bluuebunny/crossref_metadata_2025 huggingface dataset:
Intelligent Risk Prognosis and Control of Foundation Pit Excavation Based on Digital Twin
Authors: Sun Zhe , Li Haoyang , Bao Yan , Meng Xiaolin , Zhang Dongliang
Published: January 2023

Timely risk information acquisition and diagnosis during foundation pit excavation (FPE) processes are vital for ensuring the safe and effective construction of underground urban infrastructures. Unfortunately, diverse geological and hydrogeological conditions and complex shapes of the foundation pit create barriers for reliable FPE risk prognosis and control. Furthermore, typical support systems during FPE use temporary measures, which have limited capacity to confront excessive loads, large deformations, and seepage. This study aims to establish an intelligent risk prognosis and control framework based on digital twin (DT) for ensuring safe and effective FPE processes. Previous studies have conducted extensive experimental and numerical analyses for examining unsafe conditions during FPE. How to enable intelligent risk prognosis and control of tedious FPE processes by integrating physics-based models and sensory data collected in the field is still challenging. DT could help to establish the interaction and feedback mechanisms between the physical and virtual space. In this study, the authors have established a DT model that consists of a physical space model and a high-fidelity physics-based model of a foundation pit in virtual space. As a result, a mechanism for effective acquisition and fusion of heterogeneous information from both physical and virtual space is established. Then, the authors proposed an integrated model and data-driven approach for examining safety risks during FPE. In the end, the authors have validated the proposed method through a case study of the FPE of the Wuhan Metro Line. The results show that the proposed method could provide theoretical and practical support for future intelligent FPE.
A Method for Predicting the Corrosion Behavior of Structural Steel under Atmosphere
Authors: Fan Yanjing , Pan Jianrong , Wu Zhixiao , Li Bin , Wang Zhan
Published: January 2023

The durability and safety of steel structures during their life cycle are affected by steel corrosion. Limited test conditions and time hinder the reproduction of actual atmospheric steel corrosion. Most test studies have focused on the effect of pitting or uniform corrosion of steel structures, leading to the development of vague engineering methods that make it difficult to design steel structures with excellent corrosion resistance. In this study, a method involving three-dimensional cellular automata and a genetic algorithm was developed for predicting the corrosion behavior of structural steel. The calculation efficiency of three-dimensional cellular automata was improved by small iterative steps and adaptive activation for potential corrosion. Furthermore, the proposed method was tested with published tests, and the results showed that the method can simulate atmospheric corrosion with excellent accuracy and efficiency. The simulation results were used to calculate the structural steel cross-sectional performance with greater accuracy than that of the method of assuming uniform corrosion. Meanwhile, with accurate material parameters, the proposed method can also simulate the atmospheric corrosion of high-performance steel of different strengths and properties.
Predicting California Bearing Ratio of Lateritic Soils Using Hybrid Machine Learning Technique
Authors: Nagaraju T. Vamsi , Bahrami Alireza , Prasad Ch. Durga , Mantena Sireesha , Biswal Monalisa , Islam Md. Rashadul
Published: January 2023

The increase in population has made it possible for better, more cost-effective vehicular services, which warrants good roadways. The sub-base that serves as a stress-transmitting media and distributes vehicle weight to resist shear and radial deformation is a critical component of the pavement structures. Developing novel techniques that can assess the sub-base soil’s geotechnical characteristics and performance is an urgent need. Laterite soil abundantly available in the West Godavari area of India was employed for this research. Roads and highways construction takes a chunk of geotechnical investigation, particularly, California bearing ratio (CBR) of subgrade soils. Therefore, there is a need for intelligent tool to predict or analyze the CBR value without time-consuming and cumbersome laboratory tests. An integrated extreme learning machine-cooperation search optimizer (ELM-CSO) approach is used herein to predict the CBR values. The correlation coefficient is utilized as cost functions of the CSO to identify the optimal activation weights of the ELM. The statistical measures are separately considered, and best solutions are reported in this article. Comparisons are provided with the standard ELM to show the superiorities of the proposed integrated approach to predict the CBR values. Further, the impact of each input variable is studied separately, and reduced models are proposed with limited and inadequate input data without loss of prediction accuracy. When 70% training and 30% testing data are applied, the ELM-CSO outperforms the CSO with Pearson correlation coefficient (R), coefficient of determination (R2), and root mean square error (RMSE) values of 0.98, 0.97, and 0.84, respectively. Therefore, based on the prediction findings, the newly built ELM-CSO can be considered an alternative method for predicting real-time engineering issues, including the lateritic soil properties.
Prognostication in Advanced Cancer by Combining Actigraphy-Derived Rest-Activity and Sleep Parameters with Routine Clinical Data: An Exploratory Machine Learning Study
Authors: Patel Shuchita Dhwiren , Davies Andrew , Laing Emma , Wu Huihai , Mendis Jeewaka , Dijk Derk-Jan
Published: January 2023

Survival prediction is integral to oncology and palliative care, yet robust prognostic models remain elusive. We assessed the feasibility of combining actigraphy, sleep diary data, and routine clinical parameters to prognosticate. Fifty adult outpatients with advanced cancer and estimated prognosis of <1 year were recruited. Patients were required to wear an Actiwatch® (wrist actigraph) for 8 days, and complete a sleep diary. Univariate and regularised multivariate regression methods were used to identify predictors from 66 variables and construct predictive models of survival. A total of 49 patients completed the study, and 34 patients died within 1 year. Forty-two patients had disrupted rest-activity rhythms (dichotomy index (I < O ≤ 97.5%) but I < O did not have prognostic value in univariate analyses. The Lasso regularised derived algorithm was optimal and able to differentiate participants with shorter/longer survival (log rank p < 0.0001). Predictors associated with increased survival time were: time of awakening sleep efficiency, subjective sleep quality, clinician’s estimate of survival and global health status score, and haemoglobin. A shorter survival time was associated with self-reported sleep disturbance, neutrophil count, serum urea, creatinine, and C-reactive protein. Applying machine learning to actigraphy and sleep data combined with routine clinical data is a promising approach for the development of prognostic tools.
E3 Ubiquitin Ligase TRIP12 Controls Exit from Mitosis via Positive Regulation of MCL-1 in Response to Taxol
Authors: Keyan Kripa S. , Alanany Rania , Kohil Amira , Khan Omar M.
Published: January 2023

Chemotherapy resistance is a major hurdle in cancer treatment. Taxol-based chemotherapy is widely used in the treatment of cancers including breast, ovarian, and pancreatic cancer. Loss of function of the tumor suppressor F-box WD-40 domain containing 7 (FBW7) mutations leads to the accumulation of its substrate MCL-1 which is associated with Taxol resistance in human cancers. We recently showed that E3 ubiquitin ligase TRIP12 is a negative regulator of FBW7 protein. In this study, we find that Taxol-induced mitotic block in cancer cells is partly controlled by TRIP12 via its positive regulation of MCL-1 protein. Genetic inhibition of TRIP12 accelerates MCL-1 protein degradation in mitosis. Notably, introducing double-point mutations in lysines 404/412 of FBW7 to arginine which makes it resistant to proteasomal degradation, leads to the sharp reduction of MCL-1 protein levels and sensitizes cancer cells to Taxol-induced cell death. Finally, TRIP12 deletion leads to enhanced mitotic arrest and cell death in an FBW7 and MCL-1 dependent manner in multiple cell lines including colorectal and ovarian cancer but not in breast cancer. Thus, the TRIP12/FBW7/MCL-1 axis may provide a therapeutic target to overcome Taxol-associated chemotherapy resistance in cancer.
Ultrasound-Guided Percutaneous Thermal Ablation of Renal Cancers—In Search for the Ideal Tumour
Authors: Jasinski Milosz , Bielinska Marta , Siekiera Jerzy , Kamecki Krzysztof , Salagierski Maciej
Published: January 2023

Over the recent years, the progress in imaging techniques has led to an increased detection of kidney tumours, including small renal masses. While surgery is still the standard of care, there is a growing interest in minimally invasive methods. Ultrasound (US)-guided percutaneous ablation is particularly attractive because it is a safe and relatively simple procedure. In this study, we investigated the success of percutaneous radiofrequency ablation (RFA) in relation to kidney tumour diameter and location. Between August 2016 and September 2021, 253 patients with 259 renal tumours underwent US-guided RFA as a primary treatment in our institution. A total of 67 patients were excluded from this study. Abdominal computed tomography (CT) and tumour biopsy were performed before the procedure. Patients were followed with contrast-enhanced CT, the average follow-up time was 28 months. The studied group was composed of 186 patients with 191 renal tumours—only biopsy-confirmed renal cancers were included. During the follow-up, 46 cases of residual disease and 4 cases of local progression were found. There was a significant correlation between tumour size and the ablation success rate. The success rate was 73.5% and 87.6% for lesions ≤25 mm, 94.6% for lesions ≤25 mm and exophytic, 79.1% for lesions 26–30 mm and 84.4% for lesions 26–30 mm and exophytic, respectively. Four Clavien-Dindo grade ≥2 complications were observed. US-guided percutaneous RFA of T1a renal cancers is safe and well-tolerated. Its effectiveness depends on tumour size, with best results for exophytic lesions smaller than 3 cm. Most of the recurrent or residual tumours can be successfully re-treated with US-guided percutaneous RFA.
Notch Signaling Suppresses Melanoma Tumor Development in BRAF/Pten Mice
Authors: Mikheil Dareen , Prabhakar Kirthana , Ng Tun Lee , Teertam Sireesh , Longley B. Jack , Newton Michael A. , Setaluri Vijayasaradhi
Published: January 2023

Both oncogenic and tumor suppressor roles have been assigned to Notch signaling in melanoma. In clinical trials, Notch inhibitors proved to be ineffective for melanoma treatment. Notch signaling has also been implicated in melanoma transdifferentiation, a prognostic feature in primary melanoma. In this study, we investigated the role of Notch signaling in melanoma tumor development and growth using the genetic model of mouse melanoma by crossing BRAFCA/+/Pten+/+/Tyr-CreER+ (B) and BRAFCA/+/Pten-/-/Tyr-CreER + (BP) mice with Notch1 or Notch2 floxed allele mice. The topical application of tamoxifen induced tumors in BP mice but not in B mice with or without the deletion of either Notch1 or Notch2. These data show that the loss of either Notch1 nor Notch2 can substitute the tumor suppressor function of Pten in BRAFV600E-induced melanomagenesis. However, in Pten-null background, the loss of either Notch1 or Notch2 appeared to accelerate BRAFV600E-induced tumor development, suggesting a tumor suppressor role for Notch1 and Notch2 in BRAFV600E/Pten-null driven melanomagenesis. Quantitative immunochemical analysis of a human cutaneous melanoma tissue microarray that consists of >100 primary tumors with complete clinical history showed a weak to moderate correlation between NOTCH protein levels and clinical and pathological parameters. Our data show that Notch signaling is involved during melanomagenesis and suggest that the identification of genes and signaling pathways downstream of Notch could help devise strategies for melanoma prevention.
Real World Data for Pancreatic Adenocarcinoma from a Population-Based Study in France
Authors: Badic Bogdan , Morvan Marie , Quénéhervé Lucille , Bouzeloc Servane , Kermarrec Tiphaine , Nousbaum Jean-Baptiste , Reboux Noémi
Published: January 2023

Pancreatic cancer is associated with high mortality rates, and most cases are diagnosed at advanced stages. This study aimed to evaluate the prognostic factors for survival in pancreatic adenocarcinoma. Data from the Finistere registry of digestive database were used in this analysis. This retrospective population-based study included 2117 patients with pancreatic adenocarcinoma diagnosed between 2005 and 2019. Cox regression was used to assess the impact of different prognostic factors. The overall median age was 74 (IQR 65.0–81.0). The majority of pancreatic adenocarcinoma 1120 (52.90%) occurred in the head of the pancreas. The type of surgical resection correlated with age (pancreaticoduodenectomy performed in 13.39% of patients aged under 65 years and only 1.49% of patients aged ≥ 80 years). For the entire cohort, 1-year mortality rate after diagnosis was 77.81%. Chemotherapy was associated with better survival for both operated (HR 0.17 95% CI 0.22; 0.64 p < 0.001) and unoperated patients (HR 0.41 95% CI 0.27; 0.61 p < 0.001). Palliative radiotherapy was associated with improved survival (HR 0.69 95% CI 0.56; 0.85 p < 0.001). Among operated patients, the presence of lung metastases (median 34.06; CI 20.06; 34.66) was associated with better survival compared with liver metastases (median 21.10; CI 18.10; 28.96), peritoneal carcinomatosis (median 11.00; CI 8.53; 14.63), or distant metastases (median 15.16; CI 12.66; 18.13) (p = 0.0001). Age, curative surgery, positive lymph nodes, chemotherapy, and palliative radiotherapy were corelated with overall survival. Surgical resection is the only potentially curative treatment, but less than a quarter of patients were eligible.
E3 Ubiquitin Ligase NEDD4 Affects Estrogen Receptor α Expression and the Prognosis of Patients with Hormone Receptor-Positive Breast Cancer
Authors: Natori Yutaka , Suga Junko , Tokuda Emi , Tachibana Kazunoshin , Imai Jun-ichi , Honma Reiko , Azami Yusuke , Noda Masaru , Sasaki Eisaku , Watanabe Shinya , Ohtake Tohru , Saji Shigehira
Published: January 2023

Neural precursor cell-expressed developmentally downregulated 4–1 (NEDD4) is an E3 ligase that leads to the degradation of proteins, including estrogen receptor α. We evaluated whether the expression level of NEDD4 affected the outcome of breast cancer patients. We performed a retrospective cohort study enrolling 143 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Of the 66 patients with high NEDD4 mRNA levels (high NEDD4 group) and 77 patients with low NEDD4 mRNA levels (low NEDD4 group), 98.4% and 96.1%, respectively, of the patients had received neoadjuvant/adjuvant hormone therapy. Disease-free survival and overall survival were significantly longer in the low NEDD4 group than in the high NEDD4 group (p = 0.048 and p = 0.022, respectively). Western blotting revealed a high expression of estrogen receptor α in the NEDD4-knockdown culture cells. The proliferation of NEDD4-knockdown cells treated with tamoxifen or estradiol deprivation was suppressed, compared with that of NEDD4-expressing cells. Knockdown of NEDD4 in breast cancer cells induced the accumulation of estrogen receptor α and increased sensitivity to hormone therapy. In summary, this mechanism may lead to a better prognosis in hormone receptor-positive breast cancer patients with a low expression of NEDD4.
The Prime and Integral Cause of Cancer in the Post-Warburg Era
Authors: Harguindey Salvador , Reshkin Stephan J. , Alfarouk Khalid O.
Published: January 2023

Back to beginnings. A century ago, Otto Warburg published that aerobic glycolysis and the respiratory impairment of cells were the prime cause of cancer, a phenomenon that since then has been known as “the Warburg effect”. In his early studies, Warburg looked at the effects of hydrogen ions (H+), on glycolysis in anaerobic conditions, as well as of bicarbonate and glucose. He found that gassing with CO2 led to the acidification of the solutions, resulting in decreased rates of glycolysis. It appears that Warburg first interpreted the role of pH on glycolysis as a secondary phenomenon, a side effect that was there just to compensate for the effect of bicarbonate. However, later on, while talking about glycolysis in a seminar at the Rockefeller Foundation, he said: “Special attention should be drawn to the remarkable influence of the bicarbonate…”. Departing from the very beginnings of this metabolic cancer research in the 1920s, our perspective advances an analytic as well as the synthetic approach to the new “pH-related paradigm of cancer”, while at the same time addressing the most fundamental and recent changing concepts in cancer metabolic etiology and its potential therapeutic implications.
Revealing Prognostic and Immunotherapy-Sensitive Characteristics of a Novel Cuproptosis-Related LncRNA Model in Hepatocellular Carcinoma Patients by Genomic Analysis
Authors: Mao Zhenzhen , Nie Ye , Jia Weili , Wang Yanfang , Li Jianhui , Zhang Tianchen , Lei Xinjun , Shi Wen , Song Wenjie , Zhang Xiao
Published: January 2023

Immunotherapy has shown strong anti-tumor activity in a subset of patients. However, many patients do not benefit from the treatment, and there is no effective method to identify sensitive immunotherapy patients. Cuproptosis as a non-apoptotic programmed cell death caused by excess copper, whether it is related to tumor immunity has attracted our attention. In the study, we constructed the prognostic model of 9 cuproptosis-related LncRNAs (crLncRNAs) and assessed its predictive capability, preliminarily explored the potential mechanism causing treatment sensitivity difference between the high-/low-risk group. Our results revealed that the risk score was more effective than traditional clinical features in predicting the survival of HCC patients (AUC = 0.828). The low-risk group had more infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells), mainly with anti-tumor immune function (p < 0.05). It showed higher sensitivity to immune checkpoint inhibitors (ICIs) treatment (p < 0.001) which may exert the effect through the AL365361.1/hsa-miR-17-5p/NLRP3 axis. In addition, NLRP3 mutation-sensitive drugs (VNLG/124, sunitinib, linifanib) may have better clinical benefits in the high-risk group. All in all, the crLncRNAs model has excellent specificity and sensitivity, which can be used for classifying the therapy-sensitive population and predicting the prognosis of HCC patients.
Ni-Pd-Incorporated Fe3O4 Yolk-Shelled Nanospheres as Efficient Magnetically Recyclable Catalysts for Reduction of N-Containing Unsaturated Compounds
Authors: Wang Dong , Li Yi , Wen Liangsong , Xi Jiangbo , Liu Pei , Hansen Thomas Willum , Li Ping
Published: January 2023

The use of metal-based heterogeneous catalysts for the degradation of N-containing organic dyes has attracted much attention due to their excellent treatment efficiency and capability. Here, we report the synthesis of heterometals (Ni and Pd)-incorporated Fe3O4 (Ni-Pd/Fe3O4) yolk-shelled nanospheres for the catalytic reduction of N-containing organic dyes using a facile combination of solvothermal treatment and high-temperature annealing steps. Benefiting from the magnetic properties and the yolk-shelled structure of the Fe3O4 support, as well as the uniformly dispersed active heterometals incorporated in the shell and yolk of spherical Fe3O4 nanoparticles, the as-prepared Ni-Pd/Fe3O4 composite shows excellent recyclability and enhanced catalytic activity for three N-containing organic dyes (e.g., 4-nitrophenol, Congo red, and methyl orange) compared with its mono metal counterparts (e.g., Ni/Fe3O4 and Pd/Fe3O4). In the 4-nitrophenol reduction reaction, the catalytic activity of Ni-Pd/Fe3O4 was superior to many Fe3O4-supported nanocatalysts reported within the last five years. This work provides an effective strategy to boost the activity of iron oxide-based catalytic materials via dual or even multiple heterometallic incorporation strategy and sheds new light on environmental catalysis.
Alkaline Media Regulated NiFe-LDH-Based Nickel–Iron Phosphides toward Robust Overall Water Splitting
Authors: Xu Xiaohu , Yu Xinyue , Guo Kaiwei , Dong Lijuan , Miao Xiangyang
Published: January 2023

The search for low-cost, high-performance, and robust stability bifunctional electrocatalysts to substitute noble metals-based counterparts for overall water splitting to generate clean and sustainable hydrogen energy is of great significance and challenges. Herein, a high-efficient bi-functional nickel–iron phosphide on NiFe alloy foam (denoted as e-NFP/NFF) with 3D coral-like nanostructure was controllably constructed by means of alkali etching and the introduction of non-metallic atoms P. The unique superhydrophilic coral-like structure can not only effectively facilitate the exposure of catalytic active sites and increase the electroactive surface area, but also accelerate charge transport and bubble release. Furthermore, owing to the synergistic effect between the bicomponent of nickel–iron phosphides as well as the strong electronic interactions of the multiple metal sites, the as-fabricated catalyst behaves with excellent bifunctional performance for the hydrogen evolution reaction (overpotentials of 132 and 286 mV at 10 and 300 mA·cm−2, respectively) and oxygen evolution reaction (overpotentials of 181 and 303 mV at 10 and 300 mA·cm−2, respectively) in alkaline electrolytes. Impressively, cells with integrated e-NFP/NFF electrodes as a cathode and anode require only a low cell voltage (1.58 V) to drive a current density of 10 mA·cm−2 for overall water splitting, along with remarkable stability in long-term electrochemical durability tests. This study provides a tunable synthetic strategy for the development of efficient and durable non-noble metal bifunctional catalysts based on the construction of an elaborate structure framework and rational design of the electronic structure.
Fabrication and Photocatalytic Activity of Single Crystalline TiO2 Hierarchically Structured Microspheres
Authors: Huang Haisheng , Kong Qi , Yue Xin , Wang Kunlei , Wei Zhishun , Chang Ying
Published: January 2023

Single crystalline anatase TiO2 microspheres with co-exposed {001}/{101} facets were prepared by a facile one-pot hydrothermal method using NaF as a morphology controlling agent. The influences of the NaF amount on the morphology and also on the photocatalytic activity were investigated systematically. The obtained microspheres possessed better morphology when the concentration of NaF was chosen at 0.1 mol/L, and the experimental results indicated that the crystal structure and morphology played important roles on the photocatalytic activity, based on the experimental results it was found that the photocatalytic degradation efficiency of TiO2 microspheres on Tetracycline hydrochloride could reach 76.4% in 2 h. Finally, a growth mechanism was proposed by investigating the growth process, i.e., a synergistic effect of F ions modified Ostwald ripening and oriented attachment.
IRF8 Regulates Intrinsic Ferroptosis through Repressing p53 Expression to Maintain Tumor Cell Sensitivity to Cytotoxic T Lymphocytes
Authors: Poschel Dakota B. , Kehinde-Ige Mercy , Klement John D. , Yang Dafeng , Merting Alyssa D. , Savage Natasha M. , Shi Huidong , Liu Kebin
Published: January 2023

Ferroptosis has emerged as a cytotoxic T lymphocyte (CTL)-induced tumor cell death pathway. The regulation of tumor cell sensitivity to ferroptosis is incompletely understood. Here, we report that interferon regulatory factor 8 (IRF8) functions as a regulator of tumor cell intrinsic ferroptosis. Genome-wide gene expression profiling identified the ferroptosis pathway as an IRF8-regulated pathway in tumor cells. IRF8.KO tumor cells acquire resistance to intrinsic ferroptosis induction and IRF8-deficient tumor cells also exhibit decreased ferroptosis in response to tumor-specific CTLs. Irf8 deletion increased p53 expression in tumor cells and knocking out p53 in IRF8.KO tumor cells restored tumor cell sensitivity to intrinsic ferroptosis induction. Furthermore, IRF8.KO tumor cells grew significantly faster than WT tumor cells in immune-competent mice. To restore IRF8 expression in tumor cells, we designed and synthesized codon usage-optimized IRF8-encoding DNA to generate IRF8-encoding plasmid NTC9385R-mIRF8. Restoring IRF8 expression via a lipid nanoparticle-encapsulated NTC9385R-mIRF8 plasmid therapy suppressed established tumor growth in vivo. In human cancer patients, nivolumab responders have a significantly higher IRF8 expression level in their tumor cells as compared to the non-responders. Our data determine that IRF8 represses p53 expression to maintain tumor cell sensitivity to intrinsic ferroptosis.
Implications of Crosstalk between Exosome-Mediated Ferroptosis and Diseases for Pathogenesis and Treatment
Authors: Zhou Zixuan , You Benshuai , Ji Cheng , Zhang Leilei , Wu Feng , Qian Hui
Published: January 2023

Ferroptosis is a type of iron-dependent cell death caused by ferrous iron overload, reactive oxygen species generation through the Fenton reaction, and lipid peroxidation, leading to antioxidative system dysfunction and, ultimately, cell membrane damage. The functional role of ferroptosis in human physiology and pathology is considered a cause or consequence of diseases. Circulating exosomes mediate intercellular communication and organ crosstalk. They not only transport functional proteins and nucleic acids derived from parental cells but also serve as vehicles for the targeted delivery of exogenous cargo. Exosomes regulate ferroptosis by delivering the biological material to the recipient cell, affecting ferroptosis-related proteins, or transporting ferritin-bound iron out of the cell. This review discusses pathogenesis mediated by endogenous exosomes and the therapeutic potential of exogenous exosomes for ferroptosis-related diseases. In addition, this review explores the role of exosome-mediated ferroptosis in ferroptosis-related diseases with an emphasis on strategies for engineering exosomes for ferroptosis therapy.
PDE6D Mediates Trafficking of Prenylated Proteins NIM1K and UBL3 to Primary Cilia
Authors: Faber Siebren , Letteboer Stef J. F. , Junger Katrin , Butcher Rossano , Tammana Trinadh V. Satish , van Beersum Sylvia E. C. , Ueffing Marius , Collin Rob W. J. , Liu Qin , Boldt Karsten , Roepman Ronald
Published: January 2023

Mutations in PDE6D impair the function of its cognate protein, phosphodiesterase 6D (PDE6D), in prenylated protein trafficking towards the ciliary membrane, causing the human ciliopathy Joubert Syndrome (JBTS22) and retinal degeneration in mice. In this study, we purified the prenylated cargo of PDE6D by affinity proteomics to gain insight into PDE6D-associated disease mechanisms. By this approach, we have identified a specific set of PDE6D-interacting proteins that are involved in photoreceptor integrity, GTPase activity, nuclear import, or ubiquitination. Among these interacting proteins, we identified novel ciliary cargo proteins of PDE6D, including FAM219A, serine/threonine-protein kinase NIM1 (NIM1K), and ubiquitin-like protein 3 (UBL3). We show that NIM1K and UBL3 localize inside the cilium in a prenylation-dependent manner. Furthermore, UBL3 also localizes in vesicle-like structures around the base of the cilium. Through affinity proteomics of UBL3, we confirmed its strong interaction with PDE6D and its association with proteins that regulate small extracellular vesicles (sEVs) and ciliogenesis. Moreover, we show that UBL3 localizes in specific photoreceptor cilium compartments in a prenylation-dependent manner. Therefore, we propose that UBL3 may play a role in the sorting of proteins towards the photoreceptor outer segment, further explaining the development of PDE6D-associated retinal degeneration.
A Structural View at Vaccine Development against M. tuberculosis
Authors: Romano Maria , Squeglia Flavia , Kramarska Eliza , Barra Giovanni , Choi Han-Gyu , Kim Hwa-Jung , Ruggiero Alessia , Berisio Rita
Published: January 2023

Tuberculosis (TB) is still the leading global cause of death from an infectious bacterial agent. Limiting tuberculosis epidemic spread is therefore an urgent global public health priority. As stated by the WHO, to stop the spread of the disease we need a new vaccine, with better coverage than the current Mycobacterium bovis BCG vaccine. This vaccine was first used in 1921 and, since then, there are still no new licensed tuberculosis vaccines. However, there is extremely active research in the field, with a steep acceleration in the past decades, due to the advance of technologies and more rational vaccine design strategies. This review aims to gather latest updates in vaccine development in the various clinical phases and to underline the contribution of Structural Vaccinology (SV) to the development of safer and effective antigens. In particular, SV and the development of vaccine adjuvants is making the use of subunit vaccines, which are the safest albeit the less antigenic ones, an achievable goal. Indeed, subunit vaccines overcome safety concerns but need to be rationally re-engineered to enhance their immunostimulating effects. The larger availability of antigen structural information as well as a better understanding of the complex host immune response to TB infection is a strong premise for a further acceleration of TB vaccine development.
Long-Term Memory Formation in Drosophila Depends on the 3′UTR of CPEB Gene orb2
Authors: Kozlov Eugene N. , Tokmatcheva Elena V. , Khrustaleva Anastasia M. , Grebenshchikov Eugene S. , Deev Roman V. , Gilmutdinov Rudolf A. , Lebedeva Lyubov A. , Zhukova Mariya , Savvateeva-Popova Elena V. , Schedl Paul , Shidlovskii Yulii V.
Published: January 2023

Activation of local translation in neurites in response to stimulation is an important step in the formation of long-term memory (LTM). CPEB proteins are a family of translation factors involved in LTM formation. The Drosophila CPEB protein Orb2 plays an important role in the development and function of the nervous system. Mutations of the coding region of the orb2 gene have previously been shown to impair LTM formation. We found that a deletion of the 3’UTR of the orb2 gene similarly results in loss of LTM in Drosophila. As a result of the deletion, the content of the Orb2 protein remained the same in the neuron soma, but significantly decreased in synapses. Using RNA immunoprecipitation followed by high-throughput sequencing, we detected more than 6000 potential Orb2 mRNA targets expressed in the Drosophila brain. Importantly, deletion of the 3′UTR of orb2 mRNA also affected the localization of the Csp, Pyd, and Eya proteins, which are encoded by putative mRNA targets of Orb2. Therefore, the 3′UTR of the orb2 mRNA is important for the proper localization of Orb2 and other proteins in synapses of neurons and the brain as a whole, providing a molecular basis for LTM formation.
Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea
Authors: Patnam Mehul , Dommaraju Sunil R. , Masood Faisal , Herbst Paula , Chang Jin-Hong , Hu Wen-Yang , Rosenblatt Mark I. , Azar Dimitri T.
Published: January 2023

Corneal lymphangiogenesis is one component of the neovascularization observed in several inflammatory pathologies of the cornea including dry eye disease and corneal graft rejection. Following injury, corneal (lymph)angiogenic privilege is impaired, allowing ingrowth of blood and lymphatic vessels into the previously avascular cornea. While the mechanisms underlying pathological corneal hemangiogenesis have been well described, knowledge of the lymphangiogenesis guidance mechanisms in the cornea is relatively scarce. Various signaling pathways are involved in lymphangiogenesis guidance in general, each influencing one or multiple stages of lymphatic vessel development. Most endogenous factors that guide corneal lymphatic vessel growth or regression act via the vascular endothelial growth factor C signaling pathway, a central regulator of lymphangiogenesis. Several exogenous factors have recently been repurposed and shown to regulate corneal lymphangiogenesis, uncovering unique signaling pathways not previously known to influence lymphatic vessel guidance. A strong understanding of the relevant lymphangiogenesis guidance mechanisms can facilitate the development of targeted anti-lymphangiogenic therapeutics for corneal pathologies. In this review, we examine the current knowledge of lymphatic guidance cues, their regulation of inflammatory states in the cornea, and recently discovered anti-lymphangiogenic therapeutic modalities.
Molecular Modeling Insights into the Structure and Behavior of Integrins: A Review
Authors: Tvaroška Igor , Kozmon Stanislav , Kóňa Juraj
Published: January 2023

Integrins are heterodimeric glycoproteins crucial to the physiology and pathology of many biological functions. As adhesion molecules, they mediate immune cell trafficking, migration, and immunological synapse formation during inflammation and cancer. The recognition of the vital roles of integrins in various diseases revealed their therapeutic potential. Despite the great effort in the last thirty years, up to now, only seven integrin-based drugs have entered the market. Recent progress in deciphering integrin functions, signaling, and interactions with ligands, along with advancement in rational drug design strategies, provide an opportunity to exploit their therapeutic potential and discover novel agents. This review will discuss the molecular modeling methods used in determining integrins’ dynamic properties and in providing information toward understanding their properties and function at the atomic level. Then, we will survey the relevant contributions and the current understanding of integrin structure, activation, the binding of essential ligands, and the role of molecular modeling methods in the rational design of antagonists. We will emphasize the role played by molecular modeling methods in progress in these areas and the designing of integrin antagonists.
Sex-Specific Whole-Transcriptome Analysis in the Cerebral Cortex of FAE Offspring
Authors: Mishra Nitish K. , Shrinath Pulastya , Rao Radhakrishna , Shukla Pradeep K.
Published: January 2023

Fetal alcohol spectrum disorders (FASDs) are associated with systemic inflammation and neurodevelopmental abnormalities. Several candidate genes were found to be associated with fetal alcohol exposure (FAE)-associated behaviors, but a sex-specific complete transcriptomic analysis was not performed at the adult stage. Recent studies have shown that they are regulated at the developmental stage. However, the sex-specific role of RNA in FAE offspring brain development and function has not been studied yet. Here, we carried out the first systematic RNA profiling by utilizing a high-throughput transcriptomic (RNA-seq) approach in response to FAE in the brain cortex of male and female offspring at adulthood (P60). Our RNA-seq data analysis suggests that the changes in RNA expression in response to FAE are marked sex-specific. We show that the genes Muc3a, Pttg1, Rec8, Clcnka, Capn11, and pnp2 exhibit significantly higher expression in the male offspring than in the female offspring at P60. FAE female mouse brain sequencing data also show an increased expression of Eno1, Tpm3, and Pcdhb2 compared to male offspring. We performed a pathway analysis using a commercial software package (Ingenuity Pathway Analysis). We found that the sex-specific top regulator genes (Rictor, Gaba, Fmri, Mlxipl) are highly associated with eIF2 (translation initiation), synaptogenesis (the formation of synapses between neurons in the nervous system), sirtuin (metabolic regulation), and estrogen receptor (involved in obesity, aging, and cancer) signaling. Taken together, our transcriptomic results demonstrate that FAE differentially alters RNA expression in the adult brain in a sex-specific manner.
Erk1/2-Dependent HNSCC Cell Susceptibility to Erastin-Induced Ferroptosis
Authors: Savic Dragana , Steinbichler Teresa Bernadette , Ingruber Julia , Negro Giulia , Aschenbrenner Bertram , Riechelmann Herbert , Ganswindt Ute , Skvortsov Sergej , Dudás József , Skvortsova Ira-Ida
Published: January 2023

Unfavorable clinical outcomes mean that cancer researchers must attempt to develop novel therapeutic strategies to overcome therapeutic resistance in patients with HNSCC. Recently, ferroptosis was shown to be a promising pathway possessing druggable targets, such as xCT (SLC7A11). Unfortunately, little is known about the molecular mechanisms underlying the susceptibility of HNSCC cells to ferroptosis. The goal of this study was to determine whether HNSCC cells with activated Erk1/2 are vulnerable to ferroptosis induction. Our results have shown that xCT (SLC7A11) was overexpressed in malignant tissues obtained from the patients with HNSCC, whereas normal mucosa demonstrated weak expression of the protein. In order to investigate the role of Erk1/2 in the decrease in cell viability caused by erastin, xCT-overexpressing FaDu and SCC25 HNSCC cells were used. The ravoxertinib-dependent inhibition of Erk1/2 signaling led to the decrease in erastin efficacy due to the effect on ROS production and the upregulation of ROS scavengers SOD1 and SOD2, resulting in repressed lipid peroxidation. Therefore, it was concluded that the erastin-dependent activation of ferroptosis seems to be a promising approach which can be further developed as an additional strategy for the treatment of HNSCC. As ferroptosis induction via erastin is strongly dependent on the expression of Erk1/2, this MAP kinase can be considered as a predictor for cancer cells’ response to erastin.
Abnormal Cellular Phenotypes Induced by Three TMPO/LAP2 Variants Identified in Men with Cardiomyopathies
Authors: Vadrot Nathalie , Ader Flavie , Moulin Maryline , Merlant Marie , Chapon Françoise , Gandjbakhch Estelle , Labombarda Fabien , Maragnes Pascale , Réant Patricia , Rooryck Caroline , Probst Vincent , Donal Erwan , Richard Pascale , Ferreiro Ana , Buendia Brigitte
Published: January 2023

A single missense variant of the TMPO/LAP2α gene, encoding LAP2 proteins, has been associated with cardiomyopathy in two brothers. To further evaluate its role in cardiac muscle, we included TMPO in our cardiomyopathy diagnostic gene panel. A screening of ~5000 patients revealed three novel rare TMPO heterozygous variants in six males diagnosed with hypertrophic or dilated cardiomypathy. We identified in different cellular models that (1) the frameshift variant LAP2α p.(Gly395Glufs*11) induced haploinsufficiency, impeding cell proliferation and/or producing a truncated protein mislocalized in the cytoplasm; (2) the C-ter missense variant LAP2α p.(Ala240Thr) led to a reduced proximity events between LAP2α and the nucleosome binding protein HMGN5; and (3) the LEM-domain missense variant p.(Leu124Phe) decreased both associations of LAP2α/β with the chromatin-associated protein BAF and inhibition of the E2F1 transcription factor activity which is known to be dependent on Rb, partner of LAP2α. Additionally, the LAP2α expression was lower in the left ventricles of male mice compared to females. In conclusion, our study reveals distinct altered properties of LAP2 induced by these TMPO/LAP2 variants, leading to altered cell proliferation, chromatin structure or gene expression-regulation pathways, and suggests a potential sex-dependent role of LAP2 in myocardial function and disease.
Experimentally Created Magnetic Force in Microbiological Space and On-Earth Studies: Perspectives and Restrictions
Authors: Ermolaeva Svetlana A. , Parfenov Vladislav A. , Karalkin Pavel A. , Khesuani Yusef D. , Domnin Pavel A.
Published: January 2023

Magnetic force and gravity are two fundamental forces affecting all living organisms, including bacteria. On Earth, experimentally created magnetic force can be used to counterbalance gravity and place living organisms in conditions of magnetic levitation. Under conditions of microgravity, magnetic force becomes the only force that moves bacteria, providing an acceleration towards areas of the lowest magnetic field and locking cells in this area. In this review, we consider basic principles and experimental systems used to create a magnetic force strong enough to balance gravity. Further, we describe how magnetic levitation is applied in on-Earth microbiological studies. Next, we consider bacterial behavior under combined conditions of microgravity and magnetic force onboard a spacecraft. At last, we discuss restrictions on applications of magnetic force in microbiological studies and the impact of these restrictions on biotechnological applications under space and on-Earth conditions.
Indium Oxide Powder Synthesis in a Low-Current Discharge Plasma at Atmospheric Pressure
Authors: Savkin Konstantin , Sorokin Dmitry , Beloplotov Dmitry , Ostapenko Marina , Semin Viktor , Oks Efim
Published: January 2023

The results of a study of the processes involved in the production of indium oxide In2O3 powder, which is widely used to create transparent and electrically conducting ceramics, are described. The powder was produced in a flow of rare gas (argon or helium) at atmospheric pressure under conditions for the formation of metal-containing plasma in a non-arc discharge mode. The discharge operated in pulsed mode with a pulse repetition rate of 70 kHz and pulse duration of 12 μs. The discharge current was 670 mA and discharge voltages were 180 V and 250 V when the working gases were argon and helium, respectively. These parameters ensure a mode in which the indium cap of a molybdenum cathode suffers thermal erosion. The morphology and elemental and phase composition of the erosion products were studied using transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) analysis. It was shown that the structure of the synthesized powder particles corresponded to a phase of indium oxide (III) with a body-centered cubic (bcc) lattice with lattice parameter a = 1.013 nm. The powder particles, regardless of the working gas (Ar or He), consisted of non-stoichiometric indium oxide In2O3 with a nanocrystalline structure. The average particle diameter was  = 13–16 nm.
Acknowledgment to the Reviewers of Chemistry in 2022
Authors:   Chemistry Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Synthesis of Graphene-Oxide-Decorated Porous ZnO Nanosheet Composites and Their Gas Sensing Properties
Authors: Li Jie , Jin Zhen , Chao Yang , Wang Aijing , Wang Decai , Chen Shaohua , Qian Quan
Published: January 2023

In this work, graphene-oxide-decorated porous ZnO nanosheets were prepared using a hydrothermal method. The graphene oxide/porous ZnO nanosheet (GO/ZnO nanosheet) composites were characterized with SEM, HRTEM, XRD, Raman spectroscopy, XPS and BET. The results indicate that the ZnO nanosheets have a porous, single-crystal structure. Thin GO nanosheets closely cover the surface of porous ZnO nanosheets. The sensing performance of GO/ZnO nanosheet composites is investigated. At the optimized temperature of 300 °C, the GO/ZnO nanosheet composites exhibit a superior sensing performance in n-propanol detection. In a wide range of 5–200 ppm, the composites exhibit a linear response to n-propanol. Moreover, the sensing performance of the GO/ZnO nanosheet composites to n-propanol is largely higher than that to other VOC gases, indicating a high selectivity in n-propanol detection. This can be ascribed to the higher electron-separation efficiency and larger depletion layer brought by the modification of the GO on ZnO nanosheets. It is considered that the GO/ZnO nanosheet composites have a great application potential in n-propanol detection.
Fast Protein and Metabolites (Nucleotides and Nucleosides) Liquid Chromatography Technique and Chemical Sensor for the Assessment of Fish and Meat Freshness
Authors: Kuznetsov Artur , Frorip Aleksandr , Sünter Alar , Kasvand Nensi , Korsakov Vadim , Konoplev Georgii , Stepanova Oksana , Rusalepp Linda , Anton Dea , Püssa Tõnu , Roasto Mati , Abramova Liubov , Kozin Andrey , Toom Lauri , Hirsch Soeren , Mukhin Nikolay
Published: January 2023

Fast protein and metabolite liquid chromatography (FPLMC) was introduced years ago to enable the easy separation of high-molecular compounds such as proteins from small molecules and the identification of the low-molecular substances. In this paper, the method is applied for the rapid evaluation of freshness and monitoring the aging of animal meat and fish. A novel chromatographic sensor was developed with a deep UV LED-based photometric detection unit (255–265 nm), an original flow cuvette and registration scheme; the processing of a chromatogram with the sensor takes approximately 15 min. Strict isochronism between the elution of ATP metabolites, mainly hypoxanthine (Hx) and inosine monophosphate (IMP), and the time of maturation of meat or fish, was discovered. A new freshness index H* = [Hx]/[IMP] was introduced, which is proportional to the instrumental delay time in the FPMLC chromatograms: the H* index < 0.5 indicates the presence of inosine monophosphate (IMP) and the high quality of the meat or fish. Reasonably strong correlations were revealed between data obtained by FPMLC and total volatile basic nitrogen TVB-N (for fish) or volatile fatty acids VFA (for meat) content. Moreover, putative nucleotide salvage and an increase in the concentration of IMP were observed in fish after heat treatment using the FPMLC sensor and NMR technique.
Acknowledgment to the Reviewers of Chemosensors in 2022
Authors:   Chemosensors Editorial Office
Published: January 2023

High-quality academic publishing is built on rigorous peer review [...]
Change in Prevalence of Hypertension among Korean Children and Adolescents during the Coronavirus Disease 2019 (COVID-19) Outbreak: A Population-Based Study
Authors: Song Kyungchul , Jung Se Yong , Yang Juyeon , Lee Hye Sun , Kim Ho-Seong , Chae Hyun Wook
Published: January 2023

During the coronavirus disease 2019 (COVID-19) outbreak, the prevalence of obesity increased globally; this may be associated with hypertension incidence. However, investigations on the changes in the prevalence of hypertension among children and adolescents are limited. This cross-sectional study investigated the prevalence of hypertension among 1428 youths aged 10–18 years using data from the Korea National Health and Nutrition Examination Survey 2018–2020. We assessed the prevalence of hypertension according to sex, age, body mass index (BMI), and residential district. The prevalence of hypertension increased from 7.1% to 12.5% in all participants. In the sex-specific analysis, the prevalence was found to be increased in boys. In the age-specific analysis, the prevalence was found to be increased in youths aged 13–15 years. In the BMI-specific analysis, an increase in the prevalence was prominent in the normal BMI group. In the residential district-specific analysis, the prevalence of hypertension among youth increased in urban areas. Our results show that the prevalence of hypertension increased among Korean children and adolescents during the COVID-19 outbreak. These findings suggest the importance of close monitoring of hypertension among youth during the COVID-19 pandemic.