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Alzheimer's disease is neurodegenerative and characterized by progressive cognitive impairment. Synaptic dysfunction appears in the early stage of Alzheimer's disease and is significantly correlated with cognitive impairment. However, the specific regulatory mechanism remains unclear. Here, we found the transcription factor Maf1 to be upregulated in Alzheimer's disease and determined that conditional knockout of Maf1 in a transgenic mouse model of Alzheimer's disease restored learning and memory function; the downregulation of Maf1 reduced the intraneuronal calcium concentration and restored neuronal synaptic morphology. We also demonstrated that Maf1 regulated the expression of NMDAR1 by binding to the promoter region of Grin1, further regulating calcium homeostasis and synaptic remodelling in neurons. Our results clarify the important role and mechanism of the Maf1-NMDAR1 signalling pathway in stabilizing synaptic structure, neuronal function and behaviour during Alzheimer's disease pathogenesis. This therefore serves as a potential diagnostic and therapeutic target for the early stage of Alzheimer's disease.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Ratones Transgénicos , Anciano , Animales , Femenino , Humanos , Masculino , Ratones , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Disfunción Cognitiva/genética , Disfunción Cognitiva/metabolismo , Espinas Dendríticas/metabolismo , Espinas Dendríticas/patología , Modelos Animales de Enfermedad , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Proteínas Represoras/genética , Proteínas Represoras/metabolismoRESUMEN
Breast cancer (BC) is one of the most common malignant tumors in women and still poses a significant threat to women worldwide. Recurrence of BC in situ, metastasis to distant organs, and resistance to chemotherapy are all attached to high mortality in patients with BC. Non-coding RNA (ncRNA) of the type known as "circRNA" links together from one end to another to create a covalently closed, single-stranded circular molecule. With characteristics including plurality, evolutionary conservation, stability, and particularity, they are extensively prevalent in various species and a range of human cells. CircRNAs are new and significant contributors to several kinds of disorders, including cardiovascular disease, multiple organ inflammatory responses and malignancies. Recent studies have shown that circRNAs play crucial roles in the occurrence of breast cancer by interacting with miRNAs to regulate gene expression at the transcriptional or post-transcriptional levels. CircRNAs offer the potential to be therapeutic targets for breast cancer treatment as well as prospective biomarkers for early diagnosis and prognosis of BC. Here, we are about to present an overview of the functions of circRNAs in the proliferation, invasion, migration, and resistance to medicines of breast cancer cells and serve as a promising resource for future investigations on the pathogenesis and therapeutic strategies.
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Neoplasias de la Mama , MicroARNs , Humanos , Femenino , ARN Circular/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , MicroARNs/genética , BiomarcadoresRESUMEN
Sarcopenia is a complex age-associated syndrome of progressive loss of muscle mass and strength. Although this condition is influenced by many factors, age-related changes in immune function including immune cell dynamics, and chronic inflammation contribute to its progression. The complex interplay between the immune system, gut-muscle axis, and autophagy further underscores their important roles in sarcopenia pathogenesis. Immunomodulation has emerged as a promising strategy to counteract sarcopenia. Traditional management approaches to treat sarcopenia including physical exercise and nutritional supplementation, and the emerging technologies of biophysical stimulation demonstrated the importance of immunomodulation and regulation of macrophages and T cells and reduction of chronic inflammation. Treatments to alleviate low-grade inflammation in older adults by modulating gut microbial composition and diversity further combat sarcopenia. Furthermore, some pharmacological interventions, nano-medicine, and cell therapies targeting muscle, gut microbiota, or autophagy present additional avenues for immunomodulation in sarcopenia. This narrative review explores the immunological underpinnings of sarcopenia, elucidating the relationship between the immune system and muscle during ageing. Additionally, the review discusses new areas such as the gut-muscle axis and autophagy, which bridge immune system function and muscle health. Insights into current and potential approaches for sarcopenia management through modulation of the immune system are provided, along with suggestions for future research directions and therapeutic strategies. We aim to guide further investigation into clinical immunological biomarkers and identify indicators for sarcopenia diagnosis and potential treatment targets to combat this condition. We also aim to draw attention to the importance of considering immunomodulation in the clinical management of sarcopenia.
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PURPOSE: As a minimally invasive procedure, laser hemorrhoidoplasty (LHP) can not only relieve the symptoms of hemorrhoids, but also protect the anal cushion structure. This study aimed to investigate the clinical efficacy of LHP in the treatment of grade II hemorrhoids. METHODS: A total of 70 patients with grade II hemorrhoids were randomly assigned to receive LHP or Rubber Band Ligation (RBL) (n = 35 per group) in 2019 from a single center. The postoperative pain, bleeding, feeling of anal distension(local falling, swelling, foreign body sensation, stool) and postoperative recurrence rate were compared between the two groups. RESULTS: The postoperative pain, bleeding, and feeling of anal distension in the LHP group were improved significantly as compared with the RBL group within 2 weeks after surgery (P < 0.01). Both methods can relieve the symptoms of grade II hemorrhoids. There was no difference in the recurrence rate between the two groups at 1 year after surgery (P > 0.05). The patients in LHP group took less time to return to normal activities (P < 0.001). CONCLUSIONS: As a minimally invasive treatment, LHP is easy and not traumatic and results in mild postoperative pain and few complications. It is an ideal choice for grade II hemorrhoids.
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Hemorreoidectomía , Hemorroides , Terapia por Láser , Humanos , Hemorroides/cirugía , Masculino , Ligadura/métodos , Femenino , Persona de Mediana Edad , Hemorreoidectomía/métodos , Adulto , Terapia por Láser/métodos , Resultado del Tratamiento , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnóstico , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , RecurrenciaRESUMEN
BACKGROUND: Surgical site infection (SSI) remains a critical postoperative complication after total hip and knee arthroplasty (THA and TKA). Frailty, a condition characterized by decreased physiological reserve and increased vulnerability to stressors, may influence the risk of SSI in these patients. This meta-analysis aims to evaluate the association between frailty and the incidence of SSI following THA or TKA. METHODS: A systematic search of databases including PubMed, EMBASE, Web of Science, Wanfang, and CNKI was conducted to identify relevant studies. Data were extracted and pooled using a random-effects model to calculate the overall risk ratio (RR) and 95 % confidence intervals (CIs). RESULTS: A total of ten studies comprising 1,036,787 patients met the inclusion criteria. The meta-analysis revealed that frail patients undergoing THA or TKA had a significantly higher risk of developing SSI compared to non-frail patients (RR = 1.64, 95 % CI: 1.39-1.93, p < 0.001, I2 = 66 %). Subgroup analyses indicated that the type of arthroplasty (hip vs. knee) and the method of frailty assessment did not significantly alter the association. Further subgroup analysis suggested that frailty was significantly associated with a higher incidence of deep SSI including joint infection (RR = 1.77, 95 % CI: 1.27-1.48, p < 0.001), but not the incidence of superficial SSI (RR = 1.57, 95 % CI: 0.45-5.42, p = 0.48). The association between frailty and SSI remains in subgroup of multivariate studies only (RR = 1.56, 95 % CI: 1.34 to 1.80, p < 0.001). CONCLUSIONS: Frailty is a potential predictor of SSI following TKA/THA.
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N95 respirators are the core equipment used by healthcare workers to prevent the spread of respiratory diseases. The protective effect of N95 against infection spread depends on the fit of the N95 to the wearer, which is related to the wearer's facial dimensions. The purpose of this cross-sectional study was to assess the relationship between the fit of three types of N95 and facial dimensions. A total of 305 healthcare workers from ten hospitals in Beijing were recruited for this study. Facial dimensions of workers were measured using Intel RealSense Depth Camera D435. Fit testing was conducted on three types of N95 using the TSI-8038 Porta Count Pro + Respirator Fit Tester. Possible associations between the fit test results and facial dimension data were examined. A Porta Count reading of 100 was used as the criterion for an acceptable fit. The fit of the folding respirators was positively correlated with nose length (r = 0.13, p = 0.02), nose height (r = 0.14, p = 0.02), and face width (r = 0.12, p = 0.03), whereas that of flat respirators was correlated with nose width (r = 0.16, p < 0.01), chin length (r = 0.18, p < 0.01), and pro-face width (r = 0.13, p = 0.02), and that of arched respirators was correlated with the nose length (r = 0.13, p = 0.03). The fit of N95 for wearers depends on their facial features. The results of this study can provide advice for medical workers to choose the appropriate N95. Medical staff should fully consider their facial dimensions when choosing an appropriate N95 to improve the protective efficacy of respirators and to reduce the risk of infection by respiratory diseases.
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Cara , Respiradores N95 , Humanos , Cara/anatomía & histología , Adulto , Masculino , Estudios Transversales , Femenino , Persona de Mediana Edad , Personal de Salud , Diseño de Equipo , Beijing , Dispositivos de Protección Respiratoria/normas , Exposición Profesional/prevención & controlRESUMEN
This study investigated the mechanism of Gegen Qinlian Decoction(GQD) in improving glucose metabolism in vitro and in vivo by alleviating endoplasmic reticulum stress(ERS). Molecular docking was used to predict the binding affinity between the main effective plasma components of GQD and ERS-related targets. Liver tissue samples were obtained from normal rats, high-fat-induced diabetic rats, rats treated with metformin, and rats treated with GQD. RNA and protein were extracted. qPCR was used to measure the mRNA expression of ERS marker glucose-regulated protein 78(GRP78), and unfolded protein response(UPR) genes inositol requiring enzyme 1(Ire1), activating transcription factor 6(Atf6), Atf4, C/EBP-homologous protein(Chop), and caspase-12. Western blot was used to detect the protein expression of GRP78, IRE1, protein kinase R-like ER kinase(PERK), ATF6, X-box binding protein 1(XBP1), ATF4, CHOP, caspase-12, caspase-9, and caspase-3. The calcium ion content in liver tissues was determined by the colorimetric assay. The ERS-HepG2 cell model was established in vitro by inducing with tunicamycin for 6 hours, and 2.5%, 5%, and 10% GQD-containing serum were administered for 9 hours. The glucose oxidase method was used to measure extracellular glucose levels, flow cytometry to detect cell apoptosis, glycogen staining to measure cellular glycogen content, and immunofluorescence to detect the expression of GRP78. The intracellular calcium ion content was measured by the colorimetric assay. Whereas Western blot was used to detect GRP78 and ERS-induced IRE1, PERK, ATF6, and eukaryotic translation initiation factor 2α(eIF2α) phosphorylation. Additionally, the phosphorylation levels of insulin receptor substrate 1(IRS1), phosphatidylinositol 3-kinase regulatory subunit p85(PI3Kp85), and protein kinase B(Akt), which were involved in the insulin signaling pathway, were also measured. In addition, the phosphorylation levels of c-Jun N-terminal kinases(JNKs), which were involved in both the ERS and insulin signaling pathways, were measured by Western blot. Molecular docking results showed that GRP78, IRE1, PERK, ATF4, and various compounds such as baicalein, berberine, daidzein, jateorhizine, liquiritin, palmatine, puerarin and wogonoside had strong binding affinities, indicating that GQD might interfere with ERS-induced UPR. In vivo results showed that GQD down-regulated the mRNA transcription of Ire1, Atf6, Atf4, Grp78, caspase-12, and Chop in diabetic rats, and down-regulated GRP78, IRE1, PERK, as well as ERS-induced apoptotic factors ATF4 and CHOP, caspase-12, caspase-9, and caspase-3, while up-regulating XBP1 to enhance adaptive UPR. In addition, GQD increased the calcium ion content in liver tissues, which facilitated correct protein folding. In vitro results showed that GQD increased glucose consumption in ERS-induced HepG2 cells without significantly affecting cell viability, increased liver glycogen synthesis, down-regulated ATF6 and p-eIF2α(Ser51), and down-regulated IRE1, PERK, and GRP78, as well as p-IRS1(Ser312) and p-JNKs(Thr183/Tyr185), while up-regulating p-PI3Kp85(Tyr607) and p-Akt(Ser473). These findings suggested that GQD alleviates excessive ERS in the liver, reduces insulin resistance, and improves hepatic glucose metabolism in vivo and in vitro.
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Diabetes Mellitus Experimental , Proteínas Proto-Oncogénicas c-akt , Ratas , Animales , Chaperón BiP del Retículo Endoplásmico , Caspasa 3 , Caspasa 9 , Caspasa 12 , Calcio/farmacología , Simulación del Acoplamiento Molecular , Estrés del Retículo Endoplásmico , Proteínas Serina-Treonina Quinasas/genética , Hígado , Apoptosis , Insulina , Glucosa , Glucógeno/farmacología , ARN MensajeroRESUMEN
Workers' compensation insurance, which provides no-fault coverage for work-related injuries, is mandatory in nearly all states. We use administrative data from a unique market without a coverage mandate to estimate the demand for workers' compensation insurance, leveraging regulatory premium updates for identification. We find that a 1 percent increase in premiums leads to approximately a 0.3 percent decline in coverage. Drawing upon these estimates and data on costs, we examine potential justifications for government intervention to increase coverage. This analysis suggests that several forms of market failure-such as adverse selection, market power, and externalities-may not justify a mandate in this setting.
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Rosacea is a chronic and recurrent inflammatory skin disease affecting the center of the face that causes burning and itching sensations and changes in aesthetics. Liang Xue Wu Hua Tang (LXWHT) is a classic herbal formulation that is efficacious and has been widely used in the clinical treatment of rosacea; however, the pharmacological mechanisms remain unclear. The aim of the present study was to investigate the mechanism of action of LXWHT using network pharmacology and molecular docking. The Traditional Chinese Medicine System Pharmacology database was searched to identify the active ingredients and pharmacological targets of LXWHT, and the GeneCard, Disgenet, and Gene Expression Omnibus databases were applied to screen rosacea-related targets. Cytoscape software was used to visualize the protein-protein interaction network, and network topology analysis was used to identify core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for the core targets. Molecular docking simulations and visualization were performed using Maestro and PyMOL, respectively. A total of 43 active compounds and 28 potential targets for LXWHT treatment of rosacea were selected for analysis. The Gene Ontology/Kyoto Encyclopedia of Genes and Genomes results indicated that LXWHT may exert therapeutic effects on rosacea by intervening in immune pathways including tumor necrosis factor pathway, interleukin-17 pathways, and Toll-like receptor signaling pathways. Chemokine ligand 2, interferon-γ, interleukin-1ß, peroxisome proliferator-activated receptor-γ, and matrix metallopeptidase 9 may be the core therapeutic target. Quercetin, stigmasterol, kaempferol, beta-sitosterol, luteolin, beta-carotene, baicalein, acetin, and isorhamnetin were predicted to be the key active ingredients. LXWHT may exert therapeutic effects in the treatment of rosacea by modulating immunity and angiogenesis, laying the foundation for further research.
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Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Farmacología en Red , Rosácea , Rosácea/tratamiento farmacológico , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Mapas de Interacción de Proteínas/efectos de los fármacos , Medicina Tradicional China/métodosRESUMEN
Introduction: The current study aimed to compare the outcomes of endoscopic and minimally invasive surgical treatment for infected necrotizing pancreatitis. Material and methods: A meta-analysis of clinical studies on minimally invasive operations for necrotic infection was conducted. A systematic review and study inclusion were done on multiple databases. English-language prospective comparison studies were included. Random design was used to analyze research with continuous and dichotomous variables. Results: Ten studies were included in the current study. When compared to minimally invasive surgery, endoscopic procedures showed significant beneficial outcomes regarding low post-operative complication rates (p = 0.006), new onset organ failure (p < 0.001), and pancreatic fistula (p < 0.001). However, there was no significant difference between the two interventions regarding hospital stay, postoperative bleeding, incisional hernia, endocrine insufficiency, and perforation of a visceral organ. Conclusions: Endoscopic therapy appears to have potential advantages over minimally invasive surgery. However, there is no difference between interventions regarding several parameters.
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To investigate the infection status of coronavirus disease 2019 (COVID-19) among people in Anhui Province, China after the epidemic prevention and control measures were lifted, and to study and analyze its related influencing factors. From March 11 to May 20, 2023, questionnaires on COVID-19 were distributed on the Questionnaire Star platform, and Statistical Product and Service Solutions software (version 19.0) was used for statistical processing. The results showed that the infection rate of COVID-19 among respondents reached 72.24%. 58.81% of the infected people reported post COVID-19 symptoms. Fever, fatigue, and cough were the main symptoms during infection. The results of multi-factor logistic regression analysis showed that there is statistical significance between age (Pâ =â .002), residential area (Pâ =â .025), number of vaccine injections (Pâ <â .001) and the risk of new coronavirus infection. COVID-19 had a high infection rate, and children had a lower risk of COVID-19. People living in cities were more susceptible to COVID-19, and it was necessary to increase the number of vaccine doses.
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COVID-19 , Vacunas , Niño , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Estudios Transversales , SARS-CoV-2 , Prevalencia , China/epidemiología , Factores de RiesgoRESUMEN
Personalized neoantigen vaccines have achieved major advancements in recent years, with studies in melanoma leading progress in the field. Early clinical trials have demonstrated their feasibility, safety, immunogenicity, and potential efficacy. Advances in sequencing technologies and neoantigen prediction algorithms have substantively improved the identification and prioritization of neoantigens. Innovative delivery platforms now support the rapid and flexible production of vaccines. Several ongoing efforts in the field are aimed at improving the integration of large datasets, refining the training of prediction models, and ensuring the functional validation of vaccine immunogenicity.
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Hemospray (TC-325; Cook Medical, Winston-Salem, NC) has been used effectively in hemostasis in non-variceal upper gastrointestinal (GI) bleeding. Current guidelines suggest using Hemospray as a temporizing measure or adjunct technique. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Hemospray as a modality for primary hemostasis. We searched MEDLINE, CENTRAL, and CINAHL (Cumulative Index of Nursing and Allied Health Literature) databases from inception to August 1, 2022. Three independent reviewers performed a comprehensive review of all original articles describing the application of Hemospray as the primary method of hemostasis in non-variceal upper GI bleeding patients. Three reviewers independently reviewed and abstracted data and assessed study quality using the Cochrane risk of bias tool. Primary outcomes were (1) primary hemostasis rate, (2) rebleeding rate until hospital discharge or death, (3) need for surgery, and (4) overall mortality rate. Of the 211 studies identified, 146 underwent title and abstract review, and four were included in the systematic review. Pooled results from 303 patients showed that compared to standard of care, Hemospray has significantly higher odds of primary hemostasis (OR: 3.48, 95% CI: 1.09-11.18, p = 0.04). There was no statistically significant difference in terms of rebleeding rates (OR: 0.79, 95% CI: 0.24-2.55, p = 0.69), need for surgery (OR: 1.62, 95% CI: 0.35-7.41, p = 0.54), or overall mortality (OR: 1.08, 95% CI: 0.56-2.08, p = 0.83). This systematic review and meta-analysis prove that Hemospray is a better modality of primary hemostasis in non-variceal upper GI bleeding when used as a primary method. At the same time, there is no significant difference in complications, including rebleeding, need for surgical intervention, and all-cause mortality.
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Background: Wolffian tumors in females are rare gynecological neoplasms, with fewer than 100 cases reported. Existing literature primarily focuses on the pathology, and reports involving imaging are limited. Objective: This study presents a case of Wolffian tumor, emphasizing its magnetic resonance imaging (MRI) characteristics to enhance preoperative diagnostic accuracy. Case report: A 56-year-old woman presented with a year-long history of irregular vaginal bleeding. MRI revealed a solid mass in the right adnexal region. On T2-weighted images, the mass exhibited slightly elevated signal intensity with a distinctive low-signal intensity rim. Diffusion-weighted imaging displayed markedly increased signal intensity, and the contrast enhancement was moderate. The patient underwent laparoscopic right adnexectomy and received a Wolffian tumor diagnosis. No recurrence was observed during a 6-month follow-up. Conclusions: Wolffian tumors exhibit distinctive MRI presentations. Notably, the prominent low-signal intensity rim on MRI may aid in accurate preoperative tumor diagnosis.
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Composed of obesity and lipid parameters, the cardiometabolic index (CMI) has emerged as a novel diagnostic tool. Originally developed for diabetes diagnosis, its application has expanded to identifying patients with cardiovascular diseases, such as atherosclerosis and hypertension. However, the relationship between CMI and non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in the US population remains unclear. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2017-2020, involving 2996 participants aged 20 years or older. Vibration controlled transient elastography using a FibroScan® system (model 502, V2 Touch) with controlled attenuation parameter measurements identified NAFLD at a threshold of ≥ 274 dB/m, while liver stiffness measurement (LSM) results (median, ≥ 8.2 kPa) indicated fibrosis. A multifactorial logistic regression model explored the relationship between CMI and NAFLD and fibrosis. The effectiveness of CMI in detecting NAFLD and liver fibrosis was assessed through receiver operating characteristic curve analysis. Controlling for potential confounders, CMI showed a significant positive association with NAFLD (adjusted OR = 1.44, 95% CI 1.44-1.45) and liver fibrosis (adjusted OR = 1.84, 95% CI 1.84-1.85). The Areas Under the Curve for predicting NAFLD and fibrosis were 0.762 (95% CI 0.745 ~ 0.779) and 0.664(95% CI 0.633 ~ 0.696), respectively, with optimal cut-off values of 0.462 and 0.527. There is a positive correlation between CMI and NAFLD and fibrosis, which is a suitable and simple predictor of NAFLD and fibrosis.
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Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Cirrosis Hepática/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adulto , Encuestas Nutricionales , Diagnóstico por Imagen de Elasticidad , Curva ROC , Enfermedades Cardiovasculares , Factores de Riesgo Cardiometabólico , AncianoRESUMEN
RATIONALE AND OBJECTIVES: Pulmonary nodules or masses are highly prevalent worldwide, and differential diagnosis of benign and malignant lesions remains difficult. Magnetic resonance imaging (MRI) can provide functional and metabolic information of pulmonary lesions. This study aimed to establish a nomogram model based on clinical features, imaging features, and multi-sequence MRI radiomics to identify benign and malignant solid pulmonary nodules or masses. MATERIALS AND METHODS: A total of 145 eligible patients (76 male; mean age, 58.4 years ± 13.7 [SD]) with solid pulmonary nodules or masses were retrospectively analyzed. The patients were randomized into two groups (training cohort, n = 102; validation cohort, n = 43). The nomogram was used for predicting malignant pulmonary lesions. The diagnostic performance of different models was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Of these patients, 95 patients were diagnosed with benign lesions and 50 with malignant lesions. Multivariate analysis showed that age, DWI value, LSR value, and ADC value were independent predictors of malignant lesions. Among the radiomics models, the multi-sequence MRI-based model (T1WI+T2WI+ADC) achieved the best diagnosis performance with AUCs of 0.858 (95%CI: 0.775, 0.919) and 0.774 (95%CI: 0.621, 0.887) for the training and validation cohorts, respectively. Combining multi-sequence radiomics, clinical and imaging features, the predictive efficacy of the clinical-imaging-radiomics model was significantly better than the clinical model, imaging model and radiomics model (all P < 0.05). CONCLUSION: The MRI-based clinical-imaging-radiomics model is helpful to differentiate benign and malignant solid pulmonary nodules or masses, and may be useful for precision medicine of pulmonary diseases.
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OBJECTIVES: Although observational studies have suggested a link between hypothyroidism and myasthenia gravis (MG), a causal relationship has not been established. We aimed to investigate the causal association using a two-sample Mendelian randomization (MR) study. METHODS: Using summary statistics from genome-wide association studies involving 494,577 and 38,243 individuals, single-nucleotide polymorphisms exhibiting no linkage disequilibrium (r2 ≤ 0.001) and displaying significant differences (p ≤ 5 × 10-8) were selected for hypothyroidism and MG. To assess the potential causality relationship between hypothyroidism and MG, MR analysis was conducted using inverse variance weighted (IVW), weighted median method, and MR-Egger. The MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were employed to examine sensitivity analyses. In addition, validation datasets were used to validate the relevant results. RESULTS: Genetic liability to hypothyroidism was positively associated with MG (IVW, OR: 1.36, 95% CI: 1.17-1.58, p = 7.53 × 10-05; weighted median, OR: 1.19, 95% CI: 0.70-2.02, p = 0.522; MR-Egger, OR: 1.19, 95% CI: 0.98-1.45, p = 0.080). Among the three MR methods, the correlation between hypothyroidism and MG genetic prediction was consistent. The independent validation set (IVW, OR: 466.47, 95% CI: 4.70 -46,285.95, p = 0.01) further supported this. Additionally, bidirectional studies showed that using IVW, there was no reverse causality (OR: 1.104, 95%CI: 0.96-1.27, p = 0.170). DISCUSSION: This MR study showed that hypothyroidism can increase the risk of MG. Further investigation into the underlying mechanisms of this potential causality is warranted to offer novel therapeutic options for MG in the future.
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Hipotiroidismo , Miastenia Gravis , Humanos , Estudio de Asociación del Genoma Completo , Hipotiroidismo/complicaciones , Hipotiroidismo/genética , Desequilibrio de Ligamiento , Análisis de la Aleatorización Mendeliana , Miastenia Gravis/complicaciones , Miastenia Gravis/genéticaRESUMEN
Amphiphilic aromatic poly (amino acids) polymers were designed as biodegradability demulsifiers with higher aromaticity, stronger polarity, and side chain-like combs. The effects of demulsifier dosage, structural characteristics and emulsion properties such as pH, salinity, and oil content on the demulsification efficiency were investigated. The results show that the poly (L-glutamic-benzyl ester)-block-poly (L-phenylalanine) (PBLG15-b-PPA15) as the demulsifier can remove more than 99.97% of the oil in a 5.0 wt% oil-in-water (O/W) emulsion at room temperature within 2 min. The poly (L-tyrosine)-block-poly (L-phenylalanine) (PTyr15-b-PPA15) with environmental durability demonstrates high effectiveness, universality, and demulsification speed. It achieves a remarkable demulsification efficiency of up to 99.99% for a 20.0 wt% O/W emulsion at room temperature. The demulsification mechanism indicates that demulsifiers have sufficient interfacial activity can quickly migrate to the oil-water interface after being added to the emulsions. Additionally, when demulsifiers are present in a continuous phase in the molecular form, their "teeth" side chains are beneficial for increasing coalescence and flocculation capacities. Furthermore, according to the Density Functional Theory (DFT) calculations, enhancing the intermolecular interactions between demulsifiers and the primary native surfactants that form an oil-water interfacial film is a more efficient approach to reducing demulsification temperature and improving demulsification efficiency and rate.
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In the realm of marine environmental engineering, the swift and accurate detection of underwater targets is of considerable significance. Recently, methods based on Convolutional Neural Networks (CNN) have been applied to enhance the detection of such targets. However, deep neural networks usually require a large number of parameters, resulting in slow processing speed. Meanwhile, existing methods present challenges in accurate detection when facing small and densely arranged underwater targets. To address these issues, we propose a new neural network model, YOLOv8-LA, for improving the detection performance of underwater targets. First, we design a Lightweight Efficient Partial Convolution (LEPC) module to optimize spatial feature extraction by selectively processing input channels to improve efficiency and significantly reduce redundant computation and storage requirements. Second, we developed the AP-FasterNet architecture for small targets that are commonly found in underwater datasets. By integrating depth-separable convolutions with different expansion rates into FasterNet, AP-FasterNet enhances the model's ability to capture detailed features of small targets. Finally, we integrate the lightweight and efficient content-aware reorganization (CARAFE) up-sampling operation into YOLOv8 to enhance the model performance by aggregating contextual information over a large perceptual field and mitigating information loss during up-sampling.Evaluation results on the URPC2021 dataset show that the YOLOv8-LA model achieves 84.7% mean accuracy (mAP) on a single Nvidia GeForce RTX 3090 and operates at 189.3 frames per second (FPS), demonstrating that it outperforms existing state-of-the-art methods in terms of performance. This result demonstrates the model's ability to ensure high detection accuracy while maintaining real-time processing capabilities.