Chromium nanoparticles improve bone turnover regulation in rats fed a high-fat, low-fibre diet.

The aim of the study was to investigate the effect of returning to a balanced diet combined with chromium picolinate (CrPic) or chromium nanoparticles (CrNPs) supplementation at a pharmacologically relevant dose of 0.3 mg/kg body weight on the expression level of selected genes and bone turnover markers in the blood and bones of rats fed an obese diet. The results of the study showed that chronic intake of a high-fat obesogenic diet negatively affects bone turnover by impairing processes of both synthesis and degradation of bones. The switch to a healthy diet proved insufficient to regulate bone metabolism disorders induced by an obesogenic diet, even when it was supplemented with chromium, irrespective of its form. Supplementation with CrPic with no change in diet stimulated bone metabolism only at the molecular level, towards increased osteoclastogenesis (bone resorption). In contrast, CrNPs added to the high-fat diet effectively regulated bone turnover by increasing both osteoblastogenesis and osteoclastogenesis, with these changes directed more towards bone formation. The results of the study suggest that unfavourable changes in bone metabolism induced by chronic intake of a high-fat diet can be mitigated by supplementation with CrNPs, whereas a change in eating habits fails to achieve a similar effect.

One touch is all it takes: the supramolecular interaction between ubiquitin and lanthanide complexes revisited by paramagnetic NMR and molecular dynamics.

The supramolecular interaction between lanthanide complexes and proteins is at the heart of numerous chemical and biological studies. Some of these complexes have demonstrated remarkable interaction properties with proteins or peptides in solution and in the crystalline state. Here we have used the paramagnetism of lanthanide ions to characterize the affinity of two lanthanide complexes for ubiquitin. As the interaction process is dynamic, the acquired NMR data only reflect the time average of the different steps. We have used molecular dynamics (MD) simulations to get a deeper insight into the detailed interaction scenario at the microsecond scale. This NMR/MD approach enabled us to establish that the tris-dipicolinate complex interacts specifically with arginines and lysines, while the crystallophore explores the protein surface through weak interactions with carboxylates. These observations shed new light on the dynamic interaction properties of these complexes, which will ultimately enable us to propose a crystallization mechanism.

Investigation into the Synthesis, Bioactivity, and Mechanism of Action of the Novel 6-Pyrazolyl-2-picolinic Acid as a Herbicide.

A series of new 4-amino-3,5-dicholo-6-(5-aryl-substituted-1H-pyrazol-1-yl)-2-picolinic acid compounds were designed and prepared to discover herbicidal molecules. The inhibitory activities of all new compounds against the root growth ofArabidopsis thaliana were assayed. On the whole, the new synthesized compounds displayed good inhibition effects and had excellent herbicidal activities on root growth of weed at 500 µM. Importantly, a selection of compounds demonstrated comparable herbicidal properties to picloram. At the dosage of 250 g/ha, most of the compounds showed a 100% postemergence herbicidal activity to control Chenopodium album and Amaranthus retroflexus. Using compound V-2, the mechanism of action was investigated based on a phenotype study using AFB5-deficient Arabidopsis thaliana. It was found that the novel 6-pyrazolyl-2-picolinic acids were auxinic compounds. In addition, it was proposed that V-2 may be an immune activator due to its upregulation of defense genes and the increased content of jasmonic acid.

Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis.

Intestinal barrier dysfunction usually occurred in acute pancreatitis (AP) but the mechanism remains unclear. In this study, RNA sequencing of ileum in L-arginine-induced AP mice demonstrated that phosphoenolpyruvate kinase 1 (Pck1) was significantly up-regulated. Increased Pck1 expression in intestinal epithelial cells (IECs) was further validated in ileum of AP mice and duodenum of AP patients. In AP mice, level of Pck1 was positively correlated with pancreatic and ileal histopathological scores, serum amylase activity, and intestinal permeability (serum diamine oxidase (DAO), D-lactate, and endotoxin). In AP patients, level of Pck1 had a positive correlation with Ranson scores, white blood cell count and C-reactive protein. Inhibition of Pck1 by 3-Mercaptopicolinic acid hydrochloride (3-MPA) alleviated pancreatic and ileal injuries in AP mice. AP + 3-MPA mice showed improved intestinal permeability, including less epithelial apoptosis, increased tight junction proteins (TJPs) expression, decreased serum DAO, D-lactate, endotoxin, and FITC-Dextran levels, and reduced bacteria translocation. Lysozyme secreted by Paneth cells and mucin2 (MUC2) secretion in goblet cells were also partly restored in AP + 3-MPA mice. Meanwhile, inhibition of Pck1 improved intestinal immune response during AP, including elevation of M2/M1 macrophages ratio and secretory immunoglobulin A (sIgA) and reduction in neutrophils infiltration. In vitro, administration of 3-MPA dramatically ameliorated inflammation and injuries of epithelial cells in enteroids treated by LPS. In conclusion, inhibition of Pck1 in IECs might alleviate AP via modulating intestinal homeostasis.

Dual-mode detection of 2,6-pyridinedicarboxylic acid based on the enhanced peroxidase-like activity and fluorescence property of novel Eu-MOFs.

2,6-Pyridinedicarboxylic acid (DPA) is a significant biomarker of anthrax, which is a deadly infectious disease for human beings. However, the development of a convenient anthrax detection method is still a challenge. Herein, we report a novel europium metal-organic framework (Eu-MOF) with an enhanced peroxidase-like activity and fluorescence property for DPA detection. The Eu-MOF was one-step synthesized using Eu3+ ions and 2-methylimidazole. In the presence of DPA, the intrinsic fluorescence of Eu3+ ions is sensitized, the fluorescence intensity linearly increases with an increase in DPA concentration, and the fluorescence color changes from blue to purple. Simultaneously, the peroxide-like activity of the Eu-MOF is enhanced by DPA, which can promote the oxidation of TMB to oxTMB. The absorbance values increase linearly with DPA concentrations, and the colorimetric images change from colorless to blue. The dual-mode detection of DPA has good sensitivity with a colorimetric detection limit of 0.67 µM and a fluorescent detection limit of 16.67 nM. Moreover, a simple detection method for DPA was developed using a smartphone with the RGB analysis system. A portable kit with standard color cards was developed using paper test strips. The proposed methods have good practicability for DPA detection in real samples. In conclusion, the developed Eu-MOF biosensor offers a valuable and general platform for anthrax diagnosis.

A Dual-Mode Fluorescent Nanoprobe for the Detection and Visual Screening of Pathogenic Bacterial Spores.

Bacterial vegetative cells turn into metabolically dormant spores in certain environmental situations. Once suitable conditions trigger the germination of spores belonging to the pathogenic bacterial category, public safety and environmental hygiene will be threatened, and lives will even be endangered when encountering fatal ones. Instant identification of pathogenic bacterial spores remains a challenging task, since most current approaches belonging to complicated biological methods unsuitable for onsite sensing or emerging alternative chemical techniques are still inseparable from professional instruments. Here we developed a polychromatic fluorescent nanoprobe for ratiometric detection and visual inspection of the pathogenic bacterial spore biomarker, dipicolinic acid (DPA), realizing rapidly accurate screening of pathogenic bacterial spores such as Bacillus anthracis spores. The nanoprobe is made of aminoclay-coated silicon nanoparticles and functionalized with europium ions, exhibiting selective and sensitive response toward DPA and Bacillus subtilis spores (simulants for Bacillus anthracis spores) with excellent linearity. The proposed sensing strategy allowing spore determination of as few as 0.3 × 105 CFU/mL within 10 s was further applied to real environmental sample detection with good accuracy and reliability. Visual quantitative determination can be achieved by analyzing the RGB values of the corresponding test solution color via a color recognition APP on a smartphone. Different test samples can be photographed at the same time, hence the efficient accomplishment of examining bulk samples within minutes. Potentially employed in various on-site sensing occasions, this strategy may develop into a powerful means for distinguishing hazardous pathogens to facilitate timely and proper actions of dealing with multifarious security issues.

Gram-negative bacteria recognition and photodynamic elimination by Zn-DPA based sensitizers.

The abuse and overuse of antibiotics let drug-resistant bacteria emerges. Antibacterial photodynamic therapy (APDT) has shown outstanding merits to eliminate the drug-resistant bacteria via cytotoxic reactive oxygen species produced by irradiating photosensitizer. However, most of photosensitizers are not effective for Gram-negative bacteria elimination. Herein conjugates of NBS, a photosensitizer, linked with one (NBS-DPA-Zn) or two (NBS-2DPA-Zn) equivalents of zinc-dipicolylamine (Zn-DPA) have been designed to achieve the functional recognition of different bacteria. Due to the cationic character of NBS and metal transfer channel effect of Zn-DPA, NBS-DPA-Zn exhibited the first regent to distinguish P. aeruginosa from other Gram-negative bacteria. Whereas NBS-2DPA-Zn showed broad-spectrum antibacterial effect because the two arm of double Zn-DPA enhanced interactions with anionic membranes of bacteria, led the bacteria aggregation and thus provided the efficacy of APDT to bacteria and corresponding biofilm. In combination with a hydrogel of Pluronic, NBS-2DPA-Zn@gel shows promising clinical application in mixed bacterial diabetic mouse model infection. This might propose a new method that can realize functional identification and elimination of bacteria through intelligent regulation of Zn-DPA, and shows excellent potential for antibacterial application.

Development and validation of a simple and efficient method for the analysis of commercial formulations containing clopyralid, picloram and aminopyralid as active ingredients.

Liquid chromatography plays a pivotal role in evaluating pesticide formulations as it enables the determination of multiple active substances in plant protection products. An adaptable separation technique has been developed, enabling the qualitative and quantitative analysis of clopyralid, picloram, and aminopyralid within pesticide formulations in line with SANCO/3030/99 rev. 5 guidelines. This article offers an insight into the validation procedure encompassing key aspects such as selectivity, linearity, accuracy, precision, and recovery. It places emphasis on critical stages, including sample preparation, chromatographic separation, detection, quantification, and data analysis. The active ingredients are separated using chromatography with isocratic elution, utilizing a mobile phase consisting of a mixture of water, acetonitrile, and acetic acid in a specific ratio (83:15:2 v/v/v). This separation is carried out on a YMC-Pack ODS-AQ column (250 mm x 4.6 mm, 5 µm) at a flow rate of 1.5 mL/min. The method's validation parameters have produced satisfactory outcomes. The recovery rates for each individual compound were found to be in the range of 98.6% to 101.0%. Precision, as indicated by the relative standard deviation (%RSD), was lower than the values predicted by the modified Horwitz equation. Furthermore, the correlation coefficients assessing the linearity of the response exceeded 0.99.

Factors affecting responsiveness of vadadustat in patients with anemia associated with chronic kidney disease: a post-hoc subgroup analysis of Japanese phase 3 randomized studies.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor developed for treating anemia in chronic kidney disease (CKD). The purpose of this post-hoc analysis was to investigate the factors affecting the responsiveness to vadadustat in anemia patients with nondialysis-dependent (NDD) or hemodialysis-dependent (HDD) CKD in two Japanese phase 3 studies. METHODS: Of 151 and 162 patients enrolled in NDD-CKD and HDD-CKD studies, 136 and 140 patients, respectively, were included and divided into subgroups for the analysis. To assess vadadustat responsiveness, the resistance index was defined as the mean body weight-adjusted dose of vadadustat (mg/kg) at weeks 20-24 divided by the mean hemoglobin (g/dL) at weeks 20-24. Multivariate analysis was performed to identify the variables affecting the resistance index. RESULTS: Independent factors identified as determinants for better response to vadadustat were as follows: high baseline hemoglobin, low baseline eGFR, high week-20-24 ferritin, and CKD not caused by autoimmune disease/glomerulonephritis/vasculitis in NDD-CKD; and male sex, high baseline C-reactive protein, and low baseline erythropoiesis-stimulating agent resistance index (ERI) in HDD-CKD. CONCLUSIONS: In this post-hoc analysis, several factors were identified as affecting the response to vadadustat. These results may provide useful information leading to an appropriate dose modification for vadadustat. CLINICAL TRIAL REGISTRATION: NCT03329196 (MT-6548-J01) and NCT03439137 (MT-6548-J03).

Chromium Picolinate Regulates Bone Metabolism and Prevents Bone Loss in Diabetic Rats.

Diabetic osteoporosis (DOP) is an abnormal metabolic disease caused by long-term hyperglycemia. In this study, a model rat of streptozotocin (STZ)-induced diabetes was established, and chromium picolinate (5 mg·kg-1) was given; the changes in blood glucose and body weight were detected before and after administration; and bone mineral density (BMD), bone morphology, bone turnover markers, inflammatory cytokines, and oxidative stress indicators were observed in each group. We found that after chromium picolinate (CP) intervention for 8 weeks, the blood glucose level was decreased; the BMD, the bone histomorphology parameters, and the pathological structure were improved; the expression of bone resorption-related proteins was downregulated; and the expression of bone formation-related proteins was upregulated. Meanwhile, serum antioxidant activity was increased, and inflammatory cytokine levels were decreased. In conclusion, CP could alleviate DOP by anti-oxidation, inhibition of bone turnover, anti-inflammation, and regulation of the OPG/RANKL/RANK signaling pathway. Therefore, CP has important application values for further development as a functional food or active medicine in DOP treatment.

Targeting of G-quadruplex DNA with 99mTc(I)/Re(I) Tricarbonyl Complexes Carrying Pyridostatin Derivatives.

The main goal of this work was to elucidate the potential relevance of (radio)metal chelates of 99mTc and Re targeting G-quadruplex structures for the design of new tools for cancer theranostics. 99mTc provides the complexes with the ability to perform single-photon-emission computed tomography imaging studies, while the Re complexes should act as anticancer agents upon interaction with specific G4 DNA or RNA structures present in tumor tissues. Towards this goal, we have developed isostructural 99mTc(I) and Re(I) tricarbonyl complexes anchored by a pyrazolyl-diamine (Pz) chelator carrying a pendant pyridostatin (PDS) fragment as the G4-binding motif. The interaction of the PDF-Pz-Re (8) complex with different G4-forming oligonucleotides was studied by circular dichroism, fluorescence spectroscopy and FRET-melting assays. The results showed that the Re complex retained the ability to bind and stabilize G4-structures from different DNA or RNA sequences, namely those present on the SRC proto-oncogene and telomeric RNA (TERRA sequence). PDF-Pz-Re (8) showed low to moderate cytotoxicity in PC3 and MCF-7 cancer cell lines, as typically observed for G4-binders. Biodistribution studies of the congener PDF-Pz-99mTc (12) in normal mice showed that the complex undergoes a fast blood clearance with a predominant hepatobiliary excretion, pointing also for a high in vitro stability.

The Interaction Mechanism of Picolinamide Fungicide Targeting on the Cytochrome bc1 Complex and Its Structural Modification.

Picolinamide fungicides, structurally related to UK-2A and antimycin-A, bind into the Qi-site in the bc1 complex. However, the detailed binding mode of picolinamide fungicides remains unknown. In the present study, antimycin-A and UK-2A were selected to study the binding mode of picolinamide inhibitors with four protonation states in the Qi-site by integrating molecular dynamics simulation, molecular docking, and molecular mechanics Generalized Born surface area (MM/GBSA) calculations. Subsequently, a series of new picolinamide derivatives were designed and synthesized to further understand the effects of substituents on the tail phenyl ring. The computational results indicated that the substituted aromatic rings in antimycin-A and UK-2A were the pharmacophore fragments and made the primary contribution when bound to a protein. Compound 9g-hydrolysis formed H-bonds with Hie201 and Ash228 and showed an IC50 value of 6.05 ± 0.24 µM against the porcine bc1 complex. Compound 9c, with a simpler chemical structure, showed higher control effects than florylpicoxamid against cucumber downy mildew and expanded the fungicidal spectrum of picolinamide fungicides. The structural and mechanistic insights obtained from the present study will provide a valuable clue for the future designing of new promising Qi-site inhibitors.

Assessing CaDPA levels, metabolic activity, and spore detection through deuterium labeling.

Many strains among spore-forming bacteria species are associated with food spoilage, foodborne disease, and hospital-acquired infections. Understanding the impact of environmental conditions and decontamination techniques on the metabolic activity, viability, and biomarkers of these spores is crucial for combatting them. To distinguish and track spores and to understand metabolic mechanisms, spores must be labeled. Staining or genetic modification are current methods for this, however, these methods can be time-consuming, and affect the viability and function of spore samples. In this work, we investigate the use of heavy water for permanent isotope labeling of spores and Raman spectroscopy for tracking sporulation/germination mechanisms. We also discuss the potential of this method in observing decontamination. We find that steady-state deuterium levels in the spore are achieved after only ∼48 h of incubation with 30% D2O-infused broth and sporulation, generating Raman peaks at cell silent region of 2200 and 2300 cm-1. These deuterium levels then decrease rapidly upon spore germination in non-deuterated media. We further find that unlike live spores, spores inactivated using various methods do not lose these Raman peaks upon incubation in growth media, suggesting these peaks may be used to indicate the viability of a spore sample. We further observe several Raman peaks exclusive to deuterated DPA, a spore-specific chemical biomarker, at e.g. 988 and 2300 cm-1, which can be used to track underlying changes in spores involving DPA. In conclusion, permanent spore labeling using deuterium offers a robust and non-invasive way of labeling bacterial spores for marking, viability determination, and characterising spore activity.

Spatial confinement of styryl pyridine salt derivative in MCM-22 molecular sieve network for boosted fluorescence emission and stable ratiometric sensing of bacillus anthracis biomarkers.

In this work, a stable ratiometric nanofluorescent probe for the detection of 2,6-dipicolinic acid (DPA), a Bacillus anthracis biomarker, was developed based on confinement-induced emission enhancement of cationic styrylpyridine salt derivative L in MCM-22 molecular sieve pores. The cationic L and the lanthanide Tb3+ were loaded into the pores of the molecular sieve by electrostatic interaction with the negatively charged AlO4 tetrahedron unit, and L exhibited enhanced red fluorescence emission as a stable fluorescence reference mark in the nanoprobe platform due to the restricted molecular torsion of L in the pores of MCM-22. At the same time, the characteristic green fluorescence emission of Tb3+ can be excited by energy transfer due to the "antenna effect" of DPA. The prepared Tb-L@MCM-22 nanoprobe showed specific selectivity and stable fluorescence ratiometric detection of DPA in tap water, lake water, bovine serum and actual bacterial spores. Benefiting from the confinement-induced fluorescence enhancement effect of L in the MCM-22 molecular sieve pores, the obtained Tb-L@MCM-22 can provide a stable reference signal for the fluorescence ratiometric detection of DPA with a limit of detection (LOD) of 78.6 nM and 1.310 × 104 spores per mL. More importantly, combining of the Tb-L@MCM-22 based DPA detection test strips with a smartphone app demonstrated a stable, convenient and rapid method for detecting of anthrax biomarkers.

Ratiometric fluorescent and electrochemiluminescent dual modal assay for detection of 2,6-pyridinedicarboxylic acid as an anthrax biomarker.

2,6-pyridinedicarboxylic acid (DPA) is an excellent biomarker of Bacillus anthracis (B. anthracis). The sensitive detection of DPA, especially through visual point-of-care testing, was significant for accurate and rapid diagnosis of anthrax to timely prevent anthrax disease or biological terrorist attack. Herein, a ratiometric fluorescent (R-FL) and electrochemiluminescent (ECL) dual-mode detection platform with a lanthanide ion-based metal-organic framework (Ln-MOF, i.e., M/Y-X: M = Eu, Y = Tb, and X = 4,4',4″-s-triazine-1,3,5-triyltri-m-aminobenzoic acid) was developed. Eu/Tb-TATAB nanoparticles were constructed to identify DPA. The R-FL detection platform quantitatively detected DPA by monitoring the I545/I617 ratio of the characteristic fluorescence peak intensities of Tb3+ ions and Eu3+ ions. The ECL sensing platform successfully quantified DPA by exploiting the burst effect of DPA on the ECL signal. The above methods had highly sensitive and rapid detection of DPA in water and serum samples. The results showed that this dual-mode detection platform may be projected to be a powerful instrument for preventing related biological warfare and bio-terrorism.

Study on Design, Synthesis and Herbicidal Activity of Novel 6-Indazolyl-2-picolinic Acids.

Thirty-eight new 4-amino-3,5-dicholo-6-(1H-indazolyl)-2-picolinic acids and 4-amino-3,5-dicholo-6-(2H-indazolyl)-2-picolinic acids were designed by scaffold hopping and synthesized to discover potential herbicidal molecules. All the new compounds were tested to determine their inhibitory activities against Arabidopsis thaliana and the root growth of five weeds. In general, the synthesized compounds exhibited excellent inhibition properties and showed good inhibitory effects on weed root growth. In particular, compound 5a showed significantly greater root inhibitory activity than picloram in Brassica napus and Abutilon theophrasti Medicus at the concentration of 10 µM. The majority of compounds exhibited a 100% post-emergence herbicidal effect at 250 g/ha against Amaranthus retroflexus and Chenopodium album. We also found that 6-indazolyl-2-picolinic acids could induce the up-regulation of auxin genes ACS7 and NCED3, while auxin influx, efflux and auxin response factor were down-regulated, indicating that 6-indazolyl-2-picolinic acids promoted ethylene release and ABA production to cause plant death in a short period, which is different in mode from other picolinic acids.

Pulmonary RNA interference against acute lung injury mediated by mucus- and cell-penetrating nanocomplexes.

Trans-mucosal delivery of anti-inflammatory siRNA into alveolar macrophages represents a promising modality for the treatment of acute lung injury (ALI). However, its therapeutic efficacy is often hurdled by the lack of effective carriers that can simultaneously overcome the mucosal barrier and cell membrane barrier. Herein, we developed mucus/cell membrane dual-penetrating, macrophage-targeting polyplexes which enabled efficient intratracheal delivery of TNF-α siRNA (siTNF-α) to attenuate pulmonary inflammation against lipopolysaccharide (LPS)-induced ALI. P-G@Zn, a cationic helical polypeptide bearing both guanidine and zinc dipicolylamine (Zn-DPA) side charged groups, was designed to condense siTNF-α and promote macrophage internalization due to its helicity-dependent membrane activity. Coating of the polyplexes with charge-neutralizing carboxylated mannan (Man-COOH) greatly enhanced the mucus penetration potency due to shielding of the electrostatic adhesive interactions with the mucus, and it cooperatively enabled active targeting to alveolar macrophages to potentiate the intracellular delivery efficiency of siTNF-α. As such, intratracheally administered Man-COOH/P-G@Zn/siTNF-α polyplexes provoked notable TNF-α silencing by ∼75 % in inflamed lung tissues at 500 µg siRNA/kg, and demonstrated potent anti-inflammatory performance to treat ALI. This study provides an effective tool for the synchronized trans-mucosal delivery of siRNA into macrophages, and the unique properties of the polyplexes render remarkable potentials for anti-inflammatory therapy against ALI. STATEMENT OF SIGNIFICANCE: siRNA-mediated anti-inflammatory management of acute lung injury (ALI) is greatly challenged by the insufficient delivery across the mucus layer and cell membrane. To address such critical issue, mucus/cell membrane dual-penetrating, macrophage-targeting polyplexes are herein developed, which are comprised of an outer shell of carboxylated mannan (Man-COOH) and an inner nanocore formed by TNF-α siRNA (siTNF-α) and a cationic helical polypeptide P-G@Zn. Man-COOH coating endowed the polyplexes with high mucus-penetrating capability and macrophage-targeting ability, while P-G@Zn bearing both guanidine and zinc dipicolylamine afforded potent siTNF-α condensation capacity and high intracellular delivery efficiency with reduced cytotoxicity. Intratracheally administered polyplexes solicit pronounced TNF-α silencing and anti-inflammatory efficiencies in ALI mice. This study renders an effective example for overcoming the multiple barriers against trans-mucosal delivery of siRNA into macrophages, and holds profound potentials for gene therapy against ALI.

Dipicolylamine-Zn Induced Targeting and Photo-Eliminating of Pseudomonas aeruginosa and Drug-Resistance Gram-Positive Bacteria.

The emergence of drug-resistant bacteria, particularly resistant strains of Gram-negative bacteria, such as Pseudomonas aeruginosa, poses a significant threat to public health. Although antibacterial photodynamic therapy (APDT) is a promising strategy for combating drug-resistant bacteria, actively targeted photosensitizers (PSs) remain unknown. In this study, a PS based on dipicolylamine (DPA), known as WZK-DPA-Zn, is designed for the selective identification of P. aeruginosa and drug-resistant Gram-positive bacteria. WZK-DPA-Zn exploits the synergistic effects of DPA-Zn2+ coordination and cellular uptake, which could effectively anchor P. aeruginosa within a brief period (10 min) without interference from other Gram-negative bacteria. Simultaneously, the cationic nature of WZK-DPA-Zn enhances its interaction with Gram-positive bacteria via electrostatic forces. Compared to traditional clinical antibiotics, WZK-DPA-Zn shows exceptional antibacterial activity without inducing drug resistance. This effectiveness is achieved using the APDT strategy when irradiated with white light or sunlight. The combination of WZK-DPA-Zn with Pluronic-based thermosensitive hydrogel dressings (WZK-DPA-Zn@Gel) effectively eliminates mixed bacterial infections and accelerates wound healing, thereby achieving a synergistic effect where "1+1>2." In summary, this study proposes a precise strategy employing DPA-Zn as the targeting moiety of a PS, facilitating the rapid elimination of P. aeruginosa and drug-resistant Gram-positive bacteria using APDT.

Pd-Catalyzed Picolinamide-Directed Late-Stage Chalcogenation of Tryptophan-Containing Peptides.

This report describes the Pd-catalyzed late-stage chalcogenation of tryptophan-containing peptides with disulfides/diselenides in moderate to good yields. It comprises broad substrate scope, functional group diversity, late-stage modification of drug molecules, and various valuable synthetic transformations, including room temperature easy removal of the picolinamide auxiliary, which could be applicable to tune the structure and function of peptides.

Fluorescent silica nanoparticles as nano-chemosensors for the sequential detection of Pb2+ ions and bacterial-spore biomarker dipicolinic acid (DPA) in aqueous solution.

Herein, we report fluorescein-labelled silica nanoparticles (FSNP) which serve as fluorescent nano-chemosensors for sequential detection of Pb2+ (which is a toxic heavy metal) and dipicolinic acid (DPA) (which is a distinctive indicator biomarker of bacterial spores) with high sensitivity and selectivity. The fluorescence of FSNP is quenched because of the complex formation between Pb2+ ions and surface amide groups, however, the fluorescence is recovered in contact with DPA, resulting from the association of DPA with surface bound Pb2+ ions. FSNP-Pb2+ complexes show high sensitivity towards DPA with a low detection limit of 850 nM which is approximately seventy times lower than the infectious dosage of bacterial spores (60 µM). Lateral flow test platform was further developed to show the applicability and practicability of our system.