bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Priority Conditions and Access to Care, Treatment of an Ongoing Condition, and Ability to Obtain Prescription Medications among Medicare Beneficiaries during the COVID-19 Pandemic
Authors: Dickson Matthew C. , Skrepnek Grant H.
Published: December 2023

Several comorbid conditions have been observed to be associated with an increased risk of poor outcomes following a diagnosis of COVID-19. The purpose of this investigation was to assess associations between Centers for Medicare and Medicaid Services (CMS) designated priority conditions and an inability to access care, treat ongoing conditions, and obtain prescription medications among Medicare beneficiaries in the United States during the COVID-19 pandemic. Nationally representative CMS Medicare Current Beneficiary Survey (MCBS) COVID-19 Supplement Public Use Files (PUF) were analyzed via bivariable, binomial generalized linear models across three time periods: (1) Summer 2020; (2) Fall 2020; and (3) Winter 2021. Across an estimated 55.3–57.4 million Medicare beneficiaries, approximately one-fifth reported an inability to access at least one type of care at the onset of the pandemic. Significantly worse odds of an ability to get care across various time periods was observed among several priority conditions including immune disorders, cancer, depression, osteoporosis, diabetes, arthritis, and numerous cardiovascular and pulmonary conditions. Among those reporting an inability to access care, approximately one-third involved treatment of an ongoing condition, and under one-tenth involved prescription medications. To identify modifiable risk factors and to develop active interventions, future work should continue to assess the complex associations between outcomes, access to care, comorbidities, evolving healthcare infrastructures, computerization, and various public health initiatives.
Management of Uveal Melanoma: Updated Cancer Care Alberta Clinical Practice Guideline
Authors: Weis Ezekiel , Surgeoner Brae , Salopek Thomas G. , Cheng Tina , Hyrcza Martin , Kostaras Xanthoula , Larocque Matthew , McKinnon Greg , McWhae John , Menon Geetha , Monzon Jose , Murtha Albert D. , Walker John , Temple-Oberle Claire
Published: December 2023

Objective: The purpose of this guideline update is to reassess and update recommendations in the prior guideline from 2016 on the appropriate management of patients with uveal melanoma. Methods: In 2021, a multidisciplinary working group from the Provincial Cutaneous Tumour Team, Cancer Care Alberta, Alberta Health Services was convened to update the guideline. A comprehensive review of new research evidence in PubMed as well as new clinical practice guidelines from prominent oncology groups informed the update. An enhancement in methodology included adding levels of evidence and strength of recommendations. The updated guideline was circulated to all members of the Provincial Cutaneous Tumour Team for review and endorsement. Results: New and modified recommendations address provider training requirements, diagnostic imaging for the detection of metastases, neo-adjuvant pre-enucleation radiotherapy, intravitreal anti-vascular endothelial growth factor agents for radiation retinopathy, genetic prognostic testing, surveillance following definitive local therapy, and systemic therapy for patients with metastatic uveal melanoma. Discussion: The recommendations represent evidence-based standards of care agreed to by a large multidisciplinary group of healthcare professionals.
Application of Neural Network Feedforward in Fuzzy PI Controller for Electric Vehicle Thermal Management System: Modeling and Simulation Studies
Authors: Fei Fan , Wang Dong
Published: December 2023

The electric vehicle thermal management system (EVTMS) plays a crucial role in ensuring battery efficiency, driving range, and passenger comfort. However, EVTMSs still face unresolved challenges, such as accurate modeling, compensating for temperature variations, and achieving efficient control strategies. Addressing these issues is crucial for enhancing the performance, reliability, and energy efficiency of electric vehicles. Therefore, this study presents a cooling EVTMS model, considering both the battery pack temperature and the cabin comfort, and utilizes the prediction of neural network as a feedforward in a fuzzy PI controller to compensate for the model temperature variations. The simulation results reveal that, compared with PI controller and MPC, the neural network fuzzy PI (NN-Fuzzy PI) controller can well predict and compensate for the system’s nonlinear characteristics as well as the time-delay caused by heat transfer, achieving superior control performance and reducing energy consumption. The battery pack temperature and PMV fluctuations are effectively constrained within [−0.5, 0.5] and [−0.1, 0.1], reducing up to 150% and 164%, and the energy consumption of the pump and compressor are reduced by up to 0.23 and 100.1 KJ, with ranges of 18% and 2.68%. Meanwhile, the neural network feedforward also works effectively in different controllers. The findings of this research can provide valuable insights for TMS engineers to select advanced control strategies.
Synergic Design and Simulation of Battery-Operated Trains on Partially Electrified Lines: A Case Study regarding the Firenze Faenza Line
Authors: Pugi Luca
Published: December 2023

A full electrification of many local railway lines is often not feasible or sustainable in terms of construction and maintenance costs or alternatively for the presence of additional constraints and limitations deriving from environmental or infrastructural limitations. Battery Operated or other kind of hybrid solutions powertrains are currently proposed as sustainable alternatives to Internal combustion engines for the propulsion of rolling stock on not electrified lines. In this work, authors propose the adoption of a partial electrification of lines to assure higher performances and reliability of battery-operated rolling stock designed to be recharged and feed using standard technologies such as pantographs gathering power from suspended catenaries. This innovative solution is designed and sized for a vehicle inspired from an existing one and simulated for two different existing lines, also proposing an optimal distribution of electrified sections dedicated to train recharge. This Case Study is simulated considering some possible applications to some existing railway lines in Italy.
Short-Term Photovoltaic Power Generation Prediction Model Based on Improved Data Decomposition and Time Convolution Network
Authors: Cao Ranran , Tian He , Li Dahua , Feng Mingwen , Fan Huaicong
Published: December 2023

In response to the volatility of photovoltaic power generation, this paper proposes a short-term photovoltaic power generation prediction model (HWOA-MVMD-TPA-TCN) based on a Hybrid Whale Optimization Algorithm (HWOA), multivariate variational mode decomposition (MVMD), temporal pattern attention mechanism (TPA), and temporal convolutional network (TCN). In order to improve the accuracy of photovoltaic power generation forecasting, HWOA-MVMD is used for data decomposition, the Minimum Mode Overlap Component (MMOC) is used as the objective function, the photovoltaic power generation sequence is decomposed into finite Intrinsic Mode Functions (IMFs) according to the optimal solution, and the training set is formed with key meteorological variable data such as total radiation (unit: W/m2), ambient temperature, and humidity. Then, the TPA-TCN model is used to train the sub-sequences, the final predicted values are obtained after superimposing the reconstruction of the prediction results, and finally the prediction error of the photovoltaic power generation data is studied. The proposed method is applied to real photovoltaic power generation data from a commercial center in Tianjin and is compared with HWOA-MVMD-BiLSTM, GWO-MVMD-TPA-TCN, and TPA-TCN prediction models. The simulation results demonstrate that the MAE value of the forecast method proposed in this paper is 1.95 MW and the RMSE value is 2.55 MW, which can be reduced by up to 33.74% and 38.85%, respectively. The HWOA-MVMD-TPA-TCN-based short-term photovoltaic power generation prediction model presented in this paper achieves higher prediction accuracy and superior performance, serving as a valuable reference for related research.
Optimization and Stabilization of Distributed Secondary Voltage Control with Time Delays and Packet Losses Using LMIs
Authors: Bouzid Allal El Moubarek , Marinescu Bogdan , Xavier Florent , Denis Guillaume
Published: December 2023

The proposed hierarchical secondary voltage control is a spatially distributed control system using communication networks which are disturbed by both a time delays and packet data dropouts. A state feedback integral control is adopted to eliminate the effect of non-zero disturbance and provide exact tracking of the references of the pilot points and alignment of the reactive powers of the generators that participate in the control. The system is modeled as a discrete-time switched system, and the control gains are synthesized by solving LMIs for a stability condition based on a state-dependent Lyapunov function. For that, the cone complementarity linearization (CCL) algorithm is used. The effectiveness of the proposed control strategy in preventing time delays and packet losses is simulated, considering the model of a realistic electric power grid under typical operational conditions using MATLAB.
Wind Load Effects and Gust Loading Factor for Cable-Suspended Photovoltaic Structures
Authors: Li Junlong , Hong Guanhao , Xu Haiwei
Published: December 2023

The cable-suspended PV system has gained increasing popularity due to its large span and good site adaptability. However, this structure is quite sensitive to wind actions, and wind-induced module damage and structure failure have been frequently reported. Therefore, in this study, we carried out wind tunnel tests to study wind load effects on PV arrays with different lengths and widths. Considering the wind sheltering effects of upstream modules, reduction factors for the wind load were proposed in different array zones. Numerical simulations of wind-induced vibration and equivalent static analysis were conducted to yield gust loading factors for the PV array. This study showed that the maximum wind suction and pressure for the middle zone occurred at 0° and 180°, respectively, while those for the outermost zone appeared under oblique flows (e.g., 30° and 150°). For the PV modules beyond the windward fourth row, the reduction factors of the wind loads were 0.4 (maximum suction) and 0.2 (maximum pressure) for the middle zone and 0.5 (maximum suction) and 0.75 (maximum pressure) for the outermost zone. The gust loading factors for the typical wind directions of 0° and 180° varied from 2.2 to 2.7 for the middle zone and from 1.3 to 1.5 for the outermost zone.
Coppicing Abilities of Decapitated Elite Tree Trunks of Selected Acacia Species Genotypes in Mixed-Species Plantation
Authors: Muniandi Sures Kumar , Muhammad Norwati , Md Ariff Farah Fazwa , Taheri Yaghoob
Published: December 2023

Maturation-related loss in the shooting and rooting ability of a species through macro or micropropagation techniques has been a limiting factor in any forest tree improvement program. The rejuvenation capacity of mature elite trees of Acacia mangium, Acacia crassicarpa, Acacia auriculiformis, and Acacia aulococarpa was investigated by evaluating the sprouting ability of decapitated trunks. Thus, a total of 120 trees were selected based on their superior phenotypic characteristics from four provenance and five progenies of each species, and trunks of the elite trees were decapitated into two different height groups to induce coppicing from the collar and base of the trunk. Coppicing ability varies with species, provenance, progeny, and cutting height. A. auriculiformis was the easiest to produce shoots by having the highest shooting percentage (84%) and the number of shoots per trunk (13.5), followed by A. mangium (75%) and A. aulococarpa (40%). The total shoot number increased significantly with the increase in the height of the stumps. Data indicated that there is a possibility to rejuvenate matured cutting through coppicing in the natural environment. This study will help in the standardization of the stumping procedure for the rejuvenation of elite Acacia genotypes while simultaneously assisting in preserving germplasm through clonal propagation.
An Achaemenid God in Color
Authors: Ebbinghaus Susanne , Eremin Katherine , Lerner Judith A. , Nagel Alexander , Chang Angela
Published: December 2023

A limestone relief fragment with a figure in a winged disk from the fifth-century BCE Hall of 100 Columns at Persepolis in southwestern Iran that entered the Harvard Art Museums’ collections in 1943 preserves significant traces of its original coloration and has played a key role in the rediscovery of polychromy at the Achaemenid Persian capital. After tracing the fragment’s journey to Cambridge, MA, this article presents the results of recent technical studies of its pigment remains, including visible light-induced infrared luminescence (VIL) imaging, X-ray fluorescence (XRF) spectroscopy, and the analysis of micro samples by Raman spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and polarizing light microscopy (PLM). The new scientific data is compared to the findings of ongoing investigations of polychromies at Persepolis and other Achaemenid Persian sites and evaluated for the information it can and cannot provide on the original appearance of the figure in the winged disk, likely the Zoroastrian god Ahuramazda. The article reviews past attempts at reconstructing the relief’s coloration and the assumptions that guided them, recounts the experience of creating a tangible three-dimensional color reconstruction for an exhibition, and concludes with some general thoughts on the valuation of colorfulness.
Job Satisfaction of Nurses in the Context of Clinical Supervision: A Systematic Review
Authors: Hudays Ali , Gary Faye , Voss Joachim G. , Hazazi Ahmed , Arishi Amal , Al-sakran Fatimah
Published: December 2023

The purpose of this systematic review is to gather and analyze data from existing research on the effects of clinical supervision (CS) intervention on nurses’ job satisfaction and related outcomes such as stress levels, burnout, and care quality. Using the PRISMA (preferred reporting items for systematic reviews and meta-analysis) criteria, a systematic review of the research available in the databases PubMed, PsycInfo, Cochrane Library, and CINAHL, well as Google Scholar, between January 2010 and May 2023 was carried out. Out of the 760 studies assessed, only 8 met the criteria for inclusion in the review based on Hawker’s assessment tool. The results indicate that CS has a positive impact on nurses’ job satisfaction and related outcomes such as reduced burnout, stress levels, and the quality of care. The study also found that the effectiveness of CS in enhancing job satisfaction was most evident during the 6-month follow-up period. However, nurses who did not receive CS did not show any noticeable improvement in their knowledge or practice. Additionally, nurses who required more efficient clinical oversight reported little to no positive impact on their practice or training. The review also highlighted gaps in knowledge regarding the frequency and number of sessions required for the impact of CS on nurses’ job satisfaction and other outcomes. Due to the limited number of studies included in this review, further research is recommended to evaluate the influence of CS on nurses’ job satisfaction.
Vascular Endothelial Growth Factor A VEGFA Inhibition: An Effective Treatment Strategy for Psoriasis
Authors: Chen Ya , Tai Zongguang , Zhu Congcong , Yu Qin , Zhu Quangang , Chen Zhongjian
Published: December 2023

Psoriasis is an inflammatory skin disease mediated by the immune system and characterized by an inflammatory ring, also known as an epithelial immune microenvironment (EIME). The interaction between the epithelial tissue of the skin and the immune system has a crucial role in the immune cycle of psoriasis. Although the formation of new blood vessels in skin lesions provides energy support for the proliferation of epidermal keratinocytes, the role of angiogenesis in psoriasis has not been extensively studied. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis that has an important role in the development of psoriasis. VEGFA promotes angiogenesis and directly stimulates epidermal keratinocytes and infiltrating immune cells, thus contributing to the progression of psoriasis. Measuring VEGFA levels to identify angiogenic characteristics in psoriasis patients may be a predictive biomarker for disease severity and response to anti-angiogenic therapy. Clinical data have shown that anti-angiogenic therapy can improve skin lesions in psoriasis patients. Therefore, this study aimed to uncover the underestimated role of blood vessels in psoriasis, explore the relationship between VEGFA and keratinocytes in the EIME, and inspire innovative drug therapies for the treatment of psoriasis.
Bifunctional Silica-Supported Ionic Liquid Phase (SILP) Catalysts in Silane Production: Their Synthesis, Characterization and Catalytic Activity
Authors: Abarbanel Nataliia V. , Suvorov Sergey S. , Petukhov Anton N. , Belousov Artem S. , Markov Artem N. , Zarubin Dmitriy M. , Barysheva Alexandra V. , Vorotyntsev Ilya V. , Kapinos Alexander A. , Kulikov Artem D. , Vorotyntsev Andrey V.
Published: December 2023

A mesoporous silica support was synthesized using the sol–gel method from trichlorosilane. There is a tendency for the specific surface area and the proportion of silica particles mesopores to increase during all stages of sol–gel synthesis. It has been shown that the insertion of hexane and toluene, as additional solvents, into the structure-forming polyethylene glycol, makes it possible to regulate the pore size and specific surface area of silica. Silica functionalization was carried out using SILP technology. The activities of the catalytic systems based on polymer and inorganic supports immobilized by imidazole-based ionic liquids during the trichlorosilane disproportionation reaction were compared. There is a tendency for the monosilane yield for catalytic systems based on an inorganic support to increase. We identified the most promising catalyst in terms of monosilane yield and proposed a bifunctional catalyst that exhibited activity in two parallel reactions: trichlorosilane disproportionation and silicon tetrachloride hydrogenation.
Cannabinoids in Treating Chemotherapy-Induced Nausea and Vomiting, Cancer-Associated Pain, and Tumor Growth
Authors: Bathula Pavana P. , Maciver M. Bruce
Published: December 2023

Cannabis has been used as an herbal remedy for thousands of years, and recent research indicates promising new uses in medicine. So far, some studies have shown cannabinoids to be safe in helping mitigate some cancer-associated complications, including chemotherapy-induced nausea and vomiting, cancer-associated pain, and tumor growth. Researchers have been particularly interested in the potential uses of cannabinoids in treating cancer due to their ability to regulate cancer-related cell cycle pathways, prompting many beneficial effects, such as tumor growth prevention, cell cycle obstruction, and cell death. Cannabinoids have been found to affect tumors of the brain, prostate, colon and rectum, breast, uterus, cervix, thyroid, skin, pancreas, and lymph. However, the full potential of cannabinoids is yet to be understood. This review discusses current knowledge on the promising applications of cannabinoids in treating three different side effects of cancer—chemotherapy-induced nausea and vomiting, cancer-associated pain, and tumor development. The findings suggest that cannabinoids can be used to address some side effects of cancer and to limit the growth of tumors, though a lack of supporting clinical trials presents a challenge for use on actual patients. An additional challenge will be examining whether any of the over one hundred naturally occurring cannabinoids or dozens of synthetic compounds also exhibit useful clinical properties. Currently, clinical trials are underway; however, no regulatory agencies have approved cannabinoid use for any cancer symptoms beyond antinausea.
Inhaled CD24-Enriched Exosomes (EXO-CD24) as a Novel Immune Modulator in Respiratory Disease
Authors: Shapira Shiran , Schwartz Reut , Tsiodras Sotirios , Bar-Shai Amir , Melloul Ariel , Borsekofsky Sarah , Peer Michael , Adi Nimrod , MacLoughlin Ronan , Arber Nadir
Published: December 2023

Acute Respiratory Distress Syndrome (ARDS) is a major health concern with urgent unmet need for treatment options. There are three million new ARDS cases annually, and the disease’s mortality rate is high (35–46%). Cluster of differentiation 24 (CD24), a long-known protein with multifaceted functions, is a small, heavily glycosylated, membrane-anchored protein which functions as an immune checkpoint control. CD24 allows for immune discrimination between Damage-Associated Molecular Patterns and Pathogen-Associated Molecular Patterns derived from pathogens. Exosomes are intraluminal vesicles which play an important role in intercellular communication. Exosomes offer the advantage of targeted delivery, which improves safety and efficacy. The safety and efficacy of EXO-CD24 is promising, as was shown in >180 ARDS patients in phase 1b/2a, phase 2b, and compassionate use. CD24 binds Damage-associated molecular patterns (DAMPs) and inhibits the activation of the NF-ĸB pathway, a pivotal mediator of inflammatory responses. In contrast to anti-inflammatory therapies that are cytokine-specific or steroids that shut down the entire immune system, EXO-CD24 acts upstream, reverting the immune system back to normal activity. Herein, the safety and efficacy of mEXO-CD24 is shown in murine models of several pulmonary diseases (sepsis, allergic asthma, Chronic Obstructive Pulmonary Disease(COPD), fibrosis). EXO CD24 can suppress the hyperinflammatory response in the lungs in several pulmonary diseases with a significant unmet need for treatment options.
Lipid-Related Domestication Accounts for the Extreme Cold Sensitivity of Semiwild and Tropic Xishuangbanna Cucumber (Cucumis sativus L. var. xishuangbannanesis)
Authors: Zhang Rui-Jing , Liu Bin , Song Shan-Shan , Salah Radwa , Song Chang-Jiang , Xia Shi-Wei , Hao Qian , Liu Yan-Jun , Li Yu , Lai Yun-Song
Published: December 2023

Xishuangbanna (XIS) cucumber (Cucumis sativus L. var. xishuangbannanesis) is a semiwild variety originating from low latitude tropic areas, and therefore shows extreme cold sensitivity and heat tolerance. Here, we mapped the quantitative trait loci (QTLs) that control the cold sensitivity and heat tolerance of XIS cucumber seedlings. Using bulked segregant analysis (BSA), we identified three QTLs (HTT1.1, HTT3.1, and HTT3.2, with a total length of 11.98 Mb) for heat tolerance and two QTLs (LTT6.1 and LTT6.2, with a total length of 8.74 Mb) for cold sensitivity. The QTL LTT6.1 was then narrowed down to a length of 641 kb by using kompetitive allele-specific PCR (KASP) markers. Based on structural variants (SVs) and single-nucleotide polymorphisms (SNPs), we found the LTT6.1 is covered by a high divergent region including a 50 kb deletion in the XIS49 genome, which affects the gene structure of lipase abhydrolase domain containing 6 (ABHD6, Csa_6G032560). Accordingly, there is a very big difference in lipid composition, but not in other osmoprotectants like free amino acids and fatty acids, between XIS49 and cultivated cucumber CL. Moreover, we calculated the composite likelihood ratio (CLR) and identified selective sweeps from 115 resequencing data, and found that lipid- and fatty-acid-related processes are major aspects in the domestication of the XIS group cucumber. LTT6.1 is a particularly special region positioned nearby lipid-related selective sweeps. These studies above suggested that the lipid-related domestication of XIS cucumbers should account for their extreme cold sensitivity.
Sensitivity of Human Induced Pluripotent Stem Cells and Thereof Differentiated Kidney Proximal Tubular Cells towards Selected Nephrotoxins
Authors: Mboni-Johnston Isaac Musong , Kouidrat Nazih Mohamed Zakari , Hirsch Cornelia , Weber Andreas Georg , Meißner Alexander , Adjaye James , Schupp Nicole
Published: December 2023

Proximal tubular epithelial cells (PTEC) are constantly exposed to potentially toxic metabolites and xenobiotics. The regenerative potential of the kidney enables the replacement of damaged cells either via the differentiation of stem cells or the re-acquisition of proliferative properties of the PTEC. Nevertheless, it is known that renal function declines, suggesting that the deteriorated cells are not replaced by fully functional cells. To understand the possible causes of this loss of kidney cell function, it is crucial to understand the role of toxins during the regeneration process. Therefore, we investigated the sensitivity and function of human induced pluripotent stem cells (hiPSC), hiPSC differentiating, and hiPSC differentiated into proximal tubular epithelial-like cells (PTELC) to known nephrotoxins. hiPSC were differentiated into PTELC, which exhibited similar morphology to PTEC, expressed prototypical PTEC markers, and were able to undergo albumin endocytosis. When treated with two nephrotoxins, hiPSC and differentiating hiPSC were more sensitive to cisplatin than differentiated PTELC, whereas all stages were equally sensitive to cyclosporin A. Both toxins also had an inhibitory effect on albumin uptake. Our results suggest a high sensitivity of differentiating cells towards toxins, which could have an unfavorable effect on regenerative processes. To study this, our model of hiPSC differentiating into PTELC appears suitable.
Essential-Oils-Loaded Biopolymeric Nanoparticles as Strategies for Microbial and Biofilm Control: A Current Status
Authors: Romero-Montero Alejandra , Melgoza-Ramírez Luis Javier , Ruíz-Aguirre Jesús Augusto , Chávez-Santoscoy Alejandra , Magaña Jonathan Javier , Cortés Hernán , Leyva-Gómez Gerardo , Del Prado-Audelo María Luisa
Published: December 2023

The emergence of bacterial strains displaying resistance to the currently available antibiotics is a critical global concern. These resilient bacteria can form biofilms that play a pivotal role in the failure of bacterial infection treatments as antibiotics struggle to penetrate all biofilm regions. Consequently, eradicating bacteria residing within biofilms becomes considerably more challenging than their planktonic counterparts, leading to persistent and chronic infections. Among various approaches explored, essential oils loaded in nanoparticles based on biopolymers have emerged, promising strategies that enhance bioavailability and biological activities, minimize side effects, and control release through regulated pharmacokinetics. Different available reviews analyze nanosystems and essential oils; however, usually, their main goal is the analysis of their antimicrobial properties, and progress in biofilm combat is rarely discussed, or it is not the primary objective. This review aims to provide a global vision of biofilm conformation and describes mechanisms of action attributed to each EO. Furthermore, we present a comprehensive overview of the latest developments in biopolymeric nanoparticles research, especially in chitosan- and zein-based nanosystems, targeting multidrug-resistant bacteria in both their sessile and biofilm forms, which will help to design precise strategies for combating biofilms.
Dithioethanol (DTE)-Conjugated Deoxyribose Cyclic Dinucleotide Prodrugs (DTE-dCDNs) as STING Agonist
Authors: Xie Zhiqiang , Yang Yuchen , Wang Zhenghua , Ma Dejun , Xi Zhen
Published: December 2023

To improve the chemical regulation on the activity of cyclic dinucleotides (CDNs), we here designed a reduction-responsive dithioethanol (DTE)-based dCDN prodrug 9 (DTE-dCDN). Prodrug 9 improved the cell permeability with the intracellular levels peaking in 2 h in THP-1 cells. Under the reductive substance such as GSH or DTT, prodrug 9 could be quickly decomposed in 30 min to release the parent dCDN. In THP1-Lucia cells, prodrug 9 also retained a high bioactivity with the EC50 of 0.96 μM, which was 51-, 43-, and 3-fold more than the 2′,3′-cGAMP (EC50 = 48.6 μM), the parent compound 3′,3′-c-di-dAMP (EC50 = 41.3 μM), and ADU-S100 (EC50 = 2.9 μM). The high bioactivity of prodrug 9 was validated to be highly correlated with the activation of the STING signaling pathway. Furthermore, prodrug 9 could also improve the transcriptional expression levels of IFN-β, CXCL10, IL-6, and TNF-α in THP-1 cells. These results will be helpful to the development of chemically controllable CDN prodrugs with a high cellular permeability and potency.
The Relationship between Trop-2, Chemotherapeutic Drugs, and Chemoresistance
Authors: Koltai Tomas , Fliegel Larry
Published: December 2023

Trop-2 is a highly conserved one-pass transmembrane mammalian glycoprotein that is normally expressed in tissues such as the lung, intestines, and kidney during embryonic development. It is overexpressed in many epithelial cancers but is absent in non-epithelial tumors. Trop-2 is an intracellular calcium signal transducer that participates in the promotion of cell proliferation, migration, invasion, metastasis, and probably stemness. It also has some tumor suppressor effects. The pro-tumoral actions have been thoroughly investigated and reported. However, Trop-2’s activity in chemoresistance is less well known. We review a possible relationship between Trop-2, chemotherapy, and chemoresistance. We conclude that there is a clear role for Trop-2 in some specific chemoresistance events. On the other hand, there is no clear evidence for its participation in multidrug resistance through direct drug transport. The development of antibody conjugate drugs (ACD) centered on anti-Trop-2 monoclonal antibodies opened the gates for the treatment of some tumors resistant to classic chemotherapies. Advanced urothelial tumors and breast cancer were among the first malignancies for which these ACDs have been employed. However, there is a wide group of other tumors that may benefit from anti-Trop-2 therapy as soon as clinical trials are completed.
Effect of Vagus Nerve Stimulation on the GASH/Sal Audiogenic-Seizure-Prone Hamster
Authors: Gonçalves-Sánchez Jaime , Sancho Consuelo , López Dolores E. , Castellano Orlando , García-Cenador Begoña , Servilha-Menezes Gabriel , Corchado Juan M. , García-Cairasco Norberto , Gonçalves-Estella Jesús M.
Published: December 2023

Vagus nerve stimulation (VNS) is an adjuvant neuromodulation therapy for the treatment of refractory epilepsy. However, the mechanisms behind its effectiveness are not fully understood. Our aim was to develop a VNS protocol for the Genetic Audiogenic Seizure Hamster from Salamanca (GASH/Sal) in order to evaluate the mechanisms of action of the therapy. The rodents were subject to VNS for 14 days using clinical stimulation parameters by implanting a clinically available neurostimulation device or our own prototype for laboratory animals. The neuroethological assessment of seizures and general behavior were performed before surgery, and after 7, 10, and 14 days of VNS. Moreover, potential side effects were examined. Finally, the expression of 23 inflammatory markers in plasma and the left-brain hemisphere was evaluated. VNS significantly reduced seizure severity in GASH/Sal without side effects. No differences were observed between the neurostimulation devices. GASH/Sal treated with VNS showed statistically significant reduced levels of interleukin IL-1β, monocyte chemoattractant protein MCP-1, matrix metalloproteinases (MMP-2, MMP-3), and tumor necrosis factor TNF-α in the brain. The described experimental design allows for the study of VNS effects and mechanisms of action using an implantable device. This was achieved in a model of convulsive seizures in which VNS is effective and shows an anti-inflammatory effect.
Mitochondrial Protein SLIRP Affects Biosynthesis of Cytochrome c Oxidase Subunits in HEK293T Cells
Authors: Baleva Mariia V. , Piunova Uliana , Chicherin Ivan , Vasilev Ruslan , Levitskii Sergey , Kamenski Piotr
Published: December 2023

Mitochondria carry out various vital roles in eukaryotic cells, including ATP energy synthesis, the regulation of apoptosis, Fe-S cluster formation, and the metabolism of fatty acids, amino acids, and nucleotides. Throughout evolution, mitochondria lost most of their ancestor’s genome but kept the replication, transcription, and translation machinery. Protein biosynthesis in mitochondria is specialized in the production of highly hydrophobic proteins encoded by mitochondria. These proteins are components of oxidative phosphorylation chain complexes. The coordination of protein synthesis must be precise to ensure the correct assembly of nuclear-encoded subunits for these complexes. However, the regulatory mechanisms of mitochondrial translation in human cells are not yet fully understood. In this study, we examined the contribution of the SLIRP protein in regulating protein biosynthesis in mitochondria. Using a click-chemistry approach, we discovered that deletion of the SLIRP gene disturbs mitochondrial translation, leading to the dysfunction of complexes I and IV, but it has no significant effect on complexes III and V. We have shown that this protein interacts only with the small subunit of the mitochondrial ribosome, which may indicate its involvement in the regulation of the mitochondrial translation initiation stage.
Genome-Wide Identification and Expression Analysis of the SQUAMOSA Promoter-Binding Protein-like (SPL) Transcription Factor Family in Catalpa bungei
Authors: Fan Erqin , Liu Caixia , Wang Zhi , Wang Shanshan , Ma Wenjun , Lu Nan , Liu Yuhang , Fu Pengyue , Wang Rui , Lv Siyu , Qu Guanzheng , Wang Junhui
Published: December 2023

As a plant-specific transcription factor, the SPL gene family plays a critical role in plant growth and development. Although the SPL gene family has been identified in diverse plant species, there have been no genome-wide identification or systematic study reports on the SPL gene family in Catalpa bungei. In this study, we identified 19 putative SPL gene family members in the C. bungei genome. According to the phylogenetic relationship, they can be divided into eight groups, and the genes in the same group have a similar gene structure and conserved motifs. Synteny analysis showed that fragment duplication played an important role in the expansion of the CbuSPL gene family. At the same time, CbuSPL genes have cis-acting elements and functions related to light response, hormone response, growth and development, and stress response. Tissue-specific expression and developmental period-specific expression analysis showed that CbuSPL may be involved in flowering initiation and development, flowering transition, and leaf development. In addition, the ectopic expression of CbuSPL4 in Arabidopsis confirmed that it can promote early flowering and induce the expression of related flowering genes. These systematic research results will lay a foundation for further study on the functional analysis of SPL genes in C. bungei.
The Expression Patterns and Implications of MALAT1, MANCR, PSMA3-AS1 and miR-101 in Esophageal Adenocarcinoma
Authors: Syllaios Athanasios , Gazouli Maria , Vailas Michail , Mylonas Konstantinos S. , Sakellariou Stratigoula , Sougioultzis Stavros , Karavokyros Ioannis , Liakakos Theodoros , Schizas Dimitrios
Published: December 2023

Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression.
Genome-Wide Identification of Proline Transporter Gene Family in Non-Heading Chinese Cabbage and Functional Analysis of BchProT1 under Heat Stress
Authors: Tian Jun , Chang Kaizhen , Lei Yingxiao , Li Shuhao , Wang Jinwei , Huang Chenxin , Zhong Fenglin
Published: December 2023

Non-heading Chinese cabbage prefers cool temperatures, and heat stress has become a major factor for reduced yield. The proline transporter protein (ProT) is highly selective for proline transport, contributing to the heat tolerance of non-heading Chinese cabbage. However, there has been no systematic study on the identification and potential functions of the ProT gene family in response to heat stress in non-heading Chinese cabbage. We identified six BchProT genes containing 11–12 transmembrane helices characteristic of membrane proteins through whole-genome sequencing. These genes diverged into three evolutionary branches and exhibited similarity in motifs and intron/exon numbers. Segmental duplication is the primary driving force for the amplification of BchProT. Notably, many stress-related elements have been identified in the promoters of BchProT using cis-acting element analysis. The expression level of BchProT6 was the highest in petioles, and the expression level of BchProT1 was the highest under high-temperature stress. Subcellular localization indicated their function at cell membranes. Heterologous expression of BchProT1 in Arabidopsis plants increased proline transport synthesis under heat-stress conditions. This study provides valuable information for exploring the molecular mechanisms underlying heat tolerance mediated by members of the BchProT family.
Role of Single-Nucleotide Polymorphisms in Genes Implicated in Capecitabine Pharmacodynamics on the Effectiveness of Adjuvant Therapy in Colorectal Cancer
Authors: Cura Yasmin , Sánchez-Martín Almudena , Márquez-Pete Noelia , González-Flores Encarnación , Martínez-Martínez Fernando , Pérez-Ramírez Cristina , Jiménez-Morales Alberto
Published: December 2023

Colorectal cancer (CRC) is a highly prevalent form of neoplasm worldwide. Capecitabine, an oral antimetabolite, is widely used for CRC treatment; however, there exists substantial variation in individual therapy response. This may be due to genetic variations in genes involved in capecitabine pharmacodynamics (PD). In this study, we investigated the role of single-nucleotide polymorphisms (SNPs) related to capecitabine’s PD on disease-free survival (DFS) in CRC patients under adjuvant treatment. Thirteen SNPs in the TYMS, ENOSF1, MTHFR, ERCC1/2, and XRCC1/3 genes were genotyped in 142 CRC patients using real-time PCR with predesigned TaqMan® probes. A significant association was found between favorable DFS and the ENOSF1 rs2612091-T allele (p = 0.010; HR = 0.34; 95% CI = 0.14–0.83), as well as with the TYMS/ENOSF1 region ACT haplotype (p = 0.012; HR = 0.37; 95% CI = 0.17–0.80). Other factors such as low histological grade (p = 0.009; HR = 0.34; 95% CI = 0.14–0.79) and a family history of cancer (p = 0.040; HR = 0.48; 95% CI = 0.23–0.99) were also linked to improved DFS. Therefore, the SNP ENOSF1 rs2612091 could be considered as a predictive genetic biomarker for survival in CRC patients receiving capecitabine-based adjuvant regimens.
The p66Shc Redox Protein and the Emerging Complications of Diabetes
Authors: Biondi Giuseppina , Marrano Nicola , Borrelli Anna , Rella Martina , D’Oria Rossella , Genchi Valentina Annamaria , Caccioppoli Cristina , Cignarelli Angelo , Perrini Sebastio , Laviola Luigi , Giorgino Francesco , Natalicchio Annalisa
Published: December 2023

Diabetes mellitus is a chronic metabolic disease, the prevalence of which is constantly increasing worldwide. It is often burdened by disabling comorbidities that reduce the quality and expectancy of life of the affected individuals. The traditional complications of diabetes are generally described as macrovascular complications (e.g., coronary heart disease, peripheral arterial disease, and stroke), and microvascular complications (e.g., diabetic kidney disease, retinopathy, and neuropathy). Recently, due to advances in diabetes management and the increased life expectancy of diabetic patients, a strong correlation between diabetes and other pathological conditions (such as liver diseases, cancer, neurodegenerative diseases, cognitive impairments, and sleep disorders) has emerged. Therefore, these comorbidities have been proposed as emerging complications of diabetes. P66Shc is a redox protein that plays a role in oxidative stress, apoptosis, glucose metabolism, and cellular aging. It can be regulated by various stressful stimuli typical of the diabetic milieu and is involved in various types of organ and tissue damage under diabetic conditions. Although its role in the pathogenesis of diabetes remains controversial, there is strong evidence regarding the involvement of p66Shc in the traditional complications of diabetes. In this review, we will summarize the evidence supporting the role of p66Shc in the pathogenesis of diabetes and its complications, focusing for the first time on the emerging complications of diabetes.
The Pivotal Role of the Membrane-Bound O-Acyltransferase Domain Containing 7 in Non-Alcoholic Fatty Liver Disease
Authors: Chandrasekaran Preethi , Weiskirchen Ralf
Published: December 2023

Non-alcoholic fatty liver disease (NAFLD) is a common and prevalent disorder affecting 25 percent of the adults in the United States and 32 percent of adults globally. It is one of the common causes of chronic liver disease characterized by steatosis, which can lead to inflammation, fibrosis, and cirrhosis. NAFLD is strongly associated with obesity and insulin resistance. Multiple genetic variants have been consistently found to be associated with NAFLD; one of them is found in the TMC4-MBOAT7 loci. One variant (rs641738 C>T) within MBOAT7 encoding lysophosphatidyl inositol acyltransferase increases the risk for NAFLD development and triggers hepatic inflammation by regulating arachidonic acid levels. This review provides an overview of the MBOAT7 gene, pathogenesis of NAFLD, understanding the regulation of MBOAT7 and mechanistic link between MBOAT7 and NAFLD. It further summarizes pathophysiologically relevant in vivo and in vitro studies on MBOAT7 and challenges in treating complex NAFLD with recent progress made in the treatment of NAFLD. As such, this review provides useful information on MBOAT7 and NAFLD interrelation, which has the potential of deciphering novel therapeutic targets rather than well-known genetic variants such as PNPLA3 and TM6SF2.
Residual Stresses in Ribbed Reinforcing Bars
Authors: Robl Tobias , Hegele Patrick , Krempaszky Christian , Werner Ewald
Published: December 2023

Ribbed reinforcing bars (rebars) are used for the reinforcement of concrete structures. In service, they are often subjected to cyclic loading. In general, the fatigue performance of rebars may be influenced by residual stresses originating from the manufacturing process. Knowledge about residual stresses in rebars and their origin, however, is sparse. So far, residual stress measurements are limited to individual stress components, viz., to the non-ribbed part of the rebar surface. At critical points of the rebar surface, where most of the fatigue cracks originate, i.e., the foot radius regions of transverse ribs, the residual stress state has not yet been investigated experimentally. To extend the knowledge about residual stresses in rebars within the scope of this work, residual stress measurements were carried out on a rebar specimen with a diameter of 28 mm made out of the rebar steel grade B500B. In addition, numerical simulations of the TempCoreTM process were carried out. The results of the experimental investigations show tensile residual stresses in the core and the transition zone of the examined rebar specimen. Low compressive residual stresses are measured at the non-ribbed part of the rebar surface, while high compressive residual stresses are present at the tip of the transverse ribs. The results of the numerical investigations are in reasonable accordance with the experimental results. Furthermore, the numerical results indicate moderate tensile stresses occurring on the rebar surface in the rib foot radius regions of the transverse ribs. High stress gradients directly beneath the rebar surface, which are reported in the literature and which are most likely related to a thin decarburized surface layer, could be reproduced qualitatively with the numerical model developed.
Experiment on Compressive Properties and Microscopic Analysis of Sea Sand Geopolymer-Based Recycled Concrete
Authors: Xu Deyi , An Guanfeng , Chen Yuliang , Liu Zhihua , Liu Xiangli
Published: December 2023

For marine and coastal engineering, construction resources have become scarce due to a limited local supply. Sea sand geopolymer-based recycled concrete (SSGRC) is an innovative cementitious material known for its eco-friendly benefits and corrosion resistance. This study explores the mechanical properties of SSGRC. The influences of the replacement rate of mineral slag, alkali activator concentrations, fine aggregate types, and curing ages on the compression strength of SSGRC were studied. The failure mechanism was analyzed using the failure patterns and compressive stress–strain curves. The results show that sea sand had a positive effect on geopolymer-based material. The SSGRC reached peak strength with an alkali activator concentration of 10 mol/L and a mineral slag replacement rate of 60%. The maximum stress and strain increased with an increasing curing age. The ratios of strength to the peak value were 55% and 85% after 1 day and 7 days, respectively. Using SEM, in the last hydration stage, the C-(A)-S-H gel was formed with a dense microstructure, and the geopolymer exhibited a favorable bonding performance. The constitutive models describing the complete stress–strain relationship under compression were developed.