Association between dietary choline intake and asthma and pulmonary inflammation and lung function: NHANES analysis 2009-2018.

BACKGROUND: Asthma is a chronic inflammatory condition, and choline may alleviate airway inflammation and oxidative stress but studies on the association between dietary choline and asthma remain limited. The purpose of this study is to investigate the associations between dietary choline intake and asthma, as well as pulmonary inflammation and lung function in children and adults. METHODS: In our research, we employed the data of the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018, including 7,104 children and 16,580 adults. We used fractional exhaled nitric oxide (FENO) to assess pulmonary inflammation and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), the FEV1/FVC ratio, peak expiratory flow rate (PEF), predicted FEV1% and predicted FVC% to assess lung function. Binary logistic regression, linear regression, and the restricted cubic splines were used to analyze the associations between dietary choline intake and asthma and pulmonary inflammation and lung function. RESULTS: In children, we observed the positive associations between the natural logarithmic transformation of choline (ln-choline) and ln-FEV1 [ ß:0.011; 95%CI: (0.004,0.018)] and ln-FVC [ ß:0.009; 95%CI: (0.002,0.016)]. In adult males, the ln-choline was positively associated with ln-FEV1[ ß:0.018; 95%CI: (0.011,0.024)], ln-FVC [ ß:0.020; 95%CI: (0.014,0.026)], ln-PEF [ ß:0.014; 95%CI: (0.007,0.022)], ln-predicted FEV1% [ ß: 0.007; 95%CI: (0.001, 0.013)] and ln-predicted FVC%[ ß: 0.010; 95%CI: (0.005, 0.015)] and negatively associated with FENO [ ß: -0.029; 95%CI: (-0.049, -0.009)]. In unadjusted and partially adjusted models, adult females with ln-choline in the highest quartile had 25.2% (95%CI:9.4-38.3%) and 23.8% (95%CI:7.6-37.1%) decreased odds of asthma compared to those with the lowest quartile group. In the dose-response relationships of dietary choline and pulmonary inflammation and lung function indicators in adults, there existed threshold and saturation effects. CONCLUSION: The associations between dietary choline and lung function indicators such as FEV1 and FVC are positive in children and adults. The association between dietary choline and pulmonary inflammation is negative only in adults.

Association between plasma trans fatty acids and serum α-klotho levels in adults in the United States of America: an analysis of the NHANES 2009-2010 datasets.

BACKGROUND: This study aimed to explore the potential associations between trans fatty acid (TFA) and α-klotho levels. METHODS: Datasets from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) were analysed for this study. Multivariable linear regression and restricted cubic spline (RCS) analyses were performed to examine the relationships between plasma TFA and serum α-klotho levels. RESULTS: A total of 1,205 participants were included, with a geometric mean (GM) of 803.60 (95% CI: 787.45, 820.00) pg/mL for serum α-klotho levels. RCS analysis revealed L-shaped relationships between TFA and α-klotho levels. The inflection points for palmitelaidic acid (PA), vaccinic acid (VA), elaidic acid (EA), and total TFA levels were 4.55, 20.50, 18.70, and 46.40 µmol/L, respectively. Before reaching the inflection point, serum α-klotho levels were negatively correlated with plasma PA, VA, EA and total TFA levels, with ß values (95% CI) of -0.15 (-0.24, -0.06), -0.16 (-0.23, -0.09), -0.14 (-0.22, -0.05) and - 0.19 (-0.27, -0.11), respectively. Linolelaidic acid (LA) levels exhibited an inverse and linear association with α-klotho levels ( Pnonlinearity=0.167, Poverall<0.001). L-shaped relationships between TFA and α-klotho levels were also observed in the subgroups of participants who were aged < 65 years, were male, did not exercise, were ex-smokers, and were overweight/obese. CONCLUSIONS: L-shaped correlations between plasma PA, VA, EA, and total TFA levels and serum α-klotho levels were observed among adults in the United States.

A qualitative study of head nurses' experience in China: forced growth during patient safety incidents.

BACKGROUND: In patient safety accidents, nurse managers are indirectly victimized by the pressures from many aspects and become the second victim. This study delves into the experiences of nurse managers in China, aiming to uncover their cognition and provide reference for relevant managers. METHODS: A descriptive phenomenological approach was used to gain insight into the inner reality of nurse leaders' experiences and management perceptions of experiencing patient safety incidents. The data of 15 nurse leaders who experienced patient safety incidents in Bethune Hospital, Shanxi Province, China, were collected via face‒to‒face semi-structured interviews, and the data were analyzed via the 7-step analysis method of Colaizzi. RESULTS: On the basis of the content of the interviews, three themes were identified, the emotional experience of experiencing patient safety events, role dilemmas, the obstruction and conceptual reshaping of nursing management. Eight subthemes as follows: physical and mental health-related symptoms due to passive coping and life and work disorder, self-relief, playing multiple roles with lack of role adjustment ability, blurred role positioning and initial signs of job burnout, event replay is impeded, Inaccurate analysis of safety incidents, subversion and remolding of the nursing management concept. Finally, it can be abstracted as "forced growth in patient safety events". CONCLUSION: Patient safety incidents can lead to negative impacts, role dilemmas, and management confusion for head nurses, but they also promote purposeful rumination, meditation, and growth. Medical institutions should pay attention to special groups that are second victims of head nurses and construct a safety event support system for nurse leaders to improve the post-training and education system for nurse leaders, help them better adapt to their roles, break through their role dilemmas, improve their post-competence, and construct an effective safety event management system.

Associations of perfluoroalkyl substances with metabolic-associated fatty liver disease and non-alcoholic fatty liver disease: NHANES 2017-2018.

OBJECTIVES: This study investigated the potential effects of perfluoroalkyl substance (PFAS) in serum on MAFLD, NAFLD, and liver fibrosis. METHODS: Our sample included 696 participants (≥ 18 years) from the 2017-2018 NHANES study with available serum PFASs, covariates, and outcomes. Using the first quartile of PFAS as the reference group, we used weighted binary logistic regression and multiple ordered logistic regression used to analyze the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and multiple ordinal logistic regression to investigate the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and calculated the odds ratio (OR) and 95% confidence interval for each chemical. Finally, stratified analysis and sensitivity analysis were performed according to gender, age, BMI, and serum cotinine concentration. RESULTS: A total of 696 study subjects were included, including 212 NAFLD patients (weighted 27.03%) and 253 MAFLD patients (weighted 32.65%). The quartile 2 of serum PFOA was positively correlated with MAFLD and NAFLD (MAFLD, OR 2.29, 95% CI 1.05-4.98; NAFLD, OR 2.37, 95% CI 1.03-5.47). PFAS were not significantly associated with liver fibrosis after adjusting for potential confounders in MAFLD and NAFLD. Stratified analysis showed that PFOA was strongly associated with MAFLD, NAFLD, and liver fibrosis in males and obese subjects. In women over 60 years old, PFHxS was also correlated with MAFLD, NAFLD, and liver fibrosis. CONCLUSION: The serum PFOA was positively associated with MAFLD and NAFLD in US adults. After stratified analysis, the serum PFHxS was correlated with MFALD, NAFLD, and liver fibrosis.

Competitive Inhibition of Okanin against Plasmodium falciparum Tyrosyl-tRNA Synthetase.

Malaria is a severe disease that presents a significant threat to human health. As resistance to current drugs continues to increase, there is an urgent need for new antimalarial medications. Aminoacyl-tRNA synthetases (aaRSs) represent promising targets for drug development. In this study, we identified Plasmodium falciparum tyrosyl-tRNA synthetase (PfTyrRS) as a potential target for antimalarial drug development through a comparative analysis of the amino acid sequences and three-dimensional structures of human and plasmodium TyrRS, with particular emphasis on differences in key amino acids at the aminoacylation site. A total of 2141 bioactive compounds were screened using a high-throughput thermal shift assay (TSA). Okanin, known as an inhibitor of LPS-induced TLR4 expression, exhibited potent inhibitory activity against PfTyrRS, while showing limited inhibition of human TyrRS. Furthermore, bio-layer interferometry (BLI) confirmed the high affinity of okanin for PfTyrRS. Molecular dynamics (MD) simulations highlighted the stable conformation of okanin within PfTyrRS and its sustained binding to the enzyme. A molecular docking analysis revealed that okanin binds to both the tyrosine and partial ATP binding sites of the enzyme, preventing substrate binding. In addition, the compound inhibited the production of Plasmodium falciparum in the blood stage and had little cytotoxicity. Thus, okanin is a promising lead compound for the treatment of malaria caused by P. falciparum.

Dietary calcium is inversely associated with hepatitis B virus infection: an analysis of US National Health and Nutrition Examination Survey (NHANES) 2007-2020.

BACKGROUND: There have been studies on the relationship between hepatitis B virus (HBV) infection and diet. We hypothesized HBV infection is related to dietary calcium intake, but the evidence is limited. This study aimed to examine whether dietary calcium intake is independently related to HBV infection in the United States population. METHODS: A total of 20,488 participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES), conducted from 2007 to 2020, were included in this study. Pearson correlation was used to test the association between dietary calcium and serum calcium. The relationships of HBV infection with dietary calcium and serum calcium were assessed by logistic regression models. RESULTS: There was a weak correlation between dietary calcium and serum calcium (r = 0.048). Logistic regression models indicated that HBV infection had a linear negative correlation with dietary calcium (OR 0.37; 95%CI 0.19, 0.76). For each additional 10 mg dietary calcium, the possibility of HBV infection was reduced by 63%. Hepatitis B positive participants had lower serum calcium content than negative participants. Stratified analysis shown the linear relationship between calcium and HBV infection varied among sex, race/ethnicity, and body mass index. CONCLUSION: Our findings demonstrated HBV infection was linearly and inversely correlated with dietary calcium. The current study is expected to offer a fresh perspective on reducing HBV infection.

Evaluation of the Abbott Alinity i Thyroid-Stimulating Hormone Receptor Antibody (TRAb) Chemiluminescent Microparticle Immunoassay (CMIA).

Background: We evaluated the performance of the Abbott thyroid-stimulating hormone receptor antibody chemiluminescent microparticle immunoassay (CMIA) on the Alinity i. Methods: Verification studies for precision, linearity, analytical measuring range, diagnostic cut offs for Graves' disease were performed. We compared the Abbott CMIA to an established TRAb assay (Roche electrochemiluminescence immunoassay). Method comparison analysis was performed between serum and plasma samples on the Abbott CMIA. Results: Repeatability (CV%) for TRAb were 4.07, 1.56, 0.71 and within-laboratory imprecision (CV%) were 4.07, 1.90, 0.71 at 3.0, 10.0, 30.0 IU/L of TRAb, respectively. Linearity and analytical measuring range were verified from 1.07-47.9 IU/L. The limit of the blank was 0 IU/L, limit of detection was 0.15 IU/L, and limit of quantification was 0.5 IU/L. Passing-Bablok analysis showed agreement between the two assays; Y-intercept = 0.787, slope = 1.04. Passing-Bablok analysis also showed agreement between the plasma and serum samples run on the Abbott CMIA; Y-intercept -0.17, slope = 0.97. Conclusions: The Abbott TRAb CMIA on the Alinity i performs within the manufacturer claims for assay precision, linearity, analytical measuring range, limit of blank, limit of detection, limit of quantitation and diagnostic cut offs for Graves' disease. Thus, the Abbott TRAb CMIA on the Alinity i is fit for clinical use.

210-Day Kinetics of Total, IgG, and Neutralizing Spike Antibodies across a Course of 3 Doses of BNT162b2 mRNA Vaccine.

Introduction: We tested the total spike antibody (S-Ab), IgG/IgM S-Ab, and neutralizing antibody (N-Ab) responses of COVID-19-naïve subjects from before their first BNT162b2 vaccination up to 210 days after boosting. Methods: We studied 136 COVID-19-naïve subjects who received three doses of the Pfizer mRNA vaccine (39 males, 97 females, mean age 43.8 ± 13.5 years) from January 2021 to May 2022. Serum was assessed for total S-Ab (Roche), IgG/M (Abbott), and N-Ab (Snibe). Results: Peak antibody levels were measured 20-30 days after each dose, with booster dosing eliciting significantly higher peak antibodies than the second dose: total S-Ab 2219 vs. 19,551 BAU/mL (difference 16,667 BAU/mL, p < 0.0001); IgG 2270 vs. 2932 BAU/mL (difference 660 BAU/mL, p = 0.04); and N-Ab 3.52 vs. 26.4 µg/mL (difference 21.4 µg/mL, p < 0.0001). Only IgM showed a lower peak post-booster antibody titer (COI 2.11 vs. 0.23, difference 1.63, 95% CI 1.05 to 2.38, p < 0.0001). By 180−210 days after the second or third vaccination, total S-Ab/IgG/N-Ab had decreased by 68.7/93.8/73.6% vs. 82.8/86.3/79.5%. The half-lives of IgG and N-Ab antibodies were longer after the third vaccination (IgG: 65 vs. 34 days, N-Ab: 99 vs. 78 days). Conclusion: Total S-Ab/IgG/N-Ab showed a greater increase post-booster, with IgG/N-Ab having a longer half-life.

[Sleep patterns of infants and young children and their association with breastfeeding: a study based on K-means clustering]. / 基于K-meansèšç±»åˆ†æžçš„å©´å¹¼å„¿ç¡çœ æ¨¡å¼åŠä¸Žæ¯ä¹³å–‚å »å ³ç³»çš„ç ”ç©¶.

OBJECTIVES: To investigate the sleep patterns and characteristics of infants and young children and the association between sleep patterns and breastfeeding. METHODS: A general information questionnaire, Brief Infant Sleep Questionnaire (BISQ), and a questionnaire on feeding were used to investigate the sleep quality and feeding patterns of 1 148 infants and young children aged 7-35 months. The K-means clustering method was used to identify sleep patterns and characteristics. A multivariate logistic regression analysis was used to investigate the association between sleep patterns and breastfeeding. RESULTS: Three typical sleep patterns were identified for the 1 148 infants and young children aged 7-35 months: early bedtime and long sleep time; short sleep latency and moderate sleep time; late bedtime, prolonged sleep latency, and insufficient sleep time. The third pattern showed sleep disorders. The multivariate logistic regression analysis showed that compared with formula feeding, exclusive breastfeeding within 6 months after birth reduced the risk of sleep disorder patterns by 69% (OR=0.31, 95%CI: 0.11-0.81). The risk of sleep disorder patterns was reduced by 40% (OR=0.60, 95%CI: 0.38-0.96) in the infants receiving breastfeeding for 4-6 months compared with those receiving breastfeeding for 1-3 months. CONCLUSIONS: There are different sleep patterns in infants and young children, and breastfeeding can reduce the development of sleep disorder patterns.

AtPRMT5-mediated AtLCD methylation improves Cd2+ tolerance via increased H2S production in Arabidopsis.

Arabidopsis (Arabidopsis thaliana) PROTEIN ARGININE METHYLTRANSFERASE5 (PRMT5), a highly conserved arginine (Arg) methyltransferase protein, regulates multiple aspects of the growth, development, and environmental stress responses by methylating Arg in histones and some mRNA splicing-related proteins in plants. Hydrogen sulfide (H2S) is a recently characterized gasotransmitter that also regulates various important physiological processes. l-cysteine desulfhydrase (LCD) is a key enzyme of endogenous H2S production. However, our understanding of the upstream regulatory mechanisms of endogenous H2S production is limited in plant cells. Here, we confirmed that AtPRMT5 increases the enzymatic activity of AtLCD through methylation modifications during stress responses. Both atprmt5 and atlcd mutants were sensitive to cadmium (Cd2+), whereas the overexpression (OE) of AtPRMT5 or AtLCD enhanced the Cd2+ tolerance of plants. AtPRMT5 methylated AtLCD at Arg-83, leading to a significant increase in AtLCD enzymatic activity. The Cd2+ sensitivity of atprmt5-2 atlcd double mutants was consistent with that of atlcd plants. When AtPRMT5 was overexpressed in the atlcd mutant, the Cd2+ tolerance of plants was significantly lower than that of AtPRMT5-OE plants in the wild-type background. These results were confirmed in pharmacological experiments. Thus, AtPRMT5 methylation of AtLCD increases its enzymatic activity, thereby strengthening the endogenous H2S signal and ultimately improving plant tolerance to Cd2+ stress. These findings provide further insights into the substrates of AtPRMT5 and increase our understanding of the regulatory mechanism upstream of H2S signals.

Ultra-Hard (41 GPa) Isotopic Pure 10BP Semiconductor Microwires for Flexible Photodetection and Pressure Sensing.

An urgent demand for electronic and optoelectronic devices able to work in extreme environments promotes a series of research studies on semiconductor materials. Cubic boron phosphide (BP) as a semiconductor material with excellent characteristics shows great application potential. However, since the synthesis conditions required are difficult to achieve and the growth mechanism of BP is still unclear, there are few reports on the basic properties of BP and pure isotope BP, resulting in a narrow understanding of their special physical properties. Here, we successfully obtained highly pure isotopic 10BP crystals by a vapor-liquid-solid (VLS) method unconventionally designed, which successfully overcomes the thermodynamic conflict between the high melting point of the boron element and low sublimation temperature of the phosphorus element. The 10BP achieved owns an aspect ratio as high as 104 and a hardness up to 41 GPa. Besides, as an indirect bandgap semiconductor, it has ultrawide red emission spectra, a p-type conductivity with extremely low resistivity, and excellent photoelectronic and piezoelectric characteristics. Furthermore, compared with other superhard semiconductors like cubic BN and diamond, 10BP has an obvious advantage of lower growth temperature (1200 °C). All these characteristics confirm the prospects owned by 10BP in its applications to the field of high-conductivity, optoelectronic, strain-sensing, and superhard semiconductors.

Adsorption of Cu2+, Cd2+ and Pb2+ in wastewater by modified chitosan hydrogel.

Heavy metal pollution is extraordinary critical, so it is urgent to develop an effective adsorbent to dispose of such pollution. Modified chitosan was combined with polyacrylic acid to form N-carboxymethyl chitosan hydrogel (NCS-hydrogel) adsorbent. The morphology and structure of NCS-hydrogel were analyzed and identified by infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis and other characterization methods. NCS-hydrogel adsorption was used to treat water pollution of Cu, Cd and Pb ions, and the influencing factors of adsorption performance were studied. The intrinsic mechanism of adsorption process was discussed by thermodynamic, kinetic and isotherm models. The results show that the adsorption process of metal ions by NCS-hydrogel meets the spontaneous monolayer chemisorption, and the adsorption process is accompanied by heat release.

Analysis of malnutrition factors for inpatients with chronic kidney disease.

Objective: Malnutrition is a common complication of Chronic Kidney Disease (CKD), and it is the risk factor of CKD prognosis. This study aim to evaluate the nutritional status of inpatients with CKD by using the Subjective Global Assessment (SGA), and to analyze the related factors of malnutrition; and to provide effective reference for early detection of malnutrition status in patients with CKD and timely nutrition intervention. Methods: A total of 426 patients (238 male patients, 188 female patients) aged 62.62 ± 14.61 and 61.14 ± 14.82, respectively admitted to the Nephrology Department of Wannan Medical College from February 2020 to December 2020 were selected and included in to this study by convenience sampling. 426 patients with CKD were evaluated by SGA. Human body weight, hemoglobin (Hb), total protein (TP), albumin (ALB), pre-albumin (PA), qualitative analysis of urinary protein and other laboratory indexes were collected and measured. The correlation between malnutrition and age, education, gender, diet, CKD stage and other factors was analyzed by spearman correlation analysis. Results: The incidence of malnutrition was 85.7% among 426 patients with CKD. Gender, age, education level, CKD stage, diabetes mellitus, weight loss and reduced food intake were related to SGA nutritional assessment (P < 0.05). The expression levels of ALB, PA and Hb in the malnutrition group were significantly lower than those in the normal group (P < 0.05). The degree of malnutrition in CKD patients was significant negatively correlated with the expression levels of ALB (r = -0.188), PA (r = -0.262) and Hb (r = -0.176) (P < 0.05). The multivariate Logistic regression analysis model showed that female (OR = 2.155), ≥60 years old (OR = 7.671), weight loss (OR = 10.691), reduced food intake (OR = 28.953), moderate and severe serum ALB expression (OR = 3.391 and 8.326) were risk factors for malnutrition in patients with CKD (P < 0.05). Malnutrition was correlated with the results of qualitative examination of urinary protein (r = 0.268, P < 0.05). Conclusion: Gender, age, weight loss, reduced food intake, serum ALB expression were independently associated with malnutrition in patients with chronic kidney disease, Hence, the medical staff should take timely and effective nutrition intervention for the patients with malnutrition, delay the renal function damage of patients with CKD and improve the quality of life of patients. Inpatients with CKD, especially women, should increase their dietary intake, maintain normal weight and improve their nutritional status.

Robust SARS-CoV-2 Antibody Responses in Asian COVID-Naïve Subjects 180 Days after Two Doses of BNT162b2 mRNA COVID-19 Vaccine.

BACKGROUND: Subjects with previous COVID-19 have augmented post-vaccination responses. However, the antibody response in COVID-naïve subjects from Southeast Asia is not well known. METHODS: 77 COVID-naïve vaccinees were tested with a full antibody panel [spike antibodies (total (T-Ab), IgG, IgM) and neutralizing antibodies (N-Ab)] pre-vaccination, 10 days after dose 1, and 20/40/60/90/120/150/180 days after dose 2. RESULTS: 10 days after dose 1, 67.6% (48/71)/69.0% (49/71) were T-Ab/IgG positive; only 15.5% (11/71)/14.1% (10/71) were N-Ab/IgM positive. While all (100%) subjects had brisk T-Ab, IgG and N-Ab antibody responses 20 days after complete vaccination, only 79.1% (53/67) were IgM positive. At 180 days (n = 8), T-Ab/IgG/N-Ab were still reactive (lowest T-Ab 186 U/mL, IgG 617 AU/mL, N-Ab 0.39 µg/mL), but IgM was negative in all samples. Spike antibody thresholds of T-Ab 74.1 U/mL (r = 0.95) and IgG 916 AU/mL (r = 0.95) corresponded to N-Ab reactivity (>0.3 µg/mL). Non-linear regression analysis showed that N-Ab would decrease to 0.3 µg/mL by 241 days, whereas T-Ab/IgG would need 470/163 days to reach titers of T-Ab/IgG associated with a N-Ab 0.3 µg/mL (76.4 U/mL and 916 AU/mL respectively). CONCLUSIONS: The antibody responses of T-Ab, IgG and N-Ab remain high and durable even at 180 days. N-Ab titers are expected to remain reactive up to 241 days post-vaccination.

Super-hard "Tanghulu": cubic BP microwire covered with amorphous SiO2 balls.

Superhard materials, which are widely used in metallurgy, petroleum drilling, and mechanical processing, have become the key to the development of processing and manufacturing industry. Boron phosphide is an excellent Superhard candidate material with excellent inert, high thermostability and heat conductivity. However, since synthesizing BP is a hard task, studies of its basic physical properties and applications are hindered to some extent. Here, we obtained a micron-scale "Tanghulu", in the process of synthesizing boron phosphide single crystals using high-temperature flux method. Under a special appearance, "Tanghulu" is a superhard BP microwire covered by melted or amorphous SiO2 and the hardness of the BP microwires is 40.16GPa. On the basis of a comprehensive material analysis, we established the formation mechanism of this Superhard "Tanghulu" as follows: during the heating process with continuous high temperature, SiO2 molecules on the wall of quartz tube escape and diffuse freely and adhere to the boron phosphide rod-shaped single crystal, which will aggregate then under the effect of surface tension to form an isotropic spherical amorphous SiO2 and form the "Tanghulu" finally. Our work can help to broaden the understanding of micro-scale materials.

High-Efficiency Down-Conversion Radiation Fluorescence and Ultrafast Photoluminescence (1.2 ns) at the Interface of Hybrid Cs4PbBr6-CsI Nanocrystals.

The research of fast scintillators in positron emission tomography and other applications based on time-of-flight technology promotes the development of radiation detection. However, because of the current lack of efficient and fast carrier radiation recombination pathways, the research on scintillator radioluminescence (RL) still faces severe challenges. Here, we propose an effective interface carrier transport mechanism: CsI:Na crystal and Cs4PbBr6 nanocrystals (NCs) interface to form a new phase and a continuous heterostructure, providing an effective channel for X-ray excited carrier transfer to Cs4PbBr6. Then, the excited carriers realize efficient recombination luminescence through the self-trapped excitons inside Cs4PbBr6. On the basis of this mechanism, the heterostructure composite scintillator composed of CsI:Na/Cs4PbBr6 exhibits high-efficiency radiant fluorescence and an ultrafast photoluminescence (PL) decay time of 1.22 ns. The effective interface carrier transport shown in this work provides an optimization idea that can be used for reference in the research of fast scintillators.

End-to-end application of model-informed drug development for ertugliflozin, a novel sodium-glucose cotransporter 2 inhibitor.

Model-informed drug development (MIDD) is critical in all stages of the drug-development process and almost all regulatory submissions for new agents incorporate some form of modeling and simulation. This review describes the MIDD approaches used in the end-to-end development of ertugliflozin, a sodium-glucose cotransporter 2 inhibitor approved for the treatment of adults with type 2 diabetes mellitus. Approaches included (1) quantitative systems pharmacology modeling to predict dose-response relationships, (2) dose-response modeling and model-based meta-analysis for dose selection and efficacy comparisons, (3) population pharmacokinetics (PKs) modeling to characterize PKs and quantify population variability in PK parameters, (4) regression modeling to evaluate ertugliflozin dose-proportionality and the impact of uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A9 genotype on ertugliflozin PKs, and (5) physiologically-based PK modeling to assess the risk of UGT-mediated drug-drug interactions. These end-to-end MIDD approaches for ertugliflozin facilitated decision making, resulted in time/cost savings, and supported registration and labeling.

Meta-Analysis of Noncompartmental Pharmacokinetic Parameters of Ertugliflozin to Evaluate Dose Proportionality and UGT1A9 Polymorphism Effect on Exposure.

Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor, is primarily metabolized via glucuronidation by the uridine 5'-diphospho-glucuronosyltransferase (UGT) isoform UGT1A9. This noncompartmental meta-analysis of ertugliflozin pharmacokinetics evaluated the relationship between ertugliflozin exposure and dose, and the effect of UGT1A9 genotype on ertugliflozin exposure. Pharmacokinetic data from 25 phase 1 studies were pooled. Structural models for dose proportionality described the relationship between ertugliflozin area under the plasma concentration-time curve (AUC) or maximum observed plasma concentration (Cmax ) and dose. A structural model for the UGT1A9 genotype described the relationship between ertugliflozin AUC and dose, with genotype information on 3 UGT1A9 polymorphisms (UGT1A9-2152, UGT1A9*3, UGT1A9*1b) evaluated as covariates from the full model. Ertugliflozin AUC and Cmax increased in a dose-proportional manner over the dose range of 0.5-300 mg, and population-predicted AUC and Cmax values for the 5- and 15-mg ertugliflozin tablets administered in the fasted state demonstrated good agreement with the observed data. The largest change in ertugliflozin AUC was in subjects carrying the UGT1A9*3 heterozygous variant, with population-predicted AUC (90% confidence interval) values of 485 ng·h/mL (458 to 510 ng·h/mL) and 1560 ng·h/mL (1480 to 1630 ng·h/mL) for ertugliflozin 5 and 15 mg, respectively, compared with 436 ng·h/mL (418 to 455 ng·h/mL) and 1410 ng·h/mL (1350 to 1480 ng·h/mL), respectively, in wild-type subjects. Overall, the mean effects of the selected UGT1A9 variants on ertugliflozin AUC were within ±10% of the wild type. UGT1A9 genotype did not have any clinically meaningful effects on ertugliflozin exposure in healthy subjects. No ertugliflozin dose adjustment would be required in patients with the UGT1A9 variants assessed in this study.

Raman Tensor of Layered SnS2.

Recently, tin disulfide (SnS2) has become a hot research focus in various fields due to its advantages of a high transistor switching ratio, an adjustable band gap in visible light range, excellent Li storage performance, sensitive gas recognition, and efficient photocatalytic capability. However, at present, studies of its basic structure mostly stay on the regulation related to the number of layers. To maximize the value of SnS2 in the application design, this paper analyzes the angle-resolved polarized Raman spectra of SnS2 crystals grown under high-temperature sealing systems. Under the parallel scattering configuration test of both the sample basal plane and the cross plane, we observed that how the Raman scattering intensity of the two test planes varies with the polarization angle is different. Combining this experimental result with theory support allows us to reach a conclusion that the differential polarizability of the phonon vibration mode along the z-axis of the cross plane of SnS2 is proven to be the strongest. This finding is expected to provide favorable support for the application of structural regulation of SnS2 and work as a reference for studying other van der Waals layered materials with greater potential.

Bioequivalence and Bioavailability of an Orodispersible Tablet of Sildenafil Citrate in Healthy Chinese Male Subjects.

Sildenafil citrate is approved to treat erectile dysfunction. An orally disintegrating tablet (ODT) of sildenafil citrate that does not require swallowing or administration with fluids has been developed. The bioequivalence and bioavailability of sildenafil citrate ODT (50 mg) without and with water were compared with conventional sildenafil citrate tablets (50 mg) in an open-label, randomized crossover study. Healthy Chinese male subjects (n = 36) were allocated to 1 of 6 sildenafil citrate treatment sequences under fasted conditions, and plasma samples for determination of sildenafil concentrations were collected predose through 14 hours postdose. Bioequivalence was demonstrated for sildenafil citrate ODT administered without water relative to the sildenafil citrate tablet administered with water; 90%CIs for the ratios of adjusted geometric means for sildenafil AUClast , Cmax , and AUCinf (ratio, 101.41%; 90%CI, 95.49%-107.70%; ratio, 93.55%; 90%CI, 84.15%-104.00%; and ratio, 101.03%; 90%CI, 94.80%-107.66%; respectively) were wholly contained within the bioequivalence acceptance range of 80% to 125%, indicating bioequivalence criteria were met. Relative bioavailability of sildenafil citrate ODT administered with water to the sildenafil citrate tablet (50 mg) administered with water was 97.10%, 91.43%, and 97.09% with respect to sildenafil AUClast , Cmax , and AUCinf , respectively (90%CI, 91.43%-03.12%, 82.25%-101.65%, and 90.90%-103.71%, respectively). Both sildenafil citrate formulations were generally well tolerated in healthy Chinese men. Sildenafil citrate ODT administered without or with water was bioequivalent to or met bioequivalence criteria compared with conventional sildenafil citrate tablets administered with water under fasted conditions in healthy Chinese men, thus offering a convenient alternative method of oral administration.