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461 papers

Radiolabeled Angiopep-2 Peptide Vector as a Preclinical Platform for Blood-Brain Barrier Targeting: Synthesis, Radiolabeling, and Preliminary In Vivo Biodistribution in Mice.

Fotou E et al. · Jul 1, 2026

Brain tumor therapy remains limited by the blood-brain barrier (BBB), which restricts drug access. BBB-penetrating peptides offer a promising strategy for delivering therapeutic and diagnostic payloads. Angiopep-2 is a well-established vector, yet novel radioconjugates based on this vector remain of interest. We report the synthesis and evaluation of DOTA-Angiopep-2 for radiolabeling with Lutetium-177 ( 177 Lu) and Terbium-161 ( 161 Tb). Notably, 177 Lu serves as a β- and γ-emitter, whereas 161 Tb is an Auger and β-emitter; both are utilized in therapy and SPECT imaging. Peptides were synthesized via solid-phase peptide synthesis. Cytotoxicity assays in T98 glioblastoma cells showed that Angiopep-2 is well-tolerated, maintaining ~100% viability at 20 μM and a moderate decline up to 100 μM. Radiolabeling achieved yields > 95% with excellent radiochemical stability at room temperature for up to 10 days and moderate stability in the presence of human serum. Biodistribution in healthy CFW mice showed a brain-associated radioactivity of 0.24% ± 0.05% IA/g at 5 min p.i. and a 12-fold increase in the brain-to-blood ratio (0.028-0.339) by 60 min p.i. These results support DOTA-Angiopep-2 as a versatile platform for radionuclide delivery and a potential candidate for future glioma-targeted studies. Further studies in tumor-bearing models are ongoing to evaluate therapeutic efficacy and translational potential.

Materials Science

Healthy Public Policy Must Build Capacity: Analysing the Implementation of 3.2.2A, Australia's New Food Safety Standard.

Barnes J et al. · Jul 1, 2026

Issue addressed The integration of a new standard for food safety in Australia signifies a notable step toward national unity in the adoption of Hazard Analysis and Critical Control Point (HACCP) principles and contemporary food safety management tools for the food service and retail sector. The standard introduces key measures, including certification of food safety supervisors, food safety training requirements for food handlers, and means for substantiating control of food safety hazards throughout key food handling processes. Methods This study explored the experiences and perspectives of local regulators regarding the implementation and feasibility of the new standard. Data were collected via an online survey and semi-structured interviews with Environmental Health Practitioners across two Australian states. Results Findings reveal that implementation of the standard varied between states, largely shaped by the degree of support provided by respective state authorities. Six key barriers to effective implementation emerged from participant accounts. Conclusions In response, five targeted recommendations are proposed, grounded in established health promotion principles. Until these challenges are adequately addressed, the standard risks remaining ineffectual, limiting its capacity to enhance public health outcomes. SO WHAT?: The key to effective implementation and realisation of Standard 3.2.2A as healthy public policy lies within the central tenets of public health theory and practice.

Agricultural and Biological Sciences

Diffusion-weighted Imaging Distortion in Prostate MRI: A Cross-sectional Study Comparing Supine and Prone Positioning.

Lee KL et al. · Jul 1, 2026

Objectives Diffusion weighted imaging (DWI) is a key component of multiparametric (mp) prostate MRI. DWI using echo-planar techniques is susceptible to distortion at the recto-prostatic air-tissue interface. This study was to determine whether prone patient positioning reduces adjacent rectal air and DW image distortion when compared with standard-of-care supine positioning. Materials and methods This prospective study included consecutive patients undergoing mpMRI for suspected PCa between 2023 and 2024. Prostate segmentation was performed on DW and contrast-enhanced images. DWI distortion was measured quantitatively. Qualitative image quality of DWI and T2-weighted imaging (T2WI) was evaluated using PI-QUAL version 2; a separate 5-point clinically based Likert scale was employed to evaluate the volume of rectal air adjacent to the prostate. Results Fifty-two patients were enrolled. In total, 58% of patients expressed a preference for supine imaging versus 20% for prone imaging. Qualitative DWI image quality improved significantly in the prone position [median: 4 (3 to 4)] versus supine [3 (1 to 4)]; P 4 cm 3 of supine rectal air (n = 19), distortion was significantly reduced by prone imaging [3.49 mm (2.84 to 4.03)] compared with supine [4.60 mm (3.17 to 5.95)]; P = 0.02. The mean additional scanning time for the necessary prone imaging was 8 minutes 18 seconds. Conclusions Prone positioning significantly reduces DWI distortion artefact when rectal air is present, but consistently results in degraded T2WI quality.

Medicine

Mex-3 RNA-binding family member A limits macrophage ferroptosis-associated injury linked to the SLC7A11/GPX4 pathway in diabetic atherosclerosis.

Ma Y et al. · Jul 1, 2026

Background Diabetes accelerates atherosclerotic plaque expansion and loss of stability, but the plaque-resident mechanisms through which the diabetic milieu promotes macrophage lipid-oxidative injury are not fully understood. Methods We used apolipoprotein E-deficient (ApoE -/- ) mice with Mex-3 RNA-binding family member A (MEX3A) deficiency and primary bone marrow-derived macrophage (BMDM) experiments under diabetic conditions to investigate the role of MEX3A in diabetic atherosclerosis and macrophage lipid-peroxidation injury. Results MEX3A loss worsened diabetic atherosclerosis while leaving body weight, glycaemia and lipid measurements largely unchanged relative to diabetes alone. MEX3A deficiency enlarged aortic lesions, enhanced lipid deposition, increased macrophage content, expanded necrotic cores and thinned fibrous caps, while reducing collagen content. In lesional macrophages, loss of MEX3A coincided with increased lipid reactive oxygen species, malondialdehyde, increased labile iron, 4-hydroxynonenal, a disturbed glutathione redox state, mitochondrial abnormalities compatible with ferroptotic stress, lower GPX4/SLC7A11 and higher ACSL4. CRISPR/Cas9-mediated Mex3a knockout in BMDMs recapitulated this phenotype, whereas restoring MEX3A blunted it. RNA immunoprecipitation-qPCR together with actinomycin D decay analyses demonstrated preferential recovery of Slc7a11 and Gpx4 transcripts with MEX3A and decreased stability of Slc7a11 and Gpx4 mRNAs after Mex3a knockout. GPX4 or SLC7A11 overexpression reduced lipid-peroxidation injury in Mex3a-knockout macrophages, whereas Gpx4 or Slc7a11 knockdown weakened the protection conferred by MEX3A re-expression. Ferrostatin-1 partially attenuated macrophage lipid peroxidation and plaque injury. Conclusions Together, these results place MEX3A among the protective regulators of diabetic plaque stability and support a MEX3ASLC7A11/GPX4-linked ferroptosis-associated mechanism in plaque macrophages. Key points MEX3A deficiency worsens diabetic atherosclerosis without further aggravating systemic metabolic indices. Loss of MEX3A promotes plaque lipid deposition, macrophage accumulation, necrotic core expansion and fibrous cap thinning. MEX3A limits macrophage lipid-peroxidation injury linked to the SLC7A11/GPX4 pathway. Ferrostatin-1 partially attenuates macrophage lipid peroxidation and plaque injury associated with MEX3A deficiency.

Medicine

Feasibility and Acceptability of a Breastfeeding Support Intervention Among Mothers of Infants Under Six Months Old Discharged From Malnutrition Treatment in Kilifi County.

Unda J et al. · Jul 1, 2026

Malnourished infants under 6 months experience poor growth and development. A pilot study applied the WHO guideline for treatment of acute malnutrition and found that it was possible to re-establish exclusive breastfeeding during inpatient treatment. However, weight gain could not be sustained 6 weeks after discharge suggesting that follow-up breastfeeding support may be required. Our study aimed to pilot the feasibility and acceptability of a follow-up intervention among infants discharged from malnutrition treatment. A home-based post-discharge breastfeeding support intervention was developed to be delivered by breastfeeding peer supporters in a series of three home visits and three intervention phone calls over a period of 7 weeks after discharge from the hospital. The intervention was piloted among 20 mother-infant pairs providing quantitative and qualitative data from a standardized questionnaire and in-depth interviews. Data was analyzed descriptively and using thematic analysis. The median infant birth weight was 2.07 kg and > 50% of the mothers had primary education or less. The intervention was feasible with 100% reach of the target participants with a geographic spread of 25% urban and 75% rural areas. All intervention components were applied consistently, resulting in 100% adherence over a 6-month period. The intervention was accepted by mothers, perceived to be beneficial, and reported to increase breastfeeding confidence. It was adaptable, adjusting to emerging challenges, and was successfully integrated into existing health services. The pilot demonstrated high feasibility and widespread acceptance of the intervention. Its effectiveness to improve weight gain among recovering infants is being determined in a trial.

Nursing

Combined electrospun fibre-microneedle patches for enhanced transmucosal delivery of benzodiazepines and proteins.

Berry C et al. · Jul 1, 2026

The oral mucosa is highly vascularised, which permits rapid drug uptake into the systemic circulation, avoiding first-pass metabolism for chemicals that penetrate the epithelial permeability barrier. Electrospun mucoadhesive patches have been developed for controlled drug delivery and although contact times and drug distribution are improved, transmucosal drug permeation is still limited to small lipophilic molecules. Incorporation of solid microneedles with an electrospun patch to physically disrupt the epithelial barrier whilst simultaneously delivering a payload, can overcome these issues whilst addressing the drug-loading limitations often experienced with microneedles. Here, we developed a mucoadhesive patch and microneedle composite for delivery of the benzodiazepine, midazolam hydrochloride, required for rapid, systemic delivery to treat status epilepticus and antigen-binding fragments (f(ab)), proteins too large to cross the epithelial permeability barrier. Solid polylactic acid microneedles were manufactured through reverse micromoulding, optimised for buccal permeation and imaged using optical coherence tomography. Electrospun mucoadhesive patches, loaded with midazolam hydrochloride or f(ab), were combined with the microneedles and permeation through tissue-engineered buccal mucosa quantified by high-performance liquid chromatography or immunoassay and imaged by fluorescence confocal microscopy. Microneedle-mediated patch delivery enhanced patch retention time, drug delivery rates and overall permeation when compared to patch-only controls, facilitating rapid delivery of time-sensitive midazolam within minutes, and a 15-fold increase in f(ab) permeation over 2 h, importantly delivering it through the epithelium into the underlying lamina propria. This study demonstrates that microneedle-mediated mucoadhesive patches can enhance transmucosal drug delivery for poorly-permeable drugs and holds significant potential when rapid, systemic drug delivery is required.

Pharmacology, Toxicology and Pharmaceutics

2-Pyrazoline-5-One Derivative Suppresses Cell Proliferation and Induces Apoptosis With Upregulation of Bax in Breast Cancer Cells.

Sevinc SK et al. · Jul 1, 2026

The most common cancer in women worldwide is still breast cancer. Among its subtypes, luminal A and triple-negative breast cancers present significant therapeutic challenges due to intrinsic drug resistance and absence of effective targeted treatments. The pharmacological potential of heterocyclic compounds has garnered more attention in recent years, and structures like pyrazolines, hydrazones, and triazoles are important in the development of new drugs. Compounds incorporating these scaffolds have been shown in numerous studies to have strong anticancer action. In this regard, pyrazoline derivatives have become a viable field of study for focused treatment approaches. This study focused on evaluating the cytotoxic potential of the 2-pyrazoline-5-one derivative compound against luminal-A (MCF-7) and triple-negative (MDA-MB-231) breast cancer cell lines. The CCK-8 test was used to assess the impact on cell viability. Additionally, Annexin V/PI staining was used to identify the apoptotic effects, and fluorescence microscopy was used for analysis. The wound healing experiment was used to measure the capacity of cells to migrate, and migration process was monitored following scratch formation. The colony formation assay was used to assess the potential for cell proliferation, and clonal growth capacities were compared. Bax protein levels in compound-treated cancer cells were quantified by ELISA to investigate the apoptotic mechanism. IC50 values in MCF-7 and MDA-MB-231 cell lines were used to evaluate the cytotoxic effects of the 2-pyrazoline-5-one derivative. The compound exhibited strong cytotoxic activity and reduced cell viability in both cell lines in a concentration-dependent manner, with IC 50 values of 13 µM in MCF-7 cells and 16 µM in MDA-MB-231 cell. Furthermore, the compound effectively induced apoptosis and significantly suppressed colony formation and cell migration in both cell lines. Additionally, it showed a concentration-dependent rise in Bax protein levels, suggesting a pro-apoptotic action. These results confirm that the 2-pyrazoline-5-one derivative has strong antiproliferative and pro-apoptotic activity through Bax activation, providing a possible pathway for the creation of targeted treatments for breast cancer.

Chemistry

Efficacy of Metformin in Prevention of Glucocorticoid-Induced Hyperglycemia in Patients Without Diabetes: A Meta-Analysis.

Murtaza S et al. · Jul 1, 2026

Purpose The glucocorticoids are increasingly being used in the management of different autoimmune conditions and cancers. Our meta-analysis aims to leverage metformin's potential to reverse the metabolic complications of glucocorticoids by activating AMP-activated protein kinase (AMPK), while sparing their anti-inflammatory benefits. Methods PubMed, Cochrane Library, trial registries and Google Scholar were searched from inception to June 2025 for Randomized Controlled Trials (RCTs) and observational studies comparing metformin and placebo to prevent metabolic side effects of glucocorticoid therapy in non-diabetic patients. After screening by two independent reviewers according to PRISMA guidelines, four studies involving 187 patients were analysed using the random-effects model in RevMan 5.4.1, and mean differences (MD) were calculated. Results Preventive metformin administration during glucocorticoid treatment is superior to placebo with respect to glycaemic control as shown by statistically significant reduction in fasting blood glucose [MD = -0.60 (95% CI: -0.86 to -0.34)], HOMA index of insulin resistance [MD = -0.53 (95% CI: -0.97 to -0.08)], LDL levels [MD = -0.20 (95% CI: -0.40 to -0.00)] and total cholesterol [MD = -0.27 (95% CI: -0.54 to -0.01)]. However, our study failed to show significant improvement in area under the curve glucose (mmol/L × min) after challenge [MD = -176.66 (95% CI: -415.42, 62.11)], basal metabolic rate (BMR) [MD = 51.99 (95% CI: -53.08, 157.07)], HDL [MD = -0.04 (95% CI: -0.13, 0.05)], insulin levels [MD = -2.26 (95% CI: -5.90, 1.38)], triglycerides [MD = -0.15 (95% CI: -0.42, 0.13)] and body weight [MD = -0.93 (95% CI: -2.29 to 0.44)]. Conclusion While glucocorticoids remain essential in various clinical contexts, their detrimental effects on glucose metabolism are well documented. This study supports metformin as a promising preventive treatment in non-diabetic patients receiving systemic glucocorticoid therapy. Improvement in insulin sensitivity and resulting fasting glucose levels may offset glucocorticoid-exacerbated inflammation. Further studies are needed to address long-term outcomes, including adiposity, bone metabolism, appetite, liver function and muscle wasting, as well as to identify possible predictors of therapeutic response. Trial registration International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD420251104082.

Biochemistry, Genetics and Molecular Biology

Improving image quality in terbium-161 phantom imaging: Quantitative evaluation of DEW and TEW scatter correction methods.

Can M et al. · Jul 1, 2026

Background Terbium-161 (Tb-161) emits gamma rays and beta radiation, enabling both therapeutic and imaging applications. However, the multiple gamma emissions of 161 Tb can affect image quality by increasing the scattering rate during SPECT imaging. To improve image quality, appropriate scatter correction methods, such as Dual-Energy Window (DEW) and Triple-Energy Window (TEW) need to be optimized. Although these methods are used in clinical practice, studies investigating the efficacy of spectral analysis approaches for next-generation radionuclides with multiple gamma emissions, such as 161 Tb, are limited. Purpose This study aims to evaluate the effects of DEW and TEW scatter correction methods on image quality and quantitative accuracy in 161 Tb SPECT imaging compared to uncorrected images. Methods Three distinct reference geometries were utilized to determine the gamma camera calibration factor (CF) and to evaluate the image quality parameters. Five image protocols were used, each with different combinations of main photopeak and scatter energy windows. Image quality parameters (CF, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), spatial resolution) and activity bias (%) were compared using LifeX software in both uncorrected and corrected SPECT images. Results The CF calculated in images acquired with an energy window of 48.9 keV was found to be higher than that calculated in an energy window of 74.6 keV. The best CNR was calculated for images acquired in air with a photopeak of 48.9 keV ± 10% and a scatter window of 6%. In scattered media, it was observed in images obtained with a photopeak of 74.6 keV ± 10% and a scatter window of 6%. When scatter correction was applied, the images' SNR values decreased slightly, ranging from 1.188 to 1.724 across all media. Scatter correction techniques reduced the FWHM values for all protocols except the air medium, thereby improving spatial resolution. Activity bias results showed an overestimation in uncorrected protocols including the 48.9 keV peak. Conversely, utilizing the 74.6 keV peak with TEW correction improved quantitative accuracy to a 3.7%-4.2% absolute bias. Conclusion Our results show that both DEW and TEW correction approaches improve spatial resolution and increase CNR by reducing scattering contributions and background noise. However, as expected with the subtraction of scattered effects, these enhancements are accompanied by a slight decrease in SNR. The TEW method performed better than the DEW method in terms of quantitative accuracy under scattering conditions. In SPECT imaging using therapeutic amounts of Tb-161, high image quality can be achieved with an energy window of 74.6 keV ± 10%.

Medicine

Dipolar Order Mapping Based on Spin-Lock Magnetic Resonance Imaging.

Gao Z et al. · Jul 1, 2026

Inhomogeneous magnetization transfer (ihMT) is sensitive to dipolar order associated with motion-restricted macromolecules and can be characterized by the dipolar relaxation time T1D$$ {T}_{1D} $$ . In this study, we propose a spin-lock MRI framework for T1D$$ {T}_{1D} $$ quantification. Specifically, we introduce a T1D$$ {T}_{1D} $$ -sensitive metric, RATIOdosl$$ RATI{O}_{dosl} $$ , derived from the distinct relaxation rate Rdosl$$ {R}_{dosl} $$ , defined as the difference between dual-frequency and single-frequency R1ρ$$ {R}_{1\rho } $$ measurements. To enable dual-frequency spin-lock acquisition, we developed a dedicated rotary-echo spin-lock sequence. Based on this framework, we further estimated T1D$$ {T}_{1D} $$ and the macromolecular proton fraction (MPF) within a unified acquisition. The proposed method was evaluated using numerical simulations, phantom experiments, and in vivo imaging in the healthy human brain. Simulations demonstrated high sensitivity of RATIOdosl$$ RATI{O}_{dosl} $$ to T1D$$ {T}_{1D} $$ and supported the robustness of the proposed approach under the investigated conditions. Phantom experiments showed measurable ihMT contrast and supported the feasibility of T1D$$ {T}_{1D} $$ estimation using RATIOdosl$$ RATI{O}_{dosl} $$ . In vivo experiments demonstrated simultaneous T1D$$ {T}_{1D} $$ and MPF mapping using only three spin-lock-prepared images. Across 10 healthy volunteers, mean white matter T1D$$ {T}_{1D} $$ values ranged from approximately 3.70 to 4.80 ms. By requiring only three contrast-prepared images, the proposed technique provides a rapid framework for simultaneous T1D$$ {T}_{1D} $$ and MPF mapping and may facilitate further investigation of dipolar-order-sensitive microstructural imaging in vivo.

Medicine