Commercial Availability Research Articles

Direct Organocatalytic Chemoselective Synthesis of Pharmaceutically Active 1,2,3-Triazoles and 4,5'-Bitriazoles.

Carbonyl-containing 1,4,5-trisubstituted- and 1,4-disubstituted-1,2,3-triazoles are well-known for their wide range of applications in pharmaceutical and medicinal chemistry, but their high-yielding metal-free synthesis has always remained challenging, as no comprehensive protocol has been outlined to date. Owing to their structural and medicinal importance, herein, we synthesized various carbonyl-containing 1,4,5-trisubstituted- and 1,4-disubstituted-1,2,3-triazoles and unsymmetrical 4,5'-bitriazoles with high yields and chemo-/regioselectivity from the library of 2,4-diketoesters and azides in a sequential one-pot manner through the combination of organocatalytic enolization, in situ [3 + 2]-cycloaddition, and hydrolysis reactions. The commercial availability of the starting materials/catalysts, diverse substrate scope, performance in a one-pot manner, chemo-/regioselectivity of organo-click reaction, quick synthesis of unsymmetrical 4,5'-bitriazoles, a large number of synthetic applications, and numerous medicinal applications of carbonyl-containing 1,2,3-triazoles are the key attractions of this metal-free organo-click work.

Quality of Propolis Commercially Available on Podkarpacki Beekeeping Market

Abstract Eight samples of propolis commercially available on south-eastern Poland’s beekeeping market were compared in terms of quality, chemical composition and biological activity, including antioxidant and antimicrobial properties. The organoleptic characteristics and physicochemical requirements indicated that only 50% of tested propolis samples was classified to class II regarding obligatory limits, while the others were out-class. A big variation in mineral composition was determined by the ICP-OES method but all samples were free of heavy metals (Pb, Cd and Ni). Although mesophilic bacteria, yeasts and moulds occurred in tested propolis (in general lower than 102 CFU/g), E. coli and spore-forming sulphite-reducing bacteria as well as Salmonella and Shigella bacteria were not detected. High antioxidant activity and total phenolic content for all samples was confirmed, which was correlated with antibacterial activity tested against E. coli ATCC 11775 strain. Additionally, the propolis sample with the strongest antibacterial activity (MIC 0.33 mg/mL) inhibited biofilm formation of S. aureus and S. epidermidis ATCC 35984 (MBIC 0.66 and 5.25 mg/mL, respectively). However, great variation in terms of antioxidant activity and HPLC polyphenolic profile were observed, and sakuranetin and pinobanksin were identified as the most effective antioxidant components. Moreover, the usefulness of ATR-FTIR spectra analysis was confirmed as a quick method for initial testing of propolis quality.

Dosimetry of lutetium-177 PSMA-targeted radiopharmaceutical therapies for prostate cancer patients: A comparative systematic review and meta-analysis.

e17033 Background: Novel theranostic approaches using radiopharmaceuticals targeting PSMA have emerged for treating metastatic castrate resistant prostate cancer (mCRPC). The physical properties and commercial availability of Lutetium-177 (Lu177) makes it one of the most used radionuclides for radiopharmaceutical therapy (RPT). In this review we aimed at comparing the dosimetry of the most used Lu177-PSMA RPT compounds. Methods: This is a systematic review and meta-analysis of Lu177-PSMA RPT (617, I&T, and J591) dosimetry for prostate cancer. Absorbed doses in Gy/GBq for each organ (kidney, parotid and submandibular glands, bone marrow, liver, lacrimal glands) and for tumor lesions (bone and non- bone lesions) were extracted. These were used to estimate the pooled average absorbed dose of each RPT, and normalize each to the respective injected activity (Gy/cycle) as determined by the dose per cycles used in VISION (7.4 GBq), SPLASH (6.8 GBq), and PROSTACT Trials (5.8 GBq). Results: 29 published manuscripts comprising 535 patients were included in the meta-analysis. The pooled dose was calculated for kidney based on (28 studies, 485 patients), parotid (20, 309), submandibular (7, 100) and lacrimal glands (9, 174), bone marrow (18, 293), and liver (14, 245) were 4.04 and 4.70, 5.85 and 2.62, 5.15 and 4.35, 11.03 and 19.23, 0.24 and 0.19 and 1.11 and 0.56 Gy respectively for Lu177-PSMA-617 and Lu177-PSMA-I&T. Lu177-PSMA-J591 reported absorbed doses to the kidney, bone marrow and liver were 3.95, 0.90, and 5.88 Gy respectively. There was no significant difference between Lu177-PSMA-I&T and Lu177-PSMA-617 for the dose to kidneys (p=0.10), submandibular glands (p=0.56), bone marrow (p=0.31), lacrimal glands (p=0.20), or tumors (p=0.16). However, parotid dose from Lu177-PSMA-617 was higher than that of Lu177-PSMA-I&T (p=<0.01). Average tumor doses tended to be higher for Lu177-PSMA-617 than for Lu177-PSMA-I&T, (27.94 vs. 21.31 Gy); p=0.16. Lu177-PSMA-J591 exposed the bone marrow and liver, to a significantly higher dose while resulting in a lower dose to the kidney than either of the two small molecule compounds. Absorbed doses to the salivary glands, lacrimal glands, and tumors after the treatment with Lu177-PSMA-J591 have not been published yet. Conclusions: The clinical impact of higher tumor to kidney dose ratio for Lu177-PSMA-617 than Lu177-PSMA-I&T has yet to be determined. Data for Lu177-PSMA-J591 are thus far too limited to draw firm conclusions.

CXL and the Return of Scale-Up Database Engines

The trend toward specialized processing devices such as TPUs, DPUs, GPUs, and FPGAs has exposed the weaknesses of PCIe in interconnecting these devices and their hosts. Several attempts have been proposed to improve, augment, or downright replace PCIe, and more recently, these efforts have converged into a standard called Compute Express Link (CXL). CXL is already on version 2.0 in terms of commercial availability, but its potential to radically change the conventional server architecture has only just started to surface. For example, CXL can increase the bandwidth and quantity of memory available to any single machine beyond what that machine can originally provide, most importantly, in a manner that is fully transparent to software applications. We argue, however, that CXL can have a broader impact beyond memory expansion and deeply affect the architecture of data-intensive systems. In a nutshell, while the cloud favored scale-out approaches that grew in capacity by adding full servers to a rack, CXL brings back scale-up architectures that can grow by fine-tuning individual resources, all while transforming the rack into a large shared-memory machine. In this paper, we describe why such architectural transformations are now possible, how they benefit emerging heterogeneous hardware platforms for data-intensive systems, and the associated research challenges.

Reducing Commercial Tobacco Sales to Youth On and Around California Tribal Reservations With a Reward and Reminder Retail Intervention.

High prevalence of commercial tobacco product (CTP) use among American Indian and Alaska Native (AI/AN) youth is a public health crisis. A multi-level Tribal-community-based participatory research project under Tribal public health authority implemented a retailer-focused intervention to reduce AI/AN youth CTP use. We sought resolutions in support of a retailer-focused CTP intervention from Tribal Nations organized by a Tribally directed research program. We identified tobacco retail outlets operating on and within five miles of nine Tribal reservations, and CTP products sold at these outlets. We conducted a four-wave Reward and Reminder intervention with apparent minor buyers. Clerks who complied with the law received a modest reward and commendation in social media posts to the local Tribal communities, while clerks who sold without age verification were reminded of the laws. Of 18 retail outlets selling CTP, eight sold e-cigarettes, and all sold combustible cigarettes. The Reward and Reminder intervention showed an approximate 25% reduction in sales of CTP to apparent minors, with a 33% baseline CTP sales rate without age verification and an 8% intervention CTP sales rate without age verification. The intervention increased awareness of laws prohibiting CTP sales to minors and mandating age verification for young adults seeking to buy CTP. The intervention, which had support from all governing Tribal Nations, builds the evidence base of effective practices which Tribal public health authorities may utilize to reduce youth access to CTP on and around Tribal reservations. Sovereign Tribes have authority over commercial businesses operating on their lands. Tobacco 21 laws aiming to restrict commercial tobacco availability to youth are supported by Tribes. A retailer intervention in which apparent minors attempt commercial tobacco purchases can offer accountability feedback to retailers both on and near Tribal reservations. Obtaining Tribal support and publicizing the interventions helps mobilize Tribal communities to support commercial tobacco prevention and promote healthy youth.

Public Attitudes, Interests, and Concerns Regarding Polygenic Embryo Screening

Polygenic embryo screening (PES) is a novel technology that estimates the likelihood of developing future conditions (eg, diabetes or depression) and traits (eg, height or cognitive ability) in human embryos, with the goal of selecting which embryos to use. Given its commercial availability and concerns raised by researchers, clinicians, bioethicists, and professional organizations, it is essential to inform key stakeholders and relevant policymakers about the public's perspectives on this technology. To survey US adults to examine general attitudes, interests, and concerns regarding PES use. For this survey study, data were collected from 1 stratified sample and 1 nonprobability sample (samples 1 and 2, respectively) between March and July 2023. The surveys measured approval, interest, and concerns regarding various applications of PES. In the second sample, presentation of a list of potential concerns was randomized (presented at survey onset vs survey end). The survey was designed using Qualtrics and distributed to participants through Prolific, an online sampling firm. Sample 1 was nationally representative with respect to gender, age, and race and ethnicity; sample 2 was recruited without specific demographic criteria. Analyses were conducted between March 2023 and February 2024. Participants reported their approval, interest, and concerns regarding various applications of PES and outcomes screened (eg, traits and conditions). Statistical analysis was conducted using independent samples t tests and repeated-measures analyses of variance. Of the 1435 respondents in sample 1, demographic data were available for 1427 (mean [SD] age, 45.8 [16.0] years; 724 women [50.7%]). Among these 1427 sample 1 respondents, 1027 (72.0%) expressed approval for PES and 1169 (81.9%) expressed some interest in using PES if already undergoing in vitro fertilization (IVF). Approval among these respondents for using PES for embryo selection was notably high for physical health conditions (1109 [77.7%]) and psychiatric health conditions (1028 [72.0%]). In contrast, there was minority approval for embryo selection based on PES for behavioral traits (514 [36.0%]) and physical traits (432 [30.3%]). Nevertheless, concerns about PES leading to false expectations and promoting eugenic practices were pronounced, with 787 of 1422 (55.3%) and 780 of 1423 (54.8%) respondents finding them very to extremely concerning, respectively. Sample 2 included 192 respondents (mean [SD] age 37.7 [12.2] years; 110 men [57.3%]). These respondents were presented concerns at survey onset (n = 95) vs survey end (n = 97), which was associated with less approval (28-percentage point decrease) and more uncertainty (24 percentage-point increase) but with only slightly higher disapproval (4 percentage-point increase). These findings suggest that it is critical for health care professionals and medical societies to consider and understand the perspectives of diverse stakeholders (eg, patients undergoing IVF, clinicians, and the general public), given the absence of regulation and the recent commercial availability of PES.

MicroSimACC: an open database for field experiments on the potential capacity impact of commercial Adaptive Cruise Control (ACC)

Commercial availability of vehicle automation has become mainstream. Most of today’s new vehicles can perform longitudinal car following autonomously via Adaptive Cruise Control (ACC). Field experiments demonstrate that today’s commercially available ACC vehicles provide similar headways and capacities as human-driven vehicles on freeways under steady-state and free-flow conditions. However, field tests also demonstrated that the design of today’s commercially available ACC vehicles can lead to further capacity reduction when operating in non-steady-state conditions where queues are present and speeds frequently fluctuate. These experiments generated MicroSimACC, a comprehensive set of field data that encompasses full speed range car following with interruptions from lane change manoeuvres. This will benefit the research community by providing benchmark data for developing models to be integrated into microscopic simulations for more prospective analyses and planning.

BINOL‐based Chiral Macrocycles and Cages

Chirality, a fundamental principle in chemistry, biology, and medicine, is prevalent in nature and in organisms. Chiral molecules, such as DNA, RNA, and proteins, are crucial in biomolecular synthesis, as well as in the development of functional materials. Among these, 1,1´‐binaphthyl‐2,2´‐diol (BINOL) stands out for its stable chiral configuration, versatile functionality, and commercial availability. BINOL is widely employed in asymmetric catalysis and chiral materials. This review mainly focuses on recent research over the past five years concerning the use of BINOL derivatives for constructing chiral macrocycles and cages. Their contributions to chiral luminescence, enantiomeric separation, transmembrane transport, and asymmetric catalysis were examined.

Altering central atoms and bromination sites of phosphorescence units to control ultralong organic room temperature phosphorescence

We report two strategies to expand the library of Phosphorescence Units, including altering the central atom and bromination. Directed by these two strategies, numerous new Phosphorescence Units can be designed. Due to the limitation of organic synthesis and commercial availability, eight organic units (BCz, NBF, BNT, BrBCz-1, BrBCz-2, BrBCz-3, BrBCz-4 and BrBNT) were obtained to verify our proposed methods and study the impact of central atoms and bromination sites on organic room temperature phosphorescence. Considering BCz, NBF and BNT (Group Ⅰ) together, when the central atom is N or S, the room temperature phosphorescence is on as BCz and BNT have higher ISC (Intersystem Crossing) efficiency than NBF; from N to S, phosphorescence wavelength red shifts because the T1 energy level is closely related to the central atom and the lifetime shortens due to different ISC efficiency. Considering BCz, BrBCz-1, BrBCz-2 and BrBCz-3 (Group Ⅱ), bromination and different bromination sites on the benzene ring matters much to ISC efficiency but little to the intrinsic T1 energy level, leading to dramatical increase of phosphorescence intensity, sharp drop of phosphorescence lifetime and subtle change of phosphorescence wavelength (color). Considering BrBCz-4 and BrBNT (Group Ⅲ), bromination on the naphthalene moiety greatly affects both ISC efficiency and the intrinsic T1 energy level, resulting in dramatical increase of phosphorescence intensity, sharp drop of phosphorescence lifetime and significant red shift of phosphorescence color. Therefore, BNT, BrBCz-1, BrBCz-2, BrBCz-3, BrBCz-4 and BrBNT can be regarded as new Phosphorescence Units while NBF cannot be. To our best knowledge, this work for the first time gives design suggestions of organic room temperature materials from the atomic level. This work may give a deep insight into organic phosphorescence from the perspective of Phosphorescence Units and lay foundation for their future applications.

An overview of heavy metals treatment & management for laboratory waste liquid (LWL)

The laboratory waste liquid (LWL) is the discarded liquid after the completion of analysis and is produced from the testing laboratories including regulatory institutions, colleges, universities and research organizations. This LWL is laden with a variety of heavy metals due to the use of heavy metal salts in analysis and the treatment and safe disposal of LWL is seldom given due consideration. Thus, the management of hazardous laboratory waste liquid (HLWL) containing heavy metals is essential at the source itself. Accordingly, this article presents systematic review of three processes for heavy metals removal viz. precipitation, adsorption, and membrane separation. The review covers various factors such as heavy metal removal efficiencies & concentration ranges, optimum pH, most frequently studied methods, less studied aspects, its commercial availability, operational ease, and the potential of risk minimization with due concern to toxic heavy metals. The concentrations of heavy metals in LWL is also presented. Based on the review, activated carbon (AC) adsorption appears to be the best option for LWL having heavy metals concentration of less than 10 mg/L. The heavy metals removal efficiency of more than 95% can be achieved at an AC dose of 0.2–1 g/L. The hydroxide precipitation was found to achieve more than 95% removal efficiencies at higher heavy metals concentrations. Thus, for concentrations higher than 10 mg/L up to 3000 mg/L, the hydroxide precipitation followed by activated carbon adsorption may prove beneficial.

Imaging of Structural Timber Based on In Situ Radar and Ultrasonic Wave Measurements: A Review of the State-of-the-Art.

With the rapidly growing interest in using structural timber, a need exists to inspect and assess these structures using non-destructive testing (NDT). This review article summarizes NDT methods for wood inspection. After an overview of the most important NDT methods currently used, a detailed review of Ground Penetrating Radar (GPR) and Ultrasonic Testing (UST) is presented. These two techniques can be applied in situ and produce useful visual representations for quantitative assessments and damage detection. With its commercial availability and portability, GPR can help rapidly identify critical features such as moisture, voids, and metal connectors in wood structures. UST, which effectively detects deep cracks, delaminations, and variations in ultrasonic wave velocity related to moisture content, complements GPR's capabilities. The non-destructive nature of both techniques preserves the structural integrity of timber, enabling thorough assessments without compromising integrity and durability. Techniques such as the Synthetic Aperture Focusing Technique (SAFT) and Total Focusing Method (TFM) allow for reconstructing images that an inspector can readily interpret for quantitative assessment. The development of new sensors, instruments, and analysis techniques has continued to improve the application of GPR and UST on wood. However, due to the hon-homogeneous anisotropic properties of this complex material, challenges remain to quantify defects and characterize inclusions reliably and accurately. By integrating advanced imaging algorithms that consider the material's complex properties, combining measurements with simulations, and employing machine learning techniques, the implementation and application of GPR and UST imaging and damage detection for wood structures can be further advanced.

Evolving Advances in the Cosmetic use of Probiotics and Postbiotics: Health, Regulatory and Marketing Aspects.

Ongoing development in cosmetics is increasingly making use of probiotics, which are defined as "live microorganisms with health-enhancing properties mediated through ingestion or topical application to the host". The observation that several bacterial strains augment normal processes of healthy tissue maintenance, particularly for the skin, has opened up new avenues for the use of bacterial strains in cosmetics. A principal feature of such "cosmeceuticals" is an application of increasing insight into the biochemical nature of the skin's normal microbial flora, also called its microbiome. The opportunity of manipulating the skin microbiome to address various skin disorders has revealed novel routes for treatment. The skin microbiome manipulation approaches to address various skin disorders include skin microbiome transplantation, skin bacteriotherapy, and prebiotic stimulation. Research in this field has revealed that medical outcome-targeted manipulation of skin microbiome bacterial strain makeup may significantly increase skin health and appearance. Commercial availability of probiotic skincare products is rapidly expanding worldwide due to satisfactory laboratory results and public perception of probiotics as being intrinsically more wholesome than other bioactive substances, such as synthetics. Major outcomes of probiotic use include a significant reduction in skin wrinkling, acne and other conditions adversely affecting skin appearance and healthy function. Moreover, probiotics may additionally promote normal skin hydration, resulting in a vibrant and lustrous appearance. Nevertheless, significant technical challenges remain for the full optimization of probiotics in cosmetic products. This article summarizes the evolving nature of this field and explores current probiotic research initiatives, along with regulatory aspects and significant challenges in the manufacturing of cosmetics in the context of market expansion for these products.

Differentiation of regioisomeric N-substituted meta-chlorophenylpiperazine derivatives

A series ofN,N-disubstituted piperazines were synthesized containing the structural elements of meta-chlorophenylpiperazine (mCPP) in combination with methoxybenzyl-, and dimethoxybenzyl substituents to yield nineN,N-disubstituted piperazine compounds. These nine potential designer-like drug analogs were prepared based on common designer trends and regioisomeric differentiation was based on gas chromatography-mass spectrometry (GC–MS) and gas chromatography-vapor phase infrared (GC–vpIR) studies.The compounds in this study have not been reported as drugs of abuse at this time. However, commercial availability of precursor chemicals including mCPP suggests the possibility of further designer exploration. Capillary GC separation showed the regioisomers to elute according to the position of aromatic ring substitution and/or the degree of substituent crowding on the aromatic ring. Numerous electron ionization (EI) mass spectral fragment ions occur via processes initiated by one of the two nitrogen atoms of the piperazine ring. The major EI-MS fragment ions observed in all nine spectra occur at m/z 195 from the loss of the substituted benzyl radical and the cation atm/z56 (C3H6N)+from the piperazine ring. Unique radical cations at m/z 136 and m/z 152 are characteristic of the 2,3- and 3,5-dimethoxybenzyl isomers, respectively. The vapor phase infrared spectra for all nine compounds show a strong absorption band in the 1591–1593 cm−1region indicative of the chloroaniline moiety. Numerous bands in the 1600–650 cm−1region provide data for the differentiation of the methoxy and dimethoxybenzyl ring substitution patterns. Thus, a combination of EI-MS and vapor phase IR allow for the differentiation and specific identification of each regioisomer in this study.

PROSPECTIVE LITHIUM ALUMINOSILICATE GLASS-CERAMIC MATERIALS FOR PULSE RANGEFINDERS

The relevance of creating multi-functional nanosecond pulsed laser devices with a generation wavelength that lies in the conditionally eye-safe region of the spectrum of 1.5÷1.6 μm has been established. The prospects of using the mode of passive Q-switching when receiving powerful nanosecond laser pulses with a radiation divergence close to the diffraction one have been determined. Materials for shutters that function in the mode of passive Q-switching were analyzed: solid-state nonlinear optical materials based on single crystals of yttrium-aluminum garnet doped with cations of neodymium, chromium, vanadium and other Nd- or Yb-doped crystals in the wavelength range of 0.8–1.2 μm. The promising use of oxide single crystals activated by Co2+ ions in four-coordinated oxygen positions for MgAl2O4, LiGa5O8, LaMgAl11O19 has been confirmed. The feasibility of developing transparent glass-ceramics based on aluminomagnesium and lithium gallium spinel for pulsed ranging was determined, taking into account its commercial availability, the simplicity of the production technology, as well as the homogeneity of the distribution of the activator in the volume. The feasibility of creating a new type of nonlinear optical materials based on nanostructured heat-resistant lithium aluminosilicate glass ceramics with spinel nanocrystals activated by Co2+ ions under low-temperature heat treatment conditions, has been determined. The purpose and tasks of the work are formulated, which consist in justifying the choice of the system and compositions of glasses for obtaining glass-ceramic materials as a passive laser shutter for powerful lasers that operate at a wavelength of 1.54 μm and are characterized by high heat resistance. The choice of the lithium aluminosilicate system R2O – RO – RO2 – P2O5 – R2O3 – SiO2 based on phase-forming SiO2, Al2O3, Li2O, modifying K2O is substantiated; RO – MgO, ZnO, CaO, SrO, BaO components and a complex crystallization catalyst of P2O5, CeO2, TiO2, SnO2, ZrO2 and ZnO. The structural criteria for the glass matrix were formulated. Compositions of model glasses were designed taking into account the calculated parameters fSi > 0.22, Kсr ≥ 3.5, Ktr ≥ 2.1, and the probability of obtaining transparent glass-ceramic materials with a sitallized structure for pulse rangefinders was established on their basis.

Liquid Chromatographic Enantioseparation of Newly Synthesized Fluorinated Tryptophan Analogs Applying Macrocyclic Glycopeptides-Based Chiral Stationary Phases Utilizing Core-Shell Particles.

Due to the favorable features obtained through the incorporation of fluorine atom(s), fluorinated drugs are a group with emerging pharmaceutical importance. As their commercial availability is still very limited, to expand the range of possible candidates, new fluorinated tryptophan analogs were synthesized. Control of enantiopurity during the synthesis procedure requires that highly efficient enantioseparation methods be available. In this work, the enantioseparation of seven fluorinated tryptophans and tryptophan was studied and compared systematically to (i) develop analytical methods for enantioselective separations and (ii) explore the chromatographic features of the fluorotrytophans. For enantioresolution, macrocyclic glycopeptide-based selectors linked to core-shell particles were utilized, applying liquid chromatography-based methods. Application of the polar-ionic mode resulted in asymmetric and broadened peaks, while reversed-phase conditions, together with mobile-phase additives, resulted in baseline separation for all studied fluorinated tryptophans. The marked differences observed between the methanol and acetonitrile-containing eluent systems can be explained by the different solvation abilities of the bulk solvents of the applied mobile phases. Among the studied chiral selectors, teicoplanin and teicoplanin aglycone were found to work effectively. Under optimized conditions, baseline separations were achieved within 6 min. Ionic interactions were semi-quantitatively characterized and found to not influence enantiorecognition. Interestingly, fluorination of the analytes does not lead to marked changes in the chromatographic characteristics of the methanol-containing eluents, while larger differences were noticed when the polar but aprotic acetonitrile was applied. Experiments conducted on the influence of the separation temperature indicated that the separations are enthalpically driven, with only one exception. Enantiomeric elution order was found to be constant on both teicoplanin and teicoplanin aglycone-based chiral stationary phases (L < D) under all applied chromatographic conditions.

Novel assaying method for the accurate and rapid analysis of antioxidant total capacity based on hexachloroiridate(IV)

We introduce a novel method, namely IrRAC, for assessing total antioxidant capacity utilizing the single electron oxidant hexachloroiridate(IV). This method leverages the 488 nm absorption band of [IrCl6]2− largely reducing interferences from antioxidants and their oxidation products. [IrCl6]2− is stable 6 h in phosphate-buffered saline (PBS) ensuring consistent and reproducible absorbance readings and rendering spectrophotometric determinations under physiological neutrality. Individual assessments of 23 antioxidants reveal a linear correlation between decreasing absorbance and increasing antioxidant concentration. When the IrRAC assay was compared with several established water-based methods, strong correlations were found. Importantly, [IrCl6]2− shows a minimal oxidation of non-antioxidative substances. Moreover, IrRAC performs well with synthetic antioxidant mixtures and real samples, highlighting that the nature of antioxidants dominates the assay without much disturbance. Commercial availability of K2[IrCl6] eliminates the need of pretreatment of the oxidant. Undoubtedly, the new method confers a compelling and cost-effective alternative to the existing electron transfer-based methodologies.

Bridging the Gap from Bench to Bedside: A Call for In Vivo Preclinical Models to Advance Endometrial Cancer and Cervical Cancer Immuno-oncology Research.

Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, in which immunotherapy is now incorporated as the standard of care up front for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor. Continued preclinical research and clinical trial development are crucial for our understanding of resistance mechanisms to immunotherapy and maximization of therapeutic efficacy. In this setting, syngeneic models are preferred over xenograft models as they allow for the evaluation of the tumor-immune interaction in an immunocompetent host, most closely mimicking the tumor-immune interaction in patients with cancer. Unfortunately, significant disparities exist about syngeneic models in gynecologic malignancy, in which queries from multiple large bioscience companies confirm no commercial availability of endometrial or cervical cancer syngeneic cell lines. Published data exist about the recent development of several endometrial and cervical cancer syngeneic cell lines, warranting further investigation. Closing the disparity gap for preclinical models in endometrial and cervical cancers will support physician scientists, basic and translational researchers, and clinical trialists who are dedicated to improving outcomes for our patients with advanced disease and poor prognosis.

Breaking barriers in electrochemical biosensing using bioinspired peptide and phage probes.

Electrochemical biosensing continues to advance tirelessly, overcoming barriers that have kept it from leaving research laboratories for many years. Among them, its compromised performance in complex biological matrices due to fouling or receptor stability issues, the limitations in determining toxic and small analytes, and its use, conditioned to the commercial availability of commercial receptors and the exploration of natural molecular interactions, deserved to be highlighted. To address these challenges, in addition to the intrinsic properties of electrochemical biosensing, its coupling with biomimetic materials has played a fundamental role, among which bioinspired phage and peptide probes stand out. The versatility in design and employment of these probes has opened an unimaginable plethora of possibilities for electrochemical biosensing, improving their performance far beyond the development of highly sensitive and selective devices. The state of the art offers robust electroanalytical biotools, capable of operating in complex samples and with exciting opportunities to discover and determine targets regardless of their toxicity and size, the commercial availability of bioreceptors, and prior knowledge of molecular interactions. With all this in mind, this review offers a panoramic, novel, and updated vision of both the tremendous advances and opportunities offered by the combination of electrochemical biosensors with bioinspired phage and peptide probes and the challenges and research efforts that are envisioned in the immediate future.

Stereodivergent, Kinetically Controlled Isomerization of Terminal Alkenes via Nickel Catalysis.

Because internal alkenes are more challenging synthetic targets than terminal alkenes, metal-catalyzed olefin mono-transposition (i.e., positional isomerization) approaches have emerged to afford valuable E- or Z- internal alkenes from their complementary terminal alkene feedstocks. However, the applicability of these methods has been hampered by lack of generality, commercial availability of precatalysts, and scalability. Here, we report a nickel-catalyzed platform for the stereodivergent E/Z-selective synthesis of internal alkenes at room temperature. Commercial reagents enable this one-carbon transposition of terminal alkenes to valuable E- or Z-internal alkenes via a Ni-H-mediated insertion/elimination mechanism. Though the mechanistic regime is the same in both systems, the underlying pathways that lead to each of the active catalysts are distinct, with the Z-selective catalyst forming from comproportionation of an oxidative addition complex followed by oxidative addition with substrate and the E-selective catalyst forming from protonation of the metal by the trialkylphosphonium salt additive. In each case, ligand sterics and denticity control stereochemistry and prevent over-isomerization.

Stereodivergent, Kinetically Controlled Isomerization of Terminal Alkenes via Nickel Catalysis

AbstractBecause internal alkenes are more challenging synthetic targets than terminal alkenes, metal‐catalyzed olefin mono‐transposition (i.e., positional isomerization) approaches have emerged to afford valuable E‐ or Z‐ internal alkenes from their complementary terminal alkene feedstocks. However, the applicability of these methods has been hampered by lack of generality, commercial availability of precatalysts, and scalability. Here, we report a nickel‐catalyzed platform for the stereodivergent E/Z‐selective synthesis of internal alkenes at room temperature. Commercial reagents enable this one‐carbon transposition of terminal alkenes to valuable E‐ or Z‐internal alkenes via a Ni−H‐mediated insertion/elimination mechanism. Though the mechanistic regime is the same in both systems, the underlying pathways that lead to each of the active catalysts are distinct, with the Z‐selective catalyst forming from comproportionation of an oxidative addition complex followed by oxidative addition with substrate and the E‐selective catalyst forming from protonation of the metal by the trialkylphosphonium salt additive. In each case, ligand sterics and denticity control stereochemistry and prevent over‐isomerization.