Low Selectivity Research Articles

Enhancing Analytical Sensitivity and Selectivity for Methylene Blue Determination in Water Samples by Using Multiphase Electroextraction Coupled with Optical Absorption Spectroscopy and Surface-Enhanced Raman Scattering.

While optical analysis spectroscopy offers operational ease and low cost, it suffers from limitations regarding sensitivity when it comes to analyzing analytes at low concentrations. On the other hand, surface-enhanced Raman spectroscopy (SERS) offers high sensitivity but low selectivity in complex matrices. In this study, we have effectively addressed these challenges by integrating multiphase electroextraction (MPEE) as a sample preparation technique with these two spectroscopic methods for determining methylene blue (MB) dye in tap water samples. A Box-Behnken design was utilized for optimizing electroextraction parameters such as extraction time, pH, and acetonitrile percentage in the donor phase. After optimization, optical absorption spectroscopy results in a linear analytical curve within the range of 30 to 375 mg L-1 of MB, with method validation demonstrating high precision (relative standard deviation between 3.0 and 9.9%), recovery (99-105%), and detection and quantification limits of 1.3 and 4.0 μg L-1, respectively. On the other hand, using SERS, it was possible to detect MB in concentrations as low as 0.05 μg L-1. The extremely low concentrations of MB detected (in the range of a few ppb and ppt) and the acceptable validation performance parameters obtained highlight the potential of MPEE to enhance the applicability of spectroscopic techniques in routine analyses, especially when dealing with complex and challenging samples.

Synthesis, biochemistry, and in silico investigations of isatin-based hydrazone derivatives as monoamine oxidase inhibitors

Ten isatin-based hydrazone derivatives were synthesized using two subseries, IA (isatin + acetophenone) and IB (isatin + benzaldehyde), and evaluated for their monoamine oxidases (MAOs) inhibitory activity. All the compounds showed stronger MAO-A inhibition than MAO-B, and the IB series showed more effective MAO-A inhibitory activity than IA series. Compound IB4 most potently inhibited MAO-A (half maximal inhibitory concentration IC50 = 0.015 µM), followed by IB3 (IC50 = 0.019 µM). On the contrary, compound IB3 showed the highest MAO-B inhibition (IC50 = 0.068 µM), followed by IB4 (IC50 = 1.87 µM). Compound IB3 and IB4 had low selectivity indices of 3.68 and 8.50, respectively. Structurally, the methyl group of IA series decreased the inhibition of both MAO-A and MAO-B. Among them, IB3 and IB4 (4-Cl and 4-Br in B-ring, respectively) showed higher MAO-A and MAO-B inhibition than the other substitutions. Inhibition constant Ki values of IB3 and IB4 for MAO-A were 0.0088 and 0.0063 µM, respectively, and those for MAO-B were 0.048 and 0.060 µM, respectively. IB3 and IB4 were competitive, reversible inhibitors of MAO-A and MAO-B. Molecular docking analysis predicted that IB3 and IB4 formed stable hydrogen bonds between Asn181 and the NH atom of isatin in the ligand-protein complex. Dynamic analysis revealed that IB3 and IB4 are stable with both MAO isoforms. These observations suggest IB3 and IB4 are potent and reversible MAO-A and MAO-B inhibitors and both compounds can be used as therapeutic agents for neurological disorders.

Enhanced Charge-Carrier Dynamics and Efficient Photoelectrochemical Nitrate-to-Ammonia Conversion on Antimony Sulfide-Based Photocathodes.

The photoelectrochemical reduction of nitrate to ammonia (PEC NO3RR) has emerged as a promising pathway for facilitating the natural nitrogen cycle. The PEC NO3RR can lower the reduction potential needed for ammonia synthesis through photogenerated voltage, showcasing the significant potential for merging abundant solar energy with sustainable nitrogen fixation. However, it is influenced by the selective photocathodes with poor carrier kinetics, low catalytic selectivity, and ammonia yields. There are few reports on suitable photoelectrodes owning efficient charge transport on PEC NO3RR at low overpotentials. Herein, we rationally constructed the CuSn alloy co-catalysts on the antimony sulfides with a highly selective PEC ammonia and an ultra-low onset potential (0.62 VRHE). CuSn/TiO2/Sb2S3 photoelectrodes achieved an ammonia faradic efficiency of 97.82 % at a low applied potential of 0.4 VRHE, and an ammonia yield of 16.96 μmol h-1 cm-2 at 0 VRHE under one sun illumination. Dynamics experiments and theoretical calculations have demonstrated that CuSn/TiO2/Sb2S3 has an enhanced charge separation and transfer efficiency, facilitating photogenerated electrons to participate in PEC NO3RR quickly. Meanwhile, moderate NO2* adsorption on this photocathode optimizes the catalytic activity and increases the NH4 + yield. This work opens an avenue for designing sulfide-based photocathodes for the efficient route of solar-to-ammonia conversion.

Optimization of e-beam lithography parameters for nanofabrication of sub-50 nm gold nanowires and nanogaps based on a bilayer lift-off process

Electron beam lithography (EBL) stands out as a powerful direct-write tool offering nanometer-scale patterning capability and is especially useful in low-volume R&D prototyping when coupled with pattern transfer approaches like etching or lift-off. Among pattern transfer approaches, lift-off is preferred particularly in research settings, as it is cost-effective and safe and does not require tailored wet/dry etch chemistries, fume hoods, and/or complex dry etch tools; all-in-all offering convenient, ‘undercut-free’ pattern transfer rendering it useful, especially for metallic layers and unique alloys with unknown etchant compatibility or low etch selectivity. Despite the widespread use of the lift-off technique and optical/EBL for micron to even sub-micron scales, existing reports in the literature on nanofabrication of metallic structures with critical dimension in the 10–20 nm regime with lift-off-based EBL patterning are either scattered, incomplete, or vary significantly in terms of experimental conditions, which calls for systematic process optimization. To address this issue, beyond what can be found in a typical photoresist datasheet, this paper reports a comprehensive study to calibrate EBL patterning of sub-50 nm metallic nanostructures including gold nanowires and nanogaps based on a lift-off process using bilayer polymethyl-methacrylate as the resist stack. The governing parameters in EBL, including exposure dose, soft-bake temperature, development time, developer solution, substrate type, and proximity effect are experimentally studied through more than 200 EBL runs, and optimal process conditions are determined by field emission scanning electron microscope imaging of the fabricated nanostructures reaching as small as 11 nm feature size.

Robust Electrocatalytic CO2 Reduction in Acid Enabled by "Molecularly Charged" Cobalt Phthalocyanine: A Profound Understanding from Electric Double Layer.

Electrocatalytic CO2 reduction (eCO2R) in acid holds promise in renewable electricity-powered CO2 utilization with high efficiency, but the hydrogen evolution reaction (HER) often prevails and results in a low eCO2R selectivity. Here, using cobalt phthalocyanine/Ketjen black (CoPc/KB) as the model catalysts, we systematically study the effect of active site density, operational current density, and hydrated cations on the acidic eCO2R selectivity and decipher it through the componential dynamics of electric double layer (EDL). The optimal CoPc-4/KB demonstrates a near-unity CO Faradaic efficiency from 50 to 400 mA cm-2 and superb operational stability (>120 h) at 100 mA cm-2. Aided by in situ Raman and infrared spectroscopies, we reveal that the proper cations establish an electrostatic shield for mitigating bulk H+ penetration and mediate the interfacial water structure for suppressing HER. This study should elicit further profound thinking on robust eCO2R system design from the perspective of multiphasic and dynamic EDL.

Bacteriocins in Cancer Treatment: Mechanisms and Clinical Potentials.

Cancer poses a severe threat to human health. Although conventional chemotherapy remains a cornerstone of cancer treatment, its significant side effects and the growing issue of drug resistance necessitate the urgent search for more efficient and less toxic anticancer drugs. In recent years, bacteriocins, antimicrobial peptides of microbial origin, have garnered significant attention due to their targeted antitumor activity. This unique activity is mainly attributed to their cationic and amphiphilic nature, which enables bacteriocins to specifically kill tumor cells without harming normal cells. When involving non-membrane-disrupting mechanisms, such as apoptosis induction, cell cycle blockade, and metastasis inhibition, the core mechanism of action is achieved by disrupting cell membranes, which endows bacteriocins with low drug resistance and high selectivity. However, the susceptibility of bacteriocins to hydrolysis and hemolysis in vivo limits their clinical application. To overcome these challenges, structural optimization of bacteriocins or their combination with nanotechnology is proposed for future development. This review aims to study the mechanism of action and current research status of bacteriocins as anticancer treatments, thus providing new insights for their clinical development and application.

One-pot conversion of xylose to 1,2-pentanediol catalyzed by an organic acid-assisted Pt/NC in aqueous phase.

The direct synthesis of 1,2-pentanediol (1,2-PeD) from renewable xylose and its derivatives derived from hemicellulose is appealing yet challenging due to its low selectivity for the target product. In this study, one-pot catalytic conversion of xylose to 1,2-PeD was performed by using nitrogen-doped carbon (NC) supported Pt catalysts with the assistance of organic acids. A remarkable yield of 49.3% for 1,2-PeD was achieved by reacting 0.1869 g xylose in 30 mL water at 200 °C under a hydrogen pressure of 3 MPa for 8 h in the presence of 0.1 g of 2.5Pt/NC600 catalyst and 0.1869 g propanoic acid co-catalyst. The presence of vicinal Pt-acid pair sites on the surface of the 2.5Pt/NC600 catalyst exhibited a synergistic effect in promoting the hydrogenation of furfural to furfuryl alcohol intermediate and subsequent hydrogenation and ring-opening reactions leading to the formation of 1,2-PeD. The addition of organic acids, may serve as both acid catalyst for dehydration of xylose and hydrogen donor for hydrogenation of furfural and furfuryl alcohol, thereby promoting the one-pot conversion of xylose to 1,2-PeD. Remarkably, the 2.5Pt/NC600 catalyst demonstrated outstanding catalytic performance and good reusability over five consecutive cycles without significant deactivation.

A near-infrared hepatocyte-targeting probe based on Tricyanofuran to detect cysteine in vivo: Design, synthesis and evaluation

In this work, a near-infrared hepatocyte-targeting fluorescence probe TCF-Gal-Cys was developed. The TCF-Gal-Cys exhibited a low detection limit, good sensitivity and selectivity toward Cys. The responsive mechanism of TCF-Gal-Cys was proposed that the acrylate of TCF-Gal-Cys was subsequently attacked by the thiol group and the amino group of Cys, releasing a strong near-infrared fluorescent group. TCF-Gal-Cys displayed a good hepatocyte-targeting capacity and could specifically distinguish hepatocytes from A549, Hela, SGC-7901 cells because the galactose group of TCF-Gal-Cys can be recognized by HepG2 cells overexpressing ASGPR. The TCF-Gal-Cys has achieved excellently imaging performance to Cys in the zebrafish, so TCF-Gal-Cys has potential to be an effective tool to in real time monitor Cys-related diseases in vitro and in vivo.

The sensing of circRNA with tetrahedral DNA nanostructure modified microfluidic chip

BackgroundCircular ribonucleic acids (circRNAs) are a type of covalently closed noncoding RNA with disease-relevant expressions, making them promising biomarkers for diagnosis and prognosis. Accurate quantification of circRNA in biological samples is a necessity for their clinical application. So far, methods developed for detecting circRNAs include northern blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), microarray analysis, and RNA sequencing. These methods generally suffer from disadvantages such as large sample consumption, cumbersome process, low selectivity, leading to inaccurate quantification of circRNA. It was thought that the above drawbacks could be eliminated by the construction of a microfluidic sensor. ResultsHerein, for the first time, a microfluidic sensor was constructed for circRNA analysis by using tetrahedral DNA nanostructure (TDN) as the skeleton for recognition probes and target-initiated hybridization chain reaction (HCR) as the signal amplification strategy. In the presence of circRNA, the recognition probe targets the circRNA-specific backsplice junction (BSJ). The captured circRNA then triggers the HCR by reacting with two hairpin species whose ends were labeled with 6-FAM, producing long DNA strands with abundant fluorescent labels. By using circ_0061276 as a model circRNA, this method has proven to be able to detect circRNA of attomolar concentration. It also eliminated the interference of linear RNA counterpart, showing high selectivity towards circRNA. The detection process can be implemented isothermally and does not require expensive complicated instruments. Moreover, this biosensor exhibited good performance in analyzing circRNA targets in total RNA extracted from cancer cells. SignificanceThis represents the first microfluidic system for detection of circRNA. The biosensor showed merits such as ease of use, low-cost, small sample consumption, high sensitivity and specificity, and good reliability in complex biological matrix, providing a facile tool for circRNA analysis and related disease diagnosis in point-of care application scenes.

Unacclimated activated sludge improved nitrate reduction and N2 selectivity in iron filling/biochar systems

Iron (Fe)-based denitrification is a proven technology for removing nitrate from water, yet challenges such as limited pH preference range and low N2 selectivity (reduction of nitrate to N2) persist. Adding biochar (BC) can improve the pH preference range but not N2 selectivity. This study aimed to improve nitrate reduction and N2 selectivity in iron filling/biochar (Fe/BC) systems with a simplified approach by coupling unacclimated microbes (M) in the system. Factors such as initial pH, Fe/BC ratio, and Fe/BC dosage on nitrate removal efficiency and N2 selectivity were evaluated. Results show that the introduction of microbes significantly enhanced nitrate removal and N2 selectivity, achieving 100 % nitrate removal and 79 % N2 selectivity. The Fe/BC/M system exhibited efficient nitrate reduction at pH of 2–10. Moreover, the Fe/BC/M system demonstrated an improved electrochemical active surface area (ECSA), lower electron transfer resistance and lower corrosion potential, leading to enhanced nitrate reduction. The high i0 value in Fe/BC/M system means more Hads could be generated, thus improving the N2 selectivity. This study provides valuable insights into a novel approach for effective nitrate removal, offering a potential solution to the environmental challenges posed by excessive nitrate in wastewater, surface water and ground water.

Lappanolides A−N, fourteen undescribed sesquiterpenoids from Saussurea costus (Syn. Saussurea lappa) and their anti HBV activity

Lappanolides A−N (1–14), 14 undescribed sesquiterpenoids, along with 23 known ones (15–37), were isolated from the roots of Saussurea costus, which were primarily categorized into eudesmane, guaiane, and germacrane types. Lappanolide A (1) possessed an unprecedented pseudo-disesquiterpenoids. Their structures and absolute configurations were established using physical data analyses (HRESIMS, IR, 1D and 2D NMR) and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (1, 9, 11, 12, 19, 22, 28, 29, 31, and 36) exhibited activities against HBsAg secretions as determined by ELISA assay, with IC50 values ranging from 5.2 to 45.7 μM. In particular, compounds 28 and 29 showed inhibition of HBsAg secretion with IC50 values of 5.28 and 5.30 μM, and CC50 values of 9.85 and 6.37 μM, respectively, though they all exhibited low selectivity. Several compounds displayed cytotoxicity in the MTT assay. Among them, compound 28 was the most notable and was chosen for further study using flow cytometry. The result showed that it significantly induced HepG2 cell arrest in the S phase and induced apoptosis.

Fischer-Tropsch Synthesis of C4-C5 Isoparaffins via CoxMn1-xO Nanocomposites with Suppressed CO2.

The synthesis of a specific product via the Fischer-Tropsch synthesis remains challenging due to the uncontrollable coupling of CHx on active sites. Isoparaffins, essential high-quality petroleum additives for improving octane numbers, are primarily derived from petroleum or natural gas. With petroleum reserves dwindling and the associated low selectivity, the direct conversion of syngas to isoparaffins has emerged as a promising alternative. This study presents a tandem catalyst comprising CoxMn1-xO and zeolites for catalyzing the direct conversion of syngas to C4-C5 isoparaffins. The relay catalyst exhibited an impressive selectivity of 55.6% toward the desired products while maintaining a low CO2 selectivity of approximately 20%. Notably, the selectivity of isobutane reached 43.5%, exceeding predictions based on the Anderson-Schulz-Flory distribution. Syngas undergoes conversion into olefins on CoxMn1-xO nanocomposites, diffuses into microporous zeolites, and interacts with Brønsted acids to produce isoparaffins. The stability of the relay catalyst relied significantly on the pore characteristics and acidic density of the zeolites.

Application of Bimetallic Hydroxide/Graphene Composites in Wastewater Treatment.

The increasing discharge of antibiotic wastewater leads to increasing water pollution. Most of these antibiotic wastewaters are persistent, strongly carcinogenic, easy to bioaccumulate, and have other similar characteristics, seriously jeopardizing human health and the ecological environment. As a commonly used wastewater treatment technology, non-homogeneous electro-Fenton technology avoids the hazards of H2O2 storage and transportation as well as the loss of desorption and reabsorption. It also facilitates electron transfer on the electrodes and the reduction of Fe3+ on the catalysts, thereby reducing sludge production. However, the low selectivity and poor activity of electro-synthesized H2O2, along with the low concentration of its products, combined with the insufficient activity of electrically activated H2O2, results in a low ∙OH yield. To address the above problems, composites of layered bimetallic hydroxides and carbon materials were designed and prepared in this paper to enhance the performance of electro-synthesized H2O2 and non-homogeneous electro-Fenton by changing the composite mode of the materials. Three composites, NiFe layered double hydroxides (LDHs)/reduced graphene oxide (rGO), NiMn LDHs/rGO, and NiMnFe LDHs/rGO, were constructed by the electrostatic self-assembly of exfoliated LDHs with few-layer graphene. The LDHs/rGO was loaded on carbon mats to construct the electro-Fenton cathode materials, and the non-homogeneous electro-Fenton oxidative degradation of organic pollutants was realized by the in situ electrocatalytic reduction of O2 to ∙OH. Meanwhile, the effects of solution pH, applied voltage, and initial concentration on the performance of non-homogeneous electro-Fenton were investigated with ceftazidime as the target pollutant, which proved that the cathode materials have an excellent electro-Fenton degradation effect.

Modulating the Electrolyte Microenvironment in Electrical Double Layer for Boosting Electrocatalytic Nitrate Reduction to Ammonia.

Electrochemical nitrate reduction reaction (NO3RR) is a promising approach to achieve remediation of nitrate-polluted wastewater and sustainable production of ammonia. However, it is still restricted by the low activity, selectivity and Faraday efficiency for ammonia synthesis. Herein, we propose an effective strategy to modulate the electrolyte microenvironment in electrical double layer (EDL) by mediating alkali metal cations in the electrolyte to enhance the NO3RR performance. Taking bulk Cu as a model catalyst, the experimental study reveals that the NO3 --to-NH3 performance in different electrolytes follows the trend Li+<Cs+<Na+<K+. Theoretical studies illustrate that the proton transport rate in NO3RR and the activity of the rate-determining step (NO3 - to NO2 -) increase in the order Li+<Cs+<Na+<K+. The cation effects are also general for two typical nanostructured catalysts including copper/cuprous oxide and nickel phosphides, achieving near-100 % Faradaic efficiency and over 99 % conversion of NO3 - to NH3. Furthermore, we demonstrate that NO3 - can be converted to high-purity NH4Cl by copper/cuprous oxide catalyst in K+-containing electrolyte.

Modulating the Electrolyte Microenvironment in Electrical Double Layer for Boosting Electrocatalytic Nitrate Reduction to Ammonia

AbstractElectrochemical nitrate reduction reaction (NO3RR) is a promising approach to achieve remediation of nitrate‐polluted wastewater and sustainable production of ammonia. However, it is still restricted by the low activity, selectivity and Faraday efficiency for ammonia synthesis. Herein, we propose an effective strategy to modulate the electrolyte microenvironment in electrical double layer (EDL) by mediating alkali metal cations in the electrolyte to enhance the NO3RR performance. Taking bulk Cu as a model catalyst, the experimental study reveals that the NO3−‐to‐NH3 performance in different electrolytes follows the trend Li+&lt;Cs+&lt;Na+&lt;K+. Theoretical studies illustrate that the proton transport rate in NO3RR and the activity of the rate‐determining step (NO3− to NO2−) increase in the order Li+&lt;Cs+&lt;Na+&lt;K+. The cation effects are also general for two typical nanostructured catalysts including copper/cuprous oxide and nickel phosphides, achieving near‐100 % Faradaic efficiency and over 99 % conversion of NO3− to NH3. Furthermore, we demonstrate that NO3− can be converted to high‐purity NH4Cl by copper/cuprous oxide catalyst in K+‐containing electrolyte.

Supramolecular organic frameworks (SOFs) membrane with ultra-high hydrogen permeability for hydrogen purification: Microstructural design of JLU-SOF2

Simulating results showed that JLU-SOF2 has ultra-high hydrogen permeability (0.696 × 106 GPU) but low selectivity (7.46). Given the good structural designability of JLU-SOF2, it is valuable to develop the structure design of JLU-SOF2 for on-site hydrogen purification to improve selectivity and maintain high H2 permeability. In this study, the functional groups of JLU-SOF2 were modified to construct 13 membrane materials containing functional groups of different lengths. The effect of membrane materials modified with each functional group on hydrogen permeability and selectivity in mixed gases (CO2, CO, and H2) was investigated from a microscopic point of view utilizing molecular simulations. Results showed that all 13 functional groups could improve the gas selectivity, especially the -SO3H, -OCH3, and -CH2NH2 modified JLU-SOF2 membrane materials, which can 100 % intercept CO2 and CO and maintain an excellent H2 permeability (0.54 × 106GPU), which exceeded the industry standard by nearly 105 times. Molecular motion behavior analysis showed that stretching direction and length of functional groups are the key factors leading to different membrane pore sizes and play a crucial role in affecting gas transport.

Особенности межличностного взаимодействия подростков, склонных к проявлению агрессии

&lt;p style="text-align: justify;"&gt;The article provides an analysis of the results of a study of the unique aspects of interpersonal interaction among adolescents prone to aggression. The theoretical basis for the purpose of the work was provided by modern research, showing the versatility of the process of interpersonal interaction between adolescents and manifestations of aggression. The respondents of the study were teenagers from educational schools in Moscow, numbering 68 people aged 15-16 years. The empirical study used the aggressiveness test by L.G. Pochebut, &amp;ldquo;Aggressive behavior&amp;rdquo; methodology by E.P. Ilyin and P.A. Kovalev, interpersonal relations questionnaire by A.A. Rukavishnikov, emotional empathy questionnaire by A. Mehrabian, N. Epstein. The results of the empirical study established significant differences in the interpersonal interaction of adolescents prone to aggression. They are characterized by a desire to dominate, a lack of willingness to control their behavior, low selectivity and criticality in choosing communication partners, as well as a low level of empathy development. The obtained results can be used in work with adolescents aimed at creating favorable interactions among adolescents and reducing aggression.&lt;/p&gt;

Discovery of GPR84 Fluorogenic Probes Based on a Novel Antagonist for GPR84 Bioimaging.

GPR84 is a promising therapeutic target and biomarker for a range of diseases. In this study, we reported the discovery of BINOL phosphate (BINOP) derivatives as GPR84 antagonists. By investigating the structure-activity relationship, we identified 15S as a novel GPR84 antagonist. 15S exhibits low nanomolar potency and high selectivity for GPR84, while its enantiomer 15R is less active. Next, we rationally designed and synthesized a series of GPR84 fluorogenic probes by conjugating Nile red and compound 15S. The leading hybrid, probe F8, not only retained GPR84 activity but also exhibited low nonspecific binding and a turn-on fluorescent signal in an apolar environment. F8 enabled visualization and detection of GPR84 in GPR84-overexpressing HEK293 cells and lipopolysaccharide-stimulated neutrophils. Furthermore, we demonstrated that F8 can detect upregulated GPR84 protein levels in mice models of inflammatory bowel disease and acute lung injury. Thus, compound F8 represents a promising tool for studying GPR84 functions.

In Silico Study of Acetogenin Compounds from Soursop (Annona muricata) Leaves as Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

Acetogenin derived from soursop (Annona muricata) leaves are known to have antidiabetic and anticancer activities. Nevertheless, there has been no study related to the compounds found in A. muricata leaves, such as acetogenin, as SGLT2 inhibitors. This research aims to investigate the activity of acetogenin compounds as SGLT2 inhibitors while maintaining low selectivity against SGLT1 using molecular docking methods using Molegro Virtual Docker (MVD). Based on the Rerank score, five acetogenin compounds, namely muricin H, annonacin A, annopentocin B, murihexocin C, and corossolone, are predicted to be SGLT2 inhibitors with better selectivity compared to empagliflozin. Among these five compounds, muricin H and corossolone exhibit the most similarity in interaction with amino acid residues in the SGLT2 A-chain compared to empagliflozin. In silico ADMET analysis results indicate that both compounds have absorption, distribution, and metabolism capabilities, similar to empagliflozin. However, it should be noted that both compounds are more toxic, with muricin H predicted to have hepatotoxic properties.

Selection Bias Risk in Randomized Controlled Trials Rated as Low Bias Using Risk of Bias, Version 2 (RoB2) Tool.

Our study aimed to establish the risk of selection bias in randomized controlled trials (RCT) that were overall rated as having "low bias" riskaccording to Cochrane's Risk of Bias, version 2 (RoB 2) tool. A systematic literature search of current systematic reviews of RCTs was conducted. From the identified reviews, RCTs with overall "high bias" and "low bias" RoB 2 risk ratings were extracted. All RCTs were statistically tested for selection bias risk. From the test results, true positive, true negative, false positive, or false negative ratings were established, and the false omission rate (FOR) with a 95% confidence interval (CI) was computed. Subgroup analysis was conducted by computing the negative likelihood ratio (-LR) concerning RoB 2 domain 1 ratings: bias arising from the randomization process. A total of 1070 published RCTs (median publication year: 2018; interquartile range: 2013-2020) were identified and tested.We found that 7.61% of all "low bias" (RoB 2)-rated RCTs were of high selection bias risk (FOR 7.61%; 95% CI: 6.31%-9.14%) and that the likelihood for high selection bias risk in "low bias" (RoB 2 domain 1)-rated RCTs was 6% higher than that for low selection bias risk (-LR: 1.06; 95% CI: 0.98-1.15). These findings raise issues about the validity of "low bias" risk ratings using Cochrane's RoB 2 toolas well as about the validity of some of the results from recently published RCTs.Our results also suggest that the likelihood of a "low bias" risk-rated body of clinical evidence being actually bias-free is low, and that generalization based on a limited, pre-specified set of appraisal criteria may not justify a high level of confidence that such evidence reflects the true treatment effect.