ABSTRACT
Effects of hot pixels on pixel performance in light and dark environments have been investigated in pinned photodiode 0.18 µm backside illuminated CMOS image sensors irradiated by 10 MeV protons. After exposure to protons, hot pixels and normal pixels are selected from the whole pixel array, and their influences on key parameters are analyzed. Experimental results show that radiation-induced hot pixels have a significant impact on pixel performance in dark environments, such as dark signal nonuniformity, long integration time, and random telegraph signal. Hot pixels are caused by defects with complex structures, i.e., cluster defects. Furthermore, the dark current activation energy result confirms that the defects causing the hot pixels have defect energy levels close to mid-gap.
Subject(s)
Protons , Semiconductors , Oxides/chemistry , Signal Processing, Computer-AssistedABSTRACT
UNLABELLED: Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH), to initiate growth, protect liver cells, and sustain remnant liver functions. Extracellular adenosine triphosphate rises in blood and bile after PH and contributes to liver regeneration, although purinergic receptors and mechanisms remain to be precisely explored. In this work we analyzed during regeneration after PH the involvement of P2X4 purinergic receptors, highly expressed in the liver. P2X4 receptor expression in the liver, liver histology, hepatocyte proliferation, plasma bile acid concentration, bile flow and composition, and lysosome distribution in hepatocytes were studied in wild-type and P2X4 knockout (KO) mice, before and after PH. P2X4 receptors were expressed in hepatocytes and Kupffer cells; in hepatocytes, P2X4 was concentrated in subcanalicular areas closely costained with lysosomal markers. After PH, delayed regeneration, hepatocyte necrosis, and cholestasis were observed in P2X4-KO mice. In P2X4-KO mice, post-PH biliary adaptation was impaired with a smaller increase in bile flow and HCO3 (-) biliary output, as well as altered biliary composition with reduced adenosine triphosphate and lysosomal enzyme release. In line with these data, lysosome distribution and biogenesis were altered in P2X4-KO compared with wild-type mice. CONCLUSION: During liver regeneration after PH, P2X4 contributes to the complex control of biliary homeostasis through mechanisms involving pericanalicular lysosomes, with a resulting impact on hepatocyte protection and proliferation. (Hepatology 2016;64:941-953).
Subject(s)
Biliary Tract/physiology , Liver Regeneration , Liver/metabolism , Lysosomes/physiology , Receptors, Purinergic P2X4/metabolism , Adenosine Triphosphate/metabolism , Animals , Bile Acids and Salts/blood , Cell Proliferation , Cells, Cultured , Hepatectomy , Hepatocytes/physiology , Homeostasis , Liver/ultrastructure , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
UNLABELLED: Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH) to initiate growth, protect liver cells, and sustain functions of the remnant liver. Bile acids (BAs), whose levels rise in the blood early after PH, stimulate both hepatocyte proliferation and protection, in part through their binding to the nuclear farnesoid X receptor (FXR). However, the effect of the BA receptor, TGR5 (G-protein-coupled BA receptor 1) after PH remains to be studied. Liver histology, hepatocyte proliferation, BA concentrations (plasma, bile, liver, urine, and feces), bile flow and composition, and cytokine production were studied in wild-type (WT) and TGR5 KO (knockout) mice before and after PH. BA composition (plasma, bile, liver, urine, and feces) was more hydrophobic in TGR5 KO than in WT mice. After PH, severe hepatocyte necrosis, prolonged cholestasis, exacerbated inflammatory response, and delayed regeneration were observed in TGR5 KO mice. Although hepatocyte adaptive response to post-PH BA overload was similar in WT and TGR5 KO mice, kidney and biliary adaptive responses were strongly impaired in TGR5 KO mice. Cholestyramine treatment, as well as Kupffer cell depletion, significantly improved the post-PH TGR5 KO mice phenotype. After bile duct ligation or upon a cholic acid-enriched diet, TGR5 KO mice exhibited more severe liver injury than WT as well as impaired BA elimination in urine. CONCLUSION: TGR5 is crucial for liver protection against BA overload after PH, primarily through the control of bile hydrophobicity and cytokine secretion. In the absence of TGR5, intrahepatic stasis of abnormally hydrophobic bile and excessive inflammation, in association with impaired bile flow adaptation and deficient urinary BA efflux, lead to BA overload-induced liver injury and delayed regeneration.
Subject(s)
Bile Acids and Salts/adverse effects , Bile Acids and Salts/metabolism , Hepatitis/etiology , Liver Regeneration/physiology , Liver/metabolism , Receptors, G-Protein-Coupled/metabolism , Animals , Cell Proliferation , Cholestyramine Resin/pharmacology , Cytokines/metabolism , Disease Models, Animal , Hepatectomy , Hepatitis/metabolism , Hepatitis/pathology , Liver/pathology , Liver/surgery , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Necrosis , Phenotype , Receptors, G-Protein-Coupled/deficiency , Receptors, G-Protein-Coupled/geneticsABSTRACT
BACKGROUND: Cancer-related fatigue and its associated symptoms of sleep disorder and depression are prevalent in cancer survivors especially among breast, lung, and colorectal cancer survivors. While there is no gold standard for treating cancer-related fatigue currently, studies of mind-body exercises such as Qigong have reported promise in reducing symptoms. This study was designed to evaluate the feasibility and effect of Guolin Qigong on cancer-related fatigue and other symptoms in breast, lung and colorectal cancer survivors while exploring their perceptions and experiences of Guolin Qigong intervention. METHODS: This is an open-label randomized controlled trial with 60 participants divided into 2 study groups in a 1:1 ratio. The intervention group will receive 12 weeks of Guolin Qigong intervention with a 4-week follow-up while control will receive usual care under waitlist. The primary outcome will be feasibility measured based on recruitment and retention rates, class attendance, home practice adherence, nature, and quantum of missing data as well as safety. The secondary subjective outcomes of fatigue, sleep quality and depression will be measured at Week-1 (baseline), Week-6 (mid-intervention), Week-12 (post-intervention), and Week-16 (4 weeks post-intervention) while an objective 24-hour urine cortisol will be measured at Week-1 (baseline) and Week-12 (post-intervention). We will conduct a semi-structured interview individually with participants within 3 months after Week-16 (4 weeks post-intervention) to obtain a more comprehensive view of practice adherence. DISCUSSION: This is the first mixed-method study to investigate the feasibility and effect of Guolin Qigong on breast, lung, and colorectal cancer survivors to provide a comprehensive understanding of Guolin Qigong's intervention impact and participants' perspectives. The interdisciplinary collaboration between Western Medicine and Chinese Medicine expertise of this study ensures robust study design, enhanced participant care, rigorous data analysis, and meaningful interpretation of results. This innovative research contributes to the field of oncology and may guide future evidence-based mind-body interventions to improve cancer survivorship. TRIAL REGISTRATION: This study has been registered with ANZCTR (ACTRN12622000688785p), was approved by Medical Research Ethic Committee of University Malaya Medical Centre (MREC ID NO: 2022323-11092) and recognized by Western Sydney University Human Research Ethics Committee (RH15124).
Subject(s)
Cancer Survivors , Fatigue , Qigong , Adult , Female , Humans , Male , Middle Aged , Cancer Survivors/psychology , Depression/therapy , Fatigue/therapy , Fatigue/etiology , Mind-Body Therapies/methods , Neoplasms/complications , Neoplasms/therapy , Neoplasms/psychology , Qigong/methods , Quality of Life , Randomized Controlled Trials as Topic , Sleep Quality , Sleep Wake Disorders/therapy , Sleep Wake Disorders/etiologyABSTRACT
Background: Rice disease can significantly reduce yields, so monitoring and identifying the diseases during the growing season is crucial. Some current studies are based on images with simple backgrounds, while realistic scene settings are full of background noise, making this task challenging. Traditional artificial prevention and control methods not only have heavy workload, low efficiency, but are also haphazard, unable to achieve real-time monitoring, which seriously limits the development of modern agriculture. Therefore, using target detection algorithm to identify rice diseases is an important research direction in the agricultural field. Methods: In this article a total of 7,220 pictures of rice diseases taken in Jinzhai County, Lu'an City, Anhui Province were chosen as the research object, including rice leaf blast, bacterial blight and flax leaf spot. We propose a rice disease identification method based on the improved YOLOV5s, which reduces the computation of the backbone network, reduces the weight file of the model to 3.2MB, which is about 1/4 of the original model, and accelerates the prediction speed by three times. Results: Compared with other mainstream methods, our method achieves better performance with low computational cost. It solves the problem of slow recognition speed due to the large weight file and calculation amount of model when the model is deployed in mobile terminal.
Subject(s)
Abelmoschus , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Albuminuria/drug therapy , Biphenyl Compounds , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/drug therapy , Double-Blind Method , Humans , Irbesartan/therapeutic use , Tetrazoles , Treatment OutcomeABSTRACT
Radioiodine therapy of nonthyroid cancers after sodium iodide symporter (NIS) gene delivery has been proposed as a potential application of gene therapy. However, it seems to be precluded by the rapid efflux of taken up iodine from most transduced xenografted tumors. We present an in vivo kinetic study of NIS-related hepatic iodine uptake in an aggressive model of hepatocarcinoma induced by diethylnitrosamine in immunocompetent Wistar rats. We followed the whole-body iodine distribution by repeated imaging of live animals. We constructed a rat NIS (rNIS) adenoviral vector, Ad-CMV-rNIS, using the cytomegalovirus (CMV) as a promoter. Injected in the portal vein in 5 healthy and 25 hepatocarcinoma-bearing rats and liver tumors in 9 hepatocarcinoma-bearing rats, Ad-CMV-rNIS drove expression of a functional NIS protein by hepatocytes and allowed marked (from 20 to 30% of the injected dose) and sustained (>11 days) iodine uptake. This contrasts with the massive iodine efflux found in vitro in human hepatic tumor cell lines. In vivo specific inhibition of NIS by sodium perchlorate led to a rapid iodine efflux from the liver, indicating that the sustained uptake was not attributable to an active retention mechanism but to permanent recycling of the effluent radioiodine via the high hepatic blood flow. Radioiodine therapy after Ad-CMV-rNIS administration achieved a strong inhibition of tumor growth, the complete regression of small nodules, and prolonged survival of hepatocarcinoma-bearing rats. This demonstrates for the first time the efficacy of NIS-based radiotherapy in a relevant preclinical model of nonthyroid human carcinogenesis.
Subject(s)
Genetic Therapy , Iodine Radioisotopes/therapeutic use , Liver Neoplasms, Experimental/radiotherapy , Symporters/genetics , Animals , Iodine Radioisotopes/pharmacokinetics , Liver/metabolism , Liver Neoplasms, Experimental/metabolism , Male , Rats , Rats, WistarABSTRACT
Seventy percentage of perimenopausal and early postmenopausal women will experience menopause symptoms. Primary menopause symptoms in Western countries included hot flashes, insomnia, somatic pain, depression, and fatigue. Hot flashes were most commonly treated. Menopausal hormone replacement therapy (HRT) continues to have a clinical role in the management of vasomotor symptoms, but since 2002 there has been a marked global decline in its use due to concerns about the risks and benefits of HRT; consequently many women with menopause symptoms are now seeking alternatives including acupuncture. Acupuncture has a long tradition of use for the treatment of different menopause symptoms. Its effectiveness has been studied for natural menopause or chemical and surgery induced menopause. Here we provide an update on recent advances in the field for clinicians. The recent systematic reviews on acupuncture in menopausal symptoms suggest that acupuncture is an effective and valuable option for women suffering from menopause. However, the science of acupuncture therapies is still inadequate to sufficiently support the benefits of acupuncture therapies. Finally, we discuss our points of view on clinical trials of acupuncture for menopause symptoms.
Subject(s)
Acupuncture Therapy/methods , Biomedical Research , Menopause/physiology , Female , Humans , Randomized Controlled Trials as TopicABSTRACT
The hepatocarcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg IIIalpha, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide symporter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adenoviral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radioiodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and nonhepatic cells. Nuclear imaging, tissue counting and immunohistochemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intratumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed nonhepatic cells. In rats bearing multinodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of (131)I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated (131)I therapy as a valuable option for the treatment of multinodular HCC.
Subject(s)
Antigens, Neoplasm/genetics , Biomarkers, Tumor/genetics , Lectins, C-Type/genetics , Liver Neoplasms, Experimental/radiotherapy , Liver Neoplasms, Experimental/therapy , Adenoviridae/genetics , Animals , Base Sequence , Cell Line , Cell Line, Tumor , DNA, Recombinant/genetics , Dogs , Female , Gene Expression , Gene Transfer Techniques , Genetic Vectors , Humans , Iodine Radioisotopes/administration & dosage , Iodine Radioisotopes/therapeutic use , Liver Neoplasms, Experimental/genetics , Male , Pancreatitis-Associated Proteins , Promoter Regions, Genetic , Rats , Rats, Wistar , Symporters/geneticsABSTRACT
BACKGROUND & AIMS: The ability of thyroid cells to take up iodide, which enables (131)I radiotherapy for thyroid cancer, is due to the expression of the sodium iodide symporter at their plasma membrane. Expression of this symporter has been found in some nonthyroid cancers. However, it is mostly accumulated in the cytoplasm, and its functionality has not been demonstrated. We have investigated sodium iodide symporter expression and functionality in human liver cancer, and in a diethylnitrosamine induced Wistar rat model of primary liver cancer at different stages of carcinogenesis. METHODS: Sodium iodide symporter mRNA and protein were studied in tissues from patients with hepatocellular- or cholangio-carcinomas using reverse-transcription polymerase chain reaction, immunoblot, and immunohistochemistry. We studied the dynamics of hepatic iodine uptake in the animal model using nuclear imaging. RESULTS: Sodium iodide symporter expression showed up in all 20 cholangiocarcinomas, but in only 2 of the 26 hepatocellular carcinomas, investigated. It was also found in normal bile duct cells and in the ductular reaction present in cirrhotic tissues. It was located at the plasma membrane in 10 of 20 cholangiocarcinoma. In rat liver cancer, a functional sodium iodide symporter expression was triggered as from the early preneoplastic steps, and was amplified during clonal tumor cell expansion, allowing complete tumor suppression after (131)I radiotherapy. CONCLUSIONS: A significant proportion of human cholangiocarcinomas expresses membrane sodium iodide symporter, which may permit radioiodine therapy. Our data also suggest that (131)I acts on a crucial target for liver cancer development.