A comprehensive analysis of the immune system in healthy Vietnamese people.

Lifestyle, diet, socioeconomic status and genetics all contribute to heterogeneity in immune responses. Vietnam is plagued with a variety of health problems, but there are no available data on immune system values in the Vietnamese population. This study aimed to establish reference intervals for immune cell parameters specific to the healthy Vietnamese population by utilizing multi-color flow cytometry (MCFC). We provide a comprehensive analysis of total leukocyte count, quantitative and qualitative shifts within lymphocyte subsets, serum and cytokine and chemokine levels and functional attributes of key immune cells including B cells, T cells, natural killer (NK) cells and their respective subpopulations. By establishing these reference values for the Vietnamese population, these data contribute significantly to our understanding of the human immune system variations across diverse populations. These data will be of substantial comparative value and be instrumental in developing personalized medical approaches and optimizing diagnostic strategies for individuals based on their unique immune profiles.

Proanthocyanidins and Phenolic Compounds from the Twigs of Salix chaenomeloides and Their Anti-Lipogenic Effects on 3T3-L1 Preadipocytes.

The present study investigated potential bioactive natural products from the EtOH extract of Salix chaenomeloides twigs using column chromatography, leading to the isolation of six compounds (1-6), which were characterized as two proanthocyanidins, procyanidin B2 (1) and procyanidin B1 (2), and four phenolic compounds, 4-hydroxybenzoic acid ß-D-glucosyl ester (3), di-O-methylcrenatin (4), p-coumaric acid glucoside (5), and syringin (6) by the comparison of their NMR spectra with the reported data and high-resolution (HR)-electrospray ionization mass spectroscopy (ESI-MS) analysis. We investigated the potential of six compounds (1-6) to inhibit adipogenesis in 3T3-L1 preadipocytes, which showed that the compounds (1-6) significantly reduced lipid accumulation in 3T3-L1 adipocytes without affecting cell proliferation. Notably, compound 1 demonstrated a remarkable 60% and 90% reduction in lipid levels with 50 and 100 µM treatments, respectively. Oil Red O staining results indicated that compound 1 significantly inhibits the formation of lipid droplets, comparable to the effect of T863, an inhibitor of triglyceride used as a positive control, in adipocytes. Compound 1 had no effect on the regulators PPARγ, C/EBPα, and SREBF1 of adipocyte differentiation in 3T3-L1 preadipocytes, but compound 1 activated the fatty acid oxidation regulator, PPARα, compared to the lipogenic-induced control. It also suppressed fatty acid synthesis by downregulating the expression of fatty acid synthase (FAS). Finally, compound 1 induced the mRNA and protein levels of CPT1A, an initial marker of mitochondrial fatty acid oxidation in 3T3-L1. This finding substantiates the anti-lipogenic and lipolytic effects of procyanidin B2 (1) in 3T3-L1 preadipocytes, emphasizing its pivotal role in modulating obesity-related markers.

Classification and application of metal-based nanoantioxidants in medicine and healthcare.

Antioxidants play an important role in the prevention of oxidative stress and have been widely used in medicine and healthcare. However, natural antioxidants have several limitations such as low stability, difficult long-term storage, and high cost of large-scale production. Along with significant advances in nanotechnology, nanomaterials have emerged as a promising solution to improve the limitations of natural antioxidants because of their high stability, easy storage, time effectiveness, and low cost. Among various types of nanomaterials exhibiting antioxidant activity, metal-based nanoantioxidants show excellent reactivity because of the presence of an unpaired electron in their atomic structure. In this review, we summarize some novel metal-based nanoantioxidants and classify them into two main categories, namely chain-breaking and preventive antioxidant nanomaterials. In addition, the applications of antioxidant nanomaterials in medicine and healthcare are also discussed. This review provides a deeper understanding of the mechanisms of metal-based nanoantioxidants and a guideline for using these nanomaterials in medicine and healthcare.

Cardiac DTI using short-axis PROPELLER: A feasibility study.

PURPOSE: We aimed to develop a free-breathing (FB) cardiac DTI (cDTI) method based on short-axis PROPELLER (SAP) and M2 motion compensated spin-echo EPI (SAP-M2-EPI) to mitigate geometric distortion and eliminate aliasing in acquired diffusion-weighted (DW) images, particularly in patients with a higher body mass index (BMI). THEORY AND METHODS: The study involved 10 healthy volunteers whose BMI values fell into specific categories: BMI <25 (4 volunteers), 25< BMI <28 (5 volunteers), and BMI >30 (1 volunteer). We compared DTI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and helix angle transmurality (HAT), between SAP-M2-EPI and M2-ssEPI. To evaluate the performance of SAP-M2-EPI in reducing geometric distortions in the left ventricle (LV) compared to CINE and M2-ssEPI, we utilized the DICE similarity coefficient (DSC) and assessed misregistration area. RESULTS: In all volunteers, SAP-M2-EPI yielded high-quality LV DWIs without aliasing, demonstrating significantly reduced geometric distortion (with an average DSC of 0.92 and average misregistration area of 90 mm2) and diminished signal loss due to bulk motion when compared to M2-ssEPI. DTI parameter maps exhibited consistent patterns across slices without motion related artifacts. CONCLUSION: SAP-M2-EPI facilitates free-breathing cDTI of the entire LV, effectively eliminating aliasing and minimizing geometric distortion compared to M2-ssEPI. Furthermore, it preserves accurate quantification of myocardial microstructure.

Investigating the effects of ultrafine bubbles on bacterial growth.

Several previous studies have considered ultrafine bubbles as a potential research target because their properties can be applied in many different research areas. In particular, the interaction between UFBs and microorganisms has always been one of the aspects that receives much attention due to the high difficulty in controlling a living system. The properties of UFBs, as mobile air-water interfaces, are greatly determined by their gas cores which play a critical role in regulating microbial growth. This study aims to investigate the effects of ultrafine bubbles on bacterial growth. Two well-studied organisms were chosen as models - Escherichia coli and Staphylococcus aureus. Their growing behavior was examined based on the growth rate, phenotype and biomass. Three types of Luria-Bertani cultures were tested, including a standard culture containing distilled water, an air ultrafine bubble culture, and a hydrogen ultrafine bubble culture. The UFBs were generated via ultrasonic cavitation and stabilized by 50 µM SDS, which was proven to have negligible effects on bacterial growth. By comparing among the three cultivation conditions, the bacterial growth rates were observed to be the highest in exposure to HUFBs. The results also signified that UFBs had an enhancement on cell proliferation. On the other hand, while proposing an increase in cell density, bacteria cultured in HUFB media have their sizes decreased uniformly and significantly (p-value < 0.05). This study confirmed that bacterial growth was promoted by UFBs; and better effects recorded were due to the HUFB present in the culture media. However, the average morphological size of bacteria was in negative correlation with their population size.

A comprehensive review of Langya virus and framework for future zoonotic disease control.

First reported in August 2022, the Langya virus (LayV) has emerged as a potential global health threat in the post-COVID-19 era. Preliminary reports show that 35 patients near Shandong and Henan, China experienced a febrile acute LayV infection. We conducted this review following the PRISMA protocol to synthesise current knowledge on LayV's characteristics in terms of molecular, clinical, and public health perspectives. This virus belongs to the Paramyxoviridae family and carries a non-segmented, single-stranded negative-sense RNA genome. Shrews may be the natural reservoir of the virus. Clinical symptoms range from mild flu-like symptoms to severe manifestations involving pneumonia, haematological disorders, and organ dysfunction. Diagnostic methods include PCR and ELISA assays. Despite the absence of established treatments, antiviral drugs such as ribavirin and chloroquine may be useful in some cases. In light of prevention, a comprehensive approach that emphasises multidisciplinary collaboration is crucial for early surveillance and response. Urgent global efforts are needed for vaccine development and preparedness against this potential pandemic threat. As the viral dynamics remain uncertain, a proactive approach is vital to mitigate the impact of not only LayV but also future threats on a large scale in long term.

Preventing Static Biofilm Formation of Staphylococcus aureus on Different Types of Surfaces Using Microbubbles.

Bacterial fouling and biofilm formation on surfaces have been ongoing problems in real life as well as in the medical field. Different approaches have been taken to tackle the issues, from costly surface modification to antibiotic-delivering strategies. In this study, we examined the potential of using stabilized microbubbles (MBs) to shield against bacterial adhesion. Three types of surfaces were tested: hydrophilic glass (hydrophilic surface), neutral hydrophobic polystyrene (PS)-coated surfaces, and negatively charged hydrophobic octadecyltrichlorosilane (OTS)-coated surfaces. By evaluating the colony-forming unit (CFU) values from each surface, MBs stabilized by 0.05 mM SDS were shown to only produce significant reduction of Staphylococcus aureus adhesion on PS surfaces, up to 60.29 and 82.32% compared to no-MB PS surfaces, and no-MB uncoated surfaces, correspondingly, due to the appropriate size, stability, and negative charges of the MB shielding layer. On the other hand, OTS coatings had an intrinsic antiadhesion effect (69.83% compared to uncoated surface), given that the negatively charged OTS-aqueous interface or surface porosity nature of the coating prohibited the attachment of MBs, leading to the elimination of the antifouling effect of MBs. Ultimately, MBs gave better shielding results than surface modification when compared to uncoated surfaces and hence can be applied more widely.

CT-based diagnosis in patients presenting with throat pain: A single institutional review.

RATIONALE AND OBJECTIVE: To determine if patient demographic data, medical history, physical examination, and laboratory tests will help predict likelihood of imaging-based diagnosis using CT of the neck performed in the ED for a chief complaint of throat pain. MATERIAL AND METHODS: Single institutional, retrospective review of 367 CT scans of the neck performed for the evaluation of throat pain in the ED from August 2013 to September 2019. Patients' clinical history, physical exams, lab findings, and imaging results were recorded. RESULTS: A total of 367 CT scans of the neck performed for the evaluation of throat pain included a recorded exam and clinical history. Of these cases, we noted that the presence of cervical lymphadenopathy (OR = 2.69; 95% CI, 1.37-5.49), tonsillar findings (OR = 2.94; 95% CI, 1.4-6.57), increased white blood cell count (OR = 1.08; 95% CI, 1.02-1.15), and temperature (OR = 1.94; 95% CI, 1.1-3.6) were associated with increased likelihood of obtaining a diagnostic CT scan. CONCLUSION: Consideration of tonsillar abnormalities, lymphadenopathy, body temperature, and measured leukocyte count prior to ordering CT scans of the neck for throat pain may increase the diagnostic yield of such exams and decrease CT utilization in the ED.

Review on the Significant Interactions between Ultrafine Gas Bubbles and Biological Systems.

Having sizes comparable with living cells and high abundance, ultrafine bubbles (UBs) are prone to inevitable interactions with different types of cells and facilitate alterations in physiological properties. The interactions of four typical cell types (e.g., bacterial, fungal, plant, and mammalian cells) with UBs have been studied over recent years. For bacterial cells, UBs have been utilized in creating the capillary force to tear down biofilms. The release of high amounts of heat, pressure, and free radicals during bubble rupture is also found to affect bacterial cell growth. Similarly, the bubble gas core identity plays an important role in the development of fungal cells. By the proposed mechanism of attachment of UBs on hydrophobin proteins in the fungal cell wall, oxygen and ozone gas-filled ultrafine bubbles can either promote or hinder the cell growth rate. On the other hand, reactive oxygen species (ROS) formation and mass transfer facilitation are two means of indirect interactions between UBs and plant cells. Likewise, the use of different gas cores in generating bubbles can produce different physical effects on these cells, for example, hydrogen gas for antioxidation against infections and oxygen for oxidation of toxic metal ions. For mammalian cells, the importance of investigating their interactions with UBs lies in the bubbles' action on cell viability as membrane poration for drug delivery can greatly affect cells' survival. UBs have been utilized and tested in forming the pores by different methods, ranging from bubble oscillation and microstream generation through acoustic cavitation to bubble implosion.

Multitargeted Herbal Prescription So Shiho Tang: A Scoping Review on Biomarkers for the Evaluation of Therapeutic Effects.

Alternative medicines, especially herbal remedies, have been employed to treat infections and metabolism-related chronic inflammation because their safety and multidimensional therapeutic potential outweigh those of synthetic drugs. So Shiho Tang (SSHT), a well-known Oriental prescription (Xiao Chai Hu Tang in Chinese) composed of seven herbs, is traditionally prescribed to treat various viral infections and chronic metabolic disorders in Asia with or without the support of other natural medicines. To provide a general background on how SSHT is used as a medicinal alternative, we conducted a scoping review using the PubMed database system. Among the 453 articles, 76 studies used aqueous extracts of SSHT alone. This result included seven clinical studies and 69 basic studies: cell-based, animal-based, and ex vivo studies. The in vitro and clinical reports mainly focus on hepatic infection and hepatocarcinoma, and the documentation of in vivo tests of SSHT presents a wide range of effects on cancer, fibrosis, inflammation, and several metabolic disorder symptoms. Additionally, among the seven clinical records, two reverse-effect case studies were reported in middle-aged patients. In brief, this systematic review provides general knowledge on the natural remedy SSHT and its potential in phytotherapeutic primary health care.

Perception of learners on the effectiveness and suitability of MyDispense: a virtual pharmacy simulation and its integration in the clinical pharmacy module in Viet Nam.

BACKGROUND: My Dispense is a virtual pharmacy simulation developed for students to train and practice dispensing skills in a safe environment that causes no harm to patients. This study was aimed to investigate learners' perspectives on the effectiveness of MyDispense and its suitability to integrate into the clinical pharmacy module in Viet Nam. METHODS: A mixed method approach was undertaken. Fourth- and fifth-year pharmacy students at University of Medicine and Pharmacy at Ho Chi Minh city and community pharmacists were invited to complete a survey questionnaire and to participate in semi-structured interviews. RESULTS: A total of 92/99 participants agreed to take part, of which 75% of participants were students and 65.2% were female. About three-quarters of the participants agreed or strongly agreed that MyDispense improved their dispensing skills, such as patient counselling (70.6%) and collecting patient infomation (85.9%). The majority of the participants (84.8%) considered that MyDispense was suitable to integrate into the clinical pharmacy module. Qualitative analysis from the interviews highlighted the advantages of MyDispense, comprising high interactivity with users, safe environment for practicing medication dispensing, and diversity of common marketed medications. In addition, certain barriers of this programme were also reported, including the complicated process, inconsistent quality of product images, and mixed English-Vietnamese languages. CONCLUSIONS: From learner's perspectives, MyDispense was an effective tool to enhance dispensing skills and was suitable to integrated into the clinical pharmacy module in Viet Nam.

Impact of a Powdered Meal Replacement on Metabolism and Gut Microbiota (PREMIUM) in individuals with excessive body weight: a study protocol for a randomised controlled trial.

INTRODUCTION: Excess body weight is associated with a state of low-grade chronic inflammation and alterations of the gut microbiome. Powdered meal replacements (PMR) have been shown to be an effective strategy for weight management; however, their effect on inflammation and the gut microbiome remains unclear. The aim of this 12-week randomised control clinical trial is to investigate the effects of PMR consumption, here given as a soy-yoghurt-honey formula, on inflammation, gut microbiome and overall metabolism in individuals with excessive body weight. METHODS AND ANALYSIS: Healthy adults with excess body weight (n=88) are being recruited and randomly assigned to one of the following groups: (1) Control group (CON): maintaining usual diet for 12 weeks, or (2) PMR group: replacing morning and afternoon snacks daily with a PMR for 12 weeks. Participants are asked to maintain body weight throughout the study and fill out a journal with information about PMR consumption, body weight, food intake, appetite sensations and medications. Three study visits are required: baseline, week 6 and week 12. Outcome measures include systemic inflammatory biomarkers, gut microbiome composition, metabolic blood markers, host energy metabolism, body composition, appetite sensations and host gene expression profile. ETHICS AND DISSEMINATION: This research protocol was approved by the University of Alberta Ethics Board (Pro00070712) and adheres to the Canadian Tri-Council Policy statement on the use of human participants in research. Procedures and potential risks are fully discussed with participants. Study findings will be disseminated in peer-reviewed journals, conference presentations and social media. TRIAL REGISTRATION NUMBER: NCT03235804.

A comprehensive review of micro- and nano-plastics in the atmosphere: Occurrence, fate, toxicity, and strategies for risk reduction.

Micro- and nano-plastics (MNPs) have received considerable attention over the past 10 years due to their environmental prevalence and potential toxic effects. With the increase in global plastic production and disposal, MNP pollution has become a topic of emerging concern. In this review, we describe MNPs in the atmospheric environment, and potential toxicological effects of exposure to MNPs. Studies have reported the occurrence of MNPs in outdoor and indoor air at concentrations ranging from 0.0065 items m-3 to 1583 items m-3. Findings have identified plastic fragments, fibers, and films in sizes predominantly <1000 µm with polyamide (PA), polyester (PES), polyethylene terephthalate (PET), polypropylene (PP), rayon, polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), polyacrylonitrile (PAN), and ethyl vinyl acetate (EVA) as the major compounds. Exposure through indoor air and dust is an important pathway for humans. Airborne MNPs pose health risks to plants, animals, and humans. Atmospheric MNPs can enter organism bodies via inhalation and subsequent deposition in the lungs, which triggers inflammation and other adverse health effects. MNPs could be eliminated through source reduction, policy/regulation, environmental awareness and education, biodegradable materials, bioremediation, and efficient air-filtration systems. To achieve a sustainable society, it is crucial to implement effective strategies for reducing the usage of single-use plastics (SUPs). Further, governments play a pivotal role in addressing the pressing issue of MNPs pollution and must establish viable solutions to tackle this significant challenge.

Neuroprotective Potential of Pyranocoumarins from Angelica gigas Nakai on Glutamate-Induced Hippocampal Cell Death.

Chronic neurodegenerative diseases are typically associated with oxidative stress conditions leading to neuronal cell death. We aimed to investigate the neuroprotective effect of three pyranocoumarins (decursin, decursinol angelate, and decursinol) targeting oxidative stress factors. Decursin (also known as dehydro-8-prenylnaringenin) is a prenylated coumarin compound consisting of a coumarin ring system with a prenyl group attached to one of the carbons in the ring. As a secondary metabolite of plants, pyranocoumarin decursin from Angelica gigas Nakai presented protective effects against glutamate-induced oxidative stress in HT22, a murine hippocampal neuronal cell line. Decursinol (DOH) is a metabolite of decursin, sharing same coumarin ring system but a slightly different chemical structure with the prenyl group replaced by a hydroxyl group (-OH). In our findings, DOH was ineffective while decursin was, suggesting that this prenyl structure may be important for compound absorption and neuroprotection. By diminishing the accumulation of intracellular reactive oxygen species as well as stimulating the expression of HO-1, decursin triggers the self-protection system in neuronal cells. Additionally, decursin also revealed an anti-apoptotic effect by inhibiting chromatin condensation and reducing the forming of annexin-V-positive cells.

Machine learning approaches for predicting microplastic pollution in peatland areas.

This study explored the potential for predicting the quantities of microplastics (MPs) from easily measurable parameters in peatland sediment samples. We first applied correlation and Bayesian network analysis to examine the associations between physicochemical variables and the number of MPs measured from three districts of the Long An province in Vietnam. Further, we trained and tested three machine learning models, namely Least-Square Support Vector Machines (LS-SVM), Random Forest (RF), and Long Short-Term Memory (LSTM) to predict the composite quantities of MPs using physicochemical parameters and sediment characteristics as predictors. The results indicate that the quantity of MPs and characteristics such as color and shape in the samples were mostly influenced by pH, TOC, and salinity. All three predictive models demonstrated considerable accuracies when applied to the testing dataset. This study lays the groundwork for using basic physicochemical variables to predict MP pollution in peatland sediments and potentially locations and environments.

Double free flaps for complex oromandibular defects with two teams of head and neck reconstructive surgical oncologists.

From December 2019 to July 2021, double free flaps were used by two teams of head-and-neck reconstructive surgical oncologists in 10 patients with large composite mandibulofacial defects following malignant tumor (n = 8) and osteoradionecrosis (n = 2) ablation. Our report included 10 patients. All of our patients were reconstructed by two free flaps, a combination of an anterolateral thigh flap (n = 8) or a radial forearm flap (n = 2) with an osteocutaneous fibula flap. The survival rate of these flaps was 100%. The mean operative time was 597 ± 41.7 min (range 545-660 min). There were no patients with major complications. Most of our patients had accepted functional and cosmetic results of both recipient site and donor site after a median follow-up of 22.5 months. Two teams of reconstructive surgical oncologists may shorten the operative time and reduce the rate of major complications. Main Points: Huge complex oromandibular defects may require the use of double free flap reconstruction.Double free flaps were used by two teams of head-and-neck reconstructive surgical oncologists.This approach may shorten the operative time and reduce the rate of major complications.

Association between early blood urea nitrogen-to-albumin ratio and one-year post-hospital mortality in critically ill surgical patients: a propensity score-matched study.

BACKGROUND: Blood urea nitrogen to albumin ratio (BAR) is increasingly recognized as an early predictor for short-term outcomes in critically ill patients, but the association of BAR with long-term outcomes in critically ill surgical patients remains underexplored. METHODS: We enrolled consecutive patients who were admitted to surgical intensive care units (ICUs) at Taichung Veterans General Hospital between 2015 and 2020, and the dates of death were retrieved from Taiwan's National Health Insurance Research Database. In addition to Cox regression, we also used propensity score matching to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year post-hospital mortality of the variables. RESULTS: A total of 8,073 eligible subjects were included for analyses. We found that age, male gender, high Charlson Comorbidity Index, high Acute Physiology and Chronic Health Evaluation II score, positive microbial culture, and leukocytosis were predictors for mortality, whereas high body mass index, scheduled surgery, and high platelet counts were protective factors against long-term mortality. The high BAR was independently associated with increased post-hospital mortality after adjustment for the aforementioned covariates (adjHR 1.258, 95% CI, 1.127-1.405). Notably, the association tended to be stronger in females and patients with fewer comorbidities and lower disease severity of critical illness. The propensity score matching, dividing subjects by BAR higher or lower than 6, showed a consistent association between week-one BAR and post-hospital mortality (adjHR 1.503, 95% CI 1.247-1.811). CONCLUSIONS: BAR is a newly identified predictor of short-term outcome, and we identified long-term outcome-relevant factors, including BAR, and the identified factors may be useful for risk stratification of long-term outcomes in patients discharged from surgical ICUs.

Milan system for reporting salivary gland cytology in diagnosis and surgery of parotid gland lesions.

INTRODUCTION: A cytology report is always a challenge for both head and neck surgeons and cytopathologists to diagnose and manage parotid gland (PG) diseases, because of the various similar features between the lesions. OBJECTIVES: The present study was conducted to assess our practice using the Milan System for Reporting Salivary Cytopathology (MSRSGC) and to evaluate the risk of malignancy (ROM) in different categories. PATIENTS AND METHODS: The patients with parotid gland lesions were diagnosed by clinical examination, ultrasound, and FNAC under ultrasound guidance at our hospital from 1 May 2019 to 30 April 2021. The FNAC results were divided into six categories according to the Milan system. We calculated the ROM for each category of the Milan system based on histopathological follow-up. RESULTS: This study included 204 patients. There were 115 men (56 %) aged 46-60 years. Pathology results were 33 cases for malignant and 182 cases for benign. The rate of malignancy for each category according to the MSRSGC were 23.1 % (non-neoplastic), 20 % (atypical), 50 % (neoplastic), 1 % (benign), 10.3 % (salivary neoplasm of uncertain neoplastic potential), 84.6 % (suspicious for malignancy), and 100 % (malignant) categories. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC with application of Milan system were respectively 90.9 %, 98.2 %, 90.9 %, 98.9 % and 97 %. CONCLUSION: When the Milan system was applied, FNAC had a high efficacy, suggesting that MSRSGC can improve the communication between the cytopathologist and the surgeon. This system can allow the surgeon to decide the extent of the surgery.

Nucleobase and Linker Modification for Triple-Helical Recognition of Pyrimidines in RNA Using Peptide Nucleic Acids.

Triple-helical recognition of any sequence of double-stranded RNA requires high affinity Hoogsteen hydrogen binding to pyrimidine interruptions of polypurine tracts. Because pyrimidines have only one hydrogen bond donor/acceptor on Hoogsteen face, their triple-helical recognition is a formidable problem. The present study explored various five-membered heterocycles and linkers that connect nucleobases to backbone of peptide nucleic acid (PNA) to optimize formation of X•C-G and Y•U-A triplets. Molecular modeling and biophysical (UV melting and isothermal titration calorimetry) results revealed a complex interplay between the heterocyclic nucleobase and linker to PNA backbone. While the five-membered heterocycles did not improve pyrimidine recognition, increasing the linker length by four atoms provided promising gains in binding affinity and selectivity. The results suggest that further optimization of heterocyclic bases with extended linkers to PNA backbone may be a promising approach to triple-helical recognition of RNA.