Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation.

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

Clinical and pathological features of 52 patients with glomerulonephritis with dominant C3. / C3沉积为主的肾小球肾炎52ä¾‹ä¸´åºŠä¸Žç— ç†ç‰¹å¾.

OBJECTIVES: With the in-depth study of complement dysregulation, glomerulonephritis with dominant C3 has received increasing attention, with a variety of pathologic types and large differences in symptoms and prognosis between pathologic types. This study analyzes the clinical, pathological, and prognostic characteristics of different pathological types of glomerulonephritis with dominant C3, aiming to avoid misdiagnosis and missed diagnoses. METHODS: The clinical, pathological, and follow-up data of 52 patients diagnosed as glomerulonephritis with dominant C3 by renal biopsy from June 2013 to October 2022 were retrospectively analyzed. According to the clinical feature and results of pathology, 15 patients with post-infectious glomerulonephritis (PIGN) and 37 patients with of non-infectious glomerulonephritis (N-PIGN) were classified. N-PIGN subgroup analysis was performed, and 16 patients were assigned into a C3-alone-deposition group and 21 in a C3-dominant-deposition group, or 27 in a C3 glomerulopathy (C3G) group and 10 in a non-C3 nephropathy (N-C3G) group. RESULTS: The PIGN group had lower creatinine values (84.60 µmol/L vs179.62 µmol/L, P=0.001), lower complement C3 values (0.36 g/L vs0.74 g/L, P<0.001) at biopsy, and less severe pathological chronic lesions compared with the N-PIGN group. In the N-PIGN subgroup analysis, the C3-dominant-deposition group had higher creatinine values (235.30 µmol/L vs106.70 µmol/L, P=0.004) and higher 24-hour urine protein values (4 025.62 mg vs1 981.11 mg, P=0.037) than the C3-alone-deposition group. The prognosis of kidney in the PIGN group (P=0.049), the C3-alone-deposition group (P=0.017), and the C3G group (P=0.018) was better than that in the N-PIGN group, the C3-dominant-deposition group, and the N-C3G group, respectively. CONCLUSIONS: Glomerulonephritis with dominant C3 covers a variety of pathological types, and PIGN needs to be excluded before diagnosing C3G because of considerable overlap with atypical PIGN and C3G; in addition, the deposition of C1q complement under fluorescence microscope may indicate poor renal prognosis, and relevant diagnosis, treatment, and follow-up should be strengthened.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Extending the reach of multi-core fiber via Voronoi constellations with concatenated multilevel coding.

This Letter proposes a novel, to the best of our knowledge, coded modulation scheme for randomly coupled multi-core fiber (RC-MCF) via multidimensional (MD) constellation with concatenated two-level multilevel coding (MLC). In the proposed system, the 16-dimensional (16D) Voronoi constellation (VC), naturally fitting with the 16 degrees of freedom of a four-core fiber (two quadratures, two polarizations, and four cores), is generated by a latticed-based shaping method to provide higher shaping gains. Moreover, combining it with the concatenated two-level MLC can further achieve better performance-complexity trade-off. It is demonstrated by simulation results of long-haul multi-channel RC-MCF transmission that the proposed coded modulation scheme for four-core fiber transmission offers 77% reduction in the number of decoding operations and up to 21% (585 km) reach increase over the conventional bit-interleaved coded modulation scheme for quadrature amplitude modulation.

Hypermethylation of Bmp2 and Fgfr2 Promoter Regions in Bone Marrow Mesenchymal Stem Cells Leads to Bone Loss in Prematurely Aged Mice.

Osteoporosis is an age-related, systemic skeletal disease that poses a significant public health challenge in contemporary society. Development at the epigenetic level is emerging as an important pathogenic mechanism of osteoporosis. Despite indications of a robust association between DNA methylation and osteoporosis development, a comprehensive understanding of the specific role of DNA methylation in osteoporosis remains limited. In this study, significant bone loss was detected at the beginning of eight weeks of age in mouse models of premature aging (SHJHhr mice). We identified a notable upregulation of DNA methyltransferase 3b/3l (Dnmt3b/l) and downregulation of ten eleven translocation dioxygenase 1 (Tet1) in bone marrow mesenchymal stem cells (BMSCs) isolated from SHJHhr mice, along with an increase in the overall 5-methylcytosine (5mC) levels. Moreover, methylation capture sequencing revealed genomic hypermethylation in SHJHhr mice BMSCs. Integrated methylome and transcriptome analyses revealed several crucial methylated genes and networks that are potentially associated with osteoporosis development. Notably, elevated methylation levels of genes linked to the Wnt signaling pathway, particularly bone morphogenetic protein 2 (Bmp2) and fibroblast growth factor receptor (Fgfr2), appeared to compromise the osteogenic differentiation potential of BMSCs. Concurrently, DNA methyltransferase inhibitors attenuated the methylation of the promoter regions of Bmp2 and Fgfr2 and rescued the osteogenic differentiation potential of the BMSCs from SHJHhr mice. In summary, our study provides novel insights into the role of DNA methylation in the development of osteoporosis and suggests promising prospects for employing epigenetic interventions to manage osteoporosis.

Vertically Integrated Monolithic Neuromorphic Nanowire Device for Physiological Information Processing.

This study demonstrates the conceptual design and fabrication of a vertically integrated monolithic (VIM) neuromorphic device. The device comprises an n-type SnO2 nanowire bottom channel connected by a shared gate to a p-type P3HT nanowire top channel. This architecture establishes two distinct neural pathways with different response behaviors. The device generates excitatory and inhibitory postsynaptic currents, mimicking the corelease mechanism of bilingual synapses. To enhance the signal processing efficiency, we employed a bipolar spike encoding strategy to convert fluctuating sensory signals to spike trains containing positive and negative pulses. Utilizing the neuromorphic platform for synaptic processing, physiological signals featuring bidirectional fluctuations, including electrocardiogram and breathing signals, can be classified with an accuracy of over 90%. The VIM device holds considerable promise as a solution for developing highly integrated neuromorphic hardware for healthcare and edge intelligence applications.

Clinical Significance of Serum CTRP3 Level in the Prediction of Cardiac and Intestinal Mucosal Barrier Dysfunction in Patients with Severe Acute Pancreatitis.

C1q/tumor necrosis factor-related protein 3 (CTRP3) has been demonstrated to play a protective role in mice with severe acute pancreatitis (SAP). However, its clinical significance in SAP remains unknown. This study was conducted to explore the clinical values of serum C1q/tumor necrosis factor-related protein 3 (CTRP3) level in the diagnosis of cardiac dysfunction (CD) and intestinal mucosal barrier dysfunction (IMBD) in SAP. Through RT-qPCR, we observed decreased CTRP3 level in the serum of SAP patients. Serum CTRP3 level was correlated with C-reactive protein, procalcitonin, creatine, modified computed tomography severity index score, and Acute Physiology and Chronic Health Evaluation II score. The receiver-operating characteristic curve revealed that CTRP3 serum level < 1.005 was conducive to SAP diagnosis with 72.55% sensitivity and 60.00% specificity, CTRP3 < 0.8400 was conducive to CD diagnosis with 80.49% sensitivity and specificity 65.57%, CTRP3 < 0.8900 was conducive to IMBD diagnosis with 94.87% sensitivity and 63.49% specificity, and CTRP3 < 0.6250 was conducive to the diagnosis of CD and IMBD co-existence with 65.22% sensitivity and 89.87% specificity. Generally, CTRP3 was downregulated in the serum of SAP patients and served as a candidate biomarker for the diagnosis of SAP and SAP-induced CD and IMBD.

Efficient Expression of Functionally Active Aflibercept with Designed N-glycans.

Aflibercept is a therapeutic recombinant fusion protein comprising extracellular domains of human vascular endothelial growth factor receptors (VEGFRs) and IgG1-Fc. It is a highly glycosylated protein with five N-glycosylation sites that might impact it structurally and/or functionally. Aflibercept is produced in mammalian cells and exhibits large glycan heterogeneity, which hampers glycan-associated investigations. Here, we report the expression of aflibercept in a plant-based system with targeted N-glycosylation profiles. Nicotiana benthamiana-based glycoengineering resulted in the production of aflibercept variants carrying designed carbohydrates, namely, N-glycans with terminal GlcNAc and sialic acid residues, herein referred to as AFLIGnGn and AFLISia, respectively. Both variants were transiently expressed in unusually high amounts (2 g/kg fresh leaf material) in leaves and properly assembled to dimers. Mass spectrometric site-specific glycosylation analyses of purified aflibercept showed the presence of two to four glycoforms in a consistent manner. We also demonstrate incomplete occupancy of some glycosites. Both AFLIGnGn and AFLISia displayed similar binding potency to VEGF165, with a tendency of lower binding to variants with increased sialylation. Collectively, we show the expression of functionally active aflibercept in significant amounts with controlled glycosylation. The results provide the basis for further studies in order to generate optimized products in the best-case scenario.

Construction of Nickel Single Atoms by Using the Inherent Confined Space in Template-Occupied Mesoporous Silica.

Due to their maximum atomic use of metal sites, single-atom catalysts (SACs) exhibit excellent catalytic activity in a variety of reactions. Although many techniques have been reported for the production of SACs, the construction of single atoms through a convenient strategy is still challenging. Here, we provide a facile method to prepare nickel SACs by utilizing the inherent confined space between the template and silica walls in template-occupied mesoporous silica KIT-6 (TOK). After the introduction of nickel-containing precursors into the inherent confined space of the TOK by solid-phase grinding, Ni SACs can be produced promptly during calcination. Single Ni atoms create a covalent Ni-O-Si structure in the TOK, as indicated by density functional theory (DFT) calculations and experimental data. This synthetic approach is easy to scale up, and 10 g of sample can be effortlessly synthesized using ball milling. The resultant Ni SACs were applied to the oxygen evolution reaction and exhibited higher catalytic activity and stability than the comparative sample synthesized in the absence of confined space.

A review: Mechanisms and molecular pathways of signaling lymphocytic activation molecule family 3 (SLAMF3) in immune modulation and therapeutic prospects.

The signaling lymphocytic activation molecule (SLAM) family participates in the modulation of various innate and adaptive immune responses. SLAM family (SLAMF) receptors include nine transmembrane glycoproteins, of which SLAMF3 (also known as CD229 or Ly9) has important roles in the modulation of immune responses, from the fundamental activation and suppression of immune cells to the regulation of intricate immune networks. SLAMF3 is mainly expressed in immune cells, such as T, B, and natural killer cells. It has a unique molecular structure, including four immunoglobulin-like domains in the extracellular domain and two immunoreceptor tyrosine-based signaling motifs in the intracellular structural domains. These unique structures have important implications for protein functioning. SLAMF3 is involved in pathogenesis of various disease, particularly autoimmune diseases and cancer. However, despite its potential clinical significance, a comprehensive overview of the current paradigm of SLAMF3 research is lacking. This review summarizes the structure, functional mechanisms, and therapeutic implications of SLAMF3. Our findings highlight the significance of SLAMF3 in both physiological and pathological contexts, and underline its dual role in autoimmunity and malignancies, and including disease progression and prognosis. The review also proposes that future studies on SLAMF3 should explore its context-specific inhibitory and stimulatory effects, expand on its potential in disease mapping, investigate related signaling pathways, and explore its value as a drug target. Research in these areas related to SLAMF3 can provide more precise directions for future therapeutic strategies.

Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study.

The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified.

A hyperelastic hydrogel with an ultralarge reversible biaxial strain.

Hyperelastic materials exhibit a nonlinear elastic response to large strains, whereas hydrogels typically possess a low elastic range due to the nonuniform cross-linking and limited chain segments among cross-links. We developed a hyperelastic hydrogel that possesses a broader elastic range by introducing a reversible pearl-necklace structure, in which beads are connected by strings. The subnanometric beads can efficiently unfold and refold under cyclic mechanical strains; thus, the hydrogel can rapidly recover after being stretched to an areal strain of more than 10,000%. Additionally, the hydrogel can quickly heal from minor mechanical damages such as needle punctures and cuts. These advancements make our ionic hydrogels ideal for multifunctional pneumatic gripper materials; they simultaneously offer an ultralarge gripping range, self-sensing capabilities, and fast healing abilities.

Network pharmacology and molecular docking to explore the mechanism of a clinical proved recipe for external use of clearing heat and removing dampness in the treatment of immune-related cutaneous adverse events.

Immune-related cutaneous adverse events (ircAEs) will undermine the patients' quality of lives, and interrupt the antitumor therapy. A clinical proved recipe for external use of clearing heat and removing dampness (Qing-Re-Li-Shi Formula, hereinafter referred to as "QRLSF") is beneficial to the treatment of ircAEs in clinical practice. Our study will elucidate the mechanism of QRLSF against ircAEs based on network pharmacology and molecular docking. The active components and corresponding targets of QRLSF were collected through traditional Chinese medicine systems pharmacology database. GeneCards, online Mendelian inheritance in man, and pharmacogenomics knowledgebase were used to screen the targets of ircAEs. The intersecting targets between drug and disease were acquired by venn analysis. Cytoscape software was employed to construct "components-targets" network. Search tool for the retrieval of interacting genes/proteins database was applied to establish the protein-protein interaction network and then its core targets were identified. Gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed to predict the mechanism. The molecular docking verification of key targets and related phytomolecules was accomplished by AutoDock Vina software. Thirty-nine intersecting targets related to QRLSF against ircAEs were recognized. The analysis of network clarified 5 core targets (STAT3, RELA, TNF, TP53, and NFKBIA) and 4 key components (quercetin, apigenin, luteolin, and ursolic acid). The activity of QRLSF against ircAEs could be attributed to the regulation of multiple biological effects via multi-pathways (PI3K-Akt pathway, cytokine-cytokine receptor interaction, JAK-STAT pathway, chemokine pathway, Th17 cell differentiation, IL-17 pathway, TNF pathway, and Toll-like receptor pathway). The binding activities were estimated as good level by molecular docking. These discoveries disclosed the multi-component, multi-target, and multi-pathway characteristics of QRLSF against ircAEs, providing a new strategy for such medical problem.

Efficacy Assessment of Post-nephrectomy Adjuvant Therapies in Patients with Renal Cell Carcinoma.

OBJECTIVE: The objective of our study was to integrate the efficacy results of post-nephrectomy adjuvant therapies in renal cell carcinoma (RCC) patients with risk of recurrence, and attempt to determine the optimal intervention choice. METHODS: We performed standard meta-analysis procedures in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed, Embase, and Cochrane Library databases were searched from inception to 22 September 2022. Randomized controlled trials reporting overall survival (OS) or disease-free survival (DFS) of adjuvant therapies, including immune checkpoint inhibitors (ICIs) and targeted therapies, in adult post-nephrectomy RCC patients were eligible for inclusion. RESULTS: Seven studies involving 7548 participants were included in our analyses. In contrast with placebo, DFS benefit with ICIs was only observed in female RCC patients and RCC patients with high programmed death-ligand 1 (PD-L1) expression (≥ 1%), sarcomatoid features, and M0 intermediate-high risk. Network meta-analyses demonstrated that pembrolizumab exhibited both DFS and OS benefit compared with placebo, sunitinib, sorafenib, and girentuximab, and only DFS benefit compared with atezolizumab and nivolumab plus ipilimumab. CONCLUSIONS: Our results suggest that post-nephrectomy RCC patients with sarcomatoid differentiation and high PD-L1 expression were more responsive to ICIs. Furthermore, pembrolizumab monotherapy exhibited superior DFS and OS results over other adjuvant therapies.

Integration of Network Pharmacology and Experimental Validation to Explore Jixueteng - Yinyanghuo Herb Pair Alleviate Cisplatin-Induced Myelosuppression.

Jixueteng, the vine of the bush Spatholobus suberectus Dunn., is widely used to treat irregular menstruation and arthralgia. Yinyanghuo, the aboveground part of the plant Epimedium brevicornum Maxim., has the function of warming the kidney to invigorate yang. This research aimed to investigate the effects and mechanisms of the Jixueteng and Yinyanghuo herbal pair (JYHP) on cisplatin-induced myelosuppression in a mice model. Firstly, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) screened 15 effective compounds of JYHP decoction. Network pharmacology enriched 10 genes which may play a role by inhibiting the apoptosis of bone marrow (BM) cells. Then, a myelosuppression C57BL/6 mice model was induced by intraperitoneal (i.p.) injection of cis-Diaminodichloroplatinum (cisplatin, CDDP) and followed by the intragastric (i.g.) administration of JYHP decoction. The efficacy was evaluated by blood cell count, reticulocyte count, and histopathological analysis of bone marrow and spleen. Through the vivo experiments, we found the timing of JYHP administration affected the effect of drug administration, JYHP had a better therapeutical effect rather than a preventive effect. JYHP obviously recovered the hematopoietic function of bone marrow from the peripheral blood cell test and pathological staining. Flow cytometry data showed JYHP decreased the apoptosis rate of BM cells and the western blotting showed JYHP downregulated the cleaved Caspase-3/Caspase-3 ratios through RAS/MEK/ERK pathway. In conclusion, JYHP alleviated CDDP-induced myelosuppression by inhibiting the apoptosis of BM cells through RAS/MEK/ERK pathway and the optimal timing of JYHP administration was after CDDP administration.

Research and application of deep learning-based sleep staging: Data, modeling, validation, and clinical practice.

Over the past few decades, researchers have attempted to simplify and accelerate the process of sleep stage classification through various approaches; however, only a few such approaches have gained widespread acceptance. Artificial intelligence technology, particularly deep learning, is promising for earning the trust of the sleep medicine community in automated sleep-staging systems, thus facilitating its application in clinical practice and integration into daily life. We aimed to comprehensively review the latest methods that are applying deep learning for enhancing sleep staging efficiency and accuracy. Starting from the requisite "data" for constructing deep learning algorithms, we elucidated the current landscape of this domain and summarized the fundamental modeling process, encompassing signal selection, data pre-processing, model architecture, classification tasks, and performance metrics. Furthermore, we reviewed the applications of automated sleep staging in scenarios such as sleep-disorder screening, diagnostic procedures, and health monitoring and management. Finally, we conducted an in-depth analysis and discussion of the challenges and future in intelligent sleep staging, particularly focusing on large-scale sleep datasets, interdisciplinary collaborations, and human-computer interactions.

Bacteroidaceae, Bacteroides, and Veillonella: emerging protectors against Graves' disease.

Background: Graves' disease (GD) is the most common cause of hyperthyroidism, and its pathogenesis remains incompletely elucidated. Numerous studies have implicated the gut microbiota in the development of thyroid disorders. This study employs Mendelian randomization analysis to investigate the characteristics of gut microbiota in GD patients, aiming to offer novel insights into the etiology and treatment of Graves' disease. Methods: Two-sample Mendelian randomization (MR) analysis was employed to assess the causal relationship between Graves' disease and the gut microbiota composition. Gut microbiota data were sourced from the international consortium MiBioGen, while Graves' disease data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analysis methods, including inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS, were utilized. Sensitivity analyses were conducted employing MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis as quality control measures. Results: The Mendelian randomization study conducted in a European population revealed a decreased risk of Graves' disease associated with Bacteroidaceae (Odds ratio (OR) [95% confidence interval (CI)]: 0.89 [0.89 ~ 0.90], adjusted P value: <0.001), Bacteroides (OR: [95% CI]: 0.555 [0.437 ~ 0.706], adjusted P value: <0.001), and Veillonella (OR [95% CI]: 0.632 [0.492 ~ 0.811], adjusted P value: 0.016). No significant evidence of heterogeneity, or horizontal pleiotropy was detected. Furthermore, the preliminary MR analysis identified 13 bacterial species including Eubacterium brachy group and Family XIII AD3011 group, exhibiting significant associations with Graves' disease onset, suggesting potential causal effects. Conclusion: A causal relationship exists between gut microbiota and Graves' disease. Bacteroidaceae, Bacteroides, and Veillonella emerge as protective factors against Graves' disease development. Prospective probiotic supplementation may offer a novel avenue for adjunctive treatment in the management of Graves' disease in the future.

Toward Predicting Interfacial Tension of Impure and Pure CO2-Brine Systems Using Robust Correlative Approaches.

In the context of global climate change, significant attention is being directed toward renewable energy and the pivotal role of carbon capture and storage (CCS) technologies. These innovations involve secure CO2 storage in deep saline aquifers through structural and capillary processes, with the interfacial tension (IFT) of the CO2-brine system influencing the storage capacity of formations. In this study, an extensive data set of 2811 experimental data points was compiled to model the IFT of impure and pure CO2-brine systems. Three white-box machine learning (ML) methods, namely, genetic programming (GP), gene expression programming (GEP), and group method of data handling (GMDH) were employed to establish accurate mathematical correlations. Notably, the study utilized two distinct modeling approaches: one focused on impurity compositions and the other incorporating a pseudocritical temperature variable (Tcm) offering a versatile predictive tool suitable for various gas mixtures. Among the correlation methods explored, GMDH, employing five inputs, exhibited exceptional accuracy and reliability across all metrics. Its mean absolute percentage error (MAPE) values for testing, training, and complete data sets stood at 7.63, 7.31, and 7.38%, respectively. In the case of six-input models, the GEP correlation displayed the highest precision, with MAPE values of 9.30, 8.06, and 8.31% for the testing, training, and total data sets, respectively. The sensitivity and trend analyses revealed that pressure exerted the most significant impact on the IFT of CO2-brine, showcasing an adverse effect. Moreover, an impurity possessing a critical temperature below that of CO2 resulted in an elevated IFT. Consequently, this relationship leads to higher impurity concentrations aligning with lower Tcm values and subsequently elevated IFT. Also, monovalent and divalent cation molalities exhibited a growing influence on the IFT, with divalent cations exerting approximately double the influence of monovalent cations. Finally, the Leverage approach confirmed both the reliability of the experimental data and the robust statistical validity of the best correlations established in this study.

Unraveling the mystery: a Mendelian randomized exploration of gut microbiota and different types of obesity.

Background: Numerous studies have demonstrated the influence of gut microbiota on the development of obesity. In this study, we utilized Mendelian randomization (MR) analysis to investigate the gut microbiota characteristics among different types of obese patients, aiming to elucidate the underlying mechanisms and provide novel insights for obesity treatment. Methods: Two-sample multivariable Mendelian randomization (MR) analysis was employed to assess causal relationships between gut microbiota and various obesity subtypes. Gut microbiota data were obtained from the international consortium MiBioGen, and data on obese individuals were sourced from the Finnish National Biobank FinnGen. Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables. Various analytical methods, including inverse variance weighted (IVW), MR-Egger regression, weighted median, MR-RAPS, and Lasso regression, were applied. Sensitivity analyses for quality control included MR-Egger intercept tests, Cochran's Q tests, and leave-one-out analyses and others. Results: Mendelian randomization studies revealed distinct gut microbiota profiles among European populations with different obesity subtypes. Following multivariable MR analysis, we found that Ruminococcaceae UCG010 [Odds Ratio (OR): 0.842, 95% confidence interval (CI): 0.766-0.926, Adjusted P value: 0.028] independently reduced the risk of obesity induced by excessive calorie intake, while Butyricimonas [OR: 4.252, 95% CI: 2.177-8.307, Adjusted P value: 0.002] independently increased the risk of medication-induced obesity. For localized adiposity, Pasteurellaceae [OR: 0.213, 95% CI: 0.115-0.395, Adjusted P value: <0.001] acted as a protective factor. In the case of extreme obesity with alveolar hypoventilation, lactobacillus [OR: 0.724, 95% CI: 0.609-0.860, Adjusted P value: 0.035] reduced the risk of its occurrence. Additionally, six gut microbiota may have potential roles in the onset of different types of obesity. Specifically, the Ruminococcus torques group may increase the risk of its occurrence. Desulfovibrio and Catenabacterium may serve as protective factors in the onset of Drug-induced obesity. Oxalobacteraceae, Actinomycetaceae, and Ruminiclostridium 9, on the other hand, could potentially increase the risk of Drug-induced obesity. No evidence of heterogeneity or horizontal pleiotropy among SNPs was found in the above studies (all P values for Q test and MR-Egger intercept > 0.05). Conclusion: Gut microbiota abundance is causally related to obesity, with distinct gut microbiota profiles observed among different obesity subtypes. Four bacterial species, including Ruminococcaceae UCG010, Butyricimonas, Pasteurellaceae and lactobacillus independently influence the development of various types of obesity. Probiotic and prebiotic supplementation may represent a novel approach in future obesity management.

Facile synthesis of gold nanostars for the duplex detection of pesticide residues in grapes using SERS.

In recent years, concerns have been raised regarding the contamination of grapes with pesticide residues. As consumer demand for safer food products grows, regular monitoring of pesticide residues in food has become essential. This study sought to develop a rapid and sensitive technique for detecting two specific pesticides (phosmet and paraquat) present on the grape surface using the surface-enhanced Raman spectroscopy (SERS) method. Gold nanostars (AuNS) particles were synthesized, featuring spiky tips that act as hot spots for localized surface plasmon resonance, thereby enhancing Raman signals. Additionally, the roughened surface of AuNS increases the surface area, resulting in improved interactions between the substrate and analyte molecules. Prominent Raman peaks of mixed contaminants were acquired and used to characterize and quantify the pesticides. It was observed that the SERS intensity of the Raman peaks changed in proportion to the concentration ratio of phosmet and paraquat. Moreover, AuNS exhibited superior SERS enhancement compared to gold nanoparticles. The results demonstrate that the lowest detectable concentration for both pesticides on grape surfaces is 0.5 mg/kg. These findings suggest that SERS coupled with AuNS constitutes a practical and promising approach for detecting and quantifying trace contaminants in food. PRACTICAL APPLICATION: This research established a novel surface-enhanced Raman spectroscopy (SERS) method coupled with a simplified extraction protocol and gold nanostar substrates to detect trace levels of pesticides in fresh produce. The detection limits meet the maximum residue limits set by the EPA. This substrate has great potential for rapid measurements of chemical contaminants in foods.