The host and pathogen myo-inositol-1-phosphate synthases are required for Rhizoctonia solani AG1-IA infection in tomato.

The myo-inositol-1-phosphate synthase (MIPS) catalyses the biosynthesis of myo-inositol, an important sugar that regulates various physiological and biochemical processes in plants. Here, we provide evidence that host (SlMIPS1) and pathogen (Rs_MIPS) myo-inositol-1-phosphate synthase (MIPS) genes are required for successful infection of Rhizoctonia solani, a devastating necrotrophic fungal pathogen, in tomato. Silencing of either SlMIPS1 or Rs_MIPS prevented disease, whereas an exogenous spray of myo-inositol enhanced disease severity. SlMIPS1 was upregulated upon R. solani infection, and potentially promoted source-to-sink transition, induced SWEET gene expression, and facilitated sugar availability in the infected tissues. In addition, salicylic acid (SA)-jasmonic acid homeostasis was altered and SA-mediated defence was suppressed; therefore, disease was promoted. On the other hand, silencing of SlMIPS1 limited sugar availability and induced SA-mediated defence to prevent R. solani infection. Virus-induced gene silencing of NPR1, a key gene in SA signalling, rendered SlMIPS1-silenced tomato lines susceptible to infection. These analyses suggest that induction of SA-mediated defence imparts disease tolerance in SlMIPS1-silenced tomato lines. In addition, we present evidence that SlMIPS1 and SA negatively regulate each other to modulate the defence response. SA treatment reduced SlMIPS1 expression and myo-inositol content in tomato, whereas myo-inositol treatment prevented SA-mediated defence. We emphasize that downregulation of host/pathogen MIPS can be an important strategy for controlling diseases caused by R. solani in agriculturally important crops.

Small Molecule-Mediated Stage-Specific Reprogramming of MSCs to Hepatocyte-Like Cells and Hepatic Tissue for Liver Injury Treatment.

BACKGROUND: Derivation of hepatocytes from stem cells has been established through various protocols involving growth factor (GF) and small molecule (SM) agents, among others. However, mesenchymal stem cell-based derivation of hepatocytes still remains expensive due to the use of a cocktail of growth factors, and a long duration of differentiation is needed, thus limiting its potential clinical application. METHODS: In this study, we developed a chemically defined differentiation strategy that is exclusively based on SM and takes 14 days, while the GF-based protocol requires 23-28 days. RESULTS: We optimized a stage-specific differentiation protocol for the differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) into functional hepatocyte-like cells (dHeps) that involved four stages, i.e., definitive endoderm (DE), hepatic competence (HC), hepatic specification (HS) and hepatic differentiation and growth. We further generated hepatic tissue using human decellularized liver extracellular matrix and compared it with hepatic tissue derived from the growth factor-based protocol at the transcriptional level. dHep, upon transplantation in a rat model of acute liver injury (ALI), was capable of ameliorating liver injury in rats and improving liver function and tissue damage compared to those in the ALI model. CONCLUSIONS: In summary, this is the first study in which hepatocytes and hepatic tissue were derived from MSCs utilizing a stage-specific strategy by exclusively using SM as a differentiation factor.

Liquid Biopsy in Progressing Prostate Cancer Patients Starting Docetaxel with or Without Enzalutamide: A Biomarker Study of the PRESIDE Phase 3b Trial.

BACKGROUND AND OBJECTIVE: The PRESIDE (NCT02288247) randomized trial demonstrated prolonged progression-free survival (PFS) with continuing enzalutamide beyond progression in metastatic castration-resistant prostate cancer (mCRPC) patients starting docetaxel. This study aims to test the associations of PFS and circulating tumor DNA (ctDNA) prior to and after one cycle (cycle 2 day 1 [C2D1]) of docetaxel and with a liquid biopsy resistance biomarker (LBRB; plasma androgen receptor [AR] gain and/or circulating tumor cells [CTCs] expressing AR splice variant 7 [CTC-AR-V7]) prior to continuation of enzalutamide/placebo. METHODS: Patients consenting to the biomarker substudy and donating blood before starting docetaxel with enzalutamide/placebo (N = 157) were included. Sequential plasma DNA samples were characterized with a prostate-cancer bespoke next-generation-sequencing capture panel (PCF_SELECT), and CTCs were assessed for AR-V7 (Epic Sciences, San Diego, CA, USA). Cox models, Kaplan-Meier, and restricted mean survival time (RMST) at 18 mo were calculated. KEY FINDINGS AND LIMITATIONS: There was a significant association of worse PFS with pre-docetaxel ctDNA detection (N = 86 (55%), 8.1 vs 10.8 mo hazard ratio [HR] = 1.78, p = 0.004) or persistence/rise of ctDNA at C2D1 (N = 35/134, 5.5 vs 10.9 mo, HR = 1.95, 95% confidence interval [CI] = 1.15-3.30, p = 0.019). LBRB-positive patients (N = 62) had no benefit from continuing enzalutamide with docetaxel (HR = 0.78, 95% CI = 0.41-1.48, p = 0.44; RMST: 7.9 vs 7.1 mo, p = 0.50). Conversely, resistance biomarker-negative patients (N = 87) had significantly prolonged PFS (HR = 0.49, 95% CI = 0.29-0.82, p = 0.006; RMST: 11.5 vs 8.9 mo, p = 0.005). Eight patients were unevaluable. An exploratory analysis identified increased copy-number gains (CDK6/CDK4) at progression on docetaxel. Limitations included relatively low detection of CTC-AR-V7. Validation of impact on overall survival is required. CONCLUSIONS AND CLINICAL IMPLICATIONS: Liquid biopsy gives an early indication of docetaxel futility, could guide patient selection for continuing enzalutamide, and identifies cell cycle gene alterations as a potential cause of docetaxel resistance in mCRPC. PATIENT SUMMARY: In the PRESIDE biomarker study, we found that detecting circulating tumor DNA in plasma after starting treatment with docetaxel (chemotherapy) for metastatic prostate cancer resistant to androgen deprivation therapy can predict early how long patients will take to respond to treatment. Patients negative for a liquid biopsy resistance biomarker (based on the status of androgen receptor (AR) gene and AR splice variant 7 in circulating tumor cells) benefit from continuing enzalutamide in combination with docetaxel, while patients positive for the resistance biomarker did not. Additionally, we identified alterations in the cell cycle genes CDK6 and CDK4 as a potential genetic cause of resistance to docetaxel, which may support testing of specific drugs targeting these alterations.

Rest-fMRI-A Potential Substitute for Task-fMRI?

Objective The aim of this study was to assess the reliability of resting-state functional magnetic resonance imaging (rest-fMRI) in mapping language areas for preoperative planning, versus standard task-based techniques, which are at times difficult to perform in clinical settings. Our study also aimed to evaluate the overlap between language areas identified through rest-fMRI and the standard task-fMRI, in neurosurgical cases. Materials and Methods Using a seed-based analysis of rest-fMRI with multiple template seeds, we identified functionally connected language regions in patients undergoing preoperative language mapping. Four language task paradigms (word, verb, picture, and semantics) were evaluated. We quantified the degree of overlap between language areas identified on rest-fMRI and task-fMRI, categorizing the results as more than 50% or less than 50% overlap. Results Seventy-seven percent of patients demonstrated an overlap exceeding 50% between rest- and task-fMRI maps, with the left Broca's area being the most frequently observed region of overlap. This finding was noted even in cases with lesions in Broca's or Wernicke's areas, highlighting the method's robustness. The verb task showed the best blood-oxygen-level dependent activity and overlap with rest-fMRI, highlighting its reliability. To identify a specific language area, the contralateral seed of the same area most commonly displayed connectivity with the area of interest. Conclusion Our findings demonstrate the potential of using rest-fMRI in accurately mapping eloquent language areas, in clinical settings The strong concordance observed, especially in the left Broca's area, underscores the reliability of this method. Further research and larger studies are essential to validate these results, potentially establishing the use of routine rest-fMRI, in clinical preoperative workup.

Evolutionary analysis of tonoplast intrinsic proteins (TIPs) unraveling the role of TIP3s in plant seed development.

Tonoplast intrinsic proteins (TIPs) are crucial in facilitating the transportation of water and various small solutes across biological membranes. The evolutionary path and functional roles of TIPs is poorly understood in plants. In the present study, a total of 976 TIPs were identified in 104 diverse species and subsequently studied to trace their lineage-specific evolutionary path and tissue-specific function. Interestingly, TIPs were found to be absent in lower forms such as algae and fungi and they evolved later in primitive plants like bryophytes. Bryophytes possess a distant class of TIPs, denoted as TIP6, which is not found in higher plants. The aromatic/arginine (ar/R) selectivity filter found in TIP6 of certain liverworts share similarity with hybrid intrinsic protein (HIP), suggesting an evolutionary kinship. As plants evolved to more advanced forms, TIPs diversified into five different sub-groups (TIP1 to TIP5). Notably, TIP5 is a sub-group unique to angiosperms. The evolutionary history of the TIP subfamily reveals an interesting observation that the TIP3 subgroup has evolved within seed-bearing Spermatophyta. Further, TIPs exhibit tissue-specific expression that is conserved within various plant species. Specifically, the TIP3s were found to be exclusively expressed in seeds. Quantitative PCR analysis of TIP3s showed gradually increasing expression in soybean seed developmental stages. The expression of TIP3s in different plant species was also found to be gradually increasing during seed maturation. The results presented here address the knowledge gap concerning the evolutionary background of TIPs, specifically TIP3 in plants, and provide valuable insights for a deeper comprehension of the functions of TIPs in plants.

Modulating the effective ionic radii of trivalent dopants in ceria using a combination of dopants to improve catalytic efficiency for the oxygen evolution reaction.

Aliovalent doping in ceria and defect engineering are important aspects in tuning the properties of ceria for advanced technological applications, especially in the emerging field of electrocatalytic water-splitting for harvesting renewable energy. However, the ambiguity regarding the choice of dopants/co-dopants and ways to deal with the size difference between dopants and lattice hosts remains a long-standing problem. In this study, ceria was aliovalently codoped with Sc3+ and La3+ while keeping the total concentration of dopants constant; the ionic radius of the former is smaller and that of the latter is larger than Ce4+. Variations in the relative amounts of these dopants helped to modulate the effective ionic radii and match that of the host. A systematic study on the role of these aliovalent dopants in defect evolution in ceria and in modulating the Ce3+ fraction using powder XRD, Rietveld refinement, positron annihilation lifetime spectroscopy, X-ray photoelectron spectroscopy, Eu3+ photoluminescence, and Raman spectroscopy is presented here. The evolved defects and their dependence on subtle factors other than charge compensation are further correlated with their electrocatalytic activity towards oxygen evolution reaction (OER) in alkaline medium. The catalyst with an optimum defect density, maximum Ce3+ fraction at the surface and the least effective ionic radius difference between the dopants and the host demonstrated the best performance towards the OER. This study demonstrates how effective ionic radius modulation in defect-engineered ceria through a judicious choice of codopants can enhance the catalytic property of ceria and provides immensely helpful information for designing ceria-based heterogeneous catalysts with desired functionalities.

Electrocatalytic OER behavior of the Bi-Fe-O system: an understanding from the perspective of the presence of oxygen vacancies.

This study aims to understand and correlate the role of the nature and relative concentration of oxygen vacancies with the trend observed in the OER with the Bi-Fe-O system. To understand this, we first investigated the system of oxides using X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance (EPR), which revealed the presence of oxygen vacancies in the system. Density functional theory (DFT) was employed to investigate the relative concentration of these vacancies by calculating their formation energies. Positron annihilation lifetime spectroscopy (PALS) was carried out to understand the nature of these oxygen vacancies. We observed that the presence of a higher concentration of monovacancies created due to the absence of oxygen from the structure of Bi2Fe4O9 was mainly responsible for the high performance of the oxide towards the OER compared to that of the other oxides viz-BiFeO3 and Bi25FeO40 of the Bi-Fe-O system.

Coordination Structure Modulation in Group-VIB Metal Doped Ag3PO4 Augments Active Site Density for Electrocatalytic Conversion of N2 to NH3.

Doping is considered a promising material engineering strategy in electrochemical nitrogen reduction reaction (NRR), provided the role of the active site is rightly identified. This work concerns the doping of group VIB metal in Ag3PO4 to enhance the active site density, accompanied by d-p orbital mixing at the active site/N2 interface. Doping induces compressive strain in the Ag3PO4 lattice and inherently accompanies vacancy generation, the latter is quantified with positron annihilation lifetime studies (PALS). This eventually alters the metal d-electronic states relative to Fermi level and manipulate the active sites for NRR resulting into side-on N2 adsorption at the interface. The charge density deployment reveals Mo as the most efficient dopant, attaining a minimum NRR overpotential, as confirmed by the detailed kinetic study with the rotating ring disk electrode (RRDE) technique. In fact, the Pt ring of RRDE fails to detect N2H4, which is formed as a stable intermediate on the electrode surface, as identified from in-situ attenuated total reflectance-infrared (ATR-IR) spectroscopy. This advocates the complete conversion of N2 to NH3 on Mo/Ag3PO4-10 and the so-formed oxygen vacancies formed during doping act as proton scavengers suppressing hydrogen evolution reaction resulting into a Faradaic efficiency of 54.8% for NRR.

Role of plant neurotransmitters in salt stress: A critical review.

Neurotransmitters are naturally found in many plants, but the molecular processes that govern their actions still need to be better understood. Acetylcholine, γ-Aminobutyric acid, histamine, melatonin, serotonin, and glutamate are the most common neurotransmitters in animals, and they all play a part in the development and information processing. It is worth noting that all these chemicals have been found in plants. Although much emphasis has been placed on understanding how neurotransmitters regulate mood and behaviour in humans, little is known about how they regulate plant growth and development. In this article, the information was reviewed and updated considering current thinking on neurotransmitter signaling in plants' metabolism, growth, development, salt tolerance, and the associated avenues for underlying research. The goal of this study is to advance neurotransmitter signaling research in plant biology, especially in the area of salt stress physiology.

Color tunable luminescence in ThO2:Er3+,Yb3+ nanocrystals: a promising new platform for upconversion.

Lanthanide-doped luminescent nanoparticles are an appealing system for many applications in the area of biomedical, solar cell, thermometry, anti-counterfeiting, etc. due to their sensitivity, reliability, high photochemical stability, and high optical transparency in the visible-NIR range. A color-tunable upconversion-luminescence (UCL) in a new low phonon energy ThO2 host based on modulating sensitizer concentration has been realized in this work and it may work as a potential candidate to replace corrosive and toxic fluoride based hosts in the future. Er3+-Yb3+ co-doped thoria nanoparticles were prepared using a gel combustion route and their structural and luminescence properties were determined as a function of the Yb3+ concentration. Phonon dispersion measurements have established the dynamic structural stability of the thoria nanoparticles. Density functional theory (DFT) was used to calculate the defect formation energy, highlighting the feasibility of dual ion (Er3+ and Yb3+) doping in thoria. The morphology and average size of the doped thoria was studied using high resolution transmission electron microscopy (HRTEM), and any defects evolving as a result of aliovalent doping were probed using positron annihilation lifetime spectroscopy (PALS). With 980 nm laser excitation, the nanothoria emits green and near-red light. A significant enhancement of the red-to-green intensity ratio of Er3+ ions in nanothoria was observed with an increase in Yb3+ concentration which resulted in beautiful color tunability from green to yellow light in going from lower (up to ∼5 mol%) to higher (10 and 15 mol%) Yb3+ concentration. The power dependence and the dynamics of the upconverted emission confirm the existence of two-photon upconversion processes for the green and red emissions.

ZnAl2O4:Er3+ Upconversion Nanophosphor for SPECT Imaging and Luminescence Modulation via Defect Engineering.

This work reports an "all-in-one" theranostic upconversion luminescence (UCL) system having potential for both diagnostic and therapeutic applications. Despite considerable efforts in designing upconversion nanoparticles (UCNPs) for multimodal imaging and tumor therapy, there are few reports investigating dual modality SPECT/optical imaging for theranostics. Especially, research focusing on in vivo biodistribution studies of intrinsically radiolabeled UCNPs after intravenous injection is of utmost importance for the potential clinical translation of such formulations. Here, we utilized the gamma emission from 169Er and 171Er radionuclides for the demonstration of radiolabeled ZnAl2O4:171/169Er3+ as a potent agent for dual-modality SPECT/optical imaging. No uptake of radio nanoformulation was detected in the skeleton after 4 h of administration, which evidenced the robust integrity of ZnAl2O4:169/171Er3+. Combining the therapeutics using the emission of ß- particulates from 169Er and 171Er will be promising for the radio-theranostic application of the synthesized ZnAl2O4:169/171Er3+ nanoformulation. Cell toxicity studies of ZnAl2O4:1%Er3+ nanoparticles were examined by an MTT assay in B16F10 mouse melanoma cell lines, which demonstrated good biocompatibility. In addition, we explored the mechanism of UCL modulation via defect engineering by Bi3+ codoping in the ZnAl2O4:Er3+ upconversion nanophosphor. The UCL color tuning was successfully achieved from the red to the green region as a function of Bi3+ codoping concentrations. Further, we tried to establish a correlation of UCL tuning with the intrinsic oxygen and cation vacancy defects as a function of Bi3+ codoping concentrations with the help of electron paramagnetic resonance (EPR) and positron annihilation lifetime spectroscopy (PALS) studies. This study contributes to building a bridge between nature of defects and UC luminescence that is crucial for the design of advanced UCNPs for theranostics.

High Electrical Conductivity and Hole Transport in an Insightfully Engineered Columnar Liquid Crystal for Solution-Processable Nanoelectronics.

Discotic liquid crystals (DLCs) are widely acknowledged as a class of organic semiconductors that can harmonize charge carrier mobility and device processability through supramolecular self-assembly. In spite of circumventing such a major challenge in fabricating low-cost charge transport layers, DLC-based hole transport layers (HTLs) have remained elusive in modern organo-electronics. In this work, a minimalistic design strategy is envisioned to effectuate a cyanovinylene-integrated pyrene-based discotic liquid crystal (PY-DLC) with a room-temperature columnar hexagonal mesophase and narrow bandgap for efficient semiconducting behavior. Adequately combined photophysical, electrochemical, and theoretical studies investigate the structure-property relations, logically correlating them with efficient hole transport. With a low reorganization energy of 0.2 eV, PY-DLC exhibits superior charge extraction ability from the contact electrodes at low values of applied voltage, achieving an electrical conductivity of 3.22 × 10-4 S m-1, the highest reported value for any pristine DLC film in a vertical charge transport device. The columnar self-assembly, in conjunction with solution-processable self-healed films, results in commendably elevated values of hole mobility (≈10-3 cm2 V-1s-1). This study provides an unprecedented constructive outlook toward the development of DLC semiconductors as practical HTLs in organic electronics.

Oxygen vacancy-enriched Zn2SnO4 for aliphatic alcohol sensing and enhanced selectivity towards n-butanol.

The sensitive detection of toxic flammable volatile organics using low cost efficient sensors is important for ensuring both indoor and outdoor safety. It is essential for chemical sensors to exhibit a significantly stronger response to target analytes compared to equivalent amounts of analogous competing chemicals. In line with this importance, current work evaluated the performance of Zn2SnO4, a n-type semiconducting metal oxide, for sensing n-butanol in comparison to methanol, ethanol, and propanol vapours. These vapours fall within the category of aliphatic alcohols but vary in characteristics such as molecular weight, vapour pressure, volatility, and diffusivity. In this work we have explored the sensor's performance by adjusting the operating temperature over the range of 225-300 °C while detecting 1000 ppm of each of these vapours. Efforts were made to establish a correlation between the sensor's responses with the interactions of these vapours on the sensor's surface. Prior to assessing the sensing characteristics of the solid-state-route-derived Zn2SnO4, its structural characteristics, including phase purity, crystalline structure, bonding patterns, morphology, and defect characteristics, were studied. This comprehensive analysis sheds light on the potential of Zn2SnO4 as an effective sensor for detecting n-butanol.

Detection of PSMA expression on circulating tumor cells by blood-based liquid biopsy in prostate cancer.

Background: For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA protein expression on circulating tumor cells may be beneficial for better informing therapeutic decision-making and identifying the patients most likely to benefit from PSMA-targeted radioligand therapy. Methods: Using high-throughput imaging and digital AI pathology algorithms, a four-color immunofluorescence assay has been developed to find PSMA protein expression on CTCs on a glass slide. Cell line cells (LNCaP/PC3s/22Rv1) spiked into healthy donor blood were used to study the precision, specificity, sensitivity, limit of detection, and overall accuracy of the assay. Clinical validation and low-pass whole-genome sequencing were performed in PSMA-PET-positive patients with high-risk mCRPC (N = 24) utilizing 3 mL of blood. Results: The PSMA CTC IF assay achieved analytical specificity, sensitivity, and overall accuracy above 99% with high precision. In the clinical validation, 76% (16/21) of the cases were PSMA positive with CTC heterogeneity, and 88% (21/24) of the patients contained at least one conventional CTC per milliliter of blood. Thirty-six low-pass-sequenced CTCs from 11 individuals with mCRPC frequently exhibited copy number increases in AR and MYC and losses in RB1, PTEN, TP53, and BRCA2 locus. Conclusions: The analytical validation utilizing Epic Sciences' liquid biopsy CTC platform demonstrated the potential to detect PSMA protein expression in CTCs from patients with mCRPC. This assay is positioned as an effective research tool to evaluate PSMA expression, heterogeneity, and therapeutic response in many ongoing clinical studies to target tumors that express PSMA.

Temperature-dependent hole mobility in pyrene-thiophene-based room-temperature discotic liquid crystals.

π-Conjugated pyrene-thiophene-based room-temperature discotic liquid crystals armed with four peripheral aliphatic chains are reported to study their potential use in a hole-transporting organic semiconductor. The charge carrier mobility studies using the ToF method revealed room temperature hole mobility in the order of 10-4 cm2 V-1 s-1 for both mesogens. However, the mobility values for compound 1a were observed in the order of 10-3 cm2 V-1 s-1 at high temperatures. Such molecular systems can potentially be used in nonlinear organic electronic applications.

Autocombustion Route Derived Zinc Ferrite Nanoparticles as Chemiresistive Sensor for Detection of Alcohol Vapors.

Prolonged exposure to alcohol vapors can have detrimental effects on human health, potentially leading to eye irritation, dizziness, and in some cases, damage to the nervous system. The present article aims to provide a comprehensive understanding on the synthesis and characterization of zinc ferrite (ZnFe2O4) nanoparticles, as well as their interactions with a range of alcohol vapors, including methanol, ethanol, n-propanol, and isopropanol. These alcohols differ in their molecular weight, boiling points, diffusivity, and other properties. The study reveals the semiconducting ZnFe2O4 nanoparticulate sensor's capability for reversible, repeatable, and sensitive detection of alcohol vapors. The sensor exhibits the highest response to ethanol within operating temperature range (225-300 °C). An attempt is made to establish a correlation between the properties of the target analytes and the observed sensing signals. Additionally, the response conductance transients of ZnFe2O4 under the exposure to the studied alcohol vapors are modeled based on the Langmuir-Hinshelwood adsorption mechanism. The characteristic time constants obtained from this modeling are justified with respect to the properties of the analytes.

Brachytherapy at the nanoscale with protein functionalized and intrinsically radiolabeled [169Yb]Yb2O3 nanoseeds.

PURPOSE: Classical brachytherapy of solid malignant tumors is an invasive procedure which often results in an uneven dose distribution, while requiring surgical removal of sealed radioactive seed sources after a certain period of time. To circumvent these issues, we report the synthesis of intrinsically radiolabeled and gum Arabic glycoprotein functionalized [169Yb]Yb2O3 nanoseeds as a novel nanoscale brachytherapy agent, which could directly be administered via intratumoral injection for tumor therapy. METHODS: 169Yb (T½ = 32 days) was produced by neutron irradiation of enriched (15.2% in 168Yb) Yb2O3 target in a nuclear reactor, radiochemically converted to [169Yb]YbCl3 and used for nanoparticle (NP) synthesis. Intrinsically radiolabeled NP were synthesized by controlled hydrolysis of Yb3+ ions in gum Arabic glycoprotein medium. In vivo SPECT/CT imaging, autoradiography, and biodistribution studies were performed after intratumoral injection of radiolabeled NP in B16F10 tumor bearing C57BL/6 mice. Systematic tumor regression studies and histopathological analyses were performed to demonstrate therapeutic efficacy in the same mice model. RESULTS: The nanoformulation was a clear solution having high colloidal and radiochemical stability. Uniform distribution and retention of the radiolabeled nanoformulation in the tumor mass were observed via SPECT/CT imaging and autoradiography studies. In a tumor regression study, tumor growth was significantly arrested with different doses of radiolabeled NP compared to the control and the best treatment effect was observed with ~ 27.8 MBq dose. In histopathological analysis, loss of mitotic cells was apparent in tumor tissue of treated groups, whereas no significant damage in kidney, lungs, and liver tissue morphology was observed. CONCLUSIONS: These results hold promise for nanoscale brachytherapy to become a clinically practical treatment modality for unresectable solid cancers.

Composition-dependent photoluminescence in nanocrystalline La2Hf2-xZrxO7:Eu phosphor: role of chemical twin Zr/Hf environments around a luminescent center.

Based on chemical intuition, linear trends are anticipated in Eu3+ photoluminescence performance inside a pyrochlore matrix of the chemical twins, Hf and Zr, owing to probable geometrical and chemical similarity around the luminescent center. The present work reports the drastically fluctuating result of doping Eu3+ in nanocrystalline pyrochlore, La2Hf2-xZrxO7 (LHZO), matrix on composition variation; the variation is counter to the anticipation-based chemical brotherhood of Hf and Zr. Zirconium-enriched samples of LHZO improve asymmetry around Eu3+ ion leading to enhanced photoluminescence quantum yield (PLQY). The samples with compositions 0.7Hf and 1.3Zr depict the lowest non-radiative channels with the highest theoretically calculated PLQY of ∼71% and excellent thermal stability (∼91%). Synergistic experimental and theoretical analysis reveals that Eu does not unbiasedly occupy La-sites in the pyrochlore LHZO matrix towards chemical twins of Hf and Zr; rather, it energetically prefers to occupy Zr-rich vicinal sites. When the composition with Zr is in the low-medium range, Eu has a higher probability of occupying Zr-rich vicinal sites depicting higher lifetime and PLQY. When Zr-content goes beyond 70-80%, the other site occupancies start contributing leading to a reduction in both lifetime and quantum yield. This work paves a great strategy and provides a futuristic potential to utilize europium luminescence in separating chemically close Hf-Zr for various technological applications.

Quality Assurance Considerations in Radiopharmaceutical Therapy Dosimetry Using PLANETDose: An International Atomic Energy Agency Study.

Implementation of radiopharmaceutical therapy dosimetry varies depending on the clinical application, dosimetry protocol, software, and ultimately the operator. Assessing clinical dosimetry accuracy and precision is therefore a challenging task. This work emphasizes some pitfalls encountered during a structured analysis, performed on a single-patient dataset consisting of SPECT/CT images by various participants using a standard protocol and clinically approved commercial software. Methods: The clinical dataset consisted of the dosimetric study of a patient administered with [177Lu]Lu-DOTATATE at Tygerberg Hospital, South Africa, as a part of International Atomic Energy Agency-coordinated research project E23005. SPECT/CT images were acquired at 5 time points postinjection. Patient and calibration images were reconstructed on a workstation, and a calibration factor of 122.6 Bq/count was derived independently and provided to the participants. A standard dosimetric protocol was defined, and PLANETDose (version 3.1.1) software was installed at 9 centers to perform the dosimetry of 3 treatment cycles. The protocol included rigid image registration, segmentation (semimanual for organs, activity threshold for tumors), and dose voxel kernel convolution of activity followed by absorbed dose (AD) rate integration to obtain the ADs. Iterations of the protocol were performed by participants individually and within collective training, the results of which were analyzed for dosimetric variability, as well as for quality assurance and error analysis. Intermediary checkpoints were developed to understand possible sources of variation and to differentiate user error from legitimate user variability. Results: Initial dosimetric results for organs (liver and kidneys) and lesions showed considerable interoperator variability. Not only was the generation of intermediate checkpoints such as total counts, volumes, and activity required, but also activity-to-count ratio, activity concentration, and AD rate-to-activity concentration ratio to determine the source of variability. Conclusion: When the same patient dataset was analyzed using the same dosimetry procedure and software, significant disparities were observed in the results despite multiple sessions of training and feedback. Variations due to human error could be minimized or avoided by performing intensive training sessions, establishing intermediate checkpoints, conducting sanity checks, and cross-validating results across physicists or with standardized datasets. This finding promotes the development of quality assurance in clinical dosimetry.

Tailoring Chiral Discotic Liquid Crystals: Mesophase Engineering through Alternative Approaches and Chain Lengths.

Hydrogen (H)-bonding is crucial in constructing superstructures in chemical (such as chiral discotic liquid crystals (DLCs)) as well as in biological systems due to its specific and directional nature. In this context, we achieved the successful synthesis of two branches of heptazine-based H-bonded complexes using distinct strategies. Hpz*-Es-Cn , we incorporated chiral alkyl tails (Hpz-chiral) onto the central C3 symmetric heptazine core, connected to achiral benzoic acid derivatives (Es-Cn acid) through H-bonding. In Hpz-Es-Cn -acid*, we used an achiral heptazine derivative (Hpz-Es-Cn ) linked to a chiral acid via H-bonding. On the other hand, based on the DSC results, we observed that Hpz*-Es-Cn complexes exhibited three distinct phases, whereas Hpz-Es-Cn -acid* complexes displayed only a single mesophase. In polarized optical microscopy (POM) observations, all the complexes displayed birefringence at room temperature, with the color of the POM images changing as the temperature varied. X-ray diffraction (XRD) studies at lower temperatures confirmed that Hpz*-Es-C8 exhibited the columnar rectangular (Colr ) phase, while Hpz*-Es-C10/12 exhibited the columnar oblique (Colob ) phase. However, all the H-bonded complexes exhibited the columnar hexagonal (Colh ) phase at higher temperatures. The chiroptical spectra recorded by Circular dichroism (CD) highlight the specific observations in the columnar phase of two complexes, Hpz*-Es-C10 and Hpz*-Es-C12 . This behavior has potential applications in various fields, including sensors, displays, and responsive materials.