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1.
Nanotechnology ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39137799

ABSTRACT

High-quality patterning determines the properties of patterned emerging two-dimensional (2D) conjugated polymers which is essential for potential applications in future electronic nanodevices. However, the suitable patterning method for 2D polymers is yet concluded because it's still challenging to gain comprehensive understanding of their damage mechanisms by visualizing the structural modification during patterning process. Here, the damage mechanisms during patterning of 2D polymers, induced by various patterning methods, are unveiled based on a systematic study of structural damage and edge morphology on an imine-based 2D polymer (polyimine). Patterning using focused electron beam, focused ion beam (FIB) and mechanical carving is evaluated. Focused electron beam successively introduces sputtering effect, knock-on displacement damage and massive radiolysis effect as increasing the electron dose from 9.46×107 e-/nm2 to 1.14×1010 e-/nm2. The successful pattering is enabled by knock-on damage while impeded by carbon contamination when beyond a critical sample thickness. FIB creates current-dependent edge morphologies and extensive damage from the ion implantation caused by the tail of unfocused beam. A precisely controlled tip can tear the polyimine film through grain boundaries and in hence create the patterning edge with suitable edge roughness for certain application senarios when the beam damage is avoided. Taking structural damage and the resulting quantitative edge roughness into consideration, this study provides a detailed instruction on the proper patterning techniques for 2D crystalline polymers and paves the way for tailored intrinsic properties and device fabrication using these novel materials. .

2.
Int J Biol Macromol ; : 134766, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39151858

ABSTRACT

To preserve the activity of amine groups on chitosan, chitosan resin (CR) was synthesized using the reversed-phase suspension two-step crosslinking method for the adsorption of palladium from wastewater. The effects of varying the amounts of chitosan, liquid paraffin, ethyl acetate, formaldehyde solution, and epichlorohydrin on the adsorption capacity of CR were investigated using both single-factor experiments and response surface methodology. The preparation conditions for the chitosan resin were optimized, and its adsorption properties were systematically evaluated. The results indicated that CR exhibited a high saturated adsorption capacity for palladium, reaching 195.22 mg·g-1. The adsorption kinetics followed the pseudo-second-order model, while the adsorption isotherms were well described by the Sips model. Thermodynamic analysis demonstrated that the adsorption process was spontaneous and endothermic. Furthermore, CR maintained exceptional stability, with a palladium removal efficiency exceeding 99.8 % even after eight adsorption-desorption cycles. The primary adsorption mechanism is attributed to the interaction between palladium ions and the protonated amino groups of the chitosan resin.

3.
Adv Food Nutr Res ; 111: 35-70, 2024.
Article in English | MEDLINE | ID: mdl-39103217

ABSTRACT

Integration of machine learning (ML) technologies into the realm of smart food safety represents a rapidly evolving field with significant potential to transform the management and assurance of food quality and safety. This chapter will discuss the capabilities of ML across different segments of the food supply chain, encompassing pre-harvest agricultural activities to post-harvest processes and delivery to the consumers. Three specific examples of applying cutting-edge ML to advance food science are detailed in this chapter, including its use to improve beer flavor, using natural language processing to predict food safety incidents, and leveraging social media to detect foodborne disease outbreaks. Despite advances in both theory and practice, application of ML to smart food safety still suffers from issues such as data availability, model reliability, and transparency. Solving these problems can help realize the full potential of ML in food safety. Development of ML in smart food safety is also driven by social and industry impacts. The improvement and implementation of legal policies brings both opportunities and challenges. The future of smart food safety lies in the strategic implementation of ML technologies, navigating social and industry impacts, and adapting to regulatory changes in the AI era.


Subject(s)
Food Safety , Machine Learning , Humans , Foodborne Diseases/prevention & control
5.
Polymers (Basel) ; 16(15)2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39125227

ABSTRACT

In response to the phenomenon of interlayer transport channel swelling caused by the hydration of oxygen-containing functional groups on the GO membrane surface, a moderate heat treatment method was employed to controllably reduce the graphene oxide (GO) membrane and prepare a reduced GO composite nanofiltration membrane (mixed cellulose membrane (MCE)/ethylenediamine (EDA)/reduced GO-X (RGO-X)). The associations of different heat treatment temperatures with the hydrophilicity, interlayer structure, permeability and dye/salt rejection properties of GO membranes were systematically explored. The results indicated that the oxygen-containing groups of the GO membrane were partially eliminated after heat treatment, and the hydrophilicity was weakened. This effectively weakened the hydration between the GO membrane and the water molecules and inhibited the swelling of the oxidized graphene membrane. In the dye desalination test, the MCE/EDA/RGO membrane exhibited an ultra-high rejection rate of over 97% for methylene blue (MB) dye molecules. In addition, heat treatment increased the structural defects of the GO membrane and promoted the fast passage of water molecules via the membrane. In pure water flux testing, the water flux of the membrane remained above 46.58 Lm-2h-1bar-1, while the salt rejection rate was relatively low.

6.
J Vet Pharmacol Ther ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39135274

ABSTRACT

Mycoplasma synoviae (MS) infection is a serious threat to poultry industry in China. Tilmicosin is a semisynthetic macrolide antibiotic used only in animals and has shown potential efficacy against MS, but there were no reported articles concerning the pharmacokinetics/pharmacodynamics (PK/PD) interactions of tilmicosin against MS in vitro and vivo. This study aimed to assess the antibacterial activity of tilmicosin against MS in vitro and in vivo using PK/PD model to provide maximal efficacy. The minimum inhibitory concentration (MIC) and killing rates of different drug concentrations were measured using the microdilution method in vitro. Then, tilmicosin was administered orally to the MS-infected chickens at doses of 7.5 and 60 mg/kg, and the PK parameters of tilmicosin in joint dialysates were determined using high-pressure liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) combined with the microdialysis technique. The antibacterial effect (△E) was calculated when the infected chickens were administered a single oral dose of tilmicosin at 4, 7.5, 15, 30, and 60 mg/kg b.w. The PK and PD data were fitted using the Sigmoid Emax model to evaluate the PK/PD interactions of tilmicosin against MS. The bactericidal activity of tilmicosin against MS was concentration dependent. Furthermore, the PK/PD index of AUC0-72h/MIC exhibited the most optimal fitting results (R2 = .98). The MS load decreased by 1, 2, and 3 Log10 CFU/mL, then AUC/MIC was determined as 13.99, 20.53, and 28.23 h, respectively, and the bactericidal effect can be achieved when the dose of MS-infected chickens is at 31.64 mg/kg b.w. The findings of this study hold significant implications for optimizing the treatment regimen for MS infection.

7.
Front Psychol ; 15: 1433609, 2024.
Article in English | MEDLINE | ID: mdl-39077206

ABSTRACT

Meaning in life, which has two possible sources: self-acceptance and social support, is essential to the mental health and development of college students. The current study aims to further clarify the symptom-level relations between meaning in life, self-acceptance, and social support, finding possible ways to improve meaning in the life of college students. Thousand three hundred and forty-eight Chinese college students completed the online questionnaire, including Self-acceptance Questionnaire, Social Support Rating Scale, and Meaning in Life Questionnaire and the data from 1,263 participants was used. Cross-sectional network analysis was used to examine the relation between self-acceptance and social support. We also explored the relation between dimensions of self-acceptance and social support and meaning in life using the flow network. The results show symptom "SlA" (self-acceptance) is the bridge symptom linking self-acceptance and social support. In the flow diagrams, "SlA" is directly and positively associated with the presence of meaning. Objective Support shares the strongest positive association with the search for meaning. The symptom "SIA" may be an important targeting symptom when trying to improve the meaning in life of college students. Additionally, social support is essential for college students to develop meaning in life.

8.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39072733

ABSTRACT

This paper introduces the design and implementation of a prototype Digital Delay Generator (DDG) characterized by high precision, low jitter, and a wide delay range, fully realized within a Field Programmable Gate Array (FPGA). The DDG's architecture is based on an innovative combination of an embedded time-to-digital converter (TDC) and Multi-stage Time Interpolation (MTI) delay logic. The paper explores the factors influencing delay jitter during external trigger mode and carefully selects the optimal design approach for each element. The embedded TDC, which undergoes automatic calibration, accurately measures the time difference between the arrival of an external trigger and the FPGA's internal clock signal. When paired with the MTI delay logic, this allows for highly precise control over delay durations. A key aspect of this design is its sole dependence on the FPGA's built-in resources, ensuring simplicity in implementation and adaptability to various applications. Evaluation of the prototype has shown promising results, demonstrating a delay resolution as fine as 20 ps and maintaining a low jitter of 105 ps peak-to-peak (20 ps rms) when operated in the externally triggered mode.

9.
Plant Physiol ; 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39056538

ABSTRACT

Rice (Oryza sativa) plants contain plastidial and cytosolic disproportionating enzymes (DPE1 and DPE2). Our previous studies showed that DPE2 acts on maltose, the major product of starch degradation in pollens, releasing one glucose to fuel pollen tube growth and fertilization, whereas DPE1 participates in endosperm starch synthesis by transferring maltooligosyl groups from amylose to amylopectin, and removing excess short maltooligosaccharides. However, little is known about their integrated function. Here, we report that the coordinated actions of DPE1 and DPE2 contribute to grain setting and filling in rice. The dpe1dpe2 mutants could not be isolated from the progeny of heterozygous parental plants but were obtained via anther culture. Unlike that reported in Arabidopsis (Arabidopsis thaliana) and potato (Solanum tuberosum), the dpe1dpe2 rice plants grew normally but only yielded a small number of empty, unfilled seeds. In the dpe1dpe2 seeds, nutrient accumulation was substantially reduced, and dorsal vascular bundles were also severely malnourished. Zymogram analyses showed that changes in activities of the major starch-synthesizing enzymes matched well with various endosperm phenotypes of mutant seeds. Mechanistically, DPE1 deficiency allowed normal starch mobilization in leaves and pollens but affected starch synthesis in endosperm, while DPE2 deficiency blocked starch degradation, resulting in substantially decreased levels of the sugars available for pollen tube growth and grain filling. Overall, our results demonstrate the great potential of DPE1-DPE2 as an important regulatory module to realize higher crop yields and present a promising target for regulating nutrient accumulation in cereal crop endosperm.

10.
Brain Behav ; 14(7): e3624, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39010704

ABSTRACT

INTRODUCTION: This study aims to evaluate the effects of sodium-glucose cotransporter 1 inhibitors (SGLT1i) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) on neurodegenerative disorders and to investigate the role of hemoglobin A1c (HbA1c) levels. METHODS: Utilizing drug target Mendelian randomization, we employed single nucleotide polymorphisms (SNPs) proximal to the SLC5A1 and SLC5A2 genes to analyze the influence of SGLT1i and SGLT2i on Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), frontotemporal dementia (FTD), Lewy body dementia (LBD), and amyotrophic lateral sclerosis (ALS), with type 2 diabetes (T2D) as a positive control. An additional analysis examined the impact of HbA1c levels on the same disorders. RESULTS: SGLT1i exhibited a significant association with decreased risk for ALS and MS. Conversely, SGLT2i were linked to an increased risk of AD, PD, and MS. Elevated HbA1c levels, independent of SGLT1 and SGLT2 effects, were associated with an increased risk of PD. Sensitivity analyses supported the robustness of these findings. CONCLUSION: Our study suggests that SGLT1i may confer protection against ALS and MS, whereas SGLT2i could elevate the risk of AD, PD, and MS. Additionally, elevated HbA1c levels emerged as a risk factor for PD. These findings underscore the importance of personalized approaches in the utilization of SGLT inhibitors, considering their varying impacts on the risks of neurodegenerative diseases.


Subject(s)
Glycated Hemoglobin , Mendelian Randomization Analysis , Neurodegenerative Diseases , Polymorphism, Single Nucleotide , Sodium-Glucose Transporter 1 , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Neurodegenerative Diseases/genetics , Glycated Hemoglobin/metabolism , Sodium-Glucose Transporter 1/genetics , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Sodium-Glucose Transporter 2/genetics , Sodium-Glucose Transporter 2/metabolism , Parkinson Disease/genetics , Parkinson Disease/drug therapy , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/drug therapy , Multiple Sclerosis/drug therapy , Multiple Sclerosis/genetics
11.
Front Plant Sci ; 15: 1358136, 2024.
Article in English | MEDLINE | ID: mdl-38841282

ABSTRACT

Accurate identification the species composition in mixtures poses a significant challenge, especially in processed mixtures comprising multiple species, such as those found in food and pharmaceuticals. Therefore, we have attempted to utilize shotgun metabarcoding technology to tackle this issue. In this study, the method was initially established using two mock samples of the Mongolian compound preparation Gurigumu-7 (G-7), which was then applied to three pharmaceutical products and 12 hospital-made preparations. A total of 119.72 Gb of raw data sets were obtained through shotgun metagenomic sequencing. By combining ITS2, matK, and rbcL, all the labeled bio-ingredients specified in the G-7 prescription can be detected, although some species may not be detectable in all samples. The prevalent substitution of Akebia quinata can be found in all the pharmaceutical and hospital samples, except for YN02 and YN12. The toxic alternative to Akebia quinata, Aristolochia manshuriensis, was exclusively identified in the YN02 sample. To further confirm this result, we validated it in YN02 using HPLC and real-time PCR with TaqMan probes. The results showed that aristolochic acid A (AAA) was detected in YN02 using HPLC, and the ITS2 sequence of Aristolochia manshuriensis has been validated in YN02 through qPCR and the use of a TaqMan probe. This study confirms that shotgun metabarcoding can effectively identify the biological components in Mongolian medicine compound preparation G-7. It also demonstrates the method's potential to be utilized as a general identification technique for mixtures containing a variety of plants.

12.
J Hazard Mater ; 474: 134805, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38843632

ABSTRACT

Recognizing the extent of perchlorate pollution in the environment is critical to preventing and mitigating potential perchlorate harm to human health. The presence and distribution of perchlorate in Chinese environmental matrixes (water, atmosphere, and soil) were systematically investigated and comprehensively analyzed, and cumulative perchlorate exposure at the regional level was assessed using a combined aggregate exposure pathway method. The results showed that perchlorate is ubiquitous in the environment of China with significant regional differences. The total perchlorate exposure levels in each region of China ranked as South China > Southwest China > East China > North China > Northeast China > Northwest China. Although the average exposure dose of 0.588 (95 %CI: 0.142 -1.914) µg/kg bw/day being lower than the reference dose of 0.70 µg/kg bw/day, it was observed that the intake of perchlorate in some regions exceed this reference dose. Oral ingestion was the primary route of perchlorate exposure (89.97-96.57 % of the total intake), followed by dermal contact (3.21-9.16 %) and respiratory inhalation. Food and drinking water were the main sources of total perchlorate intake, contributing 52.54 % and 31.12 % respectively, with the latter contributing significantly more in southern China than in northern China. In addition, perchlorate exposure from dust sources was also noteworthy, as its contribution was as high as 23.18 % in some regions. These findings will improve understanding of the perchlorate risk and serve as a critical reference for policymakers in crafting improved environmental management and risk mitigation strategies in China and other nations.


Subject(s)
Environmental Exposure , Perchlorates , Perchlorates/analysis , Perchlorates/toxicity , China , Environmental Exposure/analysis , Humans , Environmental Monitoring , Environmental Pollutants/analysis , Water Pollutants, Chemical/analysis , Drinking Water/analysis , Drinking Water/chemistry
13.
Article in English | MEDLINE | ID: mdl-38852903

ABSTRACT

Non-blood-feeding leeches, Whitmania pigra, have evolved unique digestive structures and physiological mechanisms to cope with fasting. However, the metabolic changes and molecular mechanisms induced by fasting remain unclear. Therefore, this study recorded the weights of leeches during the fasting process. The weight changes were divided into two stages: a rapid decline period (1-9 weeks) and a fluctuating decline period (9-24 weeks). Leeches fasted for 4 (H4), 11 (H11), and 24 (H24) weeks were selected for transcriptome sequencing. Compared to the control group (H0), 436, 1157, and 337 differentially expressed genes (DEGs) were identified, which were mainly related to glycolysis/gluconeogenesis, amino acid metabolism, and the lipid metabolism pathway. The 6-phosphofructokinase (Pfk), pyruvate kinase (PK), and phosphoenolpyruvate carboxykinase (Pck) transcription levels revealed glycolysis/gluconeogenesis activation during the early stage of fasting and peaked at 11 weeks. Decreased expression of the rate-limiting enzyme acetyl-CoA carboxylase (ACC) in fatty acid synthesis during fasting may impede fatty acid synthesis. These results indicated that the nutrient storage and energy-supplying pathways in W. pigra were modified to improve fasting resistance. The findings of this study provided guidance for exploring the mechanism underlying fasting metabolism and laid a foundation for artificial breeding to improve the resistance of leeches.


Subject(s)
Energy Metabolism , Fasting , Leeches , Animals , Leeches/metabolism , Leeches/physiology , Energy Metabolism/physiology , Fasting/metabolism , Glycolysis , Transcriptome
14.
Imeta ; 3(2): e169, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38882494

ABSTRACT

The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants (N = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0-7) and a tetracycline-mupirocin-ß-lactam-dominant phase (Months 8-14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with Escherichia (25.5%) harboring the most resistance genes. In a further analysis with all available infants (N = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years (p < 0.001). Using a random-forest approach, a set of 34 resistance genes could be used to predict age (R 2 = 68.0%). Leveraging microbial host inference analyses, we inferred the age-dependent assembly of infant resistome was a result of shifts in the gut microbiome, primarily driven by changes in taxa that disproportionately harbor resistance genes across taxa (e.g., Escherichia coli more frequently harbored resistance genes than other taxa). We performed metagenomic functional profiling and metagenomic assembled genome analyses whose results indicate that the development of gut resistome was driven by changes in microbial carbohydrate metabolism, with an increasing need for carbohydrate-active enzymes from Bacteroidota and a decreasing need for Pseudomonadota during infancy. Importantly, we observed increased acquired resistance genes over time, which was related to increased horizontal gene transfer in the developing infant gut microbiome. In summary, infant age was negatively correlated with antimicrobial resistance gene levels, reflecting a composition shift in the gut microbiome, likely driven by the changing need for microbial carbohydrate metabolism during early life.

15.
Biomed Opt Express ; 15(6): 3950-3961, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38867793

ABSTRACT

The spatial omics information analysis of heterogeneous cells or cell populations is of great importance for biomedical research. Herein, we proposed a picosecond laser capture microdissection boosted by edge catapulting combined with dielectrophoretic force (ps-LMED) that enables fast and non-invasive acquisition of uncontaminated cells and cell populations for downstream molecular assays. The target cells were positioned under a microscope and separated by a focused picosecond pulsed laser. The system employed the plasma expansion force during cutting to lift the target and captured it under dielectrophoretic force from the charged collection cap eventually. The principle of our system has been validated by both theoretical analysis and practical experiments. The results indicated that our system can collect samples ranging from a single cell with a diameter of a few microns to large tissues with a volume of 532,500 µm3 at the moment finishing the cutting, without further operations. The cutting experiments of living cells and ribonucleic acid (RNA) and protein omics analysis results of collected targets demonstrated the advantage of non-destructiveness to the samples and feasibility in omics applications.

16.
Plant Dis ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902881

ABSTRACT

Saposhnicovia divaricata (Trucz.) Schischk. is one of the traditional medicinal herbs in northeast China, and its roots are used for medicinal purposes. In 2020, a fungus isolated from S. divaricata seeds was observed to cause root rot of seedlings, leaf spot and stem spot of adult plants in Shuangyashan, Heilongjiang, China. Based on morphological and molecular data, isolates of all fungi were identified as Alternaria alternata. To our knowledge, this is the first report of A. alternata isolated from S. divaricata seeds in China. The carrying rate of S. divaricata seeds from 20 different collection sites reached 100% in 70% of the sites in Hulunbeier area, Inner Mongolia, China. The A. alternata isolate could infect the roots of cucumber, sorghum, mung bean and maize seedlings and cause root rot. Considering the control of seed-associated fungal diseases, prochloraz 45% EW had the best control effect of 92.6%, followed by flusilazole 400 g L-1 EC (88.9%) and azoxystrobin·propiconazole 18.7% SE (70.7%) of 15 fungicides. Further field control efficacy showed that 45% prochloraz EW had an 80% control efficacy on the disease at a dose of 0.225 g L-1. It is recommended that soaking seeds and spraying are the best treatments for controlling seed-associated fungi and leaf spot on S. divaricata caused by A. alternata. Therefore, above methods can effectively prevent the occurrence of fungal diseases of S. divaricata and provide a method to reduce reinfestation in the field.

17.
Front Plant Sci ; 15: 1404447, 2024.
Article in English | MEDLINE | ID: mdl-38799090

ABSTRACT

Rhodiola L. is a genus exhibiting rapid radiation and represents a typical case for studying plastid gene adaptation in species that spread from high altitudes to low altitudes. In this study, 23 samples of 18 Rhodiola species were collected from the Qinghai-Tibetan Plateau and five scattered alpine areas, and the plastid genomes (plastomes) of these species were sequenced, annotated, and compared between high-altitude and widely distributed groups. The plastomes of Rhodiola were found to be highly conserved in terms of gene size, content, and order but highly variable in several lineage-specific features, such as codon usage bias, IR boundary shifting, and distinct repeat sequence structures binding to SSRs. Codon usage in the genes of photosystem II exhibited an obvious preference, reflecting significant environmental adaptation pressures. In this study, three repeat regions compounded with trinucleotide and mononucleotide repeats were found for the first time in R. forrestii, R. himalensis, and R. yunnanensis. High-variability regions such as ndhF, ycf1, trnH-psbA, and rpoC1-rpoB were screened, laying the foundation for the precise identification of these species. The phylogenetic analysis revealed the occurrence of cyto-nuclear discordance, likely originating from the frequent interspecific hybridization events observed within Rhodiola species during rapid radiation. Dioecious and hermaphrodite species can be broadly categorized into two subclades, probably they have different environmental adaptation strategies in response to climate change. In addition, the phylogenetic tree supported the monophyly of R. forrestii and R. yunnanensis, which compose R. Sect. Pseudorhodiola. In conclusion, plastome data enrich the genetic information available for the Rhodiola genus and may provide insight into species migration events during climate change.

18.
Mitochondrial DNA B Resour ; 9(5): 652-656, 2024.
Article in English | MEDLINE | ID: mdl-38770146

ABSTRACT

The complete mitochondrial genome of Alboglossiphonia lata (basionym: Glossiphonia lata), sourced from a biodiversity hotspot of China, has been determined and reported in this study. It was 15,236 bp in length and consisted of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and three control regions. The mitogenome was deposited GenBank under the accession number PP165800. A. lata and other species within the Glossiphoniidae family were clustered together with high bootstrap values. The mitochondrial genome of A. lata provides valuable molecular data for further phylogenetic research on the Glossiphoniidae family.

19.
J Med Chem ; 67(10): 8161-8171, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38690856

ABSTRACT

The mediator kinases CDK8 and CDK19 control the dynamic transcription of selected genes in response to various signals and have been shown to be hijacked to sustain hyperproliferation by various solid and liquid tumors. CDK8/19 is emerging as a promising anticancer therapeutic target. Here, we report the discovery of compound 12, a novel small molecule CDK8/19 inhibitor. This molecule demonstrated not only decent enzymatic and cellular activities but also remarkable selectivity in CDK and kinome panels. Besides, compound 12 also displayed favorable ADME profiles including low CYP1A2 inhibition, acceptable clearance, and high oral bioavailability in multiple preclinical species. Robust in vivo PD and efficacy studies in mice models further demonstrated its potential use as mono- and combination therapy for the treatment of cancers.


Subject(s)
Antineoplastic Agents , Cyclin-Dependent Kinase 8 , Cyclin-Dependent Kinases , Protein Kinase Inhibitors , Cyclin-Dependent Kinase 8/antagonists & inhibitors , Cyclin-Dependent Kinase 8/metabolism , Humans , Animals , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacokinetics , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/chemical synthesis , Cyclin-Dependent Kinases/antagonists & inhibitors , Cyclin-Dependent Kinases/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemical synthesis , Mice , Drug Discovery , Cell Line, Tumor , Structure-Activity Relationship , Cell Proliferation/drug effects , Neoplasms/drug therapy , Rats
20.
Membranes (Basel) ; 14(5)2024 May 19.
Article in English | MEDLINE | ID: mdl-38786951

ABSTRACT

Membrane distillation (MD) is considered a promising technology for desalination. In the MD process, membrane pores are easily contaminated and wetted, which will degrade the permeate flux and salt rejection of the membrane. In this work, SiC ceramic membranes were used as the supports, and an Al2O3 micro-nano structure was constructed on its surface. The surface energy of Al2O3@SiC micro-nano composite membranes was reduced by organosilane grafting modification. The effective deposition of Al2O3 nanoflowers on the membrane surface increased membrane roughness and enhanced the anti-fouling and anti-wetting properties of the membranes. Simultaneously, the presence of nanoflowers also regulated the pore structures and thus decreased the membrane pore size. In addition, the effects of Al2(SO4)3 concentration and sintering temperature on the surface morphology and performance of the membranes were investigated in detail. It was demonstrated that the water contact angle of the resulting membrane was 152.4°, which was higher than that of the pristine membrane (138.8°). In the treatment of saline water containing 35 g/L of NaCl, the permeate flux was about 11.1 kg⋅m-2⋅h-1 and the salt rejection was above 99.9%. Note that the pristine ceramic membrane cannot be employed for MD due to its larger membrane pore size. This work provides a new method for preparing superhydrophobic ceramic membranes for MD.

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