A Multifunctional Hydrogel Fabricated by Direct Self-Assembly of Natural Herbal Small Molecule Mangiferin for Treating Diabetic Wounds.

Clinical studies have continually referred to the involvement of drug carrier having dramatic negative influences on the biocompatibility, biodegradability, and loading efficacy of hydrogel. To overcome this deficiency, researchers have proposed to directly self-assemble natural herbal small molecules into a hydrogel without any structural modification. However, it is still a formidable challenge due to the high requirements on the structure of natural molecules, leading to a rarity of this type of hydrogel. Mangiferin (MF) is a natural polyphenol of C-glucoside xanthone with various positive health benefits, including the treatment of diabetic wounds, but its poor hydrosolubility and low bioavailability significantly restrict the clinical application. Inspired by these, with heating/cooling treatment, a carrier-free hydrogel (MF-gel) is developed by assembling the natural herbal molecule mangiferin, which is mainly governed through hydrogen bonds and intermolecular π-π stacking interactions. The as-prepared hydrogel has injectable and self-healing properties and shows excellent biocompatibility, continuous release ability, and reversible stimuli-responsive performances. All of the superiorities enable the MF-based hydrogel to serve as a potential wound dressing for treating diabetic wounds, which was further confirmed by both the vitro and vivo studies. In vitro, the MF-gel could promote the migration of healing-related cells from peripheral as well as the angiogenesis and displays the capacity of mediating inflammation response by scavenging the intracellular ROS. In vivo, the MF-gel accelerates wound contraction and healing via inflammatory adjustment, collagen deposition, and angiogenesis. This study provides a facile and effective method for diabetic wound management and emphasizes the direct self-assembly hydrogel from natural herbal small molecule.

Reactive oxygen species-scavenging nanomaterials for the prevention and treatment of age-related diseases.

With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications.

Towards prolonging ovarian reproductive life: Insights into trace elements homeostasis.

Ovarian aging is marked by a reduction in the quantity and quality of ovarian follicles, leading to a decline in female fertility and ovarian endocrine function. While the biological characteristics of ovarian aging are well-established, the exact mechanisms underlying this process remain elusive. Recent studies underscore the vital role of trace elements (TEs) in maintaining ovarian function. Imbalances in TEs can lead to ovarian aging, characterized by reduced enzyme activity, hormonal imbalances, ovulatory disorders, and decreased fertility. A comprehensive understanding of the relationship between systemic and cellular TEs balance and ovarian aging is critical for developing treatments to delay aging and manage age-related conditions. This review consolidates current insights into TEs homeostasis and its impact on ovarian aging, assesses how altered TEs metabolism affects ovarian aging, and suggests future research directions to prolong ovarian reproductive life. These studies are expected to offer novel approaches for mitigating ovarian aging.

Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1.

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.

Efficacy of Da Vinci Robot-assisted Thoracoscopic Surgery in Children With Congenital Cystic Adenomatiod Malformation.

BACKGROUND: Surgical intervention is advisable for both asymptomatic and symptomatic CCAM children. This study aims to compare and analyze the efficacy of thoracoscopic and Da Vinci robot-assisted procedures in the management of CCAM among pediatric patients. METHODS: The clinical data of 188 pediatric patients diagnosed with CCAM and admitted to the Children's Hospital, Zhejiang University School of Medicine, from April 2019 to April 2023 were retrospectively analyzed. The Clavien-Dindo classification was employed for the systematic categorization of postoperative complications. RESULTS: The demographic and clinical characteristics of the patients were comparable between the two groups. Postoperative outcomes, such as the chest tube indwelling rate (92.6% vs 36.2%, p < 0.001∗), chest tube duration (2.0 (2.0-3.0) days vs 1.0 (1.0-2.0) days, p < 0.001∗), and length of postoperative hospital stay (6.0 (5.0-7.0) days vs 5.0 (5.0-6.0) days, p < 0.001∗), favored RATS over VATS. Additionally, there was no significant difference in complications between the two group, but the p-value is in a critical state. Ⅲa complications (mainly composed of postoperative thoracentesis procedures) manifesting as a higher rate in the RATS, nearly double that observed in the VATS. CONCLUSIONS: Robot-assisted thoracoscopic lung resection is demonstrated to be safe and feasible, with notable advantages in short-term postoperative clinical outcomes. Nevertheless, the practicality and long-term benefits of this technique necessitate further refinement and dedicated study. LEVEL OF EVIDENCE: LEVEL III.

Thermoelectric Properties of Zn-Doped YbMg1.85-xZnxBi1.98.

Bi-based YbMg2Bi1.98 Zintl compounds represent promising thermoelectric materials. Precise composition and appropriate doping are of great importance for this complex semiconductor. Here, the influence of Zn substitution for Mg on the microstructure and thermoelectric properties of p-type YbMg1.85-xZnxBi1.98 (x = 0, 0.05, 0.08, 0.13, 0.23) was investigated. Polycrystalline samples were prepared using induction melting and densified with spark plasma sintering. X-ray diffraction confirmed that the major phase of the samples possesses the trigonal CaAl2Si2-type crystal structure, and SEM/EDS indicated the presence of minor secondary phases. The electrical conductivity increases and the lattice thermal conductivity decreases with more Zn doping in YbMg1.85-xZnxBi1.98, whereas the Seebeck coefficient has a large reduction. The band gap decreases with increasing Zn concentration and leads to bipolar conduction, resulting in an increase in the thermal conductivity at higher temperatures. Figure of merit ZT values of 0.51 and 0.49 were found for the samples with x = 0 and 0.05 at 773 K, respectively. The maximum amount of Zn doping is suggested to be less than x = 0.1.

Multiomics insights into the female reproductive aging.

The human female reproductive lifespan significantly diminishes with age, leading to decreased fertility, reduced fertility quality and endocrine function disorders. While many aspects of aging in general have been extensively documented, the precise mechanisms governing programmed aging in the female reproductive system remain elusive. Recent advancements in omics technologies and computational capabilities have facilitated the emergence of multiomics deep phenotyping. Through the application and refinement of various high-throughput omics methods, a substantial volume of omics data has been generated, deepening our comprehension of the pathogenesis and molecular underpinnings of reproductive aging. This review highlights current and emerging multiomics approaches for investigating female reproductive aging, encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics. We elucidate their influence on fundamental cell biology and translational research in the context of reproductive aging, address the limitations and current challenges associated with multiomics studies, and offer a glimpse into future prospects.

How probiotics, prebiotics, synbiotics, and postbiotics prevent dental caries: an oral microbiota perspective.

Dental caries, a highly prevalent oral disease, impacts a significant portion of the global population. Conventional approaches that indiscriminately eradicate microbes disrupt the natural equilibrium of the oral microbiota. In contrast, biointervention strategies aim to restore this balance by introducing beneficial microorganisms or inhibiting cariogenic ones. Over the past three decades, microbial preparations have garnered considerable attention in dental research for the prevention and treatment of dental caries. However, unlike related pathologies in the gastrointestinal, vaginal, and respiratory tracts, dental caries occurs on hard tissues such as tooth enamel and is closely associated with localized acid overproduction facilitated by cariogenic biofilms. Therefore, it is insufficient to rely solely on previous mechanisms to delineate the role of microbial preparations in the oral cavity. A more comprehensive perspective should involve considering the concepts of cariogenic biofilms. This review elucidates the latest research progress, mechanisms of action, challenges, and future research directions regarding probiotics, prebiotics, synbiotics, and postbiotics for the prevention and treatment of dental caries, taking into account the unique pathogenic mechanisms of dental caries. With an enhanced understanding of oral microbiota, personalized microbial therapy will emerge as a critical future research trend.

Influence of hydrogen bonds on the reaction of guanine and hydroxyl radical: DFT calculations in C(H+)GC motif.

A comprehensive theoretical investigation was performed to illuminate the influence of hydrogen bonds (H-bonds) on the obscure reaction of a hydroxyl radical (HO˙) and guanine (G) by selecting the building block of parallel triplex DNA, C(H+)GC, as the model. By mapping the energy profiles for addition and hydrogen abstraction reactions, the favorable pathway is predicted. The results reveal that in the C(H+)GC context, barrierless hydrogen abstraction from N2 of G leading to a neutral radical G(N2-H)˙ appears to become significant, but electrophilic attack by HO˙ on C8 of G resulting in 8-oxoG is the most thermodynamically favorable course. This shows a strong structural dependence due to the context constrained by the H-bond, which is dramatically different from the situation in unencumbered G. More interestingly, it proves that the stability order of resulting adduct radicals is not altered by H-bonding, but the activity for possible sites of the hydroxylation reaction changes. The significant influence of the H-bond on elementary reactions involved in the reaction is emphasized in the C(H+)GC context but is not restricted to the H-abstraction reaction. It is greatly anticipated that the present study could provide thoughtful insights into the vague hydroxyl radical-induced oxidation chemistry.

Chitosan-coated artesunate protects against ulcerative colitis via STAT6-mediated macrophage M2 polarization and intestinal barrier protection.

Oral delivery of chitosan-coated artesunate (CPA) has been proven to be effective at preventing ulcerative colitis (UC) in mice. However, the anti-inflammatory mechanism is not fully understood. STAT6 is a key transcription factor that promotes anti-inflammatory effects by inducing M2 and Th2 dominant phenotypes, therefore we hypothesized STAT6 might play a key role in the process. To prove it, a STAT6 gene knockout macrophage cell line (STAT6-/- RAW264.7, by CRISPR/Cas9 method), and its corresponding Caco-2/RAW264.7 co-culture system combined with the STAT6 inhibitor (AS1517499, AS) in a mouse UC model were established and studied. The results showed that CPA remarkably suppressed the activation of TLR-4/NF-κB pathway and the mRNA levels of proinflammatory cytokines, while increased the IL-10 levels in RAW264.7. This effect of CPA contributed to the protection of the ZO-1 in Caco-2 which was disrupted upon the stimulation to macrophages. Simultaneously, CPA reduced the expression of CD86 but increase the expression of CD206 and p-STAT6 in LPS-stimulated RAW264.7 cells. However, above alterations were not obvious as in STAT6-/- RAW264.7 and its co-culture system, suggesting STAT6 plays a key role. Furthermore, CPA treatment significantly inhibited TLR-4/NF-κB activation, intestinal macrophage M1 polarization and mucosal barrier injury induced by DSS while promoted STAT6 phosphorylation in the UC mouse model, but this effect was also prominently counteracted by AS. Therefore, our data indicate that STAT6 is a major regulator in the balance of M1/M2 polarization, intestinal barrier integrity and then anti-colitis effects of CPA. These findings broaden our understanding of how CPA fights against UC and imply an alternative treatment strategy for UC via this pathway.

Cancer-Associated Fibroblast Mimetic AIE Probe for Precision Imaging-Guided Full-Cycle Management of Ovarian Cancer Surgery.

Fluorescence imaging can improve surgical accuracy in ovarian cancer, but a high signal-to-noise ratio is crucial for tiny metastatic cancers. Meanwhile, intraoperative fluorescent surgical navigation modalities alone are still insufficient to completely remove ovarian cancer lesions, and the recurrence rate remains high. Here, we constructed a cancer-associated fibroblasts (CAFs)-mimetic aggregation-induced emission (AIE) probe to enable full-cycle management of surgery that eliminates recurrence. AIE molecules (P3-PPh3) were packed in hollow mesoporous silica nanoparticles (HMSNs) to form HMSN-probe and then coated with a CAFs membrane to prepare CAF-probe. First, due to the negative potential of the CAF-probe, the circulation time in vivo is elevated, which facilitates passive tumor targeting. Second, the CAF-probe avoids its clearance by the immune system and improves the bioavailability. Finally, the fibronectin on the CAF-probe specifically binds to integrin α-5 (ITGA5), which is highly expressed in ovarian cancer cells, enabling fluorescence imaging with a contrast of up to 8.6. CAF-probe-based fluorescence imaging is used to evaluate the size and location of ovarian cancer before surgery (preoperative evaluation), to guide tumor removal during surgery (intraoperative navigation), and to monitor tumor recurrence after surgery (postoperative monitoring), ultimately significantly improving the efficiency of surgery and completely eliminating tumor recurrence. In conclusion, we constructed a CAFs mimetic AIE probe and established a full-cycle surgical management model based on its precise imaging properties, which significantly reduced the recurrence of ovarian cancer.

The synergy of tea tree oil nano-emulsion and antibiotics against multidrug-resistant bacteria.

AIMS: We determined the synergistic effects of tea tree essential oil nano-emulsion (nanoTTO) and antibiotics against multidrug-resistant (MDR) bacteria in vitro and in vivo. Then, the underlying mechanism of action of nanoTTO was investigated. METHODS AND RESULTS: Minimum inhibitory concentrations and fractional inhibitory concentration index (FICI) were determined. The transepithelial electrical resistance (TEER) and the expression of tight junction (TJ) protein of IPEC-J2 cells were measured to determine the in vitro efficacy of nanoTTO in combination with antibiotics. A mouse intestinal infection model evaluated the in vivo synergistic efficacy. Proteome, adhesion assays, quantitative real-time PCR, and scanning electron microscopy were used to explore the underlying mechanisms. Results showed that nanoTTO was synergistic (FICI ≤ 0.5) or partial synergistic (0.5 < FICI < 1) with antibiotics against MDR Gram-positive and Gram-negative bacteria strains. Moreover, combinations increased the TEER values and the TJ protein expression of IPEC-J2 cells infected with MDR Escherichia coli. The in vivo study showed that the combination of nanoTTO and amoxicillin improved the relative weight gain and maintained the structural integrity of intestinal barriers. Proteome showed that type 1 fimbriae d-mannose specific adhesin of E. coli was downregulated by nanoTTO. Then, nanoTTO reduced bacterial adhesion and invasion and inhibited the mRNA expression of fimC, fimG, and fliC, and disrupted bacterial membranes.

Theoretical insights into the reaction mechanism of hydroxyl radicals and guanine in G-quadruplex DNA.

A DFT investigation was performed to illuminate the obscure mechanism of hydroxyl radical (OH˙) and guanine in G-quadruplex by mapping the energy profiles for both addition and hydrogen abstraction reactions. Results revealed that in G-quadruplex, the electrophilic attack of OH˙ to C8 (G) leading to 8-oxoG is the most energetically favorable course, where direct hydrogen abstraction from N2 of G to furnish neutral radicals could compete with that. Although the addition of OH˙ to C4 and C5 positions could provide stable OH-adducts, the subsequent dehydration of C4-OH adduct and hydrogen transfer of C5-OH adduct, which is a prerequisite for neutral radical formation, is rate-limited due to the high barrier manifesting the inaccessibility for these courses. Intriguingly, the identity of the decisive neutral radical was confirmed to be G(N2-H)˙ rather than the familiar G(N1-H)˙, where the hydrogen bond plays significant roles by blocking tautomerizations.

Highly sensitive and ratiometric detection of nitrite in food based on upconversion-carbon dots nanosensor.

Nitrite (NO2-) is extensively found in the daily dietary environment. However, consuming too much NO2- can pose serious health risks. Thus, we designed a NO2--activated ratiometric upconversion luminescence (UCL) nanosensor which could realize NO2- detection via the inner filter effect (IFE) between NO2--sensitive carbon dots (CDs) and upconversion nanoparticles (UCNPs). Due to the exceptional optical properties of UCNPs and the remarkable selectivity of CDs, the UCL nanosensor exhibited a good response to NO2-. By taking advantage of NIR excitation and ratiometric detection signal, the UCL nanosensor could eliminate the autofluorescence thereby increasing the detection accuracy effectively. Additionally, the UCL nanosensor proved successful in detecting NO2- quantitatively in actual samples. The UCL nanosensor provides a simple as well as sensitive sensing strategy for NO2- detection and analysis, which is anticipated to extend the utilization of upconversion detection in food safety.

Health Care-Seeking Behaviors, Disease Progression, Medications, Knowledge of, and Attitudes Toward Systemic Lupus Erythematosus in China: Cross-sectional Survey Study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease involving multiple organs throughout the body. The health care-seeking behaviors, disease progression of SLE, and patients' knowledge of and attitudes toward SLE have not been characterized in China. OBJECTIVE: The aim of this study was to depict the health care-seeking behaviors, disease progression, and medications in patients with SLE and to examine the factors associated with their disease flares, knowledge, and attitudes toward SLE in China. METHODS: We conducted a cross-sectional survey in 27 provinces in China. Descriptive statistical methods were used to depict the demographic characteristics, health care-seeking behaviors, medications, and health status. Multivariable logistic regression models were used to identify the factors associated with disease flares, medication changes, and attitudes toward SLE. An ordinal regression model was used to examine the factors associated with the knowledge of the treatment guidelines. RESULTS: We recruited 1509 patients with SLE, and 715 had lupus nephritis (LN). Approximately 39.96% (603/1509) of the patients with SLE were primarily diagnosed with LN, and 12.4% (112/906) developed LN (mean time 5.2 years) from non-LN. Patients whose registered permanent residences or workplaces in other cities from the same province and adjacent provinces seeking health care accounted for 66.9% (569/850) and 48.8% (479/981) of the patients with SLE in the provincial capital cities, respectively. Mycophenolate mofetil was the most commonly used immunosuppressive drug in patients without LN (185/794, 23.3%) and patients with LN (307/715, 42.9%). Femoral head necrosis (71/228, 31.1%) and hypertension (99/229, 43.2%) were the most common adverse event (AE) and chronic disease during treatment, respectively. Change of hospitals for medical consultation (odds ratio [OR] 1.90, 95% CI 1.24-2.90) and development of 1 chronic disease (OR 3.60, 95% CI 2.04-6.24) and AE (OR 2.06, 95% CI 1.46-2.92) and more were associated with disease flares. A pregnancy plan (OR 1.58, 95% CI 1.18-2.13) was associated with changes in medication. Only 242 (16.03%) patients with SLE were familiar with the treatment guidelines, and patients with LN tended to be more familiar with the disease (OR 2.20, 95% CI 1.81-2.68). After receiving treatment, 891 (59.04%) patients changed their attitudes toward SLE from fear to acceptance, and patients with college education or higher (OR 2.09, 95% CI 1.10-4.04) were associated with a positive attitude toward SLE. CONCLUSIONS: A large proportion of patients seeking health care in the provincial capital cities of China migrated from other cities. Persistent monitoring of potential AEs and chronic diseases during SLE treatment and managing patients who changed hospitals for medical consultation are essential for controlling disease flares. Patients had insufficient knowledge about SLE treatment guidelines and would benefit from health education to maintain a positive attitude toward SLE.

Microneedle Device Delivering Aggregation-Induced Emission Photosensitizers for Enhanced Metronomic Photodynamic Therapy of Cancer.

Metronomic photodynamic therapy (mPDT), which induces cancer cell death by prolonged intermittent continuous irradiation at lower light power, has profoundly promising applications. However, the photobleaching sensitivity of the photosensitizer (PS) and the difficulty of delivery pose barriers to the clinical application of mPDT. Here, we constructed a microneedle-based device (Microneedles@AIE PSs) that combined with aggregation-induced emission (AIE) PSs to achieve enhanced mPDT for cancer. Due to the strong anti-photobleaching property of the AIE PS, it can maintain superior photosensitivity even after long-time light exposure. The delivery of the AIE PS to the tumor through a microneedle device allows for greater uniformity and depth. This Microneedles@AIE PSs-based mPDT (M-mPDT) offers better treatment outcomes and easier access, and combining M-mPDT with surgery or immunotherapy can also significantly improve the effectiveness of these clinical therapies. In conclusion, M-mPDT offers a promising strategy for the clinical application of PDT due to its better efficacy and convenience.

Semaphorin 4C regulates ovarian steroidogenesis through RHOA/ROCK1-mediated actin cytoskeleton rearrangement.

Semaphorins are a family of evolutionarily conserved morphogenetic molecules that were initially found to be associated with axonal guidance. Semaphorin 4C (Sema4C), a member of the fourth subfamily of semaphorins, has been demonstrated to play multifaceted and important roles in organ development, immune regulation, tumor growth, and metastasis. However, it is completely unknown whether Sema4C is involved in the regulation of ovarian function. We found that Sema4C was widely expressed in the stroma, follicles, and corpus luteum of mouse ovaries, and its expression was decreased at distinct foci in ovaries of mice of mid-to-advanced reproductive age. Inhibition of Sema4C by the ovarian intrabursal administration of recombinant adeno-associated virus-shRNA significantly reduced oestradiol, progesterone, and testosterone levels in vivo. Transcriptome sequencing analysis showed changes in pathways related to ovarian steroidogenesis and the actin cytoskeleton. Similarly, knockdown of Sema4C by siRNA interference in mouse primary ovarian granulosa cells or thecal interstitial cells significantly suppressed ovarian steroidogenesis and led to actin cytoskeleton disorganization. Importantly, the cytoskeleton-related pathway RHOA/ROCK1 was simultaneously inhibited after the downregulation of Sema4C. Furthermore, treatment with a ROCK1 agonist after siRNA interference stabilized the actin cytoskeleton and reversed the inhibitory effect on steroid hormones described above. In conclusion, Sema4C may play an important role in ovarian steroidogenesis through regulation of the actin cytoskeleton via the RHOA/ROCK1 signaling pathway. These findings shed new light on the identification of dominant factors involved in the endocrine physiology of female reproduction.

Microenvironmentally Responsive Chemotherapeutic Prodrugs and CHEK2 Inhibitors Self-Assembled Micelles: Protecting Fertility and Enhancing Chemotherapy.

Chemotherapy is a widely used and effective adjuvant treatment for cancer, and it has unavoidable damage to female fertility, with statistics showing 38% of women who have received chemotherapy are infertile. How to reduce fertility toxicity while enhancing the oncologic chemotherapy is a clinical challenge. Herein, co-delivery micelles (BML@PMP) are developed, which are composed of a reduction-sensitive paclitaxel prodrug (PMP) for chemotherapy and a CHEK2 inhibitor (BML277) for both fertility protection and chemotherapy enhancement. BML@PMP achieves fertility protection through three actions: (1) Due to the enhanced permeability and retention (EPR) effect, BML@PMP is more enriched in the tumor, while very little in the ovary (about 1/10th of the tumor). (2) Glutathione (GSH) triggers the release of PTX, and with low levels of GSH in the ovary, the amount of PTX released in the ovary is correspondingly reduced. (3) BML277 inhibits oocyte apoptosis by inhibiting the CHEK2-TAp63α pathway. Because of the different downstream targets of CHEK2 in tumor cells and oocytes, BML277 also enhances chemotherapeutic efficacy by reducing DNA damage repair which is activated through the CHEK2 pathway. This bidirectional effect of CHEK2 inhibitor-based co-delivery system represents a promising strategy for improving oncology treatment indices and preventing chemotherapy-associated fertility damage.

Tea tree oil nanoliposomes: optimization, characterization, and antibacterial activity against Escherichia coli in vitro and in vivo.

The purpose of this study was to formulate tee tree oil nanoliposomes (TTONL) and evaluate its characterization and antibacterial activity. TTONL was prepared by thin film hydration and sonication technique, and the preparation conditions were optimized by Box-behnken response surface method. The characterization (morphology, size, zeta potential, and stability) and antibacterial activity of TTONL against Escherichia coli (E. coli) in vitro and in vivo were evaluated. The optimal preparation conditions for TTONL: lecithin to cholesterol mass ratio of 3.7:1, TTO concentration of 0.5%, and pH of the hydration medium of 7.4, which resulted in a TTONL encapsulation rate of 80.31 ± 0.56%. TTONL was nearly spherical in shape and uniform in size, and the average particle size was 227.8 ± 25.3 nm with negative charge. The specific disappearance of the TTO peak in the infrared spectrum suggested the successful preparation of TTONL, which showed high stability at 4°C within 35 d. The result of MIC test found that the nanoliposomes improved antibacterial activity of TTO against various E. coli strains. TTONL exposure in vitro caused different degrees of structural damage to the E. coli. TTONL by oral administration alleviated the clinical symptoms and intestinal lesion of chickens induced with E. coli challenge. Furthermore, TTONL treatment remarkably lowered the mRNA expression of NLRP3 and NF-κB (p65) in the duodenum and cecum of E. coli-infected chickens. In conclusion, the prepared TTONL had good stability and slow-release property with dose-dependent inhibition and killing effects on different strains of E. coli, and exerted a preventive role against chicken colibacillosis through inhibition.

An Exploration of the Transformation of the 8-Oxo-7,8-Dihydroguanine Radical Cation to Protonated 2-Amino-5-Hydroxy-7,9-Dihydropurine-6,8-Dione in a Base Pair.

A theoretical investigation was performed to disclose the transformation mechanism of 8-oxo-7,8-dihydroguanine radical cation (8-oxoG⋅+ ) to protonated 2-amino-5-hydroxy-7,9-dihydropurine-6,8-dione (5-OH-8-oxoG) in base pair. The energy profiles for three possible pathways of the events were mapped. It is shown that direct loss of H7 from base paired 8-oxoG⋅+ is the only energetically favorable pathway to generate neutral radical, 8-oxoG(-H7)⋅. Further oxidation of 8-oxoG(-H7)⋅ : C to 8-oxoG(-H7)+ : C is exothermic. However, the 8-oxoG(-H7)+ : C deprotonation from all possible active sites is infeasible, indicating the inaccessible second proton loss and the lack of essential intermediate 2-amino-7,9-dihydropurine-6,8-dione (8-oxoGOX ). This makes 8-oxoG(-H7)+ act as the precursor of hydration leading to the generation of protonated 5-HO-8-oxoG by stepwise fashion in base pair, which would initiate the step down guanidinohydantoin (Gh) pathway. These results clearly specify the structure-dependent transformation for 8-oxoG⋅+ and verify the emergence of protonated 5-HO-8-oxoG in base pair.