Severity: Warning
Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 249
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File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
Line Number: 71
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File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
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Function: require_once
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Message: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated
Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
Line: 255
Function: formatAIDetailSummary
File: /var/www/html/index.php
Line: 316
Function: require_once
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Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 256
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 258
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File: /var/www/html/index.php
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 259
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/index.php
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Filename: controllers/Detail.php
Line Number: 260
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File: /var/www/html/application/controllers/Detail.php
Line: 260
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 260
Backtrace:
File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Function: require_once
Complement is a key component of the innate immune system, recognizing pathogens and promoting their elimination. Complement component 3 (C3) is the central component of the system. Activation of C3 can be initiated by three distinct routes-the classical, the lectin and the alternative pathways-with the alternative pathway also acting as an amplification loop for the other two pathways. The protease factor D (FD) is essential for this amplification process, which, when dysregulated, predisposes individuals to diverse disorders including age-related macular degeneration and paroxysmal nocturnal hemoglobinuria (PNH). Here we describe the identification of potent and selective small-molecule inhibitors of FD. These inhibitors efficiently block alternative pathway (AP) activation and prevent both C3 deposition onto, and lysis of, PNH erythrocytes. Their oral administration inhibited lipopolysaccharide-induced AP activation in FD-humanized mice. These data demonstrate the feasibility of inhibiting the AP with small-molecule antagonists and support the development of FD inhibitors for the treatment of complement-mediated diseases.
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http://dx.doi.org/10.1038/nchembio.2208 | DOI Listing |
Cancer Biother Radiopharm
December 2024
Department of Obstetrics and Gynecology, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Vascular endothelial growth factor receptor-3 (VEGFR-3) plays an indispensable role in lymphangiogenesis. Previous findings suggest that blocking the VEGFR-3 signaling pathway can inhibit lymph node metastasis effectively, thus reducing the incidence of distant metastasis. The development of new VEGFR-3-targeting drugs for early detection and effective treatments is, therefore, urgently required.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Pathology, Faculty of Veterinary, Atatürk University, Erzurum, Turkey.
This study evaluates the protective effects of sinapic acid (SA), a polyphenolic compound with diverse biological activities, against ethanol-induced gastric ulcers in rats. A gastric ulcer model was established using ethanol (ETH), and the experimental groups received either omeprazole (OMEP, 20 mg/kg) or SA at doses of 20 mg/kg and 40 mg/kg via oral gavage for 14 days. Biochemical markers, including total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA), and myeloperoxidase (MPO) activity, were assessed alongside proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6) using ELISA.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Montreal, Quebec, Canada.
The Hippo pathway plays a tumorigenic role in highly angiogenic glioblastoma (GBM), whereas little is known about clinically relevant Hippo pathway inhibitors' ability to target adaptive mechanisms involved in GBM chemoresistance. Their molecular impact was investigated here in vitro against an alternative process to tumour angiogenesis termed vasculogenic mimicry (VM) in GBM-derived cell models. In silico analysis of the downstream Hippo signalling members YAP1, TAZ and TEAD1 transcript levels in low-grade glioblastoma (LGG) and GBM tumour tissues was performed using GEPIA.
View Article and Find Full Text PDFJ Exp Zool A Ecol Integr Physiol
December 2024
Departement of Biology, Faculty of Science, Academic Assembly, University of Toyama, Gofuku, Toyama, Japan.
In euryhaline teleosts, the cystic fibrosis transmembrane conductance regulator (CFTR) in seawater (SW)-type chloride cells facilitates apical Cl secretion for SW adaptation, while alternative Cl excretion pathways remain understudied. This study investigates the role of the calcium-activated chloride channel, Anoctamin 1 (ANO1), in the gills of the euryhaline Japanese medaka (Oryzias latipes) under hyperosmolality and cortisol (CORT) influence. Acclimation to artificial SW, NaCl, mannitol, or glucose significantly upregulated ANO1 and CFTR mRNA expression in gills, unlike urea treatment.
View Article and Find Full Text PDFDis Res
December 2024
Department of Pharmacology and Toxicology, Boonshoft School of Medicine Wright State University, Dayton, OH 45435, USA.
Non-small cell lung cancer (NSCLC) is the most common and prevalent subtype of lung cancer and continues to be one of the leading causes of cancer-related deaths worldwide. Despite various treatment options, a majority of NSCLC patients continue to experience disease progression and associated side effects, which are largely attributed to drug resistance, indicating the need for alternative strategies to combat this deadly disease. Among various applicable alternative approaches, repurposed drugs such as arsenic compounds have been shown to exert anticarcinogenic properties against NSCLC and possess the ability to overcome drug resistance mechanisms.
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