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1.
Front Bioeng Biotechnol ; 12: 1450953, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39291257

RESUMEN

Objective: Sharp force injury has been and will remain to be a major cause of violent death; however, scientific evaluations on the impact of body posture of the victim and gender of the perpetrator on sharp force injury have been scarce. The purpose of this study was to evaluate the biomechanical characteristics found in individuals (male and female) when using a Chinese kitchen knife to slash the neck of a dummy while it was in the standing and supine positions. This work offers a solid basis for forensic identifications, criminal investigations, and court trials. Methods: A total of 12 male and 12 female college students participated in this study. Kinematic, kinetic, and surface electromyography (sEMG) data were evaluated when slashing the neck of a dummy while it was in the standing and supine positions using a Chinese kitchen knife. Results: When slashing the neck of a standing dummy, participants showed shorter contact time (19.5%) and slower shoulder velocities (30.9%) as well as higher hip velocity (26.0%) and increased root mean square (RMS) and integral electromyography (iEMG) for the anterior deltoid (51.3% and 51.2%, respectively) compared to those while the dummy was in the supine position (all p < 0.05), regardless of gender. When slashing a dummy's neck while it was in standing and supine positions, male participants showed higher shoulder, elbow, and wrist velocities (22.6%, 22.7%, and 24.4%, respectively) and higher slashing velocity (19.8%), slashing force (24.2%), and energy (46.2%) than female participants (all p < 0.05). In addition, male participants showed shorter contact time (17.8%), and the values of RMS and iEMG of the anterior deltoid, biceps brachii, extensor carpi radialis longus, and flexor carpi ulnaris were less than those of female participants (98.9%, 47.3%, 65.6%, and 33.4% for RMS and 115.1%, 59.4%, 80.1%, and 47.8% for iEMG, respectively). Conclusion: There was no difference in slashing speed, slashing force, and energy when using a Chinese kitchen knife to slash the dummy's neck while it was in different body postures (standing and supine), suggesting a similar level of injury severity. However, there were significant differences in slashing action patterns between the two body postures, with longer contact time, smaller hip velocity, greater shoulder velocity, and less muscle activation level of the deltoid exertion when slashing the dummy's neck in the supine position. Gender may have a greater effect on the severity of slashing, and the gender difference may be partly related to the body weight difference. The findings from this study may provide quantitative indicators and references for analyzing the motive behind the crime, as well as for case reconstruction, and for the court's conviction and sentencing processes.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39249504

RESUMEN

Ovarian cancer (OV) is the most malignant gynecological tumor in women, with poor prognosis and high mortality rate. This study aims to identify hub genes in OV and explore the role of Receptor transporter 4 (RTP4) in OV progression. Common differentially expressed genes (DEGs) were screened from two microarray datasets. GO and KEGG enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed by STING. Kaplan-Meier plotter was used to analyze prognosis. The effect of target gene on immune infiltration was analyzed by TIMER. The proliferation, migration, and invasion of OV cells were measured by CCK-8, wound healing assay, and trans-well assay, respectively. A total of 293 common DEGs were selected from GSE12470 and GSE16709 datasets. Hub genes, EPCAM, KIFC1, RTP4, TAGLN, and ZFP36 were selected by PPI network. Kaplan-Meier plotter demonstrated that high expression of RTP4 was related to low overall survival in OV patients. The TIMER result showed that high expression of RTP4 promoted immune infiltration of CD8+ T cells, B cells, neutrophils, and dendritic cells in OV. Moreover, silencing RTP4 significantly inhibited the proliferation, migration, and invasion of OV cells. RTP4 was associated with the poor prognosis in OV. In summary, silencing RTP4 inhibited the proliferation, migration, and invasion of OV cells, having the potential to be a novel therapeutic target for OV.

3.
Eur J Med Chem ; 279: 116857, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39276585

RESUMEN

Protein Arginine Methyltransferase 6 (PRMT6) is a Type I PRMT enzyme that plays a role in the epigenetic regulation of gene expression by methylating histone and non-histone proteins. It is also involved in various cellular processes, including alternative splicing, DNA repair, and cell signaling. Furthermore, PRMT6 exerts multiple effects on cellular processes such as growth, migration, invasion, apoptosis, and drug resistance in various cancers, positioning it as a promising target for anti-tumor therapeutics. In this review, we initially provide an overview of the structure and biological functions of PRMT6, along with its association with cancer. Subsequently, we focus on recent progress in the design and development of modulators targeting PRMT6. This includes a comprehensive review of PRMT6 inhibitors (isoform-selective and non-selective), dual-target inhibitors based on PRMT6, PRMT6 covalent inhibitors, and PRMT6-targeting hydrophobic tagging (HyT) degraders, from the perspectives of rational design, pharmacodynamics, pharmacokinetics, and the clinical status of these modulators. Finally, we also provided the challenges and prospective directions for PRMT6 targeting drug discovery in cancer therapy.

4.
BMC Med Genomics ; 17(1): 230, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267058

RESUMEN

BACKGROUND: Spermatogenic failure is one of the leading causes of male infertility and its genetic etiology has not yet been fully understood. METHODS: The study screened a cohort of patients (n = 167) with primary male infertility in contrast to 210 normally fertile men using whole exome sequencing (WES). The expression analysis of the candidate genes based on public single cell sequencing data was performed using the R language Seurat package. RESULTS: No pathogenic copy number variations (CNVs) related to male infertility were identified using the the GATK-gCNV tool. Accordingly, variants of 17 known causative (five X-linked and twelve autosomal) genes, including ACTRT1, ADAD2, AR, BCORL1, CFAP47, CFAP54, DNAH17, DNAH6, DNAH7, DNAH8, DNAH9, FSIP2, MSH4, SLC9C1, TDRD9, TTC21A, and WNK3, were identified in 23 patients. Variants of 12 candidate (seven X-linked and five autosomal) genes were identified, among which CHTF18, DDB1, DNAH12, FANCB, GALNT3, OPHN1, SCML2, UPF3A, and ZMYM3 had altered fertility and semen characteristics in previously described knockout mouse models, whereas MAGEC1,RBMXL3, and ZNF185 were recurrently detected in patients with male factor infertility. The human testis single cell-sequencing database reveals that CHTF18, DDB1 and MAGEC1 are preferentially expressed in spermatogonial stem cells. DNAH12 and GALNT3 are found primarily in spermatocytes and early spermatids. UPF3A is present at a high level throughout spermatogenesis except in elongating spermatids. The testicular expression profiles of these candidate genes underlie their potential roles in spermatogenesis and the pathogenesis of male infertility. CONCLUSION: WES is an effective tool in the genetic diagnosis of primary male infertility. Our findings provide useful information on precise treatment, genetic counseling, and birth defect prevention for male factor infertility.


Asunto(s)
Secuenciación del Exoma , Infertilidad Masculina , Humanos , Masculino , Infertilidad Masculina/genética , Adulto , Variaciones en el Número de Copia de ADN
5.
Curr Microbiol ; 81(10): 330, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196442

RESUMEN

The type VI secretion system 2 (T6SS2) gene cluster of Vibrio parahaemolyticus comprises three operons: VPA1027-1024, VPA1043-1028, and VPA1044-1046. AcsS is a LysR-like transcriptional regulator that play a role in activating flagella-driven motility in V. parahaemolyticus. However, its potential roles in other cellular pathways remain poorly understood. In this study, we conducted a series of experiments to investigate the regulatory effects of AcsS on the transcription of VPA1027 (hcp2), VPA1043, and VPA1044. The findings revealed that AcsS indirectly inhibits the transcription of these genes. Additionally, deletion of acsS resulted in enhanced adhesion of V. parahaemolyticus to HeLa cells. However, disruption of T6SS2 alone or in conjunction with AcsS significantly diminished the adhesion capacity of V. parahaemolyticus to HeLa cells. Therefore, it is suggested that AcsS suppresses cell adhesion in V. parahaemolyticus by downregulating the transcription of T6SS2 genes.


Asunto(s)
Adhesión Bacteriana , Proteínas Bacterianas , Regulación Bacteriana de la Expresión Génica , Transcripción Genética , Sistemas de Secreción Tipo VI , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Células HeLa , Humanos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sistemas de Secreción Tipo VI/genética , Sistemas de Secreción Tipo VI/metabolismo , Adhesión Bacteriana/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Familia de Multigenes
6.
Microb Pathog ; 195: 106882, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39197692

RESUMEN

Cyclic di-GMP (c-di-GMP), a ubiquitous secondary messenger in bacteria, affects multiple bacterial behaviors including motility and biofilm formation. c-di-GMP is synthesized by diguanylate cyclase harboring a GGDEF domain and degraded by phosphodiesterase harboring an either EAL or HD-GYP domain. Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis, harbors more than 60 genes involved in c-di-GMP metabolism. However, roles of most of these genes including vpa0198, which encodes a GGDEF-domain containing protein, are still completely unknown. AphA and OpaR are the master quorum sensing (QS) regulators operating at low (LCD) and high cell density (HCD), respectively. QsvR integrates into QS to control gene expression via direct regulation of AphA and OpaR. In this study, we showed that deletion of vpa0198 remarkably reduced c-di-GMP production and biofilm formation, whereas promoted the swimming motility of V. parahaemolyticus. Overexpression of VPA0198 in the vpa0198 mutant strain significantly reduced the swimming and swarming motility and enhanced the biofilm formation ability of V. parahaemolyticus. In addition, transcription of vpa0198 was under the collective regulation of AphA, OpaR and QsvR. AphA activated the transcription of vpa0198 at LCD, whereas QsvR and OpaR coordinately and directly repressed vpa0198 transcription at HCD, thereby leading to a cell density-dependent expression of vpa0198. Therefore, this work expanded the knowledge of synthetic regulatory mechanism of c-di-GMP in V. parahaemolyticus.


Asunto(s)
Proteínas Bacterianas , Biopelículas , GMP Cíclico , Regulación Bacteriana de la Expresión Génica , Percepción de Quorum , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Vibrio parahaemolyticus/fisiología , Biopelículas/crecimiento & desarrollo , Percepción de Quorum/genética , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Factores de Transcripción
7.
Microbiol Resour Announc ; : e0056024, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189723

RESUMEN

This announcement reports the complete genome sequence of Achromobacter sp. strain E1, which was isolated from the root of maize cultivar (Zheng dan 958) grown in Beijing, China. Achromobacter sp. strain E1 consists of a single, closed genome consisting of 5,975,307 bp, with GC content of 65.86%.

8.
Water Res ; 264: 122130, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39146847

RESUMEN

Nutrient pollution has become an important issue to solve in stormwater runoff due to the fast population growth and urbanization that impacts water quality and triggers harmful algal blooms. There is an acute need to link the dissolved organic nitrogen (DON) decomposition with the coupled nitrification and denitrification pathways to realize the pattern shifts in the nitrogen cycle. This paper presented a lab-scale cascade upflow biofiltration system for comparison of nitrate and phosphate removal from stormwater matrices through two specialty adsorbents at three influent conditions. The two specialty adsorbents are denoted as biochar iron and perlite integrated green environmental media (BIPGEM) and zero-valent iron and perlite-based green environmental media (ZIPGEM). An initial condition with stormwater runoff, a second condition with spiked nitrate, and a third condition with spiked nitrate and phosphate were used in this study. To differentiate nitrifier and denitrifier population dynamics associated with the decomposition of DON, integrative analysis of quantitative polymerase chain reaction (qPCR) and 21 tesla Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) were performed in association with nitrate removal efficiencies for both media with or without the presence of phosphate. While the qPCR may detect one gene for a single microbe or pathogen and realize the microbial population dynamics in the bioreactors, the 21 T FT-ICR MS can separate and assign elemental compositions to identify organic compounds of DON. Results indicated that ZIPGEM obtained a higher potential for nutrient removal than BIPGEM when the influent was spiked with nitrate and phosphate simultaneously. The sustainable, scalable, and adaptable upflow bioreactors operated in sequence (in a cascade mode) can be expanded flexibly on an as-needed basis to meet the local water quality standards showing process reliability, resilience, and sustainability simultaneously.


Asunto(s)
Filtración , Nitrógeno , Nitratos , Purificación del Agua/métodos , Desnitrificación , Contaminantes Químicos del Agua , Fosfatos
9.
Spine Deform ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097534

RESUMEN

OBJECTIVE: This retrospective study aims to investigate the effect of the type of atlantoaxial dislocation due to os odontoideum on the sagittal alignment and balance of the cervical spine after posterior atlantoaxial fusion. METHODS: Data of 48 consecutive patients who underwent posterior C1-C2 fusion to treat atlantoaxial dislocation/instability due to os odontoideum were retrospectively reviewed. Radiographic variables, namely the T1 slope (T1S), C1-C2 angle, C2-C7 angle, C1-C2 sagittal vertical axis (SVA), C2-C7 SVA, and modified atlas-dens interval (MADI), were measured preoperatively, immediate postoperatively, and at final follow-up. Patients were divided into three groups based on the preoperative MADI. Differences within and between groups in radiographic variables and relationships between the investigated variables were analyzed. RESULTS: The MADI was correlated with the preoperative to postoperative changes in the C1-C2 angle (r = 0.776, P < 0.05) and C2-C7 angle (r = - 0.357, P < 0.05). In the group with anterior atlantoaxial dislocation, the C1-C2 angle and C2-C7 SVA were significantly enlarged at final follow-up (P < 0.05), while the C2-C7 angle was significantly reduced (P < 0.05). The changes in C1-C2 angle and C2-C7 angle were opposite between the posterior group and the anterior dislocation group. CONCLUSION: The direction/type of atlantoaxial subluxation correlates with the changes in lower cervical curvature after atlantoaxial fusion. Patients with atlantoaxial posterior dislocation and atlantoaxial instability are less likely than those with atlantoaxial anterior dislocation to develop loss of lordosis after posterior atlantoaxial fusion.

10.
Artículo en Inglés | MEDLINE | ID: mdl-39207149

RESUMEN

BACKGROUND AND OBJECTIVES: For irreducible atlantoaxial rotary fixation (AARF), anterior or posterior release was often needed before posterior reduction and fusion. Anterior atlantoaxial joint release has potential complications such as retropharyngeal abscess, persistent hoarseness, and infection. This study aims to assess the efficacy of posterior release, reduction, and intra-articular fusion without resecting the C2 nerve root on irreducible type III AARF. METHODS: The data of 9 pediatric patients diagnosed with AARF who underwent posterior atlantoaxial release, reduction, and intra-articular fusion without resecting the C2 nerve root were retrospectively reviewed. Japanese Orthopaedic Association scores and Visual Analog Scale for Neck Pain were used to assess outcomes. The preoperative and follow-up assessments of atlantodens interval (ADI) were documented to evaluate the reduction of atlantoaxial joint. The patient demographics, surgery time, blood loss, bone fusion time, follow-up period, and surgery-related complications were meticulously documented. RESULTS: The mean follow-up duration was 35.1 ± 11.5 months. Complete reduction was achieved in 8 patients, while one patient did not achieve complete reduction. The ADI decreased significantly from 8.7 ± 2.2 mm before surgery to 2.1 ± 1.3 mm at the final follow-up. All patients demonstrated successful bone fusion, with an average fusion period of 3.7 ± 1.3 months. The Visual Analog Scale for Neck Pain at the final follow-up exhibited a significant decrease compared with preoperative values (P < .05), while no significant difference was observed in Japanese Orthopaedic Association scores. There were no complications related to surgery. CONCLUSION: Posterior atlantoaxial release, reduction, and intra-articular fusion with a C2 nerve root preservation technique is effective in the treatment of irreducible type III AARF.

11.
Open Forum Infect Dis ; 11(7): ofae335, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38957689

RESUMEN

We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.

12.
Rev Cardiovasc Med ; 25(3): 89, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39076954

RESUMEN

Background: Identifying effective pharmacological interventions to prevent the progressive enlargement and rupture of aortic aneurysms (AAs) is critical. Previous studies have suggested links between metformin use and a decreased incidence of AAs. In this study, we employed Mendelian randomization (MR) to investigate causal effects of metformin's targets on AA risk and to explore the underlying mechanisms underlying these effects. Methods: To examine the relationship between metformin use and AA risk, we implemented both two-sample MR and multivariable MR analyses. Utilizing genetic instrumental variables, we retrieved cis-expression quantitative trait loci (cis-eQTL) data for potential targets of metformin from the Expression Quantitative Trait Loci Genetics Consortium (eQTLGen) Consortium and Genotype-Tissue Expression (GTEx) project. Colocalization analysis was employed to ascertain the probability of shared causal genetic variants between single nucleotide polymorphisms (SNPs) associated with eQTLs and AA. Results: Our findings reveal that metformin use reduces AA risk, exhibiting a protective effect with an odds ratio (OR) of 4.88 × 10 - 3 (95% confidence interval [CI]: 7.30 × 10 - 5 -0.33, p = 0.01). Furthermore, the protective effect of type 2 diabetes on AA risk appears to be driven by metformin use ( OR MVMR = 1.34 × 10 - 4 , 95% CI: 3.97 × 10 - 8 -0.45, p = 0.03). Significant Mendelian randomization (MR) results were observed for the expression of two metformin-related genes in the bloodstream: NADH:ubiquinone oxidoreductase subunit A6 (NDUFA6) and cytochrome b5 type B (CYB5B), across two independent datasets ( OR CYB5B = 1.35, 95% CI: 1.20-1.51, p = 2.41 × 10 - 7 ; OR NDUFA6 = 1.12; 95% CI: 1.07-1.17, p = 1.69 × 10 - 6 ). The MR analysis of tissue-specific expression also demonstrated a positive correlation between increased NDUFA6 expression and heightened AA risk. Lastly, NDUFA6 exhibited evidence of colocalization with AA. Conclusions: Our study suggests that metformin may play a significant role in lowering the risk of AA. This protective effect could potentially be linked to the mitigation of mitochondrial and immune dysfunction. Overall, NDUFA6 has emerged as a potential mechanism through which metformin intervention may confer AA protection.

13.
Lett Appl Microbiol ; 77(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38906839

RESUMEN

Vibrio parahaemolyticus utilizes a polar flagellum for swimming in liquids and employs multiple lateral flagella to swarm on surfaces and in viscous environments. The VPA0961 protein is an LysR family transcriptional regulator that can regulate the swimming and swarming motility of V. parahaemolyticus, but the detailed regulatory mechanisms are not yet fully understood. Herein, we designated the protein as AcsS, which stands for activator of swimming and swarming motility. Our data provided evidence that deleting the acsS gene significantly reduced both swimming and swarming motility of V. parahaemolyticus. Furthermore, AcsS was found to activate the expression of both polar (flgA, flgM, flgB, and flgK) and lateral (motY, fliM, lafA, and fliD) flagellar genes. Overexpression of AcsS in Escherichia coli induced the expression of flgA, motY, and lafA, but did not affect the expression of flgB, flgK, flgM, fliM, and fliD. Interestingly, His-tagged AcsS did not bind to the upstream DNA regions of all the tested genes, suggesting indirect regulation. In conclusion, AcsS positively regulated the swimming and swarming motility of V. parahaemolyticus by activating the transcription of polar and lateral flagellar genes. This work enriched our understanding of the gene expression regulation within the dual flagellar systems of V. parahaemolyticus.


Asunto(s)
Proteínas Bacterianas , Flagelos , Regulación Bacteriana de la Expresión Génica , Factores de Transcripción , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/fisiología , Flagelos/genética , Flagelos/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo
14.
Int Immunopharmacol ; 136: 112409, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38850789

RESUMEN

BACKGROUND: Iguratimod (IGU) is widely used in clinical practice due to its stable anti-inflammatory effects. Our previous studies have confirmed that the proportion of Th17/Treg balance in patients taking IGU altered significantly. This study aims to explore the role of IGU in antibody-mediated rejection (ABMR) and its potential mechanisms. METHODS: We conducted bioinformatics analysis of sequencing data from the GEO database to analyze the abundance of immune cell infiltration in transplanted kidney tissues. In vivo, IGU was intervened in a mice secondary skin transplantation model and a mice kidney transplantation ABMR model, and histological morphology of the grafts were examined by pathological staining, while relevant indicators were determined through qRT-PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, observed T cell differentiation by flow cytometry, and preliminarily assessed the immunosuppressive effect of IGU. In vitro, we established Th17 and Treg cell induction and stimulation differentiation culture systems and added IGU for intervention to explore its effects on their differentiation. RESULTS: Through bioinformatics analysis, we found that Th17 and Treg may play important roles in the occurrence and development of ABMR. In vivo, we found that IGU could effectively reduce the damage caused by ABMR to the grafts, alleviate the infiltration of inflammatory cells in the graft tissues, and reduce the deposition of C4d in the grafts. Moreover, it is also found that IGU regulated the differentiation of Th17 and Treg cells in the spleen and peripheral blood and reduced the expression of IL-17A in the grafts and serum. In addition, same changes were observed in the induction and differentiation culture system of Th17 and Treg cells in vitro after the addition of IGU. CONCLUSION: IGU can inhibit the progression of ABMR by regulating the differentiation of Th17 and Treg cells, providing novel insights for optimizing clinical immunosuppressive treatment regimens.


Asunto(s)
Cromonas , Rechazo de Injerto , Trasplante de Riñón , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Linfocitos T Reguladores , Células Th17 , Animales , Células Th17/inmunología , Linfocitos T Reguladores/inmunología , Rechazo de Injerto/inmunología , Ratones , Cromonas/farmacología , Masculino , Inmunosupresores/uso terapéutico , Humanos , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células Cultivadas , Sulfonamidas
15.
J Hazard Mater ; 474: 134646, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38838519

RESUMEN

This study assessed the application of two specialty adsorbents, also known as green sorption media (GSM), including clay-perlite and sand sorption media (CPS) and zero-valent iron and perlite green environmental media (ZIPGEM) to remove long- and short-chain per- and polyfluoroalkyl substances (PFAS) at field scale. The field-scale demonstration employed four GSM filter cells installed near the C-23 Canal (St. Lucie County, FL), which discharges water to the ecologically sensitive St. Lucie River estuary and to the Atlantic Ocean finally. Although prior lab-scale experiments had demonstrated the effectiveness of CPS and ZIPGEM in treating long-chain PFAS, their performance in field-scale application warranted further investigation. The study reveals the critical roles of divalent cations such as Ca2+ and monovalent cations such as ammonium and hydronium ions, as well as other water quality parameters, on PFAS removal efficacy. Ammonia, most likely resulting from photo- and bacterial ammonification, gives rise to elevated ammonium ion formation in the wet season due to the decrease in pH, which ultimately worsens PFAS adsorption. Moreover, there is a strong negative correlation between pH and PFAS removal efficiency in the presence of ammonia, as evidenced by the reduced removal of PFAS during events associated with low pH.

16.
J Thorac Dis ; 16(5): 3213-3227, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38883654

RESUMEN

Background: Although immunotherapy has revolutionized the treatment landscape of lung cancer and improved the prognosis of this malignancy, many patients with lung cancer still are not able to benefit from it because of many different reasons. The expression of programmed death ligand-1 (PD-L1) in tumor cells has been approved for the prediction of immunotherapy efficacy; however, its clinical application has been limited by the invasiveness of PD-L1 determination and the heterogeneity of tumor cells. As a promising technology, radiomics has made significant progress in the diagnosis and treatment of lung cancer. Thus, we constructed a noninvasive predictive model which based on radiomics to predict the immunotherapy efficacy of lung caner patients. Methods: Data of 82 patients with stage IIIa/IVb NSCLC who received immunotherapy at the First Affiliated Hospital of Soochow University from December 2019 to January 2023 were retrospectively collected. These patients were followed up for durable clinical benefit (DCB), as defined by whether progression-free survival (PFS) reached 12 months. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen for the radiomic features in the training set, and a radiomics score (Rad-score) was calculated. The clinical baseline data were analyzed, and the peripheral blood inflammation indices were calculated. Univariate and multivariate analyses were performed to identify the applicable indices, which were combined with the Rad-score to create a comprehensive forecasting model (CFM) and nomograms. Internal validation was performed in the validation set. Results: Up to the last follow-up time, 48 of 82 patients had a PFS of more than 12 months. The area under the receiver operating characteristic (ROC) curve (AUC) of the Rad-score was 0.858 and 0.812, respectively, in the training set and validation set. A systemic immune-inflammation index (SII) score of <500.88 after two cycles of immunotherapy was a protective factor for PFS >12 months [odds ratio (OR) 0.054; P=0.003]. The CFM had an AUC of 0.930 and 0.922, respectively, in the training and validation sets. The calibration curves and decision curve analysis (DCA) demonstrated the reliability and clinical applicability of the model, respectively. Conclusions: The radiomics model performed well in predicting whether patients with locally advanced or metastatic NSCLC can achieve DCB after receiving immunotherapy. The CFM had good predictive performance and reliability.

17.
Opt Express ; 32(10): 18150-18160, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858978

RESUMEN

Perineuronal nets (PNNs) are important functional structures on the surface of nerve cells. Observation of PNNs usually requires dyeing or fluorescent labeling. As a network structure with a micron grid and sub-wavelength thickness but no special optical properties, quantitative phase imaging (QPI) is the only purely optical method for high-resolution imaging of PNNs. We proposed a Scattering Quantitative Interference Imaging (SQII) method which measures the geometric rather than transmission or reflection phase during the scattering process to visualize PNNs. Different from QIP methods, SQII method is sensitive to scattering and not affected by wavelength changes. Via geometric phase shifting method, we simplify the phase shift operation. The SQII method not only focuses on interference phase, but also on the interference contrast. The singularity points and phase lines of the scattering geometric phase depict the edges of the network structure and can be found at the valley area of the interference contrast parameter SINDR under different wavelengths. Our SQII method has its unique imaging properties, is very simple and easy to implement and has more worth for promotion.

18.
Adipocyte ; 13(1): 2339418, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38706095

RESUMEN

A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10), is involved in several metabolic and inflammatory pathways. We speculated that ADAM10 plays a modulatory role in adipose tissue inflammation and metabolism. To this end, we studied adipose tissue-specific ADAM10 knock-out mice (aKO). While young, regular chow diet-fed aKO mice showed increased insulin sensitivity, following prolonged (33 weeks) high-fat diet (HFD) exposure, aKO mice developed obesity and insulin resistance. Compared to controls, aKO mice showed less inflammatory adipokine profile despite the significant increase in adiposity. In brown adipose tissue, aKO mice on HFD had changes in CD8+ T cell populations indicating a lesser inflammatory pattern. Following HFD, both aKO and control littermates demonstrated decreased adipose tissue pro-inflammatory macrophages, and increased anti-inflammatory accumulation, without differences between the genotypes. Collectively, our observations indicate that selective deletion of ADAM10 in adipocytes results in a mitigated inflammatory response, leading to increased insulin sensitivity in young mice fed with regular diet. This state of insulin sensitivity, following prolonged HFD, facilitates energy storage resulting in increased fat accumulation which ultimately leads to the development of a phenotype of obesity and insulin resistance. In conclusion, the data indicate that ADAM10 has a modulatory effect of inflammation and whole-body energy metabolism.


Asunto(s)
Proteína ADAM10 , Tejido Adiposo , Dieta Alta en Grasa , Ratones Noqueados , Animales , Masculino , Ratones , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Dieta Alta en Grasa/efectos adversos , Inflamación/metabolismo , Resistencia a la Insulina , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Obesidad/metabolismo , Obesidad/etiología , Fenotipo
19.
Eur Spine J ; 33(8): 3060-3068, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38816537

RESUMEN

PURPOSE: To evaluate the clinical feasibility of atlantoaxial intra-articular cage (AIC) fusion via intermuscular approach for treating reducible atlantoaxial dislocation (AAD). METHODS: An analysis was conducted on the data of 10 patients who underwent C1-C2 segmental fixation and AIC fusion for AAD by unilateral intermuscular approach and contralateral open approach. Outcome assessments included Japanese Orthopaedic Association score (JOA) and Visual Analog Scale Score for Neck Pain (VASSNP). The duration of surgical exposure, screw insertion and cage insertion, and postoperative drainage volume were also compared between two approaches. Bone fusion was evaluated through computed tomography (CT) reconstruction. Postoperative paravertebral tissue edema was evaluated by paravertebral tissue cross-sectional area (CSA) and signal intensity on T2 weighted sequence of magnetic resonance imaging (MRI) at 3 days postoperatively. RESULTS: The intermuscular approach exhibited a longer exposure time but lower drainage postoperatively compared to the open approach (P < 0.05). After operation, JOA scores significant improved (P < 0.05), while VASSNP scores significantly decreased (P < 0.05). There was no significant difference in preoperative CSA between two approaches (P > 0.05). However, compared to the open approach, the intermuscular approach exhibited less CSA (P < 0.05) and lower T2 signal intensity on MRI postoperatively, indicating less invasive to the paravertebral tissues. CONCLUSIONS: AIC fusion by intermuscular approach is an effective and safe technique in the treatment of reducible AAD. Intermuscular approach could reduce the postoperative drainage volume and the extent of paravertebral tissue edema compared to open approach.


Asunto(s)
Articulación Atlantoaxoidea , Luxaciones Articulares , Fusión Vertebral , Humanos , Articulación Atlantoaxoidea/cirugía , Articulación Atlantoaxoidea/diagnóstico por imagen , Luxaciones Articulares/cirugía , Luxaciones Articulares/diagnóstico por imagen , Masculino , Fusión Vertebral/métodos , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento
20.
Clin Transl Med ; 14(5): e1686, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38769658

RESUMEN

BACKGROUND: Renal allograft interstitial fibrosis/tubular atrophy (IF/TA) constitutes the principal histopathological characteristic of chronic allograft dysfunction (CAD) in kidney-transplanted patients. While renal vascular endothelial-mesenchymal transition (EndMT) has been verified as an important contributing factor to IF/TA in CAD patients, its underlying mechanisms remain obscure. Through single-cell transcriptomic analysis, we identified Rictor as a potential pivotal mediator for EndMT. This investigation sought to elucidate the role of Rictor/mTORC2 signalling in the pathogenesis of renal allograft interstitial fibrosis and the associated mechanisms. METHODS: The influence of the Rictor/mTOR2 pathway on renal vascular EndMT and renal allograft fibrosis was investigated by cell experiments and Rictor depletion in renal allogeneic transplantation mice models. Subsequently, a series of assays were conducted to explore the underlying mechanisms of the enhanced mitophagy and the ameliorated EndMT resulting from Rictor knockout. RESULTS: Our findings revealed a significant activation of the Rictor/mTORC2 signalling in CAD patients and allogeneic kidney transplanted mice. The suppression of Rictor/mTORC2 signalling alleviated TNFα-induced EndMT in HUVECs. Moreover, Rictor knockout in endothelial cells remarkably ameliorated renal vascular EndMT and allograft interstitial fibrosis in allogeneic kidney transplanted mice. Mechanistically, Rictor knockout resulted in an augmented BNIP3-mediated mitophagy in endothelial cells. Furthermore, Rictor/mTORC2 facilitated the MARCH5-mediated degradation of BNIP3 at the K130 site through K48-linked ubiquitination, thereby regulating mitophagy activity. Subsequent experiments also demonstrated that BNIP3 knockdown nearly reversed the enhanced mitophagy and mitigated EndMT and allograft interstitial fibrosis induced by Rictor knockout. CONCLUSIONS: Consequently, our study underscores Rictor/mTORC2 signalling as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis progression, exerting its impact through regulating BNIP3-mediated mitophagy. This insight unveils a potential therapeutic target for mitigating renal allograft interstitial fibrosis.


Asunto(s)
Fibrosis , Trasplante de Riñón , Diana Mecanicista del Complejo 2 de la Rapamicina , Proteínas de la Membrana , Mitofagia , Proteína Asociada al mTOR Insensible a la Rapamicina , Transducción de Señal , Animales , Proteína Asociada al mTOR Insensible a la Rapamicina/metabolismo , Proteína Asociada al mTOR Insensible a la Rapamicina/genética , Ratones , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Humanos , Trasplante de Riñón/efectos adversos , Fibrosis/metabolismo , Masculino , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Aloinjertos , Riñón/metabolismo , Riñón/patología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Proteínas Proto-Oncogénicas
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