bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Dynamics Simulation Combined with Neural Relationship Inference and Markov Model to Reveal the Relationship between Conformational Regulation and Bioluminescence Properties of Gaussia Luciferase
Authors: Yang Xiaotang , Zhang Ruoyu , Han Weiwei , Han Lu
Published: August 2024

Gaussia luciferase (Gluc) is currently known as the smallest naturally secreted luciferase. Due to its small molecular size, high sensitivity, short half-life, and high secretion efficiency, it has become an ideal reporter gene and is widely used in monitoring promoter activity, studying protein-protein interactions, protein localization, high-throughput drug screening, and real-time monitoring of tumor occurrence and development. Although studies have shown that different Gluc mutations exhibit different bioluminescent properties, their mechanisms have not been further investigated. The purpose of this study is to reveal the relationship between the conformational changes of Gluc mutants and their bioluminescent properties through molecular dynamics simulation combined with neural relationship inference (NRI) and Markov models. Our results indicate that, after binding to the luciferin coelenterazine (CTZ), the α-helices of the 109–119 residues of the Gluc Mutant2 (GlucM2, the flash-type mutant) are partially unraveled, while the α-helices of the same part of the Gluc Mutant1 (GlucM1, the glow-type mutant) are clearly formed. The results of Markov flux analysis indicate that the conformational differences between glow-type and flash-type mutants when combined with luciferin substrate CTZ mainly involve the helicity change of α7. The most representative conformation and active pocket distance analysis indicate that compared to the flash-type mutant GlucM2, the glow-type mutant GlucM1 has a higher degree of active site closure and tighter binding. In summary, we provide a theoretical basis for exploring the relationship between the conformational changes of Gluc mutants and their bioluminescent properties, which can serve as a reference for the modification and evolution of luciferases.
Highly Efficient CoFeP Nanoparticle Catalysts for Superior Oxygen Evolution Reaction Performance
Authors: Meena Abhishek , Ahmed Abu Talha Aqueel , Singh Aditya Narayan , Sree Vijaya Gopalan , Im Hyunsik , Cho Sangeun
Published: August 2024

Developing effective and long-lasting electrocatalysts for oxygen evolution reaction (OER) is critical for increasing sustainable hydrogen production. This paper describes the production and characterization of CoFeP nanoparticles (CFP NPs) as high-performance electrocatalysts for OER. The CFP NPs were produced using a simple hydrothermal technique followed by phosphorization, yielding an amorphous/crystalline composite structure with improved electrochemical characteristics. Our results reveal that CFP NPs have a surprisingly low overpotential of 284 mV at a current density of 100 mA cm−2, greatly exceeding the precursor CoFe oxide/hydroxide (CFO NPs) and the commercial RuO2 catalyst. Furthermore, CFP NPs demonstrate exceptional stability, retaining a constant performance after 70 h of continuous operation. Post-OER characterization analysis revealed transformations in the catalyst, including the formation of cobalt–iron oxides/oxyhydroxides. Despite these changes, CFP NPs showed superior long-term stability compared to native metal oxides/oxyhydroxides, likely due to enhanced surface roughness and increased active sites. This study proposes a viable strategy for designing low-cost, non-precious metal-based OER catalysts, which will help advance sustainable energy technology.
Optical Characterization of the Interband Cascade LWIR Detectors with Type-II InAs/InAsSb Superlattice Absorber
Authors: Murawski Krzysztof , Majkowycz Kinga , Kopytko Małgorzata , Manyk Tetiana , Dąbrowski Karol , Seredyński Bartłomiej , Kubiszyn Łukasz , Martyniuk Piotr
Published: August 2024

The long-wave infrared (LWIR) interband cascade detector with type-II superlattices (T2SLs) and a gallium-free (“Ga-free”) InAs/InAsSb (x = 0.39) absorber was characterized by photoluminescence (PL) and spectral response (SR) methods. Heterostructures were grown by molecular beam epitaxy (MBE) on a GaAs substrate (001) orientation. The crystallographic quality was confirmed by high-resolution X-Ray diffraction (HRXRD). Two independent methods, combined with theoretical calculations, were able to determine the transitions between the superlattice minibands. Moreover, transitions from the trap states were determined. Studies of the PL intensity as a function of the excitation laser power allowed the identification of optical transitions. The determined effective energy gap (Eg) of the tested absorber layer was 116 meV at 300 K. The transition from the first light hole miniband to the first electron miniband was red-shifted by 76 meV. The detected defects’ energy states were constant versus temperature. Their values were 85 meV and 112 meV, respectively. Moreover, two additional transitions from acceptor levels in cryogenic temperature were determined by being shifted from blue to Eg by 6 meV and 16 meV, respectively.
Recent Advances in Graphene Adaptive Thermal Camouflage Devices
Authors: Sansone Lucia , Loffredo Fausta , Cilento Fabrizia , Miscioscia Riccardo , Martone Alfonso , Barrella Nicola , Paulillo Bruno , Bassano Alessio , Villani Fulvia , Giordano Michele
Published: August 2024

Thermal camouflage is a highly coveted technology aimed at enhancing the survivability of military equipment against infrared (IR) detectors. Recently, two-dimensional (2D) nanomaterials have shown low IR emissivity, widely tunable opto-electronic properties, and compatibility with stealth applications. Among these, graphene and graphene-like materials are the most appealing 2D materials for thermal camouflage applications. In multilayer graphene (MLG), charge density can be effectively tuned through sufficiently intense electric fields or through electrolytic gating. Therefore, MLG’s optical properties, like infrared emissivity and absorbance, can be controlled in a wide range by voltage bias. The large emissivity modulation achievable with this material makes it suitable in the design of thermal dynamic camouflage devices. Generally, the emissivity modulation in the multilayered graphene medium is governed by an intercalation process of non-volatile ionic liquids under a voltage bias. The electrically driven reduction of emissivity lowers the apparent temperature of a surface, aligning it with the background temperature to achieve thermal camouflage. This characteristic is shared by other graphene-based materials. In this review, we focus on recent advancements in the thermal camouflage properties of graphene in composite films and aerogel structures. We provide a summary of the current understanding of how thermal camouflage materials work, their present limitations, and future opportunities for development.
The Circulating miR-107 as a Potential Biomarker Up-Regulated in Castration-Resistant Prostate Cancer
Authors: Puente-Rivera Jonathan , De la Rosa Pérez David Alejandro , Olvera Stephanie I. Nuñez , Figueroa-Angulo Elisa Elvira , Saucedo José Gadú Campos , Hernández-León Omar , Alvarez-Sánchez María Elizbeth
Published: August 2024

Prostate cancer (PCa) is a prevalent malignancy in men globally. Current diagnostic methods like PSA testing have limitations, leading to overdiagnosis and unnecessary treatment. Castration-resistant prostate cancer (CRPC) emerges in some patients receiving androgen deprivation therapy (ADT). This study explores the potential of circulating microRNA-107 (miR-107) in liquid biopsies as a prognosis tool to differentiate CRPC from non-castration-resistant PCa (NCRPC). We designed a case-control study to evaluate circulating miR-107 in serum as a potential prognosis biomarker. We analyzed miR-107 expression in liquid biopsies and found significantly higher levels (p < 0.005) in CRPC patients, compared to NCRPC. Notably, miR-107 expression was statistically higher in the advanced stage (clinical stage IV), compared to stages I–III. Furthermore, CRPC patients exhibited significantly higher miR-107 levels (p < 0.05), compared to NCRPC. These findings suggest that miR-107 holds promise as a non-invasive diagnostic biomarker for identifying potential CRPC patients.
Comparative Analysis of Nutritional Advice and a Combined Approach for Addressing Impending Stunting in Infants: A Clinical Trial
Authors: Tanjung Conny , Fikri Bahrul , Prawitasari Titis , Massi Nasrum , Zainuddin Andi Alfian , Juliaty Aidah , Yullyana Dwi Sora , Dwitya Sarah , Shimojo Naoki , Ohno Hiroshi , Koletzko Berthold
Published: August 2024

Weight faltering (WF) has been associated with stunting and with long-term adverse consequences for health and development. Nutritional care for managing WF may consist of giving nutritional advice (NA) and/or provision of oral nutrition supplements (ONSs). In this study, we aimed to evaluate practical management options in the community for infants with WF aged 6–12 months. This nonrandomized clinical trial was conducted in the community of Makassar, South Sulawesi, from March 2022 to March 2023. A total of 1013 infants were enrolled for screening. Anthropometric measures were performed in 913 infants, of which 170 showed WF below the 15th percentile of the WHO weight increment table without stunting. Infants with a weight increment below P5th were assigned to receive NA plus ONS, while infants between P5th and below P15th were assigned to receive only NA. At the second and third months, ONSs were administered to WF infants who were below P15th. One month after the intervention, 87/105 infants in the NA-plus-ONS group (82.8%) and 52/65 infants in the NA-only group (80%) were no longer WF. After 3 months, infants in the NA-plus-ONS group achieved greater weight gain than infants in the NA group (264.1 g vs. 137.4 g, p < 0.001) as well as greater length gain (2.35 cm vs. 2.14 cm, p < 0.001). WF management should be started at below P15th to achieve a better result. Infants with greater nutritional deficits should be assigned to receive the combination of NA plus ONSs to achieve a higher rate of resolution of growth.
In Vitro and In Silico Analysis of PTP1B Inhibitors from Cleistocalyx operculatus Leaves and Their Effect on Glucose Uptake
Authors: Ponce-Zea Jorge-Eduardo , Ryu Byeol , Lee Ju-Yong , Park Eun-Jin , Mai Van-Hieu , Doan Thi-Phuong , Lee Hee-Ju , Oh Won-Keun
Published: August 2024

As part of our ongoing research on new anti-diabetic compounds from ethnopharmacologically consumed plants, two previously undescribed lupane-type triterpenoids (1 and 2) with dicarboxylic groups, an undescribed nor-taraxastane-type triterpenoid (3), and 14 known compounds (4–17) were isolated from the leaves of Cleistocalyx operculatus. Extensive spectroscopic analysis (IR, HRESIMS, 1D, and 2D NMR) was used for structure elucidation, while the known compounds were compared to reference data reported in the scientific literature. All the isolates (1–17) were evaluated for their inhibitory effects on the protein tyrosine phosphatase 1B (PTP1B) enzyme. Compounds 6, 9, and 17 showed strong PTP1B inhibitory activities. The mechanism of PTP1B inhibition was studied through enzyme kinetic experiments. A non-competitive mechanism of inhibition was determined using Lineweaver–Burk plots for compounds 6, 9, and 17. Additionally, Dixon plots were employed to determine the inhibition constant. Further insights were gained through a structure–activity relationship study and molecular docking analysis of isolated compounds with the PTP1B crystal structure. Moreover, all isolates (1–17) were tested for their stimulatory effects on the uptake of 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose (2-NBDG) in differentiated 3T3-L1 adipocyte cells. Compounds 6, 13, and 17 exhibited strong glucose absorption stimulation activity in a dose-dependent manner.
Effectiveness of Zinc Supplementation for Sepsis Treatment: A Single-Center Retrospective Observational Study
Authors: Kim Muneyoshi , Maruhashi Takaaki , Asari Yasushi
Published: August 2024

Background: Zinc plays an important role in sepsis; however, the effectiveness of zinc supplementation and the appropriate dose remain unclear. This study aimed to verify the effectiveness of zinc supplementation and the appropriate dose in patients with sepsis. Methods: This single-center retrospective observational study included 247 patients with sepsis from 1 April 2015 to 31 March 2023 who were receiving ventilatory management. The patients were divided into three groups according to the zinc supplementation dose: <15 mg, 15–50 mg, and ≥50 mg. Results: The <15 mg, 15–50 mg, and ≥50 mg groups had 28 (19%), six (21%), and 16 deaths (22%) at discharge, with no statistically significant difference (p = 0.36). No statistically significant differences were observed in the length of intensive care unit (ICU) stay (p = 0.06). A higher supplementation dose corresponded with a statistically significant increase in blood zinc concentration in the first week (38.5 ± 16.6 µg/dL, 58.8 ± 19.7 µg/dL, 74.2 ± 22.5 µg/dL, respectively; p < 0.01) but not in the second or third weeks (p = 0.08, 0.19, respectively). Conclusions: Zinc supplementation did not reduce the mortality rate or length of ICU stay or contribute to an increased serum zinc concentration. High-dose zinc supplementation may not be effective during acute sepsis.
Update on Nutritional Advice Post-Heart Transplant: A Cross-Sectional Study across French-Speaking European Centers
Authors: Bonnet Jean-Baptiste , Trémolières Claire , Furic-Bego Clémence , Galibert Laetitia , Sultan Ariane , Attalin Vincent , Avignon Antoine
Published: August 2024

Introduction: Heart transplantation is the standard treatment for severe heart failure. Graft preservation and infectious risk secondary to immunosuppressive drugs lead healthcare teams to offer nutritional advice to patients upon discharge from the hospital. However, no consensus or recommendation is available. Method: We conducted a study to review the practices in all 26 centers providing heart transplantation in French-speaking Europe. We requested and analyzed the written documents these centers provided to their patients. The same two dieticians categorized the highlighted pieces of advice into distinct, autonomous categories. Results: We identified 116 pieces of advice, categorized into three areas: dietary restrictions for immunosuppressant/food interaction; environmental and food preparation guidelines and prevention of foodborne infections; and healthy and active lifestyle recommendations. Except for advice on immunosuppressant/food interaction, over one-third of the centers suggest discontinuing advice within 2 years post-transplant. General dietary advice covers lipids, carbohydrates, protein, calcium, sodium, and fiber but offers limited guidance on fatty acids despite their importance in cardiovascular risk prevention. Conclusion: This study represents a pioneering exploration of the nutritional advice provided to patients following cardiac transplantation. It underscores the critical necessity of establishing consensus-based clinical guidelines in this domain.
Consumption of a Coffee Rich in Phenolic Compounds May Improve the Body Composition of People with Overweight or Obesity: Preliminary Insights from a Randomized, Controlled and Blind Crossover Study
Authors: Fernández-Cardero Álvaro , Sierra-Cinos José Luis , Bravo Laura , Sarriá Beatriz
Published: August 2024

This study analyzes the effects on body composition and variables related to metabolic syndrome of two coffees with different degree of roasting and phenolic content. Sixty participants with body mass index between 25 and 35 kg/m2 and a median age of 51.0 years (Interquartile range 46.3–56) were recruited. The study was a controlled, randomized, single-blind crossover trial consisting in drinking three cups/day of roasted coffee (RC) or lightly roasted coffee (LRC) during 12 weeks with 2-week wash-out stages before each coffee intervention. LRC contained ≈400 mg of hydroxycinnamic acids and ≈130 mg of caffeine per 200 mL/cup while RC contained ≈150 mg of hydroxycinnamic acids and ≈70 mg of caffeine per 200 mL/cup. Along the study, in each of the six visits, blood pressure, body composition by bioimpedance, anthropometric measurements, and blood biochemistry were analyzed. The mean differences and p values were calculated using a linear mixed model (JASP.v.0.18.0.3). A total of 38 participants completed the study. After the consumption of both coffees, fat mass and body fat percentage (LRC: −1.4%, p < 0.001; RC: −1.0%, p = 0.005) were reduced, whereas muscle mass and muscle mass percentage slightly increased (LRC: 0.8%, p < 0.001; RC: 0.7%, p = 0.002). The decrease in fat percentage was greater with LRC compared to RC (−0.8%; p = 0.029). There were no significant changes in metabolic syndrome variables or in body weight. In conclusion, LRC was slightly superior at inducing changes in body composition.
Evaluation of Chemical and Biological Products for Control of Crown Gall on Rose
Authors: Oksel Cansu , Liyanapathiranage Prabha , Parajuli Madhav , Avin Farhat A. , Jennings Christina , Simmons Terri , Baysal-Gurel Fulya
Published: August 2024

Crown gall is a soil-borne bacterial disease caused by Agrobacterium tumefaciens, leading to significant economic losses in many plant species. For the assessment of the biological and chemical products on crown gall, each plant’s crown region and roots were wounded, and then were dipped into their respective treatments. After the treatments, the plants were inoculated with a suspension of pathogenic A. tumefaciens isolate FBG1034 and maintained in a greenhouse for six months to assess them for gall formation. A quantitative real-time PCR assay was performed to quantify the A. tumefaciens using the chvE gene. Biological products such as the Agrobacterium radiobacter strain K1026, and strains 1 and 2, resulted in the lowest average root gall diameter and significantly reduced the crown gall diameter to stem diameter ratio, and the chemical product copper octanoate reduced the number of crown and root galls as well as the crown and root gall diameter compared to the inoculated, non-treated control. Moreover, both the A. radiobacter strain K1026 and strain 1 treatments resulted in an approximately 85% and 65% reduction in crown and root gall incidence, respectively, in both of the trials compared to the inoculated, non-treated plants. The findings of this study indicate that the use of biological and chemical products could help to suppress crown and root gall disease in rose plants.
Current Status of the Diagnosis of Brugia spp. Infections
Authors: Evans Christopher C. , Pilotte Nils , Moorhead Andrew R.
Published: August 2024

Filarial nematodes of the genus Brugia include parasites that are significant to both human and veterinary medicine. Accurate diagnosis is essential for managing infections by these parasites and supporting elimination programs. Traditional diagnostic methods, such as microscopy and serology, remain vital, especially in resource-limited settings. However, advancements in molecular diagnostics, including nucleic acid amplification tests, offer enhanced sensitivity and specificity. These techniques are becoming increasingly field-friendly, expanding their applications in diagnostics. By refining existing methods, developing novel biomarkers, and understanding the zoonotic potential of various Brugia species, it is possible to improve control measures and better support elimination efforts.
Filamentous Fungi Associated with Disease Symptoms in Non-Native Giant Sequoia (Sequoiadendron giganteum) in Germany—A Gateway for Alien Fungal Pathogens?
Authors: Langer Gitta Jutta , Bien Steffen , Bußkamp Johanna
Published: August 2024

Filamentous fungi associated with disease symptoms in non-native giant sequoia (Sequoiadendron giganteum) in Germany were investigated in ten cases of disease in Northwest Germany. During the study period from 2018 to 2023, a total of 81 species of Dikaria were isolated from woody tissue and needles of giant sequoia and morphotyped. Morphotypes were assigned to species designations based on ITS-sequence comparison and, in part, multi-locus phylogenetic analyses. Nine species were recognised as new reports for Germany or on giant sequoia: Amycosphaerella africana, Botryosphaeria parva, Coniochaeta acaciae, C. velutina, Muriformistrickeria rubi, Pestalotiopsis australis, P. monochaeta, Phacidiopycnis washingtonensis, and Rhizosphaera minteri. The threat posed to giant sequoia and other forest trees in Germany by certain, especially newly reported, fungal species is being discussed. The detection of a considerable number of new fungal records in the trees studied suggests that giant sequoia cultivation may be a gateway for alien fungal species in Germany.
Thiophene-Linked 1,2,4-Triazoles: Synthesis, Structural Insights and Antimicrobial and Chemotherapeutic Profiles
Authors: El-Emam Nada A. , El-Ashmawy Mahmoud B. , Mohamed Ahmed A. B. , Habib El-Sayed E. , Thamotharan Subbiah , Abdelbaky Mohammed S. M. , Garcia-Granda Santiago , Moustafa Mohamed A. A.
Published: August 2024

The reaction of thiophene-2-carbohydrazide 1 or 5-bromothiophene-2-carbohydrazide 2 with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 5a-e. The triazole derivatives 5a and 5b were reacted with different secondary amines and formaldehyde solution to yield the corresponding 2-aminomethyl-4-haloaryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones 6a–e, 7a–e, 8, 9, 10a and 10b in good yields. The in vitro antimicrobial activity of compounds 5a–e, 6a–e, 7a–d, 8, 9, 10a and 10b was evaluated against a panel of standard pathogenic bacterial and fungal strains. Compounds 5a, 5b, 5e, 5f, 6a–e, 7a–d, 8, 9, 10a and 10b showed marked activity, particularly against the tested Gram-positive bacteria and the Gram-negative bacteria Escherichia coli, and all the tested compounds were almost inactive against all the tested fungal strains. In addition, compounds 5e, 6a–e, 7a–d and 10a exhibited potent anti-proliferative activity, particularly against HepG-2 and MCF-7 cancer cell lines (IC50 < 25 μM). A detailed structural insight study based on the single crystals of compounds 5a, 5b, 6a, 6d and 10a is also reported. Molecular docking studies of the highly active antibacterial compounds 5e, 6b, 6d, 7a and 7d showed a high affinity for DNA gyrase. Meanwhile, the potent anti-proliferative activity of compounds 6d, 6e and 7d may be attributed to their high affinity for cyclin-dependent kinase 2 (CDK2).
Dexmedetomidine as Adjunctive Therapy for the Treatment of Alcohol Withdrawal Syndrome: A Systematic Review and Meta-Analysis
Authors: Fiore Marco , Alfieri Aniello , Torretta Giacomo , Passavanti Maria Beatrice , Sansone Pasquale , Pota Vincenzo , Simeon Vittorio , Chiodini Paolo , Corrente Antonio , Pace Maria Caterina
Published: August 2024

Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases where benzodiazepines are not adequate in controlling persistent autonomic hyperactivity or anxiety, dexmedetomidine could be utilized. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the ICUs, with the potential reduction in healthcare costs. The purpose of this systematic review and meta-analysis (PROSPERO CRD42018084370) is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care for the treatment of AWS. We retrieved literature from PubMed, EMBASE, and CENTRAL until 10 January 2024. Eligible studies were both randomized trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was tracheal intubation; secondary outcomes were (i) bradycardia and (ii) hypotension. A total of 3585 papers were retrieved: 2635 from EMBASE, 930 from Medline, and 20 from CENTRAL. After eliminating duplicates, 2960 papers were screened by title and abstract; 75 out of the 2960 papers were read in full text. The qualitative synthesis included nine of all manuscripts read in full text. The quantitative synthesis included eight studies for the primary outcome (tracheal intubation), seven for the secondary outcome bradycardia, and six for the secondary outcome hypotension. The meta-analysis showed that Dexmedetomidine, as adjunctive therapy, is not more effective than standard therapy in reducing the risk of tracheal intubation in AWS [RR: 0.57, 95% CI: 0.25–1.3, p = 0.15]. It also appears to be less safe than sedative therapy as it significantly increases the risk of bradycardia [RR: 2.68, 95% CI: 1.79–4.16, p = 0.0016]. Hypotension was not significantly different in patients who received dexmedetomidine [RR: 1.5, 95% CI: 0.69–3.49, p = 0.21].
Self-Microemulsifying Drug Delivery System to Enhance Oral Bioavailability of Berberine Hydrochloride in Rats
Authors: Chen Xiaolan , Yang Haifeng , Shi Longyu , Mao Yujuan , Niu Lin , Wang Jing , Chen Haifeng , Jia Jiping , Wang Jingxuan , Xue Jiajie , Shen Yan , Zheng Chunli , Tian Yu , Zheng Yi
Published: August 2024

Berberine hydrochloride (BH) is a versatile bioactive compound derived from the plants of the Berberis genus, known for its various pharmacological effects. However, its oral bioavailability is low due to its high hydrophilicity and limited permeability. To enhance its clinical efficacy and oral bioavailability, this study designed and prepared a BH-loaded self-microemulsifying drug delivery system (BH-SMEDDS), and characterized its in vitro and in vivo properties. Firstly, the optimal formulation of BH-SMEDDS was selected using solubility evaluations, pseudo-ternary phase diagrams, and particle size analysis. The formulation containing 55% Capmul MCM, 22.5% Kolliphor RH 40, and 22.5% 1,2-propanediol was developed. BH-SMEDDS exhibited stable physicochemical properties, with an average particle size of 47.2 ± 0.10 nm and a self-emulsification time of 26.02 ± 0.24 s. Moreover, in vitro dissolution studies showed significant improvements in BH release in simulated intestinal fluid, achieving 93.1 ± 2.3% release within 300 min. Meanwhile, BH-SMEDDS did not exhibit cytotoxic effects on the Caco-2 cells. Additionally, BH-SMEDDS achieved a 1.63-fold increase in oral bioavailability compared to commercial BH tablets. Therefore, SMEDDS presents a promising strategy for delivering BH with enhanced oral bioavailability, demonstrating significant potential for clinical application.
A Critical Analysis of the CFD-DEM Simulation of Pharmaceutical Aerosols Deposition in Upper Intra-Thoracic Airways: Considerations on Aerosol Transport and Deposition
Authors: Spasov Georgi H. , Rossi Riccardo , Vanossi Andrea , Cottini Ciro , Benassi Andrea
Published: August 2024

The reliability and accuracy of numerical models and computer simulations to study aerosol deposition in the human respiratory system is investigated for a patient-specific tracheobronchial tree geometry. A computational fluid dynamics (CFD) model coupled with discrete elements methods (DEM) is used to predict the transport and deposition of the aerosol. The results are compared to experimental and numerical data available in the literature to study and quantify the impact of the modeling parameters and numerical assumptions. Even if the total deposition compares very well with the reference data, it is clear from the present work how local deposition results can depend significantly upon spatial discretization and boundary conditions adopted to represent the respiratory act. The modeling of turbulent fluctuations in the airflow is also found to impact the local deposition and, to a minor extent, the flow characteristics at the inlet of the computational domain. Using the CFD-DEM model, it was also possible to calculate the airflow and particles splitting at bifurcations, which were found to depart from the assumption of being equally distributed among branches adopted by some of the simplified deposition models. The results thus suggest the need for further studies towards improving the quantitative prediction of aerosol transport and deposition in the human airways.
ERCC1 and ERCC2 Polymorphisms Predict the Efficacy and Toxicity of Platinum-Based Chemotherapy in Small Cell Lung Cancer
Authors: Barba Andrés , López-Vilaró Laura , Ferre Malena , Majem Margarita , Martinez-Recio Sergio , Bell Olga , Arranz María J. , Salazar Juliana , Sullivan Ivana
Published: August 2024

Standard first-line chemotherapy in small cell lung cancer (SCLC) is based on the platinum plus etoposide combination. Despite a high objective response rate, responses are not durable and chemotherapy-induced toxicity may compromise treatment. Genetic variants in genes involved in the DNA-repair pathways and in etoposide metabolization could predict treatment efficacy and safety and help personalize platinum-based chemotherapy. Germline polymorphisms in XRCC1, ERCC1, ERCC2, ABCB1, ABCC3, UGT1A1 and GSTP1 genes were investigated in 145 patients with SCLC. The tumor expression of ERCC1 was determined using immunohistochemistry, and the tumor expression of ERCC1-XPF was determined via a proximity ligation assay. Survival analyses showed a statistically significant association between the ERCC1 rs11615 variant and median progression-free survival (PFS) in patients with limited-stage (LS) SCLC (multivariate: hazard ratio 3.25, [95% CI 1.38–7.70]; p = 0.007). Furthermore, we observed differences between the ERCC1-XPF complex and median PFS in LS-SCLC, although statistical significance was not reached (univariate: positive expression 10.8 [95% CI 4.09–17.55] months versus negative expression 13.3 [95% CI 7.32–19.31] months; p = 0.06). Safety analyses showed that the ERCC2 rs1799793 variant was significantly associated with the risk of grade ≥ 3 thrombocytopenia in the total cohort (multivariate: odds ratio 3.15, [95% CI 1.08–9.17]; p = 0.04). Our results provide evidence that ERCC1 and ERCC2 variants may predict the efficacy and safety of platinum-based chemotherapy in SCLC patients. LS-SCLC patients may benefit most from ERCC1 determination, but prospective studies are needed.
Liposomal Drug Delivery against Helicobacter pylori Using Furazolidone and N-Acetyl Cysteine in Augmented Therapy
Authors: Alam Muhammad Irfan , Paget Timothy , Moosa Najla Yussuf , Alghurairy Husein , Elkordy Amal Ali
Published: August 2024

Helicobacter pylori (H. pylori) infection is a significant global health concern, affecting approximately 50% of the world’s population and leading to gastric ulcers, gastritis, and gastric cancer. The increase in antibiotic resistance has compromised the efficacy of existing therapeutic regimens, necessitating novel approaches for effective eradication. This study aimed to develop a targeted liposomal drug delivery system incorporating furazolidone and N-acetylcysteine (NAC) to enhance mucopenetration and improve Helicobacter pylori eradication. Liposomes were formulated with furazolidone, NAC, and Pluronic F-127 using a modified reverse-phase evaporation technique. The formulations were categorized based on charge as neutral, negative, and positive and tested for mucopenetration using a modified silicon tube method with coumarin-6 as a fluorescent marker. The encapsulation efficiency and particle size were analyzed using HPLC and an Izon q-nano particle size analyzer. The results indicated that charged liposomes showed a higher encapsulation efficiency than neutral liposomes with Pluronic F-127. Notably, combining furazolidone with 1% NAC achieved complete eradication of H. pylori in 2.5 h, compared to six hours without NAC. The findings of this study suggest that incorporating NAC and Pluronic F-127 into liposomal formulations significantly enhances mucopenetration and antimicrobial efficacy.
Pharmacokinetic Models of Tafenoquine: Insights for Optimal Malaria Treatment Strategies
Authors: Santos Luisa Oliveira , Alves Izabel Almeida , Azeredo Francine Johansson
Published: August 2024

Tafenoquine (TQ) is a new 8-aminoquinoline antimalarial drug developed by the US Army for Plasmodium vivax malaria treatment. Modeling and simulation are essential tools for drug development and improving rationality in pharmacotherapy, and different modeling approaches are used. This study aims to summarize and explore the pharmacokinetic (PK) models available for tafenoquine in the literature. An integrative methodology was used to collect and review published data. Fifteen articles were identified using three modeling approaches: non-compartmental analysis (NCA), population pharmacokinetic analysis (popPK), and pharmacokinetic/pharmacodynamic analysis (PK/PD). An NCA was mainly used to describe the PK profile of TQ and to compare its PK profile alone to those obtained in association with other drugs. PopPK was used to assess TQ population PK parameters, covariates’ impact, and dose selection. PK/PD helped understand the relationship between TQ concentrations, some adverse events common for 8-aminoquilones, and the efficacy assessment for Plasmodium falciparum. In summary, pharmacokinetic models were widely used during TQ development. However, there is still a need for different modeling approaches to support further therapeutic questions, such as treatment for special populations and potential drug–drug interactions.
Analogue of High-Q Transparency Band and Sensitivity in All-Dielectric Metasurfaces Supporting Bound States in the Continuum
Authors: Shuai Ling , Xie Suxia , Nan Haoxuan , Guan Xin
Published: August 2024

Bound states in the continuum (BICs), which are characterized by their high-quality factor, have become a focal point in modern optical research. This study investigates BICs within a periodic array of dielectric resonators, specifically composed of a silicon rectangular bar coupled with four silicon rectangular blocks. Through the analysis of mode coupling, we demonstrate that the interaction between the blocks significantly modulates the eigenmodes of the bar, causing a redshift in all modes and enabling the formation of electromagnetically induced transparency based on BICs (EIT-BIC). Unlike typical EIT mechanisms, this EIT-BIC arises from the coupling of “bright” and “dark” modes both from the rectangular bar, offering novel insights for nanophotonic and photonic device design. Further, our systematic exploration of BIC formation mechanisms and their sensing properties by breaking structural symmetries and changing environmental refractive indices has shed light on the underlying physics. This research not only consolidates a robust theoretical framework for understanding BIC behavior but also paves the way for high-quality factor resonator and sensor development, as well as the precise control of photonic states. The findings significantly deepen our understanding of these phenomena and hold substantial promise for future photonic applications.
Photonic Crystal Fiber Based on Surface Plasmon Resonance Used for Two Parameter Sensing for Magnetic Field and Temperature
Authors: Dai Tiantian , Yi Yingting , Yi Zao , Tang Yongjian , Yi Yougen , Cheng Shubo , Hao Zhiqiang , Tang Chaojun , Wu Pinghui , Zeng Qingdong
Published: August 2024

This paper presents a photonic crystal fiber (PCF) sensor that can be used to measure the temperature and magnetic field simultaneously, and to monitor the changes in them in the environment. When we designed the fiber structure, two circular channels of the same size were added to the fiber to facilitate the subsequent addition of materials. A gold film is added to the upper channel (ch1), and the channel is filled with a magnetic fluid (MF). The sensor can reflect changes in the temperature and magnetic field strength. The two channels containing MF and PDMS in the proposed fiber are called ch1 and ch2. The structure, mode and properties (temperature and magnetic field) were analyzed and discussed using the finite element method. By using the control variable method, the influence of Ta2O5 or no Ta2O5, the Ta2O5 thickness, the diameter of the special air hole, the distance from the fiber core and the distance between them in the displacement of the loss spectrum and the phase-matching condition of the coupling mode were studied. The resulting maximum temperature sensitivity is 6.3 nm/°C (SPR peak 5), and the maximum magnetic field sensitivity is 40 nm/Oe (SPR peak 4). Because the sensor can respond to temperature and magnetic field changes in the environment, it can play an important role in special environmental monitoring, industrial production and other fields.
Controlling the Shape of a Double DNA-like Helix as an Element of Metamaterials
Authors: Semchenko Igor V. , Mikhalka Ivan S. , Samofalov Andrey L. , Khakhomov Sergei A.
Published: August 2024

The aim of the article is to study the forces arising in a conductive DNA-like double helix in the field of a microwave electromagnetic wave. These forces must be considered for both actual DNA molecules and double DNA-like helices that serve as components of metamaterials and metasurfaces. The helix comprises twenty-and-a-half turns and has geometric parameters proportional to the size of an actual DNA molecule. The forces acting on the strands of a double helix, both in the central region and at the edges of the helix, are investigated. It has been demonstrated that the aforementioned forces induce a change in the shape of the helix, specifically the mutual repulsion of the strands, as well as their stretching and twisting in the field of electromagnetic waves. Consequently, exposure to an electromagnetic wave under half-wave resonance can damage the double helix. Conversely, the impact of electromagnetic waves has the potential to introduce novel avenues for controlling the shape of the double helix.
Endophytic Colletotrichum fructicola KL19 and Its Derived SeNPs Mitigate Cd-Stress-Associated Damages in Spinacia oleracea L.
Authors: Wu Yingxia , Huang Shiru , Tian Wei , Yang Shengyu , Shen Wenshu , Dong Jinyan
Published: August 2024

The application of nanotechnology in agriculture has received much attention in order to improve crop yield, quality and food safety. In the present study, a Cd-tolerant endophytic fungus Colletotrichum fructicola KL19 was first ever reported to produce SeNPs, and the production conditions were optimized using the Box–Behnken design in the Response Surface Methodology (RSM-BBD), achieving a peak yield of 1.06 mM under optimal conditions of 2.62 g/20 mL biomass, 4.56 mM Na2SeO3, and pH 6.25. Following this, the properties of the biogenic SeNPs were elucidated by using TEM, DLS, and FTIR, in which the 144.8 nm spherical-shaped SeNPs were stabilized by different functional groups with a negative zeta potential of −18.3 mV. Furthermore, strain KL19 and SeNPs (0, 5, 10, 20 and 50 mg/L) were inoculated in the root zone of small-leaf spinach (Spinacia oleracea L.) seedlings grown in the soil with 33.74 mg/kg Cd under controlled conditions for seven weeks. Impressively, compared with Cd stress alone, the strain KL19 and 5 mg/L SeNPs treatments significantly (p < 0.05) exhibited a reduction in Cd contents (0.62 and 0.50 folds) within the aboveground parts of spinach plants and promoted plants’ growth by improving the leaf count (0.92 and 1.36 folds), fresh weight (2.94 and 3.46 folds), root dry weight (4.00 and 5.60 folds) and root length (0.14 and 0.51 folds), boosting total chlorophyll synthesis (0.38 and 0.45 folds), enhancing antioxidant enzymes (SOD, POD) activities, and reducing the contents of reactive oxygen species (MDA, H2O2) in small-leaf spinach under Cd stress. Overall, this study revealed that utilizing endophytic fungus C. fructicola or its derived SeNPs could mitigate reactive oxygen species generation by enhancing antioxidant enzyme activity as well as diminish the absorption and accumulation of Cd in small-leaf spinach, promoting plant growth under Cd stress.
Impact of Nickel Toxicity on Growth, Fruit Quality and Antioxidant Response in Zucchini Squash (Cucurbita pepo L.)
Authors: Labidi Oumayma , Kouki Rim , Hidouri Saida , Bouzahouane Hana , Caçador Isabel , Pérez-Clemente Rosa M. , Sleimi Noomene
Published: August 2024

The impact of trace metal elements (TMEs) on plants is one current pollution problem, the severity of which is increasing with industrial development, population growth and inappropriate agricultural practices. The latter can have irreversible effects on ecosystems, including species extinction, trophic chain contamination and altered human health, particularly in the case of consumed plants such as zucchini squash (Cucurbita pepo L.). This study aims to investigate the effects of nickel on various physiological and biochemical parameters of zucchini growth, with a particular focus on how this toxic metal impacts the quality of fruit that is consumed by humans. To achieve this, plants aged 45 days were grown for one month on solid media loaded with different concentrations of Ni (0, 100, 300 and 500 µM). The results showed that exposure of plants to Ni resulted in significantly altered growth and higher accumulation of Ni in the shoots (1314 µg·g−1 DW) than in roots and fruits. Concerning non-enzymatic antioxidants, the results showed that Ni toxicity significantly increased total polyphenols, especially in shoots at 300 µM Ni, while flavonoid content decreased in the roots and shoots in response to Ni treatment. Our results also show that nickel tolerance in C. pepo is ensured by a combination of several mechanisms such as an increase in the content of proline. This species can survive and tolerate, to different degrees, toxic cations at concentrations up to 500 µM but with visible symptoms of toxicity such as chlorosis of the leaves. Indeed, based on thresholds of hyperaccumulation, we can qualify Cucurbita pepo as a hyperaccumulator species of nickel.
Ribulose 1,5-Bisphosphate Carboxylase/Oxygenase Is Required in Bradyrhizobium diazoefficiens for Efficient Soybean Root Colonization and Competition for Nodulation
Authors: Balda Rocío S. , Cogo Carolina , Falduti Ornella , Bongiorno Florencia M. , Brignoli Damián , Sandobal Tamara J. , Althabegoiti María Julia , Lodeiro Aníbal R.
Published: August 2024

The Hyphomicrobiales (Rhizobiales) order contains soil bacteria with an irregular distribution of the Calvin–Benson–Bassham cycle (CBB). Key enzymes in the CBB cycle are ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), whose large and small subunits are encoded in cbbL and cbbS, and phosphoribulokinase (PRK), encoded by cbbP. These genes are often found in cbb operons, regulated by the LysR-type regulator CbbR. In Bradyrhizobium, pertaining to this order and bearing photosynthetic and non-photosynthetic species, the number of cbbL and cbbS copies varies, for example: zero in B. manausense, one in B. diazoefficiens, two in B. japonicum, and three in Bradyrhizobium sp. BTAi. Few studies addressed the role of CBB in Bradyrhizobium spp. symbiosis with leguminous plants. To investigate the horizontal transfer of the cbb operon among Hyphomicrobiales, we compared phylogenetic trees for concatenated cbbL-cbbP-cbbR and housekeeping genes (atpD-gyrB-recA-rpoB-rpoD). The distribution was consistent, indicating no horizontal transfer of the cbb operon in Hyphomicrobiales. We constructed a ΔcbbLS mutant in B. diazoefficiens, which lost most of the coding sequence of cbbL and has a frameshift creating a stop codon at the N-terminus of cbbS. This mutant nodulated normally but had reduced competitiveness for nodulation and long-term adhesion to soybean (Glycine max (L.) Merr.) roots, indicating a CBB requirement for colonizing soybean rhizosphere.
Selection and Validation of Reference Genes in Dendrocalamus brandisii for Quantitative Real-Time PCR
Authors: Jiang Jutang , Mu Changhong , Bai Yucong , Cheng Wenlong , Geng Ruiman , Xu Junlei , Dou Yuping , Cheng Zhanchao , Gao Jian
Published: August 2024

Dendrocalamus brandisii (Munro) Kurz is a sympodial bamboo species with a wide distribution in tropical and subtropical regions. Due to its remarkable regenerative ability and exceptional flavor, this species plays a pivotal role in bolstering the economies of numerous nations across these regions. We recently published a high-quality genome of this species. To date, no study results have identified the optimal reference genes for quantitative real-time polymerase chain reaction (qRT-PCR) normalization in Dendrocalamus brandisii. qRT-PCR offers a highly accurate and effective approach to analyzing gene expression. However, the precision of the resulting quantitative data hinges on the correct choice of reference genes. Twenty-one potential reference genes were identified from the D. brandisii transcriptomes. Their expression in 23 samples, including 8 different tissue organs and 15 samples of D. brandisii under various treatment conditions, were evaluated through qRT-PCR. Subsequently, four software programs—Delta CT, geNorm, NormFinder, and RefFinder—were employed to compare their expression stability. The results revealed that the selection of optimal reference genes varied based on the particular organ and condition being examined. EF-1-α-2 consistently exhibits the most stable expression across diverse tissues, while ACTIN-1, TUBULIN-1, and EF-1-α-2 were the most consistent reference genes in roots, culms, and leaves under various treatments, respectively. In this study, we identified and characterized appropriate internal genes utilized for calibrating qRT-PCR analyses of D. brandisii across different tissue organs and under various treatments. This research will provide key insights for advancing the study of gene functionality and molecular biology in D. brandisii and related species
Identification and Mapping of QTLs for Adult Plant Resistance in Wheat Line XK502
Authors: Feng Xianli , Huang Ming , Lou Xiaoqin , Yang Xue , Yu Boxun , Huang Kebing , Yang Suizhuang
Published: August 2024

Stripe rust is a serious wheat disease occurring worldwide. At present, the most effective way to control it is to grow resistant cultivars. In this study, a population of 221 recombinant inbred lines (RILs) derived via single-seed descent from a hybrid of a susceptible wheat line, SY95-71, and a resistant line, XK502, was tested in three crop seasons from 2022 to 2024 in five environments. A genetic linkage map was constructed using 12,577 single-nucleotide polymorphisms (SNPs). Based on the phenotypic data of infection severity and the linkage map, five quantitative trait loci (QTL) for adult plant resistance (APR) were detected using the inclusive composite interval mapping (ICIM) method. These five loci are QYrxk502.swust-1BL, QYrxk502.swust-2BL, QYrxk502.swust-3AS, QYrxk502.swust-3BS, and QYrxk502.swust-7BS, explaining 5.67–19.64%, 9.63–36.74%, 9.58–11.30%, 9.76–23.98%, and 8.02–12.41% of the phenotypic variation, respectively. All these QTL originated from the resistant parent XK502. By comparison with the locations of known stripe rust resistance genes, three of the detected QTL, QYrxk502.swust-3AS, QYrxk502.swust-3BS, and QYrxk502.swust-7BS, may harbor new, unidentified genes. From among the tested RILs, 16 lines were selected with good field stripe rust resistance and acceptable agronomic traits for inclusion in breeding programs.