bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Performances and Frost Resistance of Alkali-Activated Coal Gangue Cementitious Materials
Authors: Zhao Yanbing , Yang Caiqian , Li Kefeng , Yang Jing , Wu Zhiren , Yan Chengyu
Published: December 2022

The coal gangue after composite activation treatment is considered a potential low-carbon and green cementitious material, so the feasibility of employing composite-activated gangue to partially or entirely replace cement for building materials is systematically studied in this paper. The effects of alkali content, slag content, and water-to-binder ratio on the mechanical properties and frost resistance of alkali-activated coal gangue mortar (AACGM) were experimentally investigated. An ESEM was employed to observe the microstructure of the AACGM. Moreover, the microstructure damage to the AACGM was analyzed by a pixel-based image processing algorithm. The research was carried out in accordance with standards JGJ/T70-2009 and GB/T 50082-2009. Experimental results indicated that the mechanical properties and frost resistance of the AACGM were superior to those of ordinary Portland cement mortar (OPCM). Compared with the OPC group, the compressive and flexural strength of the W0.50 group increased by 16.01% and 14.19%. Moreover, the loss rate of mass, flexural strength, compressive strength, and microstructure damage of the AACGM were less than those of the OPCM. Between freeze–thaw cycles 25 and 100, the cracks and pores of specimens gradually grew, and the maximum crack width increased by 277.78%. In addition, the slag was beneficial in improving the flexural strength, compressive strength, and frost resistance of the AACGM. Finally, the freeze–thaw damage mechanism of the CGBG mortar was systematically analyzed.
In Situ Concrete Bridge Strengthening Using Ductile Activated NSMR CFRP System
Authors: Schmidt Jacob Wittrup , Sørensen John Dalsgaard , Christensen Christian Overgaard
Published: December 2022

Novel and complex structural solutions are often challenging to introduce in the building industry since they may provide unconventional and less verified behavior combined with several novel and unique failure modes. A desired safety level may be difficult to verify due to the lack of knowledge related to failure modes and their variation. This study introduces a method that may provide a first step toward addressing such challenges. Five laboratory tests were done on a novel ductile response-controlled anchor system used for prestressed CFRP NSMR strengthening. These results were used as a basis for further implementation in a pilot project where an in situ cast concrete bridge was strengthened with the developed system. A particular focus was dedicated to the capability of the designed system response to provide a consistent load/deformation curve, yielding threshold, and yielding regime. The novel system enabled response tailoring to the specific pilot project. Installation and prestressing procedure worked as desired, where losses in the fully prestressed system, after three weeks, were approximately 0.2 to 1.6 kN (0.2–1.3 mm). In situ proof loading of all strengthening systems (20 anchor systems) was done to eliminate any possible failure modes below the proof-loading level. It was performed with no signs of distress.
Study on the Seismic Behavior of a Steel Plate–Concrete Composite Shear Wall with a Fishplate Connection
Authors: Wang Yimin , Sang Xiuxing , Shang Kaiguang , Zhang Yushuo , Ju Jinsan
Published: December 2022

The steel plate–concrete composite shear wall (SPCSW), having been widely applied to several super high-rise buildings, is currently regarded as a new type of lateral load-resisting structure. The SPCSW design does not consider the connection to the surrounding structure, normally envisaged as a buttweld connection, while the fishplate lap connection tends to be applied in construction. To explore the fishplate lap connection to achieve the performance standard of SPCSW, in this paper, an SPCSW with a fishplate connection is modeled using ABAQUS to investigate the hysteretic behavior under constant axial force and horizontal cyclic loads. Through the hysteresis curve and a load–displacement skeleton curve, the effects of fishplate thickness and lap length on its hysteretic behavior are studied. The results show that increasing the fishplate thickness contributes to a slight increase in the bearing capacity and energy dissipation and has little influence on stiffness degradation. When the fishplate thickness is more than half the steel plate thickness, the strength and energy dissipation of an SPCSW with a fishplate connection can reach the level of an SPCSW without a fishplate connection. The bearing capacity and stiffness of the SPCSW increase with the increase in lap length. When the lap length is greater than 50 mm, the strength, stiffness and energy dissipation capacity of an SPCSW with a fishplate connection are superior to those without fishplate connections. Finally, engineering suggestions on fishplate connections are put forward.
Determination of the Target Reliability Index of the Concrete Main Girder of Long-Span Structures Based on Structural Design Service Life
Authors: Zhang Zhenhao , Li Hesheng , Xiong Jun , Wang Fuming , Wei Leijun , Ke Lu
Published: December 2022

This article studies the quantitative relationship between the target reliability index and the design service life for concrete main girders of cable-stayed bridges. A resistance degradation model of the concrete components is established by quantifying the effects of concrete carbonation and steel corrosion. It is assumed that the dead load and the live load are time-invariant with the distributions of normal and extreme type I, respectively, while the resistance is considered as time-variant with the distribution of lognormal. The standard values of the most unfavorable moment under dead and live loads are calculated by ANSYS, its mean value and standard deviation are further obtained using the statistical parameters suggested by the Unified Standard for Structural Reliability Design of Highway Engineering. The mean and standard deviation of resistance are obtained using the target reliability index value provided in the code above. The resistance value and reliability index at different times in a certain design service life can be obtained through the resistance degradation model. The result shows the reliability index decreases exponentially during the service life of the structure. For different design service years, different initial resistance values and initial reliability indexes can be deduced. Based on this, the target reliability index values considering the design service life are suggested. In the example analysis, the target reliability index of the concrete main girder of a cable-stayed bridge with a design service life of 100 years is suggested as 6.24. This research provides references for the design of concrete main girders of cable-stayed bridges.
Post-Occupancy Evaluation of Sports Parks during the COVID-19 Pandemic: Taking Sports Parks in Beijing as Examples
Authors: Wu Xianfeng , Li Xiangyu
Published: December 2022

China fully built a wealthy society but faced a serious COVID-19 epidemic together with the rest of the world. The emergence of the epidemic highlights the importance of sports parks for physical activity. By reviewing national fitness policies and identifying several types of sports parks, this paper investigates urban dwellers’ usage and preferences in sports parks by means of a questionnaire, with behavioural observation and interviews as complementary research methods. Taking the Beijing Olympic Forest Park, Sun Park, and Huilongguan Park as examples, this study reveals that participants present a high overall satisfaction with the sports parks. The factor analysis indicates that Sports Facilities and Maintenance & Management are the first and second most significant factors influencing residents’ willingness to use sports parks. This research can guide the planning and construction of sports park in the future.
Research on the Preparation and Mechanical Properties of Solidified 3D Printed Concrete Materials
Authors: Shen Yuhang , Lin Li , Wei Shengjie , Yan Jie , Xu Tianli
Published: December 2022

Three-dimensional (3D) printing is an innovative manufacturing process based on 3D digital models that involves layer-by-layer addition of materials. In recent years, 3D printing has made good progress in the field of construction, thereby leading to more stringent requirements for materials. In this study, we first compare different equipment and materials used for 3D printing concrete. Subsequently, the mix ratio of extruded and cured 3D printed concrete is studied by using flow and slump as the main evaluation indexes. Through a universal test, the influence of different dosages of water reducer, retarder, and latex powder on the performance of 3D printed concrete (compression resistance strength) is studied. Furthermore, the optimum mix ratio for fiber reinforced concrete is determined, based on which axial pull-out, axial compression, and three-point bending tests are performed to elucidate the peak compressive strength, load–displacement curve, and mechanical properties of 3D printed concrete. By employing the ABAQUS finite element software, the shaft pulling force and axial compression of 3D printed concrete are simulated and analyzed to determine the parameters influencing the bonding performance of different 3D printed concrete layers. Moreover, the influence of water reducer and sand–glue ratio is observed to be greater than that of water gel ratio and sodium gluconate. The testing results showed that the mechanical strength of 3D printed concrete is lower than that of poured concrete. Meanwhile, bending and compressive strengths of 3D printed concrete and poured concrete are quite different.
Using Optimization Algorithms-Based ANN to Determine the Temperatures in Timber Exposed to Fire for a Long Duration
Authors: Nikoo Mehdi , Hafeez Ghazanfarah , Cachim Paulo
Published: December 2022

The article investigates the temperature prediction in rectangular timber cross-sections exposed to fire. Timber density, exposure time, and the point coordinates within the cross-section are treated as inputs to determine the temperatures. A total of 54,776 samples of wood cross-sections with a variety of characteristics were considered in this study. Of the sample data, 70% was dedicated to training the networks, while the remaining 30% was used for testing the networks. Feed-forward networks with various topologies were employed to examine the temperatures of timber exposed to fire for more than 1500 s. The weight of the artificial neural network was optimized using bat and genetic algorithms. The results conclude that both algorithms are efficient and accurate tools for determining the temperatures, with the bat algorithm being marginally superior in accuracy than the genetic algorithm.
Organizational Culture towards Saudi Arabia’s Vision 2030: Evidence from National Water Company
Authors: Alotaibi Hammad S. , Campbell Nadine
Published: December 2022

(1) Background: Organisational culture provides a framework and guidelines that influence behaviour and control employees’ performance and activities. (2) Methods: This study uses Hofstede’s five dimensions of organisational culture to understand better the organisational culture of three of the National Water Company’s (NWC) branches in Saudi Arabia. A random sample of 500 employees, consisting of 50 managers, 100 supervisors, and 350 officers, were surveyed, and 334 reliable responses were received. SPSS was employed to analyse the responses, and the empirical findings suggest that NWC’s corporate culture is in line with the findings of Hofstede. (3) Results: There was a sharp contrast between the male and female responses, with men ranking power distance, uncertainty avoidance, collectivism, masculinity, and short-term orientation, high, and the women ranking them low. Unfortunately, innovation and productivity suffer within this autocratic culture, resulting in the NWC not meeting Saudi Arabia’s new national mandates outlined in Vision 2030. (4) Conclusion: The study recommends how HRM can help NWC change its organisational culture to increase innovation and productivity.
Precision Medicine and Novel Therapeutic Strategies in Detection and Treatment of Cancer: Highlights from the 58th IACR Annual Conference
Authors: Kennedy Sean P. , Treacy Oliver , Allott Emma H. , Eustace Alex J. , Lynam-Lennon Niamh , Buckley Niamh , Robson Tracy
Published: December 2022

Innovation in both detection and treatment of cancer is necessary for the constant improvement in therapeutic strategies, especially in patients with novel or resistant variants of cancer. Cancer mortality rates have declined by almost 30% since 1991, however, depending on the cancer type, acquired resistance can occur to varying degrees. To combat this, researchers are looking towards advancing our understanding of cancer biology, in order to inform early detection, and guide novel therapeutic approaches. Through combination of these approaches, it is believed that a more complete and thorough intervention on cancer can be achieved. Here, we will discuss the advances and approaches in both detection and treatment of cancer, presented at the 58th Irish Association for Cancer Research (IACR) annual conference.
Metabolomic and Mitochondrial Fingerprinting of the Epithelial-to-Mesenchymal Transition (EMT) in Non-Tumorigenic and Tumorigenic Human Breast Cells
Authors: Cuyàs Elisabet , Fernández-Arroyo Salvador , Verdura Sara , Lupu Ruth , Joven Jorge , Menendez Javier A.
Published: December 2022

Epithelial-to-mesenchymal transition (EMT) is key to tumor aggressiveness, therapy resistance, and immune escape in breast cancer. Because metabolic traits might be involved along the EMT continuum, we investigated whether human breast epithelial cells engineered to stably acquire a mesenchymal phenotype in non-tumorigenic and H-RasV12-driven tumorigenic backgrounds possess unique metabolic fingerprints. We profiled mitochondrial–cytosolic bioenergetic and one-carbon (1C) metabolites by metabolomic analysis, and then questioned the utilization of different mitochondrial substrates by EMT mitochondria and their sensitivity to mitochondria-centered inhibitors. “Upper” and “lower” glycolysis were the preferred glucose fluxes activated by EMT in non-tumorigenic and tumorigenic backgrounds, respectively. EMT in non-tumorigenic and tumorigenic backgrounds could be distinguished by the differential contribution of the homocysteine-methionine 1C cycle to the transsulfuration pathway. Both non-tumorigenic and tumorigenic EMT-activated cells showed elevated mitochondrial utilization of glycolysis end-products such as lactic acid, β-oxidation substrates including palmitoyl–carnitine, and tricarboxylic acid pathway substrates such as succinic acid. Notably, mitochondria in tumorigenic EMT cells distinctively exhibited a significant alteration in the electron flow intensity from succinate to mitochondrial complex III as they were highly refractory to the inhibitory effects of antimycin A and myxothiazol. Our results show that the bioenergetic/1C metabolic signature, the utilization rates of preferred mitochondrial substrates, and sensitivity to mitochondrial drugs significantly differs upon execution of EMT in non-tumorigenic and tumorigenic backgrounds, which could help to resolve the relationship between EMT, malignancy, and therapeutic resistance in breast cancer.
Comprehensive Analysis of DMRT3 as a Potential Biomarker Associated with the Immune Infiltration in a Pan-Cancer Analysis and Validation in Lung Adenocarcinoma
Authors: Yang Donghong , Liu Meilian , Jiang Junhong , Luo Yiping , Wang Yongcun , Chen Huoguang , Li Dongbing , Wang Dongliang , Yang Zhixiong , Chen Hualin
Published: December 2022

Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.
Emerging Role of Targeted Therapy in Metastatic Pancreatic Adenocarcinoma
Authors: Huffman Brandon M. , Ellis Haley , Jordan Alexander C. , Freed-Pastor William A. , Perez Kimberly , Rubinson Douglas A. , Sethi Nilay , Singh Harshabad , Surana Rishi , Wolpin Brian M. , Aguirre Andrew J. , Cleary James M.
Published: December 2022

The aggressive biology of pancreatic ductal adenocarcinoma (PDAC), along with its limited sensitivity to many systemic therapies, presents a major challenge in the management of patients with metastatic PDAC. Over the past decade, the incorporation of combinatorial cytotoxic chemotherapy regimens has improved patient outcomes. Despite these advances, resistance to cytotoxic chemotherapy inevitably occurs, and there is a great need for effective therapies. A major focus of research has been to identify molecularly defined subpopulations of patients with PDAC who may benefit from targeted therapies that are matched to their molecular profile. Recent successes include the demonstration of the efficacy of maintenance PARP inhibition in PDAC tumors harboring deleterious BRCA1, BRCA2, and PALB2 alterations. In addition, while therapeutic targeting of KRAS was long thought to be infeasible, emerging data on the efficacy of KRAS G12C inhibitors have increased optimism about next-generation KRAS-directed therapies in PDAC. Meanwhile, KRAS wild-type PDAC encompasses a unique molecular subpopulation of PDAC that is enriched for targetable genetic alterations, such as oncogenic BRAF alterations, mismatch repair deficiency, and FGFR2, ALK, NTRK, ROS1, NRG1, and RET rearrangements. As more molecularly targeted therapies are developed, precision medicine has the potential to revolutionize the treatment of patients with metastatic PDAC.
Prophylactic and Early Thyroidectomy in RET Germline Mutation Carriers in Pediatric and Adult Population: Long-Term Outcomes of a Series of 63 Patients
Authors: Torresan Francesca , Censi Simona , Pennelli Gianmaria , Galuppini Francesca , Mian Caterina , Iacobone Maurizio
Published: December 2022

Prophylactic and early thyroidectomy in RET germline mutation carriers allows the removal of the thyroid before medullary thyroid carcinoma (MTC) develops, or while it is still confined to the gland. This study was aimed to assess the clinicopathological features in RET carriers according to the age at surgery and the long-term outcomes after prophylactic and early thyroidectomy. A retrospective analysis of 63 operated asymptomatic RET carriers diagnosed after familial genetic screening was performed. Twenty-one RET carriers were operated at pediatric (<18 yrs) and 42 at adult (≥18 yrs) age. Serum preoperative calcitonin levels were significantly lower in pediatric compared to adult patients (p = 0.04); moreover, adult RET carriers had a greater frequency of microMTC at pathology (p = 0.009). Permanent postoperative morbidity occurred in 9.5% of patients, without differences between the two groups. Biochemical postoperative cure was achieved in all patients. At a median follow-up of 14 years, all C-cell hyperplasia patients are disease-free; conversely, biochemical, and structural recurrence of disease occurred in three adults and one pediatric patient with microMTC. The independent predictive factors of MTC were the age at surgery, the preoperative calcitonin level and the RET mutational risk profile (p < 0.02). In conclusion, prophylactic and early thyroidectomy are safe and effective procedures in achieving definitive cure in most RET carriers. However, since recurrences may occur at long-term in case of microMTC, thyroidectomy should be possibly performed earlier to prevent microMTC development.
Utility of the Age Discrepancy between Frailty-Based Biological Age and Expected Life Age in Patients with Urological Cancers
Authors: Togashi Kyo , Hatakeyama Shingo , Soma Osamu , Okita Kazutaka , Fujita Naoki , Tanaka Toshikazu , Noro Daisuke , Horiguchi Hirotaka , Uemura Nozomi , Iwane Takuro , Okamoto Teppei , Yamamoto Hayato , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara
Published: December 2022

Background: The estimation of biological age is challenging in patients with cancers. We aimed to investigate frailty-based biological ages using frailty-discriminant scores (FDS) and examined the effect of biological-expected life age discrepancy on the prognosis of patients with urological cancers. Methods: We retrospectively evaluated frailty in 1035 patients having urological cancers. Their frailty-based biological age was then defined by the FDS, which is a comprehensive frailty assessment tool, using 1790 noncancer individuals as controls. An expected life age (=chronological age + life expectancy) was subsequently calculated using the 2019 life expectancy table. The primary outcome was the estimation of the biological-expected life age discrepancy between the frailty-based biological age and expected life age in patients with urological cancers. Secondary outcomes were the evaluation of the effect of the biological-expected life age discrepancy on overall survival. Results: We included 405, 466, and 164 patients diagnosed with prostate cancer, urothelial carcinoma, and renal cell carcinoma, respectively. The median chronological age, life expectancy, and estimated frailty-based biological age were 71, 17, and 83 years, respectively. The biological-expected life age discrepancy in any urological cancers, localized diseases, and metastatic diseases was −4.8, −6.3, and +0.15 years, respectively. The biological-expected life age discrepancy of >5 years was significantly associated with poor overall survival. Conclusions: The biological-expected life age discrepancy between frailty-based biological age and expected life age may be helpful in understanding the role of frailty and patient/doctor conversation.
Using Whole Slide Gray Value Map to Predict HER2 Expression and FISH Status in Breast Cancer
Authors: Yao Qian , Hou Wei , Wu Kaiyuan , Bai Yanhua , Long Mengping , Diao Xinting , Jia Ling , Niu Dongfeng , Li Xiang
Published: December 2022

Accurate detection of HER2 expression through immunohistochemistry (IHC) is of great clinical significance in the treatment of breast cancer. However, manual interpretation of HER2 is challenging, due to the interobserver variability among pathologists. We sought to explore a deep learning method to predict HER2 expression level and gene status based on a Whole Slide Image (WSI) of the HER2 IHC section. When applied to 228 invasive breast carcinoma of no special type (IBC-NST) DAB-stained slides, our GrayMap+ convolutional neural network (CNN) model accurately classified HER2 IHC level with mean accuracy 0.952 ± 0.029 and predicted HER2 FISH status with mean accuracy 0.921 ± 0.029. Our result also demonstrated strong consistency in HER2 expression score between our system and experienced pathologists (intraclass correlation coefficient (ICC) = 0.903, Cohen’s κ = 0.875). The discordant cases were found to be largely caused by high intra-tumor staining heterogeneity in the HER2 IHC group and low copy number in the HER2 FISH group.
Different Oncologic Outcomes in Early-Onset and Late-Onset Sporadic Colorectal Cancer: A Regression Analysis on 2073 Patients
Authors: Foppa Caterina , Maroli Annalisa , Lauricella Sara , Luberto Antonio , La Raja Carlotta , Bunino Francesca , Carvello Michele , Sacchi Matteo , De Lucia Francesca , Clerico Giuseppe , Montorsi Marco , Spinelli Antonino
Published: December 2022

The incidence of colorectal cancer (CRC) is increasing in the population aged ≤ 49 (early-onset CRC-EOCRC). Recent studies highlighted the biological and clinical differences between EOCRC and late-onset CRC (LOCRC-age ≥ 50), while comparative results about long-term survival are still debated. This study aimed to investigate whether age of onset may impact on oncologic outcomes in a surgical population of sporadic CRC patients. Patients operated on for sporadic CRC from January 2010 to January 2022 were allocated to the EOCRC and LOCRC groups. The primary endpoint was the recurrence/progression-free survival (R/PFS). A total of 423 EOCRC and 1650 LOCRC was included. EOCRC had a worse R/PFS (p < 0.0001) and cancer specific survival (p < 0.0001) compared with LOCRC. At Cox regression analysis, age of onset, tumoral stage, signet ring cells, extramural/lymphovascular/perineural veins invasion, and neoadjuvant therapy were independent risk factors for R/P. The analysis by tumoral stage showed an increased incidence of recurrence in stage I EOCRC (p = 0.014), and early age of onset was an independent predictor for recurrence (p = 0.035). Early age of onset was an independent predictor for worse prognosis, this effect was stronger in stage I patients suggesting a potentially—and still unknown—more aggressive tumoral phenotype in EOCRC.
Anastomotic Leakage after Colorectal Surgery in Ovarian Cancer: Drainage, Stoma Utility and Risk Factors
Authors: Mereu Liliana , Dalprà Francesca , Berlanda Valeria , Pertile Riccardo , Coser Daniela , Pecorino Basilio , D’Agate Maria Gabriella , Ciarleglio Francesco , Brolese Alberto , Tateo Saverio
Published: December 2022

Objective: to evaluate the incidence of anastomotic leakage (AL), risk factors and utility of drainage and stoma in patients undergoing intestinal surgery for ovarian cancer in a single institution and in a review of the literature. Methods: retrospective study that includes consecutive patients undergoing debulking surgery with en bloc pelvic resection with rectosigmoid colectomy for ovarian cancer between 1 November 2011 and 31 December 2021. Data regarding patient and tumour characteristics, surgical procedure, hospitalisation, complications and follow-up were recorded and analysed. The PubMed database was explored for recent publications on this topic. Results: Seventy-five patients were enrolled in the study. All anastomoses were performed at a distance of >6 cm from the anal margin, with negative leak tests and tension-free anastomosis. Diverting stoma were performed in just three patients (4%). At least one perianastomotic pelvic drain was positioned in 71 patients (94.7%) and was removed on average on postoperative day 7. Four patients (5.3%) experienced AL. In all cases, the drain content was not the only sign of complication, as the clinical signs were also highly suggestive. Just one patient received conservative treatment. Average postoperative hospitalisation was 14.6 days (SD: ±9.7). There were no deaths at 30 and 60 days after surgery. Between the AL and non-AL groups, statistically significant differences were observed for age, Charlson Comorbidity Index, length of the intestinal resection and fitness for chemotherapy at 30 days. In ovarian cancer, rectosigmoid resection is a standardised procedure with comparable results for AL, and risk factors for AL are discretely homogeneous. What is neither homogeneous nor standardised according to the literature is the use of stomas and/or drains. Conclusion: use in the future of protective stoma and/or intra-abdominal drains is to be explored in selected and standardised situations to verify their preventive role.
Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets
Authors: Alatise Kharimat Lora , Gardner Samantha , Alexander-Bryant Angela
Published: December 2022

In the United States, over 100,000 women are diagnosed with a gynecologic malignancy every year, with ovarian cancer being the most lethal. One of the hallmark characteristics of ovarian cancer is the development of resistance to chemotherapeutics. While the exact mechanisms of chemoresistance are poorly understood, it is known that changes at the cellular and molecular level make chemoresistance challenging to treat. Improved therapeutic options are needed to target these changes at the molecular level. Using a precision medicine approach, such as gene therapy, genes can be specifically exploited to resensitize tumors to therapeutics. This review highlights traditional and novel gene targets that can be used to develop new and improved targeted therapies, from drug efflux proteins to ovarian cancer stem cells. The review also addresses the clinical relevance and landscape of the discussed gene targets.
Attempting to Identify Bacterial Allies in Immunotherapy of NSCLC Patients
Authors: Grenda Anna , Iwan Ewelina , Krawczyk Paweł , Frąk Małgorzata , Chmielewska Izabela , Bomba Arkadiusz , Giza Aleksandra , Rolska-Kopińska Anna , Szczyrek Michał , Kieszko Robert , Kucharczyk Tomasz , Jarosz Bożena , Wasyl Dariusz , Milanowski Janusz
Published: December 2022

Introduction: Factors other than PD-L1 (Programmed Death Ligand 1) are being sought as predictors for cancer immuno- or chemoimmunotherapy in ongoing studies and long-term observations. Despite high PD-L1 expression on tumor cells, some patients do not benefit from immunotherapy, while others, without the expression of this molecule, respond to immunotherapy. Attention has been paid to the composition of the gut microbiome as a potential predictive factor for immunotherapy effectiveness. Materials and Methods: Our study enrolled 47 Caucasian patients with stage IIIB or IV non-small cell lung cancer (NSCLC). They were eligible for treatment with first- or second-line immunotherapy or chemoimmunotherapy. We collected stool samples before the administration of immunotherapy. We performed next-generation sequencing (NGS) on DNA isolated from the stool sample and analyzed bacterial V3 and V4 of the 16S rRNA gene. Results: We found that bacteria from the families Barnesiellaceae, Ruminococcaceae, Tannerellaceae, and Clostridiaceae could modulate immunotherapy effectiveness. A high abundance of Bacteroidaaceae, Barnesiellaceae, and Tannerellaceae could extend progression-free survival (PFS). Moreover, the risk of death was significantly higher in patients with a high content of Ruminococcaceae family (HR = 6.3, 95% CI: 2.6 to 15.3, p < 0.0001) and in patients with a low abundance of Clostridia UCG-014 (HR = 3.8, 95% CI: 1.5 to 9.8, p = 0.005) regardless of the immunotherapy line. Conclusions: The Clostridia class in gut microbiota could affect the effectiveness of immunotherapy, as well as the length of survival of NSCLC patients who received this method of treatment.
Real-Time Split-Dose PET/CT-Guided Ablation Improves Colorectal Liver Metastasis Detection and Ablation Zone Margin Assessments without the Need for Repeated Contrast Injection
Authors: Zirakchian Zadeh Mahdi , Yeh Randy , Kunin Henry S. , Kirov Assen S. , Petre Elena N. , Gönen Mithat , Silk Mikhail , Cornelis Francois H. , Soares Kevin C. , Ziv Etay , Solomon Stephen B. , Sotirchos Vlasios S. , Sofocleous Constantinos T.
Published: December 2022

Background: Real-time split-dose PET can identify the targeted colorectal liver metastasis (CLM) and eliminate the need for repeated contrast administration before and during thermal ablation (TA). This study aimed to assess the added value of pre-ablation real-time split-dose PET when combined with non-contract CT in the detection of CLM for ablation and the evaluation of the ablation zone and margins. Methods: A total of 190 CLMs/125 participants from two IRB-approved prospective clinical trials using PET/CT-guided TA were analyzed. Based on detection on pre-TA imaging, CLMs were categorized as detectable, non-detectable, and of poor conspicuity on CT alone, and detectable, non-detectable, and low FDG-avidity on PET/CT after the initial dose. Ablation margins around the targeted CLM were evaluated using a 3D volumetric approach. Results: We found that 129/190 (67.9%) CLMs were detectable on CT alone, and 61/190 CLMs (32.1%) were undetectable or of poor conspicuity, not allowing accurate depiction and targeting by CT alone. Thus, the theoretical 5- and 10-mm margins could not be defined in these tumors (32.1%) using CT alone. When TA intraprocedural PET/CT images are obtained and inspected (fused PET/CT), only 4 CLM (2.1%) remained undetectable or had a low FDG avidity. Conclusions: The addition of PET to non-contrast CT improved CLM detection for ablation targeting, margin assessments, and continuous depiction of the FDG avid CLMs during the ablation without the need for multiple intravenous contrast injections pre- and intra-procedurally.
Microfluidics Biocatalysis System Applied for the Synthesis of N-Substituted Benzimidazole Derivatives by Aza-Michael Addition
Authors: Jiang Rong-Kuan , Pan Yue , Du Li-Hua , Zheng Ling-Yan , Sheng Zhi-Kai , Zhang Shi-Yi , Lin Hang , Zhang Ao-Ying , Xie Han-Jia , Yang Zhi-Kai , Luo Xi-Ping
Published: December 2022

Benzimidazole scaffolds became an attractive subject due to their broad spectrum of pharmacological activities. In this work, a methodology was developed for the synthesis of N-substituted benzimidazole derivatives from benzimidazoles and α, β-unsaturated compounds (acrylonitriles, acrylate esters, phenyl vinyl sulfone) catalyzed by lipase TL IM from Thermomyces lanuginosus in continuous-flow microreactors. Investigations were conducted on reaction parameters such as solvent, substrate ratio, reaction temperature, reactant donor/acceptor structures, and reaction time. The transformation is promoted by inexpensive and readily available lipase in methanol at 45 °C for 35 min. A wide range of β-amino sulfone, β-amino nitrile, and β-amino carbonyl compounds were efficiently and selectively synthesized in high yields (76–97%). All in all, a microfluidic biocatalysis system was applied to the synthesis of N-substituted benzimidazole derivatives, and could serve as a promising fast synthesis strategy for further research to develop novel and highly potent active drugs.
Photocatalytic Degradation of Ciprofloxacin by UV Light Using N-Doped TiO2 in Suspension and Coated Forms
Authors: Abdulrahman Sarah A. , Shnain Zainab Y. , Ibrahim Salah S. , Majdi Hasan Sh.
Published: December 2022

The presence of organic compounds such as ciprofloxacin in untreated pharmaceutical wastewater often poses a serious health risk to human and aquatic life when discharged into water bodies. One of the most effective means of removing ciprofloxacin from wastewater is photocatalytic degradation. However, the synthesis of an effective photocatalyst that can degrade the organic pollutant in the wastewater is often a challenge. Hence, this study focuses on the synthesis and application of nitrogen-doped TiO2 (N-TiO2) in suspension and coated forms for the photocatalytic degradation of ciprofloxacin in wastewater by applying UV-light irradiation. The nitrogen-doped TiO2 photocatalyst was prepared by a co-precipitation process and characterized using energy-dispersive X-ray spectroscopy, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The effects of the initial concentration of the ciprofloxacin (6, 12, 18, or 30 ppm), pH (3, 5, 7, or 9), and flow rate (0.4, 0.8, 0.95, or 1.5 L/min) on the degradation of the ciprofloxacin over the N-TiO2 were investigated. The results showed that the removal efficiency of ciprofloxacin was enhanced by increasing the initial ciprofloxacin concentration, while it was decreased with the increase in the feed flow rate. The best operating conditions were obtained using an initial ciprofloxacin concentration of 30 ppm, pH of 5, and feed flow rate of 0.4 L/min. Under these operating conditions, removal efficiencies of 87.87% and 93.6% were obtained for net TiO2 and N-TiO2 of 5 wt% in suspension form, respectively, while 94.5% ciprofloxacin removal efficiency was obtained using coated 5 wt% N-TiO2 after 2 h of photocatalytic degradation. Based on the response surface optimization strategy, a quadratic model was suggested to obtain mathematical expressions to predict the ciprofloxacin removal efficiency under various studied operational parameters.
Study on the Formaldehyde Oxidation Reaction of Acid-Treated Manganese Dioxide Nanorod Catalysts
Authors: Li Yanqiu , Su Yuan , Yang Yunfeng , Liu Ping , Zhang Kan , Ji Keming
Published: December 2022

Formaldehyde is an important downstream chemical of syngas. Furniture and household products synthesized from formaldehyde will slowly decompose and release formaldehyde again during use, which seriously affects indoor air quality. In order to solve the indoor formaldehyde pollution problem, this paper took the catalytic oxidation of formaldehyde as the research object; prepared a series of low-cost, acid-treated manganese dioxide nanorod catalysts; and investigated the effect of the acid-treatment conditions on the catalysts’ activity. It was found that the MnNR-0.3ac-6h catalyst with 0.3 mol/L sulfuric acid for 6 h had the best activity. The conversion rate of formaldehyde reached 98% at 150 °C and 90% at 25 °C at room temperature. During the reaction time of 144 h, the conversion rate of formaldehyde was about 90%, and the catalyst maintained a high activity. It was found that acid treatment could increase the number of oxygen vacancies on the surface of the catalysts and promote the production of reactive oxygen species. The amount of surface reactive oxygen species of the MnNR-0.3ac-6h catalyst was about 13% higher than that of the catalyst without acid treatment.
Unsupported Ni—Mo—W Hydrotreating Catalyst: Influence of the Atomic Ratio of Active Metals on the HDS and HDN Activity
Authors: Nadeina Ksenia A. , Budukva Sergey V. , Vatutina Yuliya V. , Mukhacheva Polina P. , Gerasimov Evgeniy Yu. , Pakharukova Vera P. , Klimov Oleg V. , Noskov Aleksandr S.
Published: December 2022

Hydrotreating is one of the largest processes used in a refinery to improve the quality of oil products. The great demand of the present is to develop more active catalysts which could improve the energy efficiency of the process when it is necessary for heavier feedstock to be processed. Unsupported catalysts could solve this problem, because they contain the greatest amount of sulfide active sites, which significantly increase catalysts’ activity. Unfortunately, most of the information on the preparation and properties of unsupported catalysts is devoted to powder systems, while industrial plants require granular catalysts. Therefore, the present work describes a method for the preparation of granular Ni—Mo—W unsupported hydrotreating catalysts and studies the influence of the Ni/Mo/W atomic ratio on their properties. Catalysts have been prepared by plasticizing Ni—Mo—W precursor with aluminum hydroxide followed by granulation and drying stages. Ni—Mo—W precursor and granular catalysts were studied by X-ray diffraction (XRD), nitrogen adsorption–desorption method, high-resolution transmission electron microscopy (HRTEM), and thermal analysis. Granular catalysts were sulfided through a liquid-phase sulfidation procedure and tested in hydrotreating of straight-run vacuum gasoil. It was shown that the Ni/Mo/W atomic ratio influenced the formation and composition of active compounds and had almost no influence on the textural properties of catalysts. The best hydrodesulfurization (HDS) activity was obtained for the catalyst with Ni/Mo/W ratio—1/0.15/0.85, while hydrodenitrogenation (HDN) activity of the catalysts is very similar.
Insight into the Effect of Anionic–Anionic Co-Doping on BaTiO3 for Visible Light Photocatalytic Water Splitting: A First-Principles Hybrid Computational Study
Authors: Goumri-Said Souraya , Kanoun Mohammed Benali
Published: December 2022

In this research, we thoroughly studied the electronic properties and optical absorption characteristics with double-hole coupling of anions–anion combinations for designing effective photocatalysts for water redox using first-principles methods within the hybrid Heyd–Scuseria–Ernzerhof (HSE06) exchange–correlation formalisms. The findings reveal that the values of formation energy of both the anion mono- and co-doped configurations increase monotonically as the chemical potential of oxygen decreases. The N–N co-doped BaTiO3 exhibits a more favorable formation energy under an O-poor condition compared with other configurations, indicating that N and N pairs are more likely to be synthesized successfully. Interestingly, all the co-doping configurations give a band gap reduction with suitable position for oxygen production and hydrogen evolution. The obtained results demonstrate that all the co-doped systems constitute a promising candidate for photocatalytic water-splitting reactions. Furthermore, the enhanced ability of the anionic-anionic co-doped BaTiO3 to absorb visible light and the positions of band edges that closely match the oxidation-reduction potentials of water suggest that these configurations are viable photocatalysts for visible-light water splitting. Therefore, the wide-band gap semiconductor band structures can be tuned by double-hole doping through anionic combinations, and high-efficiency catalysts for water splitting using solar energy can be created as a result.
Icariin Treatment Rescues Diabetes Induced Bone Loss via Scavenging ROS and Activating Primary Cilia/Gli2/Osteocalcin Signaling Pathway
Authors: Liu Jie , Cheng Qingfeng , Wu Xiangmei , Zhu Huifang , Deng Xiaoyan , Wang Maorong , Yang Shengyong , Xu Jie , Chen Qian , Li Mengxue , Liu Xianjun , Wang Changdong
Published: December 2022

Diabetes-associated bone complications lead to fragile bone mechanical strength and osteoporosis, aggravating the disease burden of patients. Advanced evidence shows that chronic hyperglycemia and metabolic intermediates, such as inflammatory factor, reactive oxygen species (ROS), and advanced glycation end products (AGEs), are regarded as dominant hazardous factors of bone complications, whereas the pathophysiological mechanisms are complex and controversial. By establishing a diabetic Sprague-Dawley (SD) rat model and diabetic bone loss cell model in vitro, we confirmed that diabetes impaired primary cilia and led to bone loss, while adding Icariin (ICA) could relieve the inhibitions. Mechanistically, ICA could scavenge ROS to maintain the mitochondrial and primary cilia homeostasis of osteoblasts. Intact primary cilia acted as anchoring and modifying sites of Gli2, thereby activating the primary cilia/Gli2/osteocalcin signaling pathway to promote osteoblast differentiation. All results suggest that ICA has potential as a therapeutic drug targeting bone loss induced by diabetes.
A Novel Mechanism Underlying the Inhibitory Effects of Trastuzumab on the Growth of HER2-Positive Breast Cancer Cells
Authors: Maadi Hamid , Wang Zhixiang
Published: December 2022

To improve the efficacy of trastuzumab, it is essential to understand its mechanism of action. One of the significant issues that makes it difficult to determine the precise mechanism of trastuzumab action is the formation of various HER receptor dimers in HER2-positive breast cancer cells. So far, studies have focused on the role of HER2–HER3 heterodimers, and little is known regarding EGFR–HER2 heterodimers. Here, we study the role of trastuzumab on the cell signaling and cell proliferation mediated by EGFR–HER2 heterodimers in BT474 and SRBR3 cells. EGF stimulates the formation of both EGFR homodimer and EGFR–HER2 heterodimer. Trastuzumab only binds to HER2, not EGFR. Therefore, any effects of trastuzumab on EGF-induced activation of EGFR, HER2, and downstream signaling proteins, as well as cell proliferation, are through its effects on EGFR–HER2 heterodimers. We show that trastuzumab inhibits EGF-induced cell proliferation and cell cycle progression in BT474 and SKBR3 cells. Interestingly trastuzumab strongly inhibits EGF-induced Akt phosphorylation and slightly inhibits EGF-induced Erk activation, in both BT474 and SKBR3 cells. These data suggest the presence of a novel mechanism that allows trastuzumab to inhibit EGR-induced Akt activation and cell proliferation, without blocking EGF-induced EGFR–HER2 heterodimerization and activation. We show that trastuzumab inhibits EGF-induced lipid raft localization of the EGFR–HER2 heterodimer. Disruption of the lipid raft with MβCD blocks HER2-mediated AKT activation in a similar way to trastuzumab. MβCD and trastuzumab synergically inhibit AKT activation. We conclude that trastuzumab inhibits EGF-induced lipid raft localization of EGFR–HER2 heterodimer, which leads to the inhibition of Akt phosphorylation and cell proliferation, without blocking the formation and phosphorylation of the EGFR–HER2 heterodimer.
Metformin Improves Burn Wound Healing by Modulating Microenvironmental Fibroblasts and Macrophages
Authors: Shi Liangliang , Jiang Zhengying , Li Jiaqi , Lin Huan , Xu Bin , Liao Xincheng , Fu Zhonghua , Ao Haiyong , Guo Guanghua , Liu Mingzhuo
Published: December 2022

Metformin, a biguanide, exerts different functions through various signaling pathways. In order to investigate the function and mechanism of metformin in burn wounds, we established burn rat models, subcutaneously injected metformin to treat the wounds, and observed the morphologies and the expression of collagen I, collagen III, fibronectin, and pro-inflammatory markers. In vitro experiments were performed to investigate the effects of metformin on the proliferation, migration, and collagen I synthesis of the mouse embryonic fibroblast (NIH 3T3) cell line and on the proliferation, apoptosis, and immune response of the mouse mononuclear macrophage (RAW 264.7) cell line. Finally, we studied the regulatory effects of metformin on a co-culture of RAW 264.7/NIH 3T3 cells. We found that 100 mM of metformin reduced dermal thickness, collagen I deposition, and mRNA expression of IL1β and CCL2 in rat burn wounds. In vitro experiments revealed that metformin inhibited the proliferation of NIH 3T3 and RAW 264.7 cells. Metformin attenuated NIH 3T3 cell migration via the AMPK/mTOR pathway and attenuated collagen I synthesis through the TGFβ1/Smad3 pathway. Metformin inhibited the apoptosis of RAW 264.7 cells induced by 10 μg/mL LPS. Metformin downregulated the mRNA expression of IL1β and CCL2 in RAW 264.7 cells under 1 μg/mL LPS induction by inhibiting NF-κB p65 phosphorylation. In a RAW 264.7/NIH 3T3 co-culture, metformin attenuated collagen I synthesis in NIH 3T3 cells by inhibiting RAW 264.7 paracrine secretion of TGF-β1. This provides new evidence related to the development of metformin for potentially improving burn wound healing.