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BackgroundAcquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) will eventually occur in almost all advanced EGFR-mutant non-small cell lung cancer (EGFR-mutant NSCLC) patients although the therapy has been a standard treatment for such patients. But EGFR-TKIs in combination with anti-angiogenic drugsmay prolong the survival time of these patients.ObjectiveTo explore the efficacy and safety of EGFR-TKIs with anti-angiogenic drugs as the treatment for patients with advanced EGFR-mutant NSCLC.MethodsDatabases including CNKI, CQVIP, Wanfang Data Knowledge Service Platform, PubMed, EMBase, and The Cochrane Library were searched from inception to July 2021 using subject headings with free-text words, for randomized controlled trials (RCTs) about the first-line treatment of advanced EGFR-mutant NSCLC patients with EGFR-TKIs in combination with anti-angiogenic drugs (combination therapy group) versus EGFR-TKIs alone (monotherapy group) . Two researchers performed literature screening, data extraction (the first author, publication time, the country where the author coming from, study type, sample size, stage of NSCLC, sex, average age, treatment regimen, ECOG PS score, median follow-up time, pathological type, gene mutation type, outcome indicators) , separately, and assessed risk of bias in the included RCTs. STATA 15.0 was used formeta-analysis.ResultsNine RCTs were included, involving 1 553 patients. Meta-analysis results showed that the combination therapy was associated with longer progression-free survival (PFS) 〔HR=0.61, 95%CI (0.54, 0.70) , P0.05) . Moreover, the combination therapy was not superior to monotherapy in terms of prolonging the overall survival, and improving the objective response rate, and disease control rate (P>0.05) . However, the rate of adverse eventsabove grade 3〔RR=1.77, 95%CI (1.62, 1.94) , P

Irisin, a myokine derived from fibronectin type III domain-containing 5 (FNDC5), is increasingly recognized for its protective role in musculoskeletal health through the modulation of mitochondrial quality control. This review synthesizes the current understanding of irisin's impact on mitochondrial biogenesis, dynamics, and autophagy in skeletal muscle, elucidating its capacity to bolster muscle strength, endurance, and resilience against oxidative-stress-induced muscle atrophy. The multifunctional nature of irisin extends to bone metabolism, where it promotes osteoblast proliferation and differentiation, offering a potential intervention for osteoporosis and other musculoskeletal disorders. Mitochondrial quality control is vital for cellular metabolism, particularly in energy-demanding tissues. Irisin's influence on this process is highlighted, suggesting its integral role in maintaining cellular homeostasis. The review also touches upon the regulatory mechanisms of irisin secretion, predominantly induced by exercise, and its systemic effects as an endocrine factor. While the therapeutic potential of irisin is promising, the need for standardized measurement techniques and further elucidation of its mechanisms in humans is acknowledged. The collective findings underscore the burgeoning interest in irisin as a keystone in musculoskeletal health and a candidate for future therapeutic strategies. [ABSTRACT FROM AUTHOR]

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA‐coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child–Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro‐inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver‐related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes. [ABSTRACT FROM AUTHOR]

This study simulated the effects of direct predatory pressure, indirect predatory pressure, and conspecific injury signals on sea cucumber (Apostichopus japonicus) to determine changes in the activity of immune defense enzymes (lysozyme, acid phosphatase, alkaline phosphatase) and antioxidant stress enzymes (catalase, superoxide dismutase, malondialdehyde). Samples of sea cucumber juveniles were collected at 3 h, 12 h, 72 h, and 96 h post predatory stress, and six enzymes related to immune defense and antioxidant stress were selected for activity assays, namely, lysozyme (LZM), acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). The results indicate that under direct predatory pressure, the activity of catalase in sea cucumbers was significantly higher than that of the control group at 3 h (P < 0.05), while the activities of acid phosphatase, alkaline phosphatase, and catalase were significantly lower at 72 h (P < 0.05). Under indirect predatory pressure, the activity of malondialdehyde in sea cucumbers was significantly higher than that of the control group at 12 h (P < 0.05), the activity of alkaline phosphatase was significantly higher at 72 and 96 h (P < 0.05), the activity of catalase was significantly lower at 72 h, and the activity of superoxide dismutase was significantly higher at 72 h (P < 0.05). Under the influence of conspecific injury signals, the activity of malondialdehyde in sea cucumbers was significantly higher than that of the control group at 12 h (P < 0.05), and the activity of superoxide dismutase was significantly higher at 96 h (P < 0.05). The sea cucumber enhanced its antioxidant capacity 3 h after facing a predator, while its immune defense mechanism was suppressed at 72 h. When facing indirect predatory pressure, the sea cucumber may have made immune and antioxidant preparations for the arrival of unknown risks. The experimental results show that predatory pressure has a significant impact on the immune and antioxidant functions of sea cucumbers, which may be related to the physiological state and environmental adaptability of the sea cucumber. This study provides a new perspective for understanding how sea cucumbers cope with predatory pressure in the natural environment and offers theoretical support for the cultivation management of sea cucumbers. [ABSTRACT FROM AUTHOR]

Simple Summary: The presence of individual growth differentiation within the sea urchin (Strongylocentrotus intermedius) has significantly hindered the advancement of aquaculture. Despite this, the underlying causes and mechanisms driving these growth disparities remain largely unexplored. Here, we provide evidence that sea urchins of different sizes differ to varying degrees in behavior, gut microbiota compositions, and gene transcription profiles, which may collectively elucidate the observed growth disparities. Firstly, larger sea urchins demonstrated significantly heightened feeding activity compared to smaller sea urchins. Secondly, analysis of the gut microbiota revealed that larger sea urchins possess enhanced digestive efficiency and greater growth potential. Finally, the transcriptome research results prove that small-sized sea urchins were in a state of long-term stress and had some physiological responses to counteract the stress. In conclusion, we have elucidated the potential factors contributing to growth disparities in sea urchins across three distinct levels. This work provides a theoretical basis for regulating the growth of sea urchins, exploring methods to enhance aquaculture production, and promoting the sustainable and healthy development of the sea urchin aquaculture industry. Growth differentiation among farmed sea urchins (Strongylocentrotus intermedius) poses a significant challenge to aquaculture, with there being a limited understanding of the underlying molecular mechanisms. In this study, sea urchins with varying growth rates, reared under identical conditions, were analyzed for feeding behavior, gut microbiota, and transcriptomes. Large-sized sea urchins demonstrated significantly higher feeding ability and longer duration than smaller ones. The dominant phyla across all size groups were Campylobacterota, Proteobacteria, and Firmicutes, with Campylobacterota showing the highest abundance in small-sized sea urchins (82.6%). However, the families Lachnospiraceae and Pseudomonadaceae were significantly less prevalent in small-sized sea urchins. Transcriptome analysis identified 214, 544, and 732 differentially expressed genes (DEGs) in the large vs. medium, large vs. small, and medium vs. small comparisons, respectively. Gene Ontology and KEGG pathway analyses associated DEGs with key processes such as steroid biosynthesis, protein processing within the endoplasmic reticulum, and nucleotide sugar metabolism. Variations in phagosomes and signaling pathways indicated that size differences are linked to disparities in energy expenditure and stress responses. These findings provide a foundation for future investigations into the regulatory mechanisms underlying growth differences in S. intermedius and provide clues for the screening of molecular markers useful to improve sea urchin production. [ABSTRACT FROM AUTHOR]

The magmatic-hydrothermal transition in granite-related, rare-metal metallogenic systems has received great attention as economic rare metal (including rare earth) minerals reach saturation and trigger mineralization at this stage. However, deciphering the details of the melt-fluid evolution process and the distribution behavior of rare metals remains difficult. Here, we applied tourmaline chemistry and B isotopes to unravel processes at the magmatic-hydrothermal transition that are responsible for rare-metal partitioning in the Huoshibulake (HS) and Tamu (TM) REE-Nb-mineralized intrusions in Southern Tianshan, SW Central Asian Orogenic Belt. Three types of tourmaline are identified in the plutons: (1) disseminated tourmaline in the granite, with a brown-yellow core (HS-DB) and blue-green rim (HS-DG); (2) orbicular tourmaline, with a brown-yellow core (HS-OB and TM-OB) and blue-green rim (HS-OG and TM-OG); and (3) vein tourmaline (HS-V and TM-V). Compositionally, all these tourmalines exhibit extremely low Ca and Mg contents and are classified as schorl. The substitution processes of major-element variations are dominantly caused by (Al,□)(Fe,Na)−1 exchange vectors. Four generations of tourmaline crystallization are established based on the petrographic, compositional, and B isotopes evolution of the tourmaline. First, the HS-DB crystals crystallized from the highly evolved residual melt, and then HS-OB and TM-OB precipitated from immiscible B-rich aqueous melts during the magmatic-hydrothermal transition. Subsequently, the blue-green overgrowths (HS-DG, HS-OG, and TM-OG) crystallized from exsolved hydrothermal fluids. Finally, the formation of HS-V and TM-V resulted from another melt pulse from a deeper magma chamber. The magmatic tourmaline exhibits a narrow range of δ11B values between −12.6 to −10.0‰, while the hydrothermal tourmaline shows significantly heavier and variable δ11B values ranging from −10.2 to −4.9‰. The fractionation of B isotopes is reproduced by Rayleigh fractionation modeling. Lower Nb and Sn contents in the orbicular tourmaline relative to those precipitated from the residual melt, along with the lack of rare-metal minerals in the orbicules, indicate that B-rich melt/fluid exsolution does not necessarily contribute to the rare-metal mineralization. In comparison, the veins contain abundant rare-metal and REE minerals in close paragenesis with fluorite, and the vein tourmaline shows high-Nb and -Sn contents. These observations suggest that saturation of fluorite triggered the precipitation of rare metals, and fluorine played a critical role in rare metal concentration and mineralization. This study highlights the potential of tourmaline to trace the magmatic-hydrothermal transition and provide insights into rare-metal mineralization in the granitic systems. [ABSTRACT FROM AUTHOR]

This paper examines the jump risk contagion between the US and China during the financial crisis driven by COVID-19, and the impact of a series of determinants to detect the transmission mechanisms. Specifically, we employ the ARJI–GARCH model to capture jump behavior and apply the Clayton Copula to construct lower tail jump contagion. Furthermore, we conduct regression analysis on variables related to economic fundamentals and investor behavior to explore the fundamental or pure contagion hypotheses. Our results suggest an increased jump dependence during major catastrophic crises such as COVID-19, but it is closer to a memory-less process. Besides, bilateral trade, similarity in fundamentals and investor behavior are all important determinants, and pure contagion hypothesis exists between the Chinese and US stock markets during the pandemic. [ABSTRACT FROM AUTHOR]

Background: : Colorectal cancer (CRC) is one of the most common cancers worldwide. As the molecular mechanism for liver metastasis of CRC has not yet been completely discovered, identification of hub genes and pathways of this disease is of importance for revealing potential molecular mechanism of colorectal cancer progression. This study aimed to identify potential biomarkers and survival analysis of hub genes for CRC treatment. Methods: : The differentially expressed genes (DEGs) between colorectal cancer liver metastasis and primary tumor were screened using microarray data from two datasets GSE179979, GSE144259 obtained from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and KEGG pathway enrichment analyses were performed for DEGs using DAVID database, the protein-protein interaction (PPI) network was constructed using the Cytoscape software, and module analysis was performed using MCODE. Then, overall survival (OS), progression free interval (PFI) and disease specific survival (DSS) analysis of hub genes was performed by using TCGA database. The correlations between hub genes and clinical values were validated through CRN and immunohistochemistry (IHC) stain. Results: : A total of 64 DEGs were obtained, KEGG pathway analysis showed that the significant pathways included PPAR signaling pathway, Complement and coagulation cascades. Four hub genes (ITIH2, ALB, CPB2, HGFAC) and two biomarkers (CPB2, HGFAC) with significantly prognostic values were verified by Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) cohort. Conclusions: : CPB2 and HGFAC may serve as new biomarkers in diagnosing liver metastasis of CRC or potential drug target.

Background and purpose: This study aims to evaluate whether dosimetric parameters affect the intrahepatic out-field recurrence or distant metastasis-free survival following the stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC). Materials and methods: A total of 76 patients with HCC who were treated with SBRT from January 2015 to May 2020 were included in this retrospective study. The main clinical endpoints considered were intrahepatic out-field free survival (OutFFS) and distant metastasis-free survival (DMFS). The target parameters and the liver were documented including tumor diameters, gross tumor volume (GTV), Liver minus GTV volume (LGV), and Liver minus GTV mean dose (LGD). Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for OutFFS and DMFS. Maximally selected rank statistics were used to determine the most informative cut-off value for age and LGD. Results: The median follow-up was 28.2 months (range, 7.7–74.5 months). LGD higher than 12.54 Gy [HR, 0.861(0.747–0.993); p = 0.040] and age greater than 67-year-old [HR, 0.966(0.937–0.997); p = 0.030] are two independent predictors of OutFFS, previous TACE treatment [HR, 0.117(0.015–0.891); p = 0.038] was an independent predictor of DMFS. Conclusions: The results of this study suggested that the higher the dose received by the normal liver (greater than 12.54 Gy) the better the intrahepatic out-field recurrence-free survival (RFS) rate. Further study is warranted to confirm and to better understand this phenomenon.