RNA-driven phase transitions in biomolecular condensates.

RNAs and RNA-binding proteins can undergo spontaneous or active condensation into phase-separated liquid-like droplets. These condensates are cellular hubs for various physiological processes, and their dysregulation leads to diseases. Although RNAs are core components of many cellular condensates, the underlying molecular determinants for the formation, regulation, and function of ribonucleoprotein condensates have largely been studied from a protein-centric perspective. Here, we highlight recent developments in ribonucleoprotein condensate biology with a particular emphasis on RNA-driven phase transitions. We also present emerging future directions that might shed light on the role of RNA condensates in spatiotemporal regulation of cellular processes and inspire bioengineering of RNA-based therapeutics.

Dissecting the biophysics and biology of intrinsically disordered proteins.

Intrinsically disordered regions (IDRs) within human proteins play critical roles in cellular information processing, including signaling, transcription, stress response, DNA repair, genome organization, and RNA processing. Here, we summarize current challenges in the field and propose cutting-edge approaches to address them in physiology and disease processes, with a focus on cancer.

Imaging for Early Detection of Pancreatic Ductal Adenocarcinoma: Updates and Challenges in the Implementation of Screening and Surveillance Programs.

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive cancers. It has a poor 5-year survival rate of 12%, partly because most cases are diagnosed at advanced stages, precluding curative surgical resection. Early-stage PDA has significantly better prognoses due to increased potential for curative interventions, making early detection of PDA critically important to improved patient outcomes. We examine current and evolving early detection concepts, screening strategies, diagnostic yields among high-risk individuals, controversies, and limitations of standard-of-care imaging.

Direct computations of viscoelastic moduli of biomolecular condensates.

Biomolecular condensates are viscoelastic materials defined by time-dependent, sequence-specific complex shear moduli. Here, we show that viscoelastic moduli can be computed directly using a generalization of the Rouse model that leverages information regarding intra- and inter-chain contacts, which we extract from equilibrium configurations of lattice-based Metropolis Monte Carlo (MMC) simulations of phase separation. The key ingredient of the generalized Rouse model is a graph Laplacian that we compute from equilibrium MMC simulations. We compute two flavors of graph Laplacians, one based on a single-chain graph that accounts only for intra-chain contacts, and the other referred to as a collective graph that accounts for inter-chain interactions. Calculations based on the single-chain graph systematically overestimate the storage and loss moduli, whereas calculations based on the collective graph reproduce the measured moduli with greater fidelity. However, in the long time, low-frequency domain, a mixture of the two graphs proves to be most accurate. In line with the theory of Rouse and contrary to recent assertions, we find that a continuous distribution of relaxation times exists in condensates. The single crossover frequency between dominantly elastic vs dominantly viscous behaviors does not imply a single relaxation time. Instead, it is influenced by the totality of the relaxation modes. Hence, our analysis affirms that viscoelastic fluid-like condensates are best described as generalized Maxwell fluids. Finally, we show that the complex shear moduli can be used to solve an inverse problem to obtain the relaxation time spectra that underlie the dynamics within condensates. This is of practical importance given advancements in passive and active microrheology measurements of condensate viscoelasticity.

Malignancy in pregnancy: Multimodality imaging and treatment.

The diagnosis of cancer is increasingly made in the pregnant population, thought to be from the increasing average age of pregnancy and the use of prenatal fetal noninvasive screening techniques, leading to incidental detection of cancer in the mother. Complex challenges are associated with imaging, diagnosis, staging, and treatment of cancers in this patient population, which require highly specialized interdisciplinary management. This report discusses the use of multimodality imaging and safety considerations in pregnant patients, reviews the current guidelines for ionizing radiation imaging techniques, and presents a series of commonly and uncommonly encountered cancers in pregnancy with current diagnostic imaging guidelines. The authors also discuss the role of multidisciplinary management and treatment options and provide an overview of therapy-related considerations in the age of novel anticancer therapies. PLAIN LANGUAGE SUMMARY: The diagnosis and management of pregnant patients who have cancer are actively evolving as novel imaging techniques and anticancer therapies are being developed. Radiologically, there are inherent difficulties in balancing the minimization of fetal ionization while acquiring diagnostic quality imaging necessary for the diagnosis, staging, and treatment of maternal disease. Standardized imaging protocols are still being developed, with evolving imaging guidelines coupled with rapidly expanding research and development of novel anticancer therapies, which come with their side effects and complications. Caring for this patient population is especially challenging and requires specialized multidisciplinary attention.

Comparing the Safety and Efficacy of Two Commercially Available Single-Use Duodenoscopes: A Multicenter Study.

INTRODUCTION: Single-use disposable duodenoscopes (SDD) have been developed to mitigate infectious risks related to reusable duodenoscopes. The aim of this study is to compare the safety and efficacy of the two available SDDs in the United States. METHODS: We conducted a comparative study of 2 SDD in consecutive ERCP procedures performed by expert endoscopists from 9 academic centers. Performance ratings, procedure details, and adverse events were collected. RESULTS: A total of 201 patients were included: 129 patients underwent ERCP with Exalt (mean age 63, Males- 66 (51%), 72 with aScope Duodeno (mean age 65, males=30 (42%). A majority of endoscopists had performed >2000 ERCPs in both groups (71% Exalt, 93% aScope Duodeno). Technical success was 92% in both groups (n=119 Exalt-group, n=66 aScope-Duodeno-group). The procedural complexity for the ERCP cases performed were: Grade 1: 35 cases (18%), Grade 2: 83 cases (41%), Grade 3: 65 cases (32%), and Grade 4: 18 cases (9%). Thirteen patients (10%) from the Exalt group and 16 patients (22%) from the aScope Duodeno group required conversion to a reusable duodenoscope. On a scale of 1 to 5, Exalt and aScope Duodeno, respectively, were rated: 2.31 versus 2.60 for location and visualization quality, 1.38 versus 1.57 for maneuverability based on papillary orientation, 1.48 versus 1.15 for suction/air control, and 2.31 versus 2.34 for elevator efficiency. None of the adverse events were related to the SDDs. CONCLUSIONS: The 2 SDDs were comparable. Further ongoing enhancements to these devices will improve maneuverability and clinical effectiveness.

Added Value of FDG PET/MRI in Gynecologic Oncology: A Pictorial Review.

Fluorine 18-fluorodeoxyglucose (FDG) PET and MRI independently play a valuable role in the management of patients with gynecologic malignancies, particularly endometrial and cervical cancer. The PET/MRI hybrid imaging technique combines the metabolic information obtained from PET with the excellent soft-tissue resolution and anatomic details provided by MRI in a single examination. MRI is the modality of choice for assessment of local tumor extent in the pelvis, whereas PET is used to assess for local-regional spread and distant metastases. The authors discuss the added value of FDG PET/MRI in imaging gynecologic malignancies of the pelvis, with a focus on the role of FDG PET/MRI in diagnosis, staging, assessing treatment response, and characterizing complications. PET/MRI allows better localization and demarcation of the extent of disease, characterization of lesions and involvement of adjacent organs and lymph nodes, and improved differentiation of benign from malignant tissues, as well as detection of the presence of distant metastasis. It also has the advantages of decreased radiation dose and a higher signal-to-noise ratio of a prolonged PET examination of the pelvis contemporaneous with MRI. The authors provide a brief technical overview of PET/MRI, highlight how simultaneously performed PET/MRI can improve stand-alone MRI and PET/CT in gynecologic malignancies, provide an image-rich review to illustrate practical and clinically relevant applications of this imaging technique, and review common pitfalls encountered in clinical practice. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Synthesis, Structural, Spectroscopic, Fluorescence, and Dielectric Studies of Bis-(4-Aminopyridine)-Zinc(II) Acetate: A Metal-Organic Crystal.

The advancement of crystalline growth and characterization tools allows us to investigate novel nonlinear optical substances suitable for photonic applications. Bis-(4-aminopyridine)-zinc(II) acetate (B4AZA), a metal-organic crystal was produced in this study using the slow evaporation procedure at room temperature. Analytical studies such as X-ray crystallography, Fourier transform infrared (FT-IR), UV-visible (UV-Vis), fluorescence, second harmonic generation (SHG), and dielectric tests were used to characterize the as-grown B4AZA crystals. According to the solubility data, the sample has a positive temperature coefficient of solubility. The crystallographic findings show that the B4AZA crystallized in a monoclinic structure with the P21/n space group. Molecular vibrations and functional groups in the substance were determined using the FT-IR technique. The UV-Vis absorbance and transmittance spectra have shown the wide transparency and minimum absorbance of the B4AZA in the near UV and entire visible regions of the electromagnetic spectrum. The bandgap of the B4AZA has been calculated using the Tauc relation and found to be 4.32 eV. The fluorescence spectra have shown a prominent emission peak at 584 nm with an excitation wavelength of 280 nm. The larger Stokes shift found in the fluorescence spectra is advantageous for practical applications. The SHG study revealed that the powdered B4AZA samples generated a second harmonic output. The dielectric test revealed frequency-dependent changes in the dielectric constant and loss factor. Both the dielectric constant and the loss factor decrease exponentially as frequency increases, reaching low values at higher frequencies. The experimental results illustrate the suitability of the B4AZA crystals for photonic applications.

Utilization of SARS-CoV-2-Positive donors in pediatric renal transplantation.

BACKGROUND: As COVID-19-positive donors are becoming more common, there is an increasing need for the transplant community to evaluate the safety and efficacy of organ transplant from a SARS-CoV-2-infected donor. METHODS: Here we describe outcomes of two pediatric kidney transplant recipients who were vaccinated against COVID-19 and received their allograft from a SARS-CoV-2-positive donor. RESULTS: Both donors did not die from a COVID-19-related illness; the first donor had 1 week of COVID-19 symptoms 4 weeks prior to donation and the second was asymptomatic. Donor 1 had a Ct of 33.4 at 3 days and Donor 2 with a Ct of 37.2 at 16 days prior to donation. The first recipient was positive for SARS-CoV-2 anti-spike IgG on the day of transplant, but the second patient was negative and both patients received IVIg perioperatively. There was no evidence of SARS-CoV-2 transmission or compromised renal function at 86- and 80-day post-transplant, respectively. CONCLUSIONS: This case series suggests favorable short-term outcomes with accepting SARS-CoV-2-positive donors for pediatric renal transplantation, after thorough evaluation of the donor's risk for transmission, assessing the recipient's serologic status to SARS-CoV-2, and considering pre-emptive measures to mitigate the risk for severe COVID-19 should the recipient acquire donor-derived SARS-CoV-2.

Impact of Preexisting Depression and Anxiety on Hospital Readmission and Long-Term Survival After Cardiac Arrest.

BACKGROUND: While sudden cardiac arrest (CA) survivors are at risk for developing psychiatric disorders, little is known about the impact of preexisting mental health conditions on long-term survival or postacute healthcare utilization. We examined the prevalence of preexisting psychiatric conditions in CA patients who survived hospital discharge, characterized incidence and reason for inpatient psychiatry consultation during these patients' acute hospitalizations, and determined the association of pre-CA depression and anxiety with hospital readmission rates and long-term survival. We hypothesized that prior depression or anxiety would be associated with higher hospital readmission rates and lower long-term survival. METHODS: We conducted a retrospective cohort study including patients resuscitated from in- and out-of-hospital CA who survived both admission and discharge from a single hospital between January 1, 2010, and December 31, 2017. We identified patients from our prospective registry, then performed a structured chart review to abstract past psychiatric history, prescription medications for psychiatric conditions, and identify inpatient psychiatric consultations. We used administrative data to identify readmissions within 1 year and vital status through December 31, 2020. We used multivariable Cox regressions controlling for patient demographics, medical comorbidities, discharge Cerebral Performance Category and disposition, depression, and anxiety history to predict long-term survival and hospital readmission. RESULTS: We included 684 subjects. Past depression or anxiety was noted in 24% (n = 162) and 19% (n = 129) of subjects. A minority of subjects (n = 139, 20%) received a psychiatry consultation during the index hospitalization. Overall, 262 (39%) subjects had at least 1 readmission within 1 year. Past depression was associated with an increased hazard of hospital readmission (hazard ratio 1.50, 95% CI 1.11-2.04), while past anxiety was not associated with readmission. Neither depression nor anxiety were independently associated with long-term survival. CONCLUSIONS: Depression is an independent risk factor for hospital readmission in CA survivors.

Characterizing morphologic subtypes of high-grade serous ovarian cancer by CT: a retrospective cohort study.

OBJECTIVE: A novel classification system of high-grade serous ovarian carcinoma based on gross morphology observed at pre-treatment laparoscopy was recently defined. The purpose of this study was to identify radiographic features unique to each morphologic subtype. METHODS: This retrospective study included 109 patients with high-grade serous ovarian cancer who underwent pre-operative computed tomography (CT) scanning and laparoscopic assessment of disease burden between 1 April 2013 and 5 August 2015. Gross morphologic subtype had been previously assigned by laparoscopy. Two radiologists independently reviewed CT images for each patient, categorized disease at eight anatomic sites, and assessed for radiographic characteristics of interest: large infiltrative plaques, mass-like metastases, enhancing peritoneal lining, architectural distortion, fat stranding, calcifications, and lymph node involvement. Demographic and clinical information was summarized with descriptive statistics and compared using Student's t-tests, χ² tests, or Fisher exact tests as appropriate; kappa statistics were used to assess inter-reader agreement. RESULTS: Certain radiographic features were found to be associated with gross morphologic subtype. Large infiltrative plaques were more common in type 1 disease (88.7% (47/53) vs 71.4% (25/35), p=0.04), while mass-like metastases were more often present in type 2 disease (48.6% (17/35) vs 22.6% (12/53), p=0.01). Additionally, radiographic presence of disease at the falciform ligament was more common in type 1 morphology (33.9% (19/56) vs 13.2% (5/38), p=0.02). CONCLUSION: Morphologic subtypes of high-grade serous ovarian cancer were associated with specific CT findings, including the presence of large infiltrative plaques, mass-like metastases, and falciform ligament involvement.

Phase transition of RNA-protein complexes into ordered hollow condensates.

Liquid-liquid phase separation of multivalent intrinsically disordered protein-RNA complexes is ubiquitous in both natural and biomimetic systems. So far, isotropic liquid droplets are the most commonly observed topology of RNA-protein condensates in experiments and simulations. Here, by systematically studying the phase behavior of RNA-protein complexes across varied mixture compositions, we report a hollow vesicle-like condensate phase of nucleoprotein assemblies that is distinct from RNA-protein droplets. We show that these vesicular condensates are stable at specific mixture compositions and concentration regimes within the phase diagram and are formed through the phase separation of anisotropic protein-RNA complexes. Similar to membranes composed of amphiphilic lipids, these nucleoprotein-RNA vesicular membranes exhibit local ordering, size-dependent permeability, and selective encapsulation capacity without sacrificing their dynamic formation and dissolution in response to physicochemical stimuli. Our findings suggest that protein-RNA complexes can robustly create lipid-free vesicle-like enclosures by phase separation.

Incidence and Clinical Characteristics of Severe Acute Respiratory Syndrome Coronavirus 2 Infection After Vaccination in Children.

The objective of this single-center cohort study was to characterize the frequency, clinical characteristics, and molecular epidemiology of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination. Between May 15, 2021, and January 1, 2022, 171 children experienced SARS-CoV-2 infection postvaccination, 146 (86%) following the Omicron variant predominance. Outcomes were generally mild and comparable before and after Omicron predominance.

Identification of numerous novel disease-causing variants in patients with inherited retinal diseases, combining careful clinical-functional phenotyping with systematic, broad NGS panel-based genotyping.

Purpose: The widespread consensus is that genotyping is essential for patients with inherited retinal disease (IRD). Given the numerous ongoing gene therapy clinical trials for IRDs, identifying the pathogenic mutation in these patients has potential important therapeutic implications. In this study, we demonstrate how we identified with a high degree of confidence numerous novel disease-causing mutations, deletions, and duplications in a large consecutive IRD case series by using a judicious combination of careful, in-depth clinical-functional phenotyping to guide and integrate our genotyping approach. Methods: We conducted a retrospective analysis of data between November 2016 and March 2018 from the Duke Center for Retinal Degenerations and Ophthalmic Genetic Diseases IRD patient database, which encompassed 378 IRD cases that had not yet been previously genotyped. With the exception of some patients who presented with classical clinical-functional phenotypes that allowed for targeted gene testing, all other subjects systematically underwent next-generation sequencing-based broad, IRD-focused panel testing. Most cases were also tested for parental allele phase. Results were reviewed vis-à-vis the clinical-functional phenotypes for reconciliation and potential addition of supplemental testing such as deletion/duplication microarrays or copy number variant (CNV) analysis. Supplemental testing was driven by an IRD specialist-laboratory consensus, and decisions were clinically or genetically driven or both. Results: By judiciously using this two-way approach and leveraging to its full potential the benefits of careful, in-depth clinical-functional phenotyping by an experienced IRD specialist, more than 80% of the cases in this series were successfully genotyped. We also identified with a high degree of confidence 52 novel disease-causing mutations, deletions, and duplications. Conclusions: The combination of meticulous, expert clinical-functional phenotyping studies with systematic next-generation sequencing panel-based genotyping and microarray deletion/duplication testing or CNV analysis as applicable in accordance with the above-mentioned consensus was extremely effective at the diagnostic end, reduced costs, and saved time. IRD specialist-laboratory two-way interactions and case discussions would augment the efficacy of this approach and improve the diagnostic yield in successfully solving and genotyping IRD cases.

Plasticity of salmonfly (Pteronarcys californica) respiratory phenotypes in response to changes in temperature and oxygen.

Like all taxa, populations of aquatic insects may respond to climate change by evolving new physiologies or behaviors, shifting their range, exhibiting physiological and behavioral plasticity, or going extinct. We evaluated the importance of plasticity by measuring changes in growth, survival and respiratory phenotypes of salmonfly nymphs (the stonefly Pteronarcys californica) in response to experimental combinations of dissolved oxygen and temperature. Overall, smaller individuals grew more rapidly during the 6-week experimental period, and oxygen and temperature interacted to affect growth in complex ways. Survival was lower for the warm treatment, although only four mortalities occurred (91.6% versus 100%). Nymphs acclimated to warmer temperatures did not have higher critical thermal maxima (CTmax), but those acclimated to hypoxia had CTmax values (in normoxia) that were higher by approximately 1°C. These results suggest possible adaptive plasticity of systems for taking up or delivering oxygen. We examined these possibilities by measuring the oxygen sensitivity of metabolic rates and the morphologies of tracheal gill tufts located ventrally on thoracic segments. Mass-specific metabolic rates of individuals acclimated to warmer temperatures were higher in acute hypoxia but lower in normoxia, regardless of their recent history of oxygen exposure during acclimation. The morphology of gill filaments, however, changed in ways that appeared to depress rates of oxygen delivery in functional hypoxia. Our combined results from multiple performance metrics indicate that rising temperatures and hypoxia may interact to magnify the risks to aquatic insects, but that physiological plasticity in respiratory phenotypes may offset some of these risks.

Temperature-dependent reentrant phase transition of RNA-polycation mixtures.

Liquid-liquid phase separation (LLPS) of multivalent biopolymers is a ubiquitous process in biological systems and is of importance in bio-mimetic soft matter design. The phase behavior of biomolecules, such as proteins and nucleic acids, is typically encoded by the primary chain sequence and regulated by solvent properties. One of the most important physical modulators of LLPS is temperature. Solutions of proteins and/or nucleic acids have been shown to undergo liquid-liquid phase separation either upon cooling (with an upper critical solution temperature, UCST) or upon heating (with a lower critical solution temperature, LCST). However, many theoretical frameworks suggest the possibility of more complex temperature-dependent phase behaviors, such as an hourglass or a closed-loop phase diagram with concurrent UCST and LCST transitions. Here, we report that RNA-polyamine mixtures undergo a reentrant phase separation with temperature. Specifically, at low temperatures, RNA-polyamine mixtures form a homogenous phase. Increasing the temperature leads to the formation of RNA-polyamine condensates. A further increase in temperature leads to the dissolution of condensates, rendering a reentrant homogenous phase. This dual-response phase separation of RNA is not unique to polyamines but also observed with short cationic peptides. The immiscibility gap is controlled by the charge of the polycation, salt concentration, and mixture composition. Based on the existing theories of complex coacervation, our results point to a complex interplay between desolvation entropy, ion-pairing, and electrostatic interactions in dictating the closed-loop phase behavior of RNA-polycation mixtures.

Shifting of cell cycle arrest from the S-phase to G2/M phase and downregulation of EGFR expression by phytochemical combinations in HeLa cervical cancer cells.

Cervical cancer is a major human papillomavirus-related disease and is the fourth leading cause of death by cancer among women. Plants are an important source of anticancer compounds and many of them are currently used in the treatment of cancer. Several reports suggest the efficacy of plant-derived compounds increases when used in combination. This study was carried out to evaluate the effect of four plant-derived compounds such as curcumin (C), ellagic acid (E), quercetin (Q), and resveratrol (R) when used alone or in combinations using HeLa cervical cancer cells. All four phytocompounds showed effective cytotoxic activities in targeting HeLa cervical cancer cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay. The selected phytocompound combinations C + E, C + Q, and Q + R work synergistically while the combination C + R shows additive effects. All four phytocompounds reduce cell migration as determined by in vitro wound-healing assay. The expression level of the epidermal growth factor receptor is significantly downregulated both in individual and combination. The flow cytometry analysis of cell cycle indicates that individual drugs curcumin, ellagic acid, quercetin, and resveratrol, each with 20 µM effectively arrested cell cycle at the S-phase while the combination of drugs (10 + 10 µM) at the G2/M phase.

Performance of Multidetector Computed Tomography and Negative Versus Positive Enteric Contrast for Evaluation of Gastrointestinal Neuroendocrine Neoplasms.

BACKGROUND: Routine computed tomography (CT) scans are thought to have poor performance for detection of gastrointestinal (GI) neuroendocrine neoplasms (NENs), which leads to delayed workup. Detection of even 1 bowel tumor can guide diagnostic workup and management. The purposes of this study were to assess the accuracy of multidetector computed tomography (MDCT) and to compare negative versus positive enteric contrast in detecting at least 1 GI tumor per patient with suspected or confirmed diagnosis of a NEN. METHODS: This retrospective study included 107 patients with intravenous and oral contrast (65 positive, 40 negative, and 2 no oral contrast) abdominopelvic MDCT. Two abdominal radiologists independently analyzed the CTs for detection and localization of bowel NENs. Surgical pathology was considered the reference standard. Analyses included κ and summary statistics, McNemar test, Pearson χ2 test, and Fisher exact test. RESULTS: Among the 107 CT scans, there were 30 pathology negative studies and 77 studies with positive pathology for GI NEN. Interreader agreement for CT evaluation was substantial (κ = 0.61). At least 1 GI NEN per patient was detected with 51% to 53% sensitivity, 87% to 93% specificity, 91% to 95% positive predictive value (PPV), 42% negative predictive value, and 63% accuracy for each reader, and 57% accuracy when only the concordant (ie, matching) results of the 2 readers were considered. Computed tomography scans with negative enteric contrast had significantly higher sensitivity for concordant results than CTs with positive enteric contrast (58% vs 30%, P = 0.01). Specificity (100% vs 95%, P = 0.5), PPV (100% vs 93%, P = 0.49), negative predictive value (39% vs 39%, P = 0.99), and accuracy (67% vs 51%, P = 0.10) were not significantly different for negative versus positive enteric contrast for the concordant results. There was no significant difference in GI NEN localization between the readers. CONCLUSIONS: Routine MDCT with either positive or negative enteric contrast can detect at least 1 GI tumor per patient with more than 90% PPV and more than 50% accuracy in patients suspected of GI NEN. Using negative enteric contrast improves sensitivity for GI NEN versus positive enteric contrast. In addition, there is high accuracy in localizing the bowel tumor with positive or negative enteric contrast, which may guide surgery. Radiologists should have heightened awareness that evaluating such scans closely may lead to detection of primary bowel NENs at a higher rate than previously reported.

Role of Curcumin in Retinal Diseases-A review.

PURPOSE: To review the role of curcumin in retinal diseases, COVID era, modification of the molecule to improve bioavailability and its future scope. METHODS: PubMed and MEDLINE searches were pertaining to curcumin, properties of curcumin, curcumin in retinal diseases, curcumin in diabetic retinopathy, curcumin in age-related macular degeneration, curcumin in retinal and choroidal diseases, curcumin in retinitis pigmentosa, curcumin in retinal ischemia reperfusion injury, curcumin in proliferative vitreoretinopathy and curcumin in current COVID era. RESULTS: In experimental models, curcumin showed its pleiotropic effects in retinal diseases like diabetic retinopathy by increasing anti-oxidant enzymes, upregulating HO-1, nrf2 and reducing or inhibiting inflammatory mediators, growth factors and by inhibiting proliferation and migration of retinal endothelial cells in a dose-dependent manner in HRPC, HREC and ARPE-19 cells. In age-related macular degeneration, curcumin acts by reducing ROS and inhibiting apoptosis inducing proteins and cellular inflammatory genes and upregulating HO-1, thioredoxin and NQO1. In retinitis pigmentosa, curcumin has been shown to delay structural defects of P23H gene in P23H-rhodopsin transgenic rats. In proliferative vitreoretinopathy, curcumin inhibited the action of EGF in a dose- and time-dependent manner. In retinal ischemia reperfusion injury, curcumin downregulates IL-17, IL-23, NFKB, STAT-3, MCP-1 and JNK. In retinoblastoma, curcumin inhibits proliferation, migration and apoptosis of RBY79 and SO-RB50. Curcumin has already proven its efficacy in inhibiting viral replication, coagulation and cytokine storm in COVID era. CONCLUSION: Curcumin is an easily available spice used traditionally in Indian cooking. The benefits of curcumin are manifold, and large randomized controlled trials are required to study its effects not only in treating retinal diseases in humans but in their prevention too.

Quantifying viscosity and surface tension of multicomponent protein-nucleic acid condensates.

Living cells organize their internal space into dynamic condensates through liquid-liquid phase separation of multivalent proteins in association with cellular nucleic acids. Here, we study how variations in nucleic acid (NA)-to-protein stoichiometry modulate the condensed phase organization and fluid dynamics in a model system of multicomponent heterotypic condensates. Employing a multiparametric approach comprised of video particle tracking microscopy and optical tweezer-induced droplet fusion, we show that the interfacial tension, but not viscosity, of protein-NA condensates is controlled by the NA/protein ratio across the two-phase regime. In parallel, we utilize fluorescence correlation spectroscopy to quantify protein and NA diffusion in the condensed phase. Fluorescence correlation spectroscopy measurements reveal that the diffusion of the component protein and NA within the condensate core is governed by the viscosity, and hence, also remains insensitive to the changes in NA-to-protein stoichiometry. Collectively, our results provide insights into the regulation of multicomponent heterotypic liquid condensates, reflecting how the bulk mixture composition affects their core versus surface organization and dynamical properties.