Health locus of control and symptom distress: The mediating role of illness acceptance and symptom severity in acute leukemia patients.

OBJECTIVE: This study aims to explore the multiple mediating roles of illness acceptance and symptom severity between health locus of control and symptom distress in acute leukemia patients. METHODS: From June 2022 to March 2023, a convenience sampling method was used to recruit 208 acute leukemia patients in the inpatient center of a hospital in Hebei. The Chinese versions of Multidimensional Health Locus of Control Scale, Illness Acceptance Scale, and Anderson Symptom Assessment Scale was used in the cross-sectional study. RESULTS: All participants reported the presence of symptom distress. Symptom distress was significantly correlated with chance health locus of control, illness acceptance, and symptom severity (P＜0.05). Illness acceptance alone played a mediating role in the relationship between chance health locus of control and symptom distress in acute leukemia patients (ß=0.087, 95%CI 0.030-0.167). The indirect role of chance health locus of control on symptom distress through symptom severity alone was also statistically significant (ß=0.131, 95%CI 0.008-0.252). Furthermore, the multiple mediating role of chance health locus of control and symptom distress through illness acceptance and symptom severity combined was verified (ß=0.027, 95%CI 0.001-0.089). The alternative model is also valid, indicating bidirectional relationships between symptom severity, illness acceptance, and chance health locus of control, collectively influencing symptom distress. CONCLUSION: There is a positive relationship between chance health locus of control and symptom distress; additionally, increasing social psychological interventions for illness acceptance and strengthening the management of core symptoms will help alleviate the impact of health chance locus of control on symptom distress in acute leukemia patients. Longitudinal studies are needed to confirm the causal relationships among the variables explored within the model. IMPACT ON NURSING PRACTICE: It is recommended that healthcare professionals pay attention to the assessment of health locus of control in patients, identify patients with health chance locus of control in a timely manner, take measures to enhance their disease acceptance, and strengthen the management of core symptoms, thereby reducing their level of symptom distress.

Toxicity of Beauveria bassiana to Bactrocera dorsalis and effects on its natural predators.

Entomopathogenic fungi (EPF) are economical and environmentally friendly, forming an essential part of integrated pest management strategies. We screened six strains of Beauveria bassiana (B1-B6) (Hypocreales: Cordycipitaceae), of which B4 was the most virulent to Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). We further assessed the biological characteristics of strain B4 and the environmental factors influencing its ability to infect B. dorsalis. We also evaluated the effects of B4 on two of the natural predators of B. dorsalis. We found that strain B4 was the most virulent to 3rd instar larvae, pupae, and adult B. dorsalis, causing mortality rates of 52.67, 61.33, and 90.67%, respectively. B4 was not toxic to B. dorsalis eggs. The optimum B4 effects on B. dorsalis were achieved at a relative humidity of 91-100% and a temperature of 25°C. Among the six insecticides commonly used for B. dorsalis control, 1.8% abamectin emulsifiable concentrate had the strongest inhibitory effect on B4 strain germination. B4 spraying affected both natural enemies (Amblyseius cucumeris and Anastatus japonicus), reducing the number of A. cucumeris and killing A. japonicus adults. We found a valuable strain of EPF (B4) that is virulent against many life stages of B. dorsalis and has great potential for the biological control of B. dorsalis. We also provide an important theoretical and practical base for developing a potential fungicide to control B. dorsalis.

Diagnostic Performance of [18F]AlF-Thretide PET/CT in Patients with Newly Diagnosed Prostate Cancer Using Histopathology as Reference Standard.

This study aimed to assess the diagnostic value of [18F]AlF-thretide PET/CT in patients with newly diagnosed prostate cancer (PCa). Methods: In total, 49 patients with biopsy-proven PCa were enrolled in this prospective study. All patients underwent [18F]AlF-thretide PET/CT, and the scoring system of the PRIMARY trial was used for PET image analysis. The dosimetry evaluation of [18F]AlF-thretide was performed on 3 patients. Pathologic examination was used as the reference standard to evaluate the location, number, size, and Gleason score of tumors, for comparison with the [18F]AlF-thretide PET/CT results. PSMA expression was evaluated by immunohistochemical staining. Results: All patients tolerated the [18F]AlF-thretide PET/CT well. The total effective dose of [18F]AlF-thretide was 1.16E-02 mSv/MBq. For patient-based analysis of intraprostatic tumors, 46 of 49 (93.9%) patients showed pathologic uptake on [18F]AlF-thretide PET/CT. For lesion-based analysis of intraprostatic tumors, the sensitivity and positive predictive value for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively. Delayed images can detect more lesions than standard images (n = 57 vs. 49, P = 0.005), and the SUVmax and tumor-to-background ratio of the former were higher than those of the latter (SUVmax: 14.5 ± 16.7 vs. 11.4 ± 13.6, P < 0.001; tumor-to-background ratio: 37.1 ± 42.3 vs. 23.1 ± 27.4, P < 0.001). The receiver-operating-characteristic curve analysis showed that the areas under the curve for PRIMARY score-predicted true-positive and false-positive lesions were significantly higher than those for the SUVmax of standard images (P = 0.015) and seemed higher than those for the SUVmax of delayed images (P = 0.257). [18F]AlF-thretide PET/CT showed a higher detection rate than multiparametric MRI for all intraprostatic foci (53.5% vs. 40.8%, P = 0.012) and clinically significant PCa (75.0% vs. 61.4%, P = 0.031). Conclusion: [18F]AlF-thretide PET/CT showed high diagnostic value for patients with primary PCa and can be used as an excellent imaging modality for preoperative evaluation of PCa patients.

cGAS suppresses ß-cell proliferation by a STING-independent but CEBPß-dependent mechanism.

AIMS/HYPOTHESIS: cGAS (cyclic GMP-AMP synthase) has been implicated in various cellular processes, but its role in ß-cell proliferation and diabetes is not fully understood. This study investigates the impact of cGAS on ß-cell proliferation, particularly in the context of diabetes. METHODS: Utilizing mouse models, including cGAS and STING (stimulator of interferon genes) knockout mice, we explored the role of cGAS in ß-cell function. This involved ß-cell-specific cGAS knockout (cGASßKO) mice, created by breeding cGAS floxed mice with transgenic mice expressing Cre recombinase under the insulin II promoter. We analyzed cGAS expression in diabetic mouse models, evaluated the effects of cGAS deficiency on glucose tolerance, and investigated the molecular mechanisms underlying these effects through RNA sequencing. RESULTS: cGAS expression is upregulated in the islets of diabetic mice and by high glucose treatment in MIN6 cells. Both global cGAS deficiency and ß-cell-specific cGAS knockout mice lead to improved glucose tolerance by promoting ß-cell mass. Interestingly, STING knockout did not affect pancreatic ß-cell mass, suggesting a STING-independent mechanism for cGAS's role in ß-cells. Further analyses revealed that cGAS- but not STING-deficiency leads to reduced expression of CEBPß, a known suppressor of ß-cell proliferation, concurrently with increased ß-cell proliferation. Moreover, overexpression of CEBPß reverses the upregulation of Cyclin D1 and D2 induced by cGAS deficiency, thereby regulating ß-cell proliferation. These results confirm that cGAS regulation of ß-cell proliferation via a CEBPß-dependent but STING-independent mechanism. CONCLUSIONS/INTERPRETATION: Our findings highlight the pivotal role of cGAS in promoting ß-cell proliferation and maintaining glucose homeostasis, potentially by regulating CEBPß expression in a STING-independent manner. This study uncovers the significance of cGAS in controlling ß-cell mass and identifies a potential therapeutic target for enhancing ß-cell proliferation in the treatment of diabetes.

An ultrasound-activated nanoplatform remodels tumor microenvironment through diverse cell death induction for improved immunotherapy.

Although nanomaterial-based nanomedicine provides many powerful tools to treat cancer, most focus on the "immunosilent" apoptosis process. In contrast, ferroptosis and immunogenic cell death, two non-apoptotic forms of programmed cell death (PCD), have been shown to enhance or alter the activity of the immune system. Therefore, there is a need to design and develop nanoplatforms that can induce multiple modes of cell death other than apoptosis to stimulate antitumor immunity and remodel the immunosuppressive tumor microenvironment for cancer therapy. In this study, a new type of multifunctional nanocomposite mainly consisting of HMME, Fe3+ and Tannic acid, denoted HFT NPs, was designed and synthesized to induce multiple modes of cell death and prime the tumor microenvironment (TME). The HFT NPs consolidate two functions into one nano-system: HMME as a sonosensitizer for the generation of reactive oxygen species (ROS) 1O2 upon ultrasound irradiation, and Fe3+ as a GSH scavenger for the induction of ferroptosis and the production of ROS ·OH through inorganic catalytic reactions. The administration of HFT NPs and subsequent ultrasound treatment caused cell death through the consumption of GSH, the generation of ROS, ultimately inducing apoptosis, ferroptosis, and immunogenic cell death (ICD). More importantly, the combination of HFT NPs and ultrasound irradiation could reshape the TME and recruit more T cell infiltration, and its combination with immune checkpoint blockade anti-PD-1 antibody could eradicate tumors with low immunogenicity and a cold TME. This new nano-system integrates sonodynamic and chemodynamic properties to achieve outstanding therapeutic outcomes when combined with immunotherapy. Collectively, this study demonstrates that it is possible to potentiate cancer immunotherapy through the rational and innovative design of relatively simple materials.

Bayesian network analysis of factors influencing type 2 diabetes, coronary heart disease, and their comorbidities.

OBJECTIVE: Bayesian network (BN) models were developed to explore the specific relationships between influencing factors and type 2 diabetes mellitus (T2DM), coronary heart disease (CAD), and their comorbidities. The aim was to predict disease occurrence and diagnose etiology using these models, thereby informing the development of effective prevention and control strategies for T2DM, CAD, and their comorbidities. METHOD: Employing a case-control design, the study compared individuals with T2DM, CAD, and their comorbidities (case group) with healthy counterparts (control group). Univariate and multivariate Logistic regression analyses were conducted to identify disease-influencing factors. The BN structure was learned using the Tabu search algorithm, with parameter estimation achieved through maximum likelihood estimation. The predictive performance of the BN model was assessed using the confusion matrix, and Netica software was utilized for visual prediction and diagnosis. RESULT: The study involved 3,824 participants, including 1,175 controls, 1,163 T2DM cases, 982 CAD cases, and 504 comorbidity cases. The BN model unveiled factors directly and indirectly impacting T2DM, such as age, region, education level, and family history (FH). Variables like exercise, LDL-C, TC, fruit, and sweet food intake exhibited direct effects, while smoking, alcohol consumption, occupation, heart rate, HDL-C, meat, and staple food intake had indirect effects. Similarly, for CAD, factors with direct and indirect effects included age, smoking, SBP, exercise, meat, and fruit intake, while sleeping time and heart rate showed direct effects. Regarding T2DM and CAD comorbidities, age, FBG, SBP, fruit, and sweet intake demonstrated both direct and indirect effects, whereas exercise and HDL-C exhibited direct effects, and region, education level, DBP, and TC showed indirect effects. CONCLUSION: The BN model constructed using the Tabu search algorithm showcased robust predictive performance, reliability, and applicability in forecasting disease probabilities for T2DM, CAD, and their comorbidities. These findings offer valuable insights for enhancing prevention and control strategies and exploring the application of BN in predicting and diagnosing chronic diseases.

Black Phosphorus Nanosheets Protect Neurons by Degrading Aggregative α-syn and Clearing ROS in Parkinson's Disease.

Although evidence indicates that the abnormal accumulation of α-synuclein (α-syn) in dopamine neurons of the substantia nigra is the main pathological feature of Parkinson's disease (PD), no compounds that have both α-syn antiaggregation and α-syn degradation functions have been successful in treating the disease in the clinic. Here, it is shown that black phosphorus nanosheets (BPNSs) interact directly with α-syn fibrils to trigger their disaggregation for PD treatment. Moreover, BPNSs have a specific affinity for α-syn through van der Waals forces. And BPNSs are found to activate autophagy to maintain α-syn homeostasis, improve mitochondrial dysfunction, reduce reactive oxygen species levels, and rescue neuronal death and synaptic loss in PC12 cells. It is also observed that BPNSs penetrate the blood-brain barrier and protect against dopamine neuron loss, alleviating behavioral disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model and hA53T α-syn transgenic mice. Together, the study reveals that BPNSs have the potential as a novel integrated nanomedicine for clinical diagnosis and treatment of neurological diseases.

Partial hypopituitarism with ACTH deficiency as the main manifestation as a complication of hemorrhagic fever with renal syndrome.

Hypopituitarism is a relatively rare complication of hemorrhagic fever with renal syndrome. However, almost all available reported cases were total anterior pituitary hypofunction, isolated growth-hormone deficiency, or isolated gonadotropin deficiency. Here, we firstly describe a patient with partial hypopituitarism with ACTH deficiency as the main manifestation as a complication of hemorrhagic fever with renal syndrome.

Integration of Cine-cardiac Magnetic Resonance Radiomics and Machine Learning for Differentiating Ischemic and Dilated Cardiomyopathy.

RATIONALE AND OBJECTIVES: This study aims to evaluate the capability of machine learning algorithms in utilizing radiomic features extracted from cine-cardiac magnetic resonance (CMR) sequences for differentiating between ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM). MATERIALS AND METHODS: This retrospective study included 115 cardiomyopathy patients subdivided into ICM (n = 64) and DCM cohorts (n = 51). We collected invasive clinical (IC), noninvasive clinical (NIC), and combined clinical (CC) feature subsets. Radiomic features were extracted from regions of interest (ROIs) in the left ventricle (LV), LV cavity (LVC), and myocardium (MYO). We tested 10 classical machine learning classifiers and validated them through fivefold cross-validation. We compared the efficacy of clinical feature-based models and radiomics-based models to identify the superior diagnostic approach. RESULTS: In the validation set, the Gaussian naive Bayes (GNB) model outperformed the other models in all categories, with areas under the curve (AUCs) of 0.879 for IC_GNB, 0.906 for NIC_GNB, and 0.906 for CC_GNB. Among the radiomics models, the MYO_LASSOCV_MLP model demonstrated the highest AUC (0.919). In the test set, the MYO_RFECV_GNB radiomics model achieved the highest AUC (0.857), surpassing the performance of the three clinical feature models (IC_GNB: 0.732; NIC_GNB: 0.75; CC_GNB: 0.786). CONCLUSION: Radiomics models leveraging MYO images from cine-CMR exhibit promising potential for differentiating ICM from DCM, indicating the significant clinical application scope of such models. CLINICAL RELEVANCE STATEMENT: The integration of radiomics models and machine learning methods utilizing cine-CMR sequences enhances the diagnostic capability to distinguish between ICM and DCM, minimizes examination risks for patients, and potentially reduces the duration of medical imaging procedures.

Clinical significance of immune-related antigen CD58 in gliomas and analysis of its potential core related gene clusters.

Background: The clinical significance of immune-related antigen CD58 in gliomas remains uncertain. The aim of this study was to examine the clinical importance and possible core related genes of CD58 in gliomas. Methods: Pan-cancer analysis was to observe the association between CD58 and different tumors, glioma RNA sequencing data and clinical sample analyses were used to observe the relationship between CD58 and glioma, shRNA interference models were to observe the impact of CD58 on glioma cell function, and four glioma datasets and two online analysis platforms were used to explore the core related genes affecting the correlation between CD58 and glioma. Results: High CD58 expression was associated with worse prognosis in various tumors and higher malignancy in glioma. Down regulation of CD58 expression was linked to decreased proliferation, increased apoptosis, and reduced metastasis in glioma cells. The pathways involved in CD58-related effects were enriched for immune cell adhesion and immune factor activation, and the core genes were CASP1, CCL2, IL18, MYD88, PTPRC, and TLR2. The signature of CD58 and its core-related genes showed superior predictive power for glioma prognosis. Conclusion: High CD58 expression is correlated with more malignant glioma types, and also an independent risk factor for mortality in glioma. CD58 and its core-related genes may serve as novel biomarkers for diagnosing and treating glioma.

Non-invasive prediction of preeclampsia using the maternal plasma cell-free DNA profile and clinical risk factors.

Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Astragaloside IV protects against autoimmune myasthenia gravis in rats via regulation of mitophagy and apoptosis.

Astragaloside IV (AS­IV) has various pharmacological effects, including antioxidant and immunoregulatory properties, which can improve myasthenia gravis (MG) symptoms. However, the potential mechanism underlying the effects of AS­IV on MG remains to be elucidated. The present study aimed to investigate whether AS­IV has a therapeutic effect on MG and its potential mechanism of action. By subcutaneously immunizing rats with R97­116 peptide, an experimental autoimmune (EA) MG rat model was established. AS­IV (40 or 80 mg/kg/day) treatment was then applied for 28 days after modeling. The results demonstrated that AS­IV significantly ameliorated the weight loss, Lennon score and pathological changes in the gastrocnemius muscle of EAMG rats compared with the model group. Additionally, the levels of acetylcholine receptor antibody (AChR­Ab) were significantly decreased, whereas mitochondrial function [ATPase and cytochrome c (Cyt­C) oxidase activities] and ultrastructure were improved in the AS­IV treated rats. Moreover, the mRNA and protein expression levels of phosphatase and tensin homolog­induced putative kinase 1, Parkin, LC3II and Bcl­2, key signaling molecules for mitophagy and apoptosis, were upregulated, whereas the mRNA and protein expression levels of p62, Cyt­C, Bax, caspase 3 and caspase 9 were downregulated following AS­IV intervention. In conclusion, AS­IV may protect against EAMG in a rat model by modulating mitophagy and apoptosis. These findings indicated the potential mechanism underlying the effects of AS­IV on MG and provided novel insights into treatment strategies for MG.

Development of a paper-based transcription aptasensor for convenient urinary uric acid self-testing.

The abnormal uric acid (UA) level in urine can serve as warning signals of many diseases, such as gout and metabolic cardiovascular diseases. The current methods for detecting UA face limitations of instrument dependence and the requirement for non-invasiveness, making it challenging to fulfill the need for home-based application. In this study, we designed an aptasensor that combined UA-specific transcriptional regulation and a fluorescent RNA aptamer for convenient urinary UA testing. The concentration of UA can be translated into the intensity of fluorescent signals. The aptasensor showed higher sensitivity and more robust anti-interference performance. UA levels in the urine of different volunteers could be accurately tested using this method. In addition, a paper-based aptasensor for UA self-testing was manufactured, in which the urinary UA levels could be determined using a smartphone-based colorimetric approach. This work not only demonstrates a new approach for the design of disease-associated aptasensor, but also offers promising ideas for home-based detection of UA.

Multiband Omnidirectional Invisibility Cloak.

Transformation optics (TO) provides a powerful tool to manipulate electromagnetic waves, enabling the design of invisibility cloaks, which can render objects invisible. Despite many years of research, however, invisibility cloaks experimentally realized thus far can only operate at a single frequency. The narrow bandwidth significantly restricts the practical applications of invisibility cloaks and other TO devices. Here, a general design strategy is proposed to realize a multiband anisotropic metamaterial characterized by two principal permittivity components, i.e., one infinite and the other spatially gradient. Through a proper transformation and combination of such metamaterials, an omnidirectional invisibility cloak is experimentally implemented, which is impedance-matched to free space at multiple frequencies. Both far-field numerical simulations and near-field experimental mappings confirm that this cloak can successfully suppress scattering from multiple large-scale objects simultaneously at 5 and 10 GHz. The design strategy and corresponding practical realization bring multiband transformation optical devices one step closer to reality.

Recent developments in synthesis of attapulgite composite materials for refractory organic wastewater treatment: a review.

Attapulgite clay, due to its unique crystalline hydrated magnesium-aluminium silicate composition and layer-chain structure, possesses exceptional adsorption and catalytic properties, which enable it or its composites to be utilized as adsorbents and catalysts for wastewater treatment. But the drawbacks of attapulgite are also very obvious, such as relatively low specific surface area (compared to traditional adsorbents such as activated carbon and activated alumina), easy aggregation, and difficulty in dispersion. In order to fully utilize and improve the performance of attapulgite, researchers have conducted extensive research on its modification, but few specialized works have comprehensively evaluated the synthesis, applications and challenges for attapulgite-based composite materials in refractory organic wastewater treatments. This paper provides a comprehensive review of controllable preparation strategies, characterization methods and mechanisms of attapulgite-based composite materials, as well as the research progress of these materials in refractory organic wastewater treatment. Based on this review, constructive recommendations, such as deep mechanism analysis from molecular level multi-functional attapulgite-based material developments, and using biodegradable materials in attapulgite-based composites, were proposed.

Activation of the cGAS-STING pathway by viral dsDNA leading to M1 polarization of macrophages mediates antiviral activity against hepatitis B virus.

BACKGROUND AND AIMS: Activation of the cGAS-STING pathway induces the production of type I interferons, initiating the antiviral immune response, which contributes to the clearance of pathogens. Previous studies have shown that STING agonists promote hepatitis B virus (HBV) clearance; however, few studies have investigated the effect of activating the cGAS-STING pathway in macrophages on HBV. METHODS: The polarization status of HBV particle-stimulated RAW264.7 macrophages was analyzed. After stimulation with HBV particles, the analysis focused on determining whether the DNA sensors in RAW264.7 macrophages recognized the viral double-stranded DNA (dsDNA) and evaluating the activation of the cGAS-STING pathway. Coculture of mouse macrophages and hepatocytes harboring HBV was used to study the antiviral activity of HBV-stimulated RAW264.7 macrophages. RESULTS: After stimulation with HBV particles, HBV relaxed circular DNA (rcDNA) was detected in RAW264.7 macrophages, and the protein expression of phospho-STING, phospho-TBK1, and phospho-IRF3 in the STING pathway was increased, as shown by Western blot analysis, which revealed that M1 polarization of macrophages was caused by increased expression of CD86. RT-PCR analyses revealed elevated expression of M1 macrophage polarization-associated cytokines such as TNFα, IL-1ß, iNOS, and IFNα/ß. In the coculture experiment, both HBsAg and HBeAg expression levels were significantly decreased in AML12-HBV1.3 cells cocultured with the supernatants of HBV-stimulated RAW264.7 macrophages. CONCLUSION: The results suggest that macrophages can endocytose HBV particles. Additionally, viral dsDNA can be recognized by DNA pattern recognition receptors, which in turn activate the cGAS-STING pathway, promoting the M1 polarization of macrophages, while no significant M2 polarization is observed. Macrophages stimulated with HBV particles exhibit enhanced antiviral activity against HBV.

Creatine Kinase-MM/Proto-oncogene Tyrosine-Protein Kinase Receptor as a Sensitive Indicator for Duchenne Muscular Dystrophy Carriers.

Duchenne muscular dystrophy (DMD), a lethal X-linked recessive genetic disease, is characterized by progressive muscle wasting which will lead to premature death by cardiorespiratory complications in their late twenties. And 2.5-19% DMD carriers that also suffer from skeletal muscle damage or dilated cardiomyopathy when diagnosed as soon as possible is meaningful for prenatal diagnosis and advance warning for self-health. The current DMD carrier screening mainly relies on detecting serum creatine kinase activity, covering only 50-70% DMD carriers which will cause many false negatives and require the discovery of highly effective biomarker and simple detection procedure for DMD carriers. In this article, we have compiled a comprehensive summary of all documented biomarkers associated with DMD and categorized them based on their expression patterns. We specifically pinpointed novel DMD biomarkers, previously unreported in DMD carriers, and conducted further investigations to explore their potential. Compared to creatine kinase activity alone in DMD carriers, creatine kinase-MM can improve the specificity from 73 to 81%. And our investigation revealed another promising protein: proto-oncogene tyrosine-protein kinase receptor (RET). When combined with creatine kinase-MM (creatine kinase-MM/RET ratio), it significantly enhances the specificity (from 81 to 83%) and sensitivity (from 71.4 to 93%) of detecting DMD carriers in serum. Moreover, we successfully devised an efficient method for extracting RET from dried blood spots. This breakthrough allowed us to detect both creatine kinase-MM and RET using dried blood spots without compromising the detection rate.

ITGB4 is a prognostic biomarker and correlated with lung adenocarcinoma brain metastasis.

BACKGROUND: The aim of this study is to explore the prognostic value and immune signature of ITGB4 expression in lung adenocarcinoma (LUAD) brain metastasis. METHODS: We comprehensively screened genes associated with LUAD brain metastasis by integrating datasets from the GEO database and TMT-based quantitative proteomics profiles. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival, and a risk model was constructed. The biological functions were explored via GO and KEGG analysis. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. In addition, we use TIMER to explore the collection of ITGB4 Expression and Immune Infiltration Level in LUAD. The ability of ITGB4 to regulate tumor metastasis was further assessed by migration, invasion assay and Western-blot in H1975-BrM4 cells. RESULTS: We found that ITGB4 was the only gene with high clinical diagnostic and prognostic value in LUAD. Enrichment analysis indicated that ITGB4 is associated with brain metastasis, infiltration of immune cells, and the response to immunotherapy. ITGB4 expression can effectively predict the outcomes of patients with LUAD who are receiving anti-PD-1 therapy. ITGB4 knockdown inhibited the invasion, migration of H1975-BrM4 brain metastasis cells, as well as epithelial-mesenchymal transition (EMT) abilities. The heightened expression of ITGB4 protein was shown to promote EMT and enhance the metastatic potential. ITGB4 promotes the progression in H1975-BrM4 cells via MEK/ERK signaling pathway. CONCLUSIONS: Our findings indicate that the expression of ITGB4 is linked to the occurrence of brain metastasis and infiltration of immune cells, suggesting that ITGB4 might be a clinical treatment target for LUAD.