bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of a Questionnaire to Measure Adherence to a Mediterranean-Type Diet in Youth
Authors: Kwon Yu-Jin , Park Young-Hwan , Lee Yae-Ji , Lim Li-Rang , Lee Ji-Won
Published: August 2024

Proper nutrition during childhood is crucial for preventing chronic diseases and ensuring optimal growth. This study aimed to develop and validate the Korean version of the KIDMED (K-KIDMED) questionnaire to accurately measure Mediterranean diet (MD) adherence among Korean children and adolescents. A total of 226 parents, representing their children and adolescents, completed the K-KIDMED, a 112-item food frequency questionnaire (FFQ), and a 24-h dietary recall method through an anonymous online survey. The K-KIDMED comprised 11 questions, with five excluded from the original scoring as they did not apply to the FFQ. Scores were categorized into three levels of adherence to the MD: low (1 or less), average (2–4), and good (5 or more). The agreement between total MD scores from the Korean version of the Mediterranean diet adherence screener and the FFQ was moderate (intraclass correlation coefficient = 0.455, 95% confidence interval: 0.346, 0.553). Among the 226 children and adolescents, 36.7% had low adherence to the KIDMED, 43.3% had intermediate adherence, and 19.9% had good adherence. Higher K-KIDMED scores were correlated with greater intakes of fiber, vitamin K, vitamin B6, and potassium (all p < 0.05). We developed the K-KIDMED as a valid tool to assess MD adherence in Korean children and adolescents.
Comparison of the In Vitro Iron Bioavailability of Tempeh Made with Tenebrio molitor to Beef and Plant-Based Meat Alternatives
Authors: Wilson John W. , Thompson Tyler W. , Wei Yuren , Chaparro Jacqueline M. , Stull Valerie J. , Nair Mahesh N. , Weir Tiffany L.
Published: August 2024

Iron is an essential mineral that supports biological functions like growth, oxygen transport, cellular function, and hormone synthesis. Insufficient dietary iron can lead to anemia and cause fatigue, cognitive impairment, and poor immune function. Animal-based foods provide heme iron, which is more bioavailable to humans, while plant-based foods typically contain less bioavailable non-heme iron. Edible insects vary in their iron content and may have heme or non-heme forms, depending on their diet. Edible insects have been proposed as a protein source that could address issues of food insecurity and malnutrition in low resource contexts; therefore, it is important to understand the bioavailability of iron from insect-based foods. In this study, we used Inductively Coupled Plasma and Mass Spectrometry (IPC-MS) and Caco-2 cell culture models to compare the soluble and bioavailable iron among five different lab-produced tempeh formulations featuring Tenebrio molitor (mealworm) with their non-fermented raw ingredient combinations. Finally, we compared the iron bioavailability of a mealworm tempeh with two sources of conventional beef (ground beef and sirloin steaks) and two commercially available plant-based meat alternatives. The results show that while plant-based meat alternatives had higher amounts of soluble iron, particularly in the Beyond Burger samples, the fermented mealworm-based tempeh had greater amounts of bioavailable iron than the other samples within the set. While all the samples presented varying degrees of iron bioavailability, all products within the sample set would be considered good sources of dietary iron.
Serum Homocysteine Levels and All-Cause and Cause-Specific Mortality in Korean Adult Men: A Cohort Study
Authors: Kim Minyoung , Shin Sujeong , Yoo Eunsol , Kang Jae-Heon , Sung Eunju , Kim Cheol-Hwan , Shin Hocheol , Lee Mi Yeon
Published: August 2024

Background: Hyperhomocysteinemia can increase the risk of cardiovascular disease (CVD), cancer, and neurological disorders; however, hypohomocysteinemia is generally not considered harmful. This study aimed to evaluate the relationship between all levels of homocysteine, both low and high homocysteine levels, and the risk of all-cause and cause-specific mortality in adult Korean men. Methods: Adult Korean men (n = 221,356) were categorized into quintiles based on their homocysteine levels. The primary endpoints were all-cause, CVD, cancer, and dementia mortality. Hazard ratios were calculated using Cox proportional hazards models, and the dose–response relationship between homocysteine levels and mortality risk was further explored using restricted cubic spline models. Results: Compared with the reference category (Q2, 8.8–9.9 µmol/L), there was a significant increase in all-cause mortality associated with both low and high levels after multivariable adjustment (Pinteraction = 0.002). Additionally, in spline regression, a U-shaped association between homocysteine levels and all-cause and CVD mortality was observed (inflection point = 9.1 µmol/L). This association was not observed in the vitamin supplementation subgroup. Conclusion: Among Korean adult men, both low and high homocysteine levels increased the risk of all-cause and CVD mortality, indicating a U-shaped relationship. However, this relationship was not statistically significant with vitamin supplementation, suggesting a potential protective role for vitamins.
Role of Vitamin D in Oral Lichen Planus: A Case Control Study
Authors: García-Pola María , Rodríguez-Fonseca Lucía
Published: August 2024

Background: It has been reported that vitamin D deficiency may be associated with the development of oral lichen planus (OLP). Given the high prevalence of vitamin D deficiency in many countries, we sought to determine whether it constitutes a comorbidity of OLP. Methods: One hundred and twenty patients clinically and histologically diagnosed with OLP were evaluated for their serum vitamin D levels. The results were compared to results from a control series of the same number of subjects matched for age and sex. Results: Vitamin D deficiency was diagnosed in 45% (n = 54) of OLP patients and in 26.7% (n = 32) of the control group. Vitamin D supplements were being taken by 32 (26.7%) OLP patients and 15 (12.5%) subjects in the control group. A multivariate logistic regression model showed that OLP was associated with vitamin D deficiency [OR: 2.24 (1.28–3.98, p = 0.005)] and vitamin D supplementation [OR: 2.51 (1.25–5.22, p = 0.011)], even after controlling for confounding variables such as sex, age ≤60>, tobacco, and alcohol. Conclusion: The association between OLP patients and vitamin D deficiency or vitamin D supplementation suggests that further research might explore the benefits of vitamin D supplements in managing OLP patients.
Use of Dietary Supplements among Polish Children with Inflammatory Bowel Disease: A Two-Center Pilot Study
Authors: Maćków Monika , Kozioł-Kozakowska Agnieszka , Szeląg Magdalena , Pytrus Tomasz , Raczkowska Ewa , Neubauer Katarzyna , Zawiślak Ireneusz , Gajda Robert , Habánová Marta , Stawarski Andrzej
Published: August 2024

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). These diseases are characterized by inflammation, which may be a consequence of changes in the intestinal microbiota and lead to mineral and vitamin deficiencies. The aims of this study were to determine the level of dietary supplement intake in children with IBD and to determine the influence of factors such as sex, nutritional status, diet, and other comorbidities on supplement intake. The study was conducted from May 2022 to September 2023 and was a prospective study. The group of children with IBD that ultimately qualified for the study numbered 96, and the control group numbered 30. The children who participated in the study were aged 4–18 years. Most parents of children with IBD (81.4%) declared that they use supplementation for their children, while 75% of parents of children without IBD declared giving their children nutritional supplements. Vitamins in both groups were most often given to children as dietary supplements (p = 0.018), including vitamin D. Depending on the diet used, the intake of vitamin B6 (p = 0.018), vitamin E (p = 0.040) and iron (p = 0.006) was significantly different among children with IBD. Statistical significance (p = 0.021) was observed for supplementation use and disease stage among children with IBD. For 80.2% of parents of children with IBD, the main reason for using supplements was a doctor’s recommendation. In the control group, 43.3% of parents indicated that the main reason for using supplements was to correct nutritional deficiencies. Supplementation was common in both groups, but attention should be paid to other current diseases in children with IBD and to nutritional status. In our opinion, educating parents about supplementation is important, especially among parents of children with IBD.
Meal Duration and Obesity-Related Indicators among Adolescents: Insights from the EHDLA Study
Authors: Martínez-López Mayra Fernanda , López-Gil José Francisco
Published: August 2024

Purpose: This paper aims to examine the association between meal duration and obesity indicators among Spanish adolescents. Methods: We conducted a cross-sectional analysis using data from the Eating Healthy and Daily Life Activities (EHDLA) project involving 755 adolescents aged 12 to 17 years (54.8% girls) from three secondary schools in the Valle de Ricote Region of Murcia, Spain. To evaluate overall meal duration, participants were asked how long (on average) breakfast, morning snacks, lunch, afternoon snacks, and dinner typically last. Subsequently, global meal duration was measured, and the participants were categorized into tertiles. Obesity-related indicators, including body mass index (BMI) z score, waist circumference (WC), and skinfold thickness, were assessed. The analyses were adjusted for potential confounders such as sex, age, socioeconomic status, physical activity, sedentary behavior, diet quality, and energy intake. Results: Concerning meal duration status, adolescents with long meal durations had the lowest estimated marginal means of BMI z score, WC, and body fat percentage (using the sum of triceps and calf skinfolds). However, significant differences between adolescents with a long meal duration and those with a short meal duration were observed only for BMI z score (p = 0.008), and WC (p = 0.020). Furthermore, significant differences in BMI z score (p = 0.017) between adolescents with a long meal duration and those with a moderate meal duration were identified. Conclusions: These findings underscore the importance of promoting slower eating habits as part of obesity prevention strategies. Future studies should explore the causality of this association and its potential for behavioral interventions.
Is Nutrient Quality of the Locally-Existing, EAT-Lancet-like Plant-Based Diet Better or Worse than the Average Diet in Taiwan? An Example of Local Translation
Authors: Pan Wen-Harn , Wu Szu-Yun , Chang Po-Chen
Published: August 2024

The EAT-Lancet commission advocated a planetary health diet in 2019. Some have raised concerns about its nutrient adequacy. This study used data from recent Nutrition and Health Surveys in Taiwan—from 2017 to 2020 (n = 6538)—to assess food intake and nutrient adequacy among three red meat consumption levels (low/medium/high). The low red meat group, whose diet was similar to the EAT-Lancet reference, showed significantly higher/better levels of vitamins C and E, calcium, magnesium, sodium, dietary fiber, and the polyunsaturated to saturated fatty acids ratio. However, protein, B vitamins, phosphorus for females, and zinc were slightly compromised, but they were still near or above 100% of the Daily Reference Intakes (DRIs), except for zinc (74~75%). The intake levels of vitamin D, calcium, and dietary fiber in all three groups at times did not reach 70% of the DRIs, but this was more pronounced in the high red meat group compared to the low red meat group. Replacing ultra-processed foods (UPFs) with whole/healthy foods improved levels of zinc, calcium, and dietary fiber, but not vitamin D. Finally, a proposed local planetary health dietary construct was provided, suggesting maintaining the original distribution of the food groups recommended by the Taiwan Food Guide while specifying amounts of protein sources in line with the EAT-Lancet principles. The proposed diet, according to our estimation and comparison with Taiwanese DRIs, was nearly perfect in its nutrient composition.
Exploring Oxidative Stress in Disease and Its Connection with Adenosine
Authors: Correia Ana Salomé , Vale Nuno
Published: August 2024

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species and the body’s antioxidant defenses, plays an important role in the pathogenesis of various health conditions, including cancer and neurological disorders. For example, excessive ROS can lead to mutations, genomic instability, and uncontrolled cell proliferation in cancer. In neurological disorders, oxidative stress contributes to neuronal damage, inflammation, and the progression of diseases such as Alzheimer’s and Parkinson’s diseases. Adenosine, a nucleoside involved in energy transfer and signal transduction, is crucial to maintaining cellular homeostasis. Its role extends to modulating oxidative stress. Adenosine receptors are implicated in various physiological processes and in the pathophysiology of diseases. The interplay between oxidative stress and adenosine signaling is complex and critical. Adenosine can modulate oxidative stress responses, providing therapeutic potential for conditions where oxidative stress is a key player. Understanding this connection opens up avenues for novel therapeutic strategies targeting adenosine receptors to mitigate oxidative damage.
Efficacy of a New Fenbendazole Treatment Protocol against Capillaria spp. in Northern White-Breasted Hedgehog (Erinaceus roumanicus)
Authors: Alfaia Francisco , Jota Baptista Catarina , Lozano João , Sós-Koroknai Viktória , Hoitsy Márton , Madeira de Carvalho Luís M. , Sós Endre
Published: August 2024

Hedgehogs, Erinaceus spp., are commonly admitted to rescue centres in European countries. However, there are still few studies on parasitological fauna and treatment possibilities, including for E. roumanicus. This study aimed to evaluate parasitism in 34 hedgehogs directly after their admission to the Budapest Zoo and Botanical Garden Wildlife Rescue Centre, as well as the efficacy of fenbendazole treatment. The Mini-Flotac method was used to quantitatively evaluate and assess the efficacy of treatment with fenbendazole (100 mg/kg PO. BID for 7 days) in five selected individuals. Faecal samples were analysed at D0 and D14 after the beginning of the treatment. Globally, the prevalence of positive animals was 76%. Capillaria spp. were the most prevalent (68%), while coccidia showed a prevalence of 32%. Considering the range of action of this benzimidazole, the treatment provided an efficacy of 100%, eliminating all forms of Capillaria spp. Considering the high number of hedgehogs admitted to rescue centres and the potential effects of parasitism in morbidity and mortality during recovery, it is essential to improve our knowledge with regard to the parasitological fauna of these species and to attain effective treatment protocols.
A New Ex Vivo Model Based on Mouse Retinal Explants for the Study of Ocular Toxoplasmosis
Authors: Rodriguez Fernandez Veronica , Amato Rosario , Piaggi Simona , Pinto Barbara , Casini Giovanni , Bruschi Fabrizio
Published: August 2024

Ocular toxoplasmosis is the most prevalent clinical manifestation of T. gondii infection, which causes irreversible retinal damage. Different experimental models have been developed to study this pathology. In the present study, a new, ex vivo model is proposed to contribute to the elucidation of disease mechanisms and to possible therapeutic solutions. Ex-vivo retinal explants, prepared from mouse retinas following established protocols, were incubated with T. gondii tachyzoites maintained in Vero cells. At different times, starting at 12 h up to 10 days of incubation, the explants were analyzed with immunofluorescence and Western blot to investigate their responses to parasite infection. T. gondii invasion of the retinal thickness was evident after 3 days in culture, where parasites could be detected around retinal cell nuclei. This was paralleled by putative cyst formation and microglial activation. At the same time, an evident increase in inflammatory and oxidative stress markers was detected in infected explants compared to controls. Cell death also appeared to occur in retinal explants after 3 days of T. gondii infection, and it was characterized by increased necroptotic but not apoptotic markers. The proposed model recapitulates the main characteristics of T. gondii retinal infection within 3 days of incubation and, therefore, allows for studying the very early events of the process. In addition, it requires only a limited number of animals and offers easy manipulation and accessibility for setting up different experimental conditions and assessing the effects of putative drugs for therapy.
Interplay between Bile Acids and Intestinal Microbiota: Regulatory Mechanisms and Therapeutic Potential for Infections
Authors: Li Wenweiran , Chen Hui , Tang Jianguo
Published: August 2024

Bile acids (BAs) play a crucial role in the human body’s defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolase (BSH) activity but they also directly combat infections. Building upon our research group’s previous discoveries highlighting the role of BAs in combating infections, we have initiated an in-depth investigation into the interactions between BAs and intestinal microbiota. Leveraging the existing literature, we offer a comprehensive analysis of the relationships between BAs and 16 key microbiota. This investigation encompasses bacteria (e.g., Clostridioides difficile (C. difficile), Staphylococcus aureus (S. aureus), Escherichia coli, Enterococcus, Pseudomonas aeruginosa, Mycobacterium tuberculosis (M. tuberculosis), Bacteroides, Clostridium scindens (C. scindens), Streptococcus thermophilus, Clostridium butyricum (C. butyricum), and lactic acid bacteria), fungi (e.g., Candida albicans (C. albicans) and Saccharomyces boulardii), and viruses (e.g., coronavirus SARS-CoV-2, influenza virus, and norovirus). Our research found that Bacteroides, C. scindens, Streptococcus thermophilus, Saccharomyces boulardii, C. butyricum, and lactic acid bacteria can regulate the metabolism and function of BSHs and 7α-dehydroxylase. BSHs and 7α-dehydroxylase play crucial roles in the conversion of primary bile acid (PBA) to secondary bile acid (SBA). It is important to note that PBAs generally promote infections, while SBAs often exhibit distinct anti-infection roles. In the antimicrobial action of BAs, SBAs demonstrate antagonistic properties against a wide range of microbiota, with the exception of norovirus. Given the intricate interplay between BAs and intestinal microbiota, and their regulatory effects on infections, we assert that BAs hold significant potential as a novel approach for preventing and treating microbial infections.
Design, Synthesis, and Evaluation of Oleyl-WRH Peptides for siRNA Delivery
Authors: Rai Mrigank Shekhar , Sajid Muhammad Imran , Moreno Jonathan , Parang Keykavous , Tiwari Rakesh Kumar
Published: August 2024

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum stability at N/P ≥ 40. The synthesized conjugates, with a diameter of <100 nm, formed nano-complexes with siRNA and exhibited a stable range of zeta potential values (13–18 mV at N/P = 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of a successful cellular internalization of siRNA. The peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.
The Proteasome Inhibitor Marizomib Evokes Endoplasmic Reticulum Stress and Promotes Apoptosis in Human Glioblastoma Cells
Authors: Kusaczuk Magdalena , Tyszka Natalia , Krętowski Rafał , Cechowska-Pasko Marzanna
Published: August 2024

Proteasomes play an important role in the physiology of cancer cells, and inhibition of their activity may be used as a promising therapeutic strategy against glioblastoma (GBM). Although certain proteasome inhibitors (PIs) have been approved for the treatment of other malignancies, they have limited effectiveness against GBM due to low brain bioavailability. Marizomib (MZB) is an irreversible, second-generation proteasome inhibitor, which unlike other PIs can penetrate through the blood–brain barrier, making it a promising therapeutic tool in brain malignancies. The antitumor activity of MZB was investigated in LN229 and U118 cells. The MTT test and the ATP-based assay were performed to evaluate cytotoxicity. Flow cytometry analysis was used to determine the apoptotic death of GBM cells. Luminescent assays were used to assess levels of reactive oxygen species (ROS) and the activity of caspase 3/7. RT-qPCR and Western blot analyses were used to determine gene and protein expressions. Marizomib decreased the viability and caused apoptotic death of GBM cells. The proapoptotic effect was accompanied by activation of caspase 3 and overexpression of cl-PARP, Noxa, Cyt C, and DR5. Moreover, treatment with MZB triggered endoplasmic reticulum (ER) stress, as shown by increased expressions of GRP78, IRE1α, p-EIF2α, p-SAPK/JNK, CHOP, ATF6α, and ATF4. On the contrary, overproduction of ROS or increased expressions of ERO1α, LC3 II, Beclin 1, and ATG5 were not detected, suggesting that neither oxidative stress nor autophagy were involved in the process of MZB-induced cell death. Thus, marizomib represents a potentially promising compound for facilitating further progress in brain cancer therapy.
Network Pharmacology Identifies Intersection Genes of Apigenin and Naringenin in Down Syndrome as Potential Therapeutic Targets
Authors: Amir Mohd , Shafi Shabana , Parveen Shahida , Reshi Aijaz Ahmad , Ahmad Ajaz
Published: August 2024

Down Syndrome (DS), characterized by trisomy of chromosome 21, leads to the overexpression of several genes contributing to various pathologies, including cognitive deficits and early-onset Alzheimer’s disease. This study aimed to identify the intersection genes of two polyphenolic compounds, apigenin and naringenin, and their potential therapeutic targets in DS using network pharmacology. Key proteins implicated in DS, comprising DYRK1A, APP, CBS, and ETS2, were selected for molecular docking and dynamics simulations to assess the binding affinities and stability of the protein–ligand interactions. Molecular docking revealed that naringenin exhibited the highest binding affinity to DYRK1A with a score of −9.3 kcal/mol, followed by CBS, APP, and ETS2. Moreover, molecular docking studies included positive control drugs, such as lamellarin D, valiltramiprosate, benserazide, and TK216, which exhibited binding affinities ranging from −5.5 to −8.9 kcal/mol. Apigenin showed strong binding to APP with a score of −8.8 kcal/mol, suggesting its potential in modulating amyloid-beta levels. These interactions were further validated through molecular dynamics simulations, demonstrating stable binding throughout the 100 ns simulation period. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses indicated minimal fluctuations, confirming the stability of the complexes. The findings suggest that apigenin and naringenin could serve as effective therapeutic agents for DS by targeting key proteins involved in its pathology. Future studies should focus on in vivo validation, clinical trials, and exploring combination therapies to fully harness the therapeutic potential of these compounds for managing DS. This study underscores the promising role of network pharmacology in identifying novel therapeutic targets and agents for complex disorders like DS.
A Pharmacogenetic Panel-Based Prediction of the Clinical Outcomes in Elderly Patients with Coronary Artery Disease
Authors: Dong Lisha , Zhang Shizhao , Lv Chao , Xue Qiao , Yin Tong
Published: August 2024

Clinical annotations for the actionable pharmacogenetic variants affecting the efficacy of cardiovascular drugs have been collected, yet their impacts on elderly patients with coronary artery disease (CAD) undergoing polypharmacy remain uncertain. We consecutively enrolled 892 elderly patients (mean age 80.7 ± 5.2) with CAD and polypharmacy. All the included patients underwent genotyping for 13 variants in 10 pharmacogenes (CYP2C19, CYP2C9, CYP4F2, CYP2D6, VKORC1, SLCO1B1, APOE, ACE, ADRB1, and MTHFR), which have the clinical annotations for 12 drugs that are commonly prescribed for patients with CAD. We found that 80.3% of the elderly CAD patients had at least one drug–gene pair associated with a therapeutical drug change. After adjusting for covariates, the number of drug–gene pairs was independently associated with a decreased risk of both major cardiovascular events (MACEs) (adjusted hazard ratio [HR]: 0.803, 95% confidence interval [CI]: 0.683–0.945, p = 0.008) and all-cause mortality (adjusted HR: 0.848, 95% CI: 0.722–0.996, p = 0.045), but also with an increased risk of adverse drug reactions (ADRs) (adjusted HR: 1.170, 95% CI: 1.030–1.329, p = 0.016). The Kaplan–Meier survival curves showed that compared to patients without a drug–gene pair, a significantly lower risk of MACEs could be observed in patients with a drug–gene pair during a 4-year follow-up (HR: 0.556, 95% CI: 0.325–0.951, p = 0.013). In conclusion, the carrier status of the actionable drug–gene pair is predictive for the clinical outcomes in elderly patients with CAD and polypharmacy. Implementing early or preemptive pharmacogenetic panel-guided polypharmacy holds the potential to enhance clinical outcomes for these patients.
Au@CuS Nanoshells for Surface-Enhanced Raman Scattering Image-Guided Tumor Photothermal Therapy with Accelerated Hepatobiliary Excretion
Authors: Zhang Sihang , Yu Sheng , Sun Jingwen , Huang Teng , Lin Hongzheng , Li Zhe , Xiao Zeyu , Lu Wei
Published: August 2024

Gold-based nanoparticles for surface-enhanced Raman scattering (SERS) imaging show great potential for precise tumor detection and photothermal therapy (PTT). However, the metabolizability of gold nanoparticles (Au NPs) raises big concerns. Herein, we designed a core-shelled nanostructure of copper sulfide (CuS)-coated Au NPs with surface pegylation (PEG-Au@CuS NSs). The excreted Au in the gallbladders at 1 h and 4 h in mice injected with PEG-Au@CuS NSs was 8.2- and 19.1-fold of that with the pegylated Au NPs (PEG-AuNPs) of the same Au particle size, respectively. By loading the Raman reporter 3,3′-Diethylthiatricarbocyanine iodide (DTTC) in the core–shell junction of PEG-Au@CuS NSs, the PEG-Au-DTTC@CuS NSs exhibited the Raman signal-to-noise (S/N) ratio of 4.01 after 24 h of intravenous (IV) injection in the mice bearing an orthotopic CT26-Luc colon tumor. By contrast, the DTTC-coated PEG-AuNPs (PEG-Au-DTTC NPs) achieved an S/N ratio of 2.71. Moreover, PEG-Au-DTTC@CuS NSs exhibited an increased photothermal conversion effect compared with PEG-Au-DTTC NPs excited with an 808-nm laser. PEG-Au-DTTC@CuS NSs enabled intraoperative SERS image-guided photothermal therapy for a complete cure of the colon tumor-bearing mice. Our data demonstrated that the PEG-Au-DTTC@CuS NSs are promising intraoperative Raman image-guided theranostic nanoplatform with enhanced hepatobiliary excretion.
Formulation of Polymeric Nanoparticles Loading Baricitinib as a Topical Approach in Ocular Application
Authors: Beirampour Negar , Bustos-Salgado Paola , Garrós Núria , Mohammadi-Meyabadi Roya , Domènech Òscar , Suñer-Carbó Joaquim , Rodríguez-Lagunas María José , Kapravelou Garyfallia , Montes María Jesús , Calpena Ana , Mallandrich Mireia
Published: August 2024

Topical ocular drug delivery faces several challenges due to the eye’s unique anatomy and physiology. Physiological barriers, tear turnover, and blinking hinder the penetration of drugs through the ocular mucosa. In this context, nanoparticles offer several advantages over traditional eye drops. Notably, they can improve drug solubility and bioavailability, allow for controlled and sustained drug release, and can be designed to specifically target ocular tissues, thus minimizing systemic exposure. This study successfully designed and optimized PLGA and PCL nanoparticles for delivering baricitinib (BTB) to the eye using a factorial design, specifically a three-factor at five-levels central rotatable composite 23+ star design. The nanoparticles were small in size so that they would not cause discomfort when applied to the eye. They exhibited low polydispersity, had a negative surface charge, and showed high entrapment efficiency in most of the optimized formulations. The Challenge Test assessed the microbiological safety of the nanoparticle formulations. An ex vivo permeation study through porcine cornea demonstrated that the nanoparticles enhanced the permeability coefficient of the drug more than 15-fold compared to a plain solution, resulting in drug retention in the tissue and providing a depot effect. Finally, the in vitro ocular tolerance studies showed no signs of irritancy, which was further confirmed by HET-CAM testing.
Prediction through Simulation-Based Corrective Models of Contra-Directional Couplers’ Experimental Results
Authors: Venâncio Inês , Tátá Joana , Carvalhais Maria João , Santos João , Teixeira António
Published: August 2024

Lithography variation presents one of the biggest challenges for photonic component optimization, especially for fabless designers. Lithography prediction models are a crucial tool for minimizing the necessary number of fabrication iterations for a device’s optimization. This paper presents one of these models specifically adapted for the contra-directional coupler structure. Through the experimental characterization of devices with a specific range of design parameters, it was possible to observe how the lithography process impacts their performance. A correction model based on effective refractive index variation and its impact on the Bragg condition of the structure was developed to predict the performance variation of a device based on the expected design variation induced by fabrication. The contra-directional couplers fabricated at CORNERSTONE foundry show a tendency to be redshifted as the gap decreases, due to an increase in waveguide width as a result of a diffraction-limited lithography process. Based on these and other findings, it was possible to correlate the design parameters to the posterior fabricated structure and ultimately predict the expected experimental response.
Co-Expression Network Analysis and Introgressive Gene Identification for Fiber Length and Strength Reveal Transcriptional Differences in 15 Cotton Chromosome Substitution Segment Lines and Their Upland and Sea Island Parents
Authors: Li Pengtao , Chen Yu , Yang Rui , Sun Zhihao , Ge Qun , Xiao Xianghui , Yang Shuhan , Li Yanfang , Liu Qiankun , Zhang Aiming , Xing Baoguang , Wu Bei , Du Xue , Liu Xiaoyan , Tang Baomeng , Gong Juwu , Lu Quanwei , Shi Yuzhen , Yuan Youlu , Peng Renhai , Shang Haihong
Published: August 2024

Fiber length (FL) and strength (FS) are the core indicators for evaluating cotton fiber quality. The corresponding stages of fiber elongation and secondary wall thickening are of great significance in determining FL and FS formation, respectively. QTL mapping and high-throughput sequencing technology have been applied to dissect the molecular mechanism of fiber development. In this study, 15 cotton chromosome segment substitution lines (CSSLs) with significant differences in FL and FS, together with their recurrent parental Gossypium hirsutum line CCRI45 and donor parent G. barbadense line Hai1, were chosen to conduct RNA-seq on developing fiber samples at 10 days post anthesis (DPA) and 20 DPA. Differentially expressed genes (DEGs) were obtained via pairwise comparisons among all 24 samples (each one with three biological repeats). A total of 969 DEGs related to FL-high, 1285 DEGs to FS-high, and 997 DEGs to FQ-high were identified. The functional enrichment analyses of them indicated that the GO terms of cell wall structure and ROS, carbohydrate, and phenylpropanoid metabolism were significantly enriched, while the GO terms of glucose and polysaccharide biosynthesis, and brassinosteroid and glycosylphosphatidylinositol metabolism could make great contributions to FL and FS formation, respectively. Weighted gene co-expressed network analyses (WGCNA) were separately conducted for analyzing FL and FS traits, and their corresponding hub DEGs were screened in significantly correlated expression modules, such as EXPA8, XTH, and HMA in the fiber elongation and WRKY, TDT, and RAC-like 2 during secondary wall thickening. An integrated analysis of these hub DEGs with previous QTL identification results successfully identified a total of 33 candidate introgressive DEGs with non-synonymous mutations between the Gh and Gb species. A common DEG encoding receptor-like protein kinase 1 was reported to likely participate in fiber secondary cell thickening regulation by brassionsteroid signaling. Such valuable information was conducive to enlightening the developing mechanism of cotton fiber and also provided an abundant gene pool for further molecular breeding.
Engineering the Rhizosphere Microbiome with Plant Growth Promoting Bacteria for Modulation of the Plant Metabolome
Authors: Ferreira Maria J. , Veríssimo Ana C. S. , Pinto Diana C. G. A. , Sierra-Garcia Isabel N. , Granada Camille E. , Cremades Javier , Silva Helena , Cunha Ângela
Published: August 2024

Plant-growth-promoting bacteria (PGPB) have beneficial effects on plants. They can promote growth and enhance plant defense against abiotic stress and disease, and these effects are associated with changes in the plant metabolite profile. The research problem addressed in this study was the impact of inoculation with PGPB on the metabolite profile of Salicornia europaea L. across controlled and field conditions. Salicornia europaea seeds, inoculated with Brevibacterium casei EB3 and Pseudomonas oryzihabitans RL18, were grown in controlled laboratory experiments and in a natural field setting. The metabolite composition of the aboveground tissues was analyzed using GC–MS and UHPLC–MS. PGPB inoculation promoted a reconfiguration in plant metabolism in both environments. Under controlled laboratory conditions, inoculation contributed to increased biomass production and the reinforcement of immune responses by significantly increasing the levels of unsaturated fatty acids, sugars, citric acid, acetic acid, chlorogenic acids, and quercetin. In field conditions, the inoculated plants exhibited a distinct phytochemical profile, with increased glucose, fructose, and phenolic compounds, especially hydroxybenzoic acid, quercetin, and apigenin, alongside decreased unsaturated fatty acids, suggesting higher stress levels. The metabolic response shifted from growth enhancement to stress resistance in the latter context. As a common pattern to both laboratory and field conditions, biopriming induced metabolic reprogramming towards the expression of apigenin, quercetin, formononetin, caffeic acid, and caffeoylquinic acid, metabolites that enhance the plant’s tolerance to abiotic and biotic stress. This study unveils the intricate metabolic adaptations of Salicornia europaea under controlled and field conditions, highlighting PGPB’s potential to redesign the metabolite profile of the plant. Elevated-stress-related metabolites may fortify plant defense mechanisms, laying the groundwork for stress-resistant crop development through PGPB-based inoculants, especially in saline agriculture.
Postponed Application of Phosphorus and Potassium Fertilizers Mitigates the Damage of Late Spring Coldness by Improving Winter Wheat Root Physiology
Authors: Fang Hao , Huang Jinwei , Zhu Xiatong , Hassan Muhammad Ahmad , Ren Jin , Huang Jingyao , Zheng Baoqiang , Chen Xiang , Lin Feifei , Li Jincai
Published: August 2024

Late spring coldness (LSC) is the main limiting factor threatening wheat yield and quality stability. Optimal nutrient management is beneficial in mitigating the harms of LSC by improving wheat root physiology. This study proposed a nutrient management strategy that postponed the application of phosphorus (P) and potassium (K), effectively strengthening wheat’s defense against LSC. This experiment used the winter cultivar “Yannong19” (YN 19) as plant material for two consecutive years (2021–2022 and 2022–2023). Two fertilizer treatments were used: traditional P and K fertilizers application (R1: base fertilizer: jointing fertilizer = 10:0) and postponed P and K fertilizers application (R2: base fertilizer: jointing fertilizer = 5:5); wheat plants at the anther connective formation stage shifted to temperature-controlled phytotrons for normal (T0, 11 °C/4 h) and low temperatures (T1, 4 °C/4 h; T2, −4 °C/4 h) as treatments of LSC. The results showed that under low temperature (LT) treatment, compared with R1, the R2 treatment increased the concentrations of osmotic adjustment substances (soluble sugars and soluble protein contents by 6.2–8.7% and 3.0–8.9%), enhanced activities of antioxidant enzymes (superoxide dismutase, peroxidase and catalase activities by 2.2–9.1%, 6.2–9.7% and 4.2–8.4%), balanced the hormone concentrations (increased IAA and GA3 contents by 2.8–17.5% and 10.4–14.1% and decreased ABA contents by 7.2–14.3%), and reduced the toxicity (malondialdehyde, hydrogen peroxide content and O2·− production rate by 5.7–12.4%, 17.7–22.8% and 19.1–19.1%) of the cellular membranes. Furthermore, the wheat root physiology in R2 significantly improved as the root surface area and dry weight increased by 5.0–6.6% and 4.7–6.6%, and P and K accumulation increased by 7.4–11.3% and 12.2–15.4% compared to R1, respectively. Overall, the postponed application of P and K fertilizers enhanced the physiological function of the root system, maintained root morphology, and promoted the accumulation of wheat nutrients under the stress of LSC.
Genome-Wide Characterization of Glyceraldehyde-3-Phosphate Dehydrogenase Genes and Their Expression Profile under Drought Stress in Quercus rubra
Authors: Lim Hyemin , Denison Michael Immanuel Jesse , Lee Kyungmi , Natarajan Sathishkumar , Kim Tae-Lim , Oh Changyoung
Published: August 2024

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is crucial in plant metabolism and responses to various abiotic stresses. In the glycolysis pathway, glyceraldehyde-3-phosphate (G3P) is oxidized to 1,3-bisphosphate glycerate (1,3-BPG) through the catalytic action of GAPDH. However, the GAPDH gene family in Quercus rubra has been minimally researched. In this study, we identified 13 GAPDH-encoding genes in Q. rubra through a bioinformatics analysis of genomic data. Evolutionary studies suggest that these QrGAPDH genes are closely related to those in Glycine max and Triticum aestivum. We conducted a comprehensive whole-genome study, which included predictions of subcellular localization, gene structure analysis, protein motif identification, chromosomal placement, and analysis of cis-acting regions. We also examined the expression of GAPDH proteins and genes in various tissues of Q. rubra and under drought stress. The results indicated diverse expression patterns across different tissues and differential expression under drought conditions. Notably, the expression of Qurub.02G290300.1, Qurub.10G209800.1, and Qrub.M241600.1 significantly increased in the leaf, stem, and root tissues under drought stress. This study provides a systematic analysis of QrGAPDH genes, suggesting their pivotal roles in the drought stress response of trees.
Rootstock Effects on Fruit Yield and Quality of ‘BRS Tainá’ Seedless Table Grape in Semi-Arid Tropical Conditions
Authors: Oliveira Carlos Roberto Silva de , Mendonca Junior Antônio Francisco de , Leão Patrícia Coelho de Souza
Published: August 2024

In viticulture, choosing the most suitable rootstock for a specific scion cultivar is an efficient and cost-effective way to increase yield and enhance the physicochemical characteristics of the fruit. The objective of this study was to evaluate the agronomic performance of the ‘BRS Tainá’ grapevine on different rootstocks under the conditions of the Sub-Middle São Francisco Valley. The main experimental factor consisted of eight rootstocks (IAC 313, IAC 572, IAC 766, 101-14 MgT, Paulsen 1103, Ramsey, SO4, and Teleki 5C), arranged in randomized blocks with four replicates. The experiment was conducted over four production cycles, from 2021 to 2023, in a commercial crop area in Petrolina, PE, Brazil. There were significant effects of rootstocks for the yield and number of bunches per plant, as well as berry length and firmness. ‘BRS Tainá’ achieved the highest yield (22.2 kg per plant) when grafted onto the Paulsen 1103 rootstock, which was superior to the yield on 101-14 MgT, IAC 313, and IAC 572 rootstocks. The highest number of bunches (88) was obtained with ‘BRS Tainá’ grafted on Paulsen 1103, while the lowest number (63) was obtained on IAC 572; both these rootstocks were not significantly different from the other rootstocks. For all scion–rootstock combinations, the mean values for soluble solid (SS) content, titratable acidity (TA), and the SS/TA ratio were similar to those previously described for ‘BRS Tainá’, meeting the commercialization standard. The results for the yield and number of bunches per plant indicate the suitability of grafting ‘BRS Tainá’ on Paulsen 1103 under the semi-arid tropical conditions of the São Francisco Valley.
Functions and Regulatory Mechanisms of bHLH Transcription Factors during the Responses to Biotic and Abiotic Stresses in Woody Plants
Authors: Yan Tengyue , Shu Xiaochun , Ning Chuanli , Li Yuhang , Wang Zhong , Wang Tao , Zhuang Weibing
Published: August 2024

Environmental stresses, including abiotic and biotic stresses, have complex and diverse effects on the growth and development of woody plants, which have become a matter of contention due to concerns about the outcomes of climate change on plant resources, genetic diversity, and world food safety. Plant basic helix–loop–helix (bHLH) transcription factors (TFs) are involved in a variety of physiological processes and play an important role in biotic and abiotic stress responses of woody plants. In recent years, an increasing body of studies have been conducted on the bHLH TFs in woody plants, and the roles of bHLH TFs in response to various stresses are increasingly clear and precise. Therefore, it is necessary to conduct a systematic and comprehensive review of the progress of the research of woody plants. In this review, the structural characteristics, research history and roles in the plant growth process of bHLH TFs are summarized, the gene families of bHLH TFs in woody plants are summarized, and the roles of bHLH TFs in biotic and abiotic stresses in woody plants are highlighted. Numerous studies mentioned in this review have shown that bHLH transcription factors play a crucial role in the response of woody plants to biotic and abiotic stresses. This review serves as a reference for further studies about enhancing the stress resistance and breeding of woody plants. Also, the future possible research directions of bHLH TFs in response to various stresses in woody plants will be discussed.
Functional Identification of MhPYL4 Involved in Iron-Deficiency Stress in Malus Halliana Koehne
Authors: Wang Xiaoya , Zhang Zhongxing , Dong Yongjuan , Wang Yanxiu
Published: August 2024

The PYL protein family are crucial sensors of the core signals of abscisic acid (ABA) and significantly influence the plant’s response to ABA-mediated abiotic stresses as well as its growth and development. However, research on the role of the MhPYL4 gene in iron (Fe) deficiency in apple trees is limited. Studies have shown that the MhPYL4 gene, when exposed to Fe-deficiency stress, exhibits more rapid transcriptional upregulation than other genes’ quickly elevated transcription. However, the precise mechanism by which it alleviates this stress remains unclear. The MhPYL4 gene (ID:103432868), isolated from Malus halliana, was analyzed to elucidate its function. Arabidopsis plants engineered to overexpress the MhPYL4 gene exhibited increased leaf chlorosis and slower growth in response to Fe stress compared to the unmodified controls. The transgenic plants also exhibited elevated levels of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, as well as ferric chelate reductase (FCR) activities. Levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and superoxide anion (O2−) were increased. In addition, these transgenic plants had lower concentrations of proline (Pro) and Fe2+, which indicated that their stress tolerance was reduced. Similarly, the overexpression of MhPYL4 in apple calli resulted in inhibited growth and increased susceptibility under Fe stress conditions. Physiological evaluations indicated that the overexpression of MhPYL4 in Arabidopsis reduced its Fe stress tolerance by inhibiting chlorophyll synthesis. In apple calli, it altered pH levels, antioxidant enzyme activity, and Fe-reducing capabilities under the same stress conditions. In summary, the elevated expression of the MhPYL4 gene reduced the tolerance of both Arabidopsis and apple calli to Fe stress, suggesting that MhPYL4 acts as a negative regulator in response to Fe deficiency.