key ferroptosis regulator genes were altered in cisplatin-damaged cochlear explants based on RNA sequencing, implying the induction of ferroptosis. Ferroptosis-related Gpx4 and Fsp1 knockout mice were established to investigate the specific mechanisms associated with ferroptosis in cochleae. Severe outer hair cell loss and progressive damage of synapses in inner hair cells were observed in Atoh1-Gpx4-/- mice. However, Fsp1-/- mice showed no significant hearing phenotype, demonstrating that Gpx4, but not Fsp1, may play an important role in the functional maintenance of HCs. Moreover, findings showed that FDA-approved luteolin could specifically inhibit ferroptosis and alleviate cisplatin-induced ototoxicity through decreased expression of transferrin and intracellular concentration of ferrous ions. This study indicated that ferroptosis inhibition through the reduction of intracellular ferrous ions might be a potential strategy to prevent cisplatin-induced hearing loss.

Discovery of Fungicidal Hydrazide Lead Compounds Derived from Sinapic Acid and Mycophenolic Acid.

Structure optimization based on natural products has become an effective way to develop new green fungicides. In this project, thirty-two novel NPs-derived hydrazide compounds were designed and synthesized by introducing the bioactive hydrazide substructure into sinapic acid and mycophenolic acid. The fungicidal bioassays indicated that the obtained hydrazide compounds showed excellent and selective fungicidal activity against specific pathogens, especially compounds C8, D7, and D8 with EC50 values of 0.63, 0.56, and 0.43 µg mL-1 against M. oryzae, respectively. SAR indicated that the introduction of 4-fluoro, 4-chloro, and 2,4-difluoro groups was conducive to improving the fungicidal activity, while the extension of the hydrazide bridge would affect the selectivity for inhibitory activity. Subsequently, the effects of hydrazide compounds on rice seedling and zebrafish growth were also investigated. The fungicidal mechanism implied that treatment with compound B4 would cause significant changes in metabolites of plasma membrane-related linolenic acid metabolism, arachidonic acid metabolism, and α-linolenic acid metabolism pathways, which further led to the wrinkled hyphae and the blurred plasma membrane and cytoplasm. Finally, the frontier molecular orbitals and charge distribution were calculated to analyze the differences in bioactivity from a structural perspective. These results provide important guidance for the development and practical application of novel fungicides.

Twisted moiré photonic crystal enabled optical vortex generation through bound states in the continuum.

The twisted stacking of two layered crystals has led to the emerging moiré physics as well as intriguing chiral phenomena such as chiral phonon and photon generation. In this work, we identified and theoretically formulated a non-trivial twist-enabled coupling mechanism in twisted bilayer photonic crystal (TBPC), which connects the bound state in the continuum (BIC) mode to the free space through the twist-enabled channel. Moreover, the radiation from TBPC hosts an optical vortex in the far field with both odd and even topological orders. We quantitatively analyzed the twist-enabled coupling between the BIC mode and other non-local modes in the photonic crystals, giving rise to radiation carrying orbital angular momentum. The optical vortex generation is robust against geometric disturbance, making TBPC a promising platform for well-defined vortex generation. As a result, TBPCs not only provide a new approach to manipulating the angular momentum of photons, but may also enable novel applications in integrated optical information processing and optical tweezers. Our work broadens the field of moiré photonics and paves the way toward the novel application of moiré physics.

SARS-CoV-2 Nsp15 suppresses type I interferon production by inhibiting IRF3 phosphorylation and nuclear translocation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes 2019 coronavirus disease (COVID-19), poses a significant threat to global public health security. Like other coronaviruses, SARS-CoV-2 has developed various strategies to inhibit the production of interferon (IFN). Here, we have discovered that SARS-CoV-2 Nsp15 obviously reduces the expression of IFN-ß and IFN-stimulated genes (ISG56, CXCL10), and also inhibits IRF3 phosphorylation and nuclear translocation by antagonizing the RLR-mediated antiviral signaling pathway. Mechanically, we found that the poly-U-specific endonuclease domain (EndoU) of Nsp15 directly associates with the kinase domain (KD) of TBK1 to interfere TBK1 interacting with IRF3 and the flowing TBK1-mediated IRF3 phosphorylation. Furthermore, Nsp15 also prevented nuclear translocation of phosphorylated IRF3 via binding to the nuclear import adaptor karyopherin α1 (KPNA1) and promoting it autophagy-dependent degradation. These findings collectively reveal a novel mechanism by which Nsp15 antagonizes host's innate immune response.

Natural Alkaloid Waltherione F-Derived Hydrazide Compounds Evaluated in an Agricultural Fungicidal Field.

In this project, quinoline and quinolone-containing hydrazide compounds were designed and synthesized by introducing a bioactive hydrazide group into the skeleton of waltherione F. The fungicidal activity revealed that some hydrazide compounds exhibited excellent and broad-spectrum fungicidal activity; especially, compounds E8, E12, and E16 showed more than 90% or even 100% inhibition rates against most pathogens at 50 µg·mL-1. The fungicidal mechanism indicated that compound E8 may affect the normal function of the plasma membrane, further generating changes in the morphology and subcellular structure of mycelia. Simultaneously, Fusarium graminearum may resist the E8-treated stress through the metabolic pathways related to l-glutamate, l-glutamine, and glutathione. Finally, the effect of compound E8 on wheat seedling's growth and the toxicity to zebrafish were accomplished. These results will provide important guidance to discover novel fungicidal lead compounds and explore new targets, which are effective ways to alleviate the increasingly severe drug resistance.

The p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop mediates vasoactive intestinal peptide effects on osteoarthritis chondrocytes.

Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA). Targeting inflammatory pathways is an important therapeutic strategy for OA. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide with potent anti-inflammatory effects; however, its role and mechanism in OA remain unclear. In this study, microarray expression profiling from the Gene Expression Omnibus database and integrative bioinformatics analyses were performed to identify differentially expressed lncRNAs in OA samples. qRT-PCR validation of the top ten different expressed lncRNAs indicated that the expression level of intergenic non-protein coding RNA 2203 (LINC02203, also named LOC727924) was the highest in OA cartilage compared to normal cartilage. Hence, the LOC727924 function was further investigated. LOC727924 was upregulated in OA chondrocytes, with a dominant sub-localization in the cytoplasm. In OA chondrocytes, LOC727924 knockdown boosted cell viability, suppressed cell apoptosis, reactive oxygen species (ROS) accumulation, increased aggrecan and collagen II, decreased matrix metallopeptidase (MMP)-3/13 and ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4/5 levels, and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). LOC727924 could interact with the microRNA 26a (miR-26a)/ karyopherin subunit alpha 3 (KPNA3) axis by competitively targeting miR-26a for KPNA3 binding, therefore down-regulating miR-26a and upregulating KPNA3; in OA chondrocytes, miR-26a inhibition partially abolished LOC727924 knockdown effects on chondrocytes. miR-26a inhibited the nuclear translocation of p65 through targeting KPNA3 and p65 transcriptionally activated LOC727924, forming a p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop to modulate OA chondrocyte phenotypes. In vitro, VIP improved OA chondrocyte proliferation and functions, down-regulated LOC727924, KPNA3, and p65 expression, and upregulated miR-26a expression; in vivo, VIP ameliorated destabilization of the medial meniscus (DMM)-induced damages on the mouse knee joint, down-regulated KPNA3, inhibited the nuclear translocation of p65. In conclusion, the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates OA chondrocyte apoptosis, ROS accumulation, extracellular matrix (ECM) deposition, and inflammatory response in vitro and OA development in vivo, being one of the mechanisms mediating VIP ameliorating OA.

Relevance of PUFA-derived metabolites in seminal plasma to male infertility.

Aim: This study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility. Methods: From September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022. Results: Our analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR < 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744. Conclusion: The PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men.

Single-pixel reconstructive mid-infrared micro-spectrometer.

Miniaturized spectrometers in the mid-infrared (MIR) are critical in developing next-generation portable electronics for advanced sensing and analysis. The bulky gratings or detector/filter arrays in conventional micro-spectrometers set a physical limitation to their miniaturization. In this work, we demonstrate a single-pixel MIR micro-spectrometer that reconstructs the sample transmission spectrum by a spectrally dispersed light source instead of spatially grated light beams. The spectrally tunable MIR light source is realized based on the thermal emissivity engineered via the metal-insulator phase transition of vanadium dioxide (VO2). We validate the performance by showing that the transmission spectrum of a magnesium fluoride (MgF2) sample can be computationally reconstructed from sensor responses at varied light source temperatures. With potentially minimum footprint due to the array-free design, our work opens the possibility where compact MIR spectrometers are integrated into portable electronic systems for versatile applications.

A Comprehensive Investigation of Hydrazide and Its Derived Structures in the Agricultural Fungicidal Field.

Hydrazides are present in many bioactive molecules and exhibit a variety of biological activities, such as insecticidal, herbicidal, antifungal, antitumor, and antiviral effects. In this Review, we review the application of hydrazide and its derived structures in the agricultural fungicidal field, including monohydrazides, diacylhydrazines, hydrazide-hydrazones, and sulfonyl hydrazides. In addition, the antifungal mechanism of action of the hydrazide derivatives was analyzed and summarized, mainly involving succinate dehydrogenase inhibitors, laccase inhibitors, and targeting plasma membranes. Finally, based on the structural analysis of the novel fungicidal lead compounds, the structure-activity relationship of the hydrazide derivatives was constructed and the development trend of hydrazide structures in fungicidal applications was prospected. It is hoped that this Review can provide some significant guidance for the development of new hydrazide fungicides in the future.

Dosimetric properties of PASSAG polymer gel dosimeter in electron beam radiotherapy using magnetic resonance imaging.

BACKGROUND: Several physical factors such as photon beam energy, electron beam energy, and dose rate may affect the dosimetric properties of polymer gel dosimeters. The photon beam energy and dose rate dependence of PASSAG gel dosimeter were previously evaluated. OBJECTIVE: This study aims to assess the dosimetric properties of the optimized PASSAG gel samples in various electron beam energies. METHODS: The optimized PASSAG gel samples are first fabricated and irradiated to various electron energies (5, 7, 10 and 12 MeV). Then, the response (R2) and sensitivity of gel samples are analyzed by magnetic resonance imaging technique at a dose range of 0 to 10 Gy, scanning room temperature range of 15 to 22 °C, and post-irradiation time range of 1 to 30 days. RESULTS: The R2-dose response and sensitivity of gel samples do not change under the evaluated electron beam energies (the differences are less than 5%). Furthermore, a dose resolution range of 11 to 38 cGy is obtained for the gel samples irradiated to different electron beam energies. Moreover, the findings show that the R2-dose response and sensitivity dependence of gel samples on electron beam energy varies over different scanning room temperatures and post-irradiation times. CONCLUSION: The dosimetric assessment of the optimized PASSAG gel samples provides the promising data for this dosimeter during electron beam radiotherapy.

Neutrophils promote tumor invasion via FAM3C-mediated epithelial-to-mesenchymal transition in gastric cancer.

In gastric cancer, lymph node metastasis (LNM) is the major metastasis route, and lymphatic invasion is the precursor of LNM. Tumor-associated neutrophils (TANs) promote LNM. However, the molecular mechanisms underlying TANs-mediated lymphatic invasion and/or LNM remain unclear. Herein, we revealed that high level of TANs was the independent risk factor for lymphatic invasion and LNM respectively, and lymphatic tumor cell-neutrophil clusters were positively correlated with LNM. Crosstalk between neutrophils and tumor cells was required for enhanced tumor cell invasiveness, endowing neutrophils to boost epithelial-to-mesenchymal transition (EMT) of tumor cells and in turn promoting LNM. Mechanically, tumor cells educated neutrophils via TGFß1 to produce more FAM3C through Smad2/3 signaling activation, and FAM3C promoted tumor cell EMT through JNK-ZEB1/Snail signaling pathway. The crosstalk enhanced the affinity of neutrophils with tumor cells through interaction of integrins α6ß1 and α6ß4 with CD151. Furthermore, studies using tumor-bearing mice demonstrated that neutrophils were the important driver for gastric cancer tumorigenesis and invasiveness. The study clearly identifies the functional roles of TANs in promoting tumor invasion, and facilitates a better understanding of novel mechanisms responsible for LNM of gastric cancer, which provides potential targets for developing new strategies to prevent or treat LNM in gastric cancer.

Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy.

Advances in antibody engineering have led to the generation of more innovative antibody drugs, such as bispecific antibodies (bsAbs). Following the success associated with blinatumomab, bsAbs have attracted enormous interest in the field of cancer immunotherapy. By specifically targeting two different antigens, bsAbs reduce the distance between tumor and immune cells, thereby enhancing tumor killing directly. There are several mechanisms of action upon which bsAbs have been exploited. Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bsAbs targeting immunomodulatory checkpoints. Cadonilimab (PD-1 × CTLA-4) is the first approved bsAb targeting dual inhibitory checkpoints, which confirms the feasibility of bsAbs in immunotherapy. In this review we analyzed the mechanisms by which bsAbs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.

Influences of point defects on electron transport of two-dimensional gep semiconductor device.

The quantum transport properties of defective two-dimensional (2D) GeP semiconductor nanodevice consisting of typical point defects, such as antisite defect, substitutional defect, and Schottky defect, have been studied by using density functional theory combined with non-equilibrium Green's function calculation. The antisite defect has indistinctive influences on electron transport. However, both substitutional and Schottky defect have introduced promising defect state at the Fermi level, indicating the possibility of improvement on the carrier transport. Our quantitative quantum transport calculations ofI-Vbbehavior have revealed that the electrical characters are enhanced. Moreover, the P atom vacancy could induce significant negative differential resistance phenomenon, and the physical mechanism is unveiled by detailed analysis. The transfer characteristic properties could be prominently improved by substitutional defect and vacancy defect. Most importantly, we have proposed a computational design of GeP-based electronic device with improved electrical performance by introducing vacancy defect. Our findings could be helpful to the practical application of novel 2D GeP semiconductor nanodevice in future.