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1.
Eur Radiol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940828

RESUMO

OBJECTIVES: This study aimed to compare the safety and effectiveness of tunneled peripherally inserted central catheters (T-PICC) vs. conventional PICCs (C-PICC) in adult cancer patients. METHODS: A multicentre randomized controlled trial was conducted between April 2021 and January 2022 in seven hospitals in China. 564 participants were randomly assigned to T-PICC or C-PICC. These data were collected and compared: the baseline characteristics and catheterization-related characteristics, periprocedural complications, and long-term complications. RESULTS: Five-hundred fifty-three participants (aged, 52.6 ± 12.3 years; female, 39.1%) were ultimately analyzed. No significant differences in periprocedural complications were found between the T-PICC and C-PICC groups (all p > 0.05). Compared with C-PICC, T-PICC significantly reduced the incidence of long-term complications (26.4% vs. 39.9%, p < 0.001). Specifically, reduced complications were found in central line-associated bloodstream infection (1.8% vs. 5.1%, p = 0.04), thrombosis (1.1% vs. 4.0%, p = 0.03), catheter dislodgement (4.7% vs. 10.1%, p = 0.01), non-infectious oozing (17.3% vs. 28.6%, p = 0.002), local infection (3.6% vs. 7.6%, p = 0.04), skin irritation (6.1% vs. 10.9%, p = 0.046), and reduced unplanned catheter removal (2.2% vs. 7.2%, p = 0.005). No significant differences were found between T-PICC and C-PICC regarding catheter occlusion (6.5% vs. 5.8%, p = 0.73) or skin damage (2.2% vs. 2.9%, p = 0.58). CONCLUSION: T-PICC is safe and effectively reduces long-term complications. CLINICAL RELEVANCE STATEMENT: The tunneled technique is effective in reducing PICC-related long-term complications. Thus, it is recommended for cancer patients at high risk of PICC-related complications. TRIAL REGISTRATION: The registration number on https://www.chictr.org.cn/ is ChiCTR2100044632. The name of the trial registry is "A multicenter randomized controlled study of clinical use of tunneled vs. non-tunneled PICC". KEY POINTS: Cather-related complications are associated with the technique of catheterization. Compared with conventional PICC, tunneled PICC reduced catheter-related long-term complications. Tunneled PICC placement provides an alternative catheterization method for cancer patients.

2.
Glob Chang Biol ; 30(6): e17381, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38923235

RESUMO

In 2020, anthropogenic methane (CH4) emissions decreased due to COVID-19 containment policies, but there was a substantial increase in the concentration of atmospheric CH4. Previous research suggested that this abnormal increase was linked to higher wetland CH4 emissions and a decrease in the atmospheric CH4 sink. However, the impact of changes in the soil CH4 sink remained unknown. To address this, we utilized a process-based model to quantify alterations in the soil CH4 sink of terrestrial ecosystems between 2019 and 2020. By implementing the model with various datasets, we consistently observed an increase in the global soil CH4 sink, reaching up to 0.35 ± 0.06 Tg in 2020 compared to 2019. This increase was primarily attributed to warmer soil temperatures in northern high latitudes. Our results emphasize the importance of considering the CH4 sink in terrestrial ecosystems, as neglecting this component can lead to an underestimation of both emission increases and reductions in atmospheric CH4 sink capacity. Furthermore, these findings highlight the potential role of increased soil warmth in terrestrial ecosystems in slowing the growth of CH4 concentrations in the atmosphere.


Assuntos
Atmosfera , Metano , Solo , Metano/análise , Solo/química , Atmosfera/química , Ecossistema , Modelos Teóricos , Temperatura
3.
J Med Phys ; 49(1): 110-119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828073

RESUMO

Purpose: We have developed a bone-dedicated collimator with higher sensitivity but slightly degraded resolution on single-photon emission computed tomography (SPECT) for planar bone scintigraphy, compared with conventional low-energy high-resolution collimator. In this work, we investigated the feasibility of using the blind deconvolution algorithm to improve the resolution of planar images on bone scintigraphy. Materials and Methods: Monte Carlo simulation was performed with the NCAT phantom for modeling bone scintigraphy on the clinical dual-head SPECT scanner (Imagine NET 632, Beijing Novel Medical Equipment Ltd.) equipped with the bone-dedicated collimator. Maximum likelihood estimation method was used for the blind deconvolution algorithm. The initial estimation of point spread function (PSF) and iteration number for the method were determined by comparing the deblurred images obtained from different input parameters. We simulated different tumors in five different locations and with five different diameters to evaluate the robustness of the initial inputs. Furthermore, we performed chest phantom studies on the clinical SPECT scanner. The quantified increased contrast ratio (CR) between the tumor and the background was evaluated. Results: The 2 mm PSF kernel and 10 iterations provided a practical and robust deblurred image on our system. Those two inputs can generate robust deblurred images in terms of the tumor location and size with an average increased CR of 21.6%. The phantom studies also demonstrated the ability of blind deconvolution, using those two inputs, with increased CRs of 17%, 17%, 22%, 20%, and 13% for lesions with diameters of 1 cm, 2 cm, 3 cm, 4 cm, and 5 cm, respectively. Conclusions: It is feasible to use the blind deconvolution algorithm to deblur the planar images for SPECT bone scintigraphy. The appropriate values of the PSF kernel and the iteration number for the blind deconvolution can be determined using simulation studies.

4.
Ultrasonics ; 142: 107363, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38833817

RESUMO

Thick-walled structures (TWSs) are frequently utilized as primary load-bearing structures. The early detection of damage is crucial to ensure the operational safety and integrity of these structures. Nonlinear elastic-wave-based techniques provide a potential solution to the problem, which heavily relies on the good understanding of nonlinear wave generation and propagation characteristics. The task, however, is technically challenging due to the complex wave modes existing in a TWS. Targeting a meticulously manufactured local plasticized damage region on the surface of a TWS, which can be regarded as the precursor of incipient damage, this study investigates the scattering features of nonlinear elastic waves resulting from the interaction between the fundamental quasi-surface wave and the local plasticity. Finite element simulations and experiments show that, upon interacting with the nonlinear material zone, both nonlinear quasi-surface waves and shear bulk waves can be generated, with the latter scattered towards the opposite surface of the TWS. The scattered nonlinear shear waves exhibit a strong and predictable directivity with high nonlinear energy content, which is conducive to the detection and localization of the incipient surface damage of the TWS.

5.
Int J Pharm ; 659: 124295, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38823469

RESUMO

Opioids are powerful analgesics; however, their significant systemic adverse effects and the need for frequent administration restrict their use. Nalbuphine (NA) is a κ-agonist narcotic with limited adverse effects, but needs to be frequently administrated due to its short elimination half-life. Whereas sebacoyl dinalbuphine ester (SDE) is a NA prodrug, which can effectively prolong the analgesic effect, but lacks immediate pain relief. Therefore, in this study, a rapid and sustained local delivery formulation to introduce NA and SDE directly into surgical sites was developed. An amphiphilic nanostructured lipid carrier (NLC) poloxamer 407 (P407) gel (NLC-Gel) was developed to permit concurrent delivery of hydrophobic SDE from the NLC core and hydrophilic NA from P407, offering a dual rapid and prolonged analgesic effect. Benefiting from the thermal-sensitive characteristic of P407, the formulation can be injected in liquid phase and instantly transit into gel at wound site. NLC-Gel properties, including particle size, drug release, rheology, and stability, were assessed. In vivo evaluation using a rat spinal surgery model highlighted the effect of the formulation through pain behavior test and hematology analysis. NLC-Gels demonstrated an analgesic effect comparable with that of commercial intramuscular injected SDE formulation (IM SDE), with only 15 % of the drug dosage. The inclusion of supplemental NA in the exterior gel (PA12-Gel + NA) provided rapid drug onset owing to swift NA dispersion, addressing acute pain within hours along with prolonged analgesic effects. Our findings suggest that this amphiphilic formulation significantly enhanced postoperative pain management in terms of safety and efficacy.


Assuntos
Analgésicos Opioides , Portadores de Fármacos , Liberação Controlada de Fármacos , Géis , Nalbufina , Dor Pós-Operatória , Poloxâmero , Ratos Sprague-Dawley , Nalbufina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Animais , Masculino , Poloxâmero/química , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/química , Portadores de Fármacos/química , Ratos , Lipídeos/química , Tamanho da Partícula , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Ésteres/química
6.
Sci Rep ; 14(1): 14171, 2024 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898074

RESUMO

The tailwater from wastewater treatment plants serves as an important water resource in arid regions, alleviating the conflict between supply and demand. However, the effects of different tailwater discharge proportions on microbial community dynamics remain unclear. In this study, we investigated the effects of different tailwater discharge proportions on the water quality and microbial community characteristics of sediments in receiving water bodies under controlled conditions (WF-1, WF-2, WF-3, WF-4, and WF-5, containing 0% tailwater + 100% natural water, 25% tailwater + 75% natural water, 50% tailwater + 50% natural water, 75% tailwater + 25% natural water, and 100% tailwater + 0% natural water, respectively). Microbial co-occurrence networks and structural equation model were used to unveil the relationship between microbial communities and their shaping factors. Results showed that distinct microbial community compositions were found in the sediments with low- (< 50%) and high- (> 50%) proportions of tailwater. Specifically, WCHB1-41 and g_4-29-1, which are involved in organic degradation-related functions, were the key genera in the high-proportion cluster. A total of 21 taxa were more abundant in the low-proportion (< 50%) cluster than that in high-proportion (> 50%). Moreover, higher modularity was observed in the low-proportion. Total phosphorus directly affected while ammonia nitrogen indirectly affected the microbial community structure. Our findings support the distinct heterogeneity of microbial communities driven by tailwater discharge in receiving water bodies, and further confirmed that high-proportion tailwater depletes sensitive microbial communities, which may be avoided through scientific management.


Assuntos
Sedimentos Geológicos , Microbiota , Sedimentos Geológicos/microbiologia , Águas Residuárias/microbiologia , Microbiologia da Água , Bactérias/classificação , Bactérias/genética , Qualidade da Água
7.
Int J Biol Macromol ; 273(Pt 1): 132828, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38834125

RESUMO

Intervertebral disc degeneration arises from damage or degeneration of the nucleus pulposus (NP). In this study, we developed a photo-crosslinkable hydrogel incorporating FG4592 to support the growth and differentiation of bone-marrow-derived mesenchymal stem cells (BMSC). Initially, hyaluronic acid was modified with tyramine and combined with collagen to introduce riboflavin as a photo-crosslinker. This hydrogel transitioned from liquid to gel upon exposure to blue light in 3 min. The results showed that the hydrogel was biodegradable and had mechanical properties comparable to those of human NP tissues. Scanning electron microscopy after BMSC seeding in the hydrogel revealed an even distribution, and cells adhered to the collagen fibers in the hydrogel with minimal cell mortality. The effect of FG4592 on BMSC proliferation and differentiation was examined, revealing the capability of FG4592 to promote BMSC proliferation and direct differentiation resembling human NP cells. After cultivating BMSCs in the photo-crosslinked hydrogel, there was an upregulation in the expression of glycosaminoglycans, aggrecan, type II collagen, and keratin 19 proteins. Cross-species analyses of rat and human BMSCs revealed consistent results. For potential clinical applications, BMSC loaded with photo-crosslinked hydrogels can be injected into damaged intervertebral disc to facilitate NP regeneration.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38837010

RESUMO

BACKGROUND AND OBJECTIVE: The complex risk factors of liver injury have prevented the establishment of causal relationships. This study aimed to explore the effects of antidepressant class, cumulative days of medication exposure, presence of comorbidities, and the use of confounding drugs on the risk of antidepressant-induced liver injury. METHODS: The population-based case-control study sample included individuals registered on the Taiwan National Health Insurance Database between 2000 and 2018. Hospitalized patients with suspected drug-induced liver injury were considered as cases, while control subjects were matched 1:1 by age, gender, and index date (the first observed diagnosis of liver injury). Multivariable regression models were performed to evaluate the association between antidepressants and liver injury. RESULTS: The findings showed that antidepressant users exhibited a higher risk of liver injury (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.12-1.20), particularly those prescribed non-selective serotonin reuptake inhibitors (NSRIs; aOR 1.05; 95% CI 1.01-1.10), selective serotonin reuptake inhibitors (SSRIs; aOR 1.22; 95% CI 1.16-1.29), serotonin-norepinephrine reuptake inhibitors (SNRIs; aOR 1.18; 95% CI 1.13-1.24), and others (aOR 1.27; 95% CI 1.14-1.42). Moreover, cases exhibited a more significant proportion of antidepressant usage and longer durations of treatment compared with controls. The risk of liver injury was higher in the first 30 days of use across all classes of antidepressants (aOR 1.24; 95% CI 1.18-1.29). CONCLUSION: SSRIs or SNRIs are commonly used to treat depression and other psychological disorders, and consideration of their potential effects on the liver is essential.

9.
Cogn Neurodyn ; 18(3): 973-986, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38826661

RESUMO

Sex differences in the brain have been widely reported and may hold the key to elucidating sex differences in many medical conditions and drug response. However, the molecular correlates of these sex differences in structural and functional brain measures in the human brain remain unclear. Herein, we used sample entropy (SampEn) to quantify the signal complexity of resting-state functional magnetic resonance imaging (rsfMRI) in a large neuroimaging cohort (N = 1,642). The frontoparietal control network and the cingulo-opercular network had high signal complexity while the cerebellar and sensory motor networks had low signal complexity in both men and women. Compared with those in male brains, we found greater signal complexity in all functional brain networks in female brains with the default mode network exhibiting the largest sex difference. Using the gene expression data in brain tissues, we identified genes that were significantly associated with sex differences in brain signal complexity. The significant genes were enriched in the gene sets that were differentially expressed between the brain cortex and other tissues, the estrogen-signaling pathway, and the biological function of neural plasticity. In particular, the G-protein-coupled estrogen receptor 1 gene in the estrogen-signaling pathway was expressed more in brain regions with greater sex differences in SampEn. In conclusion, greater complexity in female brains may reflect the interactions between sex hormone fluctuations and neuromodulation of estrogen in women. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09954-y.

10.
Opt Express ; 32(8): 14133-14142, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859367

RESUMO

Compact efficient high-power continuous-wave Nd:YVO4 Raman lasers for selectable wavelengths within 559-603 nm are achieved by using KGW crystal for intracavity stimulated Raman scattering (SRS) and lithium triborate (LBO) crystal for intracavity sum frequency generation (SFG) and second harmonic generation (SHG). The LBO crystal with the cut angle in the XY plane for the type-I phase matching is used to perform intracavity SHG or SFG. Experimental results reveal that the participated Stokes lines include the internal vibration mode at 901 cm-1, the external vibrational mode at 209 cm-1, and the combination mode of the 901 cm-1 and 209 cm-1 Raman shifts. By tuning LBO temperature for attaining the maximum output power, the output spectrum reveals the triple peaks of 588.7, 595.7, and 603.1 nm with the intensity ratio of 10:4:1. Under this circumstance, the output power can reach the highest value of 10.8 W at a pump power of 40 W. Furthermore, the output spectrum can be simply concentrated on the single peaks among 588.7 (orange), 565.7 (yellow), and 559.1 nm (lime) by tuning LBO temperature to fulfill the selection of the critical phase matching. The output powers at a pump power of 40 W can be up to 8.0, 6.1, and 9.8 W for the single-peak emission at 588.7, 565.7, and 559.1 nm, respectively. Finally, a dual-peak emission of 565.7 and 572.3 nm with total output power of 5.2 W can be generated by tuning LBO temperature to match the SFG for 572.3 nm.

11.
Opt Express ; 32(8): 14461-14470, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38859390

RESUMO

High-power efficient continuous-wave Nd:YVO4/KGW Raman lasers at 555 and 559 nm are achieved by using a double-sided dichroic coating output coupler to improve the resonance quality factor. The Np-cut potassium gadolinium tungstate (KGW) is used to generate the Stokes waves at 1159 and 1177 nm by placing the polarization of the1064 nm fundamental wave parallel to the Ng and Nm axes, respectively. The lithium triborate (LBO) crystal with the cut angle in the XY plane for the type-I phase matching is used to perform the intracavity sum frequency generation for yielding the green light at 555 nm and the lime light at 559 nm at the optimal phase matching temperature. Experimental results were systematically accomplished to comprehend the optimal cavity length for the conversion efficiency. Under the optimal cavity length, the output powers can reach 6.6 and 6.3 W at a pump power of 22 W for the wavelengths of 555 and 559 nm, respectively. The conversion efficiencies can be up to 30% and 28.6% for 555 and 559 nm, respectively.

12.
Materials (Basel) ; 17(12)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38930356

RESUMO

As the reliability and lifespan requirements of modern equipment continues to escalate, the problems with very high cycle fatigue (VHCF) has obtained increasingly widespread attention, becoming a hot topic in fatigue research. Titanium alloys, which are the most extensively used metal materials in the modern aerospace industry, are particularly prone to VHCF issues. The present study systematically reviewed and summarized the latest (since 2010) developments in VHCF research on titanium alloy, with special focus on the (i) experimental methods, (ii) macroscopic and microscopic characteristics of the fatigue fractures, and (iii) construction of fatigue fracture models. More specifically, the review addresses the technological approaches that were used, mechanisms of fatigue crack initiation, features of the S-N curves and Goodman diagrams, and impact of various factors (such as processing, temperature, and corrosion). In addition, it elucidates the damage mechanisms, evolution, and modeling of VHCF in titanium alloys, thereby improving the understanding of VHCF patterns in titanium alloys and highlighting the current challenges in VHCF research.

13.
Acta Pharmacol Sin ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914676

RESUMO

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38872241

RESUMO

STUDY DESIGN: The study included two fresh-frozen cadavers. OBJECTIVE: To elucidate the positional relationship between surgical instruments and nerve roots during full endoscopic facet-sparing (FE fs-TLIF) and facet-resecting (FE fr-TLIF) lumbar interbody fusion and propose safe instrumentation insertion procedures and recommend cage glider designs aimed at protecting nerve roots. SUMMARY OF BACKGROUND DATA: Endoscopic surgical techniques are increasingly used for minimally invasive lumbar fusion surgery with FE fr-TLIF and FE fs-TLIF being common approaches. However, the risk of nerve root injury remains a significant concern during these procedures. METHODS: Eight experienced endoscopic spine surgeons performed uniportal FE fr-TLIF and FE fs-TLIF on cadaveric lumbar spines, totaling 16 surgeries. Post-operation, soft tissues were removed to assess the positional relationship between the cage entry point and nerve roots. Distances between the cage entry point, traversing nerve root, and exiting nerve root were measured. Safe instrumentation design and insertion procedures were determined. RESULTS: In FE fr-TLIF, the mean distance between the cage entry point and traversing nerve root was significantly shorter compared to FE fs-TLIF (3.30±1.35 mm vs. 8.58±2.47 mm, respectively; P<0.0001). Conversely, the mean distance between the cage entry point and the exiting nerve root was significantly shorter in FE fs-TLIF compared to FE fr-TLIF (3.73±1.97 mm vs. 6.90±1.36 mm, respectively; P<0.0001). For FE fr-TLIF, prioritizing the protection of the traversing root using a two-bevel tip cage glider was crucial. In contrast, for FE fs-TLIF, a single-bevel tip cage glider placed in the caudal location was recommended. CONCLUSION: This study elucidates the anatomical relationship between cage entry points and nerve roots in uniportal endoscopic lumbar fusion surgery. Protection strategies should prioritize the traversing root in FE fr-TLIF and the exiting root in FE fs-TLIF, with corresponding variations in surgical techniques. LEVEL OF EVIDENCE: V.

15.
J Fish Dis ; : e13982, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899543

RESUMO

Edwardsiella anguillarum, a highly virulent species within the Edwardsiella genus, causes significant mortality in milkfish farms in Taiwan. This study aimed to investigate the comparison of milkfish susceptibility, a newly identified host species in Taiwanese aquaculture, with other species Nile tilapia (Oreochromis niloticus) and Asian seabass (Lates calcarifer), to E. anguillarum, elucidating its pathogenicity across both seawater and freshwater aquaculture environments. The results showed milkfish exhibited the highest mortality rate of 85% within 48 h of infection, whereas Nile tilapia exhibited a mortality rate of 70% between the second- and tenth-day post challenge, and seabass exhibited a mortality rate of 25% between the second- and sixth-day post challenge. Gross lesions observed in milkfish included splenomegaly and haemorrhage, whereas Nile tilapia exhibited signs of ascites, exophthalmia and brain haemorrhage. Seabass displayed spleen granulomas and haemorrhage at the injection site. Histopathological analysis revealed common features across all three species, including multifocal necrosis, bacterial presence in the necrotic areas, serositis and oedema. Asian seabass also exhibited chronic lesions in the form of splenic granulomas. This study highlights the high susceptibility of milkfish and Nile tilapia to E. anguillarum, emphasizing the urgent need for further investigation into targeted vaccine development for these fish species. These results not only deepen our understanding of the differing levels of pathogenicity among the three species but also offer valuable insights for improving disease prevention and management strategies in aquaculture, including those applied within polyculture systems and for the maintenance of aquaculture water environments.

16.
Bioorg Med Chem Lett ; 108: 129816, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38806101

RESUMO

As our ongoing work, a novel series of the amide-based CA-4 analogues were successfully designed, synthesized, and explored for their biological evaluation. Among these compounds, 7d and 8a illustrated most potent antiproliferative activity toward A549, HeLa, HCT116, and HT-29 cell lines. Most importantly, these two compounds didn't display noticeable cytotoxic activity on the non-tumoural cell line HEK-293. Further mechanism studies revealed that analogue 8a was identified as a novel tubulin polymerization inhibitor with an IC50 value of 6.90 µM, which is comparable with CA-4. The subsequent investigations unveiled that analogue 8a not only effectively caused cell cycle arrest at the G2/M phase but also induced apoptosis in A549 cells via a concentration-dependent manner. The molecular docking revealed that 8a could occupy well the colchicine-binding site of tubulin. Collectively, these findings indicate that amide-based CA-4 scaffold could be worthy of further evaluation for development of novel tubulin inhibitors with improved safety profile.


Assuntos
Amidas , Antineoplásicos , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Estilbenos , Moduladores de Tubulina , Tubulina (Proteína) , Humanos , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química , Tubulina (Proteína)/metabolismo , Relação Estrutura-Atividade , Amidas/química , Amidas/farmacologia , Amidas/síntese química , Proliferação de Células/efeitos dos fármacos , Estilbenos/química , Estilbenos/farmacologia , Estilbenos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Estrutura Molecular , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Células HEK293
17.
Curr Gene Ther ; 24(4): 292-306, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38783529

RESUMO

BACKGROUND: Many studies have suggested that tea has antidepressant effects; however, the underlying mechanism is not fully studied. As the main anti-inflammatory polyphenol in tea, catechin may contribute to the protective role of tea against depression. OBJECTIVE: The objective of this study is to prove that catechin can protect against lipopolysaccharide (LPS)-induced depressive-like behaviours in mice, and then explore the underlying molecular mechanisms. METHODS: Thirty-one C57BL/6J mice were categorized into the normal saline (NS) group, LPS group, catechin group, and amitriptyline group according to their treatments. Elevated Plus Maze (EPM), Tail Suspension Test (TST), and Open Field Test (OFT) were employed to assess depressive- like behaviours in mice. RNA sequencing (RNA-seq) and subsequent Bioinformatics analyses, such as differential gene analysis and functional enrichment, were performed on the four mouse groups. RESULTS: In TST, the mice in the LPS group exhibited significantly longer immobility time than those in the other three groups, while the immobility times for the other three groups were not significantly different. Similarly in EPM, LPS-treated mice exhibited a significantly lower percentage in the time/path of entering open arms than the mice in the other three groups, while the percentages of the mice in the other three groups were not significantly different. In OFT, LPS-treated mice exhibited significantly lower percentages in the time/path of entering the centre area than those in the other three groups. The results suggested that the LPS-induced depression models were established successfully and catechin can reverse (LPS)-induced depressive-like behaviours in mice. Finally, RNA-seq analyses revealed 57 differential expressed genes (DEGs) between LPS and NS with 19 up-regulated and 38 down-regulated. Among them, 13 genes were overlapped with the DEGs between LPS and cetechin (in opposite directions), with an overlapping p-value < 0.001. The 13 genes included Rnu7, Lcn2, C4b, Saa3, Pglyrp1, Gpx3, Lyz2, S100a8, S100a9, Tmem254b, Gm14288, Hbb-bt, and Tmem254c, which might play key roles in the protection of catechin against LPS-induced depressive-like behaviours in mice. The 13 genes were significantly enriched in defense response and inflammatory response, indicating that catechin might work through counteracting changes in the immune system induced by LPS. CONCLUSION: Catechin can protect mice from LPS-induced depressive-like behaviours through affecting inflammatory pathways and neuron-associated gene ontologies.


Assuntos
Comportamento Animal , Catequina , Depressão , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Animais , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/efeitos adversos , Catequina/farmacologia , Camundongos , Depressão/tratamento farmacológico , Depressão/induzido quimicamente , Depressão/genética , Masculino , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/induzido quimicamente , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos
18.
J Glob Antimicrob Resist ; 38: 98-102, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38719187

RESUMO

Over 1 year, two KPC-producing and two non-KPC-producing Klebsiella pneumoniae strains were isolated from a patient. Genome and DNA hybridization analyses revealed the first three strains as a clonal lineage, with carbapenem resistance changes due to a Tn2-like transposon on an IncR/IncFII plasmid. The fourth strain, carrying three plasmids, caused a lethal infection and represented a different lineage. All strains belonged to the ST11-SL47-OL101 type. This study highlights the Tn2-like transposon's role in carbapenemase gene spread and the importance of distinguishing between bacterial colonization and infection.

19.
Langmuir ; 40(22): 11411-11418, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38778044

RESUMO

Enhanced electrokinetic phenomena, manifested through the observation of a large streaming potential (Vs), were obtained in microchannels with single-layer graphene (SLG)-coated and few-layer graphene (FLG)-coated surfaces. In comparison to silicon microchannels, the Vs obtained for a given pressure difference along the channel (ΔP) was higher by 75% for the graphene-based channels, with larger values in the SLG case. Computational modeling was used to correlate the surface charge density, tuned through plasma processing, and related zeta potential to measured Vs. The implications related to deploying lower dimensional material surfaces for modulating electrokinetic flows were investigated.

20.
Regen Ther ; 26: 33-41, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38798745

RESUMO

Background: The morbidity and mortality of sepsis are increasing year by year. Statistically, 40-50% of patients with sepsis have concomitant myocardial injury, and its mortality rate is higher than that of patients with sepsis only. Therefore, it is of great significance to elucidate the mechanism of sepsis-induced myocardial injury. Methods and results: Human monocytes (THP-1) were used to induce M0 macrophages, followed by treated with lipopolysaccharide (LPS). Cardiomyocytes (AC16) were co-cultured with the conditioned medium of LPS-induced macrophages to induce injury. Quantitative real-time PCR was employed to detect the mRNA levels of peroxisome proliferator-activated receptor α (PPARA) and dual specificity phosphatase 1 (DUSP1). Protein levels of PPARA, macrophage polarization-related markers, apoptosis-related markers, mitochondria-related proteins, and DUSP1 were analyzed by Western blot. Flow cytometry was used to assess M1/M2 cell rates and apoptosis. Low PPARA expression could serve as a biomarker for patients with sepsis. PPARA overexpression enhanced M2 polarization and suppressed M1 polarization in LPS-induced macrophages, and it could alleviate cardiomyocyte injury in co-cultured system. PPARA bound to the DUSP1 promoter region and facilitated its expression. DUSP1 knockdown reversed the effect of PPARA overexpression on M2 polarization and cardiomyocyte injury. Conclusion: PPARA attenuated cardiomyocyte injury by promoting macrophage M2 polarization through increasing DUSP1 expression, suggesting that PPARA might be a therapy target for sepsis-induced myocardial injury.

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