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1.
Environ Sci Technol ; 58(15): 6552-6563, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38571383

RESUMO

Extracellular polymeric substances (EPS) ubiquitously encapsulate microbes and play crucial roles in various environmental processes. However, understanding their complex interactions with dynamic bacterial behaviors, especially during the disinfection process, remains very limited. In this work, we investigated the impact of EPS on bacterial disinfection kinetics by developing a permanent EPS removal strategy. We genetically disrupted the synthesis of exopolysaccharides, the structural components of EPS, in Pseudomonas aeruginosa, a well-known EPS-producing opportunistic pathogen found in diverse environments, creating an EPS-deficient strain. This method ensured a lasting absence of EPS while maintaining bacterial integrity and viability, allowing for real-time in situ investigations of the roles of EPS in disinfection. Our findings indicate that removing EPS from bacteria substantially lowered their susceptibility threshold to disinfectants such as ozone, chloramine B, and free chlorine. This removal also substantially accelerated disinfection kinetics, shortened the resistance time, and increased disinfection efficiency, thereby enhancing the overall bactericidal effect. The absence of EPS was found to enhance bacterial motility and increase bacterial cell vulnerability to disinfectants, resulting in greater membrane damage and intensified reactive oxygen species (ROS) production upon exposure to disinfectants. These insights highlight the central role of EPS in bacterial defenses and offer promising implications for developing more effective disinfection strategies.


Assuntos
Desinfetantes , Desinfecção , Desinfecção/métodos , Matriz Extracelular de Substâncias Poliméricas , Desinfetantes/farmacologia , Cloro/farmacologia , Cinética
2.
Histochem Cell Biol ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613646

RESUMO

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with high incidence and mortality globally. Emerging evidence suggests that circular RNAs (circRNAs) exert critical functions in human cancers, including LUAD. CircRNA_100549 (circ_100549) has been reported to be significantly upregulated in non-small cell lung cancer (NSCLC) samples, while its role in modulating LUAD progression remains to be explored. The current study aims at investigating the functional roles of circ_100549 in LUAD and its downstream molecular mechanism. First, we found that the expression of circ_100549 was higher in LUAD cell lines. Loss-of-function assays verified that depletion of circ_100549 repressed LUAD cell proliferation but accelerated cell apoptosis. Furthermore, in vivo experiments demonstrated that silencing of circ_100549 suppressed tumor growth. Subsequently, based on database analysis, we carried out a series of experiments to explore the mechanisms and effects of circ_100549 underlying LUAD progression, including RNA-binding protein immunoprecipitation (RIP), RNA/DNA pull-down, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays. The results indicated that circ_100549 serves as a ceRNA by sponging miR-95-5p to upregulate BPTF expression, thus upregulating BIRC6 expression at a transcriptional level in LUAD. In summary, our study demonstrated that circ_100549 facilitates LUAD progression by upregulating BIRC6 expression.

3.
BMC Genomics ; 25(1): 372, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627613

RESUMO

BACKGROUND: Alternative polyadenylation (APA), alternative splicing (AS), and long non-coding RNAs (lncRNAs) play regulatory roles in post-transcriptional processes in plants. However, little is known about their involvement in xylem development in Dalbergia odorifera, a valuable rosewood species with medicinal and commercial significance. We addressed this by conducting Isoform Sequencing (Iso-Seq) using PacBio's SMRT technology and combined it with RNA-seq analysis (RNA sequencing on Illumina platform) after collecting xylem samples from the transition zone and the sapwood of D. odorifera. RESULTS: We identified 14,938 full-length transcripts, including 9,830 novel isoforms, which has updated the D. odorifera genome annotation. Our analysis has revealed that 4,164 genes undergo APA, whereas 3,084 genes encounter AS. We have also annotated 118 lncRNAs. Furthermore, RNA-seq analysis identified 170 differential alternative splicing (DAS) events, 344 genes with differential APA site usage (DE-APA), and 6 differentially expressed lncRNAs in the transition zone when compared to the sapwood. AS, APA, and lncRNAs are differentially regulated during xylem development. Differentially expressed APA genes were enriched for terpenoid and flavonoid metabolism, indicating their role in the heartwood formation. Additionally, DE-APA genes were associated with cell wall biosynthesis and terpenoid metabolism, implying an APA's role in wood formation. A DAS gene (involved in chalcone accumulation) with a significantly greater inclusion of the last exon in the transition zone than in the sapwood was identified. We also found that differentially expressed lncRNAs targeted the genes related to terpene synthesis. CONCLUSIONS: This study enhances our understanding of the molecular regulatory mechanisms underlying wood formation in D. odorifera, and provides valuable genetic resources and insights for its molecular-assisted breeding.


Assuntos
Dalbergia , RNA Longo não Codificante , Madeira/genética , Madeira/metabolismo , Dalbergia/genética , Dalbergia/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA-Seq , Processamento Alternativo , Isoformas de Proteínas/genética , Terpenos/metabolismo
4.
Front Immunol ; 15: 1368322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558821

RESUMO

Introduction: Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA. Methods: Dose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control. Results: The FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation. Discussion: The new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.


Assuntos
Glomerulonefrite por IGA , Lacticaseibacillus casei , Camundongos , Animais , Fator H do Complemento/genética , Camundongos Endogâmicos C57BL , Glomerulonefrite por IGA/patologia , Proteínas do Sistema Complemento/genética , Imunoglobulina A , Mutação
6.
Ultrasound Q ; 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38470974

RESUMO

ABSTRACT: Patients with compensated advanced chronic liver disease (cACLD) can safely spared screening esophagogastroduodenoscopy (EGD) when they meet the Baveno VI criteria as assessed by transient elastography. Recently, the cutoff values of the Baveno VI criteria assessed by 2-dimensional shear wave elastography (2D-SWE) were proposed. We aimed to validate it to rule out high-risk varices (HRVs) in cACLD patients; combine spleen diameter (SPD) with the Baveno VI criteria and assess whether it can spare more screening EGD. A total of 173 cACLD patients with successful liver stiffness (LS) measurements and EGD examinations were included. We analyzed the risk factors that predicted HRVs and compared the performances of different models for ruling out HRVs. The platelet count, LS, and SPD were independent predictors of HRVs. The AUCs of platelet count, LS, spleen stiffness and SPD for diagnosing HRVs were 0.797, 0.757, 0.834, and 0.804, respectively. The Baveno VI criteria assessed by 2D-SWE spared 25.4% of EGD screenings and missed 2.4% of the HRV patients. Combining SPD ≤11.1 cm with the Baveno VI criteria could spare more EGD screenings than just applying the Baveno VI criteria (45.1% vs 25.4%, P < 0.001), and missed 4.9% of the HRV patients. The Baveno VI criteria assessed by 2D-SWE could be safely applied in cACLD patients to rule out HRV patients. The combined model Baveno VI/SPD could safely and significantly increase the rate of spared EGD.

7.
Int J Biol Macromol ; 264(Pt 1): 130609, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38437933

RESUMO

5-Hydroxytryptophan (5-HTP), as the precursor of serotonin and melatonin in animals, can regulate mood, sleep, and behavior, which is widely used in pharmaceutical and health products industry. The enzymatic production of 5-hydroxytryptophan (5-HTP) from L-tryptophan (L-Trp) using tryptophan hydroxylase (TPH) show huge potential in application due to its advantages, such as mild reaction conditions, avoidance of protection/deprotection processes, excellent regioselectivity and considerable catalytic efficiency, compared with chemical synthesis and natural extraction. However, the low thermostability of TPH restricted its hydroxylation efficiency toward L-Trp. In this study, we aimed to improve the thermostability of TPH via semi-rational design guided by (folding free energy) ΔΔG fold calculation. After two rounds of evolution, two beneficial mutants M1 (S422V) and M30 (V275L/I412K) were obtained. Thermostability evaluation showed that M1 and M30 possessed 5.66-fold and 6.32-fold half-lives (t1/2) at 37 °C, and 4.2 °C and 6.0 °C higher melting temperature (Tm) than the WT, respectively. The mechanism behind thermostability improvement was elucidated with molecular dynamics simulation. Furthermore, biotransformation of 5-HTP from L-Trp was performed, M1 and M30 displayed 1.80-fold and 2.30-fold than that of WT, respectively. This work provides important insights into the thermostability enhancement of TPH and generate key mutants that could be robust candidates for practical production of 5-HTP.


Assuntos
5-Hidroxitriptofano , Triptofano Hidroxilase , Animais , 5-Hidroxitriptofano/metabolismo , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo , Triptofano/metabolismo , Serotonina/metabolismo , Engenharia de Proteínas
8.
J Med Chem ; 67(5): 3778-3794, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482826

RESUMO

It is an urgent need to tackle the global crisis of multidrug-resistant bacterial infections. We report here an innovative strategy for large-scale screening of new antibacterial agents using a whole bacteria-based DNA-encoded library (DEL) of vancomycin derivatives via peripheral modifications. A bacterial binding affinity assay was established to select the modification fragments in high-affinity compounds. The optimal resynthesized derivatives demonstrated excellently enhanced activity against various resistant bacterial strains and provided useful structures for vancomycin derivatization. This work presents the new concept in a natural product-templated DEL and in antibiotic discovery through bacterial affinity screening, which promotes the fight against drug-resistant bacteria.


Assuntos
Antibacterianos , Vancomicina , Vancomicina/farmacologia , Vancomicina/química , Antibacterianos/química , Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla , DNA , Testes de Sensibilidade Microbiana
9.
Med Sci Monit ; 30: e943072, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433445

RESUMO

BACKGROUND The incidence of placenta accreta spectrum disorder (PAS) has been increasing in past decades, and women with PAS are a high-risk maternal population. This study aimed to explore the performance of Bakri intrauterine balloon tamponade (IUBT) in the treatment of postpartum hemorrhage (PPH), among those with and without PAS. MATERIAL AND METHODS The outcomes of 198 women who underwent treatment for PPH using IUBT were retrospectively analyzed. The demographics and maternal outcomes were analyzed for vaginal and cesarean births, with PAS and without PAS. RESULTS Compared to women with vaginal births (n=130), women who underwent cesarean births (n=68) showed a higher proportion of age ≥35 years (χ²=6.85, P=0.013), multiple births (χ²=13.60, P<0.001), preeclampsia (χ²=9.81, P=0.002), use of transabdominal IUBT (χ²=84.12, P<0.001) and pre-IUBT interventions (χ²=41.61, P<0.001), but had less infused volume of physiological saline (t=6.41, P<0.001). Women with PAS (n=105) showed a higher rate of pre-IUBT intervention (χ²=4.96, P=0.029) and transabdominal IUBT placement (χ²=9.37, P=0.002) than non-PAS women (n=93). The 36 women with PAS (n=36) showed a higher rate of preeclampsia (χ²=4.80, P=0.029), pre-IUBT intervention (χ²=5.90, P=0.015), and transabdominal IUBT placement (χ²=14.94, P<0.001) and a shorter duration from delivery to Bakri insertion (χ²=3.31, P=0.002), than non-PAS women (n=32). CONCLUSIONS PAS was a major cause of PPH at 198 vaginal and cesarean births. An accurate and timely pre-IUBT intervention and Bakri IUBT placement was critical for controlling PPH in cesarean births, especially in women with PAS.


Assuntos
Placenta Acreta , Hemorragia Pós-Parto , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Adulto , Placenta Acreta/terapia , Hemorragia Pós-Parto/terapia , Estudos Retrospectivos , Cesárea
10.
Exp Ther Med ; 27(5): 177, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38515648

RESUMO

The aim of the present study was to explore the effectiveness of Bakri intrauterine balloon tamponade (IUBT) in treating severe postpartum hemorrhage (SPPH). A cohort of 198 women with SPPH using IUBT were retrospectively selected. The baseline and maternal outcome characteristics were examined. The results demonstrated that women with SPPH had a high proportion of placenta accrete (53.0%). Bakri IUBT demonstrated a global effectiveness of 84.5% in SPPH treatment, accounting for 82.9% in women with placenta accrete. Compared with women with Bakri failure, women who experienced Bakri success had reduced rates of less use of pre-/post-IUBT intervention, blood transfusion, lower genital tract trauma, estimated blood loss (EBL), and a longer indwelling duration (P<0.05). Logistic regression revealed that the pre-IUBT intervention (OR=3.910; 95% CI: 1.684-9.079; P=0.002) was positively associated with hemostasis success, while lower genital tract trauma was negatively associated with Bakri success (OR=0.091; 95% CI: 0.009-0.894; P=0.040). Moreover, women diagnosed with placenta accrete underwent a greater number of transabdominal placed Bakri IUBT and pre-IUBT interventions than those without placenta accrete (P<0.05). No significant differences were observed in Bakri success, total EBL, pre-/post-IUBT EBL, infused volume of IUBT, IUBT indwelling duration, even the rate of hemostasis, lower genital tract trauma, blood transfusion, post-IUBT intervention, and puerperal fever between women with and without placenta accrete (P>0.05). In conclusion, placenta accrete may be the leading cause of SPPH. Bakri IUBT is an effective and safe measure for SPPH. Pre-IUBT intervention may be predictive of Bakri's success. The timely use of IUBT during labor may mitigate the impact of risk factors identified on PPH.

11.
Child Adolesc Psychiatry Ment Health ; 18(1): 38, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504321

RESUMO

BACKGROUND: An extensive literature has shown a strong connection between maternal parenting practices and adolescent mental health problems. However, it has been difficult for previous research to map a dynamic concurrent and prospective relationships within and between types of parenting practices and adolescent mental health problems. The present study addressed these issues using a network analysis approach and a longitudinal design. METHODS: This study involved 591 Chinese adolescents (249 males; mean age at T1 = 13.53) and their mothers (mean age at T1 = 39.71) at two time points (T1 and T2) with eighteen months apart. Mothers reported their parenting practices including warmth, monitoring, inductive reasoning, hostility, and harshness, while adolescents reported their mental health problems including anxiety, depression, aggression, and conduct problems. Network analysis was conducted for contemporaneous networks at T1 and T2 and temporal networks from T1 to T2. RESULTS: The contemporaneous networks revealed the negative association between monitoring and conduct problems served as the main pathway through which parenting practices and adolescent mental health mutually influenced each other, and further, warmth was the most influential parenting practice on adolescent mental health. The temporal network revealed that maternal hostility exerted the most influence on adolescent mental health problems, whereas adolescents' depression was most influenced by maternal parenting practices. Moreover, maternal hostility was most predicted by maternal harshness. CONCLUSIONS: This study presents a novel perspective to gain a better understanding of the dynamics between and within maternal parenting practices and adolescent mental health problems. Findings highlight maternal harshness and warmth as potential prevention and intervention targets for adolescent mental health problems.

12.
J Med Chem ; 67(5): 3400-3418, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38387069

RESUMO

The use of ß-lactam (BL) and ß-lactamase inhibitor combination to overcome BL antibiotic resistance has been validated through clinically approved drug products. However, unmet medical needs still exist for the treatment of infections caused by Gram-negative (GN) bacteria expressing metallo-ß-lactamases. Previously, we reported our effort to discover pan inhibitors of three main families in this class: IMP, VIM, and NDM. Herein, we describe our work to improve the GN coverage spectrum in combination with imipenem and relebactam. This was achieved through structure- and property-based optimization to tackle the GN cell penetration and efflux challenges. A significant discovery was made that inhibition of both VIM alleles, VIM-1 and VIM-2, is essential for broad GN coverage, especially against VIM-producing P. aeruginosa. In addition, pharmacokinetics and nonclinical safety profiles were investigated for select compounds. Key findings from this drug discovery campaign laid the foundation for further lead optimization toward identification of preclinical candidates.


Assuntos
Antibacterianos , Inibidores de beta-Lactamases , Humanos , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/uso terapêutico , Inibidores de beta-Lactamases/química , Antibacterianos/química , Imipenem/farmacologia , beta-Lactamases , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana
13.
Curr Med Imaging ; 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38310551

RESUMO

BACKGROUND: Lung cancer patients with post-chemotherapy may have disconnected or weakened function connections within brain networks. OBJECTIVE: This study aimed to explore the abnormality of brain functional networks in lung cancer patients with post-chemotherapy by modular edge analysis. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 40 patients after chemotherapy, 40 patients before chemotherapy and 40 normal controls. Patients in all three groups were age and sex well-matched. Then, modular edge analysis was applied to assess brain functional network alterations. RESULTS: Post-chemotherapy patients had the worst MoCA scores among the three groups (p < 0.001). In intra-modular connections, compared with normal controls, the patients after chemotherapy had decreased connection strengths in the occipital lobe module (p < 0.05). Compared with the nonchemotherapy group, the patients after chemotherapy had decreased connection strengths in the subcortical module (p < 0.05). In inter-modular connections, compared with normal controls, the patients after chemotherapy had decreased connection strength in the frontal-temporal lobe modules (p < 0.05). Compared with the non-chemotherapy group, the patients after chemotherapy had decreased connection strength in the subcortical-temporal lobe modules (p < 0.05). CONCLUSION: The results reveal that chemotherapy can disrupt connections in brain functional networks. As far as we know, the use of modular edge analysis to report changes in brain functional brain networks associated with chemotherapy was rarely reported. Modular edge analysis may play a crucial part in predicting the clinical outcome for the patients after chemotherapy.

14.
Soft Robot ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38330424

RESUMO

The field of soft robotics is rapidly evolving, and there is a growing interest in developing soft robots with bioinspired features for use in various applications. This research presented the design and development of 3D-printed origami actuators for a soft robot with amphibious locomotion and tongue hunting capabilities. Two different types of programmable origami actuators were designed and manufactured, namely Z-shaped and twist tower actuators. In addition, two actuator variations were developed based on the Z-shaped actuator, including the pelvic fin and the coiling/uncoiling types. The Z-shaped actuators were used for the rear legs to facilitate the locomotion of the water-like frogs. Meanwhile, the twisted tower actuators were used for the rotation joints in the forelegs and for locomotion on land. The pelvic fin actuator was developed to imitate the land locomotion of the mudskipper, and the coiling/uncoiling actuator was designed for tongue hunting motion. The origami actuators and soft robot prototype were tested through a series of experiments, which showed that the robot was capable of efficiently moving in water and on land and performing tongue hunting motions. Our results demonstrate the effectiveness of these actuators in producing the desired motions and provide insights into the potential of applying 3D-printed origami actuators in the development of soft robots with bioinspired features.

15.
Eur J Med Chem ; 268: 116221, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382392

RESUMO

The formation of biofilm is one of the important factors for bacteria to develop drug-resistant. A series of halogenated-pyrroles or pyrazoles containing thiazole groups as antibacterial agents were designed and synthesized to target biofilms. Among them, compound 8c showed antibacterial activity against various Gram-positive bacteria, particularly against vancomycin-resistant Enterococcus faecalis (MIC ≤0.125 µg/mL). Additionally, this compound significantly inhibited biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa at sub-MIC doses. Furthermore, compound 8c exhibited significantly lower mammalian cell toxicity compared to pyrrolomycin C and its hepatic microsomal metabolic stability in various species was also evaluated. Further experiment on the infection model of Galleria mellonella proved that the compound was effective in vivo.

16.
Heliyon ; 10(3): e25217, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38327399

RESUMO

In recent years, English as a foreign language (EFL) reading instruction has emerged as a prominent and recurring research theme in the realm of education. Despite this growing interest, prior studies have not outlined the research status of EFL reading instruction from a bibliometric lens. Addressing this gap, the present study aims to provide valuable insights into the research landscape of EFL reading instruction by using scientific mapping analysis on documents sourced from the Web of Science Database between 1994 and 2023. The study found that: 1) The analysis of publication trends suggests that the field of EFL reading instruction continues to evolve, with a foreseeable ongoing increase in research output. 2) Asian countries, specifically Iran, China, and Saudi Arabia emerge as leading contributors and collaborators in terms of research on EFL reading instruction. 3) Authors mainly from Asian countries demonstrate the highest levels of productivity and citation impact. 4) The most productive and cited journals primarily originate from developed countries, notably the United Kingdom and the United States. 5) The research foci identified cover various aspects such as "technology-based instruction," "critical thinking," and "literacy skills." However, there is an emerging shift in research focus towards themes "English proficiency," "Covid-19," "technology," "blended learning" and "mobile-assisted language learning (MALL)." By shedding light on the significant concepts and trends of the research field, this study adds to the burgeoning body of literature and provides valuable guidance to new scholars seeking to enrich their knowledge and perspectives on this particular topic.

17.
J Am Heart Assoc ; 13(2): e031928, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38214265

RESUMO

BACKGROUND: We assessed the impact of pre- and postprocedural plasma corin levels on the recurrence of atrial fibrillation (AF) after catheter ablation (CA). METHODS AND RESULTS: This prospective, single-center, observational study included patients undergoing their first CA of AF. Corin was measured before and 1 day after CA. The primary end point was recurrent AF between 3 and 12 months after ablation. From April 2019 through May 2021, we analyzed 616 patients with AF (59.09% men) with a mean age of 62.86±9.42 years. Overall, 153 patients (24.84%) experienced recurrent AF. In the recurrence group, the pre- and postprocedure corin concentrations were 539.14 (329.24-702.08) and 607.37 (364.50-753.80) pg/mL, respectively, which were significantly higher than the nonrecurrence group's respective concentrations of 369.05 (186.36-489.28) and 489.12 (315.66-629.05) pg/mL (both P<0.0001). A multivariate Cox regression analysis with confounders found that elevated preablation corin levels were significantly associated with an increased risk of AF recurrence after CA. Receiver operating characteristic curve analysis identified that a preablation corin threshold of >494.85 pg/mL predicted AF recurrence at 1 year. An increase of 1 SD in corin concentrations before CA (264.94 pg/mL) increased the risk of recurrent AF by 54.3% after adjusting for confounding variables (hazard ratio, 1.465 [95% CI, 1.282-1.655]; P<0.0001). CONCLUSIONS: Plasma corin levels at baseline is a valuable predictor of AF recurrence after CA, independent of established conventional risk factors. Risk stratification before ablation for AF may be useful in selecting treatment regimens for patients.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Curva ROC , Fatores de Risco , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Recidiva
18.
J Invest Dermatol ; 144(5): 1148-1160.e15, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38242315

RESUMO

Long noncoding RNAs are pivotal contributors to the development of human diseases. However, their significance in the context of diabetic wound healing regulated by human umbilical cord mesenchymal stem cells (hUCMSCs) remains unclear. This study sheds light on the involvement of lncCCKAR5 in this process. We found that hUCMSCs exposed to high glucose conditions exhibited a significant downregulation of lncCCKAR5 expression, and lncCCKAR5 played a critical role in modulating autophagy, thus inhibiting apoptosis in hUCMSCs. In addition, the reduction of lncCCKAR5 in cells exposed to high glucose effectively thwarted cellular senescence and facilitated filopodium formation. Mechanistically, lncCCKAR5 served as a scaffold that facilitated the interaction between MKRN2 and LMNA, a key regulator of cytoskeletal function and autophagy. The lncCCKAR5/LMNA/MKRN2 complex played a pivotal role in promoting the ubiquitin-mediated degradation of LMNA, with this effect being further augmented by N6-adenosine methylation of lncCCKAR5. Consequently, our findings underscore the critical role of lncCCKAR5 in regulating the autophagic process in hUCMSCs, particularly through protein ubiquitination and degradation. This intricate regulatory network presents a promising avenue for potential therapeutic interventions in the context of diabetic wound healing involving hUCMSCs.


Assuntos
Adenosina , Adenosina/análogos & derivados , Autofagia , Lamina Tipo A , Células-Tronco Mesenquimais , RNA Longo não Codificante , Cordão Umbilical , Cicatrização , Humanos , Autofagia/efeitos dos fármacos , Adenosina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Cordão Umbilical/citologia , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/genética , Lamina Tipo A/metabolismo , Lamina Tipo A/genética , Camundongos , Células Cultivadas , Animais , Apoptose/efeitos dos fármacos , Glucose/metabolismo , Glucose/farmacologia , Senescência Celular/efeitos dos fármacos
19.
Indian J Ophthalmol ; 72(Suppl 2): S319-S322, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38271430

RESUMO

To evaluate a novel technique for six-point scleral fixation of a three-looped haptics posterior chamber intraocular lens (PCIOL) by a single suture. Nine eyes of nine patients were studied from September 2021 to March 2023. All patients had undergone vitrectomy. Only a single 9-0 polypropylene suture was used for scleral fixation. The three looped haptics were fixed at 12, 4, and 8 o'clock with six-point scleral fixation. The entire procedure took about 30 min. Among the nine patients, eight (88.8%) eyes had a significant improvement in best-corrected visual acuity, whereas one (11.2%) eye showed no change. No intraoperative or postoperative complications were observed. By ultrasonic biomicroscopy examination, intraocular lenses were well positioned and stable with no tilt in the horizontal and vertical axis. The method of six-point scleral fixation of a three-looped haptics PCIOL by a single suture is safe and effective.


Assuntos
Implante de Lente Intraocular , Lentes Intraoculares , Humanos , Implante de Lente Intraocular/métodos , Tecnologia Háptica , Técnicas de Sutura , Acuidade Visual , Esclera/cirurgia , Suturas , Estudos Retrospectivos
20.
Neurologist ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38251449

RESUMO

OBJECTIVE: We mainly explore the predictive value of Barthel Index (BI), SPAN-100, and National Institute of Health stroke scale (NIHSS) scores on clinical prognosis and functional outcomes in thrombolytic patients and compare the differences in the predictive values of the above 3 scales so as to provide an effective basis to evaluate the prognosis of thrombolytic patients. METHODS: Data were collected from 212 patients with the first-onset AIS (acute ischemic stroke). The enrolled patients were treated with recombinant tissue plasminogen activator thrombolytic therapy and were divided into 2 groups according to the modified Rankin Scale (mRS) score at discharge: the prognosis group (mRS≤2 points) and the poor prognosis group (mRS≥3 points). Logistic multivariate analysis was used to analyze the predictors of poor prognosis in patients with thrombolysis. MedCalc software was used to plot receiver operating characteristic (ROC) curves, calculate the area under the ROC curve (AUC), and compare the prediction performance of the 3 scales by the Delong and colleagues' method, and the difference of P<0.05 was statistically significant. RESULTS: Logistic binary regression multivariate analysis suggested that BI was a predictor of poor prognosis for thrombolytic therapy in patients with AIS. The lower the BI score, the poorer the prognosis. The AUC for BI score was 0.862, 95% CI (0.808-0.906), NIHSS score AUC was 0.665, 95% CI (0.597-0.728), and SPAN-100 score AUC was 0.640, 95% CI (0.572-0.705). AUC comparison of 3 scoring ROC curves suggested statistically significant differences between BI and NIHSS (PC=0.0000), BI and SPAN-100 (PC=0.0000); no significant difference was observed between SPAN-100 and NIHSS (PC=1.7997). CONCLUSIONS: Simple BI scores have a high prognostic value for thrombolytic therapy in AIS.

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