Embracing Nature's Wisdom: Liposome-Mediated Amplification of Electrochemiluminescence for the Sensitive and Selective Immunoassay of Serum Amyloid A.

Serum amyloid A (SAA) is a key biomarker for diagnosing inflammatory responses in diseases like influenza and COVID-19. An electrochemiluminescence (ECL) biosensor has been constructed for signal enhancement in SAA detection by encapsulating 4,4',4″,4‴-(1,3,6,8-pyrenetetrayl) tetrakis-benzoic acid (TBAPy) into liposomes. Such biomimetic encapsulation shields the biologically important membrane to avoid aggregation of TBAPy and prevents quenching.

A novel light-harvesting ZIF-9-TCPP as a promising FRET-based ratiometric fluorescence probe for sperm mobility.

The concentration of zinc ions in semen is significantly correlated with sperm viability and male fertility. In this work, a reliable ratiometric fluorescence probe (ZIF-9-TCPP) based on the efficient Förster resonance energy transfer (FRET) process between two luminophores, benzimidazole (BIM) and -tetra (4-carboxyphenyl) porphyrin (TCPP) for Zn detection has been constructed, where the emissions of BIM and TCPP are used as reference and detection signals. The proximity of BIM and TCPP in one framework (ZIF-9-TCPP) and the overlapped spectra between BIM and TCPP afford the attainment of a highly efficient FRET (around 90% efficiency).

Synthesis, Characterization, and Properties of a Titanium(IV)-Tetrathiafulvalene-Based Complex.

To deeply investigate the interaction between a tetrathiafulvalene (TTF) unit and a Ti(IV) center, a monomeric heteroleptic octahedral Ti(IV) complex containing a diimine ligand composed of a 1,10-phenanthroline core fused with a TTF fragment (ligand ) was prepared. The stable complex formulated as Ti()(), where is a 2,2'-biphenolato derivative, was efficiently synthesized by following a one-step approach. This complex and its model species [Ti()()] were fully characterized in solution, and their solid-state structures were established by single-crystal X-ray diffraction analysis.

l-Cysteine-Tuned the Hierarchical Structure Based on Benzimidazole: Synthesis, Characterization, and Application in Ratiometric Electrochemiluminescence Immunoassay.

Efficient and robust electrochemiluminescence (ECL) emitters are crucial for enhancing the ECL immunosensor sensitivity. This study introduces a novel ECL emitter, CoBIM/Cys, featuring a hierarchical core-shell structure. The core of the structure is created through the swift coordination between the sulfhydryl and carboxyl groups of l-cysteine (l-Cys) and cobalt ions (Co), while the shell is constructed by sequentially coordinating benzimidazole (BIM) with Co.

Fine tuning of porphyrin based-paddlewheel framework by imidazole derivative to boost electrochemiluminescence performance.

Precise tuning the structure of catalytic center is of great importance for the construction of enhanced electrochemiluminescence (ECL) emitters and the development of ECL amplification strategies, which is a key factor in improving the sensitivity of biosensors. In this work, we report the enhanced ECL emitters based on the porphyrin-based paddlewheel framework (PPF) with axial coordinated imidazole-like ligands (PPF/X, X = 2-methylimidazole (MeIm), imidazole (Im), benzimidazole (BIM)). In this system, the electron-donating ability of the axial ligands is positively correlated to its coordination ability to the paddlewheel units and the catalytic ability of the axially coordinated paddlewheel units.

EMPOWER: Toward the Global Dissemination of Psychosocial Interventions.

Even before the COVID-19 pandemic, the needs for care of persons with mental illness remained largely unmet worldwide, testifying to the inadequacy of current approaches to mental health care and their unsuitability for the rising demand. One hurdle to improved access to quality care is the reliance on expensive specialist providers, particularly for the delivery of psychosocial interventions. This article describes EMPOWER, a not-for-profit program that builds on the clinical science demonstrating the effectiveness of brief psychosocial interventions for a range of psychiatric conditions; implementation science demonstrating the effectiveness of delivery of these interventions by non-specialist providers (NSPs); and pedagogical science demonstrating the effectiveness of digital approaches for training and quality assurance.

Fluorescent Peptomer Substrates for Differential Degradation by Metalloproteases.

Proteases, especially MMPs, are attractive biomarkers given their central role in both physiological and pathological processes. Distinguishing MMP activity with degradable substrates, however, is a difficult task due to overlapping substrate specificity profiles. Here, we developed a system of peptomers (peptide-peptoid hybrids) to probe the impact of non-natural residues on MMP specificity for an MMP peptide consensus sequence.

Electrochemical Properties of a Rhodium(III) Mono-Terpyridyl Complex and Use as a Catalyst for Light-Driven Hydrogen Evolution in Water.

Molecular hydrogen (H) is considered one of the most promising fuels to decarbonize the industrial and transportation sectors, and its photocatalytic production from molecular catalysts is a research field that is still abounding. The search for new molecular catalysts for H production with simple and easily synthesized ligands is still ongoing, and the terpyridine ligand with its particular electronic and coordination properties, is a good candidate to design new catalysts meeting these requirements. Herein, we have isolated the new mono-terpyridyl rhodium complex, [Rh(tpy)(CHCN)Cl](CFSO) (), and shown that it can act as a catalyst for the light-induced proton reduction into H in water in the presence of the [Ru(bpy)]Cl () photosensitizer and ascorbate as sacrificial electron donor.

CRISPR/Cas9-mediated fine-tuning of miRNA expression in tetraploid potato.

MicroRNAs (miRNAs) are small noncoding RNAs, which modulate the abundance and spatiotemporal accumulation of target mRNAs at transcriptional and post-transcriptional levels and through that play important roles in several biological processes in plants. Here we show that in polyploid species, CRISPR/Cas9 system can be used for fine-tuning of miRNA expression, which can have broader range of applications compared to knock-out mutants. We established the complete pipeline for CRISPR-Cas9-mediated modulation of miRNA expression in potato.

Hydropersulfides Inhibit Lipid Peroxidation and Protect Cells from Ferroptosis.

Hydropersulfides (RSSH) are believed to serve important roles , including as scavengers of damaging oxidants and electrophiles. The α-effect makes RSSH not only much better nucleophiles than thiols (RSH), but also much more potent H-atom transfer agents. Since HAT is the mechanism of action of the most potent small-molecule inhibitors of phospholipid peroxidation and associated ferroptotic cell death, we have investigated their reactivity in this context.

Relation between Plasma Trough Concentration of Pazopanib and Progression-Free Survival in Metastatic Soft Tissue Sarcoma Patients.

Background: Pazopanib (PAZ) is an oral angiogenesis inhibitor approved to treat soft tissue sarcoma (STS) but associated with a large interpatient pharmacokinetic (PK) variability and narrow therapeutic index. We aimed to define the specific threshold of PAZ trough concentration (Cmin) associated with better progression-free survival (PFS) in STS patients. Methods: In this observational study, PAZ Cmin was monitored over the treatment course.

Tim-3 mediates T cell trogocytosis to limit antitumor immunity.

T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) negatively regulates innate and adaptive immunity in cancer. To identify the mechanisms of Tim-3 in cancer immunity, we evaluated the effects of Tim-3 blockade in human and mouse melanoma. Here, we show that human programmed cell death 1-positive (PD-1+) Tim-3+CD8+ tumor-infiltrating lymphocytes (TILs) upregulate phosphatidylserine (PS), a receptor for Tim-3, and acquire cell surface myeloid markers from antigen-presenting cells (APCs) through transfer of membrane fragments called trogocytosis.

Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1.

Ample evidence indicates that the gut microbiome is a tumor-extrinsic factor associated with antitumor response to anti-programmed cell death protein-1 (PD-1) therapy, but inconsistencies exist between published microbial signatures associated with clinical outcomes. To resolve this, we evaluated a new melanoma cohort, along with four published datasets. Time-to-event analysis showed that baseline microbiota composition was optimally associated with clinical outcome at approximately 1 year after initiation of treatment.

Prime Editing in the model plant Physcomitrium patens and its potential in the tetraploid potato.

Since its discovery and first applications for genome editing in plants, the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology has revolutionized plant research and precision crop breeding. Although the classical CRISPR-Cas9 system is a highly efficient tool for disruptive targeted mutagenesis, this system is mostly inefficient for the introduction of precise and predictable nucleotide substitutions. Recently, Prime Editing technology has been developed, allowing the simultaneous generation of nucleotide transitions and transversions but also short defined indels.

Adaptive dosing of sunitinib in a metastatic renal cell carcinoma patient: when in silico modeling helps to go quicker to the point.

Purpose: Adaptive dosing strategy with oral targeted therapies in oncology is mostly based upon clinical signs. Using pharmacokinetics (PK) models to customize dosing could help saving time, i.e.

Gene Editing in Potato Using CRISPR-Cas9 Technology.

Genome editing in the cultivated potato (Solanum tuberosum), a vegetatively propagated and highly heterozygous species, constitutes a promising trail to directly improve traits into elite cultivars. With the recent and successful development of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system in eukaryotic cells, the plant science community has gained access to a powerful, inexpensive, and easy-to-use toolbox to target and inactivate/modify specific genes. The specificity and versatility of the CRISPR-Cas9 system rely on a variable 20 bp spacer sequence at the 5' end of a single-guide RNA (sgRNA), which directs the SpCas9 (Streptococcus pyogenes) nuclease to cut the target DNA at a precise locus with no or low off-target events.

Clinical-Based vs. Model-Based Adaptive Dosing Strategy: Retrospective Comparison in Real-World mRCC Patients Treated with Sunitinib.

Different target exposures with sunitinib have been proposed in metastatic renal cell carcinoma (mRCC) patients, such as trough concentrations or AUCs. However, most of the time, rather than therapeutic drug monitoring (TDM), clinical evidence is preferred to tailor dosing, i.e.

Estradiol Regulates mRNA Levels of Estrogen Receptor Beta 4 and Beta 5 Isoforms and Modulates Human Granulosa Cell Apoptosis.

Estrogen receptor beta (ERβ) plays a critical role in granulosa cell (GC) functions. The existence of four human ERβ splice isoforms in the ovary suggests their differential implication in 17β-estradiol (E2) actions on GC apoptosis causing follicular atresia. In this study, we investigated whether E2 can regulate ERβ isoforms expression to fine tune its apoptotic activities in human GC.

A novel method based on unbiased correlations tests for covariate selection in nonlinear mixed effects models: The COSSAC approach.

Building a covariate model is a crucial task in population pharmacokinetics and pharmacodynamics in order to understand the determinants of the interindividual variability. Identifying a good covariate model usually requires many runs. Several procedures have been proposed in the past to automatize this task.