Enantioselective Paternò-Büchi Reactions: Strategic Application of a Triplet Rebound Mechanism for Asymmetric Photocatalysis.

The Paternò-Büchi reaction is the [2 + 2] photocycloaddition of a carbonyl with an alkene to afford an oxetane. Enantioselective catalysis of this classical photoreaction, however, has proven to be a long-standing challenge. Many of the best-developed strategies for asymmetric photochemistry are not suitable to address this problem because the interaction of carbonyls with Brønsted or Lewis acidic catalysts can alter the electronic structure of their excited state and divert their reactivity toward alternate photoproducts. We show herein that a triplet rebound strategy enables the stereocontrolled reaction of an excited-state carbonyl compound in its native, unbound state. These studies have resulted in the development of the first highly enantioselective catalytic Paternò-Büchi reaction, catalyzed by a novel hydrogen-bonding chiral Ir photocatalyst.

Timosaponin A3 Induces Anti-Obesity and Anti-Diabetic Effects In Vitro and In Vivo.

Obesity is a serious global health challenge, closely associated with numerous chronic conditions including type 2 diabetes. Anemarrhena asphodeloides Bunge (AA) known as Jimo has been used to address conditions associated with pathogenic heat such as wasting-thirst in Korean Medicine. Timosaponin A3 (TA3), a natural compound extracted from AA, has demonstrated potential therapeutic effects in various disease models. However, its effects on diabetes and obesity remain largely unexplored. We investigated the anti-obesity and anti-diabetic properties of TA3 using in vitro and in vivo models. TA3 treatment in NCI-H716 cells stimulated the secretion of glucagon-like peptide 1 (GLP-1) through the activation of phosphorylation of protein kinase A catalytic subunit (PKAc) and 5'-AMP-activated protein kinase (AMPK). In 3T3-L1 adipocytes, TA3 effectively inhibited lipid accumulation by regulating adipogenesis and lipogenesis. In a high-fat diet (HFD)-induced mice model, TA3 administration significantly reduced body weight gain and food intake. Furthermore, TA3 improved glucose tolerance, lipid profiles, and mitigated hepatic steatosis in HFD-fed mice. Histological analysis revealed that TA3 reduced the size of white adipocytes and inhibited adipose tissue generation. Notably, TA3 downregulated the expression of lipogenic factor, including fatty-acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP1c), emphasizing its potential as an anti-obesity agent. These findings revealed that TA3 may be efficiently used as a natural compound for tackling obesity, diabetes, and associated metabolic disorders, providing a novel approach for therapeutic intervention.

Highly Enantioselective 6π Photoelectrocyclizations Engineered by Hydrogen Bonding.

Photochemical electrocyclization reactions are valued for both their ability to produce structurally complex molecules and their central role in elucidating fundamental mechanistic principles of photochemistry. We present herein a highly enantioselective 6π photoelectrocyclization catalyzed by a chiral Ir(III) photosensitizer. This transformation was successfully realized by engineering a strong hydrogen-bonding interaction between a pyrazole moiety on the catalyst and a basic imidazolyl ketone on the substrate. To shed light on the origin of stereoinduction, we conducted a comprehensive investigation combining experimental and computational mechanistic studies. Results from density functional theory calculations underscore the crucial role played by the prochirality and the torquoselectivity in the electrocyclization process as well as the steric demand in the subsequent [1,4]-H shift step. Our findings not only offer valuable guidance for developing chiral photocatalysts but also serve as a significant reference for achieving high levels of enantioselectivity in the 6π photoelectrocyclization reaction.

Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua Cham. et Schltdl tubers. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrate that ACN inhibited c-Myc expression through CNOT2 and MID1IP1, and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.

Optimization of polyhydroxyalkanoate production in Halomonas sp. YLGW01 using mixed volatile fatty acids: a study on mixture analysis and fed-batch strategy.

Polyhydroxyalkanoate (PHA) is one of the most promising materials for replacing petroleum-based plastics, and it can be produced from various renewable biomass sources. In this study, PHA production was conducted using Halomonas sp. YLGW01 utilizing mixed volatile fatty acids (VFAs) as carbon sources. The ratio and concentration of carbon and nitrogen sources were optimized through mixture analysis and organic nitrogen source screening, respectively. It was found that the highest cell dry weight (CDW) of 3.15 g/L and PHA production of 1.63 g/L were achieved when the ratio of acetate to lactate in the mixed VFAs was 0.45:0.55. Furthermore, supplementation of organic nitrogen sources such as soytone resulted in a ninefold increase in CDW (reaching 2.32 g/L) and a 22-fold increase in PHA production (reaching 1.60 g/L) compared to using inorganic nitrogen sources. Subsequently, DO-stat, VFAs consumption rate stat, and pH-stat fed-batch methods were applied to investigate and evaluate PHA productivity. The results showed that when pH-stat-based VFAs feeding was employed, a CDW of 7 g/L and PHA production of 5.1 g/L were achieved within 68 h, with a PHA content of 73%. Overall, the pH-stat fed-batch strategy proved to be effective in enhancing PHA production by Halomonas sp. YLGW01 utilizing VFAs.

Momordicae Semen inhibits migration and induces apoptotic cell death by regulating c-Myc and CNOT2 in human pancreatic cancer cells.

Pancreatic cancer(PC) is less common than other cancers; however, it has a poor prognosis. Therefore, studying novel target signaling and anticancer agents is necessary. Momordicae Semen (MS), the seed of Momordica sochinensis Spreng, mainly found in South-East Asia, including China and Bangladesh, is used to treat various diseases because of its anticancer, antioxidant, anti-inflammatory, and antibacterial properties. However, the effect of the MS extract on pancreatic cancer cells remains unknown. In this study investigated whether the MS extract exerted an anti-cancer effect by regulating c-Myc through CNOT2. Cytotoxicity and proliferation were investigated using MTT and colony formation assays. The levels of apoptotic, oncogenic, and migration-associated factors were confirmed using immunoblotting and immunofluorescence. Wound closure was analyzed using a wound healing assay. The chemical composition of the MS methanol extracts was analyzed using liquid chromatography-mass spectrometry. We confirmed that the MS extract regulated apoptotic factors and attenuated the stability of c-Myc and its sensitivity to fetal bovine serum. Furthermore, the MS extract increased apoptosis by regulating c-Myc and CNOT2 expression and enhanced the sensitivity of 5-FU in pancreatic cancer. This study showed that the MS extract is a promising new drug for PC.

Viscum album Induces Apoptosis by Regulating STAT3 Signaling Pathway in Breast Cancer Cells.

In this study, we investigated the potential anticancer effects of Viscum album, a parasitic plant that grows on Malus domestica (VaM) on breast cancer cells, and explored the underlying mechanisms. VaM significantly inhibited cell viability and proliferation and induced apoptosis in a dose-dependent manner. VaM also regulated cell cycle progression and effectively inhibited activation of the STAT3 signaling pathway through SHP-1. Combining VaM with low-dose doxorubicin produced a synergistic effect, highlighting its potential as a promising therapeutic. In vivo, VaM administration inhibited tumor growth and modulated key molecular markers associated with breast cancer progression. Overall, our findings provide strong evidence for the therapeutic potential of VaM in breast cancer treatment and support further studies exploring clinical applications.

The impact of comorbid anxiety on quantitative EEG heterogeneity in children with attention-deficit/hyperactivity disorder.

Objective: The objective of this study was to compare quantitative electroencephalography (Q-EEG) characteristics of children with Attention-deficit/hyperactivity disorder (ADHD), taking into account the presence of a comorbidity for anxiety disorder. It also sought to investigate the impact of comorbid anxiety on the Q-EEG heterogeneity of children with ADHD. Method: A total of 141 children with ADHD but without comorbid anxiety (ADHD-Only), 25 children with a comorbidity for anxiety disorder (ADHD-ANX) and 43 children in the control group were assessed. To compare Q-EEG characteristics between groups, we performed ANCOVA (Analysis of Covariance) on relative power and theta/beta ratio (TBR) controlling for covariates such as age, sex, and FSIQ. Relative power values from 19 electrodes were averaged for three regions (frontal, central and posterior). Furthermore, cluster analysis (Ward's method) using the squared Euclidian distance was conducted on participants with ADHD to explore the impact of anxiety on the heterogeneity of Q-EEG characteristics in ADHD. Results: There were no significant group differences in cognitive and behavioral measures. However, significant differences between groups were observed in the theta values in the central region, and the beta values in the frontal, central and posterior regions. In post hoc analyses, It was found that the ADHD-ANX group has significantly higher beta power values than the ADHD-Only group in all regions. For the theta/beta ratio, the ADHD-Only group had significantly higher values than the ADHD-ANX group in frontal, central and posterior regions. However, the control group did not show significant differences compared to both the ADHD-Only and ADHD-ANX group. Through clustering analysis, the participants in the ADHD-Only and ADHD-ANX groups were classified into four clusters. The ratios of children with comorbidities for anxiety disorder within each cluster were significantly different (χ2 = 10.018, p = 0.019). Conclusion: Attention-deficit/hyperactivity disorder children with comorbid anxiety disorder showed lower theta power in the central region, higher beta power in all regions and lower TBR in all regions compared to those without comorbid anxiety disorder. The ratios of children with comorbidities for anxiety disorder within each cluster were significantly different.

Longitudinal Relations among Identity Distinctiveness, Continuity, and Integration among Dutch Adolescents.

Identity distinctiveness, continuity, and coherence are all components of adolescents' identity development, but their longitudinal relations have rarely been examined. Data were analyzed on these three constructs collected over three years from 349 Dutch adolescents (Mage = 14.7, SDage = 0.7, 215 [61.6%] girls and 133 [38.1%] boys). A cross-lagged panel model of the three constructs showed that stability was relatively high for distinctiveness and continuity, whereas coherence was less stable. Distinctiveness and continuity were correlated positively within time, but cross-lagged associations were mostly not significant: Only distinctiveness and coherence negatively predicted each other across waves. Results suggest that distinctiveness, continuity, and coherence may be interrelated, but may not drive the development of each other.

Euonymus sachalinensis Induces Apoptosis by Inhibiting the Expression of c-Myc in Colon Cancer Cells.

We hypothesized that Euonymus sachalinensis (ES) induces apoptosis by inhibiting the expression of c-Myc in colon cancer cells, and this study proved that the methanol extract of ES has anticancer effects in colon cancer cells. ES belongs to the Celastraceae family and is well known for its medicinal properties. Extracts of species belonging to this family have been used to treat diverse diseases, including rheumatoid arthritis, chronic nephritis, allergic conjunctivitis, rhinitis, and asthma. However, ES has been targeted because there are currently few studies on the efficacy of ES for various diseases, including cancer. ES lowers cell viability in colon cancer cells and reduces the expression of c-Myc protein. We confirm that the protein level of apoptotic factors such as PARP and Caspase 3 decrease when ES is treated with Western blot, and confirm that DNA fragments occur through TUNEL assay. In addition, it is confirmed that the protein level of oncogenes CNOT2 and MID1IP1 decrease when ES is treated. We have also found that ES enhances the chemo-sensitivity of 5-FU in 5-FU-resistant cells. Therefore, we confirm that ES has anticancer effects by inducing apoptotic cell death and regulating the oncogenes CNOT2 and MID1IP1, suggesting its potential for use in the treatment of colon cancer.

Polymorphobacter megasporae sp. nov., isolated from an Antarctic lichen.

A Gram-stain-negative, aerobic, orange-coloured, rod-shaped and non-motile bacterial strain, PAMC 29362T, was isolated from an Antarctic lichen, Megaspora verrucosa. Phylogenetic and phylogenomic analyses indicated that strain PAMC 29362T belongs to the genus Polymorphobacter and was most closely related to Polymorphobacter arshaanensis (97.0% of 16S rRNA gene similarity), Polymorphobacter fuscus (96.3 %), Polymorphobacter multimanifer (95.3 %) and Polymorphobacter glacialis (95.2 %). Genomic relatedness analyses showed that strain PAMC 29362T is clearly distinguished from type strains of the genus Polymorphobacter based on values of average nucleotide identity (<74.3 %) and digital DNA-DNA hybridization (<20.4 %). The genomic DNA G+C content of PAMC 29362T was 65.5 %. The major fatty acids (>10 %) were summed feature 8 (C18:1 ω7c; 38.5 %) and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c; 31.5 %). The major respiratory quinone was Q-10. Based on the results of phylogenetic, genome-based relatedness and physiological analyses, strain PAMC 29362T is proposed to represent a novel species of the genus Polymorphobacter, with the name Polymorphobacter megasporae sp. nov. The type strain is PAMC 29362T (=KCTC 82 578T=JCM 34545T).

DFT-Guided Discovery of Ethynyl-Triazolyl-Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling.

We report the density functional theory (DFT) guided discovery of ethynyl-triazolyl-phosphinates (ETPs) as a new class of electrophilic warheads for cysteine selective bioconjugation. By using CuI -catalysed azide alkyne cycloaddition (CuAAC) in aqueous buffer, we were able to access a variety of functional electrophilic building blocks, including proteins, from diethynyl-phosphinate. ETP-reagents were used to obtain fluorescent peptide-conjugates for receptor labelling on live cells and a stable and a biologically active antibody-drug-conjugate. Moreover, we were able to incorporate ETP-electrophiles into an azide-containing ubiquitin under native conditions and demonstrate their potential in protein-protein conjugation. Finally, we showcase the excellent cysteine-selectivity of this new class of electrophile in mass spectrometry based, proteome-wide cysteine profiling, underscoring the applicability in homogeneous bioconjugation strategies to connect two complex biomolecules.

Complete genome sequence of Rhodoferax sp. PAMC 29310 from a marine sediment of the East Siberian Sea.

Rhodoferax sp. PAMC 29310 was isolated from a surface marine sediment of the East Siberian Sea, Arctic. Whole-genome sequencing of the strain Rhodoferax sp. PAMC 29310 was achieved using PacBio RS II and Illumina platform. The resulting complete genome comprised of 4,593,249 base pairs (G + C content of 58.0%) with a single chromosome, 4546 protein-coding genes, 57 tRNAs and 6 rRNA operons. A complete set of genes encoding the enzymes of glycolysis and citric acid cycle were identified. No genes encoding ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and nitrogenase reductase (nif) were present indicating that strain PAMC 29310 is not capable of fixing of carbon and nitrogen. PAMC 29310 genome contains genes for dissimilatory and assimilatory nitrate reduction. Gene encoding choline dehydrogenase enzyme which functions at the first step in the synthesis of betaine, one of the most effective osmoprotectants, was detected. In particular, among the genomes of the genus Rhodoferax strains, gene encoding nitrite reductase (nirK), which reduces nitrite to nitric oxide and tetA gene encoding tetracycline resistance protein involved in the resistance to tetracycline were identified only in the genome of Rhodoferax sp. PAMC 29310. As the first genome from the strain which was isolated from marine sediment in the genus Rhodoferax, investigation of physiological characteristics based on the complete genome sequences will help understand the adaptation of Rhodoferax sp. PAMC 29310 in the marine sediment.

Hymenobacter siberiensis sp. nov., isolated from a marine sediment of the East Siberian Sea and Hymenobacter psoromatis sp. nov., isolated from an Antarctic lichen.

Gram-stain-negative, strictly aerobic, red-pink-coloured, rod-shaped and non-motile bacterial strains PAMC 29290, PAMC 29294T and PAMC 29296 were isolated from marine surface sediment sampled in the East Siberian Sea and strains PAMC 26553 and PAMC 26554T were obtained from an Antarctic lichen. Strains PAMC 29290, PAMC 29294T and PAMC 29296 were closely related to Hymenobacter artigasi (98.8 % 16S rRNA gene similarity), Hymenobacter antarcticus (97.3 %) and Hymenobacter glaciei (96.9 %), and PAMC 26553 and PAMC 26554T showed high similarity to Hymenobacter ginsengisoli (97.0 %), Hymenobacter rivuli (96.1 %) and Hymenobacter setariae (95.9 %). Genomic relatedness analyses showed that strains PAMC 29290, PAMC 29294T and PAMC 29296 could be distinguished from H. artigasi by average nucleotide identity (ANI; 93.1-93.2 %) and digital DNA-DNA hybridization (dDDH; 50.3-51.0 %) values. Strains PAMC 26553 and PAMC 26554T could be clearly distinguished from H. ginsengisoli with ANI values <79.8 % and dDDH values <23.3 %. The major fatty acids of strains PAMC 29290, PAMC 29294T and PAMC 29296 were C15 : 0 iso (21.0-26.0 %), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 17.4-18.2 %), C15 : 0 anteiso (12.7-19.1 %) and summed feature 4 (C17 : 1 iso I and/or anteiso B; 8.6-16.1 %) and those of strains PAMC 26553 and PAMC 26554T were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 20.7-22.2 %), C15 : 0 anteiso (17.5-19.7 %) and summed feature 4 (C17 : 1 iso I and/or anteiso B; 15.5-18.1 %). The major respiratory quinone was MK-7. The genomic DNA G+C contents were 60.6-60.8 mol%. The polar lipids of PAMC 29294T were found to consist of phosphatidylethanolamine, four unidentified aminolipids, an unidentified aminophospholipid and five unidentified lipids; those of PAMC 26554T were phosphatidylethanolamine, three unidentified aminolipids, four unidentified aminophospholipid and two unidentified lipids. The distinct phylogenetic position and some physiological characteristics distinguished the novel strains from closely related type strains in the genus Hymenobacter. Thus, two novel species are proposed, with the names Hymenobacter siberiensis sp. nov. (type strain, PAMC 29294T=KCTC 82466T=JCM 34574T) and Hymenobacter psoromatis sp. nov. (type strain, PAMC 26554T=KCTC 82464T=JCM 34572T), respectively.

Opuntia ficus-indica Alleviates Particulate Matter 10 Plus Diesel Exhaust Particles (PM10D)-Induced Airway Inflammation by Suppressing the Expression of Inflammatory Cytokines and Chemokines.

Particulate matter (PM) exposure may cause adverse health effects such as respiratory disorders. We evaluated the protective effects of various Opuntia ficus-indica (OFI) extracts on airway inflammation associated with exposure to PM10D with an aerodynamic diameter <10 µm (PM10) and diesel exhaust particles (DEP). BALB/c mice were exposed to PM10D via intranasal tracheal injection three times over a period of 12 days and various OFI extracts (water, 30% ethanolic, or 50% ethanolic extracts) were administered orally for 12 days. All OFI extracts suppressed neutrophil infiltration and the number of immune cells (CD3+/CD4+, CD3+/CD8+, and Gr-1+/CD11b) in bronchoalveolar lavage fluid (BALF) and lungs. OFI extracts decreased the expression of cytokines and chemokines, including chemokine (C-X-C motif) ligand (CXCL)-1, interleukin (IL)-17, macrophage inflammatory protein-2, tumor necrosis factor (TNF)-α, cyclooxygenase-2, IL-1α, IL-1ß, IL-5, IL-6, transient receptor potential cation channel subfamily V member 1, and mucin 5AC, and inhibited IRAK-1, TNF-α, and CXCL-1 localization in BALF and lungs of mice with PM10D-induced airway inflammation. Serum asymmetric and symmetric dimethyl arginine levels were also decreased by OFI extracts treatment. Moreover, all OFI extracts restored histopathological damage in the trachea and lungs of mice with PM10D-induced airway inflammation. These results indicate that OFI extracts may be used to prevent and treat airway inflammation and respiratory diseases.

I Am Whatever I Say I Am: The Salient Identity Content of U.S. Adolescents.

Research about identity development has focused primarily on researcher-chosen domains or overlooked content entirely. To investigate the content that is salient to adolescents, we analyzed responses to a shortened Twenty Statements Test (ten answers to the question, "Who am I?") from 415 adolescents in the northeastern United States (Mage = 13.59 years; 63.7% girls, about 50% identified as White/European American). Inductive content analysis identified four Content codes (what the participants wrote: Personal, Social categories, Relationships, Self-evaluation) and two Structure codes (how they wrote their statements: Qualifiers and Verb Tense). Content codes appeared in eight patterns, and there were between-group differences in content and patterns. Results expand our understanding of adolescents' identity content and demonstrate its complexity.

Metagenomic, Metabolomic, and Functional Evaluation of Kimchi Broth Treated with Light-Emitting Diodes (LEDs).

The light-emitting diode (LED) has been widely used in the food industry, and its application has been focused on microbial sterilization, specifically using blue-LED. The investigation has been recently extended to characterize the biotic and abiotic (photodynamic) effects of different wavelengths. Here, we investigated LED effects on kimchi fermentation. Kimchi broths were treated with three different colored-LEDs (red, green, and blue) or kept in the dark as a control. Multiomics was applied to evaluate the microbial taxonomic composition using 16S rRNA gene amplicon sequencing, and the metabolomic profiles were determined using liquid chromatography-Orbitrap mass spectrometry. Cell viability was tested to determine the potential cytotoxicity of the LED-treated kimchi broths. First, the amplicon sequencing data showed substantial changes in taxonomic composition at the family and genus levels according to incubation (initial condition vs. all other groups). The differences among the treated groups (red-LED (RLED), green-LED (GLED), blue-LED (BLED), and dark condition) were marginal. The relative abundance of Weissella was decreased in all treated groups compared to that of the initial condition, which coincided with the decreased composition of Lactobacillus. Compositional changes were relatively high in the GLED group. Subsequent metabolomic analysis indicated a unique metabolic phenotype instigated by different LED treatments, which led to the identification of the LED treatment-specific and common compounds (e.g., luteolin, 6-methylquinoline, 2-hydroxycinnamic acid, and 9-HODE). These results indicate that different LED wavelengths induce characteristic alterations in the microbial composition and metabolomic content, which may have applications in food processing and storage with the aim of improving nutritional quality and the safety of food.

Phosphorus-Atom Transfer from Phosphaethynolate to an Alkylidyne.

A low-spin and mononuclear vanadium complex, (Me nacnac)V(CO)(η2 -P≡Ct Bu) (2) (Me nacnac- =[ArNC(CH3 )]2 CH, Ar=2,6-i Pr2 C6 H3 ), was prepared upon treatment of the vanadium neopentylidyne complex (Me nacnac)V≡Ct Bu(OTf) (1) with Na(OCP)(diox)2.5 (diox=1,4-dioxane), while the isoelectronic ate-complex [Na(15-crown-5)]{([ArNC(CH2 )]CH[C(CH3 )NAr])V(CO)(η2 -P≡Ct Bu)} (4), was obtained via the reaction of Na(OCP)(diox)2.5 and ([ArNC(CH2 )]CH[C(CH3 )NAr])V≡Ct Bu(OEt2 ) (3) in the presence of crown-ether. Computational studies suggest that the P-atom transfer proceeds by [2+2]-cycloaddition of the P≡C bond across the V≡Ct Bu moiety, followed by a reductive decarbonylation to form the V-C≡O linkage. The nature of the electronic ground state in diamagnetic complexes, 2 and 4, was further investigated both theoretically and experimentally, using a combination of density functional theory (DFT) calculations, UV/Vis and NMR spectroscopies, cyclic voltammetry, X-ray absorption spectroscopy (XAS) measurements, and comparison of salient bond metrics derived from X-ray single-crystal structural characterization. In combination, these data are consistent with a low-valent vanadium ion in complexes 2 and 4. This study represents the first example of a metathesis reaction between the P-atom of [PCO]- and an alkylidyne ligand.

The mechanism behind enhanced reactivity of unsaturated phosphorus(v) electrophiles towards thiols.

Vinyl- and ethynyl phosphorus(v) electrophiles are a versatile class of thiol-reactive reagents suitable for cysteine-selective peptide and protein modifications, especially for the generation of antibody conjugates. Herein we investigated the reactivity of various P(v) reagents towards thiol addition. Complementing previous studies, we observed that the heteroatoms X (X = S, O, NH) as well as the vinyl- vs. ethynyl-substituent bound to phosphorus greatly influence the overall reactivity. These experimentally observed trends, as well as the high Z-selectivity for thiol additions to ethynyl derivatives, were further elucidated using DFT calculations. Hyperconjugation was a key means of stabilizing the intermediate generated upon the thiol addition, thus determining both the reactivity and stereoselectivity of unsaturated P(v) electrophiles. Specifically, the energetically low-lying σ antibonding orbital of the P-S bond more readily stabilizes the electron density from the lone pair (LP) of the generated carbanion, rendering the phosphonothiolates more reactive compared to the derivatives bearing oxygen and nitrogen. Our studies provide a detailed mechanistic picture for designing P(v)-based electrophiles with fine-tuned reactivity profiles.

Development of new strategy combining heat treatment and phage cocktail for post-contamination prevention.

Heat treatment is an effective method for ensuring food safety and quality by controlling microbial contamination. However, food poisoning outbreaks have continuously occurred in heat-treated products due to improper thermal treatment and/or post-contamination of foodborne pathogens. This study proposes a novel strategy combining thermostable bacteriophages with thermal processing of food production plants to control foodborne pathogens and even bacterial contamination. Typically, bacteriophages' susceptibility to heat is a major challenge to their application with thermal processing, we isolated thermostable bacteriophages by a modified isolation method of applying heat to samples and characterized the thermostable bacteriophages. Furthermore, we optimized the bacteriophage cocktail components to expand the controllable host range and reduce the risk of bacteriophage resistance development. Finally, we verified this antibacterial strategy by combining heat treatment with thermostable bacteriophages in model systems, including milk and chicken breast. After the phage cocktail and heat treatment, we artificially contaminated the food products to mimic the post-contamination event. Surprisingly, the remaining bacteriophages that withstood heat treatment significantly reduced the number of post-contaminated Salmonella. Altogether, thermostable phages could be applied as complementary tools to control post-contamination after thermal processing of food products.