Advances in the application of machine learning in the identification and authentication of synthetic cannabinoids / 中国药科大学学报

@#Abstract: Synthetic cannabinoids (SCs) are synthetic psychoactive substances that can pose a public health risk. The SCs are structurally variable and susceptible to structural modification. The rapid emergence of structurally unknown synthetic cannabinoids has led to new challenges in their identification. In recent years, machine learning has made great progress and has been widely applied to other fields, providing new strategies for the identification of unknown synthetic cannabinoids and the inference of possible sources. This paper describes the principles of commonly used machine learning methods and the application of machine learning techniques to mass spectrometry, Raman spectroscopy, metabolomics and quantitative conformational relationships of synthetic cannabinoids, aiming to provide new ideas for the identification of unknown synthetic cannabinoids.

Study on enzymatic hydrolysis conditions of cannabis,MDMB-4en-PINACA and ADB-BUTINACA in urine / 中国法医学杂志

Objective Synthetic cannabinoids(SCs)will be widely metabolized to phase I metabolites and glucuronide metabolites after entering human body.It is usually difficult to detect the parent drug of SCs in urine.Therefore,it is necessary to undergo de-glucuronidation in the preparation of urine samples.We aimed to optimize the enzymatic hydrolysis methods for SCs detection in urine.Methods We studied enzymatic hydrolysis for the determination of 11-demethyl-9-carboxyl-THC(Δ9-THC-COOH)in THC positive urine samples by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and compared it with the alkaline digestion method.Meanwhile,we studied enzymatic hydrolysis for the determination of the related metabolites in MDMB-4en-PINACA and ADB-BUTINACA positive urine samples.Results The Δ9-THC-COOH glucuronic acid conjugate could be hydrolyzed by adding 3μL β-d-glucuronidase solution(＞100 000 units/mL)for 30 min at 55℃.The MDMB-4en-PINACA M and ADB-BUTINACA M glucuronide conjugates were hydrolyzed by adding 3μL β-d-glucuronidase solution(＞100 000 units/mL)for 30 min at 75℃.Conclusion This study can provide reference for the establishment of rapid,accurate and reliable enzymatic hydrolysis methods when detecting SCs in urine.

Correlation of left atrial function and pulmonary edema in patients with left heart failure on cardiopulmonary ultrasonography.

Objective: Patients with heart failure with pulmonary edema may have declining left atrial (LA) function. Left atrial strain (LAS) imaging enables quantitative assessment of LA function. The aim of this prospective study was to assess the LA function and pulmonary edema in patients with heart failure evaluated by cardiopulmonary ultrasonography. Methods: Two-dimensional speckle-tracking echocardiography for LAS was performed in 115 consecutive patients with congestive heart failure. A semiquantitative B-lines score of pleural effusions was derived by pulmonary ultrasound almost at the same time by combined cardiopulmonary ultrasound. Results: Compared with those who did not have pulmonary edema, patients with pulmonary edema had lower LAS (LASreservoir, 21.5 ± 4.9% vs. 9.2 ± 3.7% [P < 0.001]; LASconduit, 10.7 ± 3.5% vs. 5.1 ± 2.1% [P < 0.001]; LASpump, 11.3 ± 5.4% vs. 4.0 ± 2.7% [P < 0.001]), lower LVEF, TAPSE; and higher SPAP, E/e', larger LA, LV, RV; more severe MR. However, there were no significant between-group differences with respect to sex and body surface area. In patients with pulmonary edema, B-lines score was independently associated with LASreservoir (R = -0.71, P < 0.001); LASpump (R = -0.66, P < 0.001) and LASconduit (R = -0.56, P < 0.001). On multiple linear regression, decreased LASreservoir (beta = -0.61, B = -0.71, P < 0.001) and elevated SPAP (beta = 0.31, B = 0.13, P = 0.01) were significantly associated with B-lines score in heart failure. Conclusion: Declining LA function, especially the reservoir function, assessed by speckle-tracking echocardiography is related to the degree and occurrence of pulmonary edema in patients with left heart failure.

Research Progress on Machine Learning Assisted Non-Targeted Screening Strategy for Identification of Fentanyl Analogs / 法医学杂志

In recent years, the types and quantities of fentanyl analogs have increased rapidly. It has become a hotspot in the illicit drug control field of how to quickly identify novel fentanyl analogs and to shorten the blank regulatory period. At present, the identification methods of fentanyl analogs that have been developed mostly rely on reference materials to target fentanyl analogs or their metabolites with known chemical structures, but these methods face challenges when analyzing new compounds with unknown structures. In recent years, emerging machine learning technology can quickly and automatically extract valuable features from massive data, which provides inspiration for the non-targeted screening of fentanyl analogs. For example, the wide application of instruments like Raman spectroscopy, nuclear magnetic resonance spectroscopy, high resolution mass spectrometry, and other instruments can maximize the mining of the characteristic data related to fentanyl analogs in samples. Combining this data with an appropriate machine learning model, researchers may create a variety of high-performance non-targeted fentanyl identification methods. This paper reviews the recent research on the application of machine learning assisted non-targeted screening strategy for the identification of fentanyl analogs, and looks forward to the future development trend in this field.

Design of children's growth and development data traceability system based on blockchain / 医疗卫生装备

Objective To design a blockchain-based child growth and development data traceability system.Methods A blockchain-based child growth and development data traceability system was designed with B/S architecture,programmed with PHP,HTML5 and JavaScript languages and constructed with the technologies of blockchain data structure,digital signature,hash function and peer-to-peer network,which was composed of five functional modules for user management,patient management,medical examination management,blockchain management and system log.Results The system recorded and shared child growth and development data,realizing traceability of child growth and development data.Conclusion The system developed gains advantages in easy operation,decentralization,high security and privacy,solves the problems in child growth and development data traceability and provides assistance to pediatricians effectively.[Chinese Medical Equipment Journal,2023,44(10):38-43]

Research progress on iron nutritional status of plateletpheresis donors / 中国输血杂志

Apheresis platelets are extensively utilized in clinical practice due to high purity and minimal side effects. These platelets are primarily obtained from regular blood donors. However, there is no consensus on whether plateletpheresis leads to iron deficiency among blood donors. In recent years, increasing attention has been given to the impact of plateletpheresis on the iron nutritional status of these donors. Numerous studies have indicated a prevalence of iron deficiency among plateletpheresis donors. The process of plateletpheresis involves the loss of red blood cells, which can accumulate over time and disrupt iron metabolism, ultimately resulting in iron deficiency anemia. This condition not only affects the physical well-being of the donors but also leads to a decline in their willingness to donate blood. Blood collection and supply institutions should enhance their focus on the iron nutritional status of plateletpheresis donors and implement various measures, such as intensifying health education regarding the significance of iron supplementation, implementing programs for testing iron deficiency, considering the provision of iron supplements and extending blood donation intervals. It is crucial to prevent iron deficiency in plateletpheresis donors. These institutions should explore calculation models that can predict personalized blood donation intervals and iron supplementation strategies, and seek a balanced approach that is optimal for maintaining adequate collections while safeguarding donor health. The article comprehensively reviews literature at home and abroad on the etiology and hazards of iron deficiency in plateletpheresis donors, as well as detection methods and response measures. It serves as a foundation for developing scientific and reasonable care measures for blood donation, while also achieving personalized and scientific management and recruitment strategies for blood donors.

Construction and Validation of Risk Prediction Model for Colorectal Polyps / 胃肠病学

Background: Colorectal polyp is a common lower gastrointestinal disease. Study of its risk factors is of great significance for prevention and treatment of colorectal polyps in clinical practice. Aims: To construct and verify a prediction model for risk of colorectal polyps. Methods: According to the inclusion and exclusion criteria, 254 subjects who were hospitalized for health examination in the Special Internal Medicine Ward of Shanghai Huadong Hospital from January 2019 to June 2021 were enrolled in the study. They were allocated into colorectal polyps group and non⁃polyp group based on the results of colonoscopy. The relevant risk factors of colorectal polyp were collected, including gender, age, cigarette smoking, alcohol drinking, hypertension, diabetes, hyperlipidemia, hyperuricemia, polyps/stones of gallbladder, fatty liver, etc. After screened by LASSO regression model, the selected factors were analyzed by multivariate Logistic regression to build the prediction model and nomogram. Furthermore, the prediction model was evaluated by ROC curve, C index, calibration curve and decision curve, and validated by internal samples. Results: Of the 254 subjects enrolled in the study, 116 cases were in colorectal polyps group and 138 in non⁃polyp group. The risk prediction model identified that gender (OR=2.11, 95% CI: 1.06⁃4.27), age (OR=2.76, 95% CI: 1.17⁃6.73), hypertension (OR=3.23, 95% CI: 1.52⁃7.12), diabetes (OR=4.37, 95% CI: 1.52⁃14.64), hyperlipidemia (OR=3.20, 95% CI: 1.74⁃5.95) and fatty liver (OR= 2.21, 95% CI: 1.13⁃4.35) were independent risk factors for colorectal polyps. The model showed good area under the ROC curve (0.807) and C index (0.807). The decision curve demonstrated that if the threshold probability of colorectal polyps was more than 12%, the model would be of clinical significance. Internal samples were randomly selected for validation, and the C index was 0.793. Conclusions: The prediction model and nomogram constructed by combination of risk factors including gender, age, hypertension, diabetes, hyperlipidemia and fatty liver have a substantial reference value for risk prediction of colorectal polyps.

Matrine inhibits inflammatory response induced by TNF-α in human umbilical vein endothelial cells through miR-25-3p-mediated Klf4 pathway / 中国中药杂志

This study aimed to analyze the effect of matrine on tumor necrosis factor-α(TNF-α)-induced inflammatory response in human umbilical vein endothelial cells(HUVECs) and explore whether the underlying mechanism was related to the miR-25-3p-mediated Krüppel-like factor 4(Klf4) pathway. The HUVEC cell inflammation model was induced by TNF-α stimulation. After 24 or 48 hours of incubation with different concentrations of matrine(0.625, 1.25, and 2.5 mmol·L~(-1)), CCK-8 assay was used to detect cell proliferation. After treatment with 2.5 mmol·L~(-1) matrine for 48 h, the expression of TNF-α, interleukin-6(IL-6), interleukin-1β(IL-1β), and Klf4 mRNA and miR-25-3p was detected by real-time fluorescence-based quantitative PCR, and the protein expression of TNF-α, IL-6, IL-1β, and Klf4 was detected by Western blot. The anti-miR-25-3p was transfected into HUVECs, and the effect of anti-miR-25-3p on TNF-α-induced cell proliferation and inflammatory factors was detected by the above method. The cells were further transfected with miR-25-3p and incubated with matrine to detect the changes in proliferation and expression of related inflammatory factors, miR-25-3p, and Klf4. The targeting relationship between miR-25-3p and Klf4 was verified by bioinformatics analysis and dual luciferase reporter gene assay. The results displayed that matrine could inhibit TNF-α-induced HUVEC proliferation, decrease the mRNA and protein expression of TNF-α, IL-6, and IL-1β, increase the mRNA and protein expression of Klf4, and reduce the expression of miR-25-3p. Bioinformatics analysis showed that there were specific complementary binding sites between miR-25-3p and Klf4 sequences. Dual luciferase reporter gene assay confirmed that miR-25-3p negatively regulated Klf4 expression in HUVECs by targeting. The inhibition of miR-25-3p expression can reduce TNF-α-induced cell proliferation and mRNA and protein expression of TNF-α, IL-6, and IL-1β. MiR-25-3p overexpression could reverse the effect of matrine on TNF-α-induced cell proliferation and the mRNA and protein expression of TNF-α, IL-6, IL-1β, and Klf4. This study shows that matrine inhibits the inflammatory response induced by TNF-α in HUVECs through miR-25-3p-mediated Klf4 pathway.

Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic / 亚洲男科学杂志(英文版)

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

Analysis of Forty-Two Psychoactive Substances in a Single Hair by Micro-Segmental Technique / 法医学杂志

OBJECTIVES@#To establish an LC-MS/MS method based on single hair micro-segmental technique, and verify the detection of 42 psychoactive substances in 0.4 mm hair segments.@*METHODS@#Each piece of single hair was cut into 0.4 mm segments and extracted by sonication and the segments were immersed in dithiothreitol-containing extraction medium. Mobile phase A was the aqueous solution containing 20 mmol/L ammonium acetate, 0.1% formic acid, and 5% acetonitrile. Mobile phase B was acetonitrile. An electrospray ionization source in positive ion mode was used for data acquisition in multiple reaction monitoring (MRM) mode.@*RESULTS@#The 42 psychoactive substances in hair had a good linear relationship within their respective linear ranges (r>0.99), the limits of detection were 0.2-10 pg/mm, the limits of quantification were 0.5-20 pg/mm, the intra-day and inter-day precisions were 1.5%-12.7%, the intra-day and inter-day accuracies were 86.5%-109.2%, the recovery rates were 68.1%-98.2%, and the matrix effects were 71.3%-111.7%. The method was applied to hair samples collected from one volunteer at 28 d after a single dose of zolpidem, with zolpidem detected in 5 hairs was 1.08-1.60 cm near the root tip, and the concentration range was 0.62-20.5 pg/mm.@*CONCLUSIONS@#The micro-segmental technique of single hair analysis can be applied to the investigation of drug-facilitated sexual assault cases.

Research progress on elimination of drugs from human hair after abstinence / 中国法医学杂志

In recent years,forensic toxicologists have conducted a lot of research on the relationship between the concentration of drugs in hair,and the dosage,drug history,etc.Furthermore,the identification and evaluation system of various drugs in hair has been established.Hair analysis technology has been widely used in clinical and forensic medicine.Hair analysis has been widely carried out to identify drug addiction in China.Scientifically judging drug abuse history is of great significance to formulating drug rehabilitation programs and sentencing.The elimination rule of drugs in hair after abstinence,especially in head hair,has attracted the attention of forensic toxicologists,but the related research is relatively few.In this study,the elimination rules of opioids,amphetamines,cocaine,cannabis,and other related markers after abstinence in head hair are reviewed.The factors influencing the elimination of markers in head hair are analyzed and discussed.It is expected to provide a scientific basis for the monitoring and determination of drug rehabilitation.

Cardiopulmonary ultrasound correlates of pleural effusions in patients with congestive heart failure.

BACKGROUND: Pleural effusions are common in patients with congestive heart failure. However, there is a need to assess systematically the correlation between effusion volume, extravascular lung water and echocardiographic parameters. We used combined cardiopulmonary ultrasound to evaluate the relationship between effusion volume, extravascular lung water, and echocardiographic parameters in patients with congestive heart failure. METHODS: Patients who were hospitalized for congestive heart failure underwent combined cardiopulmonary ultrasound. A semiquantitative score of pleural effusions was derived by pulmonary ultrasound and extravascular lung water was estimated by ultrasound lung comets. The measurements were compared with echocardiographic and clinical results. RESULTS: Among 168 patients (median age 66 years, 69.6% men), 102 (60.7%) had pleural effusions, 84.3% bilateral, 10.8% right-sided, and 4.9% left-sided. High pleural effusion scores were associated with high ultrasound lung comet scores (P < 0.0001). Compared with patients without pleural effusions, patients with pleural effusions were significantly older and had higher systolic pulmonary artery pressure (SPAP), NT-proBNP, New York Heart Association scale, larger left atrium, larger right ventricle, more severe mitral regurgitation, and worse left and right heart function. Adjusted for age, multiple logistic regression analysis showed that SPAP (OR 5.688, P = 0.006) and E/A (OR 3.941, P = 0.043) were the significant variables and risk factors associated with pleural effusions in heart failure. CONCLUSION: For patients with left heart failure, the degree of pleural effusions was associated with pulmonary congestion. Elevated SPAP and E/A were the main risk factors for the formation of pleural effusions in patients with congestive heart failure.

Analysis of the Distribution of Total Phosphine and the Characteristics of Phosphine Poisoning in 29 Victims / 法医学杂志

OBJECTIVES@#To study the distribution of total phosphine in phosphine poisoning victims and summarize the characteristics of phosphine poisoning cases.@*METHODS@#The phosphine and its metabolites in the biological samples of 29 victims in 16 phosphine poisoning cases were qualified and quantified by headspace gas chromatography-mass spectrometry.@*RESULTS@#Five victims among 29 were poisoned by ingestion of aluminium phosphide and 24 by inhalation of phosphine gas. Phosphine metabolites were detected in the biological samples of 23 victims, and the concentrations of total phosphine in blood ranged 0.5-34.0 μg/mL. The total concentration of phosphine in liver tissue was up to 71.0 μg/g. Phosphine was not detected in the blood of the other six survived victims, which may be related to the small amount of phosphine exposure and the delay in blood sampling.@*CONCLUSIONS@#The total concentration of phosphine in blood and tissues caused by aluminum phosphine ingestion is higher than that caused by phosphine gas inhalation. The death cases of phosphine inhalation are characterized by long exposure time, repeated exposures and age susceptibility.

Application of Metabonomics in Substance Abuse Toxicology Research / 法医学杂志

Abstrct: Metabonomics is a relative discipline that develops after genomics and proteomics, and it is an important component of systems biology. It uses high-throughput and high-sensitivity instruments to perform qualitative and quantitative analysis of all metabolic components in specific biological samples under limited conditions and combines with multivariate statistics to analyze and process the data to obtain information about physiological, pathological or toxicological changes in organisms. In recent years, because of the complicated mechanism of substance abuse and the continuous emergence of new psychoactive substances, metabonomics is increasingly used in substance abuse research. Therefore, this article reviews the application of metabonomics of substance abuse in the toxic mechanism, the mechanism of addiction and the discovery of biomarkers.

Forensic Analysis of 9 Poisoning Death Cases Caused by Oral Administration of Diphenidol / 法医学杂志

OBJECTIVES@#To analyze the characteristics of diphenidol poisoning cases and to provide clues and technical means for the identification of such cases.@*METHODS@#Biological samples of 9 deaths caused by diphenidol poisoning were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the characteristics of these cases were analyzed retrospectively.@*RESULTS@#Most of the deaths caused by diphenidol poisoning were young females. The dosage was between 60 and 300 tablets, and the mass concentration of diphenidol in the postmortem blood ranged from 0.87 to 99.00 μg/mL. There was no correlation between the dosage and the concentration of diphenidol in the blood.@*CONCLUSIONS@#Diphenidol poisoning has the characteristics of high concealment and lethality. More attention should be paid to suicide cases, and diphenidol should be recommended as a routine detection item to avoid missing detection.

Strategies for Collection and Analysis of Samples in Simple Asphyxiant Gas Acute Poisoning Death Cases / 法医学杂志

At present, the death cases of simple asphyxiant gas acute poisoning are increasing sharply. Common asphyxiant gases in death cases include nitrogen, helium, carbon dioxide, methane, propane, laughing gas, etc. Simple asphyxiant gas has no affinity for biological matrices and escapes quickly, which puts forward new requirements for autopsy procedures, selection and collection of samples, laboratory analysis and identification. This paper reviews the research and development process of death cases caused by simple asphyxiant gas acute poisoning and put forwards the collection and analysis strategy of the samples in such cases. The most valuable biological samples in such cases should be lung tissues associated with the airways, followed by brain tissue and cardiac blood. Gaseous samples from the esophageal cavity, tracheal cavity, pulmonary bronchi, gastric and cardiac areas are also recommended as valuable samples. In the case of postmortem examination, the gas should be injected into gas sample bag directly. Biological materials such as tissue and blood should be directly sealed in head-space vials and analyzed by using the headspace gas chromatography-mass spectrometry.

Application of a UPLC-MS/MS method for quantitative analysis of 29 synthetic cannabinoids and their metabolites, such as ADB-BUTINACA and MDMB-4en-PINACA in human hair in real cases.

In recent years, an increasing number of new synthetic cannabinoids have appeared on the drug trade market. Many of the new synthetic cannabinoids have not previously been reported. At present, there are relatively few methods available for detecting synthetic cannabinoids and their metabolites in hair matrices. Therefore, we established a simple and fast method to simultaneously identify 29 synthetic cannabinoids and their metabolites in human hair by UPLC-MS/MS. Twenty milligrams of hair was used and processed by cryo-grinding and extraction with methanol. A Waters Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 µm) was used for chromatographic separation. Mobile phase A was comprised of 20 mmol/L ammonium acetate, 0.1% formic acid, and 5% acetonitrile and water, and mobile phase B was acetonitrile. The method was fully validated and proved to have good selectivity, accuracy, precision, and satisfactory linearity within the calibrated range. The limit of detection (LOD) ranged from 0.5 to 5 pg/mg, and the lower limit of quantitation (LLOQ) ranged from 1 to 10 pg/mg. The extraction recovery was 36.1-93.3%, and the matrix effect was 19.1-110.0%. The validated method was successfully used to qualitatively and quantitatively analyze 29 synthetic cannabinoids and their metabolites in 59 actual hair samples. MDMB-4en-PINACA had the highest positive detection rate followed by ADB-BUTINACA, and there are multiple synthetic cannabinoid mixed ingestions. This methodology has great potential for the detection of 29 synthetic cannabinoids and their metabolites in forensic cases.

Research hotspots and frontier trends of flame retardants-induced adverse health effects on humans: A visualized bibliometric analysis / 环境与职业医学

Background As emerging environmental contaminants with ecological risks, flame retardants (FRs) exhibit obvious toxicity and persistence. In recent years, as FRs have been widely detected in indoor environments and human samples, the human health risks after FRs exposure are of great concern. Objective To systematically understand the topic evolution, research status, progress, and development trends on the toxicity and health effects of FRs on humans worldwide. Methods We retrieved the literature regarding toxicity of FRs and their effects on human health through the Web of Science database from 2000 to 2020, screened and processed the literature using Endnote software, and analyzed annual publications, important citations, and authors. CiteSpace and VOSviewer were employed to draw co-citation network, keyword co-occurrence network, and keyword clustering map for bibliometric visualization analysis. Results From 2000 to 2020, 472 international papers on toxic effects and human health impacts of FRs were published. In terms of publication years, FRs-related research was mainly divided into three stages: the infancy and exploration stage (2001—2006), when the research on the toxic effects of FRs was just starting; the growth stage (2007—2015), when the risk assessments of FRs on human health were conducted; and the acceleration stage (2016—), when the studies have shifted to the mechanism of FRs damage to human health. In this field, China published the largest number of published articles in the world (177 papers), but the intermediary centrality (reflecting academic influence) was only 0.19, far lower than that of European and American countries such as the Netherlands (0.78), Britain (0.51), and Germany (0.44). Among the top 10 research institutions in terms of the number of articles published, the Chinese Academy of Sciences topped the list with 49 articles. Van der Veen and other researchers had a strong influence on the research of the toxic effects of phosphorous FRs since their papers published in 2012 were cited 1319 times and in the most prominent node in the literature co-citation network. The high-frequency keywords in the literature on the human health effects of FRs were polybrominated diphenyl ethers (217 times), brominated FRs (166 times), toxicity (147 times), FRs (102 times), exposure, polychlorinated biphenyls, in vitro experiment, plasticizer, etc. Through keyword clustering and co-occurrence analyses, it was found that current research is systematically exploring the toxic mechanism of FRs from a perspective integrating pollution source-exposure route-final receptor of pollutants, and is evaluating the environmental health risks via different exposure routes. The visualized bibliometric analysis findings suggested that future studies understand the underlying mechanisms of various cell damage caused by FRs toxicity, identify the key factors of change and their relationships, aiming to provide a scientific basis for targeted prevention of health effects of FRs. Conclusion The research hotspots on the toxic effects of FRs and their effects on human health have changed over time, and the breadth and depth have been increasing. The toxic effects of brominated/phosphorus FRs have always been the mainstream direction in this field. Further studies will focus on the molecular mechanisms of human toxicity after FRs exposure.

The bioinformatics and metabolomics research on anti-hypoxic molecular mechanisms of Salidroside via regulating the PTEN mediated PI3K/Akt/NF-κB signaling pathway.

Salidroside (SAL), a major bioactive compound of Rhodiola crenulata, has significant anti-hypoxia effect, however, its underlying molecular mechanism has not been elucidated. In order to explore the protective mechanism of SAL, the lactate dehydrogenase (LDH), reactive oxygen species (ROS), superoxide dismutase (SOD) and hypoxia-induced factor 1α (HIF-1α) were measured to establish the PC12 cell hypoxic model. Cell staining and cell viability analyses were performed to evaluate the protective effects of SAL. The metabolomics and bioinformatics methods were used to explore the protective effects of salidroside under hypoxia condition. The metabolite-protein interaction networks were further established and the protein expression level was examined by Western blotting. The results showed that 59 endogenous metabolites changed and the expression of the hub proteins of CK2, p-PTEN/PTEN, PI3K, p-Akt/Akt, NF-κB p65 and Bcl-2 were increased, suggesting that SAL could increase the expression of CK2, which induced the phosphorylation and inactivation of PTEN, reduced the inhibitory effect on PI3K signaling pathways and activated the PI3K/Akt/NF-κB survival signaling pathway. Our study provided an important insight to reveal the protective molecular mechanism of SAL as a novel drug candidate.

LY-CoV1404 potently neutralizes SARS-CoV-2 variants

SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization when administered early during COVID-19 disease. However, the emergence of variants of concern has negatively impacted the therapeutic use of some authorized mAbs. Using a high throughput B-cell screening pipeline, we isolated a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody called LY-CoV1404 (also known as bebtelovimab). LY-CoV1404 potently neutralizes authentic SARS-CoV-2 virus, including the prototype, B.1.1.7, B.1.351 and B.1.617.2). In pseudovirus neutralization studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant and retains binding to spike proteins with a variety of underlying RBD mutations including K417N, L452R, E484K, and N501Y. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved with the exception of N439 and N501. Notably, the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of reactivity to amino acid substitutions present among current VOC together with broad and potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants causing COVID-19. In BriefLY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and whose epitope is rarely mutated. HighlightsO_LILY-CoV1404 potently neutralizes SARS-CoV-2 authentic virus and known variants of concern including the B.1.1.529 (Omicron), the BA.2 Omicron subvariant, and B.1.617.2 (Delta) variants C_LIO_LINo loss of potency against currently circulating variants C_LIO_LIBinding epitope on RBD of SARS-CoV-2 is rarely mutated in GISAID database C_LIO_LIBreadth of neutralizing activity and potency supports clinical development C_LI