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The three-dimensional structure of DNA is a biophysical determinant of transcription. The density of chromatin condensation is one determinant of transcriptional output. Chromatin condensation is generally viewed as enforcing transcriptional suppression, and therefore, transcriptional output should be inversely proportional to DNA compaction. We coupled stable isotope tracers with multi-isotope imaging mass spectrometry to quantify and image nanovolumetric relationships between DNA density and newly made RNA within individual nuclei. Proliferative cell lines and cycling cells in the murine small intestine unexpectedly demonstrated no consistent relationship between DNA density and newly made RNA, even though localized examples of this phenomenon were detected at nuclear-cytoplasmic transitions. In contrast, non-dividing hepatocytes demonstrated global reduction in newly made RNA and an inverse relationship between DNA density and transcription, driven by DNA condensates at the nuclear periphery devoid of newly made RNA. Collectively, these data support an evolving model of transcriptional plasticity that extends at least to a subset of chromatin at the extreme of condensation as expected of heterochromatin., (© 2024 Guillermier et al.)

Herein, we report the synthesis and biological evaluation of a novel series of heparinoid amphiphiles as inhibitors of heparanase and SARS-CoV-2. By employing a tailor-made synthetic strategy, a library of highly sulfated homo-oligosaccharides bearing d-glucose or a C5-epimer (i.e., l-idose or l-iduronic acid) conjugated with various lipophilic groups was synthesized and investigated for antiviral activity. Sulfated higher oligosaccharides of d-glucose or l-idose with lipophilic aglycones displayed potent anti-SARS-CoV-2 and antiheparanse activity, similar to or better than pixatimod (PG545), and were more potent than their isosteric l-iduronic acid congeners. Lipophilic groups such as cholestanol and C 18 -aliphatic substitution are more advantageous than functional group appended lipophilic moieties. These findings confirm that fine-tuning of higher oligosaccharides, degree of sulfation, and lipophilic groups can yield compounds with potent anti-SARS-CoV-2 activity.

In the years 2021-2022 and 2022-2023, an experiment was carried out at the IFS Unit, College of Agriculture, PJTSAU, Rajendranagar in order to determine the best one-acre integrated farming system model for Telangana's small and marginal farmers. Seven farm models among which six models were developed by combining the various components i.e., cropping systems, fruit cropfodder crops and livestock components, in different proportions, and compared with rice-groundnut system which is a major farming approach in Telangana using randomized block design. The seven models were as follows: M1: Rice-Groundnut; M2: Rice-Groundnut, Pigeonpea + Sweetcorn (1:3)-Bajra, Bt cotton + Greengram (1:2)-Maize; M3: Rice-Groundnut, Pigeonpea + Sweetcorn (1:3)-Bajra, Pigeonpea + Maize (1:3)-Sunhemp; Napier grass, Sheep (5 + 1); M4: Rice-Groundnut, Pigeonpea + Sweetcorn (1:3)-Bajra, Bt cotton + Greengram (1:2)-Maize, Pigeonpea + Maize (1:3)-Sunhemp, Poultry unit; M5: Guava, Hedge Lucerne, Napier grass, Bt cotton + Greengram (1:2)-Maize, Sheep (5 + 1); M6: Guava, Bt cotton + Greengram (1:2)-Maize, Rice-Groundnut, Poultry; M7: Rice-Groundnut, Pigeonpea + Sweetcorn (1:3)-Bajra, Pigeonpea + Maize (1:3)-Sunhemp; Napier grass, Hedge lucerne, Poultry (100), Sheep (5 + 1). Based on a 2-year average, the Model M7 system produced 9980 Rice Grain Equivalent Yield(RGEY)kg of output per acre, with gross and net returns of ₹210,439 and ₹124,953 respectively, and recovered a B:C ratio of 2.46. It has recorded highest sustainable yield index (SYI) of 0.673 and value index of 0.772 with the lowest water footprint of 259.0 L/kg. This study reveals that adopting an integrated farming system is the optimal approach for effectively combining productive, financially rewarding, and diversified enterprises within a single acre of land.d. This system should be recommended for maximum benefits to smallto small and marginal farmers in Telangana's southern hills and plateau., (© 2024. The Author(s).)

Identifying cell types and states remains a time-consuming, error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data. TACIT uses unbiased thresholding to distinguish positive cells from background, focusing on relevant markers to identify ambiguous cells in multiomic assays. Using five datasets (5,000,000-cells; 51-cell types) from three niches (brain, intestine, gland), TACIT outperformed existing unsupervised methods in accuracy and scalability. Integrating TACIT-identified cell types with a novel Shiny app revealed new phenotypes in two inflammatory gland diseases. Finally, using combined spatial transcriptomics and proteomics, we discovered under- and overrepresented immune cell types and states in regions of interest, suggesting multimodality is essential for translating spatial biology to clinical applications., Competing Interests: Conflict of interest: The authors had access to the study data and reviewed and approved the final manuscript. Although the authors view each of these as noncompeting financial interests, KMB, QTE, BFM, and BMW are all active members of the Human Cell Atlas; furthermore, KMB is a scientific advisor at Arcato Laboratories. All other authors declare no competing interests.

Cognitive decline and dementia are significant public health challenges influenced by various modifiable and non-modifiable risk factors. Kundalini yoga (KY) has emerged as a promising non-pharmacological intervention to enhance cognitive function and memory in older adults at risk of cognitive decline. This systematic review aims to evaluate the effects of KY on cognitive function, memory impairment, and related neurobiological and psychological outcomes in older adults. A comprehensive literature search was conducted across PubMed, MEDLINE, Scopus, Web of Science, and the Cochrane Library, covering studies published from January 2000 to December 2023. Randomised controlled trials (RCTs) were included to compare KY with other cognitive enhancement strategies, such as memory enhancement training (MET) and psychoeducation. Five RCTs with 215 participants met the inclusion criteria. The studies varied in sample size (11 to 81 participants) and duration (12 to 24 weeks). The participants were older adults (≥55 years) with mild cognitive impairment (MCI) or subjective cognitive decline (SCD). The interventions compared KY with MET or psychoeducation. KY consistently improved memory performance and executive function. Significant mood enhancements, increased hippocampal volume, and better neural connectivity were observed. KY also reduced pro-inflammatory cytokines and altered ageing-related gene expression, demonstrating both cognitive and neurobiological benefits. KY appears to be a promising intervention for enhancing cognitive function, mood, and neurobiological health in older adults at risk of cognitive decline and dementia. While further research with more extensive, well-designed RCTs is needed to confirm these findings and optimise intervention strategies, the existing evidence supports the integration of KY into cognitive health programmes. Practitioners should ensure proper training and gradual progression to maximise benefits and minimise risks., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Giridharan et al.)

Purpose: The study was undertaken to look into the clinicodemographic profile, management, and clinical outcomes of advanced retinoblastoma at a tertiary care center., Methods: A prospective cohort study was conducted from Jan 2019 to Dec 2022. Forty-two patients of intraocular advanced retinoblastoma were assessed. The treatment protocol was formulated based on size, extension of tumor, and laterality. Primary outcome measure was response to the treatment in terms of regression of tumor and seeds and no evidence of recurrence after 12 month in enucleated eyes. Secondary outcome measures were complications like implant exposure, metastasis, and death associated with each treatment modality., Results: The mean age of the study group was 13 months. The most common presentation was leukocoria with diminished vision. Most of the patients had group E retinoblastoma ( n = 40, 95%) as per the International Classification of Retinoblastoma. In 12 patients with group E retinoblastoma, primary enucleation was performed and in six patients, secondary enucleation was done, in which initially, globe salvage treatment was tried. In 30 patients, globe salvage treatment was attempted and we could manage to save 23 eyes. The most common treatment modality was intra-arterial chemotherapy using a triple-drug regimen. One patient developed intracranial spread and died due to systemic metastasis during the follow-up period., Conclusion: The current study showed that globe salvage is possible in advanced retinoblastoma if appropriate therapy is instituted depending upon the extent of the tumor and availability of latest treatment modalities. Intra-arterial chemotherapy using triple drugs can be offered as a first-line therapy in advanced unilateral retinoblastoma as it has been found to be very effective in the present study., (Copyright © 2023 Copyright: © 2023 Indian Journal of Ophthalmology.)

This literature review presents a bibliometric analysis of the randomized controlled trials conducted between 2014 and 2023 on the potential benefits of yoga as a complementary therapy for cancer patients. To conduct this analysis, we searched medical and scientific databases, such as Scopus, Cochrane, and PubMed, using relevant keywords. Our search yielded 58 clinical trials involving 4,762 patients, which indicates a growing trend in this field of research. The studies we reviewed mainly focused on breast cancer patients and demonstrated the adaptability and versatility of yoga, offering a ray of hope and optimism. Among the various styles of yoga, Hatha yoga was the most frequently practiced style in these clinical trials. The analysis we conducted reveals that yoga interventions have a promising role in cancer care and can be a valuable complementary therapy for cancer patients. However, significant gaps and limitations still need to be addressed in this area of research. For instance, more rigorous and diverse investigations are needed to further establish the potential benefits of yoga interventions for cancer patients. Additionally, the standardization of yoga interventions is crucial to optimize therapeutic benefits. By addressing these gaps and limitations, we can further enhance the potential of yoga as a complementary therapy for cancer patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Giridharan et al.)

Zika virus (ZIKV) remains a public health concern, with epidemics in endemic regions and sporadic outbreaks in new areas posing significant threats. Several mosquito-borne flaviviruses that can cause human illness, including West Nile, Usutu, and St. Louis encephalitis, have associations with birds. However, the susceptibility of chickens to ZIKV and their role in viral epidemiology is not currently known. We investigated the susceptibility of chickens to experimental ZIKV infection using chickens ranging from 1-day-old chicks to 6-week-old birds. ZIKV caused no clinical signs in chickens of all age groups tested. Viral RNA was detected in the blood and tissues during the first 5 days post-inoculation in 1-day and 4-day-old chicks inoculated with a high viral dose, but ZIKV was undetectable in 6-week-old birds at all timepoints. Minimal antibody responses were observed in 6-week-old birds, and while present in younger chicks, they waned by 28 days post-infection. Innate immune responses varied significantly between age groups. Robust type I interferon and inflammasome responses were measured in older chickens, while limited innate immune activation was observed in younger chicks. Signal transducer and activator of transcription 2 (STAT2) is a major driver of host restriction to ZIKV, and chicken STAT2 is distinct from human STAT2, potentially contributing to the observed resistance to ZIKV infection. The rapid clearance of the virus in older chickens coincided with an effective innate immune response, highlighting age-dependent susceptibility. Our study indicates that chickens are not susceptible to productive ZIKV infection and are unlikely to play a role in the ZIKV epidemiology.

Pranayama, a set of yogic breathing techniques, is being studied as a potential supportive care option for cancer patients. This review intends to evaluate the effectiveness of Pranayama in enhancing the quality of life and well-being of cancer patients based on evidence from randomized controlled trials. We thoroughly searched databases for studies published between 2013 and 2023. We focused on randomized controlled trials that compared Pranayama interventions with non-yoga control groups. We assessed the primary outcomes, including psychological well-being, quality of life, physiological parameters, and treatment-related side effects. The review indicates that practicing Pranayama can lead to significant improvements in antioxidant levels, stress, anxiety, sleep quality, and overall quality of life for cancer patients. However, the evidence comes from a limited number of studies, which vary in sample sizes and methodologies. Pranayama shows promise as a complementary therapy for cancer patients, potentially enhancing their well-being and quality of life. Nonetheless, the current evidence base is limited, necessitating further research with larger sample sizes and more rigorous study designs to confirm these findings and elucidate the underlying mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Giridharan et al.)

Crop residues in agriculture pose disposal challenges and contribute to air pollution when burned. This study aims to use pigeonpea and maize stalks to produce biochar at different pyrolysis temperatures. Biochar can serve in carbon sequestration, as a soil amendment, and as an alternative fuel source. Pyrolysis was conducted at 400, 500, and 600 °C to examine the effects on physicochemical properties, fuel, and energy related properties. Increase in temperatures resulted in decrease of biochar yield, volatile matter, and O/C and H/C atomic ratios, while ash content and essential nutrients increased. Yield was observed to be higher in pigeonpea stalks derived biochar compared to maize stalks derived biochar at same pyrolysis temperatures. The yields of pigeonpea stalks derived biochar at 400 °C, 500 °C, and 600 °C are 34, 33 and 29%, respectively, and the yields of maize biomass-derived biochar at 400 °C, 500 °C, and 600 °C are 29, 28, and 26%, respectively. The organic carbon content is found to be higher in the biochar samples prepared at 600 °C, i.e., 10.44%, and 10.39% for pigeonpea and maize-derived biochar, respectively. The essential elements of biochar were increased with an increase in pyrolysis temperature except nitrogen which is conversely related to temperature. The biochar obtained through pyrolysis at 400 °C demonstrated superior characteristics compared to biochar produced at other temperatures. It exhibited a higher biochar yield, with approximately 84.60% for pigeonpea and 64.85% for maize fixed carbon content. Additionally, the energy retention efficiency was higher, reaching 67.33% for pigeonpea and 42.70% for maize-derived biochar at a pyrolysis temperature of 400 °C. The fixed carbon recovery efficiency was also notable at around 200.44% for PPS and 142.37% for maize biochar which is higher compared to biochar produced at other temperatures. Furthermore, the higher heating value (HHV) was approximately 30.75 MJ kg -1 for both the biochars, indicating their suitability as alternative solid fuels. A significant CO 2 reduction potential of 84 CO 2 eq kg -1 and 55 CO 2 eq kg -1 was observed for pigeonpea and maize biochar, respectively. Hence, biochar is a promising and effective option for carbon sequestration, offering environmental benefits., (© 2024. The Author(s).)

Importance: Ensuring valid informed consent (IC) prior to enrollment in clinical trials is a fundamental ethical right., Objective: To assess whether social determinants of health (SDOH) and related sociocontextual factors are associated with parental IC comprehension in therapeutic childhood cancer clinical trials., Design, Setting, and Participants: This cross-sectional study prospectively enrolled 223 parents of children with newly diagnosed cancer at Rady Children's Hospital San Diego, a large quaternary academic center in California, from October 1, 2014, to March 31, 2021. Linear mixed effects models were used to assess whether IC comprehension overall and by domain (purpose, procedures, and randomization; risks and benefits; alternatives; and voluntariness) were associated with SDOH and sociocontextual factors. Data were analyzed from January 1, 2022, to July 31, 2023., Exposures: Informed consent for a therapeutic childhood cancer clinical trial., Main Outcomes and Measures: The primary outcome of interest was IC comprehension and its associations with SDOH (marital status, language, educational attainment, employment, insurance type, socioeconomic status, and health literacy) and sociocontextual factors (ethnicity, satisfaction with informed consent, and cancer type)., Results: Of 223 parents, 172 (77.1%) were aged 18 to 44 years, 111 (49.8%) were Hispanic, 152 (68.2%) were women, and 163 (73.1%) were married. In terms of race, 2 (0.9%) were American Indian or Alaska Native, 22 (9.9%) were Asian or Pacific Islander, 8 (3.6%) were Black, 149 (66.8%) were White, and 42 (18.8%) were more than 1 race. In multivariable linear mixed-effects analyses, limited vs adequate health literacy was associated with lower comprehension of informed consent overall (mean [SD], 68.28 [11.81] vs 79.24 [11.77]; β estimate, -9.02 [95% CI, -12.0 to -6.07]; P < .001) and with lower comprehension of the purpose, procedures, and randomization (mean [SD], 65.00 [12.64] vs 76.14 [11.53]; β estimate, -7.87 [95% CI, -10.9 to -4.85]; P < .001); risks and benefits (mean [SD], 62.84 [20.24] vs 73.14 [20.86]; β estimate, -10.1 [95% CI, -15.6 to -4.59]; P < .001); alternatives (mean [SD], 54.27 [43.18] vs 82.98 [34.24]; β estimate, -14.3 [95% CI, -26.1 to -2.62]; P  .02); and voluntariness (mean [SD], 76.52 [24.33] vs 95.39 [13.89]; β estimate, -9.14 [95% CI, -14.9 to -3.44]; P = .002) domains. Use of Spanish vs English language for medical communication was associated with lower comprehension overall (mean [SD], 66.45 [12.32] vs 77.25 [12.18]; β estimate, -5.30 [95% CI, -9.27 to -1.34]; P = .01) and with lower comprehension of the purpose, procedures, and randomization (mean [SD], 63.33 [11.98] vs 74.07 [12.52]; β estimate, -4.33 [95% CI, -8.43 to -0.23]; P = .04) and voluntariness (mean [SD], 70.83 [24.02] vs 92.54 [17.27]; β estimate, -9.69 [95% CI, -16.8 to -2.56]; P = .009) domains., Conclusions and Relevance: In this cross-sectional study including parents of children with newly diagnosed cancer who provided IC for their child's participation in a therapeutic clinical trial, limited health literacy and use of Spanish language for medical communication were associated with lower comprehension of IC. These findings suggest that, in this setting, parents with limited health literacy or those who use Spanish language for medical communication may not fully comprehend IC and therefore may not make truly informed decisions. These findings support the investigation of interventions, across pediatric disciplines, tailored to the participant's language and health literacy level to improve IC comprehension, particularly in racial and ethnic minority populations.

A homogeneous PCR-based assay for sensitive and specific detection of antibodies in serum or dried blood spots (DBS) is presented and the method is used to monitor individuals infected with or vaccinated against SARS-CoV-2. Detection probes were prepared by conjugating the recombinant spike protein subunit 1 (S1), containing the receptor binding domain (RBD) of SARS-CoV-2, to each of a pair of specific oligonucleotides. The same was done for the nucleocapsid protein (NP). Upon incubation with serum or DBS samples, the bi- or multivalency of the antibodies (IgG, IgA or IgM) brings pairs of viral proteins with their conjugated oligonucleotides in proximity, allowing the antibodies to be detected by a modified proximity extension assay (PEA). Anti-S1 and anti-NP antibodies could be detected simultaneously from one incubation reaction. This Antibody PEA (AbPEA) test uses only 1 µl of neat or up to 100,000-fold diluted serum or one ø1.2 mm disc cut from a DBS. All 100 investigated sera and 21 DBS collected prior to the COVID-19 outbreak were negative, demonstrating a 100% specificity. The area under the curve, as evaluated by Receiver Operating Characteristic (ROC) analysis reached 0.998 (95%CI: 0.993-1) for samples taken from 11 days after symptoms onset. The kinetics of antibody responses were monitored after a first and second vaccination using serially collected DBS from 14 individuals. AbPEA offers highly specific and sensitive solution-phase antibody detection without requirement for secondary antibodies, no elution step when using DBS sample in a simple procedure that lends itself to multiplex survey of antibody responses., Competing Interests: Declaration of Competing Interest UL is a founder and shareholder of Olink Proteomics, having rights to the PEA technology. All other authors declare that they have no competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

The loop-mediated isothermal amplification (LAMP) was standardized for rapid detection of Dichelobacter nodosus and Fusobacterium necrophorum. A total of 250 foot swabs were screened from sheep (200) and goats (50) from different districts of Rayalaseema, viz., Chittoor, Nellore, Kadapa, and Anantapur. Out of 250 samples 75 (30.0%) and 85 (34.0%) were positive for D. nodosus and F. necrophorum, respectively. All the 250 samples were screened individually for both the organisms by LAMP. Among them, 104 (41.6%) were found to be positive for D. nodosus and 120 (48.0%) were positive for F. necrophorum. The efficacy of LAMP in terms of sample DNA detection limit was compared with the PCR by using standard dilutions of DNA extracted from D. nodosus and F. necrophorum cultures. The detection limit was found to be higher than PCR for both the organisms. The sensitivity of LAMP is compared with PCR by targeting 16S rRNA gene of D. nodosus and lktA gene of F. necrophorum. In case of D. nodosus, out of 250 samples, 75 (30.0%) were positive by PCR and 104 (41.6%) were positive by LAMP. Among 250 samples, 85 (34.0%) were positive by PCR and 120 (48.0%) were positive by LAMP in case of F. necrophorum. The LAMP was found to be more sensitive than PCR in detecting the organisms with high statistical significance., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Recently, the activity of heparan sulfate (HS) has led to the discovery of many drug candidates that have the potential to impact both medical science and human health. However, structural diversity and synthetic challenges impede the progress of HS research. Here, we report a library of novel l-iduronic acid (IdoA)-based HS mimics that are highly tunable in conformation plasticity and sulfation patterns to produce many of the functions of native HS oligosaccharides. The NMR analysis of HS mimics confirmed that 4- O -sulfation enhances the population of the 1 C 4 geometry. Interestingly, the 1 C 4 conformer becomes exclusive upon additional 2- O -sulfation. HS mimic microarray binding studies with different growth factors showed that selectivity and avidity are greatly modulated by the oligosaccharide length, sulfation code, and IdoA conformation. Particularly, we have identified 4- O -sulfated IdoA disaccharide ( I-21 ) as a potential ligand for vascular endothelial growth factor (VEGF 165 ), which in a multivalent display modulated endothelial cell proliferation, migration, and angiogenesis. Overall, these results encourage the consideration of HS mimics for therapeutic applications.

Fibrosis is a pathological state characterized by excessive deposition of the extracellular matrix components leading to impaired tissue function in the affected organ. It results in scarring of the affected tissue akin to an over-healing wound as a consequence of chronic inflammation and repair in response to injury. Persistent trauma of susceptible oral mucosa due to habitual chewing of betel quid resulting in zealous healing of the mucosal tissue is one plausible explanation for the onset of oral submucous fibrosis (OSF). The irreversibility and resistance of collagen to degradation and its high potential to undergo malignant change are a major reason for morbidity in OSF. Hence, early diagnosis and timely treatment are crucial to prevent the progression of OSF to malignancy. This review focuses on the mechanistic insight into the role of collagen cross-links in advancing fibrosis and possible therapeutic targets that bring about a reversal of fibrosis. These options may be beneficial if attempted as a specific therapeutic modality in OSF as is in organ fibrosis. The upregulation of lysyl oxidase and lysyl hydroxylase has been shown to exhibit the higher levels of the hydroxylysine aldehyde-derived cross-links in fibrosis and tumor stroma promoting the tumor cell survival, resistance, and invasion. The in silico analysis highlights the potential drugs that may target the genes regulating collagen crosslinking., Competing Interests: All the authors of the manuscript hereby state that there is no financial implication or personal relationship with other people or organization that could inappropriately influence the outcome of this work., (Copyright: © 2021 Journal of Carcinogenesis.)

Dengue virus (DENV), a member of the family Flaviviridae, is a threat for global health as it infects more than 100 million people yearly. Approved antiviral therapies or vaccines for the treatment or prevention of DENV infections are not available. In the present study, natural compounds were screened for their antiviral activity against DENV by in vitro cell line-based assay. α-Mangostin, a xanthanoid, was observed to exert antiviral activity against DENV-2 under pre-, co- and post-treatment testing conditions. The antiviral activity was determined by foci forming unit (FFU) assay, quantitative RT-PCR and cell-based immunofluorescence assay (IFA). A complete inhibition of DENV-2 was observed at 8 µM under the co-treatment condition. The possible inhibitory mechanism of α-Mangostin was also determined by docking studies. The molecular docking experiments indicate that α-Mangostin can interact with multiple DENV protein targets such as the NS5 methyltransferase, NS2B-NS3 protease and the glycoprotein E. The in vitro and in silico findings suggest that α-Mangostin possesses the ability to suppress DENV-2 production at different stages of its replication cycle and might act as a prophylactic/therapeutic agent against DENV-2.

Importance: Obtaining voluntary informed consent prior to enrollment in clinical trials is a fundamental ethical requirement., Objective: To assess whether health literacy, contextual factors, or sociodemographic characteristics are associated with perception of voluntariness among parents who had consented for their child's participation in a leukemia therapeutic clinical trial., Design, Setting, and Participants: This cross-sectional study prospectively enrolled 97 parents of children diagnosed as having leukemia at Rady Children's Hospital San Diego, a large tertiary academic center in California, from 2014 to 2017. Health literacy, contextual factors (acculturation, decisional regret, and satisfaction with informed consent), sociodemographic characteristics, and perception of voluntariness after consenting for a therapeutic clinical trial were measured. Univariable and multivariable regression were used to determine significant associations. The analyses for the present study were conducted from May 2019 to May 2020., Exposures: Informed consent for a therapeutic leukemia clinical trial., Main Outcomes and Measures: The primary outcome of interest was perception of voluntariness and its associations with health literacy and other contextual factors (acculturation, decisional regret, and satisfaction with informed consent) and sociodemographic characteristics, including age, race/ethnicity, parental language, educational level, insurance type, marital status, and socioeconomic status., Results: Of 97 parents included, the majority were women (65 [67%]), married (71 [73%]), and of self-reported Hispanic ethnicity (50 [52%]). Lower perception of voluntariness was significantly associated with lower health literacy (r = 0.30; 95% CI, 0.11-0.47; P = .004), Spanish language (x̅ = -4.50, P = .05), lower acculturation if of Hispanic ethnicity (r = 0.30; 95% CI, 0.02-0.54; P = .05), greater decisional regret (r = -0.54; 95% CI, -0.67 to -0.38; P < .001), and lower satisfaction with informed consent (r = 0.39; 95% CI, 0.21-0.54; P < .001) in univariable analysis. Lower health literacy remained significantly associated with lower perception of voluntariness in multivariable analysis after adjustment for contextual factors and sociodemographic characteristics (β = 4.06; 95% CI, 1.60-6.53; P = .001). Lower health literacy was significantly associated with Hispanic ethnicity (mean, 4.16; 95% CI, 3.75-4.57; P < .001), Spanish language spoken at home (mean, 3.17; 95% CI, 1.94-4.40; P < .001), high school or less educational level (mean, 3.41; 95% CI, 2.83-3.99; P < .001), public insurance (mean, 4.00; 95% CI, 3.55-4.45; P < .001), and unmarried status (mean, 3.71; 95% CI, 2.91-4.51; P = .03)., Conclusions and Relevance: Among parents of children with newly diagnosed leukemia who had consented for their child's participation in a therapeutic clinical trial, lower perception of voluntariness was significantly associated with lower health literacy. These results suggest that parents with low health literacy may perceive external influences in their decision for their child's participation in clinical trials. This finding highlights the potential role of recruitment interventions tailored to the participant's health literacy level to improve voluntary informed consent in underserved populations.

Astragalus L. is widely distributed throughout the temperate regions of Europe, Asia, and North America. The genus is widely used in folk medicine and in dietary supplements, as well as in cosmetics, teas, coffee, vegetable gums, and as forage for animals. The major phytoconstituents of Astragalus species with beneficial properties are saponins, flavonoids, and polysaccharides. Astragalus extracts and their isolated components exhibited promising in vitro and in vivo biological activities, including antiaging, antiinfective, cytoprotective, antiinflammatory, antioxidant, antitumor, antidiabesity, and immune-enhancing properties. Considering their proven therapeutic potential, the aim of this work is to give a comprehensive summary of the Astragalus spp. and their active components, in an attempt to provide new insight for further clinical development of these xenobiotics. This is the first review that briefly describes their ethnopharmacology, composition, biological, and toxicological properties., (© 2020 John Wiley & Sons, Ltd.)

Achieving selective inhibition of chemokine activity by structurally well-defined heparan sulfate (HS) or HS mimetic molecules can provide important insights into their roles in individual physiological and pathological cellular processes. Here, we report a novel tailor-made HS mimetic, which furnishes an exclusive iduronic acid (IdoA) scaffold with different sulfation patterns and oligosaccharide chain lengths as potential ligands to target chemokines. Notably, highly sulfated-IdoA tetrasaccharide ( I-45 ) exhibited strong binding to CCL2 chemokine thereby blocking CCL2/CCR2-mediated in vitro cancer cell invasion and metastasis. Taken together, IdoA-based HS mimetics offer an alternative HS substrate to generate selective and efficient inhibitors for chemokines and pave the way to a wide range of new therapeutic applications in cancer biology and immunology.

Background: Chikungunya virus (CHIKV), a serious health problem in several tropical countries, is the causative agent of chikungunya fever. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. As diverse natural phenolic compounds have been shown to possess antiviral activities, we explored the antiviral activity of α-Mangostin, a xanthanoid, against CHIKV infection., Methods: The in vitro prophylactic and therapeutic effects of α-Mangostin on CHIKV replication in Vero E6 cells were investigated by administering it under pre, post and cotreatment conditions. The antiviral activity was determined by foci forming unit assay, quantitative RT-PCR and cell-based immune-fluorescence assay. The molecular mechanism of inhibitory action was further proposed using in silico molecular docking studies., Results: In vitro studies revealed that 8 µM α-Mangostin completely inhibited CHIKV infectivity under the cotreatment condition. CHIKV replication was also inhibited in virus-infected mice. This is the first in vivo study which clearly showed that α-Mangostin is effective in vivo by significantly reducing virus replication in serum and muscles. Molecular docking indicated that α-Mangostin can efficiently interact with the E2-E1 heterodimeric glycoprotein and the ADP-ribose binding cavity of the nsP3 macrodomain., Conclusions: The findings suggest that α-Mangostin can inhibit CHIKV infection and replication through possible interaction with multiple CHIKV target proteins and might act as a prophylactic/therapeutic agent against CHIKV.

Purpose: Treatment of children with CNS tumors (CNSTs) demands a complex, interdisciplinary approach that is rarely available in low- and middle-income countries. We established the Cross-Border Neuro-Oncology Program (CBNP) between Rady Children's Hospital, San Diego (RCHSD), and Hospital General, Tijuana (HGT), Mexico, to provide access to neuro-oncology care, including neurosurgic services, for children with CNSTs diagnosed at HGT. Our purpose was to assess the feasibility of the CBNP across the United States-Mexico border and improve survival for children with CNSTs at HGT by implementing the CBNP., Patients and Methods: We prospectively assessed clinicopathologic profiles, the extent of resection, progression-free survival, and overall survival (OS) in children with CNSTs at HGT from 2010 to 2017., Results: Sixty patients with CNSTs participated in the CBNP during the study period. The most common diagnoses were low-grade glioma (24.5%) and medulloblastoma (22.4%). Of patients who were eligible for surgery, 49 underwent resection at RCHSD and returned to HGT for collaborative management. Gross total resection was achieved in 78% of cases at RCHSD compared with 0% at HGT ( P < .001) and was a predictor of 5-year OS (hazard ratio, 0.250; 95% CI, 0.067 to 0.934; P = .024). Five-year OS improved from 0% before 2010 to 52% in 2017., Conclusion: The CBNP facilitated access to complex neuro-oncology care for underserved children in Mexico through binational exchanges of resources and expertise. Survival for patients in the CBNP dramatically improved. Gross total resection at RCHSD was associated with higher OS, highlighting the critical role of experienced neurosurgeons in the treatment of CNSTs. The CBNP model offers an attractive alternative for children with CNSTs in low- and middle-income countries who require complex neuro-oncology care, particularly those in close proximity to institutions in high-income countries with extensive neuro-oncology expertise.

Analysis of the most relevant studies on the pharmacological properties and molecular mechanisms of psoralidin, a bioactive compound from the seeds of Cullen corylifolium (L.) Medik. confirmed its complex therapeutic potential. In the last years, the interest of the scientific community regarding psoralidin increased, especially after the discovery of its benefits in estrogen-related diseases and as a chemopreventive agent. Growing preclinical pieces of evidence indicate that psoralidin has anticancer, antiosteoporotic, anti-inflammatory, anti-vitiligo, antibacterial, antiviral, and antidepressant-like effects. Here, we provide a comprehensive and critical review of psoralidin on its bioavailability, pharmacological activities with focus on molecular mechanisms and cell signaling pathways. In this review, we conducted literature research on the PubMed database using the following keywords: "Psoralidin" or "therapeutic effects" or "biological activity" or " Cullen corylifolium " in order to identify relevant studies regarding PSO bioavailability and mechanisms of therapeutic effects in different diseases based on preclinical, experimental studies. In the light of psoralidin beneficial actions for human health, this paper gathers complete information on its pharmacotherapeutic effects and opens new natural therapeutic perspectives in chronic diseases., (Copyright © 2020 Sharifi-Rad, Kamiloglu, Yeskaliyeva, Beyatli, Alfred, Salehi, Calina, Docea, Imran, Anil Kumar, Eugenia Romero-Román, Maroyi and Martorell.)

The family Arecaceae includes 181 genera and 2,600 species with a high diversity in physical characteristics. Areca plants, commonly palms, which are able to grow in nearly every type of habitat, prefer tropical and subtropical climates. The most studied species Areca catechu L. contains phytochemicals as phenolics and alkaloids with biological properties. The phenolics are mainly distributed in roots followed by fresh unripe fruits, leaves, spikes, and veins, while the contents of alkaloids are in the order of roots, fresh unripe fruits, spikes, leaves, and veins. This species has been reputed to provide health effects on the cardiovascular, respiratory, nervous, metabolic, gastrointestinal, and reproductive systems. However, in many developing countries, quid from this species has been associated with side effects, which include the destruction of the teeth, impairment of oral hygiene, bronchial asthma, or oral cancer. Despite these side effects, which are also mentioned in this work, the present review collects the main results of biological properties of the phytochemicals in A. catechu. This study emphasizes the in vitro and in vivo antioxidant, antimicrobial, anticancer, and clinical effectiveness in humans. In this sense, A. catechu have demonstrated effectiveness in several reports through in vitro and in vivo experiments on disorders such as antimicrobial, antioxidant, or anticancer. Moreover, our findings demonstrate that this species presents clinical effectiveness on neurological disorders. Hence, A. catechu extracts could be used as a bioactive ingredient for functional food, nutraceuticals, or cosmeceuticals. However, further studies, especially extensive and comprehensive clinical trials, are recommended for the use of Areca in the treatment of diseases., (© 2020 John Wiley & Sons, Ltd.)

Oxidative stress plays an essential role in the pathogenesis of chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Long term exposure to increased levels of pro-oxidant factors can cause structural defects at a mitochondrial DNA level, as well as functional alteration of several enzymes and cellular structures leading to aberrations in gene expression. The modern lifestyle associated with processed food, exposure to a wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed., (Copyright © 2020 Sharifi-Rad, Anil Kumar, Zucca, Varoni, Dini, Panzarini, Rajkovic, Tsouh Fokou, Azzini, Peluso, Prakash Mishra, Nigam, El Rayess, Beyrouthy, Polito, Iriti, Martins, Martorell, Docea, Setzer, Calina, Cho and Sharifi-Rad.)

Activator protein 1 (AP-1) is one of the largest families of basic leucine zipper (bZIP) transcription factors in eukaryotic cells. How AP-1 proteins achieve target DNA binding specificity remains elusive. In Saccharomyces cerevisiae, the AP-1-like protein (Yap) family comprises eight members (Yap1 to Yap8) that display distinct genomic target sites despite high sequence homology of their DNA binding bZIP domains. In contrast to the other members of the Yap family, which preferentially bind to short (7-8 bp) DNA motifs, Yap8 binds to an unusually long DNA motif (13 bp). It has been unclear what determines this unique specificity of Yap8. In this work, we use molecular and biochemical analyses combined with computer-based structural design and molecular dynamics simulations of Yap8-DNA interactions to better understand the structural basis of DNA binding specificity determinants. We identify specific residues in the N-terminal tail preceding the basic region, which define stable association of Yap8 with its target promoter. We propose that the N-terminal tail directly interacts with DNA and stabilizes Yap8 binding to the 13 bp motif. Thus, beside the core basic region, the adjacent N-terminal region contributes to alternative DNA binding selectivity within the AP-1 family., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)