Clinically Applicable Pan-Origin Cancer Detection for Lymph Nodes via AI-Based Pathology.

Lymph node metastasis is one of the most common ways of tumour metastasis. The presence or absence of lymph node involvement influences the cancer's stage, therapy, and prognosis. The integration of artificial intelligence systems in the histopathological diagnosis of lymph nodes after surgery is urgent. Here, we propose a pan-origin lymph node cancer metastasis detection system. The system is trained by over 700 whole slide images and is composed of two deep learning models to locate the lymph nodes and detect cancers. It achieved a area under the receiver operating characteristic (ROC) curve (AUC) of 0.958, with a 95.2% sensitivity and 72.2% specificity, on 1,402 whole-slide images (WSIs) from 49 organs at the National Cancer Center, China. Moreover, we demonstrated that the system could perform robustly with 1,051 WSIs from 52 organs from another medical center, with a AUC of 0.925. Our research represents a step forward in a pan-origin lymph node metastasis detection system, providing accurate pathological guidance by reducing the probability of missed diagnosis in routine clinical practice.

Development of efficient and economic Bi2O3/BN/Co3O4 composite photocatalyst: Degradation mechanism, pathway and toxicity study of norfloxacin.

The production of cheap, efficient, and stable photocatalysts for degrading antibiotic contaminants remains challenging. Herein, Bi2O3/boron nitride (BN)/Co3O4 ternary composites were synthesized using the impregnation method. The morphological characteristics, structural features, and photochemical properties of the prepared photocatalysts were investigated via X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, and ultraviolet-visible (Vis) diffuse reflectance spectrum techniques. BN was used as a charge transfer bridge in the ternary composites, which afforded a heterojunction between the two semiconductors. The formation of the heterojunction substantially enhanced the charge separation and improved the photocatalyst performance. The degradation activity of the Bi2O3/BN/Co3O4 ternary composites against norfloxacin (NOR) under Vis light irradiation was investigated. The degradation rate of NOR using 5-wt% Bi2O3/BN/Co3O4 reached 98% in 180 min, indicating excellent photocatalytic performance. The ternary composites also exhibited high photostability with a degradation efficiency of 88.4% after five cycles. Hydroxyl radicals (•OH), superoxide radicals (•O2-), and holes (h+) played a synergistic role in the photocatalytic reaction, where h+ and •O2- were more important than •OH. Consequently, seven intermediates and major photocatalytic degradation pathways were identified. Toxicity experiments showed that the toxicity of the degradation solution to Chlorella pyrenoidosa decreased. Finally, the ecotoxicity of NOR and its intermediates were analyzed using the Toxicity Estimation Software Tool, with most intermediates exhibiting low toxicity.

Emulsifiable oil-formulated Beauveria bassiana competes with imidacloprid for seasonal control of cereal aphids in Zhejiang, China.

BACKGROUND: Alternatives to neonicotinoids against cereal aphids are needed to mitigate aphid resistance and non-target effects. The emulsifiable oil formulations of two Beauveria bassiana strains, namely Bb registered as a mycoinsecticide and TBb overexpressing an endogenous virulence factor, were tested for seasonal control of cereal aphids at the elongating (April 7) to milk ripening (May 12) stages of winter wheat crop in Yuhang, Zhejiang. Each of three field trials consisted of blank control and the treatments (three randomized 100-m2 plots per capita) of each fungal strain sprayed biweekly at rates of 1.0 × 1013 and 1.5 × 1013 conidia ha-1 and 10% imidacloprid WP sprayed biweekly at a label rate. RESULTS: Tiller infestation percentage and aphid density in the 5-week field trials after the first spray were reduced to 18.7-22.4% and 9.1-12.4 aphids per tiller in the fungal treatments, and 12.8-25.3% and 2.8-20.9 aphids per tiller in the chemical treatment, contrasting with 49.2-60.3% and 37.1-108.5 aphids per tiller in the control. Percent control efficacies (±SD) computed with weekly aphid densities over the period averaged 84.0 ± 1.6 and 85.3 ± 1.8 versus 78.0 ± 4.0 and 79.9 ± 3.2 in the high-rate versus low-rate treatments of Bb and TBb, respectively, and 84.5 ± 7.8 in the chemical treatment. Imidacloprid showed faster kill action but more variable efficacy than the fungal treatments throughout the trials. CONCLUSION: Either Bb or TBb formulation competes with imidacloprid in reducing percent infestation and aphid density. The overall efficacy was significantly higher in the treatments of TBb than of Bb. © 2024 Society of Chemical Industry.

Slow conduction velocity predicts atrial fibrillation recurrence after radiofrequency ablation.

OBJECTIVE: To evaluate the progression of electrophysiological phenomena in atrial fibrillation (AF) and elucidate the association between the left atrial conduction velocity (LACV) and AF recurrence after pulmonary vein isolation. METHODS: A total of 188 AF patients (121 paroxysmal AF and 67 persistent AF) who underwent PVI for the first time were enrolled in this prospective study. The left atrium was mapped using a 20-pole electrode catheter combined with the CARTO3 system. The conduction distances and conduction times of the left atrium from the Bachmann bundle area to the mitral isthmus were calculated. Anterior, posterior, and septal LACV were calculated as conduction distance divided by conduction time. RESULTS: The anterior, posterior, and septal LACVs in the AF recurrence group were slower than those in the nonrecurrence group (anterior: 0.807 [0.766, 0.848] and 1.048 [1.000, 1.093] m/s, p < .05; posterior: 1.037 [0.991, 1.084] vs. 1.315 [1.249, 1.380] m/s, p < .05; septal: 0.904 [0.862, 0.946] vs. 1.163 [1.107, 1.219] m/s, p < .05). The best cut-off value of anterior LACV for predicting AF recurrence was 0.887 m/s (sensitivity 73.9% and specificity 76.5%). Multivariate analysis showed slow anterior LACV <0.887 m/s was an independent predictor of AF recurrence with an adjusted odds ratio of 1.42 (1.04, 1.94). CONCLUSIONS: Slowing conduction velocity is a predictor of AF recurrence after pulmonary vein isolation.

Comprehensive analysis of ovarian granulosa cell proteomics and phosphoproteomics in PCOS patients without insulin resistance.

PCOS is a complex and heterogeneous metabolic disorder that affects 6-20% of women of reproductive age. However, research on phosphorylation modification proteomics in PCOS remains lacking. PCOS can be divided into two groups based on the presence or absence of insulin resistance: PCOS with insulin resistance (PCOS-IR) and PCOS non-insulin resistant (PCOS-NIR). This study focused on the group without insulin resistance. Twenty-one PCOS-NIR and 39 control-NIR (Ctrl-NIR) patients were included in this study. All participants underwent ICSI or IVF-embryo transfer (IVF-ET) treatment in a reproductive center from July 2020 to November 2020. During oocyte retrieval, fresh follicular fluid was aspirated, collected, and sent to the laboratory for analysis of the granulosa cells. A 4D-label-free proteome quantification method was performed in this study; this was used to analyze protein enzymatic peptide fragments by liquid chromatography-mass spectrometry (LC-MS). Bioinformatic analysis was performed on differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs). A total of 713 DEPs were identified between the two groups, including 293 upregulated and 420 downregulated DEPs in the PCOS-NIR group. There were 522 and 159 proteins with increased and decreased phosphorylation, respectively, in the PCOS-NIR group. After analyzing the different phosphorylation modification sites, 933 sites with upregulated and 211 sites with downregulated phosphorylation were found in the PCOS-NIR group. In this study, we describe the quantitative protein expression profiles and phosphorylation-modified protein expression profiles of ovarian granulosa cells from patients with PCOS-NIR, providing a new research perspective for these patients. Further studies are required to elucidate the role of protein phosphorylation in PCOS.

Long-term outcomes of pelvic exenterations for gynecological malignancies: a single-center retrospective cohort study.

BACKGROUND: Recently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China. PATIENTS AND METHODS: PE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed. RESULTS: Forty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%. CONCLUSION: PE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.

A Systematic Review and Meta-Analysis of the Impacts of Time-Restricted Eating on Metabolic Homeostasis.

This meta-analysis investigated the effect of time-restricted eating (TRE) as an economical lifestyle intervention for the prevention of metabolic syndrome and improving the related metabolic variables. The Cochrane library, MEDLINE, EMBASE, clinical trials, and other databases were searched for randomized controlled trials (RCTs). We included 22 RCTs (1004 participants, aged 18-75 years, including healthy subjects, prediabetes and overweight patients) designed to evaluate the effect of TRE on metabolic parameters. Body mass index (BMI) (-0.56 kg/m2, 95% CI: -1.00, -0.13, P < .01), fasting blood glucose (-1.74 mmol/L, 95% CI: -3.34, -0.14, P < .01), and body weight (-0.48 kg, 95% CI: -0.74, -0.22, P < .01) in the TRE intervention group were decreased to varying degrees compared with controls. In contrast, high-density lipoprotein cholesterol (HDL-C) levels were significantly increased in the TRE group compared with the control group (P < .01). The change in waist circumference, blood pressure, triglycerides, low-density lipoprotein cholesterol (LDL-C), and total cholesterol did not vary markedly across the groups. In conclusion, this meta-analysis found a significant reduction in BMI, weight, and fasting glucose, as well as a rise in HDL-C level with TRE compared with control. TRE could be used as an adjuvant treatment for metabolic dysfunctions.

Insidious transmission of Mycobacterium tuberculosis in Ordos, China: a molecular epidemiology study.

BACKGROUND: In this study, we conducted this population-based study to evaluate the genetic diversity and clustering rate of Mycobacterium tuberculosis (MTB) strains using the whole-genome sequencing (WGS), to better understand its transmission in Ordos. METHODS: All patients with culture-positive TB notified in Ordos from January 2021 to December 2022 were recruited. WGS was performed to analyze single-nucleotide polymorphism (SNP) and to identify genotypic drug susceptibilities of MTB isolates. RESULTS: Overall, a total of 186 patients were included in the present study, of whom 35 (18.8%) had no symptoms suggestive of active TB. Lineage 2 was the predominant MTB sublineage, accounting for 186 of isolates tested. When the pairwise SNP difference ≤ 12 was used as the cutoff for WGS-based clusters, we identified 17 genotypic clusters, and 38 isolates belonged to these 17 clusters, resulting in a clustering rate of 20.4%. The Beijing genotype was an independent factor associating with genomic-clustering (adjusted OR 4.219, 95% CI 0.962-18.502). The overall sensitivity on WGS-based resistance prediction was 85.7% for rifampicin, 73.1% for isoniazid, 60.0% for Ethambutol, 72.7% for streptomycin, and 72.7% for fluoroquinolones. CONCLUSION: To conclude, the present study demonstrates the extensive recent transmission of Beijing genotype strains in the community of Ordos. The failure to provide a comprehensive pattern of transmission indicated the missed diagnosis of active TB within the community. A substantial proportion of subclinical TB cases are recognized in the bacteria-positive cases, emphasizing that we must interrupt transmission by finding people with active TB before they infect others.

Analgesic onset and efficacy of a fast-acting formulation of acetaminophen in a postoperative dental impaction pain model.

OBJECTIVES: Speed of onset can be critical to an analgesic's efficacy treating acute pain. To enhance onset, a new oral acetaminophen formulation intended to be fast acting was developed. Two studies evaluated the analgesic onset, efficacy, and safety of this fast-acting acetaminophen (FA-acetaminophen) tablet relative to commercial acetaminophen caplets (ES-acetaminophen) and commercial ibuprofen liquid-filled gelatin capsules (LG-ibuprofen). METHODS: Two single-center, single-dose, inpatient, randomized, double-blind, triple-dummy, placebo-controlled, parallel group design clinical trials were conducted using the postoperative dental impaction pain model. Subjects were healthy men and women aged 17-50 years experiencing moderate-to-severe pain after surgical extraction of at least three impacted third molars. In both studies, four treatment groups were evaluated: 1,000 mg acetaminophen as two 500 mg FA-acetaminophen tablets, 1,000 mg as two 500 mg ES-acetaminophen caplets, 400 mg ibuprofen as two 200 mg LG-ibuprofen capsules, and placebo. To maintain blinding, each subject received six units of study medication. Times to confirmed perceptible pain relief (TCPR) and meaningful pain relief (TMPR) were obtained using the double-stopwatch method. Pain intensity and relief were measured over 6 h following drug administration using a 0-10 numerical rating scale. Time to use of rescue medication (naproxen sodium) and subject global evaluations of study medications at 6 h were collected. Pharmacokinetic blood sampling and safety assessments were performed. RESULTS: Studies 1 and 2 enrolled 240 and 420 subjects, respectively. No clinically important differences among treatment groups were observed for any demographic or baseline characteristics. Efficacy results showed all active treatments statistically superior to placebo. In Study 1, TCPR was statistically significantly shorter for FA-acetaminophen compared to ES-acetaminophen and LG-ibuprofen. In Study 2, no statistically significant differences in TCPR were noted across the active treatment groups. In Study 1, FA-acetaminophen 1,000 mg provided significantly shorter TMPR compared with LG-ibuprofen but not compared with ES-acetaminophen. In Study 2, no significant differences in TMPR were noted across the active treatment groups. In both Study 1 and 2 at 15 min after administration of study drug, PID and PAR scores were greater for FA-acetaminophen than LG-ibuprofen. CONCLUSIONS: Both studies suggested FA-acetaminophen had faster onset of action compared to ES-acetaminophen and LG-Ibuprofen. In light of the difference in TCPR and TMPR results between Study 1 and 2, an additional study is needed to further investigate time to analgesic onset of FA-acetaminophen compared with ES-acetaminophen and LG-Ibuprofen. STUDY REGISTRY NUMBERS: Study 1: NCT02735122; Study 2: NCT03224403.

Astrocytic calcium waves: unveiling their roles in sleep and arousal modulation.

Neuron-astrocyte interactions are vital for the brain's connectome. Understanding astrocyte activities is crucial for comprehending the complex neural network, particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals. Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons. Astrocytes, outnumbering neurons by nearly fivefold, support and regulate neuronal and synaptic function. Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling. This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep, wakefulness, and arousal levels, exploring the involvement of noradrenaline signaling, ion channels, and glutamatergic signaling in different cortical states. These findings highlight the significant impact of astrocytes on large-scale neuronal networks, influencing brain activity and responsiveness. Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation. More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states, requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep- and arousal-related disorders.

Corrigendum: Fertility-enhancing effect of oil-based contrast agents during hysterosalpingography and the variation of this effect within a 3-year follow-up period in infertile patients.

[This corrects the article DOI: 10.3389/fmed.2022.948945.].

Polyphyllin VII induces CTC anoikis to inhibit lung cancer metastasis through EGFR pathway regulation.

Circulating tumor cells (CTCs) are cells that detach from the primary tumor and enter the bloodstream, playing a crucial role in the metastasis of lung cancer. Unfortunately, there is currently a lack of drugs specifically designed to target CTCs and prevent tumor metastasis. In this study, we present evidence that polyphyllin VII, a potent anticancer compound, effectively inhibits the metastasis of lung cancer by inducing a process called anoikis in CTCs. We observed that polyphyllin VII had significant cytotoxicity and inhibited colony formation, migration, and invasion in both our newly established cell line CTC-TJH-01 and a commercial lung cancer cell line H1975. Furthermore, we found that polyphyllin VII induced anoikis and downregulated the TrkB and EGFR-MEK/ERK signaling pathways. Moreover, activation of TrkB protein did not reverse the inhibitory effect of polyphyllin VII on CTCs, while upregulation of EGFR protein effectively reversed it. Furthermore, our immunodeficient mouse models recapitulated that polyphyllin VII inhibited lung metastasis, which was associated with downregulation of the EGFR protein, and reduced the number of CTCs disseminated into the lungs by inducing anoikis. Together, these results suggest that polyphyllin VII may be a promising compound for the treatment of lung cancer metastasis by targeting CTCs.

Identification of exosome protein panels as predictive biomarkers for non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes. METHODS: Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes. RESULTS: Our study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients. CONCLUSIONS: These findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.

Spatiotemporal distribution and ecological risk assessment of pharmaceuticals and personal care products (PPCPs) from Luoma Lake, an important node of the South-to-North Water Diversion Project.

PPCPs (pharmaceuticals and personal care products) are widely found in the environment and can be a risk to human and ecosystem health. In this study, spatiotemporal distribution, critical risk source identification and potential risks of 14 PPCPs found in water collected from sampling points in Luoma Lake and its inflowing rivers in two seasons in 2019 and 2020 were investigated. The PPCPs concentrations ranged from 27.64 ng·L-1 to 613.08 ng·L-1 in December 2019, and from 16.67 ng·L-1 to 3287.41 ng·L-1 in April 2020. Ketoprofen (KPF) dominated the PPCPs with mean concentrations of 125.85 ng·L-1 and 640.26 ng·L-1, respectively. Analysis of sources showed that the pollution in Luoma Lake mostly originated from sewage treatment plant effluents, inflowing rivers and domestic wastewater. Among them, the inflowing rivers contributed the most (82.95%) to the concentration of total PPCPs. The results of ecological risk assessment showed that there was a moderate risk (0.1 < RQs < 1) from carbamazepine (CBZ) in December 2019 and a high risk (RQs > 1) from naproxen (NPX) in April 2020. The results of human risk assessment found that NPX posed a high risk to infant health, and we found that NPX was associated with 83 diseases according to Comparative Toxicogenomics Database. NPX was identified as a substance requiring major attention. The results provide an understanding of the concentrations and ecological risks of PPCPs in Luoma Lake. We believe the data will support environmental departments to develop management strategies and prevent PPCPs pollution.

Relationship between anatomical characteristics of pulmonary veins and atrial fibrillation recurrence after radiofrequency catheter ablation: a systematic review and meta-analysis.

Background: The aim of the current study was to investigate the potential relationship between anatomical characteristics of pulmonary veins (PVs) and atrial fibrillation recurrence (AFR) following radiofrequency catheter ablation (RFCA), specifically focusing on PV diameter and cross-sectional orifices index (CSOA). The analysis was based on a comprehensive review of currently available literature, providing valuable insights for the prevention and treatment of AFR. Methods: Data was collected from five databases, including PubMed, MEDLINE, EMBASE, and Cochrane, spanning the period from 2004 to October 2022. The search strategy utilized Medical Subject Headings (MeSH) terms related to PV diameter, PV size, PV anatomy, and AFR. Indicators of PV diameter and CSOA from the included studies were collected and analyzed, with Weight mean difference (WMD) and 95% confidence intervals (CIs) representing continuous variables. Results: The meta-analysis included six studies. The results revealed that patients with AFR had a significant larger mean PV diameter compared to those without AFR (MD 0.33; 95% CI: 0.01, 0.66; P = 0.04; I2 = 33.80%). In a meta-analysis of two studies involving a total of 715 participants, we compared the diameters of the left superior pulmonary vein (LSPV), left inferior pulmonary vein (LIPV), right superior pulmonary vein (RSPV), right inferior pulmonary vein (RIPV) between patients with AFR and patients without AFR. The results showed that there were no statistically significant differences between the two groups in any of the four data items (all P > 0.05). Additionally, the pooled estimate revealed that LSPV-CSOA, LIPV-COSA, RSPV-COSA, and RIPV-CSOA were greater in the AFR group compared to the non-AFR group, but the differences were not statistically significant (all P > 0.05). Conclusion: We found evidence supporting the notion that the PV diameter of patients who experienced AFR after RFCA was significantly larger than that of patients without AFR. The findings suggested that the PV diameter could serve as a potential predictor of the risk of AFR following RFCA.

Pathogens and antibiotic resistance genes during the landfill leachate treatment process: Occurrence, fate, and impact on groundwater.

Landfill leachate is an essential source of pathogens and antibiotic resistance genes (ARGs) in the environment. However, information on the removal behavior of pathogens and ARGs during the leachate treatment and the impact on surrounding groundwater is limited. In this study, we investigated the effects of leachate treatment on the removal of pathogens and ARGs with metagenomic sequencing, as well as the impact of landfill effluent on groundwater. It is shown that the leachate treatment could not completely remove pathogens and ARGs. Twenty-nine additional pathogens and twenty-nine ARGs were newly identified in the landfill effluent. The relative abundance of pathogens and multiple antibiotic resistance genes decreased after ultrafiltration but relative abundance increased after reverse osmosis. In addition, the relative abundances of Acinetobacter baumannii, Erwinia amylovora, Escherichia coli, Fusarium graminearum, Klebsiella pneumoniae, and Magnaporthe oryzae, as well as mdtH, VanZ, and blaOXA-53 increased significantly in the landfill effluent compared to the untreated leachate. The relative abundance of some mobile genetic elements (tniA, tniB, tnpA, istA, IS91) in leachate also increased after ultrafiltration and reverse osmosis. The size of pathogens, the size and properties of ARGs and mobile genetic elements, and the materials of ultrafiltration and reverse osmosis membranes may affect the removal effect of pathogens, ARGs and mobile genetic elements in leachate treatment process. Interestingly, the pathogens and ARGs in landfill effluent were transferred to groundwater according to SourceTracker. The ARGs, mobile genetic elements, and pathogens that are difficult to remove in the leachate treatment process, provide a reference for optimizing the leachate treatment process and improving the control of pathogens and ARGs. Furthermore, this study clarifies the effect of landfill leachate sources of pathogens and ARGs in groundwater.

Comprehensive overview of antibiotic distribution, risk and priority: A study of large-scale drinking water sources from the lower Yangtze River.

Antibiotics have attracted widespread attention around the world because they are ubiquitous in the environment and can lead to antibiotic-resistant microbes developing and pose ecotoxicological risks. In this study, we determined the spatiotemporal distributions of 39 antibiotics in 19 drinking water sources in Jiangsu area of the lower Yangtze River and attempted to identify the sources of the antibiotics and to prioritize the antibiotics. The total antibiotic concentrations in spring and fall were 234.56-6515.99 and 151.12-2562.59 ng/L, respectively. In spring, the total antibiotic concentration gradually increased from upstream to downstream. In fall, the antibiotic concentration did not markedly vary upstream to downstream (total concentrations 151.12-432.17 ng/L) excluding site S9 and S10. Analysis using a positive matrix factorization (PMF) model indicated that the antibiotics had four main sources. Pharmaceutical wastewater was the main source, contributing 34.1% and 41.2% of total antibiotics in spring and fall, respectively, and domestic wastewater was the second most important source, contributing 24.4% and 43% of total antibiotics in spring and fall, respectively. Pharmaceutical wastewater was the main source from midstream to downstream, but the other sources made different contributions in different areas because of the various ranges of human activities. An ecological risk assessment was performed. Stronger risks were posed by antibiotics in spring than fall, and fluoroquinolone antibiotics posed the strongest risks. Optimized risk quotients indicated that norfloxacin was a high-risk contaminant. An assessment of the risk of resistance development indicated that norfloxacin, ciprofloxacin, and enrofloxacin posed moderate to high risks of resistance development and should be prioritized for risk management. The results of this study are important reference data for identifying key sources of antibiotics and developing strategies to manage antibiotic contamination in similar areas.

Identification of new aptamer BC-3 targeting RPS7 from rapid screening for bladder carcinoma.

Aptamers, short single DNA or RNA oligonucleotides, have shown immense application potential as molecular probes for the early diagnosis and therapy of cancer. However, conventional cell-SELEX technologies for aptamer discovery are time-consuming and laborious. Here we discovered a new aptamer BC-3 by using an improved rapid X-Aptamer selection process for human bladder carcinoma, for which there is no specific molecular probe yet. We show that BC-3 exhibited excellent affinity in bladder cancer cells but not normal cells. We demonstrate that BC-3 displayed high selectivity for tumor cells over their normal counterparts in vitro, in mice, and in patient tumor tissue specimens. Further endocytosis pathway analysis revealed that BC-3 internalized into bladder cancer cells via clathrin-mediated endocytosis. Importantly, we identified ribosomal protein S7 (RPS7) as the binding target of BC-3 via an integrated methodology (mass spectrometry, colocalization assay, and immunoblotting). Together, we report that a novel aptamer BC-3 is discovered for bladder cancer and its properties in the disease are unearthed. Our findings will facilitate the discovery of novel diagnostic and therapeutic strategies for bladder cancer.