Effectiveness and Safety of Pyrotinib-Based Therapy in the Treatment of HER2-Positive Breast Cancer Patients with Brain Metastases: A Multicenter Real-World Study.

BACKGROUND: Approximately 30% to 50% of patients with human epidermal growth factor receptor 2-positive metastatic breast cancer develop brain metastasis (BMs). Pyrotinib has shown promising efficacy in these patients. However, real-world evidence supporting its use is scarce. Therefore, we evaluate the efficacy and safety of pyrotinib-based regimens in the real world. MATERIALS AND METHODS: We enrolled patients with BMs from various healthcare facilities in China's Shandong region and used an updated breast-graded prognostic assessment (breast-GPA) to predict survival outcomes. RESULTS: Efficacy and toxicity were assessed in 101 patients. Overall, the median progression-free survival (PFS) was 11.0 months (95% CI, 7.6-14.4 months). PFS was shorter in patients with a breast-GPA of 0 to 2.0 (P< .001). Previous treatment with pertuzumab plus trastuzumab (P = .039) and varying numbers of BMs (P = .028) had a significant positive correlation with PFS. Additionally, radiotherapy (P = .033) for BMs, especially pyrotinib concurrent with radiotherapy (P = .013), significantly prolonged the PFS. In patients with a breast-GPA of 0 to 2.0, a significant difference in PFS was observed depending on whether the brain was the first metastatic site (P< .001). Furthermore, a breast-GPA (0-2.0 vs. 2.5-4.0), and radiotherapy for BMs were found to be independent predictors of PFS. Overall, the objective response rate was 42.6%, while the disease control rate was 88.1%. Diarrhea emerged as the most common adverse event. CONCLUSION: Pyrotinib-based therapy is effective and tolerable in human epidermal growth factor receptor 2-positive metastatic breast cancer with BMs. Patients who underwent radiotherapy for BMs, particularly those who received pyrotinib concurrently with radiotherapy, exhibited a more favorable prognosis.

Functional mechanism of hypoxia-like conditions mediating resistance to ferroptosis in cervical cancer cells by regulating KDM4A SUMOylation and the SLC7A11/GPX4 pathway.

The discovery of ferroptosis has unveiled new perspectives for cervical cancer (CC) management. We elucidated the functional mechanism of hypoxia-like conditions in CC cell ferroptosis resistance. CC cells were subjected to normoxia or hypoxia-like conditions, followed by erastin treatment to induce ferroptosis. The assessment of cell viability/ferroptosis resistance was performed by MTT assay/Fe2+, MDA, and glutathione measurement by colorimetry. KDM4A/SUMO1/Ubc9/SENP1 protein levels were determined by Western blot. Interaction and binding sites between KDM4A and SUMO1 were analyzed and predicted by immunofluorescence/co-immunoprecipitation and GPS-SUMO 1.0 software, with the target relationship verified by mutation experiment. SLC7A11/GPX4/H3K9me3 protein levels, and H3K9me3 level in the SLC7A11 gene promoter region were determined by RT-qPCR and Western blot/chromatin immunoprecipitation. H3H9me3/SLC7A11/GPX4 level alterations, and ferroptosis resistance after KDM4A silencing or KDM4A K471 mutation were assessed. Hypoxia-like conditions increased CC cell ferroptosis resistance and KDM4A, SUMO1, and Ubc9 protein levels, while it decreased SENP1 protein level. KDM4A and SUMO1 were co-localized in the nucleus, and hypoxia-like conditions promoted their interaction. Specifically, the K471 locus of KDM4A was the main locus for SUMO1ylation. Hypoxia-like conditions up-regulated SLC7A11 and GPX4 expression levels and decreased H3K9me3 protein level and H3K9me3 abundance in the SLC7A11 promoter region. KDM4A silencing or K471 locus mutation resulted in weakened interaction between KDM4A and SUMO1, elevated H3K9me3 levels, decreased SLC7A11 expression, ultimately, a reduced CC cell ferroptosis resistance. CoCl2-stimulated hypoxia-like conditions enhanced SUMO1 modification of KDM4A at the K471 locus specifically, repressed H3K9me3 levels, and up-regulated SLC7A11/GPX4 to enhance CC cell ferroptosis resistance.

Efficacy and safety of pyrotinib combined with albumin-bound paclitaxel as first-line treatment for HER2-positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single-arm, phase 2 prospective clinical trial.

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Anti-Staphylococcus aureus effects of natural antimicrobial peptides and the underlying mechanisms.

Staphylococcus aureus can cause localized infections such as abscesses and pneumonia, as well as systemic infections such as bacteremia and sepsis. Especially, methicillin-resistant S. aureus often presents multidrug resistance, which becomes a major clinical challenge. One of the most common reasons for methicillin-resistant S. aureus antibiotic resistance is the presence of biofilms. Natural antimicrobial peptides derived from different species have shown effectiveness in combating S. aureus biofilms. In this review, we summarize the inhibitory activity of antimicrobial peptides against S. aureus planktonic cells and biofilms. We also summarize the possible inhibitory mechanisms, involving cell adhesion inhibition, membrane fracture, biofilm disruption and DNA disruption. We believe this can provide the basis for further research against S. aureus biofilm-associated infections.

When a bacterial infection is treated, sometimes not all bacteria are killed. This is because they have ways to evade the treatment's action. Therefore, it is important to develop new drugs, although this is difficult, expensive and time-consuming. This paper summarizes new types of natural antimicrobials that could be used against bacteria, how they work and how well.

CRISPR/Cas systems combined with DNA nanostructures for biomedical applications.

DNA nanostructures are easy to design and construct, have good biocompatibility, and show great potential in biosensing and drug delivery. Numerous distinctive and versatile DNA nanostructures have been developed and explored for biomedical applications. In addition to DNA nanostructures that are completely assembled from DNA, composite DNA nanostructures obtained by combining DNA with other organic or inorganic materials are also widely used in related research. The CRISPR/Cas system has attracted great attention as a powerful gene editing technology and is also widely used in biomedical diagnosis. Many researchers are committed to exploring new possibilities by combining DNA nanostructures with CRISPR/Cas systems. These explorations provide support for the development of new detection methods and cargo delivery pathways, provide inspiration for improving relevant gene editing platforms, and further expand the application scope of DNA nanostructures and CRISPR/Cas systems. This paper mainly reviews the design principles and biomedical applications of CRISPR/Cas combined with DNA nanostructures based on the types of DNA nanostructures. Finally, the application status, challenges and development prospects of CRISPR/Cas combined with DNA nanostructures in detection and delivery are summarized. It is expected that this review will enable researchers to better understand the current state of the field and provide insights into the application of CRISPR/Cas systems and the development of DNA nanostructures.

Rare primary angiitis of the central nervous system affecting the clivus: A case report.

Diseases involving the clivus are highly variable, and the incidence of each disease is rare. Primary central nervous system vasculitis (PACNS) is a rare disease with very heterogeneous clinical manifestations, its diagnosis is often challenging, and histopathology is the gold standard. We report a patient with PACNS of the clivus, with a 1-month history of headache and diplopia, who was misdiagnosed as having a tumor of the clivus during prior treatment, due to computed tomography findings of clivus occupation and bone destruction. Endoscopic resection of the nasal clivus lesions was performed. Pathological examination revealed a small abscess with hemorrhage, necrosis, extensive infiltration of lymphocytes and plasma cells, and granulation tissue scar formation. After histopathological examination, the diagnosis was confirmed, and oral glucocorticoid and cyclophosphamide were commenced. This study is the first to report a tumor-like PACNS, that occurs in the clivus, thereby enriching our understanding of PACNS.

Difference of Antrochoanal Polyps Between Children and Adults in the Chinese Population.

OBJECTIVE: This study aims to find the difference in clinical and immunopathological characteristics between children and adults with antrochoanal polyps (ACPs) in the Chinese population. METHODS: The clinical data of 69 patients diagnosed with ACPs were retrospectively analyzed. Cytokine levels in 16 controls and 40 ACPs tissues were determined by quantitative real-time polymerase chain reaction (qPCR). The expression of matrix metalloproteinase (MMP)-9 was measured using qPCR, immunofluorescent staining, and western blot. RESULTS: There were 51 (73.9%) children (<18 years old) and 18 (26.1%) adults (≥18 years old). The sex ratio differed significantly between the two groups (p = 0.0032). There were no significant differences in the nasal side of ACPs and approaches to surgery between the two groups. In both groups, the most common symptom was nasal obstruction, followed by nasal discharge. As for associated nasal diseases, there was a significant difference between the two groups in septal deviation (p = 0.0223). Adult patients showed significantly higher expression of IL-8 mRNA than children (p = 0.0424). The mRNA and protein levels of MMP-9 were also significantly higher in adult patients than in children (p = 0.0498 and 0.0009, respectively). CONCLUSION: In the Chinese population, the comorbidities and immunopathological characteristics of adult ACP patients are different from those of children. The level of IL-8 and MMP-9 was significantly higher in ACPs of adults than in children, which may contribute to the more severe tissue remolding in adult ACP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2093-2099, 2024.

The metastasis patterns and their prognostic features in patients with de novo metastatic breast cancer of different ages.

PURPOSE: The prognostic outcomes of metastasis patterns in patients with de novo metastatic breast cancer (dnMBC) of different ages are unknown. Our study used a large-scale data to investigate the metastasis patterns and prognostic features in dnMBC of different ages. METHODS: Total 24,698 women with dnMBC in the Surveillance, Epidemiology and End Results database (2010-2018) were divided into three groups by age. Chi-squared test was used to compare metastasis patterns and logistic regression was performed to investigate the risk of age and specific organ metastases. Kaplan-Meier survival curves were used to compare the overall survival. RESULTS: In three groups, young group had the largest proportion of liver metastases (35.2% vs. 28.2% vs. 21.1%, p < 0.001), and elderly group had the largest proportion of lung metastases (22.6% vs. 30.0% vs. 35.0%, p < 0.001) and the lowest proportion of bone metastases (65.7% vs. 67.6% vs. 64.4%, p < 0.001). In young group, patients with liver metastases had better prognosis than patients with lung metastases (MST: 34 months vs. 29 months, p = 0.041), but in middle-aged and elderly groups, the prognosis of lung metastases was better than that of liver metastases (MST in middle-aged group: 24 months vs. 20 months, p = 0.002; MST in elderly group: 12 months vs. 6 months, p < 0.001). CONCLUSION: DnMBC patients at different age have distinct metastasis patterns and prognostic features. The findings lend support to consideration of tailored management and surveillance strategies for different age patients.

Clinical Characteristics of Sphenoid Sinus Fungus Ball: A Nine-year Retrospective Study of 77 Cases.

OBJECTIVE: This study aimed to investigate the clinical characteristics of sphenoid sinus fungus ball (SSFB) to help increase the accuracy of diagnosis and efficiency of treatment. METHODS: We retrospectively analyzed the data of 77 patients who were histopathologically diagnosed with SSFB. RESULTS: The mean age of SSFB patients was 52.4 years (range 25-84), and 47 patients (61.0%) were female. Compared to age-matched and sex-matched chronic rhinosinusitis (CRS) patients, headache was more common in SSFB patients (79.2%; p < 0.0001). SSFB patients also had higher prevalence of diabetes than CRS (p = 0.0420). The features of computed tomography (CT) were sphenoid sinus opacification (100%), sclerosis (93.5%), calcification (76.6%), and bone erosion (41.6%). Functional endoscopic sinus surgery (FESS) was the best treatment option, and the trans-ethmoid (n = 64, 83.1%) was the most commonly used approach. No one experienced a recurrence of SSFB in 44 successfully contacted patients. Six months after FESS, 91.0% of patients (40/44) established proper drainage in the sphenoid sinus. The recovery rates for headache and nasal symptoms were 91.7% (33/36) and 77.8% (7/9) respectively. CONCLUSION: SSFB is more prevalent in older women and usually presents as unilateral headache. Diabetes is a potential risk factor for SSFB. CT findings provide evidence for diagnosis and suggestions for surgical approaches. FESS is the optimal treatment for SSFB. After FESS, most patients had good prognosis with no recurrence of SSFB. However, regular endoscopic follow-up is required due to the possibility of the postoperative closure of sphenoid ostium. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3292-3298, 2023.

Potential predictive value of circulating tumor DNA (ctDNA) mutations for the efficacy of immune checkpoint inhibitors in advanced triple-negative breast cancer.

Background: In recent years, tumor immunotherapy has become a viable treatment option for triple negative breast cancer (TNBC). Among these, immune checkpoint inhibitors (ICIs) have demonstrated good efficacy in advanced TNBC patients with programmed death-ligand 1 (PD-L1) positive expression. However, only 63% of PD-L1-positive individuals showed any benefit from ICIs. Therefore, finding new predictive biomarkers will aid in identifying patients who are likely to benefit from ICIs. In this study, we used liquid biopsies and next-generation sequencing (NGS) to dynamically detect changes in circulating tumor DNA (ctDNA) in the blood of patients with advanced TNBC treated with ICIs and focused on its potential predictive value. Methods: From May 2018 to October 2020, patients with advanced TNBC treated with ICIs at Shandong Cancer Hospital were included prospectively. Patient blood samples were obtained at the pretreatment baseline, first response evaluation, and disease progression timepoints. Furthermore, 457 cancer-related genes were evaluated by NGS, and patients' ctDNA mutations, gene mutation rates, and other indicators were determined and coupled with clinical data for statistical analysis. Results: A total of 11 TNBC patients were included in this study. The overall objective response rate (ORR) was 27.3%, with a 6.1-month median progression-free survival (PFS) (95% confidence interval: 3.877-8.323 months). Of the 11 baseline blood samples, 48 mutations were found, with the most common mutation types being frame shift indels, synonymous single-nucleotide variations (SNVs), frame indel missenses, splicing, and stop gains. Additionally, univariate Cox regression analysis revealed that advanced TNBC patients with one of 12 mutant genes (CYP2D6 deletion and GNAS, BCL2L1, H3F3C, LAG3, FGF23, CCND2, SESN1, SNHG16, MYC, HLA-E, and MCL1 gain) had a shorter PFS with ICI treatment (p < 0.05). To some extent, dynamic changes of ctDNA might indicate the efficacy of ICIs. Conclusion: Our data indicate that ICI efficacy in patients with advanced TNBC may be predicted by 12 mutant ctDNA genes. Additionally, dynamic alterations in peripheral blood ctDNA might be used to track the effectiveness of ICI therapy in those with advanced TNBC.

Insight into oxygen reduction activity and pathway on pure titanium using scanning electrochemical microscopy and theoretical calculations.

HYPOTHESIS: Unlike noble metals, the oxygen reduction reaction (ORR) behavior on Ti is more complicated due to its spontaneously formed oxide film. This film results in sluggish ORR kinetics and tends to be reduced within ORR potential region, causing the weak and multi-reaction coupled current. Though Ti is being used in chemical and biological fields, its ORR research is still underexplored. EXPERIMENTS: We innovatively employed the modified reactive tip generation-substrate collection (RTG/SC) mode of scanning electrochemical microscopy (SECM) with high efficiency of 97.2 % to quantitatively study the effects of film characteristics, solution environment (pH, anion, dissolved oxygen), and applied potential on the ORR activity and selectivity of Ti. Then, density functional theory (DFT) and molecular dynamics (MD) analyses were employed to elucidate its ORR behavior. FINDINGS: On highly reduced Ti, film properties dominate ORR behavior with promoted 4e- selectivity. Rapid film regeneration in alkaline/O2-saturated conditions inhibits ORR activity. Besides, ORR is sensitive to anion species in neutral solutions while showing enhanced 4e- reduction in alkaline media. All the improved 4e- selectivities originate from the hydrogen bond/electrostatic stabilization effect, while the decayed ORR activity by Cl- arises from the suppressed O2 adsorption. This work provides theoretical support and possible guidance for ORR research on oxide-covered metals.

Effects of the fungicide trifloxystrobin on the structure and function of soil bacterial community.

Trifloxystrobin has been widely applied to prevent fungal diseases because of its high efficiency and desirable safety characteristics. In the present study, the effects of trifloxystrobin on soil microorganisms were integrally investigated. The results showed that trifloxystrobin inhibited urease activity, promoted dehydrogenase activity. Downregulated expressions of the nitrifying gene (amoA), denitrifying genes (nirK and nirS), and carbon fixation gene (cbbL) were also observed. Soil bacterial community structure analysis showed that trifloxystrobin changed the abundance of bacteria genera related to nitrogen and carbon cycle in soil. Through the comprehensive analysis of soil enzymes, functional gene abundance, and soil bacterial community structure, we concluded that trifloxystrobin inhibited both nitrification and denitrification of soil microorganisms, and also diminished the carbon-sequestration ability. Integrated biomarker response analysis showed that dehydrogenase and nifH were the most sensitive indicators of trifloxystrobin exposure. It provides new insights about trifloxystrobin environmental pollution and its influence on soil ecosystem.

Comparative analysis of three common imaging modalities for nasolabial cysts.

OBJECTIVE: To compare the clinical diagnostic value of ultrasonography (USG), computed tomography (CT), and magnetic resonance imaging (MRI) for nasolabial cysts. METHODS: The clinical and imaging data of 20 patients with 21 nasolabial cysts confirmed surgically and histopathologically were retrospectively analyzed. RESULTS: The largest cyst was 3.4 × 2.7 × 2.3 cm, and the smallest cyst was 1.1 × 0.7 × 0.5 cm. All cysts were located in the soft tissue between the nasolabial fold and maxillary bone. USG showed sensitivity of 95%, accuracy of 95%, and a missed diagnosis rate of 5%; CT showed sensitivity of 80%, accuracy of 80%, and a missed diagnosis rate of 20%; and MRI showed sensitivity of 85%, accuracy of 85%, and a missed diagnosis rate of 15%. CONCLUSIONS: USG showed higher sensitivity and accuracy and a lower missed diagnosis rate than CT and MRI. Therefore, USG is worth popularizing on a large scale for the diagnosis of nasolabial cysts.

Antifungal activity and potential mechanism of action of caspofungin in combination with ribavirin against Candida albicans.

The number of invasive fungal infections has increased dramatically, resulting in high morbidity and mortality among immunocompromised patients. With increasing use of caspofungin (CAS), resistant strains have emerged frequently and led to limitations in the treatment of patients with severe invasive Candida albicans infections. Combination therapy is an important method to deal with this issue. As such, this study investigated the activity of CAS in combination with ribavirin (RBV) against C. albicans. The results of this in-vitro study showed that the minimum inhibitory concentrations (MICs) of CAS and RBV when they were used as monotherapy were 0.5-1 µg/mL and 2-8 µg/mL, respectively, while the MIC of CAS decreased from 0.5-1 µg/mL to 0.0625-0.25 µg/mL when used in combination with RBV, with a fractional inhibitory concentration index (FICI) ≤0.5. In addition, the RBV + CAS combination group displayed synergistic effects against C. albicans biofilm over 4 h; the sessile MIC (sMIC) of CAS decreased from 0.5-1 µg/mL to 0.0625-0.25µg/mL and the sMIC of RBV decreased from 4-16 µg/mL to 1-2 µg/mL, with FICI <0.5. The survival of C. albicans-infected Galleria mellonella was prolonged, the fungal burden was decreased, and the area of tissue damage was reduced after combination therapy. Further study showed that the mechanisms of action of the synergistic effect were related to the inhibition of biofilm formation, the inhibition of hyphal growth, and the activation of metacaspases, but were not related to the accumulation of reactive oxygen species. It is hoped that these findings will contribute to the understanding of drug resistance in C. albicans, and provide new insights for the application of RBV.

Preparation, characterization, and removal of nitrate from water using vacant polyoxometalate/TiO2 composites.

Due to the rapid development of industry and agriculture, nitrate pollution in groundwater has been continuously increasing. NO3-N is a chemically stable nitrogen species and is quite difficult to remove. In this study, using heteropoly silicotungstate K8[α-SiW11O39] and Cu2+ as the active components, SiW11 and Cu2+ were loaded onto TiO2 by a sol-gel method to prepare a composite photocatalyst SiW11/TiO2/Cu. The photocatalytic reduction of dissolved NO3-N was subsequently performed using SiW11/TiO2/Cu under UV irradiation, and the influence of different experimental parameters on the photocatalytic performance was investigated. The mechanism of NO3-N reduction by the composite catalyst was also investigated. Free radicals existing within the system were detected by ESR spectroscopy, and the results indicated that CO2- anion free-radicals were generated by the reaction of photogenerated holes and formic acid (HCOOH). At a SiW11/TiO2/Cu dose of 1.2 g L-1 and in the presence of HCOOH as a hole scavenger, the proposed composite catalytically reduced NO3-N anddemonstrated significantadvantages in terms of its photocatalytic activity in comparison with pure TiO2. In particular, the removal efficiency of NO3-N and the selectivity of nitrogen achieved a maximum of 96% and 77%, respectively.

Schwannoma in the Olfactory Groove: Two Case Reports.

The occurrence of an isolated schwannoma in the olfactory groove is extremely rare. We herein present 2 cases of schwannomas in the olfactory groove that were treated with endoscopic excision. In these 2 cases, the tumor originated in the cribriform plate and cerebrospinal fluid rhinorrhea occurred after tumor resection, which was repaired using tissue grafts.

Endoscopic nasal surgery for mucocele and pyogenic mucocele of turbinate: Three case reports.

BACKGROUND: Cases of turbinate mucocele or pyogenic mucocele are extremely rare. During nasal endoscopy, turbinate hypertrophy can be detected in patients with turbinate or pyogenic mucocele. However, in many instances, differentiating between turbinate hypertrophy and turbinate mucocele is difficult. Radiological examinations, such as computed tomography (CT) or magnetic resonance imaging (MRI), are essential for the accurate diagnosis of turbinate mucocele. Herein, we report three cases of mucocele or pyogenic mucocele of turbinate, including their clinical presentation, imaging findings, and treatments, to help rhinologists understand this condition better. CASE SUMMARY: Three cases of turbinate and pyogenic mucocele were encountered in our hospital. In all patients, nasal obstruction and headache were the most common symptoms, and physical examination revealed hypertrophic turbinates. On CT scan, mucocele appeared as non-enhancing, homogeneous, hypodense, well-defined, rounded, and expansile lesions. Meanwhile, MRI clearly illustrated the cystic nature of the lesion on T2 sequences. Two patients with inferior turbinate mucocele underwent mucocele lining removal, while the patient with pyogenic mucocele underwent endoscopic middle turbinate marsupialization. The patients were followed up on the first, third, sixth month, and 1 year after discharge, and no complaints of headache and nasal congestion were reported during this period. CONCLUSION: In conclusion, both CT and MRI are helpful in the diagnosis of turbinate or pyogenic mucocele. Additionally, endoscopic nasal surgery is considered to be the most effective treatment method.

Effect of live and inactivated Chlamydomonas reinhardtii on the removal of tetracycline in aquatic environments.

With the development of medical drugs, the widely used tetracycline has brought many adverse effects on the ecosystem and human health. Tetracycline pollution of water environment is becoming more and more serious, and has become an emerging environmental problem. As single celled organisms, microalgae are not only model organisms for risk assessment of aquatic ecosystems, but also can efficiently purify sewage. Microalgae-mediated pollutant remediation has attracted more and more attention from researchers. In this paper, Chlamydomonas reinhardtii (C. reinhardtii) was used to remove tetracycline in aqueous solution, and the removal efficiency and mechanism of microalgae on tetracycline were studied. The results showed that the removal rates of tetracycline by active and inactivated microalgae at a density of 5 × 106 cells·mL-1 were 81.9% and 89.8%, respectively. C. reinhardtii removed tetracycline through biosorption and nonmetabolic processes. Microalgal cell supernatant and hydroxyl radicals could significantly promote the removal of tetracycline. The positively charged tetracycline was electrostatically adsorbed on the microalgae surface and extracellular polymeric substances. Microalgae biomass can promote the production of ROS and enhance the ability of microalgae to remove tetracycline.

Endogenous Stimuli-Responsive Autonomous Separation of Dual-Targeting DNA Guided Missile from Nanospacecraft for Intelligent Targeted Cancer Therapy.

Most conventional chemotherapeutics indiscriminately kill both cancerous and healthy cells and cause toxic side effects, limiting the maximum tolerated dose and thereby compromising therapeutic efficacy. To address this challenge, here dual-targeting intelligent DNA guided missile (GM)-integrated nanospacecraft (NSC) (abbreviated as GM-NSC) is demonstrated for staged chemotherapeutic drug delivery exclusively into cancer cells and then mitochondria (not into healthy cells). GM-NSC is essentially a core/shell nanocomposite composed of gold nanoparticles (AuNPs) surrounded by a high-density multilayer DNA crown that is self-assembled from DNA tetrahedral units (DNA Tetra) in a highly ordered manner. Each tetrahedral structural unit is equipped with three functional components: a cancer cell-targeting aptamer pointing toward the outside environment, a hidden mitochondria-targeting triphenylphosphonium (TPP), and an explosive bolt (E-bolt). GM-NSC can remain intact in fetal bovine serum solution over 12 h and has 53-fold improved systemic stability. Each GM-NSC accommodates 1250 anticancer doxorubicin (Dox), achieving a 48-63-fold improved drug payload capacity. When systemically administrated into a tumor-bearing xenograft murine model, Dox-loaded GM-NSC enters into tumor sites with 18-fold improved specificity followed by autonomous separation of GMs from the NSC core and specific mitochondrial accumulation due to the explosion of E-bolt upon stimuli of endogenous miRNAs. About 80% of Dox uptaken is transferred into mitochondria and induces mitochondria-mediated apoptosis. As a result, the growth of malignant tumor is almost 100% inhibited without detectable toxicity to healthy tissues. Due to the desirable systemic stability, good biocompatibility, high cargo loading capability, satisfactory in vivo biodistribution, and therapeutic efficacy without adverse effects, intelligible GM-NSC is expected to become an alternative drug delivery system for precision cancer therapy.

Chelerythrine reverses the drug resistance of resistant Candida albicans and the biofilm to fluconazole.

Aim: To evaluate the antifungal activity of chelerythrine in combination with fluconazole against planktonic Candida albicans strains and preformed biofilm. Materials & methods: A broth microdilution assay was used to reveal the antifungal activity of chelerythrine combined with fluconazole against C. albicans and the preformed biofilm. A fractional inhibitory concentration index model was used to evaluate the interaction. Results: Chelerythrine strongly synergized with fluconazole against fluconazole-resistant C. albicans and the biofilm preformed for less than 12 h. In addition, chelerythrine combined with fluconazole exhibited a synergistic effect against C. albicans morphogenesis. Conclusion: Chelerythrine could reverse the drug resistance of resistant C. albicans and its biofilm to fluconazole, providing new insights for overcoming the drug resistance of C. albicans.