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1.
BMC Microbiol ; 24(1): 206, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858614

RESUMO

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.


Assuntos
Mutação , Mycobacterium tuberculosis , Polimorfismo de Nucleotídeo Único , Tuberculose , Sequenciamento Completo do Genoma , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , China/epidemiologia , Humanos , Tuberculose/transmissão , Tuberculose/microbiologia , Tuberculose/epidemiologia , Genoma Bacteriano , Feminino , Masculino , Proteínas de Bactérias/genética , Adulto
2.
Bioorg Chem ; 149: 107487, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38805910

RESUMO

The peel of Trichosanthes kirilowii Maxim, is considered one of the primary sources for Trichosanthis pericarpium in traditional Chinese medicine, exhibiting lipid-lowering properties. The impact on hyperlipidemia mice of the crude polysaccharide from the peel of T. Kirilowii (TRP) was investigated in this study. The findings revealed that TRP exhibited a significant improvement in hepatic lipid deposition. Moreover, it significantly decreased serum levels of TC, TG, and LDL-C, while concurrently increasing HDL-C. 16S rRNA amplicon sequencing technique revealed that TRP group exhibited an increased relative abundance of Actinobacteria, a down-regulated relative abundance of Ruminiclostridium, and an up-regulated relative abundance of Ileibacterium. Therefore, TRP might play a role in anti-hyperlipidemia through regulation of the intestinal milieu and enhancement of microbial equilibrium. Consequently, targeted fractionation of TRP resulted in the isolation of a homogeneous acidic polysaccharide termed TRP-1. The TRP-1 polysaccharide, with an average molecular weight of 1.00 × 104 Da, and was primarily composed of Rha, GlcA, GalA, Glc, Gal and Ara. TRP-1 possessed a backbone consisting of alternating connections between â†’ 6)-α-Galp-(1 â†’ 4)-α-Rhap-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ 6)-α-Galp-(2 â†’ 6)-ß-Galp-(1 â†’ units and branched chain containing â†’ 6)-α-Glcp-(1→, 2,4)-ß-Glcp-(1, and â†’ 4)-α-GlapA-(1→. Both TRP and TRP-1 exhibited significant disruption of cholesterol micelles, highlighting their potential as lipid-lowering agents that effectively inhibit cholesterol absorption pathways.


Assuntos
Colesterol , Microbioma Gastrointestinal , Hiperlipidemias , Polissacarídeos , Trichosanthes , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Trichosanthes/química , Camundongos , Hiperlipidemias/tratamento farmacológico , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Colesterol/metabolismo , Colesterol/sangue , Hipolipemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/isolamento & purificação , Masculino , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga
3.
Org Lett ; 26(20): 4340-4345, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38743916

RESUMO

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of ß,ß-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

4.
ACS Omega ; 9(13): 15151-15164, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38585108

RESUMO

In order to promote site screening for high-level radioactive waste (HLW) disposal purposes, the characteristics of argillaceous rock (potential host rock) from the Yingejing Sag of the Bayingebi Basin, Northwest China have been well discussed. Results show that (1) Unlike argillaceous host rocks in foreign countries, the argillaceous rock mainly consists of analcite, dolomite, and albite; the contents of clay minerals are only about 10%. Five typical structures could be categorized, dominating by the massive structure. (2) Geochemical characteristics have the characteristics of abundance in deep source gas and liquid trace elements, a gentle right dip in the distribution pattern of rare-earth elements. (3) Petrological and geochemical characteristics determine the argillaceous rock as the genesis of lacustrine hydrothermal sedimentary rock. The hydrothermal sedimentary model also has been constructed, mainly controlled by tectonic activity of the Altyn Tagh fault from 100 to 120 Ma. The massive argillites with analcite and dolomite would lay the foundation for confirming the site for HLW disposal purposes in China.

5.
Inorg Chem ; 63(17): 7746-7753, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38609344

RESUMO

A novel two-dimensional (2D) Hofmann-type coordination polymer, {FeII(PyHbim)2[Pd(CN)4]}·2CH3OH [1·2CH3OH, PyHbim = 2-(4-pyridyl)benzimidazole], has been synthesized, which can undergo a spontaneous guest exchange, transforming to 1·2H2O in a single-crystal-to-single-crystal (SCSC) manner, shifting from orthorhombic Cmmm to monoclinic C2/m involving the displacement of 2D layers. The solvent-induced SCSC transformation process was reversible and verified through powder X-ray diffraction (PXRD) and single-crystal X-ray crystallography analyses. Both 1·2CH3OH and 1·2H2O exhibit complete and abrupt spin crossover (SCO) behaviors in two steps, while their SCO temperature ranges drastically shift by ca.100 K, spanning room temperature, owing to different intermolecular interactions resulting from diverse interlayer packing manners and host-guest interactions. Besides, a structural phase transition is observed in 1·2CH3OH, contributing to the two-step spin transition.

6.
Int J Biol Macromol ; 266(Pt 2): 131391, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582456

RESUMO

Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine (PPA) have various biological activities, but their properties after oral administration are not clear. In this study, the absorption, digestion and fermentation properties of PPA were studied using in vivo fluorescence tracking, in vitro simulated digestion and fecal fermentation experiments. The absorption experiment showed that fluorescence was only observed in the gastrointestinal system, indicating that PPA could not be absorbed. Simulated digestion results showed that there were no significant changes in the molecular weight, Fourier transform infrared spectroscopy (FT-IR) spectrum, monosaccharides and reducing sugar of PPA during the digestion process, showing that the overall structure of PPA was not damaged. However, the carbohydrate gel electrophoresis bands of PPA enzymatic hydrolysates after simulated digestion were significantly changed, indicating that simulated digestion might impact the configuration of PPA. In vitro fermentation showed that PPA could be degraded by microorganisms to produce short chain fatty acids, leading to a decrease in pH value. PPA can promote the proliferation of Bacteroideaceae, Megasphaera, Bacteroideaceae, and Bifidobacteriaceae, and inhibit the growth of Desulfobacteriota and Enterobacteriaceae. The results indicated that PPA could treat diseases by regulating gut microbiota, providing a scientific basis for the application and development of PPA.


Assuntos
Digestão , Fezes , Fermentação , Microbioma Gastrointestinal , Polissacarídeos , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/química , Polissacarídeos/farmacologia , Humanos , Fezes/microbiologia , Fezes/química , Digestão/efeitos dos fármacos , Pinellia/química , Animais
7.
Ther Drug Monit ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38531816

RESUMO

BACKGROUND: Ibrutinib and zanubrutinib are Bruton tyrosine kinase inhibitors used to treat mantle cell lymphoma, chronic lymphocytic leukemia, and small lymphocytic lymphoma. Dihydroxydiol ibrutinib (DHI) is an active metabolite of the drug. A liquid chromatography-tandem mass spectrometry method was developed to detect ibrutinib, DHI, and zanubrutinib in human plasma. METHODS: The method involved a protein precipitation step, followed by chromatographic separation using a gradient of 10 mM ammonium acetate (containing 0.1% formic acid)-acetonitrile. Ibrutinib-d5 was used as an internal standard. Analytes were separated within 6.5 minutes. The optimized multiple reaction monitoring transitions of m/z 441.1 → 304.2, 475.2 → 304.2, 472.2 → 455.2, and 446.2 → 309.2 were selected to inspect ibrutinib, DHI, zanubrutinib, and the internal standards in positive ion mode. RESULTS: The validated curve ranges included 0.200-800, 0.500-500, and 1.00-1000 ng/mL for ibrutinib, DHI, and zanubrutinib, respectively. The precisions of the lower limit of quantification of samples were below 15.5%, the precisions of the other level samples were below 11.4%, and the accuracies were between -8.6% and 8.4%. The matrix effect and extraction recovery of all compounds ranged between 97.6%-109.0% and 93.9%-105.2%, respectively. The selectivity, accuracy, precision, matrix effect, and extraction recovery results were acceptable according to international method validation guidelines. CONCLUSIONS: A simple and rapid method was developed and validated in this study. This method was used to analyze plasma concentrations of ibrutinib and zanubrutinib in patients with mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, or diffuse large B-cell lymphoma. The selected patients were aged between 44 and 74 years.

8.
Biometals ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483766

RESUMO

Iron is an essential element for the normal functioning of living organisms, but excessive iron deposition can lead to organ damage. This study aims to investigate the interaction between the endoplasmic reticulum stress signaling pathway and the PI3K/AKT/mTOR signaling pathway in liver injury induced by iron overload in chicks. Rspectively, 150 one-day-old broilers were divided into three groups and supplemented with 50 (C), 500 (E1), and 1000 (E2) mg ferrous sulfate monohydrate/kg in the basal diet. Samples were taken after continuous feeding for 14 days. The results showed that iron overload could upregulate the levels of ALT and AST. Histopathological examination revealed bleeding in the central vein of the liver accompanied by inflammatory cell infiltration. Hoechst staining showed that the iron overload group showed significant bright blue fluorescence, and ultrastructural observations showed chromatin condensation as well as mitochondrial swelling and cristae disorganization in the iron overload group. RT-qPCR and Western blot results showed that iron overload upregulated the expression of Bax, Caspase-3, Caspase-9, GRP78, GRP94, P-PERK, ATF4, eIF2α, IRE1, and ATF6, while downregulating the expression of Bcl-2 and the PI3K/AKT/mTOR pathway. XBP-1 splicing experiment showed significant splicing of XBP-1 gene after iron overload. PCA and correlation analysis suggested a potential association between endoplasmic reticulum stress, the PI3K/AKT/mTOR signaling pathway, and liver injury in chicks. In summary, iron overload can induce cell apoptosis and liver injury by affecting endoplasmic reticulum stress and the PI3K/AKT/mTOR signaling pathway.

10.
Mar Drugs ; 22(2)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38393029

RESUMO

Five new diisoprenyl cyclohexene-type meroterpenoids, aspergienynes J-N (1-5), along with three known analogues (6-8), were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85. The chemical structures, including their absolute configurations, were established via spectroscopic data and comparison of experimental and calculated ECD spectra. Cytotoxicity assay results indicated that compound 8 had strong cytotoxicity against HeLa cancer cells, and its IC50 value was 11.8 µM. In addition, flow cytometry analysis revealed that the cytotoxicity of 8 was due to the induction of G1 cell cycle arrest and apoptosis in HeLa cells.


Assuntos
Antineoplásicos , Aspergillus , Humanos , Estrutura Molecular , Células HeLa , Aspergillus/química , Análise Espectral , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo
11.
Environ Int ; 185: 108496, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38359549

RESUMO

Artificial sweeteners (AS) are extensively utilized as sugar substitutes and have been recognized as emerging environmental contaminants. While the effect of AS on aquatic organisms has garnered recent attention, their effects on soil invertebrates and gut microbial communities remain unclear. To address this knowledge gap, we exposed springtails (Folsomia candida) to both single and combined treatments of four typical AS (sucralose [SUC], saccharin [SAC], cyclamate [CYC], and acesulfame [ACE]) at environmentally relevant concentrations of 0.01, 0.1 and 1 mg kg-1 in soil. Following the first-generational exposure, the reproduction of juveniles showed a significant increase under all the AS treatments of 0.1 mg kg-1. The transcriptomic analysis revealed significant enrichment of several Kyoto Encyclopedia of Gene and Genome pathways (e.g., glycolysis/gluconeogenesis, pentose and glucuronate interconversions, amino sugar, and nucleotide sugar metabolism, ribosome, and lysosome) in springtails under all AS treatments. Analysis of gut bacterial microbiota indicated that three AS (SUC, CYC, and ACE) significantly decreased alpha diversity, and all AS treatments increased the abundance of the genus Achromobacter. After the sixth-generational exposure to CYC, weight increased, but reproduction was inhibited. The pathways that changed significantly (e.g., extracellular matrix-receptor interaction, amino sugar and nucleotide sugar metabolism, lysosome) were generally similar to those altered in first-generational exposure, but with opposite regulation directions. Furthermore, the effect on the alpha diversity of gut microbiota was contrary to that after first-generational exposure, and more noticeable disturbances in microbiota composition were observed. These findings underscore the ecological risk of AS in soils and improve our understanding of the toxicity effects of AS on living organisms.


Assuntos
Microbioma Gastrointestinal , Poluentes Químicos da Água , Edulcorantes/toxicidade , Edulcorantes/análise , Edulcorantes/metabolismo , Solo , Poluentes Químicos da Água/análise , Ciclamatos/análise , Amino Açúcares , Nucleotídeos
12.
Int J Spine Surg ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413236

RESUMO

BACKGROUND: The formation of sandwiched vertebrae (SDVs) after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) has become a common phenomenon. Whether SDVs are more likely to fracture is still controversial. Therefore, we conducted a meta-analysis to provide medical evidence for whether SDVs are more prone to refracture than non-SDVs (NSDVs) after PVP or PKP. METHODS: This study was conducted in accordance with the criteria of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Several databases, including PubMed, Embase, Medline databases, China National Knowledge Infrastructure, Wanfang, and Weipu, were thoroughly searched for relevant studies included from any point up until June 2022. Statistical analyses were performed using Revman 5.4. RESULTS: A total of 4052 individuals from 9 studies were enrolled. Overall, patients with SDV presented more risk to have refracture than patients with NSDV (OR = 1.57, P = 0.04). The incidences of refracture were comparable between the 2 cohorts in studies with a follow-up time less than 3 years (OR = 1.28, P = 0.49). However, patients with SDV were more prone to have refracture than patients with NSDV in studies with a follow-up time longer than 3 years (OR = 1.92, P = 0.009). Moreover, patients with SDV were more likely to have refracture than patients with NSDV in studies that involved both PVP and PKP (OR = 1.62, P = 0.002). In addition, age, low bone density, and postoperative kyphosis angle of sandwich fracture segments >10° were independent factors to predict refracture. CONCLUSIONS: Patients with SDV were more likely to have refracture after PVP or PKP, especially when the follow-up time was longer than 3 years.

13.
BMC Surg ; 24(1): 63, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368321

RESUMO

AIM: Small bowel obstruction is a common condition that requires emergency surgery. Slow recovery of bowel function after surgery or the occurrence of one or more complications can exacerbate the disease and result in severe small bowel obstruction (SSBO), significantly impacting recovery. It is characterized by a failure to regain enteral nutrition promptly, requiring long-term intensive care. Therefore, it is necessary to identify factors that predict SSBO, to allow early intervention for patients likely to develop this condition. METHODS: Of the 260 patients who underwent emergency or elective surgery for small bowel obstruction between January 2018 and December 2022, 45 developed SSBO. The least absolute shrinkage and selection operator regression model was applied to optimize factor selection and multivariable logistic regression analysis was used to construct a predictive model. The performance and clinical utility of the nomogram were determined and internal validation was conducted. In addition, the effects of the Houpu Paiqi mixture on postoperative recovery were analyzed by comparing the clinical data of 28 patients who were treated with the mixture and 61patients who did not receive it. RESULTS: The predictors included in the prediction nomogram were age, peritonitis, intestinal resection and anastomosis, complications, operation time, Acute Physiology and Chronic Health Evaluation II score, white blood cell count, and procalcitonin level. The model had an area under the receiver operating characteristic curve of 0.948 (95% confidence interval: 0.814-0.956). Decision curve analysis demonstrated that the SSBO risk nomogram had a good net clinical benefit. In addition, treatment with the Houpu Paiqi mixture reduced postoperative exhaust time, postoperative defecation time, time to first postoperative liquid feed, and length of stay in hospital. CONCLUSIONS: We developed a nomogram that can assist clinicians in identifying patients at greater risk of SSBO, which may aid in early diagnosis and intervention. Additionally, we found that the Houpu Paiqi mixture promoted postoperative recovery.


Assuntos
Obstrução Intestinal , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Nomogramas , Anastomose Cirúrgica/efeitos adversos , Estudos Retrospectivos
14.
Angew Chem Int Ed Engl ; 63(19): e202402274, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38415322

RESUMO

The high theoretical energy density (1274 Wh kg-1) and high safety enable the all-solid-state Na-S batteries with great promise for stationary energy storage system. However, the uncontrollable solid-liquid-solid multiphase conversion and its associated sluggish polysulfides redox kinetics pose a great challenge in tunning the sulfur speciation pathway for practical Na-S electrochemistry. Herein, we propose a new design methodology for matrix featuring separated bi-catalytic sites that control the multi-step polysulfide transformation in tandem and direct quasi-solid reversible sulfur conversion during battery cycling. It is revealed that the N, P heteroatom hotspots are more favorable for catalyzing the long-chain polysulfides reduction, while PtNi nanocrystals manipulate the direct and full Na2S4 to Na2S low-kinetic conversion during discharging. The electrodeposited Na2S on strongly coupled PtNi and N, P-codoped carbon host is extremely electroreactive and can be readily recovered back to S8 without passivation of active species during battery recharging, which delivers a true tandem electrocatalytic quasi-solid sulfur conversion mechanism. Accordingly, stable cycling of the all-solid-state soft-package Na-S pouch cells with an attractive specific capacity of 876 mAh gS -1 and a high energy of 608 Wh kgcathode -1 (172 Wh kg-1, based on the total mass of cathode and anode) at 60 °C are demonstrated.

15.
Nat Commun ; 15(1): 501, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218730

RESUMO

The photovoltaic effect lies at the heart of eco-friendly energy harvesting. However, the conversion efficiency of traditional photovoltaic effect utilizing the built-in electric effect in p-n junctions is restricted by the Shockley-Queisser limit. Alternatively, intrinsic/bulk photovoltaic effect (IPVE/BPVE), a second-order nonlinear optoelectronic effect arising from the broken inversion symmetry of crystalline structure, can overcome this theoretical limit. Here, we uncover giant and robust IPVE in one-dimensional (1D) van der Waals (vdW) grain boundaries (GBs) in a layered semiconductor, ReS2. The IPVE-induced photocurrent densities in vdW GBs are among the highest reported values compared with all kinds of material platforms. Furthermore, the IPVE-induced photocurrent is gate-tunable with a polarization-independent component along the GBs, which is preferred for energy harvesting. The observed IPVE in vdW GBs demonstrates a promising mechanism for emerging optoelectronics applications.

16.
Biol Trace Elem Res ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38196053

RESUMO

This article aims to study the correlation between dietary magnesium intake and pulmonary function, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. This cross-sectional study examined representative samples of adults from the USA (n = 818; NHANES 2007-2012) to explore the correlation between magnesium intake and pulmonary function. We obtained the average magnesium intake over 2 days, as well as measured pulmonary function parameters, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow rate (PEF), and forced expiratory flow between 25 and 75% of FVC (FEF25-75%). Weighted multivariable linear regression was used to investigate the relationship between magnesium intake and pulmonary function. Additionally, subgroup analyses, interaction tests, and sensitivity analyses were conducted. Weighted multiple linear regression models revealed a significant positive correlation between magnesium and pulmonary function, even after adjusting for all included confounding variables. When we categorized magnesium intake into tertiles, we found that participants in the highest tertile of magnesium intake had significantly higher values for FVC (ß: 898.54, 95%CI: 211.82-1585.25), FEV1 (ß: 858.16, 95%CI: 212.41-1503.91), FEV1/FVC (ß: 0.024, 95%CI: 0.004-0.044), PEF (ß: 1324.52, 95%CI: 481.71-2167.33), and FEF25-75% (ß: 831.39, 95%CI: 84.93-1577.84). Upon stratifying the data by age and sex, it was observed that this positive correlation was particularly pronounced among men aged 40-79. At the same time, the stability of the results was further confirmed by sensitivity analyses. This study suggested that dietary magnesium intake may improve pulmonary function.

17.
Mol Divers ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240951

RESUMO

Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.

18.
Int J Infect Dis ; 140: 124-131, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37863309

RESUMO

OBJECTIVES: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. METHODS: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. RESULTS: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. CONCLUSIONS: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Filogenia , Filogeografia , Genótipo , Tuberculose/epidemiologia , Tuberculose/microbiologia , China/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
19.
Biomater Adv ; 157: 213728, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38134731

RESUMO

TiCu coatings with controlled copper release and nano-porous structures were fabricated as biocompatible, blood-contacting interfaces through a two-step process. Initially, coatings with 58 % Cu were created using HiPIMS/DC magnetron co-sputtering, followed by immersion in a dilute HF solution for varying durations to achieve dealloying. The presence of Ti elements in the as-deposited TiCu coatings facilitated their dissolution upon exposure to the dilute HF solution, resulting in the formation of nanopores and increased nano-roughness. Dealloying treatment time correlated with higher Cu/(Ti + Cu) values, nanopore size, and nano-roughness in the dealloyed samples. The dealloyed TiCu coatings with 87 % Cu exhibited a controlled release of copper ions and displayed nanopores (approximately 80 nm in length and 31.0 nm in width) and nano-roughness (Ra roughness: 82 nm). These coatings demonstrated inhibited platelet adhesion and suppressed smooth muscle cell behavior, while supporting favorable endothelial cell viability and proliferation, attributed to the controlled release of copper ions and the extent of nanostructures. In contrast, the as-deposited TiCu coatings with 85 % Cu showed high copper ion release, leading to decreased viability and proliferation of endothelial cells and smooth muscle cells, as well as suppressed platelet adhesion. The TiCu coatings met medical safety standards, exhibiting hemolysis rates of <5 %. The technology presented here paves the way for the simple, controllable, and cost-effective fabrication of TiCu coatings, opening new possibilities for surface modification of cardiovascular devices such as vascular stents and inferior vena cava filters.


Assuntos
Sistema Cardiovascular , Cobre , Cobre/farmacologia , Células Endoteliais , Preparações de Ação Retardada , Íons
20.
Appl Radiat Isot ; 205: 111152, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160569

RESUMO

Radon measurement is crucial in assessing the damage to the human body caused by natural radiation. Pulsed ionization chambers are effective for real-time radon measurement and have widespread applications in other radiation techniques. However, due to practical constraints such as limited space and portability concerns, it becomes imperative to consider not only the detection efficiency but also their ease of transportation. This work utilizes the Geant4 Monte Carlo simulation toolkit to characterize the detection models of small cylindrical and flat plate-type pulsed ionization chambers, and carry out a simulation study to analyze the three crucial factors that influence detection efficiency, including the geometry of the chamber, electrode size, and operating temperature. The results indicate that the cylindrical pulse ionization chamber, with a length of 8 cm and radius of 2 cm, has the best detection efficiency and portability in terms of geometric dimensions, achieving a detection efficiency of (58 ± 4)%. Meanwhile, the flat plate pulse ionization chamber, with dimensions of 7 cm in length and 3 cm in width, achieves the best detection efficiency and portability, with a detection efficiency of (54 ± 3)%. In terms of electrode wire size, the cylindrical ionization chamber electrode wire with a length of 7 cm and a radius of 2.5 mm was optimal with a detection efficiency of (59 ± 4)%. In terms of operating temperature, the detection efficiency of the flat-plate pulsed ionization chamber was the highest at 30 °C, which was (58 ± 4)%, and that of the cylindrical pulsed ionization chamber was the highest at 20 °C, which was (63 ± 4)%. By analyzing the influencing factors of the detection efficiency of the pulsed ionization chamber, it has a certain reference value and guiding significance for the research and design of small pulsed ionization chamber detectors for radon measuring instruments.

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