Construction and validation of a ubiquitination-related prognostic risk score signature in breast cancer.

Background: Breast cancer (BC) is a highly common form of cancer that occurs in many parts of the world. However, early -stage BC is curable. Many patients with BC have poor prognostic outcomes owing to ineffective diagnostic and therapeutic tools. The ubiquitination system and associated proteins were found influencing the outcome of individuals with cancer. Therefore, developing a biomarker associated with ubiquitination genes to forecast BC patient outcomes is a feasible strategy. Objective: The primary goal of this work was to develop a novel risk score signature capable of accurately estimate the future outcome of patients with BC by targeting ubiquitinated genes. Methods: Univariate Cox regression analysis was conducted utilizing the E1, E2, and E3 ubiquitination-related genes in the GSE20685 dataset. Genes with p < 0.01 were screened again using the Non-negative Matrix Factorization (NMF) algorithm, and the resulting hub genes were composed of a risk score signature. Patients were categorized into two risk groups, and the predictive effect was tested using Kaplan-Meier (KM) and Receiver Operating Characteristic (ROC) curves. This risk score signature was later validated using multiple external datasets, namely TCGA-BRAC, GSE1456, GSE16446, GSE20711, GSE58812 and GSE96058. Immuno-microenvironmental, single-cell, and microbial analyses were also performed. Results: The selected gene signature comprising six ubiquitination-related genes (ATG5, FBXL20, DTX4, BIRC3, TRIM45, and WDR78) showed good prognostic power in patients with BC. It was validated using multiple externally validated datasets, with KM curves showing significant differences in survival (p < 0.05). The KM curves also demonstrated superior predictive ability compared to traditional clinical indicators. Single-cell analysis revealed that Vd2 gd T cells were less abundantin the low-risk group, whereas patients in the high-risk group lacked myeloid dendritic cells. Tumor microbiological analysis revealed a notable variation in microorganism diversity between the high- and low-risk groups. Conclusion: This study established an risk score signature consisting of six ubiquitination genes, that can accurately forecast the outcome of patients with BC using multiple datasets. It can provide personalized and targeted assistance to provide the evaluation and therapy of individuals having BC.

Effect of acacetin on inhibition of apoptosis in Helicobacter pylori-infected gastric epithelial cell line.

BACKGROUND: Helicobacter pylori (H. pylori) infection can cause extensive apoptosis of gastric epithelial cells, serving as a critical catalyst in the progression from chronic gastritis, gastrointestinal metaplasia, and atypical gastric hyperplasia to gastric carcinoma. Prompt eradication of H. pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer. Acacetin, which has multifaceted pharmacological activities such as anti-cancer, anti-inflammatory, and antioxidative properties, has been extensively investigated across various domains. Nevertheless, the impact and underlying mechanisms of action of acacetin on H. pylori-infected gastric mucosal epithelial cells remain unclear. AIM: To explore the defensive effects of acacetin on apoptosis in H. pylori-infected GES-1 cells and to investigate the underlying mechanisms. METHODS: GES-1 cells were treated with H. pylori and acacetin in vitro. Cell viability was assessed using the CCK-8 assay, cell mortality rate via lactate dehydrogenase assay, alterations in cell migration and healing capacities through the wound healing assay, rates of apoptosis via flow cytometry and TUNEL staining, and expression levels of apoptosis-associated proteins through western blot analysis. RESULTS: H. pylori infection led to decreased GES-1 cell viability, increased cell mortality, suppressed cell migration, increased rate of apoptosis, increased expressions of Bax and cle-caspase3, and decreased Bcl-2 expression. Conversely, acacetin treatment enhanced cell viability, mitigated apoptosis induced by H. pylori infection, and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3. CONCLUSION: Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H. pylori-infected GES-1 cells, thereby exerting a protective effect on gastric mucosal epithelial cells.

Transcriptomic analysis of mRNA and miRNA reveals new insights into the regulatory mechanisms of Anadara granosa responses to heat stress.

Temperature fluctuations resulting from climate change and global warming pose significant threats to various species. The blood clam, Anadara granosa, a commercially important marine bivalve, predominantly inhabits intertidal mudflats that are especially susceptible to elevated temperatures. This vulnerability has led to noticeable declines in the survival rates of A. granosa larvae, accompanied by an increase in malformations. Despite these observable trends, there is a lack of comprehensive research on the regulatory mechanisms underlying A. granosa's responses to heat stress. In this study, we examined the survival rates of A. granosa under varying high temperature conditions, selecting 34 °C as heat stress temperature. Enzyme activity assays have shed light on A. granosa's adaptive response to heat stress, revealing its ability to maintain redox balance and transition from aerobic to anaerobic metabolic pathways. Subsequently, mRNA and miRNA transcriptome analyses were conducted, elucidating several key responses of A. granosa to heat stress. These responses include the upregulation of transcription and protein synthesis, downregulation of proteasome activity, and metabolic pattern adjustments. Furthermore, we identified miRNA-mRNA networks implicated in heat stress responses, potentially serving as valuable candidate markers for A. granosa's heat stress response. Notably, we validated the involvement of agr-miR-3199 in A. granosa's heat stress response through its regulation of the target gene Foxj1. These findings not only deepen our understanding of the molecular mechanisms underlying the blood clam's response to heat stress but also offer valuable insights for enhancing heat stress resilience in the blood clam aquaculture industry. Moreover, they contribute to improved cultivation strategies for molluscs in the face of global warming and have significant implications for the conservation of marine resources and the preservation of ecological balance.

Genome-wide CRISPR screening identifies critical role of phosphatase and tensin homologous (PTEN) in sensitivity of acute myeloid leukemia to chemotherapy. / å ¨åŸºå› ç»„CRISPR筛选揭示PTENåŸºå› åœ¨æ€¥æ€§é«“ç³»ç™½è¡€ç— åŒ–ç–—æ•æ„Ÿæ€§ä¸­çš„å ³é”®ä½œç”¨.

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia (AML) in recent years, chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients. Here, we demonstrated the antileukemia activity of a novel small molecular compound NL101, which is formed through the modification on bendamustine with a suberanilohydroxamic acid (SAHA) radical. NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells. It induces DNA damage and caspase 3-mediated apoptosis. A genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) library screen revealed that phosphatase and tensin homologous (PTEN) gene is critical for the regulation of cell survival upon NL101 treatment. The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome (MDS) cells, accompanied by the activation of protein kinase B (AKT) signaling pathway. The inhibition of mammalian target of rapamycin (mTOR) by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death. These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

Synaptic gene expression changes in frontotemporal dementia due to the MAPT 10 + 16 mutation.

AIMS: Mutations in the MAPT gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer's disease, the most common tauopathy, synapse loss is the strongest pathological correlate of cognitive decline. Recently, Positron Emission Tomography (PET) imaging with synaptic tracers revealed clinically relevant loss of synapses in primary tauopathies; however, the molecular mechanisms leading to synapse degeneration in primary tauopathies remain largely unknown. In this study, we examined post-mortem brain tissue from people who died with frontotemporal dementia with tau pathology (FTDtau) caused by the MAPT intronic exon 10 + 16 mutation, which increases splice variants containing exon 10 resulting in higher levels of tau with four microtubule-binding domains. METHODS: We used RNA sequencing and histopathology to examine temporal cortex and visual cortex, to look for molecular phenotypes compared to age, sex and RNA integrity matched participants who died without neurological disease (n = 12 FTDtau10 + 16 and 13 controls). RESULTS: Bulk tissue RNA sequencing reveals substantial downregulation of gene expression associated with synaptic function. Upregulated biological pathways in human MAPT 10 + 16 brain included those involved in transcriptional regulation, DNA damage response and neuroinflammation. Histopathology confirmed increased pathological tau accumulation in FTDtau10 + 16 cortex as well as a loss of presynaptic protein staining and region-specific increased colocalization of phospho-tau with synapses in temporal cortex. CONCLUSIONS: Our data indicate that synaptic pathology likely contributes to pathogenesis in FTDtau10 + 16 caused by the MAPT 10 + 16 mutation.

Silicone-modified black peanut shell (BPS) biochar adsorbents: Preparation and their adsorptions for copper(II) from water.

Novel silicone-modified biochar adsorbents (BPS-MBCs) were prepared by utilizing waste black peanut shell (BPS) as a raw biochar and gamma-amino-propyl triethoxysilane (silicone) as an inorganic modifier. The novelty of this work is that the incorporation of silicone into BPS can rise the specific surface area and porosity of BPS-MBCs and elevate their adsorptions for copper (II). Sorption kinetics data for copper (II) were molded using five kinetic equations [i.e. Lagergren 1st-order and 2nd-order, intraparticle diffusion (IN-D), Elovich, and Diffusion-chemisorption]. The equilibrium adsorption data for copper (II) were analyzed using two-parameter isotherm equations [i.e. Langmuir, Freundlich, Dubinin-Radushkevich, and Temkin] and three-parameter Sips, Redlich-Peterson and Toth isotherm models. It was validated that copper (II) sorption on BPS-MBCs matched better with pseudo-2nd-order kinetic, Diffusion-chemisorption and Langmuir isotherm models. The maximal qmLan of BPS-MBC-400 was near 284 mg/g at 45 °C. By multi-phase fitting of IN-D modelling, intra-particle diffusion coefficient (kin-d) and diffusion coefficient of external mass-transfer (DEx-Di) for copper (II) were calculated. The low sorption energy from Temkin and mean free energy from D-R modellings implied that copper (II) sorption was initiated by weak non-covalent bond interactions. Thermodynamic parameters indicated that copper (II) on BPS-MBCs was an endothermic and spontaneous process. Recycling of BPS-MBC-400 for copper (II) suggested it has excellent reusability. The major mechanism of copper (II) on BPS-MBCs is possibly comprised of multiple processes, such as physical adsorption (electrostatic attraction), chemical adsorption (adsorption from functional groups, chelation, and ion exchange) and diffusion-chemisorption. Based on these findings, it is expects that BPS-MBCs are promising sorbents for copper (II) eradication from Cu(II)-including wastewater.

[Application of ion chromatographic fingerprint analysis for quality evaluation of tobacco flavors].

Tobacco flavor, an important tobacco additive, is an essential raw material in cigarette production that can effectively improve the quality of tobacco products, add aroma and taste, and increase the suction flavor. The quality consistency of tobacco flavors affects the quality stability of branded cigarettes. Therefore, the quality control of tobacco flavors is a major concern for cigarette and flavor manufacturers. Physical and chemical indices, odor similarity, and sensory efficacy are employed to evaluate the quality of tobacco flavors, and the analysis of chemical components in tobacco flavors is usually conducted using gas chromatography (GC) and high performance liquid chromatography (HPLC). However, because the composition of tobacco flavors is complex, their quality cannot be fully reflected using a single component or combination of components. Therefore, establishing an objective analytical method for the quality control of tobacco flavors is of extreme importance. Chromatographic fingerprint analysis is routinely used for the discriminative analysis of tobacco flavors. Chromatographic fingerprints refer to the general characteristics of the concentration profiles of different chemical compounds. In the daily procurement process, fingerprints established by GC and HPLC are effective for the evaluation and identification of tobacco flavors. However, given continuous improvements in aroma-imitation technology, some flavors with high similarity cannot be directly distinguished using existing methods. In this study, a method for the determination of organic acids and inorganic anions in tobacco flavors based on ion chromatography (IC) was developed to ensure the quality consistency of tobacco flavors. A 1.0 g sample of tobacco flavors and 10 mL of deionized water were mixed and vibrated for 30 min. The aqueous sample solution was passed through a 0.45 µm membrane filter and RP pretreatment column in succession to eliminate interferences and then subjected to IC. Standard solutions containing nine organic acids and seven inorganic anions were used to identify the anions in the tobacco flavors, and satisfactory reproducibility was obtained. The relative standard deviations (RSDs) for retention times and peak areas were <0.71% and <6.02%, respectively. The chromatographic fingerprints of four types of tobacco flavors (samples A-D) from five different batches were obtained. Nine tobacco flavor samples from different manufacturers (samples AY1-AY3, BY1-BY2, CY1-CY2, DY1-DY2) were also analyzed to obtain their chromatographic fingerprints. Hierarchical cluster and similarity analyses were used to evaluate the quality of tobacco flavors from different manufacturers. Hierarchical clustering refers to the process of subdividing a group of samples into clusters that exhibit a high degree of intracluster similarity and intercluster dissimilarity. The dendrograms obtained using SPSS 12.0 indicated good quality consistency among the samples in different batches. Samples AY3, BY2, CY2, and DY1 clustered with the batches of standard tobacco flavors. Therefore, hierarchical cluster analysis can effectively distinguish the quality of products from different manufacturers. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (version 2.0) was used to evaluate the similarity between the standard tobacco flavors and products from different manufacturers. Among the samples analyzed, samples AY3, BY2, CY2, and DY1 showed the highest similarity values (>97.7%), which was consistent with the results of the hierarchical cluster analysis. This finding indicates that IC combined with chromatographic fingerprint analysis could accurately determine the quality of tobacco flavors. GC combined with ultrasonic-assisted liquid-liquid extraction was also used to analyze the tobacco flavors and verify the accuracy of the proposed method. Compared with GC coupled with ultrasonic-assisted liquid-liquid extraction, IC demonstrated more significant quality differences among certain tobacco flavors.

Dilemma in patients with amyotrophic lateral sclerosis and expectations from brain-machine interfaces.

OBJECTIVE: We hypothesized that patients with amyotrophic lateral sclerosis (ALS) face a dilemma between motivation to live and difficulty in living, and brain-machine interfaces (BMIs) can reduce this dilemma. This study aimed to investigate the present situation of patients with ALS and their expectations from BMIs. MATERIALS AND METHODS: Our survey design consisted of an anonymous mail-in questionnaire comprising questions regarding the use of tracheostomy positive pressure ventilation (TPPV), motivation to live, anxiety about the totally locked-in state (TLS), anxiety about caregiver burden, and expectations regarding the use of BMI. Primary outcomes were scores for motivation to live and anxiety about caregiver burden and the TLS. Outcomes were evaluated using the visual analogue scale. RESULTS: Among 460 participants, 286 (62.6%) were already supported by or had decided to use TPPV. The median scores for motivation to live, anxiety about TLS, and anxiety about caregiver burden were 8.0, 9.0, and 7.0, respectively. Overall, 49% of patients intended to use BMI. Among patients who had refused TPPV, 15.9% intended to use BMI and TPPV. Significant factors for the use of BMI were motivation to live (p = .003), anxiety about TLS (p < .001), younger age (p < .001), and advanced disease stage (p < .001). CONCLUSIONS: These results clearly revealed a serious dilemma among patients with ALS between motivation to live and their anxiety about TLS and caregiver burden. Patients expected BMI to reduce this dilemma. Thus, the development of better BMIs may meet these expectations.

Long-Term Stable Dispersion of Multiwalled Carbon Nanotubes by Peroxydisulfate upon Ultrasonication Activation.

Poor dispersibility of carbon nanotubes greatly hinders their practical applications. Herein, a long-term stable dispersion of multiwalled carbon nanotubes (MWCNTs) in peroxydisulfate (PDS) is achieved. MWCNTs at 40 mg L-1 are completely dispersed by PDS upon ultrasonication (US/PDS) within 64 min and a stable dispersion is maintained at least 20 days. Mechanistically, US created defects on the nanomaterial and PDS-origin free radicals attacked these defects to introduce O-containing moieties (─OH and ─COOH). Interestingly, dispersion efficiency of MWCNTs by US/PDS initially at pH 7 and 3.8 is comparable, but lower than that initially at pH 12. Both •OH and SO4 •- are produced under alkaline condition, while SO4 •- is the dominant free radicals initially at pH 7 and 3.8 during the whole dispersion period. Stronger dispersion of MWCNTs initially at pH 12 resulted from greater amounts of O-containing moieties mainly in ─OH (46.32%) rather than ─COOH (24.19%) form. This differential more strongly promotes MWCNTs-water interaction via hydrogen bonding, thereby enhancing the dispersion. Notably, no significant mass loss of MWCNTs occurred during dispersion. Overall, the developed method achieves long-term stable dispersion of MWCNTs in a manner that can significantly extend their applications.

A new crystalline daidzein-piperazine salt with enhanced solubility, permeability, and bioavailability.

To overcome the poor solubility, permeability, and bioavailability of the plant isoflavone daidzein (DAI), a novel salt of DAI with anhydrous piperazine (PIP) was obtained based on cocrystallization strategy. The new salt DAI-PIP was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, and optical microscopy. The results showed that the maximum apparent solubility (Smax) of DAI-PIP increased by 7.27-fold and 1000-fold compared to DAI in pH 6.8 buffer and water, respectively. The peak apparent permeability coefficient (P app ) of DAI-PIP in the Caco-2 cell model was 30.57 ± 1.08 × 10-6 cm/s, which was 34.08% higher than that of DAI. Additionally, compared to DAI, the maximum plasma concentration (Cmax) value of DAI-PIP in beagle dogs was approximately 4.3 times higher, and the area under the concentration-time curve (AUC0-24) was approximately 2.4 times higher. This study provides a new strategy to enhance the dissolution performance and bioavailability of flavonoid drugs, laying a foundation for expanding their clinical applications.

Hypoxia-induced LAMB2-enriched extracellular vesicles promote peritoneal metastasis in gastric cancer via the ROCK1-CAV1-Rab11 axis.

Peritoneal metastasis is one of the most common risk factors contributing to the poor prognosis of gastric cancer. We previously reported that extracellular vesicles from gastric cancer cells could facilitate peritoneal metastasis. However, their impact on gastric cancer-induced peritoneal metastasis under hypoxic conditions remains unclear. This study aims to elucidate how hypoxia-resistant gastric cancer cell-derived extracellular vesicles affect the peritoneal metastasis of normoxic gastric cancer cells. Proteomic analysis revealed elevated levels of Caveolin1 and Laminin ß2 in hypoxia-resistant gastric cancer cells and their corresponding extracellular vesicles. Importantly, Caveolin1 was found to play a central role in mediating Laminin ß2 sorting into extracellular vesicles derived from hypoxia-resistant gastric cancer cells, and subsequently, extracellular vesicle-associated Laminin ß2 promoted peritoneal metastasis in normoxic gastric cancer cells by activating the AKT pathway. Further investigation confirmed that Caveolin1 activation by Rho-related Coiled-coil kinase 1-mediated phosphorylation of Y14 residue is a key factor facilitating Laminin ß2 sorting into extracellular vesicles. Moreover, Y14 phosphorylated- Caveolin1 enhanced Laminin ß2 sorting by activating Rab11. Finally, our study demonstrated that a combined assessment of plasma extracellular vesicle-associated Caveolin1 and extracellular vesicle-associated Laminin ß2 could provide an accurate predictive tool for peritoneal metastasis occurrence in gastric cancer.

Sofalcone attenuates neurodegeneration in MPTP-induced mouse model of Parkinson's disease by inhibiting oxidative stress and neuroinflammation.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by oxidative stress and neuroinflammation. Sofalcone (SFC), a chalcone derivative known for its antioxidative and anti-inflammatory properties, is widely used clinically as a gastric mucosa protective agent. However, its therapeutic potential in PD remains to be fully explored. In this study, we investigated the neuroprotective effects of SFC in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. METHODS AND RESULTS: We found that SFC ameliorated MPTP-induced motor impairments in mice, as assessed by the rotarod and wire tests. Moreover, SFC administration prevented the loss of dopaminergic neurons and striatal degeneration induced by MPTP. Subsequent investigations revealed that SFC reversed MPTP-induced downregulation of NRF2, reduced elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased total antioxidant capacity (TAOC). Furthermore, SFC suppressed MPTP-induced activation of microglia and astrocytes, downregulated the pro-inflammatory cytokine TNF-α, and upregulated the anti-inflammatory cytokine IL-4. Additionally, SFC ameliorated the MPTP-induced downregulation of phosphorylation of Akt at Ser473. CONCLUSIONS: This study provides evidence for the neuroprotective effects of SFC, highlighting its antioxidative and anti-inflammatory properties and its role in Akt activation in the PD model. These findings underscore SFC's potential as a promising therapeutic candidate for PD, warranting further clinical investigation.

Investigation on the solidification effect and mechanism of loess utilizing magnesium oxysulfate cement as a curing agent.

In this study, magnesium oxysulfate cement (MOS) was used as a binder for curing loess. The changes in bulk density, porosity, mineral structure and microstructure of the consolidated loess were systematically studied and verified. The porosity decreased from 40.97 % in pure loess to 28.75 % in 13 % MOS solidified sample. Scanning electron microscopy, energy spectrum analysis and thermogravimetric analysis revealed that the addition of MOS binder resulted in the formation of hydrated products, including Mg(OH)2, MgO·mSiO2·nH2O (M-S-H), and 3Mg(OH)2·MgSO4·8H2O (3·1·8 phase), which effectively filled the voids between the grains and facilitated strong bonding among them. After a curing period of 28 days, the compressive strength of loess stabilized with 13 % MOS exhibited an increase to 7.9 MPa. Moreover, following immersion in water for 24 h, the softening coefficient K remained at 0.66. Furthermore, after undergoing five cycles of freeze-thaw cycling, the rate of change in compressive strength RP was only 6.3 %. All the results indicate that MOS exhibits promising potential as a binder for soil stabilization applications.

Novel glucomannan-like polysaccharide from Lycium barbarum L. ameliorates renal fibrosis via blocking macrophage-to-myofibroblasts transition.

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-ß. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.

Composition and function of plant chromatin remodeling complexes.

ATP-dependent chromatin remodelers play a crucial role in modifying chromatin configuration by utilizing the energy of ATP hydrolysis. They are involved in various processes, including transcription, DNA replication, and maintaining genome stability. These remodeling remodelers usually form multi-subunit chromatin remodeling complexes in eukaryotes. In plants, chromatin remodeling complexes have diverse functions in regulating plant development and stress response. Recent studies have conducted extensive research on plant chromatin remodeling complexes. This review focuses on recent advances in the classification and composition of plant chromatin remodeling complexes, the protein-protein interactions within the complexes, their impact on chromatin configuration, and their interactions with chromatin modifications and transcription factors.

Association between homocysteine levels and hyperlipidemia prevalence as well as all-cause mortality of hyperlipidemia patients in the US population: results from NHANES database.

Objective: Several studies have investigated the correlation between blood lipids and homocysteine, but no clear conclusions have been defined yet. Therefore, we utilized data from National Health and Nutrition Examination Survey (NHANES) to explore the correlation between serum homocysteine (Hcy) levels and hyperlipidemia, which is determined by the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). We believe this study can provide a scientific basis for the prevention and treatment of lipid abnormalities. Methods: The data used in this study were sourced from NHANES 1999-2006, linked with National Death Index mortality data from January 1999 to December 2019. We employed logistic regression to assess the associations between Hcy levels and the presence of hyperlipidemia. Additionally, survival analysis using Kaplan-Meier estimate and Cox proportional hazards regression model was conducted to evaluate the associations between Hcy levels and all-cause mortality in the hyperlipidemia population. Results: (1) A total of 13,661 subjects were included in the study. There were statistically significant differences in Hcy levels across different groups based on gender, age, race, marital status, education level, hypertension status, diabetes status, and Body Mass Index (BMI) (P < 0.05). (2) In the overall population, hyperhomocysteinemia (HHcy) was associated with an increased risk of high-TC hyperlipidemia (P < 0.05). Subgroup analysis by gender showed that HHcy in females was associated with an increased risk of dyslipidemia (OR = 1.30, 95% CI: 1.07-1.59, P < 0.05) and high-LDL-C hyperlipidemia (OR = 1.30, 95% CI: 1.00-1.68, P < 0.05). In addition, subgroup analysis by age revealed that HHcy in middle-aged people was associated with an increased risk of high-TC hyperlipidemia (OR = 1.21, 95% CI: 1.03-1.41, P < 0.05) and high-LDL-C hyperlipidemia (OR = 1.23, 95% CI: 1.06-1.43, P < 0.05). (3) HHcy was consistently associated with an increased mortality risk in the hyperlipidemia population (HR = 1.49, 95% CI: 1.35-1.65, P < 0.05). Conclusion: There was positive correlation between Hcy levels and the presence of hyperlipidemia. In the overall population, HHcy was associated with an increased risk of high-TC hyperlipidemia. Among females, HHcy is linked to an increased risk of dyslipidemia and high-LDL-C hyperlipidemia. In middle-aged people, HHcy was associated with an elevated risk of high-TC hyperlipidemia and high-LDL-C hyperlipidemia. In addition, HHcy increased the all-cause mortality rate in hyperlipidemia patients.

Ca2+-mediated chitosan/sodium alginate encapsulated Red Monascus Pigment hydrogel beads: Preparation, characterization and release kinetic.

Red Monascus Pigment (RMP), a natural pigment, has attracted significant attention due to its suitability for food use and potential health benefits. However, preserving its stability and exploring value-added development opportunities remain crucial challenges. This study outlined the utilization of RMP, by successfully preparing hydrogel beads encapsulating RMP crude extract (RMPCE) through Ca2+-mediated chitosan (CS)/sodium alginate (SA) encapsulation (CO-RMPHB). A systematic investigation into the fabrication and stability parameters, including preparation conditions, temperature, monochromatic light and storage time, was undertaken. Through optimization (SA: 2.50 wt%; CaCl2: 6.00 wt%; CS: 0.50 wt%), maximum encapsulation efficiency of 73.54 ±â€¯2.16 % was achieved. The maximum swelling degree of blank hydrogel beads (BHB) in simulated gastric solution (pH = 1.2, 1.50 ±â€¯0.97 %) was significantly lower than in simulated intestinal solution (pH = 7.0, 28.05 ±â€¯1.43 %), confirming their sensitivity to pH changes. Additionally, the CO-RMPHB (66.08 %, 1000 µL) exhibited superior DPPH radical scavenging capability compared to individual RMPCE or BHB. Furthermore, analysis of the release kinetics based on zero-order, first-order, Higuchi, and Ritger-Peppas models revealed that RMPCE release from CO-RMPHB under in vitro digestion models followed non-Fickian diffusion. This discovery effectively addresses the challenges of the stability and controlled release of RMP, expanding its applications in the food and pharmaceutical industries.

A study on the configuration of factors influencing overweight and obesity in adolescents based on fuzzy set qualitative comparative analysis.

OBJECTIVE: Overweight and obesity among adolescents are grave public health issues around the world. Although the conditions that contribute to obesity have been extensively researched, little is known about how multiple conditions interact to cause overweight and obesity. The current study intends to investigate the histomorphic configuration pathways of several conditions of adolescent overweight and obesity by gender. METHOD: The data came from a social survey conducted in June 2021 in Changchun, Jilin Province, China. The sample collected was 14-year-old adolescents, including 167 boys and 137 girls. The school physicians examined the participants' weight and height, and questionnaires were used to collect risk indicators from adolescents, such as sleep duration, electronic screens times, consumption of sugary drinks and fried foods, and physical activity. Simultaneously, a Fuzzy Qualitative Comparative Analysis will be performed to investigate the combinations of diverse conditions. RESULT: We found that there is no determining necessary condition that, once present, directly determines that an individual is in a state of overweight and obesity. Simultaneously, this study revealed nine alternative configurational paths of overweight and obesity in teenagers of different genders, with a concordance of 0.805 for six male groupings and 0.916 for three female groupings. The outcomes of overweight obesity in adolescents under different genders are similar but not identical. CONCLUSION: This study examined the interactions of a number of conditions from the individual, behavioral, learning and living environment that led to the same overweight obese outcome among adolescents of different genders. Our research will be useful to policymakers in that interventions should take into account the combined effects of a number of different aspects rather than focusing on a single factor that causes overweight and obesity.

Gut fungi of black-necked cranes (Grus nigricollis) respond to dietary changes during wintering.

BACKGROUND: Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis). RESULTS: In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P < 0.05, LDA > 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal. CONCLUSIONS: This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host's food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.

Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus.

BACKGROUND & AIMS: Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for hepatitis B virus (HBV). However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection. METHODS: Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection. RESULTS: Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of the HBV envelope protein LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both in vitro and in vivo. CONCLUSIONS: Our findings indicate that NRP1 is a novel host factor for HBV infection, which interacts with preS1 and NTCP to modulate HBV entry into hepatocytes. IMPACT AND IMPLICATIONS: HBV infection is a global public health problem, but the understanding of the early infection process of HBV remains limited. Through single-cell sequencing, we identified a novel host factor, NRP1, which modulates HBV entry by interacting with HBV preS1 and NTCP. Moreover, antagonists targeting NRP1 can inhibit HBV infection both in vitro and in vivo. This study could further advance our comprehension of the early infection process of HBV.