The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.

Experimental Simultaneous Learning of Multiple Nonclassical Correlations.

Nonclassical correlations can be regarded as resources for quantum information processing. However, the classification problem of nonclassical correlations for quantum states remains a challenge, even for finite-size systems. Although there exists a set of criteria for determining individual nonclassical correlations, a unified framework that is capable of simultaneously classifying multiple correlations is still missing. In this Letter, we experimentally explored the possibility of applying machine-learning methods for simultaneously identifying nonclassical correlations. Specifically, by using partial information, we applied an artificial neural network, support vector machine, and decision tree for learning entanglement, quantum steering, and nonlocality. Overall, we found that, for a family of quantum states, all three approaches can achieve high accuracy for the classification problem. Moreover, the run time of the machine-learning methods to output the state label is experimentally found to be significantly less than that of state tomography.

The effect of ultrasonic power on the physicochemical properties and antioxidant activities of frosted figs pectin.

Ultrasound has been widely used in industry due to its high energy and efficiency. This study optimized the ultrasonic-assisted extraction (UAE) process of frosted figs pectin (FFP) using response surface methodology (RSM), and further investigated the effect of ultrasonic power on the structural characteristics and antioxidant activities of FFPs. The UAE method of FFP through RSM was optimized, and the optimal extraction process conditions, particle size of 100 mesh, pH value of 1.95, liquid-solid ratio of 47:1 (mL/g), extraction temperature of 50 °C and extraction time of 65 min, were obtained. The extraction rate of FFP under this condition was 37.97 ± 2.56 %. Then, the four FFPs modified by ultrasound were obtained by changing the ultrasonic power. Research had found that ultrasonic power had little effect on the monosaccharide composition, Zeta potential, as well as the thermal stability and appearance structure of the four FFPs. However, ultrasonic power had a significant impact on other properties of FFP: as the ultrasonic power increased, the DM% and particle size decreased continuously, while the total carbohydrate content increased. Meanwhile, ultrasonic power also had a significant impact on antioxidant activities of FFPs. From the research results, it could be seen that different ultrasonic power had certain changes in its spatial structure and properties, and the structural changes also affected the biological activity of FFP. The study of the effects of ultrasonic power on the physicochemical properties and biological activity of FFP lays the foundation for the development and application of FFP in food additives and natural drug carriers.

Postprandial glucagon-like peptide 1 secretion is associated with urinary albumin excretion in newly diagnosed type 2 diabetes patients.

BACKGROUND: Microalbuminuria is an early and informative marker of diabetic nephropathy. Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus (T2DM). AIM: To investigate the association between glucagon-like peptide 1 (GLP-1) and microalbuminuria in newly diagnosed T2DM patients. METHODS: In total, 760 patients were recruited for this cross-sectional study. The GLP-1 levels during a standard meal test and urinary albumin-creatinine ratio (UACR) were determined. RESULTS: Patients with microalbuminuria exhibited lower GLP-1 levels at 30 min and 120 min during a standard meal test than patients with normal albuminuria (30 min GLP-1, 16.7 ± 13.3 pmol vs 19.9 ± 15.6 pmol, P = 0.007; 120 min GLP-1, 16.0 ± 14.1 pmol vs 18.4 ± 13.8 pmol, P = 0.037). The corresponding area under the curve for active GLP-1 (AUCGLP-1) was also lower in microalbuminuria patients (2257, 1585 to 3506 vs 2896, 1763 to 4726, pmol × min, P = 0.003). Postprandial GLP-1 levels at 30 min and 120 min and AUCGLP-1 were negatively correlated with the UACR (r = 0.159, r = 0.132, r = 0.206, respectively, P < 0.001). The prevalence of microalbuminuria in patients with newly diagnosed T2DM was 21.7%, which decreased with increasing quartiles of AUCGLP-1 levels (27.4%, 25.3%, 18.9% and 15.8%). After logistic regression analysis adjusted for sex, age, hemoglobin A1c, body mass index, systolic blood pressure, estimated glomerular filtration rate, homeostasis model assessment of insulin resistance, AUCglucose and AUCglucagon, patients in quartile 4 of the AUCGLP-1 presented a lower risk of microalbuminuria compared with the patients in quartile 1 (odds ratio = 0.547, 95% confidence interval: 0.325-0.920, P = 0.01). A consistent association was also found between 30 min GLP-1 or 120 min GLP-1 and microalbuminuria. CONCLUSION: Postprandial GLP-1 levels were independently associated with microalbuminuria in newly diagnosed Chinese T2DM patients.

[Socio-economic metabolism research: Connotation, discovery, and prospect]. / ç¤¾ä¼šç»æµŽä»£è°¢ç ”ç©¶:å† æ¶µã€å‘çŽ°å’Œå±•æœ›.

Socio-economic metabolism refers to the human-driven migration and transformation of material and energy within and at the boundary of the socio-economic system. The research of socio-economic metabolism has become the core in industrial ecology. We introduced the connotation and basic steps of socio-economic metabolism research with typical cases, and summarized the main findings of socio-economic metabolism research. The research provide a method and model to track the sources, sinks, and flow path of materials in the socio-economic system, reveal how materials and their socio-economic metabolic processes supported modern production and lifestyle. Related studies have clarified the mechanism by which human activities driving the ecological and environmental problems related to material metabolism. It provides the model and database for evaluating the resource efficiency, the trend of resource supply and demand, and the potential of urban mining. We put forward the future directions of socio-economic metabolism research: to increase research objects and enhance the research precision of each object; to expand and deepen the temporal and spatial boundaries of the research system; to introduce and integrate new data sources and research methods; to connect the material flows of socio-economic metabolism with its related ecological and environmental impacts; and to establish a data platform that could be shared, expanded and accumulated.

[The protection of islet ß-cells in db/db mice by combination pioglitazone and glucagon like peptide-1 treatment].

OBJECTIVES: To evaluate the effect of combination of liraglutide, a glucagon-like peptide-1 analogue and pioglitazone, an insulin sensitizer, on diabetic db/db mice. METHODS: Thirty-five 8-week old male db/db mice were divided into control group (n = 8), pioglitazone group (n = 9), liraglutide group (n = 9) and combined therapeutic group (n = 9), which was given normal saline 0.1 ml, 2/d, pioglitazone 24 mg×kg(-1)×d(-1) (feed contained 0.02% pioglitazone) + normal saline 0.1 ml, 2/d, liraglutide 300 mg/kg, 2/d, and pioglitazone 20 mg×kg(-1)×d(-1) (feed contained 0.02% pioglitazone) + liraglutide 300 mg/kg, 2/d, respectively. Liraglutide were given at 8:00 and 16:00 via subcutaneous injection after having been diluted with sterilized normal saline. Effect on glucose, lipid metabolism and islet ß-cell preservation were assessed after 4 weeks. Oneway ANOVA was adopted for statistical analysis. RESULTS: Combination therapy displayed promising anti-hyperglycemic [glycosylated hemoglobin A1c: (4.5 ± 0.6)% vs. (7.3 ± 0.4)%, P < 0.001]. Glucose tolerance were improved assessed by area under curve (AUC) of glucose by intraperitoneal glucose tolerance test (IPGTT) [(1814 ± 91) mmol×min×L(-1) vs. (4042 ± 183) mmol×min×L(-1), P < 0.001]; insulin release response to glucose were also preserved as AUC of insulin by IPGTT was higher [(1639 ± 372) µg×min×L(-1) vs.(834 ± 201) µg×min×L(-1)]. Combination therapy also reduced circulated free fatty acids and TG [(202.0 ± 20.4) µmol/L vs. (272.5 ± 21.7) µmol/L, (0.81 ± 0.28) mmol/L vs. (1.35 ± 0.21) mmol/L], and increased plasma adiponectin [(16.7 ± 2.0) mg/L vs. (10.2 ± 1.8) mg/L]. All P value < 0.05. Islet immunohistochemistry showed that combination therapy significantly increased insulin positive area were [(59.5 ± 1.5)% vs. (22.4 ± 1.5)%] and ratio of Brdu positive ß-cells was three folds than vehicle-treated mice [(2.4 ± 0.5)% vs. (0.8 ± 0.3)%], both greater than each single treatment. Combined therapy significantly improved islet ß cell/α cell distribution, which led to islet recovery. CONCLUSIONS: Combined therapy improves glucose and lipid metabolism, preserves islet ß-cell function and stimulates ß-cell proliferation, greater than either liraglutide or pioglitazone treatment alone.

Factors associated with improvement in waist-to-height ratio among newly diagnosed type 2 diabetes patients treated with acarbose or metformin: A randomized clinical trial study.

BACKGROUND: The waist-to-height ratio (WHtR) is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients. The metformin and acarbose in Chinese as the initial hypoglycaemic treatment trial demonstrated that acarbose and metformin reduced the WHtR after 24 wk of treatment. AIM: To investigate the factors associated with a decrease in the WHtR in newly diagnosed Chinese type 2 diabetes patients receiving acarbose or metformin monotherapy. METHODS: At 24 wk, 343 patients in the acarbose treatment and 333 patients in the metformin treatment were included in this analysis. On the basis of the reduction in the WHtR, these participants were divided into the following two groups: Low ΔWHtR group and high ΔWHtR group. Metabolic and related parameters associated with a high ΔWHtR were investigated using univariate and multivariate logistic regression analyses. RESULTS: A significant decrease in the WHtR was observed in both treatment groups (acarbose: -0.015, 95% confidence interval [CI]: -0.018 to -0.012, P < 0.001; metformin: -0.013, 95%CI: -0.016 to -0.010, P < 0.001). In both the acarbose and metformin groups, the WHtR of the women was more likely to be reduced than that of the men. In the acarbose group, a lower baseline area under the curve of glucagon-like peptide 1 (AUCGLP-1) was associated with a high ΔWHtR (odds ratio [OR] = 0.796, P < 0.001), while a higher baseline AUCGLP-1 was associated with a high ΔWHtR in the patients treated with metformin (OR = 1.133, P = 0.025). Regarding the changes from baseline, an increase in AUCGLP-1 was associated with a high ΔWHtR in the acarbose (OR = 1.121, P = 0.016) but not metformin group. A higher reduction in high-density lipoprotein cholesterol/non-high-density lipoprotein cholesterol was also associated with a high ΔWHtR in the acarbose arm (OR = 20.735, P = 0.001). In the metformin arm, a higher reduction in fasting plasma glucose (OR = 0.843, P = 0.039) and total cholesterol was associated with a high ΔWHtR (OR = 0.743, P = 0.013). CONCLUSION: A lower glucagon-like peptide 1 level and higher increase in glucagon-like peptide 1 are associated with a high reduction in the WHtR in newly diagnosed Chinese diabetes patients receiving treatment with acarbose.

[Mutation analysis in families with 21-hydroxylase deficiency].

OBJECTIVE: To investigate the steroid 21-hydroxylase gene (CYP21) mutations in families with 21-hydroxylase deficiency (21-OHD). METHODS: The CYP21 gene mutations were detected in four patients with 21-hydroxylase deficiency and their relatives. The genomic DNA of the patients was isolated from whole blood.Two pairs of primers were used to amplify the CYP21 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. RESULTS: Six kinds of mutations were found. In the first family, the patient was a compound heterozygote carrying four different mutations (cluster E6, Q318X, A391T, P459H) onCYP21 gene, three mutations (cluster E6, Q318X, A391T) were on her maternal allele, a novel mutation was found:P459H. It located at codon 459 in exon 10 and changing a proline (CCC) to a histidine (CAC), and A391T was a rare mutation. In the second family, two kinds of mutations were found:cluster E6 and R483W. R483W was also a rare mutation. In the third family, the sequencing of the CYP21 gene of two patients revealed a homozygous T to A transition in codon 172 leading to substitution of isoleucine by asparagine (I172N). CONCLUSION: Six kinds of mutations were found in three families with 21-hydroxylase deficiency. Using DNA sequencing we have identified a novel mutation (P459H) and two rare mutations (A391T, R483W) of the CYP21 gene. Although microconversion events are the main cause of mutations in the CYP21 gene, random mutations can also be the cause of 21-hydroxylase deficiency.

Parity and risk of ovarian cysts: Cross-sectional evidence from the Dongfeng-Tongji cohort study.

Little is known about the association between parity and the risk of ovarian cysts. The aim of this study was to examine the association between parity and the risk of ovarian cysts among a population of Chinese women. A total of 20 502 women aged 45-86 years from the Dongfeng-Tongji Cohort study completed baseline questionnaires, medical examination and provided baseline blood samples. Participants were categorized into four groups according to parity (one, two, three, and four or more live births). Logistic regression models were used to investigate the association between parity and the risk of ovarian cysts. The prevalence of ovarian cysts in the study population was 4.0% (816/20 502). Increasing parity was associated with decreasing risk of ovarian cysts without adjustment for any covariates and after age-adjusted model (P<0.001). After adjusting for potential confounders, women who had had four or more live births had lower risk of ovarian cysts (OR: 0.51; 95% CI: 0.27-0.96) compared with women who had had one live birth. There was a consistent but non-significant decreased risk of ovarian cysts for women who had had two, and three live births (OR: 0.85; 95% CI: 0.68-1.05) and (OR: 0.84; 95% CI: 0.59-1.20) respectively compared with women who had had one live birth. It was concluded that higher parity was associated with decreasing risk of ovarian cysts in this population of Chinese women. These findings could be helpful in decision making in clinical practice for gynecologists when evaluating women suspected to have ovarian cysts.