The high-throughput approach of our method further allowed us to determine the robustness of four types of tristable responses that originate from the relative locations of four bifurcation points. Using the method, we also analyzed the role of additional mutual inhibition loops in stabilizing the mixed state.Neonicotinoids are the most widely used insecticides in modern agriculture, and their residues have been found in the environment and food. Previous studies reported that neonicotinoids exert toxic effects in various tissues, but whether they interfered with the female reproductive process remains unknown. In our present research, thiamethoxam was selected as a representative neonicotinoid to establish a mouse toxicity model with gavage. We found that thiamethoxam decreased the ovarian coefficient and disrupted the expression of female hormone receptors, subsequently affecting follicle development. Ovarian granulosa cells from the thiamethoxam exposure group underwent a high level of apoptosis. Using transcriptome analysis, we showed that thiamethoxam exposure altered the expression of multiple oocyte genes related to inflammation, apoptosis, and endoplasmic reticulum stress. Thiamethoxam also adversely affected oocyte and embryo development. Western blotting and fluorescence staining results confirmed that thiamethoxam affected the integrity of DNA, triggered apoptosis, promoted oxidative stress and endoplasmic reticulum stress, and impaired mitochondrial function. Collectively, our results indicated that thiamethoxam exposure disrupts ovarian homeostasis and decreases oocyte quality via endoplasmic reticulum stress and apoptosis induction.Saccharomyces cerevisiae (S. cerevisiae)invertase is encoded by a family of closely related SUC genes. To identify and understand the molecular basis for differences in substrate specificity, we examined 29 SUC alleles from industrialS. cerevisiaestrains and cloned alleles with small sequence differences into an invertase-negative strain. Our study showed that an F102Y substitution in Suc-enzymes lowers yeast invertase activity toward fructo-oligosaccharides (FOS) by 36% and the specificity factor by 43%. By contrast, an A409P substitution in Suc-enzymes resulted in an increased capacity of the yeast to hydrolyze FOS and Fibruline by 17 and 41%, respectively, likely because of a change in the loop conformation resulting in a wider active site. Bread dough fermentation experiments revealed that sucrose and fructan hydrolysis during fermentation is influenced by this natural variation in SUC sequences. Our research thus opens the door for the selection or engineering of yeasts and Suc-enzymes with specific activities that may ultimately allow controlling fructan hydrolysis.Genomes can be viewed as constantly updated memory systems where information propagated in cells is refined over time by natural selection. This process, commonly known as heredity and evolution, has been the sole domain of DNA since the origin of prokaryotes. Now, some 3.5 billion years later, the pendulum of discovery has swung in a new direction, with carefully trained practitioners enabling the replication and evolution of “xeno-nucleic acids” or “XNAs”-synthetic genetic polymers in which the natural sugar found in DNA and RNA has been replaced with a different type of sugar moiety. XNAs have attracted significant attention as new polymers for synthetic biology, biotechnology, and medicine because of their unique physicochemical properties that may include increased biological stability, enhanced chemical stability, altered helical geometry, or even elevated thermodynamics of Watson-Crick base pairing.This Account describes our contribution to the field of synthetic biology, where chemical synthesis and priptase activity on XNA templates.The final passage of this Account will examine the role that XNAs have played in synthetic biology by highlighting examples in which engineered polymerases have enabled the evolution of biologically stable affinity reagents (aptamers) and catalysts (XNAzymes) as well as the storage and retrieval of binary information encoded in electronic word and picture file formats. Because these examples provide only a glimpse of what the future may have in store for XNA, I will conclude the Account with my thoughts on how synthetic genetic polymers could help drive new innovations in synthetic biology and molecular medicine.The opioid epidemic remains a dire public health crisis with millions of people currently suffering from opioid use disorder (OUD) and tens of thousands dying each year. Synthetic opioids are most responsible for the crisis because of their extreme potency and ease of manufacture. Carfentanil for example has an estimated potency 10,000 times greater than morphine and thus is highly dangerous for human use. Herein, we report two synthetic opioid vaccines that elicited high-affinity antibodies against carfentanil and fentanyl with cross-reactivity to other synthetic opioids in mice and offered protection against opioid-induced respiratory depression, the primary cause of overdose deaths. These vaccines also successfully diminished drug biodistribution to the brain and shielded against opioid analgesic effects. Collectively, these findings provide new insights into the development of immunotherapeutic strategies aimed at opioid abuse and overdose.Staphylococcus aureus enterotoxins (SEs, involving SEA, SEB, SEC, SED, and SEE) are considered to be the common toxins causing food poisoning and are not allowed to be detected in food. Accurate and anti-interfering SE detection in a complex food matrix is urgently required for food safety. Dual-modal optical sensors are able to avoid mutual interference of optical signals and possess the advantages of high accuracy and sensitivity. Herein, Au nanobipyramids (Au NBPs) and persistent luminescence ZnGeGaOCr,Er,Yb nanoparticle (ZGGO NP) nanocomposites are fabricated using the SEC antibody/antigen as templates, which display enhanced persistent luminescence (PL) and surface-enhanced Raman scattering (SERS) strength. find more The enhanced PL of Au NBP-ZGGO NP nanocomposites is ascribed to plasmon-enhanced radiative transitions. It is first found that ZGGO NPs display unique upconversion fluorescence, which can be absorbed by Au NBPs and that they largely excite the intensive electromagnetic field for SERS enhancement. Dual-model optical immunoassay achieved anti-interfering and specific SEC detection with a limit of detection of 7.