bluuebunny/crossref_metadata_2025 huggingface dataset:
Inosine enhances tumor mitochondrial respiration by inducing Rag GTPases and nascent protein synthesis under nutrient starvation
Authors: Li Mei-Xin , Wu Xiao-Ting , Jing Wen-Qiang , Hou Wen-Kui , Hu Sheng , Yan Wei
Published: August 2023

Metabolic heterogeneity of tumor microenvironment (TME) is a hallmark of cancer and a big barrier to cancer treatment. Cancer cells display diverse capacities to utilize alternative carbon sources, including nucleotides, under poor nutrient circumstances. However, whether and how purine, especially inosine, regulates mitochondrial metabolism to buffer nutrient starvation has not been well-defined yet. Here, we identify the induction of 5′-nucleotidase, cytosolic II (NT5C2) gene expression promotes inosine accumulation and maintains cancer cell survival in the nutrient-poor region. Inosine elevation further induces Rag GTPases abundance and mTORC1 signaling pathway by enhancing transcription factor SP1 level in the starved tumor. Besides, inosine supplementary stimulates the synthesis of nascent TCA cycle enzymes, including citrate synthesis (CS) and aconitase 1 (ACO1), to further enhance oxidative phosphorylation of breast cancer cells under glucose starvation, leading to the accumulation of iso-citric acid. Inhibition of the CS activity or knockdown of ACO1 blocks the rescue effect of inosine on cancer survival under starvation. Collectively, our finding highlights the vital signal role of inosine linking mitochondrial respiration and buffering starvation, beyond serving as direct energy carriers or building blocks for genetic code in TME, shedding light on future cancer treatment by targeting inosine metabolism.
Gas6 in chronic liver disease—a novel blood-based biomarker for liver fibrosis
Authors: Staufer Katharina , Huber Heidemarie , Zessner-Spitzenberg Jasmin , Stauber Rudolf , Finkenstedt Armin , Bantel Heike , Weiss Thomas S. , Huber Markus , Starlinger Patrick , Gruenberger Thomas , Reiberger Thomas , Sebens Susanne , McIntyre Gail , Tabibiazar Ray , Giaccia Amato , Zoller Heinz , Trauner Michael , Mikulits Wolfgang
Published: August 2023

The expression of the receptor tyrosine kinase Axl and its cleavage product soluble Axl (sAxl) is increased in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this multicenter study, we evaluated the diagnostic value of Gas6, the high-affinity ligand of Axl, in patients with chronic liver disease. Levels of sAxl and Gas6, and their albumin (alb) ratios were analyzed in serum samples of patients with biopsy-proven liver fibrosis, end-stage liver disease, HCC, and healthy controls, and were compared to Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF™) test, Child-Pugh score (CPS), model of end-stage liver disease (MELD) score, hepatic venous pressure gradient, and α-fetoprotein, respectively. A total of 1111 patients (median age 57.8 y, 67.3% male) was analyzed. Gas6/alb showed high diagnostic accuracy for the detection of significant (≥F2: AUC 0.805) to advanced fibrosis (≥F3: AUC 0.818), and was superior to Fib-4 for the detection of cirrhosis (F4: AUC 0.897 vs. 0.878). In addition, Gas6/alb was highly predictive of liver disease severity (Odds ratios for CPS B/C, MELD ≥ 15, and clinically significant portal hypertension (CSPH) were 16.534, 10.258, and 12.115), and was associated with transplant-free survival (Hazard ratio 1.031). Although Gas6 and Gas6/alb showed high diagnostic accuracy for the detection of HCC in comparison to chronic liver disease patients without cirrhosis (AUC 0.852, 0.868), they failed to discriminate between HCC in cirrhosis versus cirrhosis only. In conclusion, Gas6/alb shows a high accuracy to detect significant to advanced fibrosis and cirrhosis, and predicts severity of liver disease including CSPH.
Lack of apoptosis leads to cellular senescence and tumorigenesis in Drosophila epithelial cells
Authors: Garcia-Arias Juan Manuel , Pinal Noelia , Cristobal-Vargas Sara , Estella Carlos , Morata Ginés
Published: August 2023

Programmed cell death (apoptosis) is a homeostasis program of animal tissues designed to remove cells that are unwanted or are damaged by physiological insults. To assess the functional role of apoptosis, we have studied the consequences of subjecting Drosophila epithelial cells defective in apoptosis to stress or genetic perturbations that normally cause massive cell death. We find that many of those cells acquire persistent activity of the JNK pathway, which drives them into senescent status, characterized by arrest of cell division, cell hypertrophy, Senescent Associated ß-gal activity (SA-ß-gal), reactive oxygen species (ROS) production, Senescent Associated Secretory Phenotype (SASP) and migratory behaviour. We have identified two classes of senescent cells in the wing disc: 1) those that localize to the appendage part of the disc, express the upd, wg and dpp signalling genes and generate tumour overgrowths, and 2) those located in the thoracic region do not express wg and dpp nor they induce tumour overgrowths. Whether to become tumorigenic or non-tumorigenic depends on the original identity of the cell prior to the transformation. We also find that the p53 gene contributes to senescence by enhancing the activity of JNK.
Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures
Authors: Yang Annie S. P. , Dutta Devanjali , Kretzschmar Kai , Hendriks Delilah , Puschhof Jens , Hu Huili , Boonekamp Kim E. , van Waardenburg Youri , Chuva de Sousa Lopes Susana M. , van Gemert Geert-Jan , de Wilt Johannes H. W. , Bousema Teun , Clevers Hans , Sauerwein Robert W.
Published: August 2023

Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains. Single-cell messenger RNA sequencing (scRNAseq) of Pf-infected HepOrg cells has identified 80 Pf-transcripts upregulated on day 5 post-infection. Transcriptional profile changes are found involving distinct metabolic pathways in hepatocytes with Scavenger Receptor B1 (SR-B1) transcripts highly upregulated. A novel functional involvement in schizont maturation is confirmed in fresh primary hepatocytes. Thus, HepOrgs provide a strong foundation for a versatile in vitro model for Pf liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control.
Nitroalkanes as thioacyl equivalents to access thioamides and thiopeptides
Authors: Wang Xiaonan , Xu Silong , Tang Yuhai , Lear Martin J. , He Wangxiao , Li Jing
Published: August 2023

Thioamides are an important, but a largely underexplored class of amide bioisostere in peptides. Replacement of oxoamide units with thioamides in peptide therapeutics is a valuable tactic to improve biological activity and resistance to enzymatic hydrolysis. This tactic, however, has been hampered by insufficient methods to introduce thioamide bonds into peptide or protein backbones in a site-specific and stereo-retentive fashion. In this work, we developed an efficient and mild thioacylation method to react nitroalkanes with amines directly in the presence of elemental sulfur and sodium sulfide to form a diverse range of thioamides in high yields. Notably, this convenient method can be employed for the controlled thioamide coupling of multifunctionalized peptides without epimerization of stereocenters, including the late stage thioacylation of advanced compounds of biological and medicinal interest. Experimental interrogation of postulated mechanisms currently supports the intermediacy of thioacyl species.
A numeric-based machine learning design for detecting organized retail fraud in digital marketplaces
Authors: Mutemi Abed , Bacao Fernando
Published: August 2023

Organized retail crime (ORC) is a significant issue for retailers, marketplace platforms, and consumers. Its prevalence and influence have increased fast in lockstep with the expansion of online commerce, digital devices, and communication platforms. Today, it is a costly affair, wreaking havoc on enterprises’ overall revenues and continually jeopardizing community security. These negative consequences are set to rocket to unprecedented heights as more people and devices connect to the Internet. Detecting and responding to these terrible acts as early as possible is critical for protecting consumers and businesses while also keeping an eye on rising patterns and fraud. The issue of detecting fraud in general has been studied widely, especially in financial services, but studies focusing on organized retail crimes are extremely rare in literature. To contribute to the knowledge base in this area, we present a scalable machine learning strategy for detecting and isolating ORC listings on a prominent marketplace platform by merchants committing organized retail crimes or fraud. We employ a supervised learning approach to classify postings as fraudulent or real based on past data from buyer and seller behaviors and transactions on the platform. The proposed framework combines bespoke data preprocessing procedures, feature selection methods, and state-of-the-art class asymmetry resolution techniques to search for aligned classification algorithms capable of discriminating between fraudulent and legitimate listings in this context. Our best detection model obtains a recall score of 0.97 on the holdout set and 0.94 on the out-of-sample testing data set. We achieve these results based on a select set of 45 features out of 58.
Testing a relational account of search templates in visual foraging
Authors: Grössle Inga M. , Schubö Anna , Tünnermann Jan
Published: August 2023

Search templates guide human visual attention toward relevant targets. Templates are often seen as encoding exact target features, but recent studies suggest that templates rather contain “relational properties” (e.g., they facilitate “redder” stimuli instead of specific hues of red). Such relational guidance seems helpful in naturalistic searches where illumination or perspective renders exact feature values unreliable. So far relational guidance has only been demonstrated in rather artificial single-target search tasks with briefly flashed displays. Here, we investigate whether relational guidance also occurs when humans interact with the search environment for longer durations to collect multiple target elements. In a visual foraging task, participants searched for and collected multiple targets among distractors of different relationships to the target colour. Distractors whose colour differed from the environment in the same direction as the targets reduced foraging efficiency to the same amount as distractors whose colour matched the target colour. Distractors that differed by the same colour distance but in the opposite direction of the target colour did not reduce efficiency. These findings provide evidence that search templates encode relational target features in naturalistic search tasks and suggest that attention guidance based on relational features is a common mode in dynamic, real-world search environments.
Close-kin mark-recapture informs critically endangered terrestrial mammal status
Authors: Lloyd-Jones Luke R. , Bravington Mark V. , Armstrong Kyle N. , Lawrence Emma , Feutry Pierre , Todd Christopher M. , Dorrestein Annabel , Welbergen Justin A. , Martin John M. , Rose Karrie , Hall Jane , Phalen David N. , Peters Isabel , Baylis Shane M. , Macgregor Nicholas A. , Westcott David A.
Published: August 2023

Reliable information on population size is fundamental to the management of threatened species. For wild species, mark-recapture methods are a cornerstone of abundance estimation. Here, we show the first application of the close-kin mark-recapture (CKMR) method to a terrestrial species of high conservation value; the Christmas Island flying-fox (CIFF). The CIFF is the island's last remaining native terrestrial mammal and was recently listed as critically endangered. CKMR is a powerful tool for estimating the demographic parameters central to CIFF management and circumvents the complications arising from the species’ cryptic nature, mobility, and difficult-to-survey habitat. To this end, we used genetic data from 450 CIFFs captured between 2015 and 2019 to detect kin pairs. We implemented a novel CKMR model that estimates sex-specific abundance, trend, and mortality and accommodates observations from the kin-pair distribution of male reproductive skew and mate persistence. CKMR estimated CIFF total adult female abundance to be approximately 2050 individuals (95% CI (950, 4300)). We showed that on average only 23% of the adult male population contributed to annual reproduction and strong evidence for between-year mate fidelity, an observation not previously quantified for a Pteropus species in the wild. Critically, our population estimates provide the most robust understanding of the status of this critically endangered population, informing immediate and future conservation initiatives.
β-mannanase supplemented in diets saved 85 to 100 kcal of metabolizable energy/kg, supporting growth performance and improving nutrient digestibility in grower pigs
Authors: Genova Jansller Luiz , Azevedo Liliana Bury de , Rupolo Paulo Evaristo , Cordeiro Flávia Beatriz Carvalho , Vilela Hellen Lazarino Oliveira , Careli Pedro Silva , de Castro Fidelis Toledo Damares , Carvalho Silvana Teixeira , Kipper Marcos , Rennó Luciana Navajas , Faveri Juliana Canto , de Oliveira Carvalho Paulo Levi
Published: August 2023

The effects of β-mannanase supplementation in metabolizable energy (ME)-reduced diets containing xylanase-phytase were investigated on growth performance, fecal score, ultra-sounded backfat thickness and loin depth, blood profile, apparent total tract digestibility (ATTD), digesta passage rate, and fecal microbiome in grower pigs (n = 40, 26.09 ± 0.96 kg) randomly assigned within 4 treatments: a control diet containing isolated phytase and xylanase valued at 40 kcal of ME/kg (CD0), CD0 + β-mannanase (0.3 g/kg valued at 30 kcal of ME/kg) (CD70), CD0 + β-mannanase (0.3 g/kg valued at 45 kcal of ME/kg) (CD85), and CD0 + β-mannanase (0.3 g/kg valued at 60 kcal of ME/kg) (CD100). Growth performance was not affected in pigs fed ME-reduced diets containing β-mannanase. Pigs with CD100 had lower serum IL-1β concentration, and higher IL-10 was observed in pigs on CD0 than those fed β-mannanase. Coefficients of ATTD, and ATTD of DM and CP were higher in animals fed CD85 or CD100. Pigs with CD85 had higher alpha diversity richness but lower Firmicutes:Bacteroidota ratio. Acidaminococcaceae and Ruminococcaceae were more abundant in pigs fed CD0, but lower for Christensenellaceae NSJ-63 and NSJ-63 sp014384805. Pigs in CD85 showed higher Bacteroidaceae and Prevotella abundance, and lower for Streptococcaceae and Streptococcus. In conclusion, supplementation of β-mannanase in diets containing xylanase-phytase saved 85 to 100 kcal of ME/kg by supporting growth performance and improving nutrient digestibility in grower pigs.
Optimized sliding mode controller for trajectory tracking of flexible joints three-link manipulator with noise in input and output
Authors: Azeez Muhammad I. , Abdelhaleem A. M. M. , Elnaggar S. , Moustafa Kamal A. F. , Atia Khaled R.
Published: August 2023

The aim of this study is to enhance the performance of a nonlinear three-rigid-link maneuver (RLM) in terms of trajectory tracking, disturbance and noise cancellation, and adaptability to joint flexibility. To achieve this, an optimized sliding mode controller with a proportional integral derivative surface (SMC-PID) is employed for maneuver control. An improved artificial bee colony algorithm with multi-elite guidance (MGABC) is utilized to obtain optimal values for the sliding surface and switching mode gain and attain the best performance for the robot maneuver system. The selection of the MGABC algorithm is based on its efficient exploration and exploitation techniques. The performance of the optimized SMC-PID robotic system is compared against other optimization algorithms found in existing literature, including Particle Swarm Optimization (PSO), Genetic Algorithm (GA), Artificial Bee Colony (ABC), Ant Lion Optimizer (ALO), and Grey Wolf Optimizer (GWO). The implemented controller effectively reduces the tracking error to 0.00691 radians, eliminates chattering phenomena in the control effort, and demonstrates robustness against disturbances and noise. The controller ensures that the objective function (OBJF) is minimized, with 0.954% increase in OBJF under low disturbance and noise conditions and 14.55% under severe disturbance and noise conditions. Moreover, the optimized controller exhibits resilience to variations in payload mass analysis, with the percentage increase in OBJF values ranging from 5.726% under low uncertainty conditions to 18.887% under severe uncertainty conditions. Flexible-link maneuvers (FLM) offer advantages such as improved safety and increased operating speeds in real-world applications. In this study, we investigated the impact of joint flexibility on the performance of the FLM system. Our proposed controller demonstrated superior tracking performance, characterized by minimal vibrations in the movement of the end effector.
Preoperative prediction of sinonasal papilloma by artificial intelligence using nasal video endoscopy: a retrospective study
Authors: Yui Ryosuke , Takahashi Masahiro , Noda Katsuhiko , Yoshida Kaname , Sakurai Rinko , Ohira Shinya , Omura Kazuhiro , Otori Nobuyoshi , Wada Kota , Kojima Hiromi
Published: August 2023

Sinonasal inverted papilloma (IP) is at risk of recurrence and malignancy, and early diagnosis using nasal endoscopy is essential. We thus developed a diagnostic system using artificial intelligence (AI) to identify nasal sinus papilloma. Endoscopic surgery videos of 53 patients undergoing endoscopic sinus surgery were edited to train and evaluate deep neural network models and then a diagnostic system was developed. The correct diagnosis rate based on visual examination by otolaryngologists was also evaluated using the same videos and compared with that of the AI diagnostic system patients. Main outcomes evaluated included the percentage of correct diagnoses compared to AI diagnosis and the correct diagnosis rate for otolaryngologists based on years of practice experience. The diagnostic system had an area under the curve of 0.874, accuracy of 0.843, false positive rate of 0.124, and false negative rate of 0.191. The average correct diagnosis rate among otolaryngologists was 69.4%, indicating that the AI was highly accurate. Evidently, although the number of cases was small, a highly accurate diagnostic system was created. Future studies with larger samples to improve the accuracy of the system and expand the range of diseases that can be detected for more clinical applications are warranted.
Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy
Authors: Tumas Sarunas , Meldgaard Trine Sundebo , Vaaben Troels Holger , Suarez Hernandez Sara , Rasmussen Annemette Tengstedt , Vazquez-Uribe Ruben , Hadrup Sine Reker , Sommer Morten O. A.
Published: August 2023

In this study we performed a step-wise optimization of biologically active IL-2 for delivery using E. coli Nissle 1917. Engineering of the strain was coupled with an in vitro cell assay to measure the biological activity of microbially produced IL-2 (mi-IL2). Next, we assessed the immune modulatory potential of mi-IL2 using a 3D tumor spheroid model demonstrating a strong effect on immune cell activation. Finally, we evaluated the anticancer properties of the engineered strain in a murine CT26 tumor model. The engineered strain was injected intravenously and selectively colonized tumors. The treatment was well-tolerated, and tumors of treated mice showed a modest reduction in tumor growth rate, as well as significantly elevated levels of IL-2 in the tumor. This work demonstrates a workflow for researchers interested in engineering E. coli Nissle for a new class of microbial therapy against cancer.
hsa-miR-199b-3p suppresses osteosarcoma progression by targeting CCDC88A, inhibiting epithelial-to-mesenchymal transition, and Wnt/beta-catenin signaling pathway
Authors: Zhu Dongsheng , Qi Han , Zhu Hongqi
Published: August 2023

The present study investigated microRNA (miR)-199b-3p expression in osteosarcoma (OS) and aimed to identify its potential mechanism of action contributing to the development of this disease. Firstly, miR-199b-3p and coiled-coil domain containing 88A (CCDC88A) expression data were evaluated from Gene Expression Profiling Interactive Analysis and Kaplan Meier plotter was used to assess the survival data. By analyzing the GSE65071 dataset from gene expression omnibus, it was found that miR-199b-3p was expressed at a low level. By using reverse transcription-quantitative PCR analysis in OS cells and tissues, CCDC88A was found to be expressed at a high level. Moreover, TargetScan predicted CCDC88A to be a downstream target of miR-199b-3p. Luciferase reporter assays were used to verify this prediction. In vitro overexpression of miR-199b-3p decreased the invasive and proliferative activity of OS cells. Mechanistic studies indicated that decreased miR-199b-3p resulted in increased expression of CCDC88A. Concomitantly, it impeded the Wnt/beta-catenin pathway and the epithelial-to-mesenchymal transition process. Overall, the results of the present study emphasized the pivotal role of the miR-199b-3p in the formation and progression of OS, suggesting that it could be used as a potential tumor biomarker.
Spatial attention-based residual network for human burn identification and classification
Authors: Yadav D. P. , Aljrees Turki , Kumar Deepak , Kumar Ankit , Singh Kamred Udham , Singh Teekam
Published: August 2023

Diagnosing burns in humans has become critical, as early identification can save lives. The manual process of burn diagnosis is time-consuming and complex, even for experienced doctors. Machine learning (ML) and deep convolutional neural network (CNN) models have emerged as the standard for medical image diagnosis. The ML-based approach typically requires handcrafted features for training, which may result in suboptimal performance. Conversely, DL-based methods automatically extract features, but designing a robust model is challenging. Additionally, shallow DL methods lack long-range feature dependency, decreasing efficiency in various applications. We implemented several deep CNN models, ResNeXt, VGG16, and AlexNet, for human burn diagnosis. The results obtained from these models were found to be less reliable since shallow deep CNN models need improved attention modules to preserve the feature dependencies. Therefore, in the proposed study, the feature map is divided into several categories, and the channel dependencies between any two channel mappings within a given class are highlighted. A spatial attention map is built by considering the links between features and their locations. Our attention-based model BuRnGANeXt50 kernel and convolutional layers are also optimized for human burn diagnosis. The earlier study classified the burn based on depth of graft and non-graft. We first classified the burn based on the degree. Subsequently, it is classified into graft and non-graft. Furthermore, the proposed model performance is evaluated on Burns_BIP_US_database. The sensitivity of the BuRnGANeXt50 is 97.22% and 99.14%, respectively, for classifying burns based on degree and depth. This model may be used for quick screening of burn patients and can be executed in the cloud or on a local machine. The code of the proposed method can be accessed athttps://github.com/dhirujis02/Journal.gitfor the sake of reproducibility.
Interannual climate variability improves niche estimates for ectothermic but not endothermic species
Authors: Karger Dirk Nikolaus , Saladin Bianca , Wüest Rafael O. , Graham Catherine H. , Zurell Damaris , Mo Lidong , Zimmermann Niklaus E.
Published: August 2023

Climate is an important limiting factor of species’ niches and it is therefore regularly included in ecological applications such as species distribution models (SDMs). Climate predictors are often used in the form of long-term mean values, yet many species experience wide climatic variation over their lifespan and within their geographical range which is unlikely captured by long-term means. Further, depending on their physiology, distinct groups of species cope with climate variability differently. Ectothermic species, which are directly dependent on the thermal environment are expected to show a different response to temporal or spatial variability in temperature than endothermic groups that can decouple their internal temperature from that of their surroundings. Here, we explore the degree to which spatial variability and long-term temporal variability in temperature and precipitation change niche estimates for ectothermic (730 amphibian, 1276 reptile), and endothermic (1961 mammal) species globally. We use three different species distribution modelling (SDM) algorithms to quantify the effect of spatial and temporal climate variability, based on global range maps of all species and climate data from 1979 to 2013. All SDMs were cross-validated and accessed for their performance using the Area under the Curve (AUC) and the True Skill Statistic (TSS). The mean performance of SDMs using only climatic means as predictors was TSS = 0.71 and AUC = 0.90. The inclusion of spatial variability offers a significant gain in SDM performance (mean TSS = 0.74, mean AUC = 0.92), as does the inclusion of temporal variability (mean TSS = 0.80, mean AUC = 0.94). Including both spatial and temporal variability in SDMs shows the highest scores in AUC and TSS. Accounting for temporal rather than spatial variability in climate improved the SDM prediction especially in ectotherm groups such as amphibians and reptiles, while for endothermic mammals no such improvement was observed. These results indicate that including long term climate interannual climate variability into niche estimations matters most for ectothermic species that cannot decouple their physiology from the surrounding environment as endothermic species can.
Effects of N-acetylcysteine on CG8005 gene-mediated proliferation and apoptosis of Drosophila S2 embryonic cells
Authors: Chen Wanyin , Yin Yifei , Zhang Zheng
Published: August 2023

To investigate the effect of the antioxidant N-acetylcysteine (NAC) on the proliferation and apoptosis in CG8005 gene-interfering Drosophila S2 embryonic cells by scavenging intracellular reactive oxygen species (ROS). The interfering efficiency of CG8005 gene in Drosophila S2 embryonic cells was verified by real-time quantitative PCR (qRT-PCR). Different concentrations of NAC and phosphate buffered saline (PBS) were used to affect the Drosophila S2 embryonic cells. The growth state of Drosophila S2 embryonic cells was observed by light microscope. Two probes dihydroethidium (DHE) and 2,7-dichlorodihydrofluorescein-acetoacetate (DCFH-DA) were used to observe the ROS production in each group after immunofluorescence staining. TUNEL staining and flow cytometry were used to investigate the apoptosis level of Drosophila S2 embryos, and CCK-8 (Cell Counting Kit-8) was used to detect the cell viability of Drosophila S2 embryos. The knockdown efficiency of siCG8005-2 fragment was high and stable, which was verified by interference efficiency (P < 0.05). There was no significant change in the growth of Drosophila S2 embryonic cells after the treatment of NAC as compared to PBS group. Moreover, knockdowning CG8005 gene resulted in an increase in ROS and apoptosis in Drosophila S2 embryonic cells (P < 0.05) and a decrease in proliferation activity (P < 0.05). In addition, the pretreatment of antioxidant NAC could inhibit ROS production in Drosophila S2 embryonic cells (P < 0.05), reduce cell apoptosis (P < 0.05), and improve cell survival (P < 0.05). The CG8005 gene in Drosophila S2 embryonic cells could regulate the proliferation and apoptosis of S2 embryonic cells by disrupting the redox homeostasis, and antioxidant NAC could inhibit cell apoptosis and promotes cell proliferation by scavenging ROS in Drosophila S2 embryonic cells, which is expected to provide novel insights for the pathogenesis of male infertility and spermatogenesis.
Equivalent circuit of a silicon–lithium p–i–n nuclear radiation detector
Authors: Saymbetov Ahmet , Muminov Ramizulla , Jing Zhang , Nurgaliyev Madiyar , Japashov Nursultan , Toshmurodov Yorkin , Kuttybay Nurzhigit , Kapparova Ainur , Zholamanov Batyrbek , Orynbassar Sayat , Koshkarbay Nursultan
Published: August 2023

Nuclear radiation detectors are indispensable for research in the field of nuclear radiation, X-ray spectroscopy and other areas. Interest in silicon p–i–n detectors of nuclear radiation is increasing today due to the possibility of their operation under normal conditions. In this paper, an equivalent circuit of a silicon–lithium p–i–n nuclear radiation detector is proposed. The proposed circuit is obtained using the classical Shockley equation for silicon semiconductors and the telegraph equations. The parameters of the equivalent circuit were determined using the multiple regression method. As a result of simulation of the model in the MATLAB Simulink graphical development environment, the amplitude-frequency and phase-frequency characteristics of the proposed model were obtained. Using the Monte Carlo method, the alpha-decay of the uranium isotope$${}_{92}{}^{233}\mathrm{U}$$92233U, thorium isotope$${}_{90}{}^{227}\mathrm{Th}$$90227Thand americium isotope$${}_{95}{}^{241}\mathrm{Am}$$95241Amthe alpha-decay spectrum was obtained. Obtained alpha-decay spectra coincides with the experimental data, presented in previous works of other authors.
A machine learning model for distinguishing Kawasaki disease from sepsis
Authors: Li Chi , Liu Yu-chen , Zhang De-ran , Han Yan-xun , Chen Bang-jie , Long Yun , Wu Cheng
Published: August 2023

KD is an acute systemic vasculitis that most commonly affects children under 5 years old. Sepsis is a systemic inflammatory response syndrome caused by infection. The main clinical manifestations of both are fever, and laboratory tests include elevated WBC count, C-reactive protein, and procalcitonin. However, the two treatments are very different. Therefore, it is necessary to establish a dynamic nomogram based on clinical data to help clinicians make timely diagnoses and decision-making. In this study, we analyzed 299 KD patients and 309 sepsis patients. We collected patients' age, sex, height, weight, BMI, and 33 biological parameters of a routine blood test. After dividing the patients into a training set and validation set, the least absolute shrinkage and selection operator method, support vector machine and receiver operating characteristic curve were used to select significant factors and construct the nomogram. The performance of the nomogram was evaluated by discrimination and calibration. The decision curve analysis was used to assess the clinical usefulness of the nomogram. This nomogram shows that height, WBC, monocyte, eosinophil, lymphocyte to monocyte count ratio (LMR), PA, GGT and platelet are independent predictors of the KD diagnostic model. The c-index of the nomogram in the training set and validation is 0.926 and 0.878, which describes good discrimination. The nomogram is well calibrated. The decision curve analysis showed that the nomogram has better clinical application value and decision-making assistance ability. The nomogram has good performance of distinguishing KD from sepsis and is helpful for clinical pediatricians to make early clinical decisions.
Direct inference and control of genetic population structure from RNA sequencing data
Authors: Fachrul Muhamad , Karkey Abhilasha , Shakya Mila , Judd Louise M. , Harshegyi Taylor , Sim Kar Seng , Tonks Susan , Dongol Sabina , Shrestha Rajendra , Salim Agus ,   STRATAA study group, Adhikari Anup , Banda Happy Chimphako , Blohmke Christoph , Darton Thomas C. , Farooq Yama , Ghimire Maheshwar , Hill Jennifer , Hoang Nhu Tran , Jere Tikhala Makhaza , Kamzati Moses , Kao Yu-Han , Masesa Clemens , Mbewe Maurice , Msuku Harrison , Munthali Patrick , Nga Tran Vu Thieu , Nkhata Rose , Saad Neil J. , Van Tan Trinh , Thindwa Deus , Khanam Farhana , Meiring James , Clemens John D. , Dougan Gordon , Pitzer Virginia E. , Qadri Firdausi , Heyderman Robert S. , Gordon Melita A. , Voysey Merryn , Baker Stephen , Pollard Andrew J. , Khor Chiea Chuen , Dolecek Christiane , Basnyat Buddha , Dunstan Sarah J. , Holt Kathryn E. , Inouye Michael
Published: August 2023

RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.
C-reactive protein kinetics as a predictive marker for long-term outcome of immune checkpoint inhibitors in oesophagogastric cancer
Authors: Nose Yohei , Saito Takuro , Kurokawa Yukinori , Takahashi Tsuyoshi , Yamamoto Kazuyoshi , Momose Kota , Yamashita Kotaro , Tanaka Koji , Makino Tomoki , Eguchi Hidetoshi , Doki Yuichiro , Wada Hisashi
Published: August 2023

Background

The treatment efficacy of immune checkpoint inhibitors (ICIs) is limited, and biomarkers that identify responders are urgently needed. We investigated whether C-reactive protein (CRP) kinetics are associated with the treatment efficacy of ICIs and prognosis in oesophagogastric cancers.

Methods

We analysed 76 gastric cancer patients treated with nivolumab monotherapy. Patients were classified as CRP-spike, CRP-flat or CRP-increase according to CRP kinetics within 6 weeks after nivolumab initiation, and the treatment response and prognosis were compared. We further validated this classification in 71 oesophageal cancer patients with nivolumab monotherapy.

Results

In the gastric cancer cohort, the CRP-spike, CRP-flat, and CRP-increase subgroups included 9, 37 and 30 patients, respectively. The CRP-spike subgroup had higher disease control rates than the CRP-increase subgroup (P = 0.0068) and had significantly better progression-free survival (PFS) (vs. CRP-flat: P = 0.045, CRP-increase: P = 0.0001). Multivariate analysis for PFS identified CRP-spike (HR = 0.38, P = 0.029) as an independent favourable prognostic factor. In the oesophageal cancer cohort, the CRP-spike, CRP-flat, and CRP-increase subgroups included 13, 27 and 31 patients, respectively, and multivariate analysis for PFS also identified CRP-spike (HR = 0.28, P = 0.0044) as an independent favourable prognostic factor.

Conclusions

CRP kinetics may be useful in predicting the long-term outcome of nivolumab treatment in oesophagogastric cancers.
The role of virtual consultations in cancer genetics: challenges and opportunities introduced by the COVID-19 pandemic
Authors: Redman Melody G. , Aguda Vernie , Dore Rhys , Lim Jen O. , Speight Beverley , McVeigh Terri P.
Published: August 2023

The COVID-19 pandemic changed the delivery of healthcare within the United Kingdom. A virtual model of care, utilising telephone and video consultations, was rapidly imposed upon cancer genetics teams. This large-scale change in service delivery has led to new opportunities that can be harnessed to improve patient care. There is a clear potential to mitigate geographical barriers, meet increasing patient expectations of implementing virtual consultations, reduce hospital carbon footprints, and decrease hospital costs while increasing efficiency. However, there are also significant challenges introduced by this model of care. Virtual healthcare consultations introduce another new level of digital exclusion for patients and clinicians. There are also potential challenges for maintaining patient confidentiality, and limited utility in circumstances where a physical exam may be warranted. For clinicians, there may be impacts on empathetic responses delivered and challenges in workflow and workload. Virtual consultations are likely to continue being a feature of cancer genetics services. A flexible approach is needed to allow for virtual and traditional models of care to work together and best meet patients’ needs. Cancer genetics services should harness the opportunities provided by virtual processes to improve patient care, whilst collaborating with patient groups and other stakeholders to carefully examine and address the challenges that virtual consultations introduce.
Chemistry of Metal–Organic Frameworks
Authors: Bazargan Maryam , Lotfian Nahid , Mirzaei Masoud
Published: August 2023

Metal–organic frameworks (MOFs), which are a class of porous crystalline materials formed by the self-assembly of organic and inorganic components, have received widespread interest over the past decades. Due to their extraordinarily high porosity, adjustable pore sizes, controllable surface functionality, and potential scalability, MOFs have great potential for application in areas such as gas capture and storage, sorbents, catalysis, and drug delivery. The judicious choice of both the organic and inorganic constituents of MOFs enables vast opportunities for framework design, leading to materials with intrinsically variable structures and properties. This chapter focuses on introducing MOFs as versatile materials and discussing how they can be synthesized by different synthesis methods and also characterized by several techniques. Finally, some important properties of MOFs, including electrochemical, optical, mechanical, thermal, and magnetic properties, are summarized.
Metal–Organic Framework Nanocomposites
Authors: Khajavian Ruhollah , Mirzaei Masoud
Published: August 2023

Considering their high porosity, well-defined channels with tunable size and shape, and flexibility in pore/surface functionalization, metal–organic frameworks (MOFs) have been used by researchers from different disciplines. In modern analytical chemistry in particular, they have been used as new stationary phases, sorbents for solid-phase extraction, etc. However, the limited processability and stability hinder their widespread application. The appropriate combination of MOFs with suitable guests is an effective way to overcome these shortcomings. In this chapter, various aspects of MOF-based composites with species such as polymers, polyoxometalates (POMs), carbonaceous materials, and ionic liquids from synthesis to applications in various analytical techniques are summarized.
Cleanup and Remediation Based on MOFs
Authors: Vergara-Barberán M. , Martínez-Pérez-Cejuela H. , Herrero-Martínez J. M.
Published: August 2023

The growing increase in industrial pollution has led to the presence of several contaminants in the environment, becoming a serious threat globally. Therefore, the development of strategies and technologies to mitigate water and air pollution is relevant in order to avoid adverse effects. The development of porous (nano)materials with high efficiency for environmental cleanup and remediation has attracted significant attention. Among them, metal–organic frameworks (MOFs), with tailorable porous architectures and tunable chemistry, have been demonstrated to be efficient adsorbents or (photo)catalytic removal agents to decontaminate pollutants from the environment. In this chapter, the application of MOF-based materials toward the removal of hazardous contaminants from water and air is addressed. Thus, updated information and references regarding MOF-based materials including their design, engineering, and formats devoted to the remediation of pollutants in aqueous and atmospheric environments are presented.
Metal–Organic Frameworks in the Sample Preparation Stage of Analysis
Authors: Amiri Amirhassan , Ghaemi Ferial , Abdar Abbas
Published: August 2023

Metal–organic frameworks (MOFs) have been regarded as one of the most effective classes of sorbents in the analytical sample preparation step. Notably, the current limitation of MOFs is related to their chemical and thermal stabilities. MOFs have been captivating as a direct result of their crystalline structures, extremely high porosities, large surface area, and various potential applications. In addition, the structure, pore design, morphology/size, and usefulness of MOFs can be additionally tuned to upgrade their effectiveness specifically in applications. In this manner, upgrading the resistance and strength of MOFs through ligand improvement or composite formation of MOFs with some materials like carbon-based nanomaterials, quantum dots, monoliths, polymers, metal/metal oxide nanoparticles, silica, and polyoxometalates can overcome these limitations significantly. In this chapter, the applications of MOFs for various extraction methods will be discussed. Meanwhile, the challenges and positive and negative points of each method will also be discussed.
Metal–Organic Frameworks in Solid Phase Extraction of Organic and Inorganic Trace Analytes from Food and Environmental Samples
Authors: Gumus Zinar Pinar , Soylak Mustafa
Published: August 2023

Separation and preconcentration of organic and inorganic analytes from food and environmental samples requires sample preparation methods based on solid and liquid phase extraction techniques. Studies in which metal–organic frameworks (MOFs) have been used as adsorbents in sample preparation steps in solid phase extraction (SPE) for trace determination of these analytes for food safety and environmental health are discussed. Due to their excellent properties such as adsorption capacity, chemical and thermal stability, and easy functionalization, MOFs have been used in various studies for the detection and removal of pesticides, drugs, and dyes (organic pollutants) and toxic metals (inorganic pollutants) from food and environmental matrices, and the separation techniques and detection methods used in these studies are explained. Thus, this chapter will shed light on the development of new materials and making different techniques more effective.
Metal–Organic Framework/Enzyme Composites
Authors: Hosseini Sayedeh Somayeh , Salimi Abdollah
Published: August 2023

This chapter provides a comprehensive and useful explanation of the unique properties of metal–organic frameworks (MOFs), as novel supporting matrices for immobilization, encapsulation, adsorption or protection of enzymes. MOFs have emerged as promising matrices for enzyme stabilization with improved catalytic performance due to their special properties such as highly adjustable porosity, high specific surface area, high pore volume and relatively high physical/chemical stability in the environment around the enzyme. Different methods for preparation of MOF/enzyme composites and various characterization techniques for structure investigations are discussed. Then, the applications of these compounds in the fabrication of biosensors based on enzymatic substrates, biosensors based on MOF/enzyme composites as catalyst systems and biosensors based on activity modulation are reviewed. Furthermore, magnetic MOF/enzyme composites, their preparation methods, their property characterization and their applications are introduced. In summary, despite the many challenges that MOFs provide as new supports for enzyme immobilization, this is a fledgling field that will have great potential for future advancement.
Variation in pnictogen–oxygen bonding unlocks greatly enhanced Brønsted basicity for the monomeric stibine oxide
Authors: Wenger John S. , Getahun Addis , Johnstone Timothy C.
Published: August 2023

We recently reported the first example of a monomeric stibine oxide. Herein, we assess the Brønsted basicity of a series of monomeric pnictine oxides (Dipp3PnO; Pn = P, As, and Sb).
Research progress on gel-based nanocomposites for diagnosis and treatment of respiratory diseases
Authors: Ye Jing , Pei Wenjing , Zhu Jing , Li Ping , Liu Hui , Gao Lei , Ma Changxiu , Gu Rongrong , Ye Sheng , Zhao Dahai
Published: August 2023

This paper summarizes the classification of respiratory diseases and gels, and focuses on the application of gels in the diagnosis and treatment of respiratory diseases.
Structure and single-molecule conductance of two endohedral metallofullerenes with large C88cage
Authors: Li Wang , Qu Fayu , Liu Linshan , Zhang Zhuxia , Zheng Chaofeng , Wang Lin , Wang Chunru , Wang Taishan
Published: August 2023

Two metallofullerenes (Ce2O@C88and Ce3N@C88) with an identical large C88-D2(35) cage, and their molecular structures and single-molecule conductance properties were investigated comparatively.
Selective binding of oxalate by a tris-ureido calix[6]tube in a protic environment
Authors: Lavendomme Roy , Moerkerke Steven , Mariaule Gaëlle , Jabin Ivan
Published: August 2023

Tubular-shaped bis-calix[6]arenes possessing a small and rigid anion binding pocket are able to distinguish oxalate from other dicarboxylates.
Organic photoredox-catalyzed oxidative azolation of unactivated fluoroarenes
Authors: Ju Guodong , Li Yalong , Zhao Yingsheng
Published: August 2023

We report a method for the nucleophilic defluorination of unactivated fluoroaromatics using 2,4,6-triphenylpyrylium tetrafluoroborate (TPT) as a photosensitizer.
Visible light-induced radical cascade acylmethylation/cyclization of 2-(allyloxy)arylaldehydes with α-bromo ketones: access to cyclic 1,5-dicarbonyl-containing chroman-4-one skeletons
Authors: Huang Xiao-Hong , Liu Feng-Lin , Fu Ting-Feng , Hu Xiao , Wang Ya-Yu , Liu Bo , Teng Ming-Yu , Huang Guo-Li
Published: August 2023

A visible light-induced, metal- and oxidant-free procedure for the acylmethyl radical-triggered cascade cyclization of 2-(allyloxy)arylaldehydes with α-bromo ketones under mild reaction conditions is reported.
Effects and mechanisms of anion and cation on the gelation of nanosilica sol by all-atom molecular dynamics simulation: promotion or inhibition?
Authors: Zhang Zhuqin , Wen Liyang , Zhang Fusheng , Dang Zhi , Zhang Lijuan
Published: August 2023

Different types of ions affect the gelation of silicic acid solution (above: ions increase the hydrogen bond formation probability (HBP), accelerate the gel process; below: ions decrease the HBP, slow down the gel process).