Search Results (2,526)

Background: Cadmium (Cd) pollution poses a significant environmental challenge. Microbially induced carbonate precipitation (MICP), an advanced bioremediation approach, relies on the co-precipitation of soluble metals with the microbial hydrolysate from urea. This study isolated a urease-producing strain and evaluated its Cd remediation potential. Methods: The isolated strain UA7 was identified through 16S rDNA gene sequencing. Urease production was enhanced by optimizing the culture conditions, including temperature, dissolved oxygen levels—which were affected by the rotational speed and the design of the Erlenmeyer flask, and the concentration of urea added. Its Cd remediation efficacy was assessed both in water and soil. Results: UA7 was identified as Lysinibacillus sp., achieving peak urease activity of 188 U/mL. The immobilization rates of soluble Cd reached as high as 99.61% and 63.37%, respectively, at initial concentrations of 2000 mg/L in water and 50 mg/kg in soil. The mechanism of Cd immobilization by strain UA7 via MICP was confirmed by the microstructure of the immobilized products with attached bacteria, characteristic absorption peaks, and the formed compound Ca_0.67Cd_0.33CO₃, which were analyzed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The Cd-remediation effect of strain UA7, which reduces lodging in wheat plants, prevents the thinning and yellowing of stems and leaves, and hinders the transition of soluble Cd to the above-ground parts of the plant, was also demonstrated in a pot experiment. Conclusions: Therefore, Lysinibacillus sp. UA7 exhibited high potential for efficiently remediating contaminated Cd. Full article

Understanding heavy metal behavior in arid saline soils is critical for phytoremediation in degraded lands. This study investigated metal distribution and plant enrichment in the Tarim Basin using 323 soil and 55 plant samples (Populus euphratica, Tamarix ramosissima, cotton, jujube). Analyses included redundancy analysis (RDA) and bioconcentration factor (BCF) assessments. Key findings reveal that elevated salinity (total salts, TS > 200 g/kg) and alkalinity (pH > 8.5) immobilized As, Cd, Cu, and Zn. Precipitation and competitive leaching reduced metal mobility by 42–68%. Plant enrichment strategies diverged significantly: P. euphratica hyperaccumulated Cd (BCF = 1.59) and Zn (BCF = 2.41), while T. ramosissima accumulated As and Pb (BCF > 0.05). Conversely, cotton posed Hg transfer risks (BCF = 2.15), and jujube approached Cd safety thresholds in phosphorus-rich soils. RDA indicated that pH and total salinity (TS) jointly suppressed metal bioavailability, explaining 57.6% of variance. Total phosphorus (TP) and soil organic carbon (SOC) enhanced metal availability (36.8% variance), with notable TP-Cd synergy (Pearson’s r = 0.42). We propose a dual-threshold management framework: (1) leveraging salinity–alkalinity suppression (TS > 200 g/kg + pH > 8.5) for natural immobilization; and (2) implementing TP control (TP > 0.8 g/kg) to mitigate crop Cd risks. P. euphratica demonstrates targeted phytoremediation potential for degraded saline agricultural systems. This framework guides practical management by spatially delineating zones for natural immobilization versus targeted remediation (e.g., P. euphratica planting in Cd/Zn hotspots) and implementing phosphorus control in high-risk croplands. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4⁺ and CD8⁺ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article

Vitamin D deficiency is highly prevalent in the Middle East despite abundant sunlight; however, most genetic studies have focused on common variants in Europeans only. We analyzed whole-genome sequences from 13,808 Qatar Biobank participants, evaluating rare variants (minor allele frequency 0.01–0.0001) for associations with serum 25-hydroxyvitamin D (25(OH)D) levels and deficiency risk (≤20 ng/mL) in independent discovery (n = 5885) and replication (n = 7767) cohorts, followed by meta-analyses. In quantitative analyses, the discovery cohort identified 41 genome-wide significant signals, including CD36 rs192198195 (p = 2.48 × 10⁻⁸), and replication found 46, including SLC16A7 rs889439631 (p = 2.19 × 10⁻⁸), implicating lipid metabolism pathways. In binary analyses, replication revealed POTEB3 rs2605913 (p = 2.8 × 10⁻⁸), while meta-analysis (n = 13,652) uncovered SLC25A37 rs952825245 (p = 5.15 × 10⁻¹²), a locus associated with cancer and vitamin D signaling. Rare-variant polygenic scores derived from discovery significantly predicted continuous (R² = 0.146, p = 9.08 × 10⁻¹²) and binary traits (AUC = 0.548, OR = 0.99, p = 9.22 × 10⁻⁶) in replication. This first rare-variant GWAS of vitamin D in Middle Easterners identifies novel loci and pathways, underscores the contribution of ancestry-specific rare alleles, and supports integrating rare and common variants to guide precision management in high-burden populations. Full article

Vascular calcification (V) is an independent risk factor for all-cause and cardiovascular mortality. Vascular smooth muscle cells (VSMCs) play a major role in VC as they can acquire mineralizing properties when exposed to osteogenic conditions. Despite its clinical impact, there are still no dedicated therapeutic strategies targeting VC. To address this issue, we used human calcified and non-calcified atherosclerotic arteries (ECLAGEN Biocollection) to screen and identify microRNA (miR) associated with VC. We combined non-biased miRNomic (microfluidic arrays) and transcriptomic analysis to select miR candidates and their putative target genes with expression associated with VC and ossification. We further validated miR functional regulation and function in relation to cell mineralization using primary human VSMCs. Our study identified 12 miRs associated with VC in carotid and femoral arteries. Among those, we showed that miR136, miR155, and miR183 expression were regulated during VSMC mineralization and that overexpression of these miRs promoted VSMC mineralization. Cross-analysis of this miRNomic and a transcriptomic analysis led to the identification of CD73 and Smad3 pathways as putative target genes responsible for mediating the miR155 pro-mineralizing function. These results highlight the potential benefit of miR155 inhibition in limiting VC development in peripheral atherosclerotic arteries. Full article

Background: A range of cancer cells are significantly inhibited by FTY720. It is unknown, nevertheless, how FTY720 influences the onset of non-small cell lung cancer (NSCLC). Using bioinformatics techniques, we analyzed and the possible molecular mechanisms and targets of FTY720 for the treatment of NSCLC. Methods: DEGs (Differentially expressed genes) were acquired by differential analysis of the dataset GSE10072. Obtained FTY720 target genes and NSCLC disease genes from databases such as Swiss-TargetPrediction and GeneCard. Subsequently, target and disease genes, as well as DEGs, were merged for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, gene ontology (GO), and protein interaction analysis. The overlapping genes of DEGs and target genes, and disease genes were also obtained separately and subjected to survival as well as expression analyses. We constructed the regulatory network of miRNAs and transcription factors (TFs) on hub genes. Finally, the immune cell association of hub genes was evaluated using the ssGSEA method, molecular docking of FTY720 to hub genes was carried out utilizing Autodock, and molecular dynamics simulations were conducted. Results: In this study, 444 DEGs, 232 target genes of FTY720, and 466 disease genes were obtained. Moreover, a total of 1062 genes were obtained by removing duplicate values after merging, among which PIK3R1, Akt1, and S1PR1 had the highest DEGREE values in the protein interactions network, and these genes were primarily enriched in MAPK, PI3K-Akt signaling pathways, with the PI3K-Akt signaling pathway being the most prominent. Among the overlapping genes, three potential targets of FTY720 for NSCLC treatment were found: S1PR1, ZEB2, and HBEGF. ZEB2 and S1PR1 were determined to be hub genes and to significantly affect NSCLC prognosis by survival analysis. Furthermore, hsa-miR-132-3p, hsa-miR-192-5p, and hsa-miR-6845-3p were strongly associated with FTY720 for the treatment of NSCLC; CTBP1 (carboxy-terminal binding protein 1), EZH2 (protein lysine N-methyltransferase), and ZNF610 (zinc-finger protein 610) may all influence the expression of ZEB2 and S1PR1. Hub genes had a substantial negative link with memory B cells and a significant positive correlation with memory CD8 T cells and Th17 helper T cells. The molecular docking and kinetic simulation results of FTY720 with the two hub genes indicate that the protein-ligand complex has good stability. Conclusion: Our research indicates that FTY720 may inhibit NSCLC via possible targets ZEB2 and S1PR1, further laying the theoretical foundation for the utilization of FTY720 in NSCLC treatment. Full article

Elevated levels of circulating β₂-microglobulin (β₂M) are linked to an increased risk of hypertension and mortality from diabetes. The present study tests the hypothesis that the environmental pollutants, cadmium (Cd) and lead (Pb), by increasing plasma β₂M levels, promote the development of hypertension and progression of diabetic kidney disease. Herein, we analyzed data from a Thai cohort of 72 individuals with diabetes and 65 controls without diabetes who were chronically exposed to low levels of Cd and Pb. In all subjects, serum concentrations of β₂M inversely correlated with the estimated glomerular filtration rate (eGFR) (r = −0.265) and directly with age (r = 0.200), fasting plasma glucose (r = 0.210), and systolic blood pressure (r = 0.229). The prevalence odds ratio (POR) for hyperglycemia increased 7.7% for every 1-year increase in age and increased 3.9-fold, 3.1-fold, and 3.7-fold in those with serum β₂M levels ≥ 5 mg/L, Cd/Pb exposure categories 2 and 3, respectively. The POR for hypertension increased 2.9-fold, 3-fold, and 4-fold by hyperglycemia (p = 0.011), Cd/Pb exposure categories 2 and 3. The POR for albuminuria increased 3.5-fold by hyperglycemia. In conclusion, kidney damage, evident from albuminuria, was particularly pronounced in participants with diabetes who had a serum β₂M above 5 mg/L plus chronic exposure to low-dose Cd and Pb. For the first time, through a mediation analysis, we provide evidence that links Cd exposure to the SH2B3-β₂M pathway of blood pressure homeostasis in people with and without diabetes. Full article

Atherosclerosis (AS), a major contributor to cardiovascular disease, hypertension, and stroke, is associated with significant morbidity and mortality. Antimicrobial peptides (AMPs) 3-13, W3R6, and chensinin-1b were engineered based on the sequence of chensinin-1, originally isolated from the skin secretion of Rana chensinensis. This study investigated their therapeutic potential in ApoE^-/- AS mice and THP-1-derived foam cells, focusing on the regulation of cholesterol metabolism. AMP 3-13 markedly reduced body weight gain, aortic root plaque formation, and plasma cholesterol levels in ApoE^-/- mice. Transcriptomic analysis revealed that AMP 3-13 significantly altered gene expression related to cholesterol metabolism and the PPAR signaling pathway. Specifically, AMP 3-13 upregulated PPARγ, ABCA1, and ABCG1, while downregulating CD36 in aortic root plaques. In THP-1-derived foam cells, AMP 3-13 and its analogs activated the PPARγ–ABCA1/ABCG1 axis, enhancing cholesterol efflux. Concurrently, they inhibited CD36 expression by competing with PPARγ for promoter binding, thereby reducing ox-LDL uptake. These findings suggested that AMP 3-13 and its analogs represented promising therapeutic agents for AS through their ability to reduce cholesterol accumulation in foam cell. Full article

Beyond sensing bitter-tasting compounds, bitter taste receptors (TAS2Rs) have been demonstrated to play a functional role in proton secretion as a key mechanism of gastric acid secretion (GAS) and the cellular uptake of the zinc metal ion. Given its chemical similarity and comparable effects in GAS, we focused this work on cadmium and hypothesized that gastric TAS2Rs are involved in (i) cadmium-induced inhibition of proton secretion and (ii) in its cellular uptake. To test this hypothesis, immortalized human parietal HGT-1 cells were exposed to 62.5–1000 µM CdCl₂ for 30 min to elucidate TAS2R-mediated proton secretory activity (PSA) using a fluorescence-based pH cell assay and to quantitate cellular cadmium uptake by ICP-MS. HGT-1 cells exposed to CdCl₂ exhibited a dose-dependent decrease in PSA, accompanied by a corresponding increase in intracellular cadmium concentrations. Following a TAS2R RT-qPCR screening, the functional roles of TAS2R8 and TAS2R10 were clarified using a siRNA knockdown approach, demonstrating that TAS2R8 promotes and TAS2R10 mediates protection against excessive cellular cadmium accumulation. An additional cDNA microarray screening revealed, via gene ontology analysis, a distinct gene association of TAS2R8 and TAS2R10 with several metal ion transporters. These results provide the first evidence for a specific role of individual TAS2Rs beyond taste perception, particularly in metal ion homeostasis and gastric physiology. Full article

Background/Objectives: Fissidens crispulus Brid. is a dioicous moss with conspicuous axillary hyaline nodules and serrulate leaf margins. It features Neoamblyothallia-type peristome teeth and serves as an ecologically significant model for studying adaptation in the hyperdiverse genus Fissidens (>440 species). Methods: In this study, the complete chloroplast genome of F. crispulus was sequenced and de novo assembled, enabling detailed comparative genomic, phylogenetic, and codon usage bias studies. Results: As the third fully sequenced member of Fissidentaceae, this study deciphers its 124,264–124,440 bp quadripartite genome encoding 129 genes (83 CDS, 32 tRNAs, 8 rRNAs). Repeat analysis identified 125–127 SSRs, dominated by mono-/di-nucleotide A/T repeats (>70%), and dispersed repeats predominantly forward (F) and palindromic (P) (>85%), confirming profound AT-biased composition (GC content: 28.7%). We established 7 hypervariable loci (matK, ycf2, etc.) as novel Dicranidae-wide phylogenetic markers. Codon usage exhibited significant A/U-ending preference, with 12 optimal codons (e.g., GCA, UGU, UUU) determined. Maximum likelihood analyses resolved F. crispulus and F. protonematicola as sister groups with high support value (MBP = 100%). Conclusions: This work provides the foundational cpDNA resource for Fissidens, filling a major gap in bryophyte chloroplast genomics and establishing a framework for resolving the genus’s infrageneric conflicts. Furthermore, it offers critical insights into bryophyte plastome evolution and enables future codon-optimized biotechnological applications. Full article

Glioblastoma (GBM) is an aggressive brain tumor with a highly immunosuppressive microenvironment that promotes tumor progression and therapy resistance. Tumor-associated macrophages (TAMs), comprising up to 50% of the tumor mass, are recruited via chemokine axes such as CCL2/CCR2, CX3CL1/CX3CR1, and CXCL12/CXCR4 and adopt an M2-like immunosuppressive phenotype, facilitating immune escape and angiogenesis. Key signaling pathways, including CSF1R, STAT3, NF-κB, PI3K/Akt, and HIF-1α, regulate TAM function, making them promising therapeutic targets. Strategies such as TAM depletion, reprogramming, and immune checkpoint blockade (PD-1/PD-L1, and CD47-SIRPα) have shown potential in preclinical models. Emerging approaches, including CAR-macrophage (CAR-M) therapy, nanotechnology-based drug delivery, and exosome-mediated modulation, offer new avenues for intervention. However, clinical translation remains challenging due to GBM’s heterogeneity and adaptive resistance mechanisms. Future research should integrate multi-omics profiling and AI-driven drug discovery to refine TAM-targeted therapies and improve patient outcomes. This review provides a comprehensive analysis of TAM-mediated immune regulation in GBM and explores evolving therapeutic strategies aimed at overcoming its treatment barriers. Full article

Sichuan Paocai is a representative traditional fermented vegetable in China, which is deeply embedded in local geographical and cultural heritage. However, regional differences in product characteristics remain poorly understood. In this study, the physicochemical properties, volatile compounds, and microbial communities of Paocai from seven production regions in Sichuan (named FB, AB, BZ, CD, DZ, MY, and YS) were systematically investigated. Parameters including pH, salinity, nitrite, organic acids, and color were determined, while volatile profiles were analyzed using an electronic nose and comprehensive two-dimensional gas chromatography–mass spectrometry. A total of 294 volatile compounds were identified, with alcohols, esters, and isothiocyanates emerging as the major contributors to flavor differentiation. UMAP and OPLS-DA analyses revealed distinct regional clustering, which was consistent with electronic nose profiling, and 111 volatile compounds were identified as key aroma markers. Microbial diversity was assessed using 16S rRNA gene sequencing, demonstrating that Lactobacillus, Lentilactobacillus, Pediococcus, and Weissella were the dominant taxa, although the richness varied significantly across regions. An LEfSe analysis further identified region-specific biomarkers, including Pediococcus, Lactococcus, and Leuconostoc in FB; Lactobacillus in AB; Pediococcus ethanolidurans in BZ; Levilactobacillus in DZ; Lentilactobacillus in MY; and a more diverse microbiota in MS. A correlation analysis highlighted the pivotal roles of distinct microbial groups in shaping and transforming flavor compounds across different regions. Overall, these findings provide scientific guidance for the development of high-quality, region-specific products and contribute to the protection, branding, and market competitiveness of geographically indicated foods. Full article

Objective: This study aims to explore the mechanism of regulated cell death-related genes in the development of endometrial carcinoma. Methods: Endometrial carcinoma-related datasets were yielded via the Cancer Genome Atlas and Gene Expression Omnibus databases, and regulated cell death-related genes were extracted from the literature. Differential expression analysis, weighted gene co-expression network analysis, and protein interaction analysis were performed to identify critical regulated cell death-related genes. Gene set enrichment analysis was used to identify the functional pathways involved in these critical genes. Afterward, the best clustering approach for tumor samples was yielded via consensus clustering analysis, and nomogram prediction models were built. Shiny Methylation Analysis Resource Tool was used to compare the expression levels of CpG methylation probes for critical genes between tumor and normal samples. Spearman correlation analysis was conducted to investigate the relationship between critical genes and various immune features. Eventually, immuno-infiltrative analysis was implemented, and potential therapeutic agents were screened targeting critical genes. The data were analyzed and visualized by R software using different packages. In addition, the expressions of critical genes were validated by quantitative real-time polymerase chain reaction and immunochemistry. Results: Four critical genes, namely GBP2, SLC11A1, P2RX7, and HCLS1, were identified, and they were involved in various functional pathways such as leukocyte-mediated cytotoxicity. There were substantial differences in CpG methylation in GBP2, SLC11A1, and HCLS1 between tumor and normal samples. As for immune features, all critical genes were positively connected with immunosuppressive factors such as TIGIT and most HLA molecules in endometrial carcinoma. The critical genes high/low expression groups of tumor samples showed different immune responses towards PD-1, PD-L1, and CTLA-4 immunotherapy. The infiltration of 24 immune cells, such as effector memory CD8⁺ T cells, was notably different between tumor and normal samples. Based on sensitivity analysis of chemotherapeutic agents, we found the highest positive correlation between SLC11A1 and “BI.2536” and the strongest passive correlation of HCLS1 and GBP2 with “Ribociclib”, as well as P2RX7 with “BMS.754807”. Quantitative real-time polymerase chain reaction suggested that the expression trends of GBP2, P2RX7, and HCLS1 were consistent with the results of bioinformatic analysis. Conclusions: Regulated cell death-related genes (GBP2, SLC11A1, P2RX7, and HCLS1) may play a role in endometrial carcinoma development, which can provide new ideas for the treatment and prognosis prediction of this disease. Full article

Sunset yellow (SY) is a synthetic azo dye widely used in food and cosmetics. However, concerns have been raised about its potential health risks, including its nephrotoxicity and genotoxicity, when used in excessive amounts. Illegal addition of SY may cause allergic reactions or genetic damage. Therefore, a rapid method for detecting SY is needed. To develop a rapid detection method for sunset yellow (SY) with the aim of preventing its illegal addition in food, this study utilized agricultural waste asparagus peel (AP) as a carbon source and synthesized amino-functionalized carbon quantum dots (AP-CDs) via a green hydrothermal method. A highly sensitive detection platform was established based on the fluorescence quenching mechanism of AP-CDs in the presence of SY. The microstructure of AP-CDs was characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Their optical properties were assessed via ultraviolet–visible absorption spectroscopy (UV-vis) and fluorescence spectroscopy (FS). Furthermore, key experimental parameters affecting SY detection were systematically optimized. Results revealed that the synthesized AP-CDs possessed surface hydrophilic functional groups, including hydroxyl, amide, and carboxyl groups, and were composed of carbon (C), oxygen (O), and nitrogen (N) elements. Optical performance studies demonstrated that AP-CDs exhibited a strong fluorescence emission at 470 nm under 380 nm excitation, with a quantum yield (Φ) of 15.9%. Under the optimized conditions (pH 7.0, 0.5 mg/mL AP-CDs), the fluorescence intensity showed a linear response to the concentration of SY over the range of 0.1 to 100 μM (R² = 0.9929), achieving a detection limit of 0.92 μM. This strategy not only enables sustainable resource utilization but also provides a sensitive and practical approach for food safety monitoring, demonstrating significant potential for real-world applications. Full article

Background and Objectives: To find morphological features on optical coherence tomography (OCT) and OCT-angiography (OCTA) influencing contrast sensitivity (CS) in patients with retinitis pigmentosa (RP). Materials and Methods: Cross-sectional study enrolling 18 eyes of 18 patients with RP. They were examined with CSV1000-E (VectorVision) under mesopic conditions (logarithmic scale), spectral-domain OCT (SD-OCT, Spectralis), swept-source OCT (SS-OCT, Triton), and OCTA (Triton). Automatic thickness measurements of every retinal layer were obtained in grids of 8 × 8 and 10 × 10 cubes. Foveal avascular zone and vascular densities (VD) were also analyzed. Statistical analysis included multiple lineal regression analyses, and a correlation analysis between age, axial length, and intraocular pressure, and retinal nerve fiber layer (RNFL) thickness. Results: Mean age was 47.34 ± 13.77 years. Mean CS with 3, 6, 12, and 18 cycles/degree (c/d) was 1.48 ± 0.37, 1.51 ± 0.39, 1.00 ± 0.42, and 0.44 ± 0.39, respectively. The most related variables to 3 c/d frequency were nasal RFNL thickness (R² = 0.54) and central outer plexiform layer (OPL) (R² = 0.33). In case of 6 c/d frequency, it was central VD in deep plexus (R² = 0.66), and retinal pigment epithelium (RPE) (R² = 0.22). As for 12 c/d frequency, it was central RNFL (R² = 0.50), and central VD in deep plexus (R² = 0.26). Regarding 18 c/d frequency, it was central RNFL (R² = 0.70). Conclusions: Central and nasal RNFL thickness seem to be main predictors of CS in patients with RP, as well as VD in deep retinal plexus. Others with limited influence might be central and nasal OPL thickness, and central RPE thickness. Full article