Backgrounds: Colorectal cancer (CRC) is a highly malignant gastrointestinal malignancy with a poor prognosis, which imposes a significant burden on patients and healthcare providers globally. Previous studies have established that genes related to glutamine metabolism play a crucial role in the development of CRC. However, no studies have yet explored the prognostic significance of these genes in CRC. Methods: CRC patient data were downloaded from The Cancer Genome Atlas (TCGA), while glutamine metabolism-related genes were obtained from the Molecular Signatures Database (MSigDB) database. Univariate COX regression analysis and LASSO Cox regression were utilized to identify 15 glutamine metabolism-related genes associated with CRC prognosis. The risk scores were calculated and stratified into high-risk and low-risk groups based on the median risk score. The model's efficacy was assessed using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve analysis. Cox regression analysis was employed to determine the risk score as an independent prognostic factor for CRC. Differential immune cell infiltration between the high-risk and low-risk groups was assessed using the ssGSEA method. The clinical applicability of the model was validated by constructing nomograms based on age, gender, clinical staging, and risk scores. Immunohistochemistry (IHC) was used to detect the expression levels of core genes. Results: We identified 15 genes related to glutamine metabolism in CRC: NLGN1, RIMKLB, UCN, CALB1, SYT4, WNT3A, NRCAM, LRFN4, PHGDH, GRM1, CBLN1, NRG1, GLYATL1, CBLN2, and VWC2. Compared to the high-risk group, the low-risk group demonstrated longer overall survival (OS) for CRC. Clinical correlation analysis revealed a positive correlation between the risk score and the clinical stage and TNM stage of CRC. Immune correlation analysis indicated a predominance of Th2 cells in the low-risk group. The nomogram exhibited excellent discriminatory ability for OS in CRC. Immunohistochemistry revealed that the core gene CBLN1 was expressed at a lower level in CRC, while GLYATL1 was expressed at a higher level. Conclusions: In summary, we have successfully identified and comprehensively analyzed a gene signature associated with glutamine metabolism in CRC for the first time. This gene signature consistently and reliably predicts the prognosis of CRC patients, indicating its potential as a metabolic target for individuals with CRC.
Antimicrobial resistance poses a serious threat to human health due to the high morbidity and mortality caused by drug-resistant microbial infections. Therefore, the development of rapid, sensitive and selective identification methods is key to improving the survival rate of patients. In this paper, a sandwich-type electrochemical DNA biosensor based on a polyadenine-DNA tetrahedron probe was constructed. The key experimental conditions were optimized, including the length of polyadenine, the concentration of the polyadenine DNA tetrahedron, the concentration of the signal probe and the hybridization time. At the same time, poly-avidin-HRP80 was used to enhance the electrochemical detection signal. Finally, excellent biosensor performance was achieved, and the detection limit for the synthetic DNA target was as low as 1 fM. In addition, we verified the practicability of the system by analyzing E. coli with the MCR-1 plasmid and realized multi-channel detection of the drug resistance genes MCR-1, blaNDM, blaKPC and blaOXA. With the ideal electrochemical interface, the polyA-based biosensor exhibits excellent stability, which provides powerful technical support for the rapid detection of antibiotic-resistant strains in the field.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, with epidemiological studies indicating a 25% prevalence. NAFLD is considered to be a progressive disease that progresses from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), then to liver fibrosis, and finally to cirrhosis or hepatocellular carcinoma (HCC). Existing research has mostly elucidated the etiology of NAFLD, yet its particular molecular processes remain uncertain. Long non-coding RNAs (LncRNAs) have been linked in a wide range of biological processes in recent years, with the introduction of microarray and high-throughput sequencing technologies, and previous studies have established their tight relationship with several stages of NAFLD development. Existing studies have shown that lncRNAs can regulate the signaling pathways related to hepatic lipid metabolism, NASH, NASH-related fibrosis and HCC. This review aims to provide a basic overview of NAFLD and lncRNAs, summarize and describe the mechanisms of lncRNAs action involved in the development of NAFLD, and provide an outlook on the future of lncRNAs-based therapy for NAFLD. (AU)
La enfermedad del hígado graso no alcohólico (NAFLD) es la enfermedad hepática más común en el mundo, con estudios epidemiológicos que indican una prevalencia del 25%. La NAFLD se considera una enfermedad progresiva que avanza de esteatosis hepática simple a esteatohepatitis no alcohólica (NASH), luego a fibrosis hepática y, finalmente, a cirrosis o carcinoma hepatocelular (HCC). La investigación existente ha dilucidado principalmente la etiología de NAFLD. Sin embargo, sus procesos moleculares particulares siguen siendo inciertos. Los ARN largos no codificantes (lncRNA) se han relacionado en una amplia gama de procesos biológicos en los últimos años, con la introducción de microarrays y tecnologías de secuenciación de alto rendimiento, y estudios previos han establecido su estrecha relación con varias etapas del desarrollo de NAFLD. Los estudios existentes han demostrado que los lncRNA pueden regular las vías de señalización relacionadas con el metabolismo lipídico hepático, NASH, fibrosis relacionada con NASH y HCC. Esta revisión tiene como objetivo proporcionar una visión general básica de NAFLD y lncRNA, resumir y describir los mecanismos de acción de lncRNA involucrados en el desarrollo de NAFLD, y proporcionar una perspectiva sobre el futuro de la terapia basada en lncRNA para NAFLD. (AU)
Humans , Non-alcoholic Fatty Liver Disease , RNA, Long Noncoding
Currently, endoscopic treatment for small gastrointestinal stromal tumors (GIST) has been widely accepted. However, for tumors larger than 5 cm, endoscopic treatment has not been recognized by national guidelines as the standard therapy due to concerns about safety and adverse tumor outcomes. Therefore, this study compares the long-term survival outcomes of endoscopic treatment and surgical treatment for GIST in the range of 5-10 cm. We selected patients with GIST from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Kaplan-Meier analysis and the log-rank test were employed to compare the long-term survival outcomes between endoscopic treatment and surgical treatment. A multivariate Cox proportional hazards model was used for analysis to identify risk factors influencing patient prognosis. To balance baseline data, we performed 1:1 propensity score matching (PSM). A total of 1223 GIST patients were included, with 144 patients (11.8%) received endoscopic treatment and 1079 patients (88.2%) received surgical treatment. Before PSM, there was no significant difference in the long-term survival rates between the two groups [5-year OS (86.5% vs. 83.5%, P = 0.42), 10-year OS (70.4% vs. 66.7%, P = 0.42)]. After adjusting for covariates, we found that the overall survival (HR = 1.26, 95% CI 0.89-1.77, P = 0.19) and cancer-specific survival (HR = 1.69, 95% CI 0.99-2.89, P = 0.053) risks were comparable between the endoscopic treatment group and the surgical treatment group. In the analysis after PSM, there was no significant difference between the endoscopic treatment group and the surgical treatment group. Our study found that for GIST patients with tumor sizes between 5 and 10 cm, the long-term OS and CSS outcomes were similar between the endoscopic treatment group and the surgical treatment group.
Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/surgery , Endoscopy , Databases, Factual , Kaplan-Meier Estimate , Propensity Score
The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD.
BACKGROUND: Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis. METHODS: We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach. RESULTS: A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23). CONCLUSION: Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence.
Acupuncture Therapy , Antidepressive Agents, Tricyclic , Tension-Type Headache , Humans , Tension-Type Headache/therapy , Tension-Type Headache/prevention & control , Tension-Type Headache/drug therapy , Antidepressive Agents, Tricyclic/therapeutic use , Acupuncture Therapy/methods , Randomized Controlled Trials as Topic
Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT.
Isoflavones , Macrophages , Isoflavones/pharmacology , Isoflavones/therapeutic use , Animals , Mice , Macrophages/immunology , Macrophages/drug effects , Humans , Female , Disease Models, Animal , Thyroiditis, Autoimmune/drug therapy , Thyroiditis, Autoimmune/immunology , Hashimoto Disease/drug therapy , Hashimoto Disease/immunology , Macrophage Activation/drug effects , Macrophage Activation/immunology , Pyroptosis/drug effects , Signal Transduction/drug effects
The discrimination and recognition of biological targets, such as proteins, cells, and bacteria, are of utmost importance in various fields of biological research and production. These include areas like biological medicine, clinical diagnosis, and microbiology analysis. In order to efficiently and cost-effectively identify a specific target from a wide range of possibilities, researchers have developed a technique called differential sensing. Unlike traditional "lock-and-key" sensors that rely on specific interactions between receptors and analytes, differential sensing makes use of cross-reactive receptors. These sensors offer less specificity but can cross-react with a wide range of analytes to produce a large amount of data. Many pattern recognition strategies have been developed and have shown promising results in identifying complex analytes. To create advanced sensor arrays for higher analysis efficiency and larger recognizing range, various nanomaterials have been utilized as sensing probes. These nanomaterials possess distinct molecular affinities, optical/electrical properties, and biological compatibility, and are conveniently functionalized. In this review, our focus is on recently reported optical sensor arrays that utilize nanomaterials to discriminate bioanalytes, including proteins, cells, and bacteria.
Biosensing Techniques , Nanostructures , Humans , Bacteria , Proteins/analysis
The antibodies in the natural biological world utilize bivalency/multivalency to achieve a higher affinity for antigen capture. However, mimicking this mechanism on the electrochemical sensing interface and enhancing biological affinity through precise spatial arrangement of bivalent aptamer probes still pose a challenge. In this study, we have developed a novel self-assembly layer (SAM) incorporating triblock polyA DNA to enable accurate organization of the aptamer probes on the interface, constructing a "lock-and-key-like" proximity hybridization assay (PHA) biosensor. The polyA fragment acts as an anchoring block with a strong affinity for the gold surface. Importantly, it connects the two DNA probes, facilitating one-to-one spatial proximity and enabling a controllable surface arrangement. By precisely adjusting the length of the polyA fragment, we can tailor the distance between the probes to match the molecular dimensions of the target protein. This design effectively enhances the affinity of the aptamers. Notably, our biosensor demonstrates exceptional specificity and sensitivity in detecting PDGF-BB, as confirmed through successful validation using human serum samples. Overall, our biosensor presents a novel and versatile interface for proximity assays, offering a significantly improved surface arrangement and detection performance.
Aptamers, Nucleotide , Becaplermin , Biosensing Techniques , Nucleic Acid Hybridization , Poly A , Biosensing Techniques/methods , Humans , Aptamers, Nucleotide/chemistry , Becaplermin/blood , Poly A/chemistry , Gold/chemistry , DNA Probes/chemistry
This study aimed to investigate the role of SERPINB5 in colorectal cancer (CRC). We established knockdown and overexpression models of SERPINB5 in CRC cells and conducted bioinformatics analysis to assess the clinicopathological significance of SERPINB5 expression in CRC patients. Human CRC cells were transfected with LV-SERPINB5 and sh-SERPINB5 lentivirus for subsequent functional and mechanistic studies. Results showed that high SERPINB5 expression correlated positively with CEA levels, N stage and lymphatic infiltration, while displaying a negative correlation with progression-free survival. Overexpression of SERPINB5 in CRC cells upregulated the expression of TNF-α, p-NF-κB/p65, N-cadherin, MMP2 and MMP9, accompanied by decreased E-cadherin expression. In addition, SERPINB5 overexpression enhanced the migration, invasion, and proliferation of CRC cells. Furthermore, overexpression of SERPINB5 in CRC cells increased VEGFA expression, and the conditioned medium from SERPINB5-overexpressing CRC cells promoted tube formation of HUVECs. Conversely, overexpression of SERPINB5 in HUVECs decreased VEGFA expression and inhibited tube formation. Notably, these changes in CRC cells were reversed by QNZ, a specific inhibitor of the TNF-α/NF-κB pathway. In summary, our findings revealed that high SERPINB5 expression correlated with poor progression-free survival in CRC patients. Moreover, SERPINB5 could induce EMT and angiogenesis by activating the TNF-α/NF-κB pathway, thereby promoting the invasion and migration of CRC cells.
Colorectal Neoplasms , NF-kappa B , Humans , Angiogenesis , Cadherins/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , NF-kappa B/metabolism , Signal Transduction , Tumor Necrosis Factor-alpha/metabolism
Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.
Gastrointestinal Diseases , Integrative Medicine , Humans , Medicine, Chinese Traditional , Gastrointestinal Diseases/prevention & control , Evidence-Based Medicine
Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer's disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD+- or GPR162+-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD+- and GPR162+-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD+- or GPR162+-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.
Alzheimer Disease , Extracellular Vesicles , Humans , Alzheimer Disease/diagnosis , Diagnosis, Differential , NAD , Proteomics
Background and objective: The brain-computer interface (BCI) system based on steady-state visual evoked potentials (SSVEP) is expected to help disabled patients achieve alternative prosthetic hand assistance. However, the existing study still has some shortcomings in interaction aspects such as stimulus paradigm and control logic. The purpose of this study is to innovate the visual stimulus paradigm and asynchronous decoding/control strategy by integrating augmented reality technology, and propose an asynchronous pattern recognition algorithm, thereby improving the interaction logic and practical application capabilities of the prosthetic hand with the BCI system. Methods: An asynchronous visual stimulus paradigm based on an augmented reality (AR) interface was proposed in this paper, in which there were 8 control modes, including Grasp, Put down, Pinch, Point, Fist, Palm push, Hold pen, and Initial. According to the attentional orienting characteristics of the paradigm, a novel asynchronous pattern recognition algorithm that combines center extended canonical correlation analysis and support vector machine (Center-ECCA-SVM) was proposed. Then, this study proposed an intelligent BCI system switch based on a deep learning object detection algorithm (YOLOv4) to improve the level of user interaction. Finally, two experiments were designed to test the performance of the brain-controlled prosthetic hand system and its practical performance in real scenarios. Results: Under the AR paradigm of this study, compared with the liquid crystal display (LCD) paradigm, the average SSVEP spectrum amplitude of multiple subjects increased by 17.41%, and the signal-noise ratio (SNR) increased by 3.52%. The average stimulus pattern recognition accuracy was 96.71 ± 3.91%, which was 2.62% higher than the LCD paradigm. Under the data analysis time of 2s, the Center-ECCA-SVM classifier obtained 94.66 ± 3.87% and 97.40 ± 2.78% asynchronous pattern recognition accuracy under the Normal metric and the Tolerant metric, respectively. And the YOLOv4-tiny model achieves a speed of 25.29fps and a 96.4% confidence in the prosthetic hand in real-time detection. Finally, the brain-controlled prosthetic hand helped the subjects to complete 4 kinds of daily life tasks in the real scene, and the time-consuming were all within an acceptable range, which verified the effectiveness and practicability of the system. Conclusion: This research is based on improving the user interaction level of the prosthetic hand with the BCI system, and has made improvements in the SSVEP paradigm, asynchronous pattern recognition, interaction, and control logic. Furthermore, it also provides support for BCI areas for alternative prosthetic control, and movement disorder rehabilitation programs.
Background: Prior reports have indicated an inconsistent relationship between vitamin D levels and myopia in children and adolescents with limited sample size. This study was undertaken to further clarify this relationship with a repeated cross-section study. Methods: The National Health and Nutrition Examination Survey (NHANES) database with samples <19 years old was utilized. Data on rates of myopia (spherical equivalent less than or equal to -1.0 D), serum 25-hydroxyvitamin D [25(OH)D] level (high performance liquid chromatography), and other key variables were extracted and analyzed. Three models were utilized to evaluate the dose response of vitamin D levels using stepwise logistic regression. Logistic regressions for sex subgroups and other covariates were also performed, and Forest plots were drawn. Results: Data were available from 6,814 children (49.5% girls; mean age: 14.9±1.85 years). The myopia and non-myopia differed in serum 25(OH)D level, gender, race, poverty income ratio (PIR), and body mass index (BMI). Serum 25(OH)D levels were negatively correlated with myopia [odds ratio (OR) =0.98, 95% confidence interval (CI): 0.77-0.99, P<0.05] regardless of sex. Although the relationship did not appear to be linear, there was a dose effect with higher serum 25(OH)D levels linked with lower rates of myopia. In addition, rates of myopia were increased in females compared with males (OR =1.12, 95% CI: 1.01-1.24, P=0.03), those with a high PIR (OR =1.08, 95% CI: 1.04-1.11, P<0.001), and those with high BMI (OR =1.19, 95% CI: 1.11-1.27, P<0.001). White ethnicity (OR =0.78, 95% CI: 0.68-0.90, P<0.001) and leisure-time exercise (OR =0.94, 95% CI: 0.92-0.97, P=0.02) were associated with lower rates of myopia. Conclusions: These findings indicate that higher serum 25(OH)D levels and increased amounts of leisure-time exercise are associated with lower rates of myopia in this group of children and adolescents. Meanwhile, female gender, high PIR level, and high BMI were associated with greater rates of myopia. The findings indicated that children and adolescents needed leisure-time exercise to lower the risk of myopia.
OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.
Age of Onset , Phenotype , Sjogren's Syndrome , Humans , Sjogren's Syndrome/epidemiology , Sjogren's Syndrome/physiopathology , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/complications , Sjogren's Syndrome/immunology , Female , Male , Middle Aged , China/epidemiology , Adult , Time Factors , Prevalence , Fatigue/epidemiology , Fatigue/etiology , Fatigue/physiopathology , Medical Records , Xerostomia/epidemiology , Xerostomia/etiology , Xerostomia/diagnosis , Xerostomia/physiopathology , Aged , Arthralgia/etiology , Arthralgia/epidemiology , Arthralgia/diagnosis , Arthralgia/physiopathology , Retrospective Studies , Antibodies, Antinuclear/blood
Ammonia-oxidizing archaea (AOA) are among the most ubiquitous and abundant archaea on Earth, widely distributed in marine, terrestrial, and geothermal ecosystems. However, the genomic diversity, biogeography, and evolutionary process of AOA populations in subsurface environments are vastly understudied compared to those in marine and soil systems. Here, we report a novel AOA order Candidatus (Ca.) Nitrosomirales which forms a sister lineage to the thermophilic Ca. Nitrosocaldales. Metagenomic and 16S rRNA gene-read mapping demonstrates the abundant presence of Nitrosomirales AOA in various groundwater environments and their widespread distribution across a range of geothermal, terrestrial, and marine habitats. Terrestrial Nitrosomirales AOA show the genetic capacity of using formate as a source of reductant and using nitrate as an alternative electron acceptor. Nitrosomirales AOA appear to have acquired key metabolic genes and operons from other mesophilic populations via horizontal gene transfer, including genes encoding urease, nitrite reductase, and V-type ATPase. The additional metabolic versatility conferred by acquired functions may have facilitated their radiation into a variety of subsurface, marine, and soil environments. We also provide evidence that each of the four AOA orders spans both marine and terrestrial habitats, which suggests a more complex evolutionary history for major AOA lineages than previously proposed. Together, these findings establish a robust phylogenomic framework of AOA and provide new insights into the ecology and adaptation of this globally abundant functional guild.
Ammonia , Archaea , Ammonia/metabolism , Ecosystem , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Oxidation-Reduction , Phylogeny , Soil , Soil Microbiology
ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Quhan Zhiwang decoction (BQZD), a formula in traditional Chinese medicine (TCM), effectively delays bone destruction in rheumatoid arthritis (RA) patients. However, its chemical constituents, absorbed components, and metabolites remain unrevealed, and its mechanism in treating bone destruction in RA needs further investigation. AIM OF THE STUDY: Our objective is to identify the chemical constituents, absorbed components, and metabolites of BQZD and explore the potential mechanisms of BQZD in treating bone destruction in RA. MATERIALS AND METHODS: This study systematically identified the chemical constituents, absorbed components, and metabolites of BQZD using ultra-performance liquid chromatography with Q-Exactive Orbitrap mass spectrometry combined with parallel reaction monitoring. The absorbed components and metabolites were subjected to network pharmacology analysis to predict the potential mechanisms of BQZD in treating bone destruction in RA. The in vivo anti-osteoclastogenic and underlying mechanism were further verified in collagen-induced arthritis (CIA) rats. RESULTS: A total of 182 compounds were identified in BQZD, 27 of which were absorbed into plasma and organs and 42 metabolites were identified in plasma and organs. The KEGG analysis revealed that MAPK signaling pathway was highly prioritized. BQZD treatment attenuated paw swelling and the arthritis index; suppressed synovial hyperplasia, bone destruction, and osteoclast differentiation; and inhibited the levels of TNF-α, IL-1ß, and IL-6 in CIA rats. Mechanically, BQZD significantly decreased the protein expression levels of TRAF6, NFATc1, p-JNK, and p-p38, which might be related to 9 absorbed components and 1 metabolite. CONCLUSION: This study revealed the key active components and metabolites of BQZD. BQZD exhibits bone-protective effects via TRAF6/p38/JNK MAPK pathway, which may be associated with 9 absorbed components and 1 metabolite.
Arthritis, Experimental , Arthritis, Rheumatoid , Drugs, Chinese Herbal , Humans , Rats , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Network Pharmacology , TNF Receptor-Associated Factor 6 , Arthritis, Rheumatoid/drug therapy , Medicine, Chinese Traditional , Arthritis, Experimental/drug therapy
Starch is a major storage carbohydrate in plants and is critical in crop yield and quality. Starch synthesis is intricately regulated by internal metabolic processes and external environmental cues; however, the precise molecular mechanisms governing this process remain largely unknown. In this study, we revealed that high red to far-red (high R:FR) light significantly induces the synthesis of leaf starch and the expression of synthesis-related genes, whereas low R:FR light suppress these processes. Arabidopsis phytochrome B (phyB), the primary R and FR photoreceptor, was identified as a critical positive regulator in this process. Downstream of phyB, basic leucine zipper transcription factor ELONGATED HYPOCOTYL5 (HY5) was found to enhance starch synthesis, whereas the basic helix-loop-helix transcription factors PHYTOCHROME INTERACTING FACTORs (PIF3, PIF4, and PIF5) inhibit starch synthesis in Arabidopsis leaves. Notably, HY5 and PIFs directly compete for binding to a shared G-box cis-element in the promoter region of genes encoding starch synthases GBSS, SS3, and SS4, which leads to antagonistic regulation of their expression and, consequently, starch synthesis. Our findings highlight the vital role of phyB in enhancing starch synthesis by stabilizing HY5 and facilitating PIFs degradation under high R:FR light conditions. Conversely, under low R:FR light, PIFs predominantly inhibit starch synthesis. This study provides insight into the physiological and molecular functions of phyB and its downstream transcription factors HY5 and PIFs in starch synthesis regulation, shedding light on the regulatory mechanism by which plants synchronize dynamic light signals with metabolic cues to module starch synthesis.
OBJECTIVE: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation. METHODS: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms. RESULTS: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model. CONCLUSION: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.
Artemisinins , Sjogren's Syndrome , Mice , Animals , Mice, Inbred NOD , Interleukin-17 , Molecular Docking Simulation , Network Pharmacology , Phosphatidylinositol 3-Kinases , Sjogren's Syndrome/drug therapy , Artemisinins/pharmacology , Artemisinins/therapeutic use
Amyloid-ß, tau pathology, and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease (AD). However, these proteins represent only a fraction of the complex biological processes underlying AD, and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers. More AD-specific early diagnostic and disease staging biomarkers are needed. In this study, we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid (CSF) and serum samples in a discovery cohort comprising 98 participants. Candidate biomarkers were validated by parallel reaction monitoring-based targeted proteomic assays in an independent multicenter cohort comprising 288 participants. We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort, identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers, respectively. In the validation cohort, 58 and 21 CSF proteins, as well as 12 and 18 serum proteins, were verified as early diagnostic and staging biomarkers, respectively. Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment (MCI) due to AD from normal cognition with areas under the curve of 0.984 and 0.881, respectively. The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases. Moreover, we identified 21 CSF and 18 serum stage-associated proteins reflecting AD stages. Our findings provide a foundation for developing blood-based tests for AD screening and staging in clinical practice.
