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1.
J Extracell Vesicles ; 13(7): e12457, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39007430

RESUMEN

Seminal plasma induces immune tolerance towards paternal allogenic antigens within the female reproductive tract and during foetal development. Recent evidence suggests a role for extracellular vesicles in seminal plasma (spEVs). We isolated spEVs from seminal plasma that was donated by vasectomized men, thereby excluding any contributions from the testis or epididymis. Previous analysis demonstrated that such isolated spEVs originate mainly from the prostate. Here we observed that when isolated fluorescently labelled spEVs were mixed with peripheral blood mononuclear cells, they were endocytosed predominantly by monocytes, and to a lesser extent also by T-cells. In a mixed lymphocyte reaction, T-cell proliferation was inhibited by spEVs. A direct effect of spEVs on T-cells was demonstrated when isolated T cells were activated by anti-CD3/CD28 coated beads. Again, spEVs interfered with T cell proliferation, as well as with the expression of CD25 and the release of IFN-γ, TNF, and IL-2. Moreover, spEVs stimulated the expression of Foxp3 and IL-10 by CD4+CD25+CD127- T cells, indicating differentiation into regulatory T-cells (Tregs). Prior treatment of spEVs with proteinase K revoked their effects on T-cells, indicating a requirement for surface-exposed spEV proteins. The adenosine A2A receptor-specific antagonist CPI-444 also reduced effects of spEVs on T-cells, consistent with the notion that the development of Tregs and their immune suppressive functions are under the influence of adenosine-A2A receptor signalling. We found that adenosine is highly enriched in spEVs and propose that spEVs are targeted to and endocytosed by T-cells, after which they may release their adenosine content into the lumen of endosomes, thus allowing endosome-localized A2A receptor signalling in spEVs targeted T-cells. Collectively, these data support the idea that spEVs can prime T cells directly for differentiation into Tregs.


Asunto(s)
Diferenciación Celular , Vesículas Extracelulares , Semen , Linfocitos T Reguladores , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Semen/metabolismo , Semen/inmunología , Masculino , Proliferación Celular , Activación de Linfocitos/inmunología
2.
Artículo en Inglés | MEDLINE | ID: mdl-39002082

RESUMEN

Dioxins are endocrine disruptors that may disturb male sexual and reproductive function. Studies on human populations are limited, and their results are controversial. This study evaluated the impact of dioxin exposure on reproductive and thyroid hormone levels and sexual function in men. A total of 140 men working in four military airbases (three bases were formerly contaminated with dioxin by the herbicide spraying campaign in the Vietnam War) were recruited to measure the serum dioxin levels. Four reproductive hormones (testosterone, follicle-stimulating hormone, luteinizing hormone (LH), and prolactin) and three thyroid hormones (free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone) were measured. Male sexual function endpoints including sexual drive, erection, ejaculation, problems, and overall satisfaction were assessed by the Brief Male Sexual Function Inventory. The percentage of subjects with low testosterone and LH levels was 19.6% and 16.7%, respectively. Dioxins, especially 2,3,7,8-tetrachlorodibenzo-P-dioxin and toxic equivalent concentrations of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, were inversely associated with testosterone and prolactin levels, but positively associated with FT3 and FT4, and showed adverse relationships with sexual function, such as sexual drive, problems, and overall satisfaction. Our results suggested that exposure to dioxin disrupts the homeostasis of reproductive and thyroid hormones leading to adverse effects on male sexual function.

3.
Biopolymers ; : e23613, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38989603

RESUMEN

Hydrogels are notable for their outstanding absorbent qualities, satisfactory compatibility with biological systems, ability to degrade, and inherent safety, all of which contribute to their high demand in the field of biomedicine. This study focuses on the fabrication of hydrogels using environmentally friendly cellulosic material. Cellulose hydrogel beads were prepared by physical cross-linking in a NaOH/urea medium. Furthermore, nano polydopamine was integrated into the hydrogel matrix as functional polymers and α-mangostin was employed as an active pharmaceutical ingredient. The physicochemical properties were comprehensively analyzed using Fourier-transform infrared spectrometer, 13C cross-polarization/magic angle spinning nuclear magnetic resonance, thermogravimetric analysis, and scanning electron microscope. The drug delivery properties, including water content, swelling ratio, and drug release profiles, were evaluated. In vitro cytotoxicity against MC3T3-E1 cells was assessed using sulforhodamine B staining. All test hydrogels exhibited inhibitory activity against the growth of MC3T3-E1 cells. These results indicated the potential use of these hydrogels as a drug delivery carrier for α-mangostin in the treatment of ankylosing spondylitis.

4.
Life Sci Alliance ; 7(9)2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38969364

RESUMEN

The transmembrane E3 ligases RNF43 and ZNRF3 perform key tumour suppressor roles by inducing endocytosis of members of the Frizzled (FZD) family, the primary receptors for WNT. Loss-of-function mutations in RNF43 and ZNRF3 mediate FZD stabilisation and a WNT-hypersensitive growth state in various cancer types. Strikingly, RNF43 and ZNRF3 mutations are differentially distributed across cancer types, raising questions about their functional redundancy. Here, we compare the efficacy of RNF43 and ZNRF3 of targeting different FZDs for endocytosis. We find that RNF43 preferentially down-regulates FZD1/FZD5/FZD7, whereas ZNRF3 displays a preference towards FZD6. We show that the RNF43 transmembrane domain (TMD) is a key molecular determinant for inducing FZD5 endocytosis. Furthermore, a TMD swap between RNF43 and ZNRF3 re-directs their preference for FZD5 down-regulation. We conclude that RNF43 and ZNRF3 preferentially down-regulate specific FZDs, in part by a TMD-dependent mechanism. In accordance, tissue-specific expression patterns of FZD homologues correlate with the incidence of RNF43 or ZNRF3 cancer mutations in those tissues. Consequently, our data point to druggable vulnerabilities of specific FZD receptors in RNF43- or ZNRF3-mutant human cancers.


Asunto(s)
Endocitosis , Receptores Frizzled , Ubiquitina-Proteína Ligasas , Receptores Frizzled/metabolismo , Receptores Frizzled/genética , Humanos , Endocitosis/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Células HEK293 , Mutación , Vía de Señalización Wnt/genética , Regulación hacia Abajo/genética
5.
Int J Food Sci Nutr ; : 1-12, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38946436

RESUMEN

This study aims to investigate longitudinal associations between the dietary glycemic index (GI) and glycemic load (GL) and changes in glycemic and cardio-metabolic outcomes. A 28-month retrospective cohort study included 110 Vietnamese diabetic patients, collecting their dietary GI and GL values along with blood biochemical data from baseline 24-h dietary recall and medical records. Latent class growth modelling identified three distinct HbA1c trajectories during the follow-up period, with 51% of patients achieving good glycemic control. The adjusted linear mixed-effect model showed that 1 unit increase in logarithms in dietary GL was associated with a 0.14% increase in the log-HbA1c. Among poorly controlled diabetic patients, baseline GL values were positively correlated with increases in HbA1c; GI showed effects on changes in fasting plasma glucose and the triglyceride-glucose (TyG) index. No significant association was observed in patients with good glycemic control.

6.
J Couns Psychol ; 71(4): 267, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38949779

RESUMEN

Reports an error in "Defining racial allies: A qualitative investigation of White allyship from the perspective of people of color" by Cassandra L. Hinger, Cirleen DeBlaere, Rebecca Gwira, Michelle Aiello, Arash Punjwani, Laura Cobourne, Ngoc Tran, Madison Lord, Jordan Mike and Carlton Green (Journal of Counseling Psychology, 2023[Nov], Vol 70[6], 631-644). An additional citation was added for the structure of the definition of White allies in the second paragraph of the introduction. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2024-23216-002.) While interdisciplinary scholars and activists urge White allies to engage in racial justice work led by the voices of Black, Indigenous, and people of color (BIPOC), to date, most research on racial allyship has centered exclusively on the perspective of White allies themselves. Thus, the purpose of this study was to create a framework of racial allyship from the perspective of BIPOC. Utilizing constructivist grounded theory (Charmaz, 2014), focus groups were conducted to understand how BIPOC describe the knowledge, skills, and actions of White allies. Participants across eight focus groups described allyship as an ongoing interpersonal process that included a lifelong commitment to (a) building trust, (b) engaging in antiracist action, (c) critical awareness, (d) sociopolitical knowledge, (e) accountability, and (f) communicating and disseminating information. The findings of this study point to several avenues through which White counseling psychologists can incorporate racial allyship in their research, training, clinical, and advocacy work that align with our field's emphasis on social justice, multiculturalism, and prevention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Investigación Cualitativa , Humanos , Femenino , Adulto , Masculino , Racismo/psicología , Población Blanca/psicología , Justicia Social , Persona de Mediana Edad
7.
J Med Virol ; 96(6): e29746, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38884391

RESUMEN

Head and neck cancers (HNCs), primarily head and neck squamous cell carcinoma (HNSCC), are associated with high-risk human papillomavirus (HR HPV), notably HPV16 and HPV18. HPV status guides treatment and predicts outcomes, with distinct molecular pathways in HPV-driven HNSCC influencing survival rates. HNC incidence is rising globally, with regional variations reflecting diverse risk factors, including tobacco, alcohol, and HPV infection. Oropharyngeal cancers attributed to HPV have significantly increased, particularly in regions like the United States. The HPV16 genome, characterized by oncoproteins E6 and E7, disrupts crucial cell cycle regulators, including tumor protein p53 (TP53) and retinoblastoma (Rb), contributing to HNSCC pathogenesis. P16 immunohistochemistry (IHC) is a reliable surrogate marker for HPV16 positivity, while in situ hybridization and polymerase chain reaction (PCR) techniques, notably reverse transcription-quantitative PCR (RT-qPCR), offer sensitive HPV detection. Liquid-based RT-qPCR, especially in saliva, shows promise for noninvasive HPV detection, offering simplicity, cost-effectiveness, and patient compliance. These molecular advancements enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes in HNC management. In conclusion, advances in HPV detection and molecular understanding have significant clinical management implications. Integrating these advancements into routine practice could ultimately improve patient outcomes.


Asunto(s)
Neoplasias de Cabeza y Cuello , Infecciones por Papillomavirus , Humanos , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Neoplasias de Cabeza y Cuello/virología , Neoplasias de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/patogenicidad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Virus del Papiloma Humano
8.
J Extracell Biol ; 3(1): e123, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38938676

RESUMEN

Cells can communicate via the release and uptake of extracellular vesicles (EVs), which are nano-sized membrane vesicles that can transfer protein and RNA cargo between cells. EVs contain microRNAs and various other types of non-coding RNA, of which Y RNA is among the most abundant types. Studies on how RNAs and their binding proteins are sorted into EVs have mainly focused on comparing intracellular (cytoplasmic) levels of these RNAs to the extracellular levels in EVs. Besides overall transcriptional levels that may regulate sorting of RNAs into EVs, the process may also be driven by local intracellular changes in RNA/RBP concentrations. Changes in extracellular Y RNA have been linked to cancer and cardiovascular diseases. Although the loading of RNA cargo into EVs is generally thought to be influenced by cellular stimuli and regulated by RNA binding proteins (RBP), little is known about Y RNA shuttling into EVs. We previously reported that immune stimulation alters the levels of Y RNA in EVs independently of cytosolic Y RNA levels. This suggests that Y RNA binding proteins, and/or changes in the local Y RNA concentration at EV biogenesis sites, may affect Y RNA incorporation into EVs. Here, we investigated the subcellular distribution of Y RNA and Y RNA binding proteins in activated and non-activated THP1 macrophages. We demonstrate that Y RNA and its main binding protein Ro60 abundantly co-fractionate in organelles involved in EV biogenesis and in EVs. Cellular activation led to an increase in Y RNA concentration at EV biogenesis sites and this correlated with increased EV-associated levels of Y RNA and Ro60. These results suggest that Y RNA incorporation into EVs may be controlled by local intracellular changes in the concentration of Y RNA and their protein binding partners.

9.
Int J Mol Sci ; 25(11)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38891959

RESUMEN

The tyrosine kinase domain of the FMS-Like tyrosine kinase 3 (FLT3-TKD) is recurrently mutated in acute myeloid leukemia (AML). Common molecular techniques used in its detection include PCR and capillary electrophoresis, Sanger sequencing and next-generation sequencing with recognized sensitivity limitations. This study aims to validate the use of droplet digital PCR (ddPCR) in the detection of measurable residual disease (MRD) involving the common FLT3-TKD mutations (D835Y, D835H, D835V, D835E). Twenty-two diagnostic samples, six donor controls, and a commercial D835Y positive control were tested using a commercial Bio-rad® ddPCR assay. All known variants were identified, and no false positives were detected in the wild-type control (100% specificity and sensitivity). The assays achieved a limit of detection suitable for MRD testing at 0.01% variant allelic fraction. Serial samples from seven intensively-treated patients with FLT3-TKD variants at diagnosis were tested. Five patients demonstrated clearance of FLT3-TKD clones, but two patients had FLT3-TKD persistence in the context of primary refractory disease. In conclusion, ddPCR is suitable for the detection and quantification of FLT3-TKD mutations in the MRD setting; however, the clinical significance and optimal management of MRD positivity require further exploration.


Asunto(s)
Leucemia Mieloide Aguda , Mutación , Neoplasia Residual , Reacción en Cadena de la Polimerasa , Tirosina Quinasa 3 Similar a fms , Humanos , Tirosina Quinasa 3 Similar a fms/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
10.
Sex Reprod Healthc ; 41: 100998, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38906085

RESUMEN

PURPOSE: While programs had been implemented by both the government and non-governmental organizations to address inequity in maternal health care in mountainous areas in Vietnam, the expected outcomes were not fully reached due to existing barriers from health workers mainly providing the health services. This study explores prominent issues faced by health workers in delivering maternal care in Cao Bang, focusing on their impact on the local population's daily lives and overall development. METHODS: A qualitative study was conducted with 15 participants working as health managers, commune health workers, commune midwives, and village health workers in selected communes of a mountainous and border district located in the Northeast Cao Bang province. RESULTS: Main barriers include the incompetent healthcare workforce, ineffective use of facility resources, lack of work commitment, and unscientific traditional beliefs. CONCLUSION: Future community programs should implement strict policies, defined rights, and clear responsibilities for health workers handling these obstacles to optimize the quality of maternal health care services in these remote areas.

11.
Langmuir ; 40(25): 13292-13302, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38871669

RESUMEN

In this study, surface-enhanced Raman scattering substrates were investigated by the electrodeposition method to detect low concentrations of pesticides via the electrodeposition method with different agents from silver and gold precursors on APTES-modified ITO glass. A dual-potential method supplied three electrodes and was performed with a nucleation potential of 0.7 V for 2 s and a growth potential of -0.2 V for 500 s. The Ag film produced by the electrodeposition approach has great surface uniformity and good SERS signal amplification for the thiram insecticide at low concentrations. Interestingly, the ITO/APTES/Ag substrate extensively increased the sensitivity than the other investigated ones, thanks to the adequate assistance of amino groups of APTES in the denser and hierarchical deposition of Ag NPs. These observations were additionally elucidated via finite-difference time-domain (FDTD) calculation. For thiram, the detection was set at 10-8 M with an enhancement factor of up to 3.6 × 107 times. Comparing the SERS spectra of thiram at concentrations of 10-3, 10-4, and 10-5 M with a relative standard deviation (RSD) of less than 7.0% demonstrates excellent reproducibility of the ITO/APTES/Ag substrate. In addition, the special selectivity of the ITO/APTES/Ag substrate for thiram demonstrates that these nanostructures can identify pesticides with extreme sensitivity.

12.
ACS Appl Mater Interfaces ; 16(22): 28625-28637, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38767316

RESUMEN

Metal node engineering, which can optimize the electronic structure and modulate the composition of poor electrically conductive metal-organic frameworks, is of great interest for electrochemical natural seawater splitting. However, the mechanism underlying the influence of mixed-metal nodes on electrocatalytic activities is still ambiguous. Herein, a strategic design is comprehensively demonstrated in which mixed Ni and Co metal redox-active centers are uniformly distributed within NH2-Fe-MIL-101 to obtain a synergistic effect for the overall enhancement of electrocatalytic activities. Three-dimensional mixed metallic MOF nanosheet arrays, consisting of three different metal nodes, were in situ grown on Ni foam as a highly active and stable bifunctional catalyst for urea-assisted natural seawater splitting. A well-defined NH2-NiCoFe-MIL-101 reaches 1.5 A cm-2 at 360 mV for the oxygen evolution reaction (OER) and 0.6 A cm-2 at 295 mV for the hydrogen evolution reaction (HER) in freshwater, substantially higher than its bimetallic and monometallic counterparts. Moreover, the bifunctional NH2-NiCoFe-MIL-101 electrode exhibits eminent catalytic activity and stability in natural seawater-based electrolytes. Impressively, the two-electrode urea-assisted alkaline natural seawater electrolysis cell based on NH2-NiCoFe-MIL-101 needs only 1.56 mV to yield 100 mA cm-2, much lower than 1.78 V for alkaline natural seawater electrolysis cells and exhibits superior long-term stability at a current density of 80 mA cm-2 for 80 h.

13.
Beilstein J Nanotechnol ; 15: 475-489, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715710

RESUMEN

A simple approach was developed to synthesize cobalt ferrite nanoparticles/graphene quantum dots (CF/GQDs). The material was prepared from a homogeneous mixture of iron nitrate, cobalt nitrate, and starch at 140, 180 and 200 °C in a 24 h thermal hydrolysis process. The obtained materials were characterised by using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet-visible diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, vibrating-sample magnetometry, and nitrogen adsorption/desorption isotherms. Cobalt ferrite crystals of around 8-10 nm and graphene quantum dots formed directly at 200 °C. Stacking GQDs sheets onto the CF nanoparticles resulted in CF/GQDs nanoparticles. The nanocomposite exhibits satisfactory fluorescent and superparamagnetic properties, which are vital for catalytic applications. The CF/GQDs catalyse significantly the degradation of methylene blue (MB) under visible light. The catalyst can be recycled with an external magnetic field and displays suitable stability. Also, it was reused in three successive experiments with a loss of efficiency of about 5%. The CF/GQDs are considered as an efficient photocatalyst for MB degradation and other dyes.

14.
Front Neurosci ; 18: 1344653, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38726030

RESUMEN

Introduction: Effects of dioxin exposure on gray matter volume have been reported in previous studies, but a few studies reported effects of dioxin exposure on white matter structure. Therefore, this study was undertaken to investigate the impact of dioxin exposure on white matter microstructure in men living in the most severely dioxin-contaminated areas in Vietnam. Methods: In 2019 brain MRI scans from 28 men living near Bien Hoa airbase were obtained at Dong Nai General Hospital, Vietnam, on a 3 T scanner using a conventional diffusion tensor imaging sequence. Two exposure markers were indicated by perinatal exposure estimated by assessment of maternal residency in a dioxin-contaminated area during pregnancy and by measurement of blood dioxin levels. A general linear model was used to compare fractional anisotropy (FA) values in 11 white matter tracts in both hemispheres between groups with and without perinatal dioxin exposure and groups with high and low blood dioxin levels after adjusting for covariates. Results: The adjusted mean FA value in the left cingulum hippocampal part (CGH) was significantly lower in the perinatal dioxin exposure group compared with the group without perinatal dioxin exposure. The high blood TCDD group showed significantly reduced FA values in the left and right CGH and right uncinate fasciculus (UNC). Moreover, the high blood TEQ-PCDDs group showed significantly lower FA values in the left and right CGH and the left UNC. There were no significant differences in FA values between the groups with high and low TEQ-PCDFs levels or between the groups with high and low TEQ-PCDD/Fs levels. Discussion: It was concluded that dioxin exposure during the perinatal period and adulthood may alter the microstructure of white matter tracts in individuals with neurodevelopmental disorders.

15.
Cureus ; 16(5): e60352, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38756712

RESUMEN

BACKGROUND: There are several types of benign renal diseases, such as urological stones, ureteropelvic junction obstruction, renal vascular disease, and inflammation, which are responsible for nonfunctioning kidneys. Laparoscopic nephrectomy (LN) is the gold standard for treating nonfunctioning kidneys with complications. This study presents the results of our initial experiences with 3D laparoscopic nephrectomy (3D-LN) for benign, nonfunctioning kidneys. METHODS: From July 2021 to July 2023, 40 consecutive patients who underwent 3D transperitoneal laparoscopic nephrectomy were retrospectively evaluated at the Department of Urology and Department of General Surgery, Hue Central Hospital, Hue, Vietnam. Patient demographics, intraoperative and early postoperative results, postoperative recovery, complications, and three-month follow-up results were recorded. RESULTS: The mean age was 58.35 ± 14.9 years. There were 13 (32.5%) male and 27 (67.5%) female patients. Flank pain was the main reason for hospitalization in 33 cases (82.5%); the common cause of a nonfunctioning kidney was urological stones (62.5%). Twenty-three out of 40 patients underwent a left nephrectomy. The average operative time was 92.57 ± 28.69 minutes. A statistically significant difference in surgery time was found between the group with no adhesion and the group with mild adhesion, as well as between the first 19 patients and the last 18 patients (p <0.05). The mean blood loss was 51.62 ± 24.35 ml. Three cases were converted to open surgery due to severe adhesions. The postoperative complications rate was 8.1%. The average length of the postoperative hospital stay was 7.89 ± 3.59 days. CONCLUSIONS: Three-dimensional laparoscopic nephrectomy is a safe and effective method that increases depth perception and spatial orientation for surgeons and can compensate for the remaining shortcomings of traditional 2D systems.

16.
Front Chem ; 12: 1382319, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38690013

RESUMEN

Introduction: 3D pharmacophore models describe the ligand's chemical interactions in their bioactive conformation. They offer a simple but sophisticated approach to decipher the chemically encoded ligand information, making them a valuable tool in drug design. Methods: Our research summarized the key studies for applying 3D pharmacophore models in virtual screening for 6,944 compounds of APJ receptor agonists. Recent advances in clustering algorithms and ensemble methods have enabled classical pharmacophore modeling to evolve into more flexible and knowledge-driven techniques. Butina clustering categorizes molecules based on their structural similarity (indicated by the Tanimoto coefficient) to create a structurally diverse training dataset. The learning method combines various individual pharmacophore models into a set of pharmacophore models for pharmacophore space optimization in virtual screening. Results: This approach was evaluated on Apelin datasets and afforded good screening performance, as proven by Receiver Operating Characteristic (AUC score of 0.994 ± 0.007), enrichment factor of (EF1% of 50.07 ± 0.211), Güner-Henry score of 0.956 ± 0.015, and F-measure of 0.911 ± 0.031. Discussion: Although one of the high-scoring models achieved statistically superior results in each dataset (AUC of 0.82; an EF1% of 19.466; GH of 0.131 and F1-score of 0.071), the ensemble learning method including voting and stacking method balanced the shortcomings of each model and passed with close performance measures.

17.
Arch Pathol Lab Med ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38802102

RESUMEN

CONTEXT.­: The subspecialty workforce in pathology globally is inadequate for the demands of many modern therapies. The Open Pathology Education Network (OPEN) was formed to augment the global pathology workforce. The International Gynecologic Cancer Society (IGCS) virtual gynecologic-oncology (gyn-onc) fellowship training identified needs for higher-level pathology support. OBJECTIVE.­: To report on an OPEN-IGCS pilot project to support gyn-onc and pathology education efforts in a developing country. DESIGN.­: Curriculum with learning objectives and content from open sources was assembled. Mentoring sessions included bidirectional case sharing. Trainees received sequential curricula assignments and had options for communication outside mentoring sessions. Pretest and posttest digital slide assessments were included. Mentors attended the gynecology tumor board, allowing for the assessment of quality and accuracy of pathology diagnosis for cases discussed. RESULTS.­: Learners completing the pretest and posttest showed substantial improvement, with 2 practicing pathologists improving their diagnostic scores from 60% to an average of 95%. A third trainee-level participant also improved, but to a lesser degree. Qualitative assessments included increased confidence in presentation and an increased ability to anticipate questions, raise issues of expanded differential diagnoses, and articulate appropriate workup. Observations of clinicians who participated also noted increased confidence in participating pathologists. Secondary value included establishing an expanded network of support in other subspecialties for participants. Pathologic issues at the tumor board decreased, from more than 50% in the first 3 months of study to 0% in the last 3 months of study. The curriculum was embedded into a self-paced learning portal at courses.open-pathology.org. CONCLUSIONS.­: The OPEN-IGCS collaboration model shows the potential to provide subspecialty pathology training remotely.

18.
Microb Biotechnol ; 17(5): e14484, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38801349

RESUMEN

The human gut hosts numerous ecological niches for microbe-microbe and host-microbe interactions. Gut lactate homeostasis in humans is crucial and relies on various bacteria. Veillonella spp., gut lactate-utilizing bacteria, and lactate-producing bacteria were frequently co-isolated. A recent clinical trial has revealed that lactate-producing bacteria in humans cross-feed lactate to Veillonella spp.; however, their interspecies interaction mechanisms remain unclear. Veillonella dispar, an obligate anaerobe commonly found in the human gut and oral cavity, ferments lactate into acetate and propionate. In our study, we investigated the interaction between V. dispar ATCC 17748T and three representative phylogenetically distant strains of lactic acid bacteria, Lactobacillus acidophilus ATCC 4356T, Lacticaseibacillus paracasei subsp. paracasei ATCC 27216T, and Lactiplantibacillus plantarum ATCC 10241. Bacterial growth, viability, metabolism and gene level adaptations during bacterial interaction were examined. V. dispar exhibited the highest degree of mutualism with L. acidophilus. During co-culture of V. dispar with L. acidophilus, both bacteria exhibited enhanced growth and increased viability. V. dispar demonstrated an upregulation of amino acid biosynthesis pathways and the aspartate catabolic pathway. L. acidophilus also showed a considerable number of upregulated genes related to growth and lactate fermentation. Our results support that V. dispar is able to enhance the fermentative capability of L. acidophilus by presumably consuming the produced lactate, and that L. acidophilus cross-feed not only lactate, but also glutamate, to V. dispar during co-culture. The cross-fed glutamate enters the central carbon metabolism in V. dispar. These findings highlight an intricate metabolic relationship characterized by cross-feeding of lactate and glutamate in parallel with considerable gene regulation within both L. acidophilus (lactate-producing) and V. dispar (lactate-utilizing). The mechanisms of mutualistic interactions between a traditional probiotic bacterium and a potential next-generation probiotic bacterium were elucidated in the production of short-chain fatty acids.


Asunto(s)
Ácidos Grasos Volátiles , Ácido Glutámico , Ácido Láctico , Veillonella , Ácido Láctico/metabolismo , Ácidos Grasos Volátiles/metabolismo , Ácido Glutámico/metabolismo , Veillonella/metabolismo , Veillonella/crecimiento & desarrollo , Veillonella/genética , Simbiosis , Interacciones Microbianas , Humanos , Lactobacillus acidophilus/metabolismo , Lactobacillus acidophilus/crecimiento & desarrollo , Lactobacillus acidophilus/genética , Lactobacillus/metabolismo , Lactobacillus/genética , Lactobacillus/crecimiento & desarrollo , Viabilidad Microbiana , Fermentación
19.
PLoS One ; 19(5): e0303491, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38768167

RESUMEN

In the digital age, firms should continually innovate and adapt to remain competitive and enhance performance. Innovation and adaptation require firms to take a holistic approach to their corporate structuring to ensure efficiency and effectiveness to stay competitive. This study examines how corporate restructuring impacts firm performance in Vietnam. We then investigate the moderating role of digital transformation in the corporate restructuring-firm performance nexus. We use content analysis, with a focus on particular terms, including "digitalization," "big data," "cloud computing," "blockchain," and "information technology" for 11 years, from 2011 to 2021. The frequency index from these keywords is developed to proxy the digital transformation for the Vietnamese listed firms. A final sample includes 118 Vietnamese listed firms with sufficient data for the analysis using the generalized method of moments (GMM) approach. The results indicate that corporate restructuring, including financial, portfolio, and operational restructuring, has a negative effect on firm performance in Vietnam. Digital transformation also negatively affects firm performance. However, corporate restructuring implemented in conjunction with digital transformation improves the performance of Vietnamese listed firms. These findings largely remain unchanged across various robustness analyses.


Asunto(s)
Comercio , Vietnam , Humanos , Tecnología de la Información
20.
Public Health Nutr ; : 1-37, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38804077

RESUMEN

OBJECTIVE: SEANUTS II Vietnam aims to obtain an in-depth understanding of the nutritional status and nutrient intake of children between 0.5-11.9 years old. DESIGN: Cross-sectional survey. SETTING: A multistage cluster systematic random sampling method was implemented in different regions in Vietnam: North Mountainous, Central Highlands, Red River Delta, North Central and Coastal Area, Southeast and Mekong River Delta. PARTICIPANTS: 4001 children between 6 months and 11.9 years of age. RESULTS: Prevalence of stunting and underweight was higher in rural than in urban children, whereas overweight and obese rates were higher in urban areas. 12.0% of the children had anemia and especially children 0.5-1-year-old were affected (38.6%). Low serum retinol was found in 6.2% of children ≥ 4 years old. Prevalence of vitamin D insufficiency was 31.1% while 60.8% had low serum zinc. For nutrient intake, overall, 80.1% of the children did not meet the estimated energy requirements. For calcium intake, ∼60% of the younger children did not meet the RNI while it was 92.6% in children >7 years old. For vitamin D intake, 95.0% of the children did not meet RNI. CONCLUSIONS: SEANUTS II Vietnam indicated that overnutrition was more prevalent than undernutrition in urban areas, while undernutrition was found more in rural areas. The high prevalence of low serum zinc, vitamin D insufficiency and the inadequate intakes of calcium and vitamin D are of concern. Nutrition strategies for Vietnamese children should consider three sides of malnutrition and focus on approaches for the prevention malnutrition.

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