Theoretical advances in understanding and enhancing the thermostability of energetic materials.

The quest for thermally stable energetic materials is pivotal in advancing the safety of applications ranging from munitions to aerospace. This perspective delves into the role of theoretical methodologies in interpreting and advancing the thermal stability of energetic materials. Quantum chemical calculations offer an in-depth understanding of the molecular and electronic structure properties of energetic compounds related to thermal stability. It is also essential to incorporate the surrounding interactions and their impact on molecular stability. Ab initio molecular dynamics (AIMD) simulations provide detailed theoretical insights into the reaction pathways and the key intermediates during thermal decomposition in the condensed phase. Analyzing the kinetic barrier of rate-determining steps under various temperature and pressure conditions allows for a comprehensive assessment of thermal stability. Recent advances in machine learning have demonstrated their utility in constructing potential energy surfaces and predicting thermal stability for newly designed energetic materials. The machine learning-assisted high-throughput virtual screening (HTVS) methodology can accelerate the discovery of novel energetic materials with improved properties. As a result, the newly identified and synthesized energetic molecule ICM-104 revealed excellence in performance and thermostability. Theoretical approaches are pivotal in elucidating the mechanisms underlying thermal stability, enabling the prediction and design of enhanced thermal stability for emerging EMs. These insights are instrumental in accelerating the development of novel energetic materials that optimally balance performance and thermal stability.

The role of Keap1-Nrf2 signaling pathway in the treatment of respiratory diseases and the research progress on targeted drugs.

Lungs are exposed to external oxidants from the environment as in harmful particles and smog, causing oxidative stress in the lungs and consequently respiratory ailment. The NF-E2-related factor 2 (Nrf2) is the one with transcriptional regulatory function, while its related protein Kelch-like ECH-associated protein 1 (Keap1) inhibits Nrf2 activity. Together, they form the Keap1-Nrf2 pathway, which regulates the body's defense against oxidative stress. This pathway has been shown to maintain cellular homeostasis during oxidative stressing, inflammation, oncogenesis, and apoptosis by coordinating the expression of cytoprotective genes and making it a potential therapeutic target for respiratory diseases. This paper summarizes this point in detail in Chapter 2. In addition, this article summarizes the current drug development and clinical research progress related to the Keap1-Nrf2 signaling pathway, with a focus on the potential of Nrf2 agonists in treating respiratory diseases. Overall, the article reviews the regulatory mechanisms of the Keap1-Nrf2 signaling pathway in respiratory diseases and the progress of targeted drug research, aiming to provide new insights for treatment.

The ability of different diffusing enhancers to deliver chlorhexidine into dentinal tubules: An in vitro evaluation.

Background/purpose: Root canal irrigants are difficult to diffuse deep into the dentinal tubules for root canal disinfection. The purpose of this study was to assess the ability of different diffusing enhancers to deliver chlorhexidine (CHX) into dentinal tubules. Materials and methods: The diffusing property of five diffusing enhancers (acetone, DMSO, Triton X-100, JFC-E and azone) into dentinal tubules was firstly assessed using the Rhodamine B. The ability of the diffusing enhancers to deliver CHX into dentinal tubules was then evaluated both qualitatively and quantitatively. A deep dentinal tubule Enterococcus faecalis infection model was further established to test the bactericidal effect of CHX delivered by different diffusing enhancers. Finally, the in vitro cytotoxicity of these diffusing enhancers was tested using the CCK-8 method. Results: Azone, Triton X-100 and JFC-E exhibited the largest maximum diffusing depths at all root canal parts (P < 0.05). Azone group also showed the highest percentage of diffusing depths for all root canal parts, followed by Triton X-100 (P < 0.05). The percentage of dead bacteria in dentinal tubules close to cementum layer was significantly higher in the CHX + azone group than in the other groups (P < 0.05), followed by CHX + Triton X-100 and CHX + JFC-E groups. The concentration of CHX diffusing onto the exterior surface of root was significantly higher in CHX + azone group than in the other groups (P < 0.05). All the diffusing enhancers showed relatively low cytotoxicity. Conclusion: Azone showed the highest diffusing ability with low cytotoxicity and might be employed as a carrier agent for either intracanal irrigants or medications to achieve more thorough root canal disinfection.

Thoracic epithelioid inflammatory myofibroblastic sarcoma: a rare and aggressive disease with case report and literature review.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a rare subtype of inflammatory myofibroblastic tumor, characterized to be an aggressive disease with high frequency of ALK rearrangement, rapid recurrence, and poor prognosis. Primary EIMS of thoracic origin is rarely observed. Herein, we described a case of 28-year-old female developed primary EIMS in the anterior mediastinum with hepatic metastasis. The EIMS displayed sheet-like growth of epithelioid and spindle cells with enlarged nuclei, abundant and eosinophilic cytoplasm, and infiltration of inflammatory cells. Immunohistochemical staining revealed positive expression of ALK in the nuclear membrane, and ALK rearrangement was identified by polymerase chain reaction assay. Alectinib showed partial response, and achieved a meaningful survival benefit for four months. Based on this case report and literature review, ALK inhibitor reveals promising activity on the rare but aggressive EIMS. Awareness of EIMS in thoracic disease and its clinicopathological features is essential to avoid erroneous diagnosis.

Metformin reduced the alkaline resistance of Enterococcus faecalis against calcium hydroxide via Man-PTS EII: in vitro and in vivo studies.

OBJECTIVES: The mannose phosphotransferase system (Man-PTS) plays crucial roles in the adaptive metabolic activity of Enterococcus faecalis (E. faecalis) in adverse environments. The aim of this study was to evaluate the role of Man-PTS in the alkaline resistance of E. faecalis against calcium hydroxide (CH) and the effect of metformin (Met) on the alkaline resistance of E. faecalis to CH. MATERIALS AND METHODS: The regulatory role of Man-PTS EII in the alkaline resistance of E. faecalis was firstly investigated using a wild-type highly alkaline-resistant E. faecalis XS 003, standard ATCC 29212 and Man-PTS EIID gene deficient (△mptD) and overexpressing (+mptD) strains of E. faecalis. RNA sequencing of Met-treated E. faecalis was performed to further validate the effect of Met on Man-PTS. The effect of Met on CH resistance of E. faecalis was verified by evaluating the survival, membrane potential and permeability, intracellular pH and ATP, and the expression of Man-PTS EII and membrane transporter-related genes of E. faecalis. The effect of Met on the ability of CH to remove E. faecalis biofilm on the dentin surface was also tested. The in vivo therapeutic effect of Met plus CH (CHM) was further investigated in a rat apical periodontitis model induced by E. faecalis XS 003. RESULTS: Man-PTS EII significantly promoted the survival ability of E. faecalis in CH and enhanced its resistance to CH. The inhibition of Man-PTS EII by Met resulted in reduced alkaline resistance of E. faecalis in the presence of CH, while also enhancing the antimicrobial properties of CH against E. faecalis biofilm on dentin. Additionally, Met plus CH showed the synergistically promoted intra-canal E. faecalis infection control and healing of periapical lesion in rats. CONCLUSIONS: Met could significantly reduce the alkaline resistance of E. faecalis against CH through the modulation of Man-PTS EII, and improved the antibacterial effect of CH against E. faecalis infection both in vitro and in vivo. CLINICAL RELEVANCE: Met could significantly enhance the ability of CH to control E. faecalis infection through reducing the alkaline resistance of E. faecalis.

Progress in culture technology and active substance research on Nostoc sphaeroides Kützing.

Nostoc sphaeroides Kützing is a freshwater edible cyanobacterium that is rich in active substances such as polysaccharides, proteins and lipids; it has a variety of pharmacological effects such as antioxidant, anti-inflammatory, antitumor and cholesterol-lowering effects; and is often used as a traditional Chinese medicine with many potential applications in food, cosmetics, medical diagnostics and disease treatment. However, to meet the needs of different fields, such as medicine, there is an urgent need for basic research and technological innovation in culture technology, extraction and preparation of active substances, and the pharmacological mechanism of N. sphaeroides. This paper reviews the pharmacological effects of N. sphaeroides active substances, discusses current culture techniques and methods for extracting active components, and outlines the challenges encountered in cultivating and industrializing N. sphaeroides while discussing future development trends. © 2024 Society of Chemical Industry.

Roles of naïve CD4+ T cells and their differentiated subtypes in lung adenocarcinoma and underlying potential regulatory pathways.

BACKGROUND: Naïve CD4+ T cells and their differentiated counterparts play a significant regulatory role in the tumor immune microenvironment, yet their effects on lung adenocarcinoma (LUAD) are not fully understood. METHODS: We utilized Mendelian randomization to assess the causal association between naïve CD4+ T cells and LUAD. Employing a modified single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm with The Cancer Genome Atlas (TCGA) database, we determined the infiltration levels of naïve CD4+ T cells and their differentiation subtypes and investigated their correlation with clinical characteristics. Potential regulatory pathways of T helper cells were identified through Mantel tests and Kyoto Encyclopedia of Genes and Genomes (KEGG) database enrichment analysis. RESULTS: Mendelian randomization analysis revealed an inhibitory effect of naïve CD4+ T cells on LUAD (false discovery rate < 0.05), which was corroborated by observational experiments using TCGA database. Specifically, T helper cell type 2 demonstrated a promotive effect on LUAD in terms of overall, disease-free, and progression-free survival (p < 0.05). Moreover, regulatory T cells exhibited a protective effect on LUAD in terms of disease-specific survival (p < 0.01). Concurrently, we explored the overall impact of naïve CD4+ T cell differentiation subtypes on LUAD, revealing upregulation in pathways such as neutrophil degranulation, MAPK family signaling pathways, and platelet activation, signaling, and aggregation. CONCLUSION: Naïve CD4+ T cells and their differentiated counterparts play essential regulatory roles in the tumor immune microenvironment, demonstrating bidirectionality in their effects.Thus, elucidating the mechanisms and developing novel cell differentiation-inducing agents will benefit anti-cancer therapy.

Effect of indwelling ureteral stents on sexual function: a real-world observational study.

BACKGROUND: Ureteral DJ stents are commonly used devices in urology. However, stent placement may cause LUTS and affect the quality of life. We evaluated the direct relationship between ureteral stents and sexual function. METHODS: From October 2022 to December 2023, 82 male and 90 female sexually active patients who underwent ureteroscopy at Beijing Tiantan Hospital, Capital Medical University, were enrolled. The basic information, surgical data, and two questionnaire data including the International Index of Erectile Function-5 and the Female Sexual Function Index of patients before the operation (baseline, T0), on the day of the ureteral DJ tube extraction (T1), and 4 weeks after ureteral DJ tube extraction (T2) were collected to analyze the changes in the patients' sexual function. RESULTS: The average age of male patients was 36 years and of female patients 39 years. Before the ureteral DJ stent placement, the mean ± SD IIEF-5 score was 22.86 ± 0.91, and the average FSFI score was 31.66 ± 1.44. On the day of the ureteral DJ stent removal, the IIEF-5 score was 16.37 ± 2.62 (p < 0.01) and the FSFI score was 15.83 ± 4.05 (p < 0.01). Four weeks after ureteral DJ stent removal, the average IIEF-5 score was 22.77 ± 1.06 (p = 0.61) and the average FSFI score was 30.99 ± 1.79 (p = 0.78). CONCLUSIONS: Indwelling ureteral stents after ureteroscopy can temporarily affect the sexual function of both male and female patients, typically recovering within 4 weeks after stent removal.

Clinical and structural insights into the rare but oncogenic HER2-activating missense mutations in non-small cell lung cancer: a retrospective ATLAS cohort study.

BACKGROUND: Unlike human epidermal growth factor receptor 2 (HER2) amplification or exon 20 insertions, missense mutations in the extracellular domain (ECD), transmembrane domain (TMD), and intracellular domain (ICD) of the HER2 protein have been implicated as oncogenic in non-small cell lung cancer (NSCLC). However, their molecular subtypes, structural disparities, and clinical responses to current medical treatments, particularly HER2-targeted tyrosine kinase inhibitors (TKIs), remain unclear in NSCLC and warrant investigation. METHODS: A real-world observational ATLAS study was conducted to gather and analyze therapeutic outcomes of chemotherapy or TKIs for heterogeneous HER2 missense mutations in NSCLC. Computational models of typical ECD, TMD, and ICD mutations were utilized to explore their structural variances. RESULTS: We screened 37 eligible patients with HER2-activating missense mutations, of which 35 patients who had received chemotherapy or HER2-targeted TKIs as first-line therapy were available for response assessment. The median progression-free survival (PFS) for chemotherapy was 4.43 months (95% confidence interval [CI], 3.77-5.10), with an objective response rate (ORR) of 26.1% (6/23) and a disease control rate (DCR) of 17/23 (73.9%). The administration of afatinib, dacomitinib, and pyrotinib, HER2-targeted TKIs, achieved a median PFS of 4.65 months, with an ORR of 33.3% (4/12) and a DCR of 83.3% (10/12). Molecular modeling and computational simulations of ECD, TMD, and ICD mutations revealed their distinct structural characteristics. CONCLUSION: In comparison to chemotherapy, HER2-targeted TKIs demonstrated similar activity and PFS benefits for HER2-activating missense mutations in NSCLC.

Wavelength-tunable high-fidelity entangled photon sources enabled by dual Stark effects.

The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits.

Single-Photon Interference over 8.4 km Urban Atmosphere: Toward Testing Quantum Effects in Curved Spacetime with Photons.

The emergence of quantum mechanics and general relativity has transformed our understanding of the natural world significantly. However, integrating these two theories presents immense challenges, and their interplay remains untested. Recent theoretical studies suggest that the single-photon interference covering huge space can effectively probe the interface between quantum mechanics and general relativity. We developed an alternative design using unbalanced Michelson interferometers to address this and validated its feasibility over an 8.4 km free-space channel. Using a high-brightness single-photon source based on quantum dots, we demonstrated single-photon interference along this long-distance baseline. We achieved a phase measurement precision of 16.2 mrad, which satisfied the measurement requirements for a gravitational redshift at the geosynchronous orbit by 5 times the standard deviation. Our results confirm the feasibility of the single-photon version of the Colella-Overhauser-Werner experiment for testing the quantum effects in curved spacetime.

Selection and characterization of spontaneous phage-resistant mutant of Limosilactobacillus fermentum.

Phage infection remains a major cause of fermentation failures in the dairy industry. The development of phage-resistant mutants of important fermentation strains is an effective measure used to address phage-related issues. This study employed the secondary culture method to screen for spontaneous phage-resistant mutants from the phage sensitive strain Limosilactobacillus fermentum IMAU32646 (L. fermentum IMAU32646). The phenotypic characteristics, technological attributes, probiotic characterization, adsorption characteristics and mutant genes were investigated. The results showed that the mutant strain displayed a high degree of phage-resistance and stability. The mutant strain produced more lactic acid during fermentation than the sensitive strain, while maintaining identical cell structure and morphologies. The mutant strain exhibited superior tolerance to acid and bile salts compared to the sensitive strain. Furthermore, the adsorption rate of phage LFP01 on the mutant strain was significantly lower than that of the sensitive strain. Following genome re-sequencing analysis showed that adsorption interference and blocked DNA injection were responsible for its phage-resistance. These results may provide a new strategy for avoiding phage contamination and industrial application of phage-resistant strains with good characteristics.

Rule-based omics mining reveals antimicrobial macrocyclic peptides against drug-resistant clinical isolates.

Antimicrobial resistance remains a significant global threat, driving up mortality rates worldwide. Ribosomally synthesized and post-translationally modified peptides have emerged as a promising source of novel peptide antibiotics due to their diverse chemical structures. Here, we report the discovery of new aminovinyl-(methyl)cysteine (Avi(Me)Cys)-containing peptide antibiotics through a synergistic approach combining biosynthetic rule-based omics mining and heterologous expression. We first bioinformatically identify 1172 RiPP biosynthetic gene clusters (BGCs) responsible for Avi(Me)Cys-containing peptides formation from a vast pool of over 50,000 bacterial genomes. Subsequently, we successfully establish the connection between three identified BGCs and the biosynthesis of five peptide antibiotics via biosynthetic rule-guided metabolic analysis. Notably, we discover a class V lanthipeptide, massatide A, which displays excellent activity against gram-positive pathogens, including drug-resistant clinical isolates like linezolid-resistant S. aureus and methicillin-resistant S. aureus, with a minimum inhibitory concentration of 0.25 µg/mL. The remarkable performance of massatide A in an animal infection model, coupled with a relatively low risk of resistance and favorable safety profile, positions it as a promising candidate for antibiotic development. Our study highlights the potential of Avi(Me)Cys-containing peptides in expanding the arsenal of antibiotics against multi-drug-resistant bacteria, offering promising drug leads in the ongoing battle against infectious diseases.

Highly Stable Cesium Molybdenum Chloride Perovskite Nanocrystals for Photothermal Semihydrogenation Applications.

Metal halide perovskite materials with excellent carrier transport properties have been regarded as a new class of catalysts with great application potential. However, their development is hampered by their instability in polar solvents and high temperatures. Herein, we report a solution-processed Cs2MoCl6 perovskite nanocrystals (NCs) capped with the Mo6+, showing high thermostability in polar solvents. Furthermore, the Pd single atoms (PdSA) can be anchored on the surface of Cs2MoCl6 NCs through the unique coordination structure of Pd-Cl sites, which exhibit excellent semihydrogenation of different alkyne derivatives with high selectivity at full conversion at room temperature. Moreover, the activity could be improved greatly under Xe lamp irradiation. Detailed experimental characterization and DFT calculations indicate the improved activity under light illumination is due to the synergistic effect of photo-to-heat conversion and photoinduced electron transfer from Cs2MoCl6 to PdSA, which facilitates the activation of the C≡C group. This work not only provides a new catalyst for high selective semihydrogenation of alkyne derivatives but also opens a new avenue for metal halides as photothermal catalysts.

Dacomitinib exhibits promising activity against the rare HER2 exon 20 insertion M774delinsWLV in lung cancer: A case report and literature review.

A775_G776insYVMA, the typical and predominant HER2 exon 20 insertion variant in non-small cell lung cancer, exhibits relative insensitivity to covalent HER2-targeted tyrosine kinase inhibitors. However, other less common insertions have shown better responses to HER2-targeted inhibitors. M774delinsWLV is a rare HER2 exon 20 insertion subtype and its clinical sensitivity to HER2-targeted inhibitors remains unclear. Furthermore, there is a lack of current studies to elucidate its structure and predict its sensitivity to HER2-targeted tyrosine kinase inhibitors. Herein, we presented a case of non-small cell lung cancer harboring M774delinsWLV who derived favorable response and significant survival benefit from HER2-targeted tyrosine kinase inhibitors. A 60-year-old male with metastatic lung adenocarcinoma carrying M774delinsWLV received pyrotinib monotherapy as first-line treatment. After rapid disease progression at three months, sequential combination therapy with pyrotinib and bevacizumab yielded promising antitumor activity and sustained progression-free survival benefits for nearly a year. Subsequent dacomitinib monotherapy displayed significant activity against this uncommon insertion, resulting in a rapid decrease in tumor markers and partial response, along with progression-free survival of one year. The molecular simulation revealed no significant differences in the overall protein structure and binding pocket region between M774delinsWLV and the HER2 wild type. Drug binding dynamics simulation indicated that dacomitinib exhibited the most potent binding activity compared to afatinib, pyrotinib and poziotinib. Conclusively, dacomitinib exhibited promising efficacy against the rare HER2 exon 20 insertion M774delinsWLV. Extensive investigation is needed to elucidate the effects of HER2-targeted tyrosine kinase inhibitors on non-small cell lung cancer with different HER2 insertion subtypes.

Experimental Generation of Spin-Photon Entanglement in Silicon Carbide.

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

Phenotypic characterization and genomic analysis of Limosilactobacillus fermentum phage.

Limosilactobacillus (L.) fermentum is widely utilized for its beneficial properties, but lysogenic phages can integrate into its genome and can be induced to enter the lysis cycle under certain conditions, thus accomplishing lysis of host cells, resulting in severe economic losses. In this study, a lysogenic phage, LFP03, was induced from L. fermentum IMAU 32510 by UV irradiation for 70 s. The electron microscopy showed that this phage belonged to Caudoviricetes class. Its genome size was 39,556 bp with a GC content of 46.08%, which includes 20 functional proteins. Compared with other L. fermentum phages, the genome of phage LFP03 exhibited deletions, inversions and translocations. Biological analysis showed that its optimal multiplicity of infection was 0.1, with a burst size of 133.5 ± 4.9 PFU/infective cell. Phage LFP03 was sensitive to temperature and pH value, with a survival rate of 48.98% at 50 °C. It could be completely inactivated under pH 2. The adsorption ability of this phage was minimally affected by temperature and pH value, with adsorption rates reaching 80% under all treated conditions. Divalent cations could accelerate phage adsorption, while chloramphenicol expressed little influence. This study might expand the related knowledge of L. fermentum phages, and provide some theoretical basis for improving the stability of related products and establishing phage control measures.

Triton X-100 enhanced antibacterial effect of photodynamic therapy against Enterococcus faecalis infection: an in vitro study.

Photodynamic therapy (PDT) is an effective method for bacterial infection control in root canals of teeth with a broad-spectrum antibacterial activity. However, its application in root canal treatment is limited due to its inefficiency under hypoxic conditions and dentin staining. Triton X-100 (TX) shows great potential in enhancing the efficiency of antimicrobial agents through improving bacterial membrane permeability. The present study employed a combination of toluidine blue O (TB)-mediated PDT with TX to target the Enterococcus faecalis (E. faecalis), a bacterium with strong resistance to various antibacterial agents and mostly detected in infected root canals. PDT combined with TX showed enhanced antibacterial efficiency against both planktonic cells and biofilms of E. faecalis. At the same time, TX enhanced the antibacterial effect in dentinal tubules and reduced the incubation time. Mechanism studies revealed that TX improved reactive oxygen species (ROS) production through increasing the proportion of TB monomers. Additionally, increased membrane permeability and wettability were also observed. The findings demonstrated the PDT combined with TX could be used as a highly effective method for the root canal disinfection of teeth.

In vitro assessment of thyroid peroxidase inhibition by chemical exposure: comparison of cell models and detection methods.

Disruption of the thyroid hormone (TH) system is connected with diverse adverse health outcomes in wildlife and humans. It is crucial to develop and validate suitable in vitro assays capable of measuring the disruption of the thyroid hormone (TH) system. These assays are also essential to comply with the 3R principles, aiming to replace the ex vivo tests often utilised in the chemical assessment. We compared the two commonly used assays applicable for high throughput screening [Luminol and Amplex UltraRed (AUR)] for the assessment of inhibition of thyroid peroxidase (TPO, a crucial enzyme in TH synthesis) using several cell lines and 21 compounds from different use categories. As the investigated cell lines derived from human and rat thyroid showed low or undetectable TPO expression, we developed a series of novel cell lines overexpressing human TPO protein. The HEK-TPOA7 model was prioritised for further research based on the high and stable TPO gene and protein expression. Notably, the Luminol assay detected significant peroxidase activity and signal inhibition even in Nthy-ori 3-1 and HEK293T cell lines without TPO expression, revealing its lack of specificity. Conversely, the AUR assay was specific to TPO activity. Nevertheless, despite the different specificity, both assays identified similar peroxidation inhibitors. Over half of the tested chemicals with diverse structures and from different use groups caused TPO inhibition, including some widespread environmental contaminants suggesting a potential impact of environmental chemicals on TH synthesis. Furthermore, in silico SeqAPASS analysis confirmed the high similarity of human TPO across mammals and other vertebrate classes, suggesting the applicability of HEK-TPOA7 model findings to other vertebrates.

Triton X-100 counteracts antibiotic resistance of Enterococcus faecalis: An in vitro study.

OBJECTIVES: The high prevalence of antibiotic-resistant bacteria poses a threat to the global public health. The appropriate use of adjuvants to restore the antimicrobial activity of antibiotics against resistant bacteria could be an effective strategy for combating antibiotic resistance. In this study, we investigated the counteraction of Triton X-100 (TX-100) and the mechanisms underlying the antibiotic resistance of Enterococcus faecalis (E. faecalis). METHODS: Standard, wild-type (WT), and induced antibiotic-resistant E. faecalis strains were used in this study. In vitro antibacterial experiments were conducted to evaluate the antimicrobial activities of gentamicin sulfate and ciprofloxacin hydrochloride in the presence and absence of 0.02 % TX-100 against both planktonic and biofilm bacteria. Transcriptomic and untargeted metabolomic analyses were performed to explore the molecular mechanisms of TX-100 as an antibiotic adjuvant. Additionally, membrane permeability, membrane potential, glycolysis-related enzyme activity, intracellular adenosine triphosphate (ATP), and expression levels of virulence genes were assessed. The biocompatibility of different drug combinations was also evaluated. RESULTS: A substantially low TX-100 concentration improved the antimicrobial effects of gentamicin sulfate or ciprofloxacin hydrochloride against antibiotic-resistant E. faecalis. Mechanistic studies demonstrated that TX-100 increased cell membrane permeability and dissipated membrane potential. Moreover, antibiotic resistance and pathogenicity of E. faecalis were attenuated by TX-100 via downregulation of the ABC transporter, phosphotransferase system (PTS), and ATP supply. CONCLUSIONS: TX-100 enhanced the antimicrobial activity of gentamicin sulfate and ciprofloxacin hydrochloride at a low concentration by improving antibiotic susceptibility and attenuating antibiotic resistance and pathogenicity of E. faecalis. CLINICAL SIGNIFICANCE: These findings provide a theoretical basis for developing new root canal disinfectants that can reduce antibiotic resistance.