Advantages and Challenges of Total-Body PET/CT at a Tertiary Cancer Center: Insights from Sun Yat-sen University Cancer Center.

In recent decades, researchers worldwide have directed their efforts toward enhancing the quality of PET imaging. The detection sensitivity and image resolution of conventional PET scanners with a short axial field of view have been constrained, leading to a suboptimal signal-to-noise ratio. The advent of long-axial-field-of-view PET scanners, exemplified by the uEXPLORER system, marked a significant advancement. Total-body PET imaging possesses an extensive scan range of 194 cm and an ultrahigh detection sensitivity, and it has emerged as a promising avenue for improving image quality while reducing the administered radioactivity dose and shortening acquisition times. In this review, we elucidate the application of the uEXPLORER system at the Sun Yat-sen University Cancer Center, including the disease distribution, patient selection workflow, scanning protocol, and several enhanced clinical applications, along with encountered challenges. We anticipate that this review will provide insights into routine clinical practice and ultimately improve patient care.

Brain-gut photobiomodulation restores cognitive alterations in chronically stressed mice through the regulation of Sirt1 and neuroinflammation.

BACKGROUND: Chronic stress is an important risk factor for the development of major depressive disorder (MDD). Recent studies have shown microbiome dysbiosis as one of the pathogenic mechanisms associated with MDD. Thus, it is important to find novel non-pharmacological therapeutic strategies that can modulate gut microbiota and brain activity. One such strategy is photobiomodulation (PBM), which involves the non-invasive use of light. OBJECTIVE/HYPOTHESIS: Brain-gut PBM could have a synergistic beneficial effect on the alterations induced by chronic stress. METHODS: We employed the chronic unpredictable mild stress (CUMS) protocol to induce a depressive-like state in mice. Subsequently, we administered brain-gut PBM for 6 min per day over a period of 3 weeks. Following PBM treatment, we examined behavioral, structural, molecular, and cellular alterations induced by CUMS. RESULTS: We observed that the CUMS protocol induces profound behavioral alterations and an increase of sirtuin1 (Sirt1) levels in the hippocampus. We then combined the stress protocol with PBM and found that tissue-combined PBM was able to rescue cognitive alterations induced by CUMS. This rescue was accompanied by a restoration of hippocampal Sirt1 levels, prevention of spine density loss in the CA1 of the hippocampus, and the modulation of the gut microbiome. PBM was also effective in reducing neuroinflammation and modulating the morphology of Iba1-positive microglia. LIMITATIONS: The molecular mechanisms behind the beneficial effects of tissue-combined PBM are not fully understood. CONCLUSIONS: Our results suggest that non-invasive photobiomodulation of both the brain and the gut microbiome could be beneficial in the context of stress-induced MDD.

Characterization of a novel amidohydrolase with promiscuous esterase activity from a soil metagenomic library and its application in degradation of amide herbicides.

Amide herbicides have been extensively used worldwide and have received substantial attention due to their adverse environmental effects. Here, a novel amidohydrolase gene was identified from a soil metagenomic library using diethyl terephthalate (DET) as a screening substrate. The recombinant enzyme, AmiH52, was heterologously expressed in Escherichia coli and later purified and characterized, with the highest activity occurring at 40 ℃ and pH 8.0. AmiH52 was demonstrated to have both esterase and amidohydrolase activities, which exhibited highly specific activity for p-nitrophenyl butyrate (2669 U/mg) and degrading activity against several amide herbicides. In particular, it displayed the strongest activity against propanil, with a high degradation rate of 84% at 8 h. A GC-MS analysis revealed that propanil was transformed into 3,4-dichloroaniline (3,4-DCA) during this degradation. The molecular interactions and binding stability were then analyzed by molecular docking and molecular dynamics simulation, which revealed that several key amino acid residues, including Tyr164, Trp66, Ala59, Val283, Arg58, His33, His191, and His226, are involved in the specific interactions with propanil. This study provides a function-driven screening method for amide herbicide hydrolase from the metagenomic libraries and a promising propanil-degrading enzyme (AmiH52) for potential applications in environmental remediation.

Up-regulation of RAN by MYBL2 maintains osteosarcoma cancer stem-like cells population during heterogeneous tumor generation.

Intratumor heterogeneity is one of the major features of cancers, leading to aggressive disease and treatment failure. Cancer stem-like cells (CSCs) are believed to give rise to the heterogeneous cell types within tumors. Hence, understanding the regulatory mechanism underlying the recurrence process of heterogeneous tumor by CSCs could facilitate the development of CSC-targeted therapies. Here, utilizing single-cell transcriptomics, we present the molecular profile of osteosarcoma CSCs-derived heterogeneous tumors consisting of CSC clusters, osteoprogenitor and differentiated cell types, such as pre-osteoblasts, osteoblasts and chondroblasts. Furthermore, by constructing the comprehensive map of modulated genes during CSCs self-renewal and differentiation, we identify RAN exhibiting specific peak expression in osteosarcoma CSCs clusters which is transcriptionally up-regulated by MYBL2. Functionality, MYBL2-RAN pathway promotes the CSCs self-renewal by enhancing the nuclear accumulation of MYC protein, which in turn boosts the overexpression of RAN as a positive feedback. Importantly, blockage of MYBL2-RAN pathway sensitizes CSCs to cisplatin treatment and synergistically enhanced the cisplatin-induced cytotoxicity. Both MYBL2 and RAN are highly expressed in clinical osteosarcoma tissues which indicate poor prognosis. Collectively, our study provides advanced insights into the regeneration process of heterogeneous tumor originating from CSCs and highlights the MYBL2-RAN pathway as a promising target for CSC-based therapy in osteosarcoma.

Contactin-associated protein-like 2 (CNTNAP2) mutations impair the essential α-secretase cleavages, leading to autism-like phenotypes.

Mutations in the Contactin-associated protein-like 2 (CNTNAP2) gene are associated with autism spectrum disorder (ASD), and ectodomain shedding of the CNTNAP2 protein plays a role in its function. However, key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown, and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive. In this report we showed that CNTNAP2 undergoes sequential cleavages by furin, ADAM10/17-dependent α-secretase and presenilin-dependent γ-secretase. We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96, and the main α-cleavage product C79 by ADAM10 is required for the subsequent γ-secretase cleavage to generate CNTNAP2 intracellular domain (CICD). ASD-associated CNTNAP2 mutations impair the α-cleavage to generate C79, and the inhibition leads to ASD-like repetitive and social behavior abnormalities in the Cntnap2-I1254T knock-in mice. Finally, exogenous expression of C79 improves autism-like phenotypes in the Cntnap2-I1254T knock-in and Cntnap2-/- knockout mice. This data demonstrates that the α-secretase is essential for CNTNAP2 processing and its function. Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis, and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

Heterotopic pregnancy after a single embryo transfer with successful perinatal outcome: case report and literature review.

A heterotopic pregnancy is a rare and serious pathological pregnancy. In this paper, we report a rare case of heterotopic pregnancy and perform a literature review. A 30-year-old patient with a history of left adnexectomy presented with persistent lower abdominal pain and hemorrhagic shock after single embryo transfer. Emergency laparoscopic exploration revealed a ruptured mass in the right isthmus of the fallopian tube, for which right salpingectomy was performed. After anti-inflammatory treatment and fetal preservation, the intrauterine pregnancy progressed smoothly, and a healthy baby was delivered at 39 weeks gestation. In this case, the patient's heterotopic pregnancy was possibly due to a natural pregnancy caused by sexual intercourse during treatment, so we recommend that sexual intercourse be avoided during transfer cycles.

Augmenting L3MBTL2-induced condensates suppresses tumor growth in osteosarcoma.

Osteosarcoma is a highly aggressive cancer and lacks effective therapeutic targets. We found that L3MBTL2 acts as a tumor suppressor by transcriptionally repressing IFIT2 in osteosarcoma. L3MBTL2 recruits the components of Polycomb repressive complex 1.6 to form condensates via both Pho-binding pockets and polybasic regions within carboxyl-terminal intrinsically disordered regions; the L3MBTL2-induced condensates are required for its tumor suppression. Multi-monoubiquitination of L3MBTL2 by UBE2O results in its proteasomal degradation, and the UBE2O/L3MBTL2 axis was crucial for osteosarcoma growth. There is a reverse correlation between L3MBTL2 and UBE2O in osteosarcoma tissues, and higher UBE2O and lower L3MBTL2 are associated with poorer prognosis in osteosarcoma. Pharmacological blockage of UBE2O by arsenic trioxide can enhance L3MBTL2-induced condensates and consequently suppress osteosarcoma growth. Our findings unveil a crucial biological function of L3MBTL2-induced condensates in mediating tumor suppression, proposing the UBE2O-L3MBTL2 axis as a potential cancer therapeutic target in osteosarcoma.

Thalamic Foxp2 regulates output connectivity and sensory-motor impairments in a model of Huntington's Disease.

BACKGROUND: Huntington's Disease (HD) is a disorder that affects body movements. Altered glutamatergic innervation of the striatum is a major hallmark of the disease. Approximately 30% of those glutamatergic inputs come from thalamic nuclei. Foxp2 is a transcription factor involved in cell differentiation and reported low in patients with HD. However, the role of the Foxp2 in the thalamus in HD remains unexplored. METHODS: We used two different mouse models of HD, the R6/1 and the HdhQ111 mice, to demonstrate a consistent thalamic Foxp2 reduction in the context of HD. We used in vivo electrophysiological recordings, microdialysis in behaving mice and rabies virus-based monosynaptic tracing to study thalamo-striatal and thalamo-cortical synaptic connectivity in R6/1 mice. Micro-structural synaptic plasticity was also evaluated in the striatum and cortex of R6/1 mice. We over-expressed Foxp2 in the thalamus of R6/1 mice or reduced Foxp2 in the thalamus of wild type mice to evaluate its role in sensory and motor skills deficiencies, as well as thalamo-striatal and thalamo-cortical connectivity in such mouse models. RESULTS: Here, we demonstrate in a HD mouse model a clear and early thalamo-striatal aberrant connectivity associated with a reduction of thalamic Foxp2 levels. Recovering thalamic Foxp2 levels in the mouse rescued motor coordination and sensory skills concomitant with an amelioration of neuropathological features and with a repair of the structural and functional connectivity through a restoration of neurotransmitter release. In addition, reduction of thalamic Foxp2 levels in wild type mice induced HD-like phenotypes. CONCLUSIONS: In conclusion, we show that a novel identified thalamic Foxp2 dysregulation alters basal ganglia circuits implicated in the pathophysiology of HD.

Flatband λ-Ti3O5 towards extraordinary solar steam generation.

Solar steam interfacial evaporation represents a promising strategy for seawater desalination and wastewater purification owing to its environmentally friendly character1-3. To improve the solar-to-steam generation, most previous efforts have focused on effectively harvesting solar energy over the full solar spectrum4-7. However, the importance of tuning joint densities of states in enhancing solar absorption of photothermal materials is less emphasized. Here we propose a route to greatly elevate joint densities of states by introducing a flat-band electronic structure. Our study reveals that metallic λ-Ti3O5 powders show a high solar absorptivity of 96.4% due to Ti-Ti dimer-induced flat bands around the Fermi level. By incorporating them into three-dimensional porous hydrogel-based evaporators with a conical cavity, an unprecedentedly high evaporation rate of roughly 6.09 kilograms per square metre per hour is achieved for 3.5 weight percent saline water under 1 sun of irradiation without salt precipitation. Fundamentally, the Ti-Ti dimers and U-shaped groove structure exposed on the λ-Ti3O5 surface facilitate the dissociation of adsorbed water molecules and benefit the interfacial water evaporation in the form of small clusters. The present work highlights the crucial roles of Ti-Ti dimer-induced flat bands in enchaining solar absorption and peculiar U-shaped grooves in promoting water dissociation, offering insights into access to cost-effective solar-to-steam generation.

Neural circuits provide insights into reward and aversion.

Maladaptive changes in the neural circuits associated with reward and aversion result in some common symptoms, such as drug addiction, anxiety, and depression. Historically, the study of these circuits has been hampered by technical limitations. In recent years, however, much progress has been made in understanding the neural mechanisms of reward and aversion owing to the development of technologies such as cell type-specific electrophysiology, neuronal tracing, and behavioral manipulation based on optogenetics. The aim of this paper is to summarize the latest findings on the mechanisms of the neural circuits associated with reward and aversion in a review of previous studies with a focus on the ventral tegmental area (VTA), nucleus accumbens (NAc), and basal forebrain (BF). These findings may inform efforts to prevent and treat mental illnesses associated with dysfunctions of the brain's reward and aversion system.

Meridianins Inhibit GSK3ß In Vivo and Improve Behavioral Alterations Induced by Chronic Stress.

Major depression disorder (MDD) is a severe mental alteration with a multifactorial origin, and chronic stress is one of the most relevant environmental risk factors associated with MDD. Although there exist some therapeutical options, 30% of patients are still resistant to any type of treatment. GSK3ß inhibitors are considered very promising therapeutic tools to counteract stress-related affectations. However, they are often associated with excessive off-target effects and undesired secondary alterations. Meridianins are alkaloids with an indole framework linked to an aminopyrimidine ring from Antarctic marine ascidians. Meridianins could overcome several of the aforementioned limitations since we previously demonstrated that they can inhibit GSK3ß activity without the associated neurotoxic or off-target effects in rodents. Here, we show that meridianins delivered into the lateral ventricle inhibited GSK3ß in several brain regions involved with stress-related symptoms. We also observed changes in major signaling pathways in the prefrontal cortex (Akt and PKA) and hippocampus (PKC and GluR1). Moreover, meridianins increased synaptic activity, specifically in the CA1 but not in the CA3 or other hippocampal subfields. Finally, we chronically treated the mice subjected to an unpredictable mild chronic stress (CUMS) paradigm with meridianins. Our results showed improvements produced by meridianins in behavioral alterations provoked by CUMS. In conclusion, meridianins could be of therapeutic interest to patients with stress-related disorders such as MDD.

Co-effect assessment on regional air quality: A perspective of policies and measures with greenhouse gas reduction potential.

Clean air policies have achieved remarkable air quality improvement in China for the last decade. However, as more importance was attached to climate issues and further improvement of air quality, policies with greenhouse gas (GHG) reduction potential were supposed to play a significant role. Here, we designed a conventional legislation pathway scenario (CLP) and an enhanced greenhouse gas reduction scenario (EGR), to estimate the co-effects of policies effective in GHG reduction on air pollutant control and air quality improvement in the Yangtze River Delta (YRD) region from 2014 to 2020, adopting a measure-specific evaluation method and an integrated WRF-CAMx model simulation. Results showed that: 1) With the implementation of enhanced measures with GHG reduction potential, emissions of SO2, NOx, PM2.5, PM10, VOCs and NH3 decreased by 16.4 %, 21.6 %, 18.6 %, 16.5 %, 23.9 % and 15.4 % in EGR scenario respectively, compared with CLP scenario. And the annual mean simulated concentrations of PM2.5, SO2 and NO2 of the YRD decreased by 11.2 %, 15.4 % and 20.6 %, respectively. 2) The average 8-h maxima (MDA8) concentration of O3 presented a slightly increasing trend under the impacts of measures with GHG reduction potential, which might be on account of the unbalanced control of NOx and VOCs, the two major precursors of O3. 3) Based on the source apportionment analysis, major partition of total ozone in the four receptors in YRD was from regional transportation, rather than local formation. And the major sectors contributing to ozone were industry and transportation sector. This study quantitatively assessed the co-benefits of GHG-control-effective policies and specific measures on air quality improvement, which would help to provide implications for future policy-making to achieve air pollution and climate change co-control.

New Framework for Dynamic Water Environmental Capacity Estimation Integrating the Hydro-Environmental Model and Load-Duration Curve Method-A Case Study in Data-Scarce Luanhe River Basin.

A better understanding of river capacity for contaminants (i.e., water environmental capacity, WEC) is essential for the reasonable utilization of water resources, providing government's with guidance about sewage discharge management, and allocating investments for pollutant reduction. This paper applied a new framework integrating a modified hydro-environmental model, Soil and Water Assessment Tool (SWAT) model, and load-duration curve (LDC) method for the dynamic estimation of the NH3-N WEC of the data-scarce Luanhe River basin in China. The impact mechanisms of hydrological and temperature conditions on WEC are discussed. We found that 77% of the WEC was concentrated in 40% hydrological guarantee flow rates. While the increasing flow velocity promoted the pollutant decay rate, it shortened its traveling time in streams, eventually reducing the river WEC. The results suggest that the integrated framework combined the merits of the traditional LDC method and the mechanism model. Thus, the integrated framework dynamically presents the WEC's spatiotemporal distribution under different hydrological regimes with fewer data. It can also be applied in multi-segment rivers to help managers identify hot spots for fragile water environmental regions and periods at the basin scale.

Evaluation of pediatric malignancies using total-body PET/CT with half-dose [18F]-FDG.

PURPOSE: To explore the impact of a true half dose of [18F]-FDG on image quality in pediatric oncological patients undergoing total-body PET/CT and investigate short acquisition times with half-dose injected activity. METHODS: One hundred pediatric oncological patients who underwent total-body PET/CT using the uEXPLORER scanner after receiving a true half dose of [18F]-FDG (1.85 MBq/kg) were retrospectively enrolled. The PET images were first reconstructed using complete 600-s data and then split into 300-s, 180-s, 60-s, 40-s, and 20-s duration groups (G600 to G20). The subjective analysis was performed using 5-point Likert scales. Objective quantitative metrics included the maximum standard uptake value (SUVmax), SUVmean, standard deviation (SD), signal-to-noise ratio (SNR), and SNRnorm of the background. The variabilities in lesion SUVmean, SUVmax, and tumor-to-background ratio (TBR) were also calculated. RESULTS: The overall image quality scores in the G600, G300, G180, and G60 groups were 4.9 ± 0.2, 4.9 ± 0.3, 4.4 ± 0.5, and 3.5 ± 0.5 points, respectively. All the lesions identified in the half-dose images were localized in the G60 images, while 56% of the lesions could be clearly identified in the G20 images. With reduced acquisition time, the SUVmax and SD of the backgrounds were gradually increased, while the TBR values showed no statistically significant differences among the groups (all p > 0.1). Using the half-dose images as a reference, the variability in the lesion SUVmax gradually increased from the G180 to G20 images, while the lesion SUVmean remained stable across all age groups. SNRnorm was highly negatively correlated with age. CONCLUSION: Total-body PET/CT with a half dose of [18F]-FDG (1.85 MBq/kg, estimated whole-body effective dose: 1.76-2.57 mSv) achieved good performance in pediatric patients, with sufficient image quality and good lesion conspicuity. Sufficient image quality and lesion conspicuity could be maintained at a fast scanning time of 60 s with half-dose activity.

Meridianins Rescue Cognitive Deficits, Spine Density and Neuroinflammation in the 5xFAD Model of Alzheimer's Disease.

Glycogen synthase kinase 3ß (GSK3ß) is a core protein, with a relevant role in many neurodegenerative disorders including Alzheimer's disease. The enzyme has been largely studied as a potential therapeutic target for several neurological diseases. Unfortunately, preclinical and clinical studies with several GSK3ß inhibitors have failed due to many reasons such as excessive toxicity or lack of effects in human subjects. We previously reported that meridianins are potent GSK3ß inhibitors without altering neuronal viability. In the present work, we examine whether meridianins are capable to inhibit neural GSK3ß in vivo and if such inhibition induces improvements in the 5xFAD mouse model of Alzheimer's Disease. Direct administration of meridianins in the third ventricle of 5xFAD mice induced robust improvements of recognition memory and cognitive flexibility as well as a rescue of the synaptic loss and an amelioration of neuroinflammatory processes. In summary, our study points out meridianins as a potential compound to treat neurodegenerative disorders associated with an hyperactivation of GSK3ß such as Alzheimer's disease.

1,3-Butadiene: a ubiquitous environmental mutagen and its associations with diseases.

1,3-Butadiene (BD) is a petrochemical manufactured in high volumes. It is a human carcinogen and can induce lymphohematopoietic cancers, particularly leukemia, in occupationally-exposed workers. BD is an air pollutant with the major environmental sources being automobile exhaust and tobacco smoke. It is one of the major constituents and is considered the most carcinogenic compound in cigarette smoke. The BD concentrations in urban areas usually vary between 0.01 and 3.3 µg/m3 but can be significantly higher in some microenvironments. For BD exposure of the general population, microenvironments, particularly indoor microenvironments, are the primary determinant and environmental tobacco smoke is the main contributor. BD has high cancer risk and has been ranked the second or the third in the environmental pollutants monitored in most urban areas, with the cancer risks exceeding 10-5. Mutagenicity/carcinogenicity of BD is mediated by its genotoxic metabolites but the specific metabolite(s) responsible for the effects in humans have not been determined. BD can be bioactivated to yield three mutagenic epoxide metabolites by cytochrome P450 enzymes, or potentially be biotransformed into a mutagenic chlorohydrin by myeloperoxidase, a peroxidase almost specifically present in neutrophils and monocytes. Several urinary BD biomarkers have been developed, among which N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine is the most sensitive and is suitable for biomonitoring BD exposure in the general population. Exposure to BD has been associated with leukemia, cardiovascular disease, and possibly reproductive effects, and may be associated with several cancers, autism, and asthma in children. Collectively, BD is a ubiquitous pollutant that has been associated with a range of adverse health effects and diseases with children being a subpopulation with potentially greater susceptibility. Its adverse effects on human health may have been underestimated and more studies are needed.

3D bioprinted tumor model with extracellular matrix enhanced bioinks for nanoparticle evaluation.

The traditional evaluation of nanoparticles (NPs) is mainly based on 2D cell culture and animal models. However, these models are difficult to accurately represent human tumor microenvironment (TME) and fail to systematically study the complex transportation of NPs, thus limiting the translation of nano-drug formulations to clinical studies. This study reports a tumor model fabricated via 3D bioprinting with adipose decellularized extracellular matrix (ECM) enhanced hybrid bioink. Compared with 2D cultured cells, the 3D printed tumor models with multicellular spheroids formation are closer to real tumor in protein, gene expression and tumorigenicity bothin vitroandin vivo. Two characteristics of TME, ECM remodeling and epithelial-mesenchymal transition, are tracked simultaneously under 3D conditions. Furthermore, the cellular uptake efficiency of two different NPs is significantly lower in the printed 3D tumor model than the 2D individual cells, and higher drug resistance is observed in 3D group, which suggest the ECM barrier of tumor can significantly affect the permeability of NPs. These results suggest that this 3D printed tumor model is capable of mimicking the multiple TME, potentially providing a more accurate platform for the design and development of NPs before moving into animal and clinical trials.

Effects of oncolytic viruses and viral vectors on immunity in glioblastoma.

Glioblastoma (GBM) is regarded as an incurable disease due to its poor prognosis and limited treatment options. Virotherapies were once utilized on cancers for their oncolytic effects. And they are being revived on GBM treatment, as accumulating evidence presents the immunogenic effects of virotherapies in remodeling immunosuppressive GBM microenvironment. In this review, we focus on the immune responses induced by oncolytic virotherapies and viral vectors in GBM. The current developments of GBM virotherapies are briefly summarized, followed by a detailed depiction of their immune response. Limitations and lessons inferred from earlier experiments and trials are discussed. Moreover, we highlight the importance of engaging the immune responses induced by virotherapies into the multidisciplinary management of GBM.

Autophagy of hepatic stellate cell induced by Clonorchis sinensis.

BACKGROUND: Clonorchis sinensis was a food-borne zoonotic parasite in the worldwide and also an important risk factor of hepatic fibrosis. Excretory/secretion products of C. sinensis (CsESPs) are involved in parasite-host interactions and contribute to the development of hepatic damage. The aim of the present study was to investigate whether CsESPs and CsTP (adult protein) could induce autophagy of hepatic stellate cells (HSCs) and further activate HSCs so as to participate in the pathogenesis of hepatic fibrosis. METHODS AND RESULTS: The human hepatic stellate cell line LX-2 was stimulated by CsESPs and CsTP. CsESPs showed the effect on cell proliferation in methyl thiazolyl tetrazolium (MTT) assay while CsTP failed. Autophagosomes and autolysosomes were observed after the transmission mRFP-EGFP-LC3 plasmid into the LX-2 cells. CsESPs had more powerful to induce the accumulation of autophagosomes and autolysosomes to enhance autophagic flux compared with CsTP. Western-blotting analysis confirmed that the ratio of LC3-II/I in LX-2 cells was up-regulated after CsESPs treatment for 6 h, which further proved that CsESPs could induce autophagy in LX-2 cells. Meanwhile, q-PCR results showed that the mRNA levels of collagen I, collagen III and α-SMA decreased in LX-2 cells after treatment with autophagy inhibitor chloroquine, whereas they increased when combination with CsESPs. CONCLUSIONS: These results suggested that CsESPs-induced autophagy might be involved in the activation of HSCs, and consequently participate in the pathogenesis of hepatic fibrosis caused by C. sinensis infection.

Automatic Segmentation of Clinical Target Volume and Organs-at-Risk for Breast Conservative Radiotherapy Using a Convolutional Neural Network.

OBJECTIVE: Delineation of clinical target volume (CTV) and organs at risk (OARs) is important for radiotherapy but is time-consuming. We trained and evaluated a U-ResNet model to provide fast and consistent auto-segmentation. METHODS: We collected 160 patients' CT scans with breast cancer who underwent breast-conserving surgery (BCS) and were treated with radiotherapy. CTV and OARs were delineated manually and were used for model training. The dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) were used to assess the performance of our model. CTV and OARs were randomly selected as ground truth (GT) masks, and artificial intelligence (AI) masks were generated by the proposed model. Two clinicians randomly compared CTV score differences of the contour. The consistency between two clinicians was tested. Time cost for auto-delineation was evaluated. RESULTS: The mean DSC values of the proposed method were 0.94, 0.95, 0.94, 0.96, 0.96 and 0.93 for breast CTV, contralateral breast, heart, right lung, left lung and spinal cord, respectively. The mean 95HD values were 4.31mm, 3.59mm, 4.86mm, 3.18mm, 2.79mm and 4.37mm for the above structures, respectively. The average CTV scores for AI and GT were 2.89 versus 2.92 when evaluated by oncologist A (P=0.612), and 2.75 versus 2.83 by oncologist B (P=0.213), with no statistically significant differences. The consistency between two clinicians was poor (kappa=0.282). The time for auto-segmentation of CTV and OARs was 10.03 s. CONCLUSION: Our proposed model (U-ResNet) can improve the efficiency and accuracy of delineation compared with U-Net, performing equally well with the segmentation generated by oncologists.