3,134 publications from this institution
The formation of inclusion complexes between alkylsulfonate guests and a cationic pillar[5]arene receptor in water was investigated by NMR and ITC techniques. The results show the formation of host-guest complexes stabilized by electrostatic interactions and hydrophobics effects with binding constants of up to 107 M-1 for the guest with higher hydrophobic character. Structurally, the alkyl chain of the guest is included in the hydrophobic aromatic cavity of the macrocycle while the sulfonate groups are hold in the multicationic portal by ionic interactions.
The growing application of immune checkpoint inhibitors (ICIs) in cancer immunotherapy has underscored the critical need for reliable methods to identify patient populations likely to respond to ICI treatments, particularly in lung cancer treatment. Currently, the tumor proportion score (TPS), a crucial biomarker for patient selection, relies on manual interpretation by pathologists, which often shows substantial variability and inconsistency. To address these challenges, we innovatively developed multi-instance learning for TPS (MiLT), an innovative artificial intelligence (AI)-powered tool that predicts TPS from whole slide images. Our approach leverages multiple instance learning (MIL), which significantly reduces the need for labor-intensive cell-level annotations while maintaining high accuracy. In comprehensive validation studies, MiLT demonstrated remarkable consistency with pathologist assessments (intraclass correlation coefficient = 0.960, 95% confidence interval = 0.950-0.971) and robust performance across both internal and external cohorts. This tool not only standardizes TPS evaluation but also adapts to various clinical standards and provides time-efficient predictions, potentially transforming routine pathological practice. By offering a reliable, AI-assisted solution, MiLT could significantly improve patient selection for immunotherapy and reduce inter-observer variability among pathologists. These promising results warrant further exploration in prospective clinical trials and suggest new possibilities for integrating advanced AI in pathological diagnostics. MiLT represents a significant step toward more precise and efficient cancer immunotherapy decision-making.
Abstract In a highly influential paper, Muller (1950) put forward the idea that deleterious mutations affecting the heterozygote appear at a high rate in populations, thus, imposing a reduction in fitness (mutational load) that could become unbearable. As shown by Haldane (1937), this load is mainly determined by the rate of deleterious mutations and is practically independent of their severity, although it is modulated by their degree of dominance. It took a long time until adequate experimental data for Drosophila viability were first obtained by Mukai (1964), who estimated a high genomic rate of mutations (haploid rate A > = 0.3, the number of deleterious mutations appearing per gamete and generation) showing very little dominance (average coefficient of dominance E(h) = 0.4, where h = 0, 0.5, and 1 denotes recessive, additive and dominant gene action of mutations, respectively) and mild average effects (average selection coefficient E(s) < 007E 0.03, the relative reduction in fitness of the homozygous mutant).
Abstract Genetic rescue is increasingly considered a promising and underused conservation strategy to reduce inbreeding depression and restore genetic diversity in endangered populations, but the empirical evidence supporting its application is limited to a few generations. Here we discuss on the light of theory the role of inbreeding depression arising from partially recessive deleterious mutations and of genetic purging as main determinants of the medium to long-term success of rescue programs. This role depends on two main predictions: (1) The inbreeding load hidden in populations with a long stable demography increases with the effective population size; and (2) After a population shrinks, purging tends to remove its (partially) recessive deleterious alleles, a process that is slower but more efficient for large populations than for small ones. We also carry out computer simulations to investigate the impact of genetic purging on the medium to long term success of genetic rescue programs. For some scenarios, it is found that hybrid vigor followed by purging will lead to sustained successful rescue. However, there may be specific situations where the recipient population is so small that it cannot purge the inbreeding load introduced by migrants, which would lead to increased fitness inbreeding depression and extinction risk in the medium to long term. In such cases, the risk is expected to be higher if migrants came from a large non-purged population with high inbreeding load, particularly after the accumulation of the stochastic effects ascribed to repeated occasional migration events. Therefore, under the specific deleterious recessive mutation model considered, we conclude that additional caution should be taken in rescue programs. Unless the endangered population harbors some distinctive genetic singularity whose conservation is a main concern, restoration by continuous stable gene flow should be considered, whenever feasible, as it reduces the extinction risk compared to repeated occasional migration and can also allow recolonization events.
Multiple component rhythmometry, a method that fits a model consisting of several significant cosine functions, was used to describe the nonsinusoidal circadian pattern of growth hormone secretion in groups of prepubertal children divided according to stature. Results reveal prominent ultradian components for every group investigated, that should be taken into consideration in the design and later evaluation of a time-specified treatment of children with short stature.
Litchi is recognized as a famous functional food for the management of various ailments. This study provides a comprehensive review of its phytochemistry, medicinal properties, and product development.
Bioactive peptides generated from food proteins have great potential as functional foods and nutraceuticals. Bioactive peptides possess several significant functions, such as antioxidative, anti-inflammatory, anticancer, antimicrobial, immunomodulatory, and antihypertensive effects in the living body. In recent years, numerous reports have been published describing bioactive peptides/hydrolysates produced from various food sources. Herein, we reviewed the bioactive peptides or protein hydrolysates found in the plant, animal, marine, and dairy products, as well as their by-products. This review also emphasizes the health benefits, bioactivities, and utilization of active peptides obtained from the mentioned sources. Their possible application in functional product development, feed, wound healing, pharmaceutical and cosmetic industries, and their use as food additives have all been investigated alongside considerations on their safety.