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1.
J Hazard Mater ; 478: 135492, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39141938

RESUMEN

Effectively treating phenolic substances is a crucial task in environmental protection. This study aims to determine whether bacterial-algae biofilm reactors offer superior treatment efficacy compared to traditional activated sludge and biofilm reactors. The average degradation ratios of 2,4-dimethylphenol (40, 70, 150, 300, and 230 mg/L) were found to be 98 %, 99 %, 92.1 %, 84.7 %, and 63.7 % respectively. The bacterial-algae biofilm demonstrates a higher tolerance to toxicity, assimilation ability, and efficacy recovery ability. The cell membrane of Chlorella in the bacteria-algae biofilm is not easily compromised, thus ensuring a stable pH environment. High concentrations of tightly bound extracellular polymers (TB-EPS) enhance the efficacy in treating toxic pollutants, promote the stable structure. Intact Chlorella, bacilli, and EPS were observed in bacterial-algal biofilm. The structural integrity of bacteria-algae consistently enhances its resistance to the inhibitory effects of high concentrations of phenolic compounds. Cloacibacterium, Comamonas, and Dyella were the main functional bacterial genera that facilitate the formation of bacterial-algal biofilms and the degradation of phenolic compounds. The dominant microalgal families include Aspergillaceae, Chlorellales, Chlorellaceae, and Scenedesmaceae have certain treatment effects on phenolic substances. Chlorellales and Chlorellaceae have the ability to convert NH4+-N. The Aspergillaceae is also capable of generating synergistic effects with Chlorellales, Chlorellaceae, and Scenedesmaceae, thereby establishing a stable bacterial-algal biofilm system.


Asunto(s)
Bacterias , Biodegradación Ambiental , Biopelículas , Reactores Biológicos , Contaminantes Químicos del Agua , Biopelículas/efectos de los fármacos , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/química , Bacterias/metabolismo , Bacterias/efectos de los fármacos , Microalgas/metabolismo , Fenoles/metabolismo , Fenoles/química , Chlorella/metabolismo , Chlorella/efectos de los fármacos
2.
Asia Pac J Ophthalmol (Phila) ; 13(4): 100091, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39209217

RESUMEN

Generative Artificial Intelligence (GenAI) are algorithms capable of generating original content. The ability of GenAI to learn and generate novel outputs alike human cognition has taken the world by storm and ushered in a new era. In this review, we explore the role of GenAI in healthcare, including clinical, operational, and research applications, and delve into the cybersecurity risks of this technology. We discuss risks such as data privacy risks, data poisoning attacks, the propagation of bias, and hallucinations. In this review, we recommend risk mitigation strategies to enhance cybersecurity in GenAI technologies and further explore the use of GenAI as a tool in itself to enhance cybersecurity across the various AI algorithms. GenAI is emerging as a pivotal catalyst across various industries including the healthcare domain. Comprehending the intricacies of this technology and its potential risks will be imperative for us to fully capitalise on the benefits that GenAI can bring.


Asunto(s)
Inteligencia Artificial , Seguridad Computacional , Humanos , Algoritmos , Atención a la Salud
3.
Heliyon ; 10(13): e34220, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39091930

RESUMEN

Background: Colorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment. Methods: A retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival. Results: The blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma. Conclusions: Our study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC.

4.
Sensors (Basel) ; 24(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39000907

RESUMEN

With the rapid development of fully automatic operation (FAO) and location-based services, the evaluation criteria of average localization accuracy can no longer meet our demands, in favor of deterministic localization. However, most localization researches modeled localization performance function and enhanced it by minimizing average localization root mean square error (RMSE). The performance degradation in a small region was not considered. In this paper, we present a survey of deterministic localization and analyze the relationship between accuracy and certainty. In this paper, two common solutions of localization enhancement are presented and their localization certainties are discussed. Furthermore, we carry out related localization enhancement experiments in rail transit line and analyze their improvement on deterministic localization. The experimental results show that the overall localization performance is improved, while the deterministic localization requires the stricter solution to promote.

5.
Sci Rep ; 14(1): 9705, 2024 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678158

RESUMEN

The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case-control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall's tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding.


Asunto(s)
Plaquetas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/inmunología , Masculino , Femenino , Persona de Mediana Edad , Plaquetas/inmunología , Estudios de Casos y Controles , Trombocitopenia/sangre , Trombocitopenia/inmunología , Trombocitopenia/etiología , Anciano , Adulto , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Anemia/sangre , Anemia/inmunología , Factores de Riesgo , Citopenia
6.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38612816

RESUMEN

The implantation of human embryos is a complex process involving various cytokines and receptors expressed by both endometrium and embryos. However, the role of cytokines produced by a single embryo in successful implantation is largely unknown. This study aimed to investigate the role of IL-1ß expressed in a single-embryo-conditioned medium (ECM) in embryo implantation. Seventy samples of single ECM were analyzed by a specially designed magnetic-beads-based microfluidic chip from 15 women. We discovered that IL-1ß level increased as the embryo developed, and the difference was significant. In addition, receiver operator characteristic (ROC) curves analysis showed a higher chance of pregnancy when the IL-1ß level on day 5 ECM was below 79.37 pg/mL and the difference between day 5 and day 3 was below 24.90 pg/mL. Our study discovered a possible association between embryonic proteomic expression and successful implantation, which might facilitate single-embryo transfer in the future by helping clinicians identify the embryo with the greatest implantation potential.


Asunto(s)
Microfluídica , Proteómica , Embarazo , Humanos , Femenino , Medios de Cultivo Condicionados , Interleucina-1beta , Blastocisto , Implantación del Embrión , Citocinas
7.
Chemosphere ; 357: 142039, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38621488

RESUMEN

The coexistence of free chlorine and bromide under sunlight irradiation (sunlight/FC with Br-) is unavoidable in outdoor seawater swimming pools, and the formation of brominated disinfection byproducts could act more harmful than chlorinated disinfection byproducts. In this study, benzotriazole was selected as a model compound to investigate the degradation rate and the subsequent formation of disinfection byproducts via sunlight/FC with Br- process. The rate constants for the degradation of benzotriazole under pseudo first order conditions in sunlight/FC with Br- and sunlight/FC are 2.3 ± 0.07 × 10-1 min-1 and 6.0 ± 0.7 × 10-2 min-1, respectively. The enhanced degradation of benzotriazole can be ascribed to the generation of HO•, bromine species, and reactive halogen species (RHS) during sunlight/FC with Br-. Despite the fact that sunlight/FC with Br- process enhanced benzotriazole degradation, the reaction results in increasing tribromomethane (TBM) formation. A high concentration (37.8 µg/L) of TBM was detected in the sunlight/FC with Br-, which was due to the reaction of RHS. The degradation of benzotriazole was notably influenced by the pH value (pH 4 - 11), the concentration of bromide (0 - 2 mM), and free chlorine (1 - 6 mg/L). Furthermore, the concentration of TBM increased when the free chlorine concentrations increased, implying the formation potential of harmful TBM in chlorinated seawater swimming pools.


Asunto(s)
Bromuros , Cloro , Luz Solar , Triazoles , Contaminantes Químicos del Agua , Triazoles/química , Bromuros/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Cloro/química , Desinfección , Trihalometanos/química , Agua de Mar/química , Desinfectantes/química , Desinfectantes/análisis
8.
Nat Commun ; 15(1): 1757, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413612

RESUMEN

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.


Asunto(s)
Candida albicans , Proteínas Fúngicas , Humanos , Ratones , Animales , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Candida albicans/metabolismo , Péptidos/metabolismo
9.
Diabetol Metab Syndr ; 15(1): 199, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37833779

RESUMEN

BACKGROUND: Hypoglycemia is one of the most common complications in patients with DN during hemodialysis. The purpose of the study is to construct a clinical automatic calculation to predict risk of hypoglycemia during hemodialysis for patients with diabetic nephropathy. METHODS: In this cross-sectional study, patients provided information for the questionnaire and received blood glucose tests during hemodialysis. The data were analyzed with logistic regression and then an automated calculator for risk prediction was constructed based on the results. From May to November 2022, 207 hemodialysis patients with diabetes nephropathy were recruited. Patients were recruited at blood purifying facilities at two hospitals in Beijing and Inner Mongolia province, China. Hypoglycemia is defined according to the standards of medical care in diabetes issued by ADA (2021). The blood glucose meter was used uniformly for blood glucose tests 15 minutes before the end of hemodialysis or when the patient did not feel well during hemodialysis. RESULTS: The incidence of hypoglycemia during hemodialysis was 50.2% (104/207). The risk prediction model included 6 predictors, and was constructed as follows: Logit (P) = 1.505×hemodialysis duration 8~15 years (OR = 4.506, 3 points) + 1.616×hemodialysis duration 16~21 years (OR = 5.032, 3 points) + 1.504×having hypotension during last hemodialysis (OR = 4.501, 3 points) + 0.788×having hyperglycemia during the latest hemodialysis night (OR = 2.199, 2 points) + 0.91×disturbance of potassium metabolism (OR = 2.484, 2 points) + 2.636×serum albumin<35 g/L (OR = 13.963, 5 points)-4.314. The AUC of the prediction model was 0.866, with Matthews correlation coefficient (MCC) of 0.633, and Hosmer-Lemeshow χ2 of 4.447(P = 0.815). The automatic calculation has a total of 18 points and four risk levels. CONCLUSIONS: The incidence of hypoglycemia during hemodialysis is high in patients with DN. The risk prediction model in this study had a good prediction outcome. The hypoglycemia prediction automatic calculation that was developed using this model can be used to predict the risk of hypoglycemia in DN patients during hemodialysis and also help identify those with a high risk of hypoglycemia during hemodialysis.

10.
BMC Med Educ ; 23(1): 787, 2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37875886

RESUMEN

BACKGROUND: Mentoring plays a pivotal yet poorly understood role in shaping a physician's professional identity formation (PIF) or how they see, feel and act as professionals. New theories posit that mentoring nurtures PIF by functioning as a community of practice through its structured approach and its support of a socialisation process made possible by its assessment-directed personalized support. To test this theory and reshape the design, employ and support of mentoring programs, we evaluate peer-mentor experiences within the Palliative Medicine Initiative's structured research mentoring program. METHODS: Semi-structured interviews with peer mentors under the Palliative Medicine Initiative (PMI) at National Cancer Centre Singapore were conducted and triangulated against mentoring diaries to capture longitudinal data of their PMI experiences. The Systematic Evidence-Based Approach (SEBA) was adopted to enhance the trustworthiness of the data. SEBA employed concurrent content and thematic analysis of the data to ensure a comprehensive review. The Jigsaw Perspective merged complementary themes and categories identified to create themes/categories. The themes/categories were compared with prevailing studies on mentoring in the Funnelling Process to reaffirm their accuracy. RESULTS: Twelve peer-mentors participated in the interviews and eight peer-mentors completed the mentoring diaries. The domains identified were community of practice and identity work. CONCLUSIONS: The PMI's structured mentoring program functions as a community of practice supporting the socialisation process which shapes the peer-mentor's belief system. Guided by a structured mentoring approach, stage-based assessments, and longitudinal mentoring and peer support, peer-mentors enhance their detection and evaluation of threats to their regnant belief system and adapt their self-concepts of identity and personhood to suit their context. These insights will help structure and support mentoring programs as they nurture PIF beyond Palliative Medicine.


Asunto(s)
Tutoría , Mentores , Humanos , Identificación Social , Grupo Paritario , Socialización
11.
BMC Med Educ ; 23(1): 799, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880728

RESUMEN

BACKGROUND: Medical education has enjoyed mixed fortunes nurturing professional identity formation (PIF), or how medical students think, feel and act as physicians. New data suggests that structured mentoring programs like the Palliative Medicine Initiative (PMI) may offer a means of developing PIF in a consistent manner. To better understand how a well-established structured research mentoring program shapes PIF, a study of the experiences of PMI mentees is proposed. METHODOLOGY: Acknowledging PIF as a sociocultural construct, a Constructivist approach and Relativist lens were adopted for this study. In the absence of an effective tool, the Ring Theory of Personhood (RToP) and Krishna-Pisupati Model (KPM) model were used to direct this dual Systematic Evidence-Based Approach (Dual-SEBA) study in designing, employing and analysing semi-structured interviews with PMI mentees and mentoring diaries. These served to capture changes in PIF over the course of the PMI's mentoring stages. Transcripts of the interviews and mentoring diaries were concurrently analysed using content and thematic analysis. Complementary themes and categories identified from the Split Approach were combined using the Jigsaw Approach and subsequently compared with mentoring diaries in the Funnelling Process. The domains created framed the discussion. RESULTS: A total of 12 mentee interviews and 17 mentoring diaries were analysed, revealing two domains-PMI as a Community of Practice (CoP) and Identity Formation. The domains confirmed the centrality of a structured CoP capable of facilitating longitudinal mentoring support and supporting the Socialisation Process along the mentoring trajectory whilst cultivating personalised and enduring mentoring relationships. CONCLUSION: The provision of a consistent mentoring approach and personalised, longitudinal mentoring support guided along the mentoring trajectory by structured mentoring assessments lay the foundations for more effective mentoring programs. The onus must now be on developing assessment tools, such as a KPM-based tool, to guide support and oversight of mentoring relationships.


Asunto(s)
Educación Médica , Tutoría , Médicos , Humanos , Identificación Social , Mentores/educación
12.
Ying Yong Sheng Tai Xue Bao ; 34(8): 2113-2122, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37681375

RESUMEN

To explore the adaptive mechanism of leaf photosynthetic capacity in different light environments within Cinnamomum camphora canopy and enhance carbon sequestration, we investigated morphological structures, nutritional and physiological traits and photosynthetic characteristics of leaves in different orientations of C. camphora canopy, southern side in the outer layer (100% full light), southern side in the inner layer (34% full light) and northern side (21% full light). We analyzed the main limitation resulting in down-regulation of photosynthetic capacity in low light environments. Results showed that specific leaf weight, the thickness of lower and upper epidermal cuticle, lower epidermis, palisade tissue as well as cell number and width of palisade tissue, the thickness ratio of palisade to spongy tissue, cell structure closely degree significantly decreased with decreasing light intensity within canopy, opposite to the responses of spongy tissue thickness, cell length-width ratio of palisade tissue, and cell structure loose degree. The contents of leaf carbon, soluble protein, soluble sugar and starch were significantly lower in two low light environments compared with full light, whereas nitrogen content was markedly higher in north side. Low light prominently reduced gas exchange parameters, i.e., net photosynthetic rate (Pn), dark respiration rate, stomatal conductance to CO2(gsc), mesophyll conductance to CO2(gm), total conductance to CO2(gtot), intercellular CO2 concentration (Ci), CO2 concentration at the chloroplast (Cc). Pn was positively correlated with gsc, gm, gtot and Cc. There were no differences in maximum quantum photochemical efficiency, actual quantum photochemical efficiency, photochemical quenching coefficient, maximum rate of Rubisco carboxylation (Vc max) and maximum rate of electron transport (Jmax) among light environments. Vc max and Jmax were positively correlated to Pn. Of the shading-induced limitations to photosynthesis, gm limitation was the most important, and gsc limitation was enhanced with further weakened light intensity while biochemical limitation was rather limited. In summary, the results suggested that full light could improve leaf photosynthetic potential in C. camphora canopy leaves, reduce the effects of gm and gsc limitation on photosynthesis, and consequently enhance carbon assimilation capacity.


Asunto(s)
Cinnamomum camphora , Dióxido de Carbono , Fotosíntesis , Luz , Carbono
13.
Nat Chem Biol ; 19(12): 1480-1491, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37322158

RESUMEN

Hyperactivated glycolysis is a metabolic hallmark of most cancer cells. Although sporadic information has revealed that glycolytic metabolites possess nonmetabolic functions as signaling molecules, how these metabolites interact with and functionally regulate their binding targets remains largely elusive. Here, we introduce a target-responsive accessibility profiling (TRAP) approach that measures changes in ligand binding-induced accessibility for target identification by globally labeling reactive proteinaceous lysines. With TRAP, we mapped 913 responsive target candidates and 2,487 interactions for 10 major glycolytic metabolites in a model cancer cell line. The wide targetome depicted by TRAP unveils diverse regulatory modalities of glycolytic metabolites, and these modalities involve direct perturbation of enzymes in carbohydrate metabolism, intervention of an orphan transcriptional protein's activity and modulation of targetome-level acetylation. These results further our knowledge of how glycolysis orchestrates signaling pathways in cancer cells to support their survival, and inspire exploitation of the glycolytic targetome for cancer therapy.


Asunto(s)
Fenómenos Bioquímicos , Neoplasias , Humanos , Glucólisis , Neoplasias/metabolismo , Transducción de Señal , Línea Celular
14.
Molecules ; 28(7)2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37049886

RESUMEN

To bridge the technical gap of heterojunction induction control in conventional semiconductor photocatalysts, a method of regulating the growth of heterojunctions utilizing biomimetic structures was designed to prepare a series of Bi2WO6/Bi2O3 vertical heterojunction nanocomposites for the disposal of environmentally hazardous tetracycline wastewater difficult to degrade by conventional microbial techniques. Porous Bi2O3 precursors with high-energy crystalline (110) dominant growth were produced using the sunflower straw bio-template technique (SSBT). Bi2WO6 with a (131) plane grew preferentially into 2.8 to 4 nm pieces on the (110) plane of Bi2O3, causing a significant density reduction between Bi2WO6 pieces and a dimensional decrease in the agglomerated Bi2WO6 spheres from 3 µm to 700 nm since Bi2WO6 grew on the structure of the biomimetic Bi2O3. The optimal 1:8 Bi2WO6/Bi2O3 coupling catalyst was obtained via adapting the ratio of the two semiconductors, and the coupling ratio of 1:8 minimized the adverse effects of the overgrowth of Bi2WO6 on degradation performance by securing the quantity of vertical heterojunctions. The material degradation reaction energy barrier and bandgap were significantly reduced by the presence of a large number of vertical heterojunction structures, resulting in a material with lower impedance and higher electron-hole separation efficiency; thus, the degradation efficiency of 1:8 Bi2WO6/Bi2O3 for tetracycline hydrochloride reached 99% within 60 min. In conclusion, this study not only successfully synthesized a novel photocatalyst with potential applications in water pollution remediation but also introduced a pioneering approach for semiconductor-driven synthesis.

15.
Hum Reprod ; 38(6): 1124-1134, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37071897

RESUMEN

STUDY QUESTION: Does YAP1 inhibition alleviate progesterone resistance in endometriosis? SUMMARY ANSWER: YAP1 inhibition reduces progesterone resistance in vitro and in vivo. WHAT IS KNOWN ALREADY: Progesterone resistance not only causes treatment failure for endometriosis but also inhibits eutopic endometrial cell proliferation, dysregulates decidualization, and reduces the success rates of pregnancy. Hippo/yes-associated protein 1 (YAP1) signaling pathway plays an important role in the pathogenesis of endometriosis. STUDY DESIGN, SIZE, DURATION: Paraffin-embedded tissues containing paired endometriotic and endometrial specimens (n = 42) and serum samples isolated from normal controls (n = 15) or endometriotic patients with (n = 25) or without (n = 21) prior dienogest treatment were analyzed. A mouse model of endometriosis was also used to evaluate the effects of YAP1 inhibition on progesterone resistance. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary endometriotic and endometrial stromal cells treated with YAP1 inhibitor or miR-21 mimic/inhibitor were used for the in vitro studies including decidualization induction, chromatin immunoprecipitation (ChIP), and RNA immunoprecipitation. Tissue specimens and serum from human and mouse were used for immunohistochemistry staining, exosome isolation, and microRNA (miRNA) quantification, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Herein, we report, by using ChIP-PCR and RNA-IP, that YAP1 inhibits progesterone receptor (PGR) expression through upregulation of miR-21-5p. Upregulation of miR-21-5p not only reduces PGR expression but also inhibits endometrial stromal cell decidualization. Indeed, levels of YAP1 and miR-21-5p are inversely correlated with the level of PGR in human endometrial samples. In contrast, knockdown of YAP1 or treatment with verteporfin (VP), a YAP1 inhibitor, reduces miR-21-5p expression, thus leading to an increase in PGR expression in ectopic endometriotic stromal cells. In the mouse model of endometriosis, treatment with VP increases PGR expression and enhances decidualization. More importantly, VP synergistically increases the treatment effect of progestin in causing the regression of endometriotic lesions and improves the decidualization capability of the endometrium. Interestingly, treatment with dienogest, a synthetic progestin, reduces YAP1 and miR-21-5p expression in human cells and in the mouse model of endometriosis. Patients who received dienogest treatment for 6 months show a significant decrease in serum extracellular vesicle-associated miR-21-5p level. LARGE SCALE DATA: A public dataset (GSE51981) containing a large cohort of endometriotic tissues is available from the Gene Expression Omnibus (GEO). LIMITATIONS, REASONS FOR CAUTION: A large cohort of clinical samples is needed to verify the current diagnostic value of miR-21-5p in future studies. WIDER IMPLICATIONS OF THE FINDINGS: The reciprocal regulation of YAP1 and PGR suggests that combined YAP1 inhibitor and progestin may be a better therapeutic approach for treating endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Ministry of Science and Technology, Taiwan (MOST-111-2636-B-006-012, MOST-111-2314-B-006-075-MY3, and MOST-106-2320-B-006-072-MY3). The authors have no conflict of interest to disclose.


Asunto(s)
Endometriosis , MicroARNs , Embarazo , Femenino , Humanos , Animales , Ratones , Endometriosis/patología , Progestinas/uso terapéutico , Endometrio/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Progesterona/metabolismo , Factores de Transcripción/metabolismo , Células del Estroma/metabolismo
16.
BMJ Open ; 13(3): e067048, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36977542

RESUMEN

OBJECTIVES: Guiding the development of longitudinal competencies in communication, ethics and professionalism underlines the role of portfolios to capture and evaluate the multiple multisource appraisals and direct personalised support to clinicians. However, a common approach to these combined portfolios continues to elude medical practice. A systematic scoping review is proposed to map portfolio use in training and assessments of ethics, communication and professionalism competencies particularly in its inculcation of new values, beliefs and principles changes attitudes, thinking and practice while nurturing professional identity formation. It is posited that effective structuring of portfolios can promote self-directed learning, personalised assessment and appropriate support of professional identity formation. DESIGN: Krishna's Systematic Evidence-Based Approach (SEBA) is employed to guide this systematic scoping review of portfolio use in communication, ethics and professionalism training and assessment. DATA SOURCES: PubMed, Embase, PsycINFO, ERIC, Scopus and Google Scholar databases. ELIGIBILITY CRITERIA: Articles published between 1 January 2000 and 31 December 2020 were included. DATA EXTRACTION AND SYNTHESIS: The included articles are concurrently content and thematically analysed using the split approach. Overlapping categories and themes identified are combined using the jigsaw perspective. The themes/categories are compared with the summaries of the included articles in the funnelling process to ensure their accuracy. The domains identified form the framework for the discussion. RESULTS: 12 300 abstracts were reviewed, 946 full-text articles were evaluated and 82 articles were analysed, and the four domains identified were indications, content, design, and strengths and limitations. CONCLUSIONS: This review reveals that when using a consistent framework, accepted endpoints and outcome measures, longitudinal multisource, multimodal assessment data fashions professional and personal development and enhances identity construction. Future studies into effective assessment tools and support mechanisms are required if portfolio use is to be maximised.


Asunto(s)
Médicos , Estudiantes de Medicina , Humanos , Profesionalismo , Aprendizaje
17.
Front Public Health ; 11: 986550, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36860388

RESUMEN

Introduction: The mechanism of internet game addiction is unclear. Whether anxiety mediates between resourcefulness and internet game addiction and whether gender affect its mediation role have not been studied previously. Methods: A total of 4,889 college students from a college in southwest China were included in this study to complete the investigation, in which three questionnaires were used for evaluation. Results: Pearson's correlation analysis indicated a remarkable negative correlation between resourcefulness with internet game addiction and anxiety, as well as a significant positive correlation between anxiety and this addiction. The structural equation model confirmed the mediation role of anxiety. The multi-group analysis confirmed the moderating role of gender in the mediation model. Discussion: These findings have advanced the results of existing studies, indicating the buffering effect of resourcefulness on internet game addiction and revealing the potential mechanism of this relationship.


Asunto(s)
Ansiedad , Conducta Adictiva , Humanos , Ansiedad/epidemiología , Trastornos de Ansiedad , Conducta Adictiva/epidemiología , Estudiantes , Internet
18.
Front Oncol ; 13: 1044327, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36824127

RESUMEN

Background: Several randomized controlled trials (RCTs) have confirmed the favorable clinical benefit of pembrolizumab in advanced non-small cell lung cancer (NSCLC). However, considering the strict inclusion and exclusion criteria in clinical research, there are certain differences between patients in the real-world, it is unclear whether the findings of clinical trials are fully representative of the treatment efficacy in patients who will eventually use it. Therefore, to further comprehensively assess the efficacy and safety of pembrolizumab in NSCLC, we conducted a systematic review and meta-analysis based on the latest RCTs and real-world studies (RWSs). Methods: We systematically searched PubMed, Embase, The Cochrane Library, The Web of Science, and clinical trials.gov as of December 2021. RCTs and RWSs of patients receiving pembrolizumab monotherapy or in combination with chemotherapy for advanced NSCLC were included. Results: The meta-analysis ultimately included 11 RCTs and 26 RWSs with a total of 10,695 patients. The primary outcomes of this study were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), serious adverse events (SAEs), the incidence of severe pneumonia reactions, and drug-related mortality. Direct meta-analysis results showed that in RCTs, pembrolizumab in combination with chemotherapy was superior to chemotherapy in terms of OS (HR=0.60, 95%CI:0.50-0.73), PFS (HR=0.47, 95%CI:0.38-0.58) and ORR (OR=3.22, 95%CI:2.57-4.03); pembrolizumab monotherapy was superior to chemotherapy in terms of OS (HR=0.73, 95%CI:0.66-0.80) and ORR (OR=1.90, 95%CI:1.17-3.09), but comparable to chemotherapy in terms of PFS (HR=0.83, 95%CI:0.66-1.04). The ORR values in retrospective single-arm studies were 45% (40%-51%). Conclusion: In RCTs, pembrolizumab monotherapy or in combination with chemotherapy is more effective and safer than chemotherapy for advanced NSCLC. In RWSs, ECOG PS 0-1 was shown to correlate with PFS and OS for patients with NSCLC.

19.
Orthop Surg ; 15(4): 1179-1186, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36750671

RESUMEN

BACKGROUND: Total dislocation of the talus from all its surrounding joints (talonavicular, tibiotalar, subtalar) is one kind of serious injury of the lower extremity with rare occurrence. It is usually accompanied by fractures of the talus and its periphery, as well as severe soft tissue injury, which is difficult to reset. Complications such as skin necrosis and infection are prone to occur in the early stage, and talus necrosis are prone to occur in the late stage, all of which aggravate disease severity and increase difficulties for its treatment. CASE PRESENTATION: Herein, we reported a case of right talus total dislocation accompanied by medial malleolus fracture and posterior tubercle fracture caused by traffic accident. One hour after injury, the doctor tried to perform manual reduction but failed. Then, we successfully performed manual reduction and plaster external fixation on this patient under anesthesia 6 h after injury, followed by the oral administration of Chinese medicine for 3 months. Twenty months of follow-up investigations revealed that no skin necrosis, talus dislocation, talus necrosis, or other complications occurred; no obvious joint degeneration was observed and the fractures of medial malleolus and talus healed well. MRI of ankle joint indicated the disappearance of ankle effusion caused by injury, and the bone marrow edema had also subsided at talus, medial malleolus, and lateral malleolus and calcaneus. Patient presented with no ligament relaxation, ankle instability, pain, swelling, or functional limitation of the injured limb. AOFAS score reached 100. Daily functions and recreation activities were recovered back to the normal level. CONCLUSION: For patients with closed total dislocation of the talus, fine therapeutic effects can be achieved by early closed manual reduction and plaster external fixation under anesthesia, in combination with oral Chinese herbal medicine afterwards. It is worthy of reference for clinicians.


Asunto(s)
Fracturas de Tobillo , Luxaciones Articulares , Astrágalo , Humanos , Astrágalo/cirugía , Fijación Interna de Fracturas , Fijadores Externos , Fijación de Fractura , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/cirugía , Fracturas de Tobillo/complicaciones , Luxaciones Articulares/cirugía , Extremidad Inferior , Resultado del Tratamiento
20.
J Exp Bot ; 74(5): 1358-1371, 2023 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-36609593

RESUMEN

Aluminium (Al) toxicity is one of the major constraints for crop growth and productivity in most of the acid soils worldwide. The primary lesion of Al toxicity is the rapid inhibition of root elongation. The root apex, especially the transition zone (TZ), has been identified as the major site of Al accumulation and injury. The signalling, in particular through phytohormones in the root apex TZ in response to Al stress, has been reported to play crucial roles in the regulation of Al-induced root growth inhibition. The binding of Al in the root apoplast is the initial event leading to inhibition of root elongation. Much progress has been made during recent years in understanding the molecular functions of cell wall modification and Al resistance-related genes in Al resistance or toxicity, and several signals including phytohormones, Ca2+, etc. have been reported to be involved in these processes. Here we summarize the recent advances in the understanding of Al-induced signalling and regulatory networks in the root apex involved in the regulation of Al-induced inhibition of root growth and Al toxicity/resistance. This knowledge provides novel insights into how Al-induced signals are recognized by root apical cells, transmitted from the apoplast to symplast, and finally initiate the defence system against Al. We conclude that the apoplast plays a decisive role in sensing and transmitting the Al-induced signals into the symplast, further stimulating a series of cellular responses (e.g. exudation of organic acid anions from roots) to adapt to the stress. We expect to stimulate new research by focusing on the signalling events in the root apex in response to Al stress, particularly taking into consideration the signal transduction between the meristem zone, TZ, and elongation zone and the apoplast and symplast.


Asunto(s)
Reguladores del Crecimiento de las Plantas , Raíces de Plantas , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/metabolismo , Aluminio/toxicidad , Aluminio/metabolismo , Meristema/metabolismo , Transducción de Señal
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