Proteomic insights from extracellular vesicles into the molecular mechanisms of health effects induced by Per- and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances (PFASs) can induce a range of adverse health effects, with the precise molecular mechanisms remaining elusive. Extracellular vesicles (EVs) have demonstrated their potential to elucidate unknown molecular mechanisms. Building upon the close alignment of their biological functions with the observed health effects of PFASs, this study innovatively focuses on proteomic insights from EVs into the molecular mechanisms underlying the systemic health effects of PFASs. Through rat exposure experiments and proteomics technology, it not only demonstrated the occurrence of PFASs in EVs but also revealed the alterations in the serum EVs and the expression of their protein cargos following mixed exposure to PFASs, leading to changes in related pathways. These changes encompass various biological processes, including proteasome activity, immune response, cytoskeletal organization, oxidative stress, cell signaling, and nervous system function. Particularly noteworthy is the uncovering of the activation of the proteasome pathway, highlighting significant key contributing proteins. These novel findings provide a new perspective for exploring the molecular mechanism underlying the systemic health effects of PFASs and offer reliable screening for potential biomarkers. Additionally, comparisons with serum confirmed the potential of serum EVs as biological responders and measurable endpoints for evaluating PFASs-induced toxicity.

Interaction of Ca2+ and Fe3+ in co-precipitation process induced by Virgibacillus dokdonensis and its application.

Biomineralization has garnered significant attention in the field of wastewater treatment due to its notable cost reduction compared to conventional methods. The reinjection water from oilfields containing an exceedingly high concentration of calcium and ferric ions will pose a major hazard in production. However, the utilization of biomineralization for precipitating these ions has been scarcely investigated due to limited tolerance among halophiles towards such extreme conditions. In this study, free and immobilized halophiles Virgibacillus dokdonensis were used to precipitate these ions and the effects were compared, at the same time, biomineralization mechanisms and mineral characteristics were further explored. The results show that bacterial concentration and carbonic anhydrase activity were higher when additionally adding ferric ion based on calcium ion; the content of protein, polysaccharides, deoxyribonucleic acid and humic substances in the extracellular polymers also increased compared to control. Calcium ions were biomineralized into calcite and vaterite with multiple morphology. Due to iron doping, the crystallinity and thermal stability of calcium carbonate decreased, the content of OC = O, NC = O and CO-PO3 increased, the stable carbon isotope values became much more negative, and ß-sheet in minerals disappeared. Higher calcium concentrations facilitated ferric ion precipitation, while ferric ions hindered calcium precipitation. The immobilized bacteria performed better in ferric ion removal, with a precipitation ratio exceeding 90%. Free bacteria performed better in calcium removal, and the precipitation ratio reached a maximum of 56%. This research maybe provides some reference for the co-removal of calcium and ferric ions from the oilfield wastewater.

Emission Library and Applications of 2,1,3-Benzothiadiazole and Its Derivative-Based Luminescent Metal-Organic Frameworks.

Organic linker-based luminescent metal-organic frameworks (LMOFs) have received extensive attention due to their promising applications in chemical sensing, energy transfer, solid-state-lighting and heterogeneous catalysis. Benefiting from the virtually unlimited emissive organic linkers and the intrinsic advantages of MOFs, significant progress has been made in constructing LMOFs with specific emission behaviors and outstanding performances. Among these reported organic linkers, 2,1,3-benzothiadiazole and its derivatives, as unique building units with tunable electron-withdrawing abilities, can be used to synthesize numerous emissive linkers with a donor-bridge-acceptor-bridge-donor type structure. These linkers were utilized to coordinate with different metal nodes, forming LMOFs with diverse underlying nets and optical properties. In this Minireview, 2,1,3-benzothiadiazole and its derivative-based organic linkers and their corresponding LMOFs are summarized with which an emission library is built between the linker structures and the emission behaviors of constructed LMOFs. In particular, the preparation of LMOFs with customized emission properties ranging from deep-blue to near-infrared and sizes from dozens to hundreds of nanometers is discussed in detail. The applications of these LMOFs, including chemical sensing, energy harvesting and transfer, and catalysis, are then highlighted. Key perspectives and challenges for the future development of LMOFs are also addressed.

Remote sensing image road network detection based on channel attention mechanism.

Extracting and detecting road network consistency from high-resolution remote sensing images has been a hot and difficult problem in the computer vision. Although it has made significant progress, there is still a phenomenon of high training accuracy but unsatisfactory actual extraction and detection results. The attention mechanism is one of the efficient and practical mechanisms in deep learning. It improves the performance of deep learning by selectively focusing on a portion of all information while ignoring other visible information, while effectively utilizing computing resources. Numerous experiments have also confirmed that the attention mechanism is resource-saving and effective. Its plug and play feature brings great convenience to programmers. In order to provide better road network detection results and solve the above problem, this paper combines the channel attention mechanism with ResNet and proposes SE-ResNet and ECA-ResNet for remote sensing image road network detection, making networks extract and learn road network features and ignore some non-road network features. The experimental results show that on the Massachusetts roads (MR) and CHN6-CUG roads datasets, ECA-ResNet and SE-ResNet based on channel attention mechanism perform similar to LeNet7 and ResNet in terms of accuracy, loss, accuracy convergence, and loss convergence, and even increase a certain computational burden. However, their final road network detection results (including road network detection pixel count, precision, recall, accuracy, IOU, F1 score, and actual road network detection result) of the former are significantly better than those of the latter. The channel attention mechanism makes the deep neural network pay more attention to the extraction and learning of road network features, while ignoring the extraction and learning of some non-road network features, which improves the accuracy of containing road network samples and reduces the accuracy of not containing road network samples. Therefore, the performance of ECA-ResNet and SE-ResNet is similar to that of LeNet7 and ResNet in the accuracy, loss, accuracy convergence and loss convergence, but the final road network detection results of ECA-ResNet and SE-ResNet are significantly better than those of LeNet7 and ResNet. Therefore, the proposed ECA-ResNet and SE-ResNet have broad application prospects in road network detection, especially ECA-ResNet.

Orthostatic Hypotension: a clinical marker for the body-first subtype of patients with Parkinson's Disease.

Our study aimed to investigate the clinical characteristics of PD patients stratified by OH status before and after levodopa challenge to explore the hypothesis that OH might serve as a clinical marker for the body-first subtype of PD. Supine and standing blood pressure were measured in a large cross-sectional cohort of PD patients at the OFF status before and after levodopa challenge test (LCT). Based on OH status, patients were divided into three groups: spontaneous OH (SOH), only levodopa-induced OH (LOH) and non-OH (NOH). Clinical characteristics and associated factors were compared among the groups. A total of 928 patients with a mean age of 62.4 years and average disease duration of 7.9 years were included. There were 224 (24.1%) patients with SOH, 321 (34.6%) with LOH, and 383 (41.3%) with NOH. Compared to NOH, both SOH and LOH were associated with older age, motor fluctuations, and probable rapid eye movement sleep behavior disorder (pRBD). In addition, OH was more associated with cardiovascular and digestive dysfunction, disease severity and worse quality of life. Results of the current study suggest that PD patients developed OH which is more likely to comorbid with RBD, severe autonomic dysfunction and motor fluctuations, consistent with the body-first subtype of PD.

Full-Color Emissive Zirconium-Organic Frameworks Constructed via in situ "One-Pot" Single-Site Modification for Tryptophan Detection and Energy Transfer.

Organic linker-based luminescent metal-organic frameworks (LMOFs) have received extensive studies due to the unlimited species of emissive organic linkers and tunable structure of MOFs. However, the multiple-step organic synthesis is always a great challenge for the development of LMOFs. As an alternative strategy, in situ "one-pot" strategy, in which the generation of emissive organic linkers and sequential construction of LMOFs happen in one reaction condition, can avoid time-consuming pre-synthesis of organic linkers. In the present work, we demonstrate the successful utilization of in situ "one-pot" strategy to construct a series of LMOFs via the single-site modification between the reaction of aldehydes and o-phenylenediamine-based tetratopic carboxylic acid. The resultant MOFs possess csq topology with emission covering blue to near-infrared. The nanosized LMOFs exhibit excellent sensitivity and selectivity for tryptophan detection. In addition, two component-based LMOFs can also be prepared via the in situ "one-pot" strategy and used to study energy transfer. This work not only reports the construction of LMOFs with full-color emissions, which can be utilized for various applications, but also indicates that in situ "one-pot" strategy indeed is a useful and powerful method to complement the traditional MOFs construction method for preparing porous materials with tunable functionalities and properties.

Echocardiography-Guided Radiofrequency Ablation for Cardiac Tumors.

Background: Patients with cardiac tumors may present challenges for surgical resection due to poor clinical condition. Echocardiography-guided transapical radiofrequency ablation for cardiac tumors (TARFACT) potentially offers a less invasive palliative therapy option. Objectives: This study aimed to evaluate the safety and efficacy of TARFACT. Methods: Five patients with cardiac tumors (mucinous liposarcoma, myocardial hypertrophy with inflammatory cell infiltration mass, fibrous tissue tumor hyperplasia, myocardial clear cell sarcoma, and cardiac rhabdomyoma) were included. All patients underwent TARFACT and were assessed with electrocardiogram, echocardiographic imaging, biochemical analysis, and pathological confirmation. Results: The median follow-up for all patients was 9 (range 4-12) months. Three surviving patients were alive at their last follow-up (9, 12, and 12 months, respectively), whereas 2 patients with late-stage tumors survived 6 months and 13 months after TARFACT, respectively. After TARFACT, all patients showed significant reductions in tumor size: the mean length decreased from 6.7 ± 2.0 cm to 4.7 ± 1.8 cm (P = 0.007); and the mean width decreased from 5.0 ± 2.1 cm to 2.5 ± 0.7 cm (P = 0.041). NYHA functional class also improved: median (IQR) decreased from 3.0 (1.5) to 2.0 (1.0) (P = 0.038), Peak E-wave on echocardiography showed a mean increase from 64.4 ± 15.7 cm/s to 76.6 ± 18.6 cm/s (P = 0.008), and NT-pro BNP levels had a median (IQR) reduction from 115.7 (252.1) pg/mL to 55.0 (121.6) pg/mL (P = 0.043). Conclusions: TARFACT is a novel palliative treatment option for cardiac tumors, reducing accessible tumors and improving clinical symptoms in a preliminary group of patients. (Cardiac Tumors Interventional [Radio Frequency/Laser Ablation] Therapy [CTIH]; NCT02815553).

Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway.

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells, and can thus be used as substitutes for stem cells in stem cell therapy, thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments. This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke. However, the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear, presenting challenges for clinical translation. To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside, we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke. We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis. The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B, and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor. These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Finally, we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile. Therefore, human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

Impact of Imine Bond Orientations and Acceptor Groups on Photocatalytic Hydrogen Generation of Donor-Acceptor Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as one of the most studied photocatalysts owing to their adjustable structure and bandgaps. However, there is limited research on regulating the light-harvesting capabilities of acceptor building blocks in donor-acceptor (D-A) isomer COFs with different bond orientations. This investigation is crucial for elucidating the structure-property-performance relationship of COF photocatalysts. Herein, a series of D-A isostructural COFs are synthesized with different imine bond orientations using benzothiadiazole and its derivatives-based organic building units. Extended light absorption is achieved in COFs with acceptor groups that have strong electron-withdrawing capacities, although this resulted a decreased hydrogen generation efficiency. Photocatalytic experiments indicated that dialdehyde benzothiadiazole-based COFs, HIAM-0015, exhibit the highest hydrogen generation rate (17.99 mmol g-1 h-1), which is 15 times higher than its isomer. The excellent photocatalytic performance of HIAM-0015 can be attributed to its fast charge separation and migration. This work provides insights into the rational design and synthesis of D-A COFs to achieve efficient photocatalytic activity.

Correction: Polydopamine-capped AgNPs as a novel matrix overcoming the ion suppression of phosphatidylcholine for MALDI MS comprehensive imaging of glycerophospholipids and sphingolipids in impact-induced injured brain.

Correction for 'Polydopamine-capped AgNPs as a novel matrix overcoming the ion suppression of phosphatidylcholine for MALDI MS comprehensive imaging of glycerophospholipids and sphingolipids in impact-induced injured brain' by Chao Han et al., Analyst, 2019, 144, 6304-6312, https://doi.org/10.1039/C9AN01361J.

Inhibition of complement factor C5a or C5aR for cholesterol crystal embolism-related vascular thrombosis with microvascular injury and its consequences.

Cholesterol crystal embolism (CCE) implies immunothrombosis, tissue necrosis, and organ failure but no specific treatments are available. As CCE involves complement activation, we speculated that inhibitors of the C5a/C5aR axis would be sufficient to attenuate the consequences of CCE like that with systemic vasculitis. Cholesterol microcrystal injection into the kidney artery of wild-type mice initiated intra-kidney immunothrombosis within a few hours followed by a sudden drop of glomerular filtration rate and ischemic kidney necrosis after 24 hours. Genetic deficiency of either C3 or C5aR prevented immunothrombosis, glomerular filtration rate drop, and ischemic necrosis at 24 hours as did preemptive treatment with inhibitors of either C5a or C5aR. Delayed C5a blockade after crystal injection still resolved crystal clots and prevented all consequences. Thus, selective blockade of C5a or C5aR is sufficient to attenuate the consequences of established CCE and prospective inhibition in high-risk patients may be clinically feasible and safe.

Binding adaptability of chemical ligands to polymorphic α-synuclein amyloid fibrils.

α-synuclein (α-syn) assembles into structurally distinct fibril polymorphs seen in different synucleinopathies, such as Parkinson's disease and multiple system atrophy. Targeting these unique fibril structures using chemical ligands holds diagnostic significance for different disease subtypes. However, the molecular mechanisms governing small molecules interacting with different fibril polymorphs remain unclear. Here, we investigated the interactions of small molecules belonging to four distinct scaffolds, with different α-syn fibril polymorphs. Using cryo-electron microscopy, we determined the structures of these molecules when bound to the fibrils formed by E46K mutant α-syn and compared them to those bound with wild-type α-syn fibrils. Notably, we observed that these ligands exhibit remarkable binding adaptability, as they engage distinct binding sites across different fibril polymorphs. While the molecular scaffold primarily steered the binding locations and geometries on specific sites, the conjugated functional groups further refined this adaptable binding by fine-tuning the geometries and binding sites. Overall, our finding elucidates the adaptability of small molecules binding to different fibril structures, which sheds light on the diagnostic tracer and drug developments tailored to specific pathological fibril polymorphs.

Phase 1 Safety and Pharmacokinetics Study of TAVO101, an Anti-Human Thymic Stromal Lymphopoietin Antibody for the Treatment of Allergic Inflammatory Conditions.

TAVO101 is a humanized anti-human thymic stromal lymphopoietin (TSLP) monoclonal antibody under clinical development for the treatment of atopic dermatitis (AD) and other allergic inflammatory conditions. The crystallizable fragment region of the antibody was engineered for half-life extension and attenuated effector functions. This Phase 1, double-blinded, randomized, placebo-controlled study assessed the safety, tolerability, pharmacokinetics, and immunogenicity of TAVO101 in healthy adult subjects in seven ascending dose cohorts. Subjects received a single intravenous administration of TAVO101 or placebo with a 195-day follow-up. TAVO101 was safe and well tolerated. The incidences and severities of treatment-emergent adverse events were mostly mild and comparable between the active and placebo groups, with no trends of dose relationship. There were no severe adverse events, deaths, or treatment-related withdrawals. TAVO101 exhibited a linear pharmacokinetic profile, low clearance, and a median elimination half-life of 67 days in healthy subjects. All TAVO101-treated subjects tested negative for anti-drug antibodies. To support development in AD, TAVO101 was studied in an oxazolone-induced AD model in hTSLP transgenic mice and demonstrated efficacy. This long-acting anti-TSLP antibody has the potential for stronger and sustained allergic inflammatory disease control. The results from this study warranted further clinical development of TAVO101 in patients.

Spatiotemporal distribution, risk levels, and transport variations in neonicotinoids and fipronil and its metabolites cross a river-to-sea continuum.

Neonicotinoids (NEOs) and fipronil are widely used in pest control, but their spatiotemporal distribution and risk levels in the "river-estuary-bay" system remain unclear. Between 2018 and 2021, 148 water samples from rivers to inshore and offshore seawater in Laizhou Bay, China were collected to investigate the presence of eight NEOs and fipronil and its metabolites (FIPs). Significant seasonal variations in NEOs were observed under the influence of different cultivation practices and climatic conditions, with higher levels in the summer than in the spring. The average concentrations of total neonicotinoids (ΣNEOs) and ∑FIPs decreased from rivers (63.64 ng/L, 2.41 ng/L) to inshore (22.62 ng/L, 0.14 ng/L) and offshore (4.48 ng/L, 0.10 ng/L) seawater of Laizhou Bay. The average concentrations of ΣNEOs decreased by 85.3 % from 2018 to 2021. The predominant insecticides in the study area were acetamiprid, thiamethoxam, imidacloprid, and fipronil sulfone, with a gradual shift toward low-toxicity and environmentally friendly species over time. Influenced by agricultural intensity, ∑NEOs were mostly distributed in the Yellow River, Xiaoqing River, and their estuaries, where they pose chronic ecological risks. However, FIP exhibited high risk in certain rivers and sewage treatment plants owing to the use of animal repellents or landscape gardening insecticides. This study provides evidence of the transfer of NEOs and FIPs from rivers to the ocean and also clarifies their transition dynamics and changes in risk levels from rivers to oceans. Additionally, the study offers data support for identifying critical pesticide control areas.

Determination of chlordimeform and its metabolite residue in milk by gas chromatography-tandem mass spectrometry.

Herein, the determination of chlordimeform and its metabolite 4-chloro-2-methylaniline residue in milk was performed for the first time using gas chromatography-tandem mass spectrometry (GC-MS/MS). Samples were extracted using acetonitrile, and cleaned using a quick, easy, cheap, effective, rugged, and safe (QuEChERS) method. Separation was performed using the DB-17 MS column. It was detected in a selected reaction monitoring (SRM) mode and quantified using a matrix-matched isotope internal standard method. Under optimal conditions, a good linear relationship was observed in the concentration range of 10-200 µg/kg. The limit of quantitation was 10.0 µg/kg. The spiked recoveries for the target substance ranged from 84.5 % to 107.3 %, with relative standard deviations (RSD) of <7.2 %. The spiked samples were further confirmed by gas chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (GC-Orbitrap HRMS). The combined method resulted in high accuracy and sensitivity and was suitable for the determination of chlordimeform and its metabolite 4-chloro-2-methylaniline residue in milk.

Evaluating deep learning techniques for identifying tongue features in subthreshold depression: a prospective observational study.

Objective: This study aims to evaluate the potential of using tongue image features as non-invasive biomarkers for diagnosing subthreshold depression and to assess the correlation between these features and acupuncture treatment outcomes using advanced deep learning models. Methods: We employed five advanced deep learning models-DenseNet169, MobileNetV3Small, SEResNet101, SqueezeNet, and VGG19_bn-to analyze tongue image features in individuals with subthreshold depression. These models were assessed based on accuracy, precision, recall, and F1 score. Additionally, we investigated the relationship between the best-performing model's predictions and the success of acupuncture treatment using Pearson's correlation coefficient. Results: Among the models, SEResNet101 emerged as the most effective, achieving an impressive 98.5% accuracy and an F1 score of 0.97. A significant positive correlation was found between its predictions and the alleviation of depressive symptoms following acupuncture (Pearson's correlation coefficient = 0.72, p<0.001). Conclusion: The findings suggest that the SEResNet101 model is highly accurate and reliable for identifying tongue image features in subthreshold depression. It also appears promising for assessing the impact of acupuncture treatment. This study contributes novel insights and approaches to the auxiliary diagnosis and treatment evaluation of subthreshold depression.

Study of long-term effects of pelvic radiotherapy on the function of bone marrow in recurrent cervical cancer patients.

Purpose: To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. Methods and materials: The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. Results: Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ2=16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. Conclusions: The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy.

Correction: Can the improvement of the social credit environment enhance corporate ESG scores?

[This corrects the article DOI: 10.1371/journal.pone.0300247.].

Trends in research on nanomedicine in urologic cancer: a bibliometric and visualized analysis.

Increasing research efforts are focused on studying the synthesis and mechanisms of nanomedicine in urologic cancer. We performed a bibliometric study of the literature on nanomedicine in urologic cancer over the last 23 years, focusing on aspects such as researchers, institutions, nations, and keywords. We searched for papers in the Web of Science Core Collection from January 1, 2001, to December 29, 2023. Only reviews and original articles written in English were considered. A total of 2386 papers satisfied the given criteria for inclusion. The publications included in the study originated from 90 nations. The United States had the largest number of published papers, accounting for more than 31.01% of the total. The leading institution in this field is the Chinese Academy of Sciences, with a publishing output of 2.35%. Farokhzad, Omid C., is the most prolific author, with 21 articles, and has garnered the most citations, totaling 6271. The latest phrase to enter the top ten most common lists was "gold nanoparticles." We searched for papers in the Web of Science Core Collection from January 1, 2000, to November 28, 2023. Only reviews and original articles written in English were considered. This is the first bibliometric study of nanomedicine in urologic cancer. This article provides a comprehensive analysis of the current state of research on nanomedicine in urologic cancer over the last 23 years. On the basis of this study, future researchers can identify noteworthy publications, journals, and potential collaborators and explore cutting-edge research directions.

The prognostic significance of circulating tumor cell enumeration and HER2 expression by a novel automated microfluidic system in metastatic breast cancer.

BACKGROUND: The prognostic value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) has been extensively studied and verified by the CellSearch® system. Varieties of microfluidic systems have been developed to improve capture efficiency with the lack of standardization and automation. This study systematically verified the positive threshold for prognosis and its guidance value in anti-HER2 therapy based on a novel automated microfluidic system OmiCell®. METHODS: CTCs isolation, enumeration and labeling were performed using the OmiCell® system. CTCs identification and reporting were performed using the DeepSight® scanning system. RESULTS: The capture efficiency and specificity of OmiCell® system was 91.9% and 90%, respectively. Then, 65 MBC patients with known HER2 status of their metastatic tumors were enrolled. In the cohort, we detected ≥ 1 CTCs in 59 patients (90.8%, range: 1-55 CTCs, median = 6), < 8 CTCs in 45 (69.2%) and ≥ 8 CTCs in 20 (30.8%) patients at baseline. The patients with < 8 CTCs had longer PFS than ≥ 8 CTCs (median, 7 vs. 4.4 months, p = 0.028). CTC enumeration was found to be an independent prognostic factor in our cohort. Moreover, we found a weak concordance between tissue HER2 (tHER2) status and the corresponding CTCs (k = 0.16, p = 0.266). The patients with tHER2 positive and cHER2 negative had better PFS compared with patients with both tHER2 and cHER2 positive (median, 8.2 vs. 3.3 months, p = 0.022). CONCLUSIONS: This clinical study shows the prognosis value of a new threshold of CTC number and meanwhile the guidance value of cHER2 status in anti-HER2 therapy.