Syntheses, Structural Analyses, and Properties of Condensed Arenes with Multihelicity.

A C1-symmetric hexapole helicene (HH) and a C3-symmetric dodecapole helicene (DH) were prepared, and their three-dimensional structures were verified by X-ray crystallography and density functional theory calculations. The molecular geometries and local helical configurations of their most stable diastereomers were correctly predicted by arranging suitable conformations of the peripheral aryl rings. Importantly, the outermost three [5]helicenes with a consistent configuration in DH were observed to increase the thermostability, enantiomerization barrier (ΔH⧧ = 40.5 kcal/mol), specific rotation ([α]24D = -4228°) and absorption dissymmetry factor (gabs = 1.35 × 10-3 at 453 nm).

Ultrasound probe enhanced enzymatic hydrolysis for rapid separation of ß2-adrenergic agonists from animal urine and livestock wastewater: Applicability to biomonitoring investigation.

BACKGROUND: An increasing number of ß2-adrenergic agonists are illicitly used for growth promoting and lean meat increasing in animal husbandry in recent years, but the development of analytical methods has lagged behind these emerging drugs. RESULTS: Here, we designed and developed an ultrasound probe enhanced enzymatic hydrolysis reactor for quick separation and simultaneously quantification of 22 ß2-adrenergic agonists in animal urine and livestock wastewater. Owing to the enhancement of the conventional enzymatic digestion through the ultrasound acoustic probe power, only 2 min was required for the comprehensively separation of ß2-adrenergic agonists from the sample matrices, making it a much more desirable alternative tool for high-throughput investigation. The swine, bovine and sheep urines (n = 287), and livestock wastewater (n = 15) samples, collected from both the north and south China, were examined to demonstrate the feasibility and capability of the proposed approach. Six kinds of ß2-adrenergic agonists (clenbuterol, salbutamol, ractopamine, terbutaline, clorprenaline and cimaterol) were found in animal urines, with concentrations ranged between 0.056 µg/L (terbutaline) and 5.79 µg/L (clenbuterol). Up to nine ß2-adrenergic agonists were detected in wastewater samples, of which four were found in swine farms and nine in cattle/sheep farms, with concentration levels from 0.069 µg/L (tulobuterol) to 2470 µg/L (clenbuterol). SIGNIFICANCE: Interestingly, since ß2-adrenergic agonists are usually considered to be abused mainly in the pig farms, our data indicate that both the detection frequencies and concentrations of these agonists in the ruminant farms were higher than the pig farms. Furthermore, the findings of this work indicated that there is a widespread occurrence of ß2-adrenergic agonists in livestock farms, especially for clenbuterol and salbutamol, which may pose both food safety and potential ecological risks. We recommend that stricter controls should be adopted to prevent the illegally usage of these ß2-adrenergic agonists in agricultural animals, especially ruminants, and they should also be removed before discharging to the environment.

Synergistic delivery of hADSC-Exos and antioxidants has inhibitory effects on UVB-induced skin photoaging.

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging. In cellular and 3D skin models, we showed that vitamin E (VE) and hADSC-Exos were optimal anti-photoaging combinations. In vivo, VE and hADSC-Exos increased skin tightening and elasticity in UVB-induced photoaging mice Combined treatment with VE and hADSC-Exos inhibited SIRT1/NF-κB pathway. These findings contribute to the understanding of hADSC-Exos in conjunction with other antioxidants, thereby providing valuable insights for the future pharmaceutical and cosmetic industries.

Annexin A family: A new perspective on the regulation of bone metabolism.

Osteoblast-mediated bone formation and osteoclast-mediated bone resorption are critical processes in bone metabolism. Annexin A, a calcium-phospholipid binding protein, regulates the proliferation and differentiation of bone cells, including bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts, and has gradually become a marker gene for the diagnosis of osteoporosis. As calcium channel proteins, the annexin A family members are closely associated with mechanical stress, which can target annexins A1, A5, and A6 to promote bone cell differentiation. Despite the significant clinical potential of annexin A family members in bone metabolism, few studies have reported on these mechanisms. Therefore, based on a review of relevant literature, this article elaborates on the specific functions and possible mechanisms of annexin A family members in bone metabolism to provide new ideas for their application in the prevention and treatment of bone diseases, such as osteoporosis.

Kernel Masked Image Modeling Through the Lens of Theoretical Understanding.

Masked image modeling (MIM) has been considered as the state-of-the-art (SOTA) self-supervised learning (SSL) technique in terms of visual pretraining. The impressive generalization ability of MIM also paves the way for the remarkable success of large-scale vision foundation models. In this article, we further discuss the validity and advantages of implementing MIM techniques in the reproducing kernel Hilbert spaces (RKHSs) and we associate the analysis with a novel MIM method named R-MIM (short for RKHS-MIM). Through the careful construction of an augmentation graph and by using spectral decomposition techniques, we establish a systematic theoretical understanding between the proposed R-MIM's generalization ability and the choice of kernel function used during training. Specifically, we reach a conclusion that both of the local Lipschitz constant of the resultant R-MIM model and the corresponding expected pretraining error can have a strong composite effect on bounding downstream task error, depending on the kernel options. We demonstrate that under mild mathematical assumptions, R-MIM method is guaranteed to return a lower bound on downstream tasks in comparison to vanilla MIM techniques, such as masked autoencoder (MAE) and SimMIM. Empirical justification well corroborates our theoretical hypothesis and analysis in showing the superior generalization of the proposed R-MIM and the theoretical link to kernel choices. The code is available at: https://github.com/yurui-q/R-MIM.

Pathogenic Detection by Metagenomic Next-generation Sequencing in Skin and Soft Tissue Infection.

BACKGROUND/AIM: Skin and soft tissue infections (SSTIs) can be life-threatening, but the conventional bacterial cultures have low sensitivity and are time-consuming. Metagenomic next-generation sequencing (mNGS) is widely used as a diagnostic tool for detecting pathogens from infection sites. However, the use of mNGS for pathogen detection in SSTIs and related research is still relatively limited. PATIENTS AND METHODS: From January 2020 to October 2021, 19 SSTI samples from 16 patients were collected in a single center (Taichung Veterans General Hospital, Taichung, Taiwan). The clinical samples were simultaneously subjected to mNGS and conventional bacterial culture methods to detect pathogens. Clinical characteristics were prospectively collected through electronic chart review. The microbiological findings from conventional bacterial culture and mNGS were analyzed and compared. RESULTS: The mNGS method detected a higher proportion of multiple pathogens in SSTIs compared to conventional bacterial culture methods. Pseudomonas spp. was among the most commonly identified Gram-negative bacilli using mNGS. Additionally, the mNGS method identified several rare pathogens in patients with SSTIs, including Granulicatella adiacens, Bacillus thuringiensis, and Bacteroides fragilis. Antimicrobial resistance genes were detected in 10 samples (52.6%) using the mNGS method, including genes for extended-spectrum beta-lactamase, Ambler class C ß-lactamases, and carbapenemase. CONCLUSION: mNGS not only plays an important role in the detection of pathogens in soft tissue infections, but also informs clinical professionals about the presence of additional microbes that may be important for treatment decisions. Further studies comparing conventional pathogen culture with the mNGS method in SSTIs are required.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Disease: Success Rate and Complications among Different Patient Populations.

INTRODUCTION: Balloon pulmonary angioplasty (BPA) is an effective intervention for patients with chronic thromboembolic pulmonary disease (CTEPD). We aimed to identify the patient group with a low success rate or high complication rate of BPA, which is still unclear. METHODS: Both CTEPD patients with or without pulmonary hypertension (CTEPH and NoPH-CTEPD) were included. CTEPH patients were divided into groups with or without pulmonary endarterectomy (PEA-CTEPH and NoPEA-CTEPH). The efficacy and safety of BPA were compared among the groups. RESULTS: There were 450, 66, and 41 sessions in the NoPEA-CTEPH, PEA-CTEPH, and NoPH-CTEPD groups, respectively. The success rate (≥1 degree improvement in flow grade) in the PEA-CTEPH group was 94.5%, significantly lower than that in the NoPEA-CTEPH (97.1%) and NoPH-CTEPD (98.4%) groups (p = 0.014). The percentage of complete flow recovery in treated vessels was also lower in PEA-CTEPH group. BPA-related complication rate in NoPEA-CTEPH, PEA-CTEPH, and NoPH-CTEPD patients was 6.1%, 6.0%, and 0.0%, respectively (p = 0.309). One BPA-related death occurred (solely in NoPEA-CTEPH). Mean pulmonary artery pressure ≥41.5 mm Hg was a predictor of BPA-related complications. NoPEA-CTEPH patients had more improvement in 6-min walk distance (6MWD, 87 ± 93 m NoPEA-CTEPH vs. 40 ± 43 m PEA-CTEPH vs. 18 ± 20 m NoPH-CTEPD, p = 0.012). CONCLUSIONS: BPA was safe and effective for all CTEPD groups with less improvement for the PEA-CTEPH and NoPH-CTEPD groups. The success rate of BPA was lower in the PEA-CTEPH group and the complication rate was lower in the NoPH-CTEPD group. Pre-BPA treatment to lower pulmonary artery pressure should not be overlooked in CTEPD patients.

Application of dezocine patient-controlled epidural analgesia in postoperative analgesia in patients with total myomectomy.

BACKGROUND: Uterine fibroids are common benign gynecological conditions. Patients who experience excessive menstruation, anemia, and pressure symptoms should be administered medication, and severe cases require a total hysterectomy. This procedure is invasive and causes severe postoperative pain, which can affect the patient's postoperative sleep quality and, thus, the recovery process. AIM: To evaluate use of dezocine in patient-controlled epidural analgesia (PCEA) for postoperative pain management in patients undergoing total myomectomy. METHODS: We selected 100 patients undergoing total abdominal hysterectomy for uterine fibroids and randomized them into two groups: A control group receiving 0.2% ropivacaine plus 0.06 mg/mL of morphine and an observation group receiving 0.2% ropivacaine plus 0.3 mg/mL of diazoxide in their PCEA. Outcomes assessed included pain levels, sedation, recovery indices, PCEA usage, stress factors, and sleep quality. RESULTS: The observation group showed lower visual analog scale scores, shorter postoperative recovery indices, fewer mean PCEA compressions, lower cortisol and blood glucose levels, and better polysomnographic parameters compared to the control group (P < 0.05). The cumulative incidence of adverse reactions was lower in the observation group than in the control group (P < 0.05). CONCLUSION: Dezocine PCEA can effectively control the pain associated with total myomectomy, reduce the negative impact of stress factors, and have less impact on patients' sleep, consequently resulting in fewer adverse effects.

Circulating inflammatory cytokines influencing schizophrenia: a Mendelian randomization study.

Introduction: Schizophrenia (SCZ) is a severe psychiatric disorder whose pathophysiology remains elusive. Recent investigations have underscored the significance of systemic inflammation, particularly the impact of circulating inflammatory proteins, in SCZ. Methods: This study explores the potential causal association between certain inflammatory proteins and SCZ. Bidirectional Mendelian randomization (MR) analyses were conducted utilizing data from expansive genome-wide association studies (GWAS). Data regarding circulating inflammatory proteins were sourced from the GWAS Catalog database, encompassing 91 inflammatory cytokines. SCZ-related data were derived from the Finngen database, incorporating 47,696 cases and 359,290 controls. Analytical methods such as inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode were employed to evaluate the association between inflammatory cytokines and SCZ. Sensitivity analyses were also performed to affirm the robustness of the results. Results: Following FDR adjustment, significant associations were observed between levels of inflammatory cytokines, including Fibroblast Growth Factor 5 (OR = 1.140, 95%CI = 1.045, 1.243, p = 0.003, FDR=0.015), C-C Motif Chemokine 4 (OR = 0.888, 95%CI = 0.816, 0.967, p = 0.006, FDR = 0.015), C-X-C Motif Chemokine 1 (OR = 0.833, 95%CI = 0.721, 0.962, p = 0.013, FDR = 0.064), and C-X-C Motif Chemokine 5 (OR = 0.870, 95%CI = 0.778, 0.973, p = 0.015, FDR = 0.074), and the risk of SCZ. Conclusion: Our results from MR analysis suggest a potential causal link between circulating inflammatory cytokines and SCZ, thereby enriching our understanding of the interactions between inflammation and SCZ. Furthermore, these insights provide a valuable foundation for devising therapeutic strategies targeting inflammation.

Christensenella minuta Alleviates Acetaminophen-Induced Hepatotoxicity by Regulating Phenylalanine Metabolism.

Acetaminophen (APAP)-induced liver injury (AILI), even liver failure, is a significant challenge due to the limited availability of therapeutic medicine. Christensenella minuta (C. minuta), as a probiotic therapy, has shown promising prospects in metabolism and inflammatory diseases. Our research aimed to examine the influence of C. minuta on AILI and explore the molecular pathways underlying it. We found that administration of C. minuta remarkably alleviated AILI in a mouse model, as evidenced by decreased levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and improvements in the histopathological features of liver sections. Additionally, there was a notable decrease in malondialdehyde (MDA), accompanied by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and superoxide dismutase (SOD) activity. Furthermore, there was a significant reduction in inflammatory markers (IL6, IL1ß, TNF-α). C. minuta regulated phenylalanine metabolism. No significant difference in intestinal permeability was observed in either the model group or the treatment group. High levels of phenylalanine aggravated liver damage, which may be linked to phenylalanine-induced dysbiosis and dysregulation in cytochrome P450 metabolism, sphingolipid metabolism, the PI3K-AKT pathway, and the Integrin pathway. Furthermore, C. minuta restored the diversity of the microbiota, modulated metabolic pathways and MAPK pathway. Overall, this research demonstrates that supplementing with C. minuta offers both preventive and remedial benefits against AILI by modulating the gut microbiota, phenylalanine metabolism, oxidative stress, and the MAPK pathway, with high phenylalanine supplementation being identified as a risk factor exacerbating liver injury.

Hesperetin Alleviated Experimental Colitis via Regulating Ferroptosis and Gut Microbiota.

Hesperetin (HT) is a type of citrus flavonoid with various pharmacological activities, including anti-tumor, anti-inflammation, antioxidant, and neuroprotective properties. However, the role and mechanism of HT in ulcerative colitis (UC) have been rarely studied. Our study aimed to uncover the beneficial effects of HT and its detailed mechanism in UC. Experimental colitis was induced by 2.5% dextran sodium sulfate (DSS) for seven days. HT ameliorated DSS-induced colitis in mice, showing marked improvement in weight loss, colon length, colonic pathological severity, and the levels of TNFα and IL6 in serum. A combination of informatics, network pharmacology, and molecular docking identified eight key targets and multi-pathways influenced by HT in UC. As a highlight, the experimental validation demonstrated that PTGS2, a marker of ferroptosis, along with other indicators of ferroptosis (such as ACSL4, Gpx4, and lipid peroxidation), were regulated by HT in vivo and in vitro. Additionally, the supplement of HT increased the diversity of gut microbiota, decreased the relative abundance of Proteobacteria and Gammaproteobacteria, and restored beneficial bacteria (Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001). In conclusion, HT is an effective nutritional supplement against experimental colitis by suppressing ferroptosis and modulating gut microbiota.

Oxylipin profiling analyses reveal that ω-3 PUFA is more susceptible to lipid oxidation in sheep testis under oxidative stress.

Reactive oxygen species causes oxidative stress, which oxidizes polyunsaturated fatty acids (PUFAs) to form oxidative metabolites. Sertoli cell is an important cellular metabolism of PUFA in testicular cells, and it regulates the testis development and spermatogenesis. However, the oxylipins generated in testes with different developmental statuses are lacking. In this study, twelve 6-month-old Hu sheep were selected and divided into large testicular group (L) and the small testicular group (S) (n=6). UPLC-MS/MS was conducted to screen oxylipins in the testis, and the total oxylipin and ω-3 PUFA-derived oxylipin contents in the S group were higher. A total of 20 differential oxylipins between the two groups were screened. Among them, the contents of ω-3 PUFA, DHA-derived oxylipins were increased in the S group. The arachidonic acid-derived oxylipin was lower in the S group. The mRNA expression levels of genes related to oxylipin regulation (AKR1B1, PTGER2, and PTGDS) were higher in the S group (P < 0.05). In vitro, 200 µM α-linolenic acid alleviated oxidative stress damage to Sertoli cells and improved cell viability by increasing the superoxide dismutase contents and mRNA expression levels of GPX4 and Bcl2. These results indicate that ω-3 PUFA is more susceptible to lipid oxidation in the S group under oxidative stress, which might alleviate the damage of oxidative stress to testis. Moreover, ALA could stimulate the proliferation of Sertoli cells by increasing the capacity of antioxidants. This work may provide a theoretical basis for further studies on the antioxidant properties of the testis for Hu sheep.

Teaching Masked Autoencoder With Strong Augmentations.

Masked autoencoder (MAE) has been regarded as a capable self-supervised learner for various downstream tasks. Nevertheless, the model still lacks high-level discriminability, which results in poor linear probing performance. In view of the fact that strong augmentation plays an essential role in contrastive learning, can we capitalize on strong augmentation in MAE? The difficulty originates from the pixel uncertainty caused by strong augmentation that may affect the reconstruction, and thus, directly introducing strong augmentation into MAE often hurts the performance. In this article, we delve into the potential of strong augmented views to enhance MAE while maintaining MAE's advantages. To this end, we propose a simple yet effective masked Siamese autoencoder (MSA) model, which consists of a student branch and a teacher branch. The student branch derives MAE's advanced architecture, and the teacher branch treats the unmasked strong view as an exemplary teacher to impose high-level discrimination onto the student branch. We demonstrate that our MSA can improve the model's spatial perception capability and, therefore, globally favors interimage discrimination. Empirical evidence shows that the model pretrained by MSA provides superior performances across different downstream tasks. Notably, linear probing performance on frozen features extracted from MSA leads to 6.1% gains over MAE on ImageNet-1k. Fine-tuning (FT) the network on VQAv2 task finally achieves 67.4% accuracy, outperforming 1.6% of the supervised method DeiT and 1.2% of MAE. Codes and models are available at https://github.com/KimSoybean/MSA.

Machine learning-derived prognostic signature for progression-free survival in non-metastatic nasopharyngeal carcinoma.

BACKGROUND: Early detection of high-risk nasopharyngeal carcinoma (NPC) recurrence is essential. We created a machine learning-derived prognostic signature (MLDPS) by combining three machine learning (ML) models to predict progression-free survival (PFS) in patients with non-metastatic NPC. METHODS: A cohort of 653 patients with non-metastatic NPC was divided into a training (n = 457) and validation (n = 196) dataset (7:3 ratio). The study included clinicopathological characteristics, hematologic markers, and MRI findings in three machine learning models-random forest (RF), extreme gradient boosting (XGBoost), and least absolute shrinkage and selection operator (LASSO)-to predict progression-free survival (PFS). A Venn diagram identified the overlapping signatures from the three ML algorithms. Cox proportional hazard analysis determined the MLDPS for PFS. RESULTS: The RF, XGBoost, and LASSO algorithms identified six consensus factors from the 33 signatures. Cox proportional hazards analysis showed that the MLDPS includes age, lymphocyte count, number of positive lymph nodes, and regional lymph node density. Additionally, MLDPS effectively stratified prognosis, with low-risk individuals showing better PFS than high-risk individuals (p < 0.001). CONCLUSION: MLDPS, based on clinicopathological characteristics, hematologic markers, and MRI findings, is crucial for guiding clinical management and personalizing treatments for patients with non-metastatic NPC.

The mechanism of Sangdantongluo granule in treating post-stroke spasticity based on multimodal fMRI combined with TMS: Study protocol.

Introduction: Post-stroke spasticity (PSS) is among the prevalent complications of stroke, greatly affecting motor function recovery and reducing patients' quality of life without timely treatment. Sangdantongluo granule, a modern traditional Chinese patent medicine, has significant clinical efficacy in treating PSS. However, the mechanism of Sangdantongluo granule in treating PSS is still unknown. We designed this study to explore the mechanism of Sangdantongluo granule in treating PSS through multimodal functional magnetic resonance imaging (fMRI) combined with transcranial magnetic stimulation (TMS). Methods and analysis: In a single-center, randomized, double-blind, parallel placebo-controlled study, 60 PSS patients will be recruited in China and randomly assigned to either the experimental or control groups at a ratio of 1:1. For eight weeks, Sangdantongluo granule or placebo will be utilized for intervention. The main outcome is the Modified Ashworth Scale (MAS), the secondary outcome includes the Fugl-Meyer Assessment Scale-upper Extremity (FMA-UE), National Institute of Health Stroke Scale (NIHSS), and Modified Rankin Scale (mRS), the mechanism measure is the changes in cortical excitability and multimodal fMRI at baseline and after eight weeks. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine (approval number: [202364]). Clinical trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2300074793. Registered on 16 August 2023.

Enhancing C2+ product selectivity in CO2 electroreduction by enriching intermediates over carbon-based nanoreactors.

Electrochemical CO2 reduction reaction (CO2RR) to multicarbon (C2+) products faces challenges of unsatisfactory selectivity and stability. Guided by finite element method (FEM) simulation, a nanoreactor with cavity structure can facilitate C-C coupling by enriching *CO intermediates, thus enhancing the selectivity of C2+ products. We designed a stable carbon-based nanoreactor with cavity structure and Cu active sites. The unique geometric structure endows the carbon-based nanoreactor with a remarkable C2+ product faradaic efficiency (80.5%) and C2+-to-C1 selectivity (8.1) during the CO2 electroreduction. Furthermore, it shows that the carbon shell could efficiently stabilize and highly disperse the Cu active sites for above 20 hours of testing. A remarkable C2+ partial current density of-323 mA cm-2 was also achieved in a flow cell device. In situ Raman spectra and density functional theory (DFT) calculation studies validated that the *COatop intermediates are concentrated in the nanoreactor, which reduces the free energy of C-C coupling. This work unveiled a simple catalyst design strategy that would be applied to improve C2+ product selectivity and stability by rationalizing the geometric structures and components of catalysts.

exo-6b2-Methyl-Substituted Pentabenzocorannulene: Synthesis, Structural Analysis, and Properties.

exo-6b2-Methyl-substituted pentabenzocorannulene (exo-PBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π ⋅ ⋅ ⋅ π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone.

Characterization of CRISPR-Cas Systems in Shewanella algae and Shewanella haliotis: Insights into the Adaptation and Survival of Marine Pathogens.

CRISPR-Cas systems are adaptive immune mechanisms present in most prokaryotes that play an important role in the adaptation of bacteria and archaea to new environments. Shewanella algae is a marine zoonotic pathogen with worldwide distribution, which accounts for the majority of clinical cases of Shewanella infections. However, the characterization of Shewanella algae CRISPR-Cas systems has not been well investigated yet. Through whole genome sequence analysis, we characterized the CRISPR-Cas systems in S. algae. Our results indicate that CRISPR-Cas systems are prevalent in S. algae, with the majority of strains containing the Type I-F system. This study provides new insights into the diversity and function of CRISPR-Cas systems in S. algae and highlights their potential role in the adaptation and survival of these marine pathogens.

Two-component system RstAB promotes the pathogenicity of adherent-invasive Escherichia coli in response to acidic conditions within macrophages.

Adherent-invasive Escherichia coli (AIEC) strain LF82, isolated from patients with Crohn's disease, invades gut epithelial cells, and replicates in macrophages contributing to chronic inflammation. In this study, we found that RstAB contributing to the colonization of LF82 in a mouse model of chronic colitis by promoting bacterial replication in macrophages. By comparing the transcriptomes of rstAB mutant- and wild-type when infected macrophages, 83 significant differentially expressed genes in LF82 were identified. And we identified two possible RstA target genes (csgD and asr) among the differentially expressed genes. The electrophoretic mobility shift assay and quantitative real-time PCR confirmed that RstA binds to the promoters of csgD and asr and activates their expression. csgD deletion attenuated LF82 intracellular biofilm formation, and asr deletion reduced acid tolerance compared with the wild-type. Acidic pH was shown by quantitative real-time PCR to be the signal sensed by RstAB to activate the expression of csgD and asr. We uncovered a signal transduction pathway whereby LF82, in response to the acidic environment within macrophages, activates transcription of the csgD to promote biofilm formation, and activates transcription of the asr to promote acid tolerance, promoting its replication within macrophages and colonization of the intestine. This finding deepens our understanding of the LF82 replication regulation mechanism in macrophages and offers new perspectives for further studies on AIEC virulence mechanisms.

Metal-polyphenol coordination nanosheets with synergistic peroxidase-like and photothermal properties for efficient antibacterial treatment.

Bacterial infections pose a serious threat to human health and socioeconomics worldwide. In the post-antibiotic era, the development of novel antimicrobial agents remains a challenge. Polyphenols are natural compounds with a variety of biological activities such as intrinsic antimicrobial activity and antioxidant properties. Metal-polyphenol obtained by chelation of polyphenol ligands with metal ions not only possesses efficient antimicrobial activity but also excellent biocompatibility, which has great potential for application in biomedical and food packaging fields. Herein, we developed metal-polyphenol coordination nanosheets named copper oxidized tannic acid quinone (CuTAQ) possessing efficient antibacterial and anti-biofilm effects, which was synthesized by a facile one-pot method. The synthesis was achieved by chelation of partially oxidized tannic acid (TA) with Cu2+ under mild conditions, which supports low-cost and large-scale production. It was demonstrated that CuTAQ exhibited high antibacterial activity via disrupting the integrity of bacterial cell membranes, inducing oxidative stress, and interfering with metabolism. In addition, CuTAQ exhibits excellent peroxidase catalytic activity and photothermal conversion properties, which play a significant role in enhancing its bactericidal and biofilm scavenging abilities. This study provides insights for rational design of innovative metal-polyphenol nanomaterials with efficient antimicrobial properties.