Mechanisms of cuproptosis and its relevance to distinct diseases.

Copper is a trace element required by the organism, but once the level of copper exceeds the threshold, it becomes toxic and even causes death. The underlying mechanisms of copper-induced death are inconclusive, with different studies showing different opinions on the mechanism of copper-induced death. Multiple investigations have shown that copper induces oxidative stress, endoplasmic reticulum stress, nucleolar stress, and proteasome inhibition, all of which can result in cell death. The latest research elucidates a copper-dependent death and denominates it as cuproptosis. Cuproptosis takes place through the combination of copper and lipoylated proteins of the tricarboxylic acid cycle, triggering agglomeration of lipoylated proteins and loss of iron-sulfur cluster proteins, leading to proteotoxic stress and ultimately death. Given the toxicity and necessity of copper, abnormal levels of copper lead to diseases such as neurological diseases and cancer. The development of cancer has a high demand for copper, neurological diseases involve the change of copper contents and the binding of copper to proteins. There is a close relationship between these two kinds of diseases and copper. Here, we summarize the mechanisms of copper-related death, and the association between copper and diseases, to better figure out the influence of copper in cell death and diseases, thus advancing the clinical remedy of these diseases.

Antibacterial, antioxidant, Cr(VI) adsorption and dye adsorption effects of biochar-based silver nanoparticles­sodium alginate-tannic acid composite gel beads.

Ultrasonic extraction of Osmanthus fragrans was used for reducing Ag+ to prepare AgNPs, which were further loaded on barley distiller's grains shell biochar. By supplementary of sodium alginate and tannic acid, composite gel beads were prepared. The physical properties of biochar-based AgNPs­sodium alginate-tannic acid composite gel beads (C-Ag/SA/TA) were characterized. SEM, FTIR, and XRD showed that biochar-based AgNPs were compatible with sodium alginate-tannic acid. CAg greatly improved the dissolution, swelling, and expansion of gel beads. Through the analysis by the agar diffusion method, C-Ag/SA/TA gel beads had high antibacterial activity (inhibition zone: 22 mm against Escherichia coli and 20 mm against Staphylococcus aureus). It was observed that C-Ag/SA/TA composite gel beads had high antioxidant capacity and the free radical scavenging rate reached 89.0 %. The dye adsorption performance of gel beads was studied by establishing a kinetic model. The maximum adsorption capacities of C-Ag/SA/TA gel beads for methylene blue and Congo red were 166.57 and 318.06 mg/g, respectively. The removal rate of Cr(VI) reached 96.4 %. These results indicated that the prepared composite gel beads had a high adsorption capacity for dyes and metal ions. Overall, C-Ag/SA/TA composite gel beads were biocompatible and had potential applications in environmental pollution treatment.

An Immune-Regulating Polysaccharide Hybrid Hydrogel with Mild Photothermal Effect and Anti-Inflammatory for Accelerating Infected Wound Healing.

Bacterial infections and excessive inflammation present substantial challenges for clinical wound healing. Hydrogels with mild photothermal (PTT) effects have emerged as promising agents owing to their dual actions: positive effects on cells and negative effects on bacteria. Here, an injectable self-healing hydrogel of oxidized konjac glucomannan/arginine-modified chitosan (OKGM/CS-Arg, OC) integrated with protocatechualdehyde-@Fe (PF) nanoparticles capable of effectively absorbing near-infrared radiation is synthesized successfully. The OC/PF hydrogels exhibit excellent mechanical properties, biocompatibility, and antioxidant activity. Moreover, in synergy with PTT, OC/PF demonstrates potent antibacterial effects while concurrently stimulating cell migration and new blood vessel formation. In methicillin-resistant Staphylococcus aureus-infected full-thickness mouse wounds, the OC/PF hydrogel displays remarkable antibacterial and anti-inflammatory activities, and accelerates wound healing by regulating the wound immune microenvironment and promoting M2 macrophage polarization. Consequently, the OC/PF hydrogel represents a novel therapeutic approach for treating multidrug-resistant bacterial infections and offers a technologically advanced solution for managing infectious wounds in clinical settings.

Laser-induced graphene-based digital microfluidics (gDMF): a versatile platform with sub-one-dollar cost.

Digital microfluidics (DMF), is an emerging liquid-handling technology, that shows promising potential in various biological and biomedical applications. However, the fabrication of conventional DMF chips is usually complicated, time-consuming, and costly, which seriously limits their widespread applications, especially in the field of point-of-care testing (POCT). Although the paper- or film-based DMF devices can offer an inexpensive and convenient alternative, they still suffer from the planar addressing structure, and thus, limited electrode quantity. To address the above issues, we herein describe the development of a laser-induced graphene (LIG) based digital microfluidics chip (gDMF). It can be easily made (within 10 min, under ambient conditions, without the need of costly materials or cleanroom-based techniques) by a computer-controlled laser scribing process. Moreover, both the planar addressing DMF (pgDMF) and vertical addressing DMF (vgDMF) can be readily achieved, with the latter offering the potential of a higher electrode density. Also, both of them have an impressively low cost of below $1 ($0.85 for pgDMF, $0.59 for vgDMF). Experiments also show that both pgDMF and vgDMF have a comparable performance to conventional DMF devices, with a colorimetric assay performed on vgDMF as proof-of-concept to demonstrate their applicability. Given the simple fabrication, low cost, full function, and the ease of modifying the electrode pattern for various applications, it is reasonably expect that the proposed gDMF may offer an alternative choice as a versatile platform for POCT.

Natural History and Prognostic Model of Untreated Papillary Thyroid Cancer: A SEER Database Analysis.

PURPOSE: This investigation leveraged the SEER database to delve into the progression patterns of PTC when left untreated. Furthermore, it aimed to devise and authenticate a nomogram for prognosis prediction for such patients. METHODS: We extracted data from the SEER database, focusing on PTC-diagnosed individuals from 2004-2020. To discern disease progression intervals, median survival times across stages were gauged, and the disease progression time was estimated by subtracting the median survival time of a more severe stage from its preceding stage. Prognostic determinants in the training set were pinpointed using both univariate and multivariate Cox regression. Using these determinants, a prognostic nomogram was crafted. RESULTS: In untreated PTC patients, those in stages I and II had a favorable prognosis, with 10-year overall survival rates of 86.34% and 66.03%, respectively. Patients in stages III and IV had a relatively poorer prognosis. The median survival time of stage III, stage IVA, stage IVB and stage IVC patients was 108months, 43 months, 20 months and 8 months, respectively. The deduced progression intervals from stages III-IVC were 65, 23, and 12 months. In the training set, age, tumor stage, gender, and marital status were identified as independent risk factors influencing the prognosis of untreated PTC, and a nomogram was constructed using these variables. CONCLUSION: In the absence of treatment intervention, early-stage PTC progressed slowly with an overall favorable prognosis. However, in mid to advanced-stage PTC, as tumor stage increased, disease progression accelerated, and prognosis gradually worsened. Age, tumor stage, marital status, and gender were independent risk factors influencing the prognosis of untreated PTC, and the nomogram based on these factors demonstrated good prognostic capability.

PurposeThis investigation leveraged the SEER database to delve into the progression patterns of PTC when left untreated. Furthermore, it aimed to devise and authenticate a nomogram for prognosis prediction for such patients.MethodsWe extracted data from the SEER database, focusing on PTC-diagnosed individuals from 2004-2020. To discern disease progression intervals, median survival times across stages were gauged, and the disease progression time was estimated by subtracting the median survival time of a more severe stage from its preceding stage. Prognostic determinants in the training set were pinpointed using both univariate and multivariate Cox regression. Using these determinants, a prognostic nomogram was crafted.ResultsIn untreated PTC patients, those in stages I and II had a favorable prognosis, with ten-year overall survival rates of 86.34% and 66.03%, respectively. Patients in stages III and IV had a relatively poorer prognosis. The median survival time of stage III, stage IVA, stage IVB and stage IVC patients was 108months, 43 months, 20 months and 8 months, respectively. The deduced progression intervals from stages III-IVC were 65, 23, and 12 months. In the training set, age, tumor stage, gender, and marital status were identified as independent risk factors influencing the prognosis of untreated PTC, and a nomogram was constructed using these variables.ConclusionIn the absence of treatment intervention, early-stage PTC progressed slowly with an overall favorable prognosis. However, in mid to advanced-stage PTC, as tumor stage increased, disease progression accelerated, and prognosis gradually worsened. Age, tumor stage, marital status, and gender were independent risk factors influencing the prognosis of untreated PTC, and the nomogram based on these factors demonstrated good prognostic capability.

HSP70 positively regulates translation by interacting with the IRES and stabilizes the viral structural proteins VP1 and VP3 to facilitate duck hepatitis A virus type 1 replication.

The maintenance of viral protein homeostasis depends on the interaction between host cell proteins and viral proteins. As a molecular chaperone, heat shock protein 70 (HSP70) has been shown to play an important role in viral infection. Our results showed that HSP70 can affect translation, replication, assembly, and release during the life cycle of duck hepatitis A virus type 1 (DHAV-1). We demonstrated that HSP70 can regulate viral translation by interacting with the DHAV-1 internal ribosome entry site (IRES). In addition, HSP70 interacts with the viral capsid proteins VP1 and VP3 and promotes their stability by inhibiting proteasomal degradation, thereby facilitating the assembly of DHAV-1 virions. This study demonstrates the specific role of HSP70 in regulating DHAV-1 replication, which are helpful for understanding the pathogenesis of DHAV-1 infection and provide additional information about the role of HSP70 in infection by different kinds of picornaviruses, as well as the interaction between picornaviruses and host cells.

Lung-Gut Microbiota and Tryptophan Metabolites Changes in Neonatal Acute Respiratory Distress Syndrome.

Purpose: Neonatal Acute Respiratory Distress Syndrome (NARDS) is a severe respiratory crisis threatening neonatal life. We aim to identify changes in the lung-gut microbiota and lung-plasma tryptophan metabolites in NARDS neonates to provide a differentiated tool and aid in finding potential therapeutic targets. Patients and Methods: Lower respiratory secretions, faeces and plasma were collected from 50 neonates including 25 NARDS patients (10 patients with mild NARDS in the NARDS_M group and 15 patients with moderate-to-severe NARDS in the NARDS_S group) and 25 control patients screened based on gestational age, postnatal age and birth weight. Lower airway secretions and feces underwent 16S rRNA gene sequencing to understand the microbial communities in the lung and gut, while lower airway secretions and plasma underwent LC-MS analysis to understand tryptophan metabolites in the lung and blood. Correlation analyses were performed by comparing differences in microbiota and tryptophan metabolites between NARDS and control, NARDS_S and NARDS_M groups. Results: Significant changes in lung and gut microbiota as well as lung and plasma tryptophan metabolites were observed in NARDS neonates compared to controls. Proteobacteria and Bacteroidota were increased in the lungs of NARDS neonates, whereas Firmicutes, Streptococcus, and Rothia were reduced. Lactobacillus in the lungs decreased in NARDS_S neonates. Indole-3-carboxaldehyde decreased in the lungs of NARDS neonates, whereas levels of 3-hydroxykynurenine, indoleacetic acid, indolelactic acid, 3-indole propionic acid, indoxyl sulfate, kynurenine, and tryptophan decreased in the lungs of the NARDS_S neonates. Altered microbiota was significantly related to tryptophan metabolites, with changes in lung microbiota and tryptophan metabolites having better differentiated ability for NARDS diagnosis and grading compared to gut and plasma. Conclusion: Significant changes occurred in the lung-gut microbiota and lung-plasma tryptophan metabolites of NARDS neonates. Alterations in lung microbiota and tryptophan metabolites were better discriminatory for the diagnosis and grading of NARDS.

Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study.

BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

E-M349E and NS2A/2B-P1(T) are compensatory mutations of rDTMUV-NS2AB-P1P1'(AA), which regain virus proliferation by enhancing the virus package and restoring NS2A/2B cleavage.

Duck Tembusu virus (DTMUV) belongs to the Flaviviridae family and mainly infects ducks. The genome of DTMUV is translated into a polyprotein, which is further cleaved into several protein by viral NS2B3 protease and host proteases. Crucially, the cleavage of the NS2A/2B precursor during this process is essential for the formation of replication complexes and viral packaging. Previous research has demonstrated that alanine mutations in NS2A/2B (P1P1' (AA)) result in an attenuated strain (rDTMUV-NS2A/2B-P1P1' (AA)) by disrupting NS2A/2B cleavage. In this study, we investigate the effects of the P1P1' (AA) mutation on the viral life cycle and explore compensatory mutations in rDTMUV-NS2A/2B-P1P1' (AA). Infected ducklings exhibit similar body weight gain and viral tissue loads to DTMUV-WT. Compensatory mutations E-M349E and P1(T) emerge, restoring proliferation levels to those of rDTMUV-WT. Specifically, E-M349E enhances viral packaging, while P1(T) reinstates NS2A/2B proteolysis in vitro. Thus, our findings reveal novel compensatory sites capable of restoring the attenuated DTMUV during polyprotein cleavage and packaging.

GLP-2 ameliorates D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a signaling pathway in C2C12 cells and mice.

BACKGROUND: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. METHODS: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 µg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. RESULTS: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. CONCLUSIONS: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.

Universal scaling law for chiral antiferromagnetism.

The chiral antiferromagnetic (AFM) materials, which have been widely investigated due to their rich physics, such as non-zero Berry phase and topology, provide a platform for the development of antiferromagnetic spintronics. Here, we find two distinctive anomalous Hall effect (AHE) contributions in the chiral AFM Mn3Pt, originating from a time-reversal symmetry breaking induced intrinsic mechanism and a skew scattering induced topological AHE due to an out-of-plane spin canting with respect to the Kagome plane. We propose a universal AHE scaling law to explain the AHE resistivity ( ρ A H ) in this chiral magnet, with both a scalar spin chirality (SSC)-induced skew scattering topological AHE term, a s k and non-collinear spin-texture induced intrinsic anomalous Hall term, b i n . We found that a s k and b i n can be effectively modulated by the interfacial electron scattering, exhibiting a linear relation with the inverse film thickness. Moreover, the scaling law can explain the anomalous Hall effect in various chiral magnets and has far-reaching implications for chiral-based spintronics devices.

Microplastic accumulation in groundwater: Data-scaled insights and future research.

Given that microplastics (MPs) in groundwater have been concerned for risks to humans and ecosystems with increased publications, a Contrasting Analysis of Scales (CAS) approach is developed by this study to synthesize all existing data into a hierarchical understanding of MP accumulation in groundwater. Within the full data of 386 compiled samples, the median abundance of MPs in Open Groundwater (OG) and Closed Groundwater (CG) were 4.4 and 2.5 items/L respectively, with OG exhibiting a greater diversity of MP colors and larger particle sizes. The different pathways of MP entry (i.e., surface runoff and rock interstices) into OG and CG led to this difference. At the regional scale, median MP abundance in nature reserves and landfills were 17.5 and 13.4 items/L, respectively, all the sampling points showed high pollution load risk. MPs in agricultural areas exhibited a high coefficient of variation (716.7%), and a median abundance of 1.0 items/L. Anthropogenic activities at the regional scale are the drivers behind the differentiation in the morphological characteristics of MPs, where groundwater in residential areas with highly toxic polymers (e.g., polyvinylchloride) deserves prolonged attention. At the local scale, the transport of MPs is controlled by groundwater flow paths, with a higher abundance of MP particles downstream than upstream, and MPs with regular surfaces and lower resistance (e.g., pellets) are more likely to be transported over long distances. From the data-scaled insight this study provides on the accumulation of MPs, future research should be directed towards network-based observation for groundwater-rich regions covered with landfills, residences, and agricultural land.

Tartaric acid ameliorates experimental non-alcoholic fatty liver disease by activating the AMP-activated protein kinase signaling pathway.

Tartaric acid (TA) has been shown beneficial effects on blood pressure and lipid levels. However, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. This study aimed to investigate the role of TA in experimental NAFLD. Mice were fed a Western diet for 8 weeks, followed by administration of TA or a vehicle for an additional 12 weeks while continuing on the Western diet. Blood biochemistry including transaminases and glucose tolerance test and liver tissue RNA sequencing (RNA-seq), lipid content, and histology were investigated. The HepG2 cell line was used to explore the mechanism by which TA regulates lipid metabolism. We found that TA significantly improved weight gain, insulin resistance, hepatic steatosis, inflammation and fibrosis in Western diet-fed mice. By comparing gene expression differences, we found that TA affects pathways related to lipid metabolism, inflammatory response, and fibrosis. Furthermore, TA effectively reduced oleic acid-induced lipid accumulation in HepG2 cells and downregulated the genes associated with fatty acid synthesis, which were enriched in the AMP-activated protein kinase (AMPK) signaling pathway. TA also enhanced the phosphorylation of AMPK which could be reverted by the AMPK inhibitor Compound C in HepG2 cells. Our study suggests that TA improves experimental NAFLD by activating the AMPK signaling pathway. These findings indicate that TA may serve as a potential therapy for the human NAFLD.

A role for subducting clays in the water transportation into the Earth's lower mantle.

Subducting sedimentary layer typically contains water and hydrated clay minerals. The stability of clay minerals under such hydrous subduction environment would therefore constraint the lithology and physical properties of the subducting slab interface. Here we show that pyrophyllite (Al2Si4O10(OH)2), one of the representative clay minerals in the alumina-silica-water (Al2O3-SiO2-H2O, ASH) system, breakdowns to contain further hydrated minerals, gibbsite (Al(OH)3) and diaspore (AlO(OH)), when subducts along a water-saturated cold subduction geotherm. Such a hydration breakdown occurs at a depth of ~135 km to uptake water by ~1.8 wt%. Subsequently, dehydration breakdown occurs at ~185 km depth to release back the same amount of water, after which the net crystalline water content is preserved down to ~660 km depth, delivering a net amount of ~5.0 wt% H2O in a phase assemblage containing δ-AlOOH and phase Egg (AlSiO3(OH)). Our results thus demonstrate the importance of subducting clays to account the delivery of ~22% of water down to the lower mantle.

Qualitative and Quantitative Analysis of Chemical Components in Yinhua Pinggan Granule with High-Performance Liquid Chromatography Coupled with Q-Exactive Mass Spectrometry.

Yinhua Pinggan Granule (YPG) is an approved compounded traditional Chinese medicine (TCM) prescription for the treatment of cold, cough, viral pneumonia, and related diseases. Due to its complicated chemical composition, the material basis of YPG has not been systematically investigated. In this study, an analytical method based on high-performance liquid chromatography (HPLC) coupled with Q-Exactive mass spectrometry was established. Together with the help of a self-built compound database and Compound Discoverer software 3.1, the chemical components in YPG were tentatively identified. Subsequently, six main components in YPG were quantitatively characterized with a high-performance liquid chromatography-diode array detector (HPLC-DAD) method. As a result, 380 components were annotated, including 19 alkaloids, 8 organic acids, 36 phenolic acids, 27 other phenols, 114 flavonoids, 75 flavonoid glycoside, 72 terpenes, 11 anthraquinones, and 18 other compounds. Six main components, namely, chlorogenic acid, puerarin, 3'-methoxypuerarin, polydatin, glycyrrhizic acid, and emodin, were quantified simultaneously. The calibration curves of all six analytes showed good linearity (R2 > 0.9990) within the test ranges. The precision, repeatability, stability, and recovery values were all in acceptable ranges. In addition, the total phenol content and DPPH scavenging activity of YPG were also determined. The systematic elucidation of the chemical components in YPG in this study may provide clear chemical information for the quality control and pharmacological research of YPG and related TCM compounded prescriptions.

Solvent and monomer regulation synthesis of core-shelled magnetic ß-cyclodextrin microporous organic network for efficient extraction of estrogens in biological samples prior to HPLC analysis.

The abnormal estrogens levels in human body can cause many side effects and diseases, but the quantitative detection of the trace estrogens in complex biological samples still remains great challenge. Here we reported the fabrication of a novel core-shell structured magnetic cyclodextrin microporous organic network (Fe3O4@CD-MON) for rapid magnetic solid phase extraction (MSPE) of four estrogens in human serum and urine samples prior to HPLC-UV determination. The uniform spherical core-shell Fe3O4@CD-MONs was successfully regulated by altering the reactive monomers and solvents. The Fe3O4@CD-MONs owned high specific surface area, good hydrophobicity, large superparamagnetism, and abundant extraction sites for estrogens. Under optimal conditions, the proposed MSPE-HPLC-UV method provided wide linearity range (2.0-400 µg L-1), low limits of detection (0.5-1.0 µg L-1), large enrichment factors (183-198), less adsorbent consumption (3 mg), short extraction time (3 min), and good stability and reusability (at least 8 cycles). The established method had also been successfully applied to the enrichment and detection of four estrogens in serum and urine samples with a recovery of 88.4-105.1 % and a relative standard deviation of 1.0-5.9 %. This work confirmed the feasibility of solvent and monomer regulation synthesis of Fe3O4@CD-MON composites, and revealed the great prospects of magnetic CD-MONs for efficient enrichment of trace estrogens in complex biological samples.

Serum Albumin-to-Creatinine Ratio: A Novel Predictor of Pulmonary Infection in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

AIM: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), a low serum albumin-to-creatinine ratio (sACR) is associated with elevated risk of poor short- and long-term outcomes. However, the relationship between sACR and pulmonary infection during hospitalization in patients with STEMI undergoing PCI remains unclear. METHODS: A total of 4,507 patients with STEMI undergoing PCI were enrolled and divided into three groups according to sACR tertile. The primary outcome was pulmonary infection during hospitalization, and the secondary outcome was in-hospital major adverse cardiovascular events (MACE) including stroke, in-hospital mortality, target vessel revascularization, recurrent myocardial infarction, and all-cause mortality during follow-up. RESULTS: Overall, 522 (11.6%) patients developed pulmonary infections, and 223 (4.9%) patients developed in-hospital MACE. Cubic spline models indicated a non-linear, L-shaped relationship between sACR and pulmonary infection (P=0.039). Receiver operating characteristic curve analysis indicated that sACR had good predictive value for both pulmonary infection (area under the ROC curve [AUC]=0.73, 95% CI=0.70-0.75, P＜0.001) and in-hospital MACE (AUC=0.72, 95% CI=0.69-0.76, P＜0.001). Kaplan-Meier survival analysis indicated that higher sACR tertiles were associated with a greater cumulative survival rate (P＜0.001). Cox regression analysis identified lower sACR as an independent predictor of long-term all-cause mortality (hazard ratio [HR]=0.96, 95% CI=0.95-0.98, P＜0.001). CONCLUSIONS: A low sACR was significantly associated with elevated risk of pulmonary infection and MACE during hospitalization, as well as all-cause mortality during follow-up among patients with STEMI undergoing PCI. These findings highlighted sACR as an important prognostic marker in this patient population.

Integrative and conjugative elements of Pasteurella multocida: Prevalence and signatures in population evolution.

Pasteurella multocida (P. multocida) is a bacterial pathogen responsible for a range of infections in humans and various animal hosts, causing significant economic losses in farming. Integrative and conjugative elements (ICEs) are important horizontal gene transfer elements, potentially enabling host bacteria to enhance adaptability by acquiring multiple functional genes. However, the understanding of ICEs in P. multocida and their impact on the transmission of this pathogen remains limited. In this study, 42 poultry-sourced P. multocida genomes obtained by high-throughput sequencing together with 393 publicly available P. multocida genomes were used to analyse the horizontal transfer of ICEs. Eighty-two ICEs were identified in P. multocida, including SXT/R391 and Tn916 subtypes, as well as three subtypes of ICEHin1056 family, with the latter being widely prevalent in P. multocida and carrying multiple resistance genes. The correlations between insertion sequences and resistant genes in ICEs were also identified, and some ICEs introduced the carbapenem gene blaOXA-2 and the bleomycin gene bleO to P. multocida. Phylogenetic and collinearity analyses of these bioinformatics found that ICEs in P. multocida were transmitted vertically and horizontally and have evolved with host specialization. These findings provide insight into the transmission and evolution mode of ICEs in P. multocida and highlight the importance of understanding these elements for controlling the spread of antibiotic resistance.

NLRP4E regulates actin cap formation through SRC and CDC42 during oocyte meiosis.

BACKGROUND: Members of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing (NLRP) family regulate various physiological and pathological processes. However, none have been shown to regulate actin cap formation or spindle translocation during the asymmetric division of oocyte meiosis I. NLRP4E has been reported as a candidate protein in female fertility, but its function is unknown. METHODS: Immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were employed to examine the localization and expression levels of NLRP4E and related proteins in mouse oocytes. small interfering RNA (siRNA) and antibody transfection were used to knock down NLRP4E and other proteins. Immunoprecipitation (IP)-mass spectrometry was used to identify the potential proteins interacting with NLRP4E. Coimmunoprecipitation (Co-IP) was used to verify the protein interactions. Wild type (WT) or mutant NLRP4E messenger RNA (mRNA) was injected into oocytes for rescue experiments. In vitro phosphorylation was employed to examine the activation of steroid receptor coactivator (SRC) by NLRP4E. RESULTS: NLRP4E was more predominant within oocytes compared with other NLRP4 members. NLRP4E knockdown significantly inhibited actin cap formation and spindle translocation toward the cap region, resulting in the failure of polar body extrusion at the end of meiosis I. Mechanistically, GRIN1, and GANO1 activated NLRP4E by phosphorylation at Ser429 and Thr430; p-NLRP4E is translocated and is accumulated in the actin cap region during spindle translocation. Next, we found that p-NLRP4E directly phosphorylated SRC at Tyr418, while p-SRC negatively regulated p-CDC42-S71, an inactive form of CDC42 that promotes actin cap formation and spindle translocation in the GTP-bound form. CONCLUSIONS: NLRP4E activated by GRIN1 and GANO1 regulates actin cap formation and spindle translocation toward the cap region through upregulation of p-SRC-Tyr418 and downregulation of p-CDC42-S71 during meiosis I.

[Study on mechanism of Chinese Yam polysaccharide synergizing nucleoside analogues against hepatitis B virus through p38 MAPK signaling pathway].

This study explore the molecular mechanism of the synergistic effect of Chinese Yam polysaccharides and nucleoside analogues(NAs) on hepatitis B virus(HBV) resistance. Different concentrations of Chinese Yam polysaccharide and entecavir were ad-ded to HepG2.2.15 cells. After the cytotoxicity was detected by cell counting kit-8(CCK-8), the optimal concentration and time of the two drugs to inhibit HepG2.2.15 cells were screened out. They were divided into control group, Chinese Yam polysaccharide group, entecavir group and combination drug group(Chinese Yam polysaccharide + entecavir). The drugs were added to HepG2.2.15 cells, ELISA was used to detect the effects of each group of drugs on the secretion of hepatitis B virus surface antigen(HBsAg) and hepatitis B virus e antigen(HBeAg) in cell supernatant, probe quantitative real-time PCR(probe qRT-PCR) was used to detect the effects of drugs on HBV-DNA in HepG2.2.15 cells, and Western blot was used to detect the effects of each group of drugs on the expression of p38 MAPK, p-p38 MAPK, NTCP proteins in HepG2.2.15 cells. The qRT-PCR was used to detect the effect of drugs on the expression of p38 MAPK and NTCP mRNA in HepG2.2.15 cells. The results showed that compared with control group, the concentrations of HBeAg and HBsAg in Chinese Yam polysaccharide group, entecavir group and combination group decreased(P<0.01 or P<0.001), and both of them inhibited HBV-DNA in HepG2.2.15 cells(P<0.01), and the HBV-DNA inhibition of HepG2.2.15 cells in the combination group was more obvious(P<0.001), and the protein expression levels of p-p38 MAPK and NTCP were significantly decreased(P<0.05 or P<0.01), the mRNA expression level of p38 MAPK increased, and the mRNA expression level of NTCP decreased(P<0.05 or P<0.01). To sum up, Chinese Yam polysaccharide can reduce the expression of NTCP protein and mRNA through p38 MAPK signaling pathway and cooperate with entecavir in anti-HBV.