Search Results (32,623)

The Sichuan–Yunnan–Guizhou Pb-Zn metallogenic belt (SYG metallogenic belt), a crucial metallogenic unit on the southwestern margin of the Yangtze Block, is a key part of the South China low-temperature metallogenic domain. The incorporation mechanisms and distribution of trace elements (e.g., Ge, Ga, Cd) widely enriched in Pb-Zn sulfides throughout this region remain poorly understood. This study investigates main-ore-stage sulfides (sphalerite and pyrite) from the Maoping Pb-Zn deposit using in situ laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analyses and mapping to systematically elucidate the partitioning and occurrence of these trace elements. The key findings are as follows: (1) Sulfides show distinct elemental partitioning: sphalerite preferentially concentrates Cd, Ag, Ge, Ga, and Se, whereas pyrite is significantly enriched in Mn, Ni, As, and Co. (2) Sphalerite is the primary host for many trace elements. Cadmium, Ge, Mn, Cu, and Ag mainly enter the sphalerite lattice by substituting for Zn²⁺. Coupled substitution mechanisms, such as Zn²⁺ ↔ Cd²⁺, 2Zn²⁺ ↔ Ge²⁺ + Cu²⁺, and 2Zn²⁺ ↔ Ga³⁺ + Cu⁺, facilitate the incorporation of Ge and Ga. (3) The sphalerite exhibits a trace element assemblage of high Cd-Ge and low Fe-Mn, which is geochemically similar to typical Mississippi Valley-type (MVT) deposits and differs significantly from sedimentary exhalative (SEDEX) and magmatic–hydrothermal deposits, indicating a medium- to low-temperature metallogenic environment. Based on these geochemical signatures and epigenetic textures, we confirm that the Maoping Pb-Zn deposit exhibits similarities with MVT deposits. Nevertheless, distinct differences in the tectonic setting and metal grades suggest it is a unique SYG-type Pb-Zn deposit. Full article

Heavy metal contamination poses critical challenges for the cultivation of medicinal plants. This study explores cadmium (Cd)-induced morpho-physiological and metabolic responses in Salvia officinalis (So) and the rare endemic Salvia ceratophylloides (Sc). Plants were exposed to cadmium contamination corresponding to 5 and 10 mg kg⁻¹ Cd (100% and 200% of the Italian regulatory limit) and assessed through gas exchange, leaf anatomy, mineral profiling, polyphenol composition, antioxidant activity, and a preliminary ecotoxicological evaluation using the Artemia salina lethality bioassay. Cd predominantly accumulated in roots, reflecting a partial exclusion strategy, and caused alterations in leaf traits, water relations, and nutrient balance. While total polyphenols generally declined, species-specific responses emerged: S. ceratophylloides increased caffeic acid derivatives, whereas S. officinalis accumulated caffeic acid, lithospermic acid A, quercetin 3-O-glucuronide, and apigenin-O-pentoside at the highest Cd exposure. Polyphenol shifts were strongly associated with antioxidant capacity. Despite higher growth sensitivity, S. ceratophylloides extracts exhibited no toxicity in the A. salina assay, indicating effective metal sequestration and low bioavailability, whereas S. officinalis extracts induced moderate to high toxicity. These findings reveal contrasting Cd tolerance and detoxification strategies, highlighting the potential of integrating plant stress physiology with ecotoxicological assessment and phytostabilization approaches to safely cultivate medicinal species on contaminated soils. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and is characterized by excessive lipid accumulation in hepatocytes. Endoplasmic reticulum (ER) stress and inflammation play important roles in hepatic lipid accumulation. Although CILP2 has been implicated in lipid metabolism, its role in MASLD remains unclear. Hepatic steatosis was induced in mice by a high-fat diet in this study. CILP2 was overexpressed in mouse livers and in vitro hepatocytes using the Ad-CILP2 adenovirus. CILP2 KO mice were also used in the experiments. Liver tissues and hepatocytes were collected for further analysis. CILP2 expression was upregulated in steatotic liver tissue and hepatocytes. CILP2 overexpression upregulated genes related to fatty acid synthesis (Srebp-1c, Fasn, Acc, Scd1, and Cd36), promoted lipid accumulation, and elevated the expression of proinflammatory cytokines (Il6, Tnf, and Il1b). Conversely, CILP2 knockout reduced high-fat diet-induced hepatic steatosis and improved glucose metabolism. Mechanistically, CILP2 activated the IRE1α/XBP1 branch of the ER stress pathway, thereby promoting lipid synthesis and inflammation, effects that were partially alleviated by 4-PBA and STF-083010 treatments. Our findings indicate that CILP2 contributes to hepatic lipid accumulation and inflammation via the IRE1α/XBP1 pathway and may represent a potential therapeutic target for MASLD intervention. Full article

Background: The characteristics and prognosis of HIV-associated Kaposi sarcoma (KS) among people living with HIV (PLWH), and their association with HHV-8 viral load are not well understood in Japan. Methods: We conducted a retrospective study of PLWH diagnosed with KS at Tokyo Medical University from 2000 to 2023. Results: Seventy cases of KS were identified; HHV-8 viral load data were available for twenty-three of these cases. The median age was 43 years (interquartile range [IQR], 11 years). The median HIV viral load at diagnosis was 150,000 copies/mL (IQR, 560,000 copies/mL). The median CD4 count was 76.0/μL (IQR, 157/μL). Lesions other than those of the skin were observed in the gastrointestinal tract (nine cases, 39.1%), oropharynx (three cases, 13.0%), and bronchial/lung (two cases, 8.7%). The median HHV-8 viral load was 0.0 copies/10⁶ WBC (IQR, 1500 copies/10⁶ WBC). Among the nine deceased PLWH, KS inflammatory cytokine syndrome (KICS) was diagnosed in five PLWH. Older age (≥50 years) and a high HHV-8 viral load (>615 copies/10⁶ WBCs) were significantly associated with worse survival. Conclusion: A high HHV-8 viral load may be a risk factor for mortality in PLWH with KS. Notably, all PLWH diagnosed with KICS in this study died, underscoring the poor prognosis associated with this condition. Full article

Insects are increasingly recognized as sustainable protein sources due to their high feed conversion efficiency and low environmental impact. Among them, the superworm, Zophobas morio (Fabricius) (Coleoptera: Tenebrionidae), has strong potential for large-scale production; however, optimized feeding strategies under tropical conditions remain limited. This study aimed (1) to determine the optimal feed formulations and feeding rate using wheat bran supplemented with the KMITL Protein Innovation source (a protein feed ingredient developed by the School of Agricultural Technology, King Mongkut’s Institute of Technology Ladkrabang, KMITL), and (2) evaluate the influence of plant-based supplementary foods on larval performance. In Phase I, larvae were reared on 13 formulations with three protein levels (CP00, CP21, and CP24) and five feeding rates (A–E). Diets CP21–21 and CP24–21 (21 and 24% CP; wheat bran/protein = 2:1) resulted in the highest survival (83.4–84.1%) and the lowest feed conversion ratios (FCR = 2.29–2.34). Moderate feeding rates (C–D; 925–1110 g feed per tray for 50 days) produced the greatest larval weights (700–760 mg), whereas ad libitum feeding provided no additional benefit. In Phase II, larvae reared on CP21–21 with a restricted rate of 1100 g per tray and supplemented with ten plant-derived foods achieved comparable final weights (716–760 mg), but survival varied significantly among treatments. Mulberry leaf yielded the highest survival (95.3%), followed by banana, watermelon rind, winter melon, and jicama (>90%). Pumpkin and jicama accelerated pupation and adult emergence, showing a female-biased sex ratio among emerged adults (59.2–65.5%), suggesting enhanced developmental rates. These results establish a practical framework for cost-effective and sustainable Z. morio production under tropical conditions, contributing to circular bioeconomy strategies and supporting insect-protein innovation. Full article

As a critically important global food crop, wheat has been increasingly threatened by the frequent occurrence of extreme high-temperature events, which impairs its growth and development, resulting in reduced seed-setting rate, compromised grain quality and diminished yield. Therefore, identifying heat-tolerant genes and enhancing thermotolerance through molecular breeding are essential strategies for wheat improvement. In this study, we retrieved spatial transcriptomic data from the public database PRJNA427246, which captured gene expression profiles in flag leaves and grains of the heat-sensitive wheat cultivar Chinese Spring (CS) under 37 °C heat stress at time points of 0 min, 5 min, 10 min, 30 min, 1 h, and 4 h. Weighted Gene Co-expression Network Analysis (WGCNA) was used to construct co-expression networks for flag leaf and grain transcriptomes. One highly significant module was identified in each tissue, along with 35 hub genes that showed a strong temporal association with heat stress progression. Notably, both modules contained the previously characterized thermotolerance gene TaMBF1c, suggesting that additional heat-responsive genes may be present within these modules. Simultaneous analysis of the expression data from four groups (encompassing different tissues and high-temperature treatments) for the 35 core genes revealed that genes from the TaHSP20 family, TaMBF1c family, and other related genes exhibit coordinated expression patterns in terms of the temporal dynamics and tissue distribution of stress responses. Additionally, 27 genes of the small heat shock protein (HSP20) family are predicted to be involved in the endoplasmic reticulum-associated degradation (ERAD) pathway. They assist in clearing misfolded proteins induced by stress, thereby helping to maintain endoplasmic reticulum homeostasis and cellular functions under stress conditions. Finally, the expression levels of three core genes, TaHSP20-1, TaPCDP4, and TaMBF1c-D, were validated by qRT-PCR in two wheat cultivars with distinct thermotolerance: S116 (Zhehuamai 2008) and S128 (Yangmai 33). These findings provide new insights into the molecular mechanisms underlying heat tolerance in wheat and offer valuable genetic resources for breeding thermotolerant varieties. Full article

Diet plays a central role in shaping the composition and metabolic activity of the oral microbiota, thereby influencing both oral and systemic health. Disturbances in this delicate host–microbe balance, triggered by dietary factors, smoking, poor oral hygiene, or antibiotic use, can lead to microbial dysbiosis and increase the risk of oral diseases such as periodontitis, as well as chronic systemic disorders including diabetes, cardiovascular disease, Alzheimer’s disease, and certain cancers. Among dietary contaminants, exposure to toxic heavy metals such as cadmium (Cd), lead (Pb), mercury (Hg), nickel (Ni), and arsenic (As) represents an underrecognized modifier of the oral microbial ecosystem. Even at low concentrations, these elements can disrupt microbial diversity, promote inflammation, and impair metabolic homeostasis. Saliva has recently emerged as a promising, non-invasive biofluid for monitoring nutritional status and early metabolic alterations induced by diet and environmental exposures. Salivary biomarkers, including metabolites, trace elements, and microbial signatures, offer potential for assessing the combined effects of diet, microbiota, and toxicant exposure. This review synthesizes current evidence on how diet influences the oral microbiota and modulates susceptibility to heavy metal toxicity. It also examines the potential of salivary biomarkers as integrative indicators of nutritional status and metabolic health, highlights methodological challenges limiting their validation, and outlines future research directions for developing saliva-based tools in personalized nutrition and precision health. Full article

Chronic lymphocytic leukemia (CLL) is a dynamic malignancy in which intraclonal subfractions differ in activation history and responsiveness to microenvironmental signals. Here, we investigated the expression and inducibility of IL-12 family receptor subunits (IL-23R, IL-12Rβ1, IL-12Rβ2) and the related receptor complexes in recirculating CLL cells, with a focus on CXCR4/CD5-defined fractions: the proliferative fraction (PF; CXCR4^dim/CD5^bright; most recently divided, tissue-emigrated cells) and the resting fraction (RF; CXCR4^bright/CD5^dim; older, quiescent cells). At baseline, IL-12Rβ1 was enriched in the PF and was associated with a higher proportion of cells expressing IL-23R and IL-12R receptor complexes. Concomitantly, RT-qPCR disclosed higher IL-12Rβ1 mRNA levels. Following antigen-independent activation with CpG or CpG + IL-15, there was a marked increase in IL-23R and IL-12Rβ1 but not in IL-12Rβ2 surface expression, resulting in preferential upregulation of the IL-23R complex over the IL-12R complex. Fraction-specific analyses showed stronger induction of IL-23R and IL-23R complex expression in PF compared with RF. These findings identify an intraclonal bias toward IL-23 responsiveness in the CLL cells with a phenotype of recently divided, tissue-emigrated cells and suggest the IL-23/IL-23R axis as a potential therapeutic target. Full article

Cervical dystonia (CD), blepharospasm (BSP), and idiopathic hemifacial spasm (HFS) are focal hyperkinetic movement disorders with distinct underlying mechanisms. While CD and BSP involve central network dysfunctions within the basal ganglia-thalamo-cortical and cerebellar circuits, HFS primarily results from peripheral facial nerve hyperexcitability. Still, people living with all three conditions often struggle with mood issues like depression and anxiety, which can originate from both the burden of illness and changes in brain biology. We studied 61 patients (CD, n = 30; BSP, n = 9; HFS, n = 22) and assessed depression and anxiety before and three weeks after botulinum neurotoxin type A (BoNT-A) therapy, considering injection site and dose. BoNT-A significantly reduced depressive and anxiety symptoms across all groups, regardless of disease type, dose, or glabellar injection. These psychiatric improvements were not associated with the degree of motor symptom reduction, suggesting a partially independent mechanism of mood modulation. Our findings indicate that BoNT-A’s mood benefits may extend beyond local motor effects, possibly involving broader sensorimotor-limbic interactions. These results highlight the therapeutic potential of BoNT-A for addressing non-motor symptoms in both dystonic and non-dystonic hyperkinetic disorders. Future studies employing imaging and neurophysiological methods are necessary to explain the neural pathways underlying these effects. Full article

Background and Objectives: Glioblastoma (GBM) is the most aggressive primary tumor of the central nervous system, characterized by high invasiveness and poor prognosis. Inflammation in the tumor microenvironment, including the presence of immunosuppressive M2-macrophages (CD163+), plays a key role in disease progression. The aim of this study was to evaluate serum levels of interleukin-22 (IL-22) in Bulgarian patients with GBM and to analyze its diagnostic role, its relationship with systemic inflammatory markers (NLR), metabolic parameters, and the infiltration of CD163+ cells. Materials and Methods: The study included 41 newly diagnosed patients with GBM and 46 healthy controls. Serum IL-22 levels were measured by ELISA, and the density of CD163+ cells in the tumor tissue was analyzed immunohistochemically. Statistical analysis included Mann–Whitney test, ROC analysis, binary logistic regression, and Kaplan–Meier survival analysis. Results: GBM patients showed significantly higher levels of IL-22 compared to healthy controls (p = 0.001). ROC analysis demonstrated moderate diagnostic ability of IL-22 (AUC = 0.713), with high levels being a potential risk factor for the disease (OR= 2.51). A weak inverse correlation was found between IL-22 and neutrophil-to-lymphocyte ratio (NLR) (p = 0.048). Although IL-22 levels alone did not affect overall survival, patients with high levels of the cytokine and dense stromal infiltration of CD163+ macrophages tended to have shorter overall survival (p = 0.080). Conclusions: IL-22 is a potential diagnostic biomarker, probably reflecting the systemic inflammatory response in GBM. Its prognostic value might be contextually dependent on the tumor microenvironment, as high levels of IL-22 in combination with immunosuppressive macrophages may contribute to a more aggressive course of the disease. Full article

Flammulina filiformis is the key industrial edible fungus that requires elevated CO₂ to promote the growth of long stipe and small pileus fruiting bodies. Heat shock transcription factors (HSFs) play vital roles in stress response and development regulation; yet the HSF gene family and its expression dynamics during fruiting body development in F. filiformis remain uncharacterized. This study aims to identify and characterize the HSF gene family in F. filiformis and to investigate their expression patterns during fruiting body development and in response to CO₂ treatments. In this study, 7 FfHSFs were identified, and their structures, sequence features, and phylogenetics were further analyzed. Expression patterns under CO₂ regulation were examined via qRT-PCR. The FfHSFs exhibited CDS lengths of 618–2298 bp, encoding 301–765 hydrophilic amino acids, with molecular weights ranging from 23.4 to 83.8 kDa and theoretical pI values between 4.75 and 9.15. All were predicted to be nuclear-localized. Cis-element analysis revealed motifs associated with growth regulation and stress responses such as low temperature, drought, and hypoxia. Phylogenetically, fungal HSFs were grouped into five clusters, with FfHSFs distributed across four. In this study, we examined the expression levels at four time points (0 h, 2 h, 12 h, and 36 h), under three different carbon dioxide concentrations (0.1%, 5%, and 20%) and in two types of tissues (pileus and stipe) for each six biological replicates. CO₂ treatments showed that 5% CO₂ significantly suppressed pileus expansion but not stipe elongation, while 20% CO₂ inhibited both. Under 20% CO₂ treatment, the pileus diameter decreased by approximately 40%, and simultaneously, the expression level of FfHSF1 decreased by about 70%. qRT-PCR indicated that FfHSF1 decreased with pileus expansion, whereas FfHSF4 increased. All FfHSFs were highly expressed in the stipe elongation zone. Elevated CO₂ down-regulated FfHSF1 in pileus and FfHSF6 in stipes. Based on these findings, it could be proposed that FfHSF1 and FfHSF6 might be candidate regulators in CO₂-mediated morphogenesis, providing insights into hormonal and environmental control of fruiting body development in F. filiformis. Full article

A subset of patients with inflammatory bowel disease (IBD) remains refractory to treatment despite multiple lines of advanced therapies. These patients are often categorized as having difficult-to-treat (DTT) IBD. We retrospectively analyzed 354 patients with IBD (including 112 with Crohn’s disease [CD] and 242 with ulcerative colitis [UC]) from a real-world cohort. Baseline demographic and disease characteristics, treatment history, and outcomes were compared between the DTT-IBD and non-DTT-IBD groups. Logistic regression analysis was performed to identify factors associated with DTT-IBD in CD and UC cohorts. Approximately 10.6% of the patients exposed to advanced therapy fulfilled the definition of DTT-IBD (CD: 9.8%, UC: 11.4%). Compared with patients with non-DTT-IBD, those with DTT-IBD exhibited a significantly higher exposure to multiple biologic classes, including antitumor necrosis factor (94.1% vs. 59.0%), anti-integrin (94.1% vs. 47.2%), anti-interleukin-12/23 (88.2% vs. 19.4%), and Janus kinase inhibitors (35.3% vs. 0.7%). The DTT-IBD group had a significantly lower clinical remission rate at the last follow-up than the non-DTT-IBD group (52.9% vs. 85.4%, p = 0.001). A longer interval from diagnosis to the initiation of advanced therapy was independently associated with DTT-IBD in CD (OR: 1.014 per month, 95% CI: 1.001–1.026, p = 0.026). No significant predictors for UC were identified. In conclusion, DTT-IBD, characterized by extensive biologic exposure and suboptimal long-term remission rates, accounts for approximately 10% of patients with IBD receiving advanced therapy. In CD, delayed initiation of advanced therapy may contribute to refractoriness. These findings emphasize the unmet need for earlier therapeutic intervention, better predictive markers of treatment response, and novel therapeutic mechanisms. Full article

Phytoremediation is an eco-friendly and in situ solution for remediating heavy metal-contaminated soils, yet practical application requires timely and accurate effectiveness evaluation. However, conventional chemical analysis of plant parts and soils is labor-intensive, time-consuming and limited for large-scale monitoring. This study proposed a rapid sensing framework integrating laser-induced breakdown spectroscopy (LIBS) with deep transfer learning and spectral indices to assess phytoremediation effectiveness of Sedum alfredii (a Cd/Zn co-hyperaccumulator). LIBS spectra were collected from plant tissues and diverse soil matrices. To overcome strong matrix effects, fine-tuned convolutional neural networks were developed for simultaneous multi-matrix quantification, achieving high-accuracy prediction for Cd and Zn (R²_test > 0.99). These predicted concentrations enabled calculating conventional phytoremediation indicators like bioconcentration factor (BCF), translocation factor (TF), plant effective number (PEN), and removal efficiency (RE), yielding recovery rates near 100% for TF and PEN. Additionally, novel spectral indices (SIs)—directly derived from characteristic wavelength combinations—were constructed to bypass intermediate quantification. SIs significantly improved the direct evaluation of Zn removal and translocation. Finally, a decision-level fusion strategy combining concentration predictions and SIs enhanced Cd removal assessment accuracy. This study validates LIBS combined with intelligent algorithms as a rapid sensor tool for monitoring phytoremediation performance, facilitating sustainable environmental management. Full article

Microplastics (MPs) can serve as bearers of microorganisms and additional contaminants. However, the functional composition and assembly processes of plastisphere bacteria in co-contaminated soil–plant systems are not yet well understood. Using a pot experiment, we examined the effects of both individual and combined cadmium (Cd) and polypropylene (PP) MP contamination on the development of the bioenergy plant sorghum. The bacterial community, co-occurrence networks, and assembly processes in the rhizosphere soil and PP plastisphere were investigated using high-throughput sequencing. Compared with contamination by a single compound, combined contamination with Cd and PP had a more potent inhibitory effect on the development of sorghum. PCoA and diversity indices indicate that the bacterial community on PP plastics is structurally simpler than that in rhizosphere soil. The PP plastisphere could recruit bacteria from the genera Sphingomonas, Rhizobium, and Bacillus. The bacterial communities in the soil and the PP plastisphere were mostly formed by stochastic processes, with diffusion limitation playing a greater role in the bacterial community in the PP plastisphere. Co-occurrence network analysis revealed differences between the bacterial communities in the soil and in the PP plastisphere, with the network in the PP plastisphere showing lower complexity and connectivity. Functional prediction revealed that the prevalence of nitrogen cycling genes was greater in the PP plastisphere than in the dirt and that the PP plastisphere presented greater metabolic activity. The relative prevalence of metabolic pathways associated with human diseases was markedly elevated in the PP plastisphere, which may be correlated with the dissemination of pathogenic microorganisms. These findings indicate that the PP plastisphere, as a distinct microbial niche, might attract certain bacteria, consequently affecting the functional characteristics of cocontaminated soil–plant systems. Full article

A four-compartment tumor–immune interaction model is studied in a belief-based uncertain framework. The deterministic dynamics for tumor cells, natural killer cells, dendritic cells, and cytotoxic CD8${}^{+}$ T lymphocytes are extended to an uncertain differential system driven by a canonical Liu process, with therapeutic effects represented through treatment-related parameters acting on the respective populations. The analysis establishes well-posedness in the biologically relevant positive orthant under structural conditions compatible with the model nonlinearities, and it characterizes stability properties in the sense appropriate to uncertain dynamical systems. Sufficient conditions are derived for the existence of a global attracting set describing the long-time behavior of trajectories. The analytical results are complemented by numerical experiments based on $\alpha$-path dynamics to illustrate uncertainty-aware therapeutic scenarios and to connect the qualitative theory with observable system behavior. Full article