Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: subgroup analysis from CIRCULATE-Japan GALAXY.

BACKGROUND: The prognostic role of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection and its utility for postsurgical risk stratification has been reported in colorectal cancer. In this study, we explored the use of ctDNA-based MRD detection in patients with colorectal liver metastases (CLM), for whom the survival benefit of adjuvant chemotherapy (ACT) after surgical resection remains unclear. METHODS: Patients with CLM without extrahepatic disease from the GALAXY study (UMIN000039205) were included. The disease-free survival (DFS) benefit of ACT was evaluated in MRD-positive and -negative groups after adjusting for age, gender, number, and size of liver metastases, RAS status, and previous history of oxaliplatin for primary cancer. ctDNA was detected using a personalized, tumor-informed 16-plex polymerase chain reaction-next-generation sequencing (mPCR-NGS) assay. ctDNA-based MRD status was evaluated 2-10 weeks after curative surgery, before the start of ACT. RESULTS: Among 6061 patients registered in GALAXY, 190 surgically resected CLM patients without any preoperative chemotherapy were included with a median follow-up of 24 months (1-48 months). ctDNA positivity in the MRD window was 32.1% (61/190). ACT was administered to 25.1% (48/190) of patients. In the MRD-positive group, 24-month DFS was higher for patients treated with ACT [33.3% versus not reached, adjusted hazard ratio (HR): 0.07, P < 0.0001]; whereas no benefit of ACT was seen in the MRD-negative group (24-month DFS: 72.3% versus 62.2%, adjusted HR: 0.68, P = 0.371). Multivariate analysis showed that the size of liver metastases (HR: 3.94, P = 0.031) was prognostic of DFS in the MRD-positive group. In the MRD-negative group, however, none of the clinicopathological factors were prognostic of DFS. CONCLUSIONS: Our data suggest that ACT may offer notable clinical benefits in MRD-positive patients with CLM. MRD status-based risk stratification could be potentially incorporated in future clinical trials for CLM.

Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY trial.

BACKGROUND: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel compared with placebo plus carboplatin-paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the first interim analysis, the trial met one of its dual primary endpoints with statistically significant progression-free survival benefits in the mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. PATIENTS AND METHODS: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or first recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. RESULTS: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence interval (CI) 0.54-0.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel versus carboplatin-paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile for dostarlimab plus carboplatin-paclitaxel was consistent with the first interim analysis. CONCLUSIONS: Dostarlimab in combination with carboplatin-paclitaxel demonstrated a statistically significant and clinically meaningful OS benefit in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile.

Coherent control of an optical tweezer phonon laser.

The creation and manipulation of coherence continues to capture the attention of scientists and engineers. The optical laser is a canonical example of a system that, in principle, exhibits complete coherence. Recent research has focused on the creation of coherent, laser-like states in other physical systems. The phonon laser is one example where it is possible to amplify self-sustained mechanical oscillations. A single mode phonon laser in a levitated optical tweezer has been demonstrated through appropriate balance of active feedback gain and damping. In this work, coherent control of the dynamics of an optical tweezer phonon laser is used to share coherence between its different modes of oscillation, creating a multimode phonon laser. The coupling of the modes is achieved by periodically rotating the asymmetric optical potential in the transverse focal plane of the trapping beam via trap laser polarization rotation. The presented theory and experiment demonstrate that coherence can be transferred across different modes of an optical tweezer phonon laser, and are a step toward using these systems for precision measurement and quantum information processing.

Dispersion-Driven Cooperativity in Alkyl Perylene Diimide Oligomers: Insights from Density Functional Theory.

The cooperative mechanism is of paramount importance in the synthesis of supramolecular polymers with desired characteristics, including molecular mass, polydispersity, and morphology. It is primarily driven by the presence of intermolecular interactions, which encompass strong hydrogen bonding, metal-ligand interactions, and dipole-dipole interactions. In this study, we utilize density functional theory and energy decomposition analysis to investigate the cooperative behavior of perylene diimide (PDI) oligomers with alkyl chains at their imide positions, which lack the previously mentioned interactions. Our systematic examination reveals that dispersion interactions originating from the alkyl side-chain substituents play an important role in promoting cooperativity within these PDIs. This influence becomes even more pronounced for alkyl chain lengths beyond hexyl groups. The energy decomposition analysis reveals that the delicate balance between dispersion energy and Pauli repulsion energy is the key driver of cooperative behavior in PDIs. Additionally, we have developed a mathematical model capable of predicting the saturated binding energies for PDI oligomers of varying sizes and alkyl chain lengths. Overall, our findings emphasize the previously undervalued significance of dispersion forces in cooperative supramolecular polymerization, enhancing our overall understanding of the cooperative mechanism.

Decoupling of ion-transport from polymer segmental relaxation and higher ionic-conductivity in poly(ethylene oxide)/succinonitrile composite-based electrolytes having low lithium salt doping.

Only limited enhancement in room-temperature ionic-conductivity for poly(ethylene oxide), PEO, based electrolytes is possible due to coupling between ionic-conductivity and segmental relaxation. In the present study, we have achieved ionic-conductivity of 1.07 × 10-3 and 6.20 × 10-4 S cm-1 at 313 and 298 K, respectively, by adding 45 wt% of succinonitrile (SN) in PEO having low LiTFSI loading (Li : EO = 1 : 20). This enhancement in the ionic-conductivity is attributed to faster ion transport (diffusion coefficient, D = 3.63 × 10-5 cm2 s-1) occurring through the ion-transport channels as confirmed by positron annihilation lifetime spectroscopy. The ionic-transport through these channels is observed to be highly decoupled from the segmental relaxations as confirmed using broadband dielectric spectroscopy through Ratner's approach. The observed decoupling of ionic-conductivity from PEO segmental relaxation in PEO-SN composite-based electrolytes would be useful to design rather inexpensive all solid-state polymer electrolytes for Li ion batteries.

In vitro and in silico analysis unravelled clinically desirable attributes of Bacillus altitudinis L-asparaginase.

AIMS: To identify a marine L-asparaginase with clinically desirable attributes and characterize the shortlisted candidate through in silico tools. METHODS AND RESULTS: Marine bacterial strains (number = 105) isolated from marine crabs were evaluated through a stepwise strategy incorporating the crucial attributes for therapeutic safety. The results demonstrated the potential of eight bacterial species for extracellular L-asparaginase production. However, only one isolate (Bacillus altitudinis CMFRI/Bal-2) showed clinically desirable attributes, viz. extracellular production, type-II nature, lack of concurrent L-glutaminase and urease activities, and presence of ansZ (functional gene for clinical type). The enzyme production was 22.55 ± 0.5 µM/mg protein/min within 24 h without optimization. The enzyme also showed good activity and stability in pH 7-8 and temperature 37°C, predicting the functioning inside the human body. The Michealis-Menten constant (Km) was 14.75 µM. Detailed in silico analysis based on functional gene authenticating the results of in vitro characterization and predicted the nonallergenic characteristic of the candidate. Docking results proved the higher affinity of the shortlisted candidate to L-asparagine than L-glutamine and urea. CONCLUSION: Comprehensively, the study highlighted B. altitudinis type II asparaginase as a competent candidate for further research on clinically safe asparaginases.

RASPA3: A Monte Carlo code for computing adsorption and diffusion in nanoporous materials and thermodynamics properties of fluids.

We present RASPA3, a molecular simulation code for computing adsorption and diffusion in nanoporous materials and thermodynamic and transport properties of fluids. It implements force field based classical Monte Carlo/molecular dynamics in various ensembles. In this article, we introduce the new additions and changes compared to RASPA2. RASPA3 is rewritten from the ground up in C++23 with speed and code readability in mind. Transition-matrix Monte Carlo is added to compute the density of states and free energies. The Monte Carlo code for rigid molecules is based on quaternions, and the atomic positions needed in the energy evaluation are recreated from the center of mass position and quaternion orientation. The expanded ensemble methodology for fractional molecules, with a scaling parameter λ between 0 and 1, now also keeps track of analytic expressions of dU/dλ, allowing independent verification of the chemical potential using thermodynamic integration. The source code is freely available under the MIT license on GitHub. Using this code, we compare four Monte Carlo (MC) insertion/deletion techniques: unbiased Metropolis MC, Configurational-Bias Monte Carlo (CBMC), Continuous Fractional Component MC (CFCMC), and CB/CFCMC. We compare particle distribution shapes, acceptance ratios, accuracy and speed of isotherm computation, enthalpies of adsorption, and chemical potentials, over a wide range of loadings and systems, for the grand canonical ensemble and for the Gibbs ensemble.

Virulent and Multi-drug-Resistant Edwardsiella tarda Infection in Oscar Fish: Unveiling the Threat of Mass Mortality and AMR Dissemination.

The Oscar fish (Astronotus ocellatus) is among the most commonly domesticated and exported ornamental fish species from Kerala. The ornamental fish industry faces a significant challenge with the emergence of diseases caused by multi-drug-resistant bacteria. In the present study, six isolates were resolved from the diseased Oscar fish showing haemorrhages, necrosis, and loss of pigmentation. After phenotypic and genotypic characterization, the bacteria were identified as Edwardsiella tarda, Klebsiella pneumoniae, Enterococcus faecalis, Escherichia coli, Brevibacillus borstelensis, and Staphylococcus hominis. Experimental challenge studies in healthy Oscar fish showed that E. tarda caused 100% mortality within 240 h with 6.99 × 106 CFU/fish as LD50 and histopathology revealed the typical signs of infection. The pathogen was re-recovered from the moribund fish thereby confirming Koch's postulates. E. tarda was confirmed through the positive amplification of tarda-specific gene and virulence genes viz., etfD and escB were also detected using PCR. Antibiotic susceptibility tests using disc diffusion displayed that the pathogen is multi-drug-resistant towards antibiotics belonging to aminoglycosides, tetracyclines, and quinolones categories with a MAR index of 0.32, which implicated the antibiotic pressure in the farm. Plasmid curing studies showed a paradigm shift in the resistance pattern with MAR index of 0.04, highlighting the resistance genes are plasmid-borne except for the chromosome-borne tetracycline resistance gene (tetA). This study is the first of its kind in detecting mass mortality caused by E. tarda in Oscar fish. Vigilant surveillance and strategic actions are crucial for the precise detection of pathogens and AMR in aquaculture.

In vitro efficacy of aquaculture antimicrobials and genetic determinants of resistance in bacterial isolates from tropical aquaculture disease outbreaks.

Understanding the efficacy of antimicrobials against pathogens from clinical samples is critical for their responsible use. The manuscript presents in vitro efficacy and antimicrobial resistance (AMR) genes in seven species of fish pathogens from the disease outbreaks of Indian aquaculture against oxytetracycline, florfenicol, oxolinic acid, and enrofloxacin. In vitro efficacy was evaluated by minimum inhibitory concentration and minimum bactericidal concentration. The gene-specific PCR screened AMR genes against quinolones (qnrA, qnrB, and qnrS) and tetracyclines (tetM, tetS, tetA, tetC, tetB, tetD, tetE, tetH, tetJ, tetG, and tetY). The results showed that Aeromonas veronii (45%) showed the maximum resistance phenotype, followed by Streptococcus agalactiae (40%), Photobacterium damselae (15%), Vibrio parahaemolyticus (10%), and Vibrio vulnificus (5%). There was no resistance among Vibrio harveyi and Vibrio alginolyticus against the tested antimicrobials. The positive association between tetA, tetB, tetC, tetM, or a combination of these genes to oxytetracycline resistance and qnrS to quinolone resistance indicated their potential in surveillance studies. The prevalence of resistance phenotypes (16.43%) and evaluated AMR genes (2.65%) against aquaculture antimicrobials was low. The resistance phenotype pattern abundance was 0.143. All the isolates showed susceptibility to florfenicol. The results help with the appropriate drug selection against each species in aquaculture practices.

Cryopreservation and assessment of genetic fidelity Acorus calamus Linn., an endangered medicinal plant.

BACKGROUND: Acorus calamus Linn. is a medicinally valuable monocot plant belonging to the family Acoraceae. Over-exploitation and unscientific approach towards harvesting to fulfill an ever-increasing demand have placed it in the endangered list of species. OBJECTIVE: To develop vitrification-based cryopreservation protocols for A. calamus shoot tips, using conventional vitrification and V cryo-plate. MATERIALS AND METHODS: Shoot tips (2 mm in size) were cryopreserved with the above techniques by optimizing various parameters such as preculture duration, sucrose concentration in the preculture medium, and PVS2 dehydration time. Regenerated plantlets obtained post-cryopreservation were evaluated by random amplified polymorphic DNA (RAPD) to test their genetic fidelity. RESULTS: The highest regrowth of 88.3% after PVS2 exposure of 60 min was achieved with V cryo-plate as compared to 75% after 90 min of PVS2 exposure using conventional vitrification. After cryopreservation, shoot tips developed into complete plantlets in 28 days on regrowth medium (0.5 mg/L BAP, 0.3 mg/L GA3, and 0.3 mg/L ascorbic acid). RAPD analysis revealed 100% monomorphism in all cryo-storage derived regenerants and in vitro donor (120-days-old) plants. CONCLUSION: Shoot tips of A. calamus that were cryopreserved had 88.3% regrowth using V cryo-plate technique and the regerants retained genetic fidelity. https://doi.org/10.54680/fr24210110412.

Profiling the antioxidant biomarkers in marine fish larvae: a comparative assessment of different storage conditions to select the optimal strategy.

Research on antioxidant biomarkers can generate profound insights into the defense mechanisms of fish larvae against different stressors and can reveal manipulation strategies for improved growth and survival. However, the number of samples to process and unavailability of required infrastructure in larval-rearing facilities limit the immediate processing, requiring the preservation of specimens. Silver pompano (Trachinotus blochii), a potential marine aquaculture species, shows a low larval survival rate due to poorly developed antioxidant mechanism. In this context, 39 storage conditions, including three storage temperatures and different buffers, were scrutinized to select the most suitable preservation strategy for five important antioxidant biomarkers of fish larvae, viz. catalase activity, superoxide dismutase (SOD) activity, measurement of lipid peroxidation, reduced glutathione (GSH), and ascorbic acid contents. The paper proposes the optimum larval storage conditions for these five evaluated antioxidant biomarkers to generate similar results in preserved and non-preserved larval samples. Larval samples preserved in PBS at lower temperatures (- 20 °C and - 80 °C) are recommended for evaluating catalase activity and ascorbic acid content. Catalase activity can also be evaluated by preserving the larval samples at - 20 °C or - 80 °C without buffers. Larval samples held in PBS or without any buffers at - 20 °C and at - 80 °C were found to be suitable for SOD and GSH evaluation, respectively. Preservation in 50% glacial acetic acid at - 80 °C or - 20 °C was preferred for the lipid peroxidation assays. Apart from methodological perspectives, the paper provides insights into the dynamics of larval antioxidant profiles of T. blochii, for the first time.

Conventional and Scientific uses of Rice-washed water: A Systematic Review.

Rice is considered the king of cereals. It is the only cereal that is being consumed by half of the population in the world. Rice and rice products have potential health benefits. One such rice aided product is rice washed water which is discussed in this article. Rice-washed water, which is commonly regarded as waste water and discarded, is a rich source of minerals and nutrients. The processing of rice washed water, nutritional analysis; edible fungi productions are detailed in this review. The article goes into detail about rice-washed water, which has been used for various purposes since our ancestors' time. The article provides a comprehensive report on the uses of rice-washed water in plant growth, Ayurveda, food, Cosmetics and a variety of other applications. Rice washed water is being utilized for various ailments since primitive times. The detailed report on the treatment utilizing rice washed water is also provided in this article. There are scarce researches with rice washed water, this article address the conventional uses of rice washed water, which can be taken up by the research community which needs more scientific validation. This review article also includes details about the composition and a variety of other important information about rice-washed water. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05722-2.

Spontaneous α-C-H Carboxylation of Ketones by Gaseous CO2 at the Air-water Interface of Aqueous Microdroplets.

We present a catalyst-free route for the reduction of carbon dioxide integrated with the formation of a carbon-carbon bond at the air/water interface of negatively charged aqueous microdroplets, at ambient temperature. The reactions proceed through carbanion generation at the α-carbon of a ketone followed by nucleophilic addition to CO2. Online mass spectrometry reveals that the product is an α-ketoacid. Several factors, such as the concentration of the reagents, pressure of CO2 gas, and distance traveled by the droplets, control the kinetics of the reaction. Theoretical calculations suggest that water in the microdroplets facilitates this unusual chemistry. Furthermore, such a microdroplet strategy has been extended to seven different ketones. This work demonstrates a green pathway for the reduction of CO2 to useful carboxylated organic products.

Diabetic Foot Ulcer and its Associated Risk Factors in Diabetic Patients with Peripheral Arterial Disease Presenting in the University Hospital of Nepal.

Background Diabetic foot ulcers (DFUs) are a common complication in diabetic patients especially in those with peripheral arterial disease (PAD). However, it can be prevented if its risk factors can be identified and adjusted. Objective To investigate the frequency of diabetic foot ulcers and their associated risk factors in diabetic patients with peripheral artery disease. Method Diabetic patients under medication with known peripheral arterial disease diagnosed with Doppler ultrasonography were recruited from the outpatient department of the cardiothoracic and vascular unit, at Dhulikhel Hospital. The patients were interviewed about their demographic details, presenting clinical symptoms, and the risk factors such as smoking, hypertension, cardiovascular diseases, duration of diabetes, and hyperlipidemia. Also, the patients were assessed for any ulcers in their feet. Descriptive statistics and chi-square tests were used to analyze the data. Result The analysis demonstrated diabetic foot ulcers in 24.1% of the total 54 diabetic patients with peripheral arterial disease. The risk factors such as smoking (24.1%), increasing age (68.5%), hypertension (31.5%), and duration of diabetes (72.2%) were found in the majority of the patients. Out of these risk factors, smoking (Odds ratio: 6.81) and increasing age (Odds ratio: 0.28) were significantly associated with diabetic foot ulcers. (p < 0.05) Conclusion Diabetic foot ulcers affected about a quarter of diabetic patients with peripheral arterial disease and were found to be associated with increasing age and smoking.

Evaluating Osteoarthritis Management Programs: outcome domain recommendations from the OARSI Joint Effort Initiative.

OBJECTIVE: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). DESIGN: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7. RESULTS: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. CONCLUSION: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context.

First Evidence of Axial Shape Asymmetry and Configuration Coexistence in

The excited states of N=44 ^{74}Zn were investigated via γ-ray spectroscopy following ^{74}Cu ß decay. By exploiting γ-γ angular correlation analysis, the 2_{2}^{+}, 3_{1}^{+}, 0_{2}^{+}, and 2_{3}^{+} states in ^{74}Zn were firmly established. The γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+}, 3_{1}^{+}, and 2_{3}^{+} states were measured, allowing for the extraction of relative B(E2) values. In particular, the 2_{3}^{+}→0_{2}^{+} and 2_{3}^{+}→4_{1}^{+} transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the N=40 gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize ^{74}Zn in its ground state. Furthermore, an excited K=0 band with a significantly larger softness in its shape is identified. A shore of the N=40 "island of inversion" appears to manifest above Z=26, previously thought as its northern limit in the chart of the nuclides.

Amygdala DCX and blood Cdk14 are implicated as cross-species indicators of individual differences in fear, extinction, and resilience to trauma exposure.

Doublecortin (DCX) has long been implicated in, and employed as a marker for, neurogenesis, yet little is known about its function in non-neurogenic brain regions, including the amygdala. This study sought first to explore, in rodents, whether fear learning and extinction modulate amygdala DCX expression and, second, to assess the utility of peripheral DCX correlates as predictive biomarkers of trauma response in rodents and humans. Pavlovian conditioning was found to alter DCX protein levels in mice 24 h later, resulting in higher DCX expression associated with enhanced learning in paradigms examining both the acquisition and extinction of fear (p < 0.001). This, in turn, is associated with differences in freezing on subsequent fear expression tests, and the same relationship between DCX and fear extinction was replicated in rats (p < 0.001), with higher amygdala DCX levels associated with more rapid extinction of fear. RNAseq of amygdala and blood from mice identified 388 amygdala genes that correlated with DCX (q < 0.001) and which gene ontology analyses revealed were significantly over-represented for neurodevelopmental processes. In blood, DCX-correlated genes included the Wnt signaling molecule Cdk14 which was found to predict freezing during both fear acquisition (p < 0.05) and brief extinction protocols (p < 0.001). High Cdk14 measured in blood immediately after testing was also associated with less freezing during fear expression testing (p < 0.01). Finally, in humans, Cdk14 expression in blood taken shortly after trauma was found to predict resilience in males for up to a year post-trauma (p < 0.0001). These data implicate amygdala DCX in fear learning and suggest that Cdk14 may serve as a predictive biomarker of trauma response.

On enhancing the Li-ion conductivity of quasi-solid-state electrolytes by suppressing the flexibility of zeolitic imidazolate framework-8 via a mixed ligand strategy.

Zeolitic imidazole frameworks (ZIFs) have emerged as potential conductive materials for Li ion-transport in polymer solid state electrolytes. However, developing ZIFs with high Li ionic conductivity is rather limited due to their flexible frameworks allowing dual ion conduction. Herein, we have used a mixed ligand strategy for fine-tuning the aperture and enhancing the rigidity of ZIF-8, which restricts the passage of large size anions. Poly(ethylene oxide)-based quasi-solid state electrolytes utilizing mixed ligand ZIF-7-8 frameworks as passive fillers show a continuous enhancement in Li ion-conductivity exclusively attributed to modifications in the flexibility and pore architecture of ZIF-8 as confirmed through broadband dielectric spectroscopy and positron annihilation spectroscopy. This study shows that polymer segmental relaxation and conductivity relaxation processes are decoupled in these electrolytes. Consequently, our proposed approach provides a new strategy for manufacturing a polymer-based electrolyte with enhanced ionic conductivity.

Promising anode materials for alkali metal ion batteries: a case study on cobalt anti-MXenes.

There is continuous demand for energy storage devices with high energy densities in consumer electronics, electric vehicles, and the grid energy market. Although commercial lithium-ion batteries (LIBs) satisfy the current needs, the limited availability of their raw materials and the moderate specific charge capacities (SCCs) of LIBS have motivated scientists to search for alternate anode materials for LIBs and create technologies beyond LIBs. In this work, we studied the potential of six cobalt anti-MXenes (CoAs, CoB, CoP, CoS, CoSe, and CoSi), a class of newly discovered 2D materials, as anode materials for lithium, sodium, and potassium ion batteries (LIBs, NIBs, and KIBs). We found that these materials are good electrical conductors and have high adsorption stability for alkali metal ions, which helps to prevent the formation of dendrites and increase the cycle life of the battery. They also show moderate to low migration energy barriers (MEBs), indicating the potential for faster charge-discharge kinetics. We also explain the slightly counter-intuitive result of observing low MEBs along with high adsorption stability. Furthermore, Co-anti-MXenes can adsorb multiple alkali atoms per formula unit, resulting in high specific charge capacities and low average anodic voltages. For example, as anode materials for lithium-ion batteries, CoP and CoSi have SCC values of 1075.4 mA h g-1 and 934 mA h g-1, and anodic voltages as low as 0.28 V and 0.43 V, respectively. Moreover, even the maximally metalated Co-anti-MXenes did not show agglomeration tendency at room temperature. Furthermore, the volume expansion of these materials is minimum for both Li and Na adsorption. As a whole, we find that Co-anti-MXenes are promising as anode materials for alkali metal ion batteries.

Species-differences in the in vitro biotransformation of trifluoroethene (HFO-1123).

1,1,2-Trifluoroethene (HFO-1123) is anticipated for use as a refrigerant with low global warming potential. Inhalation studies on HFO-1123 in rats indicated a low potential for toxicity (NOAELs ≥ 20,000 ppm). In contrast, single inhalation exposure of Goettingen® minipigs (≥ 500 ppm) and New Zealand white rabbits (≥ 1250 ppm) resulted in severe toxicity. It has been suggested that these pronounced species-differences in toxicity may be attributable to species-differences in biotransformation of HFO-1123 via the mercapturic acid pathway. Therefore, the overall objective of this study was to evaluate species-differences in glutathione (GSH) dependent in vitro metabolism of HFO-1123 in susceptible versus less susceptible species and humans as a basis for human risk assessment. Biotransformation of HFO-1123 to S-(1,1,2-trifluoroethyl)-L-glutathione (1123-GSH) and subsequent cysteine S-conjugate ß-lyase-mediated cleavage of the corresponding cysteine conjugate (1123-CYS) was monitored in hepatic and renal subcellular fractions of mice, rats, minipigs, rabbits, and humans. While 1123-GSH formation occurred at higher rates in rat and rabbit liver S9 compared to minipig and human S9, increased ß-lyase cleavage of 1123-CYS was observed in minipig kidney cytosol as compared to cytosolic fractions of other species. Increased ß-lyase activity in minipig cytosol was accompanied by time-dependent formation of monofluoroacetic acid (MFA), a highly toxic compound that interferes with cellular energy production via inhibition of aconitase. Consistent with the significantly lower ß-lyase activity in human cytosols, the intensity of the MFA signal in human cytosols was only a fraction of the signal obtained in minipig subcellular fractions. Even though the inconsistencies between GSH and ß-lyase-dependent metabolism do not allow to draw a firm conclusion on the overall contribution of the mercapturic acid pathway to HFO-1123 biotransformation and toxicity in vivo, the ß-lyase data suggest that humans may be less susceptible to HFO-1123 toxicity compared to minipigs.