bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of Osimertinib and Olaparib Therapy to Treat Non-Small Cell Lung Cancer and High-Grade Serous Ovarian Carcinoma: A Case Report
Authors: Lin Jane , Welch Stephen , Sanatani Michael , Ramadan Sherif
Published: January 2024

We present the case of a 75-year-old female with simultaneous EGFR-mutated stage IV lung cancer and advanced BRCA2-mutated ovarian cancer, treated with a unique regimen. In this case report, the patient was treated with alternating months of osimertinib and olaparib to control her lung and ovarian cancers, respectively. When both diseases showed progression, the patient underwent a trial of concurrent therapy with both drugs, yet this was discontinued due to patient-reported adverse side effects. Combination targeted drug therapy may be required to treat complex diagnoses such as dual malignancies. However, combination drug therapy consisting of osimertinib and olaparib has not previously been explored. This case report represents the first to demonstrate osimertinib and olaparib combination therapy as a unique treatment regimen for concurrent lung and ovarian cancers. These two drugs can either be given in an alternating way or given together, short-term, with a higher but tolerable toxicity profile.
Numerical Study on Peak Shaving Performance of Combined Heat and Power Unit Assisted by Heating Storage in Long-Distance Pipelines Scheduled by Particle Swarm Optimization Method
Authors: Ju Haoran , Wang Yongxue , Feng Yiwu , Zheng Lijun
Published: January 2024

Thermal energy storage in long-distance heating supply pipelines can improve the peak shaving and frequency regulation capabilities of combined heat and power (CHP) units participating in the power grid. In this study, a one-dimensional numerical model was established to predict the thermal lag in long-distance pipelines at different scale levels. The dynamic response of the temperature at the end of the heating pipeline was considered. For the one-way pipe lengths of 10 km, 15 km and 20 km, the response times of the temperature at the distal end were 2.33 h, 2.94 h and 3.54 h, respectively. The longer the flow period, the further the warming-up time is delayed. An optimization scheduling approach was also created to illustrate the peak shaving capabilities of a CHP unit combined with a long-distance pipeline thermal energy storage component. It was demonstrated that the maximum heating load of the unit increased up to 503.08 MW, and the heating load could be expanded in the range of 17.88 MW to 203.76 MW at the minimum electric load of the unit of 104.08 MW. Finally, the particle swarm optimization method was adopted to guide the operating strategy through a whole day to meet both the electric power and heating power requirements. For the optimized case, the comprehensive energy utilization efficiency and the exergy efficiency increase to 64.4% and 56.73%. The thermal energy storage applications based on long-distance pipelines were simulated quantitively and proved to be effective in promoting the operational flexibility of the CHP unit.
Green Space Reverse Pixel Shuffle Network: Urban Green Space Segmentation Using Reverse Pixel Shuffle for Down-Sampling from High-Resolution Remote Sensing Images
Authors: Jiang Mingyu , Shao Hua , Zhu Xingyu , Li Yang
Published: January 2024

Urban green spaces (UGS) play a crucial role in the urban environmental system by aiding in mitigating the urban heat island effect, promoting sustainable urban development, and ensuring the physical and mental well-being of residents. The utilization of remote sensing imagery enables the real-time surveying and mapping of UGS. By analyzing the spatial distribution and spectral information of a UGS, it can be found that the UGS constitutes a kind of low-rank feature. Thus, the accuracy of the UGS segmentation model is not heavily dependent on the depth of neural networks. On the contrary, emphasizing the preservation of more surface texture features and color information contributes significantly to enhancing the model’s segmentation accuracy. In this paper, we proposed a UGS segmentation model, which was specifically designed according to the unique characteristics of a UGS, named the Green Space Reverse Pixel Shuffle Network (GSRPnet). GSRPnet is a straightforward but effective model, which uses an improved RPS-ResNet as the feature extraction backbone network to enhance its ability to extract UGS features. Experiments conducted on GaoFen-2 remote sensing imagery and the Wuhan Dense Labeling Dataset (WHDLD) demonstrate that, in comparison with other methods, GSRPnet achieves superior results in terms of precision, F1-score, intersection over union, and overall accuracy. It demonstrates smoother edge performance in UGS border regions and excels at identifying discrete small-scale UGS. Meanwhile, the ablation experiments validated the correctness of the hypotheses and methods we proposed in this paper. Additionally, GSRPnet’s parameters are merely 17.999 M, and this effectively demonstrates that the improvement in accuracy of GSRPnet is not only determined by an increase in model parameters.
Synergistic Effects of Heating Platens’ Temperature and Compression Ratio on the Periodic Hot-Press Drying of Chinese Fir Lumber
Authors: Weng Xiang , Zhang Xingying , Huang Chengjian , Wang Shipeng , Hou Junfeng
Published: January 2024

The effects of periodic hot-press drying on drying behavior and mechanical damage to Chinese fir lumber were investigated by taking the heating platens’ temperature (TP) and compression ratio (Rc) as experimental factors. The temperature and pressure inside lumber were analyzed during drying process. The results were as follows. The drying rate of lumber was significantly increased with increasing TP and Rc. Scanning electron microscope (SEM) micrographs showed that bordered pit membranes, cross-field pits, middle lamella between adjacent cells, and tracheid walls were damaged after drying, and the damage became more severe with higher TP and Rc. Detachments between ray parenchyma cells and tracheids were observed at 170 °C. Nitrogen-adsorption measurement results demonstrated that more cell wall pores in the 2.5~6.2 nm pore diameter range were generated at higher TP, resulting in an enlarged specific surface area and pore volume of cell walls. These structural changes contributed to accelerating moisture migration and decreasing the drying time. Furthermore, fluctuating pressure inside lumber was the main driving force leading to moisture migration and cell tissue damage in lumber during drying. The influence of TP on internal temperature (TM) and pressure (PM) was greater than Rc. With the increase in TP from 130 to 170 °C at the Rc of 10%, the maximum TM and PM were increased by 30.90% and 39.84%, respectively. However, TP should not be too high to prevent the formation of macro-cracks caused by high pressure, which may significantly affect wood’s mechanical properties. These results provide theoretical support for periodic hot-press drying processes’ improvement and high-value utilization of Chinese fir.
Exploring Immune-Related Gene Profiling and Infiltration of Immune Cells in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma
Authors: Li Jialu , Xi Juqun
Published: January 2024

Cervical cancer is a widespread malignancy among women, leading to a substantial global health impact. Despite extensive research, our understanding of the basic molecules and pathogenic processes of cervical squamous cell carcinoma is still insufficient. This investigation aims to uncover immune-related genes linked to CESC and delineate their functions. Leveraging data from the GEO and ImmPort databases, a total of 22 immune-related genes were identified. Multiple tools, including DAVID, the human protein atlas, STRING, GeneMANIA, and TCGA, were employed to delve into the expression and roles of these immune genes in CESC, alongside their connections to the disease’s pathological features. Through RT-PCR, the study confirmed notable disparities in CXCL8 and CXCL10 mRNA expression between CESC and normal cervical tissue. The TCGA dataset’s immune-related information reinforced the association of CXCL8 and CXCL10 with immune infiltration in CESC. This research sheds light on the potential of CXCL8 and CXCL10 as promising therapeutic targets and essential prognostic factors for individuals diagnosed with CESC.
A Circular RNA Derived from the Pumilio 1 Gene Could Regulate PTEN in Human Cumulus Cells
Authors: Caponnetto Angela , Ferrara Carmen , Fazzio Anna , Agosta Noemi , Scribano Marianna , Vento Maria Elena , Borzì Placido , Barbagallo Cristina , Stella Michele , Ragusa Marco , Scollo Paolo , Barbagallo Davide , Purrello Michele , Di Pietro Cinzia , Battaglia Rosalia
Published: January 2024

CircRNAs are a class of non-coding RNAs able to regulate gene expression at multiple levels. Their involvement in physiological processes, as well as their altered regulation in different human diseases, both tumoral and non-tumoral, is well documented. However, little is known about their involvement in female reproduction. This study aims to identify circRNAs potentially involved in reproductive women’s health. Candidate circRNAs expressed in ovary and sponging miRNAs, already known to be expressed in the ovary, were selected by a computational approach. Using real time PCR, we verified their expression and identified circPUM1 as the most interesting candidate circRNA for further analyses. We assessed the expression of circPUM1 and its linear counterpart in all the follicle compartments and, using a computational and experimental approach, identified circPUM1 direct and indirect targets, miRNAs and mRNAs, respectively, in cumulus cells. We found that both circPUM1 and its mRNA host gene are co-expressed in all the follicle compartments and proposed circPUM1 as a potential regulator of PTEN, finding a strong positive correlation between circPUM1 and PTEN mRNA. These results suggest a possible regulation of PTEN by circPUM1 in cumulus cells and point out the important role of circRNA inside the pathways related to follicle growth and oocyte maturation.
A Study of Polish Family with Scoliosis and Limb Contractures Expands the MYH3 Disease Spectrum
Authors: Frasuńska Justyna , Pollak Agnieszka , Turczyn Paweł , Kutkowska-Kaźmierczak Anna , Pepłowski Jakub , Płoski Rafał , Tarnacka Beata
Published: January 2024

A disease associated with malfunction of the MYH3 gene is characterised by scoliosis, contractures of the V fingers, knees and elbows, dysplasia of the calf muscles, foot deformity and limb length asymmetry. The aim of this study was to identify the cause of musculoskeletal deformities in a three-generation Polish family by exome sequencing. The segregation of the newly described c.866A>C variant of the MYH3 gene in the family indicates an autosomal dominant model of inheritance. The detected MYH3 variant segregates the disease within the family. The presented results expand the MYH3 disease spectrum and emphasize the clinical diagnostic challenge in syndromes harbouring congenital spine defects and joint contractures.
The Relationship between Clinical Environment and Adverse Events Reporting: Evidence from Lithuania
Authors: Kiviliene Juste , Paukstaitiene Renata , Stievano Alessandro , Blazeviciene Aurelija
Published: January 2024

Background: The clinical environment plays a crucial role in patient safety, as it encompasses the physical, organizational, and cultural aspects of healthcare delivery. Adverse events, such as active errors, can often be attributed to systemic issues within the clinical environment. Addressing and improving environmental factors is essential for minimizing adverse events and enhancing overall patient care quality. Methods: A descriptive, cross-sectional design was applied. The study utilized two questionnaires: the Reporting of Clinical Adverse Events Scale (RoCAES) and the Revised Professional Practice Environment (RPPE) scale. A total of 1388 questionnaires were fully filled out, with a response rate of 71 percent. Results: Nurses who expressed higher levels of satisfaction with various aspects of the clinical environment were more inclined to indicate their intention to report adverse events in the future. These positive relationships suggest that a contented clinical environment fosters a greater willingness among nurses to report adverse event occurrences. Conclusion: The findings of our study support the evidence that demonstrated that the clinical environment plays a significant role in influencing the reporting of adverse events in healthcare settings. It significantly influences nurses’ attitudes, quality of care, and adverse event reporting rate.
Survival Outcomes of Patients with Mantle Cell Lymphoma: A Retrospective, 15-Year, Real-Life Study
Authors: Cencini Emanuele , Calomino Natale , Franceschini Marta , Dragomir Andreea , Fredducci Sara , Esposito Vangone Beatrice , Lucco Navei Giulia , Fabbri Alberto , Bocchia Monica
Published: January 2024

Mantle cell lymphoma (MCL) prognosis has significantly improved in recent years; however, the possible survival benefit of new treatment options should be evaluated outside of clinical trials. We investigated 73 consecutive MCL patients managed from 2006 to 2020. For younger patients <65 years old, the median PFS was 72 months and we reported a 2-year, 5-year, and 10-year PFS of 73%, 62%, and 41%; median OS was not reached and we reported a 2-year, 5-year, and 10-year OS of 88%, 82%, and 66%. For patients aged 75 years or older, the median PFS was 36 months and we reported a 2-year, 5-year, and 10-year PFS of 52%, 37%, and 37%; median OS was not reached and we reported a 2-year, 5-year, and 10-year OS of 72%, 55%, and 55%. The median PFS was significantly reduced for patients treated between 2006 and 2010 compared to patients treated between 2011 and 2015 (p = 0.04). Interestingly, there was a trend towards improved OS for patients treated between 2016 and 2020 compared to between 2006 and 2010 and between 2011 and 2015 (5-year OS was 91%, 44%, and 33%). These findings could be due to the introduction of BR as a first-line regimen for elderly patients and to the introduction of ibrutinib as a second-line regimen.
Monitoring Genomic Structural Rearrangements Resulting from Gene Editing
Authors: Bailey Susan M. , Cross Erin M. , Kinner-Bibeau Lauren , Sebesta Henry C. , Bedford Joel S. , Tompkins Christopher J.
Published: January 2024

The cytogenomics-based methodology of directional genomic hybridization (dGH) enables the detection and quantification of a more comprehensive spectrum of genomic structural variants than any other approach currently available, and importantly, does so on a single-cell basis. Thus, dGH is well-suited for testing and/or validating new advancements in CRISPR-Cas9 gene editing systems. In addition to aberrations detected by traditional cytogenetic approaches, the strand specificity of dGH facilitates detection of otherwise cryptic intra-chromosomal rearrangements, specifically small inversions. As such, dGH represents a powerful, high-resolution approach for the quantitative monitoring of potentially detrimental genomic structural rearrangements resulting from exposure to agents that induce DNA double-strand breaks (DSBs), including restriction endonucleases and ionizing radiations. For intentional genome editing strategies, it is critical that any undesired effects of DSBs induced either by the editing system itself or by mis-repair with other endogenous DSBs are recognized and minimized. In this paper, we discuss the application of dGH for assessing gene editing-associated structural variants and the potential heterogeneity of such rearrangements among cells within an edited population, highlighting its relevance to personalized medicine strategies.
Effect of α″-Ti Martensitic Phase Formation on Plasticity in Ti–Fe–Sn Ultrafine Eutectic Composites
Authors: Neelakandan Deva Prasaad , Kim Wonhyeong , Prorok Barton C. , Mirkoohi Elham , Kim Dong-Joo , Liaw Peter K. , Song Gian , Lee Chanho
Published: January 2024

Extensive research has been conducted on Ti–Fe–Sn ultrafine eutectic composites due to their high yield strength, compared to conventional microcrystalline alloys. The unique microstructure of ultrafine eutectic composites, which consists of the ultrafine-grained lamella matrix with the formation of primary dendrites, leads to high strength and desirable plasticity. A lamellar structure is known for its high strength with limited plasticity, owing to its interface-strengthening effect. Thus, extensive efforts have been conducted to induce the lamellar structure and control the volume fraction of primary dendrites to enhance plasticity by tailoring the compositions. In this study, however, it was found that not only the volume fraction of primary dendrites but also the morphology of dendrites constitute key factors in inducing excellent ductility. We selected three compositions of Ti–Fe–Sn ultrafine eutectic composites, considering the distinct volume fractions and morphologies of β-Ti dendrites based on the Ti–Fe–Sn ternary phase diagram. As these compositions approach quasi-peritectic reaction points, the α″-Ti martensitic phase forms within the primary β-Ti dendrites due to under-cooling effects. This pre-formation of the α″-Ti martensitic phase effectively governs the growth direction of β-Ti dendrites, resulting in the development of round-shaped primary dendrites during the quenching process. These microstructural evolutions of β-Ti dendrites, in turn, lead to an improvement in ductility without a significant compromise in strength. Hence, we propose that fine-tuning the composition to control the primary dendrite morphology can be a highly effective alloy design strategy, enabling the attainment of greater macroscopic plasticity without the typical ductility and strength trade-off.
Water Exchange from the Buried Binding Sites of Cytochrome P450 Enzymes 1A2, 2D6, and 3A4 Correlates with Conformational Fluctuations
Authors: Guvench Olgun
Published: January 2024

Human cytochrome P450 enzymes (CYPs) are critical for the metabolism of small-molecule pharmaceuticals (drugs). As such, the prediction of drug metabolism by and drug inhibition of CYP activity is an important component of the drug discovery and design process. Relative to the availability of a wide range of experimental atomic-resolution CYP structures, the development of structure-based CYP activity models has been limited. To better characterize the role of CYP conformational fluctuations in CYP activity, we perform multiple microsecond-scale all-atom explicit-solvent molecular dynamics (MD) simulations on three CYP isoforms, 1A2, 2D6, and 3A4, which together account for the majority of CYP-mediated drug metabolism. The MD simulations employ a variety of positional restraints, ranging from keeping all CYP atoms close to their experimentally determined coordinates to allowing full flexibility. We find that, with full flexibility, large fluctuations in the CYP binding sites correlate with efficient water exchange from these buried binding sites. This is especially true for 1A2, which, when restrained to its crystallographic conformation, is unable to exchange water between the binding site and bulk solvent. These findings imply that, in addition to crystal structures, a representative ensemble of conformational states ought to be included when developing structure-based CYP activity models.
The Sixth Brainstorming Research Assembly for Young Neuroscientists (BraYn), Naples, Italy, 27–29 September 2023
Authors: Ferrara Giovanni
Published: January 2024

The BraYn association aims to bolster young neuroscientists’ research endeavors through collaborative support, fundraising assistance, and events promoting knowledge exchange and collaboration across Europe. Central to its mission is the annual BraYn conference, tailored for PhD students, postdocs, junior PIs, neurologists, and clinicians. This gathering champions cooperation, offering talks by key figures, educational workshops, and opportunities for attendees to present their work, compete for grants, and engage in international scientific experiences. The conference, established in 2018, has grown substantially in attendance and industry support and was adapted during the pandemic with virtual editions. The last sixth edition in Naples (27–29 September 2023) attracted over 300 delegates, focusing on peer-to-peer discussions, interdisciplinary collaboration, and interaction with renowned speakers, solidifying its place as a flagship event for Europe’s budding neuroscience researchers.
Rapamycin as a Potential Alternative Drug for Squamous Cell Gingiva Carcinoma (Ca9-22): A Focus on Cell Cycle, Apoptosis and Autophagy Genetic Profile
Authors: Papadakos Sofia , Issa Hawraa , Alamri Abdulaziz , Alamri Abdullah , Semlali Abdelhabib
Published: January 2024

Oral cancer is considered as one of the most common malignancies worldwide. Its conventional treatment primarily involves surgery with or without postoperative adjuvant therapy. The targeting of signaling pathways implicated in tumorigenesis is becoming increasingly prevalent in the development of new anticancer drug candidates. Based on our recently published data, Rapamycin, an inhibitor of the mTOR pathway, exhibits selective antitumor activity in oral cancer by inhibiting cell proliferation and inducing cancer cell apoptosis, autophagy, and cellular stress. In the present study, our focus is on elucidating the genetic determinants of Rapamycin’s action and the interaction networks accountable for tumorigenesis suppression. To achieve this, gingival carcinoma cell lines (Ca9-22) were exposed to Rapamycin at IC50 (10 µM) for 24 h. Subsequently, we investigated the genetic profiles related to the cell cycle, apoptosis, and autophagy, as well as gene–gene interactions, using QPCR arrays and the Gene MANIA website. Overall, our results showed that Rapamycin at 10 µM significantly inhibits the growth of Ca9-22 cells after 24 h of treatment by around 50% by suppression of key modulators in the G2/M transition, namely, Survivin and CDK5RAP1. The combination of Rapamycin with Cisplatin potentializes the inhibition of Ca9-22 cell proliferation. A P1/Annexin-V assay was performed to evaluate the effect of Rapamycin on cell apoptosis. The results obtained confirm our previous findings in which Rapamycin at 10 μM induces a strong apoptosis of Ca9-22 cells. The live cells decreased, and the late apoptotic cells increased when the cells were treated by Rapamycin. To identify the genes responsible for cell apoptosis induced by Rapamycin, we performed the RT2 Profiler PCR Arrays for 84 apoptotic genes. The blocked cells were believed to be directed towards cell death, confirmed by the downregulation of apoptosis inhibitors involved in both the extrinsic and intrinsic pathways, including BIRC5, BNIP3, CD40LG, DAPK1, LTA, TNFRSF21 and TP73. The observed effects of Rapamycin on tumor suppression are likely to involve the autophagy process, evidenced by the inhibition of autophagy modulators (TGFβ1, RGS19 and AKT1), autophagosome biogenesis components (AMBRA1, ATG9B and TMEM74) and autophagy byproducts (APP). Identifying gene–gene interaction (GGI) networks provided a comprehensive view of the drug’s mechanism and connected the studied tumorigenesis processes to potential functional interactions of various kinds (physical interaction, co-expression, genetic interactions etc.). In conclusion, Rapamycin shows promise as a clinical agent for managing Ca9-22 gingiva carcinoma cells.
Exploring Potentilla nepalensis Phytoconstituents: Integrated Strategies of Network Pharmacology, Molecular Docking, Dynamic Simulations, and MMGBSA Analysis for Cancer Therapeutic Targets Discovery
Authors: Praveen Mallari , Ullah Ihsan , Buendia Ricardo , Khan Imran Ahmad , Sayed Mian Gul , Kabir Rahmul , Bhat Mashooq Ahmad , Yaseen Muhammad
Published: January 2024

Potentilla nepalensis belongs to the Rosaceae family and has numerous therapeutic applications as potent plant-based medicine. Forty phytoconstituents (PCs) from the root and stem through n-hexane (NR and NS) and methanolic (MR and MS) extracts were identified in earlier studies. However, the PCs affecting human genes and their roles in the body have not previously been disclosed. In this study, we employed network pharmacology, molecular docking, molecular dynamics simulations (MDSs), and MMGBSA methodologies. The SMILES format of PCs from the PubChem was used as input to DIGEP-Pred, with 764 identified as the inducing genes. Their enrichment studies have shown inducing genes’ gene ontology descriptions, involved pathways, associated diseases, and drugs. PPI networks constructed in String DB and network topological analyzing parameters performed in Cytoscape v3.10 revealed three therapeutic targets: TP53 from MS-, NR-, and NS-induced genes; HSPCB and Nf-kB1 from MR-induced genes. From 40 PCs, two PCs, 1b (MR) and 2a (MS), showed better binding scores (kcal/mol) with p53 protein of −8.6 and −8.0, and three PCs, 3a, (NR) 4a, and 4c (NS), with HSP protein of −9.6, −8.7, and −8.2. MDS and MMGBSA revealed these complexes are stable without higher deviations with better free energy values. Therapeutic targets identified in this study have a prominent role in numerous cancers. Thus, further investigations such as in vivo and in vitro studies should be carried out to find the molecular functions and interlaying mechanism of the identified therapeutic targets on numerous cancer cell lines in considering the PCs of P. nepalensis.
LC-AMP-F1 Derived from the Venom of the Wolf Spider Lycosa coelestis, Exhibits Antimicrobial and Antibiofilm Activities
Authors: Song Yuxin , Wang Junyao , Liu Xi , Yu Shengwei , Tang Xing , Tan Huaxin
Published: January 2024

In recent years, there has been a growing interest in antimicrobial peptides as innovative antimicrobial agents for combating drug-resistant bacterial infections, particularly in the fields of biofilm control and eradication. In the present study, a novel cationic antimicrobial peptide, named LC-AMP-F1, was derived from the cDNA library of the Lycosa coelestis venom gland. The sequence, physicochemical properties and secondary structure of LC-AMP-F1 were predicted and studied. LC-AMP-F1 was tested for stability, cytotoxicity, drug resistance, antibacterial activity, and antibiofilm activity in vitro compared with melittin, a well-studied antimicrobial peptide. The findings indicated that LC-AMP-F1 exhibited inhibitory effects on the growth of various bacteria, including five strains of multidrug-resistant bacteria commonly found in clinical settings. Additionally, LC-AMP-F1 demonstrated effective inhibition of biofilm formation and disruption of mature biofilms. Furthermore, LC-AMP-F1 exhibited favorable stability, minimal hemolytic activity, and low toxicity towards different types of eukaryotic cells. Also, it was found that the combination of LC-AMP-F1 with conventional antibiotics exhibited either synergistic or additive therapeutic benefits. Concerning the antibacterial mechanism, scanning electron microscopy and SYTOX Green staining results showed that LC-AMP-F1 increased cell membrane permeability and swiftly disrupted bacterial cell membranes to exert its antibacterial effects. In summary, the findings and studies facilitated the development and clinical application of novel antimicrobial agents.
Chemistry and Art of Developing Lipid Nanoparticles for Biologics Delivery: Focus on Development and Scale-Up
Authors: John Rijo , Monpara Jasmin , Swaminathan Shankar , Kalhapure Rahul
Published: January 2024

Lipid nanoparticles (LNPs) have gained prominence as primary carriers for delivering a diverse array of therapeutic agents. Biological products have achieved a solid presence in clinical settings, and the anticipation of creating novel variants is increasing. These products predominantly encompass therapeutic proteins, nucleic acids and messenger RNA. The advancement of efficient LNP-based delivery systems for biologics that can overcome their limitations remains a highly favorable formulation strategy. Moreover, given their small size, biocompatibility, and biodegradation, LNPs can proficiently transport therapeutic moiety into the cells without significant toxicity and adverse reactions. This is especially crucial for the existing and upcoming biopharmaceuticals since large molecules as a group present several challenges that can be overcome by LNPs. This review describes the LNP technology for the delivery of biologics and summarizes the developments in the chemistry, manufacturing, and characterization of lipids used in the development of LNPs for biologics. Finally, we present a perspective on the potential opportunities and the current challenges pertaining to LNP technology.
Biodegradable Polymer Packaging System for ‘Benitaka’ Table Grapes during Cold Storage
Authors: Silva Ricardo Josue , de Aguiar Aline Cristina , Simões Bruno Matheus , da Silva Samuel Camilo , Higuchi Maíra Tiaki , Roberto Sergio Ruffo , Yamashita Fabio
Published: January 2024

A biodegradable polymer packaging system for ‘Benitaka’ table grapes (Vitis vinifera L.) was developed to inhibit the development of gray mold during refrigerated storage. The system consisted of packages and sachets containing Na2S2O5 to release sulfur dioxide (SO2), both produced with biodegradable films of starch, glycerol, and poly (adipate co-butylene terephthalate) (PBAT) produced via blown extrusion. The films were characterized in terms of thickness, density, mass loss in water, water vapor permeability, sorption isotherms, and mechanical properties. The table grapes were packed with biodegradable plastic bags containing SO2-releasing sachets inside. The experimental design was completely randomized, with four repetitions and five treatments: (a) control, without sachet containing Na2S2O5 and SiO2; (b) 2 g of Na2S2O5 + 2 g of SiO2; (c) 4 g of Na2S2O5 + 1 g of SiO2; (d) 4 g of Na2S2O5 + 2 g of SiO2; and (e) 4 g of Na2S2O5 + 4 g of SiO2. The bunches were stored in a refrigerated chamber at 1 ± 1 °C and relative humidity above 90%. The treatments were evaluated 30 and 45 days after the beginning of refrigerated storage and 3 days at room temperature. The grapes were evaluated based on the incidence of gray mold, mass loss, stem browning, shattered berries, and berry bleaching. The data were subjected to the analysis of variance, and the means were compared using Tukey’s test at 5%. The biodegradable films had good processability during the production via blown extrusion, with good physical properties to be used in the packaging of grapes and the production of SO2-releasing sachets. The biodegradable polymer packaging system (biodegradable plastic bags + SO2-releasing sachets) inhibited the development of gray mold on ‘Benitaka’ table grapes for 45 days at 1 °C, preserving their quality, with low mass loss, few shattered berries, and rachis freshness.
Development of a UiO-66 Based Waterborne Flame-Retardant Coating for PC/ABS Material
Authors: Chen Shaojun , Zeng Youhan , Bi Weifeng , Zhuo Haitao , Zhong Haiqiang
Published: January 2024

The flame-retardancy of polymeric materials has garnered great interest. Most of the flame retardants used in copolymers are functionalized additives, which can deteriorate the intrinsic properties of these materials. As a new type of flame retardant, functionalized metal–organic frameworks (MOFs) can be used in surface coatings of polymers. To reduce the flammability, a mixture of phytic acid, multi-wall carbon nanotubes, zirconium-based MOFs, and UiO-66 was coated on a PC/ABS substrate. The structure of the UiO-66-based flame retardant was established by FT-IR, XRD, XPS, and SEM. The flammable properties of coated PC/ABS materials were assessed by LOI, a vertical combustion test, TGA, CCT, and Raman spectroscopy. The presence of a UiO-66-based coating on the PC/ABS surface resulted in a good flame-retardant performance. Heat release and smoke generation were significantly reduced. Importantly, the structure and mechanical properties of PC/ABS were less impacted by the presence of the flame-retardant coating. Hence, this work presents a new strategy for the development of high-performance PC/ABC materials with both excellent flame-retardancy and good mechanical properties.
Influence of Novel SrTiO3/MnO2 Hybrid Nanoparticles on Poly(methyl methacrylate) Thermal and Mechanical Behavior
Authors: Elhmali Houda Taher , Stajcic Ivana , Stajcic Aleksandar , Pesic Ivan , Jovanovic Marija , Petrovic Milos , Radojevic Vesna
Published: January 2024

While dental poly methyl methacrylate(PMMA) possesses distinctive qualities such as ease of fabrication, cost-effectiveness, and favorable physical and mechanical properties, these attributes alone are inadequate to impart the necessary impact strength and hardness. Consequently, pure PMMA is less suitable for dental applications. This research focused on the incorporation of Strontium titanate (SrTiO3-STO) and hybrid filler STO/Manganese oxide (MnO2) to improve impact resistance and hardness. The potential of STO in reinforcing PMMA is poorly investigated, while hybrid filler STO/MnO2 has not been presented yet. Differential scanning calorimetry is conducted in order to investigate the agglomeration influence on the PMMA glass transition temperature (Tg), as well as the leaching of residual monomer and volatile additives that could pose a threat to human health. It has been determined that agglomeration with 1 wt% loading had no influence on Tg, while the first scan revealed differences in evaporation of small molecules, in favor of composite PMMA-STO/MnO2, which showed the trapping potential of volatiles. Investigations of mechanical properties have revealed the significant influence of hybrid STO/MnO2 filler on microhardness and total absorbed impact energy, which were increased by 89.9% and 145.4%, respectively. Results presented in this study revealed the reinforcing potential of hybrid nanoparticles that could find application in other polymers as well.
Correction: Zhu et al. Mineralized Collagen/Polylactic Acid Composite Scaffolds for Load-Bearing Bone Regeneration in a Developmental Model. Polymers 2023, 15, 4194
Authors: Zhu Wenbo , Li Wenjing , Yao Mengxuan , Wang Yan , Zhang Wei , Li Chao , Wang Xiumei , Chen Wei , Lv Hongzhi
Published: January 2024

In the original publication [...]
Repair of Infected Bone Defects with Hydrogel Materials
Authors: Cao Zhenmin , Qin Zuodong , Duns Gregory J. , Huang Zhao , Chen Yao , Wang Sheng , Deng Ruqi , Nie Libo , Luo Xiaofang
Published: January 2024

Infected bone defects represent a common clinical condition involving bone tissue, often necessitating surgical intervention and antibiotic therapy. However, conventional treatment methods face obstacles such as antibiotic resistance and susceptibility to postoperative infections. Hydrogels show great potential for application in the field of tissue engineering due to their advantageous biocompatibility, unique mechanical properties, exceptional processability, and degradability. Recent interest has surged in employing hydrogels as a novel therapeutic intervention for infected bone repair. This article aims to comprehensively review the existing literature on the anti-microbial and osteogenic approaches utilized by hydrogels in repairing infected bones, encompassing their fabrication techniques, biocompatibility, antimicrobial efficacy, and biological activities. Additionally, the potential opportunities and obstacles in their practical implementation will be explored. Lastly, the limitations presently encountered and the prospective avenues for further investigation in the realm of hydrogel materials for the management of infected bone defects will be deliberated. This review provides a theoretical foundation and advanced design strategies for the application of hydrogel materials in the treatment of infected bone defects.
Effects of the PMMA Molecular Weight on the Thermal and Thermo-Oxidative Decomposition as the First Chemical Stage of Flaming Ignition
Authors: Galgano Antonio , Di Blasi Colomba
Published: January 2024

The piloted and the spontaneous ignition of low and high molecular weight (LMW and HMW) polymethyl methacrylate are simulated using a one-dimensional condensed-gas phase model for constant heat fluxes in the range of 25–150 kW/m2. Purely thermal (nitrogen) and thermo-oxidative (air) decomposition is considered, described by a single and four-step kinetics for the low and high molecular weight polymer, respectively. Different optical properties are also examined. The same trends of the ignition time and other ignition parameters are always observed. Due to a more significant role of the chemical kinetics, the effects of the sample molecular weight and reaction atmosphere are higher at low heat fluxes. Times are shorter for the black HMW samples and thermo-oxidative kinetics. For piloted ignition, factors are around 2.8–1.6, whereas for thermal decomposition, they are 1.3–1.2. The corresponding figures are 1.8–1.3 and 1.3–1.1, in the same order, for the spontaneous ignition. Overall, the effects of the molecular weight are more important than those related to the reaction kinetics environment. These differences are confirmed by the comparison between predictions and measurements.
Orthodoxy in China and the West: The Jesuit Interpretation of Analects 2.16
Authors: Qi Feizhi
Published: January 2024

The Confucius Sinarum Philosophus (1687) resulted from Jesuit research into Chinese classical texts. Upon its publication, the work conformed to the Jesuits’ accommodationist policy, facing challenges over its orthodoxy from both China and the West. The Latin translation and commentary on Analects 2.16 mirror these challenges and the Jesuit rebuttal. Compared to earlier translations, this version adheres more closely to traditional Chinese exegesis and participates actively in historical debates over orthodoxy. The annotations also delineate the heterodox teachings of the Yang (楊), Mo (墨), Daoist, and Buddhist schools, juxtaposing them with Confucianism, which they portray as a natural law to be perfected. The inclusion of these four heterodoxies introduces a novel aspect to Christian heresiology, while the portrayal of Confucianism assimilates it into the Christian orthodox framework. This article contends that the translation and commentary exemplify the Jesuits’ efforts to establish orthodoxy within both Chinese and Western contexts.
Driver-Centric Urban Route Planning: Smart Search for Parking
Authors: Ćelić Jasmin , Mandžuka Bia , Tomas Vinko , Tadić Frane
Published: January 2024

With urbanization, there is a growing need for mobility. Challenges for urban drivers include finding available parking spaces. Searching for a parking spot can be a frustrating experience, often time consuming and costly. Also, the increasing number of vehicles on the roads leads to an additional strain on traffic flow, while the search for parking spaces lowers the level of service. In inner cities, vehicles circulate in search of an available parking space, leading to an increase in travel time, fuel consumption, pollutant emissions, and a decrease in traffic safety. The search for a free parking space generates a significant increase in traffic in urban areas. To solve the parking search problem, it is necessary to develop certain strategies and measures that minimize circling in search of a parking space. The implementation of intelligent transportation systems stands out. By applying intelligent transport systems, drivers are provided with information about free parking spaces, which reduces the circulation of vehicles in search of free parking. Although initially ITS systems mainly provided services for closed parking lots and garages, with the further development of the system, the service was extended to street parking lots or open-type parking lots. These measures not only solve traffic challenges but also promote sustainability in urban areas. This article analyzes the effect of a cooperative approach of guiding vehicles to available parking spaces compared to a standard model of searching for an available parking space. Within the framework of the advanced model for searching for available space, four parking demand scenarios were defined and simulated. Based on the created traffic simulation, a comparative analysis was made between the classic and cooperative approach, while the primary differences are manifested in the load of the traffic flow A simulation model was developed using the road network from the urban center of Zagreb.
Alternative Forms of Tourism: A Comparative Study of Website Effectiveness in Promoting UNESCO Global Geoparks and International Dark Sky Parks
Authors: Xanthakis Michael , Simatou Androniki , Antonopoulos Nikos , Kanavos Andreas , Mylonas Naoum
Published: January 2024

In the digital age, effective website promotion plays a pivotal role in attracting visitors to alternative forms of tourism. This study examines the websites of 177 UNESCO Global Geoparks and 190 International Dark Sky Parks, employing specific evaluation criteria essential for enhancing the promotion of alternative tourism forms such as geotourism and astronomical tourism. Our findings reveal that geopark websites adeptly promote geotourism through a diverse array of digital tools, with the potential for minor enhancements. In contrast, the majority of dark sky park websites exhibit limited visibility in the promotion of astronomical tourism. These identified criteria and results serve as crucial benchmarks for optimizing the websites of UNESCO Global Geoparks and International Dark Sky Parks, thus ensuring the comprehensive fulfillment of established promotional standards for alternative tourism destinations.
Research on the Manufacturer’s Strategies under Different Supply Interruption Risk Based on Supply Chain Resilience
Authors: Ji Guojun , Hong Wen
Published: January 2024

In order to study the selection of coping strategies for the manufacturer facing different supply interruption risks, this paper constructs a supply chain consisting of one manufacturer and one supplier and uses no-taking coping strategies as the benchmark model to analyze the resilience of supply chain formed by the manufacturer’s adoption of penalty mechanism, emergency supplier mechanism, and strategic investment mechanism. The research shows that in the face of various levels of supply interruption risk, the manufacturer adopting a strategic investment mechanism will achieve high resilience, enabling the manufacturer and supplier to achieve mutual benefit and win-win results. In some cases of high interruption risk, the manufacturer adopting an emergency supplier mechanism can achieve higher chain resilience compared with not taking emergency measures, but its ability to improve supply chain resilience is weaker than that of a strategic investment mechanism. The penalty mechanism is applicable to situations where some interruption risk is characterized by low risk, and in such cases, both the penalty mechanism and the strategic investment mechanism can enhance the resilience of the supply chain.
Genomic Characterization and Molecular Evolution of Sapovirus in Children under 5 Years of Age
Authors: Ji Xiaolei , Guo Chen , Dai Yaoyao , Chen Lu , Chen Yujia , Wang Shifang , Sun Yihua
Published: January 2024

Sapovirus (SaV) is a type of gastroenteric virus that can cause acute gastroenteritis. It is highly contagious, particularly among children under the age of 5. In this study, a total of 712 stool samples from children under the age of 5 with acute gastroenteritis were collected. Out of these samples, 28 tested positive for SaV, resulting in a detection rate of 3.93% (28/712). Samples with Ct < 30 were collected for library construction and high-throughput sequencing, resulting in the acquisition of nine complete genomes. According to Blast, eight of them were identified as GI.1, while the remaining one was GI.6. The GI.6 strain sequence reported in our study represents the first submission of the GI.6 strain complete genome sequence from mainland China to the Genbank database, thus filling the data gap in our country. Sequence identity analysis revealed significant nucleotide variations between the two genotypes of SaV and their corresponding prototype strains. Phylogenetic and genetic evolution analyses showed no evidence of recombination events in the obtained sequences. Population dynamics analysis demonstrated potential competitive inhibition between two lineages of GI.1. Our study provides insights into the molecular epidemiological and genetic evolution characteristics of SaV prevalent in the Nantong region of China, laying the foundation for disease prevention and control, as well as pathogen tracing related to SaV in this area.
Sulfadiazine and Nitrogen Removal Performance and Mechanisms of a Saline-Resistant Strain of Acinetobacter sp. RT-6
Authors: Zhu Xiaoqiang , Wang Guobin , Xie Jieyun , Zhao Ya , Liang Donghui
Published: January 2024

The main goal of this article is to elucidate the SDZ and TN removal characteristics and mechanisms of a saline-resistant strain of Acinetobacter sp. RT-6. The SDZ and TN removal characteristics indicated that SDZ and TN removal were significantly affected by SDZ concentration and salinity. The removal curves and kinetics of different typical amounts of nitrogen showed the shortcut nitrification and denitrification present in the ammonia-N removal process; the nitrogen-containing compound was mainly transformed into N2, and approximately 19.05 ± 0.83 mM of the electrons was transferred to the nitrate respiratory chain. The intermediates of SDZ degradation were identified, and it was speculated that the main reaction sites for SDZ transformation were the N–C bond, N–S bond, pyrimidine ring, and benzene ring.
Water Performance Indicators and Benchmarks for Dairy Production Systems
Authors: Palhares Julio Cesar Pascale , Matarim Danielle Leal , de Sousa Rafael Vieira , Martello Luciane Silva
Published: January 2024

The aim of the study is to discern benchmarks for the indicators L water cow−1 day−1 and L water kg milk−1 day−1 per type of production system and season. A total of 876 commercial dairy farms underwent comprehensive water consumption monitoring from January 2021 to December 2022. The monitored water consumptions were animal drinking water and water usage for cleaning. Confined systems exhibited the highest average for animal drinking and cleaning, 87.5 L water cow−1 day−1 and 84.4 L water cow−1 day−1, respectively. Semi-confined systems presented the lowest average for animal drinking, 54.4 L water cow−1 day−1. Pasture systems showed the lowest average for cleaning, 45.2 L water cow−1 day−1. The benchmarks proposed in this study can serve as the first references for animal drinking and milking parlor washing consumption for production systems in tropical conditions.