Long wavelength-emissive Ru(II) metallacycle-based photosensitizer assisting in vivo bacterial diagnosis and antibacterial treatment.

Ruthenium (Ru) complexes are developed as latent emissive photosensitizers for cancer and pathogen photodiagnosis and therapy. Nevertheless, most existing Ru complexes are limited as photosensitizers in terms of short excitation and emission wavelengths. Herein, we present an emissive Ru(II) metallacycle (herein referred to as 1) that is excited by 808-nm laser and emits at a wavelength of ∼1,000 nm via coordination-driven self-assembly. Metallacycle 1 exhibits good optical penetration (∼7 mm) and satisfactory reactive oxygen species production properties. Furthermore, 1 shows broad-spectrum antibacterial activity (including against drug-resistant Escherichia coli) as well as low cytotoxicity to normal mammalian cells. In vivo studies reveal that 1 is employed in precise, second near-infrared biomedical window fluorescent imaging-guided, photo-triggered treatments in Staphylococcus aureus-infected mice models, with negligible side effects. This work thus broads the applications of supramolecular photosensitizers through the strategy of lengthening their wavelengths.

Mineral-element-chelating activity of food-derived peptides: influencing factors and enhancement strategies.

Mineral elements including calcium, iron, and zinc play crucial roles in human health. Their deficiency causes public health risk globally. Commercial mineral supplements have limitations; therefore, alternatives with better solubility, bioavailability, and safety are needed. Chelates of food-derived peptides and mineral elements exhibit advantages in terms of stability, absorption rate, and safety. However, low binding efficiency limits their application. Extensive studies have focused on understanding and enhancing the chelating activity of food-derived peptides with mineral elements. This includes obtaining peptides with high chelating activity, elucidating interaction mechanisms, optimizing chelation conditions, and developing techniques to enhance the chelating activity. This review provides a comprehensive theoretical basis for the development and utilization of food-derived peptide-mineral element chelates in the food industry. Efforts to address the challenge of low binding rates between peptides and mineral elements have yielded promising results. Optimization of peptide sources, enzymatic hydrolysis processes, and purification schemes have helped in obtaining peptides with high chelating activity. The understanding of interaction mechanisms has been enhanced through advanced separation techniques and molecular simulation calculations. Optimizing chelation process conditions, including pH and temperature, can help in achieving high binding rates. Methods including phosphorylation modification and ultrasonic treatment can enhance the chelating activity.

Machine Learning-Based Prediction of Helicobacter pylori Infection Study in Adults.

BACKGROUND Helicobacter pylori has a high infection rate worldwide, and epidemiological study of H. pylori is important. Artificial intelligence has been widely used in the field of medical research and has become a hotspot in recent years. This paper proposed a prediction model for H. pylori infection based on machine learning in adults. MATERIAL AND METHODS Adult patients were selected as research participants, and information on 30 factors was collected. The chi-square test, mutual information, ReliefF, and information gain were used to screen the feature factors and establish 2 subsets. We constructed an H. pylori infection prediction model based on XGBoost and optimized the model using a grid search by analyzing the correlation between features. The performance of the model was assessed by comparing its accuracy, recall, precision, F1 score, and AUC with those of 4 other classical machine learning methods. RESULTS The model performed better on the part B subset than on the part A subset. Compared with the other 4 machine learning methods, the model had the highest accuracy, recall, F1 score, and AUC. SHAP was used to evaluate the importance of features in the model. It was found that H. pylori infection of family members, living in rural areas, poor washing hands before meals and after using the toilet were risk factors for H. pylori infection. CONCLUSIONS The model proposed in this paper is superior to other models in predicting H. pylori infection and can provide a scientific basis for identifying the population susceptible to H. pylori and preventing H. pylori infection.

Correction: Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications.

Correction for 'Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications' by Chonglu Li et al., Chem. Soc. Rev., 2023, 52, 4392-4442, https://doi.org/10.1039/D3CS00227F.

Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications.

Metal agents have made incredible strides in preclinical research and clinical applications in recent years, but their short emission/absorption wavelengths continue to be a barrier to their distribution, therapeutic action, visual tracking, and efficacy evaluation. Nowadays, the near-infrared window (NIR, 650-1700 nm) provides a more accurate imaging and treatment option. Thus, there has been ongoing research focusing on developing multifunctional NIR metal agents for imaging and therapy that have deeper tissue penetration. The design, characteristics, bioimaging, and therapy of NIR metal agents are covered in this overview of papers and reports published to date. To start with, we focus on describing the structure, design strategies, and photophysical properties of metal agents from the NIR-I (650-1000 nm) to NIR-II (1000-1700 nm) region, in order of molecular metal complexes (MMCs), metal-organic complexes (MOCs), and metal-organic frameworks (MOFs). Next, the biomedical applications brought by these superior photophysical and chemical properties for more accurate imaging and therapy are discussed. Finally, we explore the challenges and prospects of each type of NIR metal agent for future biomedical research and clinical translation.

De Novo Designed Ru(II) Metallacycle as a Microenvironment-Adaptive Sonosensitizer and Sonocatalyst for Multidrug-Resistant Biofilms Eradication.

Albeit sonodynamic therapy (SDT) has achieved encouraging progress in microbial sterilization, the scarcity of guidelines for designing highly effective sonosensitizers and the intricate biofilm microenvironment (BME), substantially hamper the therapeutic efficacy against biofilm infections. To address the bottlenecks, we innovatively design a Ru(II) metallacycle-based sonosensitizer/sonocatalyst (named Ru-A3-TTD) to enhance the potency of sonotherapy by employing molecular engineering strategies tailored to BME. Our approach involves augmenting Ru-A3-TTD's production of ultrasonic-triggered reactive oxygen species (ROS), surpassing the performance of commercial sonosensitizers, through a straightforward but potent π-expansion approach. Within the BME, Ru-A3-TTD synergistically amplifies sonotherapeutic efficacy via triple-modulated approaches: (i) effective alleviation of hypoxia, leading to increased ROS generation, (ii) disruption of the antioxidant defense system, which shields ROS from glutathione consumption, and (iii) enhanced biofilm penetration, enabling ROS production in deep sites. Notably, Ru-A3-TTD sono-catalytically oxidizes NADPH, a critical coenzyme involved in antioxidant defenses. Consequently, Ru-A3-TTD demonstrates superior biofilm eradication potency against multidrug-resistant Escherichia coli compared to conventional clinical antibiotics, both in vitro and in vivo. To our knowledge, this study represents the pioneering instance of a supramolecular sonosensitizer/sonocatalyst. It provides valuable insights into the structure-activity relationship of sonosensitizers and paves a promising pathway for the treatment of biofilm infections.

A NIR-Light-Activated and Lysosomal-Targeted Pt(II) Metallacycle for Highly Potent Evoking of Immunogenic Cell Death that Potentiates Cancer Immunotherapy of Deep-Seated Tumors.

Though platinum (Pt)-based complexes have been recently exploited as immunogenic cell death (ICD) inducers for activating immunotherapy, the effective activation of sufficient immune responses with minimal side effects in deep-seated tumors remains a formidable challenge. Herein, we propose the first example of a near-infrared (NIR) light-activated and lysosomal targeted Pt(II) metallacycle (1) as a supramolecular ICD inducer. 1 synergistically potentiates immunomodulatory response in deep-seated tumors via multiple-regulated approaches, involving NIR light excitation, boosted reactive oxygen species (ROS) generation, good selectivity between normal and tumor cells, and enhanced tumor penetration/retention capabilities. Specifically, 1 has excellent depth-activated ROS production (~7 mm), accompanied by strong anti-diffusion and anti-ROS quenching ability. In vitro experiments demonstrate that 1 exhibits significant cellular uptake and ROS generation in tumor cells as well as respective multicellular tumor spheroids. Based on these advantages, 1 induces a more efficient ICD in an ultralow dose (i.e., 5 µM) compared with the clinical ICD inducer-oxaliplatin (300 µM). In vivo, vaccination experiments further demonstrate that 1 serves as a potent ICD inducer through eliciting CD8+/CD4+ T cell response and Foxp3+ T cell depletion with negligible adverse effects. This study pioneers a promising avenue for safe and effective metal-based ICD agents in immunotherapy.

Altered microbial P cycling genes drive P availability in soil after afforestation.

Soil Phosphorous (P) availability is a limiting factor for plant growth and regulates biological metabolism in plantation ecosystems. The effect of variations in soil microbial P cycling potential on the availability of soil P during succession in plantation ecosystems is unclear. In this study, a metagenomics approach was used to explore variations in the composition and diversity of microbial P genes along a 45-year recovery sequence of Robinia pseudoacacia on the Loess Plateau, as well soil properties were measured. Our results showed that the diversity of P cycling genes (inorganic P solubilization and organic P mineralization genes) increased significantly after afforestation, and the community composition showed clear differences. The gcd and ppx genes were dominant in inorganic P transformation, whereas phnM gene dominated the transformation of organic P. The abundance of genes involved in inorganic P solubilization and organic P mineralization was significantly positively correlated with P availability, particularly for phnM, gcd, ppx, and phnI genes, corresponding to the phyla Gemmatimonadetes, Acidobacteria, Bacteroidetes, and Planctomycetes. The critical drivers of the microbial main genes of soil P cycling were available P (AP) and total N (TN) in soil. Overall, these findings highlight afforestation-induced increases in microbial P cycling genes enhanced soil P availability. and help to better understand how microbial growth metabolism caused by vegetation restoration in ecologically fragile areas affects the soil P cycling.

Metal-Organic Framework-Based Artificial Organelle Corrects Microenvironment Interference for Accurate Intratumoral Glucose Analysis.

Enzymatic catalysis with high efficiency allows them a great prospect in metabolite monitoring in living cells. However, complex tumor microenvironments, such as acidity, H2 O2 , and hypoxia, are bound to disturb catalytic reactions for misleading results. Here, we report a spatially compartmentalized artificial organelle to correct intratumoral glucose analysis, where the zeolitic imidazolate framework-8 immobilized glucose oxidase-horseradish peroxidase cascade core and catalase-directed shell act as signal transduction and guarding rooms respectively. The acid-digested core and stable shell provide appropriate spaces to boost biocatalytic efficiency with good tolerability. Notably, the endogenous H2 O2 is in situ decomposed to O2 by catalase, which not only overcomes the interference in signal output but also alleviates the hypoxic states to maximize glucose oxidation. The marked protective effect and biocompatibility render artificial organelles to correct the signal transduction for dynamic monitoring glucose in vitro and in vivo, achieving our goal of accurate intratumoral metabolite analysis.

Folic Acid Inhibited Vasculogenic Mimicry in Esophageal Cancer Cell Line Eca-109, the One Target Was EphA2.

The degree of vasculogenic mimicry(VM) is correlated with the prognosis of esophageal cancer, and folic acid supplementation could decrease esophagus cancer deaths among populations. This study aimed to explore the effect of folic acid on VM formation of esophageal cancer cell, and the target. Human esophageal squamous cancer cell lines(Eca-109) were cultured with different concentrations of folic acid (0,1,10,100,200,400, 600,800 µg/ml). A cell counting kit-8 (CCK-8) assay was used to measure the cell proliferation. Then, the amount of VM under the effect of different concentrations of folic acid was observed. Target genes were screened out from several possible targets genes including MMP2, MMP9, EphA2, VE-cad or Ln-5γ2 by employing reverse transcription-quantitative polymerase chain reaction(RT-qPCR). Finally, western blot analysis was used to verify the target proteins. In conclusion, this study found that folic acid inhibited the formation of VM in Eca-109 cells, and the one target protein was EphA2.

Development and validation of a model to predict rebleeding within three days after endoscopic hemostasis for high-risk peptic ulcer bleeding.

BACKGROUND: Peptic ulcer bleeding remains a typical medical emergency with significant morbidity and mortality. Peptic ulcer rebleeding often occurs within three days after emergent endoscopic hemostasis. Our study aims to develop a nomogram to predict rebleeding within three days after emergent endoscopic hemostasis for high-risk peptic ulcer bleeding. METHODS: We retrospectively reviewed the data of 386 patients with bleeding ulcers and high-risk stigmata who underwent emergent endoscopic hemostasis between March 2014 and October 2018. The least absolute shrinkage and selection operator method was used to identify predictors. The model was displayed as a nomogram. Internal validation was carried out using bootstrapping. The model was evaluated using the calibration plot, decision-curve analyses, and clinical impact curve. RESULTS: Overall, 386 patients meeting the inclusion criteria were enrolled, with 48 patients developed rebleeding within three days after initial endoscopic hemostasis. Predictors contained in the nomogram included albumin, prothrombin time, shock, haematemesis/melena and Forrest classification. The model showed good discrimination and good calibration with a C-index of 0.854 (C-index: 0.830 via bootstrapping validation). Decision-curve analyses and clinical impact curve also demonstrated that it was clinically valuable. CONCLUSION: This study presents a nomogram that incorporates clinical, laboratory, and endoscopic features, effectively predicting rebleeding within three days after emergent endoscopic hemostasis and identifying high-risk rebleeding patients with peptic ulcer bleeding. Trial registration This clinical trial has been registered in the ClinicalTrials.gov (ID: NCT04895904) approved by the International Committee of Medical Journal Editors (ICMJE).

Amoxicillin-vonoprazan dual therapy for Helicobacter pylori eradication: A systematic review and meta-analysis.

BACKGROUND AND AIM: The efficacy and safety of amoxicillin-vonoprazan (VA) dual therapy remained unclear. METHODS: This systematic review was conducted in accordance with the PRISMA 2009 guidelines. A systematic search of the Pubmed, Embase, and Cochrane database was conducted using the combination of "Helicobacter pylori or H. pylori or Hp," "amoxicillin or penicillin," and "Vonoprazan or TAK-438 or Takecab or (potassium AND competitive) or potassium-competitive." The initial and secondary outcome of this meta-analysis was to evaluate the efficacy and safety of VA dual therapy. RESULTS: Three studies and 668 H. pylori infected patients were included in this meta-analysis. The crude eradication rate of VA dual therapy was 87.5% and 89.6% by ITT and PP analysis, respectively. No significant differences were observed regarding the VA dual therapy and vonoprazan-amoxicillin-clarithromycin (VAC) triple therapy according to ITT (RR = 0.99, 95% CI, 0.93-1.05, P = 0.65) and PP (RR = 0.99, 95% CI, 0.94-1.05, P = 0.82) analysis. The side effect of VA dual therapy was 19.1% (95% CI, 5.9-32.4), which was lower than that of VAC triple therapy but there was no statistical significance (RR = 0.75, 95% CI, 0.59-1.06, P = 0.12). CONCLUSION: VA dual therapy shows acceptable efficacy, good safety and avoid unnecessary antibiotic use in the first-line treatment for H. pylori infection. However, its application in other regions need to be further explored.

Limb-Bud and Heart (LBH) Upregulation in Cardiomyocytes under Hypoxia Promotes the Activation of Cardiac Fibroblasts via Exosome Secretion.

The activation of cardiac fibroblasts (CFs) after myocardial infarction (MI) is essential for post-MI infarct healing, during which the regulation of transforming growth factor beta1 (TGF-ß1) signaling is predominant. We have demonstrated that TGF-ß1-mediated upregulation of LBH contributes to post-MI CF activation via modulating αB-crystallin (CRYAB), after being upregulated by TGF-ß1. In this study, the effect of LBH-CRYAB signaling on the cardiac microenvironment via exosome communication and the corresponding mechanisms were investigated. The upregulation of LBH and CRYAB was verified in both cardiomyocytes (CMs) and CFs in hypoxic, post-MI peri-infarct tissues. CM-derived exosomes were isolated and identified, and LBH distribution was elevated in exosomes derived from LBH-upregulated CMs under hypoxia. Treatment with LBH+ exosomes promoted cellular proliferation, differentiation, and epithelial-mesenchymal transition-like processes in CFs. Additionally, in primary LBHKO CFs, western blotting showed that LBH knockout partially inhibited TGF-ß1-induced CF activation, while LBH-CRYAB signaling affected TGF-ß1 expression and secretion through a positive feedback loop. The administration of a Smad3 phosphorylation inhibitor to LBHKO CFs under TGF-ß1 stimulation indicated that Smad3 phosphorylation partially accounted for TGF-ß1-induced LBH upregulation. In conclusion, LBH upregulation in CMs in post-MI peri-infarct areas correlated with a hypoxic cardiac microenvironment and led to elevated exosomal LBH levels, promoting the activation of recipient CFs, which brings new insights into the studies and therapeutic strategies of post-MI cardiac repair.

Melanin-dot-mediated delivery of metallacycle for NIR-II/photoacoustic dual-modal imaging-guided chemo-photothermal synergistic therapy.

Discrete Pt(II) metallacycles have potential applications in biomedicine. Herein, we engineered a dual-modal imaging and chemo-photothermal therapeutic nano-agent 1 that incorporates discrete Pt(II) metallacycle 2 and fluorescent dye 3 (emission wavelength in the second near-infrared channel [NIR-II]) into multifunctional melanin dots with photoacoustic signal and photothermal features. Nano-agent 1 has a good solubility, biocompatibility, and stability in vivo. Both photoacoustic imaging and NIR-II imaging in vivo confirmed that 1 can effectively accumulate at tumor sites with good signal-to-background ratio and favorable distribution. Guided by precise dual-modal imaging, nano-agent 1 exhibits a superior antitumor performance and less severe side effects compared with a single treatment because of the high efficiency of the chemo-photothermal synergistic therapy. This study shows that nano-agent 1 provides a promising multifunctional theranostic platform for potential applications in biomedicine.

Rhomboidal Pt(II) metallacycle-based NIR-II theranostic nanoprobe for tumor diagnosis and image-guided therapy.

Fluorescent theranostics probes at the second near-IR region (NIR-II; 1.0-1.7 µm) are in high demand for precise theranostics that minimize autofluorescence, reduce photon scattering, and improve the penetration depth. Herein, we designed and synthesized an NIR-II theranostic nanoprobe 1 that incorporates a Pt(II) metallacycle 2 and an organic molecular dye 3 into DSPE-mPEG5000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000]). This design endows 1 with good photostability and passive targeting ability. Our studies show that 1 accurately diagnoses cancer with high resolution and selectively delivers the Pt(II) metallacycle to tumor regions via an enhanced permeability and retention effect. In vivo studies reveal that 1 efficiently inhibits the growth of tumor with minimal side effects. At the same time, improved fluorescent imaging quality and signal-to-noise ratios are shown due to the long emission wavelengths. These studies demonstrate that 1 is a potential theranostic platform for tumor diagnosis and treatment in the NIR-II region.

Design of a Metallacycle-Based Supramolecular Photosensitizer for In Vivo Image-Guided Photodynamic Inactivation of Bacteria.

Bacterial infection is one of the greatest threats to public health. In vivo real-time monitoring and effective treatment of infected sites through non-invasive techniques, remain a challenge. Herein, we designed a PtII metallacycle-based supramolecular photosensitizer through the host-guest interaction between a pillar[5]arene-modified metallacycle and 1-butyl-4-[4-(diphenylamino)styryl]pyridinium. Leveraging the aggregation-induced emission supramolecular photosensitizer, we improved fluorescence performance and antimicrobial photodynamic inactivation. In vivo studies revealed that it displayed precise fluorescence tracking of S. aureus-infected sites, and in situ performed image-guided efficient PDI of S. aureus without noticeable side effects. These results demonstrated that metallacycle combined with host-guest chemistry could provide a paradigm for the development of powerful photosensitizers for biomedicine.

Rational Design of a Multifunctional Molecular Dye with Single Dose and Laser for Efficiency NIR-II Fluorescence/Photoacoustic Imaging Guided Photothermal Therapy.

Multifunctional probes integrating accurate multidiagnosis and efficient therapy hold great prospects in biomedical research. However, the sophisticated construction and difficulties in matching the ratios of doses and laser triggers of probes for each modal imaging and therapy still hinder the extensive practice of multifunctional probes in biomedicine. We herein rationally designed an organic dye SY1080 with intrinsic multifunction by introducing both 3,4-ethylenedioxy thiophene (EDOT) and the selenium containing acceptor unit into the backbone to balance the fluorescent brightness and emission wavelength. Under single dose and 808 nm laser irradiation conditions, SY1080 not only carried out NIR-II fluorescence/photoacoustic imaging of real-time and noninvasive tumor delineation with excellent contrast, but also effectively ablated tumors with laser irradiation to perform photothermal therapy under the guidance of dual-modal imaging. These exciting results highlight SY1080 as a multifunctional and universal phototheranostic platform for potential applications.

Genetic variants in microRNAs are associated with cervical cancer risk.

Because genetic variants in microRNAs (miRNAs) or their surrounding regions can alter miRNA processing, expression and final biological function, we investigated whether miRNA single-nucleotide polymorphisms (SNPs) are associated with cervical cancer (CC) susceptibility. Common miRNA SNPs (i.e. miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, miR-499 rs3746444, miR-605 rs2043556 and miR-618 rs2682818) were genotyped in the 954 patients and 1339 controls. The results showed that the miR-149 rs2292832 TC/CC genotypes were associated with a 21% increased risk of CC compared with the TT genotype [odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.00-1.47]. The association was more prominent among the subjects with age ≤ 48 years (OR = 1.55, 95% CI = 1.16-2.06), having history of abortion (OR = 1.44, 95% CI = 1.12-1.86), premenopausal status (OR = 1.41, 95% CI = 1.08-1.85) and patients with clinical stage II of CC (OR = 1.43, 95% CI = 1.08-1.90). The expression plasmids containing the pre-miR-149 sequence with C allele of rs2292832 transcribed higher amount of mature miR-149-5p/3p than these with T allele in the HeLa and SiHa cells. Therefore, the rs2292832 polymorphism might influence CC susceptibility through modulation of the procession of pre-miR-149 to mature miRNAs.

Facile Cu(ii)-mediated conjugation of thioesters and thioacids to peptides and proteins under mild conditions.

The bioconjugation of peptide derivatives such as polypeptides, peptide-based probes and proteins is a vibrant area in many scientific fields. However, reports on metal-mediated chemical methods towards native peptides especially non-engineering protein modification under mild conditions are still limited. Herein, we describe a novel Cu(ii)-mediated strategy for the conjugation of thioesters/thioacids to peptides under mild conditions with high functional group tolerance. Based on this strategy, polypeptides, even peptide-based fluorescent probes, can be efficiently constructed. Finally, the selective modification of lysine residues of native Ub with thioesters could be realized and complete conjugation of Ub could be achieved even under equivalent Cu(ii). These promising results could greatly expand Cu(ii)-mediated reaction strategies on chemical biology and molecular imaging.

Characterization of a highly Al3+ -selective fluorescence probe based on naphthalimide-Schiff base and its application to practical water samples.

A new fluorescent Al3+ -probe, N-allyl-4-[3,3'-((2-aminoethyl)azanediyl)-bis(N´-(2-hydroxybenzylidene)propanehy-drazide)]-1,8-naphthalimide (L), was designed and synthesized based on 1,8-naphthalimide. The probe L contains 1,8-naphthalimide moiety as the fluorophore and a Schiff base as the recognition group. The structure of L was determined by single crystal X-ray. L emission at 526 nm increased on addition of Al3+ under excitation wavelength at 350 nm. L exhibited high selectivity and sensitivity fluorescence emission towards to Al3+ in ethanol/Tris-HCl buffer solution (1:1, v/v, pH = 7.2) as compared with other tested metal ions. A good linearity with a correlation coefficient (R2 ) of 0.99 was observed in the concentration range 2-10 µM. The binding constant and the detection limit of L for Al3+ were calculated to 2.6 × 104  M-1 and 0.34 µM, respectively. The results of experiments that including Job plot, ultraviolet-visible (UV-Vis) light titration, fluorescence titration, ESI-MS and 1 H NMR titration, indicated a 1:1 stoichiometric complex between L and Al3+ . L was highly effective in monitoring Al3+ in real-life Yellow River and tap water samples.