Light-Responsive Layer-By-Layer Film Containing Gold Nanorods for Sequential Drug Release

Chemically and physically stable multidrug-loaded layer-by-layer (LbL) films are promising candidates for sequential and on-demand drug release at concentrations suitable for various applications. The synergistic effect of the sequential release of drugs may enhance their therapeutic efficacy in treating skin cancer and other complex medical conditions. In this study, we prepared LbL films by alternating the deposition of cationic linear polyethylenimine, camptothecin (CPT)-loaded gold nanorods (GNRs), anionic poly­(styrenesulfonate), and doxorubicin (DOX) based on electrostatic interactions. The film exhibited loading of CPT and DOX, which could be tuned according to the requirements of the application by changing the parameters of the LbL process. Herein, CPT was encapsulated in GNRs and showed good stability and absorption in the near-infrared (NIR) range (650–900 nm). The prepared LbL film showed a pH-dependent DOX release. Subsequently, the functionalized GNRs showed excellent photothermal properties, which assisted the on-demand release of CPT upon NIR irradiation with further release of DOX. Our results suggest that the LbL approach for sequential drug release can be an effective drug delivery platform owing to its cytocompatibility, anticancer effects, and stimuli-responsive properties

Carbofunctional Silatrane Possessing Imidazole Moiety: Synthesis, Characterization, and Antibacterial Studies

<div><p>GRAPHICAL ABSTRACT</p><p></p></div

Table_2_Omics Path to Increasing Productivity in Less-Studied Crops Under Changing Climate—Lentil a Case Study.XLSX

Conventional breeding techniques for crop improvement have reached their full potential, and hence, alternative routes are required to ensure a sustained genetic gain in lentils. Although high-throughput omics technologies have been effectively employed in major crops, less-studied crops such as lentils have primarily relied on conventional breeding. Application of genomics and transcriptomics in lentils has resulted in linkage maps and identification of QTLs and candidate genes related to agronomically relevant traits and biotic and abiotic stress tolerance. Next-generation sequencing (NGS) complemented with high-throughput phenotyping (HTP) technologies is shown to provide new opportunities to identify genomic regions and marker-trait associations to increase lentil breeding efficiency. Recent introduction of image-based phenotyping has facilitated to discern lentil responses undergoing biotic and abiotic stresses. In lentil, proteomics has been performed using conventional methods such as 2-D gel electrophoresis, leading to the identification of seed-specific proteome. Metabolomic studies have led to identifying key metabolites that help differentiate genotypic responses to drought and salinity stresses. Independent analysis of differentially expressed genes from publicly available transcriptomic studies in lentils identified 329 common transcripts between heat and biotic stresses. Similarly, 19 metabolites were common across legumes, while 31 were common in genotypes exposed to drought and salinity stress. These common but differentially expressed genes/proteins/metabolites provide the starting point for developing high-yielding multi-stress-tolerant lentils. Finally, the review summarizes the current findings from omic studies in lentils and provides directions for integrating these findings into a systems approach to increase lentil productivity and enhance resilience to biotic and abiotic stresses under changing climate.</p

Table_1_Omics Path to Increasing Productivity in Less-Studied Crops Under Changing Climate—Lentil a Case Study.XLSX

Conventional breeding techniques for crop improvement have reached their full potential, and hence, alternative routes are required to ensure a sustained genetic gain in lentils. Although high-throughput omics technologies have been effectively employed in major crops, less-studied crops such as lentils have primarily relied on conventional breeding. Application of genomics and transcriptomics in lentils has resulted in linkage maps and identification of QTLs and candidate genes related to agronomically relevant traits and biotic and abiotic stress tolerance. Next-generation sequencing (NGS) complemented with high-throughput phenotyping (HTP) technologies is shown to provide new opportunities to identify genomic regions and marker-trait associations to increase lentil breeding efficiency. Recent introduction of image-based phenotyping has facilitated to discern lentil responses undergoing biotic and abiotic stresses. In lentil, proteomics has been performed using conventional methods such as 2-D gel electrophoresis, leading to the identification of seed-specific proteome. Metabolomic studies have led to identifying key metabolites that help differentiate genotypic responses to drought and salinity stresses. Independent analysis of differentially expressed genes from publicly available transcriptomic studies in lentils identified 329 common transcripts between heat and biotic stresses. Similarly, 19 metabolites were common across legumes, while 31 were common in genotypes exposed to drought and salinity stress. These common but differentially expressed genes/proteins/metabolites provide the starting point for developing high-yielding multi-stress-tolerant lentils. Finally, the review summarizes the current findings from omic studies in lentils and provides directions for integrating these findings into a systems approach to increase lentil productivity and enhance resilience to biotic and abiotic stresses under changing climate.</p

Table_3_Omics Path to Increasing Productivity in Less-Studied Crops Under Changing Climate—Lentil a Case Study.XLSX

Conventional breeding techniques for crop improvement have reached their full potential, and hence, alternative routes are required to ensure a sustained genetic gain in lentils. Although high-throughput omics technologies have been effectively employed in major crops, less-studied crops such as lentils have primarily relied on conventional breeding. Application of genomics and transcriptomics in lentils has resulted in linkage maps and identification of QTLs and candidate genes related to agronomically relevant traits and biotic and abiotic stress tolerance. Next-generation sequencing (NGS) complemented with high-throughput phenotyping (HTP) technologies is shown to provide new opportunities to identify genomic regions and marker-trait associations to increase lentil breeding efficiency. Recent introduction of image-based phenotyping has facilitated to discern lentil responses undergoing biotic and abiotic stresses. In lentil, proteomics has been performed using conventional methods such as 2-D gel electrophoresis, leading to the identification of seed-specific proteome. Metabolomic studies have led to identifying key metabolites that help differentiate genotypic responses to drought and salinity stresses. Independent analysis of differentially expressed genes from publicly available transcriptomic studies in lentils identified 329 common transcripts between heat and biotic stresses. Similarly, 19 metabolites were common across legumes, while 31 were common in genotypes exposed to drought and salinity stress. These common but differentially expressed genes/proteins/metabolites provide the starting point for developing high-yielding multi-stress-tolerant lentils. Finally, the review summarizes the current findings from omic studies in lentils and provides directions for integrating these findings into a systems approach to increase lentil productivity and enhance resilience to biotic and abiotic stresses under changing climate.</p

Green synthesis and biological evaluation of glaucanic acid and dihydrocompactin acid by endophytic fungus <i>Penicillium polonicum</i> from <i>Zingiber officinal</i>e

Fungal endophytes are valued for biosynthesizing chemically diverse metabolic cascade with interesting biological activities. In the current investigation, two compounds were isolated from Penicillium polonicum, an endophyte of Zingiber officinale. The active moieties, glaucanic acid (1) and dihydrocompactin acid (2) were isolated from the ethyl acetate extract of P. polonicum and characterized by NMR and mass spectroscopy. Further, bioactive potential of the isolated compounds was evaluated by antimicrobial, antioxidant and cytotoxicity assays. Compounds 1 and 2 displayed antifungal activity against phytopathogen Colletotrichum gloeosporioides with more than 50% reduction in its growth. Both the compounds exhibited antioxidant activity against free radicals (DPPH and ABTS) and cytotoxicity activity against cancer cell lines respectively. The compounds, glaucanic acid and dihydrocompactin acid are being reported for the first time from an endophytic fungus. This is the first report on the biological activities of Dihydrocompactin acid produced by endophytic fungal strain.</p

Data_Sheet_1_Quantitative liver SPECT/CT is a novel tool to assess liver function, prognosis, and response to treatment in cirrhosis.DOCX

BackgroundFunctional liver reserve is an important determinant of survival in cirrhosis. The traditional indocyanine green test (ICG) is cumbersome. Hence, we developed and validated a novel liver imaging, a hybrid of SPECT and CT (Q-SPECT/CT), for evaluating disease severity, outcomes, and response to treatment in decompensated cirrhosis (DC).MethodsWe recruited a cohort of DC patients at a tertiary institute between 2016–2019. First, we standardized the Q-SPECT/CT across a predefined range of volumes through phantom experiments. Then we performed clinical and laboratory evaluations, ICG test (retention at 15 min), and Q-SPECT/CT at baseline and 12 months of granulocyte colony-stimulating factor (G-CSF) and standard medical treatment (SMT).ResultsIn 109 DC patients, 87.1% males, aged 51 ± 10 years, MELD: 14 (7–21), the percent quantitative liver uptake (%QLU) on Q-SPECT/CT exhibited a strong correlation with CTP (r = −0.728, p  0.05). %QLU > 25 (adj.H.R.: 0.234, p = 0.003) and G-CSF treatment (adj.H.R.: 0.414, p = 0.009) were independent predictors of better 12-months survival in DC.ConclusionQ-SPECT/CT (%QLU) is a novel non-invasive, diagnostic, prognostic, and theragnostic marker of liver reserve and its functions in cirrhosis patients.Clinical trial registrationClinicaltrials.gov, NCT02451033 and NCT03415698.</p

Data_Sheet_2_Quantitative liver SPECT/CT is a novel tool to assess liver function, prognosis, and response to treatment in cirrhosis.DOCX

BackgroundFunctional liver reserve is an important determinant of survival in cirrhosis. The traditional indocyanine green test (ICG) is cumbersome. Hence, we developed and validated a novel liver imaging, a hybrid of SPECT and CT (Q-SPECT/CT), for evaluating disease severity, outcomes, and response to treatment in decompensated cirrhosis (DC).MethodsWe recruited a cohort of DC patients at a tertiary institute between 2016–2019. First, we standardized the Q-SPECT/CT across a predefined range of volumes through phantom experiments. Then we performed clinical and laboratory evaluations, ICG test (retention at 15 min), and Q-SPECT/CT at baseline and 12 months of granulocyte colony-stimulating factor (G-CSF) and standard medical treatment (SMT).ResultsIn 109 DC patients, 87.1% males, aged 51 ± 10 years, MELD: 14 (7–21), the percent quantitative liver uptake (%QLU) on Q-SPECT/CT exhibited a strong correlation with CTP (r = −0.728, p  0.05). %QLU > 25 (adj.H.R.: 0.234, p = 0.003) and G-CSF treatment (adj.H.R.: 0.414, p = 0.009) were independent predictors of better 12-months survival in DC.ConclusionQ-SPECT/CT (%QLU) is a novel non-invasive, diagnostic, prognostic, and theragnostic marker of liver reserve and its functions in cirrhosis patients.Clinical trial registrationClinicaltrials.gov, NCT02451033 and NCT03415698.</p

[^99mTc]Tc-DTPA-Bis(cholineethylamine) as an Oncologic Tracer for the Detection of Choline Transporter (ChT) and Choline Kinase (ChK) Expression in Cancer

Objective: The elevated choline transporters (ChT), choline kinase (ChK), choline uptake, and phosphorylation in certain tumor cells have influenced the development of radiolabeled choline derivatives as diagnostic probes for imaging cell membrane proliferation. We, therefore, aimed to develop a choline-based moiety for imaging choline kinase-overexpressed tumors by single-photon emission tomography (SPECT). A novel choline-based diagnostic probe was synthesized and evaluated preclinically in various ChT- and ChK-overexpressed tumor models for SPECT imaging applications. Methods: The synthesis of diethylenetriaminepentaacetic acid-bis-choline ethylamine [DTPA-bis­(ChoEA)] featured the conjugation of dimethylaminoethanol to a bifunctional chelator DTPA anhydride. [99mTc]­Tc-DTPA-bis­(ChoEA) was prepared, and its in vivo characteristics were evaluated in BALB/c mice and tumor-xenografted PC3, A549, and HCT116 athymic mouse models. The in vitro parameters, including cell binding and cytotoxicity, were assessed in PC3, A549, and HCT116 cell lines. To evaluate the specificity of the radioprobe, competitive binding studies were performed. Small-animal SPECT/CT diagnostic imaging was performed for in vivo evaluation. The mouse biodistribution data was further investigated to estimate the radiation dose in humans. Results: In silico studies suggested high binding with enhanced specificity. A standard radiolabeling procedure using stannous chloride as a reducing agent showed a labeling yield of 99.5 ± 0.5%. The in silico studies suggested high binding with enhanced specificity. [99mTc]­Tc-DTPA-bis­(ChoEA) showed high in vitro stability and specificity. The pharmacokinetic studies of [99mTc]­Tc-DTPA-bis­(ChoEA) in mice showed an increased tumor-to-background ratio after few minutes of intravenous administration. The first-in-human trial was also conducted. The effective dose was estimated to be 0.00467 mSv/MBq (4.67 mSv/GBq), resulting in a radiation dose of up to 1.73 mSv for the 370 MBq injection of [99mTc]­Tc-DTPA-bis­(ChoEA). Conclusions: The synthesized radioprobe [99mTc]­Tc-DTPA-bis­(ChoEA) accumulates specifically in choline kinase-overexpressed tumors with a high signal-to-noise ratio. The preclinical and first-in-man data suggested that [99mTc]­Tc-DTPA-bis­(ChoEA) could potentially be used as a diagnostic SPECT tracer in the monitoring and staging of cancer

Discovery of 7‑(Prolinol‑<i>N</i>‑yl)-2-phenylamino-thiazolo[5,4‑<i>d</i>]pyrimidines as Novel Non-Nucleoside Partial Agonists for the A_2A Adenosine Receptor: Prediction from Molecular Modeling

We describe the identification of 7-(prolinol-<i>N</i>-yl)-2-phenylamino-thiazolo­[5,4-<i>d</i>]­pyrimidines as a novel chemotype of non-nucleoside partial agonists for the A_2A adenosine receptor (A_2AAR). Molecular-modeling indicated that the (<i>S</i>)-2-hydroxymethylene-pyrrolidine could mimic the interactions of agonists’ ribose, suggesting that this class of compounds could have agonistic properties. This was confirmed by functional assays on the A_2AAR, where their efficacy could be associated with the presence of the 2-hydroxymethylene moiety. Additionally, the best compound displays promising affinity, selectivity profile, and physicochemical properties