Mucosal microbiota characterization in gastric cancer identifies immune-activated-related transcripts relevant gastric microbiome signatures.

Tumor microenvironment (TME) immune cells and gastric mucosal microbiome constitute two vital elements of tumor tissue. Increasing evidence has elucidated their clinicopathological significance in predicting outcomes and therapeutic efficacy. However, comprehensive characterization of immune cell-associated microbiome signatures in the TME is still in the early stages of development. Here, we characterized the gastric mucosa microbiome and its associations with immune-activated related transcripts (IATs) in 170 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and quantitative reverse transcription-PCR. Microbial diversity and richness were significantly higher in GC tumor tissues than in non-tumor tissues. Differences in microbial composition between the groups were evident, with Firmicutes, Proteobacteria, Bacteroidota, Campilobacterota, Actinobacteria, Fusobacteriota, Verrucomicrobiota, Acidobacteriota, and Cyanobacteria being the dominant phyla in the gastric mucosal microbiota. Microbial interaction network analysis revealed distinctive centralities of oral bacteria (such as Fusobacterium, Porphyromonas, Prevotella, etc.) in both tumor and normal mucosae networks, suggesting their significant influence on GC microbial ecology. Furthermore, we analyzed the expression of IATs (CXCL9, CXCL10, GZMA, GZMB, PRF1, CD8A, IFNG, TBX2, and TNF) and characterized IAT-relevant gastric microbiome signatures in GC patients. Our results showed that the expression of CXCL9, CXCL10, GZMA, GZMB, PRF1 and IFNG was significantly higher in tumor tissues than in adjacent normal tissues in GC patients. Notably, high expression of IATs in tumor tissues was associated with improved survival in GC patients and could serve as a powerful predictor for disease-free survival. Additionally, analysis of IAT levels and mucosal microbiota diversity revealed a correlation between higher IAT expression and increased microbiota richness and evenness in the IATs high group, suggesting potential interactions between mucosal microbiota and tumor immunopathology. Spearman correlation analysis showed positive associations between IAT expression and specific mucosal bacterial species. Notably, Akkermansia muciniphila demonstrated potential involvement in modulating GZMB expression in the GC mucosal microenvironment. These findings underscore the importance of mucosal microbiota alterations in GC and suggest potential therapeutic targets focusing on modulating the tumor microbiota for improved clinical outcomes. The detailed characterization of these elements has profound implications for both treatment and survival prediction in GC. We observed that microbial diversity and richness were significantly higher in GC tumor tissues compared to non-tumor tissues. These differences highlight the unique microbial landscape of GC tumors and suggest that the microbiome could influence tumor development and progression. Importantly, our study demonstrated that high expression levels of IATs in GC tumor tissues were associated with improved patient survival. This suggests that IATs not only reflect immune activation but also serve as valuable biomarkers for predicting disease-free survival. The potential of IATs as predictive markers underscores their utility in guiding therapeutic strategies and personalizing treatment approaches. Moreover, the correlation between higher IAT expression and increased microbiota richness and evenness suggests that a diverse and balanced microbiome may enhance immune responses and contribute to better clinical outcomes. These findings highlight the critical need to consider mucosal microbiota alterations in GC management. Targeting the tumor microbiota could emerge as a promising therapeutic strategy, potentially leading to more effective treatments and improved patient outcomes. Understanding and modulating the microbiome's role in GC opens new avenues for innovative therapeutic interventions and personalized medicine.

The pathological significance and potential mechanism of ACLY in cholangiocarcinoma.

Background and aim: Cholangiocarcinoma (CCA) is a rare cancer, yet its incidence and mortality rates have been steadily increasing globally over the past few decades. Currently, there are no effective targeted treatment strategies available for patients. ACLY (ATP Citrate Lyase), a key enzyme in de novo lipogenesis, is aberrantly expressed in several tumors and is associated with malignant progression. However, its role and mechanisms in CCA have not yet been elucidated. Methods: The expression of ACLY in CCA was assessed using transcriptomic profiles and tissue microarrays. Kaplan-Meier curves were employed to evaluate the prognostic significance of ACLY in CCA. Functional enrichment analysis was used to explore the potential mechanisms of ACLY in CCA. A series of assays were conducted to examine the effects of ACLY on the proliferation and migration of CCA cells. Ferroptosis inducers and inhibitors, along with lipid peroxide probes and MDA assay kits, were utilized to explore the role of ACLY in ferroptosis within CCA. Additionally, lipid-depleted fetal bovine serum and several fatty acids were used to evaluate the impact of fatty acids on ferroptosis induced by ACLY inhibition. Correlation analyses were performed to elucidate the relationship between ACLY and tumor stemness as well as tumor microenvironment. Results: The expression of ACLY was found to be higher in CCA tissues compared to adjacent normal tissues. Patients with elevated ACLY expression demonstrated poorer overall survival outcomes. ACLY were closed associated with fatty acid metabolism and tumor-initiating cells. Knockdown of ACLY did not significantly impact the proliferation and migration of CCA cells. However, ACLY inhibition led to increased accumulation of lipid peroxides and enhanced sensitivity of CCA cells to ferroptosis inducers. Polyunsaturated fatty acids were observed to inhibit the proliferation of ACLY-knockdown cells; nonetheless, this inhibitory effect was diminished when the cells were cultured in medium supplemented with lipid-depleted fetal bovine serum. Additionally, ACLY expression was negatively correlated with immune cell infiltration and immune scores in CCA. Conclusion: ACLY promotes ferroptosis by disrupting the balance of saturated and unsaturated fatty acids. ACLY may therefore serve as a potential diagnostic and therapeutic target for CCA.

Programmable Artificial Skins Accomplish Antiscar Healing with Multiple Appendage Regeneration.

Functional appendage regeneration is essential for skin rehabilitation, but it has always failed by current existing healing approaches, owing to their inefficacy in preventing disfiguring scars. In this study, a novel regeneration-directing artificial skin (RDAS) system is presented, which is based on the rational design of multi-layered hydrogels that closely mimic natural skin matrices. By leveraging the programmability and architectural rigidity of DNA components, without the need for exogenous cell transplantation, such RDAS effectively minimizes tissue fibrosis by accurately guiding the regenerative process in wound fibroblasts, enabling rapid scarless wound repair, restoration of dermal function, and successful in situ regeneration of multiple appendages, such as hair follicles (HFs), sebaceous glands (SGs), and sweat glands (SwGs). Therefore, the RDAS offers a cell-free antiscarring therapeutic strategy for regenerative wound healing, resulting in improved outcomes. This innovative approach holds great potential for future clinical applications and burn rehabilitation.

Modulating Nitrogen Adsorption Mode and Microenvironment of Active Sites for Boosting Electrochemical Nitrogen Reduction.

Electrochemical reduction of N2 (NRR) offers a sustainable approach for ammonia (NH3) synthesis, serving as a complementary to the traditional emission- and energy-intensive Haber-Bosch process. However, it faces challenges in N2 activation and competing with pronounced hydrogen evolution reaction (HER). Herein an efficient electrocatalyst comprised of ultrafine Ru nanoclusters (NCs) confined by a hydrophobic molecular layer is developed on the surface of 2D Ti3C2Tx for NRR. These experimental and theoretical calculation results demonstrate that 1) ultrafine Ru NCs dispersed on the Ti3C2Tx surface form paired active sites for N2 chemisorption in a unique tilted configuration with low-energy activation 2) the hydrophobic molecular layer modulates the local microenvironment surrounding catalytically active sites, enabling efficient N2 accumulation while repelling H2O diffusion to the active sites on the Ti3C2Tx surface, thereby leading to an increased N2 concentration and suppressed HER. As a result, an exceptionally high NH3 yield rate of 33.5 µg h-1 mg-1cat and Faradaic efficiency of 65.3% are obtained at -0.25 V versus reversible hydrogen electrode (RHE) in 0.1 m Na2SO4, outperforming those previously reported Ti3C2Tx-derived electrocatalysts. This work provides a valuable strategy for the rational design of advanced electrocatalysts by manipulating active sites and local microenvironments for efficient electrocatalysis.

Stromal softness confines pancreatic cancer growth through lysosomal-cathepsin mediated YAP1 degradation.

The progression and malignancy of many tumors are associated with increased tissue stiffness. Conversely, the oncogenically transformed cells can be confined in soft stroma. Yet, the underlying mechanisms by which soft matrix confines tumorigenesis and metastasis remain elusive. Here, we show that pancreatic cancer cells are suppressed in the soft extracellular matrix, which is associated with YAP1 degradation through autophagic-lysosomal pathway rather than Hippo signal mediated proteasome pathway. In the soft stroma, PTEN is upregulated and activated, which consequently promotes lysosomal biogenesis, leading to the activation of cysteine-cathepsins for YAP1 degradation. In vitro, purified cathepsin L can directly digest YAP1 under acidic conditions. Lysosomal stress, either caused by chloroquine or overexpression of cystatin A/B, results in YAP1 accumulation and malignant transformation. Likewise, liver fibrosis induced stiffness can promote malignant potential in mice. Clinical data show that down-regulation of lysosomal biogenesis is associated with pancreatic fibrosis and stiffness, YAP1 accumulation, and poor prognosis in PDAC patients. Together, our findings suggest that soft stroma triggers lysosomal flux-mediated YAP1 degradation and induces cancer cell dormancy.

Predicting Bioaccumulation of Nanomaterials: Modeling Approaches with Challenges.

Understanding the bioaccumulation of nanomaterials (NMs) by organisms is essential in evaluating their potential ecotoxicity. However, the experimental determination of bioaccumulation is substantially challenging, which spawned the development of prediction approaches via establishing models for various NMs. Conventional modeling approaches, such as the biotic ligand model (BLM), partition coefficients, accumulation factor models, and quantitative structure-activity relationship (QSAR) models, were initially used in the application of NMs, aiming to provide a reliable quantitative dose in a resource-saving way. These methods, which are based on the uptake patterns of substances, probably lead to deviated results due to the different uptake behaviors of NMs. In this study, currently developed models to evaluate the bioaccumulation of NMs are critically reviewed, with their feasibilities and limitations being analyzed. In addition, the recently developed machine learning amended models have taken great efforts in realizing biological behaviors of NMs in organisms by providing in silico predictions. Though this data-driven approach has limitations in mechanism exploration, it may give different insights into the bioaccumulation model establishment and critical feature identification.

Construction and Optimization of a Yeast Cell Factory for Producing Active Unnatural Ginsenoside 3ß-O-Glc2-DM.

Ginsenosides are major active components of Panax ginseng, which are generally glycosylated at C3-OH and/or C20-OH of protopanaxadiol (PPD) and C6-OH and/or C20-OH of protopanaxatriol. However, the glucosides of dammarenediol-II (DM), which is the direct precursor of PPD, have scarcely been separated from P. ginseng. Because different positions and numbers of the hydroxyl and glycosyl groups lead to a diversity of structure and function of the ginsenosides, it can be inferred that DM glucosides may have different pharmacological activities compared with natural ginsenosides. Herein, we first constructed the cell factory for de novo biosynthesis of 3-O-(ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl)-dammar-24-ene-3ß,20S-diol (3ß-O-Glc2-DM) by introducing the codon-optimized genes encoding dammarenediol-II synthase, two UDP-glycosyltransferases (UGTs) including UGT74AC1-M7 from Siraitia grosvenorii and UGTPg29 from P. ginseng in Saccharomyces cerevisiae via the CRISPR/Cas9 system. The titer of 3ß-O-Glc2-DM was then increased from 18.9 to 148.0 mg/L by several metabolic engineering strategies including overexpressing the rate-limiting enzymes of triterpenoid biosynthesis, balancing carbon flux of biosynthetic pathways of triterpenoid and ergosterol, and engineering endoplasmic reticulum. Furthermore, the 3ß-O-Glc2-DM titer of 766.3 mg/L was achieved through fed-batch fermentation in a 3-L bioreactor. Finally, in vitro assays demonstrated that 3ß-O-Glc2-DM exhibited a protective effect on H/R-induced cardiomyocyte damage. This work provides a feasible approach for production of 3ß-O-Glc2-DM as a potential cardioprotective drug candidate.

Can Carbon be Used as an Anode for Water Splitting?

Carbon materials, whose structural and electronic properties can be fine-tuned, are promising material solutions for many energy-related systems. However, due to the lack of fundamental understanding of the carbon surface chemistry, especially when they are used in electrolytes, the rapid development of carbon as electrodes has led to many widely accepted misunderstandings. Focusing on the case of carbon-based electrode for water splitting, this Viewpoint tries to highlight the main problems of the area and demonstrates/presents the dynamic carbon surface chemistry in the application. The role of carbon as an anode for water splitting is revealed and if it can be practically used in water splitting is discussed.

Role of MYO1F in neutrophil and macrophage recruitment and pro-inflammatory cytokine production in Aspergillus fumigatus keratitis.

PURPOSE: Myosin 1f (Myo1f), an unconventional long-tailed class Ⅰ myosin, plays significant roles in immune cell motility and innate antifungal immunity. This study was aimed to assess the expression and role of Myo1f in Aspergillus fumigatus (AF) keratitis. METHODS: Myo1f expression in the corneas of mice afflicted with AF keratitis and in AF keratitis-related cells was assessed using protein mass spectrometry, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunofluorescence. Myo1f expression following pre-treatment with inhibitors of dendritic cell-associated C-type lectin-1 (Dectin-1), Toll-like receptor 4 (TLR-4), and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was also examined. In AF keratitis mouse models, Myo1f small interfering RNA (siRNA) was administered via subconjunctival injection to observe disease progression, inflammatory cell recruitment, and protein production using slit lamp examination, immunofluorescence, hematoxylin-eosin (HE) staining, and western blotting. RESULTS: Myo1f expression was upregulated in both AF keratitis mouse models and AF keratitis-related cells. Dectin-1, TLR-4, and LOX-1 were found to be essential for the production of Myo1f in response to the infection with AF. In mice with AF keratitis, knockdown of Myo1f reduced disease severity, decreased the recruitment of neutrophils alongside macrophages to inflammatory areas, suppressed the myeloid differentiation factor 88 (MyD88)/ nuclear factor-kappaB (NF-κB) signaling pathway, and decreased the production of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, along with IL-6. Additionally, Myo1f was associated with apoptosis and pyroptosis in mice with AF keratitis. CONCLUSIONS: These findings demonstrated that Myo1f contributed to the recruitment of neutrophils and macrophages, the production of pro-inflammatory cytokines, and was associated with apoptosis and pyroptosis during AF keratitis.

Peptide-functionalized gold nanoparticles for boron neutron capture therapy with the potential to use in Glioblastoma treatment.

Glioblastoma is a highly aggressive glioma with limited treatment options. Boron neutron capture therapy (BNCT) offers a promising approach for refractory cancers, utilizing boron-10 (10B) and thermal neutrons to generate cytotoxic particles. Effective BNCT depends on selective targeting and retention of 10B in tumors. Current BNCT drugs face issues with rapid clearance and poor tumor accumulation. To address this, we developed gold nanoparticles (AuNPs) functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides as a nanocarrier for Sodium Mercaptododecaborate (BSH), resulting in AuNPs-BSH&PEG-cRGD. In vitro, AuNPs-BSH&PEG-cRGD increased 10B content in GL261 glioma cells by approximately 2.5-fold compared to unmodified AuNPs-BSH&PEG, indicating enhanced targeting due to cRGD's affinity for integrin receptor αvß3. In a subcutaneous glioma mouse model, 6 h post-intratumoral administration, the 10B concentration in tumors was 17.98 µg/g for AuNPs-BSH&PEG-cRGD, significantly higher than 0.45 µg/g for BSH. The tumor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratios were also higher for AuNPs-BSH&PEG-cRGD, suggesting improved targeting and retention. This indicates that AuNPs-BSH&PEG-cRGD may enhance BNCT efficacy and minimize normal tissue toxicity. In summary, this study provides a novel strategy for BSH delivery and may broaden the design vision of BNCT nano-boron capture agents.

LncRNA-HMG incites colorectal cancer cells to chemoresistance via repressing p53-mediated ferroptosis.

Upon chemotherapy, excessive reactive oxygen species (ROS) often lead to the production of massive lipid peroxides in cancer cells and induce cell death, namely ferroptosis. The elimination of ROS is pivotal for tumor cells to escape from ferroptosis and acquire drug resistance. Nevertheless, the precise functions of long non-coding RNAs (lncRNAs) in ROS metabolism and tumor drug-resistance remain elusive. In this study, we identify LncRNA-HMG as a chemoresistance-related lncRNA in colorectal cancer (CRC) by high-throughput screening. Abnormally high expression of LncRNA-HMG predicts poorer prognosis in CRC patients. Concurrently, we found that LncRNA-HMG protects CRC cells from ferroptosis upon chemotherapy, thus enhancing drug resistance of CRC cells. LncRNA-HMG binds to p53 and facilitates MDM2-mediated degradation of p53. Decreased p53 induces upregulation of SLC7A11 and VKORC1L1, which contribute to increase the supply of reducing agents and eliminate excessive ROS. Consequently, CRC cells escape from ferroptosis and acquire chemoresistance. Importantly, inhibition of LncRNA-HMG by anti-sense oligo (ASO) dramatically sensitizes CRC cells to chemotherapy in patient-derived xenograft (PDX) model. LncRNA-HMG is also a transcriptional target of ß-catenin/TCF and activated Wnt signals trigger the marked upregulation of LncRNA-HMG. Collectively, these findings demonstrate that LncRNA-HMG promotes CRC chemoresistance and might be a prognostic or therapeutic target for CRC.

Effects of silicate stabilizers on cadmium reduction and the quality of rice grains in acidic paddy soil.

Silicate has been proven to be highly-effective at immobilizing soil heavy metals, but the effects of silicate stabilizers on rice grain cadmium (Cd) reduction and rice quality under field conditions are not clear. In this study, a field experiment was conducted over three consecutive years was conducted to examine the Cd reduction in rice grains and to reveal the potential effects of silicate stabilizers on rice grain nutrients, by setting different amounts of bentonite (B), silica‒calcium fertilizer (SC) and zeolite powder (ZP). The results revealed that the application of the B, SC and ZP significantly decreased the soil CaCl2‒Cd concentration (> 39%) and significantly reduced the grain Cd concentration in both early rice (> 70%) and late rice (> 18%) under field conditions; the silicate stabilizers reduced the soil available iron (Fe) but did not limit rice grain Fe nutrition. Additionally, the three silicates promoted rice yield and improved the rice grain Ca and Mg contents; and the application of B increased the amylose concentration of the late rice grains. In conclusion, high amounts of silicate stabilizers did not adversely influence the soil conventional nutrient indices, rice minerals or rice taste, but changes in rice selenium content need attention. Overall, in comparison with lime, silicate stabilizers can improve not only the safety of rice but also the nutritional and taste qualities of rice and are more eco-friendly for long-term use in soil.

A distinct neuronal ensemble of prelimbic cortex mediates spontaneous pain in rats with peripheral inflammation.

The absence of a comprehensive understanding of the neural basis of spontaneous pain limits the development of therapeutic strategies targeting this primary complaint of patients with chronic pain. Here we report a distinct neuronal ensemble within the prelimbic cortex which processes signals related to spontaneous pain in rats with chronic inflammatory pain. This neuronal ensemble specifically encodes spontaneous pain-related behaviors, independently of other locomotive and evoked behaviors. Activation of this neuronal ensemble elicits marked spontaneous pain-like behaviors and enhances nociceptive responses, whereas prolonged silencing of its activities alleviates spontaneous pain and promotes overall recovery from inflammatory pain. Notably, afferents from the primary somatosensory cortex and infralimbic cortex bidirectionally modulate the activities of the spontaneous pain-responsive prelimbic cortex neuronal ensemble and pain behaviors. These findings reveal the cortical basis of spontaneous pain at the neuronal level, highlighting a distinct neuronal ensemble within the prelimbic cortex and its associated pain-regulatory brain networks.

Effective soil remediation with fungal Co-inoculation and king grass for robust cadmium and chromium phytoextraction.

Bioremediation, an economical and environmentally friendly approach, provides a sustainable solution for mitigating heavy metal contamination in soils. This study identifies four fungal strains-Trichoderma harzianum DAA8, Trichoderma reesei DAA9, Rhizomucor variabilis DFB3, and Trichoderma asperellum LDA4-that exhibit tolerance to cadmium (Cd) and chromium (Cr). These strains were isolated from soils impacted by heavy metal contamination in mining regions. Rigorous examinations of these strains led us to determine their Minimum Inhibitory Concentrations (MICs) and optimal absorption-reduction conditions. Our microscopic data and GC-MS analysis indicate that these strains can accumulate Cd and Cr by generating compounds, such as ketones and imines, in heavy metal environments. We evaluated the remediation efficacy of both single and co-cultures of Rhizomucor variabilis DFB3 and Trichoderma asperellum LDA4 in conjunction with king grass, a plant known for its heavy metal accumulation capabilities. Our findings indicated an impressive 41.9% increase in plant biomass and 47.2% and 64.4% increase in Cd and Cr accumulation respectively. The removal rates of Cd and Cr were 16.5% and 19.0%, respectively, following the co-inoculation of Rhizomucor variabilis DFB3 and Trichoderma asperellum LDA4. These rates represent increases of 37.1% and 33.7% compared to the removal rates achieved with king grass alone. This study not only advances strategies to manage Cd-Cr contamination but also sets a pathway for efficient heavy metal soil remediation using a microbial-plant combined technique.

Global research trends and hotspots of oxidative stress in diabetic retinopathy (2000-2024).

Introduction: Oxidative stress has been identified as a major contributor to the pathogenesis of DR, and many diagnostic and therapeutic strategies have been developed to target oxidative stress. Our aim was to understand the contribution of the country of origin of the publication, the institution, the authors, and the collaborative relationship between them. Methods: We performed a bibliometric analysis to summarize and explore the research hotspots and trends of oxidative stress in the DR. Results: We observe an upward trend in the number of posts on related topics from year to year. Expanding on this, Queens University Belfast is the most influential research institution. Current research hotspots and trends focus on the mechanism of autophagy and NLRP3 inflammasome's role in oxidative stress in DR. Discussion: We conducted a multi-dimensional analysis of the research status of oxidative stress in diabetic retinopathy through bibliometric analysis, and proposed possible future research trends and hotspots.

PHGDH/SYK: a hub integrating anti-fungal immunity and serine metabolism.

Immune cells modify their metabolic pathways in response to fungal infections. Nevertheless, the biochemical underpinnings need to be better understood. This study reports that fungal infection drives a switch from glycolysis to the serine synthesis pathway (SSP) and one-carbon metabolism by inducing the interaction of spleen tyrosine kinase (SYK) and phosphoglycerate dehydrogenase (PHGDH). As a result, PHGDH promotes SYK phosphorylation, leading to the recruitment of SYK to C-type lectin receptors (CLRs). The CLR/SYK complex initiates signaling cascades that lead to transcription factor activation and pro-inflammatory cytokine production. SYK activates SSP and one-carbon metabolism by inducing PHGDH activity. Then, one-carbon metabolism supports S-adenosylmethionine and histone H3 lysine 36 trimethylation to drive the production of pro-inflammatory cytokines and chemokines. These findings reveal the crosstalk between amino acid metabolism, epigenetic modification, and CLR signaling during fungal infection.

Prognostic model for hepatocellular carcinoma based on necroptosis-related genes and analysis of drug treatment responses.

Objective: Recent studies reveal that necroptosis is pivotal in tumorigenesis, cancer metastasis, cancer immunity, and cancer subtypes. Apoptosis or necroptosis of hepatocytes in the liver microenvironment can determine the subtype of liver cancer. However, necroptosis-related genomes have rarely been analyzed in hepatocellular carcinoma (HCC). Therefore, this study aims to construct an HCC risk scoring model based on necroptosis-related genes and to validate its predictive performance in overall survival prediction and immunotherapy efficacy evaluation in HCC, as well as to analyze drug treatment responses. Methods: This study analyzed clinical information and RNA-seq expression data of liver cancer patients from TCGA public data, identified necroptosis-related genes, and conducted GO and KEGG enrichment analyses. Using Cox regression analysis and LASSO analysis to identify independent prognostic factors, a predictive model was established and validated in clinical subgroups, and correlation analysis with immune cells and ssGSEA differential analysis were conducted. Finally, potential drugs for HCC were screened to explore the drug sensitivity of different subtypes. Results: We identified 19 differentially expressed necroptosis-related genes and constructed a predictive model with 3 independent prognostic factors through stepwise Cox regression. Validation results from clinical subgroups showed that the constructed model performed well in risk prediction, and ssGSEA differential analysis results were significant. We analyzed 55 immunotherapy drugs, and clustered them by distinct IC50 values to guide drug selection for HCC patients. Notable, Bleomycin, Obatoclax. Mesylate, PF.562271, PF.02341066, QS11, X17. AAG, and Bl. D1870 exhibited significantly different sensitivities in different subtypes, providing references for clinical practice in HCC patients.

Role of LECT2 in exacerbating atopic dermatitis: insight from in vivo and in vitro models via NF-κB signaling pathway.

Leukocyte cell-derived chemotaxin 2 (LECT2) is linked to various immune diseases. Previously, we reported that serum LECT2 levels correlate with disease severity in atopic dermatitis (AD) patients. To investigate the role of LECT2 in AD and elucidate its potential mechanisms, we used LECT2 to treat an AD mouse model induced by 1-Chloro-2,4-dinitrobenzene (DNCB) in LECT2 knockout (KO) and wild-type (WT) mice, and an AD cell model using TNF-α/IFN-γ-induced HaCaT cells. Inflammatory factors and barrier proteins were analyzed by histology, immunohistochemistry, RT-qPCR, ELISA, and Western Blot. Activation of the NF-κB signaling pathway was evaluated by Western Blot and immunofluorescence. In the AD mouse model, LECT2 treatment increased epidermal and dermal thickness, mast cell infiltration, and downregulated barrier proteins. Inflammatory factors were increased in skin lesions and serum. In the AD cell model, LECT2 decreased barrier protein levels and increased inflammatory factor levels, enhancing NF-κB P65 nuclear translocation. These results indicate that LECT2 exacerbates AD-like responses by dysregulating the NF-κB signaling pathway, highlighting its potential as a therapeutic target for AD management.

Enhancing mango yield and soil health with organic and slow-release fertilizers: A multifaceted evaluation.

Excessive utilization of chemical fertilizers in mango orchards not only hampers the attainment of sustainable harvests but also poses significant ecological detriments. This investigation proposes a promising solution by advocating the judicious replacement of chemical fertilizers with organic fertilizer (OF) and slow-release fertilizer (SRF), with potential to bolster soil health and augment crop productivity. In light of the promise held by these alternatives, it is imperative to establish detailed fertilization protocols for enhanced sustainable practices in mango farming. This two-year field study employed a comprehensive suite of seven fertilization strategies, unveiling that a 25 % chemical fertilizers substitution with OF and SRF improved mango yields by 12.5 % and 11.3 %, respectively, over standard practices. Additionally, these approaches substantially augmented the nutritional quality of mangoes, evident from Vitamin C enhancements of 53.9 % to 56.9 %, and improvements in sugar-to-acid ratio (19.2 %-30.3 %) and solid-to-acid ratio (12.1 %-25.3 %). Notably, the application of OF and SRF led to increased leaf nitrogen and phosphorus concentrations, while simultaneously reducing soil phosphorus and potassium levels. Furthermore, these fertilizers fostered the growth of beneficial soil microorganisms, namely Actinobacteria and Proteobacteria, and strengthened the synergy within the soil bacterial community, hence optimizing bacterial competition and nutrient cycling. The study proposes that the adoption of OF or SRF can effectively regulate soil nutrient balance, promote resilient and functional soil bacterial ecosystems, and ultimately improve mango yield and fruit quality. It recommends a fertilization scheme incorporating 25 % organic or slow-release nitrogen to align with ecological sustainability goals, promoting a more vigorous and resilient soil and crop system.

Self-Healing Hydrogel Resulting from the Noncovalent Interaction between Ropivacaine and Low-Molecular-Weight Gelator Sodium Deoxycholate Achieves Stable and Endurable Local Analgesia in Vivo.

Regional analgesia based on the local anesthetic ropivacaine plays a crucial role in postoperative pain management and recovery; however, the short duration of analgesia limits its clinical potential. Various drug delivery systems such as microparticles and lipid carriers have been used to prolong the analgesic effect, yet most of them are prone to abrupt release from the site of administration or have poor analgesic effects of less than 48 h, which fail to meet the needs of postoperative analgesia. In this study, a low-molecular-weight gelator sodium deoxycholate-based hydrogel loaded with ropivacaine (DC-ROP gel) was designed for long-acting analgesia. The noncovalent interaction between ropivacaine and sodium deoxycholate helps to improve the stability and sustained release performance of the gel. This internal drug-binding hydrogel also avoids experiencing the burst release effect commonly seen in polymer hydrogels previously reported for the slow release of local anesthetics. DC-ROP gel exhibited the dual advantages of self-healing after compression and long-term controlled release. In mice with inflammatory pain, DC-ROP gel achieved peripheral nerve block for more than 1 week after a single injection. Histological and blood biochemical analyses confirmed that the DC-ROP gel did not produce systemic toxicity, and cytotoxicity experiments demonstrated that the DC-ROP gel resulted in low irritation. These results suggest that DC-ROP gel provides a promising strategy for local anesthetics in long-term postoperative pain management, broadening the potential of bile salt-based low-molecular-weight hydrogels for drug delivery.