High Uptake Research Articles

Stepwise tuning carbon slits at sub-angstrom scale for dynamical separation of hydrogen isotope

Heavier hydrogen isotope is indispensable for many applications such as isotope tracing and labeling, neutron scattering, and nuclear fusion reaction. Thus it calls for efficient hydrogen isotope separation. Cryogenic adsorptive separation is an energy-efficient way for deuterium/protium (D2/H2) separation, requiring nanopores with precisely tuned pore size and suitable geometry to induce the quantum sieving effect. Herein, we report on the stepwise tuned slit-shaped ultramicropores at sub-angstrom (Å) scale for highly efficient D2/H2 separation. The opening width of carbon nanoslits was precisely tuned by the devised thermal-induced molecularly imprinting method. The adsorbent with 4.0 Å centered nanoslits showed an excellent D2/H2 uptake ratio of 1.9 with a high D2 uptake of 10.1mmol/g at 40 K and 100 kPa. Column breakthrough experiments revealed a high D2/H2 selectivity of 10.1 at 40 K. It evidenced that the 4.0 Å centered slits enable an optimal balance between the barrier induced by zero-point energy and the adsorption potential at 40 K, thereby reaching a selectively quantized configurational diffusion of D2/H2. Programmed thermal desorption experiments indicated that a 0.1 Å alteration of the slit size enhanced the quantum sieving effect of D2/H2 by 180 %. These results would benefit the understanding of D2/H2 separation behavior, and the design principle may inspire other isotope separations.

Haemorrhage after thrombectomy with adjuvant thrombolysis in unknown onset stroke depends on high early lesion water uptake

Background and purposeIn wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after...

Preclinical evaluation of [225Ac]Ac-crown-TATE – An alpha-emitting radiopharmaceutical for neuroendocrine tumors

BackgroundTargeted alpha therapy (TAT) of somatostatin receptor-2 (SSTR2) positive neuroendocrine tumors (NETs) involving Ac-225 ([225Ac]Ac-DOTA-TATE) has previously demonstrated improved therapeutic efficacy over conventional beta particle-emitting peptide receptor radionuclide therapy agents. DOTA-TATE requires harsh radiolabeling conditions for chelation of [225Ac]Ac3+, which can limit the achievable molar activities and thus therapeutic efficacy of such TAT treatments. Macropa-TATE was recently highlighted as a potential alternative to DOTA-TATE, owing to the mild radiolabeling conditions and high affinity toward [225Ac]Ac3+; however, elevated liver and kidney uptake were noted as a major limitation and a suitable imaging radionuclide is yet to be reported, which will be required for patient dosimetry studies and assessment of therapeutic benefit. Previously, [155Tb]Tb-crown-TATE has shown highly effective imaging of NETs in preclinical SPECT/CT studies, with high tumor uptake and low non-target accumulation; these favourable properties and the versatile coordination behavior of the crown chelator may therefore show promise for combination with Ac-225 for TAT. MethodsCrown-TATE was labeled with Ac-225, and radiochemical yield was analyzed as the function of crown-TATE concentration. LogD7.4 was measured as the indication of hydrophilicity. Free [225Ac]Ac3+ release from [225Ac]Ac-crown-TATE in human serum was studied. Biodistribution studies of [225Ac]Ac-crown-TATE in mice bearing AR42J tumors was evaluated at 1, 4, 24, 48, and 120 h, and the absorbed dose to major organs calculated. Therapy-monitoring studies with AR42J tumor bearing mice were undertaken using 30 kBq and 55 kBq doses of [225Ac]Ac-crown-TATE and compared to controls treated with PBS or crown-TATE. Results[225Ac]Ac-crown-TATE was successfully prepared with high molar activity (640 kBq/nmol), and characterized as a moderately hydrophilic radioligand (LogD7.4 = −1.355 ± 0.135). No release of bound Ac-225 was observed over 9 days in human serum. Biodistribution studies of [225Ac]Ac-crown-TATE showed good initial tumor uptake (11.1 ± 1.7% IA/g at 4 h) which was sustained up to 120 h p.i. (6.92 ± 2.03% IA/g). Dosimetry calculations showed the highest absorbed dose was delivered to the tumors. Therapy monitoring studies demonstrated significant (log-rank test, P < 0.005) improved survival in both treatment groups compared to controls. ConclusionsThis preclinical study demonstrated the therapeutic efficacy of [225Ac]Ac-crown-TATE for treatment of NETs, and highlights the potential of using crown chelator for stable chelation of Ac-225 under mild conditions.

Lymphatic endothelial cell-targeting lipid nanoparticles delivering VEGFC mRNA improve lymphatic function after injury.

Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Advances in targeted therapy have shown promise for treating diseases where conventional therapies have been ineffective and lymphatic vessels have recently emerged as a new therapeutic target. Lipid nanoparticles (LNPs) have emerged as a promising strategy for tissue specific delivery of nucleic acids. Currently, there are no approaches to target LNPs to lymphatic endothelial cells, although it is well established that intradermal (ID) injection of nanoparticles will drain to lymphatics with remarkable efficiency. To design an LNP that would effectively deliver mRNA to LEC after ID delivery, we screened a library of 150 LNPs loaded with a reporter mRNA, for both self-assembly and delivery in vivo to lymphatic endothelial cells (LECs). We identified and validated several LNP formulations optimized for high LEC uptake when administered ID and compared their efficacy for delivery of functional mRNA with that of free mRNA and mRNA delivered with a commercially available MC3-based LNP (Onpattro™). The lead LEC-specific LNP was then loaded with VEGFC mRNA to test the therapeutic advantage of the LEC-specific LNP (namely, LNP7) for treating a mouse tail lymphatic injury model. A single dose of VEGFC mRNA delivered via LNP7 resulted in enhanced LEC proliferation at the site of injury, and an increase in lymphatic function up to 14-days post-surgery. Our results suggest a therapeutic potential of VEGFC mRNA lymphatic-specific targeted delivery in alleviating lymphatic dysfunction observed during lymphatic injury and could provide a promising approach for targeted, transient lymphangiogenic therapy.

Factors influencing vaccine acceptance in pregnancy during the COVID-19 pandemic: A multicenter study from West Bengal, India

ABSTRACT Influenza, COVID-19, tetanus, pertussis and hepatitis B pose increased risk for pregnant women and infants and could be mitigated by maternal immunization. In India Tetanus-diphtheria (Td) and COVID-19 vaccines are recommended during pregnancy, while influenza and tetanus-acellular pertussis-diphtheria (Tdap) vaccines are not. We conducted a multicenter study from November 2021 to June 2022 among pregnant women (n = 172) attending antenatal clinics in three public hospitals in West Bengal, to understand the factors that influence women’s decisions to get vaccinated during pregnancy. Questions assessed vaccination coverage, knowledge, intention and willingness to pay for influenza vaccine, and factors influencing decisions to get Td, influenza, and COVID-19 vaccines. 152/172 (88.4%) women were vaccinated with Td, 159/172 (93%) with COVID-19, 1/172 (0.6%) with influenza, and none with Tdap. 10/168 (6%) had received hepatitis B vaccine (HBV). Community health workers advice was crucial for Td uptake and, the belief of protection from COVID for COVID-19 vaccines. Most women were unaware about Tdap (96%), influenza (75%), and influenza severity during pregnancy and infancy (85%). None were advised for influenza vaccination by healthcare providers (HCP), albeit, 93% expressed willingness to take, and pay INR 100–300 (95% CI: ≤100 to 300–500) [$ 1.3–4.0 (95% CI: ≤1.3, 4–6.7)] for it. Vaccination on flexible dates and time, HCP’s recommendation, proximity to vaccination center, and husband’s support were most important for their vaccination decisions. Women were generally vaccine acceptors and had high uptake of vaccines included in the Universal Immunization Program (UIP). Inclusion of influenza, Tdap, and HBV into UIP may improve maternal vaccine uptake.

Preclinical ImmunoPET Imaging Using a Zr-89-Labeled Anti-CD146 Monoclonal Antibody for Diagnosis of Melanoma.

The aim of this study was to evaluate the preclinical efficacy of [89Zr]Zr-DFO-Ab253 as a novel positron emission tomography (PET) tracer for CD146-positive malignant melanoma imaging. Considering the high expression of CD146 in malignant melanoma, this study investigated the effect of different CD146 expression levels on the tumor uptake of [89Zr]Zr-DFO-Ab253. CD146 selectivity was investigated by using the CD146-positive human melanoma cell A375 and the CD146-negative human alveolar epithelial cell A549. The cell uptake of [89Zr]Zr-DFO-Ab253 tracers was investigated, and receptor-binding affinities were measured by radioactive enzyme-linked immunosorbent assay. Biodistribution studies and micro-PET imaging of the radiotracers were performed on mice bearing A375 and A549 xenografts under baseline and blocking conditions. An immunohistochemical test was performed using A375 and A549 tissue sections for CD146 expression level analysis. [89Zr]Zr-DFO-Ab253 was obtained with a high radiochemical yield (87.86 ± 4.66%) and a satisfactory radiochemical purity (>98.0%). The specificity and affinity of [89Zr]Zr-DFO-Ab253 were confirmed in melanoma A375 cells and in vivo PET imaging of A375 tumor models. [89Zr]Zr-DFO-IgG and A549 lung tumors were prepared as control radiotracers and negative models to verify the specificity of [89Zr]Zr-DFO-Ab253 on CD146. [89Zr]Zr-DFO-Ab253 has a Kd of 4.01 ± 0.50 nM. PET imaging and biodistribution showed a higher uptake of [89Zr]Zr-DFO-Ab253 in A375 melanomas than that in A549 tumors (42.1 ± 4.04% vs 7.87 ± 1.30% ID/g at 120 h, P < 0.05). A low tumor uptake of [89Zr]Zr-DFO-IgG was observed with uptakes of 1.91 ± 0.41 and 2.80 ± 0.14 ID%/g when blocked at 120 h. The radiation-absorbed dose was calculated to be 0.13 mSv/MBq. This study demonstrates the synthesis and preclinical evaluation of [89Zr]Zr-DFO-Ab253 and indicates that the novel tracer has promising applications in malignant melanoma-specific PET imaging because of its high uptake and long-time retention in malignant melanoma. It also provides feasibility for the development of integrated molecular probes for diagnosis and treatment based on the CD146 target.

Green and Scalable Preparation of an Isomeric CALF-20 Adsorbent with Tailored Pore Size for Molecular Sieving of Propylene from Propane.

Molecular sieving of propylene (C3H6) from propane (C3H8) is highly demanded for C3H6 purification. However, delicate control over aperture size to achieve both high C3H6 uptake and C3H6/C3H8 selectivity with low cost remains a significant challenge. Herein, a green and scalable approach is reported for preparing an isomeric CALF-20 adsorbent, termed as NCU-20, using water as the only solvent with a cost of $10 per kilogram. NCU-20 features a contracted pore size (4.2×4.7Å2) compared to CALF-20 (5.2×5.7Å2), which enables molecular sieving of C3H6 (4.16×4.65Å2) from C3H8 (4.20×4.80Å2). Notably, NCU-20 exhibits record-high C3H6 adsorption capacity (94.41 cm3cm-3) at 298K and 1.0bar, outperforming all C3H6/C3H8 molecular sieving adsorbents. The sieving performances of C3H6/C3H8 are well maintained at elevated temperatures. Therefore, a delicate balance between C3H6 adsorption capacity (91.62 cm3cm-3) and C3H6/C3H8 selectivity (uptake ratio of 22.2) is obtained on NCU-20 at 298K and 0.5bar. Furthermore, dynamic breakthrough experiments demonstrate a high productivity of 65.39 cm3cm-3 for high-purity C3H6 (>99.5%) from an equimolar C3H6/C3H8 gas-mixture.

All-solid-waste-derived CaO-based sorbents for simultaneously enhanced calcium looping CO2 capture and thermochemical energy storage

Calcium looping (CaL) process relying on CaO as high-temperature CO2 sorbents is a prospective alternative technology for simultaneously cyclic CO2 capture and thermochemical energy storage. However, the cyclic stability and the energy storage density of the CaO-based sorbents decay drastically over repeated carbonation-calcination cycles. Herein, we yielded CaO-based sorbents derived from all industrial solid wastes with carbide slag (CS) as precursor and coal fly ash (CFA) as stabilizer featuring superior carbonation characteristics, stable CO2 cyclic uptake and high thermochemical energy storage density over multiple operation cycles. The optimal sorbent (CCS–H-G-CFA-D) exhibited a high initial CO2 uptake of 0.38 gCO2/gsorbent, superior cyclic stability with an average decay rate of 1.05% per cycle and remarkably stable energy storage density of 1375 kJ/kg, retaining 89.5% after 10 repeated cycles. Thereby, the simultaneously enhanced cyclic CO2 capture and thermochemical energy storage are attributed to adding CFA stabilizers in CS-derived CaO-based sorbents, forming stable skeleton to alleviate sintering, improving the uniform mixing degree between sorbent particles and promoting the carbonation reaction via synergistic effect. This simple and eco-friendly approach of cost-effective sorbents totally derived from industrial solid wastes provides a new avenue for large-scale practical CO2 capture and energy storage processes.

"Two-birds-one-stone" oral nanotherapeutic designed to target intestinal integrins and regulate redox homeostasis for UC treatment.

Designing highly efficient orally administrated nanotherapeutics with specific inflammatory site-targeting functions in the gastrointestinal tract for ulcerative colitis (UC) management is a noteworthy challenge. Here, we focused on exploring a specific targeting oral nanotherapy, serving as "one stone," for the directed localization of inflammation and the regulation of redox homeostasis, thereby achieving effects against "two birds" for UC treatment. Our designed nanotherapeutic agent OPNs@LMWH (oxidation-sensitive ε-polylysine nanoparticles at low-molecular weight heparin) exhibited specific active targeting effects and therapeutic efficacy simultaneously. Our results indicate that OPNs@LMWH had high integrin αM-mediated immune cellular uptake efficiency and preferentially accumulated in inflamed tissues. We also confirmed its effectiveness in the treatment experiment of colitis in mice by ameliorating oxidative stress and inhibiting the activation of inflammation-associated signaling pathways while simultaneously bolstering the protective mechanisms of the colonic epithelium. Overall, these findings underscore the compelling dual functionalities of OPNs@LMWH, which enable effective oral delivery to inflamed sites, thereby facilitating precise UC management.

Lactate-mediated mixotrophic co-cultivation of Clostridium drakei and recombinant Acetobacterium woodii for autotrophic production of volatile fatty acids

BackgroundAcetogens, a diverse group of anaerobic autotrophic bacteria, are promising whole-cell biocatalysts that fix CO2 during their growth. However, because of energetic constraints, acetogens exhibit slow growth and the product spectrum is often limited to acetate. Enabling acetogens to form more valuable products such as volatile fatty acids during autotrophic growth is imperative for cementing their place in the future carbon neutral industry. Co-cultivation of strains with different capabilities has the potential to ease the limiting energetic constraints. The lactate-mediated co-culture of an Acetobacterium woodii mutant strain, capable of lactate production, with the Clostridium drakei SL1 type strain can produce butyrate and hexanoate. In this study, the preceding co-culture is characterized by comparison of monocultures and different co-culture approaches.ResultsC. drakei grew with H2 + CO2 as main carbon and energy source and thrived when further supplemented with D-lactate. Gas phase components and lactate were consumed in a mixotrophic manner with acetate and butyrate as main products and slight accumulation of hexanoate. Formate was periodically produced and eventually consumed by C. drakei. A lactate-mediated co-culture of the A. woodii [PbgaL_ldhD_NFP] strain, engineered for autotrophic lactate production, and C. drakei produced up to 4 ± 1.7 mM hexanoate and 18.5 ± 5.8 mM butyrate, quadrupling and doubling the respective titers compared to a non-lactate-mediated co-culture. Further co-cultivation experiments revealed the possible advantage of sequential co-culture over concurrent approaches, where both strains are inoculated simultaneously. Scanning electron microscopy of the strains revealed cell-to-cell contact between the co-culture partners. Finally, a combined pathway of A. woodii [PbgaL_ldhD_NFP] and C. drakei for chain-elongation with positive ATP yield is proposed.ConclusionLactate was proven to be a well-suited intermediate to combine the high gas uptake capabilities of A. woodii with the chain-elongation potential of C. drakei. The cell-to-cell contact observed here remains to be further characterized in its nature but hints towards diffusive processes being involved in the co-culture. Furthermore, the metabolic pathways involved are still speculatory for C. drakei and do not fully explain the consumption of formate while H2 + CO2 is available. This study exemplifies the potential of combining metabolically engineered and native bacterial strains in a synthetic co-culture.

Engagement with health research summaries via digital communication to All of Us participants.

Summaries of health research can be a complementary way to return value to participants. We assess how research participants engage with summaries via email communication and how this can be improved. We look at correlations between demographic subgroups and engagement in a longitudinal dataset of 305626 participants (77% are classified as underrepresented in biomedical research) from the All of Us Research Program. We compare this against engagement with other program communications and use impact evaluations (N = 421510) to measure the effect of tailoring communication by (1) eliciting content preferences, (2) Spanish focused content, (3) informational videos, and (4) article content in the email subject line. Between March 2020 and October 2021, research summaries reached 67% of enrolled participants, outperforming other program communication (60%) and return of results (31%), which have a high uptake rate but have been extended to a subset of eligible participants. While all demographic subgroups engage with research summaries, participants with higher income, educational attainment, White, and older than 45 years open and click content most often. Surfacing article content in the email subject line and Spanish focused content had negative effects on engagement. Video and social media content and eliciting preferences led to a small directional increase in clicks. Further individualization of tailoring efforts may be needed to drive larger engagement effects (eg, delivering multiple articles in line with stated preferences, expanding preference options). Our findings are likely a conservative representation of engagement effects, given the coarseness of our click rate measure. Health research summaries show promise as a way to return value to research participants, especially if individual-level results cannot be returned. Personalization of communication requires testing to determine whether efforts are having the expected effect.

Conductive hydrogel as stress‐strain sensor for human motion monitoring

AbstractHydrogel‐based stress‐strain sensors have attracted immense attention recently for developing wearable electronic devices and health‐monitoring systems owing to their intrinsic soft characteristics and flexible nature. Developing hydrogel that has high conductivity, better mechanical performance, and elasticity is necessary for better analysis or getting accurate measurement data. Hence, this study focuses on the development of novel conductive hydrogels with enhanced mechanical, swelling, and sensing properties targeting the advancement of stress‐strain sensitive hydrogel sensors. Polyvinyl alcohol (PVA) and citric acid (CA) have been used to prepare esterified PVA/CA hydrogels while using a simple one‐pot method followed by doping with a conductive polymer (polyaniline, PANI). The resultant PVA/CA/PANI hydrogel displayed a high water uptake capacity of ∼4200%, a high mechanical strain of 700%, high puncture resistance, large durability, and a fast response time when applied as soft human‐motion sensors in real‐time measurement of large‐scale and subtle human physiological stress activities (i.e., joint motions in the forefinger, elbow, wrist, and neck). The high strain sensitivity and ultrahigh stretchability of hydrogel sensors allow them to detect small mechanical changes caused by human movement showing their great potential for hydrogel‐based sensor device fabrication.

Radiolabeling and Preclinical Evaluation of Therapeutic Efficacy of 225Ac-ch806 in Glioblastoma and Colorectal Cancer Xenograft Models.

The epidermal growth factor receptor (EGFR) protein is highly expressed in a range of malignancies. Although therapeutic interventions directed toward EGFR have yielded therapeutic responses in cancer patients, side effects are common because of normal-tissue expression of wild-type EGFR. We developed a novel tumor-specific anti-EGFR chimeric antibody ch806 labeled with 225Ac and evaluated its invitro properties and therapeutic efficacy in murine models of glioblastoma and colorectal cancer. Methods: 225Ac-ch806 was prepared using different chelators, yielding [225Ac]Ac-macropa-tzPEG3Sq-ch806 and [225Ac]Ac-DOTA-dhPzPEG4-ch806. Radiochemical yield, purity, apparent specific activity, and serum stability of 225Ac-ch806 were quantified. In vitro cell killing effect was examined. The biodistribution and therapeutic efficacy of 225Ac-ch806 were investigated in mice with U87MG.de2-7 and DiFi tumors. Pharmacodynamic analysis of tumors after therapy was performed, including DNA double-strand break immunofluorescence of γH2AX, as well as immunohistochemistry for proliferation, cell cycle arrest, and apoptosis. Results: [225Ac]Ac-macropa-tzPEG3Sq-ch806 surpassed [225Ac]Ac-DOTA-dhPzPEG4-ch806 in radiochemical yield, purity, apparent specific activity, and serum stability. [225Ac]Ac-macropa-tzPEG3Sq-ch806 was therefore used for both invitro and invivo studies. It displayed a significant, specific, and dose-dependent invitro cell-killing effect in U87MG.de2-7 cells. 225Ac-ch806 also displayed high tumor uptake and minimal uptake in normal tissues. 225Ac-ch806 significantly inhibited tumor growth and prolonged survival in both U87MG.de2-7 and DiFi models. Enhanced γH2AX staining was observed in 225Ac-ch806-treated tumors compared with controls. Reduced Ki-67 expression was evident in all 225Ac-ch806-treated tumors. Increased expression of p21 and cleaved caspase 3 was shown in U87MG.de2-7 and DiFi tumors treated with 225Ac-ch806. Conclusion: In glioblastoma and colorectal tumor models, 225Ac-ch806 significantly inhibited tumor growth via induction of double-strand breaks, thereby constraining cancer cell proliferation while inducing cell cycle arrest and apoptosis. These findings underscore the potential clinical applicability of 225Ac-ch806 as a potential therapy for EGFR-expressing solid tumors.

Minding the margins: Evaluating the impact of COVID-19 among Latinx and Black communities with optimal qualitative serological assessment tools.

COVID-19 disproportionately affected minorities, while research barriers to engage underserved communities persist. Serological studies reveal infection and vaccination histories within these communities, however lack of consensus on downstream evaluation methods impede meta-analyses and dampen the broader public health impact. To reveal the impact of COVID-19 and vaccine uptake among diverse communities and to develop rigorous serological downstream evaluation methods, we engaged racial and ethnic minorities in Massachusetts in a cross-sectional study (April-July 2022), screened blood and saliva for SARS-CoV-2 and human endemic coronavirus (hCoV) antibodies by bead-based multiplex assay and point-of-care (POC) test and developed across-plate normalization and classification boundary methods for optimal qualitative serological assessments. Among 290 participants, 91.4% reported receiving at least one dose of a COVID-19 vaccine, while 41.7% reported past SARS-CoV-2 infections, which was confirmed by POC- and multiplex-based saliva and blood IgG seroprevalences. We found significant differences in antigen-specific IgA and IgG antibody outcomes and indication of cross-reactivity with hCoV OC43. Finally, 26.5% of participants reported lingering COVID-19 symptoms, mostly middle-aged Latinas. Hence, prolonged COVID-19 symptoms were common among our underserved population and require public health attention, despite high COVID-19 vaccine uptake. Saliva served as a less-invasive sample-type for IgG-based serosurveys and hCoV cross-reactivity needed to be evaluated for reliable SARS-CoV-2 serosurvey results. The use of the developed rigorous downstream qualitative serological assessment methods will help standardize serosurvey outcomes and meta-analyses for future serosurveys beyond SARS-CoV-2.

68Ga-OncoFAP microPET/CT imaging in different breast cancer mouse models

BackgroundBreast cancer (BC) is currently the most common malignancy worldwide and the leading cause of cancer-related death in women. Positron emission tomography/computed tomography (PET/CT) with fluorine-18-2-fluoro-2-deoxy-glucose (18F-FDG-PET) plays an important role in staging breast cancer, and now many promising tracers for tumor imaging are striving for superior breast cancer detection and monitoring. Some studies have reported better results regarding the diagnostic and therapeutic value of FAP ligands, especially in the diagnostic evaluation of primary BC. MethodsIn this study, we have successfully radiolabeled the 68Ga-OncoFAP, which is FAP (Fibroblast activation protein) targeting tracer, and tested the imaging efficacy in both subcutaneous ER-positive MCF-7 breast cancer tumors models and orthotopic triple negative MDA-MB-231 breast cancer tumor models. ResultsMCF-7 subcutaneous tumors and MDA-MB-231 orthotopic tumors exhibited a high uptake of 68Ga-OncoFAP, which correlated with the corresponding pathological results. Between 30 and 100 min post injection, the tumor-to-background ratio (TBR) of MDA-MB-231 orthotopic tumors gradually decreased, but to a limited extent, all less than 10%. 68Ga-labeled OncoFAP could be applied for noninvasive imaging of breast cancer, and we could observe the metabolism of the probe by the MicroPET imaging. Conclusions68Ga-OncoFAP could selectively image fibroblast activation protein in mice models and is very promising for the diagnosis of different histological and molecular subtypes of breast cancer.

In Situ Hydrogel-Forming Powders Containing Eutectic Mixture of Curcumin-Arginine as a Multi-Drug Delivery System for Wound Healing Applications

Background: Curcumin (CUR) has antimicrobial, anti-inflammatory, and antioxidant bioactivities and is a promising molecule to treat chronic wounds. However, CUR shows limited oral bioavailability due to low aqueous solubility and dissolution, chemical instability, and rapid metabolism in the gastrointestinal tract and liver. Therefore, topical delivery seems to provide therapeutic concentrations of CUR in a controlled manner. Arginine (ARG) promotes the wound healing process. CUR and ARG form a eutectic mixture (EMCA) that can be used for simultaneous improvement of dissolution of CUR and combinational wound therapy. Here, we have formulated in situ hydrogel-forming powders of EMCA using hydrophilic carriers. Methods: EMCA was prepared by liquid-assisted grinding and analyzed by powder X-ray diffraction (PXRD) and Fourier transform infrared (FT-IR) methods. The formulations were prepared by mixing EMCA with sodium carboxy methyl cellulose, sodium alginate, and polyethylene glycol. Optical microscopy, flow property, dissolution rate, water uptake, hydrogel forming ability, release profile, and antioxidant activity of the formulated powders were measured and compared with raw CUR. Results: The solid-state analyses revealed the formation of EMCA. Photographs showed that EMCA exhibited a lower particle size than raw CUR and ARG. The formulation content significantly affected fluid uptake, hydrogel-forming ability, and dissolution rate. The optimized formulation (FEP5) showed a considerable enhancement in the dissolution rate of CUR and could control the release. FEP5 also demonstrated promising characteristics including high fluid uptake and suitable hydrogel-forming ability. FEP5 enhanced the antioxidant activity of CUR from 9% to 50%. Additionally, FEP5 exhibited improved flow properties compared to raw CUR, which is crucial for practical applications in wound therapy. Conclusion: Current work highlighted the potential of EMCA formulated as a hydrogel-forming powder as a novel formulation with improved dissolution, rapid fluid uptake, inexpensive components, feasible method of preparation, and easy application and removal for combinational wound therapy

Radiosynthesis and Preclinical Evaluation of 18F-Labeled Estradiol Derivatives with Different Lipophilicity for PET Imaging of Breast Cancer.

About 75% of breast tumors show an overexpression of the estradiol receptor (ER), making it a valuable target for tumor diagnosis and therapy. To date, 16α-[18F]fluoroestradiol (FES) is the only FDA-approved imaging probe for the positron emission tomography (PET) imaging of ER-positive (ER+) breast cancer. However, FES has the drawback of a high retention in the liver. Therefore, the aim of this study was the development and preclinical evaluation of estradiol (E2) derivatives with different lipophilicity. Three 18F-labeled prosthetic groups (two glycosyl and one PEG azide) were chosen for conjugation with ethinyl estradiol (EE) by 18F-CuAAC (Cu-catalyzed azide-alkyne cycloaddition). The cellular uptake in ER+ MCF-7 tumor cells was highest for the less hydrophilic derivative (18F-TA-Glyco-EE). In nude mice bearing different breast tumors (ER+ MCF-7 and T47D versus ER- MDA-MB-231), 18F-TA-Glyco-EE revealed a high uptake in the liver (13%ID/g, 30 min p.i.), which decreased over 90 min to 1.2%ID/g, indicating fast hepatobiliary clearance. The statistically significant difference of 18F-TA-Glyco-EE uptake in T47D compared to MDA-MB-231 tumors at 60-90 min p.i. indicated ER-specific uptake, whereas in vivo PET imaging did not provide evidence for specific uptake of 18F-TA-Glyco-EE in MCF-7 tumors, probably due to ER occupation by E2 after E2-dependent MCF-7 tumor growth in mice. However, in vitro autoradiography revealed a high specific binding of 18F-TA-Glyco-EE to ER+ tumor slices. We conclude that 18F-TA-Glyco-EE, with its increased hydrophilicity after deacetylation in the blood and thus rapid washout from non-target tissues, may be a viable alternative to FES for the PET imaging of breast cancer.

Sheffield One-Stop Service: A potential model to improve the screening uptake of diabetic peripheral neuropathy and other microvascular complications of diabetes.

The world is experiencing an enormous rise in the prevalence of diabetes, which is associated with massive healthcare costs that threaten to overwhelm many healthcare systems. Most of the diabetes expenditure is attributed to the management of chronic diabetes complications, including diabetic peripheral neuropathy (DPN)/diabetic foot complications, chronic kidney disease, sight-threatening retinopathy and cardiovascular diseases. Of these complications, the most overlooked is DPN. Most consultations around the world do not even involve taking off shoes and socks to carry out a foot examination, and even when carried out, the peripheral neurological examination using the 10-g monofilament diagnoses DPN when it is already at an advanced stage. Thus, all too often diabetes complications are diagnosed late, resulting in devastating outcomes, particularly in low- to middle-income countries. There is, therefore, an urgent need to instigate new strategies to improve microvascular screening uptake using a holistic protocol for annual diabetes health checks outside the busy diabetes clinic. One such approach, the Sheffield One-Stop Microvascular Screening Service, which involves modern point of care devices to diagnose DPN, has been shown to be feasible and effective, resulting in high uptake and early management of diabetes complications. This article outlines the advantages of this One-Stop Microvascular Screening Service and a plan to trial an adapted version of this service to a resource-limited country, the Philippines. If successful, this model has the potential for implementation in other countries around the world.

A novel anti-angiogenesis peptide in combination with cisplatin self-assembling into tube-like nanomedicine for oral treatment of gastric cancer

Cisplatin is a broad-spectrum antitumour agent, but its toxic side effects are severe. In clinical practice, cisplatin is typically administered intravenously, leading to unavoidable systemic toxicity, whereas oral administration of cisplatin is ineffective. In order to enhance the oral effectiveness of cisplatin and decrease its toxicity, a novel peptide was developed to act as an orally delivering carrier for platinum-based nanomedicine. This peptide naturally exhibited inhibitory effects on endothelial cells and angiogenesis. After being modified into a circular structure, its stability and tissue penetration ability were enhanced. Interestingly, it also demonstrated the ability to undergo self-assembly in aqueous environments and form tube-like nanomedicine when cisplatin was added. Oral administration of these nanotubes has shown remarkable structural stability, permeability across mucosal membranes, and a high selective uptake of cancer cells, resulting in a synergistic antitumour effect through the combined action of inhibiting blood vessel formation and suppressing cell proliferation in gastric cancer (GC). Our research has successfully demonstrated that Pt-chelated peptides possess the self-assembling potential to construct platinum-based nanomedicine for the oral treatment of GC.

Suitable Pore Confinement with Multiple Interactions in a Low-Cost Zeolitic Imidazolate Framework for Efficient Xe Capture and Separation

The increasing industrial demand for the noble gases xenon (Xe) and krypton (Kr), along with growing environmental concerns on their radionuclides, has made the efficient separation and purification of Xe and Kr a critical issue. Leveraging advanced porous materials to achieve highly efficient adsorptive Xe/Kr separation has been recognized as an energy-saving and economical alternative to the widely used cryogenic distillation technology. Herein, we present a stable, low-cost, and easily scalable zeolitic imidazolate framework (ZIF) material, ZIF-4, for effective xenon adsorption and separation. ZIF-4 possesses uniformly distributed pore cavities with ideally matched pore size (4.3 Å) with that of Xe atom (4.047 Å), providing appropriate pore confinement for Xe binding. Sorption isotherms of ZIF-4 demonstrate the remarkably high Xe uptake (1.64 mmol/g at 0.2 bar and 298 K) and excellent Xe/Kr separation selectivity (16.2 for IAST selectivity of 20/80 Xe/Kr gas mixtures). Breakthrough experiments further validate the efficient separation performance of ZIF-4 in both binary Xe/Kr (20/80) gas mixtures and under dilute conditions. Single-crystal X-ray diffraction studies of activated and Xe-loaded ZIF-4 crystals reveal that the flexible pore cavities of ZIF-4 can self-adaptively adsorb and accommodate Xe atoms through the rotation of imidazolate rings, forming multiple Xe···H and Xe···π interactions to create strong binding sites for Xe capture and discrimination. The stability, economic feasibility, and scalability of ZIF-4 underscore its significant potential for industrial Xe/Kr separation.