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1.
Plant J ; 118(6): 1907-1921, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38491869

RESUMO

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA3, showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants.


Assuntos
Regulação da Expressão Gênica de Plantas , Giberelinas , Proteínas de Plantas , Spinacia oleracea , Flores/genética , Flores/fisiologia , Giberelinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Spinacia oleracea/genética , Spinacia oleracea/fisiologia , Spinacia oleracea/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
2.
FASEB J ; 38(11): e23717, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38837270

RESUMO

Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise function of Selenoi in the liver remains elusive. In the study, we generated hepatocyte-specific Selenoi conditional knockout (cKO) mice on a high-fat diet to identify the physiological function of Selenoi. The cKO group exhibited a significant increase in body weight, with a 15.6% and 13.7% increase in fat accumulation in white adipose tissue (WAT) and the liver, respectively. Downregulation of the lipolysis-related protein (p-Hsl) and upregulation of the adipogenesis-related protein (Fasn) were observed in the liver of cKO mice. The cKO group also showed decreased oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (p < .05). Moreover, various metabolites of the steroid hormone synthesis pathway were affected in the liver of cKO mice. A potential cascade of Selenoi-phosphatidylethanolamine-steroid hormone synthesis might serve as a core mechanism that links hepatocyte-specific Selenoi cKO to biochemical and molecular reactions. In conclusion, we revealed that Selenoi inhibits body fat accumulation and hepatic steatosis and elevates energy consumption; this protein could also be considered a therapeutic target for such related diseases.


Assuntos
Fígado Gorduroso , Hepatócitos , Camundongos Knockout , Obesidade , Animais , Camundongos , Obesidade/metabolismo , Obesidade/genética , Obesidade/etiologia , Hepatócitos/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Selenoproteínas/metabolismo , Selenoproteínas/genética , Dieta Hiperlipídica/efeitos adversos , Masculino , Fígado/metabolismo , Metabolismo Energético , Metabolismo dos Lipídeos , Camundongos Endogâmicos C57BL , Tecido Adiposo Branco/metabolismo
3.
Genes Chromosomes Cancer ; 63(7): e23258, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39011998

RESUMO

Lung cancer is the leading cause of cancer-related deaths globally. Gene fusion, a key driver of tumorigenesis, has led to the identification of numerous driver gene fusions for lung cancer diagnosis and treatment. However, previous studies focused on Western populations, leaving the possibility of unrecognized lung cancer-associated gene fusions specific to Inner Mongolia due to its unique genetic background and dietary habits. To address this, we conducted DNA sequencing analysis on tumor and adjacent nontumor tissues from 1200 individuals with lung cancer in Inner Mongolia. Our analysis established a comprehensive fusion gene landscape specific to lung cancer in Inner Mongolia, shedding light on potential region-specific molecular mechanisms underlying the disease. Compared to Western cohorts, we observed a higher occurrence of ALK and RET fusions in Inner Mongolian patients. Additionally, we discovered eight novel fusion genes in three patients: SLC34A2-EPHB1, CCT6P3-GSTP1, BARHL2-APC, HRAS-MELK, FAM134B-ERBB2, ABCB1-GIPC1, GPR98-ALK, and FAM134B-SALL1. These previously unreported fusion genes suggest potential regional specificity. Furthermore, we characterized the fusion genes' structures based on breakpoints and described their impact on major functional gene domains. Importantly, the identified novel fusion genes exhibited significant clinical and pathological relevance. Notably, patients with SLC34A2-EPHB1, CCT6P3-GSTP1, and BARHL2-APC fusions showed sensitivity to the combination of chemotherapy and immunotherapy. Patients with HRAS-MELK, FAM134B-ERBB2, and ABCB1-GIPC1 fusions showed sensitivity to chemotherapy. In summary, our study provides novel insights into the frequency, distribution, and characteristics of specific fusion genes, offering valuable guidance for the development of effective clinical treatments, particularly in Inner Mongolia.


Assuntos
Neoplasias Pulmonares , Proteínas de Fusão Oncogênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Feminino , China , Proteínas de Fusão Oncogênica/genética , Pessoa de Meia-Idade , Idoso , Adulto
4.
Artigo em Inglês | MEDLINE | ID: mdl-39119898

RESUMO

OBJECTIVES: Mechanisms of non-typhoidal Salmonella (NTS) resistance to azithromycin have rarely been reported. Here we investigate the epidemiology and genetic features of 10 azithromycin-resistant NTS isolates. METHODS: A total of 457 NTS isolates were collected from a tertiary hospital in Guangzhou. We performed antimicrobial susceptibility tests, conjugation experiments, efflux pump expression tests, whole-genome sequencing and bioinformatics analysis to conduct the study. RESULTS: The results showed that 10 NTS isolates (2.8%) were resistant to azithromycin with minimum inhibitory concentration values ranging from 128 to 512 mg/L and exhibited multidrug resistance. The phylogenetic tree revealed that 5 S. London isolates (AR1-AR5) recognized at different times and departments were closely related [3-74 single-nucleotide polymorphisms (SNPs)] and 2 S. Typhimurium isolates (AR7 and AR8) were clones (<3 SNPs) at 3-month intervals. The azithromycin resistance was conferred by mph(A) gene found on different plasmids, including IncFIB, IncHI2, InFII, IncC and IncI plasmids. Among them, IncFIB, InFII and IncHI2 plasmids carried different IS26-class 1 integron (intI1) arrangement patterns that mediated multidrug resistance transmission. Conjugative IncC plasmid encoded resistance to ciprofloxacin, ceftriaxone and azithromycin. Furthermore, phylogenetic analysis demonstrated that mph(A)-positive plasmids closely related to 10 plasmids in this study were mainly discovered from NTS, Escherichia coli, Klebsiella pneumonia and Enterobacter hormaechei. The genetic environment of mph(A) in 10 NTS isolates was IS26-mph(A)-mrx(A)-mphR(A)-IS6100/IS26 that co-arranged with intI1 harbour multidrug-resistant (MDR) gene cassettes on diverse plasmids. CONCLUSIONS: These findings highlighted that the dissemination of these plasmids carrying mph(A) and various intI1 MDR gene cassettes would seriously restrict the availability of essential antimicrobial agents for treating NTS infections.

5.
J Med Virol ; 96(1): e29348, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180275

RESUMO

Ground glass hepatocytes (GGHs) have been associated with hepatocellular carcinoma (HCC) recurrence and poor prognosis. We previously demonstrated that pre-S expression in some GGHs is resistant to current hepatitis B virus (HBV) antiviral therapies. This study aimed to investigate whether integrated HBV DNA (iDNA) is the primary HBV DNA species responsible for sustained pre-S expression in GGH after effective antiviral therapy. We characterized 10 sets of micro-dissected, formalin-fixed-paraffin-embedded, and frozen GGH, HCC, and adjacent hepatitis B surface antigen-negative stained tissues for iDNA, pre-S deletions, and the quantity of covalently closed circular DNA. Eight patients had detectable pre-S deletions, and nine had detectable iDNA. Interestingly, eight patients had integrations within the TERT and CCNE1 genes, which are known recurrent integration sites associated with HCC. Furthermore, we observed a recurrent integration in the ABCC13 gene. Additionally, we identified variations in the type and quantity of pre-S deletions within individual sets of tissues by junction-specific PacBio long-read sequencing. The data from long-read sequencing indicate that some pre-S deletions were acquired following the integration events. Our findings demonstrate that iDNA exists in GGH and can be responsible for sustained pre-S expression in GGH after effective antiviral therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Vírus da Hepatite B/genética , DNA Viral/genética , Neoplasias Hepáticas/genética , Hepatócitos , Mutação , Antivirais/uso terapêutico
6.
Ann Hematol ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105740

RESUMO

Chronic neutrophil leukemia (CNL) is a rare and life-threatening disease. Cases of CNL combined with lymphoma are rare. Here, we report a case of CNL with T-acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) in a 28-year-old male. After a regimen of ruxolitinib, VICLP (Vincristine, Idarubicin, Cyclophosphamide, Prednisone, Peg-asparaginase) regimen, high-dose cytarabine, and methotrexate regimens, the patient's bone marrow condition partially resolved. However, when the disease relapsed four months later, despite attempts with selinexor, venetoclax, and CAG(aclarubicin hydrochloride, Algocytidine, Granulocyte Stimulating Factor) chemotherapy, the leukocytes and peripheral blood primitive cells reduced, but the bone marrow did not achieve remission. This pathogenesis may be related to microenvironmental immune escape under prolonged inflammatory stimulation and gene disruption affecting protein function due to colony-stimulating factor 3 receptor gene (CSF3R) mutations. For this type of disease, early intervention may delay disease progression.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38940077

RESUMO

BACKGROUND: Cognitive-behavioral therapy (CBT) is an evidence-supported treatment for adolescents with binge-eating disorder (BED). Executive dysfunctions, which are associated with binge eating and elevated body weight in youth, may undermine CBT outcomes by making it difficult for youth to engage with or adhere to treatment, including recalling and/or implementing intervention strategies in real-world contexts. METHODS: We assessed 73 adolescents [82.2% female; Mage = 15.0 ± 2.5 year; M baseline standardized body mass index (zBMI) = 1.9 ± 1.0 kg/m2] with BED at baseline, posttreatment, 6-, 12-, and 24-month follow-up. Linear mixed models examined the effects of baseline executive functioning (EF) on loss of control (LOC) eating and weight change following CBT. Linear and logistic regressions probed associations between EF, attendance, and attrition. RESULTS: More impulsive decision-making, as reflected in higher baseline scores on the Iowa Gambling Task, predicted better attendance (ß = .07; p = .019) and more frequent LOC eating following treatment (ß = .12; p = .017). Lower cognitive flexibility, as reflected in lower baseline T-scores on the Comprehensive Trail Making Test complex sequencing index, predicted higher zBMI following treatment (ß = -.03; p = .003). Inhibition, concentration, attention, and parent-reported EF behavior symptoms were not associated with outcome, attendance, or attrition. CONCLUSIONS: More impulsive decision-making and lower cognitive flexibility were associated with suboptimal response to CBT for BED, although findings should be interpreted with caution in light of the sample size and waitlist control design. Future research should examine whether strengthening EF could improve eating and weight outcomes among adolescents with BED who have lower pre-treatment EF.

8.
Inorg Chem ; 63(2): 1388-1394, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38166363

RESUMO

By variation of the amount of GeO2, two organic-inorganic hybrid germanoniobate frameworks with 6-connected pcu and 10-connected bct topologies were constructed from peanut-shaped {α-Ge12Nb38} and {ß-Ge12Nb38} clusters, respectively. The {α-Ge12Nb38} and {ß-Ge12Nb38} clusters contain the most Ge centers of germanoniobates reported so far. The compounds exhibit proton conduction properties with a conductivity of 3.04 × 10-4 S·cm-3 for 1 and 1.62 × 10-4 S·cm-3 for 2 at 85 °C and 98% RH. The water vapor adsorption capacities for 1 and 2 are 5.86 and 4.40 mmol·g-1, respectively.

9.
Med Sci Monit ; 30: e942509, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561932

RESUMO

BACKGROUND Diabetic peripheral neuropathy (DPN) is a prevalent complication affecting over 60% of type 2 diabetes patients. Early diagnosis is challenging, leading to irreversible impacts on quality of life. This study explores the predictive value of combining HbA1c and Neutrophil-to-Lymphocyte Ratio (NLR) for early DPN detection. MATERIAL AND METHODS An observational study was conducted at the First People's Hospital of Linping District, Hangzhou spanning from May 2019 to July 2020. Data on sex, age, biochemical measurements were collected from electronic medical records and analyzed. Employing multivariate logistic regression analysis, we sought to comprehend the factors influencing the development of DPN. To assess the predictive value of individual and combined testing for DPN, a receiver operating characteristic (ROC) curve was plotted. The data analysis was executed using R software (Version: 4.1.0). RESULTS The univariate and multivariate logistic regression analysis identified the level of glycated hemoglobin (HbA1C) (OR=1.94, 95% CI: 1.27-3.14) and neutrophil-to-lymphocyte ratio (NLR) (OR=4.60, 95% CI: 1.15-22.62, P=0.04) as significant risk factors for the development of DPN. Receiver operating characteristic (ROC) curve analysis demonstrated that HbA1c, NLR, and their combined detection exhibited high sensitivity in predicting the development of DPN (71.60%, 90.00%, and 97.2%, respectively), with moderate specificity (63.8%, 45.00%, and 50.00%, respectively). The area under the curve (AUC) for these predictors was 0.703, 0.661, and 0.733, respectively. CONCLUSIONS HbA1c and NLR emerge as noteworthy risk indicators associated with the manifestation of DPN in patients with type 2 diabetes. The combined detection of HbA1c and NLR exhibits a heightened predictive value for the development of DPN.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/etiologia , Hemoglobinas Glicadas , Linfócitos , Neutrófilos , Qualidade de Vida , Curva ROC , Masculino , Feminino
10.
BMC Pediatr ; 24(1): 390, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858617

RESUMO

BACKGROUND: Oculocutaneous albinism (OCA) is a group of autosomal recessive hereditary disorders that affect melanin biosynthesis, resulting in abnormalities in hair, skin, and eyes. Retinopathy of prematurity (ROP) is a proliferative retinopathy mainly observed in premature infants with low birth weight and early gestational age, but it can also affect full-term infants or children with normal weight, particularly in developing countries. The coexistence of ROP and OCA is rare. There is limited documentation regarding treatment approaches, with few studies reporting positive outcomes with laser treatment due to the absence of melanin pigment. This study discusses the treatment challenges in a female infant diagnosed with ROP and OCA, and underscores the importance of genetic analysis in guiding therapeutic decisions for this rare comorbid condition. CASE PRESENTATION: The study presents a case of ROP occurring concurrently with OCA. Genetic testing revealed two variants, c.727C > T (p.R243C) and c.1832 T > C (p.L611P), in the OCA2 gene, inherited from the patient's mother and father, respectively. The identified mutations were consistent with a diagnosis of OCA2, classified as a subtype of OCA. The patient initially received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection, followed by laser photocoagulation therapy for a recurrent event. A favorable outcome was observed during the 2-month follow-up period. CONCLUSIONS: The co-occurrence of ROP and OCA is a rare phenomenon, and this is the first recorded case in the Chinese population. The current case supports the use of laser as the primary treatment modality for ROP in OCA2 patients with partial pigmentation impairment. Furthermore, genetic analysis can aid in predicting the effectiveness of laser photocoagulation in this patient population.


Assuntos
Albinismo Oculocutâneo , Retinopatia da Prematuridade , Humanos , Feminino , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/complicações , Albinismo Oculocutâneo/terapia , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/terapia , Retinopatia da Prematuridade/complicações , Recém-Nascido , Proteínas de Membrana Transportadoras/genética , Mutação , Inibidores da Angiogênese/uso terapêutico , Fotocoagulação a Laser , Bevacizumab/uso terapêutico
11.
Biochem Genet ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658494

RESUMO

Long non-coding RNAs (lncRNAs), as promising novel biomarkers for cancer treatment and prognosis, can function as tumor suppressors and oncogenes in the occurrence and development of many types of cancer, including gastric cancer (GC). However, little is known about the complex regulatory system of lncRNAs in GC. In this study, we systematically analyzed lncRNA and miRNA transcriptomic profiles of GC based on bioinformatics methods and experimental validation. An lncRNA-miRNA interaction network related to GC was constructed, and the nine crucial lncRNAs were identified. These 9 lncRNAs were found to be associated with the prognosis of GC patients by Cox proportional hazards regression analysis. Among them, the expression of lncRNA SNHG14 can affect the survival of GC patients as a potential prognostic marker. Moreover, it was shown that SNHG14 was involved in immune-related pathways and significantly correlated with immune cell infiltration in GC. Meanwhile, we found that SNHG14 affected immune function in many cancers, such as breast cancer and esophageal carcinoma. Such information revealed that SNHG14 may serve as a potential target for cancer immunotherapy. As well, our study could provide practical and theoretical guiding significance for clinical application of non-coding RNAs.

12.
Mikrochim Acta ; 191(5): 281, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38649632

RESUMO

Two chiral covalent organic frameworks (CCOFs) core-shell microspheres based on achiral organic precursors by chiral-induced synthesis strategy for HPLC enantioseparation are reported for the first time. Using n-hexane/isopropanol as mobile phase, various kinds of racemates were selected as analytes and separated on the CCOF-TpPa-1@SiO2 and CCOF-TpBD@SiO2-packed columns with a low column backpressure (3 ~ 9 bar). The fabricated two CCOFs@SiO2 chiral columns exhibited good separation performance towards various racemates with high column efficiency (e.g., 19,500 plates m-1 for (4-fluorophenyl)ethanol and 18,900 plates m-1 for 1-(4-chlorophenyl)ethanol) and good reproducibility. Some effects have been investigated such as the analyte mass and column temperature on the HPLC enantioseparation. Moreover, the chiral separation results of the CCOF-TpPa-1@SiO2 chiral column and the commercialized Chiralpak AD-H column show a good complementarity. This study demonstrates that the usage of chiral-induced synthesis strategy for preparing CCOFs core-shell microspheres as a novel stationary phase has a good application potential in HPLC.

13.
Mikrochim Acta ; 191(8): 445, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958767

RESUMO

A novel CCOF core-shell composite material (S)-DTP-COF@SiO2 was prepared via asymmetric catalytic and in situ growth strategy. The prepared (S)-DTP-COF@SiO2 was utilized as separation medium for HPLC enantioseparation using normal-phase and reversed-phase chromatographic modes, which displays excellent chiral separation performance for alcohols, esters, ketones, and epoxides, etc. Compared with chiral commercial chromatographic columns (Chiralpak AD-H and Chiralcel OD-H columns) and some previously reported chiral CCOF@SiO2 (CC-MP CCTF@SiO2 and MDI-ß-CD-modified COF@SiO2)-packed columns, there are 4, 3, 13, and 15 tested racemic compounds that could not be resolved on the Chiralpak AD-H column, Chiralcel OD-H column, CC-MP CCTF@SiO2 column, and MDI-ß-CD-modified COF@SiO2 column, respectively, which indicates that the resolution effect of (S)-DTP-COF@SiO2-packed column can be complementary to the other ones. The effects of the analyte mass, column temperature, and mobile phase composition on the enantiomeric separation were investigated. The chiral column exhibits good reproducibility after multiple consecutive injections. The RSDs (n = 5) of the peak area and retention time were less than 1.5% for repetitive separation of 2-methoxy-2-phenylethanol and 1-phenyl-1-pentanol. The chiral core-shell composite (S)-DTP-COF@SiO2 exhibited good enantiomeric separation performance, which not only demonstrates its potential as a novel CSP material in HPLC but also expands the range of applications for chiral COFs.

14.
BMC Med Educ ; 24(1): 705, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943116

RESUMO

BACKGROUND: Entrustable Professional Activities (EPA)-based assessment is easily and intuitively used in evaluating the learning outcomes of competency-based medical education (CBME). This study aimed to develop an EPA for occupational therapy focused on providing health education and consultation (TP-EPA3) and examine its validity. METHODS: Nineteen occupational therapists who had completed online training on the EQual rubric evaluation participated in this study. An expert committee identified six core EPAs for pediatric occupational therapy. TP-EPA3 was developed following the EPA template and refined through consensus meetings. The EQual rubric, a 14-item, five-point criterion-based anchor system, encompassing discrete units of work (DU), entrustable, essential, and important tasks of the profession (EEIT), and curricular role (CR), was used to evaluate the quality of TP-EPA3. Overall scores below 4.07, or scores for DU, EEIT, and CR domains below 4.17. 4.00, and 4.00, respectively, indicate the need for modifications. RESULTS: The TP-EPA3 demonstrated good validity, surpassing the required cut-off score with an average overall EQual score of 4.21 (SD = 0.41). Specific domain scores for DU, EEIT, and CR were 3.90 (SD = 0.69), 4.46 (SD = 0.44), and 4.42 (SD = 0.45), respectively. Subsequent revisions clarified observation contexts, enhancing specificity and focus. Further validation of the revised TP-EPA3 and a thorough examination of its reliability and validity are needed. CONCLUSION: The successful validation of TP-EPA3 suggests its potential as a valid assessment tool in occupational therapy education, offering a structured approach for developing competency in providing health education and consultation. This process model for EPA development and validation can guide occupational therapists in creating tailored EPAs for diverse specialties and settings.


Assuntos
Competência Clínica , Educação Baseada em Competências , Terapia Ocupacional , Humanos , Terapia Ocupacional/educação , Competência Clínica/normas , Reprodutibilidade dos Testes , Avaliação Educacional , Educação em Saúde , Encaminhamento e Consulta/normas , Currículo , Masculino , Feminino
15.
J Clin Ultrasound ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38813899

RESUMO

We present a case study detailing the occurrence of splenic lymphangioma in a 9-year-old girl. The multimodal imaging revealed a significant mass, a finding subsequently validated through histopathological examination. This case underscores the importance of considering splenic lymphangioma as a rare but notable differential diagnosis for solid masses observed in imaging studies.

16.
J Therm Biol ; 120: 103823, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38442663

RESUMO

OBJECTIVES: Although cold stress-induced damage to the heart and thyroid has been reported, specific organ associations between the heart and thyroid with delayed injury mechanisms have not been investigated. In this study, we determined the damage time and transcript levels of a large number of genes in the heart and thyroid after cold exposure. Meanwhile, we analysed the relationship between heart and thyroid injury in human medical records to determine the association of delayed injury from cold exposure. METHODS: Mice were exposed to cold stress and hysteresis injury. Gene changes at the transcriptional level were detected using high throughput sequencing technology. The most variable genes were verified at the protein level using Western Blotting and medical records were collected and analysed. RESULTS: The damage was the most severe when the animals were allowed to recover to room temperature for 4 h after exposure to cold stress. During this process, STAT1 and ATF3 genes were acutely up-regulated. Analysis of human medical records showed the highest correlation between AST and T4 under cold stress (p = 0.0011). CONCLUSIONS: Exposure to cold increases blood level of free thyroid hormone and biomarkers of myocardial injury, as well as related mRNA levels. These changes were more pronounced after return to room temperature.


Assuntos
Glândula Tireoide , Hormônios Tireóideos , Camundongos , Animais , Humanos , Temperatura Baixa , Resposta ao Choque Frio
17.
Molecules ; 29(4)2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38398632

RESUMO

The major histocompatibility complex (MHC) can recognize and bind to external peptides to generate effective immune responses by presenting the peptides to T cells. Therefore, understanding the binding modes of peptide-MHC complexes (pMHC) and predicting the binding affinity of pMHCs play a crucial role in the rational design of peptide vaccines. In this study, we employed molecular dynamics (MD) simulations and free energy calculations with an Alanine Scanning with Generalized Born and Interaction Entropy (ASGBIE) method to investigate the protein-peptide interaction between HLA-A*02:01 and the G9209 peptide derived from the melanoma antigen gp100. The energy contribution of individual residue was calculated using alanine scanning, and hotspots on both the MHC and the peptides were identified. Our study shows that the pMHC binding is dominated by the van der Waals interactions. Furthermore, we optimized the ASGBIE method, achieving a Pearson correlation coefficient of 0.91 between predicted and experimental binding affinity for mutated antigens. This represents a significant improvement over the conventional MM/GBSA method, which yields a Pearson correlation coefficient of 0.22. The computational protocol developed in this study can be applied to the computational screening of antigens for the MHC1 as well as other protein-peptide binding systems.


Assuntos
Peptídeos , Proteínas , Peptídeos/química , Proteínas/metabolismo , Ligação Proteica , Complexo Principal de Histocompatibilidade , Antígenos de Histocompatibilidade/metabolismo , Alanina/metabolismo
18.
J Community Health Nurs ; : 1-9, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38909288

RESUMO

We aimed to analyze the effects of exclusive breastfeeding duration on the occurrence and course of pneumonia in infants aged up to 6 months. Prospective case-control study. This study was conducted from August 2020 to August 2022 at a maternity and child health hospital in China. A total of 218 infants up to 6 months of age with pneumonia were included in the analyses. Health data were obtained using a hospitalization information system or an interview-based questionnaire. Univariate and multivariate logistic regression analyses were performed to analyze the data. The incidence of pneumonia, hospitalization duration, and costs to participants were significantly affected by the duration of exclusive breastfeeding (p < 0.01). The incidence of pneumonia among participants with different exclusive breastfeeding durations also differed significantly (p < 0.01). The shorter the duration of exclusive breastfeeding, the higher the incidence of pneumonia among infants. We found that the longer the exclusive breastfeeding duration in infants up to 6 months of age, the lower the recurrence of pneumonia, the shorter the hospital stay, and the lower the hospital costs. The rate of exclusive breastfeeding for infants up to 6 months of age should be increased as much as possible to reduce the occurrence of pneumonia and hospital costs.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38639112

RESUMO

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure. Methods Thirty patients undergoing cardiac transcatheter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to compare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and muscle ARNT-1 like protein-1(BMAL1),cryptochrome 1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score before and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery. Results The postoperative mRNA level of CLOCK was higher [1.38±1.23 vs.1.90±1.47;MD(95%CI):0.52(0.20-0.84),t=3.327,P=0.002] and the postoperative mRNA levels of CRY1 [1.56±1.50 vs.1.13±0.98;MD(95%CI):-0.43(-0.81--0.05),t=-2.319,P=0.028] and PER2 [0.82±0.63 vs.0.50±0.31;MD(95%CI):-0.33(-0.53--0.12),t=-3.202,P=0.003] were lower than the preoperative levels.One week after surgery,the patients presented advanced sleep chronotype [3∶03±0∶59 vs.2∶42±0∶37;MD(95%CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency [(67±64)min vs.(37±21)min;MD(95%CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration [(436±83)min vs.(499±83)min;MD(95%CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency [(87.59±10.35)% vs.(92.98±4.27)%;MD(95%CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score [1.13±0.78 vs.0.80±0.71;MD(95%CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score [6.60±3.17 vs.4.03±2.58;MD(95%CI):-2.57(-3.87--1.27),t=-4.039,P<0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery. Conclusions Total intravenous anesthesia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

20.
Front Sports Act Living ; 6: 1331586, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500549

RESUMO

Background: Psychiatric disorders (PD) pose a significant burden, with vast prevalence and mortality, inflicting substantial costs on individuals and society. Despite its widespread prevalence, the complex pathogenesis of PD remains elusive, leading to limited and challenging therapeutic development. An emerging risk factor for chronic diseases, prolonged sedentary behavior, contrasts with the therapeutic potential of exercise, regardless of its intensity, for various ailments, including PD. Yet, the diversity in exercise modalities and intensities may offer varied impacts on health. This study, leveraging Mendelian Randomization (MR), seeks to investigate the causal relationship between exercise and PD, aiming to elucidate the optimal exercise modality and intensity for PD mitigation while addressing potential confounders. Methods: This study employed a Mendelian randomization analysis using the genome-wide association study (GWAS) database to investigate the causal relationship between types of physical activity and psychiatric disorders. Sensitivity analysis was conducted to demonstrate the reliability and robustness of the results. Results: In the past 4 weeks, engaging in a substantial amount of DIY physical activity was found to have a causal relationship with psychiatric disorders (IVW: OR = 0.228, 95% CI: 0.113-0.461, P = 0.000038). As for the types of exercises, there may be a potential causal association between aerobic training (including swimming, cycling, fitness, and bowling) and psychiatric disorders (IVW: OR = 0.322, 95% CI = 0.148-0.704, P = 0.004). However, there was no causal relationship found between mild DIY physical activity and psychiatric disorders (IVW: OR = 0.918, 95% CI = 0.417-2.021, P = 0.831). Furthermore, it seems that there is no causal relationship between vigorous exercise and psychiatric disorders (IVW: OR = 2.705, 95% CI = 0.081-3.419, P = 0.578). Conclusion: Our study confirms that only a certain level of training activity can have a protective effect on psychiatric disorders, while mild physical activity or vigorous training does not have an impact on psychiatric disorders.

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