RAMP: response-aware multi-task learning with contrastive regularization for cancer drug response prediction.

The accurate prediction of cancer drug sensitivity according to the multiomics profiles of individual patients is crucial for precision cancer medicine. However, the development of prediction models has been challenged by the complex crosstalk of input features and the resistance-dominant drug response information contained in public databases. In this study, we propose a novel multidrug response prediction framework, response-aware multitask prediction (RAMP), via a Bayesian neural network and restrict it by soft-supervised contrastive regularization. To utilize network embedding vectors as representation learning features for heterogeneous networks, we harness response-aware negative sampling, which applies cell line-drug response information to the training of network embeddings. RAMP overcomes the prediction accuracy limitation induced by the imbalance of trained response data based on the comprehensive selection and utilization of drug response features. When trained on the Genomics of Drug Sensitivity in Cancer dataset, RAMP achieved an area under the receiver operating characteristic curve > 89%, an area under the precision-recall curve > 59% and an $\textrm{F}_1$ score > 52% and outperformed previously developed methods on both balanced and imbalanced datasets. Furthermore, RAMP predicted many missing drug responses that were not included in the public databases. Our results showed that RAMP will be suitable for the high-throughput prediction of cancer drug sensitivity and will be useful for guiding cancer drug selection processes. The Python implementation for RAMP is available at https://github.com/hvcl/RAMP.

Isolation of Diverse Simian Arteriviruses Causing Hemorrhagic Disease.

Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures.

Molecular Aggregation Behavior and Microscopic Heterogeneity in Binary Osmolyte-Water Solutions.

Osmolytes, small organic compounds, play a key role in modulating the protein stability in aqueous solutions, but the operating mechanism of the osmolyte remains inconclusive. Here, we attempt to clarify the mode of osmolyte action by quantitatively estimating the microheterogeneity of osmolyte-water mixtures with the aid of molecular dynamics simulation, graph theoretical analysis, and spatial distribution measurement in the four osmolyte solutions of trimethylamine-N-oxide (TMAO), tetramethylurea (TMU), dimethyl sulfoxide, and urea. TMAO, acting as a protecting osmolyte, tends to remain isolated with no formation of osmolyte aggregates while preferentially interacting with water, but there is a strong aggregation propensity in the denaturant TMU solution, characterized by favored hydrophobic interactions between TMU molecules. Taken together, the mechanism of osmolyte action on protein stability is proposed as a comprehensive one that encompasses the direct interactions between osmolytes and proteins and indirect interactions through the regulation of water properties in the osmolyte-water mixtures.

Unraveling the interplay of temperature with molecular aggregation and miscibility in TEA-water mixtures.

In the phase diagram of binary liquid mixtures, a miscibility gap is found with the concomitant liquid-liquid phase separation, wherein temperature is a key parameter in modulating the phase behavior. This includes critical temperatures such as the lower critical solution temperature (LCST) and upper critical solution temperature (UCST). Using a comprehensive approach including molecular dynamics (MD) simulation, graph theoretical analysis and spatial inhomogeneity measurement in an LCST-type mixture, we attempt to establish the relationship between the molecular aggregation pattern and phase behavior in TEA-water mixtures. At lower temperatures of binary liquid mixtures, TEA molecules tend to aggregate while simultaneously interacting with water forming a homogeneous solution. As the temperature increases, these TEA aggregates tend to self-associate by minimizing the interaction with water, which facilitates formation of two distinct liquid phases in the binary liquid. The spatial distribution analysis also reveals that the TEA aggregates compatible with water promote uniform distribution of water molecules, maintaining a homogeneous solution, while the water-incompatible ones generate isolation of water H-bond aggregates, leading to liquid-liquid phase separation in the binary system. This current study on temperature-induced molecular aggregation behavior is anticipated to contribute to a critical understanding of the phase behavior in binary liquid mixtures, including UCST, LCST, and reentrant phase behavior.

Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Short-term Blood Pressure Variability and Incident CKD in Patients With Hypertension: Findings From the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI) Study.

RATIONALE & OBJECTIVE: The association between short-term blood pressure variability (BPV) and kidney outcomes is poorly understood. This study evaluated the association between short-term BPV and kidney disease outcomes in people with hypertension. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 1,173 hypertensive participants in the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (2013-2018) Study with estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2. EXPOSURE: Short-term BPV assessed by average real variability (ARV). OUTCOME: Composite kidney disease outcome (30% decline in eGFR from baseline, new occurrence of eGFR <60mL/min/1.73m2, or onset of UACR >300mg/g). ANALYTICAL APPROACH: Multivariable Cox regression analyses to evaluate the association between systolic and diastolic BP ARV (SBP-ARV and DBP-ARV) and outcomes. RESULTS: During a median follow-up of 5.4 [4.1-6.5] years, 271 events of the composite kidney disease outcome occurred (46.5 per 1,000 person-years). Multivariable Cox analysis revealed that the highest SBP-ARV and DBP-ARV tertiles were associated with a higher risk of the composite kidney disease outcome than the lowest tertiles, independent of the 24-hour SBP or DBP levels (HR, 1.64 [95% CI, 1.16-2.33], and 1.60 [95% CI, 1.15-2.24] for SBP-ARV and DBP-ARV, respectively). These associations were consistent when SBP-ARV and DBP-ARV were treated as continuous variables (HR per 1.0-unit greater SBP-ARV, 1.03 [95% CI, 1.01-1.06]; HR per 1.0-unit greater DBP-ARV, 1.04 [95% CI, 1.01-1.08]). These associations were consistent, irrespective of subgroups (age, sex, 24-hour SBP or DBP, and moderate albuminuria). However, other measures of short-term BPV including SD, coefficient of variation, and dipping patterns were not associated with the composite kidney disease outcome. LIMITATIONS: Observational study design, the use of single measurement of 24-hour BP, lack of information on changes in antihypertensive medication during the follow-up. CONCLUSIONS: Short-term BPV is associated with the development of a composite kidney disease outcome in hypertensive patients.

Time-resolved photoluminescence analysis of ceramic Ce:GAGG scintillators.

This paper introduces the characteristics and efficiency of post-treatment methods for enhancing the timing resolution of ceramic Ce:GAGG scintillators. The thermal annealing and surface treatments were included to analyze their impact on time-resolved photoluminescence (TRPL) and thermoluminescence (TL) characteristics. Optical properties were improved by suppressing nonradiative recombination due to the reduced surface defects, while heat-treatment removes traps as confirmed by TL measurements. TRPL decay characteristics revealed that samples treated with mechanical polishing followed by heat treatment exhibited the best scintillation performance, with a slow component of 272.3 ns. These findings will aid in developing techniques for improving the luminescence of other inorganic scintillators.

Exercise in Hypertrophic Cardiomyopathy: Recent Conceptual Changes and Recommendations for Pre-Exercise Tests.

Traditionally, individuals with hypertrophic cardiomyopathy (HCM) have been advised not to participate in more than low-intensity exercises. HCM was originally described in the context of sudden death, and early literature from the registry showed that HCM was the most common cause of sudden cardiac death in young athletes. Therefore, there has long been a concern that exercise could trigger ventricular arrhythmia and sudden cardiac death. Although a few patients with HCM may progress along deteriorating disease pathways, many have no clinically significant symptoms or adverse events, no need for major treatment, and a normal life expectancy. Therefore, the routine restriction of any exercise intensity in this large group deprives them of the multiple benefits of exercise and may have detrimental effects on long-term clinical outcomes. However, it has been reported that light to moderate exercise is acceptable for many patients with HCM, and recent evidence suggests that vigorous exercise does not increase the risk of sudden death in this population. Thus, we reviewed previous literature regarding the effects of exercise in patients with HCM and provided cutting-edge information on the safety and concerns of exercise. In addition, based on our experience and previous research, we reviewed the conditions that should be met before starting exercise and the tests required to confirm them.

Arterial Stiffness is Associated with False-Positive ST-Segment Depression in Supine Bicycle Exercise Stress Echocardiography.

Background: Although exercise stress electrocardiography (ECG) is a popular tool for detecting coronary artery disease (CAD), the induced ST-depression without coronary artery stenosis (FST) remains a challenge for accurate diagnosis. Exercise-induced ST depression is related to poor prognosis even in non-obstructive disease; however, its determinants have not been fully defined. We sought to investigate whether ventriculo-vascular interactional indexes such as arterial stiffness index, exercise hemodynamic parameters and echocardiographic left ventricular (LV) functional parameters were related to FST. Methods: In the current study, 609 participants who underwent both supine bicycle exercise echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement without exercise-induced regional wall motion abnormalities (RWMA) were analyzed. Referral reasons for stress test were CAD detection or evaluation of patency of previous revascularization. Stepwise graded supine bicycle exercise was performed with simultaneous ECG recording and echocardiography after full conventional resting echocardiography. The FST was defined as newly developed > 1 mm ST depression without RWMA during exercise. Results: The median age of the study participants was 65 (59.0-70.5) years, and 222 (37%) patients were women. Among them, 103 (17%) patients showed FST during the exercise or recovery phase. The prevalence of FST did not differ between sexes. Older age, higher pulmonary arterial systolic pressure (PASP), left atrial volume index, baPWV and ankle brachial index at rest and hypertensive response, higher heart rate and rate-pressure product at peak exercise were significantly associated with FST. In multivariate analysis, higher peak heart rate, PASP, and baPWV were independently related to FST. Conclusions: Stress-induced RWMA in addition to ECG should be evaluated to detect CAD in patients with higher baPWV and PASP. FST might be linked to subclinical myocardial ischemia through arterial stiffness and diastolic dysfunction.

A conjugate of chlorin e6 and cationic amphipathic peptoid: a dual antimicrobial and anticancer photodynamic therapy agent.

Cationic amphipathic structures are often utilized in natural membrane-active host-defense peptides. Negatively charged surface membranes of rapidly proliferating bacterial and cancer cells have been targeted by various synthetic peptides and peptidomimetics adopting the structural motif. Herein, we synthesized a set of conjugates composed of cationic amphipathic peptoids (i.e., oligo-N-substituted glycines) and a chlorin photosensitizer, named chlorin e6 (Ce6)-peptoid conjugates (CPCs). Among the nine CPCs, CPC 7, composed of Ce6, a PEG linker, and guanidine-rich helical amphipathic peptoids, exhibited a distinct photoresponsive inactivation of Gram-positive and Gram-negative bacteria. Subsequent studies showed that CPC 7 effectively killed various cancer cells after irradiation with red light (655 nm), suggesting the potential of CPC 7 as a dual antimicrobial and anticancer agent. Confocal laser scanning microscopy and flow cytometry data suggested that CPC 7 could induce apoptotic cell death. Our results show the potential of peptoid-based photosensitizer conjugates as a versatile platform for antimicrobial and anticancer photodynamic therapy agents and peptoid therapeutics.

Structure-activity relationship analysis of activity-based probes targeting HTRA family of serine proteases.

High temperature requirement A serine proteases (HTRA) are ubiquitously expressed and participate in protein quality control and cellular stress responses. They are linked to several clinical illnesses, including bacterial infection, cancer, age-related macular degeneration, and neurodegenerative diseases. In addition, several recent studies have revealed HTRAs as important biomarkers and potential therapeutic targets, necessitating the development of an effective detection method to evaluate their functional states in various disease models. We developed a new series of HTRA-targeting activity-based probes with enhanced subtype selectivity and reactivity. In conjunction with our previously developed tetrapeptide probes, we established the structure-activity relationship of the new probes for different HTRA subtypes. Our probes are cell-permeable and have potent inhibitory effects against HTRA1 and HTRA2, making them valuable for identifying and validating HTRAs as an important biomarker.

Unlocking Cu(I)-Mediated Catalytic Pathways for Efficient ROS Generation by Incorporating an Oxazole-Based Histidine Surrogate into Cu(II)-ATCUN Complexes.

The catalytic redox activity of Cu(II) bound to the amino-terminal copper and nickel (ATCUN) binding motif (Xxx-Zzz-His, XZH) is stimulating the development of catalytic metallodrugs based on reactive oxygen species (ROS)-mediated biomolecule oxidation. However, low Cu(I) availability resulting from the strong Cu(II) binding affinity of the ATCUN motif is regarded as a limitation to efficient ROS generation. To address this, we replaced the imidazole moiety (pKa 7.0) of Gly-Gly-His-NH2 (GGHa, a canonical ATCUN peptide) with thiazole (pKa 2.7) and oxazole (pKa 0.8), yielding GGThia and GGOxa, respectively. A newly synthesized amino acid, Fmoc-3-(4-oxazolyl)-l-alanine, served as a histidine surrogate featuring an azole ring with the lowest pKa among known analogues. Despite similar square-planar Cu(II)-N4 geometries being observed for the three Cu(II)-ATCUN complexes by electron paramagnetic resonance spectroscopy and X-ray crystallography, the azole modification enabled the Cu(II)-ATCUN complexes to exhibit significant rate enhancement for ROS-mediated DNA cleavage. Further analyses based on Cu(I)/Cu(II) binding affinities, electrochemical measurements, density functional theory calculations, and X-ray absorption spectroscopy indicated that the azole modification enhanced the accessibility of the Cu(I) oxidation state during ROS generation. Our oxazole/thiazole-containing ATCUN motifs provide a new design strategy for peptide ligands with modulated N donor ability, with potential applications in the development of ROS-mediated metallodrugs.

Torilis japonica Extract Suppresses the Induction of Atopic Inflammation.

As one of the major intractable allergic disorders, atopic inflammation is commonly accompanied by itching, dry skin, and inflammation. Atopic inflammation deteriorates the quality of life and has no fundamental cure, so it is crucial to urgently explore and develop natural resources for long-term treatment without any side effects. This study aimed to verify Torilis japonica extract (TJE)'s relieving effect and mechanism against atopic inflammation using skin cells and skin equivalent models, as well as to investigate torilin's effect (obtained from TJE) and other unknown components as marker compounds. Torilin concentration was verified in TJE using high-performance liquid chromatography and analyzed the unknown components using nuclear magnetic resonance spectroscopy. Furthermore, TJE's cytotoxicity, regenerative effect, and cell cycle regulation effects were confirmed using skin cells with atopic inflammation (human dermal fibroblasts and HaCaT keratinocytes) by using TNF-α and IFN-γ treatments. Consequently, TJE was demonstrated to regulate TARC and CTACK expressions as chemokines and those of interleukin-4, -5, and -13 as cytokines related to atopic inflammation. TJE was further confirmed to affect the matrix metalloproteinase-1, -2, and -9 expressions, which are essential in skin damage. Lastly, this study confirmed TJE's relieving effect against atopic inflammation through a 3D skin model and RhCE model using human dermal fibroblasts and HaCaT keratinocytes. These findings on atopic inflammation verified torilin's relieving effects and TJE's other components.

Predictors of Subsequent Heart Failure After Left Atrial Appendage Closure.

BACKGROUND: Left atrial appendage occlusion (LAAO) plays an important role in preventing stroke in patients with atrial fibrillation. However, LAAO may interact unfavorably with left atrial (LA) compliance and reservoir function and thus increase the risk of heart failure (HF). The purpose of this study was to identify predictors of subsequent HF after successful LAAO.Methods and Results: A total of 98 patients (mean age 70±9 years, 68% male) who had undergone LAAO were included. The primary endpoint was unexpected HF admission after LAAO. During a mean period of 36±26 months, 16 of the 98 patients (16%) experienced hospital HF admission. In multivariate analysis, higher E/e' (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.02-1.20, P=0.014), higher left ventricular mass index (HR 1.02, 95% CI 1.00-1.03, P=0.023), history of HF (HR 4.78, 95% CI 1.55-14.7, P=0.006), and lower LA strain (HR 0.80, 95% CI 0.70-0.93, P=0.003) were independently associated with hospital HF admission. Patients with LAAO had a significantly higher incidence of subsequent HF than the control group after propensity score matching (P=0.046). CONCLUSIONS: LAAO increases the occurrence of HF, and it is not uncommon after successful LAAO. A previous history of HF, left ventricular mass index, E/e', and abnormal LA strain are independently associated with the development of HF. These parameters should be considered before attempting LAAO.

Entry inhibition of hepatitis B virus using cyclosporin O derivatives with peptoid side chain incorporation.

Hepatitis B virus (HBV) infection is a serious worldwide health problem causing liver cirrhosis and hepatocellular carcinoma. The development of novel therapeutics targeting distinct steps of the HBV life cycle and combination therapy with approved drugs (i.e., nucleot(s)ides, interferon-α) are considered effective strategies for curing HBV. Among these strategies is the development of entry inhibitors that interfere with the host entry step of HBV to prevent viral infection and transmission. Herein, we generated a novel library of cyclosporin O (CsO) derivatives that incorporate peptoid side chains. Twenty-two CsO derivatives were evaluated for membrane permeability, cytotoxicity, and in vitro HBV entry inhibitory activity. The lead compound (i.e., compound 21) showed the greatest potency in the in vitro HBV entry inhibition assay (IC50 = 0.36 ± 0.01 µM) with minimal cytotoxicity. Our peptide-peptoid hybrid CsO scaffold can readily expand chemical diversity and is applicable for screening various targets requiring macrocyclic chemical entities.

Synthesis of Alternating Polyisocyanate Copolymers by Anionic Polymerization for Mimicking Amphiphilic Helical Peptides.

The amphiphilic conformation of α-helical peptides has important biological functions, such as ion transport, antifreeze, and innate immunity, which can be mimicked by alternating polyisocyanate copolymers. We synthesized poly(allyl isocyanate-alt-(S)-(-)-α-methylbenzyl isocyanate (P(AIC-alt-SMBIC)) and ammonium-containing P(AIC-alt-SMBIC) (N-P(AIC-alt-SMBIC)), ensuring the amphiphilic helical conformation. The benzyl group of SMBIC plays an important role in alternating copolymerization with its steric and electron-withdrawing effects, while AIC provides an alkene group capable of introducing a customized functional group. The P(AIC-alt-SMBIC) with predominantly alternating sequence was acquired at fSMBIC /fAIC =8 with a controlled molecular weight and narrow dispersity. N-P(AIC-alt-SMBIC)s were synthesized from thiol-ene radical addition with P(AIC-alt-SMBIC).

Identification of Single-Atom Ni Site Active toward Electrochemical CO2 Conversion to CO.

Electrocatalytic conversion of CO2 into value-added products offers a new paradigm for a sustainable carbon economy. For active CO2 electrolysis, the single-atom Ni catalyst has been proposed as promising from experiments, but an idealized Ni-N4 site shows an unfavorable energetics from theory, leading to many debates on the chemical nature responsible for high activity. To resolve this conundrum, here we investigated CO2 electrolysis of Ni sites with well-defined coordination, tetraphenylporphyrin (N4-TPP) and 21-oxatetraphenylporphyrin (N3O-TPP). Advanced spectroscopic and computational studies revealed that the broken ligand-field symmetry is the key for active CO2 electrolysis, which subordinates an increase in the Ni redox potential yielding NiI. Along with their importance in activity, ligand-field symmetry and strength are directly related to the stability of the Ni center. This suggests the next quest for an activity-stability map in the domain of ligand-field strength, toward a rational ligand-field engineering of single-atom Ni catalysts for efficient CO2 electrolysis.

Photosensitizer-peptoid conjugates for photoinactivation of Gram-negative bacteria: structure-activity relationship and mechanistic studies.

Multitarget engagement is considered an effective strategy to overcome the threat of bacterial infection, and antimicrobials with multiple mechanisms of action have been successful as natural chemical weaponry. Here, we synthesized a library of photosensitizer-peptoid conjugates (PsPCs) as novel antimicrobial photodynamic therapy (aPDT) agents. The peptoids, linkers, and photosensitizers were varied, and their structure-antimicrobial activity relationships against Escherichia coli were evaluated; PsPC 9 was indicated to be the most promising photoresponsive antimicrobial agent among the synthesized PsPCs. Spectroscopic analyses indicated that 9 generated singlet oxygen upon absorption of visible light (420 nm) while maintaining the weakly helical conformation of the peptoid. Mechanistic studies suggested that damage to the bacterial membrane and cleavage of DNA upon light irradiation were the main causes of bactericidal activity, which was supported by flow cytometry and DNA gel electrophoresis experiments. We demonstrated that the optimal combination of membrane-active peptoids and photosensitizers can generate an efficient aPDT agent that targets multiple sites of bacterial components and kills bacteria by membrane disruption and reactive oxygen species generation.

Comparative Study on Seed Characteristics, Antioxidant Activity, and Total Phenolic and Flavonoid Contents in Accessions of Sorghum bicolor (L.) Moench.

Sorghum is a major cereal food worldwide, and is considered a potential source of minerals and bioactive compounds. Its wide adaptive range may cause variations in its agronomic traits, antioxidant properties, and phytochemical content. This extensive study investigated variations in seed characteristics, antioxidant properties, and total phenolic (TPC) and flavonoid contents (TFC) of sorghum collected from different ecological regions of 15 countries. The antioxidant potential of the seed extracts of various sorghum accessions was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis 3-ethylbenzothiazoline-6-sulfonate (ABTS) radical scavenging assays. Significant variations in TPC were observed among the sorghum accessions. All 78 sorghum accessions used in this study exhibited significant variations in TFC, with the lowest and highest amount observed in accessions C465 and J542, respectively. DPPH scavenging potential of the seed extracts for all the accessions ranged from 11.91 ± 4.83 to 1343.90 ± 81.02 µg mL-1. The ABTS assay results were similar to those of DPPH but showed some differences in the accessions. Pearson's correlation analysis revealed a wide variation range in the correlation between antioxidant activity and TPC, as well as TFC, among the sorghum accessions. A wide diversity range was also recorded for the seed characteristics (1000-seed weight and seed germination rate). A dendrogram generated from UPGMA clustering, based on seed traits, antioxidant activity, TPC, and TFC was highly dispersed for these accessions. Variations among the accessions may provide useful information regarding the phytoconstituents, antioxidant properties, and phytochemical contents of sorghum and aid in designing breeding programs to obtain sorghum with improved agronomic traits and bioactive properties.

Mitochondrion-Targeting Peptides and Peptidomimetics: Recent Progress and Design Principles.

Mitochondria are multifunctional subcellular organelles whose operations encompass energy production, signal transduction, and metabolic regulation. Given their wide range of roles, they have been studied extensively as a potential therapeutic target for the treatment of various diseases, including cancer, diabetes, and neurodegenerative diseases. Mitochondrion-mediated pathways have been identified as promising targets in the context of these diseases. However, the delivery of specific probes and drugs to the mitochondria is one of the major problems that remains to be solved. Over the past decade, much effort has been devoted to developing mitochondrion-targeted delivery methods based on the membrane characteristics and the protein import machinery of mitochondria. While various methods utilizing small molecules to polymeric particles have been introduced, it is notable that many of these compounds share common structural elements and physicochemical properties for optimal selectivity and efficiency. In this Perspective, we will review the most recently developed mitochondrion-targeting peptides and peptidomimetics to outline the key aspects of structural requirements and design principles. We will also discuss successful and potential applications of mitochondrial delivery to assess opportunities and challenges in the targeting of mitochondria.