Exposure to Endocrine-Disrupting Chemicals and Congenital Heart Diseases: The Pooled Results Based on the Current Evidence.

The relationships between maternal exposure to endocrine-disrupting chemicals (EDCs) and congenital heart diseases (CHD) are not elucidated yet. The exposure levels of EDCs are generally estimated based on self-reported questionnaires or occupational exposure evaluations in the literature. Therefore, a study based on epidemiological data from human biospecimens is required to provide stronger evidence between maternal exposure to EDC and CHD. Embase, Pubmed, Scopus, and the Cochrane Library databases were searched for related research which provided risk estimates regarding the relationships between maternal EDC exposure and CHD in human offspring. Baseline characteristics and outcomes of CHD were extracted from each included study. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to calculate the overall estimates of CHD. Subgroup and meta-regression analyses were performed to identify the sources of heterogeneity. Bootstrapping techniques were used in analyses where several studies originated from a similar population. A total of seventeen studies were involved in the meta-analyses. Maternal EDC exposure was significantly related to CHD in offspring (OR 2.15; 95%CI 1.64 to 2.83). EDC exposure was significantly associated with septal defects (OR 2.34; 95%CI 1.77 to 3.10), conotruncal defects (OR 2.54; 95%CI 1.89 to 3.43), right ventricular outflow tract obstruction (OR 2.65; 95%CI 1.73 to 4.07), left ventricular outflow tract obstruction (OR 3.58; 95%CI 2.67 to 4.79), anomalous pulmonary venous return (OR 2.31; 95%CI 1.34 to 4.00), and other heart defects (OR 2.49; 95%CI 1.75 to 3.54). In addition, maternal exposure to heavy metals, which included lead (OR 2.19; 95%CI 1.29 to 3.71), cadmium (OR 1.81; 95%CI 1.28 to 2.56), mercury (OR 2.23; 95%CI 1.13 to 4.44), and manganese (OR 2.65; 95%CI 1.48 to 4.74), increased risks for CHD significantly. In conclusion, based on the latest evidence, maternal EDC exposure may increase CHD risks in human offspring, especially in heavy metal exposure conditions.

Comparative in vitro toxicological effects of water-soluble and insoluble components of atmospheric PM2.5 on human lung cells.

Fine particulates in city air significantly impact human health, but the hazardous compositional mechanisms are still unclear. Besides the toxicity of environmental PM2.5 to in vitro human lung epithelial cells (A549), the independent cytotoxicity of PM2.5-bound water-soluble (WS-PM2.5) and water-insoluble (WIS-PM2.5) fractions were also compared by cell viability, oxidative stress (reactive oxygen species, ROS), and inflammatory injury (IL-6 and TNF-α). The cytotoxicity of PM2.5 varied significantly by sampling season and place, with degrees greater in winter and spring than in summer and autumn, related to corresponding trend of air PM2.5 level, and also higher in industrial than urban site, although their PM2.5 pollution levels were comparable. The PM2.5 bound metals (Ni, Cr, Fe, and Mn) may contribute to cellular injury. Both WS-PM2.5 and WIS-PM2.5 posed significant cytotoxicity, that WS-PM2.5 was more harmful than WIS-PM2.5 in terms of decreasing cell viability and increasing inflammatory cytokines production. In particular, industrial samples were usually more toxic than urban samples, and those from summer were generally less toxic than other seasons. Hence, in order to mitigate the health risks of PM2.5 pollution, the crucial targets might be components of heavy metals and soluble fractions, and sources in industrial areas, especially during the cold seasons.

Ferrous gluconate triggers ferroptosis in Escherichia coli: Implications of lipid peroxidation and DNA damage.

Microbial ferroptosis has been proved to combat drug-resistant pathogens, but whether this pattern can be applied to the prevention and control of Escherichia coli remains to be further explored. In this study, ferrous gluconate (FeGlu) showed remarkable efficacy in killing E. coli MG1655 with a mortality rate exceeding 99.9%, as well as enterotoxigenic E. coli H10407 (ETEC H10407) and enterohemorrhagic E. coli O157:H7 (EHEC O157:H7). Bacteria death was instigated by the infiltration of Fe2+, accompanied by a burst of intracellular reactive oxygen species (ROS) and lipid peroxidation. Notably, mitigating lipid peroxidation failed to alleviate death of E. coli. Further findings confirmed that FeGlu induced DNA damage, and ΔrecA mutant showed more sensitive, implicating that DNA damage was involved in the death of E. coli. The direct interaction of Fe2+ with DNA was demonstrated by fluorescent staining, gel electrophoresis, and circular dichroism (CD). Moreover, proteomic analysis unveiled 50 differentially expressed proteins (DEPs), including 18 significantly down-regulated proteins and 32 significantly up-regulated proteins. Among them, the down-regulation of SOS-responsive transcriptional suppressor LexA indicated DNA damage induced severely by FeGlu. Furthermore, FeGlu influenced pathways such as fatty acid metabolism (FadB, FadE), iron-sulfur cluster assembly (IscA, IscU, YadR), iron binding, and DNA-binding transcription, along with α-linolenic acid metabolism, fatty acid degradation, and pyruvate metabolism. These pathways were related to FeGlu stress, including lipid peroxidation and DNA damage. In summary, FeGlu facilitated ferroptosis in E. coli through mechanisms involving lipid peroxidation and DNA damage, which presents a new strategy for the development of innovative antimicrobial strategies targeting E. coli infections.

Ultrathin Al2O3 film modification on waterborne epoxy coatings by atomic layer deposition for augmenting the corrosion resistance.

The polar channels formed by the curing of waterborne anticorrosive coatings compromise their water resistance, leading to coating degradation and metal corrosion. To enhance the anticorrosive performance of waterborne coatings, this study proposed a novel method of depositing ultrathin Al2O3 films on the surface of waterborne epoxy coatings by atomic layer deposition (ALD), a technique that can modify the surface properties of polymer materials by depositing functional films. The Al2O3-modified coatings exhibited improved sealing and barrier properties by closing the polar channels and surface defects and cracks. The surface structure and morphology of the modified coatings were characterized by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). The hydrophilicity and corrosion resistance of the modified coatings were evaluated by water contact angle measurement, Tafel polarization curve, and electrochemical impedance spectroscopy. The results indicated that the water contact angle of the Al2O3-modified coating increased by 48° compared to the unmodified coating, and the protection efficiency of the modified coating reached 99.81%. The Al2O3-modified coating demonstrated high anticorrosive efficiency and potential applications for metal anticorrosion in harsh marine environments. .

Foliar Application of Nanoparticles Reduced Cadmium Content in Wheat (Triticum aestivum L.) Grains via Long-Distance "Leaf-Root-Microorganism" Regulation.

Foliar application of beneficial nanoparticles (NPs) exhibits potential in reducing cadmium (Cd) uptake in crops, necessitating a systematic understanding of their leaf-root-microorganism process for sustainable development of efficient nano-enabled agrochemicals. Herein, wheat grown in Cd-contaminated soil (5.23 mg/kg) was sprayed with different rates of four commonly used NPs, including nano selenium (SeNPs)/silica (SiO2NPs)/zinc oxide/manganese dioxide. SeNPs and SiO2NPs most effectively reduced the Cd concentration in wheat grains. Compared to the control, Cd concentration in grains was significantly decreased by 35.0 and 33.3% by applying 0.96 mg/plant SeNPs and 2.4 mg/plant SiO2NPs, and the grain yield was significantly increased by 33.9% with SeNPs application. Down-regulated gene expression of Cd transport proteins (TaNramp5 and TaLCT1) and up-regulated gene expression of vacuolar Cd fixation proteins (TaHMA3 and TaTM20) were observed with foliar SeNPs and SiO2NPs use. SeNPs increased the levels of leaf antioxidant metabolites. Additionally, foliar spray of SeNPs resulted in lower abundances of rhizosphere organic acids and reduced Cd bioavailability in rhizosphere soil, and soil microorganisms related to carbon and nitrogen (Solirubrobacter and Pedomicrobium) were promoted. Our findings underscore the potential of the foliar application of SeNPs and SiO2NPs as a plant and rhizosphere soil metabolism-regulating approach to reduce Cd accumulation in wheat grains.

Self-validating photothermal and electrochemical dual-mode sensing based on Hg2+ etching Ti3C2 MXene.

Mercury ions can cause serious damage to the ecological environment, and it is necessary to develop reliable and elegant mercury ion sensors. In this protocol, a label-free photothermal/electrochemical dual-mode strategy for Hg2+ is proposed based on delaminated Ti3C2 MXene nanosheets (DL-Ti3C2 MXene). Hg2+ exists in water in the form of HgCl2, Hg(OH)2, and HgClOH, and the electron-rich elements O and Cl can specifically bind to the positively charged DL-Ti3C2 MXene at the edge, and further oxidation-reduction reaction occurs to obtain TiO2/C and Hg2Cl2. In view of the reduction activity and the performance of photothermal conversion of DL-Ti3C2 MXene itself, the electrochemical and photothermal responses decrease with the increase of the logarithm of Hg2+ concentration. The corresponding linear ranges are 50 pmol L-1-500 nmol L-1 and 1 nmol L-1-50 µmol L-1, and their detection limits calculated at 3 S/N are 17.2 pmol L-1 and 0.43 nmol L-1, respectively. DL-Ti3C2 MXene has the characteristics of a wide range of raw materials, low cost, and easy preparation. In addition, the design takes full advantage of the properties of the material itself, avoids the complex assembly and detection process of conventional sensors, and enables high selectivity and sensitivity for mercury detection. In particular, the dual-mode sensing endows self-confirmation of mercury ion detection results, thereby improving the reliability of the sensor.

Programmable Entropy-Driven Circuit-Cascaded Self-Feedback DNAzyme Network for Ultra-Sensitive Fluorescence and Photoelectrochemical Dual-Mode Biosensing.

Inspired by natural DNA networks, programmable artificial DNA networks have become an attractive tool for developing high-performance biosensors. However, there is still a lot of room for expansion in terms of sensitivity, atom economy, and result self-validation for current microRNA sensors. In this protocol, miRNA-122 as a target model, an ultrasensitive fluorescence (FL) and photoelectrochemical (PEC) dual-mode biosensing platform is developed using a programmable entropy-driven circuit (EDC) cascaded self-feedback DNAzyme network. The well-designed EDC realizes full utilization of the DNA strands and improves the atomic economy of the signal amplification system. The unique and rational design of the double-CdSe quantum-dot-released EDC substrate and the cascaded self-feedback DNAzyme amplification network significantly avoids high background signals and enhances sensitivity and specificity. Also, the enzyme-free, programmable EDC cascaded DNAzyme network effectively avoids the risk of signal leakage and enhances the accuracy of the sensor. Moreover, the introduction of superparamagnetic Fe3O4@SiO2-cDNA accelerates the rapid extraction of E2-CdSe QDs and E3-CdSe QDs, which greatly improves the timeliness of sensor signal reading. In addition to the strengths of linear range (6 orders of magnitude) and stability, the biosensor design with dual signal reading makes the test results self-confirming.

High-Efficiency and Stable Colloidal One-Dimensional Core/Shell Nanorod Light-Emitting Diodes.

Anisotropic nanocrystals such as nanorods (NRs) display unique linearly polarized emission, which is expected to break the external quantum efficiency (EQE) limit of quantum dot-based light-emitting diodes (LEDs). However, the progress in achieving a higher EQE using NRs encounters several challenges, primarily involving a low photoluminescence quantum yield (PLQY) of NRs and imbalanced charge injection in NR-LEDs. In this work, we investigated NR-LEDs based on CdSe/CdZnS/ZnS rod-in-rod NRs with a high PLQY and higher linear polarization compared to those of dot-in-rod NRs. The balanced charge injection is achieved using ZnMgO nanoparticles as the electron transport layer and poly-TPD {poly[N,N'-bis(4-butylphenyl)-N,N'-bis(phenyl)benzidine]} as the hole transport layer. Therefore, the NR-LEDs exhibit a maximum EQE of 21.5% and a maximum luminance of >120 000 cd/m2 owing to the high level of in-plane transitions with a dipole moment of 90%. The NR-LEDs also have greatly inhibited droop in EQE under a high current density as well as outstanding operation lifetime and cycle stability.

Perioperative management of bronchoscopy in a child patient with central core disease: A case report and literature review.

INTRODUCTION: We described the perioperative management of a child patient with central core disease for bronchoscopy with bronchoalveolar lavage. It is safe to avoid triggering agents (volatile anesthetics and succinylcholine) probably in preventing this appearance of malignant hyperthermia (MH). It is important to recognize potential complications and know how to prevent and manage them in patients with this condition. PRESENTATION OF CASE: A 5-year-old boy (weight: 8.8 kg; height: 63 cm) presented to the pediatric department after five days of intermittent fever (highest body temperature is 39.3 °C) and cough, and aggravation 1 day, meanwhile he had phlegm in throat but he couldn't cough out. The child was found to have motor retardation at his one-month-old physical examination, then genetic analysis showed central core disease. Bronchoscopy with bronchoalveolar lavage was performed for better treatment under the premise of symptomatic treatment. DISCUSSION: The patients with central core disease are particularly to develop malignant hyperthermia, so adequate precautions are in place to prevent and treat MH before anesthetic induction. The anesthesiologists need to make adequate preoperative anesthesia management strategies to ensure the safety of the child with central core disease for bronchoscopy with bronchoalveolar lavage. The child was discharged from the hospital one week after anti-inflammatory and anti-asthmatic treatment. CONCLUSION: We summarized the anesthetic precautions and management in patients with central core disease, meanwhile we offered some suggestions about anesthetic focus on bronchoscopy with bronchoalveolar lavage.

Effects of intensity-modulated radiotherapy combined with chemotherapy and prognostic factors in patients with locally advanced oesophageal cancer.

PURPOSE: We explored the efficacy and influencing factors of chemoradiotherapy and radiotherapy alone in patients with locally advanced oesophageal squamous cell carcinoma. METHODS: We retrospectively analysed 226 locally advanced oesophageal squamous cell carcinoma patients who underwent chemoradiotherapy and radiotherapy alone. Univariate and multivariate Cox regression analyses were used to analyse the impact of relevant factors. The endpoint was overall survival and progression-free survival. RESULTS: Compared with the radiotherapy group, the chemoradiotherapy group had a significant difference in the overall survival rate and the progression-free survival rate between 3 and 5 years (both p â€‹< â€‹0.05). The incidences of radiation pneumonitis and radiation oesophagitis were analysed, and the differences were not significant (all p â€‹> â€‹0.05). The incidence of haematological toxicity in the chemoradiotherapy group was significantly higher than that in the radiotherapy group (p â€‹= â€‹0.001). There was a significant difference in the incidence of haematological toxicity between the ≤65 and the >65 age groups (p â€‹< â€‹0.05). Tumour location, T stage, tumour length, tumour target volume, and short-term curative effect were the main factors affecting the prognosis (all p â€‹< â€‹0.05). T stage, gross tumour volume, and short-term curative effect were all independent factors affecting the prognosis (all p â€‹< â€‹0.05). CONCLUSIONS: Patients with locally advanced oesophageal cancer who received intensity-modulated radiotherapy (IMRT) combined with chemotherapy had significant survival benefits compared with radiotherapy alone. Haematological toxicity was the main adverse reaction. T-stage, gross tumour volume and short-term curative effect were independent factors influencing the prognosis.

Activation of polyimide by oxygen plasma for atomic layer deposition of highly compact titanium oxide coating.

Titanium oxide (TiO2) coated polyimide has broad application prospects under extreme conditions. In order to obtain a high-quality ultra-thin TiO2coating on polyimide by atomic layer deposition (ALD), the polyimide was activated byin situoxygen plasma. It was found that a large number of polar oxygen functional groups, such as carboxyl, were generated on the surface of the activated polyimide, which can significantly promote the preparation of TiO2coating by ALD. The nucleation and growth of TiO2were studied by x-ray photoelectron spectroscopy monitoring and scanning electron microscopy observation. On the polyimide activated by oxygen plasma, the size of TiO2nuclei decreased and the quantity of TiO2nuclei increased, resulting in the growth of a highly uniform and dense TiO2coating. This coating exhibited excellent resistance to atomic oxygen. When exposed to 3.5 × 1021atom cm-2atomic oxygen flux, the erosion yield of the polyimide coated with 100 ALD cycles of TiO2was as low as 3.0 × 10-25cm3/atom, which is one order less than that of the standard POLYIMIDE-ref Kapton®film.

Ferrous sulphate triggers ferroptosis in Candida albicans and cures vulvovaginal candidiasis in a mouse model.

Candida albicans is the most leading cause of life-threatening fungal invasive infections, especially for vulvovaginal candidiasis (VVC). Resistance and tolerance to common fungicide has risen great demands on alternative strategies for treating C. albicans infections. In the present study, ferroptosis has been proven to occur in C. albicans by directly exposed to FeSO4 via induing hallmarks of ferroptosis, including Fe2+ overload burden, ROS eruption and lipid peroxidation. Transcriptomic profile gave the great hints of the possible mechanism for fungal ferroptosis that FeSO4 disturb pathways associated to ribosome, tyrosine metabolism, triglyceride metabolism and thiamine metabolism, thus mobilizing death-related gene synthesis. Inspired by the results, a FeSO4-loaded hydrogel was prepared as an antifungal agent to treat C. albicans infection. This hydrogel exhibited excellent dressing properties and maintained superior antifungal activity by characterization tests. Besides, mice treated by this composite hydrogel displayed excellent therapeutic efficacy. These results highlighted the potential therapeutic use of FeSO4 as an innovative strategy in treating C. albicans infections by targeting ferroptosis.

Interaction of tetracycline and copper co-intake in inducing antibiotic resistance genes and potential pathogens in mouse gut.

The widespread use of copper and tetracycline as growth promoters in the breeding industry poses a potential threat to environmental health. Nevertheless, to the best of our knowledge, the potential adverse effects of copper and tetracycline on the gut microbiota remain unknown. Herein, mice were fed different concentrations of copper and/or tetracycline for 6 weeks to simulate real life-like exposure in the breeding industry. Following the exposure, antibiotic resistance genes (ARGs), potential pathogens, and other pathogenic factors were analyzed in mouse feces. The co-exposure of copper with tetracycline significantly increased the abundance of ARGs and enriched more potential pathogens in the gut of the co-treated mice. Copper and/or tetracycline exposure increased the abundance of bacteria carrying either ARGs, metal resistance genes, or virulence factors, contributing to the widespread dissemination of potentially harmful genes posing a severe risk to public health. Our study provides insights into the effects of copper and tetracycline exposure on the gut resistome and potential pathogens, and our findings can help reduce the risks associated with antibiotic resistance under the One Health framework.

Identification of flavor peptides based on virtual screening and molecular docking from Hypsizygus marmoreuss.

Hypsizygus marmoreuss is an under-explored source of flavor peptides that can enhance the flavor of NaCl or MSG, allowing products to be reformulated in line with reduction policies. This study utilized advanced techniques, including UPLC-Q-TOF MS/MS and molecular docking, to identify H. marmoreuss peptides. Sensory evaluations revealed 10 peptides with pronounced umami flavors and seven with dominantly salty tastes. VLPVPQK scored highest for umami intensity (5.2), and EGNPAHQK for salty intensity (6.2). Further investigation influenced by 0.35 % MSG or 0.35 % NaCl exposed peptides with elevated umami and salty thresholds. LDSPATPEK, VVEGEPSLK, and QKLPEKPER had umami-enhancing thresholds of 0.18, 0.18, and 0.35 mM, while LDSPATPEK and VVEGEPSLK had similar thresholds for salt (0.09 mM). Molecular docking revealed that taste receptor proteins interacted with umami peptides through hydrogen, carbon-hydrogen, alkyl, and van der Waals forces. Specific amino acids in the umami receptor T1R1 had roles in bonding with umami peptides through hydrogen and carbon-hydrogen interactions. In conclusion, molecular docking proved to be an effective and efficient method for flavor peptide screening. Further, this study demonstrated that flavor peptides from H. marmoreuss had the capacity to enhance NaCl and MSG flavours and might be useful tools for reformulation, reducing salt and MSG contents.

Allelic variation in the autotetraploid potato: genes involved in starch and steroidal glycoalkaloid metabolism as a case study.

BACKGROUND: Tuber starch and steroidal glycoalkaloid (SGA)-related traits have been consistently prioritized in potato breeding, while allelic variation pattern of genes that underlie these traits is less explored. RESULTS: Here, we focused on the genes involved in two important metabolic pathways in the potato: starch metabolism and SGA biosynthesis. We identified 119 genes consisting of 81 involved in starch metabolism and 38 in the biosynthesis of steroidal glycoalkaloids, and discovered 96,166 allelic variants among 2,169 gene haplotypes in six autotetraploid potato genomes. Comparative analyses revealed an uneven distribution of allelic variants among gene haplotypes and that the vast majority of deleterious mutations in these genes are retained in heterozygous state in the autotetraploid potato genomes. Leveraging full-length cDNA sequencing data, we find that approximately 70% of haplotypes of the 119 genes are transcribable. Population genetic analyses identify starch and SGA biosynthetic genes that are potentially conserved or diverged between potato varieties with varying starch or SGA content. CONCLUSIONS: These results deepen the understanding of haplotypic diversity within functionally important genes in autotetraploid genomes and may facilitate functional characterization of genes or haplotypes contributing to traits related to starch and SGA in potato.

Data-driven analytics for student reviews in China's higher vocational education MOOCs: A quality improvement perspective.

Higher vocational education is the core component of China's national education system and shoulders the mission of cultivating high-skilled and applied talents. The wide application of Massive Open Online Courses (MOOCs) has effectively improved the curriculum system of China's higher vocational education. In the meantime, some MOOCs suffer from poor course quality. Therefore, from the perspective of sustainable course quality improvement, we propose a data-driven framework for mining and analyzing student reviews in China's higher vocational education MOOCs. In our framework, we first mine multi-level student demands hidden in MOOC reviews by combining web crawlers and text mining. Then we use an artificial neural network and the KANO model to classify the extracted student demands, thereby designing effective and sustainable MOOC quality improvement strategies. Based on the real data from China's higher vocational education MOOCs, we validate the effectiveness of the proposed data-driven framework.

Effect of Ultrasonic Treatment on the Physicochemical Properties of Bovine Plasma Protein-Carboxymethyl Cellulose Composite Gel.

In order to improve the stability of bovine plasma protein-carboxymethyl cellulose composite gels and to expand the utilization of animal by-product resources, this study investigated the impact of different ultrasound powers (300, 400, 500, 600, and 700 W) and ultrasound times (0, 10, 20, 30, and 40 min) on the functional properties, secondary structure and intermolecular forces of bovine plasma protein-carboxymethyl cellulose composite gel. The results showed that moderate ultrasonication resulted in the enhancement of gel strength, water holding capacity and thermal stability of the composite gels, the disruption of hydrogen bonding and hydrophobic interactions between gel molecules, the alteration and unfolding of the internal structure of the gels, and the stabilization of the dispersion state by electrostatic repulsive forces between the protein particles. The content of α-helices, ß-turns, and ß-sheets increased and the content of random curls decreased after sonication (p < 0.05). In summary, appropriate ultrasound power and time can significantly improve the functional and structural properties of composite gels. It was found that controlling the thermal aggregation behavior of composite gels by adjusting the ultrasonic power and time is an effective strategy to enable the optimization of composite gel texture and water retention properties.

Uniaxial-Oriented Perovskite Films with Controllable Orientation.

Perovskite films with large crystal size, preferred orientation, and facile fabrication process, combining advantages of single-crystal and polycrystalline films, have gained considerable attention recently. However, there is little research on the facet properties of perovskite films. Here, (111)- and (001)-oriented perovskite films with bandgaps ranging from 1.53 to 1.77 eV, and systematically investigated their orientation-dependent properties are achieved. The (111)-oriented films show electron-dominated traps and the (001)-oriented films show hole-dominated traps, which are related to their atomic arrangement at the surface. Compared with the (001)-oriented films, the (111)-oriented films exhibit lower work function and superior water/oxygen robustness. For the wide-bandgap films, the lattice of the (001)-oriented film provides an unobstructed passage for ion migration. Comparably, the (111)-oriented films exhibit suppressed ion migration and excellent phase stability. The optimized unencapsulated solar cells based on both (001) and (111) orientations show a similar high efficiency of ≈23%. The (111)-oriented solar cell exhibits excellent stability, maintaining 95% of its initial efficiency after 1500 h maximum power point (MPP) tracking test, and 97% initial efficiency after 3000 h aging in ambient conditions. This work paves the way for the rational design, controllable synthesis, and targeted optimization of uniaxial-oriented perovskite films for various electronic applications.

Treatment of Acute Wound Infections by Degradable Polymer Nanoparticle with a Synergistic Photothermal and Chemodynamic Strategy.

Mild-heat photothermal antibacterial therapy avoids heat-induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo-conjugated polymers PM123 with photothermal units and PFc with ferrocene (Fc) units are designed to co-assemble with DSPE-mPEG2000 into nanoparticle NPM123/Fc . NPM123/Fc under 1064 nm laser irradiation (NPM123/Fc +NIR-II) generates mild heat and additionally more toxic ∙OH from endogenous H2 O2 , displaying a strong synergistic photothermal and chemodynamic effect. NPM123/Fc +NIR-II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NPM123/Fc +NIR-II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NPM123/Fc +NIR-II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NPM123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NPM123/Fc +NIR-II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics-alternative anti-infective measure.