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1.
Ageing Res Rev ; 99: 102363, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38838785

RESUMO

The basolateral amygdala (BLA) is the subregion of the amygdala located in the medial of the temporal lobe, which is connected with a wide range of brain regions to achieve diverse functions. Recently, an increasing number of studies have focused on the participation of the BLA in many neuropsychiatric disorders from the neural circuit perspective, aided by the rapid development of viral tracing methods and increasingly specific neural modulation technologies. However, how to translate this circuit-level preclinical intervention into clinical treatment using noninvasive or minor invasive manipulations to benefit patients struggling with neuropsychiatric disorders is still an inevitable question to be considered. In this review, we summarized the role of BLA-involved circuits in neuropsychiatric disorders including Alzheimer's disease, perioperative neurocognitive disorders, schizophrenia, anxiety disorders, depressive disorders, posttraumatic stress disorders, autism spectrum disorders, and pain-associative affective states and cognitive dysfunctions. Additionally, we provide insights into future directions and challenges for clinical translation.

2.
Heliyon ; 10(11): e32187, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38868075

RESUMO

PAXLOVID™ (Co-packaging of Nirmatrelvir with Ritonavir) has been approved for the treatment of Coronavirus Disease 2019 (COVID-19). The goal of the experiment was to create an accurate and straightforward analytical method using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to simultaneously quantify nirmatrelvir and ritonavir in rat plasma, and to investigate the pharmacokinetic profiles of these drugs in rats. After protein precipitation using acetonitrile, nirmatrelvir, ritonavir, and the internal standard (IS) lopinavir were separated using ultra performance liquid chromatography (UPLC). This separation was achieved with a mobile phase composed of acetonitrile and an aqueous solution of 0.1% formic acid, using a reversed-phase column with a binary gradient elution. Using multiple reaction monitoring (MRM) technology, the analytes were detected in the positive electrospray ionization mode. Favorable linearity was observed in the calibration range of 2.0-10000 ng/mL for nirmatrelvir and 1.0-5000 ng/mL for ritonavir, respectively, within plasma samples. The lower limits of quantification (LLOQ) attained were 2.0 ng/mL for nirmatrelvir and 1.0 ng/mL for ritonavir, respectively. Both drugs demonstrated inter-day and intra-day precision below 15%, with accuracies ranging from -7.6% to 13.2%. Analytes were extracted with recoveries higher than 90.7% and without significant matrix effects. Likewise, the stability was found to meet the requirements of the analytical method under different conditions. This UPLC-MS/MS method, characterized by enabling accurate and precise quantification of nirmatrelvir and ritonavir in plasma, was effectively utilized for in vivo pharmacokinetic studies in rats.

3.
Neuropharmacology ; 257: 110032, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852839

RESUMO

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

4.
Transl Oncol ; 46: 102018, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38838436

RESUMO

Invasion and migration are the primary factors for mortality in lung adenocarcinoma (LUAD) patients. The precise role of RNA-binding motif protein15 (RBM15)-mediated m6A modification in LUAD is not yet fully clarified. This research aims to elucidate the mechanism of RBM15 in the invasion and migration of LUAD. Western blot and dot blot assay results showed that RBM15 and methylation levels of m6A were highly expressed in LUAD tissues. Overexpression of RBM15 by lentivirus transfection increased m6A levels and promoted the invasion, migration, and proliferation of A549 and H1734 cells. Knockdown of RBM15 by lentivirus transfection had opposite effects on m6A levels, invasion, migration, and proliferation of A549 and H1734 cells. The results of nude mouse proliferation models confirmed that RBM15 knockdown inhibited in vivo tumor proliferation . Sequencing and immunoprecipitation identified RASSF8 as an interacting protein of RBM15 involved in cell invasion and migration. RBM15-mediated m6A modification inhibited RASSF8 protein levels and increased LUAD cell invasion and migration. The rescue assays demonstrated that the regulation of RBM15 on LUAD cell invasion and migration was partially rescued by RASSF8. In conclusion, RBM15-mediated m6A modification inhibits the RASSF8 protein levels and increases cell invasion and migration. Thus, targeting the RBM15-m6A-RASSF8 axis may be a promising strategy for repressing LUAD cell invasion and migration.

5.
Front Optoelectron ; 17(1): 16, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833110

RESUMO

In current documented studies, it has been observed that wavelength converters utilizing AlGaAsOI waveguides exhibit suboptimal on-chip wavelength conversion efficiency from the C-band to the 2 µm band, generally falling below -20.0 dB. To address this issue, we present a novel wavelength conversion device assisted by a waveguide amplifier, incorporating both AlGaAs wavelength converter and erbium-ytterbium co-doped waveguide amplifier, thereby achieving a notable conversion efficiency exceeding 0 dB. The noteworthy enhancement in efficiency can be attributed to the specific dispersion design of the AlGaAs wavelength converter, which enables an upsurge in conversion efficiency to -15.54 dB under 100 mW of pump power. Furthermore, the integration of an erbium-ytterbium co-doped waveguide amplifier facilitates a loss compensation of over 15 dB. Avoiding the use of external optical amplifiers, this device enables efficient and high-bandwidth wavelength conversion, showing promising applications in various fields, such as optical communication, sensing, imaging, and beyond.

6.
Phys Rev Lett ; 132(22): 221802, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38877918

RESUMO

To enhance the scientific discovery power of high-energy collider experiments, we propose and realize the concept of jet-origin identification that categorizes jets into five quark species (b,c,s,u,d), five antiquarks (b[over ¯],c[over ¯],s[over ¯],u[over ¯],d[over ¯]), and the gluon. Using state-of-the-art algorithms and simulated νν[over ¯]H,H→jj events at 240 GeV center-of-mass energy at the electron-positron Higgs factory, the jet-origin identification simultaneously reaches jet flavor tagging efficiencies ranging from 67% to 92% for bottom, charm, and strange quarks and jet charge flip rates of 7%-24% for all quark species. We apply the jet-origin identification to Higgs rare and exotic decay measurements at the nominal luminosity of the Circular Electron Positron Collider and conclude that the upper limits on the branching ratios of H→ss[over ¯],uu[over ¯],dd[over ¯] and H→sb,db,uc,ds can be determined to 2×10^{-4} to 1×10^{-3} at 95% confidence level. The derived upper limit for H→ss[over ¯] decay is approximately 3 times the prediction of the standard model.

7.
J Pharm Sci ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876368

RESUMO

The use of recombinant adeno-associated virus (AAV) vectors is a popular choice for in vivo gene therapy, with hundreds of ongoing clinical trials targeting various genetic diseases. However, due to limited material availability and the complexity of AAV structure, there is a critical lack of comprehensive studies on AAV degradation pathways. In this study, we intended to elucidate the degradation pathways for a model AAV9 with GFP as the transgene under relevant stressed conditions. We assessed a diverse set of critical quality attributes and examined the overall impact of various stresses on transgene expression. This assessment revealed various degradation mechanisms of AAV9 and demonstrated the potential risk of a base formulation in causing AAV9 instability and potency loss under thermal stress at 25 and 40°C while maintaining stability under freeze-thaw stress, interfacial stress due to membrane filtration, and short-term storage of up to 4 weeks at 5°C.

8.
J Pain ; : 104598, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866121

RESUMO

The voltage-gated sodium channel ß2 subunit protein (SCN2B) plays a crucial role in neuropathic pain. However, the role and mechanisms of SCN2B in orofacial neuropathic pain are still unclear. This study aimed to investigate the upstream regulatory mechanisms of SCN2B in the trigeminal ganglion (TG) underlying orofacial neuropathic pain. Chronic constriction injury of the infraorbital nerve (CCI-ION) of mice was performed to establish the model of orofacial neuropathic pain. Von-Frey filament test was performed to detect the head withdrawal threshold (HWT) of mice. RT-qPCR, WB, FISH, and IF were used to detect the expression and distribution of SCN2B and miR-6954-3p in the TG of mice. A luciferase activity assay was carried out to prove the binding between SCN2B mRNA and miR-6954-3p. After the CCI-ION surgery, the levels of Scn2b mRNA and protein significantly increased and miR-6954-3p decreased in the TG of mice with decreasing HWT. IF staining revealed that SCN2B was expressed specifically in the TG neurons. Silencing SCN2B in the TG of CCI-ION mice significantly increased the HWT. Importantly, the 3' untranslated region (UTR) of Scn2b mRNA was proved to bind with miR-6954-3p. FISH and IF staining demonstrated that miR-6954-3p was expressed in TG neurons and co-expressed with SCN2B. Furthermore, intra-ganglionic injection of miR-6954-3p agomir into the TG of CCI-ION mice resulted in the down-regulation of SCN2B and increased the HWT. These findings suggest that the down-regulation of miR-6954-3p in the TG promotes orofacial neuropathic pain by promoting SCN2B expression following trigeminal nerve injury. PERSPECTIVE: This study points to the important role of SCN2B in orofacial neuropathic pain. Furthermore, miR-6954-3p is proven to regulate the expression of SCN2B by binding to the 3' UTR of Scn2b mRNA. These findings indicate that SCN2B and miR-6954-3p are potential therapeutic targets for the treatment of orofacial neuropathic pain.

9.
Biosensors (Basel) ; 14(6)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38920578

RESUMO

A fluorogenic aptamer (FA)-based hybridization chain reaction (HCR) could provide a sensitive and label-free signal amplification method for imaging molecules in living cells. However, existing FA-HCR methods usually face some problems, such as a complicated design and significant background leakage, which greatly limit their application. Herein, we developed an FA-centered HCR (FAC-HCR) method based on a remote toehold-mediated strand displacement reaction. Compared to traditional HCRs mediated by four hairpin probes (HPs) and two HPs, the FAC-HCR displayed significantly decreased background leakage and improved sensitivity. Furthermore, the FAC-HCR was used to test a non-nucleic acid target, apurinic/apyrimidinic endonuclease 1 (APE1), an important BER-involved endonuclease. The fluorescence analysis results confirmed that FAC-HCR can reach a detection limit of 0.1174 U/mL. By using the two HPs for FAC-HCR with polyetherimide-based nanoparticles, the activity of APE1 in living cells can be imaged. In summary, this study could provide a new idea to design an FA-based HCR and improve the performance of HCRs in live cell imaging.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA Liase (Sítios Apurínicos ou Apirimidínicos) , Hibridização de Ácido Nucleico , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Humanos , Corantes Fluorescentes
10.
ACS Appl Mater Interfaces ; 16(25): 32503-32515, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38875477

RESUMO

Hierarchically structural particles (HSPs) are highly regarded as favorable nanomaterials for superhydrophobic coating due to their special multiscale structure and surface physicochemical properties. However, most of the superhydrophobic coatings constructed from HSPs are monofunctional, constraining their broader applications. Moreover, traditional methods for constructing HSPs mostly rely on complicated chemical routes and template removal. Herein, we propose an innovative strategy (one-pot method) for producing multifunctional hierarchical hybrid particles (HHPs). Polysilsesquioxane (PSQ), generated from hydrolysis condensation of methyltriethoxylsilane, is used as the sole stabilizer to anchor on the surface of styrene and short fluoroalkyl compound tridecafluorooctyl acrylate comonomers droplets, forming a mesoporous PSQ shell. Subsequently, the comonomers inside of the shell perform restricted polymerization to generate the HHP due to the driving of the mesoporous capillary force. The HHP is then mixed with waterborne polyurethane (WPU) to develop a robust nanocomposite coating (WPU-HHP). Through the deliberate design of the HHP components, the WPU-HHP coating has thermal insulation, photoluminescence properties, and the ability to achieve a wettability transition during abrasion. Our research has achieved the integration of multifunctionality in one waterborne hybrid system, broadening the application areas of nanocomposite coatings.

11.
Sci Rep ; 14(1): 14439, 2024 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-38910214

RESUMO

Transjugular intrahepatic portosystemic shunt (TIPS) creation using the Viatorr stent remains relatively uncommon in underdeveloped and high-burden disease regions in Asia-Pacific, and there is a lack of comparative studies regarding its prognostic effects compared with the generic stent-graft/bare stent combination. The purpose of this retrospective study is to compare the prognostic endpoints of these two treatments in patients who underwent TIPS creation. Clinical data from 145 patients were collected, including 82 in the combination group and 63 in the Viatorr group. Differences in prognostic endpoints (shunt dysfunction, death, overt hepatic encephalopathy [OHE], rebleeding) between the two groups were analyzed using Kaplan-Meier curves. The Cox proportional hazards model was used to identify independent risk factors for post-TIPS shunt dysfunction. The TIPS procedure was successful in all patients. After TIPS creation, both groups showed a significant decrease in porto-caval pressure gradient compared to that before TIPS creation. The stent patency rates at 6, 12, and 18 months were high in both the combination and Viatorr groups (93.7%, 88.5%, and 88.5% vs. 96.7%, 93.4%, and 93.4%, respectively). The stent patency rates was higher in the combination group than in the Viatorr group, although not statistically significant (HR = 2.105, 95% CI 0.640-6.922, Log-rank P = 0.259). There were no significant differences in other prognostic endpoints (death, OHE, rebleeding) between the two groups. The Cox model identified portal vein diameter (HR = 0.807, 95% CI 0.658-0.990, P = 0.040) and portal vein thrombosis (HR = 13.617, 95% CI 1.475-125.678, P = 0.021) as independent risk factors for post-TIPS shunt dysfunction. The shunt patency rates between the Viatorr stent and the generic stent-graft/bare stent combination showed no significant difference and the generic stent-graft/bare stent combination may be a viable alternative in areas where the Viatorr stent is not yet available.


Assuntos
Derivação Portossistêmica Transjugular Intra-Hepática , Stents , Humanos , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Stents/efeitos adversos , Estudos Retrospectivos , Idoso , Adulto , Resultado do Tratamento , Prognóstico , Fatores de Risco , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/cirurgia , Modelos de Riscos Proporcionais , Estimativa de Kaplan-Meier
12.
Materials (Basel) ; 17(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38793268

RESUMO

Commercial oxygen-free copper sheets were cold-rolled with reduction rates ranging from 20% to 87% and annealed at 400, 500 and 600 °C. The microstructure and texture evolution during the cold-rolling and annealing processes were studied using optical microscopy (OM), scanning electron microscopy (SEM) and electron back-scattered diffraction (EBSD). The results show that the deformation textures of {123}<634> (S), {112}<111> (Copper) and {110}<112> (Brass) were continuously enhanced with the increase in cold-rolling reduction. The orientations along the α-oriented fiber converged towards Brass, and the orientation density of ß fiber obviously increased when the rolling reduction exceeded 60%. The recrystallization texture was significantly affected by the cold-rolling reduction. After 60% cold-rolling reduction, Copper and S texture components gradually decreased, and the {011}<511> recrystallization texture component formed with the increase in annealing temperature. After 87% cold-rolling reduction, a strong Cube texture formed, and other textures were inhibited with the increase in annealing temperature. The strong Brass and S deformation texture was conducive to the formation of a strong Cube annealing texture. The density of the annealing twin boundary decreased with the increase in annealing temperature, and more annealing twin boundaries formed in the oxygen-free copper sheets with the increase in cold-rolling reduction.

13.
Heliyon ; 10(10): e31380, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803927

RESUMO

Objective: Our aim was to develop and validate a nomogram for predicting the in-hospital 14-day (14 d) and 28-day (28 d) survival rates of patients with coronavirus disease 2019 (COVID-19). Methods: Clinical data of patients with COVID-19 admitted to the Renmin Hospital of Wuhan University from December 2022 to February 2023 and the north campus of Shanghai Ninth People's Hospital from April 2022 to June 2022 were collected. A total of 408 patients from Renmin Hospital of Wuhan University were selected as the training cohort, and 151 patients from Shanghai Ninth People's Hospital were selected as the verification cohort. Independent variables were screened using Cox regression analysis, and a nomogram was constructed using R software. The prediction accuracy of the nomogram was evaluated using the receiver operating characteristic (ROC) curve, C-index, and calibration curve. Decision curve analysis was used to evaluate the clinical application value of the model. The nomogram was externally validated using a validation cohort. Result: In total, 559 patients with severe/critical COVID-19 were included in this study, of whom 179 (32.02 %) died. Multivariate Cox regression analysis showed that age >80 years [hazard ratio (HR) = 1.539, 95 % confidence interval (CI): 1.027-2.306, P = 0.037], history of diabetes (HR = 1.741, 95 % CI: 1.253-2.420, P = 0.001), high APACHE II score (HR = 1.083, 95 % CI: 1.042-1.126, P < 0.001), sepsis (HR = 2.387, 95 % CI: 1.707-3.338, P < 0.001), high neutrophil-to-lymphocyte ratio (NLR) (HR = 1.010, 95 % CI: 1.003-1.017, P = 0.007), and high D-dimer level (HR = 1.005, 95 % CI: 1.001-1.009, P = 0.028) were independent risk factors for 14 d and 28 d survival rates, whereas COVID-19 vaccination (HR = 0.625, 95 % CI: 0.440-0.886, P = 0.008) was a protective factor affecting prognosis. ROC curve analysis showed that the area under the curve (AUC) of the 14 d and 28 d hospital survival rates in the training cohort was 0.765 (95 % CI: 0.641-0.923) and 0.814 (95 % CI: 0.702-0.938), respectively, and the AUC of the 14 d and 28 d hospital survival rates in the verification cohort was 0.898 (95 % CI: 0.765-0.962) and 0.875 (95 % CI: 0.741-0.945), respectively. The calibration curves of 14 d and 28 d hospital survival showed that the predicted probability of the model agreed well with the actual probability. Decision curve analysis (DCA) showed that the nomogram has high clinical application value. Conclusion: In-hospital survival rates of patients with COVID-19 were predicted using a nomogram, which will help clinicians in make appropriate clinical decisions.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38691150

RESUMO

Urinary tract infection (UTI) is one of the most prevalent bacterial infectious diseases worldwide. However, the resistance of urinary pathogens to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole increased. Pivmecillinam is a prodrug of mecillinam, which is effective for the treatment of urinary tract infections. The purpose of this study was to assess the safety, and pharmacokinetics of pivmecillinam and mecillinam after single- and multiple-dose oral administration of pivmecillinam tablets in healthy Chinese subjects. The study also investigated the profile of urinary excretion of mecillinam, as well as the effect of food and gender on the pharmacokinetics of pivmecillinam and mecillinam. This study was a single-center, open-label phase I study carried out in three groups. In total, 34 subjects were included in the study: group 1-food effect study with pivmecillinam 200 mg (n = 12); group 2-single- and multiple-dose study with pivmecillinam 400 mg (n = 12); group 3-single dose study with pivmecillinam 600 mg (n = 10). The plasma and urine concentrations of pivmecillinam and mecillinam were measured, and their pharmacokinetics were calculated. Treatment-emergent adverse events were evaluated and recorded in safety assessments for three groups. No severe adverse events were found in this study. After a single dose of pivmecillinam was taken orally, the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) of pivmecillinam increased in a dose-proportional manner, nor did mecillinam. Food had significant effects on Cmax and AUC0-t of pivmecillinam and Cmax of mecillinam. The mean cumulative percentage of urine excretion of mecillinam at 0 to 24 h ranged from 35.5 to 44.0%. Urinary cumulative excretion is relative to the drug dose, but the diet and multiple-dose administration did not affect the urinary cumulative excretion rate. The safety and pharmacokinetics of pivmecillinam and mecillinam after single- (200/400/600 mg) or multiple-dose (400 mg) administration were demonstrated in healthy Chinese subjects. Food affected the pharmacokinetics of pivmecillinam and mecillinam.

15.
J Fluoresc ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691280

RESUMO

A novel fluorescent sensor for the detection of Cu2+ was developed based on carbazole derivatives. After the addition of Cu2+, the sensor exhibited obvious fluorescence quenching phenomenon, and the optical signal variation also enabled the sensor to quantitatively analyze Cu2+ due to the formation of a stable 1:1 metal-ligand complex in a short time. In addition, the sensor possessed chemical reversibility and pH stability. The cell imaging and zebra fish experiments also verified its application value in biological system.

16.
Environ Sci Technol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38757358

RESUMO

PFAS (poly- and per-fluorinated alkyl substances) represent a large family of recalcitrant organic compounds that are widely used and pose serious threats to human and ecosystem health. Here, palladium (Pd0)-catalyzed defluorination and microbiological mineralization were combined in a denitrifying H2-based membrane biofilm reactor to remove co-occurring perfluorooctanoic acid (PFOA) and nitrate. The combined process, i.e., Pd-biofilm, enabled continuous removal of ∼4 mmol/L nitrate and ∼1 mg/L PFOA, with 81% defluorination of PFOA. Metagenome analysis identified bacteria likely responsible for biodegradation of partially defluorinated PFOA: Dechloromonas sp. CZR5, Kaistella koreensis, Ochrobacterum anthropic, and Azospira sp. I13. High-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and metagenome analyses revealed that the presence of nitrate promoted microbiological oxidation of partially defluorinated PFOA. Taken together, the results point to PFOA-oxidation pathways that began with PFOA adsorption to Pd0, which enabled catalytic generation of partially or fully defluorinated fatty acids and stepwise oxidation and defluorination by the bacteria. This study documents how combining catalysis and microbiological transformation enables the simultaneous removal of PFOA and nitrate.

17.
Sci China Life Sci ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38748354

RESUMO

Dynamic crosstalk between the embryo and mother is crucial during implantation. Here, we comprehensively profile the single-cell transcriptome of pig peri-implantation embryos and corresponding maternal endometrium, identifying 4 different lineages in embryos and 13 cell types in the endometrium. Cell-specific gene expression characterizes 4 distinct trophectoderm subpopulations, showing development from undifferentiated trophectoderm to polar and mural trophectoderm. Dynamic expression of genes in different types of endometrial cells illustrates their molecular response to embryos during implantation. Then, we developed a novel tool, ExtraCellTalk, generating an overall dynamic map of maternal-foetal crosstalk using uterine luminal proteins as bridges. Through cross-species comparisons, we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 could target the STRA6 receptor on stromal cells to regulate the interaction with other endometrial cells. These results provide insight into the maternal-foetal crosstalk during embryo implantation and represent a valuable resource for further studies to improve embryo implantation.

18.
Hum Gene Ther ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767512

RESUMO

Genome editing has the potential to treat genetic diseases in a variety of tissues including the lung. We have previously developed and validated a dual adeno-associated virus (AAV) CRISPR platform that supports effective editing in the airways of mice. To validate this delivery vehicle in a large animal model, we have shown that intratracheal instillation of CRISPR/Cas9 in AAV5 can edit a housekeeping gene or a disease-related gene in the lungs of young rhesus monkeys. We observed up to 8% editing of ACE2 in lung lobes after single-dose administration. Single-nuclear RNA-sequencing revealed that AAV5 transduces multiple cell types in the caudal lung lobes, including alveolar cells, macrophages, fibroblasts, endothelial cells, and B cells. These results demonstrate that AAV5 is efficient in the delivery of CRISPR/Cas9 in the lung lobes of young rhesus monkeys.

19.
Biosensors (Basel) ; 14(5)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38785718

RESUMO

A novel indolium-based fluorescent probe for the detection of CN- was developed based on the conjugation of 1, 2, 3, 3-Tetramethyl-3H-indolium iodide and 2-acetyl benzothiophene. The introduction of external CN- caused a nucleophilic attack to the quaternary amine salt structure in the probe and resulted in the departure of iodide ions and the steric rotation of the index salt group, which caused fluorescence quenching. The titration experiments showed that the probe had rapid qualitative and quantitative analysis capabilities for CN-. Moreover, the relevant biocompatibility experiments also demonstrated the potential application value of the probe.


Assuntos
Cianetos , Corantes Fluorescentes , Indóis , Espectrometria de Fluorescência , Corantes Fluorescentes/química , Indóis/química , Cianetos/análise , Técnicas Biossensoriais
20.
Biomed Mater ; 19(4)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38815605

RESUMO

Traditional dressings exhibit several disadvantages, as they frequently lead to bacterial infections, cause severe tissue adhesion and perform a relatively single function. Therefore, in this study, a composite sponge dressing with antibacterial properties and excellent physicochemical properties was developed. Six groups of tobramycin-loaded calcium alginate microspheres were prepared by changing the amount of tobramycin added, and the optimal group was selected. Then, seven groups of tobramycin-loaded calcium alginate microsphere/chitosan composite sponges were fabricated via a solvent blending process and a freeze-drying method. The surface morphology, physicochemical properties,in vitrodegradation properties,in vitrodrug release properties, antibacterial properties and cytotoxicity of the composite sponges were examined. Group 3.0 contained the best microspheres with the largest drug loading capacity, good swelling performance and cumulative drug release rate, obvious and sustained antibacterial activity, and good cytocompatibility. The tobramycin-loaded calcium alginate microsphere/chitosan composite sponges exhibited three-dimensional porous structures, and their porosity, swelling rate, water absorption and water retention rates and water vapor transmission rate met the standards needed for an ideal dressing. The comprehensive performance of the sponge was best when 20 mg of drug-loaded microspheres was added (i.e. group 20). The cumulative drug release rate of the sponge was 29.67 ± 4.14% at 7 d, the diameters of the inhibition zones against the three bacteria were greater than 15 mm, and L929 cell proliferation was promoted. These results demonstrated that the tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with 20 mg of tobramycin-loaded microspheres shows promise as a dressing for infected wounds.


Assuntos
Alginatos , Antibacterianos , Bandagens , Quitosana , Microesferas , Tobramicina , Cicatrização , Alginatos/química , Quitosana/química , Antibacterianos/farmacologia , Antibacterianos/química , Tobramicina/farmacologia , Tobramicina/química , Tobramicina/administração & dosagem , Animais , Cicatrização/efeitos dos fármacos , Porosidade , Camundongos , Materiais Biocompatíveis/química , Teste de Materiais , Staphylococcus aureus/efeitos dos fármacos , Linhagem Celular , Liberação Controlada de Fármacos , Testes de Sensibilidade Microbiana , Humanos , Escherichia coli/efeitos dos fármacos
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