Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling.

Cadmium (Cd) is a ubiquitous toxic metal and environmental pollutant. Increasing studies have shown that Cd exposure increases the incidence of various endocrine system diseases, including thyrotoxicity reflected by thyroid structural damage and endocrine toxicity. However, the observed outcomes are complex and conflicting, leading to the mechanism of Cd-induced thyrotoxicity remaining obscure. In this study, 4-week-old male C57BL/6 mice were given 2 or 7 mg/kg Cadmium Chloride (CdCl2) intragastrically for 4 and 8 weeks, and the Cd-mediated thyrotoxicity was evaluated by determining alterations in thyroid structure and endocrine function, and alterations of oxidant stress, apoptosis, and pyroptosis. Our data showed that Cd exposure could reduce body weight and induce thyrotoxicity by impairing thyroid follicular morphology and endocrine function, accompanied by elevated oxidative stress and apoptosis, macrophage infiltration, and inflammatory cytokine secretion. Importantly, Cd significantly promoted thyroid follicular cell pyroptosis by increasing Nlrp3, Asc, Caspase-1, Gsdmd, IL-1ß, and IL-18 expression. Mechanistical analysis suggested that Cd treatment could inhibit antioxidant pathway by downregulating antioxidant response protein, Nrf2, and upregulating its negative feedback regulator, Keap1. Collectively, our in vivo findings suggest that Cd exposure could facilitate thyroid follicular cell pyroptosis by inhibiting Nrf2/Keap1 signaling, thereby disrupting thyroid tissue structure and endocrine function, which offers novel insights into the Cd-mediated detrimental consequences on thyroid homeostasis.

Evaluation of the Antimicrobial Properties of a Natural Peptide from Vespa mandarinia Venom and Its Synthetic Analogues as a Possible Route to Defeat Drug-Resistant Microbes.

Antimicrobial peptides (AMPs) from wasp venom have a good track record and potential for drug development as tools against development of antimicrobial resistance. Herein, the biological function and activity profile of peptide VM, which was discovered in the venom of the wasp, Vespamandarinia, and several of its third-position substituted analogues, were investigated. VM had potent antimicrobial activity against Gram-positive bacteria and biofilm, and all modified peptides achieved the significant enhancement of these capacities. The various physicochemical properties of amino acids substituted in analogues, generated the different mechanisms of action of bacterial membrane disruption. VM-3K showed a maximum 8-fold enhancement of antibacterial activity against Gram-positive bacteria and also presented microbicidal properties against Gram-negative bacteria and fungi. This peptide also exhibited a high killing efficiency at low concentration and had a comparable selectivity index to VM. Furthermore, VM-3K produced a 90% survival of S. aureus-infected waxworms at a concentration of 5.656 mg/kg, at which concentration the natural template peptide only achieved 50% survival. This peptide also lacked short-term resistance generation. Thus, peptide VM-3K could be a promising broad-spectrum antimicrobial candidate for addressing the current antibiotic-resistant infection crisis. It is worth mentioning that this investigation on the relationship between peptide structure and mechanism of action could become an important aspect of drug research on short peptides.

Postrecording Pixel-Reconstruction Approach for Correcting the Lateral Drifts in Surface Plasmon Resonance Microscope.

Surface plasmon resonance microscope (SPRM) sample stage inevitably suffers from lateral drifts as a result of many environmental factors including thermal fluctuation, mechanical vibration, and relaxation. It places great obstacles to time-lapsed imaging and measurements that need high spatial resolution or long recording time. Existing solutions often require experimental efforts such as the addition of optical markers together with piezoelectric stage-based active feedback configurations. Herein, we propose an all-digital, postrecording image-processing method to remove the lateral drift in a series of time-lapsed SPRM images. The method first calculates the value of lateral drift at subpixel accuracy by combining image cross-correlation analysis and superlocalization strategy. It subsequently reconstructed the drift-free image sequences in a pixel-by-pixel and frame-by-frame manner, according to the linear decomposition and reconstruction principle. This method purely relies on image processing, and it does not require any experimental efforts or hardware. In addition to SPRM, we further demonstrated the applicability of the present method in other types of optical imaging techniques including bright-field transmission microscope and dark-field scattering microscope.

[Isolation,screening and identification of endophytic fungi and detection of its antifungal effects against Alternaria panax].

To obtain biocontrol fungus for Alternaria panax,the antifungal effects of one strain of endophytic fungi isolated from leaves of healthy ginseng were screened and evaluated by using dual-culture method,and the taxonomic assignment of the screened strain was identified based on the morphological characters and ITS sequence analysis. The results of dual-culture showed that one of the endophytes marked as FS-01 had good antifungal effects and the inhibitory rates of FS-01 strain to A. panax was( 60. 21±0. 12) %.The hyphae junction of the both strains,A. panax dissolved,broke and winded,while the hyphae of FS-01 strain remained normal. The inhibitory rates of non-sterilized FS-01 strain fermentation liqud was( 13. 94±0. 21) %. Strain FS-01 identified as Chaetomium globosum.

Identification of new centrosome proteins by autoimmune patient sera.

Compared to other subcellular organelles, centrosome proteome can hardly be studied, due to the difficulties in separation and purification of centrosome. Auto-antisera from 6 autoimmune patients, which recognized centrosome specifically in immunofluorescence, were used to identify the corresponding centrosomal proteins. The sera were first tested by Western blot on whole cell lysate, and all bound antibodies were then eluted from each single band in Western blot membrane to assure which antibody was responsible for the centrosome specific immunofluorescence staining. The corresponding proteins were obtained by immunoprecipitation and identified by mass spectrometry. Six centrosomal proteins, including 2 known centrosomal proteins and 4 proteins with unknown localization or reportedly non-centrosomal localization, were identified. These proteins apparently involve in cell cycle regulation, signal transduction pathways, molecular chaperons, and metabolism enzymes, which may reflect the expected functional diversity of centrosome.

Multigate single-photon detection and timing discrimination with an InGaAs/lnP avalanche photodiode.

Multigate detection of single photons at 1550 nm is achieved by using capacitor-balanced InGaAs/InP avalanche photodiodes, with which we experimentally demonstrate the efficient discrimination of single-photon timing by counting single-photon clicks and the corresponding afterpulses within the multiple gates. Results show that the technique of multigate detection is a practical method for the single-photon timing information process.