An esophagectomy surgical Apgar score-based nomogram-a risk-based postoperative triage system: a phase II randomised trial.

Background: The esophagectomy surgical Apgar score (eSAS) has been found to be a predictor of postoperative complications in esophagectomy. In our previous study, we built a graphic nomogram based on eSAS and demonstrated that it can effectively predict the risk of major morbidity after esophagectomy. In this study, we aimed to assess the benefits of using an eSAS-based nomogram model as a postoperative risk-based triage system for patients undergoing esophagectomy. Methods: We enrolled 119 patients diagnosed with esophageal carcinoma and randomly assigned them to a nomogram group (NG) or control group (CG) from January 2019 to December 2020. Patients in the NG were assigned to a low-risk group and high-risk group based on the nomogram. Patients in the high-risk group were admitted to the intensive care unit (ICU) after esophagectomy. Risk estimation in the CG patients was based on the surgeon's clinical experience. Thirty-day major complications, postoperative hospital stay, hospital costs, and quality of life (QOL) during the follow-up were compared between the two groups. Results: Baseline clinicopathological characteristics were comparable between the NG (n=58) and CG (n=61). All patients underwent esophagectomy. Postoperative complications were significantly higher in the CG (30, 49.2%) than in the NG (14, 24.1%) (P=0.008), with pneumonia being the most common (CG: 23, 37.7%; NG: 12, 20.7%; P=0.042). There was no significant difference in anastomotic leakage (NG: 1, 1.7%; CG: 6, 9.8%; P=0.12). Postoperative median hospital stay was shorter in the NG (14 days) than in the CG (16 days) (P=0.041). Hospital costs (NG: ¥60,045.1; CG: ¥63,961.5; P=0.21) and postoperative QOL did not differ significantly between groups. Conclusions: An eSAS-based nomogram as a triage system can reduce the overall occurrence of postoperative complications and shorten postoperative hospital stay without increasing hospital costs. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900021636.

Modified Unit-Mediated Strand Displacement Reactions for Direct Detection of Single Nucleotide Variants in Active Double-Stranded DNA.

Accurate identification of single nucleotide variants (SNVs) in key driver genes holds a significant value for disease diagnosis and treatment. Fluorescent probes exhibit tremendous potential in specific, high-resolution, and rapid detection of SNVs. However, additional steps are required in most post-PCR assays to convert double-stranded DNA (dsDNA) products into single-stranded DNA (ssDNA), enabling them to possess hybridization activity to trigger subsequent reactions. This process not only prolongs the complexity of the experiment but also introduces the risk of losing target information. In this study, we proposed two strategies for enriching active double-stranded DNA, involving PCR based on obstructive groups and cleavable units. Building upon this, we explored the impact of modified units on the strand displacement reaction (SDR) and assessed their discriminatory efficacy for mutations. The results showed that detection of low variant allele frequencies (VAF) as low as 0.1% can be achieved. The proposed strategy allowed orthogonal identification of 45 clinical colorectal cancer tissue samples with 100% specificity, and the results were generally consistent with sequencing results. Compared to existing methods for enriching active targets, our approach offers a more diverse set of enrichment strategies, characterized by the advantage of being simple and fast and preserving original information to the maximum extent. The objective of this study is to offer an effective solution for the swift and facile acquisition of active double-stranded DNA. We anticipate that our work will facilitate the practical applications of SDR based on dsDNA.

Deep sequencing identified miR-193b-3p as a positive regulator of autophagy targeting Akt3 in Ctenopharyngodon idella CIK cells during GCRV infection.

Recent research has highlighted complex and close interaction between miRNAs, autophagy, and viral infection. In this study, we observed the autophagy status in CIK cells infected with GCRV at various time points. We found that GCRV consistently induced cellar autophagy from 0 h to 12 h post infection. Subsequently, we performed deep sequencing on CIK cells infected with GCRV at 0 h and 12 h respectively, identifying 38 DEMs and predicting 9581 target genes. With the functional enrichment analyses of GO and KEGG, we identified 35 autophagy-related target genes of these DEMs, among which akt3 was pinpointed as the most central hub gene using module assay of the PPI network. Then employing the miRanda and Targetscan programs for prediction, and verification through a double fluorescent enzyme system and qPCR method, we confirmed that miR-193 b-3p could target the 3'-UTR of grass carp akt3, reducing its gene expression. Ultimately, we illustrated that grass carp miR-193 b-3p could promote autophagy in CIK cells. Above results collectively indicated that miRNAs might play a critical role in autophagy of grass carp during GCRV infection and contributed significantly to antiviral immunity by targeting autophagy-related genes. This study may provide new insights into the intricate mechanisms involved in virus, autophagy, and miRNAs.

DNA-based molecular classifiers for the profiling of gene expression signatures.

Although gene expression signatures offer tremendous potential in diseases diagnostic and prognostic, but massive gene expression signatures caused challenges for experimental detection and computational analysis in clinical setting. Here, we introduce a universal DNA-based molecular classifier for profiling gene expression signatures and generating immediate diagnostic outcomes. The molecular classifier begins with feature transformation, a modular and programmable strategy was used to capture relative relationships of low-concentration RNAs and convert them to general coding inputs. Then, competitive inhibition of the DNA catalytic reaction enables strict weight assignment for different inputs according to their importance, followed by summation, annihilation and reporting to accurately implement the mathematical model of the classifier. We validated the entire workflow by utilizing miRNA expression levels for the diagnosis of hepatocellular carcinoma (HCC) in clinical samples with an accuracy 85.7%. The results demonstrate the molecular classifier provides a universal solution to explore the correlation between gene expression patterns and disease diagnostics, monitoring, and prognosis, and supports personalized healthcare in primary care.

Analysis and prediction of central nervous system tumor burden in China during 1990-2030.

Central nervous system (CNS) tumors, due to their unique locations, pose a serious threat to human health and present challenges to modern medicine. These tumors exhibit notable epidemiological characteristics across various ethnicities, regions, and age groups. This study investigated the trend of disease burden of CNS tumors in China from 1990-2019 and predicted the incidence and death rate from 2020-2030. Employing data from the 2019 Global Burden of Disease (GBD) database, we utilized key indicators to scrutinize the disease burden associated with CNS tumors in China. The analysis employed the Joinpoint model to track the trend in disease burden, calculating both the annual percentage change (APC) and average annual percentage change (AAPC). Additionally, the Matlab software facilitated the creation of a gray model to forecast the incidence and death rate of CNS tumors in China spanning from 2020 to 2030." In 2019, the age-standardized incidence rate, prevalence rate, death rate, and disability-adjusted life years (DALYs) associated with CNS tumors in China were among the high level in the world. The standardized prevalence rate and DALYs of CNS tumors in China residents showed a stable fluctuation trend with age; however, age-standardized death and incidence rate demonstrated a generally upward trend with age. In China, the age-standardized prevalence and incidence rate of males were lower than those for female residents, while the age-standardized death rate and DALYs among males surpassed those of females. From 1990-2019, the age-standardized prevalence and incidence rate of CNS tumors in China exhibited an increasing trend. The age-standardized death rate and DALYs showed a contrasting trend. According to the gray model's prediction, incidence rate of CNS tumors would continue rising while the death rate is expected to decline in China from 2020-2023. The burden of CNS tumors in China has shown an upward trajectory, posing significant challenges to their treatment. It is necessary to pay attention to tertiary prevention, start from the perspective of high-risk groups and high-risk factors to reduce the burden of disease, and achieve "early detection, early diagnosis, and early treatment".

Incorporating Lycium barbarum residue in diet boosts survival, growth, and liver health in juvenile grass carp (Ctenopharyngodon idellus).

This research elucidates the potential of Lycium barbarum residue (LBR), a by-product rich in bioactive substances, as a dietary supplement in aquaculture, especially for herbivorous fish like grass carp. In a detailed 120-day feeding trial, the impacts of varying LBR levels on juvenile grass carp were assessed, focusing on growth performance, survival rate, biochemical markers, and liver health. The study identified a 6% inclusion rate of LBR as optimal for enhancing survival and growth while mitigating hepatic lipid accumulation. Composition analysis of this diet revealed high concentrations of polysaccharides and flavonoids. Notably, the intake of LBR was found to enhance the antioxidant and immune-related enzymatic activities in the liver. Furthermore, it contributed to a reduction in hepatic fat deposition by decreasing the levels of triglycerides (TG) and total cholesterol (T-CHO) both in the liver and serum. Transcriptomic analysis of the liver highlighted LBR's substantial influence on lipid metabolism pathways, including the PPAR signaling pathway, primary bile acid biosynthesis, cholesterol metabolism, bile secretion, fat digestion and absorption, fatty acid degradation and fatty acid biosynthesis. Further, the expression level of genes pinpointed significant downregulation of fasn and dgat2, alongside upregulation of genes like pparda, cpt1b, cpt1ab and abca1b, in response to LBR supplementation. Overall, the findings present LBR as a promising enhancer of growth and survival in grass carp, with significant benefits in promoting fat metabolism and liver health, offering valuable insights for aquacultural nutrition strategies.

Susceptibility of TSPAN5 polymorphisms to Kawasaki disease and immunoglobulin therapy resistance in southern Chinese children.

Kawasaki disease (KD) is a condition characterized by acute multi-system vasculitis and high fever in infants and children. Intravenous immunoglobulin (IVIG) is the established therapeutic approach of KD,foralleviating inflammation and mitigate the risk of arterial wall dilation and the development of coronary artery aneurysms (CAA). But almost 20% of the patients developed resistance to IVIG and displayed persistent fever after standard primary treatment. TSPAN5, belonging to the Tetraspanin family, has been demonstrated to modulate innate immunity in a range of human diseases. It accomplishes this by engaging with integrins and actively participating in the process of infection recognition. However, its relevance to susceptibility and IVIG therapy response of KD was unexposed. In the present study, our Integrative analysis of KD transcriptomic data and GTEx data revealed that the eQTL rs12504972 might modify the downregulation of TSPAN5 in KD patients. Moreover, our findings suggest a potential association between TSPAN5/rs12504972 and an elevated susceptibility as well as IVIG resistance among patients with Kawasaki disease in southern China. The results provided a new insight that TSPAN5 triggered KD susceptibility and resistance of IVIG therapy on the genomic level.

Sporoderm-broken spores of Ganoderma lucidum modulate hepatoblastoma malignancy by regulating RACK1-mediated autophagy and tumour immunity.

Hepatoblastoma (HB), a primary liver tumour, is notorious for its high metastatic potential and poor prognosis. Ganoderma lucidum, an edible mushroom species utilized in traditional Chinese medicine for addressing various tumour types, presents an intriguing avenue for HB treatment. However, the effectiveness of G. lucidum in managing HB and its underlying molecular mechanism necessitates further exploration. Standard in vitro assays were conducted to evaluate the impact of sporoderm-broken spores of G. lucidum (SBSGL) on the malignant characteristics of HB cells. The mechanism of SBSGL in treating HB and its tumour immunomodulatory effects were explored and validated by various experiments, including immunoprecipitation, Western blotting, mRFP-GFP-LC3 adenovirus transfection and co-localization analysis, as well as verified with in vivo experiments in this regard. The results showed that SBSGL effectively inhibited the malignant traits of HB cells and suppressed the O-GlcNAcylation of RACK1, thereby reducing its expression. In addition, SBSGL inhibited immune checkpoints and regulated cytokines. In conclusion, SBSGL had immunomodulatory effects and regulated the malignancy and autophagy of HB by regulating the O-GlcNAcylation of RACK1. These findings suggest that SBSGL holds promise as a potential anticancer drug for HB treatment.

MicroRNA-30e-3p regulates the inflammatory response by targeting the gimap8 gene in Ctenopharyngodon idella kidney (CIK) cells.

Recent studies have increasingly linked miRNAs with the modulation of inflammatory responses and immunosuppressive activities. This investigation reveals that mir-30e-3p selectively binds to and modulates gimap8, as demonstrated by luciferase reporter assays and qPCR analyses. Upon LPS stimulation of CIK cells, mir-30e-3p expression was notably elevated, inversely correlating with a decrease in gimap8 mRNA levels. Overexpression of mir-30e-3p attenuated the mRNA levels of pro-inflammatory cytokines beyond the effect of LPS alone, suggesting a regulatory role of mir-30e-3p in inflammation mediated by the gimap8 gene. These insights contribute to our understanding of the complex mechanisms governing inflammatory and immune responses.

The cadmium tolerance enhancement through regulating glutathione conferred by vacuolar compartmentalization in Aspergillus sydowii.

Aspergillus was found to be a vital hyperaccumulation species for heavy metal removal with admirable tolerance capacity. But the potential tolerance mechanism has not been completely studied. This study quantified the amounts of total cadmium (Cd), Cd2+, glutathione (GSH), and reactive oxygen species (ROS) in the protoplasts and vacuoles of mycelium. We modulated GSH synthesis using buthionine sulfoximine (BSO) and 2-oxothiazolidine-4-carboxylic acid (OTC) to investigate the subcellular regulatory mechanisms of GSH in the accumulation of Cd. The results confirmed that GSH plays a crucial role in vacuolar compartmentalization under Cd stress. GSH and GSSG as a redox buffer to keep the cellular redox state in balance and GSH as a metal chelating agent to reduce toxicity. When regulating the decreased GSH content with BSO, and increased GSH content with OTC, the system of Cd-GSH-ROS can change accordingly, this also supported that vacuolar compartmentalization is a detoxification strategy that can modulate the transport and storage of substances inside and outside the vacuole reasonably. Interestingly, GSH tended to be distributed in the cytoplasm, the battleground of redox takes place in the cytoplasm but not in the vacuole. These finding potentially has implications for the understanding of tolerance behavior and detoxification mechanisms of cells. In the future bioremediation of Cd in soil, the efficiency of soil remediation can be improved by developing organisms with high GSH production capacity.

miR-193b-5p promotes GCRV replication by inhibiting autophagy via targeting deptor in grass carp (Ctenopharyngodon idellus).

miRNAs are increasingly recognized for their crucial role in autophagy processes. Recent research has highlighted the significant function of autophagy in modulating immune responses. Within this context, specific miRNAs have been identified as indirect mediators of immune functions through their modulation of autophagy. In this study, we verified that miR-193b-5p simultaneously targeted the grass carp autophagy-related gene deptor, thereby reducing autophagy levels in CIK cells. Moreover, we found the expression levels of miR-193b-5p and deptor responding to pathogen infections in the GCRV-infected CIK cells. Notably, the overexpression of miR-193b-5p was found to induce the GCRV replication and reduce the irf3, irf7 and IFN1 expression. These findings also demonstrated that grass carp miR-193b-5p impacted the proliferation, migration, and antiapoptotic abilities of CIK cells. All the above results indicated that miR-193b-5p was linked to grass carp autophagy and played a vital role in antiviral immunity by targeting deptor. Our study may provide important insights into autophagy-related miRNAs and their roles in defense and immune mechanisms against pathogens in teleost.

Structurally diverse deformed phenanthrenes from Strophioblachia fimbricalyx with cytotoxic activities by inducing cell apoptosis.

A group of phenanthrene derivatives with different deformed types, including four previously undescribed derivatives (1-4), an undescribed natural product (5) and five known compounds (6-10), were isolated from the leaves and stems of Strophioblachia fimbricalyx by molecular networking based on UPLC-MS/MS method. Their structures were established by 1D/2D NMR spectroscopy, HRESIMS, quantum chemistry calculation, and single crystal X-ray diffraction. In biogenic pathways, series of deformed phenanthrenes were all suspected to be derived from 6/6/6 tricyclic phenanthrenes with a gem-dimethyl unit in one ring as characteristic components of Strophioblachia. Fimbricalyxone (1) and trigoxyphin M (6) with a 6/6/5 tricyclic carbon skeleton were reported for the first time from the genus and fimbricalyxanhydride C (2) is the first example of anhydride type bearing a rare 8,9-oxycycle. All the isolates were evaluated for their cytotoxic activity against three tumor cell lines, and compounds 8 and 10 exhibited significant activity with IC50 values of 4.65-9.02 µM, and the structure-activity relationship of the deformed phenanthrenes was discussed. In addition, the X-ray structure of 8 and 10 and the antineoplastic activity of 10 are reported herein for the first time. Trigohowilol G (10) inhibiting the proliferation of A549 cells might be related to cell cycle distribution and the induction of S phase arrest, and it induced cell apoptosis through Bad/Bax/Cleaved PARP1 pathway.

Dielectric Design of High Dielectric Constant Poly(Urea-Urethane) Elastomer for Low-Voltage High-Mobility Intrinsically Stretchable All-Solution-Processed Organic Transistors.

Stretchable organic transistors for skin-like biomedical applications require low-voltage operation to accommodate limited power supply and safe concerns. However, most of the currently reported stretchable organic transistors operate at relatively high voltages. Decreasing their operational voltage while keeping the high mobility still remains a key challenge. Here, the study presents a new dielectric design to achieve high-dielectric constant poly(urea-urethane) (PUU) elastomer, by incorporating a flexible small-molecular diamine crosslinking agent 4-aminophenyl disulfide (APDS) into the main chain of (poly (propylene glycol), tolylene 2,4-diiso-cyanate terminated) (PPG-TDI). Compared with commercial elastomers, the PUU elastomer as dielectric of the stretchable organic transistors shows the outstanding advantages including lower surface roughness (0.33 nm), higher adhesion (45.18 nN), higher dielectric constant (13.5), as well as higher stretchability (896%). The PUU dielectric enables the intrinsically stretchable, all-solution-processed organic transistor to operate at a low operational voltage down to -10 V, while preserving a substantial mobility of 1.39 cm2  V-1  s-1 . Impressively, the transistor also demonstrates excellent electrical stability under repeated switching of 10 000 cycles, and remarkable mechanical robustness when stretched up to 100%. The work opens up a new molecular engineering strategy to successfully realize low-voltage high-mobility stretchable all-solution-processed organic transistors.

A simple and sensitive liquid chromatography triple quadrupole mass spectrometry method for the determination of XL092 in monkey plasma and its application to pharmacokinetic study.

XL092 is a potent ATP-competitive inhibitor of multiple receptor tyrosine kinases that is undergoing clinical development for the treatment of lung cancer. In this study, an LC triple quadrupole mass spectrometry method was established to measure XL092 in monkey plasma. A Waters ACQUITY UPLC BEH C18 column was used for chromatographic separation. The mobile phase consisted of water containing 0.1% formic acid and acetonitrile with a gradient elution at the flow rate of 0.4 mL/min. Multiple reaction monitoring mode was used for quantitative analysis of XL092 in positive electrospray ionization. In the concentration range of 0.5-1000 ng/mL, XL092 showed excellent linearity in monkey plasma with a correlation coefficient greater than 0.995 (r > 0.995). The lowest limit of quantification was 0.5 ng/mL. The intra- and inter-day relative standard deviations were <9.99%, while the relative error ranged from -12.50% to 8.10%. The mean recovery was over 82.51%. XL092 was stable in monkey plasma after storage under certain conditions. The validated method was demonstrated to be selective, sensitive, and reliable, and has been successfully applied to the pharmacokinetic study of XL092 in monkey plasma. XL092 showed moderate short half-life (~3.81 h) and good oral bioavailability (80%).

[Construction of a Prognostic Prediction Model of Patients with Pathologic N0 
in Resected Invasive Mucinous Adenocarcinoma of the Lung].

BACKGROUND: Invasive mucinous adenocarcinoma (IMA) was a rare and specific type of lung adenocarcinoma, which was often characterized by fewer lymphatic metastases. Therefore, it was difficult to evaluate the prognosis of these tumors based on the existing tumor-node-metastasis (TNM) staging. So, this study aimed to develop Nomograms to predict outcomes of patients with pathologic N0 in resected IMA. METHODS: According to the inclusion criteria and exclusion criteria, IMA patients with pathologic N0 in The Affiliated Lihuili Hospital of Ningbo University (training cohort, n=78) and Ningbo No.2 Hospital (validation cohort, n=66) were reviewed between July 2012 and May 2017. The prognostic value of the clinicopathological features in the training cohort was analyzed and prognostic prediction models were established, and the performances of models were evaluated. Finally, the validation cohort data was put in for external validation. RESULTS: Univariate analysis showed that pneumonic type, larger tumor size, mixed mucinous/non-mucinous component, and higher overall stage were significant influence factors of 5-year progression-free survival (PFS) and overall survival (OS). Multivariate analysis further indicated that type of imaging, tumor size, mucinous component were the independent prognostic factors for poor 5-year PFS and OS. Moreover, the 5-year PFS and OS rates were 62.82% and 75.64%, respectively. In subgroups, the survival analysis also showed that the pneumonic type and mixed mucinous/non-mucinous patients had significantly poorer 5-year PFS and OS compared with solitary type and pure mucinous patients, respectively. The C-index of Nomograms with 5-year PFS and OS were 0.815 (95%CI: 0.741-0.889) and 0.767 (95%CI: 0.669-0.865). The calibration curve and decision curve analysis (DCA) of both models showed good predictive performances in both cohorts. CONCLUSIONS: The Nomograms based on clinicopathological characteristics in a certain extent, can be used as an effective prognostic tool for patients with pathologic N0 after IMA resection.

Simultaneous determination of sinomenine and its metabolites desmethyl-sinomenine and sinomenine N-oxide in rat plasma by liquid chromatography tandem mass spectrometry.

Sinomenine is an active ingredient extracted from herb medicine, which has been prescribed to treat rheumatoid arthritis in clinics. The present work was to develop a simple method to simultaneously determine sinomenine and its metabolites desmethyl sinomenine and sinomenine N-oxide in rat plasma by liquid chromatography tandem mass spectrometry. Precursor-to-product transitions for detection were m/z 330.2 > 239.1 for sinomenine, m/z 316.2 > 239.1 for desmethyl-sinomenine, m/z 346.2 > 314.1 for sinomenine N-oxide and m/z 286.2 > 153.2 for morphine (internal standard), respectively. During the validation and sample quantification, an excellent linear calibration range was observed for all the analytes with correlation coefficients more than 0.999 (r > 0.99). The extraction recovery was more than 85%. No significant matrix effect and carryover were observed. The precision was less than 6.45%, whereas accuracy ranged from -4.10% to 7.23%. The validated method has been successfully applied to the pharmacokinetic study of sinomenine, desmethyl sinomenine, and sinomenine N-oxide in rat plasma after oral administration of sinomenine at a single dose of 5 mg/kg. The results suggested that sinomenine was rapidly metabolized into its metabolite desmethyl sinomenine and sinomenine N-oxide.

Evidence for cytochrome P450 3A4-mediated metabolic activation of SCO-267.

SCO-267 is a potent G-protein-coupled receptor 40 agonist that is undergoing clinical development for the treatment of type 2 diabetes mellitus. The current work was undertaken to investigate the bioactivation potential of SCO-267 in vitro and in vivo. Three SCO-267-derived glutathione (GSH) conjugates (M1-M3) were found both in rat and human liver microsomal incubations supplemented with GSH and nicotinamide adenine dinucleotide phosphate. Two GSH conjugates (M1-M2) together with two N-acetyl-cysteine conjugates (M4-M5) were detected in the bile of rats receiving SCO-267 at 10 mg/kg. The identified conjugates suggested the generation of quinone-imine and ortho-quinone intermediates. CYP3A4 was demonstrated to primarily catalyze the bioactivation of SCO-267. In addition, SCO-267 concentration-, time-, and NADPH-dependently inactivated CYP3A in human liver microsomes using testosterone as a probe substrate, along with KI and kinact values of 4.91 µM and 0.036 min-1 , respectively. Ketoconazole (a competitive inhibitor of CYP3A) displayed no significant protective effect on SCO-267-induced CYP3A inactivation. However, inclusion of GSH showed significant protection. These findings revealed that SCO-267 undergoes a facile CYP3A4-catalyzed bioactivation with the generation of quinone-imine and ortho-quinone intermediates, which were assumed to be involved in SCO-267 induced CYP3A inactivation. These findings provide further insight into the bioactivation pathways involved in the generation of reactive, potentially toxic metabolites of SCO-267. Further studies are needed to evaluate the influence of SCO-267 metabolism on the safety of this drug in vivo.

Stability and function of RCL1 are dependent on the interaction with BMS1.

During ribosome biogenesis, the small subunit (SSU) processome is responsible for 40S assembly. The BMS1/RCL1 complex is a core component of the SSU processome that plays an important role in 18S rRNA processing and maturation. Genetic studies using zebrafish mutants indicate that both Bms1-like (Bms1l) and Rcl1 are essential for digestive organ development. In spite of vital functions of this complex, the mutual dependence of these two nucleolar proteins for the stability and function remains elusive. In this study, we identified an RCL1-interacting domain in BMS1, which is conserved in zebrafish and humans. Moreover, both the protein stability and nucleolar entry of RCL1 depend on its interaction with BMS1, otherwise RCL1 degraded through the ubiquitination-proteasome pathway. Functional studies revealed that overexpression of RCL1 in BMS1-knockdown cells can partially rescue the defects in 18S rRNA processing and cell proliferation, and hepatocyte-specific overexpression of Rcl1 can resume zebrafish liver development in the bms1l substitution mutant bms1lsq163/sq163but not in the knockout mutant bms1lzju1/zju1, which is attributed to the nucleolar entry of Rcl1 in the former mutant. Our data demonstrate that BMS1 and RCL1 interaction is essential for not only pre-rRNA processing but also the communication between ribosome biogenesis and cell cycle regulation.

Airborne magnetite nanoparticles induced early vascular pathologies by disrupting lipid metabolism under high-fat dietary patterns.

Magnetite nanoparticles (MNPs) have been extensively detected in the atmospheric environment and implicated as a prominent threat to atherosclerosis, a chronic vascular inflammatory disease. Due to globalization and economic development, the dramatic shift in diet from traditional to high-fat dietary patterns aggravated atherosclerosis progression induced by environmental factors. However, limited knowledge is available regarding vascular risks and underlying mechanisms of airborne MNPs in high-risk populations with high-fat dietary habits. Herein, we demonstrated that MNPs exerted a proatherogenic effect under high-fat dietary patterns, leading to aortic wall thickening, elastic fiber disorganization, macrophage infiltration, and local inflammation. Based on the correlation analysis between MNPs and PM group, we identified that MNPs might be a key PM component in atherogenic toxicity. MNPs exposure disturbed the dynamic process of lipid metabolism, manifested as aortic lipid accumulation, dyslipidemia, and hepatic lipid metabolism disorder, which was modulated by the JAK-STAT pathway. Overall, these findings provide new insight into understanding the cardiovascular risks and mechanisms of MNPs among high-risk populations.

Resonance-Assisted Surface-Enhanced Raman Spectroscopy Amplification on Hierarchical Rose-Shaped MoS2/Au Nanocomposites.

Surface-enhanced Raman spectroscopy (SERS) has emerged as a highly sensitive trace detection technique in recent decades, yet its exceptional performance remains elusive in semiconductor materials due to the intricate and ambiguous nature of the SERS mechanism. Herein, we have synthesized MoS2 nanoflowers (NFs) decorated with Au nanoparticles (NPs) by hydrothermal and redox methods to explore the size-dependence SERS effect. This strategy enhances the interactions between the substrate and molecules, resulting in exceptional uniformity and reproducibility. Compared to the unadorned Au nanoparticles (NPs), the decoration of Au NPs induces an n-type effect on MoS2, resulting in a significant enhancement of the SERS effect. This augmentation empowers MoS2 to achieve a low limit of detection concentration of 2.1 × 10-9 M for crystal violet (CV) molecules and the enhancement factor (EF) is about 8.52 × 106. The time-stability for a duration of 20 days was carried out, revealing that the Raman intensity of CV on the MoS2/Au-6 substrate only exhibited a reduction of 24.36% after undergoing aging for 20 days. The proposed mechanism for SERS primarily stems from the synergistic interplay among the resonance of CV molecules, local surface plasma resonance (LSPR) of Au NPs, and the dual-step charge transfer enhancement. This research offers comprehensive insights into SERS enhancement and provides guidance for the molecular design of highly sensitive SERS systems.