A Classification-Based Adaptive Segmentation Pipeline: Feasibility Study Using Polycystic Liver Disease and Metastases from Colorectal Cancer CT Images.

Automated segmentation tools often encounter accuracy and adaptability issues when applied to images of different pathology. The purpose of this study is to explore the feasibility of building a workflow to efficiently route images to specifically trained segmentation models. By implementing a deep learning classifier to automatically classify the images and route them to appropriate segmentation models, we hope that our workflow can segment the images with different pathology accurately. The data we used in this study are 350 CT images from patients affected by polycystic liver disease and 350 CT images from patients presenting with liver metastases from colorectal cancer. All images had the liver manually segmented by trained imaging analysts. Our proposed adaptive segmentation workflow achieved a statistically significant improvement for the task of total liver segmentation compared to the generic single-segmentation model (non-parametric Wilcoxon signed rank test, n = 100, p-value << 0.001). This approach is applicable in a wide range of scenarios and should prove useful in clinical implementations of segmentation pipelines.

The Fastest Capillary Flow in Root-like Networks under Gravity.

Capillary flow has garnered significant attention due to its unique dynamic characteristics that require no external force. Creating a quantitative analytical model to evaluate capillary flow behaviors in root-like networks is essential for enhancing fluid control properties in functional textiles. In this study, we explore the capillary dynamics within root-like networks under the influence of gravity and derive the most rapid capillary flow via structural optimization. The flow time in a capillary is dominated by the capillary pressure, viscous pressure loss, and gravity, each of which exhibits diverse sensitivities to the structures of root-like networks. We scrutinize various structural parameters to understand their impact on capillary flow in root-like networks. Subsequently, optimal structural parameters (namely, the mother tube diameter and diameter ratio) are identified to minimize capillary flow time. Moreover, we discovered that the correlation between flow time and distance for capillary flow in root-like networks does not obey the classical Lucas-Washburn equation. These results affirm that root-like networks can enhance capillary flow, providing critical insights for numerous capillary-flow-dependent engineering applications.

Bee colonies map the short- and medium-chain chlorinated paraffin contamination from the apiary environment.

Chlorinated paraffins (CPs) are industrial chemicals that have potential adverse effects in the environment and on human health. This study investigated CPs in apiary environment, honeybees, and bee products from two rural areas of Beijing, China. The median concentrations of short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) were 22 and 1.6 ng/m3 in the ambient air, 1350 and 708 ng/g dry mass (dw) in bees, 1050 and 427 ng/g dw in flowers, 37 and 54 ng/g in honey, 78 and 53 ng/g dw in bee pollen, 36 and 30 ng/g dw in soil, and 293 and 319 ng/g dw in bee wax. C10Cl6-7 and C14Cl7-8 dominated SCCPs and MCCPs in these samples, respectively. The concentrations and distributions of CPs in samples from apiaries located in the two regions varied. Long-range transportation of air masses was identified as an important source of CPs in apiaries. A close relationship between CPs in bees and the apiary environment indicated that bees could act as bioindicators for CP contamination in the environment. A human health risk assessment found that there were low risks for adults and children exposed to CPs through consumption of honey and pollen from the studied regions.

The status and challenges for prostate SBRT treatments in United States proton therapy centers: An NRG Oncology practice survey.

A survey was designed to inquire about the practice of proton SBRT treatment for prostate cancer. The survey was distributed to all 30 proton therapy centers in the United States that participate in the National Clinical Trial Network in Feb. 2023. The survey focused on usage, patient selection criteria, prescriptions, target contours, dose constraints, treatment plan optimization and evaluation methods, patient-specific QA, and IGRT methods. Results: We received responses from 25 centers (83% participation). Only 8 respondent proton centers (32%) reported performing SBRT of the prostate. The remaining 17 centers cited three primary reasons for not offering this treatment: no clinical need, lack of volumetric imaging, and/or lack of clinical evidence. Only 1 center cited the reduction in overall reimbursement as a concern for not offering prostate SBRT. Several common practices among the 8 centers offering SBRT for the prostate were noted, such as using Hydrogel spacers, fiducial markers, and MRI for target delineation. Most proton centers (87.5%) utilized pencil beam scanning (PBS) delivery and completed Imaging and Radiation Oncology Core (IROC) phantom credentialing. Treatment planning typically used parallel opposed lateral beams, and consistent parameters for setup and range uncertainties were used for plan optimization and robustness evaluation. Measurements-based patient-specific QA, beam delivery every other day, fiducial contours for IGRT, and total doses of 35-40 GyRBE were consistent across all centers. However, there was no consensus on the risk levels for patient selection. Conclusion: Prostate SBRT is used in about 1/3 of proton centers in the US. There was a significant consistency in practices among proton centers treating with proton SBRT. It is possible that the adoption of proton SBRT may become more common if proton SBRT is more commonly offered in clinical trials.

The transcription factor ThDof8 binds to a novel cis-element and mediates molecular response to salt stress in Tamarix hispida.

Salt stress is a commom abiotic factor that restricts plant growth and development. As a halophyte plant, it is of great significance to explore the salt tolerance genes and regulatory mechanisms of Tamarix hispida. Dof (DNA-bining with one finger), as an important transcription factor (TF), influences and controls various signaling substances involved in diverse biological processes related to plant growth and development. However, the regulatory mechanisms of Dof TFs, in response to salt stress, are largely unknown in T. hispida. In the present study, ThDof8, a new Dof gene, was cloned from T. hispida, and ThDof8 gene expression was induced by salt stress. Transient overexpression of the ThDof8 enhanced T. hispida salt tolerance by enhancing proline levels, and the activities of antioxidant enzymes, superoxide dismutase (SOD) and peroxidase (POD). These results were also verified in stably transformed Arabidopsis thaliana. The results of a TF-Centered Yeast One-Hybrid (TF-centered Y1H) assay and electrophoretic mobility shift assay (EMSA) showed that ThDof8 bound to a new cis-element (TGCG). Expression profile gene chip analysis identified four potential direct gene targets of ThDof8, CRK10, CRK26, GAD41 and GAD42, which were also verified by chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR), EMSA, yeast one hybrid (Y1H) assays, and beta-glucuronidase (GUS) enzyme activity assays. ThDof8 can bind to the TGCG element in the promoter regions of downstream target genes. Transient overexpression of ThCRK10 also enhanced T. hispida salt tolerance. In brief, a new regulatory mechanism model of ThDof8 was founded that ThDof8 binds to the TGCG cis-element in the promoter of the downstream gene CRK10 to regulate its expression and improve salt tolerance in T. hispida. This study provides a basis for further understanding the role of the Dof TFs and identifying other downstream candidate genes for improving plant salt tolerance via molecular breeding.

Polychlorinated naphthalenes in freshwater fish from Beijing markets: Species-specific differences, effects of cooking, and health risk assessment.

Fish are an important source of human dietary exposure to polychlorinated naphthalenes (PCNs). The occurrence and sources of PCNs in different species of freshwater fish are unknown, and few studies have assessed human exposure risks to PCNs through freshwater fish. In this study, 140 freshwater fish samples from 10 species were collected from Beijing markets, China. The Σ75CNs concentration range in the fish was 20.7-1310 pg/g wet weight (ww). The highest median Σ75PCNs concentration (80.4 pg/g ww) was found in mandarin fish (Siniperca chuatsi), and the lowest (29.6 pg/g ww) in snakehead (Channa argus). Di- and tri-CNs were the dominant PCN homologues with contributions of 35.3 % and 30.8 %, respectively. Unintentionally produced PCNs from metal smelting might be the source of PCN contamination in freshwater fish. The cooking temperature and time did not significantly affect the PCN concentrations in fish or the PCN homologue profiles. The highest toxic equivalent (TEQ) value was observed in sturgeon (Acipenser sinensis), followed by mandarin fish. Hexa-CNs were the most abundant homologue for the PCN TEQs. A risk assessment indicated that the dietary exposure risks for local residents to PCNs through freshwater fish were low. However, the relatively high concentrations of PCNs in the samples deserve attention to avoid PCNs exposure risks for groups with high fish consumption rates. Furthermore, freshwater fish likely contain a mixture of contaminants including dioxin and furans which also display a similar mode of toxicity as the PCNs and could enhance the risk to fish consumers.

A preliminary study on short- and medium-chain chlorinated paraffins in duck farms: Concentrations, distribution, and dietary exposure risks.

Chlorinated paraffins (CPs) in poultry feed and the farm environment might bioaccumulate in poultry eggs. Unlike chickens, which are mostly raised in cages, ducks are commonly raised free range. This would expose ducks to CPs in the environment. However, information on the presence of CPs on duck farms is scarce. In the present study, samples of duck eggs, duck feathers, poultry feed, and soil were collected from 25 duck farms in South China. Forty-eight congener groups of short- and medium-chain CPs (SCCPs and MCCPs) were detected in the samples. Interestingly, relatively high concentrations of SCCPs and MCCPs were found in the duck feathers. The median concentrations of SCCPs and MCCPs in the duck eggs, feathers, feed and soil were: 46 and 18 ng/g wet weight, 2460 and 992 ng/g, 103 and 47 ng/g, and 24 and 10 ng/g dry weight, respectively. The dominant groups of SCCPs and MCCPs were C10Cl6-7 and C14Cl7-8, respectively. The close relationship between duck feathers and poultry feed indicated that the duck feathers might act as a bioindicator for the exposure of ducks to CPs. The margin of exposure approach was used to assess the health risk, with the results showing that the consumption of duck eggs posed a low risk to different age groups from exposure to SCCPs and MCCPs.

Unravelling bioaccumulation, depletion and metabolism of organophosphate triesters in laying hens: Insight of in vivo biotransformation assisted by diester metabolites.

Organophosphate triesters (tri-OPEs) threaten human health through dietary exposure, but little is known about their feed-to-food transfer and in vivo behavior in farm animals. Herein 135 laying hens were fed with contaminated feed (control group, low-level group and high-level group) to elucidate the bioaccumulation, distribution, and metabolism of the six most commonly reported tri-OPEs. The storage (breast muscle), metabolism and mobilization (liver and blood) and non-invasive (feather) tissues were collected. The exposure-increase (D1∼14) and depuration-decrease (D15∼42) trends indicated that feed exposure caused tri-OPE accumulation in animal tissues. Tissue-specific and moiety-specific behavior was observed for tri-OPEs. The highest transfer factor (TF) and transfer rate (TR) were observed in liver (TF: 14.8%∼82.3%; TR: 4.40%∼24.5%), followed by feather, breast muscle, and blood. Tris(2-chloroisopropyl) phosphate (TCIPP) had the longest half-life in feather (72.2 days), while triphenyl phosphate (TPhP) showed the shortest half-life in liver (0.41 days). Tri-OPEs' major metabolites (organophosphate diesters, di-OPEs) were simultaneously studied, which exhibited dose-dependent and time-dependent variations following administration. In breast muscle, the inclusion of di-OPEs resulted in TF increases of 735%, 1108%, 798%, and 286% than considering TCIPP, tributyl phosphate, tris(2-butoxyethyl) phosphate and tris(2-ethylhexyl) phosphate alone. Feather was more of a proxy of birds' long-term exposure to tri-OPEs, while short-term exposure was better reflected by di-OPEs. Both experimental and in silico modeling methods validated aryl-functional group facilitated the initial accumulation and metabolism of TPhP in the avian liver compared to other moiety-substituted tri-OPEs.

Selective gold extraction from electronic waste using high-temperature-synthesized reagents.

For over two hundred years, cyanide has served as the primary reagent for gold extraction. However, due to its high toxicity, the use of cyanide poses significant risks. Traditional low-toxicity leaching reagents have limitations that restrict their widespread industrial application, leading to the necessity for the development of new, efficient, and low-toxic gold leaching reagents to support sustainable gold production. In this study, a novel, efficient, and low-toxicity gold extraction reagent was synthesized at high temperatures by combining urea, sodium carbonate, and a specific iron salt. The research delved into the leaching ability of the reagent under different synthesis conditions and examined the generation of free cyanide content as a by-product. Findings indicated that reagents synthesized with either potassium ferrocyanide or potassium ferricyanide displayed comparable leaching capabilities. Reagents synthesized at 800 °C exhibited lower levels of free cyanide ions and reduced toxicity. Additionally, this reagent demonstrated exceptional selectivity for gold, while in minimal dissolution of copper, iron, nickel, lead, and iron from computer central processing unit (CPU) pins. Under optimal conditions, the efficiency of gold extraction from CPU pins reached 94.65%. Hence, this reagent holds significant potential for the low-toxicity extraction of gold from electronic waste or auriferous concentrates.

Identification and validation of 5-methylcytosine-associated genes in diffuse large B-cell lymphoma.

5-methylcytosine modifications play a significant role in carcinogenesis; however, studies exploring 5-methylcytosine-related genes in diffuse large B-cell lymphoma patients are lacking. In this study, we aimed to understand the potential role and clinical prognostic impact of 5-methylcytosine regulators in diffuse large B-cell lymphoma and identify a prognostic biomarker based on 5-methylcytosine-associated genes. Gene expression profiles and corresponding clinical information of diffuse large B-cell lymphoma patients and normal controls were obtained from The Cancer Genome Atlas, Gene Expression Omnibus, and Genotype-Tissue Expression databases. Diffuse large B-cell lymphoma was divided into three clusters according to the 5-methylcytosine regulators, and differentially expressed genes were screened among the three clusters. Univariate Cox and Lasso-Cox regression analyses were used to screen prognostic genes and construct a prognostic risk model. Kaplan-Meier curve analysis, univariate and multivariate Cox regression analyses, and time-dependent receiver operator characteristic curve analysis were used to evaluate prognostic factors. GSVA was used to enrich potential pathways associated with 5-methylcytosine modification patterns. SsGSEA and CIBERSORT were used to assess immune cell infiltration. Six 5-methylcytosine-related genes (TUBB4A, CD3E, ZNF681, HAP1, IL22RA2, and POSTN) were used to construct a prognostic risk model, which was proved to have a good predictive effect. In addition, univariate and multivariate Cox regression risk scores were independent prognostic factors for diffuse large B-cell lymphoma. Further analysis showed that the 5-methylcytosine risk score was significantly correlated with immune cell infiltration and immune checkpoint of diffuse large B-cell lymphoma. Our study reveals for the first time a potential role for 5-methylcytosine modifications in diffuse large B-cell lymphoma, provides novel insights for future studies on diffuse large B-cell lymphoma, and offers potential prognostic biomarkers and therapeutic targets for patients with diffuse large B-cell lymphoma.

Microfluidic Chip-Based Modeling of Three-Dimensional Intestine-Vessel-Liver Interactions in Fluorotelomer Alcohol Biotransformation.

Plyfluoroalkyl substance (PFAS), featured with incredible persistence and chronic toxicity, poses an emerging ecological and environmental crisis. Although significant progress has been made in PFAS metabolism in vivo, the underlying mechanism of metabolically active organ interactions in PFAS bioaccumulation remains largely unknown. We developed a microfluidic-based assay to recreate the intestine-vessel-liver interface in three dimensions, allowing for high-resolution, real-time images and precise quantification of intestine-vessel-liver interactions in PFAS biotransformation. In contrast to the scattered arrangement of vascular endothelium on the traditional d-polylysine-modified two-dimensional (2D) plate, the microtubules in our three-dimensional (3D) platform formed a dense honeycomb network through the ECM, with longer tubular structures. Additionally, the slope culture of epithelial cells in our platform exhibited a closely arranged and thicker cell layer than the planar culture. To dynamically monitor the metabolic crosstalk in the intestinal-vascular endothelium-liver interaction under exposure to fluorotelomer alcohols (FTOHs), we combined the chip with a solid-phase extraction-mass spectrometry (SPE-MS) system. Our findings revealed that endothelial cells were involved in the metabolic process of FTOHs. The transformation of intestinal epithelial and hepatic epithelial cells produces toxic metabolite fluorotelomer carboxylic acids (FTCAs), which circulate to endothelial cells and affect angiogenesis. This system shows promise as an enhanced surrogate model and platform for studying pollutant exposure as well as for biomedical and pharmaceutical research.

Hormone effects of eighteen bisphenol analogues and their effects on cellular homeostasis and the typical signal pathways.

Through the transfer chain of surroundings from feed to the farmed-animals and ultimately the corresponding livestock and poultry products, people are exposed to large amounts of bisphenol analogues (BPs), such as rational emissions from manufacturing plants, feed packaging bags and food packaging contact. Some BPs have been reported to show certain toxicological effects, especially, estrogen and endocrine disrupting effect. With the increasing application of BPs, the problem is becoming more and more serious. We systematically studied the hormonal effects of 18 BPs and their effects on cell homeostasis and classical signaling pathways by using classical E-SCREEN assay, fluorescent probes and western blotting. The results confirmed the estrogen-like effect of 13 BPs and 6 BPs obtained high docking scores (Scores < -9.0) for the three receptors simultaneously with the main interactions of hydrophobic, hydrogen and π-stacking of T-type bonds. BPAP regulates cells via apoptosis and steroid signaling pathway by intracellular ROS and mitochondrial followed the caspase pathway. BPE and BPS were involved in the classical NF-κB and Hippo signaling pathways. All data provides scientific basis for the safety risk assessment of endocrine disrupting and cellular homeostasis evaluation of BPs as chronic environmental pollution.

Photoredox-Catalyzed Synthesis of 3-Sulfonylated Pyrrolin-2-ones via a Regioselective Tandem Sulfonylation Cyclization of 1,5-Dienes.

A mild, visible-light-induced, regioselective cascade sulfonylation-cyclization of 1,5-dienes with sulfonyl chlorides through the intermolecular radical addition/cyclization of alkenes C(sp2)-H was developed. This procedure proceeds well and affords a mild and efficient route to a range of monosulfonylated pyrrolin-2-ones at room temperatures.

Stress Response in the Honeybee (Apis mellifera L.) Gut Induced by Chlorinated Paraffins at Residue Levels Found in Bee Products.

Chlorinated paraffins (CPs) have become global pollutants and are of considerable concern as a result of their persistence and long-distance transmission in the environment and toxicity to mammals. However, their risks to pollinating insects are unknown. Honeybees are classical pollinators and sensitive indicators of environmental pollution. Herein, the effects of CPs on the gut microenvironment and underlying mechanisms were evaluated and explored using Apis mellifera L. Both short- and medium-chain CPs had significant sublethal effects on honeybees at a residue dose of 10 mg/L detected in bee products but did not significantly alter the composition or diversity of the gut microbiota. However, this concentration did induce significant immune, detoxification, and antioxidation responses and metabolic imbalances in the midgut. The mechanisms of CP toxicity in bees are complicated by the complex composition of these chemicals, but this study indicated that CPs could substantially affect intestinal physiology and metabolic homeostasis. Therefore, CPs in the environment could have long-lasting impacts on bee health. Future studies are encouraged to identify novel bioindicators of CP exposure to detect early contamination and uncover the detailed mechanisms underlying the adverse effects of CPs on living organisms, especially pollinating insects.

In situ investigation of detoxification and metabolic effects of polyfluoroalkyl substances on metal-organic frameworks combined with cell-cultured microfluidics.

Over 9000 types of per- and polyfluoroalkyl substances (PFASs) have been produced that exhibit environmental persistence, bioaccumulation and biotoxicity, and pose a potential hazard to human health. Although metal-organic frameworks (MOFs) are promising structure-based materials for adsorbing PFASs, the enormous structural diversity and variability of the pharmacologic action of PFASs present challenges to the development of structure-based adsorbents. To address this issue, we propose an in situ platform for the high-throughput identification of efficient MOF sorbents that can adsorb PFASs and their metabolism using a filter-chip-solid phase extraction-mass spectrometry (SPE-MS) system. As a proof of concept, we screened BUT-16 as an attractive material for in situ fluorotelomer alcohol (FTOH) adsorption. The results demonstrated that FTOH molecules were adsorbed around the surface of the large hexagonal pores of BUT-16 by forming multiple hydrogen bonding interactions with its Zr6 clusters. The FTOH removal efficiency of the BUT16 filter was 100% over a period of 1 min. To determine the FTOH metabolism effects in different organs, HepG2 human hepatoma, HCT116 colon cancer, renal tubular HKC, and vascular endothelial HUVEC cells were cultured on a microfluidic chip, and SPE-MS was used to track a variety of cell metabolites in real time. Overall, the filter-Chip-SPE-MS system is a versatile and robust platform for the real-time monitoring of noxious pollutant detoxification, biotransformation, and metabolism, which facilitates pollutant antidote development and toxicology assay.

Zr-MOF-Induced Smart Accumulation Enables Surface-Enhanced Raman Spectroscopic Detection of Dioxin at ppt Level in Food Samples.

The fast and economical detection of trace polychlorinated dibenzo-p-dioxins (PCDDs) in food samples by current mass spectrum-based methods is hindered by tedious sample preparation and bulky & expensive analytical instruments. Surface-enhanced Raman spectroscopy (SERS) successfully detects many organic pollutants in foods but not dioxins because the employed metal nanoparticles weakly adsorb hydrophobic PCDDs. Herein, we report the detection of PCDDs in milk with SERS for the first time using a bifunctional substrate consisting of Au nanoparticles embedded in a zirconium-based metal-organic framework shell (AuNP/Zr-MOF). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), as the most toxic PCDD, is detected as low as 1.2 parts per trillion (ppt) in real milk samples with massive interfering substances in 30 min, which is the lowest among all reported methods. The aromatic rings of Zr-MOF promote the smart accumulation of TCDD through π-π interactions, and Au-Cl interactions drive TCDD onto Au surfaces. Zr-MOF shells with pore sizes of 12.7 and 20 Å block the accessibility of larger interfering molecules. A one-step apparatus and protocol are established to be superior to traditional methods in terms of time and cost. This work provides new insight into a rational screening method for the detection of persistent organic pollutants in a real sample matrix.

Polychlorinated naphthalenes in milk-based infant and toddler formula sold on the Chinese market.

Polychlorinated naphthalenes (PCNs) are dioxin-like compounds that have been reported to be present in a wide variety of foodstuffs. Milk-based infant and toddler formula sometimes plays an important role in the diet of young children and could potentially cause adverse effects if contaminated with PCNs. This study investigated the concentrations of PCNs in commercial milk-based formula produced in different countries and sold on the Chinese market for three age groups: 0-6, 6-12 and 12-36 months. The total concentrations of PCNs in 72 samples from different countries of formula based on cow milk ranged from 7.8 to 30.3 pg/g whole weight (ww). Although the PCN concentrations in formula produced in Asia, Europe and South Pacific varied, all had comparable toxic equivalent (TEQ) values. Tri-CNs were the predominant PCN homologue in all samples. No significant differences in the concentrations of PCNs were found between samples of formula for each of the three age groups. The mean TEQ for PCNs in goat milk formula samples (0.0031 pg TEQ/g ww) was higher than the value for cow milk formula (0.0009 pg TEQ/g ww) produced in China, and the proportion of higher chlorinated PCNs in goat milk formula was also higher. Based on dry weight, the mean concentration of PCNs in the raw cow milk (119 pg/g dry weight (dw)) used to produce infant and toddler formula was higher than that in the actual formula (24.2 pg/g dw), and the PCN profiles also varied between the raw milk and formula. A risk assessment indicated that, in China, consuming formula poses a lower risk to infants and toddlers from based on exposure to PCNs compared with consuming breast milk.

Efficient and simultaneous removal of aflatoxin B1, B2, G1, G2, and zearalenone from vegetable oil by use of a metal-organic framework absorbent.

Vegetable oils are usually cocontaminated with different mycotoxins, including aflatoxins and zearalenone, which cause significant food safety issues. Establishment of multitarget, high-efficiency, and low-cost adsorption methods are considered to be ideal solutions for mycotoxin removal in vegetable oils. In this study, we used metal-organic frameworks (MOFs) were used for the simultaneous removal of aflatoxins and zearalenone from vegetable oils. The results showed that MOF-235 simultaneously removed, within 30 min, more than 96.1% of aflatoxins and 83.3% of zearalenone from oils, and oils treated with MOF-235 exhibited di minimis cytotoxicity. Thus, synthesized MOF-235 exhibited sufficient efficacy to remove the targeted residues, as well as safety and reusability, which could be applied as a novel potential adsorbent in the removal of multiple mycotoxins from contaminated vegetable oils.