Greening the pathways: a comprehensive review of sustainable synthesis strategies for silica nanoparticles and their diverse applications.

Silica nanoparticles (SiNPs) have emerged as a multipurpose solution with wide-ranging applications in various industries such as medicine, agriculture, construction, cosmetics, and food production. In 1961, Stöber introduced a ground-breaking sol-gel method for synthesizing SiNPs, which carried a new era of exploration both in academia and industry, uncovering numerous possibilities for these simple yet multifaceted particles. Inspite of numerous reported literature with wide applicability, the synthesis of these nanoparticles with the desired size and functionalities poses considerable challenges. Over time, researchers have strived to optimize the synthetic route, particularly by developing greener approaches that minimize environmental impact. By reducing hazardous chemicals, energy consumption, and waste generation, these greener synthesis methods have become an important focus in the field. This review aims to provide a comprehensive analysis of the various synthetic approaches available for different types of SiNPs. Starting from the Stöber' method, we analyze other methods as well to synthesis different types of SiNPs including mesoporous, core-shell and functionalized nanoparticles. With increasing concerns with the chemical methods associated for environmental issues, we aim to assist readers in identifying suitable greener synthesis methods tailored to their specific requirements. By highlighting the advancements in reaction time optimization, waste reduction, and environmentally friendly precursors, we offer insights into the latest techniques that contribute to greener and more sustainable SiNPs synthesis. Additionally, we briefly discuss the diverse applications of SiNPs, demonstrating their relevance and potential impact in fields such as medicine, agriculture, and cosmetics. By emphasizing the greener synthesis methods and economical aspects, this review aims to inspire researchers and industry professionals to adopt environmentally conscious practices while harnessing the immense capabilities of SiNPs.

Rational design of MIPs for the detection of Myxovirus resistance protein A (MxA), a biomarker for viral infection.

Accurate diagnosis is crucial for effective patient care and the containment of antimicrobial resistance outbreaks. The intricate challenge of distinguishing bacterial from viral infections, coupled with limited diagnostic tools and overlapping symptoms has driven the utilization of molecular imprinting techniques. This study focuses on developing cost-effective, chemically stable antibody analogs for the interferon-induced protein myxovirus resistance protein A (MxA). MxA is an intracellular, cytoplasmic GTPase having activity against a wide range of viruses and serves as a distinctive biomarker for viral infections. We utilized computational design to guide the polymer assembly, centering on epitope imprinting to target MxA-specific regions crucial for interaction. Molecular docking calculations, alongside a pioneering multi-monomer simultaneous docking (MMSD) protocol, efficiently elucidate cooperativity during pre-polymerization. Monomer binding affinity scores, such as for APTMS, exhibited notable increase, ranging from -3.11 to -13.03 kcal/mol across various MMSD combinations compared to a maximum of -2.78 kcal/mol in single monomer docking, highlighting the capacity of MMSD in elucidating crucial monomer-monomer interactions. This computational approach provides a theoretical alternative to labor-intensive experimental optimization, streamlining the development process for synthetic receptors. Simulations reveal unique interactions enhancing MIP-peptide complementarity, yielding optimized receptors selectively binding to MxA epitopes. The obtained MIPs demonstrated a maximum adsorption capacity of approximately 12 mg/g and captured 1.6 times more epitope and 2.6 times more epitope containing MxA protein than corresponding NIPs. A proof-of-concept study demonstrates MxA protein binding to synthetic receptors, highlighting the potential of MIPs, analogous to antibodies, in overcoming current diagnostic challenges for precise detection of viral infection.

Biocompatible carbon quantum dots as versatile imaging nanotrackers of fungal pathogen - Candida albicans.

Aim: The development of carbon quantum dots (C-QDs) as nanotrackers to understand drug-pathogen interactions, virulence and multidrug resistance. Methods: Microwave synthesis of C-QDs was performed using citric acid and polyethylene glycol. Further, in vitro toxicity was evaluated and imaging applications were demonstrated in Candida albicans isolates. Results: Well-dispersed, ultra small C-QDs exhibited no cyto/microbial/reactive oxygen species-mediated toxicity and internalized effectively in Candida yeast and hyphal cells. C-QDs were employed for confocal imaging of drug-sensitive and -resistant cells, and a study of the yeast-to-hyphal transition using atomic force microscopy in Candida was conducted for the first time. Conclusion: These biocompatible C-QDs have promising potential as next-generation nanotrackers for in vitro and in vivo targeted cellular and live imaging, after functionalization with biomolecules and drugs.

Scientists have used radiolabeled drugs and radioactive tracking agents for the imaging and study of drug resistance in microbial pathogens. But, these radiolabeled drugs or radiotrackers pose health hazards and environmental risks. However, such limitations can be overcome by designing nontoxic, environment-friendly, nanotechnology-based fluorescent imaging agents. This study demonstrates the development and application of cost-effective, nontoxic carbon-based quantum dots for imaging of drug-sensitive and -resistant microbial strains and transition to different morphological forms (yeast-to-hyphae transition) in fungal pathogens. The results demonstrated the suitability of carbon quantum dots as next-generation nano-based bioimaging/tracking agents for cellular imaging. The availability of such nontoxic fluorescent tracking agents is likely to offer promising solutions in therapeutics and diagnostics by providing insight into various mechanisms and functional links related to drug resistance, virulence and pathogenicity.

Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability.

Acetyl-CoA carboxylase (ACC) promotes prandial liver metabolism by producing malonyl-CoA, a substrate for de novo lipogenesis and an inhibitor of CPT-1-mediated fat oxidation. We report that inhibition of ACC also produces unexpected secondary effects on metabolism. Liver-specific double ACC1/2 knockout (LDKO) or pharmacologic inhibition of ACC increased anaplerosis, tricarboxylic acid (TCA) cycle intermediates, and gluconeogenesis by activating hepatic CPT-1 and pyruvate carboxylase flux in the fed state. Fasting should have marginalized the role of ACC, but LDKO mice maintained elevated TCA cycle intermediates and preserved glycemia during fasting. These effects were accompanied by a compensatory induction of proteolysis and increased amino acid supply for gluconeogenesis, which was offset by increased protein synthesis during feeding. Such adaptations may be related to Nrf2 activity, which was induced by ACC inhibition and correlated with fasting amino acids. The findings reveal unexpected roles for malonyl-CoA synthesis in liver and provide insight into the broader effects of pharmacologic ACC inhibition.

Morin ameliorates myocardial injury in diabetic rats via modulation of inflammatory pathways.

BACKGROUND: High blood glucose levels in diabetes lead to vascular inflammation which accelerates atherosclerosis. Herein, Morin was orally administered in male Wistar rats, at the dose of 40 mg/kg for 28 days, and on the 27th and 28th day, ISO was administered to designate groups at the dose of 85 mg/kg s.c., to induce myocardial infarction. RESULTS: Free radical generation, including ROS, in diabetes following ISO administration, leads to the activation of both intrinsic and extrinsic pathways of apoptosis. Morin significantly (p ≤ 0.05) reduced oxidative stress (GSH, MDA, SOD), cardiac injury markers (CK-MB, LDH), inflammation (TNF, IL-6), and apoptosis (Bax, BCl2, Caspase-3). In addition, it also reduced insulin and blood glucose levels. Akt/eNOS, Nrf2/HO-1, MAPK signaling pathways, and Insulin signal transduction pathways were positively modulated by morin pre-treatment. CONCLUSIONS: Morin attenuated oxidative stress and inflammation and also modified the activity of various molecular pathways to mitigate cardiomyocyte damage during ISO-induced MI in diabetic rats.

Jejunovesical Fistula Diagnosis After Normal Vaginal Delivery: A Case Report.

Enterovesical fistula represents an abnormal communication between the intestine and bladder. The causes are diverticulitis (56.3%), malignant tumours, which are located mainly in the intestine (20.1%), and Crohn's disease (9.1%). Other causes include iatrogenic injury (3.2%); trauma; foreign bodies in the intestinal tract; radiotherapy; chronic appendicitis; tuberculosis; and syphilis. Normal vaginal delivery as a cause for enterovesical fistula has not been reported in many publications yet. We report a case of a 30-year-old female, who developed an jejunovesical fistula after normal vaginal delivery. It was diagnosed after diagnostic cystoscopy and computed tomography of the abdomen and pelvis. There was jejuno-vesical fistula. Resection of the segment of the jejunum with side-to-side anastomosis with bladder repair was done. A follow-up cystogram was done which showed no contrast extravasation into the peritoneum. The patient was followed up for 9 months after surgery. Keywords: case reports; fistula; jejunum; urinary bladder.

Multiresponsive Nanoscale Self-Assembly of Azurin-Elastin-like Polypeptide Fusion Protein for Enhanced Prostate Cancer Therapy.

A fusion protein composed of a bacterial protein, azurin, having antineoplastic properties and a thermally responsive structural cationic elastin-like protein (ELP), is designed, cloned, expressed, and purified. A simple method of inverse transition cycle (ITC) is employed to purify the fusion protein azurin-ELP diblock copolymer (d-bc). The molecular weight of the azurin-ELP fusion protein is ∼32 kDa. Further, its self-assembly properties are investigated. Interestingly, the engineered azurin-ELP d-bc in response to increasing temperature shows a dual-step phase separation into biofunctional nanostructures. Around the physiological temperature, azurin-ELP d-bc forms stable coacervates, which is dependent on the concentration and time of incubation. These coacervates are formed below the lower critical solubility temperature (LCST) of the ELP block at physiological temperature. Above LCST, i.e., 50-55°C, micelles of size ranging from 25 to 30 nm are formed. The cytotoxicity of azurin-ELP d-bc depends on the size of the coacervates formed and their cellular uptake at physiological temperature. Further, MTT assay of azurin-ELP d-bc in the cross-linked micelles prepared ex situ shows > six times higher killing of LNCaP cells than the unimeric form of azurin-ELP at 5 µM concentration. The flow cytometric results of these micelles at 20 µM concentration show ∼97% LNCaP cells in the apoptotic phase. Thus, azurin-ELP cross-linked micelles have enhanced potential for anticancer therapy due to their higher avidity.

Engineered Recombinant EGFP-Azurin Theranostic Nanosystem for Targeted Therapy of Prostate Cancer.

Erythropoietin-producing hepatocellular (Eph) receptors and their ligands, ephrins, are the largest subfamily of receptor tyrosine kinases (RTKs) that have emerged as a new class of cancer biomarkers due to their aberrant expression in cancer progression. The activation of Eph receptors either due to their hyperexpression or via high affinity binding with their respective ephrin ligands initiates a cascade of signals that impacts cancer development and progression. In prostate cancer, the overexpression of the EphA6 receptor has been correlated with increased metastatic potential. Azurin, a small redox protein, is known to prevent tumor progression by binding to cell surface Eph receptors, inhibiting its autophosphorylation in the kinase domain and thereby disrupting Eph-ephrin signaling. Hence, a self-assembled, theranostic nanosystem of recombinant fusion protein his6EGFP-azu (80-128) was designed by conjugating enhanced green fluorescent protein (EGFP) with the C-terminal region of azurin. This design was inspired by the in silico binding study, where the analogue of ephrinA, his6EGFP-azu (80-128) showed higher binding affinity for the EphA6 receptor than the ephrinA ligands. The his6EGFP-azu (80-128) nanosystem which assembled as nanoparticles was tested for its ability to simultaneously detect and kill the prostate cancer cells, LNCaP. This was achieved by specifically targeting EphA6 receptors overexpressed on the cancer cell surface via C-terminal peptide, azu (80-128). Herein, we report antiproliferative, apoptotic, antimigratory, and anti-invasive effects of this nanosystem on LNCaP cells, while having no similar effects on EphA6 negative human normal lung cells, WI-38.

Impact of COVID-19 vaccination on mortality after acute myocardial infarction.

BACKGROUND: COVID-19 vaccines are highly immunogenic but cardiovascular effects of these vaccines have not been properly elucidated. OBJECTIVES: To determine impact of COVID-19 vaccination on mortality following acute myocardial infarction (AMI). METHODS: This was a single center retrospective observation study among patients with AMI enrolled in the the North India ST-Elevation Myocardial Infarction (NORIN-STEMI) registry. In all the enrolled patients, data regarding patient's vaccination status including details on type of vaccine, date of vaccination and adverse effects were obtained. All enrolled subjects were followed up for a period of six months. The primary outcome of the study was all-cause mortality both at one month and at six months of follow-up. Propensity-weighted score logistic regression model using inverse probability of treatment weighting was used to determine the impact of vaccination status on all-cause mortality. RESULTS: A total of 1578 subjects were enrolled in the study of whom 1086(68.8%) were vaccinated against COVID-19 while 492(31.2%) were unvaccinated. Analysis of the temporal trends of occurrence of AMI post vaccination did not show a specific clustering of AMI at any particular time. On 30-day follow-up, all-cause mortality occurred in 201(12.7%) patients with adjusted odds of mortality being significantly lower in vaccinated group (adjusted odds ratio[aOR]: 0.58, 95% CI: 0.47-0.71). Similarly, at six months of follow-up, vaccinated AMI group had lower odds of mortality(aOR: 0.54, 95% CI: 0.44 to 0.65) as compared to non-vaccinated group. CONCLUSIONS: COVID-19 vaccines have shown to decrease all-cause mortality at 30 days and six months following AMI.

A magnetic field augmented ultra-thin layer chromatography coupled surface enhanced Raman spectroscopy separation of hemozoin from bacterial mixture.

Malaria is considered as one the most widespread disease with highest possibility of co-infection at all levels of the disease prognosis. Rapid detection and discrimination of malaria from other co-infections remains a challenge. Hemozoin is a metabolic biproduct of malaraia possessing paramagnetic property due to presence of iron at its centre. Here, we report a label free, rapid and highly sensitive magnetic field based ultra-thin layer chromatography (UTLC) coupled with surface enhanced Raman spectroscopy (SERS) technique for detection and separation of hemozoin from a bacterial mixture. Highly optimized silver nanorods chip fabricated using glancing angle deposition (GLAD) is explored for the UTLC-SERS separation. These chips possessing channel like characteristic and high surface to the volume ratio serve as excellent UTLC plates. The magnetic nature of hemozoin has been exploited for its separation from the mixture of P. aeruginosa (Gram-negative) and S. aureus (Gram-positive) by allocating a 0.6 T magnet over the UTLC flow setup. The solvent front migrated approximately to a distance of 13 mm from the sample point due to the magnetic environment. Spatially resolved SERS data was collected along the mobile phase and separation of mixture was confirmed. Further, staining of hemozoin, P. aeruginosa and S. aureus was done using methylene blue, acridine orange and rhodamine 6 G respectively. The separation was confirmed for the stained analytes. The present developed method provides plate height as low as 18 µm and hemozoin detection limit as <10 parasites/mL. Therefore, we establish a highly specific and sensitive technique capable of separating small amounts of bioanalytes, aiding in the removal of co-infections from the disease at a very early stage of infection.

A magnetically controlled microfluidic device for concentration dependent in vitro testing of anticancer drug.

Compartmentalizing magnetically controlled drug molecules is critical in several bioanalytical trials and tests, such as drug screening, digital PCR, magnetic hyperthermia, and controlled magnetic drug targeting (MDT). However, several studies have focused on diluting the nonmagnetic drug using various passive devices based on traditional microfabrication and 3D printing techniques, leading to the requirement of sterilized cleanroom facilities and expensive equipment, respectively. This work develops a strategically designed and straightforward lithography-free process to fabricate a magnetic microfluidic device using a multilayered PMMA substrate for concentration-dependent compartmentalization of a magnetically controlled anticancer drug. The device contains an array of outlet chamber wells connected to five primary separation microfluidic channels for collecting different drug concentrations. The microfluidic design geometry, magnet configuration, and fluid flow rate are optimized using FEM (Finite Element Method) simulations to attain a systematic concentration gradient region within the microfluidic channel. A stair-step-like patterned magnet creates an attenuating magnetic force between 0.01-0.24 pN on magnetic nanoparticles, capable of generating the concentration gradient for the clinically acceptable flow range of Q = 0.6-1.1 µL min-1. The chamber well of the device is designed to adapt different cell cultures and simultaneously expose five different concentrations by introducing a predefined concentration from the inlet. As a result, this innovative design provides a predictable concentration control in each well through a single injection port to minimize drug loading errors. The concentration gradient generation of the drug and exposure to cell culture chambers are controlled using the magnetic and drag forces capable of running a time-varying dose screening experiment. The concentration range of the compartmentalized drug sample in the device is determined as 10-480 µg mL-1 using inductively coupled plasma mass spectrometry (ICPMS) measurement and fluorescence intensity. The cytotoxicity test of MCF7 and NIH3T3 cells using the device was consistent with the results obtained with the manual dilution method, resulting in the reusability of the device.

Pathogenic mitochondrial DNA mutations inhibit melanoma metastasis.

Mitochondrial DNA (mtDNA) mutations are frequently observed in cancer, but their contribution to tumor progression is controversial. To evaluate the impact of mtDNA variants on tumor growth and metastasis, we created human melanoma cytoplasmic hybrid (cybrid) cell lines transplanted with wildtype mtDNA or pathogenic mtDNA encoding variants that partially or completely inhibit oxidative phosphorylation. Homoplasmic pathogenic mtDNA cybrids reliably established tumors despite dysfunctional oxidative phosphorylation. However, pathogenic mtDNA variants disrupted spontaneous metastasis of subcutaneous tumors and decreased the abundance of circulating melanoma cells in the blood. Pathogenic mtDNA did not induce anoikis or inhibit organ colonization of melanoma cells following intravenous injections. Instead, migration and invasion were reduced, indicating that limited circulation entry functions as a metastatic bottleneck amidst mtDNA dysfunction. Furthermore, analysis of selective pressure exerted on the mitochondrial genomes of heteroplasmic cybrid lines revealed a suppression of pathogenic mtDNA allelic frequency during melanoma growth. Collectively, these findings demonstrate that functional mtDNA is favored during melanoma growth and enables metastatic entry into the blood.

Guided mode resonance immunosensor for label-free detection of pathogenic bacteria Pseudomonas aeruginosa.

Photonic biosensors are promising platforms for the rapid detection of pathogens with the potential to replace conventional diagnostics based on microbiological culturing methods. Intricately designed sensing elements with robust architectures can offer highly sensitive detection at minimal development cost enabling rapid adoption in low-resource settings. In this work, an optical detection scheme is developed by structuring guided mode resonance (GMR) on a highly stable, transparent silicon nitride (SiN) substrate and further biofunctionalized to identify a specific bacteria Pseudomonas aeruginosa. The resonance condition of the GMR chip is optimized to have relatively high bulk sensitivity with a good quality factor. The biofunctionalization aims at oriented immobilization of specific antibodies to allow maximum bacteria attachment and improved specificity. The sensitivity of the assays is evaluated for clinically relevant concentrations ranging from 102 to 108 CFU/mL. From the calibration curves, the sensitivity of the chip is extracted as 0.134nm/Log10 [concentration], and the detection modality possesses a favorably good limit of detection (LOD) 89 CFU/mL. The use of antibodies as a biorecognition element complemented with a good figure of merit of GMR sensing element allows selective bacteria identification compared to other non-specific pathogenic bacteria that are relevant for testing physiological samples. Our developed GMR biosensor is low-cost, easy to handle, and readily transformable into a portable handheld detection modality for remote usage.

An Integrated Yoga and Cognitive Behavioral Therapy Intervention for Managing Excessive Use of Internet among the Youth: A Case Series.

Background: Internet addiction is a behavioral problem that is managed by pharmacological and nonpharmacological methods. The nonpharmacological methods focus on enhancing skills for healthy use of technology and promoting mindfulness and mental relaxation. Yoga therapy is an effective tool to reduce psychological stress and promote self-regulation and mindfulness. Thus, present work focused on developing an integrated yoga and cognitive behavioral therapy intervention (Y-CBT) for the management of excessive use of technology amongst adolescents and young adult students. Methods: Feasibility of the Y-CBT program was tested by implementing 10 sessions of yoga and 6 sessions of CBT program for 2 weeks by certified Yoga therapist and psychologist, respectively. This was followed by online booster sessions once a week, and post assessments were conducted at 12 weeks. A total of 4 college-going students with the excessive use of technology were recruited from tertiary specialty service for promotion of healthy use of technology. Each participant was assessed using short-version of internet addiction test (s-IAT), Smartphone Addiction Scale-Short Version, Kessler's Psychological distress scale for baseline, and follow-up assessment after completion of the program. Results: The Y-CBT program was found feasible and useful in reducing internet use, smart phone use, and psychological distress. There were no reported side-effects. A trend was observed for increase compliance toward treatment at follow-up. Future studies should explore this further with robust methodology.

Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability.

Centromere (CEN) identity is specified epigenetically by specialized nucleosomes containing evolutionarily conserved CEN-specific histone H3 variant CENP-A (Cse4 in Saccharomyces cerevisiae, CENP-A in humans), which is essential for faithful chromosome segregation. However, the epigenetic mechanisms that regulate Cse4 function have not been fully defined. In this study, we show that cell cycle-dependent methylation of Cse4-R37 regulates kinetochore function and high-fidelity chromosome segregation. We generated a custom antibody that specifically recognizes methylated Cse4-R37 and showed that methylation of Cse4 is cell cycle regulated with maximum levels of methylated Cse4-R37 and its enrichment at the CEN chromatin occur in the mitotic cells. Methyl-mimic cse4-R37F mutant exhibits synthetic lethality with kinetochore mutants, reduced levels of CEN-associated kinetochore proteins and chromosome instability (CIN), suggesting that mimicking the methylation of Cse4-R37 throughout the cell cycle is detrimental to faithful chromosome segregation. Our results showed that SPOUT methyltransferase Upa1 contributes to methylation of Cse4-R37 and overexpression of UPA1 leads to CIN phenotype. In summary, our studies have defined a role for cell cycle-regulated methylation of Cse4 in high-fidelity chromosome segregation and highlight an important role of epigenetic modifications such as methylation of kinetochore proteins in preventing CIN, an important hallmark of human cancers.

Psychosocial stress and well-being in patients presenting with acute myocardial infarction in a tertiary care center.

BACKGROUND: Psychosocial factors such as stress have been previously implicated as a risk factor for cardiovascular diseases (CVDs). There is little evidence regarding the prevalence of stress among patients with acute myocardial infarction (AMI). METHODS: A total of 903 patients with AMI enrolled in the North Indian ST-Segment Elevation Myocardial Infarction (NORIN-STEMI) registry were included in this study. Perceived stress in these subjects was evaluated using the Perceived Stress Scale-10 questionnaire while the World health Organization (WHO-5) Well-being Index was used to evaluate psychological well-being. All these patients were followed up for one month and major adverse cardiac events (MACE) were determined. RESULTS: A majority of patients with AMI had either severe (478 [52.9%]) or moderate stress (347 [38.4%]) while low stress levels were observed in 78 [8.6%] patients. Additionally, most of the patients with AMI (478 [53%]) had WHO-5 well-being index <50%. Subjects with severe stress were younger (50.86 ± 13.31; P < 0.0001), more likely to be males (403 [84.30%]; P = 0.027), were less likely to have optimal level of physical activity (P < 0.0001) and had lower WHO-5 well-being score (45.54 ± 1.94%; P < 0.0001) as compared to those with low and moderate stress levels. On 30-days follow-up, subjects with moderate/severe stress had higher MACE however, the difference was non-significant (2.1% vs 1.04%; P = 0.42). CONCLUSION: A high prevalence of perceived stress and low well-being index was observed in patients presenting with AMI in India.

Mitochondrial-Encoded Complex I Impairment Induces a Targetable Dependency on Aerobic Fermentation in Hürthle Cell Carcinoma of the Thyroid.

A metabolic hallmark of cancer identified by Warburg is the increased consumption of glucose and secretion of lactate, even in the presence of oxygen. Although many tumors exhibit increased glycolytic activity, most forms of cancer rely on mitochondrial respiration for tumor growth. We report here that Hürthle cell carcinoma of the thyroid (HTC) models harboring mitochondrial DNA-encoded defects in complex I of the mitochondrial electron transport chain exhibit impaired respiration and alterations in glucose metabolism. CRISPR-Cas9 pooled screening identified glycolytic enzymes as selectively essential in complex I-mutant HTC cells. We demonstrate in cultured cells and a patient-derived xenograft model that small-molecule inhibitors of lactate dehydrogenase selectively induce an ATP crisis and cell death in HTC. This work demonstrates that complex I loss exposes fermentation as a therapeutic target in HTC and has implications for other tumors bearing mutations that irreversibly damage mitochondrial respiration. SIGNIFICANCE: HTC is enriched in somatic mtDNA mutations predicted to affect complex I of the electron transport chain (ETC). We demonstrate that these mutations impair respiration and induce a therapeutically tractable reliance on aerobic fermentation for cell survival. This work provides a rationale for targeting fermentation in cancers harboring irreversible genetically encoded ETC defects. See related article by Gopal et al., p. 1904. This article is highlighted in the In This Issue feature, p. 1749.

Audio delivery of health information: An NLP study of information difficulty and bias in listeners.

Health literacy is the ability to understand, process, and obtain health information and make suitable decisions about health care [3]. Traditionally, text has been the main medium for delivering health information. However, virtual assistants are gaining popularity in this digital era; and people increasingly rely on audio and smart speakers for health information. We aim to identify audio/text features that contribute to the difficulty of the information delivered over audio. We are creating a health-related audio corpus. We selected text snippets and calculated seven text features. Then, we converted the text snippets to audio snippets. In a pilot study with Amazon Mechanical Turk (AMT) workers, we measured the perceived and actual difficulty of the audio using the response of multiple choice and free recall questions. We collected demographic information as well as bias about doctors' gender, task preference, and health information preference. Thirteen workers completed thirty audio snippets and related questions. We found a strong correlation between text features lexical chain, and the dependent variables, and multiple choice response, percentage of matching word, percentage of similar word, cosine similarity, and time taken (in seconds). In addition, doctors were generally perceived to be more competent than warm. How warm workers perceive male doctors correlated significantly with perceived difficulty.

Rational In Silico Design of Molecularly Imprinted Polymers: Current Challenges and Future Potential.

The rational design of molecularly imprinted polymers has evolved along with state-of-the-art experimental imprinting strategies taking advantage of sophisticated computational tools. In silico methods enable the screening and simulation of innovative polymerization components and conditions superseding conventional formulations. The combined use of quantum mechanics, molecular mechanics, and molecular dynamics strategies allows for macromolecular modelling to study the systematic translation from the pre- to the post-polymerization stage. However, predictive design and high-performance computing to advance MIP development are neither fully explored nor practiced comprehensively on a routine basis to date. In this review, we focus on different steps along the molecular imprinting process and discuss appropriate computational methods that may assist in optimizing the associated experimental strategies. We discuss the potential, challenges, and limitations of computational approaches including ML/AI and present perspectives that may guide next-generation rational MIP design for accelerating the discovery of innovative molecularly templated materials.