Enhanced fitness of SARS-CoV-2 variant of concern Alpha but not Beta.

Emerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models-the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.

SARS-CoV-2 spike D614G change enhances replication and transmission.

During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.

Steering Photooxidation of Methane to Formic Acid over A Priori Screened Supported Catalysts.

Efficient methane photooxidation to formic acid (HCOOH) has emerged as a sustainable approach to simultaneously generate value-added chemicals and harness renewable energy. However, the persistent challenge lies in achieving a high yield and selectivity for HCOOH formation, primarily due to the complexities associated with modulating intermediate conversion and desorption after methane activation. In this study, we employ first-principles calculations as a comprehensive guiding tool and discover that by precisely controlling the O2 activation process on noble metal cocatalysts and the adsorption strength of carbon-containing intermediates on metal oxide supports, one can finely tune the selectivity of methane photooxidation products. Specifically, a bifunctional catalyst comprising Pd nanoparticles and monoclinic WO3 (Pd/WO3) would possess optimal O2 activation kinetics and an intermediate oxidation/desorption barrier, thereby promoting HCOOH formation. As evidenced by experiments, the Pd/WO3 catalyst achieves an exceptional HCOOH yield of 4.67 mmol gcat-1 h-1 with a high selectivity of 62% under full-spectrum light irradiation at room temperature using molecular O2. Notably, these results significantly outperform the state-of-the-art photocatalytic systems operated under identical condition.

Tissue-, Region-, and Gene-Specific Induction of Microsomal Epoxide Hydrolase Expression and Activity in the Mouse Intestine by Arsenic in Drinking Water.

This study aimed to characterize the effects of arsenic exposure on the expression of microsomal epoxide hydrolase (mEH or EPHX1) and soluble epoxide hydrolase (sEH or EPHX2) in the liver and small intestine. C57BL/6 mice were exposed to sodium arsenite in drinking water at various doses for up to 28 days. Intestinal, but not hepatic, mEH mRNA and protein expression was induced by arsenic at 25 ppm, in both males and females, whereas hepatic mEH expression was induced by arsenic at 50 or 100 ppm. The induction of mEH was gene specific, as the arsenic exposure did not induce sEH expression in either tissue. Within the small intestine, mEH expression was induced only in the proximal, but not the distal segments. The induction of intestinal mEH was accompanied by increases in microsomal enzymatic activities toward a model mEH substrate, cis-stilbene oxide, and an epoxide-containing drug, oprozomib, in vitro, and by increases in the levels of PR-176, the main hydrolysis metabolite of oprozomib, in the proximal small intestine of oprozomib-treated mice. These findings suggest that intestinal mEH, playing a major role in converting xenobiotic epoxides to less reactive diols, but not sEH, preferring endogenous epoxides as substrates, is relevant to the adverse effects of arsenic exposure, and that further studies of the interactions between drinking water arsenic exposure and the disposition or possible adverse effects of epoxide-containing drugs and other xenobiotic compounds in the intestine are warranted. SIGNIFICANCE STATEMENT: Consumption of arsenic-contaminated water has been associated with increased risks of various adverse health effects, such as diabetes, in humans. The small intestinal epithelial cells are the main site of absorption of ingested arsenic, but they are not well characterized for arsenic exposure-related changes. This study identified gene expression changes in the small intestine that may be mechanistically linked to the adverse effects of arsenic exposure and possible interactions between arsenic ingestion and the pharmacokinetics of epoxide-containing drugs in vivo.

DeepP450: Predicting Human P450 Activities of Small Molecules by Integrating Pretrained Protein Language Model and Molecular Representation.

Cytochrome P450 enzymes (CYPs) play a crucial role in Phase I drug metabolism in the human body, and CYP activity toward compounds can significantly affect druggability, making early prediction of CYP activity and substrate identification essential for therapeutic development. Here, we established a deep learning model for assessing potential CYP substrates, DeepP450, by fine-tuning protein and molecule pretrained models through feature integration with cross-attention and self-attention layers. This model exhibited high prediction accuracy (0.92) on the test set, with area under the receiver operating characteristic curve (AUROC) values ranging from 0.89 to 0.98 in substrate/nonsubstrate predictions across the nine major human CYPs, surpassing current benchmarks for CYP activity prediction. Notably, DeepP450 uses only one model to predict substrates/nonsubstrates for any of the nine CYPs and exhibits certain generalizability on novel compounds and different categories of human CYPs, which could greatly facilitate early stage drug design by avoiding CYP-reactive compounds.

Effects of JUNCAO Ganoderma lucidum polysaccharide peptide on slaughter performance and intestinal health of Minxinan black rabbits.

This experiment was conducted to investigate the effects of JUNCAO Ganoderma lucidum polysaccharide peptide (JCGLPP) on slaughter performance and intestinal health of Minxinan black rabbits, which aimed to provide the basis for the application of JCGLPP in meat rabbits. One hundred male weaned Minxinan black rabbits of (33 ± 2) d [(initial body mass (655.65 ± 25.90) g] were randomly divided into four groups with five replicates per group and five rabbits per replicate. The diets were supplemented with 0 (control group), 50 (group I), 100 (group II) and 150 mg·kg-1 (group III) of JCGLPP, respectively. This experiment lasted for 56 days. The results are shown below: (1) The live weight before slaughter of groups I and III was significantly higher than that of control group (p < 0.05); The full net bore weight of group III was significantly higher than that of control group (p < 0.05). (2) pH value of group I was significantly higher than that of control group (p < 0.05); NH3-N content in experimental groups were significantly higher than that in control group(p < 0.05) while NH3-N content in group I was significantly higher than that in groups III and II (p < 0.05); The content of butyric acid in group II was significantly lower than that in control group (p < 0.05); There were no significant differences in acetic acid, isovaleric acid, isobutyric acid and propionic acid in experimental groups compared with control group (p > 0.05). (3) The Occludin content in duodenum, jejunum and ileum of groups I and II was significantly higher than that of control group (p < 0.05). (4) At the phylum level, Firmicutes and Bacteroidetes were the dominant phylum in each group. At the genus level, norank_f__norank_o__Clostridia_UCG-014 in group II were significantly higher than those in control group (p < 0.05). In conclusion, although dietary JCGLPP supplementation could not improve slaughter performance of Minxinan black rabbits, it could improve cecal fermentation parameters and intestinal flora structure and composition of Minxinan black rabbits to a certain extent. Our results revealed that 100 mg·kg-1 might be the optimal concentration obtained in dietary JCGLPP supplementation, which provided ideas and feasibility for drug combination.

Enabling Specific Photocatalytic Methane Oxidation by Controlling Free Radical Type.

Selective CH4 oxidation to CH3OH or HCHO with O2 in H2O under mild conditions provides a desired sustainable pathway for synthesis of commodity chemicals. However, manipulating reaction selectivity while maintaining high productivity remains a huge challenge due to the difficulty in the kinetic control of the formation of a desired oxygenate against its overoxidation. Here, we propose a highly efficient strategy, based on the precise control of the type of as-formed radicals by rational design on photocatalysts, to achieve both high selectivity and high productivity of CH3OH and HCHO in CH4 photooxidation for the first time. Through tuning the band structure and the size of active sites (i.e., single atoms or nanoparticles) in our Au/In2O3 catalyst, we show alternative formation of two important radicals, •OOH and •OH, which leads to distinctly different reaction paths to the formation of CH3OH and HCHO, respectively. This approach gives rise to a remarkable HCHO selectivity and yield of 97.62% and 6.09 mmol g-1 on In2O3-supported Au single atoms (Au1/In2O3) and an exceptional CH3OH selectivity and yield of 89.42% and 5.95 mmol g-1 on In2O3-supported Au nanoparticles (AuNPs/In2O3), respectively, upon photocatalytic CH4 oxidation for 3 h at room temperature. This work opens a new avenue toward efficient and selective CH4 oxidation by delicate design of composite photocatalysts.

Luteolin ameliorates necroptosis in Glucocorticoid-induced osteonecrosis of the femoral head via RIPK1/RIPK3/MLKL pathway based on network pharmacology analysis.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is deeply relevant to damage and dysfunction of bone microvascular endothelial cells (BMECs). Recently, necroptosis, a newly programmed cell death with necrotic appearance, has garnered increasing attention. Luteolin, a flavonoid compound derived from Rhizoma Drynariae, has numerous pharmacological properties. However, the effect of Luteolin on BMECs in GIONFH through the necroptosis pathway has not been extensively investigated. Based on network pharmacology analysis, 23 genes were identified as potential targets for the therapeutic effect of Luteolin in GIONFH via the necroptosis pathway, with RIPK1, RIPK3, and MLKL being the hub genes. Immunofluorescence staining results revealed high expression of vWF and CD31 in BMECs. In vitro experiments showed that incubation with dexamethasone led to reduced proliferation, migration, angiogenesis ability, and increased necroptosis of BMECs. However, pretreatment with Luteolin attenuated this effect. Based on molecular docking analysis, Luteolin exhibited strong binding affinity with MLKL, RIPK1, and RIPK3. Western blotting was utilized to detect the expression of p-MLKL, MLKL, p-RIPK3, RIPK3, p-RIPK1, and RIPK1. Intervention with dexamethasone resulted in a significant increase in the p-RIPK1/RIPK1 ratio, but the effects of dexamethasone were effectively counteracted by Luteolin. Similar findings were observed for the p-RIPK3/RIPK3 ratio and the p-MLKL/MLKL ratio, as anticipated. Therefore, this study demonstrates that Luteolin can reduce dexamethasone-induced necroptosis in BMECs via the RIPK1/RIPK3/MLKL pathway. These findings provide new insights into the mechanisms underlying the therapeutic effects of Luteolin in GIONFH treatment. Additionally, inhibiting necroptosis could be a promising novel approach for GIONFH therapy.

Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink (Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a "down" position, approximately 34° lower than previously reported "up" RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry.

Achieving delafossite analog by in situ electrochemical self-reconstruction as an oxygen-evolving catalyst.

Development of novel and robust oxygen evolution reaction (OER) catalysts with well-modulated atomic and electronic structure remains a challenge. Compared to the well-known metal hydroxides or (oxyhydr)oxides with lamellar structure, delafossites (ABO2) are characterized by alternating layers of A cations and edge-sharing BO2 octahedra, but are rarely used in OER due to their poor electron conductivity and intrinsic activity. Here, we propose a delafossite analog by mutation of metal oxyhydroxide and delafossite based on first-principles calculations. Modulation on the electronic structure due to distortion of the original crystal field of the BO2 layers is calculated to enhance electron conductivity and catalytic activity. Inspired by the theoretical design, we have experimentally realized the delafossite analog by electrochemical self-reconstruction (ECSR). Operando X-ray absorption spectroscopy and other experimental techniques reveal the formation of delafossite analog with Ag intercalated into bimetallic cobalt-iron (oxyhydr)oxide layers from a metastable precursor through amorphization. Benefitting from the featured local electronic and geometric structures, the delafossite analog shows superior OER activity, affording a current density of 10 mA⋅cm-2 at an overpotential of 187 mV and an excellent stability (300 h) in alkaline conditions.

Cotton swabs decorated with Ag@BPQD for the fluorescence determination of 3-aminosalicylic and 5-aminosalicylic acid.

Novel and portable cotton swab-based fluorometry was constructed for the first time for 3-aminosalicylic acid (3-ASA) and 5-aminosalicylic acid (5-ASA) detection. It was carried out by fluorescence enhancement on silver (Ag)-doped black phosphorus quantum dots (Ag@BPQD). Ag@BPQD were prepared from AgNO3 and bulk black phosphorus in N, N-dimethylformamide (DMF) solution by solvothermal decomposition after mechanical exfoliation. Ag@BPQD show blue fluorescence with a quantum yield (QY) of 2.43%. In the presence of Ag@BPQD, 3-ASA exhibited bright blue fluorescence (λex = 328 nm, λem = 448 nm). The fluorescence of 5-ASA was also enhanced significantly and exhibited bright green emission (λex = 328 nm, λem = 484 nm). The linear range of 3-ASA is 0-90 µM with a detection limit (LOD) of 0.10 µM, relative standard deviation (RSD) ≤ 2.04%, and a recovery range of 98.0-104.3%. The linear range of 5-ASA is 0-120 µM with a LOD of 0.12 µM, RSD ≤ 1.34%, and a recovery range of 98.0-101.3%. When 3-ASA and 5-ASA were mixed in different ratios, the fluorescence showed different colors. The possible mechanism of the interaction between 3-ASA (or 5-ASA) and Ag@BPQD may be ascribed to the generation of excited-state intramolecular proton transfer. To realize convenient detection of 3-ASA and 5-ASA, a Ag@BPQD portable sensing method using cotton swabs were built. The proposed approach provides the detection of 3-ASA and 5-ASA in environmental and biological samples with high efficiency, accuracy and portability.

Utilization of dental care service and associated factors among pre-school children in northwest China over the past decade.

OBJECTIVE: The purpose of this study was to analyze the factors influencing the utilization of oral health care among 5 years old children. METHODS: We conducted two observational cross-sectional studies. The studies were conducted in 2005 and 2015 and included 5-year-old children who underwent dental examination by trained dentists and the caregivers of the children were requested to answer the questionnaire. Multi-level stratified sampling method was used. Chi-square tests were used to analyze the utilization of dental care and other socio-economic variables. Logistic regression models were employed to explore the primary factors influencing the use of dental care among pre-school children. RESULTS: In 2005, a total of 399 and in 2015, 492 child-caregiver pairs were included. The majority of the caregivers in both surveys were females, comprising 68.2% and 74.8% of the caregivers in 2005 and 2015, respectively. 75.2% and 87.0% (p < 0.05) of the respondents had an education level of lesser than 9 years. The prevalence of caries was higher in 2015 (63.2%) (p < 0.05) than in 2005 (53.4%). In 2005 and 2015, the utilization of dental care services was 20.8% and 20.0%, respectively. A statistically significant association was observed between caries and dental care use in 5-year-olds over the past decade. After adjusting for confounders, dental service usage among children in urban areas was 1.62 times higher than that of rural areas in 2005 (95% CI 0.069-0.571), and the self-assessment of caregivers regarding their child's oral health significantly improved oral health use in 2015. CONCLUSION: The utilization of dental care services over the past decade is insufficient among pre-school children in northwest China. Hence, with the decreasing gap about economic and health service resources, policymakers should place greater emphasis on raising awareness among caregivers about the oral health status of their children.

Ginsenoside Rg3 Protects Mouse Islet ß-Cells Injured by High Glucose.

To investigate the effect of Ginsenoside Rg3 on insulin secretion in mouse MIN6 cells and the possible mechanism. The cultured mouse pancreatic islet MIN6 cells were divided into control group (NC), Rg3 group (Rg3, 50 µg/L), high glucose group (HG, 33 mmol/L), High glucose and Rg3 group (HG + Rg3), after 48 h of continuous culture, CCK-8 was used to detect cell viability; mouse insulin enzyme-linked immunoassay kit to detect insulin release; ATP content detection kit to detect ATP; DCFH-DA to detect intracellular reactive oxygen species (ROS) levels; total glutathione (T-GSH)/oxidized glutathione (GSSG) assay kit to detect the ratio of GSH/GSSG; Using the mitochondrial membrane channel pore (MPTP) fluorescence detection kit in MIN6 cells and collect the intensity of green fluorescence; Western blot to detect the expression of antioxidant proteins Glutathione reductase (GR). The results showed that compared with the NC group, the cell viability of the HG was decreased (P < 0.05), insulin release decreased (P < 0.001), ATP content decreased significantly (P < 0.001), and ROS content increased (P < 0.01), the GSH/GSSH ratio of pancreatic islet cells decreased (P < 0.05),the green fluorescence intensity decreased (P < 0.001), indicating that the permeability of mitochondria increased and the content of antioxidant protein in the cells decreased (P < 0.05). Compared with the HG group, the cell viability of the HG + Rg3 group was significantly increased (P < 0.05), the amount of insulin released was significantly increased (P < 0.001), ATP content was significantly increased (P < 0.01), and the ROS content was significantly decreased (P < 0.01), GSH/GSSH ratio increased significantly (P < 0.05), the green fluorescence intensity was increased (P < 0.001), indicating that the permeability of mitochondria decreased and antioxidant protein GR content increased significantly (P < 0.05). Taken together, our results suggest that Rg3 has an antioxidant protective effect on mouse pancreatic islet cells damaged by high glucose and maintains pancreatic islet cell function and promotes insulin secretion.

Up-regulated FNDC1 accelerates stemness and chemoradiation resistance in colorectal cancer cells.

Neoadjuvant chemoradiation (nCRT) followed by radical surgery is the preferred option for locally advanced colorectal cancer (CRC) treatment. However, chemo/radio-resistance remains a main obstacle in CRC therapy. In the study, we analyzed the mRNA expression profiling of CRC patients and revealed that the aberrant expression of fibronectin type III domain containing 1 (FNDC1) was associated with disease progression and poor prognosis in CRC. FNDC1 expression was consistently increased in multiple independent cohorts of CRC. Upregulated FNDC1 in pretreated primary tumor tissues predicted a poor response to nCRT, recurrence, and poor disease-free survival in nCRT-treated CRC patients. FNDC1 overexpression accelerated CRC cell survival on 5-FU or radiation treatment both in vitro and in vivo, whereas FNDC1 inhibition sensitized CRC cells to chemoradiation. In addition, FNDC1 accelerated stem cell-like properties of CRC cells. Furthermore, tumor tissues from non-responders exhibited higher activation of PI3K/Akt signaling than those from responders. FNDC1 depletion repressed 5-FU or irradiation-induced activation of PI3K/AKT in CRC cells. More importantly, pharmacological inhibition of PI3K/Akt signaling effectively decreased the effect of FNDC1 on chemoradiation resistance. Taken together, our study reveals the potential function of FNDC1 as a biomarker to predict nCRT sensitivity in CRC and a therapeutic target in CRC treatment.

External quality assessment for detection of methylated Syndecan 2 (SDC2) in China.

OBJECTIVES: Detection of Syndecan 2 (SDC2) methylation in stool DNA is a novel method for the auxiliary diagnosis of early colorectal cancer (CRC). Currently, this method has been widely applied; however, its accuracy and reliability have not been determined. The objective of this pioneering study was to evaluate the performance of clinical laboratories in China for their ability to detect SDC2 methylation from stool DNA. METHODS: We generated a sample panel consisting of clinical and cell samples. The clinical samples were stool specimens from patients with or without CRC, including four positives (prepared by serial dilution from one stool specimen), one negative and one interferential sample. Two cell samples, with positive or negative methylated SDC2, were used as controls. The panel was distributed to 32 clinical laboratories for analysis of SDC2 methylation, and the results were compared and scored. RESULTS: The sample panel was compatible with commercially available assays and it showed appropriate stability to be an external quality assessment material. There were four false results; one hospital laboratory and one commercial diagnostic laboratory had a false-positive and a false-negative result, respectively, and one commercial diagnostic laboratory had both a false-positive and false-negative result. Among the 32 participating laboratories, 29 (90.62%) obtained an acceptable or better performance score, while 3 (9.38%) laboratories required improvement. CONCLUSIONS: Our results demonstrate that the detection of SDC2 methylation from stool DNA was satisfactory in China. Additionally, the importance of external quality assessment was highlighted for monitoring the performance of clinical laboratories.

Construction of a Turn-off-on Fluorescent System Based On Aggregation Induced Emission of Acetaldehyde Using Carbonized Polymer dots and Tb3.

It was the first time to report the aggregation induced emission (AIE) of acetaldehyde (AA) on the surface of carbonized polymer dots (CPDs) with the auxiliary of Tb3+. Based on the AIE of AA, a turn-off-on fluorescence method was established for AA detection using the porous CPDs-Tb3+ system. The one-pot hydrothermal method was used to obtain CPDs, using milk and polyethyleneimine (PEI) as precursors. In the presence of Tb3+, CPDs aggregated immediately and even forming precipitate, and the fluorescence intensity decreased obviously. AA can effectively embed on the surface of CPDs-Tb3+ due to the porous structure. AA displayed obviously blue fluorescence with excitation wavelength at 370 nm (emission peak at 460 nm), while there was no fluorescence peak when excited at 460 nm. In the CPDs-Tb3+ solution, AA exhibits obvious fluorescence enhancement effect (λex 460 nm, λem 545 nm). And then, AA can be determined by the turn-off-on system based on the linear relationship between fluorescence enhancement and the concentration of AA ranging from 0.04 mM to 42.48 mM. The limit of detection (LOD) was 0.02 mM. The turn-off-on system was successfully applied to determine AA in wine samples. The strategy may be exploited to monitor AA in more drinking or foodstuff samples.

Inner-filter Effect Induced Fluorescence Quenching of Carbon Dots for Cr(VI) Detection with High Sensitivity.

Carbon dots (CDs) were used to develop a sensitive sensing technique for detecting Cr(VI). CDs were made using a hydrothermal technique from citric acid and glutamic acid. These prepared CDs emitted blue fluorescence under excitation of 350 nm (λem = 420 nm), and the fluorescence quantum yield was 48.41%. Transmission electron microscope was used to examine the morphology of the CDs, which had an average size of 2.21 ± 0.39 nm. The elementary composition and bonding structure of the CDs were conducted by XPS and FT-IR spectrum. Cr(VI) quenched the fluorescence of CDs through a static quenching effect and an inner filter effect, allowing Cr(VI) to be detected quantitatively. This approach was used to detect Cr(VI) in two samples of water, with the findings demonstrating that it is reliable and accurate. The fluorescence intensity change was linearly related to the concentration of Cr(VI) in the range from 0.5 to 400 µM, with the detection limit being 0.10 µM. This approach has the virtues of wide detection range, low cost and fast response. The strategy has a great application prospect for detecting Cr(VI) in practical samples.

Susceptibility to SARS-CoV-2 of Cell Lines and Substrates Commonly Used to Diagnose and Isolate Influenza and Other Viruses.

Co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses has been reported. We evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to SARS-CoV-2. Although multiple kidney cell lines from monkeys were susceptible to SARS-CoV-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. We analyzed MDCK cells, which are most commonly used for surveillance and study of influenza viruses, and found that they were not susceptible to SARS-CoV-2. The low expression level of the angiotensin converting enzyme 2 receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by overexpression of canine angiotensin converting enzyme 2 in trans, strengthened the cellular barrier to productive infection. Moreover, a D614G mutation in the spike protein did not appear to affect SARS-CoV-2 cell tropism. Our findings should help avert inadvertent propagation of SARS-CoV-2 from diagnostic cell lines.

Comparison of the drug-drug interactions potential of ibrutinib and acalabrutinib via inhibition of UDP-glucuronosyltransferase.

Ibrutinib and acalabrutinib are two Bruton's tyrosine kinase (BTK) inhibitors which have gained Food and Drug Administration (FDA) approval for the treatment of various B cell malignancies. Herein, we investigated the effects of the two drugs on UDP-glucuronosyltransferase (UGT) activities to evaluate their potential risk for drug-drug interactions (DDIs) via UGT inhibition. Our data indicated that ibrutinib exerted broad inhibition on most of UGTs, including a potent competitive inhibition against UGT1A1 with a Ki value of 0.90 ± 0.03 µM, a noncompetitive inhibition against UGT1A3 and UGT1A7 with Ki values of 0.88 ± 0.03 µM and 2.52 ± 0.23 µM, respectively, while acalabrutinib only exhibited weak UGT inhibition towards all tested UGT isoforms. DDI risk prediction suggested that the inhibition against UGT1A1 and UGT1A3 by ibrutinib might bring a potential DDIs risk, while acalabrutinib was unlikely to trigger clinically significant UGT-mediated DDIs due to its weak effects. Our study raises an alarm bell about potential DDI risk associated with ibrutinib, however, the extrapolation from in vitro data to in vivo drug interactions should be taken with caution, and additional systemic study is needed.

Engineering of bioactive metal sulfide nanomaterials for cancer therapy.

Metal sulfide nanomaterials (MeSNs) are a novel class of metal-containing nanomaterials composed of metal ions and sulfur compounds. During the past decade, scientists found that the MeSNs engineered by specific approaches not only had high biocompatibility but also exhibited unique physicochemical properties for cancer therapy, such as Fenton catalysis, light conversion, radiation enhancement, and immune activation. To clarify the development and promote the clinical transformation of MeSNs, the first section of this paper describes the appropriate fabrication approaches of MeSNs for medical science and analyzes the features and limitations of each approach. Secondly, we sort out the mechanisms of functional MeSNs in cancer therapy, including drug delivery, phototherapy, radiotherapy, chemodynamic therapy, gas therapy, and immunotherapy. It is worth noting that the intact MeSNs and the degradation products of MeSNs can exert different types of anti-tumor activities. Thus, MeSNs usually exhibit synergistic antitumor properties. Finally, future expectations and challenges of MeSNs in the research of translational medicine are spotlighted.