Substrate recruitment via eIF2γ enhances catalytic efficiency of a holophosphatase that terminates the integrated stress response.

Dephosphorylation of pSer51 of the α subunit of translation initiation factor 2 (eIF2αP) terminates signaling in the integrated stress response (ISR). A trimeric mammalian holophosphatase comprised of a protein phosphatase 1 (PP1) catalytic subunit, the conserved C-terminally located ~70 amino acid core of a substrate-specific regulatory subunit (PPP1R15A/GADD34 or PPP1R15B/CReP) and G-actin (an essential cofactor) efficiently dephosphorylate eIF2αP in vitro. Unlike their viral or invertebrate counterparts, with whom they share the conserved 70 residue core, the mammalian PPP1R15s are large proteins of more than 600 residues. Genetic and cellular observations point to a functional role for regions outside the conserved core of mammalian PPP1R15A in dephosphorylating its natural substrate, the eIF2 trimer. We have combined deep learning technology, all-atom molecular dynamics simulations, X-ray crystallography, and biochemistry to uncover binding of the γ subunit of eIF2 to a short helical peptide repeated four times in the functionally important N terminus of human PPP1R15A that extends past its conserved core. Binding entails insertion of Phe and Trp residues that project from one face of an α-helix formed by the conserved repeats of PPP1R15A into a hydrophobic groove exposed on the surface of eIF2γ in the eIF2 trimer. Replacing these conserved Phe and Trp residues with Ala compromises PPP1R15A function in cells and in vitro. These findings suggest mechanisms by which contacts between a distant subunit of eIF2 and elements of PPP1R15A distant to the holophosphatase active site contribute to dephosphorylation of eIF2αP by the core PPP1R15 holophosphatase and to efficient termination of the ISR in mammals.

EGF-driven EGFR/miR-27b-3p/FOXO1 promotes rat FSH synthesis and secretion.

The adenopituitary secretes follicle-stimulating hormone (FSH), which plays a crucial role in regulating the growth, development, and reproductive functions of organisms. Investigating the process of FSH synthesis and secretion can offer valuable insights into potential areas of focus for reproductive research. Epidermal growth factor (EGF) is a significant paracrine/autocrine factor within the body, and studies have demonstrated its ability to stimulate FSH secretion in animals. However, the precise mechanisms that regulate this action are still poorly understood. In this research, in vivo and in vitro experiments showed that the activation of epidermal growth factor receptor (EGFR) by EGF induces the upregulation of miR-27b-3p and that miR-27b-3p targets and inhibits Foxo1 mRNA expression, resulting in increased FSH synthesis and secretion. In summary, this study elucidates the precise molecular mechanism through which EGF governs the synthesis and secretion of FSH via the EGFR/miR-27b-3p/FOXO1 pathway.

GnRH-driven FTO-mediated RNA m6A modification promotes gonadotropin synthesis and secretion.

BACKGROUND: Gonadotropin precisely controls mammalian reproductive activities. Systematic analysis of the mechanisms by which epigenetic modifications regulate the synthesis and secretion of gonadotropin can be useful for more precise regulation of the animal reproductive process. Previous studies have identified many differential m6A modifications in the GnRH-treated adenohypophysis. However, the molecular mechanism by which m6A modification regulates gonadotropin synthesis and secretion remains unclear. RESULTS: Herein, it was found that GnRH can promote gonadotropin synthesis and secretion by promoting the expression of FTO. Highly expressed FTO binds to Foxp2 mRNA in the nucleus, exerting a demethylation function and reducing m6A modification. After Foxp2 mRNA exits the nucleus, the lack of m6A modification prevents YTHDF3 from binding to it, resulting in increased stability and upregulation of Foxp2 mRNA expression, which activates the cAMP/PKA signaling pathway to promote gonadotropin synthesis and secretion. CONCLUSIONS: Overall, the study reveals the molecular mechanism of GnRH regulating the gonadotropin synthesis and secretion through FTO-mediated m6A modification. The results of this study allow systematic interpretation of the regulatory mechanism of gonadotropin synthesis and secretion in the pituitary at the epigenetic level and provide a theoretical basis for the application of reproductive hormones in the regulation of animal artificial reproduction.

Probing Oxidation Mechanisms in Plasmonic Catalysis: Unraveling the Role of Reactive Oxygen Species.

Plasmon-induced oxidation has conventionally been attributed to the transfer of plasmonic hot holes. However, this theoretical framework encounters challenges in elucidating the latest experimental findings, such as enhanced catalytic efficiency under uncoupled irradiation conditions and superior oxidizability of silver nanoparticles. Herein, we employ liquid surface-enhanced Raman spectroscopy (SERS) as a real-time and in situ tool to explore the oxidation mechanisms in plasmonic catalysis, taking the decarboxylation of p-mercaptobenzoic acid (PMBA) as a case study. Our findings suggest that the plasmon-induced oxidation is driven by reactive oxygen species (ROS) rather than hot holes, holding true for both the Au and Ag nanoparticles. Subsequent investigations suggest that plasmon-induced ROS may arise from hot carriers or energy transfer mechanisms, exhibiting selectivity under different experimental conditions. The observations were substantiated by investigating the cleavage of the carbon-boron bonds. Furthermore, the underlying mechanisms were clarified by energy level theories, advancing our understanding of plasmonic catalysis.

Reversibly Reactive Affinity Selection-Mass Spectrometry Enables Identification of Covalent Peptide Binders.

Covalent peptide binders have found applications as activity-based probes and as irreversible therapeutic inhibitors. Currently, there is no rapid, label-free, and tunable affinity selection platform to enrich covalent reactive peptide binders from synthetic libraries. We address this challenge by developing a reversibly reactive affinity selection platform termed ReAct-ASMS enabled by tandem high-resolution mass spectrometry (MS/MS) to identify covalent peptide binders to native protein targets. It uses mixed disulfide-containing peptides to build reversible peptide-protein conjugates that can enrich for covalent variants, which can be sequenced by MS/MS after reduction. Using this platform, we identified covalent peptide binders against two oncoproteins, human papillomavirus 16 early protein 6 (HPV16 E6) and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 protein (Pin1). The resulting peptide binders efficiently and selectively cross-link Cys58 of E6 at 37 °C and Cys113 of Pin1 at room temperature, respectively. ReAct-ASMS enables the identification of highly selective covalent peptide binders for diverse molecular targets, introducing an applicable platform to assist preclinical therapeutic development pipelines.

Development and characterization of discontinuous atmospheric pressure interface - Dual pressure chamber miniature mass spectrometer.

Miniaturized mass spectrometers have become increasingly prevalent for real-time detection and analysis, owing to their compact size and portability. The pursuit of performance enhancement in these instruments is a pivotal objective within the domain of mass spectrometry miniaturization. This study introduces a novel miniature mass spectrometer featuring a discontinuous atmospheric pressure interface and a dual pressure chamber. Compared to conventional single-chamber, discontinuous sampling interface mass spectrometers, the newly developed instrument demonstrates a more than tenfold improvement in detection efficiency. This significant enhancement is achieved without the need for complex control of switch coupling time series, thereby streamlining the circuit design and improving the instrument's fault tolerance. Furthermore, by capitalizing on the benefits of discontinuous sampling, the instrument reduces the operational pressure relative to traditional continuous sampling in differential pressure vacuum chambers. It accommodates larger inlet capillary (0.38 mm) and skimmer (0.5 mm) diameters, leading to a ninefold increase in response strength for risperidone and lowering the detection limit to 0.5 ppb. The instrument's capacity for rapid drug detection, along with enhanced resolution and detection limits, underscores its potential utility. Additionally, it facilitates the use of smaller mechanical pumps, significantly diminishing both the instrument's volume and power consumption. This presents a promising avenue for further miniaturization of mass spectrometers.

Three Polyoxometalate-Based Ag-Organic Compounds as Heterogeneous Catalysts for the Synthesis of Benzimidazoles.

Three new POM-based compounds, with formulae [Na0.63Ag3(Htba)2.37(tba)0.63(H2O)2(PMo12O40)]·4H2O (Ag3PMo), [Ag4(Htba)4(H2O)2(PMo12O40)](NO3)·H2O (Ag4PMo), and [Ag3(Htba)2(tba)(PW12O40)0.5](NO3)0.5·13H2O (Ag3PW), were prepared with a 3-(4H-1,2,4-triazol-4-yl)benzoic acid (Htba) ligand, Keggin-type anions ([PMo12O40]3-/[PW12O40]3-), and a silver ion (Ag+). The structural features of these compounds are particularly different from the multinuclear subunits, which are [Ag3(tba)3] clusters in Ag3PMo, [Ag4(tba)3] chains in Ag4PMo, and [Ag3(tba)3]2 clusters in Ag3PW, connected by multidonor atom tba ligands and Ag+ ions. Meanwhile, in these compounds, polyanions act as polydentate ligands to link adjacent Ag-tba metal-organic units and expand their spatial dimensions. These compounds, as heterogeneous catalysts, exhibit high stability and excellent catalytic activity to construct benzimidazoles. Ag3PMo could efficiently catalyze the condensation of benzene-1,2-diamines and benzaldehydes and produce benzimidazoles in good yields. In addition, Ag3PMo could be reused up to 7 times and was suitable for gram-scale reactions.

Activation of autophagy promotes the inhibitory effect of curcumin analog EF-24 against MDA-MB-231 cancer cells.

Breast cancer is the leading cause of cancer deaths in women worldwide. EF-24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF-24 against one breast cancer cell line, MDA-MB-231, and its anti-migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF-24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF-24 also induced mitochondrial apoptosis in MDA-MB-231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3-MA could reduce the cleavage of PARP protein and protect cells from EF-24-induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF-24 in MDA-MB-231 cells, which suggest that EF-24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF-24 in breast cancer cells. Moreover, removal of EF-24-activated ROS with NAC significantly reversed migration ability of MDA-MB-231 cells, indicating that EF-24 exerted an inhibitory effect through a ROS-mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.

Alloy Engineering Allows On-Demand Design of Ultrasensitive Monolayer Semiconductor SERS Substrates.

The chemical mechanism (CM) of surface-enhanced Raman scattering (SERS) has been recognized as a decent approach to mildly amplify Raman scattering. However, the insufficient charge transfer (CT) between the SERS substrate and molecules always results in unsatisfying Raman enhancement, exerting a substantial restriction for CM-based SERS. In principle, CT is dominated by the coupling between the energy levels of a semiconductor-molecule system and the laser wavelength, whereas precise tuning of the energy levels is intrinsically difficult. Herein, two-dimensional transition-metal dichalcogenide alloys, whose energy levels can be precisely and continuously tuned over a wide range by simply adjusting their compositions, are investigated. The alloys enable on-demand construction of the CT resonance channels to cater to the requirements of a specific target molecule in SERS. The SERS signals are highly reproducible, and a clear view of the SERS dependences on the energy levels is revealed for different CT resonance terms.

Single-Cell Transcriptional Profile Construction of Rat Pituitary Glands before and after Sexual Maturation and Identification of Novel Marker Spp1 in Gonadotropes.

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.

Neighbouring Synergy in High-Density Single Ir Atoms on CoGaOOH for Efficient Alkaline Electrocatalytic Oxygen Evolution.

The catalytic performance of single-atom catalysts was strictly limited by isolated single-atom sites. Fabricating high-density single atoms to realize the synergetic interaction in neighbouring single atoms could optimize the adsorption behaviors of reaction intermediates, which exhibited great potential to break performance limitations and deepen mechanistic understanding of electrocatalysis. However, the catalytic behavior governed by neighbouring single atoms is particularly elusive and has yet to be understood. Herein, we revealed that the synergetic interaction in neighbouring single atoms contributes to superior performance for oxygen evolution relative to isolated Ir single atoms. Neighbouring single atoms was achieved by fabricating high-density single atoms to narrow the distance between single atoms. Electrochemical measurements demonstrated that the Nei-Ir1/CoGaOOH with neighbouring Ir single atoms exhibited a low overpotential of 170 mV at a current density of 10 mA cm-2, and long-durable stability over 2000 h for oxygen evolution. Mechanistic studies revealed that neighbouring single atoms synergetic stabilized the *OOH intermediates via extra hydrogen bonding interactions, thus significantly reducing the reaction energy barriers, as compared to isolated Ir single atoms. The discovery of the synergetic interaction in neighbouring single atoms could offer guidance for the development of efficient electrocatalysts, thus accelerating the world's transition to sustainable energy.

Gram-level NH3 Electrosynthesis via NOx reduction on a Cu Activated Co Electrode.

Ambient electrochemical ammonia (NH3 ) synthesis is one promising alternative to the energy-intensive Haber-Bosch route. However, the industrial requirement for the electrochemical NH3 production with amperes current densities or gram-level NH3 yield remains a grand challenge. Herein, we report the high-rate NH3 production via NO2 - reduction using the Cu activated Co electrode in a bipolar membrane (BPM) assemble electrolyser, wherein BPM maintains the ion balance and the liquid level of electrolyte. Benefited from the abundant Co sites and optimal structure, the target modified Co foam electrode delivers a current density of 2.64 A cm-2 with the Faradaic efficiency of 96.45 % and the high NH3 yield rate of 279.44 mg h-1 cm-2 in H-type cell using alkaline electrolyte. Combined with in situ experiments and theoretical calculations, we found that Cu optimizes the adsorption behavior of NO2 - and facilitates the hydrogenation steps on Co sites toward a rapid NO2 - reduction process. Importantly, this activated Co electrode affords a large NH3 production up to 4.11 g h-1 in a homemade reactor, highlighting its large-scale practical feasibility.

Comprehensive analysis of differences in N6-methyladenosine RNA methylomes in the rat adenohypophysis after GnRH treatment.

N6-methyladenosine is considered to be the most common and abundant internal chemical modification among the more than 150 identified chemical RNA modifications. It is involved in most biological processes and actively participates in the regulation of animal reproduction. However, the potential function of m6 A in the pituitaries of mammals is not yet clear. It is also unknown whether m6 A is involved in the secretion and regulation of FSH by GnRH, which in turn affects mammalian reproduction. In this study, rats were treated with gonadorelin to simulate physiological GnRH-mediated regulation of FSH synthesis and secretion, and m6 A-seq was used to analyze the differential m6 A modification of the rat pituitary after gonadorelin treatment. A whole-transcriptome map of m6 A in the rat pituitary gland before and after gonadorelin treatment was successfully created. A total of 6413 differential peaks were identified, of which 3764 m6 A peaks were upregulated and 2649 m6 A peaks were downregulated. Among the 709 differentially expressed genes, 250 genes were discovered with differential methylation modifications. Intriguingly, the altered m6 A peaks within mRNAs were enriched in steroid biosynthetic processes and responses to cAMP. The results of the study will lay a foundation for further exploration of the potential role of m6 A modification in the regulation of reproductive hormone secretion and provide a theoretical basis for the application of GnRH analogs in mammalian artificial reproduction.

Long-term effects of natalizumab on MRI activity and clinical outcomes in Japanese patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is the most common phenotype of multiple sclerosis (MS), and its active stage is characterized by active T2 lesions with or without gadolinium (Gd) enhancement on magnetic resonance imaging (MRI). Natalizumab is indicated as monotherapy in adults with active RRMS in Japan. The main objective of this study was to investigate the long-term effect of natalizumab on disease progression in Japanese patients with RRMS using MRI data. METHODS: This retrospective, chart review study was conducted at a single center in Japan. The main study outcome was the yearly proportion of patients with active T2-weighted image lesions detected with or without Gd enhancement on brain MRI (incidence rate) after treatment initiation for up to 5 years. Additional endpoints included annual relapse rate (ARR) and expanded disability status scale (EDSS) score. RESULTS: This study included data from 85 patients with RRMS who had received natalizumab for ≥ 1 year; of these, 65 (76.5%) were female and the mean ± standard deviation (SD) age at baseline was 37.5 ± 10.0 years. The incidence rate of active T2 lesions was 52.9% (45/85) in the year prior to natalizumab treatment (Year - 1), which decreased to 2.4% and 1.6% in Year 0.5-1.5 and Year 1.5-2.5, respectively. No active T2 lesions were detected in Year 2.5-5.5 in patients who continued natalizumab treatment. EDSS score was stable, improved, and worsened in 61.8%, 26.3%, and 11.8% of patients, respectively. The median (range) EDSS score was 2.0 (0.0-7.0) at baseline (n = 85) and remained within a similar range (median score between 1.0 and 2.25 during Years 1-5). ARR decreased from 1.12 relapses per year at baseline to 0.12 relapses per year during Year 1 and remained below 0.15 relapses per year up to Year 5. CONCLUSION: The results of this first long-term study evaluating the effect of natalizumab on MRI activity and clinical outcomes in Japanese patients with RRMS suggest that natalizumab markedly reduced disease activity and maintained effectiveness over several years.

MRI-based volume measurement methods for staging primary lower extremity lymphedema: a single-center study of asymmetric volume difference-a diagnostic study.

BACKGROUND: Lower extremity lymphedema (LEL) staging is mainly assessed by systems that solely depend on physical examinations and lack quantitative assessment based on modern imaging. OBJECTIVE: To explore the value of MRI-based asymmetric volume measurements in the clinical staging of primary LEL. METHODS: 92 patients with unilateral primary LEL underwent MRI examinations to determine the volume of the mid-calf (Vcl) calculated using the clinical dermatome method as well as the total volume (Vmri), musculoskeletal volume (VM), and subcutaneous volume (VS) volume of the middle calves. The difference between Vmri (DVmri) and VS (DVS) of the affected and unaffected calves was obtained and defined as the asymmetric volume difference. Meanwhile, the volume of the mid-calf (Vcl) and the difference in volume (DVcl) were calculated using the clinical circumferential method. The relationship between the asymmetric volume difference and clinical staging was then evaluated. Interobserver consistency was assessed through the intraclass correlation coefficient (ICC). Volume comparisons between the three groups were performed using the one-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Spearman's correlation was used to assess volume and clinical stage correlation. The receiver operating characteristic (ROC) curve was used to evaluate the value of asymmetric volume difference for clinical staging. RESULTS: The asymmetric volume difference was statistically significant in stage I compared to stages II and III (p < 0.05). The asymmetric volume difference (DVmri: r = 0.753; DVS: r = 0.759) correlated more with the clinical stage than the affected Vcl (r = 0.581), Vmri (r = 0.628), VS (r = 0.743), and DVcl (r = 0.718). The area under the ROC curve (AUC) for identifying the clinical stage by the asymmetric volume difference was greater than that for the affected Vcl, Vmri, VS, and DVcl, with DVS (AUC = 0.951) having the largest area under the curve to distinguish between stages I and II. CONCLUSION: MRI-based asymmetric volume difference is an adjunctive measure for LEL clinical staging with good reproducibility. DVS could be the best indicator for differentiating between stages I and II of primary LEL.

Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila.

Apoptosis is executed by a cascade of caspase activation. The autocatalytic activation of an initiator caspase, exemplified by caspase-9 in mammals or its ortholog, Dronc, in fruit flies, is facilitated by a multimeric adaptor complex known as the apoptosome. The underlying mechanism by which caspase-9 or Dronc is activated by the apoptosome remains unknown. Here we report the electron cryomicroscopic (cryo-EM) structure of the intact apoptosome from Drosophila melanogaster at 4.0 Å resolution. Analysis of the Drosophila apoptosome, which comprises 16 molecules of the Dark protein (Apaf-1 ortholog), reveals molecular determinants that support the assembly of the 2.5-MDa complex. In the absence of dATP or ATP, Dronc zymogen potently induces formation of the Dark apoptosome, within which Dronc is efficiently activated. At 4.1 Å resolution, the cryo-EM structure of the Dark apoptosome bound to the caspase recruitment domain (CARD) of Dronc (Dronc-CARD) reveals two stacked rings of Dronc-CARD that are sandwiched between two octameric rings of the Dark protein. The specific interactions between Dronc-CARD and both the CARD and the WD40 repeats of a nearby Dark protomer are indispensable for Dronc activation. These findings reveal important mechanistic insights into the activation of initiator caspase by the apoptosome.

Integrative Proteomics and Phosphoproteomics Analysis of the Rat Adenohypophysis after GnRH Treatment.

The regulation of mammalian reproductive activity is tightly dependent on the HPG axis crosstalk, in which several reproductive hormones play important roles. Among them, the physiological functions of gonadotropins are gradually being uncovered. However, the mechanisms by which GnRH regulates FSH synthesis and secretion still need to be more extensively and deeply explored. With the gradual completion of the human genome project, proteomes have become extremely important in the fields of human disease and biological process research. To explore the changes of protein and protein phosphorylation modifications in the adenohypophysis after GnRH stimulation, proteomics and phosphoproteomics analyses of rat adenohypophysis after GnRH treatment were performed by using TMT markers, HPLC classification, LC/MS, and bioinformatics analysis in this study. A total of 6762 proteins and 15,379 phosphorylation sites contained quantitative information. Twenty-eight upregulated proteins and fifty-three downregulated proteins were obtained in the rat adenohypophysis after GnRH treatment. The 323 upregulated phosphorylation sites and 677 downregulated phosphorylation sites found in the phosphoproteomics implied that a large number of phosphorylation modifications were regulated by GnRH and were involved in FSH synthesis and secretion. These data constitute a protein-protein phosphorylation map in the regulatory mechanism of "GnRH-FSH," which provides a basis for future studies on the complex molecular mechanisms of FSH synthesis and secretion. The results will be helpful for understanding the role of GnRH in the development and reproduction regulated by the pituitary proteome in mammals.

Allicin Alleviated LPS-Induced Mastitis via the TLR4/NF-κB Signaling Pathway in Bovine Mammary Epithelial Cells.

Dairy farming is the most important economic activity in animal husbandry. Mastitis is the most common disease in dairy cattle and has a significant impact on milk quality and yield. The natural extract allicin, which is the main active ingredient of the sulfur-containing organic compounds in garlic, has anti-inflammatory, anticancer, antioxidant, and antibacterial properties; however, the specific mechanism underlying its effect on mastitis in dairy cows needs to be determined. Therefore, in this study, whether allicin can reduce lipopolysaccharide (LPS)-induced inflammation in the mammary epithelium of dairy cows was investigated. A cellular model of mammary inflammation was established by pretreating bovine mammary epithelial cells (MAC-T) with 10 µg/mL LPS, and the cultures were then treated with varying concentrations of allicin (0, 1, 2.5, 5, and 7.5 µM) added to the culture medium. MAC-T cells were examined using RT-qPCR and Western blotting to determine the effect of allicin. Subsequently, the level of phosphorylated nuclear factor kappa-B (NF-κB) was measured to further explore the mechanism underlying the effect of allicin on bovine mammary epithelial cell inflammation. Treatment with 2.5 µM allicin considerably decreased the LPS-induced increase in the levels of the inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in cow mammary epithelial cells. Further research revealed that allicin also inhibited the phosphorylation of inhibitors of nuclear factor kappa-B-α (IκB-α) and NF-κB p65. In mice, LPS-induced mastitis was also ameliorated by allicin. Therefore, we hypothesize that allicin alleviated LPS-induced inflammation in the mammary epithelial cells of cows probably by affecting the TLR4/NF-κB signaling pathway. Allicin will likely become an alternative to antibiotics for the treatment of mastitis in cows.

[Preclinical Image Quality Evaluation of Simultaneous Vision Intraocular Lenses].

Three different preclinical evaluation methods of MTF through-frequency response, MTF through-focus-response and expected visual acuity were used to compare and analyze the imaging differences of IOLs with four different optical designs. The research work could be used in the simultaneous vision IOLs in the optical design stage and verify the optical quality of the IOLs, the results can predict the visual representation of the patients better. The evaluation results can provide reference for IOL manufacturers and users in product design, development, validation and application selection.

Verification and Analysis of Single-Molecule SERS Events via Polarization-Selective Raman Measurement.

We propose polarization-selective Raman measurement as a decent method for single-molecule surface-enhanced Raman scattering (SMSERS) verification. This approach features rapid acquisition of SMSERS events and appeals liberal requirements for analyte concentration. It is demonstrated as an efficient tool in sorting out dozens of SMSERS events from a large-scale plasmonic dimer array. In addition, it allows identification of a mixed SMSERS event containing two different individual molecules. In this article, the RPM method is employed to explore the underlying mechanisms of signal blinking, spectral wandering, and other unique characteristics in SMSERS. We observed synchronized blinking of different modes from one Rhodamine 6G (R6G) molecule, but a disagreement is found in a mixed SMSERS event containing one R6G molecule and one crystal violet molecule. Our approach offers a reliable means to interpret SMSERS events in statistical terms and facilitate the fundamental understanding of SMSERS.