The discovery of novel imidazo[1,2-a]pyridine derivatives as covalent anticancer agents.

The success of targeted covalent inhibitors (TCIs) for treating cancers has spurred the search for novel scaffolds to install covalent warheads. In our endeavour, using a scaffold hopping strategy, we managed to utilize imidazo[1,2-a]pyridine as the core backbone and explored its potential for the development of covalent inhibitors, therefore, synthesizing a series of novel KRAS G12C inhibitors facilitated by the Groebke-Blackburn-Bienaymè reaction (GBB reaction). Preliminary bio-evaluation screening delivered compound I-11 as a potent anticancer agent for KRAS G12C-mutated NCI-H358 cells, whose effects were further clarified by a series of cellular, biochemical, and molecular docking experiments. These results not only indicate the potential of compound I-11 as a lead compound for the treatment of intractable cancers, but also validate the unique role of imidazo[1,2-a]pyridine as a novel scaffold suitable for the discovery of covalent anticancer agents.

Chemical antifouling strategies in sensors for food analysis: A review.

Surface biofouling induced by the undesired nonspecific adsorption of foulants (e.g., coexisting proteins and cells) in food matrices is a major issue of sensors for food analysis, hindering their reliability and accuracy of sensing. This issue can be addressed by developing antifouling strategies to prevent or alleviate nonspecific binding. Chemical antifouling strategies involve the use of chemical modifiers (i.e., antifouling materials) to strongly hydrate the surface and reduce surface biofouling. Through appropriate immobilization approaches, antifouling materials can be tethered onto sensors to form antifouling surfaces with well-ordered structures, balanced surface charges, and appropriate surface density and thickness. A rational antifouling surface can reduce the matrix effect, simplify sample pretreatment, and improve analytical performance. This review summarizes recent developments in chemical antifouling strategies in sensing. Surface antifouling mechanisms and common antifouling materials are described, and factors that may influence the antifouling effects of antifouling surfaces and approaches incorporating antifouling materials onto sensing surfaces are highlighted. Moreover, the specific applications of antifouling sensors in food analysis are introduced. Finally, we provide an outlook on future developments in antifouling sensors for food analysis.

[New Technologies and Devices of Heart Failure with Reduced Ejection Fraction].

Heart failure is the terminal stage of many heart diseases, most of which are patients with reduced ejection fraction. The efficacy of drug therapy for these patients is still limited. However, heart transplantation has not been widely carried out in clinic due to its high price, limited donors and postoperative rejection. In recent years, the development of instrumentation therapy has brought about a breakthrough in the treatment of such patients with heart failure. In this review, we introduce the principle, design, clinical trial results and recent progress of two new implantable devices for the treatment of HFrEF patients, cardiac contractility modulation (CCM) and baroreflex activation therapy (BAT), and discuss their research directions and challenges.

The nutrient requirements of Lactobacillus acidophilus LA-5 and their application to fermented milk.

Lactobacillus acidophilus LA-5 is a suitable probiotic for food application, but because of its slow growth in milk, an increase in its efficiency is desired. To shorten the time required for fermentation, the nutrient requirements of L. acidophilus LA-5 were analyzed, including the patterns of consumption of amino acids, purines, pyrimidines, vitamins, and metal ions. The nutrients required by L. acidophilus LA-5 were Asn, Asp, Cys, Leu, Met, riboflavin, guanine, uracil, and Mn2+, and when they were added to milk, the fermentation time of fermented milk prepared by L. acidophilus LA-5 alone was shortened by 9 h, with high viable cell counts that were maintained during storage of nutrient-supplemented fermented milk compared with the control. For fermented milk prepared by fermentation with Streptococcus thermophilus, Lactobacillus delbrueckii ssp. bulgaricus, and L. acidophilus LA-5, viable cell counts of L. acidophilus LA-5 increased 1.3-fold and were maintained during storage of nutrient-supplemented fermented milk compared with the control. Adding nutrients had no negative effect on the quality of the fermented milk. The results indicated that suitable nutrients enhanced the growth of L. acidophilus LA-5 and increased its viable cell counts in fermented milk prepared by L. acidophilus LA-5 alone and mixed starter culture, respectively.

A comprehensive review of the application of ultrasonication in the production and processing of edible mushrooms: Drying, extraction of bioactive compounds, and post-harvest preservation.

Edible mushrooms are high in nutrients, low in calories, and contain bioactive substances; thus, they are a valuable food source. However, the high moisture content of edible mushrooms not only restricts their storage and transportation after harvesting, but also leads to a shorter processable cycle, production and processing limitations, and a high risk of deterioration. In recent years, ultrasonic technology has been widely applied to various food production operations, including product cleaning, post-harvest preservation, freezing and thawing, emulsifying, and drying. This paper reviews applications of ultrasonic technology in the production and processing of edible mushrooms in recent years. The effects of ultrasonic technology on the drying, extraction of bioactive substances, post-harvest preservation, shelf life/preservation, freezing and thawing, and frying of edible mushrooms are discussed. In summary, the application of ultrasonic technology in the edible mushroom industry has a positive effect and promotes the development of this industry.

Influence of gelatinized octenyl succinic anhydride-modified waxy adlay seed starch on the properties of astaxanthin-loaded emulsions: Emulsion properties, stability and in vitro digestion properties.

Octenyl succinic anhydride (OSA)-modified starch is a commonly used food emulsifier and its emulsifying properties are positively correlated with the degree of substitution (DS). However, the maximum concentration of OSA in starch approved by the FDA and the China National Food Safety Standards is 3%. This study aims to enhance the emulsifying properties of OSA-modified waxy adlay seed starch by gelatinization under a limited DS and investigate its use in preparing delivery systems. The gelatinized OSA starch exhibited a more flexible macromolecular structure and better emulsifying activity (20.19 m2/g). The gelatinized OSA starch-stabilized astaxanthin-loaded emulsions showed high retention of astaxanthin (>50%) and long-term stability (56 days). In vitro digestion, the emulsion system showed a protective effect on astaxanthin, and the bioaccessibility of astaxanthin was increased to 16.32%. This study indicated that gelatinization could enhance the emulsifying properties of OSA starch, and this starch-stabilized emulsion was an effective system for astaxanthin.

Deciphering the Diversified Metabolic Behavior of Hydroxyalkyl Ferrocidiphenols as Anticancer Complexes.

Ferrocidiphenols possessing appropriate substituents in the aliphatic chain have very promising anticancer properties, but a systematic approach to deciphering their diversified metabolic behavior has so far been lacking. Herein, we show that a series of novel ferrocidiphenols bearing different hydroxyalkyl substituents exhibit strong anticancer activity as revealed in a range of in vitro and in vivo experiments. Moreover, they display diversified oxidative transformation profiles very distinct from those of previous complexes, shown by the use of chemical and enzymatic methods and in cellulo and in vivo metabolism studies. In view of this phenomenon, unprecedented chemo-evolutionary sequences that connect all the ferrocidiphenol-related intermediates and analogues have been established. In addition, a comprehensive density functional theory (DFT) study has been performed to decipher the metabolic diversification profiles of these complexes and demonstrate the delicate modulation of carbenium ions by the ferrocenyl moiety, via either α- or ß-positional participation.

How does ferrocene correlate with ferroptosis? Multiple approaches to explore ferrocene-appended GPX4 inhibitors as anticancer agents.

Ferroptosis has emerged as a form of programmed cell death and exhibits remarkable promise for anticancer therapy. However, it is challenging to discover ferroptosis inducers with new chemotypes and high ferroptosis-inducing potency. Herein, we report a new series of ferrocenyl-appended GPX4 inhibitors rationally designed in a "one stone kills two birds" strategy. Ferroptosis selectivity assays, GPX4 inhibitory activity and CETSA experiments validated the inhibition of novel compounds on GPX4. In particular, the ROS-related bioactivity assays highlighted the ROS-inducing ability of 17 at the molecular level and their ferroptosis enhancement at the cellular level. These data confirmed the dual role of ferrocene as both the bioisostere motif maintaining the inhibition capacity of certain molecules with GPX4 and also as the ROS producer to enhance the vulnerability to ferroptosis of cancer cells, thereby attenuating tumor growth in vivo. This proof-of-concept study of ferrocenyl-appended ferroptosis inducers via rational design may not only advance the development of ferroptosis-based anticancer treatment, but also illuminate the multiple roles of the ferrocenyl component, thus opening the way to novel bioorganometallics for potential disease therapies.

Design and fabrication of Zn@ZnO@Ag chip for Raman scattering analysis of norfloxacin in liquid milk, fish and animal feeds.

A novel and easy-to-prepare plasmonic nanoparticles doped semiconductor substrate-Zn@ZnO@Ag chip with ultra-high surface-enhanced Raman scattering (SERS) activity was fabricated for label-free, rapid and sensitive analysis of norfloxacin. The Zn@ZnO array was synthesized by surface oxidation at low temperature, followed by in-situ reduction to form leaf-like AgNPs on Zn@ZnO array without extra reducing agent, thus fabricating a Zn@ZnO@Ag chip. The ultra-high SERS activity is attributed to the synergistic effect of semiconductor characteristics of ZnO and surface plasmon resonance properties of leaf-like AgNPs. The possible enhancement mechanism was verified by density functional theory simulations. The proposed SERS method showed a wide linear range (3.0-500.0 µg/L) and low limit of detection (0.8 µg/L) for norfloxacin analysis. High sensitivity, good selectivity and acceptable recoveries (82.7-113.6%) in real sample analysis were obtained. This study offers a promising SERS chip-based platform for norfloxacin detection in the field.

Effect of Ultrasound Pretreatment on the Moisture Migration and Quality of Cantharellus cibarius Following Hot Air Drying.

The effect of different ultrasound pretreatment powers (0-500 W) before hot air drying on the moisture migration and quality of Cantharellus cibarius (C. cibarius) was investigated in this study. The results showed that the ultrasound pretreatment accelerated the drying rate. When the ultrasound power was 400 W, the drying time of C. cibarius was reduced by 18.90% compared with the control group. The low-field nuclear magnetic resonance (LF-NMR) and magnetic resonance imaging (MRI) results showed that the ultrasound pretreatment increased the water mobility in C. cibarius. The scanning electron microscopy (SEM) results revealed that the ultrasound pretreatment promoted the expansion of intercellular pores. In addition, the rehydration capacity and quality characteristics of the ultrasound-pretreated dried C. cibarius were better than those of the control group. Overall, this study concluded that ultrasound pretreatment is a promising pretreatment method for the hot air drying of C. cibarius products to reduce the total drying time significantly and improve the retention rate of the total phenolics and flavonoids of dried C. cibarius.

Protein-Stabilized Emulsion Gels with Improved Emulsifying and Gelling Properties for the Delivery of Bioactive Ingredients: A Review.

In today's food industry, the potential of bioactive compounds in preventing many chronic diseases has garnered significant attention. Many delivery systems have been developed to encapsulate these unstable bioactive compounds. Emulsion gels, as colloidal soft-solid materials, with their unique three-dimensional network structure and strong mechanical properties, are believed to provide excellent protection for bioactive substances. In the context of constructing carriers for bioactive materials, proteins are frequently employed as emulsifiers or gelling agents in emulsions or protein gels. However, in emulsion gels, when protein is used as an emulsifier to stabilize the oil/water interface, the gelling properties of proteins can also have a great influence on the functionality of the emulsion gels. Therefore, this paper aims to focus on the role of proteins' emulsifying and gelling properties in emulsion gels, providing a comprehensive review of the formation and modification of protein-based emulsion gels to build high-quality emulsion gel systems, thereby improving the stability and bioavailability of embedded bioactive substances.

Improving the emulsification performance of adlay seed starch by esterification combined with ultrasonication and enzymatic treatment.

In this study, superior modified starch was prepared using ultrasonic and enzymatic treatments to confirm the potential of using adlay seed starch (ASS) in Pickering emulsions. Octenyl succinic anhydride (OSA)-modified starches, such as OSA-UASS, OSA-EASS, and OSA-UEASS, were prepared using ultrasonic, enzymatic, and combined ultrasonic and enzymatic treatments, respectively. The effects of these treatments on the structure and properties of ASS were evaluated to elucidate their influence on starch modification. Ultrasonic and enzymatic treatments improved the esterification efficiency of ASS by changing its external and internal morphological characteristics and the crystalline structure to provide more binding sites for esterification. The degree of substitution (DS) of ASS modified by these pretreatments was 22.3-51.1 % higher than that of the OSA-modified starch without pretreatment (OSA-ASS). Fourier transform infrared and X-ray photoelectron spectroscopy results confirmed the esterification. Small particle size and near-neutral wettability indicated that OSA-UEASS was the promising emulsification stabilizer. The emulsion prepared using OSA-UEASS exhibited better emulsifying activity and emulsion stability and long-term stability for up to 30 days. These amphiphilic granules with improved structure and morphology were used to stabilize a Pickering emulsion.

Antibacterial Activity and Mechanism of Self-Assembly Spermidine-Capped Carbon Dots against Staphylococcus aureus.

This paper investigated the antibacterial mechanism of spermidine-capped carbon dots (S-PCDs) against Staphylococcus aureus. The results showed that there were a large number of amino groups on the surface of S-PCDs and they had a high positive charge (+47.06 mV), which could be adsorbed on the negatively charged bacterial surface through electrostatic interaction and changed the permeability of the bacterial cell membrane. The extracellular protein and nucleic acid contents of S. aureus treated with S-PCDs were 5.4 and 1.2 times higher than those of the control group, respectively. The surface folds and defects of the bacterial cell membrane, and the leakage of cell contents were observed using SEM and TEM. The expression of metabolic oxidation regulatory genes dmpI, narJ and narK was upregulated and the intracellular ROS generation was induced, causing bacterial oxidative stress and eventually bacterial death. S-PCDs can effectively inhibit biofilm formation and had low cytotoxicity. The S-PCD treatment successfully inhibited microbial reproduction when pasteurized milk was stored at 25 °C and 4 °C. These results provide important insights into the antimicrobial mechanism of S-PCDs and lay the foundation for their application in the food field as a potentially novel bacteriostatic nanomaterial.

Synthesis and bioactivity evaluation of ferrocene-based hydroxamic acids as selective histone deacetylase 6 inhibitors.

Histone deacetylase 6 (HDAC6) is involved in multiple regulatory processes and emerges as a promising target for treating cancer and neurodegenerative diseases. Benefited from the unique sandwich conformation of ferrocene, a series of ferrocene-based hydroxamic acids have been developed as novel HDAC6 inhibitors in this paper, especially the two ansa-ferrocenyl complexes with IC50s at the nanomolar level. [3]-Ferrocenophane hydroxamic acid analog II-5 displays the most potent inhibitory activity on HDAC6 and establishes remarkable selectivity towards other HDAC isoforms. Compound II-5 dose-dependently induces accumulation of acetylated α-tubulin while having a negligible effect on the level of acetylated Histone H3, confirming its isoform selectivity. Further biological evaluation of II-5 on cancer cells corroborates its antiproliferative effect, which mainly contributed to the induction of cellular apoptosis. It is worth noting that compound II-5 demonstrates an optimal profile on human plasma stability. These results strengthen ferrocene's unique role in developing selective protein inhibitors and indicate that compound II-5 may be a suitable lead for further evaluation and development for treating HDAC6-associated disorders and diseases.

Biomimetic functional material-based sensors for food safety analysis: A review.

Food may be contaminated by various hazardous substances in all stages of the food supply chain, which may pose a wide variety of human health risks. The ability to construct sensors capable of highly selective analysis in complex food matrix could offer strong support for guaranteeing food safety. The design, preparation, and introduction of biomimetic functional materials as antifouling materials or recognition receptors provide new ideas for further improvement of the anti-interference and specificity of sensory system. Herein, biomimetic functional materials commonly used in sensor preparation, including biomimetic antifouling materials [poly(ethylene glycol), zwitterionic polymers, and synthetic antifouling peptides] and biomimetic recognition receptors (molecularly imprinted polymers, aptamers, and mimetic recognition peptides) are reviewed. The mechanisms, advantages, limitations of these biomimetic functional materials and the applications of biomimetic functional material-based sensors in food safety analysis are summarized. Finally, the challenges and prospects of sensors based on biomimetic functional materials are analyzed.

Ribosome Profiling Reveals Genome-Wide Cellular Translational Regulation in Lacticaseibacillus rhamnosus ATCC 53103 under Acid Stress.

During fermentation and food processing, Lacticaseibacillus rhamnosus ATCC 53103 can encounter many adverse conditions, and acid stress is one of them. The purpose of the present study was to investigate the influence of acid stress on the global translational and transcriptional regulation of Lacticaseibacillus rhamnosus ATCC 53103. Two pH values (pH 6.0 vs. pH 5.0) were applied, the effects of which were studied via ribosome profiling and RNA sequencing assay. Under acid stress, many genes showed differential changes at the translational and transcriptional levels. A total of 10 genes showed different expression trends at the two levels. The expression of 337 genes-which mainly participated in the ABC transporters, amino acid metabolism, and ribosome functional group assembly pathways-was shown to be regulated only at the translational level. The translational efficiency of a few genes participating in the pyrimidine and amino acid metabolism pathways were upregulated. Ribosome occupancy data suggested that ribosomes accumulated remarkably in the elongation region of open reading frame regions under acid stress. This study provides new insights into Lacticaseibacillus rhamnosus ATCC 53103 gene expression under acid stress, and demonstrates that the bacterium can respond to acid stress with synergistic translational and transcriptional regulation mechanisms, improving the vitality of cells.

Transcriptome analysis of the response of Hypomyces chrysospermus to cadmium stress.

Hypomyces chrysospermus is a fungal parasite that grows on Boletus species. One isolated strain of H. chrysospermus from B. griseus was obtained and proved of strong ability to tolerate and absorb cadmium (Cd) by previous research. However, the molecular mechanisms of underlying the resistance of H. chrysospermus to Cd stress have not been investigated. This study aimed to assess the effect of Cd stress on the global transcriptional regulation of H. chrysospermus. A total of 1,839 differentially expressed genes (DEGs) were identified under 120 mg/l Cd stress. Gene ontology (GO) enrichment analysis revealed that large amounts of DEGs were associated with cell membrane components, oxidoreductase activity, and transport activity. KEGG enrichment analysis revealed that these DEGs were mainly involved in the translation, amino acid metabolism, transport and catabolism, carbohydrate metabolism, and folding/sorting and degradation pathways under Cd stress. Moreover, the expression of DEGs encoding transporter proteins, antioxidant enzymes, nonenzymatic antioxidant proteins, detoxification enzymes, and transcription factors was associated with the Cd stress response. These results provide insights into the molecular mechanisms underlying Cd tolerance in H. chrysospermus and serve as a valuable reference for further studies on the detoxification mechanisms of heavy metal-tolerant fungi. Our findings may also facilitate the development of new and improved fungal bioremediation strategies.

Removal of heavy metal ion cobalt (II) from wastewater via adsorption method using microcrystalline cellulose-magnesium hydroxide.

Microcrystalline cellulose (MCC), magnesium sulfate hexahydrate, and trisodium citrate were reacted in ammonia bath in an aqueous solution to prepare a MCC-magnesium hydroxide (MH) composite adsorbent, which was used to adsorb heavy metal Co(II) ion. The method of using MCC-MH to adsorb and remove Co(II) was studied under different pH values, adsorbent dosages, contact times, initial Co(II) ion concentrations, and temperatures. The optimal process parameters include an MCC-MH dosage of 2.5 mg/mL, a contact reaction equilibrium time of 50 min, a Co(II) solution pH of 6.0-8.0, an initial Co(II) concentration of 300 mg/L, and a temperature of 303 K. The removal rate of Co(II) solution by MCC-MH was as high as 97.67%, and the maximum adsorption capacity of MCC-MH reached 153.84 mg/g under these optimal conditions. The adsorption isotherm of Co(II) conformed to the Langmuir model, the kinetic data of Co(II) conformed to the pseudo-second-order kinetic model, and the adsorption of Co(II) by MCC-MH was a spontaneous endothermic reaction under the optimized conditions. Analytical studies showed that Co(II) adsorption on MCC-MH composites is affected by chemical adsorption and involves the influence of intraparticle diffusion to a certain extent.

Ribosome Profiling and RNA Sequencing Reveal Genome-Wide Cellular Translation and Transcription Regulation Under Osmotic Stress in Lactobacillus rhamnosus ATCC 53103.

To determine whether osmotic pressure affects the translation efficiency of Lactobacillus rhamnosus, the ribosome profiling assay was performed to analyze the changes in translation efficiency in L. rhamnosus ATCC 53103. Under osmotic stress, differentially expressed genes (DEGs) involved in fatty acid biosynthesis and metabolism, ribosome, and purine metabolism pathways were co-regulated with consistent expression direction at translation and transcription levels. DEGs involved in the biosynthesis of phenylalanine, tyrosine, and tryptophan, and the phosphotransferase system pathways also were co-regulated at translation and transcription levels, while they showed opposite expression direction at two levels. Moreover, DEGs involved in the two-component system, amino acid metabolism, and pyruvate metabolism pathways were only regulated at the transcription level. And DEGs involved in fructose and mannose metabolism were only regulated at the translation level. The translation efficiency of DEGs involved in the biosynthesis of amino acids was downregulated while in quorum sensing and PTS pathways was upregulated. In addition, the ribosome footprints accumulated in open reading frame regions resulted in impaired translation initiation and elongation under osmotic stress. In summary, L. rhamnosus ATCC 53103 could respond to osmotic stress by translation regulation and control the balance between survival and growth of cells by transcription and translation.

Danzhi Xiaoyao Powder Promotes Neuronal Regeneration by Downregulating Notch Signaling Pathway in the Treatment of Generalized Anxiety Disorder.

Background: Generalized anxiety disorder (GAD) is one of the most common types of anxiety disorders with unclear pathogenesis. Our team's previous research found that extensive neuronal apoptosis and neuronal regeneration disorders occur in the hippocampus of GAD rats. Danzhi Xiaoyao (DZXYS) Powder can improve the anxiety behavior of rats, but its molecular mechanism is not well understood. Objective: This paper discusses whether the pathogenesis of GAD is related to the abnormal expression of Notch signal pathway, and whether the anti-anxiety effect of DZXYS promotes nerve regeneration in the hippocampus by regulating the Notch signaling pathway. Methods: The animal model of GAD was developed by the chronic restraint stress and uncertain empty bottle stimulation method. After the model was successfully established, the rats in the model preparation group were divided into the buspirone, DZXYS, DZXYS + DAPT, and model groups, and were administered the corresponding drug intervention. The changes in body weight and food intake of rats were continuously monitored throughout the process. The changes in anxiety behavior of rats were measured by open field experiment and elevated plus-maze test, and morphological changes and regeneration of neurons in the rat hippocampus were observed by HE staining and double immunofluorescence staining. Changes in the expression of key targets of the Notch signaling pathway in the hippocampus were monitored by real-time fluorescence quantitative PCR and western blotting. Results: In this study, we verified that the GAD model was stable and reliable, and found that the key targets of the Notch signaling pathway (Notch1, Hes1, Hes5, etc.) in the hippocampus of GAD rats were significantly upregulated, leading to the increased proliferation of neural stem cells in the hippocampus and increased differentiation into astrocytes, resulting in neuronal regeneration. DZXYS intervention in GAD rats can improve appetite, promote weight growth, and significantly reverse the anxiety behavior of GAD rats, which can inhibit the upregulation of key targets of the Notch signaling pathway, promote the differentiation of neural stem cells in the hippocampus into neurons, and inhibit their differentiation into astrocytes, thus alleviating anxiety behavior. Conclusion: The occurrence of GAD is closely related to the upregulation of the Notch signaling pathway, which hinders the regeneration of normal neurons in the hippocampus, while DZXYS can downregulate the Notch signaling pathway and promote neuronal regeneration in the hippocampus, thereby relieving anxiety behavior.