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1.
Article in English | MEDLINE | ID: mdl-38913263

ABSTRACT

Micro-nanobubbles (MNBs) can form reactive oxygen species (ROS) with high oxidizing potential. In this study, nickel-doped metal-organic framework materials (MOFs) capable of activating molecular oxygen were synthesized using trivalent arsenic (As(III)) as a target pollutant and combined with peroxymonosulfate (PMS) to construct a MOF/MNB/PMS system. The results included the rapid oxidation of As(III), the successful absorption of oxidized As(V), and finally the efficient removal of As. The effects of pH, amount of PMS used, and preparation time of MNBs on the As removal performance of the MOF/MNB/PMS system were investigated experimentally. The changes in the properties of the materials before and after the reaction were analyzed by XPS, and it was found that the main active sites on the surface of the MOFs were the metal elements and the pyridine nitrogen near the carbon atom. The regular morphology and elemental composition of the MOFs were determined by TEM scanning and EDS test, which indicated the presence of nickel. XRD tests before and after the reaction showed that the MOFs were structurally stable. The results of the free radical burst experiments show that the single linear oxygen (1O2) is the main active substance in the system, and that the MNBs are key factors by which the system achieves efficient oxidation performance. In addition to providing a sustainable supply of molecular oxygen to the MOFs during the reaction process, coupling the MNBs with PMS was found to improve the oxidation capacity of the system. The results of this study thus provide a new concept for As removal and advanced oxidation in water bodies.

2.
Nat Commun ; 15(1): 5038, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38866771

ABSTRACT

Transition metal compounds with kagome structure have been found to exhibit a variety of exotic structural, electronic, and magnetic orders. These orders are competing with energies very close to each other, resulting in complex phase transitions. Some of the phases are easily observable, such as the charge density wave (CDW) and the superconducting phase, while others are more challenging to identify and characterize. Here we present magneto-transport evidence of a new phase below ~ 35 K in the kagome topological metal CsV3Sb5 (CVS) thin flakes between the CDW and the superconducting transition temperatures. This phase is characterized by six-fold rotational symmetry in the in-plane magnetoresistance (MR) and is connected to the orbital current order in CVS. Furthermore, the phase is characterized by a large in-plane negative magnetoresistance, which suggests the existence of a three-dimensional, magnetic field-tunable orbital current ordered phase. Our results highlight the potential of magneto-transport to reveal the interactions between exotic quantum states of matter and to uncover the symmetry of such hidden phases.

3.
PLoS One ; 19(5): e0303189, 2024.
Article in English | MEDLINE | ID: mdl-38768165

ABSTRACT

OBJECTIVES: To establish a rat model that accurately replicates the clinical characteristics of male infertility (MI) with Liver Depression and Kidney Deficiency (LD & KD) and investigate the pathogenesis. METHODS: After subjecting the rats to chronic restraint stress (CRS) and adenine treatment, a series of tests were conducted, including ethological assessments, evaluations of reproductive characteristics, measurements of biochemical parameters, histopathological examinations, and analyses of urinary metabolites. Additionally, bioinformatics predictions were performed for comprehensive analysis. RESULTS: Compared to the control, the model exhibited significant manifestations of MI with LD & KD, including reduced responsiveness, diminished frequency of capturing estrous female rats, and absence of mounting behavior. Additionally, the kidney coefficient increased markedly, while the coefficients of the testis and epididymis decreased significantly. Sperm counts and viabilities decreased notably, accompanied by an increase in sperm abnormalities. Dysregulation of reproductive hormone levels in the serum was observed, accompanied by an upregulation of proinflammatory cytokines expressions in the liver and kidney, as well as exacerbated oxidative stress in the penile corpus cavernosum and testis. The seminiferous tubules in the testis exhibited a loose arrangement, loss of germ cells, and infiltration of inflammatory cells. Furthermore, utilizing urinary metabolomics and bioinformatics analysis, 5 key biomarkers and 2 crucial targets most closely linked to MI were revealed. CONCLUSION: The study successfully established a clinically relevant animal model of MI with LD & KD. It elucidates the pathogenesis of the condition, identifies key biomarkers and targets, and provides a robust scientific foundation for the prediction, diagnosis, and treatment of MI with LD & KD.


Subject(s)
Biomarkers , Disease Models, Animal , Infertility, Male , Animals , Male , Rats , Biomarkers/metabolism , Infertility, Male/metabolism , Infertility, Male/etiology , Testis/metabolism , Testis/pathology , Kidney/metabolism , Kidney/pathology , Rats, Sprague-Dawley , Liver/metabolism , Liver/pathology , Oxidative Stress , Liver Diseases/metabolism , Liver Diseases/pathology , Renal Insufficiency/metabolism , Renal Insufficiency/pathology , Renal Insufficiency/etiology
4.
Front Public Health ; 12: 1365906, 2024.
Article in English | MEDLINE | ID: mdl-38784569

ABSTRACT

The quality of water in urban parks is closely related to people's daily lives, but the pollution caused by microplastics in park water and sediments has not been comprehensively studied. Therefore, eight typical parks in the urban area of Changsha, China, were selected, and Raman spectroscopy was used to explore the spatial distributions and compositions of the microplastics in the water and sediments, analyze their influencing factors, and evaluate their environmental risks. The results showed that the abundances of surface water microplastics in all parks ranged from 150 to 525 n L-1, and the abundances of sediment microplastics ranged from 120 to 585 n kg-1. The microplastics in the surface water included polyethylene terephthalate (PET), chlorinated polyethylene (CPE), and fluororubber (FLU), while those in the sediments included polyvinyl chloride (PVC), wp-acrylate copolymer (ACR), and CPE. Regression analyses revealed significant positive correlations between human activities and the abundances of microplastics in the parks. Among them, the correlations of population, industrial discharge and domestic wastewater discharge with the abundance of microplastics in park water were the strongest. However, the correlations of car flow and tourists with the abundance of microplastics in park water were the weakest. Based on the potential ecological risk indices (PERI) classification assessment method, the levels of microplastics in the waters and sediments of the eight parks were all within the II-level risk zone (53-8,549), among which the risk indices for Meixi Lake and Yudai Lake were within the IV risk zone (1,365-8,549), which may have been caused by the high population density near the park. This study provides new insights into the characteristics of microplastics in urban park water and sediment.


Subject(s)
Environmental Monitoring , Geologic Sediments , Lakes , Microplastics , Water Pollutants, Chemical , Wetlands , China , Microplastics/analysis , Risk Assessment , Geologic Sediments/chemistry , Water Pollutants, Chemical/analysis , Lakes/chemistry , Humans , Cities , Parks, Recreational , Spectrum Analysis, Raman
5.
J Biopharm Stat ; 34(1): 78-89, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-36710402

ABSTRACT

In vitro dissolution profile has been shown to be correlated with the drug absorption and has often been considered as a metric for assessing in vitro bioequivalence between a test product and corresponding reference one. Various methods have been developed to assess the similarity between two dissolution profiles. In particular, similarity factor f2 has been reviewed and discussed extensively in many statistical articles. Although the f2 lacks inferential statistical properties, the estimation of f2 and its various modified versions were the most widely used metric for comparing dissolution profiles. In this paper, we investigated performances of the naive f2 estimate method, bootstrap f2 confidence interval method and bias corrected-accelerated (BCa) bootstrap f2 confidence interval method for comparing dissolution profiles. Our studies show that naive f2 estimate method and BCa bootstrap f2 confidence interval method are unable to control the type I error rate. The bootstrap f2 confidence interval method can control the type I error rate under a specific level. However, it will cause great conservatism on the power of the test. To solve the potential issues of the previous methods, we recommended a bootstrap bias corrected (BC) f2 confidence interval method in this paper. The type I error rate, power and sensitivity among different f2 methods were compared based on simulations. The recommended bootstrap BC f2 confidence interval method shows better control of type I error than the naive f2 estimate method and BCa bootstrap f2 confidence interval method. It also provides better power than the bootstrap f2 confidence interval method.


Subject(s)
F Factor , Humans , Solubility , Therapeutic Equivalency , Bias
6.
Mol Neurobiol ; 61(3): 1404-1416, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37715891

ABSTRACT

Imbalance between excitation and inhibition is an important cause of epilepsy. Salt-inducible kinase 1 (SIK1) gene mutation can cause epilepsy. In this study, we first found that the expression of SIK3 is increased after epilepsy. Furthermore, the role of SIK3 in epilepsy was explored. In cultured hippocampal neurons, we used Pterosin B, a selective SIK3 inhibitor that can inhibit epileptiform discharges induced by the convulsant drug cyclothiazide (a positive allosteric modulator of AMPA receptors, CTZ). Knockdown of SIK3 inhibited epileptiform discharges and increased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). In mice, knockdown of SIK3 reduced epilepsy susceptibility in a pentylenetetrazole (a GABAA receptor antagonist, PTZ) acute kindling experiment and increased the expression of GABAA receptor α1. In conclusion, our results suggest that blockade or knockdown of SIK3 can inhibit epileptiform discharges and that SIK3 has the potential to be a novel target for epilepsy treatment.


Subject(s)
Epilepsy , Receptors, GABA-A , Animals , Mice , Rats , Epilepsy/drug therapy , Epilepsy/genetics , gamma-Aminobutyric Acid , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Rats, Sprague-Dawley , Receptors, GABA-A/genetics , Receptors, GABA-A/metabolism , Seizures/drug therapy , Seizures/genetics , Seizures/chemically induced
7.
Small ; 20(22): e2307853, 2024 May.
Article in English | MEDLINE | ID: mdl-38143294

ABSTRACT

Converting carbon dioxide (CO2) into fuel and high-value-added chemicals is considered a green and effective way to solve global energy and environmental problems. Covalent triazine frameworks (CTFs) are extensively utilized as an emerging catalyst for photo/electrocatalytic CO2 reduction reaction (CO2RR) recently recognized for their distinctive qualities, including excellent thermal and chemical stability, π-conjugated structure, rich nitrogen content, and a strong affinity for CO2, etc. Nevertheless, single-component CTFs have the problems of accelerated recombination of photoexcited electron-hole pairs and restricted conductivity, which limit their application for photo/electrocatalytic CO2RR. Therefore, emphasis will then summarize the strategies for enhancing the photocatalytic and electrocatalytic efficiency of CTFs for CO2RR in this paper, including atom doping, constructing a heterojunction structure, etc. This review first illustrates the synthesis strategies of CTFs and the advantages of CTFs in the field of photo/electrocatalytic CO2RR. Subsequently, the mechanism of CTF-based materials in photo/electrocatalytic CO2RR is described. Lastly, the challenges and future prospects of CTFs in photo/electrocatalytic CO2RR are addressed, which offers a fresh perspective for the future development of CTFs in photo/electrocatalytic CO2RR.

8.
Front Public Health ; 11: 1272347, 2023.
Article in English | MEDLINE | ID: mdl-37860799

ABSTRACT

Introduction: The effects of restoration and inspiration in the therapeutic landscape of natural environments on visitors during the COVID-19 pandemic have been well-documented. However, less attention has been paid to the heterogeneity of visitor perceptions of health and the potential impacts of experiences in wetland parks with green and blue spaces on visitors' overall perceived health. In this study, we investigate the impact of the restorative landscapes of wetland parks on visitors' health perceptions in the context of the COVID-19 pandemic. Methods: In our survey, 582 respondents participated in an online questionnaire. We analyzed the respondents' health perceptions in terms of latent class analysis, used multinomial logistic regression to determine the factors influencing the potential categorization of health perceptions, and used structural equation modeling to validate the relationships between health perceptions of different groups and landscape perceptions of wetland parks, restorative experiences, and personality optimistic tendencies. Results: The results identified three latent classes of health perceptions. Gender, marital status, education, occupation, income, distance, frequency of activities, and intensity of activities were significant predictors of potential classes of perceived health impacts among wetland park visitors. Discussion: This study revealed the nature and strength of the relationships between health perception and landscape perception, restorative experience, and dispositional optimism tendencies in wetland parks. These findings can be targeted not only to improve visitor health recovery but also to provide effective references and recommendations for wetland park design, planning, and management practices during and after an epidemic.


Subject(s)
COVID-19 , Wetlands , Humans , Pandemics , Environment , Perception
9.
Chemosphere ; 345: 140436, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37838028

ABSTRACT

Residual flotation chemicals in beneficiation wastewater seriously threaten local ecosystems, such as groundwater or soil, and must be treated effectively. Currently, the degradation of organic pollutants using nitrided MOFs-derived carbon to activate persulfate (PDS) has attracted considerable attention. Hence, we developed a new synthetic strategy to load dopamine hydrochloride (PDA) onto MOF-5-derived porous carbon (PC) to form NPC, and the degradation of a typical flotation Aniline aerofloat (AAF) at high salinity by a low dose of the NPC/PDS system was investigated. Several characterization analyses such as TEM, XRD, Raman, FT-IR and XPS demonstrated that the nitrogen-rich indolequinone unit in PDA provided nitrogen to PC during the pyrolysis process. This enabled the core-shell structure of NPC and the synergy among the multiple components to induce the AAF degradation by PDS over a wide pH scale in a short period of time. It was deduced that the degradation of AAF by the NPC-8/PDS system was a non-radical pathway dominated by 1O2, which relied mainly on the conversion of superoxide radicals (O2•-) and surface-bound radicals. Among them, the pyridine N in the sp2 hybrid carbon was considered as a possible active site. This non-radical pathway was resistant to pH changes and background substances in the water, and well overcame the inhibition of the reaction by natural organic substances and inorganic anions in natural water. In this study, A novel approach to the synthesis of homogeneous MOFs nuclear-derived porous carbon was proposed and the application of MOFs-derived porous carbon for AAF remediation of mineral processing wastewater was broadened.


Subject(s)
Carbon , Wastewater , Carbon/chemistry , Ecosystem , Spectroscopy, Fourier Transform Infrared , Aniline Compounds , Water , Nitrogen
10.
Front Pharmacol ; 14: 1207075, 2023.
Article in English | MEDLINE | ID: mdl-37693907

ABSTRACT

Background: Stroke survivors are at significantly increased risk of cognitive impairment, which affects patients' independence of activities of daily living (ADLs), social engagement, and neurological function deficit. Many studies have been done to evaluate the efficacy and safety of post-stroke cognitive impairment (PSCI) treatment, and due to the largely inconsistent clinical data, there is a need to summarize and analyze the published clinical research data in this area. Objective: An umbrella review was performed to evaluate the efficacy and safety of PSCI therapies. Methods: Three independent authors searched for meta-analyses and systematic reviews on PubMed, the Cochrane Library, and the Web of Science to address this issue. We examined ADL and Barthel index (BI), Montreal Cognitive Assessment (MoCA), neurological function deficit as efficacy endpoints, and the incidence of adverse events as safety profiles. Results: In all, 312 studies from 19 eligible publications were included in the umbrella review. The results showed that angiotensin-converting enzyme inhibitors (ACEI) and N-methyl-D-aspartate (NMDA) antagonists, cell therapies, acupuncture, and EGB76 can improve the MoCA and ADL, and the adverse effects were mild for the treatment of PSCI. Moreover, Vinpocetine, Oxiracetam, Citicoline, thrombolytic therapy, Actovegin, DL-3-n-Butylphthalide, and Nimodipine showed adverse events or low article quality in patients with PSCI. However, the research evidence is not exact and further research is needed. Conclusion: Our study demonstrated that ACEI inhibitors (Donepezil) and NMDA antagonists (Memantine), EGB761, and acupuncture are the ADL and BI, MoCA, and neurological function deficit medication/therapy, respectively, for patients with PSCI. Clinical Trial Registration: https://inplasy.com/inplasy-2022-11-0139/; Identifier: INPLASY2022110139.

11.
J Fungi (Basel) ; 9(8)2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37623590

ABSTRACT

Hyaloperonospora parasitica is a global pathogen that can cause leaf necrosis and seedling death, severely threatening the quality and yield of cabbage. However, the genome sequence and infection mechanisms of H. parasitica are still unclear. Here, we present the first whole-genome sequence of H. parasitica isolate BJ2020, which causes downy mildew in cabbage. The genome contains 4631 contigs and 9991 protein-coding genes, with a size of 37.10 Mb. The function of 6128 genes has been annotated. We annotated the genome of H. parasitica strain BJ2020 using databases, identifying 2249 PHI-associated genes, 1538 membrane transport proteins, and 126 CAZy-related genes. Comparative analyses between H. parasitica, H.arabidopsidis, and H. brassicae revealed dramatic differences among these three Brassicaceae downy mildew pathogenic fungi. Comprehensive genome-wide clustering analysis of 20 downy mildew-causing pathogens, which infect diverse crops, elucidates the closest phylogenetic affinity between H. parasitica and H. brassicae, the causative agent of downy mildew in Brassica napus. These findings provide important insights into the pathogenic mechanisms and a robust foundation for further investigations into the pathogenesis of H. parasitica BJ2020.

12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 39(6): 552-557, 2023 Jun.
Article in Chinese | MEDLINE | ID: mdl-37340924

ABSTRACT

Group 2 innate lymphoid cells (ILC2s) are the "mirror cells" of Th2 cells. Although the total cell number of ILC2s is far less than that of CD4+ Th2 cells in the body, the activated ILC2s have a more powerful biological activity than CD4+ Th2 cells and can rapidly enhanced Th2-cell inflammatory reaction. It plays an important role in the pathogenesis of allergic respiratory diseases. The transmitters that activate ILC2s include inflammatory cytokines (IL-33, IL-25, TSLP, IL-4, IL-9), lipid transmitters (prostaglandins, leukotrienes), and other activating transmitters (ICOS, Complement C3a, neuropeptide receptor, vasoactive intestinal peptide and calcitonin gene-related peptide, etc). Activated ILC2s produce large amounts of IL-4, IL-5, IL-9, IL-13, and amphiregulin and other inflammatory mediators, and induce airway hyperresponsiveness, mucus secretion and airway remodeling and other respiratory allergic reactions. Therefore, respiratory allergic diseases, especially steroid-dependent asthma, could be treated potentially by inhibiting the activation of ILC2s. Hereby, we summarized the immunobiology of ILC2s, the initiation of ILC2s in allergic inflammation, the relationship between ILC2s and respiratory allergic diseases, and the recent advances in biological agents targeted by ILC2s.


Subject(s)
Hypersensitivity , Respiratory Tract Diseases , Humans , Immunity, Innate , Interleukin-4 , Interleukin-9 , Lymphocytes , Cytokines , Inflammation
13.
CNS Neurosci Ther ; 29(11): 3460-3478, 2023 11.
Article in English | MEDLINE | ID: mdl-37269088

ABSTRACT

INTRODUCTION: As a devastating neurological disease, spinal cord injury (SCI) results in severe tissue loss and neurological dysfunction. Pregnane X receptor (PXR) is a ligand-activated nuclear receptor with a major regulatory role in xenobiotic and endobiotic metabolism and recently has been implicated in the central nervous system. In the present study, we aimed to investigate the role and mechanism of PXR in SCI. METHODS: The clip-compressive SCI model was performed in male wild-type C57BL/6 (PXR+/+ ) and PXR-knockout (PXR-/- ) mice. The N2a H2 O2 -induced injury model mimicked the pathological process of SCI in vitro. Pregnenolone 16α-carbonitrile (PCN), a mouse-specific PXR agonist, was used to activate PXR in vivo and in vitro. The siRNA was applied to knock down the PXR expression in vitro. Transcriptome sequencing analysis was performed to discover the relevant mechanism, and the NRF2 inhibitor ML385 was used to validate the involvement of PXR in influencing the NRF2/HO-1 pathway in the SCI process. RESULTS: The expression of PXR decreased after SCI and reached a minimum on the third day. In vivo, PXR knockout significantly improved the motor function of mice after SCI, meanwhile, inhibited apoptosis, inflammation, and oxidative stress induced by SCI. On the contrary, activation of PXR by PCN negatively influenced the recovery of SCI. Mechanistically, transcriptome sequencing analysis revealed that PXR activation downregulated the mRNA level of heme oxygenase-1 (HO-1) after SCI. We further verified that PXR deficiency activated the NRF2/HO-1 pathway and PXR activation inhibited this pathway in vitro. CONCLUSION: PXR is involved in the recovery of motor function after SCI by regulating NRF2/HO-1 pathway.


Subject(s)
Pregnane X Receptor , Spinal Cord Injuries , Animals , Male , Mice , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Mice, Inbred C57BL , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Pregnane X Receptor/deficiency , Pregnane X Receptor/genetics , Spinal Cord Injuries/genetics , Spinal Cord Injuries/metabolism
14.
J Hazard Mater ; 455: 131589, 2023 Aug 05.
Article in English | MEDLINE | ID: mdl-37163890

ABSTRACT

Although water metalloid pollution is widely studied, the effect of the combined pollution of organic matter and metalloids in mining water and, especially, the possible interaction mechanisms between metalloids and flotation reagents, are both poorly understood. Existence of mixed pollution of metalloids and organic compounds tends to cause more serious harm to natural organisms. In this study, a synergistic removal of arsenite (As(III)) and butyl xanthate (Bx) in an advanced oxidation system was reported using biochar-based catalyst loaded with nano-zero-valent iron from an inexpensive iron source (iron slag) to activate peroxodisulfate. The removal efficiencies were improved by 30 % in the co-existence of As(III) and Bx compared to those of the single pollutant. The theoretical calculations, especially frontier molecular orbital theory, revealed the generation of [AsO2-OH]•- by the combination of As(II) with •OH. This [AsO2-OH]•- participated in the oxidative degradation of Bx with high activity and combined with the sulfur falling off Bx after the reaction to form a novel Fe-As-S complex as indicated by X-ray absorption +fine structure analysis. Overall, this study reports the generation of low-valent arsenic active substances of [AsO2-OH]•- and their effect on the removal of organic pollution containing S atoms in advanced oxidation systems under typical mining water conditions with the coexistence of As(III) and expands the understanding and application of traditional free radicals.

15.
Molecules ; 28(5)2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36903365

ABSTRACT

Four new germacrane sesquiterpene dilactones, 2ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (1), 3ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (2), 1α,3ß-dihydroxy-4,9-germacradiene-12,8:15,6-diolide (3), and (11ß,13-dihydrodeoxymikanolide-13-yl)-adenine (4), together with five known ones (5-9) were isolated from the aerial parts of Mikania micrantha. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 4 is featured with an adenine moiety in the molecule, which is the first nitrogen-containing sesquiterpenoid so far isolated from this plant species. These compounds were evaluated for their in vitro antibacterial activity against four Gram-(+) bacteria of Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC) and Curtobacterium. flaccumfaciens (CF), and three Gram-(-) bacteria of Escherichia coli (EC), Salmonella. typhimurium (SA), and Pseudomonas Solanacearum (PS). Compounds 4 and 7-9 were found to show strong in vitro antibacterial activity toward all the tested bacteria with the MIC values ranging from 1.56 to 12.5 µg/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 µg/mL, which was close to reference compound vancomycin (MIC 3.125 µg/mL). Compounds 4 and 7-9 were further revealed to show in vitro cytotoxic activity toward human tumor A549, HepG2, MCF-7, and HeLa cell lines, with IC50 values ranging from 8.97 to 27.39 µM. No antibacterial and cytotoxic activity were displayed for the other compounds. The present research provided new data to support that M. micrantha is rich in structurally diverse bioactive compounds worthy of further development for pharmaceutical applications and for crop protection in agricultural fields.


Subject(s)
Antineoplastic Agents , Methicillin-Resistant Staphylococcus aureus , Mikania , Humans , Mikania/chemistry , Sesquiterpenes, Germacrane , HeLa Cells , Anti-Bacterial Agents/chemistry , Bacteria , Microbial Sensitivity Tests
16.
AAPS PharmSciTech ; 24(1): 35, 2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36631718

ABSTRACT

FDA's experience to date has shown that completion of stability data requirements is one of the most observed challenges for applicants of New Drug Applications (NDAs) with an expedited review designation. Since NDAs submitted under these expedited pathways often have limited available real-time stability data from the primary batches, Modeling Approaches to Reimagine Stability (MARS) have been proposed to support establishment of tentative retest periods of the drug substance and/or expiration dating period (shelf-life) of the drug product. MARS incorporate statistical principles and available tools as a part of the predictive models. In this study, a data mining exercise has been conducted with regulatory submissions of Investigational New Drug (IND) Applications, NDAs, and Abbreviated New Drug Applications (ANDAs) containing MARS data. The case studies presented herein demonstrate how MARS data has been applied to regulatory scenarios involving prediction of retest and/or shelf-life, bridging major development changes, and confirming that no degradation has been observed or predicted. Using the assumption of a linear time trend for those cases that do not display sufficient degradation to conduct MARS for projection of an expiration date, an analysis of covariance (ANCOVA) model is developed and described herein to test the hypothesis of zero slope by a p-value method. Our results show that the application of MARS adequately supported establishment of a tentative commercially viable retest date/shelf-life, thus enabling earlier access to critical drugs for patients with unmet medical needs.


Subject(s)
Time Factors , Humans , United States , Forecasting , United States Food and Drug Administration
17.
BMC Public Health ; 23(1): 14, 2023 01 03.
Article in English | MEDLINE | ID: mdl-36597050

ABSTRACT

BACKGROUND: Current studies in most Western countries have largely focused on body mass index (BMI) as an important risk factor for impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which have different pathophysiological bases. In people with obesity, the prevalence of IGT is higher and the prevalence of IFG is lower. The prevalence of IGT in the Asian population is higher than that in the white population, and the obesity rate in China is still increasing. However, few cohort studies explore the relationship between BMI and the incidence of IGT and IFG in China. We aimed to explore the relationship between BMI and the risk of IGT and IFG in Chinese adults and analyze the differences between them. METHODS: The baseline data were obtained from the 2010 China Chronic Disease and Risk Factor Surveillance, of which 20 surveillance sites were followed up from 2016 to 2017. Finally, in this study, a total of 5,578 studies were grouped into BMI categories of underweight (BMI < 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), and obesity (≥ 28.0 kg/m2). We used the unconditional logistic regression model to analyze the relationship between BMI and the risk of IGT and IFG. RESULTS: During an average follow-up of 6.4 years, 562 developed IGT and 257 developed IFG. After age, gender, urban and rural areas, physical activity, family history of diabetes, hypertension, abdominal obesity, dyslipidemia, and other factors were adjusted, overweight increased the risk of IGT by 35% [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.08-1.70], and obesity increased the risk of IGT by 77% (OR 1.77, 95% CI 1.27-1.47). After the factors consistent with the above were adjusted, only obesity increased the risk of IFG by 122% (OR 2.22, 95% CI 1.39-3.54). CONCLUSIONS: In China, obesity is an important risk factor for IGT and IFG, and the risk of IGT increases during the overweight stage.


Subject(s)
Glucose Intolerance , Prediabetic State , Adult , Humans , Glucose Intolerance/epidemiology , Body Mass Index , Prospective Studies , Overweight/epidemiology , East Asian People , Blood Glucose , Prediabetic State/epidemiology , Obesity/epidemiology , Fasting
18.
Front Public Health ; 11: 1294360, 2023.
Article in English | MEDLINE | ID: mdl-38186712

ABSTRACT

Introduction: The COVID-19 pandemic, which began in the last quarter of 2019, has had a significant impact on urban transportation. With increasing demand for urban transport, the internal roads and public spaces of university campuses play an important role in facilitating commuting and communication between various functional zones. While considerable research has been conducted on route planning, pedestrian-vehicle segregation, and safety management in the internal transportation environment of university campuses, empirical investigations exploring barrier-free inclusive campus environment design and the subjective evaluation of road and public space users in the aftermath of the COVID-19 pandemic are lacking. Recent developments in travel behavior models and positive psychology have led to an increased focus on the correlation among subjective perceptions, attitudes, emotions, and commuting satisfaction in urban transportation and planning design. Methods: To elucidate this relationship, a study was conducted on the new campus of Central South University in Changsha, Hunan Province, China. Using 312 valid samples, a structural equation model was constructed to analyse the relationship between commuting satisfaction and the barrier-free environment perception of university students regarding the internal transportation environment of the campus. Results: The results revealed that individuals' instantaneous barrier-free environment perceptions and long-term established positive emotions had a significant positive effect on commuting satisfaction. Furthermore, positive emotions were found to mediate the relationship between commuting attitudes induced by COVID-19, barrier-free environment perceptions, and commuting satisfaction. Discussion: The results of this study provide a theoretical basis for the necessity of accessibility design in the post-COVID era. In addition, this study considers the perspective of users to provide ideas for the planning and construction of barrier-free campus environments that are based on convenient and inclusive design.


Subject(s)
COVID-19 , Pandemics , Humans , Transportation , COVID-19/epidemiology , Personal Satisfaction , Perception
19.
Sci Rep ; 12(1): 18966, 2022 11 08.
Article in English | MEDLINE | ID: mdl-36347872

ABSTRACT

Humic acids (HAs) widely exist in water environment, and has an important impact on the adsorption of pollutants. Herein, HAs (both dissolved and coated) was employed to assess the effect on the removal of the organic contaminant tetracycline (TC) by K2CO3 modified magnetic biochar (KMBC). Results showed that low concentration of dissolved HAs promoted TC removal, likely due to a bridging effect, while higher concentration of dissolved HAs inhibited TC adsorption because of the competition of adsorption sites on KMBC. By characterization analysis, coated HAs changed the surface and pore characteristics of KMBC, which suppressed the TC removal. In a sequential adsorption experiment involving dissolved HAs and TC, the addition of HAs at the end of the experiment led to the formation of HAs-TC ligands with free TC, which improved the adsorption capacity of TC. TC adsorption by KMBC in the presence of dissolved HAs and coated HAs showed a downward trend with increasing pH from 5.0 to 10.0. The TC adsorption process was favorable and endothermic, and could be better simulated by pseudo-second-order kinetics and Freundlich isotherm model. Hydrogen bonds and π-π interactions were hypothesized to be the underlying influencing mechanisms.


Subject(s)
Humic Substances , Water Pollutants, Chemical , Adsorption , Water Pollutants, Chemical/chemistry , Tetracycline/chemistry , Charcoal/chemistry , Anti-Bacterial Agents/chemistry , Kinetics , Magnetic Phenomena , Hydrogen-Ion Concentration
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