Automated endometrial identification and volume calculation in normal uteri using a novel smart ERA technique.

To evaluate the repeatability of a novel automated technique called Smart ERA (Smart Endometrial Receptivity Analysis) for the automated segmentation and volume calculation of the endometrium in patients with normal uteri,, and to compare the agreement of endometrial volume measurements between Smart ERA, the semi-automated Virtual Organ Computer-aided Analysis (VOCAL) technique and manual segmentation. This retrospective study evaluated endometrial volume measurement in infertile patients who underwent frozen-thawed embryo transfer (FET). Transvaginal three-dimensional ultrasound scans were performed using a Resona R9 ultrasound machine. Data was collected from patients between 2021 and 2022. Patients with normal uteri and optimal ultrasound images were included. Endometrial volumes were measured using Smart ERA, VOCAL at 15° rotation, and manual segmentation. Intra-observer repeatability and agreement between techniques were assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. A total of 407 female patients were evaluated (mean age 33.2 ± 4.7 years). The repeatability of Smart ERA showed an ICC of 0.983 (95% CI 0.984-0.991). The agreement between Smart ERA and the manual method, Smart ERA and VOCAL, and VOCAL and the manual method, as assessed by ICC, were 0.986 (95% CI 0.977-0.990), 0.943 (95% CI 0.934-0.963), and 0.951 (95% CI 0.918-0.969), respectively. The Smart ERA technique required approximately 3 s for endometrial volume calculation, while VOCAL took around 5 min and the manual segmentation method took approximately 50 min. The Smart-ERA software, which employs a novel three-dimensional segmentation algorithm, demonstrated excellent intra-observer repeatability and high agreement with both VOCAL and manual segmentation for endometrial volume measurement in women with normal uteri. However, these findings should be interpreted with caution, as the algorithm's performance may not be generalizable to populations with different uterine characteristic. Additionally, Smart ERA required significantly less time compared to VOCAL and manual segmentation.

Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

Inhibition of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptors Ameliorates Atrial Inflammation and Vulnerability to Atrial Fibrillation in Rats with Anxiety Disorders.

ABSTRACT: Previous studies have found that anxiety disorders may increase the incidence of atrial fibrillation (AF). More and more studies have shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are involved in the occurrence and development of cardiovascular diseases. However, the role of AMPARs in AF associated with anxiety disorder remains unclear. The aim of this study was to investigate the effect of AMPARs on AF susceptibility in rats with anxiety disorder and its possible mechanism. The anxiety disorder rat model was established by unpredictable empty bottle stimulation and was treated with AMPARs agonist and antagonist. Our results showed that AMPARs antagonist treatment significantly reduced sympathetic activity, improved heart rate variability, shortened action potential duration, prolonged effective refractory period, reduced AF induction rate, and improved cardiac electrical remodeling and the expression of inflammatory factors. In addition, inhibition of AMPARs reduced the phosphorylation of IκBα and p65. Our experimental results suggest that inhibition of AMPARs can reduce autonomic remodeling, improve atrial electrical remodeling, and suppress myocardial inflammation, which provides a potential therapeutic strategy for the treatment of AF associated with anxiety disorder.

1q jumping translocation as a biomarker in myeloid malignancy: frequently mutated genes associated with bad prognosis and low survival.

1q jumping translocation (JT) is rare and its molecular profiles in myeloid malignancies are not well-known. This study evaluated gene mutations in 1q-JT cohorts (0.38%) from hematological malignant specimens that underwent genetic analysis at the Johns Hopkins Hospital (n = 11,908) and the MD Anderson Cancer Center. 1q-JT had frequent mutations in eleven genes, most of which are associated with worse prognosis. BCOR mutations significantly co-occurred with others. Patients tended to have mutations in DNA-repair, spliceosome, and epigenetic modification pathways, though genes utilized within each of these pathways were not randomly distributed. Multi-, albeit overlapping, pathway interruptions tended to manifest in mutations of two gene sets. One gene set consisted of SF3B1 (spliceosome) and TET2 (epigenetic modification), while the other consisted of STAG2 (DNA repair), SRSF2, U2AF (spliceosome), ASXL1, KMT2D (epigenetic modification), BCOR, and GATA2 (transcription factors). An "intermediate" JT-like rearrangement may represent an early sign of occurring 1q-JT. Treatments (hypomethylating agents) and unique structures of the short arms of acrocentric chromosomes may contribute to 1q-JT formation in myeloid malignancies. The median overall survival after identification of a JT was 10 months (95% confidence interval, 5-15 months). Our cohort represents the largest number of myeloid malignancies from multi-centers with before and after the 1q-JT event analyzed to date. Overall, this study identified specific molecular profiles that are associated with 1q-JT in myeloid malignancies. 1q-JT could serve as a poor prognosis biomarker in myeloid malignancies, which could be important in making well-informed clinical decisions and treatment strategies.

ERBB2/ ERBB3-mutated S100/ SOX10-positive unclassified high-grade uterine sarcoma: first detailed description of a novel entity.

With the increasing use of innovative next generation sequencing (NGS) platforms in routine diagnostic and research settings, the genetic landscape of uterine sarcomas has been dynamically evolving during the last two decades. Notably, the majority of recently recognized genotypes in uterine sarcomas represent gene fusions, while recurrent oncogene mutations of diagnostic and/ or therapeutic value have been rare. Recently, a distinctive aggressive uterine sarcoma expressing S100 and SOX10, but otherwise lacking diagnostic morphological, immunophenotypic and molecular features of other uterine malignancies has been presented in a scientific abstract form (USCAP, 2023), but detailed description and delineation of the entity is still missing. We herein describe two high-grade unclassified uterine sarcomas characterized by spindle to round cell morphology and diffuse expression of S100 and SOX10, originating in the uterine body and cervix of 53- and 45-year-old women and carrying an ERBB3 (p.Glu928Gly) and an ERBB2 (p.Val777Leu) mutation, respectively. Both tumors harbored in addition genomic HER2 amplification, ATRX mutation and CDKN2A deletion. Methylation studies revealed a methylome most similar to MPNST-like tumors, but distinct from melanoma, MPNST, clear cell sarcoma, and endometrial stromal sarcoma. Case 1 died of progressive peritoneal metastases after multiple trials of chemotherapy 47 months after diagnosis. Case 2 is a recent case who presented with a cervical mass, which was biopsied. This study defines a novel heretofore unrecognized aggressive uterine sarcoma with unique phenotypic and genotypic features. Given the potential value of targeting HER2, recognizing this tumor type is mandatory for appropriate therapeutic strategies and for better future delineation of the entity.

Lactate triggers KAT8-mediated LTBP1 lactylation at lysine 752 to promote skin rejuvenation by inducing collagen synthesis in fibroblasts.

Decreased collagen synthesis by fibroblasts is a key aspect of skin aging. Poly-L-Lactic Acid (PLLA) is a bioabsorbable material that can release lactate continuously, stimulating endogenous collagen synthesis in the skin. Herein, this study aimed to investigate the impact of PLLA-released lactate on collagen production in fibroblasts for skin rejuvenation. Human fibroblasts were exposed to varying concentrations of PLLA in vitro, while PLLA was injected into the back skin of aged mice in vivo. Safety and efficacy of PLLA on collagen synthesis and skin rejuvenation were evaluated through Calcein-AM/PI staining, EdU proliferation assay, and analysis of collagen I and collagen III expression in fibroblasts using western blotting and immunofluorescence. To elucidate the underlying mechanisms, lactate contents in cell-free supernatant and cell lysates from PLLA-treated fibroblasts, as well as total lysine lactylation (Pan Kla) levels were measured. Additionally, we found that fibroblasts can uptake extracellular lactate released from PLLA through monocarboxylate transporter-1 (MCT1) to facilitate latent-transforming growth factor beta-binding protein 1 (LTBP1) lactylation at lysine 752 (K752) via a KAT8-dependent mechanism, then increases the protein levels of collagen I and collagen III in fibroblasts. Overall, this study highlights a valuable insight into lactylation modification of non-histone protein for skin rejuvenation.

Attention-based stackable graph convolutional network for multi-view learning.

In multi-view learning, graph-based methods like Graph Convolutional Network (GCN) are extensively researched due to effective graph processing capabilities. However, most GCN-based methods often require complex preliminary operations such as sparsification, which may bring additional computation costs and training difficulties. Additionally, as the number of stacking layers increases in most GCN, over-smoothing problem arises, resulting in ineffective utilization of GCN capabilities. In this paper, we propose an attention-based stackable graph convolutional network that captures consistency across views and combines attention mechanism to exploit the powerful aggregation capability of GCN to effectively mitigate over-smoothing. Specifically, we introduce node self-attention to establish dynamic connections between nodes and generate view-specific representations. To maintain cross-view consistency, a data-driven approach is devised to assign attention weights to views, forming a common representation. Finally, based on residual connectivity, we apply an attention mechanism to the original projection features to generate layer-specific complementarity, which compensates for the information loss during graph convolution. Comprehensive experimental results demonstrate that the proposed method outperforms other state-of-the-art methods in multi-view semi-supervised tasks.

MicroRNA-301a knockout attenuates peripheral nerve regeneration by delaying Wallerian degeneration.

Our recent study demonstrated that knockout of microRNA-301a attenuates migration and phagocytosis in macrophages. Considering that macrophages and Schwann cells synergistically clear the debris of degraded axons and myelin during Wallerian degeneration, which is a prerequisite for nerve regeneration, we hypothesized that microRNA-301a regulates Wallerian degeneration and nerve regeneration via impacts on Schwann cell migration and phagocytosis. Herein, we found low expression of microRNA-301a in intact sciatic nerves, with no impact of the microRNA-301a knockout on nerve structure and function. By contrast, we found significant upregulation of microRNA- 301a in injured sciatic nerves. We established a sciatic nerve crush model in microRNA-301a knockout mice, which exhibited attenuated morphological and functional regeneration following sciatic nerve crush injury. The microRNA-301a knockout also led to significantly inhibited Wallerian degeneration in an in vivo sciatic nerve-transection model and in an in vitro nerve explant block model. Schwann cells with the microRNA-301a knockout showed inhibition of phagocytosis and migration, which was reversible under transfection with microRNA-301a mimics. Rescue experiments involving transfection of microRNA-301a-knockout Schwann cells with microRNA-301a mimics or treatment with the C-X-C motif receptor 4 inhibitor WZ811 indicated the mechanistic involvement of the Yin Yang 1/C-X-C motif receptor 4 pathway in the role of microRNA-301a. Combined with our previous findings in macrophages, we conclude that microRNA-301a plays a key role in peripheral nerve injury and repair by regulating the migratory and phagocytic capabilities of Schwann cells and macrophages via the Yin Yang 1/C-X-C motif receptor 4 pathway.

A nomogram for risk stratification of central cervical lymph node metastasis in patients with papillary thyroid carcinoma.

Background: Whether to perform prophylactic central lymph node dissection for cN0 papillary thyroid carcinoma (PTC) patients is still controversial. This retrospective study aimed to develop and validate a nomogram based on ultrasound and dual-energy computed tomography (DECT) for the risk stratification of central lymph node metastasis (CLNM) in patients with PTC. Methods: A total of 525 patients from 2017 to 2019 [Tianjin First Central Hospital (Hospital A)] were retrospectively analyzed to form the training cohort and to conduct internal validation. Another group of 204 patients in 2020 (Hospital A) formed the temporal validation cohort. A total of 107 patients in 2020 [Binzhou Medical University Hospital (Hospital B)] formed the geographic validation cohort, which was a retrospective cohort study. The area under the curve (AUC), calibration curve, and decision curve were used to evaluate the performance of the nomogram. The locally weighted regression curve was used for risk stratification. Results: Diameter, taller-than-wide, calcification, capsular invasion, and iodine concentration in the arterial and venous phases were independent risk predictors of CLNM. The AUC of the nomogram was 0.922 (95% confidence interval: 0.895-0.943) in the training cohort. Two external validation cohorts demonstrated the good performance of the nomogram in predicting CLNM, with AUCs of 0.912 and 0.861. The significantly improved net reclassification index and integrated discriminatory improvement index indicated that DECT was a powerful supplement to ultrasound for predicting CLNM. The risk stratification system divided all patients into low-risk (0-50 points), intermediate-risk (51-100 points), and high-risk groups (>100 points). Conclusions: The nomogram and risk stratification system estimated the utility of CLNM to guide individualized treatment of patients with PTC.

Association of pyrethroids exposure with asthma in US children and adolescents: a nationally representative cross-sectional study.

Pyrethroids (PYR) are among the most widely used insecticides in households, leading to substantial exposure. Children and adolescents, especially during growth spurts, have a reduced capacity to effectively metabolize these insecticides. The relationship between PYR exposure and asthma in these age groups remains poorly understood, highlighting the need for further research.We used data from the 2007-2014 National Health and Nutrition Examination Survey, which included 1181 children aged 6-11 years and 1258 adolescents aged 12-19 years. The concentration of the PYR metabolite 3-phenoxybenzoic acid (3-PBA) in urine was quantified using solid-phase extraction-high-performance liquid chromatography-heated electrospray ionization tandem mass spectrometry. Asthma was defined based on self-reported doctor diagnoses from the questionnaire. PYR exposure was measured using urine samples collected simultaneously with the questionnaire. We explored the association between PYR exposure and asthma using multiple logistic regression analyses, adjusting for potential confounders.Multiple logistic regression analyses revealed no significant association between PYR exposure and asthma in children and adolescent boys (all P > 0.05). In contrast, PYR exposure was significantly associated with asthma in adolescent girls aged 12-19 years. Specifically, for "ever asthma," the odds ratios (ORs) were 2.49 (95% CI = 1.03-5.97) in the second quartile of PYR exposure and 2.48 (95% CI = 1.04-5.91) in the third quartile, each in comparison to the first quartile. For "current asthma," in comparison to the first quartile, the ORs were 3.99 (95% CI = 1.55-10.26) in the second quartile of PYR exposure, 3.39 (95% CI = 1.32-8.70) in the third quartile, and 2.93 (95% CI = 1.24-6.90) in the fourth quartile.Conclusions:Our study found a significant association between PYR exposure and asthma in adolescent girls, whereas no significant association was observed in children and adolescent boys. These findings suggest potential sex and age differences in susceptibility to PYR exposure. Further research is warranted to confirm these results and elucidate the underlying mechanisms.

Early blood immune molecular alterations in cynomolgus monkeys with a PSEN1 mutation causing familial Alzheimer's disease.

INTRODUCTION: More robust non-human primate models of Alzheimer's disease (AD) will provide new opportunities to better understand the pathogenesis and progression of AD. METHODS: We designed a CRISPR/Cas9 system to achieve precise genomic deletion of exon 9 in cynomolgus monkeys using two guide RNAs targeting the 3' and 5' intron sequences of PSEN1 exon 9. We performed biochemical, transcriptome, proteome, and biomarker analyses to characterize the cellular and molecular dysregulations of this non-human primate model. RESULTS: We observed early changes of AD-related pathological proteins (cerebrospinal fluid Aß42 and phosphorylated tau) in PSEN1 mutant (ie, PSEN1-ΔE9) monkeys. Blood transcriptome and proteome profiling revealed early changes in inflammatory and immune molecules in juvenile PSEN1-ΔE9 cynomolgus monkeys. DISCUSSION: PSEN1 mutant cynomolgus monkeys recapitulate AD-related pathological protein changes, and reveal early alterations in blood immune signaling. Thus, this model might mimic AD-associated pathogenesis and has potential utility for developing early diagnostic and therapeutic interventions. HIGHLIGHTS: A dual-guide CRISPR/Cas9 system successfully mimics AD PSEN1-ΔE9 mutation by genomic excision of exon 9. PSEN1 mutant cynomolgus monkey-derived fibroblasts exhibit disrupted PSEN1 endoproteolysis and increased Aß secretion. Blood transcriptome and proteome profiling implicate early inflammatory and immune molecular dysregulation in juvenile PSEN1 mutant cynomolgus monkeys. Cerebrospinal fluid from juvenile PSEN1 mutant monkeys recapitulates early changes of AD-related pathological proteins (increased Aß42 and phosphorylated tau).

Assessment of adverse events related to anti-interleukin-6 receptor monoclonal antibodies using the FDA adverse event reporting system:a real-world pharmacovigilance study.

BACKGROUND: Interleukin-6 (IL-6) monoclonal antibodies are commonly acknowledged for their efficacy in managing coronavirus disease 2019 (COVID-19); however, there remains a paucity of comprehensive studies on their potential adverse effects. RESEARCH DESIGN AND METHODS: This is a retrospective pharmacovigilance investigation. We employed FAERS using OpenVigil FDA to detect adverse reactions linked to the interleukin-6 antagonist tocilizumab and sarilumab. RESULTS: Completely 17,037,364 reports were collected from the FAERS database, with 67,976 reports identified as 'primary suspected (PS)' adverse events (AEs) for tocilizumab, and 12,560 reports for sarilumab. AEs induced by both drugs involved 27 organ systems. 109 significant disproportionality preferred terms (PTs) of tocilizumab and 158 significant disproportionality PTs meeting the criteria of sarilumab across all four algorithms were retained simultaneously. A higher incidence of adverse reactions occurred in females aged 45-64 years, with a higher rate of subsequent hospitalization. Both drugs exhibited adverse reactions consistent with previously reported side effects, such as leukopenia, elevated liver enzymes, and hypercholesterolemia. Additionally, there was a strong correlation with gastrointestinal issues. Unexpected significant adverse events, including diabetes, fluctuations in blood pressure, drug ineffectiveness, malignancies, and disorders of the nervous system, were also observed. Gender and age differences existed in AEs signals related to IL-6RAs. CONCLUSION: Our study identified significant new AE signals for interleukin-6 receptor antagonists, potentially supporting clinical monitoring and risk identification for this class of drugs.

Undifferentiated Round Cell Sarcoma With CRTC1::SS18 Fusion: Expanding Clinicopathologic Features of a Rare Translocation Sarcoma With Prominent Desmoplastic Stroma.

Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS-non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range, 12-42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round-to-epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor. Immunohistochemical results were nonspecific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exons 1 to 2 of CRTC1 (the 5' partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3' partner gene) on chromosome 18. The clinical course was variable. Although 1 previously reported case demonstrated aggressive behavior with a fatal outcome, 2 others had a relatively indolent course with gradual growth for 6 to 7 years prior to resection. Two cases developed metastatic disease, including 1 case with bilateral lung metastasis and 1 with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aimed to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.

Channel prior convolutional attention for medical image segmentation.

Characteristics such as low contrast and significant organ shape variations are often exhibited in medical images. The improvement of segmentation performance in medical imaging is limited by the generally insufficient adaptive capabilities of existing attention mechanisms. An efficient Channel Prior Convolutional Attention (CPCA) method is proposed in this paper, supporting the dynamic distribution of attention weights in both channel and spatial dimensions. Spatial relationships are effectively extracted while preserving the channel prior by employing a multi-scale depth-wise convolutional module. The ability to focus on informative channels and important regions is possessed by CPCA. A segmentation network called CPCANet for medical image segmentation is proposed based on CPCA. CPCANet is validated on two publicly available datasets. Improved segmentation performance is achieved by CPCANet while requiring fewer computational resources through comparisons with state-of-the-art algorithms. Our code is publicly available at https://github.com/Cuthbert-Huang/CPCANet.

Antibody-drug conjugates for non-small cell lung cancer: Advantages and challenges in clinical translation.

Lung cancer is the leading cause of cancer death, with non-small cell lung cancer (NSCLC) accounting for approximately 85 % of all lung cancers and having a poor treatment and prognosis. Conventional clinical chemotherapy and immunotherapy are challenged by systemic toxicity and drug resistance, so researchers are increasingly focusing on antibody-drug conjugate (ADC), an innovative concept combining chemotherapy and targeted therapy, in which a drug selectively binds to antigens on the surface of a tumor cell via antibodies, which internalize the ADC, and then transfers the ADC to the lysosome via the endosomes to degrade the drug and kill the tumor cell. Despite the promising nature of ADCs, no ADC product for any indication including NSCLC has been approved for marketing by the FDA to date. In this review, we summarize the main advantages of ADCs and discuss in depth the design of the most desirable ADCs for NSCLC therapy. In addition to preclinical studies, we focus on the current state of clinical research on ADCs as interventions for the treatment of NSCLC by summarizing real-time clinical trial data from ClinicalTrials.gov, and reasonably speculate on the direction of the design of future generations of ADCs.

Fabrication, characterization, and bioactivity of self-assembled carrier-free colloidal dispersions from Citrus × Limon 'Rosso' essential oil and tea polyphenols.

Carrier-free nanodelivery systems are fully self-assembled from active ingredients through interactions, offering the advantages of green, safe, and large-scale manufacturing. To improve the dispersion of Citrus × limon 'Rosso' peel essential oil (CEO) in water and boost the biological activity of CEO and tea polyphenols (TP), self-assembled CEO-TP colloidal dispersions (CEO-TP Colloids) were fabricated through sonication without surfactants or carriers. The optimal CEO and TP concentrations in the CEO-TP Colloids were determined to be 10.0 and 20.0 mg/mL by particle size and stability analyzer, respectively. The CEO self-assembled with TP to form spherical nanoparticles through hydrophobic and hydrogen-bonding interactions, whereas the CEO in CEO-TP Colloids weakened TP intramolecular aggregation. Meanwhile, the CEO-TP Colloids showed synergistic effects with better antibacterial, cellular antioxidant, and anti-inflammatory activities than single components. This study opens up the possibility of carrier-free co-delivery of hydrophobic and hydrophilic active components developed into food-grade formulations with multiple bioactivities.

The responses and tolerance of photosynthetic system in Chlorella vulgaris to the pharmaceutical pollutant carbamazepine.

Screening for sensitive toxicological indicators and understanding algal tolerance to pharmaceutical contaminants (PhCs) are essential for assessing PhCs risk and their removal by microalgae. Carbamazepine (CBZ) showed adverse effects on microalgae, but the specific toxicity mechanisms on the most sensitive algal photosynthetic system (PS) remain limited. This study delved into the impact of CBZ exposure on the growth, cell viability, pigment content, and PS of Chlorella vulgaris. The findings revealed a notable inhibition of C. vulgaris growth by CBZ, with an IC50 value of 27.2 mg/L at 96 h. CBZ exposure induced algal membrane damage and cell viability. Intriguingly, CBZ drastically diminished intracellular pigment levels, notably showing "low promotion and high inhibition" of chlorophyll b (Chl b) by 72 h. Moreover, the study identified a decreased number of active reaction centers (RCs) within algal PSII alongside inhibited electron transport from QA to QB on the PSII receptor side, leading to PSII disruption. As an adaptive response to CBZ stress, C. vulgaris stimulated its Chl b synthesis, increased non-photochemical quenching (NPQ), and adapted its tolerance to bright light. Additionally, the alga attempted to compensate for the CBZ-induced reduction in electron transfer efficiency at the PSII receptor side and light energy utilization by increasing its electron transfer from downstream. Principal component analysis (PCA) further verified that the parameters on non-photochemical dissipation, electron transport, and integrative performance were the most sensitive algal toxicological indicators for CBZ exposure, and algal PS has energy protection capability through negative feedback regulation. However, prolonged exposure to high doses of CBZ will eventually result in permanent damage to the algal PS. Hence, attention should be paid to the concentration of CBZ in the effluent and the exposure time, while methods to mitigate algal photodamage should be appropriately sought for algal treatment of dense effluents.